Multispecific binding agents that target CTLA4 and / or CD25 and uses thereof

Abstract

The present disclosure provides binding agents (e.g., antibodies, including multispecific binding agents, such as bispecific antibodies) that have a first binding domain that binds to CTLA4, including human CTLA4, and one or more additional binding domains that bind to one or more targets that are not CTLA4, such as CD25, and uses thereof.

Description

Attorney Docket No.209070-014003 / PCT MULTISPECIFIC BINDING AGENTS THAT TARGET CTLA4 AND / OR CD25 AND USES THEREOF CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to US Provisional Application No.63 / 610,366 filed December 14, 2023, and US Provisional Application No.63 / 551,508 filed February 8, 2024, the entire contents of each of which are herein incorporated by reference. INCORPORATION BY REFERENCE OF SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing, which has been submitted electronically. The Sequence Listing titled 209070-014003PCT_SL.xml, which was created on December 12, 2024 and is 485,364 bytes in size, is herein incorporated by reference in its entirety. FIELD

[0003] The present disclosure relates generally to binding agents, such as antibodies, that bind to CTLA4, including human CTLA4, or to CD25, including human CD25, including multispecific binding agents, such as bispecific antibodies, that have a first binding domain that binds to CTLA4 and one or more additional binding domains that bind to one or more targets that are not CTLA4, such as CD25, and methods of their use. BACKGROUND

[0004] Regulatory T cells (Tregs) play an important role in immune homeostasis and self-tolerance. They also play key roles in controlling autoimmunity, inflammation, infection, and tumor immunity. The central role of Tregs in immune homeostasis has been demonstrated by Treg ablation studies. For example, ablation of Tregs leads to the development of fatal autoimmune disorders in mice. Therefore, non-specific depletion of Tregs could negatively impact immune homeostasis and lead to undesirable autoimmune phenotypes. Page 1 of 555 ACTIVE 705104971v1

[0005] The tumor microenvironment includes various cell types such as CD8+ T-cells, CD4+ T-cells, Tregs, macrophages, natural killer (NK) cells, dendritic cells (DCs), B cells, mast cells, and other cell types. The immune cells in the tumor microenvironment contribute to its immunosuppressive nature, promoting immune evasion, and cancer progression.

[0006] Tregs are known to infiltrate tumors. Accumulation of tumor-associated FoxP3+ Tregs and high Treg / T effector ratios in the tumor microenvironment is associated with worse prognosis in many cancers.

[0007] Tumor-associated Tregs exhibit distinct phenotypes, for example by upregulating markers associated with activation and immunosuppressive activity. For example, tumor-infiltrating Tregs exhibit higher expression of, for example, CTLA4, LAG-3, TIM-3, PD-1, ICOS, GITR, CD25, CD44, NRP-1, CD69, CCR4, CCR8, CD163, and OX40 among others.

[0008] Several studies have demonstrated an important role for Tregs in tumor immune self-tolerance. Tumor-associated Tregs can also promote cancer progression in other ways, for example, by promoting tumor angiogenesis. Furthermore, many studies have shown that Treg ablation reduces tumor growth, and in some cases have resulted in tumor clearance. Other studies have shown that Treg ablation can enhance cancer immunotherapy.

[0009] There has been considerable interest in selectively targeting Tregs in the tumor microenvironment. However, the selective inactivation / depletion of tumor- infiltrating Tregs present several challenges, as tumor Tregs often share the same cell surface markers as other conventional T-cells or peripheral Tregs. For example, antibody-based approaches generally target both tumor-infiltrating Tregs and activated effector T cells.

[0010] Accordingly, there remains a need in the art for agents that overcome these concerns, and which selectively target tumor-associated Tregs. The multispecific binding agents, compositions and methods provide herein satisfy this need and provide related advantages. Summary

[0011] In some aspects, provided herein are compositions having an antibody, including a multispecific antibody, such as a bispecific antibody, or antibody fragments thereof that bind to CTLA4 and / or CD25. Such compositions are useful inPage 2 of 555 ACTIVE 705104971v1methods for treating a cancer, treating a tumor T regulatory cell mediated disease, disorder or condition, and / or depleting tumor regulatory T cells (Tregs) in a subject. The compositions and methods provided herein can target cells that express CTLA4 and / or CD25. Thus, in some aspects of the present disclosure, provided herein is an antibody or fragment thereof comprising multiple polypeptide chains that have an antigen binding domain that binds CTLA4 and / or an antigen binding domain that binds to CD25.

[0012] In some aspects, provided herein is a multispecific antibody or fragment thereof including a first binding domain that binds to CTLA4, wherein the first binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in an amino acid sequence selected from any one of SEQ ID NOs: 44, 57, 86, 95, 104, 135, 147, 151, 173, 196, and 224 , and wherein the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in an amino acid sequence selected from any one of SEQ ID NOs: 45, 58, 62, 67, 73, 87, 96, 105, 111, 116, 123, 127, 136, 142, 156, 163, 174, 178, 183, 190, 206, 211, and 225.

[0013] In some aspects, provided herein is a multispecific antibody or fragment there 1, wherein: (a) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:45; (b) the VH includes a VH CDR, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:58; (c) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:62; (d) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:67; (e) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:73; (f) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:86 and the VL includes a VL CDR1, a VL CDR2, and aPage 3 of 555 ACTIVE 705104971v1VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:87; (g) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:95 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:96; (h) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:104 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:105; (i) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:111; (j) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:116; (k) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:123; (l) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:127; (m) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:136; (n) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:57 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:142; (o) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:147 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:142; (p) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:123; (q) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:151 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:73; (r) the VH includes a VH CDR1, a VHPage 4 of 555 ACTIVE 705104971v1CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:156; (s) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:163; (t) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:173 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:174; (u) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:178; (v) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:183; (w) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:190; (x) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:196 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:45; (y) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:206; (z) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:211; or (aa) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:224 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:225.

[0014] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the multispecific antibody or fragment thereof includes a second binding domain that binds to CD25.Page 5 of 555 ACTIVE 705104971v1

[0015] In some aspects, provided herein is a multispecific antibody or fragment there 1 to 3, wherein the multispecific antibody or fragment thereof is a bispecific antibody.

[0016] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38 and (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:42.

[0017] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:47, (ii) SEQ ID NO:50, (iii) SEQ ID NO:53, and (iv) SEQ ID NO:55; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:48, (ii) SEQ ID NO:51, and (iii) SEQ ID NO:56; and (3) aPage 6 of 555 ACTIVE 705104971v1VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0018] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:59, (ii) SEQ ID NO:60, and (iii) SEQ ID NO:61; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0019] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:63, (ii) SEQ ID NO:64, (iii) SEQ ID NO:65, and (iv) SEQ ID NO:66; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.Page 7 of 555 ACTIVE 705104971v1

[0020] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:68, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:69, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:72; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0021] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:74, (ii) SEQ ID NO:444, (iii) SEQ ID NO:425, (iv) SEQ ID NO:78, and (v) SEQ ID NO:81; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:340, (ii) SEQ ID NO:341, (iii) SEQ ID NO:79, (iv) SEQ ID NO:82, and (v) SEQ ID NO:85; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:75, (ii) SEQ ID NO:77, (iii) SEQ ID NO:80, and (iv) SEQ ID NO:83; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:76, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:84; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.Page 8 of 555 ACTIVE 705104971v1

[0022] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:88, (ii) SEQ ID NO:90, (iii) SEQ ID NO:91, (iv) SEQ ID NO:92, and (v) SEQ ID NO:94; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:89, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:93; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0023] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:97, (ii) SEQ ID NO:99, (iii) SEQ ID NO:101, (iv) SEQ ID NO:103, and (v) SEQ ID NO:445 and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:98, (ii) SEQ ID NO:100, (iii) SEQ ID NO:102, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.Page 9 of 555 ACTIVE 705104971v1

[0024] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:106, (ii) SEQ ID NO:108, (iii) SEQ ID NO:109, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:107, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:110; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0025] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:112, (ii) SEQ ID NO:113, (iii) SEQ ID NO:114, and (iv) SEQ ID NO:115; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.Page 10 of 555 ACTIVE 705104971v1

[0026] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:117, (ii) SEQ ID NO:119, (iii) SEQ ID NO:120, and (iv) SEQ ID NO:121; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:118, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:122; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0027] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:124, (ii) SEQ ID NO:125, (iii) SEQ ID NO:126, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.Page 11 of 555 ACTIVE 705104971v1

[0028] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:129, (ii) SEQ ID NO:131, and (iii) SEQ ID NO:134; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0029] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes : (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:46, (ii) SEQ ID NO:49, (iii) SEQ ID NO:52, and (iv) SEQ ID NO:54; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:137, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:140; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:138, (ii) SEQ ID NO:139, and (iii) SEQ ID NO:141.Page 12 of 555 ACTIVE 705104971v1

[0030] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:143, (ii) SEQ ID NO:144, (iii) SEQ ID NO:145, and (iv) SEQ ID NO:146; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:137, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:140; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:138, (ii) SEQ ID NO:139, and (iii) SEQ ID NO:141.

[0031] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:117, (ii) SEQ ID NO:119, (iii) SEQ ID NO:120, and (iv) SEQ ID NO:121; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:118, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:122; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.Page 13 of 555 ACTIVE 705104971v1

[0032] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:148, (ii) SEQ ID NO:149, (iii) SEQ ID NO:34, (iv) SEQ ID NO:150, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:68, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:69, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:72; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0033] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:152, (ii) SEQ ID NO:10, (iii) SEQ ID NO:154, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:153, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:155.Page 14 of 555 ACTIVE 705104971v1

[0034] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:157, (ii) SEQ ID NO:159, (iii) SEQ ID NO:161, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:158, (ii) SEQ ID NO:160, and (iii) SEQ ID NO:162; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30,.

[0035] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:164, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:170, and (v) SEQ ID NO:172; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:165, (ii) SEQ ID NO:167 (iii) SEQ ID NO:169 and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:166, (ii) SEQ ID NO:168, and (iii) SEQ ID NO:171; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30,.

[0036] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the firstPage 15 of 555 ACTIVE 705104971v1binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:175, (ii) SEQ ID NO:176, and (iii) SEQ ID NO:177.

[0037] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:179, (ii) SEQ ID NO:180, (iii) SEQ ID NO:181, and (iv) SEQ ID NO:182; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0038] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VHPage 16 of 555 ACTIVE 705104971v1CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:184, (ii) SEQ ID NO:186, and (iii) SEQ ID NO:188; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:185, (ii) SEQ ID NO:187, and (iii) SEQ ID NO:189.

[0039] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:191, (ii) SEQ ID NO:192, (iii) SEQ ID NO:193, (iv) SEQ ID NO:194, and (v) SEQ ID NO:195; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0040] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQPage 17 of 555 ACTIVE 705104971v1ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:197, (ii) SEQ ID NO:200, (iii) SEQ ID NO:202 and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:198, (ii) SEQ ID NO:201, and (iii) SEQ ID NO:204; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:199, (ii) SEQ ID NO:203, and (iii) SEQ ID NO:205.

[0041] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:207, (ii) SEQ ID NO:208, (iii) SEQ ID NO:209, and (iv) SEQ ID NO:210; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0042] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQPage 18 of 555 ACTIVE 705104971v1ID NO:212, (ii) SEQ ID NO:215, (iii) SEQ ID NO:217, (iv) SEQ ID NO:218, and (v) SEQ ID NO:220; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:213, (ii) SEQ ID NO:216, (iii) SEQ ID NO:219, (iv) SEQ ID NO:221, and (v) SEQ ID NO:223; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:214, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:222; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0043] In some aspects, provided herein is a multispecific antibody or fragment there 5 to 31, wherein the multispecific antibody includes a second binding domain that binds to CD25.

[0044] In some aspects, provided herein is a multispecific antibody or fragment there 5 to 32, which is a bispecific antibody.

[0045] In some aspects, provided herein is a multispecific antibody or fragment there 32 or 33, wherein the second binding domain that binds to CD25 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:1, (ii) SEQ ID NO:7, (iii) SEQ ID NO:12, (iv) SEQ ID NO:13, and (v) SEQ ID NO:18; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:2, (ii) SEQ ID NO:8, (iii) SEQ ID NO:14, (iv) SEQ ID NO:19, and (v) SEQ ID NO:24; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:3, (ii) SEQ ID NO:9, (iii) SEQ ID NO:15, and (iv) SEQ ID NO:20; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:6, (ii) SEQ ID NO:17, and (iii) SEQ ID NO:23.Page 19 of 555 ACTIVE 705104971v1

[0046] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41.

[0047] In some aspects, provided herein is a multispecific antibody or fragment there 35, wherein the multispecific antibody includes a second binding domain that binds to CD25.

[0048] In some aspects, provided herein is a multispecific antibody or fragment there 35 or 36, which is a bispecific antibody.

[0049] In some aspects, provided herein is a multispecific antibody or fragment there 36 or 37, wherein the second binding domain that binds to CD25 includes a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:1, (ii) SEQ ID NO:7, (iii) SEQ ID NO:12, (iv) SEQ ID NO:13, and (v) SEQ ID NO:18; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:2, (ii) SEQ ID NO:8, (iii) SEQ ID NO:14, (iv) SEQ ID NO:19, and (v) SEQ ID NO:24; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:3, (ii) SEQ ID NO:9, (iii) SEQ ID NO:15, and (iv) SEQ ID NO:20.

[0050] In some aspects, provided herein is a multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain includes a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, 98, or 63, (ii) SEQ ID NO:10, 100, or 64, (iii) SEQ ID NO:16, 102, or 65, and (iv) SEQ ID NO:21, 21, or 66; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; (3) a VL CDR3 having an amino acid sequence selected from thePage 20 of 555 ACTIVE 705104971v1group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0051] In some aspects, provided herein is a multispecific antibody or fragment there 39, wherein the multispecific antibody includes a second binding domain that binds to CD25.

[0052] In some aspects, provided herein is a multispecific antibody or fragment there 39 or 40, which is a bispecific antibody.

[0053] In some aspects, provided herein is a multispecific antibody or fragment there 40 or 41, wherein the second binding domain that binds to CD25 includes a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:6, (ii) SEQ ID NO:17, and (iii) SEQ ID NO:23.

[0054] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0055] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:47; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:48; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 21 of 555 ACTIVE 705104971v1

[0056] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:59; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0057] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:63; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0058] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:69; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0059] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:74; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:340; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:75; (2) a VL CDR2 having the amino acidPage 22 of 555 ACTIVE 705104971v1sequence of SEQ ID NO:76; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0060] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:88; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:89; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0061] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:97; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:98; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0062] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:26; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:106; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:107; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0063] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ IDPage 23 of 555 ACTIVE 705104971v1NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:112; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0064] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:117; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:118; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0065] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:124; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0066] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:129; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0067] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the aminoPage 24 of 555 ACTIVE 705104971v1acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:46; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:137; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:138.

[0068] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:143; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:137; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:138.

[0069] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:117; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:118; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0070] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:148; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:69; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 25 of 555 ACTIVE 705104971v1

[0071] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:152; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:153.

[0072] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:157; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:158; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0073] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:164; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:165; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:166; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0074] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acidPage 26 of 555 ACTIVE 705104971v1sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:175.

[0075] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:179; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0076] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:184; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:185.

[0077] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:191; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0078] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ IDPage 27 of 555 ACTIVE 705104971v1NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:197; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:198; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:199.

[0079] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:207; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0080] In some aspects, provided herein is a multispecific antibody or fragment there 1 or 2, wherein the first binding domain that binds to CTLA4 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:212; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:213; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:214; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0081] In some aspects, provided herein is a multispecific antibody or fragment there 43 to 69, wherein the multispecific antibody includes a second binding domain that binds to CD25.

[0082] In some aspects, provided herein is a multispecific antibody or fragment there 43 to 70, which is a bispecific antibody.

[0083] In some aspects, provided herein is a multispecific antibody or fragment there 70 or 71, wherein the second binding domain that binds to CD25 includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:1; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:2; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:3; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the aminoPage 28 of 555 ACTIVE 705104971v1acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:6.

[0084] In some aspects, provided herein is a multispecific antibody or fragment thereof including a first polypeptide chain, a second polypeptide chain, a third polypeptide chain, and a fourth polypeptide chain, wherein the first polypeptide chain and the second polypeptide chain include an antigen binding domain for CTLA4, wherein the third polypeptide chain and the fourth polypeptide chain include an antigen binding domain for CD25, and wherein: (a) the first polypeptide chain includes a light chain variable region (VL) and constant regions, wherein the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 amino acid sequence as set forth in an amino acid sequence selected from any one of SEQ ID NOs: 45, 58, 62, 67, 73, 87, 96, 105, 111, 116, 123, 127, 136, 142, 156, 163, 174, 178, 183, 190, 206, 211, and 225 and the constant regions include the amino acid sequence of SEQ ID NO:415; (b) the second polypeptide chain includes a heavy chain variable region (VH) and a constant region, wherein the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 amino acid sequence as set forth in an amino acid sequence selected from any one of SEQ ID NOs: 44, 57, 86, 95, 104, 135, 147, 151, 173, 196, and 224 and the constant region includes the amino acid sequence of SEQ ID NO:416; (c) the third polypeptide chain includes a light chain variable region (VL) and constant regions, wherein the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 amino acid sequence as set forth in SEQ ID NO:26 and the constant regions include the amino acid sequence of SEQ ID NO:417; (d) the fourth polypeptide chain includes a heavy chain variable region (VH) and a constant region, wherein the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 amino acid sequence as set forth in SEQ ID NO:25 and the constant region includes the amino acid sequence of SEQ ID NO:418.

[0085] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:45; (b) the VH of the second polypeptide chain includes a VH CDR, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as setPage 29 of 555 ACTIVE 705104971v1forth in the amino acid sequence of SEQ ID NO:58; (c) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:62; (d) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:67; (e) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:73; (f) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:86 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:87; (g) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:95 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:96; (h) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:104 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:105; (i) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:111; (j) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:116; (k) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:123; (l) the VH of the secondPage 30 of 555 ACTIVE 705104971v1polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:127; (m) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:136; (n) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:57 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:142; (o) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:147 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:142; (p) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:123; (q) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:151 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:73; (r) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:156; (s) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:163; (t) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:173 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:174; (u) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth inPage 31 of 555 ACTIVE 705104971v1the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:178; (v) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:183; (w) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:190; (x) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:196 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:45; (y) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:206; (z) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:211; or (aa) the VH of the second polypeptide chain includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:224 and the VL of the first polypeptide chain includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:225.

[0086] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) aPage 32 of 555 ACTIVE 705104971v1VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0087] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:47, (ii) SEQ ID NO:50, (iii) SEQ ID NO:53, and (iv) SEQ ID NO:55; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:48, (ii) SEQ ID NO:51, and (iii) SEQ ID NO:56; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0088] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:59, (ii) SEQ ID NO:60, and (iii) SEQ ID NO:61; and (3) a VL CDR3Page 33 of 555 ACTIVE 705104971v1having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0089] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:63, (ii) SEQ ID NO:64, (iii) SEQ ID NO:65, and (iv) SEQ ID NO:66; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0090] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:68, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:69, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:72; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0091] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VHPage 34 of 555 ACTIVE 705104971v1CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:74, (ii) SEQ ID NO:444, (iii) SEQ ID NO:425, (iv) SEQ ID NO:78, and (v) SEQ ID NO:81; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:340, (ii) SEQ ID NO:48, (iii) SEQ ID NO:79, (iv) SEQ ID NO:82, and (v) SEQ ID NO:85; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:75, (ii) SEQ ID NO:77, (iii) SEQ ID NO:80, and (iv) SEQ ID NO:83; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:76, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:84; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0092] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:88, (ii) SEQ ID NO:90, (iii) SEQ ID NO:91, (iv) SEQ ID NO:92, and (v) SEQ ID NO:94; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:89, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:93; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0093] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:97, (ii) SEQ ID NO:99, (iii) SEQ ID NO:101, (iv) SEQ IDPage 35 of 555 ACTIVE 705104971v1NO:103, and (v) SEQ ID NO:445; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:98, (ii) SEQ ID NO:100, (iii) SEQ ID NO:102, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0094] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:106, (ii) SEQ ID NO:108, (iii) SEQ ID NO:109, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:107, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:110; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0095] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) aPage 36 of 555 ACTIVE 705104971v1VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:112, (ii) SEQ ID NO:113, (iii) SEQ ID NO:114, and (iv) SEQ ID NO:115; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0096] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:117, (ii) SEQ ID NO:119, (iii) SEQ ID NO:120, and (iv) SEQ ID NO:121; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:118, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:122; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0097] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:46, (ii) SEQ ID NO:49, (iii) SEQ ID NO:52, and (iv) SEQ ID NO:54; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:124, (ii) SEQ ID NO:125, (iii) SEQ ID NO:126, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3Page 37 of 555 ACTIVE 705104971v1having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0098] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:129, (ii) SEQ ID NO:131, and (iii) SEQ ID NO:134; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0099] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:46, (ii) SEQ ID NO:49, (iii) SEQ ID NO:52, and (iv) SEQ ID NO:54; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:137, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:140; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:138, (ii) SEQ ID NO:139, and (iii) SEQ ID NO:141.Page 38 of 555 ACTIVE 705104971v1

[0100] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:143, (ii) SEQ ID NO:144, (iii) SEQ ID NO:145, and (iv) SEQ ID NO:146; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:137, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:140; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:138, (ii) SEQ ID NO:139, and (iii) SEQ ID NO:141.

[0101] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:117, (ii) SEQ ID NO:119, (iii) SEQ ID NO:120, and (iv) SEQ ID NO:121; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:118, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:122; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0102] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQPage 39 of 555 ACTIVE 705104971v1ID NO:148, (ii) SEQ ID NO:149, (iii) SEQ ID NO:34, (iv) SEQ ID NO:150, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:68, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:69, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:72; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0103] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:152, (ii) SEQ ID NO:10, (iii) SEQ ID NO:154, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:153, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:155.

[0104] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the groupPage 40 of 555 ACTIVE 705104971v1consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:157, (ii) SEQ ID NO:159, (iii) SEQ ID NO:161, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:158, (ii) SEQ ID NO:160, and (iii) SEQ ID NO:162; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0105] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:164, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:170, and (v) SEQ ID NO:172; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:165, (ii) SEQ ID NO:167 (iii) SEQ ID NO:169 and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:166, (ii) SEQ ID NO:168, and (iii) SEQ ID NO:171; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0106] In some aspects, provided herein is a multispecific antibody or fragment there 73 wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequencePage 41 of 555 ACTIVE 705104971v1selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:175, (ii) SEQ ID NO:176, and (iii) SEQ ID NO:177.

[0107] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:179, (ii) SEQ ID NO:180, (iii) SEQ ID NO:181, and (iv) SEQ ID NO:182; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0108] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the groupPage 42 of 555 ACTIVE 705104971v1consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:184, (ii) SEQ ID NO:186, and (iii) SEQ ID NO:188; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:185, (ii) SEQ ID NO:187, and (iii) SEQ ID NO:189.

[0109] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:191, (ii) SEQ ID NO:192, (iii) SEQ ID NO:193, (iv) SEQ ID NO:194, and (v) SEQ ID NO:195; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0110] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:197, (ii) SEQ ID NO:200, (iii) SEQ ID NO:202 and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:198, (ii) SEQ ID NO:201, and (iii) SEQ IDPage 43 of 555 ACTIVE 705104971v1NO:204; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:199, (ii) SEQ ID NO:203, and (iii) SEQ ID NO:205.

[0111] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:207, (ii) SEQ ID NO:208, (iii) SEQ ID NO:209, and (iv) SEQ ID NO:210; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0112] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:212, (ii) SEQ ID NO:215, (iii) SEQ ID NO:217, (iv) SEQ ID NO:218, and (v) SEQ ID NO:220; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:213, (ii) SEQ ID NO:216, (iii) SEQ ID NO:219, (iv) SEQ ID NO:221, and (v) SEQ ID NO:223; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:214, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:222; and (3) a VL CDR3 having an amino acid sequence selected from the groupPage 44 of 555 ACTIVE 705104971v1consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0113] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:20.

[0114] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:47; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:48; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0115] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:59; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0116] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein : (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:63; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 45 of 555 ACTIVE 705104971v1

[0117] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:69; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0118] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:74; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:340; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:75; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:76; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0119] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:88; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:89; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0120] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:97; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:98; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0121] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein : (a) the second polypeptide chain includes (1) aPage 46 of 555 ACTIVE 705104971v1VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:106; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:107; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0122] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:112; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0123] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:117; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:118; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0124] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:124; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0125] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acidPage 47 of 555 ACTIVE 705104971v1sequence of SEQ ID NO:128; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0126] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:46; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:137; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:138.

[0127] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:143; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:137; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:138.

[0128] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:117; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:118; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0129] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:148; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; (2) a VL CDR2 havingPage 48 of 555 ACTIVE 705104971v1the amino acid sequence of SEQ ID NO:69; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0130] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:152; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:153.

[0131] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:157; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:158; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0132] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:164; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:165; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:166; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0133] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:175.Page 49 of 555 ACTIVE 705104971v1

[0134] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:179; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0135] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:184; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:185.

[0136] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:191; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0137] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:197; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:198; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:199.

[0138] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VHPage 50 of 555 ACTIVE 705104971v1CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:207; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0139] In some aspects, provided herein is a multispecific antibody or fragment there 73 or 74, wherein: (a) the second polypeptide chain includes (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:212; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:213; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain includes: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:214; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0140] In some aspects, provided herein is a multispecific antibody or fragment there 75 to 101, wherein: (a) the fourth polypeptide chain includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:1, (ii) SEQ ID NO:7, (iii) SEQ ID NO:12, (iv) SEQ ID NO:13, and (v) SEQ ID NO:18; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:2, (ii) SEQ ID NO:8, (iii) SEQ ID NO:14, (iv) SEQ ID NO:19, and (v) SEQ ID NO:24; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:3, (ii) SEQ ID NO:9, (iii) SEQ ID NO:15, and (iv) SEQ ID NO:20; and (b) the third polypeptide chain includes: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:6, (ii) SEQ ID NO:17, and (iii) SEQ ID NO:23.

[0141] In some aspects, provided herein is a multispecific antibody or fragment there 102 to 128, wherein: (a) the fourth polypeptide chain includes: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:1; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 2; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 3; and (b) the third polypeptide chain includes: (1) aPage 51 of 555 ACTIVE 705104971v1VL CDR1 having the amino acid sequence of SEQ ID NO: 4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0142] In some aspects, provided herein is a multispecific antibody or fragment there 73, wherein: (a) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:45; (b) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:58; (c) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:62 ; (d) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:67; (e) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:73; (f) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:86 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:87; (g) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:95 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:96; (h) the second polypeptide chain includes the amino acid sequence of SEQ ID NO: 104 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:105; (i) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:111; (j) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:116; (k) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:123; (l) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:127; (m) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:136; (n) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:57 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:142; (o) the second polypeptide chain includes the amino acidPage 52 of 555 ACTIVE 705104971v1sequence of SEQ ID NO:147 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:142; (p) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:123; (q) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:151 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:73; (r) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:156; (s) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:163; (t) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:173 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:174; (u) the second polypeptide chain includes the amino acid sequence of SEQ ID NO: 135 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:178; (v) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:183; (w) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:190; (x) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:196 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:45; (y) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:206; (z) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:211; or (aa) the second polypeptide chain includes the amino acid sequence of SEQ ID NO:224 and the first polypeptide chain includes the amino acid sequence of SEQ ID NO:225.

[0143] In some aspects, provided herein is a multispecific antibody or fragment there 131, wherein the fourth polypeptide chain includes the amino acid sequence of SEQ ID NO:25 and the third polypeptide chain includes the amino acid sequence of SEQ ID NO:26.

[0144] In some aspects, provided herein is a multispecific antibody or fragment there 132, wherein the second polypeptide chain includes the amino acid sequence of SEQ ID NO:44, the first polypeptide chain includes the amino acidPage 53 of 555 ACTIVE 705104971v1sequence of SEQ ID NO:45, the fourth polypeptide chain includes the amino acid sequence of SEQ ID NO:25, and the third polypeptide chain includes the amino acid sequence of SEQ ID NO:26.

[0145] In some aspects, provided herein is a multispecific antibody or fragment there 132, wherein the second polypeptide chain includes the amino acid sequence of SEQ ID NO:44, the first polypeptide chain includes the amino acid sequence of SEQ ID NO:67, the fourth polypeptide chain includes the amino acid sequence of SEQ ID NO:25, and the third polypeptide chain includes the amino acid sequence of SEQ ID NO:26.

[0146] In some aspects, provided herein is a multispecific antibody or fragment there 132, wherein the second polypeptide chain includes the amino acid sequence of SEQ ID NO:104, the first polypeptide chain includes the amino acid sequence of SEQ ID NO:105, the fourth polypeptide chain includes the amino acid sequence of SEQ ID NO:25, and the third polypeptide chain includes the amino acid sequence of SEQ ID NO:26.

[0147] In some aspects, provided herein is a multispecific antibody or fragment thereof including a first polypeptide chain, a second polypeptide chain, a third polypeptide chain, and a fourth polypeptide chain, wherein the first polypeptide chain and the second polypeptide chain include an antigen binding domain for CD25, wherein the third polypeptide chain and the fourth polypeptide chain include an antigen binding domain for CTLA4, and wherein : (a) the first polypeptide chain includes a light chain variable region (VL) and constant regions, wherein the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 amino acid sequence as set forth in SEQ ID NO:25 and the constant regions include the amino acid sequence of SEQ ID NO:415; (b) the second polypeptide chain includes a heavy chain variable region (VH) and a constant region, wherein the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 amino acid sequence as set forth in SEQ ID NO:26 and the constant region includes the amino acid sequence of SEQ ID NO:416; (c) the third polypeptide chain includes a light chain variable region (VL) and constant regions, wherein the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 amino acid sequence as set forth in SEQ ID NO: 45, 58, 62, 67, 73, 87, 96, 105, 111, 116, 123, 127, 136, 142, 156, 163, 174, 178, 183, 190, 206, 211, or 225 and the constant regions include the amino acid sequence of SEQ ID NO:417; (d) the fourth polypeptide chain includes a heavy chain variable region (VH) and a constant region,Page 54 of 555 ACTIVE 705104971v1wherein the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 amino acid sequence as set forth in SEQ ID NO: 44, 57, 86, 95, 104, 135, 147, 151, 173, 196, or 224 and the constant region includes the amino acid sequence of SEQ ID NO:418.

[0148] In some aspects, provided herein is a multispecific antibody or fragment thereof including a first binding domin that binds to CTLA4, wherein the first binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1X2SYX3YYADSVKG (SEQ ID NO:450), wherein X1 is D or G, and wherein X2 is G or Y, and wherein X3is T or Y; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL includes: (d) a VL CDR1 consensus sequence of X1AX2X3X4VSX5X6VA (SEQ ID NO:388), wherein X1 is R or H, and wherein X2is S or P, wherein X3is Q, D, or F, wherein X4is S or L, wherein X5 is S or K, and wherein X6 is A or L; (e) a VL CDR2 consensus sequence of SAX1SX2X3S (SEQ ID NO:389), wherein X1 is S, A, or D, wherein X2 is L, T, or F, and wherein X3is Y or P; and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

[0149] In some aspects, provided herein is a multispecific antibody or fragment thereof including a first binding domin that binds to CTLA4, wherein the first binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSDGSYTYYADSVKG (SEQ ID NO:28); and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL includes: (d) a VL CDR1 consensus sequence of X1AX2X3X4X5X6X7X8VA (SEQ ID NO: 397), wherein X1 is R or H, and wherein X2is S or N, wherein X3is Q, F, S, or V wherein X4is S, L, or Q, wherein X5is V or L, wherein X6is S or I, wherein X7is S, K, or R, and wherein X8is A or L; (e) a VL CDR2 consensus sequence of SAX1SX2YS (SEQ ID NO:390), wherein X1is S, A, or D, and wherein X2is L, M, F, or S; and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

[0150] In some aspects, provided herein is a multispecific antibody or fragment thereof including a first binding domin that binds to CTLA4, wherein the first binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes: (a) a VH CDR1 consensus sequencePage 55 of 555 ACTIVE 705104971v1of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1X2SYX3YYADSVKG (SEQ ID NO:386), wherein X1 is D or G, wherein X2 is G or Y, and wherein X3is T or H; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL includes: (d) a VL CDR1 consensus sequence of RAX1X2SVSX3AVA (SEQ ID NO:391), wherein X1 is S, P, or N, wherein X2is Q, D, F, or V and wherein X3is S or K; (e) a VL CDR2 consensus sequence of SAX1SX2X3S (SEQ ID NO:396), wherein X1is S or D, wherein X2is L, T, or S, and wherein X3 is Y or P; and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

[0151] In some aspects, provided herein is a multispecific antibody or fragment thereof including a first binding domin that binds to CTLA4, wherein the first binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1GSYX2YYADSVKG (SEQ ID NO:393), wherein X1 is D or G, and wherein X2 is T or H; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL includes: (d) a VL CDR1 consensus sequence of RAX1X2SVSX3AVA (SEQ ID NO:398), wherein X1 is S or P, wherein X2 is Q, D, or F, and wherein X3is S or K; (e) a VL CDR2 consensus sequence of SASSLYS (SEQ ID NO:5); and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

[0152] In some aspects, provided herein is a multispecific antibody or fragment thereof including a first binding domin that binds to CTLA4, wherein the first binding domain includes a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1GSYX2YYADSVKG (SEQ ID NO:393), wherein X1is D or G, and wherein X2is T or H; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL includes: (d) a VL CDR1 consensus sequence of RAX1X2SVSSAVA (SEQ ID NO:395), wherein X1is S or P, and wherein X2is Q or D; (e) a VL CDR2 consensus sequence of SASSLYS (SEQ ID NO:5); and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

[0153] In some aspects, provided herein is a multispecific antibody or fragment thereof including a first binding domin that binds to CTLA4, wherein the first binding domain includes a heavy chain variable region (VH) and a light chainPage 56 of 555 ACTIVE 705104971v1variable region (VL), wherein the VH includes: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSDGSYTYYADSVKG (SEQ ID NO:28); and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL includes: (d) a VL CDR1 consensus sequence of RASX1SVSX2AVA (SEQ ID NO:394), wherein X1 is Q or F, and wherein X2is S or K; (e) a VL CDR2 consensus sequence of SASSLYS (SEQ ID NO:5); and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

[0154] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in an amino acid sequence selected from any one of SEQ ID NOs: 44, 57, 86, 95, 104, 135, 147, 151, 173, 196, and 224, and wherein the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in an amino acid sequence selected from any one of SEQ ID NOs: 45, 58, 62, 67, 73, 87, 96, 105, 111, 116, 123, 127, 136, 142, 156, 163, 174, 178, 183, 190, 206, 211, and 225.

[0155] In some aspects, provided herein is an antibody or fragment there 143, wherein: (a) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:45; (b) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:58; (c) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:62; (d) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:67; (e) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:73; (f) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:86 and the VL includes a VL CDR1, a VL CDR2, and aPage 57 of 555 ACTIVE 705104971v1VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:87; (g) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:95 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:96; (h) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:104 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:105; (i) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:111; (j) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:116 ; (k) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:123; (l) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:127; (m) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:136; (n) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:57 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:142; (o) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:147 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:142; (p) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:123; (q) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:151 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:73; (r) the VH includes a VH CDR1, a VHPage 58 of 555 ACTIVE 705104971v1CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:156; (s) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:163; (t) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:173 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:174; (u) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:178; (v) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:183; (w) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:190; (x) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:196 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:45; (y) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:206; (z) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:211; or (aa) the VH includes a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:224 and the VL includes a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:225.

[0156] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQPage 59 of 555 ACTIVE 705104971v1ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0157] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:47, (ii) SEQ ID NO:50, (iii) SEQ ID NO:53, and (iv) SEQ ID NO:55; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:48, (ii) SEQ ID NO:51, and (iii) SEQ ID NO:56; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0158] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ IDPage 60 of 555 ACTIVE 705104971v1NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:59, (ii) SEQ ID NO:60, and (iii) SEQ ID NO:61; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0159] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:63, (ii) SEQ ID NO:64, (iii) SEQ ID NO:65, and (iv) SEQ ID NO:66; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0160] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41;Page 61 of 555 ACTIVE 705104971v1and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:68, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:69, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:72; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0161] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:74, (ii) SEQ ID NO:444, (iii) SEQ ID NO:425, (iv) SEQ ID NO:78, and (v) SEQ ID NO:81; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:340, (ii) SEQ ID NO:48, (iii) SEQ ID NO:79, (iv) SEQ ID NO:82, and (v) SEQ ID NO:85; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:75, (ii) SEQ ID NO:77, (iii) SEQ ID NO:80, and (iv) SEQ ID NO:83; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:76, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:84; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0162] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:88, (ii) SEQ ID NO:90, (iii) SEQ ID NO:91, (iv) SEQ ID NO:92, and (v) SEQ ID NO:94; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ IDPage 62 of 555 ACTIVE 705104971v1NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:89, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:93; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0163] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:97, (ii) SEQ ID NO:99, (iii) SEQ ID NO:101, (iv) SEQ ID NO:103, and (v) SEQ ID NO:445; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:98, (ii) SEQ ID NO:100, (iii) SEQ ID NO:102, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0164] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes : (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:106, (ii) SEQ ID NO:108, (iii) SEQ ID NO:109, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:107, (ii)Page 63 of 555 ACTIVE 705104971v1SEQ ID NO:11, and (iii) SEQ ID NO:110; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0165] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:112, (ii) SEQ ID NO:113, (iii) SEQ ID NO:114, and (iv) SEQ ID NO:115; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0166] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:117, (ii) SEQ ID NO:119, (iii) SEQ ID NO:120, and (iv) SEQ ID NO:121; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:118, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:122; and (3) a VL CDR3 having an amino acidPage 64 of 555 ACTIVE 705104971v1sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0167] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:124, (ii) SEQ ID NO:125, (iii) SEQ ID NO:126, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0168] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:129, (ii) SEQ ID NO:131, and (iii) SEQ ID NO:134; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.Page 65 of 555 ACTIVE 705104971v1

[0169] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:46, (ii) SEQ ID NO:49, (iii) SEQ ID NO:52, and (iv) SEQ ID NO:54; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:137, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:140; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:138, (ii) SEQ ID NO:139, and (iii) SEQ ID NO:141.

[0170] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:143, (ii) SEQ ID NO:144, (iii) SEQ ID NO:145, and (iv) SEQ ID NO:146; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:137, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:140; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:138, (ii) SEQ ID NO:139, and (iii) SEQ ID NO:141.

[0171] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavyPage 66 of 555 ACTIVE 705104971v1chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:117, (ii) SEQ ID NO:119, (iii) SEQ ID NO:120, and (iv) SEQ ID NO:121; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:118, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:122; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0172] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:148, (ii) SEQ ID NO:149, (iii) SEQ ID NO:34, (iv) SEQ ID NO:150, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:68, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:69, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:72; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0173] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQPage 67 of 555 ACTIVE 705104971v1ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:152, (ii) SEQ ID NO:10, (iii) SEQ ID NO:154, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:153, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:155.

[0174] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:157, (ii) SEQ ID NO:159, (iii) SEQ ID NO:161, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:158, (ii) SEQ ID NO:160, and (iii) SEQ ID NO:162; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, ((ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0175] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:164, (ii)Page 68 of 555 ACTIVE 705104971v1SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:170, and (v) SEQ ID NO:172; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:165, (ii) SEQ ID NO:167 (iii) SEQ ID NO:169 and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:166, (ii) SEQ ID NO:168, and (iii) SEQ ID NO:171; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0176] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:175, (ii) SEQ ID NO:176, and (iii) SEQ ID NO:177.

[0177] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes : (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consistingPage 69 of 555 ACTIVE 705104971v1of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:179, (ii) SEQ ID NO:180, (iii) SEQ ID NO:181, and (iv) SEQ ID NO:182; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0178] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes : (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:184, (ii) SEQ ID NO:186, and (iii) SEQ ID NO:188; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:185, (ii) SEQ ID NO:187, and (iii) SEQ ID NO:189.

[0179] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes : (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:191, (ii) SEQ ID NO:192, (iii) SEQ ID NO:193, (iv) SEQ ID NO:194, and (v) SEQ ID NO:195; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 havingPage 70 of 555 ACTIVE 705104971v1an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0180] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes : (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:197, (ii) SEQ ID NO:200, (iii) SEQ ID NO:202 and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:198, (ii) SEQ ID NO:201, and (iii) SEQ ID NO:204; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:199, (ii) SEQ ID NO:203, and (iii) SEQ ID NO:205.

[0181] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes : (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:207, (ii) SEQ ID NO:208, (iii) SEQ ID NO:209, and (iv) SEQ ID NO:210; (2) a VL CDR2Page 71 of 555 ACTIVE 705104971v1having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0182] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes : (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:212, (ii) SEQ ID NO:215, (iii) SEQ ID NO:217, (iv) SEQ ID NO:218, and (v) SEQ ID NO:220; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:213, (ii) SEQ ID NO:216, (iii) SEQ ID NO:219, (iv) SEQ ID NO:221, and (v) SEQ ID NO:223; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:214, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:222; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0183] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes a heavy chain variable region (VH) including: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41.

[0184] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof includes a light chain variable region (VL) including : (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, 98, or 63, (ii) SEQ ID NO:10, 100, or 64, (iii) SEQ ID NO:16, 102, or 65, and (iv) SEQ ID NO:21, 21, or 66; (2) aPage 72 of 555 ACTIVE 705104971v1VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO:443, and (iv) SEQ ID NO:42.

[0185] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0186] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:47; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:48; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0187] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes : (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:59; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0188] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes : (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acidPage 73 of 555 ACTIVE 705104971v1sequence of SEQ ID NO:63; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0189] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:69; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0190] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:74; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 340; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:75; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:76; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0191] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:88; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:89; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0192] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes : (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:97; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:98; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 74 of 555 ACTIVE 705104971v1

[0193] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:106; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:107; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0194] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:112; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0195] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:117; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:118; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0196] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:124; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0197] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variablePage 75 of 555 ACTIVE 705104971v1region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:129; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0198] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes : (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:46; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:137; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:138.

[0199] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:143; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:137; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:138.

[0200] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:117; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:118; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0201] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ IDPage 76 of 555 ACTIVE 705104971v1NO:148; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:69; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0202] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:152; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:153.

[0203] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:157; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:158; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0204] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:164; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:165; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:166; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0205] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chainPage 77 of 555 ACTIVE 705104971v1variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:175.

[0206] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:179; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0207] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:184; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:185.

[0208] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:191; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0209] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence ofPage 78 of 555 ACTIVE 705104971v1SEQ ID NO:197; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:198; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:199.

[0210] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:207; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0211] In some aspects, provided herein is an antibody or fragment there 143 or 144, wherein the antibody or fragment thereof includes: (a) a heavy chain variable region (VH) including: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:212; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:213; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) including: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:214; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.

[0212] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:45.

[0213] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:58.

[0214] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:62.

[0215] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:67.

[0216] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:73.Page 79 of 555 ACTIVE 705104971v1

[0217] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:86 and a VL sequence that is SEQ ID NO:87.

[0218] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:95 and a VL sequence that is SEQ ID NO:96.

[0219] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:104 and a VL sequence that is SEQ ID NO:105.

[0220] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:111.

[0221] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:116.

[0222] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:123.

[0223] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:127.

[0224] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:136.

[0225] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:57 and a VL sequence that is SEQ ID NO:142.

[0226] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:147 and a VL sequence that is SEQ ID NO:142.

[0227] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:123.Page 80 of 555 ACTIVE 705104971v1

[0228] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:151 and a VL sequence that is SEQ ID NO:73.

[0229] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:156.

[0230] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:163.

[0231] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:173 and a VL sequence that is SEQ ID NO:174.

[0232] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:178.

[0233] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:183.

[0234] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:190.

[0235] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:196 and a VL sequence that is SEQ ID NO:45.

[0236] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:206.

[0237] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:211.

[0238] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a VH sequence that is SEQ ID NO:224 and a VL sequence that is SEQ ID NO:225.Page 81 of 555 ACTIVE 705104971v1

[0239] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1X2SYX3YYADSVKG (SEQ ID NO:450), wherein X1 is D or G, and wherein X2 is G or Y, and wherein X3is T or Y; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL includes: (d) a VL CDR1 consensus sequence of X1AX2X3X4VSX5X6VA (SEQ ID NO:388), wherein X1 is R or H, and wherein X2 is S or P, wherein X3 is Q, D, or F, wherein X4 is S or L, wherein X5is S or K, and wherein X6is A or L; (e) a VL CDR2 consensus sequence of SAX1SX2X3S (SEQ ID NO:389), wherein X1 is S, A, or D, wherein X2 is L, T, or F, and wherein X3 is Y or P; and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

[0240] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSDGSYTYYADSVKG (SEQ ID NO:28); and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL includes: (d) a VL CDR1 consensus sequence of X1AX2X3X4X5X6X7X8VA (SEQ ID NO: 397), wherein X1is R or H, and wherein X2 is S or N, wherein X3 is Q, F, S, or V wherein X4 is S, L, or Q, wherein X5 is V or L, wherein X6 is S or I, wherein X7 is S, K, or R, and wherein X8 is A or L; (e) a VL CDR2 consensus sequence of SAX1SX2YS (SEQ ID NO:390), wherein X1 is S, A, or D, and wherein X2 is L, M, F, or S; and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

[0241] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1X2SYX3YYADSVKG (SEQ ID NO:386), wherein X1is D or G, wherein X2is G or Y, and wherein X3 is T or H; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL includes: (d) a VL CDR1 consensus sequence of RAX1X2SVSX3AVA (SEQ ID NO:391), wherein X1is S, P, or N, wherein X2 is Q, D, F, or V and wherein X3 is S or K; (e) a VL CDR2 consensusPage 82 of 555 ACTIVE 705104971v1sequence of SAX1SX2X3S (SEQ ID NO:396), wherein X1 is S or D, wherein X2 is L, T, or S, and wherein X3 is Y or P; and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

[0242] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1GSYX2YYADSVKG (SEQ ID NO:393), wherein X1 is D or G, and wherein X2 is T or H; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29)and wherein the VL includes: (d) a VL CDR1 consensus sequence of RAX1X2SVSX3AVA (SEQ ID NO:398), wherein X1 is S or P, wherein X2 is Q, D, or F, and wherein X3 is S or K; (e) a VL CDR2 consensus sequence of SASSLYS (SEQ ID NO:5); and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

[0243] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1GSYX2YYADSVKG (SEQ ID NO:393), wherein X1 is D or G, and wherein X2 is T or H; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL includes: (d) a VL CDR1 consensus sequence of RAX1X2SVSSAVA (SEQ ID NO:395), wherein X1 is S or P, and wherein X2 is Q or D; (e) a VL CDR2 consensus sequence of SASSLYS (SEQ ID NO:5); and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

[0244] In some aspects, provided herein is an antibody or fragment thereof that binds to CTLA4 including a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSDGSYTYYADSVKG (SEQ ID NO:28); and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL includes: (d) a VL CDR1 consensus sequence of RASX1SVSX2AVA (SEQ ID NO:394), wherein X1is Q or F, and wherein X2 is S or K; (e) a VL CDR2 consensus sequence of SASSLYS (SEQ ID NO:5); and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).Page 83 of 555 ACTIVE 705104971v1

[0245] In some aspects, provided herein is a multispecific antibody or fragment there 1-142, or the antibody or fragment there 143-233, wherein the VH or the VL further includes human framework sequences.

[0246] In some aspects, provided herein is a multispecific antibody or fragment thereof, or antibody or fragment there 234, wherein the VH and the VL further includes human framework sequences.

[0247] In some aspects, provided herein is a multispecific antibody or fragment there 1-142, or the antibody or fragment there 143-233, wherein the VH or the VL further includes a framework 1 (FR1), a framework 2 (FR2), a framework 3 (FR3) and / or a framework 4 (FR4) sequence.

[0248] In some aspects, provided herein is a multispecific antibody or fragment thereof, or the antibody or fragment there 236, wherein the VH and VL further includes a framework 1 (FR1), a framework 2 (FR2), a framework 3 (FR3) and / or a framework 4 (FR4) sequence.

[0249] In some aspects, provided herein is a multispecific antibody or fragment, or the antibody or fragment there 143-233, wherein the antibody is a recombinant antibody.

[0250] In some aspects, provided herein is a multispecific antibody or fragment, or antibody or fragment there 238, wherein the recombinant antibody is a humanized, human or chimeric antibody.

[0251] In some aspects, provided herein is a multispecific antibody or fragment there 1-142, or the antibody or fragment there 143-233 which is a Fab, Fab', F(ab')2, Fv, scFv, (scFv)2, single chain antibody molecule, dual variable region antibody, diabody, single variable region antibody, linear antibody, V region, or a multispecific antibody formed from antibody fragments.

[0252] In some aspects, provided herein is a multispecific antibody or fragment there 1-142, or the antibody or fragment there 143-233 which is conjugated or recombinantly fused to a diagnostic agent, detectable agent, or therapeutic agent.

[0253] In some aspects, provided herein is a multispecific antibody or fragment there 241, wherein the therapeutic agent is a chemotherapeutic agent, cytotoxin, or drug.

[0254] In some aspects, provided herein is one or more vectors including one or more polynucleotides encoding the multispecific antibody or fragment there 1-142 or the antibody or fragment there 143-233.Page 84 of 555 ACTIVE 705104971v1

[0255] In some aspects, provided herein is a pharmaceutical composition that includes the multispecific antibody or fragment there 1-142 or the antibody, and a pharmaceutically acceptable carrier.

[0256] In some aspects, provided herein is a method for treating a cancer in a subject including administering to the subject the multispecific antibody or fragment there 1-142 or the antibody or fragment there 143-233, or the pharmaceutical composition.

[0257] In some aspects, provided herein is a method for alleviating one or more symptoms associated with a cancer in a subject including administering to the subject the multispecific antibody or fragment there 1-142, or the antibody, or the pharmaceutical composition.

[0258] In some aspects, provided herein is a method, wherein the cancer is a solid tumor.

[0259] In some aspects, provided herein is a method, wherein the subject is diagnosed with a cancer or a tumor.

[0260] In some aspects, provided herein is a method for decreasing tumor size in a subject with a tumor including administering to the subject the multispecific antibody or fragment there 1-142, the antibody or fragment there 143-233, or the pharmaceutical composition.

[0261] In some aspects, provided herein is a method for treating a tumor regulatory T cell (Treg) mediated disease, disorder or condition in a subject including administering to the subject the multispecific antibody or fragment there 1-142, the antibody or fragment there 143-233, or the pharmaceutical composition.

[0262] In some aspects, provided herein is a method for depleting tumor regulatory T cells (Tregs) in a subject including administering to the subject the multispecific antibody or fragment there 1-142, the antibody or fragment there 143- 233, or the pharmaceutical composition. BRIEF DESCRIPTION OF THE DRAWINGS

[0263] FIG.1 presents a schematic antibody construct, with respective naming conventions for the various domains in the first, second, third and fourth polypeptide chains, for the bispecific antibodies described herein. Domain A = VL; Domain B = variant CH3; Domain D = CH2; Domain E = variant CH3; Domain F =Page 85 of 555 ACTIVE 705104971v1VH; Domain G = variant CH3; Domain H = VL; Domain I = CL – Kappa; Domain J = CH2; Domain K = variant CH3; Domain L = VH; Domain M = CH1.

[0264] FIGs.2A-2C illustrates exemplary results from bead binding assays, further described in Example 3.

[0265] FIG.3A and 3B illustrates exemplary results from additional bead assays, further described in Example 3.

[0266] FIGs.4A-4C illustrates exemplary results from cell binding assays, further described in Example 3.

[0267] FIG.5 illustrates exemplary results from Octet-based CD80 / CTLA4 blocking assays, further described in Example 4.

[0268] FIG.6 illustrates exemplary results from Octet-based CD25 / IL2 blocking assays, further described in Example 4.

[0269] FIG.7A and 7B illustrate exemplary results from Fc assays with exemplary bsAbs, further described in Example 5.

[0270] FIG.8 illustrates exemplary results from signaling assays with exemplary bsAbs, further described in Example 5.

[0271] FIGs.9A-9C illustrate exemplary results from immunogenicity assays with exemplary bsAbs, further described in Example 5.

[0272] FIG.10 illustrates exemplary results from cell activity assays with exemplary bsAbs, further described in Example 5.

[0273] FIG.11A-11C illustrate exemplary results from cell activity assays with exemplary bsAbs, further described in Example 5.

[0274] FIGs.12A-12F illustrate exemplary results from cell activity assays with exemplary bsAbs, further described in Example 5.

[0275] FIGs.13A-13D illustrate exemplary results from cell activity assays with exemplary bsAbs, further described in Example 5.

[0276] FIGs.14A-14C illustrate exemplary results from cell activity assays with exemplary bsAbs, further described in Example 5.

[0277] FIGs.15A-15D illustrates exemplary results from SEC, HIC, SMAC, and SCX chromatography for an exemplary bsAb (e.g., bsAb1), further described in Example 6.

[0278] FIGs.16A-16D illustrates exemplary results from SEC, HIC, SMAC, and SCX chromatography for an exemplary bsAb (e.g., bsAb4), further described in in Example 6.Page 86 of 555 ACTIVE 705104971v1

[0279] FIGs.17A-17D show an alignment of exemplary VH sequences (e.g., SEQ ID NOs: 44, 86, 95, 104, 57, 147, 151, 135, 173, 196, and 224) and exemplary VL sequences (e.g., SEQ ID NOs: 45, 87, 96, 105, 142, 136, 58, 62, 67, 123, 73, 116, 127, 111, 156, 163, 174, 178, 183, 190, 206, 211, and 225), as well as exemplary consensus sequences of VH-CDR1-3 and VL-CDR1-3 described in Tables 2-28. Exemplary consensus sequences of VH-CDR1, CH-CDR2, VH-CDR3, VL-CDR1, CH-CDR2, and VH-CDR3 correspond to SEQ ID NOS: 380, 381, 382, and 385, respectively.

[0280] FIG.18A and 18B show an alignment of exemplary VH sequences (e.g., SEQ ID NOs: 44, 95, and 104) and exemplary VL sequences (e.g., SEQ ID NOs: 45, 96, 105, 58, 62, 67, and 73), as well as exemplary consensus sequences of VH-CDR1-3 and VL-CDR1-3 described in Tables 2-6 and 8-9. Exemplary consensus sequences of VH-CDR1, CH-CDR2, VH-CDR3, VL-CDR1, CH-CDR2, and VH-CDR3 correspond to SEQ ID NOS: 27, 386, 29, 388, 389, and 30, respectively.

[0281] FIGs.19A-19C show an alignment of exemplary VH sequences (e.g., SEQ ID NO: 44) and exemplary VL sequences (e.g., SEQ ID NOs: 45, 58, 62, 67, 123, 73, 116, 127 and 111), as well as exemplary consensus sequences of VH- CDR1-3 and VL-CDR1-3 described in Tables 2-6. Exemplary consensus sequences of VH-CDR1, CH-CDR2, VH-CDR3, VL-CDR1, CH-CDR2, and VH-CDR3 correspond to SEQ ID NOS: 27, 28, 29, 390, and 30, respectively.

[0282] FIG.20A and 20B show an alignment of exemplary VH sequences (e.g., SEQ ID NOs: 44, 95, and 104) and exemplary VL sequences (e.g., SEQ ID NOs: 45, 96, 105, 62, 67 and 111), as well as exemplary consensus sequences of VH-CDR1-3 and VL-CDR1-3 described in Tables 2, 4, 5, and 8-9. Exemplary consensus sequences of VH-CDR1, CH-CDR2, VH-CDR3, VL-CDR1, CH-CDR2, and VH-CDR3 correspond to SEQ ID NOS: 27, 386, 29, 391, 396, and 30, respectively.

[0283] FIG.21A and 21B show an alignment of exemplary VH sequences (e.g., SEQ ID NOs: 44 and 104) and exemplary VL sequences (e.g., SEQ ID NOs: 45, 105, and 67), as well as exemplary consensus sequences of VH-CDR1-3 and VL-CDR1-3 described in Tables 2, 5, and 9. Exemplary consensus sequences of VH-CDR1, CH-CDR2, VH-CDR3, VL-CDR1, CH-CDR2, and VH-CDR3 correspond to SEQ ID NOS: 27, 393, 29, 398, 5, and 30, respectively.Page 87 of 555 ACTIVE 705104971v1

[0284] FIG.22A and 22B show an alignment of exemplary VH sequences (e.g., SEQ ID NOs: 44 and 104) and exemplary VL sequences (e.g., SEQ ID NOs: 45 and 105), as well as exemplary consensus sequences of VH-CDR1-3 and VL- CDR1-3 described in Tables 2 and 9. Exemplary consensus sequences of VH- CDR1, CH-CDR2, VH-CDR3, VL-CDR1, CH-CDR2, and VH-CDR3 correspond to SEQ ID NOS: 27, 393, 29, 395, 5, and 30, respectively.

[0285] FIG.23A and 23B show an alignment of exemplary VH sequences (e.g., SEQ ID NOs: 44) and exemplary VL sequences (e.g., SEQ ID NOs: 45 and 67), as well as exemplary consensus sequences of VH-CDR1-3 and VL-CDR1-3 described in Tables 2 and 5. Exemplary consensus sequences of VH-CDR1, CH- CDR2, VH-CDR3, VL-CDR1, CH-CDR2, and VH-CDR3 correspond to SEQ ID NOS: 27, 28, 29, 394, 5, and 30, respectively. DETAILED DESCRIPTION

[0286] The present disclosure provides binding agents (e.g., antibodies) that bind to CTLA4, including human CTLA4, or CD25, including human CD25. The present disclosure also provides multispecific binding agents (e.g., antibodies, such as bispecific antibodies) that bind to CTLA4 and one or more additional targets that are not CTLA4 (e.g., CD25). Such multispecific binding agents include antibodies (e.g., antibodies, such as bispecific antibodies) that bind to CTLA4, including antibodies that bind to human CTLA4, and one or more additional targets that are not CTLA4 (e.g., CD25). Such binding agents, including multispecific binding agents (e.g., antibodies, such as bispecific antibodies) are useful in compositions and in methods of treating, preventing, or alleviating a disease, disorder or condition (e.g., a tumor regulatory T cell (tumor Treg) mediated disease, disorder, or condition), including one or more symptoms of a disease, disorder, or condition. In addition, multispecific binding agents described herein, such as multispecific antibodies (e.g., antibodies, such as bispecific antibodies), that bind to CTLA4 and one or more additional targets that are not CTLA4 (e.g., CD25), are useful to inhibit CD80 and / or CD86 signaling and / or CTLA4-mediated signaling, active depletion of CTLA4- expressing tumor Tregs function and enhance removal of tumor cells. In addition, multispecific binding agents described herein, such as multispecific antibodies (e.g., antibodies, such as bispecific antibodies) that bind to CD25 and one or more additional targets that are not CD25 (e.g., CTLA4), are useful to inhibit IL-2RPage 88 of 555 ACTIVE 705104971v1signaling and / or CD25-mediated IL-2 signaling, active depletion of CD25-expressing tumor Tregs function and / or blockade of the IL-2 survival signaling, and enhance removal of tumor cells. Multispecific binding agents (e.g., antibodies, such as bispecific antibodies) described herein, such as multispecific binding antibodies (e.g., bispecific antibodies), are also useful in compositions and in methods for depleting tumor Tregs.

[0287] The term “cytotoxic T-lymphocyte-associated protein 4”, “CTLA4” “Cytotoxic T-lymphocyte-associated antigen 4”, “CTLA-4”, “cluster of differentiation 152”, “CD152” or similar terms refer to a polypeptide (“polypeptide” and “protein” are used interchangeably herein) or any native CTLA4 from any vertebrate source, including mammals such as primates (e.g., humans, cynomolgus monkey (cyno)), dogs, and rodents (e.g., mice and rats), unless otherwise indicated. CTLA4 is a protein that in humans is encoded by the CTLA-4 gene, also known as the CD152 gene. CTLA4 has Ig-like V-type domain at positions 39-140. CTLA4 belongs to the immunoglobulin superfamily. CTLA4 is also known in the art as a protein receptor that is expressed by activated T cells and serves as an immune checkpoint. CTLA4, which is homologous to CD28, binds to CD80 and CD86, downregulating immune responses. The term CTLA4 encompasses “full-length,” CTLA4, as well as any form of CTLA4 or any fragment thereof that results from processing in the cell. The term CTLA4 also encompasses naturally occurring variants of CTLA4, such as SNP variants, splice variants and allelic variants. The full-length amino acid sequence of human CTLA4 is provided below:

[0288] MACLGFQRHKAQLNLATRTWPCTLLFFLLFIPVFCKAMHVAQPAVVL ASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSIC TGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDS DFLLWILAAVSSGLFFYSFLLTAVSLSKMLKKRSPLTTGVYVKMPPTEPECEKQFQP YFIPIN (SEQ ID NO:437).

[0289] Other related CTLA4 polypeptides that are also encompassed by the term CTLA4 include fragments, derivatives (e.g., substitution, deletion, truncations, and insertion variants), fusion polypeptides, and interspecies homologs that retain CTLA4 activity and / or are sufficient to generate an anti-CTLA4 immune response. As those skilled in the art will appreciate, a CTLA4 binding agent (e.g., an antibody) described herein can bind to a CTLA4 polypeptide, a CTLA4 polypeptide fragment, a CTLA4 antigen, and / or a CTLA4 epitope. An epitope may be part of a larger CTLA4Page 89 of 555 ACTIVE 705104971v1antigen, which may be part of a larger CTLA4 polypeptide fragment, which, in turn, may be part of a larger CTLA4 polypeptide. CTLA4 may exist in a native or denatured form. CTLA4 polypeptides described herein may be isolated from a variety of sources, such as from human tissue types or from another source, or prepared by recombinant or synthetic methods. A CTLA4 polypeptide may comprise a polypeptide having the same amino acid sequence as a corresponding CTLA4 polypeptide derived from nature. Orthologs to the CTLA4 polypeptide are also well known in the art.

[0290] The term “CD25,” “Cluster of Differentiation 25,” “CD25 antigen” or “CD25 polypeptide” or similar terms refer to a polypeptide (“polypeptide” and “protein” are used interchangeably herein) or any native CD25 from any vertebrate source, including mammals such as primates (e.g., humans, cynomolgus monkey (cyno)), dogs, and rodents (e.g., mice and rats), unless otherwise indicated. CD25, also known in the art as “Interleukin-2 receptor subunit alpha”, or “IL-2 receptor subunit alpha” has sushi 1 domain at position(s) 22-84, and sushi 2 domain at position(s) 123 – 186. The term CD25 encompasses “full-length,” unprocessed CD25, as well as any form of CD25 or any fragment thereof that results from processing in the cell, including the four known alternatively spliced isoforms of CD25 that differ in the length of the intracellular tail. The term CD25 also encompasses naturally occurring variants of CD25, such as SNP variants, splice variants and allelic variants. CD25 is known in the art to interact with IL2, leading to the promotion of immune tolerance by selectively targeting the IL-2 receptor on regulatory T cells. The full-length amino acid sequence of human CD25 is provided below:

[0291] MDSYLLMWGLLTFIMVPGCQAELCDDDPPEIPHATFKAMAYKEGTML NCECKRGFRRIKSGSLYMLCTGNSSHSSWDNQCQCTSSATRNTTKQVTPQPEEQ KERKTTEMQSPMQPVDQASLPGHCREPPPWENEATERIYHFVVGQMVYYQCVQG YRALHRGPAESVCKMTHGKTRWTQPQLICTGEMETSQFPGEEKPQASPEGRPES ETSCLVTTTDFQIQTEMAATMETSIFTTEYQVAVAGCVFLLISVLLLSGLTWQRRQR KSRRTI (SEQ ID NO:426).

[0292] Other related CD25 polypeptides that are also encompassed by the term CD25 include fragments, derivatives (e.g., substitution, deletion, truncations, and insertion variants), fusion polypeptides, and interspecies homologs that retain CD25 activity and / or are sufficient to generate an anti-CD25 immune response. AsPage 90 of 555 ACTIVE 705104971v1those skilled in the art will appreciate, a binding agent (e.g., an antibody, such as a multispecific antibody (e.g., a bispecific antibody)) described herein can bind to a CD25 polypeptide, a CD25 polypeptide fragment, a CD25 antigen, and / or a CD25 epitope. An epitope may be part of a larger CD25 antigen, which may be part of a larger CD25 polypeptide fragment, which, in turn, may be part of a larger CD25 polypeptide. CD25 may exist in a native or denatured form. CD25 polypeptides described herein may be isolated from a variety of sources, such as from human tissue types or from another source, or prepared by recombinant or synthetic methods. A CD25 polypeptide may comprise a polypeptide having the same amino acid sequence as a corresponding CD25 polypeptide derived from nature. Orthologs to the CD25 polypeptide are also well known in the art.

[0293] The term “T-lymphocyte activation antigen CD80”, “CD80”, “CD80 antigen”, “activation B7-1 antigen”,“CTLA-4 counter-receptor B7.1”, or similar term refers to a polypeptide (“polypeptide” and “protein” are used interchangeably herein) or any native CD80 from any vertebrate source, including mammals such as primates (e.g., humans, cynomolgus monkey (cyno)), dogs, and rodents (e.g., mice and rats), unless otherwise indicated. CD80, also known as cluster of differentiation 80 is a protein that in humans is encoded by the CD80 gene. The CD80 gene is also referred to as the CD28LG gene, the CD28LG1 gene, the LAB7 gene, or similar terms. CD80 has Ig-like V-type domain at positions 35-135, and Ig-like C2-type domain at positions 145-230. CD80 is a type I membrane protein in the immunoglobulin superfamily. CD80 is known in the art as a surface ligand for proteins upregulating or downregulating costimulatory signals in the immunological synapses. For instance, CD80 interaction with CD28 enhances T-cell activation, while CD80 interaction with CTLA4 inhibits T-cell effector function. The term CD80 encompasses “full-length,” CD80, as well as any form of CD80 or any fragment thereof that results from processing in the cell. The term CD80 also encompasses naturally occurring variants of CD80, such as SNP variants, splice variants and allelic variants. The full-length amino acid sequence of human CD80 is provided below:

[0294] MGHTRRQGTSPSKCPYLNFFQLLVLAGLSHFCSGVIHVTKEVKEVAT LSCGHNVSVEELAQTRIYWQKEKKMVLTMMSGDMNIWPEYKNRTIFDITNNLSIVIL ALRPSDEGTYECVVLKYEKDAFKREHLAEVTLSVKADFPTPSISDFEIPTSNIRRIICS TSGGFPEPHLSWLENGEELNAINTTVSQDPETELYAVSSKLDFNMTTNHSFMCLIKPage 91 of 555 ACTIVE 705104971v1YGHLRVNQTFNWNTTKQEHFPDNLLPSWAITLISVNGIFVICCLTYCFAPRCRERRR NERLRRESVRPV (SEQ ID NO:427).

[0295] As used herein, the term “T-lymphocyte activation antigen CD86”, “CD86”, “CD86 antigen”, “activation B7-2 antigen”, “B7-2”, “B70”, “BU63”, “CTLA-4 counter-receptor B7.2”, or similar term refers to a polypeptide (“polypeptide” and “protein” are used interchangeably herein) or any native CD86 from any vertebrate source, including mammals such as primates (e.g., humans, cynomolgus monkey (cyno)), dogs, and rodents (e.g., mice and rats), unless otherwise indicated. CD86, also known as cluster of differentiation 86 is a protein that in humans is encoded by the CD86 gene. The CD86 gene is also referred to as the CD28LG2 gene, or similar terms. CD86 has Ig-like V-type domain at positions 33-131, and Ig-like C2-type domain at positions 150-225. CD86 is a type I membrane protein in the immunoglobulin superfamily. CD86 is known in the art as a surface ligand for proteins upregulating or downregulating costimulatory signals in the immunological synapses. For instance, CD86 interaction with CD28 enhances T-cell activation, while CD86 interaction with CTLA4 inhibits T-cell effector function. The term CD86 encompasses “full-length,” CD86, as well as any form of CD86 or any fragment thereof that results from processing in the cell. The term CD86 also encompasses naturally occurring variants of CD86, such as SNP variants, splice variants and allelic variants. The full-length amino acid sequence of human CD86 is provided below:

[0296] MDPQCTMGLSNILFVMAFLLSGAAPLKIQAYFNETADLPCQFANSQN QSLSELVVFWQDQENLVLNEVYLGKEKFDSVHSKYMGRTSFDSDSWTLRLHNLQI KDKGLYQCIIHHKKPTGMIRIHQMNSELSVLANFSQPEIVPISNITENVYINLTCSSIHG YPEPKKMSVLLRTKNSTIEYDGVMQKSQDNVTELYDVSISLSVSFPDVTSNMTIFCIL ETDKTRLLSSPFSIELEDPQPPPDHIPWITAVLPTVIICVMVFCLILWKWKKKKRPRN SYKCGTNTMEREESEQTKKREKIHIPERSDEAQRVFKSSKTSSCDKSDTCF (SEQ ID NO:428).

[0297] The term “IL2,” “IL-2,” “Interleukin 2,” “T-cell growth factor”, or “TCGF” or similar terms refer to a polypeptide (“polypeptide” and “protein” are used interchangeably herein) or any native IL2 from any vertebrate source, including mammals such as primates (e.g., humans, cynomolgus monkey (cyno)), dogs, and rodents (e.g., mice and rats), unless otherwise indicated. IL2 has a signal domain. The term IL2 also encompasses naturally occurring variants of IL2, such as SNPPage 92 of 555 ACTIVE 705104971v1variants, splice variants and allelic variants. IL2 is known in the art to interact with CD25, leading to the promotion of immune tolerance by selectively targeting the IL-2 receptor on regulatory T cells. The full-length amino acid sequence of human IL2 is provided below:

[0298] MYRMQLLSCIALSLALVTNSAPTSSSTKKTQLQLEHLLLDLQMILNGIN NYKNPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLI SNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFCQSIISTLT (SEQ ID NO:429).

[0299] As used herein, the term “binding agent” or a grammatical equivalent thereof refers to a molecule (e.g., an antibody, such as a bispecific antibody) with one or more antigen binding sites that binds an antigen. In some embodiments, a multispecific binding agent as described herein is an antibody, antibody fragment, or other peptide-based molecule that binds to CTLA4, such as human CTLA4.

[0300] The term “antibody,” “immunoglobulin,” or “Ig” is used interchangeably herein, and is used in the broadest sense and specifically covers, for example polyclonal antibodies, monoclonal antibodies (including agonist, antagonist, neutralizing antibodies, full length monoclonal antibodies), antibody compositions with polyepitopic or monoepitopic specificity, recombinantly produced antibodies, monospecific antibodies, multispecific antibodies (including bispecific antibodies), synthetic antibodies, chimeric antibodies, humanized antibodies, or human versions of antibodies having full length heavy and / or light chains. The present disclosure also includes antibody fragments (and / or polypeptides that comprise antibody fragments) that retain CTLA4 binding characteristics. Non-limiting examples of antibody fragments include antigen-binding regions and / or effector regions of the antibody, e.g., Fab, Fab’, F(ab’)2, Fv, scFv, (scFv)2, single chain antibody molecule, dual variable region antibody, single variable region antibody, linear antibody, V region, a multispecific antibody formed from antibody fragments, F(ab)2, Fd, Fc, diabody, di-diabody, disulfide-linked Fvs (dsFv), single-domain antibody (e.g., nanobody) or other fragments (e.g., fragments consisting of the variable regions of the heavy and light chains that are non-covalently coupled). In general terms, a variable (V) region domain may be any suitable arrangement of immunoglobulin heavy (VH) and / or light (VL) chain variable domains. For example, the present disclosure also includes tetrameric antibodies comprising two heavy chain and two light chain molecules, an antibody light chain monomer, and an antibody heavy chain monomer. Thus, for example, the V region domain may be dimeric and contain VH-Page 93 of 555 ACTIVE 705104971v1VH, VH-VL, or VL-VL dimers that bind CTLA4. If desired, the VH and VL chains may be covalently coupled either directly or through a linker to form a single chain Fv (scFv). For ease of reference, scFv proteins are referred to herein as included in the category “antibody fragments.” Another form of an antibody fragment is a peptide comprising one or more complementarity determining regions (CDRs) of an antibody. CDRs (also termed “minimal recognition units” or “hypervariable region”) can be obtained by constructing polynucleotides that encode the CDR of interest. Such polynucleotides are prepared, for example, by using the polymerase chain reaction to synthesize the variable region using mRNA of antibody-producing cells as a template (see, for example, Larrick et al., Methods: A Companion to Methods in Enzymology, 2:106 (1991); Courtenay-Luck, “Genetic Manipulation of Monoclonal Antibodies,” in Monoclonal Antibodies Production, Engineering and Clinical Application, Ritter et al. (eds.), page 166, Cambridge University Press (1995); and Ward et al., “Genetic Manipulation and Expression of Antibodies,” in Monoclonal Antibodies: Principles and Applications, Birch et al., (eds.), page 137, Wiley-Liss, Inc. (1995)). Antibody fragments may be incorporated into single domain antibodies, maxibodies, minibodies, intrabodies, diabodies, triabodies, tetrabodies, variable domains of new antigen receptors (v-NAR), and bis-single chain Fv regions (see, e.g., Hollinger and Hudson, Nature Biotechnology, 23(9):1126-1136, 2005). The binding agent, in some embodiments, contains a light chain and / or a heavy chain constant region, such as one or more constant regions, including one or more IgG1, IgG2, IgG3 and / or IgG4 constant regions. In some embodiments, antibodies can include epitope-binding fragments of any of the above. The antibodies described herein can be of any class (e.g., IgG, IgE, IgM, IgD, and IgA) or any subclass (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2) of immunoglobulin molecule. Antibodies may be agonistic antibodies or antagonistic antibodies.

[0301] The term “monospecific” when used in reference to a binding agent (e.g., an antibody) as used herein denotes a binding agent that has one or more binding sites each of which bind to the same epitope of the same antigen.

[0302] The term “multispecific” when used in reference to a binding agent (e.g., an antibody, including a bispecific antibody) means that the binding agent has binding specificities for at least two different antigens (e.g., CTLA4 and CD25) or at least two different epitopes on the same antigen (e.g., a bispecific antibody directedPage 94 of 555 ACTIVE 705104971v1to CTLA4 with a first binding site for a first epitope of a CTLA4, and a second binding site for a second epitope of CTLA4).

[0303] The term “bispecific” when used in reference to a binding agent (e.g., an antibody) means that the binding agent is able to specifically bind to two distinct antigenic determinants, for example, two binding sites each formed by a pair of an antibody heavy chain variable region (VH) and an antibody light chain variable region (VL) binding to different antigens or to different epitopes on the same antigen. Such a bispecific binding agent may have a 1+1 format. Other bispecific binding agent (e.g., an antibody) formats may be 2+1 or 1+2 formats (comprising two binding sites for a first antigen or epitope and one binding site for a second antigen or epitope) or 2+2 formats (comprising two binding sites for a first antigen or epitope and two binding sites for a second antigen or epitope). When a bispecific binding agent (e.g., an antibody) comprises two antigen binding sites, each may bind to a different antigenic determinant. Such a bispecific binding agent (e.g., an antibody) may bind to two different epitopes on the same antigen (e.g., epitopes on CTLA4).

[0304] The terms “identical” or percent “identity” in the context of two or more nucleic acids or polypeptides, refer to two or more sequences or subsequences that are the same or have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned (introducing gaps, if necessary) for maximum correspondence, not considering any conservative amino acid substitutions as part of the sequence identity. The percent identity can be measured using sequence comparison software or algorithms or by visual inspection. Various algorithms and software that can be used to obtain alignments of amino acid or nucleotide sequences are well-known in the art. These include, but are not limited to, BLAST, ALIGN, Megalign, BestFit, GCG Wisconsin Package, and variants thereof. In some embodiments, two nucleic acids or polypeptides are substantially identical, meaning they have at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, and in some embodiments at least 95%, 96%, 97%, 98%, 99% nucleotide or amino acid residue identity, when compared and aligned for maximum correspondence, as measured using a sequence comparison algorithm or by visual inspection. In some embodiments, identity exists over a region of the amino acid sequences that is at least about 10 residues, at least about 20 residues, at least about 40-60 residues, at least about 60-80 residues in length or any integral value there between. In some embodiments, identity exists over a longer region than 60-Page 95 of 555 ACTIVE 705104971v180 residues, such as at least about 80-100 residues, and in some embodiments the sequences are substantially identical over the full length of the sequences being compared, such as the coding region of a target protein or an antibody. In some embodiments, identity exists over a region of the nucleotide sequences that is at least about 10 bases, at least about 20 bases, at least about 40-60 bases, at least about 60-80 bases in length or any integral value there between. In some embodiments, identity exists over a longer region than 60-80 bases, such as at least about 80-1000 bases or more, and in some embodiments the sequences are substantially identical over the full length of the sequences being compared, such as a nucleotide sequence encoding a protein of interest.

[0305] A “conservative amino acid substitution” is one in which one amino acid `residue is replaced with another amino acid residue having a side chain with similar chemical characteristics. Families of amino acid residues having similar side chains have been generally defined in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). For example, substitution of a phenylalanine for a tyrosine is a conservative substitution. Generally, conservative substitutions in the sequences of the polypeptides, soluble proteins, and / or antibodies of the disclosure do not abrogate the binding of the polypeptide, soluble protein, or antibody containing the amino acid sequence, to the target binding site. Methods of identifying amino acid conservative substitutions which do not eliminate binding are well-known in the art.

[0306] The terms “polypeptide” refers to polymers of amino acids of any length. The polymer can be linear or branched, it can comprise modified amino acids, and it can include (e.g., be interrupted by) non-amino acids. The terms also encompass an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as linkage to or conjugation with (directly or indirectly) a moiety such as a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnaturalPage 96 of 555 ACTIVE 705104971v1amino acids), as well as other modifications known in the art. It is understood that, because the polypeptides of this disclosure can be based upon antibodies or other members of the immunoglobulin superfamily, in some embodiments, the polypeptides can occur as single chains.

[0307] As used herein, an “antigen” is a moiety or molecule that contains an epitope to which a binding agent (e.g., an antibody, such as a bispecific antibody) can bind. As such, an antigen can be bound by an antibody. In some embodiments, the antigen, to which a binding agent (e.g., an antibody, such as a bispecific antibody) described herein binds, is CTLA4 (e.g., human CTLA4), or a fragment thereof. In some embodiments, the antigen, to which a binding agent (e.g., an antibody, such as a bispecific antibody) described herein binds, is CD25 (e.g., human CD25), or a fragment thereof.

[0308] As used herein, an “epitope” is a term in the art and refers to a localized region of an antigen to which an antibody can bind. An epitope can be a linear epitope or a conformational, non-linear, or discontinuous, epitope. In the case of a polypeptide antigen, for example, an epitope can be contiguous amino acids of the polypeptide (a “linear” epitope) or an epitope can comprise amino acids from two or more non-contiguous regions of the polypeptide (a “conformational,” “non-linear” or “discontinuous” epitope), e.g., human CTLA4 or human CD25. It will be appreciated by one of skill in the art that, in general, a linear epitope may or may not be dependent on secondary, tertiary, or quaternary structure. For example, in some embodiments, an antibody binds to a group of amino acids regardless of whether they are folded in a natural three dimensional protein structure. In other embodiments, an antibody requires amino acid residues making up the epitope to exhibit a particular conformation (e.g., bend, twist, turn or fold) in order to recognize and bind the epitope.

[0309] An antibody binds “an epitope” or “essentially the same epitope” or “the same epitope” as a reference antibody, when the two antibodies recognize identical, overlapping or adjacent epitopes in a three-dimensional space. The most widely used and rapid methods for determining whether two antibodies bind to identical, overlapping or adjacent epitopes in a three-dimensional space are competition assays, which can be configured in a number of different formats, for example, using either labeled antigen or labeled antibody. In some assays, the antigen is immobilized on a 96-well plate, or expressed on a cell surface, and the ability ofPage 97 of 555 ACTIVE 705104971v1unlabeled antibodies to block the binding of labeled antibodies is measured using radioactive, fluorescent or enzyme labels.

[0310] “Epitope binning” is the process of grouping antibodies based on the epitopes they recognize. More particularly, epitope binning comprises methods and systems for discriminating the epitope recognition properties of different antibodies, using competition assays combined with computational processes for clustering antibodies based on their epitope recognition properties and identifying antibodies having distinct binding specificities.

[0311] As used herein, the terms “specifically binds,” “specifically recognizes,” “immunospecifically binds,” “selectively binds,” “immunospecifically recognizes” and “immunospecific” are analogous terms in the context of antibodies and refer to molecules that bind to an antigen (e.g., epitope) as such binding is understood by one skilled in the art. In some embodiments, “specifically binds” means, for instance that a polypeptide or molecule interacts more frequently, more rapidly, with greater duration, with greater affinity, or with some combination of the above to the epitope, protein, or target molecule than with alternative substances, including related and unrelated proteins. For example, a molecule that specifically binds to an antigen may bind to other peptides or polypeptides, generally with lower affinity as determined by, e.g., immunoassays, Biacore™, KinExA 3000 instrument (Sapidyne Instruments, Boise, ID), or other assays known in the art. In some embodiments, an antibody or antigen binding domain binds to or specifically binds to an antigen when it binds to an antigen with higher affinity than to any cross-reactive antigen as determined using experimental techniques, such as radioimmunoassays (RIA) and enzyme linked immunosorbent assays (ELISAs). Typically, a specific or selective reaction will be at least twice background signal or noise and may be more than 10 times background. See, e.g., Fundamental Immunology 332-36 (Paul ed., 2d ed. 1989) for a discussion regarding binding specificity. In some embodiments, the extent of binding of an antibody or antigen binding domain to a “non-target” protein is less than about 10% of the binding of the antibody or antigen binding domain to its particular target antigen, for example, as determined by fluorescence activated cell sorting (FACS) analysis or RIA. In some embodiments, molecules that specifically bind to an antigen bind to the antigen with a Ka that is at least 2 logs, 2.5 logs, 3 logs, 4 logs or greater than the Ka when the molecules bind to another antigen. In some embodiments, molecules that specifically bind to an antigen do not cross reactPage 98 of 555 ACTIVE 705104971v1with other proteins. In another specific embodiment, molecules that specifically bind to an antigen do not cross react with other non-CTLA4 proteins. In another specific embodiment, molecules that specifically bind to an antigen do not cross react with other non-CTLA4 proteins. In some embodiments “specifically binds” means, for instance, that a polypeptide or molecule binds a protein or target with a KD of about 0.1mM or less, but more usually less than about 1µM. In some embodiments, “specifically binds” means that a polypeptide or molecule binds a target with a KD of at least about 0.1µM or less, at least about 0.01µM or less, or at least about 1nM or less. Because of the sequence identity between homologous proteins in different species, specific binding can include a polypeptide or molecule that recognizes a protein or target in more than one species. Likewise, because of homology within certain regions of polypeptide sequences of different proteins, specific binding can include a polypeptide or molecule that recognizes more than one protein or target. It is understood that, in some embodiments, a polypeptide or molecule that specifically binds a first target may or may not specifically bind a second target. As such, “specific binding” does not necessarily require (although it can include) exclusive binding, e.g., binding to a single target. Thus, a polypeptide or molecule can, in some embodiments, specifically bind more than one target. In some embodiments, multiple targets can be bound by the same antigen-binding site on the polypeptide or molecule. For example, an antibody can, in certain instances, comprise two identical antigen-binding sites, each of which specifically binds the same epitope on two or more proteins. In certain alternative embodiments, an antibody can be bispecific and comprise at least two antigen-binding sites with differing specificities. Generally, but not necessarily, reference to “binding” means “specific binding”.

[0312] “Binding affinity” generally refers to the strength of the sum total of noncovalent interactions between a single binding site of a binding molecule (e.g., a binding protein such as an antibody) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein, “binding affinity” refers to intrinsic binding affinity which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen). The affinity of a binding molecule X for its binding partner Y can generally be represented by the dissociation constant (KD). Affinity can be measured by common methods known in the art, including those described herein. Low-affinity antibodies generally bind antigen slowly and tend to dissociate readily, whereas high-affinity antibodies generally bind antigen faster and tend toPage 99 of 555 ACTIVE 705104971v1remain bound longer. A variety of methods of measuring binding affinity are known in the art, any of which can be used for purposes of the present disclosure. In one embodiment, the “KD” or “KDvalue” may be measured by assays known in the art, for example by a binding assay. The KD values reported herein were determined by biolayer interferometry (BLI) using, for example, the OctetQK384 system (ForteBio, Menlo Park, CA). Alternatively, the KDmay be also be measured in a radiolabeled antigen binding assay (RIA), for example, performed with the Fab version of an antibody of interest and its antigen (Chen, et al., (1999) J. Mol Biol 293:865-881) or using surface plasmon resonance (SPR) assays by Biacore, using, for example, a BIAcoreTM-2000 or a BIAcoreTM-3000 BIAcore, Inc., Piscataway, NJ). An “on-rate” or “rate of association” or “association rate” or “kon,” as well as an “off-rate” or “rate of dissociation” or “dissociation rate” or “koff,” may can also be determined with the same SPR or BLI techniques described above using, for example, the OctetQK384 sytem (ForteBio, Menlo Park, CA) or a BIAcoreTM-2000 or a BIAcoreTM-3000 (BIAcore, Inc., Piscataway, NJ), respectively.

[0313] “Binding avidity” generally refers to the overall binding strength of the total of all noncovalent interactions between all the binding sites of a binding molecule (e.g., a binding protein such as a bispecific antibody) and its binding partner(s) (e.g., antigen(s)). Binding affinity is one factor that influences the avidity of the interaction between a molecule and its binding partner(s). Other factors that can influence binding avidity include valency of the binding partner and the binding molecule, density of the binding molecule on the cellular surface, as well as the structural arrangement of their interaction. For example, if both the binding molecule and the binding partner(s) are multivalent and there is a favorable structural arrangement between them, the interaction between the binding molecule and the binding partner(s) can be very strong due to high avidity, despite one or more of the individual binding affinities of the binding molecule having low individual binding affinity to a single binding partner. A variety of methods of measuring binding avidity are known in the art, any of which can be used for purposes of the present disclosure. Examples of methods for measuring binding avidity of binding molecules (e.g., a binding protein such as a bispecific antibody) include solid-phase radioimmunoassay, surface plasmon resonance, cell binding, and modified ELISA as described in Correa et al., Biomed. J., 44(4):433-438 (2021), Brady et al., J.Page 100 of 555 ACTIVE 705104971v1Immunol. Methods., 447:31–36 (2017), Hedman et al., Rev. Med. Microbiol., 4:123– 129 (1993), and Lynch et al., J Immunol Methods., 404:1–12 (2014).

[0314] As used herein, the term “constant region” or “constant domain” is a well-known antibody term of art and refers to an antibody portion, e.g., for example, a carboxyl terminal portion of a light and / or heavy chain which is not directly involved in binding of an antibody to an antigen, but which can exhibit various effector functions, such as interaction with the Fc receptor. The term includes the portion of an immunoglobulin molecule having a generally more conserved amino acid sequence relative to an immunoglobulin variable region.

[0315] Antibody “effector functions” refer to those biological activities attributable to the Fc region (e.g., a native sequence Fc region or amino acid sequence variant Fc region) of an antibody, and vary with the antibody isotype. Examples of antibody effector functions include: C1q binding and complement dependent cytotoxicity; Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor); and B cell activation.

[0316] The term “Fc region” herein is used to define a C-terminal region of an immunoglobulin heavy chain, including, for example, native sequence Fc regions, recombinant Fc regions, and variant Fc regions. Although the boundaries of the Fc region of an immunoglobulin heavy chain might vary, the human IgG heavy chain Fc region is often defined to stretch from an amino acid residue at position Cys226 (according to the EU numbering system), or from Pro230 (according to the EU numbering system), to the carboxyl-terminus thereof. The C-terminal lysine (residue 447 according to the EU numbering system) of the Fc region may be removed, for example, during production or purification of the antibody, or by recombinantly engineering the nucleic acid encoding a heavy chain of the antibody. A first exemplary Fc region sequence is provided below (CH2 domain = bold text; CH3 domain = underline text):

[0317] CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPGK (SEQ ID NO: 430). A second exemplary Fc region sequence is provided below (CH2 domain = bold text; CH3 domain = underline text):Page 101 of 555 ACTIVE 705104971v1

[0318] CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPGK (SEQ ID NO: 431). A third exemplary Fc region sequence is provided below (CH2 domain = bold text; CH3 domain = underline text):

[0319] CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPGK (SEQ ID NO: 432).

[0320] A “functional Fc region” possesses an “effector function” of a native sequence Fc region. Exemplary “effector functions” include C1q binding; complement dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor; BCR), etc. Such effector functions generally require the Fc region to be combined with a binding region or binding domain (e.g., an antibody variable region) and can be assessed using various assays as disclosed.

[0321] A “native sequence Fc region” comprises an amino acid sequence identical to the amino acid sequence of an Fc region found in nature, and not manipulated, modified, and / or changed (e.g., isolated, purified, selected, including or combining with other sequences such as variable region sequences) by a human. Native sequence human Fc regions include a native sequence human IgG1 Fc region (non-A and A allotypes); native sequence human IgG2 Fc region; native sequence human IgG3 Fc region; and native sequence human IgG4 Fc region as well as naturally occurring variants thereof.

[0322] A “variant Fc region” comprises an amino acid sequence which differs from that of a native sequence Fc region by virtue of at least one amino acid modification, (e.g., substituting, addition, or deletion) preferably one or more amino acid substitution(s). In some embodiments, the variant Fc region has at least one amino acid substitution compared to a native sequence Fc region or to the Fc region of a parent polypeptide, for example, from about one to about ten amino acid substitutions, and preferably from about one to about five amino acid substitutions in a native sequence Fc region or in the Fc region of the parent polypeptide. ThePage 102 of 555 ACTIVE 705104971v1variant Fc region herein can possess at least about 80% homology with a native sequence Fc region and / or with an Fc region of a parent polypeptide, or at least about 90% homology therewith, for example, at least about 95% homology therewith. The variant Fc region herein described herein may have modified effector function. An first exemplary variant Fc region sequence is provided below (CH2 domain = bold text with amino acid changes underlined; CH3 domain = underline text):

[0323] CPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP EVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALKAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN HYTQKSLSLSPGK (SEQ ID NO: 433). An second exemplary variant Fc region sequence is provided below (CH2 domain = bold text with amino acid changes underlined; CH3 domain = underline text):

[0324] CPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP EVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALKAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN HYTQKSLSLSPGK (SEQ ID NO: 434). An third exemplary variant Fc region sequence is provided below (CH2 domain = bold text with amino acid changes underlined; CH3 domain = underline text):

[0325] CPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP EVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALKAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHN HYTQKSLSLSPGK (SEQ ID NO: 435). An exemplary variant CH2 domain (e.g., silent CH2) sequence useful for multispecific (e.g., bispecific) binding agents described herein is provided below (amino acid changes underlined):

[0326] APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALKAPI EKTISKAK (SEQ ID NO: 436).

[0327] As used herein, the term “heavy chain” when used in reference to an antibody refers to a polypeptide chain of about 50-70 kDa, wherein the amino- terminal portion includes a variable region of about 120 to 130 or more amino acids, and a carboxy-terminal portion includes one or more constant regions. The “heavyPage 103 of 555 ACTIVE 705104971v1chain” can refer to any distinct types, e.g., for example, alpha (α), delta (δ), epsilon (ε), gamma (γ) and mu (µ), based on the amino acid sequence of the constant domain, which give rise to IgA, IgD, IgE, IgG and IgM classes of antibodies, respectively, including subclasses of IgG, e.g., IgG1, IgG2, IgG3 and IgG4.

[0328] As used herein, the term “light chain” when used in reference to an antibody can refer to a polypeptide chain of about 25 kDa, wherein the amino- terminal portion includes a variable region of about 100 to about 110 or more amino acids, and a carboxy-terminal portion includes a constant region. The approximate length of a light chain is 211 to 217 amino acids. There are two distinct types, e.g., kappa (κ) of lambda (λ) based on the amino acid sequence of the constant domains. Light chain amino acid sequences are well known in the art.

[0329] The terms “antigen binding fragment,” “antigen binding domain,” “antigen binding region,” and similar terms refer to that portion of a binding agent (e.g., an antibody, including a bispecific antibody) that comprises the amino acid residues that interact with an antigen and confer on the binding agent, domain, or region its specificity and affinity for the antigen (e.g., the CDRs). “Antigen binding fragment” as used herein include “antibody fragment,” which comprise a portion of an antibody including one or more CDRs, such as the antigen binding or variable region of the antibody. An antigen binding domain and the binding agent comprising an antigen binding domain can be referred to as recognizing the antigen or epitope to which the antigen binding domain specifically binds. Likewise, the antigen or epitope can be referred to as being the determinant of the recognition specificity or binding specificity of the antigen binding domain.

[0330] Antibodies described herein include, but are not limited to, synthetic antibodies, monoclonal antibodies, recombinantly produced antibodies, multispecific antibodies (e.g., including bispecific antibodies), human antibodies, humanized antibodies, chimeric antibodies, intrabodies, single-chain Fvs (scFv) (e.g., including monospecific, bispecific, etc.), camelized antibodies, Fab fragments, F(ab’) fragments, disulfide-linked Fvs (sdFv), anti-idiotypic (anti-Id) antibodies, and epitope- binding fragments of any of the above.

[0331] In some embodiments, antibodies described herein include immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, including molecules that contain one or more antigen binding domains that bind to a CTLA4 antigen and one or more antigen binding domains that bind toPage 104 of 555 ACTIVE 705104971v1one or more targets other than CTLA4 (e.g., CD25). In some embodiments, antibodies described herein include immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, including molecules that contain one or more antigen binding domains that bind to a CD25 antigen and one or more antigen binding domains that bind to one or more targets other than CD25 (e.g., CTLA4).

[0332] Antibodies can be of any type (e.g., IgG, IgE, IgM, IgD, IgA or IgY), any class, (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 or IgA2), or any subclass (e.g., IgG2a or IgG2b) of immunoglobulin molecule. In some embodiments, antibodies described herein are IgG antibodies (e.g., human IgG), or a class (e.g., human IgG1, IgG2, IgG3 or IgG4) or subclass thereof.

[0333] In some embodiments, an antibody is a 4-chain antibody unit comprising two heavy (H) chain / light (L) chain pairs, wherein the amino acid sequences of the H chains are identical and the amino acid sequences of the L chains are identical. In some embodiments, the H and L chains comprise constant regions, for example, human constant regions. In some embodiments, the L chain constant region of such antibodies is a kappa or lambda light chain constant region, for example, a human kappa or lambda light chain constant region. In some embodiments, the H chain constant region of such antibodies comprise a gamma heavy chain constant region, for example, a human gamma heavy chain constant region. In some embodiments, such antibodies comprise IgG constant regions, for example, human IgG constant regions (e.g., IgG1, IgG2, IgG3, and / or IgG4 constant regions).

[0334] An antibody or fragment thereof may preferentially bind to CTLA4 , such as human CTLA4, meaning that the antibody or fragment thereof binds CTLA4 with greater affinity than it binds to an unrelated control protein and / or binds human CTLA4 with greater affinity than it binds to an unrelated control protein. For example, the antibody or fragment thereof may specifically recognize and bind CTLA4 or a portion thereof. An antibody or fragment thereof may preferentially bind to CD25, such as human CD25, meaning that the antibody or fragment thereof binds CD25 with greater affinity than it binds to an unrelated control protein and / or binds human CD25 with greater affinity than it binds to an unrelated control protein. For example, the antibody or fragment thereof may specifically recognize and bind CD25 or a portion thereof. “Specific binding” means that the antibody or fragment thereof binds to CTLA4 with an affinity that is at least 5, 10, 15, 20, 25, 50, 100, 250, 500,Page 105 of 555 ACTIVE 705104971v11000, or 10,000 times greater than the affinity for an unrelated control protein (e.g., hen egg white lysozyme). In some embodiments, the antibody or fragment thereof may bind CTLA4 substantially exclusively (e.g., is able to distinguish CTLA4 from other known polypeptides, for example, by virtue of measurable differences in binding affinity). In some embodiments, a binding agent (e.g., an antibody, such as a multispecific antibody (e.g., a bispecific antibody) may react with CTLA4 sequences other than human CTLA4 sequences (e.g., cynomolgus CTLA4 sequences). In some embodiments, the antibody or fragment thereof may bind CTLA4 substantially exclusively (e.g., is able to distinguish CD25 from CTLA4 known polypeptides, for example, by virtue of measurable differences in binding affinity). In some embodiments, a binding agent (e.g., an antibody, such as a multispecific antibody (e.g., a bispecific antibody)) may react with CD25 sequences other than human CD25 sequences (e.g., cynomolgus CD25 sequences).

[0335] The term “variable region” or “variable domain” refers to a portion of the light or heavy chains of an antibody that is generally located at the amino-terminal of the light or heavy chain and has a length of about 120 to 130 amino acids in the heavy chain and about 100 to 110 amino acids in the light chain, and are used in the binding and specificity of each particular antibody for its particular antigen. The variable region of the heavy chain may be referred to as “VH.” The variable region of the light chain may be referred to as “VL.” The term “variable” refers to the fact that certain segments of the variable regions differ extensively in sequence among antibodies. The V region mediates antigen binding and defines specificity of a particular antibody for its particular antigen. However, the variability is not evenly distributed across the 110-amino acid span of the variable regions. Instead, the V regions consist of less variable (e.g., relatively invariant) stretches called framework regions (FRs) of about 15-30 amino acids separated by shorter regions of greater variability (e.g., extreme variability) called “hypervariable regions” or alternatively called “complementarity determining regions.” The variable regions of heavy and light chains each comprise four FRs (FR1, FR2, FR3 and FR4), largely adopting a β sheet configuration, connected by three hypervariable regions, which form loops connecting, and in some cases forming part of, the β sheet structure. The hypervariable regions in each chain are held together in close proximity by the FRs and, with the hypervariable regions from the other chain, contribute to the formation of the antigen-binding site of antibodies (see, e.g., Kabat et al., Sequences ofPage 106 of 555 ACTIVE 705104971v1Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991)). The constant regions are not involved directly in binding an antibody to an antigen, but exhibit various effector functions, such as participation of the antibody in ADCC and CDC. The variable regions differ extensively in sequence between different antibodies. The variability in sequence is concentrated in the CDRs while the less variable portions in the variable region are referred to as framework regions (FR). The CDRs of the light and heavy chains are primarily responsible for the interaction of the antibody with antigen. In specific embodiments, the variable region is a human variable region.

[0336] The term “hypervariable region,” “HVR,” “HV,” “complementarity determining region,” or “CDR” when used herein refers to the regions of an antibody variable region that are hypervariable in sequence and / or form structurally defined loops. Generally, antibodies comprise six hypervariable regions; three in the VH (H1, H2, H3), and three in the VL (L1, L2, L3). A number of hypervariable region delineations are in use and are encompassed herein. The Kabat CDRs are based on sequence variability and are the most commonly used (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). Chothia refers instead to the location of the structural loops (see, e.g., Chothia and Lesk, J. Mol. Biol.196:901- 917 (1987)). The end of the Chothia CDR-H1 loop when numbered using the Kabat numbering convention varies between H32 and H34 depending on the length of the loop (this is because the Kabat numbering scheme places the insertions at H35A and H35B; if neither 35A nor 35B is present, the loop ends at 32; if only 35A is present, the loop ends at 33; if both 35A and 35B are present, the loop ends at 34). The AbM hypervariable regions represent a compromise between the Kabat CDRs and Chothia structural loops, and are used by Oxford Molecular’s AbM antibody modeling software (see, e.g., Martin, in Antibody Engineering, Vol.2, Chapter 3, Springer Verlag). The “contact” hypervariable regions are based on an analysis of the available complex crystal structures. The residues from each of these hypervariable regions or CDRs are noted below.

[0337] The term “consensus sequence” herein refers to amino acid sequences having conserved amino acids common among a number of sequences and variable amino acids that vary within a given amino acid sequence. The CDR consensusPage 107 of 555 ACTIVE 705104971v1sequences provided include CDRs corresponding to VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and / or VL CDR3.

[0338] A universal numbering system has been developed and widely adopted, ImMunoGeneTics (IMGT) Information System®(Lefranc et al., Dev. Comp. Immunol.27(1):55-77 (2003)). IMGT is an integrated information system specializing in immunoglobulins (IG), T cell receptors (TR) and major histocompatibility complex (MHC) of human and other vertebrates. Herein, the CDRs are referred to in terms of both the amino acid sequence and the location within the light or heavy chain. As the “location” of the CDRs within the structure of the immunoglobulin variable domain is conserved between species and present in structures called loops, by using numbering systems that align variable domain sequences according to structural features, CDR and framework residues and are readily identified. This information can be used in grafting and replacement of CDR residues from immunoglobulins of one species into an acceptor framework from, typically, a human antibody. An additional numbering system (AHon) has been developed by Honegger and Plückthun, J. Mol. Biol.309: 657-670 (2001). Correspondence between the numbering system, including, for example, the Kabat numbering and the IMGT unique numbering system, is well known to one skilled in the art (see, e.g., Kabat, supra; Chothia and Lesk, supra; Martin, supra; Lefranc et al., supra) and is also illustrated below. An Exemplary system, shown herein, combines Kabat and Chothia.

[0339] Hypervariable regions may comprise “extended hypervariable regions” as follows: 24-36 or 24-34 (L1), 46-56 or 50-56 (L2) and 89-97 or 89-96 (L3) in the VL and 26-35 or 26-35A (H1), 50-65 or 49-65 (H2) and 93-102, 94-102, or 95-102 (H3) in the VH. As used herein, the terms “hypervariable region,” “HVR,” “HV,” “complementarity determining region,” or “CDR” are used interchangeably.Page 108 of 555 ACTIVE 705104971v1

[0340] The term “vector” refers to a substance that is used to carry or include a nucleic acid sequences, including for example, in order to introduce a nucleic acid sequence into a host cell. Vectors applicable for use include, for example, expression vectors, plasmids, phage vectors, viral vectors, episomes and artificial chromosomes, which can include selection sequences or markers operable for stable integration into a host cell’s chromosome. Additionally, the vectors can include one or more selectable marker genes and appropriate expression control sequences. Selectable marker genes that can be included, for example, provide resistance to antibiotics or toxins, complement auxotrophic deficiencies, or supply critical nutrients not in the culture media. Expression control sequences can include constitutive and inducible promoters, transcription enhancers, transcription terminators, and the like which are well known in the art. When two or more nucleic acid molecules are to be co-expressed (e.g., both an antibody heavy and light chain or an antibody VH and VL) both nucleic acid molecules can be inserted, for example, into a single expression vector or in separate expression vectors. For single vector expression, the encoding nucleic acids can be operationally linked to one common expression control sequence or linked to different expression control sequences, such as one inducible promoter and one constitutive promoter. The introduction of nucleic acid molecules into a host cell can be confirmed using methods well known in the art. Such methods include, for example, nucleic acid analysis such as Northern blots or polymerase chain reaction (PCR) amplification of mRNA, or immunoblotting for expression of gene products, or other suitable analytical methods to test the expression of an introduced nucleic acid sequence or its corresponding gene product. It is understood by those skilled in the art that the nucleic acid molecules are expressed in a sufficient amount to produce a desired product (e.g., a multispecific binding agent as described herein), and it is further understood that expression levels can be optimized to obtain sufficient expression using methods well known in the art.

[0341] A “tumor regulatory T cell mediated disease,” “tumor regulatory T cell mediated disorder,” “tumor regulatory T cell mediated condition,” “tumor Treg mediated disease,” “tumor Treg mediated disorder,” and “tumor Treg mediated condition” are used interchangeably and refer to any disease, disorder or condition of tumor Tregs characterized by decreased responsiveness to antigenic stimulation. A tumor Treg mediated disease includes a disease, disorder or condition that isPage 109 of 555 ACTIVE 705104971v1completely or partially caused by or is the result of tumor Tregs or the interaction of tumor Tregs with other T cells and / or alternatively any disease, disorder, or condition in which it is desirable to inhibit the in vivo effects of the interaction of tumor Tregs with other T cells. In some embodiments, a tumor Treg mediated disease is a disease, disorder or condition that is specifically associated with inappropriate increased signaling through CTLA4 and / or CD25. In some embodiments, the decreased responsiveness results in ineffective control of a tumor, including but not limited to a tumor having tumor Tregs expressing CTLA4. Examples of a tumor Treg mediated disease characterized by T cell dysfunction include unresolved tumor immunity (e.g., from any cancers, including but not limited to tumor having tumor Tregs expressing CTLA4 and / or CD25).

[0342] “Tumor immunity” refers to the process in which tumors evade immune recognition and clearance. Thus, as a therapeutic concept, tumor immunity is “treated” when such evasion is attenuated, and the tumors are recognized and attacked by the immune system. Examples of tumor recognition include tumor binding, tumor shrinkage and tumor clearance.

[0343] An “effective amount” is generally an amount sufficient to reduce the severity and / or frequency of symptoms, eliminate the symptoms and / or underlying cause, prevent the occurrence of symptoms and / or their underlying cause, and / or improve or remediate the damage that results from or is associated with a disease, disorder, or condition. In some embodiments, the effective amount is a therapeutically effective amount or a prophylactically effective amount.

[0344] The term “therapeutically effective amount” as used herein refers to the amount of an agent (e.g., an antibody described herein or any other agent described herein) that is sufficient to reduce and / or ameliorate the severity and / or duration of a given disease, disorder or condition, and / or a symptom related thereto. A therapeutically effective amount of an agent, including a therapeutic agent, can be an amount necessary for (i) reduction or amelioration of the advancement or progression of a given disease, disorder, or condition, (ii) reduction or amelioration of the recurrence, development or onset of a given disease, disorder or conditions, and / or (iii) to improve or enhance the prophylactic or therapeutic effect of another therapy (e.g., a therapy other than the administration of an antibody described herein). A “therapeutically effective amount” of a substance / molecule / agent of the present disclosure (e.g., a CTLA4 antibody, a CD25 antibody, or bispecific CTLA4Page 110 of 555 ACTIVE 705104971v1and CD25 antibody) may vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of the substance / molecule / agent, to elicit a desired response in the individual. A therapeutically effective amount encompasses an amount in which any toxic or detrimental effects of the substance / molecule / agent are outweighed by the therapeutically beneficial effects. In certain embodiments, the term “therapeutically effective amount” refers to an amount of an antibody or other agent (e.g., or drug) effective to “treat” a disease, disorder, or condition, in a subject or mammal.

[0345] A “prophylactically effective amount” is an amount of a pharmaceutical composition that, when administered to a subject, will have the intended prophylactic effect, e.g., preventing or delaying the onset (or reoccurrence) of a disease, disorder or condition, or reducing the likelihood of the onset (or reoccurrence) of a disease, disorder, or condition or associated symptom(s). The full therapeutic or prophylactic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses. Thus, a therapeutically or prophylactically effective amount may be administered in one or more administrations.

[0346] The term “pharmaceutically acceptable” as used herein means being approved by a regulatory agency of the Federal or a state government, or listed in the U.S. Pharmacopeia, European Pharmacopeia or other generally recognized Pharmacopeia for use in animals, and more particularly in humans.

[0347] “Carriers” as used herein include carriers, excipients, or stabilizers that are nontoxic to the cell or mammal being exposed thereto at the dosages and concentrations employed. Often the carrier is an aqueous pH buffered solution. Examples of carriers include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid; low molecular weight ((e.g., less than about 10 amino acid residues) polypeptide; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt- forming counterions such as sodium; and / or nonionic surfactants such as TWEEN™, polyethylene glycol (PEG), and PLURONICS™. The term “carrier” can also refer to a diluent, adjuvant (e.g., Freund’s adjuvant (complete or incomplete)), excipient, or vehicle with which the therapeutic is administered. Such carriers can be sterilePage 111 of 555 ACTIVE 705104971v1liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. Water is an exemplary carrier when a composition (e.g., a pharmaceutical composition) is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Suitable excipients (e.g., pharmaceutical excipients) include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. Compositions can take the form of solutions, suspensions, emulsion, tablets, pills, capsules, powders, sustained-release formulations and the like. Oral compositions, including formulations, can include standard carriers such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc. Examples of suitable carriers are described in Remington’s Pharmaceutical Sciences (1990) Mack Publishing Co., Easton, PA. Compositions, including pharmaceutical compounds, may contain a prophylactically or therapeutically effective amount of a binding agent (e.g., an antibody, such as a multispecific antibody (e.g., a bispecific antibody), for example, in isolated or purified form, together with a suitable amount of carrier so as to provide the form for proper administration to the subject (e.g., patient). The formulation should suit the mode of administration.

[0348] In some embodiments, the present disclosure provides binding agents (e.g., antibodies, including multispecific antibodies) that can be used herein as therapeutic agents. Such agents include antibodies that binds to CTLA4, including human CTLA4. Such agents include antibodies that binds to CD25, including human CD25. Such agents include multispecific antibodies (e.g., antibodies, such as bispecific antibodies) comprising a first binding domain that binds to CTLA4, including human CTLA4, and a second binding domain that binds one or more additional targets that are not CTLA4 (e.g., CD25). Such agents include multispecific antibodies (e.g., antibodies, such as bispecific antibodies) comprising a first binding domain that binds to CTLA4, including human CTLA4, and a second binding domain that binds one or more additional targets that are not CTLA4 (e.g., CD25). Exemplary antibodies include humanized, human, bispecific, andPage 112 of 555 ACTIVE 705104971v1heteroconjugate antibodies, as well as variants thereof having increased or decreased affinity or other properties.

[0349] In some embodiments, the present disclosure also provides multispecific binding agents (e.g., antibodies, such as bispecific antibodies) having an antibody construct as described in FIG.1. For example, in some embodiments, multispecific binding agents (e.g., antibodies, such as bispecific antibodies) described herein include four polypeptide chains, wherein the first polypeptide chain includes Domains A-B-D-E, the second polypeptide chain includes Domains F-G, the third polypeptide chain includes Domains H-I-J-K, and the fourth polypeptide chain includes Domains L-M. In some embodiments, Domain A is a VL region described herein. In some embodiments, Domain B is a variant CH3 described herein (e.g., SEQ ID NO: 419). In some embodiments, Domain D is a CH2 described herein (e.g., SEQ ID NO: 420). In some embodiments, Domain E is a variant CH3 described herein (e.g., SEQ ID NO: 421). In some embodiments, Domain F is a VH region described herein. In some embodiments, Domain G is a variant CH3 described herein (e.g., SEQ ID NO: 416). In some embodiments, Domain H is a VL described herein. In some embodiments, Domain I is a CL (e.g., Kappa) described herein (e.g., SEQ ID NO: 422). In some embodiments, Domain J is a CH2 described herein (e.g., SEQ ID NO: 423). In some embodiments, Domain K is a variant CH3 described herein (e.g., SEQ ID NO: 424). In some embodiments, Domain L is a VH region. In some embodiments, Domain M is a CH1 described herein (e.g., SEQ ID NO: 418). In some embodiments, multispecific binding agents (e.g., antibodies, such as bispecific antibodies) described herein include a first polypeptide chain having domains connected (e.g., via a peptide bond) in a specific order. For example, as described herein as “Domains A-B-D-E,” the C-terminus of Domain A is connected to the N-terminus of Domain B, the C-terminus of Domain B is connected to the N- terminus of Domain D, and the C-terminus of Domain D is connected to the N- terminus of Domain E. Accordingly, in some embodiments, a multispecific binding agent (e.g., an antibody, such as a bispecific antibody) includes a first polypeptide chain having a VL region described herein (Domain A) connected to constant regions (Domains B-D-E), wherein the constant regions include the amino acid sequence of SEQ ID NO: 415. In some embodiments, multispecific binding agent (e.g., an antibody, such as a bispecific antibody) includes a first polypeptide chain having the amino acid sequence selected from the group consisting of SEQ ID NOS:Page 113 of 555 ACTIVE 705104971v1226, 230, 232, 233, 234, 235, 237, 239, 241, 242, 243, 244, 245, 247, 249, 250, 252, 253, 254, 256, 257, 258, 260, 261, and 262. In some embodiments, multispecific binding agent (e.g., an antibody, such as a bispecific antibody) includes a first polypeptide chain having the amino acid sequence selected from the group consisting of SEQ ID NO:264. In some embodiments, multispecific binding agents (e.g., antibodies, such as bispecific antibodies) described herein include a second polypeptide chain having domains connected (e.g., via a peptide bond) in a specific order. For example, as described herein as “Domains F-G,” the C-terminus of Domain F is connected to the N-terminus of Domain G. Accordingly, in some embodiments, a multispecific binding agent (e.g., an antibody, such as a bispecific antibody) includes a second polypeptide chain having a VH region described herein (Domain F) connected to a constant region (Domain G), wherein the constant region includes the amino acid sequence of SEQ ID NO: 416. In some embodiments, multispecific binding agent (e.g., an antibody, such as a bispecific antibody) includes a second polypeptide chain having the amino acid sequence selected from the group consisting of SEQ ID NOS: 227, 231, 236, 238, 240, 246, 248, 251, 255, 259, and 263. In some embodiments, multispecific binding agent (e.g., an antibody, such as a bispecific antibody) includes a second polypeptide chain having the amino acid sequence selected from the group consisting of SEQ ID NO:265. In some embodiments, multispecific binding agents (e.g., antibodies, such as bispecific antibodies) described herein include a third polypeptide chain having domains connected (e.g., via a peptide bond) in a specific order. For example, as described herein as “Domains H-I-J-K,” the C-terminus of Domain H is connected to the N- terminus of Domain I, the C-terminus of Domain I is connected to the N-terminus of Domain J, and the C-terminus of Domain J is connected to the N-terminus of Domain K. Accordingly, in some embodiments, a multispecific binding agent (e.g., an antibody, such as a bispecific antibody) includes a third polypeptide chain having a VL region described herein (Domain H) connected to constant regions (Domains I-J- K), wherein the constant region includes the amino acid sequence of SEQ ID NO: 417. In some embodiments, multispecific binding agent (e.g., an antibody, such as a bispecific antibody) includes a third polypeptide chain having the amino acid sequence selected from the group consisting of SEQ ID NOs: 228. In some embodiments, multispecific binding agent (e.g., an antibody, such as a bispecific antibody) includes a third polypeptide chain having the amino acid sequencePage 114 of 555 ACTIVE 705104971v1selected from the group consisting of SEQ ID NOS: 266, 268, 270, 271, 272, 273, 275, 277, 279, 280, 281, 282, 283, 285, 287, 288, 290, 291, 292, 294, 295, 296, 298, 299, and 300. In some embodiments, multispecific binding agents (e.g., antibodies, such as bispecific antibodies) described herein include a fourth polypeptide chain having domains connected (e.g., via a peptide bond) in a specific order. For example, as described herein as “Domains L-M,” the C-terminus of Domain L is connected to the N-terminus of Domain M. Accordingly, in some embodiments, a multispecific binding agent (e.g., an antibody, such as a bispecific antibody) includes a fourth polypeptide chain having a VH region described herein (Domain L) connected to a constant region (Domain M), wherein the constant regions include the amino acid sequence of SEQ ID NO: 418. In some embodiments, multispecific binding agent (e.g., an antibody, such as a bispecific antibody) includes a fourth polypeptide chain having the amino acid sequence selected from the group consisting of SEQ ID NO:229. In some embodiments, multispecific binding agent (e.g., an antibody, such as a bispecific antibody) includes a fourth polypeptide chain having the amino acid sequence selected from the group consisting of SEQ ID NOS: 267, 269, 274, 276, 278, 284, 286, 289, 293, 297, and 301.

[0350] In some embodiments, described herein are binding agents (e.g., antibodies,) comprising a binding domain that binds to CTLA4, including a CTLA4 polypeptide, a CTLA4 polypeptide fragment, a CTLA4 peptide or a CTLA4 epitope. In some embodiments, described herein are multispecific binding agents (e.g., antibodies, such as bispecific antibodies) comprising a first binding domain that binds to CTLA4, including a CTLA4 polypeptide, a CTLA4 polypeptide fragment, a CTLA4 peptide or a CTLA4 epitope. In some embodiments, the binding agents are human or humanized antibodies (e.g., comprising human constant regions) comprising a first binding domain that binds CTLA4, including a CTLA4 polypeptide, a CTLA4 polypeptide fragment, a CTLA4 peptide. In some embodiments, a binding agent (e.g., an antibody, such as a bispecific antibody) can bind to CTLA4 expressed on the surface of a mammalian (e.g., human) cell, including a CTLA4 expressing tumor Treg. In some embodiments, a binding agent (e.g., an antibody, such as a bispecific antibody) binds a CTLA4 extracellular epitope exposed on a cell such as a tumor cell (e.g., a CTLA4 epitope). In some embodiments, described herein is a binding agent (e.g., an antibody, such as a bispecific antibody) that binds to CTLA4, such as human CTLA4 or portions thereof. In some embodiments, CTLA4 is aPage 115 of 555 ACTIVE 705104971v1human CTLA4. In some embodiments, a binding agent is a multispecific binding agent that binds to CTLA4 (e.g., an antibody that binds to human CTLA4). An exemplary amino acid sequence of human CTLA4 is described herein.

[0351] In some embodiments, described herein are binding agents (e.g., antibodies,) comprising a binding domain that binds to CD25, including a CD25 polypeptide, a CD25 polypeptide fragment, a CD25 peptide or a CD25 epitope. In some embodiments, described herein are multispecific binding agents (e.g., antibodies, such as bispecific antibodies) comprising a first binding domain that binds to CD25, including a CD25 polypeptide, a CD25 polypeptide fragment, a CD25 peptide or a CD25 epitope. In some embodiments, the binding agents are human or humanized antibodies (e.g., comprising human constant regions) comprising a first binding domain that binds CD25, including a CD25 polypeptide, a CD25 polypeptide fragment, a CD25 peptide or a CD25 epitope. In some embodiments, a binding agent (e.g., an antibody, such as a bispecific antibody) can bind to CD25 expressed on the surface of a mammalian (e.g., human) cell, including a CD25 expressing tumor Treg. In some embodiments, a binding agent (e.g., an antibody, such as a bispecific antibody) binds a CD25 extracellular epitope exposed on a cell such as a tumor cell (e.g., a CD25 epitope). In some embodiments, described herein is a binding agent (e.g., an antibody, such as a bispecific antibody) that binds to CD25, such as human CD25 or portions thereof. In some embodiments, CD25 is a human CD25. In some embodiments, a binding agent is a multispecific binding agent that binds to CD25 (e.g., an antibody that binds to human CD25). An exemplary amino acid sequence of human CD25 is described herein.

[0352] In some embodiments, the binding agents (e.g., antibodies, such as bispecific antibodies) described herein compete for the binding to CTLA4, such as human CTLA4, with a binding agent (e.g., an antibody, such as a bispecific antibody) that comprises a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of any one of the antibodies described herein, such as an amino acid sequence of a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 depicted in Tables 2-28. Accordingly, in some embodiments, a binding agent (e.g., an antibody, such as a bispecific antibody) described herein competes for the binding to CTLA4, such as human CTLA4, with an binding agent (e.g., an antibody, such as a bispecific antibody) that comprises one, two, and / or three VH CDRs and / or one, two, and / or three VL CDRsPage 116 of 555 ACTIVE 705104971v1from the antibody designated mAb-CTLA4, as shown in Tables 2-28. In some embodiments, a binding agent (e.g., an antibody, such as a bispecific antibody) described herein competes for the binding to CTLA4, such as human CTLA4, with a binding agent (e.g., an antibody, such as a bispecific antibody) that comprises one, two, and / or three VH CDRs and one, two, and / or three VL CDRs from the antibody designated mAb-CTLA4, as shown in Tables 2-28. In some embodiments, a binding agent (e.g., an antibody, such as a bispecific antibody) described herein competes for the binding to CTLA4, such as human CTLA4, with a binding agent (e.g., an antibody, such as a bispecific antibody) that comprises a VH region and VL region from the antibody designated mAb-CTLA4, as shown in Tables 2-28. In some embodiments, a binding agent (e.g., an antibody, such as a bispecific antibody) described herein competes for the binding to CTLA4, such as human CTLA4, with a binding agent (e.g., an antibody, such as a bispecific antibody) that comprises a VH region comprising the amino acid sequence selected from the group consisting of SEQ ID NO:44, 57, 86, 95, 104, 135, 147, 151, 173, 196, and 224 and a VL region comprising the amino acid sequence selected from the group consisting of SEQ ID NO:45, 58, 62, 67, 73, 87, 96, 105, 111, 116, 123, 127, 136, 142, 156, 163, 174, 178, 183, 190, 206, 211, and 225.

[0353] In some embodiments, the binding agents (e.g., antibodies, such as bispecific antibodies) described herein compete for the binding to CD25, such as human CD25, with a binding agent (e.g., an antibody, such as a bispecific antibody) that comprises a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of any one of the antibodies described herein, such as an amino acid sequence of a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 depicted in Table 1. Accordingly, in som...

Claims

CLAIMS WHAT IS CLAIMED IS:

1. A multispecific antibody or fragment thereof comprising a first binding domain that binds to CTLA4, wherein the first binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in an amino acid sequence selected from any one of SEQ ID NOs: 44, 57, 86, 95, 104, 135, 147, 151, 173, 196, and 224 , and wherein the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in an amino acid sequence selected from any one of SEQ ID NOs: 45, 58, 62, 67, 73, 87, 96, 105, 111, 116, 123, 127, 136, 142, 156, 163, 174, 178, 183, 190, 206, 211, and 225.

2. The multispecific antibody or fragment thereof of claim 1, wherein: (a) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:45; (b) the VH comprises a VH CDR, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:58; (c) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:62; (d) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:67; (e) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VLPage 373 of 555 ACTIVE 705104971v1comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:73; (f) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:86 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:87; (g) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:95 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:96; (h) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:104 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:105; (i) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:111; (j) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:116; (k) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:123; (l) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:127; (m) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:136;Page 374 of 555 ACTIVE 705104971v1(n) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:57 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:142; (o) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:147 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:142; (p) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:123; (q) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:151 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:73; (r) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:156; (s) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:163; (t) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:173 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:174; (u) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:178; (v) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VLPage 375 of 555 ACTIVE 705104971v1comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:183; (w) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:190; (x) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:196 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:45; (y) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:206; (z) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:211; or (aa) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:224 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:

225.

3. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the multispecific antibody or fragment thereof comprises a second binding domain that binds to CD25.

4. The multispecific antibody or fragment thereof of any one of claims 1 to 3, wherein the multispecific antibody or fragment thereof is a bispecific antibody.

5. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising:Page 376 of 555 ACTIVE 705104971v1(1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; andPage 377 of 555 ACTIVE 705104971v1(3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

6. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of:Page 378 of 555 ACTIVE 705104971v1(i) SEQ ID NO:47, (ii) SEQ ID NO:50, (iii) SEQ ID NO:53, and (iv) SEQ ID NO:55; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:48, (ii) SEQ ID NO:51, and (iii) SEQ ID NO:56; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

7. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of:Page 379 of 555 ACTIVE 705104971v1(i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:59, (ii) SEQ ID NO:60, and (iii) SEQ ID NO:61; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

8. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39;Page 380 of 555 ACTIVE 705104971v1(2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:63, (ii) SEQ ID NO:64, (iii) SEQ ID NO:65, and (iv) SEQ ID NO:66; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:42.Page 381 of 555 ACTIVE 705104971v19. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:68, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:69,Page 382 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:11, and (iii) SEQ ID NO:72; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

10. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:74, (ii) SEQ ID NO:44, (iii) SEQ ID NO:425, (iv) SEQ ID NO:78, and (v) SEQ ID NO:81; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:340, (ii) SEQ ID NO:341, (iii) SEQ ID NO:79, (iv) SEQ ID NO:82, and (v) SEQ ID NO:85; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising:Page 383 of 555 ACTIVE 705104971v1(1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:75, (ii) SEQ ID NO:77, (iii) SEQ ID NO:80, and (iv) SEQ ID NO:83; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:76, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:84; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

11. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:88, (ii) SEQ ID NO:90, (iii) SEQ ID NO:91, (iv) SEQ ID NO:92, andPage 384 of 555 ACTIVE 705104971v1(v) SEQ ID NO:94; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:89, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:93; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

12. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31,Page 385 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:97, (ii) SEQ ID NO:99, (iii) SEQ ID NO:101, (iv) SEQ ID NO:103, and (v) SEQ ID NO:445; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:98, (ii) SEQ ID NO:100, (iii) SEQ ID NO:102, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, andPage 386 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:

42.

13. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:106, (ii) SEQ ID NO:108, (iii) SEQ ID NO:109, and (iv) SEQ ID NO:21;Page 387 of 555 ACTIVE 705104971v1(2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:107, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:110; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

14. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, andPage 388 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:112, (ii) SEQ ID NO:113, (iii) SEQ ID NO:114, and (iv) SEQ ID NO:115; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

15. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28,Page 389 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:117, (ii) SEQ ID NO:119, (iii) SEQ ID NO:120, and (iv) SEQ ID NO:121; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:118, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:122; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

16. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising:Page 390 of 555 ACTIVE 705104971v1(1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:124, (ii) SEQ ID NO:125, (iii) SEQ ID NO:126, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; andPage 391 of 555 ACTIVE 705104971v1(3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

17. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of:Page 392 of 555 ACTIVE 705104971v1(i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:129, (ii) SEQ ID NO:131, and (iii) SEQ ID NO:134; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

18. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises : (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; andPage 393 of 555 ACTIVE 705104971v1(3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:46, (ii) SEQ ID NO:49, (iii) SEQ ID NO:52, and (iv) SEQ ID NO:54; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:137, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:140; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:138, (ii) SEQ ID NO:139, and (iii) SEQ ID NO:

141.

19. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, andPage 394 of 555 ACTIVE 705104971v1(v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:143, (ii) SEQ ID NO:144, (iii) SEQ ID NO:145, and (iv) SEQ ID NO:146; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:137, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:140; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:138, (ii) SEQ ID NO:139, and (iii) SEQ ID NO:141.Page 395 of 555 ACTIVE 705104971v120. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:117, (ii) SEQ ID NO:119, (iii) SEQ ID NO:120, and (iv) SEQ ID NO:121; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:118,Page 396 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:11, and (iii) SEQ ID NO:122; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

21. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:148, (ii) SEQ ID NO:149, (iii) SEQ ID NO:34, (iv) SEQ ID NO:150, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising:Page 397 of 555 ACTIVE 705104971v1(1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:68, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:69, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:72; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

22. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, andPage 398 of 555 ACTIVE 705104971v1(v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:152, (ii) SEQ ID NO:10, (iii) SEQ ID NO:154, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:153, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

155.

23. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31,Page 399 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:157, (ii) SEQ ID NO:159, (iii) SEQ ID NO:161, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:158, (ii) SEQ ID NO:160, and (iii) SEQ ID NO:162; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, andPage 400 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:

42.

24. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:164, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:170, and (v) SEQ ID NO:172; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:165, (ii) SEQ ID NO:167 (iii) SEQ ID NO:169 and (iv) SEQ ID NO:21;Page 401 of 555 ACTIVE 705104971v1(2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:166, (ii) SEQ ID NO:168, and (iii) SEQ ID NO:171; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

25. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, andPage 402 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:175, (ii) SEQ ID NO:176, and (iii) SEQ ID NO:

177.

26. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32,Page 403 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:179, (ii) SEQ ID NO:180, (iii) SEQ ID NO:181, and (iv) SEQ ID NO:182; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

27. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of:Page 404 of 555 ACTIVE 705104971v1(i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:184, (ii) SEQ ID NO:186, and (iii) SEQ ID NO:188; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:185,Page 405 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:187, and (iii) SEQ ID NO:

189.

28. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:191, (ii) SEQ ID NO:192, (iii) SEQ ID NO:193, (iv) SEQ ID NO:194, and (v) SEQ ID NO:195; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21;Page 406 of 555 ACTIVE 705104971v1(2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

29. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, andPage 407 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:197, (ii) SEQ ID NO:200, (iii) SEQ ID NO:202 and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:198, (ii) SEQ ID NO:201, and (iii) SEQ ID NO:204; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:199, (ii) SEQ ID NO:203, and (iii) SEQ ID NO:

205.

30. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32,Page 408 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:207, (ii) SEQ ID NO:208, (iii) SEQ ID NO:209, and (iv) SEQ ID NO:210; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

31. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of:Page 409 of 555 ACTIVE 705104971v1(i) SEQ ID NO:212, (ii) SEQ ID NO:215, (iii) SEQ ID NO:217, (iv) SEQ ID NO:218, and (v) SEQ ID NO:220; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:213, (ii) SEQ ID NO:216, (iii) SEQ ID NO:219, (iv) SEQ ID NO:221, and (v) SEQ ID NO:223; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:214, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:222; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30,Page 410 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

32. The multispecific antibody or fragment thereof of any one of claims 5 to 31, wherein the multispecific antibody comprises a second binding domain that binds to CD25.

33. The multispecific antibody or fragment thereof of any one of claims 5 to 32, which is a bispecific antibody.

34. The multispecific antibody or fragment thereof of claims 32 or 33, wherein the second binding domain that binds to CD25 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:1, (ii) SEQ ID NO:7, (iii) SEQ ID NO:12, (iv) SEQ ID NO:13, and (v) SEQ ID NO:18; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:2, (ii) SEQ ID NO:8, (iii) SEQ ID NO:14, (iv) SEQ ID NO:19, and (v) SEQ ID NO:24; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:3, (ii) SEQ ID NO:9, (iii) SEQ ID NO:15, and (iv) SEQ ID NO:20;Page 411 of 555 ACTIVE 705104971v1and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:6, (ii) SEQ ID NO:17, and (iii) SEQ ID NO:

23.

35. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36,Page 412 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:

41.

36. The multispecific antibody or fragment thereof of claim 35, wherein the multispecific antibody comprises a second binding domain that binds to CD25.

37. The multispecific antibody or fragment thereof of claim 35 or 36, which is a bispecific antibody.

38. The multispecific antibody or fragment thereof of claims 36 or 37, wherein the second binding domain that binds to CD25 comprises a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:1, (ii) SEQ ID NO:7, (iii) SEQ ID NO:12, (iv) SEQ ID NO:13, and (v) SEQ ID NO:18; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:2, (ii) SEQ ID NO:8, (iii) SEQ ID NO:14, (iv) SEQ ID NO:19, and (v) SEQ ID NO:24; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of:Page 413 of 555 ACTIVE 705104971v1(i) SEQ ID NO:3, (ii) SEQ ID NO:9, (iii) SEQ ID NO:15, and (iv) SEQ ID NO:

20.

39. A multispecific antibody or fragment thereof with a first binding domain that binds to CTLA4, wherein the first binding domain comprises a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, 98, or 63, (ii) SEQ ID NO:10, 100, or 64, (iii) SEQ ID NO:16, 102, or 65, and (iv) SEQ ID NO:21, 21, or 66; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

40. The multispecific antibody or fragment thereof of claim 39, wherein the multispecific antibody comprises a second binding domain that binds to CD25.

41. The multispecific antibody or fragment thereof of claim 39 or 40, which is a bispecific antibody.Page 414 of 555 ACTIVE 705104971v142. The multispecific antibody or fragment thereof of claim 40 or 41, wherein the second binding domain that binds to CD25 comprises a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:6, (ii) SEQ ID NO:17, and (iii) SEQ ID NO:

23.

43. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4;Page 415 of 555 ACTIVE 705104971v1(2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

44. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:47; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:48; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

45. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising:Page 416 of 555 ACTIVE 705104971v1(1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:59; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

46. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:63; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

47. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29;Page 417 of 555 ACTIVE 705104971v1and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:69; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

48. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:74; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:340; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:75; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:76; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

49. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:88; andPage 418 of 555 ACTIVE 705104971v1(3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:89; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

50. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:97; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:98; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

51. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27;Page 419 of 555 ACTIVE 705104971v1(2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:106; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:107; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

52. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:112; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

53. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising:Page 420 of 555 ACTIVE 705104971v1(1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:117; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:118; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

54. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:124; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 421 of 555 ACTIVE 705104971v155. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:129; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

56. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:46; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:137; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; andPage 422 of 555 ACTIVE 705104971v1(3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

138.

57. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:143; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:137; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

138.

58. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:117;Page 423 of 555 ACTIVE 705104971v1(2) a VL CDR2 having the amino acid sequence of SEQ ID NO:118; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

59. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:148; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:69; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

60. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising:Page 424 of 555 ACTIVE 705104971v1(1) a VL CDR1 having the amino acid sequence of SEQ ID NO:152; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

153.

61. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:157; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:158; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

62. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:164; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29;Page 425 of 555 ACTIVE 705104971v1and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:165; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:166; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

63. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

175.

64. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; andPage 426 of 555 ACTIVE 705104971v1(3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:179; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

65. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:184; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

185.

66. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:191;Page 427 of 555 ACTIVE 705104971v1(2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

67. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:197; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:198; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

199.

68. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising:Page 428 of 555 ACTIVE 705104971v1(1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:207; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

69. The multispecific antibody or fragment thereof of claim 1 or 2, wherein the first binding domain that binds to CTLA4 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:212; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:213; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:214; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 429 of 555 ACTIVE 705104971v170. The multispecific antibody or fragment thereof of any one of claims 43 to 69, wherein the multispecific antibody comprises a second binding domain that binds to CD25.

71. The multispecific antibody or fragment thereof of any one of claims 43 to 70, which is a bispecific antibody.

72. The multispecific antibody or fragment thereof of claim 70 or 71, wherein the second binding domain that binds to CD25 comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:1; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:2; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:3; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

6.

73. A multispecific antibody or fragment thereof comprising a first polypeptide chain, a second polypeptide chain, a third polypeptide chain, and a fourth polypeptide chain, wherein the first polypeptide chain and the second polypeptide chain comprise an antigen binding domain for CTLA4, wherein the third polypeptide chain and the fourth polypeptide chain comprise an antigen binding domain for CD25, and wherein: (a) the first polypeptide chain comprises a light chain variable region (VL) and constant regions, wherein the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 amino acid sequence as set forth in an aminoPage 430 of 555 ACTIVE 705104971v1acid sequence selected from any one of SEQ ID NOs: 45, 58, 62, 67, 73, 87, 96, 105, 111, 116, 123, 127, 136, 142, 156, 163, 174, 178, 183, 190, 206, 211, and 225 and the constant regions comprise the amino acid sequence of SEQ ID NO:415; (b) the second polypeptide chain comprises a heavy chain variable region (VH) and a constant region, wherein the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 amino acid sequence as set forth in an amino acid sequence selected from any one of SEQ ID NOs: 44, 57, 86, 95, 104, 135, 147, 151, 173, 196, and 224 and the constant region comprises the amino acid sequence of SEQ ID NO:416; (c) the third polypeptide chain comprises a light chain variable region (VL) and constant regions, wherein the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 amino acid sequence as set forth in SEQ ID NO:26 and the constant regions comprise the amino acid sequence of SEQ ID NO:417; (d) the fourth polypeptide chain comprises a heavy chain variable region (VH) and a constant region, wherein the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 amino acid sequence as set forth in SEQ ID NO:25 and the constant region comprises the amino acid sequence of SEQ ID NO:

418.

74. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:45; (b) the VH of the second polypeptide chain comprises a VH CDR, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:58; (c) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequencePage 431 of 555 ACTIVE 705104971v1of SEQ ID NO:44 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:62; (d) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:67; (e) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:73; (f) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:86 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:87; (g) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:95 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:96; (h) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:104 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:105; (i) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:111;Page 432 of 555 ACTIVE 705104971v1(j) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:116; (k) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:123; (l) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:127; (m) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:136; (n) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:57 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:142; (o) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:147 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:142; (p) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain comprisesPage 433 of 555 ACTIVE 705104971v1a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:123; (q) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:151 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:73; (r) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:156; (s) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:163; (t) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:173 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:174; (u) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:178; (v) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:183; (w) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequencePage 434 of 555 ACTIVE 705104971v1of SEQ ID NO:135 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:190; (x) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:196 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:45; (y) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:206; (z) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:211; or (aa) the VH of the second polypeptide chain comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:224 and the VL of the first polypeptide chain comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:

225.

75. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39;Page 435 of 555 ACTIVE 705104971v1(2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

76. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises:Page 436 of 555 ACTIVE 705104971v1(1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:47, (ii) SEQ ID NO:50, (iii) SEQ ID NO:53, and (iv) SEQ ID NO:55; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:48, (ii) SEQ ID NO:51, and (iii) SEQ ID NO:56; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of:Page 437 of 555 ACTIVE 705104971v1(i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

77. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, andPage 438 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:59, (ii) SEQ ID NO:60, and (iii) SEQ ID NO:61; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

78. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33,Page 439 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:63, (ii) SEQ ID NO:64, (iii) SEQ ID NO:65, and (iv) SEQ ID NO:66; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

79. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28,Page 440 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:68, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:69, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:72; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

80. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of:Page 441 of 555 ACTIVE 705104971v1(i) SEQ ID NO:74, (ii) SEQ ID NO:444, (iii) SEQ ID NO:425, (iv) SEQ ID NO:78, and (v) SEQ ID NO:81; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:340, (ii) SEQ ID NO:341, (iii) SEQ ID NO:79, (iv) SEQ ID NO:82, and (v) SEQ ID NO:85; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:75, (ii) SEQ ID NO:77, (iii) SEQ ID NO:80, and (iv) SEQ ID NO:83; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:76, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:84; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38,Page 442 of 555 ACTIVE 705104971v1(iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

81. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:88, (ii) SEQ ID NO:90, (iii) SEQ ID NO:91, (iv) SEQ ID NO:92, and (v) SEQ ID NO:94; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21;Page 443 of 555 ACTIVE 705104971v1(2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:89, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:93; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

82. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:97, (ii) SEQ ID NO:99, (iii) SEQ ID NO:101, (iv) SEQ ID NO:103, and (v) SEQ ID NO:445; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, andPage 444 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:98, (ii) SEQ ID NO:100, (iii) SEQ ID NO:102, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

83. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32,Page 445 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:106, (ii) SEQ ID NO:108, (iii) SEQ ID NO:109, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:107, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:110; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

84. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27,Page 446 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:112, (ii) SEQ ID NO:113, (iii) SEQ ID NO:114, and (iv) SEQ ID NO:115; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, andPage 447 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:

42.

85. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:117, (ii) SEQ ID NO:119, (iii) SEQ ID NO:120, and (iv) SEQ ID NO:121; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of:Page 448 of 555 ACTIVE 705104971v1(i) SEQ ID NO:118, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:122; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

86. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises:Page 449 of 555 ACTIVE 705104971v1(1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:124, (ii) SEQ ID NO:125, (iii) SEQ ID NO:126, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

87. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, andPage 450 of 555 ACTIVE 705104971v1(v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:129, (ii) SEQ ID NO:131, and (iii) SEQ ID NO:134; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

88. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34,Page 451 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:46, (ii) SEQ ID NO:49, (iii) SEQ ID NO:52, and (iv) SEQ ID NO:54; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:137, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:140; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:138, (ii) SEQ ID NO:139, and (iii) SEQ ID NO:

141.

89. The multispecific antibody or fragment thereof of claim 73, wherein:Page 452 of 555 ACTIVE 705104971v1(a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:143, (ii) SEQ ID NO:144, (iii) SEQ ID NO:145, and (iv) SEQ ID NO:146; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:137, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:140; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; andPage 453 of 555 ACTIVE 705104971v1(3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:138, (ii) SEQ ID NO:139, and (iii) SEQ ID NO:

141.

90. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:117, (ii) SEQ ID NO:119,Page 454 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:120, and (iv) SEQ ID NO:121; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:118, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:122; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

91. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:148, (ii) SEQ ID NO:149, (iii) SEQ ID NO:34, (iv) SEQ ID NO:150, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29,Page 455 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:68, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:69, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:72; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

92. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of:Page 456 of 555 ACTIVE 705104971v1(i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:152, (ii) SEQ ID NO:10, (iii) SEQ ID NO:154, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:153, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

155.

93. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises:Page 457 of 555 ACTIVE 705104971v1(1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:157, (ii) SEQ ID NO:159, (iii) SEQ ID NO:161, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:158, (ii) SEQ ID NO:160, and (iii) SEQ ID NO:162; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of:Page 458 of 555 ACTIVE 705104971v1(i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

94. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:164, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:170, and (v) SEQ ID NO:172; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:165, (ii) SEQ ID NO:167 (iii) SEQ ID NO:169 andPage 459 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:166, (ii) SEQ ID NO:168, and (iii) SEQ ID NO:171; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

95. The multispecific antibody or fragment thereof of claim 73 wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130,Page 460 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:175, (ii) SEQ ID NO:176, and (iii) SEQ ID NO:

177.

96. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32,Page 461 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:179, (ii) SEQ ID NO:180, (iii) SEQ ID NO:181, and (iv) SEQ ID NO:182; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

97. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27,Page 462 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:184, (ii) SEQ ID NO:186, and (iii) SEQ ID NO:188; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:185, (ii) SEQ ID NO:187, and (iii) SEQ ID NO:189.Page 463 of 555 ACTIVE 705104971v18. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:191, (ii) SEQ ID NO:192, (iii) SEQ ID NO:193, (iv) SEQ ID NO:194, and (v) SEQ ID NO:195; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, andPage 464 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

99. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of:Page 465 of 555 ACTIVE 705104971v1(i) SEQ ID NO:197, (ii) SEQ ID NO:200, (iii) SEQ ID NO:202 and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:198, (ii) SEQ ID NO:201, and (iii) SEQ ID NO:204; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:199, (ii) SEQ ID NO:203, and (iii) SEQ ID NO:

205.

100. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of:Page 466 of 555 ACTIVE 705104971v1(i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:207, (ii) SEQ ID NO:208, (iii) SEQ ID NO:209, and (iv) SEQ ID NO:210; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

101. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:212, (ii) SEQ ID NO:215, (iii) SEQ ID NO:217, (iv) SEQ ID NO:218, and (v) SEQ ID NO:220;Page 467 of 555 ACTIVE 705104971v1(2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:213, (ii) SEQ ID NO:216, (iii) SEQ ID NO:219, (iv) SEQ ID NO:221, and (v) SEQ ID NO:223; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:214, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:222; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

102. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprisesPage 468 of 555 ACTIVE 705104971v1(1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

20.

103. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:47; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:48; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

104. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprisesPage 469 of 555 ACTIVE 705104971v1(1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:59; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

105. The multispecific antibody or fragment thereof of claim 73 or 74, wherein : (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:63; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

106. The multispecific antibody or fragment thereof of claim 73 or 74, wherein:Page 470 of 555 ACTIVE 705104971v1(a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:69; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

107. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:74; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:340; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:75; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:76; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

108. The multispecific antibody or fragment thereof of claim 73 or 74, wherein:Page 471 of 555 ACTIVE 705104971v1(a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:88; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:89; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

109. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:97; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:98; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 472 of 555 ACTIVE 705104971v1110. The multispecific antibody or fragment thereof of claim 73 or 74, wherein : (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:106; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:107; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

111. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:112; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 473 of 555 ACTIVE 705104971v1112. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:117; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:118; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

113. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:124; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 474 of 555 ACTIVE 705104971v1114. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

115. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:46; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:137; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:138.Page 475 of 555 ACTIVE 705104971v1116. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:143; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:137; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

138.

117. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:117; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:118; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 476 of 555 ACTIVE 705104971v1118. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:148; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:69; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

119. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:152; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:153.Page 477 of 555 ACTIVE 705104971v1120. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:157; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:158; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

121. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:164; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:165; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:166; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 478 of 555 ACTIVE 705104971v1122. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

175.

123. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:179; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 479 of 555 ACTIVE 705104971v1124. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:184; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

185.

125. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:191; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 480 of 555 ACTIVE 705104971v1126. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:197; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:198; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

199.

127. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:207; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 481 of 555 ACTIVE 705104971v1128. The multispecific antibody or fragment thereof of claim 73 or 74, wherein: (a) the second polypeptide chain comprises (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:212; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:213; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) the first polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:214; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

129. The multispecific antibody or fragment thereof of any one of claims 75 to, wherein: (a) the fourth polypeptide chain comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:1, (ii) SEQ ID NO:7, (iii) SEQ ID NO:12, (iv) SEQ ID NO:13, and (v) SEQ ID NO:18; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:2, (ii) SEQ ID NO:8, (iii) SEQ ID NO:14, (iv) SEQ ID NO:19, andPage 482 of 555 ACTIVE 705104971v1(v) SEQ ID NO:24; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:3, (ii) SEQ ID NO:9, (iii) SEQ ID NO:15, and (iv) SEQ ID NO:20; and (b) the third polypeptide chain comprises: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:6, (ii) SEQ ID NO:17, and (iii) SEQ ID NO:

23.

130. The multispecific antibody or fragment thereof of any one of claims 102 wherein: (a) the fourth polypeptide chain comprises: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:1; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 2; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 3;Page 483 of 555 ACTIVE 705104971v1and (b) the third polypeptide chain comprises: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

6.

131. The multispecific antibody or fragment thereof of claim 73, wherein: (a) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:45; (b) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:58; (c) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:62 ; (d) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:67; (e) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:73; (f) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:86 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:87; (g) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:95 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:96; (h) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 104 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:105;Page 484 of 555 ACTIVE 705104971v1(i) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:111; (j) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:116; (k) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:123; (l) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:44 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:127; (m) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:136; (n) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:57 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:142; (o) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:147 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:142; (p) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:123; (q) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:151 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:73; (r) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:156; (s) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:163;Page 485 of 555 ACTIVE 705104971v1(t) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:173 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:174; (u) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 135 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:178; (v) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:183; (w) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:190; (x) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:196 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:45; (y) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:206; (z) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:135 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:211; or (aa) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:224 and the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:

225.

132. The multispecific antibody or fragment thereof of claim 131, wherein the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO:25 and the third polypeptide chain comprises the amino acid sequence of SEQ ID NO:

26.

133. The multispecific antibody or fragment thereof of claim 132, wherein the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:44, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:45, the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO:25, and the third polypeptide chain comprises the amino acid sequence of SEQ ID NO:26.Page 486 of 555 ACTIVE 705104971v1134. The multispecific antibody or fragment thereof of claim 132, wherein the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:44, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:67, the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO:25, and the third polypeptide chain comprises the amino acid sequence of SEQ ID NO:

26.

135. The multispecific antibody or fragment thereof of claim 132, wherein the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:104, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:105, the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO:25, and the third polypeptide chain comprises the amino acid sequence of SEQ ID NO:

26.

136. A multispecific antibody or fragment thereof comprising a first polypeptide chain, a second polypeptide chain, a third polypeptide chain, and a fourth polypeptide chain, wherein the first polypeptide chain and the second polypeptide chain comprise an antigen binding domain for CD25, wherein the third polypeptide chain and the fourth polypeptide chain comprise an antigen binding domain for CTLA4, and wherein : (a) the first polypeptide chain comprises a light chain variable region (VL) and constant regions, wherein the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 amino acid sequence as set forth in SEQ ID NO:25 and the constant regions comprise the amino acid sequence of SEQ ID NO:415; (b) the second polypeptide chain comprises a heavy chain variable region (VH) and a constant region, wherein the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 amino acid sequence as set forth in SEQ ID NO:26 and the constant region comprises the amino acid sequence of SEQ ID NO:416; (c) the third polypeptide chain comprises a light chain variable region (VL) and constant regions, wherein the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 amino acid sequence as set forth in SEQ ID NO: 45, 58, 62, 67, 73, 87, 96, 105, 111, 116, 123, 127, 136, 142, 156, 163, 174, 178, 183, 190, 206, 211, or 225 and the constant regions comprise the amino acid sequence of SEQ ID NO:417;Page 487 of 555 ACTIVE 705104971v1(d) the fourth polypeptide chain comprises a heavy chain variable region (VH) and a constant region, wherein the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 amino acid sequence as set forth in SEQ ID NO: 44, 57, 86, 95, 104, 135, 147, 151, 173, 196, or 224 and the constant region comprises the amino acid sequence of SEQ ID NO:

418.

137. A multispecific antibody or fragment thereof comprising a first binding domin that binds to CTLA4, wherein the first binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1X2SYX3YYADSVKG (SEQ ID NO:450), wherein X1 is D or G, and wherein X2 is G or Y, and wherein X3 is T or Y; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL comprises: (d) a VL CDR1 consensus sequence of X1AX2X3X4VSX5X6VA (SEQ ID NO:388), wherein X1is R or H, and wherein X2is S or P, wherein X3is Q, D, or F, wherein X4 is S or L, wherein X5 is S or K, and wherein X6 is A or L; (e) a VL CDR2 consensus sequence of SAX1SX2X3S (SEQ ID NO:389), wherein X1 is S, A, or D, wherein X2 is L, T, or F, and wherein X3 is Y or P; and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).Page 488 of 555 ACTIVE 705104971v1138. A multispecific antibody or fragment thereof comprising a first binding domin that binds to CTLA4, wherein the first binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSDGSYTYYADSVKG (SEQ ID NO:28); and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL comprises: (d) a VL CDR1 consensus sequence of X1AX2X3X4X5X6X7X8VA (SEQ ID NO: 397), wherein X1is R or H, and wherein X2is S or N, wherein X3 is Q, F, S, or V wherein X4 is S, L, or Q, wherein X5 is V or L, wherein X6 is S or I, wherein X7 is S, K, or R, and wherein X8 is A or L; (e) a VL CDR2 consensus sequence of SAX1SX2YS (SEQ ID NO:390), wherein X1 is S, A, or D, and wherein X2 is L, M, F, or S; and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

139. A multispecific antibody or fragment thereof comprising a first binding domin that binds to CTLA4, wherein the first binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27);Page 489 of 555 ACTIVE 705104971v1(b) a VH CDR2 consensus sequence of FITSX1X2SYX3YYADSVKG (SEQ ID NO:386), wherein X1 is D or G, wherein X2 is G or Y, and wherein X3is T or H; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL comprises: (d) a VL CDR1 consensus sequence of RAX1X2SVSX3AVA (SEQ ID NO:391), wherein X1 is S, P, or N, wherein X2 is Q, D, F, or V and wherein X3 is S or K; (e) a VL CDR2 consensus sequence of SAX1SX2X3S (SEQ ID NO:396), wherein X1 is S or D, wherein X2 is L, T, or S, and wherein X3 is Y or P; and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

140. A multispecific antibody or fragment thereof comprising a first binding domin that binds to CTLA4, wherein the first binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1GSYX2YYADSVKG (SEQ ID NO:393), wherein X1 is D or G, and wherein X2 is T or H; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL comprises:Page 490 of 555 ACTIVE 705104971v1(d) a VL CDR1 consensus sequence of RAX1X2SVSX3AVA (SEQ ID NO:398), wherein X1 is S or P, wherein X2 is Q, D, or F, and wherein X3is S or K; (e) a VL CDR2 consensus sequence of SASSLYS (SEQ ID NO:5); and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

141. A multispecific antibody or fragment thereof comprising a first binding domin that binds to CTLA4, wherein the first binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1GSYX2YYADSVKG (SEQ ID NO:393), wherein X1 is D or G, and wherein X2 is T or H; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL comprises: (d) a VL CDR1 consensus sequence of RAX1X2SVSSAVA (SEQ ID NO:395), wherein X1is S or P, and wherein X2is Q or D; (e) a VL CDR2 consensus sequence of SASSLYS (SEQ ID NO:5); and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

142. A multispecific antibody or fragment thereof comprising a first binding domin that binds to CTLA4, wherein the first binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL),Page 491 of 555 ACTIVE 705104971v1wherein the VH comprises: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSDGSYTYYADSVKG (SEQ ID NO:28); and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL comprises: (d) a VL CDR1 consensus sequence of RASX1SVSX2AVA (SEQ ID NO:394), wherein X1is Q or F, and wherein X2is S or K; (e) a VL CDR2 consensus sequence of SASSLYS (SEQ ID NO:5); and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

143. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in an amino acid sequence selected from any one of SEQ ID NOs: 44, 57, 86, 95, 104, 135, 147, 151, 173, 196, and 224, and wherein the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in an amino acid sequence selected from any one of SEQ ID NOs: 45, 58, 62, 67, 73, 87, 96, 105, 111, 116, 123, 127, 136, 142, 156, 163, 174, 178, 183, 190, 206, 211, and 225.

144. The antibody or fragment thereof of claim 143, wherein: (a) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:45; (b) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VLPage 492 of 555 ACTIVE 705104971v1comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:58; (c) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:62; (d) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:67; (e) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:73; (f) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:86 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:87; (g) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:95 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:96; (h) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:104 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:105; (i) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:111; (j) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:116 ;Page 493 of 555 ACTIVE 705104971v1(k) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:123; (l) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:44 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:127; (m) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:136; (n) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:57 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:142; (o) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:147 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:142; (p) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:123; (q) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:151 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:73; (r) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:156; (s) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VLPage 494 of 555 ACTIVE 705104971v1comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:163; (t) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:173 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:174; (u) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:178; (v) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:183; (w) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:190; (x) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:196 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:45; (y) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:206; (z) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:135 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:211; or (aa) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 as set forth in the amino acid sequence of SEQ ID NO:224 and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 as set forth in the amino acid sequence of SEQ ID NO:225.Page 495 of 555 ACTIVE 705104971v1145. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5,Page 496 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

146. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising:Page 497 of 555 ACTIVE 705104971v1(1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:47, (ii) SEQ ID NO:50, (iii) SEQ ID NO:53, and (iv) SEQ ID NO:55; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:48, (ii) SEQ ID NO:51, and (iii) SEQ ID NO:56; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

147. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; andPage 498 of 555 ACTIVE 705104971v1(3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:59, (ii) SEQ ID NO:60, and (iii) SEQ ID NO:61; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

148. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34,Page 499 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:63, (ii) SEQ ID NO:64, (iii) SEQ ID NO:65, and (iv) SEQ ID NO:66; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:42.Page 500 of 555 ACTIVE 705104971v1149. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:68, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:69,Page 501 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:11, and (iii) SEQ ID NO:72; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

150. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:74, (ii) SEQ ID NO:444, (iii) SEQ ID NO:425, (iv) SEQ ID NO:78, and (v) SEQ ID NO:81; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:340, (ii) SEQ ID NO:341, (iii) SEQ ID NO:79, (iv) SEQ ID NO:82, and (v) SEQ ID NO:85; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising:Page 502 of 555 ACTIVE 705104971v1(1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:75, (ii) SEQ ID NO:77, (iii) SEQ ID NO:80, and (iv) SEQ ID NO:83; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:76, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:84; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

151. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:88, (ii) SEQ ID NO:90, (iii) SEQ ID NO:91, (iv) SEQ ID NO:92, andPage 503 of 555 ACTIVE 705104971v1(v) SEQ ID NO:94; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:89, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:93; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

152. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31,Page 504 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:97, (ii) SEQ ID NO:99, (iii) SEQ ID NO:101, (iv) SEQ ID NO:103, and (v) SEQ ID NO:445; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:98, (ii) SEQ ID NO:100, (iii) SEQ ID NO:102, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, andPage 505 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:

42.

153. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises : (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:106, (ii) SEQ ID NO:108, (iii) SEQ ID NO:109, and (iv) SEQ ID NO:21;Page 506 of 555 ACTIVE 705104971v1(2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:107, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:110; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

154. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, andPage 507 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:112, (ii) SEQ ID NO:113, (iii) SEQ ID NO:114, and (iv) SEQ ID NO:115; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

155. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28,Page 508 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:117, (ii) SEQ ID NO:119, (iii) SEQ ID NO:120, and (iv) SEQ ID NO:121; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:118, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:122; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

156. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising:Page 509 of 555 ACTIVE 705104971v1(1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:124, (ii) SEQ ID NO:125, (iii) SEQ ID NO:126, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; andPage 510 of 555 ACTIVE 705104971v1(3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

157. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of:Page 511 of 555 ACTIVE 705104971v1(i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:129, (ii) SEQ ID NO:131, and (iii) SEQ ID NO:134; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

158. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; andPage 512 of 555 ACTIVE 705104971v1(3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:46, (ii) SEQ ID NO:49, (iii) SEQ ID NO:52, and (iv) SEQ ID NO:54; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:137, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:140; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:138, (ii) SEQ ID NO:139, and (iii) SEQ ID NO:

141.

159. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, andPage 513 of 555 ACTIVE 705104971v1(v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:143, (ii) SEQ ID NO:144, (iii) SEQ ID NO:145, and (iv) SEQ ID NO:146; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:137, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:140; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:138, (ii) SEQ ID NO:139, and (iii) SEQ ID NO:141.Page 514 of 555 ACTIVE 705104971v1160. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:117, (ii) SEQ ID NO:119, (iii) SEQ ID NO:120, and (iv) SEQ ID NO:121; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:118,Page 515 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:11, and (iii) SEQ ID NO:122; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

161. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:148, (ii) SEQ ID NO:149, (iii) SEQ ID NO:34, (iv) SEQ ID NO:150, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising:Page 516 of 555 ACTIVE 705104971v1(1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:68, (ii) SEQ ID NO:70, (iii) SEQ ID NO:71, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:69, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:72; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

162. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, andPage 517 of 555 ACTIVE 705104971v1(v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:152, (ii) SEQ ID NO:10, (iii) SEQ ID NO:154, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:153, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

155.

163. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31,Page 518 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:157, (ii) SEQ ID NO:159, (iii) SEQ ID NO:161, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:158, (ii) SEQ ID NO:160, and (iii) SEQ ID NO:162; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, andPage 519 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:

42.

164. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:164, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:170, and (v) SEQ ID NO:172; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:165, (ii) SEQ ID NO:167 (iii) SEQ ID NO:169 and (iv) SEQ ID NO:21;Page 520 of 555 ACTIVE 705104971v1(2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:166, (ii) SEQ ID NO:168, and (iii) SEQ ID NO:171; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

165. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, andPage 521 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:175, (ii) SEQ ID NO:176, and (iii) SEQ ID NO:

177.

166. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises : (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32,Page 522 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:179, (ii) SEQ ID NO:180, (iii) SEQ ID NO:181, and (iv) SEQ ID NO:182; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

167. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises : (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of:Page 523 of 555 ACTIVE 705104971v1(i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:184, (ii) SEQ ID NO:186, and (iii) SEQ ID NO:188; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:185,Page 524 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:187, and (iii) SEQ ID NO:

189.

168. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises : (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:191, (ii) SEQ ID NO:192, (iii) SEQ ID NO:193, (iv) SEQ ID NO:194, and (v) SEQ ID NO:195; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21;Page 525 of 555 ACTIVE 705104971v1(2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

169. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises : (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, andPage 526 of 555 ACTIVE 705104971v1(iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:197, (ii) SEQ ID NO:200, (iii) SEQ ID NO:202 and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:198, (ii) SEQ ID NO:201, and (iii) SEQ ID NO:204; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:199, (ii) SEQ ID NO:203, and (iii) SEQ ID NO:

205.

170. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises : (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32,Page 527 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:128, (ii) SEQ ID NO:130, (iii) SEQ ID NO:132, and (iv) SEQ ID NO:133; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:207, (ii) SEQ ID NO:208, (iii) SEQ ID NO:209, and (iv) SEQ ID NO:210; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

171. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises : (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of:Page 528 of 555 ACTIVE 705104971v1(i) SEQ ID NO:212, (ii) SEQ ID NO:215, (iii) SEQ ID NO:217, (iv) SEQ ID NO:218, and (v) SEQ ID NO:220; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:213, (ii) SEQ ID NO:216, (iii) SEQ ID NO:219, (iv) SEQ ID NO:221, and (v) SEQ ID NO:223; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:41; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, (ii) SEQ ID NO:10, (iii) SEQ ID NO:16, and (iv) SEQ ID NO:21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:214, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:222; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30,Page 529 of 555 ACTIVE 705104971v1(ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

172. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:27, (ii) SEQ ID NO:31, (iii) SEQ ID NO:34, (iv) SEQ ID NO:35, and (v) SEQ ID NO:39; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:28, (ii) SEQ ID NO:32, (iii) SEQ ID NO:36, (iv) SEQ ID NO:40, and (v) SEQ ID NO:43; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:29, (ii) SEQ ID NO:33, (iii) SEQ ID NO:37, and (iv) SEQ ID NO:

41.

173. An antibody or fragment thereof that binds to CTLA4, wherein the antibody or fragment thereof comprises a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:4, 98, or 63, (ii) SEQ ID NO:10, 100, or 64,Page 530 of 555 ACTIVE 705104971v1(iii) SEQ ID NO:16, 102, or 65, and (iv) SEQ ID NO:21, 21, or 66; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:5, (ii) SEQ ID NO:11, and (iii) SEQ ID NO:22; (3) a VL CDR3 having an amino acid sequence selected from the group consisting of: (i) SEQ ID NO:30, (ii) SEQ ID NO:38, (iii) SEQ ID NO: 443, and (iv) SEQ ID NO:

42.

174. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

175. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises:Page 531 of 555 ACTIVE 705104971v1(a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:47; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:48; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

176. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises : (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:59; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:30.Page 532 of 555 ACTIVE 705104971v1177. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises : (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:63; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

178. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:69; andPage 533 of 555 ACTIVE 705104971v1(3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

179. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:425; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:340; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:75; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:76; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

180. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:88; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4;Page 534 of 555 ACTIVE 705104971v1(2) a VL CDR2 having the amino acid sequence of SEQ ID NO:89; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

181. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises : (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:97; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:98; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

182. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising:Page 535 of 555 ACTIVE 705104971v1(1) a VL CDR1 having the amino acid sequence of SEQ ID NO:106; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:107; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

183. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:112; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

184. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29;Page 536 of 555 ACTIVE 705104971v1and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:117; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:118; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

185. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:124; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

186. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; andPage 537 of 555 ACTIVE 705104971v1(3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:129; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

187. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises : (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:46; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:137; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

138.

188. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27;Page 538 of 555 ACTIVE 705104971v1(2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:143; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:137; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

138.

189. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:117; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:118; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

190. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising:Page 539 of 555 ACTIVE 705104971v1(1) a VH CDR1 having the amino acid sequence of SEQ ID NO:148; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:69; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

191. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:152; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:153.Page 540 of 555 ACTIVE 705104971v1192. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:157; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:158; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

193. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:164; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:165; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:166; andPage 541 of 555 ACTIVE 705104971v1(3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

194. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

175.

195. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:179;Page 542 of 555 ACTIVE 705104971v1(2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

196. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:184; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

185.

197. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:191; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising:Page 543 of 555 ACTIVE 705104971v1(1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

198. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:197; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:198; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

199.

199. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:128;Page 544 of 555 ACTIVE 705104971v1and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:207; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

200. The antibody or fragment thereof of claim 143 or 144, wherein the antibody or fragment thereof comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:212; (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:213; and (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:214; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:

30.

201. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:

45.

202. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:58.Page 545 of 555 ACTIVE 705104971v1203. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:

62.

204. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:

67.

205. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:

73.

206. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:86 and a VL sequence that is SEQ ID NO:

87.

207. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:95 and a VL sequence that is SEQ ID NO:

96.

208. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:104 and a VL sequence that is SEQ ID NO:

105.

209. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:

111.

210. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:

116.

211. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:

123.

212. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:44 and a VL sequence that is SEQ ID NO:

127.

213. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:

136.

214. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:57 and a VL sequence that is SEQ ID NO:142.Page 546 of 555 ACTIVE 705104971v1215. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:147 and a VL sequence that is SEQ ID NO:

142.

216. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:

123.

217. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:151 and a VL sequence that is SEQ ID NO:

73.

218. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:

156.

219. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:

163.

220. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:173 and a VL sequence that is SEQ ID NO:

174.

221. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:

178.

222. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:

183.

223. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:

190.

224. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:196 and a VL sequence that is SEQ ID NO:

45.

225. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:

206.

226. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:135 and a VL sequence that is SEQ ID NO:211.Page 547 of 555 ACTIVE 705104971v1227. An antibody or fragment thereof that binds to CTLA4 comprising a VH sequence that is SEQ ID NO:224 and a VL sequence that is SEQ ID NO:

225.

228. An antibody or fragment thereof that binds to CTLA4 comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1X2SYX3YYADSVKG (SEQ ID NO:450), wherein X1 is D or G, and wherein X2 is G or Y, and wherein X3is T or Y; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL comprises: (d) a VL CDR1 consensus sequence of X1AX2X3X4VSX5X6VA (SEQ ID NO:388), wherein X1 is R or H, and wherein X2 is S or P, wherein X3 is Q, D, or F, wherein X4is S or L, wherein X5is S or K, and wherein X6is A or L; (e) a VL CDR2 consensus sequence of SAX1SX2X3S (SEQ ID NO:389), wherein X1is S, A, or D, wherein X2is L, T, or F, and wherein X3is Y or P; and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

229. An antibody or fragment thereof that binds to CTLA4 comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27);Page 548 of 555 ACTIVE 705104971v1(b) a VH CDR2 consensus sequence of FITSDGSYTYYADSVKG (SEQ ID NO:28); and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL comprises: (d) a VL CDR1 consensus sequence of X1AX2X3X4X5X6X7X8VA (SEQ ID NO: 397), wherein X1is R or H, and wherein X2is S or N, wherein X3 is Q, F, S, or V wherein X4 is S, L, or Q, wherein X5 is V or L, wherein X6 is S or I, wherein X7 is S, K, or R, and wherein X8 is A or L; (e) a VL CDR2 consensus sequence of SAX1SX2YS (SEQ ID NO:390), wherein X1 is S, A, or D, and wherein X2 is L, M, F, or S; and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

230. An antibody or fragment thereof that binds to CTLA4 comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1X2SYX3YYADSVKG (SEQ ID NO:386), wherein X1 is D or G, wherein X2 is G or Y, and wherein X3 is T or H; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL comprises:Page 549 of 555 ACTIVE 705104971v1(d) a VL CDR1 consensus sequence of RAX1X2SVSX3AVA (SEQ ID NO:391), wherein X1 is S, P, or N, wherein X2 is Q, D, F, or V and wherein X3is S or K; (e) a VL CDR2 consensus sequence of SAX1SX2X3S (SEQ ID NO:396), wherein X1 is S or D, wherein X2 is L, T, or S, and wherein X3 is Y or P; and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

231. An antibody or fragment thereof that binds to CTLA4 comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1GSYX2YYADSVKG (SEQ ID NO:393), wherein X1 is D or G, and wherein X2 is T or H; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29)and wherein the VL comprises: (d) a VL CDR1 consensus sequence of RAX1X2SVSX3AVA (SEQ ID NO:398), wherein X1is S or P, wherein X2is Q, D, or F, and wherein X3 is S or K; (e) a VL CDR2 consensus sequence of SASSLYS (SEQ ID NO:5); and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

232. An antibody or fragment thereof that binds to CTLA4 comprising a heavy chain variable region (VH) and a light chain variable region (VL),Page 550 of 555 ACTIVE 705104971v1wherein the VH comprises: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSX1GSYX2YYADSVKG (SEQ ID NO:393), wherein X1 is D or G, and wherein X2 is T or H; and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL comprises: (d) a VL CDR1 consensus sequence of RAX1X2SVSSAVA (SEQ ID NO:395), wherein X1is S or P, and wherein X2is Q or D; (e) a VL CDR2 consensus sequence of SASSLYS (SEQ ID NO:5); and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

233. An antibody or fragment thereof that binds to CTLA4 comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: (a) a VH CDR1 consensus sequence of GFTFSSYYIH (SEQ ID NO:27); (b) a VH CDR2 consensus sequence of FITSDGSYTYYADSVKG (SEQ ID NO:28); and (c) a VH CDR3 consensus sequence of GAYVYPTVLDY (SEQ ID NO:29), and wherein the VL comprises: (d) a VL CDR1 consensus sequence of RASX1SVSX2AVA (SEQ ID NO:394), wherein X1is Q or F, and wherein X2is S or K;Page 551 of 555 ACTIVE 705104971v1(e) a VL CDR2 consensus sequence of SASSLYS (SEQ ID NO:5); and (f) a VL CDR3 consensus sequence of QQLSRTPLT (SEQ ID NO:30).

234. The multispecific antibody or fragment thereof of any one of claims 1- 142, or the antibody or fragment thereof of claims 143-233, wherein the VH or the VL further comprises human framework sequences.

235. The multispecific antibody or fragment thereof, or antibody or fragment thereof of claim 234, wherein the VH and the VL further comprises human framework sequences.

236. The multispecific antibody or fragment thereof of any one of claims 1- 142, or the antibody or fragment thereof of any one of claims 143-233, wherein the VH or the VL further comprises a framework 1 (FR1), a framework 2 (FR2), a framework 3 (FR3) and / or a framework 4 (FR4) sequence.

237. The multispecific antibody or fragment thereof, or the antibody or fragment thereof of claim 236, wherein the VH and VL further comprises a framework 1 (FR1), a framework 2 (FR2), a framework 3 (FR3) and / or a framework 4 (FR4) sequence.

238. The multispecific antibody or fragment of any one of claims 1-142, or the antibody or fragment thereof of any one of claims 143-233, wherein the antibody is a recombinant antibody.

239. The multispecific antibody or fragment, or antibody or fragment thereof of claim 238, wherein the recombinant antibody is a humanized, human or chimeric antibody.

240. The multispecific antibody or fragment thereof of any one of claims 1- 142, or the antibody or fragment thereof of any one of claims 143-233 which is a Fab, Fab’, F(ab’)2, Fv, scFv, (scFv)2, single chain antibody molecule, dual variable regionPage 552 of 555 ACTIVE 705104971v1antibody, diabody, single variable region antibody, linear antibody, V region, or a multispecific antibody formed from antibody fragments.

241. The multispecific antibody or fragment thereof of any one of claims 1- 142, or the antibody or fragment thereof of any one of claims 143-233 which is conjugated or recombinantly fused to a diagnostic agent, detectable agent, or therapeutic agent.

242. The multispecific antibody or fragment thereof or the antibody or fragment thereof of claim 241, wherein the therapeutic agent is a chemotherapeutic agent, cytotoxin, or drug.

243. One or more vectors comprising one or more polynucleotides encoding the multispecific antibody or fragment thereof of any one of claims 1-142 or the antibody or fragment thereof of any one of claims 143-233.

244. A pharmaceutical composition that comprises the multispecific antibody or fragment thereof of any one of claims 1-142 or the antibody of any one of claims 143-233, and a pharmaceutically acceptable carrier.

245. A method for treating a cancer in a subject comprising administering to the subject the multispecific antibody or fragment thereof of any one of claims 1-142 or the antibody or fragment thereof of any one of claims 143-233, or the pharmaceutical composition of claim 244.

246. A method for alleviating one or more symptoms associated with a cancer in a subject comprising administering to the subject the multispecific antibody or fragment thereof of any one of claims 1-142, or the antibody of any one of claims 143- 233, or the pharmaceutical composition of claim 244.

247. The method of claim 246, wherein the cancer is a solid tumor.

248. The method of claim 246 or 247, wherein the subject is diagnosed with a cancer or a tumor.Page 553 of 555 ACTIVE 705104971v1249. A method for decreasing tumor size in a subject with a tumor comprising administering to the subject the multispecific antibody or fragment thereof of any one of claims 1-142, the antibody or fragment thereof of any one of claims 143-233, or the pharmaceutical composition of claim 244.

250. A method for treating a tumor regulatory T cell (Treg) mediated disease, disorder or condition in a subject comprising administering to the subject the multispecific antibody or fragment thereof of any one of claims 1-142, the antibody or fragment thereof of any one of claims 143-233, or the pharmaceutical composition of claim 244.

251. A method for depleting tumor regulatory T cells (Tregs) in a subject comprising administering to the subject the multispecific antibody or fragment thereof of any one of claims 1-142, the antibody or fragment thereof of any one of claims 143- 233, or the pharmaceutical composition of claim 244.Page 554 of 555 ACTIVE 705104971v1

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