Anti-trop2 antibody-drug conjugates and methods of use

Abstract

Antibodies, antigen-binding fragments, and conjugates (e.g., antibody-drug conjugates) thereof that bind TROP2 are disclosed, as well as improved linkers for antibody-drug conjugates. The disclosure further relates to methods and compositions for use in the treatment of, e.g., cancer by administering the compositions provided herein.

Description

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 569,028, filed on March 22, 2024, the contents of which are incorporated by reference in their entirety.

[0002] The present disclosure relates to anti-TROP2 antibodies and antigen-binding fragments thereof, as well as conjugates such as antibody-drug conjugates (ADCs), e.g., those comprising eribulin, and their use in the treatment and diagnosis of cancers that express TROP2 and / or are amenable to treatment by disrupting tubulin or by administering a composition disclosed herein.

[0003] Cancer is among the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and 8.2 million cancer-related deaths in 2012. The most common causes of cancer death are cancers of: lung (1.59 million deaths); liver (745,000 deaths); stomach (723,000 deaths); colorectal (694,000 deaths); breast (521,000 deaths); and esophagus (400,000 deaths). The number of new cancer cases is expected to rise by about 70% over the next two decades, to approximately 22 million new cancer cases per year. World Cancer Report 2014. The incidence rate and mortality of rare cancers, such as bile duct cancer (also known as cholangiocarcinoma) have also been increasing worldwide in the past few decades. Banales et al. (2020) Nat Rev Gastroenterol Hepatol. 17:557-88. Unlike with more common types of cancers, the relative lack of awareness, knowledge, and effective treatment options for rare cancers, e.g., cholangiocarcinoma, has meant that patient prognosis has not improved substantially in the past decade. For example, recent reports suggest that the 5-year survival rate for cholangiocarcinoma is only 7-20%. Thus, there is an unmet need for more effective therapies for patients who suffer from rare cancer types, such as cholangiocarcinoma.

[0004] TROP2 (also known as tumor-associated calcium signal transducer 2) is a transmembrane glycoprotein encoded by the TACSTD2 gene in humans. Researchers have demonstrated that TROP2 is overexpressed in a variety of epithelial carcinomas, including, but not limited to, cholangiocarcinoma, thus making it an attractive target for antibody-based cancer therapy. Furthermore, TROP2 expression has been shown to be associated with increased tumor aggressiveness, metastasis, and decreased patient survival. Cubas et al. (2010) Mol. Cancer. 9:253.

[0005] Recent studies have implicated TROP2 in multiple intracellular signaling pathways that regulate proliferation, survival, self-renewal, and invasion in cells. Shvartsur & Bonavida (2015) Genes & Cancer. 6(3-4):84-105. For example, through its role as a calcium signal transducer, it has been shown to result in the activation of the pro-oncogenic MAPK signaling pathway. Additionally, TROP2 may also play a role in deregulating stem cell functions through the Notch, Hedgehog, and Wnt / |3-catenin pathways. Goldenburg et al. (2018) Oncotarget. 9(48):28989-29006.

[0006] In addition to its role in pro-growth signaling pathways, TROP2 expression has been implicated in the epithelial-to-mesenchymal transition (EMT) process. EMT is a mechanism by which cells achieve phenotypic plasticity, and the process is closely associated with cancer metastasis and recurrence. He et al. (2017). Mol Cancer. 16:63. EMT is thought to be a key process by which cancer cells gain motility and the ability to migrate and invade other sites in the body. Studies have demonstrated that TROP2 is associated with the epithelial phenotype in certain types of cancers, including lung cancer, breast cancer, prostate cancer, and squamous cell carcinoma. Moreover, within these cancer types, TROP2-expressing epithelial cells lose TROP2 expression upon transitioning to a mesenchymal (i.e., invasive) state. Remsik et al. (2018) Oncotarget. 39(11): 1411-18. It is believed that TROP2 may promote EMT by binding and promoting nuclear accumulation of P-catenin, thereby activating downstream pro-metastatic pathways. Zhao et al. (2019) Cancer Med. 8(3):1135-1147. TROP2 has also been shown to promote EMT in certain cancers through additional pro-oncogenic signaling axes, such as PI3K-AKT. Li et al. (2017) Oncotarget. 8(29):47052-47063. Indeed, inhibition and / or ablation of TROP2 expression has been shown to prevent the development of metastatic properties in cell lines across a broad spectrum of cancers, including gastric cancer, gall bladder cancer, breast cancer, prostate cancer, hepatocellular carcinoma, pancreatic cancer, and cholangiocarcinoma. Without wishing to be bound by theory, it is believed that inhibition of TROP2, e.g., binding by an anti-TROP2 antibody, antigen-binding fragment, and / or ADC, may reduce or prevent EMT in cancer cells. The role of TROP2 expression in EMT (and its converse pathway, mesenchymal-to-epithelial transition, or MET) is an active field of study and more research will be needed to completely elucidate the role of TROP2 in EMT and / or MET.

[0007] Given the prevalence of TROP2 expression in various cancer types, its role in promoting metastasis, and its association with poor clinical outcome, TROP2 is an attractive target for tumor antigen-specific drug delivery approaches, e.g., an antibody-mediated approach. Antibodies conjugated with cytotoxic compounds such as chemotherapeutics have also been explored to enhance the cell-killing activity of antibody-based drug delivery to tumor cells. Nevertheless, the need remains to provide suitable antibodies and / or ADCs that offer a combination of efficient tumor targeting, on-target effects, and / or reduced off-target effects.

[0008] Eribulin is a synthetic compound of the macrocyclic compound halichondrin B, which has been previously shown to exert potent anti-cancer properties through its disruption of tubulin and microtubule dynamics. Towle et al. (2001) Cancer Res. 61(3):1013-21. Tubulin makes up dynamic filamentous cytoskeletal proteins that are involved in a variety of cellular functions, including intracellular migration and transport, cell signaling, the maintenance of cell shape, and cell division. Due to their rapid cell division, cancer cells are generally more sensitive to compounds that bind to tubulin and disrupt its normal function, as compared to normal cells. For this reason, tubulin inhibitors and other microtubule-targeted agents have become a promising class of drugs for the treatment of cancer. Dumontet and Jordan (2010) Nat. Rev. DrugDiscov. 9:790-803. Halinchondrin B and eribulin in particular have demonstrated notable anti-cancer activities in vitro and in vivo. Tan et al. (2009) Clin Cancer Res. 15(12): 4213-4219; Vahdat et al. (2009) J. Clin. Oncol. 27(18): 2954-2961. The mesylate salt of eribulin (eribulin mesylate) is currently marketed under the trade name Halaven™ for the treatment of patients with refractory metastatic breast cancer.

[0009] While uses of eribulin have been reported in the art, including in the context of ADCs, there remains an unmet need to deliver eribulin in a targeted fashion to particular tissues, e.g., cancer tissues that express TROP2. Likewise, there remains a need in the art for improved antibodies that bind TROP2 with superior properties, e.g., with respect to antigen-binding and / or the ability to effectively deliver payloads such as eribulin to a target cell or tissue expressing TROP2. SUMMARY OF THE INVENTION

[0010] In various embodiments, the present disclosure provides, in part, novel antibodies and antigenbinding fragments that are capable of specifically binding TROP2 and may be used alone or linked to one or more additional agents (e.g., as ADCs) and administered as part of pharmaceutical compositions. In some embodiments, the antibodies, antigen-binding fragments, and / or ADCs of the present disclosure may be used to slow, inhibit, and / or reverse tumor growth in mammals, and may be useful for treating human cancer patients.

[0011] The present disclosure more specifically relates, in various embodiments, to antibodies and antibody-drug conjugate compounds that are capable of binding and / or killing TROP2-expressing cells. In various embodiments, the compounds are also capable of internalizing into a target TROP2-expressing cell after binding. ADC compounds comprising a linker that attaches eribulin drug moiety to an antibody moiety are disclosed. An antibody moiety may be a full-length antibody or an antigenbinding fragment.

[0012] In various embodiments, the present disclosure provides an internalizing anti-TROP2 antibody or internalizing antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment binds specifically to human TROP2, and wherein the antibody or antigen-binding fragment comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the HCDR1 comprises an amino acid sequence of SEQ ID NO: 18, the HCDR2 comprises an amino acid sequence selected from SEQ ID NO: 19 or 20, the HCDR3 comprises an amino acid sequence of SEQ ID NO: 21, the LCDR1 comprises an amino acid sequence selected from SEQ ID NO: 22 or 23, the LCDR2 comprises an amino acid sequence selected from SEQ ID NO: 24 or 25, and the LCDR3 comprises an amino acid sequence of SEQ ID NO: 26, as defined by the Rabat numbering system; or the HCDR1 comprises an amino acid sequence of SEQ ID NO: 27, the HCDR2 comprises an amino acid sequence of SEQ ID NO: 28, the HCDR3 comprises an amino acid sequence of SEQ ID NO: 29, the LCDR1 comprises an amino acid sequence of SEQ ID NO: 30, the LCDR2 comprises an amino acid sequence selected from SEQ ID NO: 31 or 32, and the LCDR3 comprises an amino acid sequence of SEQ ID NO: 33, as defined by the IMGT numbering system; or the HCDR1 comprises an amino acid sequence of SEQ ID NO: 1, the HCDR2 comprises an amino acid sequence selected from SEQ ID NO: 2 or 3, the HCDR3 comprises an amino acid sequence of SEQ ID NO: 4, the LCDR1 comprises an amino acid sequence selected from SEQ ID NO: 5, 6, 7, or 8, the LCDR2 comprises an amino acid sequence of SEQ ID NO: 9, and the LCDR3 comprises an amino acid sequence of SEQ ID NO: 10, as defined by the Kabat numbering system; or the HCDR1 comprises an amino acid sequence of SEQ ID NO: 11, the HCDR2 comprises an amino acid sequence of SEQ ID NO: 12, the HCDR3 comprises an amino acid sequence of SEQ ID NO: 13, the LCDR1 comprises an amino acid sequence selected from SEQ ID NO: 14 or 15, the LCDR2 comprises an amino acid sequence of SEQ ID NO: 16, and the LCDR3 comprises an amino acid sequence of SEQ ID NO: 17, as defined by the IMGT numbering system.

[0013] In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises three HCDRs comprising amino acid sequences of SEQ ID NO: 18 (HCDR1), SEQ ID NO: 20 (HCDR2), and SEQ ID NO: 21 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 22 (LCDR1), SEQ ID NO: 24 (LCDR2), and SEQ ID NO: 26 (LCDR3), as defined by the Kabat numbering system. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises three HCDRs comprising amino acid sequences of SEQ ID NO: 18 (HCDR1), SEQ ID NO: 20 (HCDR2), and SEQ ID NO: 21 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 23 (LCDR1), SEQ ID NO: 24 (LCDR2), and SEQ ID NO: 26 (LCDR3), as defined by the Kabat numbering system. In some embodiments, the anti-TROP2 antibody or antigenbinding fragment comprises three HCDRs comprising amino acid sequences of SEQ ID NO: 27 (HCDR1), SEQ ID NO: 28 (HCDR2), and SEQ ID NO: 29 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 30 (LCDR1), SEQ ID NO: 31 (LCDR2), and SEQ ID NO: 33 (LCDR3), as defined by the IMGT numbering system.

[0014] In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 5 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 14 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system. In some embodiments, the anti-TROP2 antibody or antigenbinding fragment comprises three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system.

[0015] In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence selected from SEQ ID NO: 67, 68, 69, 70, or 177, and a light chain variable region comprising an amino acid sequence selected from SEQ ID NO: 71, 72, 167, 73, 74,75, 76, 187,77, or 78. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence selected from SEQ ID NO: 53, 54, 55, 56,174, or 175, and a light chain variable region comprising an amino acid sequence selected from SEQ ID NO: 57, 58, 166, 59, 60, 61, 62, 63,176, 64, 65, or 66.

[0016] In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 69, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 72. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 69, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 76. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 69, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 73. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 69, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 77. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 70, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 72. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 70, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 76. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 70, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 73. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 70, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 77.

[0017] In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 58. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 63. In some embodiments, the anti-TR0P2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 61. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 56, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 58. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 56, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 63. In some embodiments, the anti-TR0P2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 56, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 61. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 56, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 58. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 63. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 61. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66.

[0018] In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 61. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66.

[0019] In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a human IgGl, IgG2, IgG3, or IgG4 heavy chain constant region.

[0020] In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises an IgGl Fc domain or an IgGl Fc domain mutated to reduce binding to a Fey receptor (FcyR) as compared to an IgGl Fc-containing antibody with a wild-type IgGl Fc domain. In some embodiments, the mutated IgGl Fc domain comprises the mutations L234A, L235A, P238S, H268Q, andK274Q.

[0021] In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a human Ig kappa light chain constant region.

[0022] In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence selected from SEQ ID NO: 118, 119,122, 123, 126, 127, or 381 and a light chain comprising an amino acid sequence selected from SEQ ID NO: 129, 130, 133, or 134. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence selected from SEQ ID NO: 96,97,100, 101, 104, 105, 179, 181,183, or 380 and a light chain comprising an amino acid sequence selected from SEQ ID NO: 107, 110,112, or 115.

[0023] In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 181 and a light chain comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 380 and a light chain comprising an amino acid sequence of SEQ ID NO: 115.

[0024] In some embodiments, the anti-TROP2 antibody or antigen-binding fragment comprises part of a bispecific or multi-specific binding construct. In some embodiments, the anti-TROP2 antibody or antigen-binding fragment is linked to a therapeutic agent or detectable agent.

[0025] In various embodiments, the present disclosure provides an antibody-drug conjugate of Formula (I): Ab-(L-D)p (I) wherein Ab is an anti-TROP2 antibody or antigen-binding fragment thereof disclosed herein; D is a cytotoxic agent; L is a cleavable linker that covalently attaches Ab to D; and p is an integer from 1 to 8.

[0026] In some embodiments, the cytotoxic agent comprises eribulin or a salt thereof.

[0027] In some embodiments,p is from 2 to 8. In some embodiments, p is 2.

[0028] In some embodiments, the cleavable linker comprises a cleavable moiety that is positioned such that no part of the linker or the antibody or antigen-binding fragment remains bound to the cytotoxic agent upon cleavage.

[0029] In some embodiments, the cleavable linker comprises a cleavable peptide moiety. In some embodiments, the cleavable peptide moiety is cleavable by an enzyme. In some embodiments, the cleavable peptide moiety is cleavable by cathepsin. In some embodiments, the cleavable peptide moiety is cleavable by cathepsin B. In some embodiments, the cleavable peptide moiety is cleavable by legumain.

[0030] In some embodiments, the cleavable peptide moiety comprises an amino acid unit. In some embodiments, the amino acid unit comprises valine-citrulline (Val-Cit). In some embodiments, the amino acid unit comprises valine-dimethylated lysine (Val-Lys(Me)2). In some embodiments, the amino acid unit comprises alanine-dimethylated lysine (Ala-Lys(Me)2). In some embodiments, the amino acid unit comprises valine-alanine (Vai-Ala). In some embodiments, the amino acid unit comprises asparagine (Asn). In some embodiments, the amino acid unit comprises aspartic acid (Asp). In some embodiments, the amino acid unit comprises methylated aspartic acid (Asp(OMe)).

[0031] In some embodiments, the cleavable linker attaches to the antibody or antigen-binding fragment via a maleimide (Mal or MAL) moiety. In some embodiments, the Mal moiety comprises a maleimidocaproyl (MC) moiety. In some embodiments, the Mal moiety comprises a dithiomaleimide (DTM) moiety. In some embodiments, the Mal moiety is reactive with a cysteine residue on the antibody or antigen-binding fragment. In some embodiments, the Mal moiety is joined to the antibody or antigen-binding fragment via a cysteine residue on the antibody or antigen-binding fragment.

[0032] In some embodiments, the cleavable linker comprises the Mal moiety and a cleavable peptide moiety. In some embodiments, the Mal moiety attaches the antibody or antigen-binding fragment to the cleavable peptide moiety in the linker. In some embodiments, the cleavable linker comprises Mal-Val-Cit. In some embodiments, the cleavable linker comprises Mal-Val-Lys(Me)2. In some embodiments, the amino acid unit comprises Mal-Ala-Lys(Me)2. In some embodiments, the cleavable linker comprises Mal-Val-Ala. In some embodiments, the cleavable linker comprises Mal-Asn. In some embodiments, the cleavable linker comprises Mal-Asp. In some embodiments, the cleavable linker comprises Mal-Asp(OMe).

[0033] In some embodiments, the cleavable linker comprises at least one spacer unit. In some embodiments, the spacer unit comprises a polyethylene glycol (PEG) moiety. In some embodiments, the PEG moiety comprises -(PEG)m- and m is an integer from 1 to 10. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4.

[0034] In some embodiments, the spacer unit comprises an alkyl moiety. In some embodiments, the alkyl moiety comprises -(CH2)h- and n is an integer from 1 to 10. In some embodiments, n is 5.

[0035] In some embodiments, the spacer unit comprises “C2” O .

[0036] In some embodiments, the spacer unit comprises C2 conjugated to a PEG moiety, wherein the PEG moiety comprises -(PEG)m- and m is an integer from 1 to 4. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3.

[0037] In some embodiments, the spacer unit comprises “C2(PEG)i” as shown in the following chemical structure:      O                          O .

[0038] In some embodiments, the spacer unit attaches to the antibody or antigen-binding fragment via the maleimide (Mal) moiety ("Mal-spacer unit"). In some embodiments, the cleavable linker comprises the Mal-spacer unit and the cleavable peptide moiety. In some embodiments, the Mal-spacer unit attaches the antibody or antigen-binding fragment to the cleavable peptide moiety in the linker.

[0039] In some embodiments, the Mal-spacer unit comprises a PEG moiety. In some embodiments, the Mal-spacer unit comprises Mal-(PEG)2-Val-Cit. In some embodiments, the Mal-spacer unit comprises Mal-(PEG)3-Val-Cit. In some embodiments, the Mal-spacer unit comprises Mal-(PEG)4-Val-Cit. In some embodiments, the Mal-spacer unit comprises Mal-(PEG)2-Val-Lys(Me)2. In some embodiments, the Mal-spacer unit comprises Mal-(PEG)2-Ala-Lys(Me)2. In some embodiments, the Mal-spacer unit comprises Mal-(PEG)2-Val-Ala. In some embodiments, the Mal-spacer unit comprises Mal-(PEG)2-Asn. In some embodiments, the Mal-spacer unit comprises Mal-(PEG)2-Asp. In some embodiments, the Mal-spacer unit comprises Mal-(PEG)2-Asp(OMe).

[0040] In some embodiments, the Mal-spacer unit comprises a C2 moiety.

[0041] In some embodiments, the Mal-spacer unit comprises C2 conjugated to a PEG moiety, wherein the PEG moiety comprises -(PEG)m- and m is an integer from 0 to 4. In some embodiments, m is 2.

[0042] In some embodiments, the Mal-spacer unit comprises a C2(PEG)m moiety. In some embodiments, the Mal-spacer unit comprises Mal-C2(PEG)m-Val-Cit. In some embodiments, the Mal-spacer unit comprises Mal-C2(PEG)m-Val-Lys(Me)2. In some embodiments, the Mal-spacer unit comprises Mal-C2(PEG)m-Ala-Lys(Me)2. In some embodiments, the Mal-spacer unit comprises Mal-C2(PEG)m-Val-Ala. In some embodiments, the Mal-spacer unit comprises Mal-C2(PEG)m-Asn. In some embodiments, the Mal-spacer unit comprises Mal-C2(PEG)m-Asp. In some embodiments, the Mal-spacer unit comprises Mal-C2(PEG)m-Asp(OMe). In some embodiments, m is an integer from 0 to 4. In some embodiments, m is 2.

[0043] In some embodiments, the cleavable moiety in the linker is directly joined to the cytotoxic agent.

[0044] In some embodiments, a spacer unit attaches the cleavable moiety in the linker to the cytotoxic agent. In some embodiments, cleavage of the conjugate releases the cytotoxic agent from the antibody and linker. In some embodiments, the spacer unit attaching the cleavable moiety in the linker to the cytotoxic agent is self-immolative. In some embodiments, the spacer unit attaching the cleavable moiety in the linker to the cytotoxic agent comprises a p-aminobenzyl (pAB). In some embodiments, the spacer unit attaching the cleavable moiety in the linker to the cytotoxic agent comprises a p-aminobenzyloxycarbonyl (pABC). In some embodiments, the pAB attaches the cleavable moiety in the linker to the cytotoxic agent. In some embodiments, the cytotoxic agent is eribulin. In some embodiments, the pAB covalently attaches to eribulin via a C-35 amine. In some embodiments, the cleavable moiety comprises Val-Cit, Vai-Ala, Val-Lys(Me)2, Ala-Lys(Me)2, Asn, Asp, or Asp(OMe).

[0045] In some embodiments, the cleavable linker comprises Val-Cit-pABC. In some embodiments, the cleavable linker comprises Val-Ala-pABC. In some embodiments, the cleavable linker comprises Val-Lys(Me)2-pABC.

[0046] In some embodiments, the cleavable linker comprises DTM-Asn.

[0047] In some embodiments, the cleavable linker comprises Mal-(PEG)2-Val-Cit-pABC. In some embodiments, the cleavable linker comprises Mal-(PEG)3-Val-Cit-pABC. In some embodiments, the cleavable linker comprises Mal-(PEG)4-Val-Cit-pABC. In some embodiments, the cleavable linker comprises Mal-(PEG)2-Val-Lys(Me)2-pABC. In some embodiments, the cleavable linker comprises Mal-(PEG)2-Val-Ala-pABC. In some embodiments, the cleavable linker comprises Mal-C2(PEG)2-Val-Cit-pABC. In some embodiments, the cleavable linker comprises Mal-C2(PEG)2-Val-Lys(Me)2-pABC. In some embodiments, the cleavable linker comprises Mal-C2(PEG)2-Val-Ala-pABC. In some embodiments, the cleavable linker comprises Mal-C2(PEG)2-Ala-Lys(Me)2-pABC.

[0048] In some embodiments, the antibody or antigen-binding fragment comprises three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 5 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system. In some embodiments, the antibody or antigen-binding fragment comprises three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system. In some embodiments, the antibody or antigen-binding fragment comprises three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 14 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system. In some embodiments, the antibody or antigen-binding fragment comprises three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system.

[0049] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 61. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 61. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66.

[0050] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 96 and a light chain comprising an amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 179 and a light chain comprising an amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 96 and a light chain comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 179 and a light chain comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 104 and a light chain comprising an amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 183 and a light chain comprising an amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 104 and a light chain comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 183 and a light chain comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 100 and a light chain comprising an amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 181 and a light chain comprising an amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 100 and a light chain comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 181 and a light chain comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 380 and a light chain comprising an amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 380 and a light chain comprising an amino acid sequence of SEQ ID NO: 115.

[0051] In some embodiments, the present disclosure provides an antibody-drug conjugate of Formula (I): Ab-(L-D)p (I) wherein Ab is an internalizing anti-TROP2 antibody or internalizing antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system; D is eribulin; L is a cleavable linker comprising Mal-(PEG)2-Val-Cit-pABC; and p is an integer from 1 to 8.

[0052] In some embodiments, the present disclosure provides an antibody-drug conjugate of Formula (I): Ab-(L-D)^     (I) wherein Ab is an internalizing anti-TROP2 antibody or internalizing antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system; D is eribulin; L is a cleavable linker comprising Mal-(PEG)2-Val-Cit-pABC; and p is an integer from 1 to 8.

[0053] In some embodiments, the present disclosure provides an antibody-drug conjugate of Formula (I): Ab-(L-D)p (I) wherein Ab is an internalizing anti-TROP2 antibody or internalizing antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system; D is eribulin; L is a cleavable linker comprising Mal-(PEG)2-Val-Ala-pABC; and p is an integer from 1 to 8.

[0054] In some embodiments, the present disclosure provides an antibody-drug conjugate of Formula (I): Ab-(L-D),     (I) wherein Ab is an internalizing anti-TR0P2 antibody or internalizing antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system; D is eribulin; L is a cleavable linker comprising Mal-(PEG)2-Val-Ala-pABC; and p is an integer from 1 to 8.

[0055] In some embodiments, the present disclosure provides an antibody-drug conjugate of Formula (I): Ab-(L-D),     (I) wherein Ab is an internalizing anti-TROP2 antibody or internalizing antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system; D is eribulin; L is a cleavable linker comprising Mal-(PEG)2-Asn; and p is an integer from 1 to 8.

[0056] In some embodiments, the present disclosure provides an antibody-drug conjugate of Formula (I): Ab-(L-D)p (I) wherein Ab is an internalizing anti-TROP2 antibody or internalizing antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system; D is eribulin; L is a cleavable linker comprising Mal-(PEG)2-Asn; and p is an integer from 1 to 8.

[0057] In some embodiments, the present disclosure provides an antibody-drug conjugate of Formula (I): Ab-(L-D)p (I) wherein Ab is an internalizing anti-TROP2 antibody or internalizing antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system; D is eribulin; L is a cleavable linker comprising Mal-C2(PEG)m-Val-Cit-pABC, wherein m is an integer from 0 to 4; and p is an integer from 1 to 8.

[0058] In some embodiments, m is 2.

[0059] In some embodiments, the present disclosure provides an antibody-drug conjugate of Formula (I): Ab-(L-D),     (I) wherein Ab is an internalizing anti-TROP2 antibody or internalizing antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system; D is eribulin; L is a cleavable linker comprising Mal-C2(PEG)m-Val-Cit-pABC, wherein m is an integer from 0 to 4; and p is an integer from 1 to 8.

[0060] In some embodiments, m is 2.

[0061] In some embodiments, the present disclosure provides an antibody-drug conjugate of Formula (I): Ab-(L-D)p (I) wherein Ab is an internalizing anti-TROP2 antibody or internalizing antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system; D is eribulin; L is a cleavable linker comprising Mal-C2(PEG)m-Val-Ala-pABC, wherein m is an integer from 0 to 4; and p is an integer from 1 to 8.

[0062] In some embodiments, m is 2.

[0063] In some embodiments, the present disclosure provides an antibody-drug conjugate of Formula (I): Ab-(L-D),     (I) wherein Ab is an internalizing anti-TR0P2 antibody or internalizing antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system; D is eribulin; L is a cleavable linker comprising Mal-C2(PEG)m-Val-Ala-pABC, wherein m is an integer from 0 to 4; and p is an integer from 1 to 8.

[0064] In some embodiments, m is 2.

[0065] In some embodiments, the present disclosure provides an antibody-drug conjugate of Formula (I): Ab-(L-D)p (I) wherein Ab is an internalizing anti-TROP2 antibody or internalizing antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system; D is eribulin; L is a cleavable linker comprising Mal-C2(PEG)m-Asn, wherein m is an integer from 0 to 4; and p is an integer from 1 to 8.

[0066] In some embodiments, m is 2.

[0067] In some embodiments, the present disclosure provides an antibody-drug conjugate of Formula (I): Ab-(L-D)p (I) wherein Ab is an internalizing anti-TROP2 antibody or internalizing antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system; D is eribulin; L is a cleavable linker comprising Mal-C2(PEG)m-Asn, wherein m is an integer from 0 to 4; and p is an integer from 1 to 8.

[0068] In some embodiments, m is 2.

[0069] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 61. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66.

[0070] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 61. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66.

[0071] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 181 and a light chain comprising an amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 183 and a light chain comprising an amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 380 and a light chain comprising an amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 179 and a light chain comprising an amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 181 and a light chain comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 179 and a light chain comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 183 and a light chain comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 380 and a light chain comprising an amino acid sequence of SEQ ID NO: 115.

[0072] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 100 and a light chain comprising an amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 104 and a light chain comprising an amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 96 and a light chain comprising an amino acid sequence of SEQ ID NO: 110. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 100 and a light chain comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 104 and a light chain comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 96 and a light chain comprising an amino acid sequence of SEQ ID NO: 115.

[0073] In some embodiments, p is 2.

[0074] In some embodiments, p is determined by hydrophobic interaction chromatography-high performance liquid chromatography (HIC-HPLC). In some embodiments, p is determined by reversephase liquid chromatography-mass spectrometry (LC-MS).

[0075] In some embodiments, the cleavable linker covalently attaches to the cytotoxic agent via a C-35 amine. In some embodiments, the cleavable linker covalently attaches to the antibody or antigenbinding fragment via a cysteine or a lysine.

[0076] In various embodiments, the present disclosure provides a composition comprising multiple copies of an antibody-drug conjugate disclosed herein. In some embodiments, the average p of the antibody-drug conjugates in the composition is about 1 to about 3. In some embodiments, the average p is about 2.

[0077] In various embodiments, the present disclosure provides a pharmaceutical composition comprising an antibody-drug conjugate disclosed herein and a pharmaceutically acceptable carrier.

[0078] In various embodiments, the present disclosure provides one or more nucleic acid(s) encoding an antibody or antigen-binding fragment disclosed herein. In some embodiments, the present disclosure provides a host cell comprising the one or more nucleic acids. In some embodiments, the present disclosure provides a method of producing an antibody or antigen-biding fragment disclosed herein, comprising culturing the host cell under conditions sufficient to produce the antibody or antigen-binding fragment.

[0079] In various embodiments, the present disclosure provides a method of producing an antibodydrug conjugate, comprising reacting an antibody or antigen-binding fragment disclosed herein with a cleavable linker joined to eribulin under conditions that allow conjugation.

[0080] In other embodiments, the present disclosure provides an antibody-drug conjugate of Formula (ni): Ab is an antibody or antigen-binding fragment thereof; D is a cytotoxic agent; Y is a cleavable moiety; Z is absent or a spacer unit; and p is an integer from 1 to 8.

[0081] In some embodiments, the cytotoxic agent comprises eribulin or a salt thereof.

[0082] In some embodiments,p is from 2 to 8. In some embodiments, p is 2.

[0083] In some embodiments, the bond to the Ab is on a cysteine residue of the antibody or antigenbinding fragment. In some embodiments, the bond to the Ab is on a cysteine-80 residue on the light chain of the antibody or antigen-binding fragment. In some embodiments, the bond to the Ab is on a cysteine-149 residue on the light chain of the antibody or antigen-binding fragment. In some embodiments, the bond to the Ab is on a cysteine-118 residue on the heavy chain of the antibody or antigen-binding fragment. In some embodiments, the bond to the Ab is on a cysteine-140 residue on the heavy chain of the antibody or antigen-binding fragment. In some embodiments, the bond to the Ab is on a cysteine-239 residue on the heavy chain of the antibody or antigen-binding fragment.

[0084] In some embodiments, the cleavable moiety comprises a cleavable peptide moiety. In some embodiments, the cleavable peptide moiety is cleavable by an enzyme. In some embodiments, the cleavable peptide moiety is cleavable by cathepsin or legumain. In some embodiments, the cleavable peptide moiety is cleavable by cathepsin B.

[0085] In some embodiments, the cleavable peptide moiety comprises an amino acid unit. In some embodiments, the amino acid unit comprises valine-citrulline (Val-Cit), valine-dimethylated lysine (Val-Lys(Me)2), alanine-dimethylated lysine (Ala-Lys(Me)2), valine-alanine (Vai-Ala), asparagine (Asn), aspartic acid (Asp), or methylated aspartic acid (Asp(OMe)). In some embodiments, the amino acid unit comprises Val-Cit. In some embodiments, the amino acid unit comprises Val-Ala. In some embodiments, the amino acid unit comprises Asn. In some embodiments, the amino acid unit comprises Asp.

[0086] In some embodiments, Z is absent, and the cleavable moiety is directly joined to the cytotoxic agent. In some embodiments, -Y-Z- comprises Asn. In some embodiments, -Y-Z- comprises Asp. In some embodiments, D comprises eribulin or a salt thereof.

[0087] In some embodiments, Z is a spacer unit which attaches the cleavable moiety to the cytotoxic agent.

[0088] In some embodiments, the spacer unit attaching the cleavable moiety to the cytotoxic agent is self-immolative. In some embodiments, the spacer unit attaching the cleavable moiety to the cytotoxic agent comprises a p-aminobenzyloxycarbonyl (pABC). In some embodiments, the cytotoxic agent is eribulin, and the pABC covalently attaches to eribulin via a C-35 amine.

[0089] In some embodiments, -Y-Z- comprises Val-Cit-pABC, Val-Ala-pABC, Val-Lys(Me)2-pABC, or Ala-Lys(Me)2-pABC. In some embodiments, -Y-Z- comprises Val-Cit-pABC. In some embodiments, -Y-Z- comprises Val-Ala-pABC. In some embodiments, D comprises eribulin or a salt thereof.

[0090] In some embodiments, Ab is an anti-TROP2 antibody or antigen-binding fragment disclosed herein.

[0091] In various embodiments, the present disclosure provides a composition comprising multiple copies of the antibody-drug conjugate of Formula (II) or Formula (III). In some embodiments, the average p of the antibody-drug conjugates in the composition is about 1 to about 3. In some embodiments, the average p is about 2.

[0092] In various embodiments, the present disclosure provides a compound of Formula (Ila): (Ila), wherein: D is a cytotoxic agent; Y is a cleavable moiety; and Z is absent or a spacer unit.

[0093] In some embodiments, the cytotoxic agent comprises eribulin or a salt thereof.

[0094] In some embodiments, the cleavable moiety comprises a cleavable peptide moiety. In some embodiments, the cleavable peptide moiety is cleavable by an enzyme. In some embodiments, the cleavable peptide moiety is cleavable by cathepsin or legumain. In some embodiments, the cleavable peptide moiety is cleavable by cathepsin B.

[0095] In some embodiments, the cleavable peptide moiety comprises an amino acid unit. In some embodiments, the amino acid unit comprises valine-citrulline (Val-Cit), valine-dimethylated lysine (Val-Lys(Me)2), alanine-dimethylated lysine (Ala-Lys(Me)2), valine-alanine (Vai-Ala), asparagine (Asn), aspartic acid (Asp), or methylated aspartic acid (Asp(OMe)). In some embodiments, the amino acid unit comprises Val-Cit. In some embodiments, the amino acid unit comprises Val-Ala. In some embodiments, the amino acid unit comprises Asn.

[0096] In some embodiments, Z is absent and the cleavable moiety is directly joined to the cytotoxic agent. In some embodiments, -Y-Z- comprises Asn. In some embodiments, -Y-Z- comprises Asp. In some embodiments, D comprises eribulin or a salt thereof.

[0097] In some embodiments, Z is a spacer unit which attaches the cleavable moiety to the cytotoxic agent. In some embodiments, the spacer unit attaching the cleavable moiety to the cytotoxic agent is self-immolative. In some embodiments, the spacer unit attaching the cleavable moiety to the cytotoxic agent comprises a p-aminobenzyloxycarbonyl (pABC). In some embodiments, the pABC covalently attaches to eribulin via a C-35 amine.

[0098] In some embodiments, -Y-Z- comprises Val-Cit-pABC, Val-Ala-pABC, or Val-Lys(Me)2-pABC, Ala-Lys(Me)2-pABC. In some embodiments, -Y-Z- comprises Val-Cit-pABC. In some embodiments, -Y-Z- comprises Val-Ala-pABC. In some embodiments, D comprises eribulin or a salt thereof.

[0099] In various embodiments, the present disclosure provides a method of preparing the antibodydrug conjugate of Formula (II). In some embodiments, the method comprises: - providing one or more compounds of Formula (Ila) O cleavable moiety; and Z is absent or the spacer unit; and (Ila), wherein: D is the cytotoxic agent; Y is the - conjugating the one or more compounds of Formula (Ila) to an antibody or antigen-binding fragment, to provide an antibody-drug conjugate of Formula (II): r ? . S &                H                                                               i K < i] °              H z i L o                           6             |; 1 (II), wherein Ab is the antibody or antigen-binding fragment.

[00100] In various embodiments, the present disclosure provides a method of preparing the antibodydrug conjugate of Formula (III). In some embodiments, the method comprises: - providing one or more compounds of Formula (Ila) O O (Ila), wherein: D is the cytotoxic agent; Y is the cleavable moiety; and Z is absent or the spacer unit; - conjugating the one or more compounds of Formula (Ila) to an antibody or antigen-binding fragment, to provide an antibody-drug conjugate of Formula (II): r o                                      1 i                                                                                                                                                                                   ' Ab"k' "n ■ ■, -K....- x o , ■ / <.. ■D ! / H ° v H sz’ i : k 0                 0 L P (II), wherein Ab is the antibody or antigen-binding fragment; and - hydrolyzing the succinimide ring in the compound of Formula (II), to provide the compound of Formula (III) p (HI).

[00101] In some embodiments, the step of hydrolyzing the succinimide ring in the compound of Formula (II) comprises a pH from about 7.4 to about 9.2. In some embodiments, the pH is from about 7.4 to about 8.5. In some embodiments, the pH is about 7.4.

[00102] In some embodiments, the step of hydrolyzing the succinimide ring in the compound of Formula (II) comprises a temperature of about 37 °C. In some embodiments, the step of hydrolyzing the succinimide ring in the compound of Formula (II) is completed in about 24 hours or less.

[00103] In various embodiments, the present disclosure provides a method of treating a patient having or at risk of having a cancer that expresses TROP2, comprising administering to the patient a therapeutically effective amount of an antibody or antigen-binding fragment disclosed herein. In various embodiments, the present disclosure provides a method of treating a patient having or at risk of having a cancer that expresses TROP2, comprising administering to the patient a therapeutically effective amount of an antibody-drug conjugate disclosed herein. In various embodiments, the present disclosure provides a method of treating a patient having or at risk of having a cancer that expresses TROP2, comprising administering to the patient a therapeutically effective amount of a composition disclosed herein. In various embodiments, the present disclosure provides a method of treating a patient having or at risk of having a cancer that expresses TROP2, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition disclosed herein. In some embodiments, the TROP2-expressing cancer is a cholangiocarcinoma, bladder cancer, breast cancer, cervical carcinoma, colorectal cancer, esophageal cancer, gastric cancer, glioma, hepatocellular carcinoma, nasopharyngeal cancer, non-small cell lung cancer (NSCLC), pancreatic cancer, endometrial cancer, ovarian cancer, or skin cancer. In some embodiments, the TROP2-expressing cancer is a cholangiocarcinoma, breast cancer, or NSCLC. In some embodiments, the patient is intolerant, non-responsive, or poorly responsive to treatment with eribulin when administered alone.

[00104] In various embodiments, the present disclosure provides a method of reducing or inhibiting growth of a TROP2-expressing tumor, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment disclosed herein. In various embodiments, the present disclosure provides a method of reducing or inhibiting growth of a TROP2-expressing tumor, comprising administering a therapeutically effective amount of an antibody-drug conjugate disclosed herein. In various embodiments, the present disclosure provides a method of reducing or inhibiting growth of a TROP2-expressing tumor, comprising administering a therapeutically effective amount of a composition disclosed herein. In various embodiments, the present disclosure provides a method of reducing or inhibiting growth of a TROP2-expressing tumor, comprising administering a therapeutically effective amount of a pharmaceutical composition disclosed herein. In some embodiments, the tumor is a TR0P2-expressing cholangiocarcinoma, bladder cancer, breast cancer, esophageal cancer, hepatocellular carcinoma, nasopharyngeal cancer, non-small cell lung cancer (NSCLC), pancreatic cancer, endometrial cancer, ovarian cancer, or skin cancer. In some embodiments, the tumor is a cholangiocarcinoma. BRIEF DESCRIPTION OF THE DRAWINGS

[00105] FIG. 1A shows FACS analysis of folate receptor alpha (FRA), HER2, and TROP2 expression on human breast cancer HCC1954 cell line. FIGs. IB and IC show average tumor volume and body weight change after single-dose treatment with the indicated compound in a human breast cancer HCC-1954 xenograft model.

[00106] FIG. 2A shows average tumor volumes in NCI-H2110 NSCLC xenograft models upon single-dose treatment with anti-TROP2-162-46.2-SN-38 or anti-FRa-eribulin. FIGs. 2B and 2C show average tumor volumes and body weight for various doses of anti-TROP2-162-46.2-eribulin ADC compared to the unconjugated antibody or eribulin.

[00107] FIGs. 3A and 3B show average tumor volume and relative body weight normalized by day of treatment with a single dose of each compound at the indicated concentration in a WHIM5 TNBC PDx model.

[00108] FIGs. 4A and 4B show average tumor volume and weight in CTG-1258 or CTG-1388 upon single-dose treatment of the indicated compound.

[00109] FIG. 5 shows pre- and post-immunization blood samples from rabbits diluted and analyzed for human TROP2 reactivity by ELISA.

[00110] FIG. 6A shows analysis of overlapping epitopes on hTROP2-Fc for each indicated antibody pair. FIG. 6B shows groupings of antibodies with similar overlapping profiles. FIG. 6C shows analysis of overlapping epitopes on hTROP2-Fc for each indicated antibody pair. FIG. 6D shows grouping of antibodies with similar overlapping profiles.

[00111] FIG. 7 shows correlation between TROP2 affinity and IC50 in BxPC3 cells.

[00112] FIG. 8 shows rabbit CDRs grafted onto the closest human germline frameworks. The frameworks (FR) and CDRs are shown above each clone as defined by Kabat (top) and IMGT (bottom). Residues that may impact antigen binding were retained in FRH2 and FRL1. Rabbit residues are in bold, humanized residues are underlined.

[00113] FIGs. 9A and 9B show in vitro cytotoxicity screening of humanized anti-TROP2 ADCs in a variety of cell types. FIG. 9C shows ADC IC50 values and max killing (%) for the identified ADCs in AsPCl, BxPC3, and SNU-308 cells. Fig. 9D shows percent cytotoxicity at different ADC concentrations for AsPCl, BxPC3, and SNU-308 cells.

[00114] FIG. 10 shows internalization of anti-TROP2 antibodies using NCI-H2110 and MDA-MB-231 cell lines.

[00115] FIG. 11 shows rabbit CDRs grafted onto the closest human germline frameworks. The FRs and CDRs are shown above each clone as defined by Kabat (top) and IMGT (bottom). Residues that may impact antigen binding were retained in FRH2 and FRL1. Rabbit residues are in bold, humanized residues are underlined.

[00116] FIG. 12A shows the ECso of 16K21 Hl-3 and Ll-3,17124 Hl-3 and Ll-3, and 20E16 Hl-3 and Ll-2 for binding human TROP2-ECD as determined by ELISA. FIG. 12B shows the EC50 of each indicated clone for binding to human TROP2-ECD as determined by ELISA.

[00117] FIG. 13 shows polyspecificity assessment of control versus anti-TROP2 antibodies. Insulin, ssDNA, dsDNA, cardiolipin, LPS, or KLH were coated on wells of a 96-well plate.

[00118] FIGs. 14A, 14B, 14C, 14D, 14E, 14F, and 14G show the thermal stability of chimeric (xi) and humanized (zu) anti-TROP2 antibodies analyzed by DSC.

[00119] FIG. 15 shows MAAS mutations.

[00120] FIG. 16A shows neutrophil differentiation over 14 days upon indicated cytokine treatment as monitored by FACS. FIG. 16B shows the percentage of viable CD66b+ cells after incubation for four days with various concentrations of anti-TROP2-ADCs with wild-type or mutant Fes in the presence or absence of Fc blocker as determined by FACS.

[00121] FIG. 17 shows immunogenicity of antibody clones predicted by Abzena’s iTope in silico immunogenicity assessment tool.

[00122] FIG. 18A shows a disulfide re-bridging strategy and the DTM-N-eribulin linker payload. FIG. 18B shows IC50 values of the indicated ADC in various cell lines.

[00123] FIG. 19 shows linker-eribulin conjugates.

[00124] FIG. 20 shows percent growth inhibition of TROP2-expressing cells treated with anti-TROP2-ADCs in mono- and co-cultured in vitro bystander assay.

[00125] FIG. 21 shows the thermal stability of the indicated linkers over time. HIC = hydrophobic interaction chromatography.

[00126] FIGs. 22A, 22B, 22C, 22D, and 22E show mouse plasma stability of RESPECT-L linkers. FIG. 22 A shows the average DAR of immunocaptured samples as analyzed by LC-MS. FIG. 22B shows percent change in DAR of immunocaptured samples. FIGs. 22C and 22D show free payload (ng / mL or percentage in plasma) in the immunodepleted plasma samples as analyzed by LC-MS after organic extraction of the free payload. FIG. 22E shows the percentage of hydrolysis of the linker for each sample as determined by LC-MS.

[00127] FIG. 23 shows average tumor volume in NSCLC NCI-H2110 xenograft model treated with a single dose of the indicated compounds at 10 mg / kg.

[00128] FIG. 24 shows average tumor volume in NSCLC NCI-H2110 xenograft model treated with subcutaneous injection of a single dose of 16K21H1L1-Eribulin, 17I24H1L1-Eribulin, or IMMU-132 (7.5 mg / kg).

[00129] FIG. 25 shows the anti-tumor activity of 16K21HlLl-ADCs comparing RESPECT-L conjugation ((PEG)2-VCP-eribulin) and re-bridging conjugation (DTM-N-eribulin).

[00130] FIGs. 26A, 26B, 26C, and 26D show the in vivo anti-tumor activity of various RESPECT-L linkers. The anti-tumor activity of 16K21HlLl-ADCs with various PEG lengths (FIG. 26A), 16K21H1L1- and 17I24HlLl-ADCs with various cathepsin-cleavable linkers (FIGs. 26B and26C), and 16K21HlLl-ADCs with legumain-cleavable linkers (FIG. 26D) was evaluated inNSCLC NCI-H2110 xenograft model.

[00131] FIGs. 27A, 27B, 27C, 27D, 27E, 27F, and 27G show in vitro cytotoxicity of humanized monoclonal antibodies and linkers.

[00132] FIGs. 28A, 28B, 28C, and 28D show IC50 values for various cell lines treated with the indicated ADCs.

[00133] FIG. 29 shows in vivo analysis of the indicated anti-TROP2-eribulin ADCs.

[00134] FIG. 30 shows an analysis of hydrolysis conditions for various maleimide-conjugated eribulin linkers.

[00135] FIG. 31A shows percent hydrolysis for antibody-drug conjugates comprising a (PEG)2 spacer unit conjugated to various cleavable moieties and at various pH. FIG. 31B shows percent hydrolysis for antibody-drug conjugates comprising a C2(PEG)2 spacer unit conjugated to various cleavable moieties and at various pH. FIG. 3 IC shows percent hydrolysis for antibody-drug conjugates comprising a C2 spacer unit conjugated to various cleavable moieties and at various pH.

[00136] FIG. 32A shows percent hydrolysis for antibody-drug conjugates comprising a Val-Cit-pABC (VCP) cleavable moiety conjugated to various spacer units and at various pH. FIG. 32B shows percent hydrolysis for antibody-drug conjugates comprising an asparagine (N) cleavable moiety conjugated to various spacer units and at various pH.

[00137] FIGs. 33A shows ADC stability of ADCs comprising VCP and C2(PEG)i, C2(PEG)2, (PEG)2, or C2 in buffer or plasma. FIG. 33B shows ADC stability of ADCs comprising N and C2(PEG)2, C2(PEG)i, (PEG)2, or C2 in buffer or plasma. “% DAR” represents the percentage of intact ADC relative to the initial DAR at the start of the experiment.

[00138] FIG. 34 shows in vitro cytotoxicity of humanized monoclonal antibodies conjugated to various linkers.

[00139] FIG. 35A shows in vivo tumor volume results after treatment with ADCs comprising C2(PEG)2. FIG. 35B shows in vivo tumor volume results after treatment with ADCs comprising (PEG)2. FIG. 35C shows in vivo tumor volume results after treatment with ADCs comprising C2. DETAILED DESCRIPTION

[00140] The disclosed compositions and methods may be understood more readily by reference to the following detailed description taken in connection with the accompanying figures, which form a part of this disclosure.

[00141] Throughout this text, the descriptions refer to compositions and methods of using said compositions. Where the disclosure describes or claims a feature or embodiment associated with a composition, such a feature or embodiment is equally applicable to the methods of using said composition. Likewise, where the disclosure describes or claims a feature or embodiment associated with a method of using a composition, such a feature or embodiment is equally applicable to the composition.

[00142] When a range of values is expressed, it includes embodiments using any particular value within the range. Further, reference to values stated in ranges includes each and every value within that range. All ranges are inclusive of their endpoints and combinable. When values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. Reference to a particular numerical value includes at least that particular value, unless the context clearly dictates otherwise. The use of “or” will mean “and / or” unless the specific context of its use dictates otherwise. All references cited herein are incorporated by reference for any purpose. Where a reference and the specification conflict, the specification will control.

[00143] It is to be appreciated that certain features of the disclosed compositions and methods, which are, for clarity, described herein in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the disclosed compositions and methods that are, for brevity, described in the context of a single embodiment, may also be provided separately or in any sub-combination. Definitions

[00144] Various terms relating to aspects of the description are used throughout the specification and claims. Such terms are to be given their ordinary meaning in the art unless otherwise indicated. Other specifically defined terms are to be construed in a manner consistent with the definitions provided herein.

[00145] As used herein, the singular forms “a,” “an,” and “the” include plural forms unless the context clearly dictates otherwise.

[00146] The terms “about” or “approximately” in the context of numerical values and ranges refer to values or ranges that approximate or are close to the recited values or ranges such that the embodiment may perform as intended, such as having a desired amount of nucleic acids or polypeptides in a reaction mixture, as is apparent to the skilled person from the teachings contained herein. In some embodiments, “about” means plus or minus 10% of a numerical amount.

[00147] The term “agent” is used herein to refer to a chemical compound, a mixture of chemical compounds, a biological macromolecule, or an extract made from biological materials. The term “therapeutic agent,” “cytotoxic agent,” “drug,” or “drug moiety” refers to an agent that is capable of modulating a biological process and / or has biological activity.

[00148] The terms “antibody-drug conjugate,” “antibody conjugate,” “immunoconjugate,” and “ADC” are used interchangeably, and refer to a compound or derivative thereof that is linked to an antibody (e.g., an anti-TROP2 antibody) and may be defined by the generic formula: Ab-(L-D)p (Formula (I)), wherein Ab = an antibody moiety (i.e., antibody or antigen-binding fragment), L = a linker moiety, D = a drug moiety, and p = the number of drug moieties per antibody moiety. In some embodiments, the linker L includes a cleavable moiety between the antibody or antigen-binding fragment and the therapeutic compound. In some embodiments, the linker L includes a cleavable moiety that can be attached to either or both the antibody or antigen-binding fragment and to the therapeutic compound, e.g., by spacer unit(s). Exemplary cleavable linkers are described and exemplified herein.

[00149] The term “antibody” is used in the broadest sense to refer to an immunoglobulin molecule that recognizes and specifically binds to a target, such as a protein, polypeptide, carbohydrate, polynucleotide, lipid, or combinations of the foregoing through at least one antigen recognition site within the variable region of the immunoglobulin molecule. The heavy chain (HC) of an antibody is composed of a heavy chain variable domain (VH) and a heavy chain constant region (CH). The light chain (LC) is composed of a light chain variable domain (VL) and a light chain constant domain (CL). As used herein, the terms “domain” and “region” maybe used interchangeably (e.g., the term “variable domain” may be used interchangeably with the term “variable region” and understood to refer to the same part of the antibody). For the purposes of this application, the mature heavy chain and light chain variable domains each comprise three complementarity determining regions (CDR1, CDR2, and CDR3; also referred to as “hypervariable regions”) within four framework regions (FR1, FR2, FR3, and FR4) arranged from N terminus to C terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. CDRs may be identified according to the Kabat and / or IMGT numbering systems. Kabat, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987 and 1991); International ImMunoGeneTics Information System (IMGT®). An “antibody” can be naturally occurring or man-made, such as monoclonal antibodies produced by conventional hybridoma technology. The term “antibody” includes full-length monoclonal antibodies and fulllength polyclonal antibodies, as well as antibody fragments such as Fab, Fab', F(ab')2, Fv, and single chain antibodies. An antibody can be any one of the five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, or subclasses thereof (e.g., isotypes IgGl, IgG2, IgG3, IgG4). An antibody of any of the aforementioned classes or subclasses can also comprise one of two functionally similar classes of light chains: IgK (also referred to herein as “Ig kappa” or “kappa”) and IgX (also referred to herein as “Ig lambda” or “lambda”). The term antibody encompasses human antibodies, chimeric antibodies, humanized antibodies and any modified immunoglobulin molecule containing an antigen recognition site, so long as it demonstrates the desired biological activity.

[00150] The term “bystander killing” or “bystander effect” refers to the killing of target-negative cells in the presence of target-positive cells, wherein killing of target-negative cells is not observed in the absence of target-positive cells. Cell-to-cell contact, or at least proximity between target-positive and target-negative cells, enables bystander killing. This type of killing is distinguishable from “off-target killing,” which refers to the indiscriminate killing of target-negative cells. “Off-target killing” may be observed in the absence of target-positive cells.

[00151] The term “chimeric antibody,” as used herein, refers to antibodies wherein the amino acid sequence of the immunoglobulin molecule is derived from two or more species. In some instances, the variable regions of both heavy and light chains correspond to the variable regions of antibodies derived from one species with the desired specificity, affinity, and activity while the constant regions are homologous to antibodies derived from another species (e.g., human) to minimize an immune response in the latter species.

[00152] The term “human antibody,” as used herein, refers to an antibody produced by a human or an antibody having an amino acid sequence of an antibody produced by a human.

[00153] As used herein, the term “humanized antibody” refers to forms of antibodies that contain sequences from non-human (e.g., murine) antibodies as well as human antibodies. Such antibodies are chimeric antibodies which contain minimal sequence derived from non-human immunoglobulin. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework (FR) regions are those of a human immunoglobulin sequence. The humanized antibody optionally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. The humanized antibody can be further modified by the substitution of residues, either in the Fv framework region and / or within the replaced non-human residues to refine and optimize antibody specificity, affinity, and / or activity. The humanized antibody can also be further modified by the substitution of residues in the Fc domain to reduce its binding to various cell receptors, such as a Fey receptor (FcyR), and other immune molecules.

[00154] The term “monoclonal antibody,” as used herein, refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic epitope. In contrast, conventional (polyclonal) antibody preparations typically include a multitude of antibodies directed against (or specific for) different epitopes. The modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the present disclosure may be made by the hybridoma method first described by Kohler et al. (1975) Nature 256:495 or may be made by recombinant DNA methods. See, e.g., U.S. Pat. No. 4,816,567. Monoclonal antibodies may also be isolated from phage antibody libraries using the techniques described in, e.g., Clackson et al. (1991) Nature 352:624-8, and Marks et al. (1991) J. Mol. Biol. 222:581-97.

[00155] The monoclonal antibodies described herein specifically include “chimeric” antibodies, in which a portion of the heavy and / or light chain is identical with or homologous to corresponding sequences in an antibody derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in an antibody derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they specifically bind the target antigen and / or exhibit the desired biological activity.

[00156] The term “antigen-binding fragment” or “antigen-binding portion” of an antibody, as used herein, refers to one or more fragments of an antibody that retain the ability to specifically bind to an antigen (e.g., TROP2). Antigen-binding fragments preferably also retain the ability to internalize into an antigen-expressing cell. In some embodiments, antigen-binding fragments also retain immune effector activity. It has been shown that fragments of a full-length antibody can perform the antigenbinding function of a full-length antibody. Examples of binding fragments encompassed within the term “antigen-binding fragment” or “antigen-binding portion” of an antibody include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL, and Cm domains; (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and Cm domains; (iv) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody; (v) a dAb fragment, which comprises a single variable domain, e.g., a VH domain, see, e.g., Ward et al. (1989) Nature 341:544-6; and Winter et al., WO 90 / 05144; and (vi) an isolated complementarity determining region (CDR). Furthermore, although the two domains of the Fv fragment, VL and VH, are coded for by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single chain Fv (scFv)). See, e.g., Bird et al. (1988) Science 242:423-6; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-83. Such single chain antibodies are also intended to be encompassed within the term “antigen-binding fragment” or “antigen-binding portion” of an antibody, and are known in the art as an exemplary type of binding fragment that can internalize into cells upon binding. See, e.g., Zhu et al. (2010) 9:2131-41; He et al. (2010) J. Nucl. Med. 51:427-32; and Fitting et al. (2015) MAbs 7:390-402. In certain embodiments, scFv molecules may be incorporated into a fusion protein. Other forms of single chain antibodies such as diabodies are also encompassed. Diabodies are bivalent, bispecific antibodies in which VH and VL domains are expressed on a single polypeptide chain, but using a linker that is too short to allow for pairing between the two domains on the same chain, thereby forcing the domains to pair with complementary domains of another chain and creating two antigen-binding sites. See, e.g., Holliger et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-8; and Poljak et al. (1994) Structure 2:1121-3. Antigen-binding fragments are obtained using conventional techniques known to those of skill in the art, and the binding fragments are screened for utility (e.g., binding affinity, internalization) in the same manner as are intact antibodies. Antigen-binding fragments may be prepared, e.g., by cleavage of the intact protein, e.g., by protease or chemical cleavage.

[00157] The term “anti-TROP2 antibody” or “antibody that specifically binds TROP2” refers to any form of antibody or fragment thereof that specifically binds TROP2, and encompasses monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, and biologically functional antibody fragments so long as they specifically bind TROP2. Preferably the anti-TROP2 antibody used in the ADCs disclosed herein is an internalizing antibody or internalizing antibody fragment. 17124, 16K21, and 20E16 are exemplary internalizing anti-human TROP2 antibodies. Sacituzumab and datopotamab are also exemplary internalizing anti-human TROP2 antibodies. As used herein, the terms “specific,” “specifically binds,” and “binds specifically” refer to the selective binding of the antibody to the target antigen or epitope over alternative antigens or epitopes. Antibodies can be tested for specificity of binding by comparing binding to an appropriate antigen to binding to an irrelevant antigen or antigen mixture under a given set of conditions. If the antibody binds to the appropriate antigen with at least 5 times, or preferably 7 or 10 times, more affinity than to an irrelevant antigen or antigen mixture, then it is considered to be specific, e.g., as measured by surface plasmon resonance, e.g., BIAcore® analysis. In one embodiment, a specific antibody is one that binds the TROP2 antigen, but does not bind (or exhibits minimal binding) to other antigens.

[00158] The term “cancer” refers to the physiological condition in mammals in which a population of cells is characterized by unregulated cell growth. Examples of cancers include, but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia. More particular examples of such cancers include squamous cell cancer, small cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, squamous carcinoma of the lung, bile duct cancer (e.g., cholangiocarcinoma), esophageal cancer, nasopharyngeal cancer, cancer of the peritoneum, hepatocellular cancer (e.g., hepatocellular carcinoma), gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, osteosarcoma, skin cancer (e.g., melanoma), colon cancer, colorectal cancer, endometrial or uterine cancer, ovarian cancer, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, and various types of head and neck cancers.

[00159] The terms “cancer cell” and “tumor cell” refer to individual cells or the total population of cells derived from a tumor, including both non-tumorigenic cells and cancer stem cells. As used herein, the term “tumor cell” will be modified by the term “non-tumorigenic” when referring solely to those tumor cells lacking the capacity to renew and differentiate to distinguish those tumor cells from cancer stem cells.

[00160] The term “chemotherapeutic agent” or “anti-cancer agent” is used herein to refer to a chemical compound that is effective in treating cancer regardless of mechanism of action. Inhibition of metastasis or angiogenesis is frequently a property of a chemotherapeutic agent. Non-limiting examples of chemotherapeutic agents include alkylating agents, for example, nitrogen mustards, ethyleneimine compounds, and alkyl sulphonates; antimetabolites, for example, folic acid, purine or pyrimidine antagonists; anti-mitotic agents, for example, anti-tubulin agents such as eribulin or eribulin mesylate (Halaven™) or derivatives thereof, vinca alkaloids, and auristatins; cytotoxic antibiotics; compounds that damage or interfere with DNA expression or replication, for example, DNA minor groove binders; and growth factor receptor antagonists. In addition, chemotherapeutic agents include antibodies, biological molecules, and small molecules. A chemotherapeutic agent may be a cytotoxic or cytostatic agent. The term “cytostatic agent” refers to an agent that inhibits or suppresses cell growth and / or multiplication of cells.

[00161] The term “co-administration” or administration “in combination with” one or more therapeutic agents includes concurrent and consecutive administration in any order.

[00162] The term “cytotoxic agent” refers to a substance that causes cell death primarily by interfering with a cell’s expression activity and / or functioning. Examples of cytotoxic agents include, but are not limited to, anti-mitotic agents, such as eribulin, auristatins (e.g., monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF)), maytansinoids (e.g., maytansine), dolastatins, duostatins, cryptophycins, vinca alkaloids (e.g., vincristine, vinblastine), taxanes, taxols, and colchicines; anthracyclines (e.g., daunorubicin, doxorubicin, dihydroxyanthracindione); cytotoxic antibiotics (e.g., mitomycins, actinomycins, duocarmycins (e.g., CC-1065), auromycins, duomycins, calicheamicins, endomycins, phenomycins); alkylating agents (e.g., cisplatin); intercalating agents (e.g., ethidium bromide); topoisomerase inhibitors (e.g., exactecan, irinotecan, etoposide, tenoposide); radioisotopes, such as At211,1131,1125, Y90, Rel86, Rel88, Sml53, Bi212 or 213, P32, and radioactive isotopes of lutetium (e.g., Lu 177); and toxins of bacterial, fungal, plant or animal origin (e.g., ricin (e.g., ricin A-chain), diphtheria toxin, Pseudomonas exotoxin A (e.g., PE40), endotoxin, mitogellin, combrestatin, restrictocin, gelonin, alpha-sarcin, abrin (e.g., abrin A-chain), modeccin (e.g., modeccin A-chain), curicin, crotin, Sapaonaria officinalis inhibitor, glucocorticoid).

[00163] An “effective amount” of an ADC as disclosed herein is an amount sufficient to perform a specifically stated purpose, for example to produce a therapeutic effect after administration, such as a reduction in tumor growth rate or tumor volume, a reduction in a symptom of cancer, or some other indicia of treatment efficacy. An effective amount can be determined in a routine manner in relation to the stated purpose. The term “therapeutically effective amount” refers to an amount of an ADC effective to treat a disease or disorder in a subject. In the case of cancer, a therapeutically effective amount of ADC can reduce the number of cancer cells, reduce tumor size, inhibit (e.g., slow or stop) tumor metastasis, inhibit (e.g., slow or stop) tumor growth, and / or relieve one or more symptoms. A “prophylactically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically, since a prophylactic dose is used in subjects prior to or at an earlier stage of disease, the prophylactically effective amount will be less than the therapeutically effective amount.

[00164] The term “epitope” refers to the portion of an antigen capable of being recognized and specifically bound by an antibody. When the antigen is a polypeptide, epitopes can be formed from contiguous amino acids or noncontiguous amino acids juxtaposed by tertiary folding of the polypeptide. The epitope bound by an antibody may be identified using any epitope mapping technique known in the art, including X-ray crystallography for epitope identification by direct visualization of the antigen-antibody complex, as well as monitoring the binding of the antibody to fragments or mutated variations of the antigen, or monitoring solvent accessibility of different parts of the antibody and the antigen. Exemplary strategies used to map antibody epitopes include, but are not limited to, array-based oligo-peptide scanning, limited proteolysis, site-directed mutagenesis, high-throughput mutagenesis mapping, hydrogen-deuterium exchange, and mass spectrometry. See, e.g., Gershoni et al. (2007) 21:145-56; and Hager-Braun and Tomer (2005) Expert Rev. Proteomics 2:74556.

[00165] Competitive binding and epitope binning can also be used to determine antibodies sharing identical or overlapping epitopes. Competitive binding can be evaluated using a cross-blocking assay, such as the assay described in “Antibodies, A Laboratory Manual,” Cold Spring Harbor Laboratory, Harlow and Lane (1st edition 1988,2nd edition 2014). In some embodiments, competitive binding is identified when a test antibody or binding protein reduces binding of a reference antibody or binding protein to a target antigen such as TROP2 (e.g., a binding protein comprising CDRs and / or variable domains selected from those identified in Tables 2, 4, and 6), by at least about 50% in the crossblocking assay (e.g., 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%, or more, or any percentage in between), and / or vice versa. In some embodiments, competitive binding can be due to shared or similar (e.g., partially overlapping) epitopes, or due to steric hindrance where antibodies or binding proteins bind at nearby epitopes. See, e.g., Tzartos, Methods in Molecular Biology (Morris, ed. (1998) vol. 66, pp. 55-66). In some embodiments, competitive binding can be used to sort groups of binding proteins that share similar epitopes, e.g., those that compete for binding can be “binned” as a group of binding proteins that have overlapping or nearby epitopes, while those that do not compete are placed in a separate group of binding proteins that do not have overlapping or nearby epitopes.

[00166] The term “eribulin,” as used herein, refers to a synthetic compound of halichondrin B. The term “eribulin drug moiety” refers to the component of an ADC that has the structure of eribulin, and is attached to the linker of the ADC, e.g., via its C-35 amine. The terms encompass salts thereof. Eribulin is a microtubule dynamics inhibitor, which is thought to bind tubulin and induce cell cycle arrest at the G2 / M phase by inhibiting mitotic spindle assembly. The term “eribulin mesylate” refers to the mesylate salt of eribulin, which is marketed under the trade name Halaven™. Compositions and methods of inhibiting tumor growth in patients comprising administering eribulin are disclosed in U.S. Patent No. 10,322,192, which is incorporated herein by reference in its entirety for all eribulin structures and methods of synthesizing those structures. The structure of eribulin is shown below:

[00167] “Fey receptor,” “Fc-gamma receptor,” or “FcyR” refers to a cell surface protein generally found on immune cells of various types, e.g., neutrophils. The binding of an Fc region of an antibody to a Fey receptor may induce different effector functions, for example antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP), which can have unwanted side effects, for example cell or tissue damage, effector cell activation, or cytokine release. The binding of an Fc region of an antibody to a Fey receptor on a neutrophil may induce cell damage, e.g., neutropenia, through non-antigen-mediated uptake of the antibody.

[00168] The term “homolog” in the context of an antibody or antigen-binding fragment refers to a protein sequence having amino acid residues that are the same or similar at corresponding positions. A homolog may refer to a similar sequence from a different species. Sequence homology, as used herein, refers to a sequence having amino acid residues that are the same or similar at corresponding positions in a reference sequence. Sequence homology may be described by percent identity with a reference sequence. Preferably, sequence homology may be determined by an algorithm such as PILEUP, BLAST, or gapped BLAST, described in further detail below for amino acid sequence identity.

[00169] The terms “IgGl Fc,” “IgGl Fc domain” or “IgGl Fc-containing antibody” as used herein refer to an antibody having at least an IgGl CH2 and CH3 domain, as identified by SEQ ID NO: 164 and SEQ ID NO: 165, respectively.

[00170] “Wild-type IgGl Fc domain” refers to a human IgGl Fc domain that comprises the amino acid sequence of SEQ ID NO: 163 or a fragment thereof.

[00171] The term “inhibit” or “inhibition of,” as used herein, means to reduce by a measurable amount, and can include but does not require complete prevention or inhibition.

[00172] “Internalizing” as used herein in reference to an antibody or antigen-binding fragment refers to an antibody or antigen-binding fragment that is capable of being taken through the cell's lipid bilayer membrane to an internal compartment (i.e., “internalized”) upon binding to the cell, preferably into a degradative compartment in the cell. For example, an internalizing anti-TROP2 antibody is one that is capable of being taken into the cell after binding to TROP2 on the cell membrane.

[00173] The term “KD” refers to the equilibrium dissociation constant of a particular antibodyantigen interaction. KD is calculated by ka / kd. The rate can be determined using standard assays, such as a BIAcore® or ELISA assay.

[00174] The term “kon” or “ka” refers to the on-rate constant for association of an antibody to the antigen to form the antibody / antigen complex. The rate can be determined using standard assays, such as a BIAcore® or ELISA assay.

[00175] The term “koff” or “ka” refers to the off-rate constant for dissociation of an antibody from the antibody / antigen complex. The rate can be determined using standard assays, such as a BIAcore® or ELISA assay.

[00176] A “linker” or “linker moiety” is any chemical moiety that is capable of covalently joining a compound, usually a drug moiety such as a chemotherapeutic agent, to another moiety such as an antibody moiety. Linkers can be susceptible to or substantially resistant to acid-induced cleavage, peptidase-induced cleavage, light-based cleavage, esterase-induced cleavage, and / or disulfide bond cleavage, at conditions under which the compound or the antibody remains active. A “cleavable linker” is any linker that comprises a cleavable moiety and can thus be susceptible to cleavage. A cleavable moiety can be a cleavable peptide moiety. The term “cleavable peptide moiety” refers to any chemical bond linking amino acids (natural or synthetic amino acid derivatives) that can be cleaved by an agent that is present in the intracellular environment.

[00177] The term “p” or “antibody:drug ratio” or “drug-to-antibody ratio” or “DAR” refers to the number of drug moieties per antibody moiety, i.e., drug loading, or the number of -L-D moieties per antibody or antigen-binding fragment (Ab) in ADCs of Formula (I). In compositions comprising multiple copies of ADCs of Formula (I), “p” refers to the average number of -L-D moieties per antibody or antigen-binding fragment, also referred to as average drug loading.

[00178] A “pharmaceutical composition” refers to a preparation which is in such form as to permit administration and subsequently provide the intended biological activity of the active ingredients) and / or to achieve a therapeutic effect, and which contains no additional components which are unacceptably toxic to a subject to which the formulation would be administered. The pharmaceutical composition may be sterile.

[00179] A “pharmaceutical excipient” comprises a material such as an adjuvant, a carrier, pH-adjusting and buffering agents, tonicity adjusting agents, wetting agents, preservative, and the like.

[00180] “Pharmaceutically acceptable” means approved or approvable by a regulatory agency of the Federal or a state government, or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia, for use in animals, and more particularly in humans.

[00181] By “protein,” as used herein, is meant at least two covalently attached amino acids. The term encompasses polypeptides, oligopeptides, and peptides. In some embodiments, the two or more covalently attached amino acids are attached by a peptide bond. The protein may be made up of naturally occurring amino acids and peptide bonds, for example when the protein is made recombinantly using expression systems and host cells. Alternatively, the protein may include synthetic amino acids (e.g., homophenylalanine, citrulline, ornithine, and norleucine), or peptidomimetic structures, e.g., peptoids. Peptoids are an exemplary class of peptidomimetics whose side chains are appended to the nitrogen atom of the peptide backbone, rather than to the a-carbons (as they are in amino acids), and have different hydrogen bonding and conformational characteristics in comparison to peptides. See, e.g., Simon et al. (1992) Proc. Natl. Acad. Sci. USA 89:9367. As such, peptoids can be resistant to proteolysis or other physiological or storage conditions, and effective at permeating cell membranes. Such synthetic amino acids may be incorporated in particular when the antibody is synthesized in vitro by conventional methods well known in the art. In addition, any combination of peptidomimetic, synthetic, and naturally occurring residues / structures can be used. “Amino acid” also includes imino acid residues, such as proline and hydroxyproline. The amino acid “R group” or “side chain” may be in either the (L)- or the (S)-configuration. In a specific embodiment, the amino acids are in the (L)- or (S)-configuration.

[00182] For amino acid sequences, sequence identity and / or similarity may be determined using standard techniques known in the art, including, but not limited to, the local sequence identity algorithm of Smith and Waterman (1981) Adv. Appl. Math. 2:482, the sequence identity alignment algorithm of Needleman and Wunsch (1970) J. Mol. Biol. 48:443, the search for similarity method of Pearson and Lipman (1988) Proc. Nat. Acad. Sci. USA 85:2444, computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Drive, Madison, Wis.), the Best Fit sequence program described by Devereux et al. (1984) Nucl. Acid Res. 12:387-95, preferably using the default settings, or by inspection.

[00183] An example of a useful algorithm is PILEUP. PILEUP creates a multiple sequence alignment from a group of related sequences using progressive, pairwise alignments. It can also plot a tree showing the clustering relationships used to create the alignment. PILEUP uses a simplification of the progressive alignment method of Feng & Doolittle (1987) J. Mol. Evol. 35:351-60; the method is similar to that described by Higgins and Sharp (1989) CABIOS 5:151-3. Useful PILEUP parameters include a default gap weight of 3.00, a default gap length weight of 0.10, and weighted end gaps.

[00184] Another example of a useful algorithm is the BLAST algorithm, described in: Altschul et al. (1990) J. Mol. Biol. 215:403-10; Altschul et al. (1997) Nucleic Acids Res. 25:3389-402; and Karin et al. (1993) Proc. Natl. Acad. Sci. USA 90:5873-87. A particularly useful BLAST program is the WU-BLAST-2 program which was obtained from Altschul et al. (1996) Methods in Enzymology 266:46080. WU-BLAST-2 uses several search parameters, most of which are set to the default values. The adjustable parameters are set with the following values: overlap span = 1, overlap fraction = 0.125, word threshold (T) = II. The HSP S and HSP S2 parameters are dynamic values and are established by the program itself depending upon the composition of the particular sequence and composition of the particular database against which the sequence of interest is being searched; however, the values may be adjusted to increase sensitivity.

[00185] An additional useful algorithm is gapped BLAST as reported by Altschul et al. (1993) Nucl. Acids Res. 25:3389-402. Gapped BLAST uses BLOSUM-62 substitution scores; threshold T parameter set to 9; the two-hit method to trigger ungapped extensions, charges gap lengths of k a cost of 10+k; Xu set to 16, and Xg set to 40 for database search stage and to 67 for the output stage of the algorithms. Gapped alignments are triggered by a score corresponding to about 22 bits.

[00186] Generally, proteins disclosed herein and variants thereof (e.g., variants that retain function of the original protein), including variants of TROP2, variants of tubulin sequences, and variants of antibody variable domains (including individual variant CDRs), have amino acid homology, similarity, or identity of at least 80%, and more typically homologies or identities of at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, and almost 100% or 100%.

[00187] In a similar manner, “percent (%) nucleic acid sequence identity” with respect to the nucleic acid sequence of the antibodies and other proteins identified herein is defined as the percentage of nucleotide residues in a candidate sequence that are identical with the nucleotide residues in the coding sequence of the antigen-binding protein. A specific method uses the BLASTN module of WU-BLAST-2 set to the default parameters, with overlap span and overlap fraction set to 1 and 0.125, respectively.

[00188] As used herein, the term “solvent” refers to any liquid in which the product is at least partially soluble (solubility of product > 1 g / L).

[00189] As used herein, the term “isomer” refers to compounds with identical molecular formula but distinct spatial arrangement of atoms or bonds. Isomers include stereoisomers, cis-trans isomers, atropisomers, and tautomers.

[00190] As used herein, the term “stereoisomer” refers to both enantiomers and diastereomers.

[00191] It will be appreciated that certain compounds of this invention may exist as separate stereoisomers or enantiomers and / or mixtures of those stereoisomers or enantiomers. As used in the chemical structures disclosed herein, a “wedge” (^ )or “hash” ( •-''' ) bond to a stereogenic atom indicates a chiral center of known absolute stereochemistry (i.e., one stereoisomer). As used herein, a stereogenic atom that is notated with an (R) or (5) indicates the stereochemical designation of the stereogenic atom under the Cahn-Ingold-Prelog convention. As used in the chemical structures disclosed herein, a (“straight”) bond to a stereogenic atom indicates where there is a mixture (e.g., a racemate or enrichment). As used herein, two (“straight”) bonds to a double-bonded carbon indicates that the double bond possesses the E / Z stereochemistry as drawn.

[00192] Certain compounds disclosed herein may exist as tautomers and both tautomeric forms are intended, even though only a single tautomeric structure is depicted.

[00193] The terms “subject” and “patient” are used interchangeably herein to refer to any animal, such as any mammal, including but not limited to, humans, non-human primates, rodents, and the like. In some embodiments, the mammal is a mouse. In some embodiments, the mammal is a human.

[00194] The term “target-negative” or “target antigen-negative” refers to the absence of target antigen expression by a cell or tissue. The term “target-positive” or “target antigen-positive” refers to the presence of target antigen expression. For example, a cell or a cell line that does not express a target antigen may be described as target-negative, whereas a cell or cell line that expresses a target antigen may be described as target-positive.

[00195] The term “tumor associated calcium signal transducer 2,” “Trop2,” or “TROP2” as used herein, refers to any native form of human TROP2. The term encompasses full-length TROP2 (e.g., NCBI Reference Sequence: NP 002344.2; SEQ ID NO: 161), as well as any form of human TROP2 that results from cellular processing. The term also encompasses naturally occurring variants of TROP2, including but not limited to allelic variants and isoforms. TROP2 can be isolated from a human, or may be produced recombinantly or by synthetic methods.

[00196] The terms “tumor” and “neoplasm” refer to any mass of tissue that results from excessive cell growth or proliferation, either benign or malignant, including precancerous lesions.

[00197] As used herein, “to treat” or “therapeutic” and grammatically related terms, refer to any improvement of any consequence of disease, such as prolonged survival, less morbidity, and / or a lessening of side effects which are the byproducts of an alternative therapeutic modality. As is readily appreciated in the art, full eradication of disease is preferred but not a requirement for a treatment act. “Treatment” or “treat,” as used herein, refers to the administration of a described ADC to a subject, e.g., a patient. The treatment can be to cure, heal, alleviate, relieve, alter, remedy, ameliorate, palliate, improve, or affect the disorder, the symptoms of the disorder, or the predisposition toward the disorder, e.g., a cancer.

[00198] As used herein, “valine-citrulline-pABC,” “Val-Cit-pABC,” and “VCP,” are used interchangeably. As used herein, “valine-alanine-pABC,” “Val-Ala-pABC,” and “VAP” are used interchangeably.

[00199] Should the name of a compound conflict with the structure of the compound anywhere in the present application, the structure supersedes the name and is intended to be controlling. Anti-TROP2 Antibodies and Antigen-Binding Fragments

[00200] The present disclosure provides antibodies that specifically bind to TROP2 and may be used alone, e.g., formulated as therapeutic or diagnostic antibody compositions, e.g., for use in treating or detecting TROP-2 expressing cancers. The antibodies may be provided packaged or prepared for therapeutic use as antibodies, antigen-binding fragments thereof, or as portions of ADCs. Antibodies include, but are not limited to, those listed in Table 1, as well as antibodies comprising CDRs and / or variable domains from the listed antibodies.

[00201] The antibodies disclosed herein may bind to TROP2 with an affinity of < 1 pM, < 100 nM or <10 nM, or any amount in between, as measured by, e.g., BIAcore® analysis. In certain embodiments, the binding affinity is 1 pM to 500 pM. In some embodiments, the binding affinity is between 500 pM to 1 nM, or 1 nM to 10 nM.

[00202] In some embodiments, the antibodies are four-chain antibodies (also referred to as an immunoglobulin), comprising two heavy chains and two light chains. In some embodiments, the antibodies are two-chain half bodies (one light chain and one heavy chain), or antigen-binding fragments of an immunoglobulin.

[00203] Any antibody or antigen-binding fragment described herein may comprise part of a bispecific or multi-specific binding construct, e.g., a construct that can bind to at least one different antigen or additional epitope on TROP2.

[00204] In some embodiments, the antibodies are internalizing antibodies or internalizing antigenbinding fragments thereof. In some embodiments, the internalizing antibodies bind to TROP2 expressed on the surface of a cell and enter the cell upon or after binding. In some embodiments, the drug moiety of the ADC is released from the antibody moiety of the ADC after the ADC enters and is present in a cell expressing TROP2 (i.e., after the ADC has been internalized).

[00205] The antibodies disclosed herein that specifically bind a TROP2 protein may comprise three heavy chain CDRs (HCDR1, HCDR2, and HCDR3) having amino acid sequences selected from the HC CDRs listed in Table 2, infra, as defined by the Kabat numbering system, and three light chain CDRs (LCDR1, LCDR2, and LCDR3) having amino acid sequences selected from the LC CDRs listed in Table 2, infra, as defined by the Kabat numbering system. In some embodiments, the antibodies comprise three heavy chain CDRs (HCDR1, HCDR2, and HCDR3) having amino acid sequences selected from the HC CDRs listed in Table 4, infra, as defined by the IMGT numbering system, and three light chain CDRs (LCDR1, LCDR2, and LCDR3) having amino acid sequences selected from the LC CDRs listed in Table 4, infra, as defined by the IMGT numbering system.

[00206] In some embodiments, an antibody disclosed herein comprises a VH domain having an amino acid sequence selected from SEQ ID NOs: 53 to 56, 67 to 70, 79 to 83, 168, 174, 175, and 177 listed in Table 6, infra. In some embodiments, the antibody comprises a VL domain having an amino acid sequence selected from SEQ ID NOs: 57 to 66,71 to 78, 84 to 93,166, 167, 176, and 187 listed in Table 6, infra.

[00207] In some embodiments, an antigen-binding fragment disclosed herein retains TROP2 binding. In some embodiments, the antigen-binding fragment retains TROP2 binding by comprising three heavy chain CDRs (HCDR1, HCDR2, and HCDR3) comprising amino acid sequences selected from the HC CDRs listed in Table 2, infra, as defined by the Kabat numbering system, and three light chain CDRs (LCDR1, LCDR2, and LCDR3) comprising amino acid sequences selected from the LC CDRs listed in Table 2, infra, as defined by the Kabat numbering system. In some embodiments, the antigen-binding fragment comprises three heavy chain CDRs (HCDR1, HCDR2, and HCDR3) comprising amino acid sequences selected from the HC CDRs listed in Table 4, infra, as defined by the IMGT numbering system, and three light chain CDRs (LCDR1, LCDR2, and LCDR3) comprising amino acid sequences selected from the LC CDRs listed in Table 4, infra, as defined by the IMGT numbering system. In some embodiments, the antigen-binding fragments disclosed herein may retain TR0P2 binding by comprising a VH domain comprising an amino acid sequence selected from SEQ ID NOs: 53 to 56,67 to 70, 79 to 83, 168, 174, 175, and 177 listed in Table 6, infra, and a VL domain comprising an amino acid sequence selected from SEQ ID NOs: 57 to 66, 71 to 78, 84 to 93, 166, 167, 176, and 187 listed in Table 6, infra.

[00208] In some embodiments, the antibodies disclosed herein may comprise an IgG constant domain, e.g., an IgGl domain or an IgGl domain that has been modified to reduce binding to an Fc receptor, e.g., an Fey receptor (FcyR) as compared to a wild-type constant domain-containing (e.g., a wild-type IgGl-containing) antibody. Reduced binding to an Fc receptor, e.g., to an FcyR, can be measured as a comparison to the binding of the wild-type antibody without the modification to the same receptor. Reduced binding may be by at least about 10-fold, and preferably at least about 100fold as compared to the antibody containing the wild-type constant domain. Reduced binding may be measured using any assay known in the art. For example, reduced binding may be measured using a fluorescence resonance energy transfer (FRET) assay.

[00209] In some embodiments, an antibody disclosed herein may comprise an IgGl comprising the mutations L234A, L235A, P238S, H268Q, and / or K274Q (e.g., comprising all of those mutations) according to the EU numbering. See, e.g.,Wang et al. (2017) Protein Cell 9(l):63-73; Vafa et al. (2014) Methods 1; 65(1): 114-26; Tametal. (lOXT) Antibodies 1; 6(3):12. Without being bound by theory, these mutations may reduce binding of the antibody to a Fey receptor (FcyR), which may reduce non-antigen mediated uptake of antibodies or ADCs by immune cells, such as neutrophils, thus reducing neutropenia. Reduced neutropenia may be measured using any assay known in the art. For example, reduced neutropenia may be measured using a flow cytometry assay, as illustrated in the Examples provided herein.

[00210] In some embodiments, an antibody that specifically binds a TROP2 protein comprises a heavy chain having an amino acid sequence selected from SEQ ID NOs: 94 to 105, 116 to 127, 136 to 150, 171 to 173, 178 to 186, 380, and 381 listed in Table 8, infra. In some embodiments, an antibody that specifically binds a TROP2 protein comprises a light chain having an amino acid sequence selected from SEQ ID NOs: 106 to 115, 128 to 135, 151 to 160, 169, 170, 188, and 189 listed in Table 8, infra.

[00211] Amino acid and nucleic acid sequences of exemplary antibodies of the present disclosure are set forth in Tables 1-9. Table 1. Antibodies inAb Type Target IgG chain SEQ ID NO: Amino acid sequence of variable region 16K21 rabbit human TROP2 Heavy chain 374 QSLEESGGRLVTPGTPLTLTCTVSGFSL SYNAMSWVRQAPGKGLEWIGYIYSSDTT YYATWAKGRFTISKTS T TVDLKIT S PT T EDTATYFCARDIGTAYYTFNIWGPGTLV TVSS 16K21 rabbit human TROP2 Light chain 375 AYDMTQTPASVEVAVGGTVTIKCQASQT IGSDLNWYQQKLGQPPKLLIYRASTLAS GVSSRFKGSGSGTQFTLTISDLECADAA TYYCQQGYSMTDVENVFGGGTEVWK 17124 rabbit human TROP2 Heavy chain 376 QSVEESGGRLVTPGTPLTLTCTVSGIDL SRHAMSWVRQAPGEGLEWIGIIYGSGST FYASWAKGRFTISKTSATMDLKIT S PT T EDTAIYFCARTMWTDSSVFLNIWGPGTL VTVSS 17124 rabbit human TROP2 Light chain 377 AQVLTQIPS S T SAAVGGTVTINCQASPS VYNNKNLAWFQKKPGQPPKLLIYEASKV ASGVSSRFKGSGSGTQFTLTISGVQCDD AATYYCQGEFSWSSGDLIAFGGGTEVW K 20E16 rabbit human TROP2 Heavy chain 378 QEQLVESGGGLVQPGGSLKLSCKASGLD FNKYGVSWVRQAPGKGPEWIGFIDPVFG NTVYASWVNGRFTISSHNAQNTLYLQLT SLTAADTATYFCVRWNSGWGNLWGPGTL VTVSS 20E16 rabbit human TROP2 Light chain 379 AIVMTQTPSSVEAAVGGTVTIKCQASQS IVTYLAWYQQKPGQPPKLLIYGASNLES GVPSRFRGTGSGTEFTLTISGMKAEDAA TYYCQSGDYSAGLTFGAGTKVETK Bolded text indicates amino acid positions corresponding to CDR sequences according to the Kabat system; underlined text indicates amino acid positions corresponding to CDR sequences according to the IMGT system. Text that is neither bolded nor underlined correspond to the rabbit-specific framework regions.

[00212] In some embodiments, the antibodies listed in Table 1 are humanized by replacing the rabbitspecific framework regions with human-specific framework regions. In some embodiments, a variant of a humanized antibody comprises three heavy chain CDRs (HCDR1, HCDR2, and HCDR3) selected from the CDR sequences listed in Table 2, infra, according to the Kabat system. For example, a humanized variant of 16K21 may comprise three heavy chain CDRs, wherein the HCDR1 comprises SEQ ID NO: 1, the HCDR2 comprises SEQ ID NO: 2 or SEQ ID NO: 3, and the HCDR3 comprises SEQ ID NO: 4. In some embodiments, a variant of a humanized antibody comprises three light chain CDRs (LCDR1, LCDR2, and LCDR3) selected from the CDR sequences listed in Table 2, infra, according to the Kabat system. For example, a humanized variant of 16K21 may comprise three light chain CDRs, wherein the LCDR1 comprises SEQ ID NO: 5, 6, 7, or 8, the LCDR2 comprises SEQ ID NO: 9, and the LCDR3 comprises SEQ ID NO: 10.

[00213] In some embodiments, a variant of a humanized antibody comprises three heavy chain CDRs (HCDR1, HCDR2, and HCDR3) selected from the CDR sequences listed in Table 4, infra, according to the IMGT system. For example, a humanized variant of 16K21 may comprise three heavy chain CDRs, wherein the HCDR1 comprises SEQ ID NO: 11, the HCDR2 comprises SEQ ID NO: 12, and the HCDR3 comprises SEQ ID NO: 13. In some embodiments, a variant of a humanized antibody comprises three light chain CDRs (LCDR1, LCDR2, and LCDR3) selected from the CDR sequences listed in Table 4, infra, according to the IMGT system. For example, a humanized variant of 16K21 may comprise three light chain CDRs, wherein the LCDR1 comprises SEQ ID NO: 14 or 15, the LCDR2 comprises SEQ ID NO: 16, and the LCDR3 comprises SEQ ID NO: 17. Table 2. Amino acid sequences of inAb Kabat CDRs Parent mAb IgG chain SEQ ID NO Amino acid sequence Heavy chain CDRs 16K21 HC CDR1 1 YNAMS HCCDR2 2 YIYSSDTTYYATWAKG 3 YIYSSDTTYYADSVKG HCCDR3 4 DIGTAYYTFNI 17124 HC CDR1 18 RHANS HCCDR2 19 IIYGSGSTFYASWAKG 20 IIYGSGSTFYADSVKG HCCDR3 21 TMWTDSSVFLNI 20E16 HC CDR1 34 KYGVS 35 KYANS HCCDR2 36 FIDPVFGNTVYASWVNG 37 FIDPVFGNTVYADSVKG HCCDR3 38 WNSGWGNL Light chain CDRs 16K21 LC CDR1 5 QASQTIGSDLN 6 RASQTIGSDLN 7 QASQSIGSDLN 8 RASQSIGSDLN LCCDR2 9 RASTLAS LCCDR3 10 QQGYSMTDVENV 17124 LC CDR1 22 QASPSVYNNKNLA 23 RASPSVYNNKNLA LCCDR2 24 EASKVAS 25 DASKVAS LCCDR3 26 QGEFSWSSGDLIA 20E16 LC CDR1 39 QASQSIVTYLA 40 QASQSIVTYLN Parent mAb IgG chain SEQ ID NO Amino acid sequence LC CDR2 41 GASNLES 42 GASNLET LCCDR3 43 QSGDYSAGLT Table 3. Nucleic acid sequences encoding mAb Kabat CDRs ‘arent mAb gG chain ;eq id no Nucleic acid sequence leavy chain CDRs 16K21 HC CDR1 190 TACAATGCCATGAGC HCCDR2 191 TACATCTACAGCAGCGACACCACCTACTACGCCACAT GGGCCAAGGGC 192 TACATCTACAGCAGCGACACCACCTACTACGCCGACA GCGTTAAGGGC HCCDR3 193 GATATCGGCACCGCCTACTACACCTTCAACATC 17124 HC CDR1 194 AGACACGCCATGAGC HCCDR2 195 ATCATCTACGGCAGCGGCAGCACCTTTTACGCCTCTT GGGCCAAGGGC 196 ATCATCTACGGCAGCGGCAGCACCTTTTACGCCGACA GCGTTAAGGGC HCCDR3 197 ACCATGTGGACCGACAGCAGCGTGTTCCTGAATATC 20E16 HC CDR1 198 AAATATGGCGTGTCC 199 AAATATGCCATGTCC HCCDR2 200 TTCATCGACCCCGTGTTCGGCAATACCGTGTACGCCT CTTGGGTCAACGGC 201 TTCATCGACCCCGTGTTCGGCAATACCGTGTACGCCG ACAGCGTTAAGGGC HCCDR3 202 TGGAACAGCGGCTGGGGCAATCTT Light chain CDRs 16K21 LC CDR1 203 CAGGCCAGCCAGACCATCGGCAGCGACCTGAAT 204 AGAGCCAGCCAGACCATCGGCAGCGACCTGAAT 205 CAGGCCAGCCAGAGCATCGGCAGCGACCTGAAT 206 AGAGCCAGCCAGAGCATCGGCAGCGACCTGAAT LCCDR2 207 AGAGCC T C TACAC T GGCCAGC LCCDR3 208 CAGCAGGGCTACAGCATGACCGACGTGGAAAATGTG 17124 LC CDR1 209 CAGGCTAGCCCCAGCGTGTACAACAACAAGAACCTGG CC 210 AGAGCTAGCCCCAGCGTGTACAACAACAAGAACCTGG CC LCCDR2 211 GAAGCCAGCAAAGTGGCCAGC 212 GATGCCAGCAAAGTGGCCAGC LCCDR3 213 CAGGGCGAGTTTAGCTGGTCCTCTGGCGATCTGATTG CC 20E16 LC CDR1 214 CAGGCCAGCCAGAGCAT CGT GACC TAT C T GGCC 215 CAGGCCAGCCAGAGCAT CGT GACC TAT C T GAAT LCCDR2 216 GGCGCCAGCAATCTGGAAAGC 217 GGCGCCAGCAATCTGGAAACC LCCDR3 218 CAGAGCGGCGATTATTCTGCCGGCCTTACA Table 4. Amino acid sequences of mAb IMGT CDRs Parent mAb |lgG chain     |SEQ ID NO Amino acid sequence Heavy chain CDRs 16K21 HC CDR1 11 GFSLSYNA HCCDR2 12 IYSSDTT HCCDR3 13 ARDIGTAYYTFNI 17124 HC CDR1 27 GIDLSRHA HCCDR2 28 IYGSGST HCCDR3 29 ARTMWTDSSVFLNI 20E16 HC CDR1 44 GLDFNKYG 45 GLDFNKYA HCCDR2 46 IDPVFGNT HC CDR3 47 VRWNSGWGNL 48 AKWNSGWGNL 49 ARWNSGWGNL Light chain CDRs 16K21 LC CDR1 14 QTIGSD 15 QSIGSD LC CDR2 16 RAS LC CDR3 17 QQGYSMTDVENV 17124 LC CDR1 30 PSVYNNKN LCCDR2 31 EAS 32 DAS LCCDR3 33 QGEFSWSSGDLIA 20E16 LC CDR1 50 QSIVTY LC CDR2 51 GAS LCCDR3 52 QSGDYSAGLT Table 5. Nucleic acid sequences encoding mAb IMGT CDRs Parent mAb |lgG chain |SEQ ID NO Nucleic acid sequence Heavy chain CDRs 16K21 HC CDR1 219 GGC T T CAGCCT GAGC TACAAT GCC HCCDR2 220 ATCTACAGCAGCGACACCACC HCCDR3 221 GCCAGAGATATCGGCACCGCCTACTACACCTTCA ACATC 17124 HC CDR1 222 GGCATCGATCTGAGCAGACACGCC HCCDR2 223 ATCTACGGCAGCGGCAGCACC HC CDR3 224 GCCAGAACCATGTGGACCGACAGCAGCGTGTTCC TGAATATC 20E16 HC CDR1 225 GGCC T GGAC T T C AACAAAT AT GGC 226 GGCC T GGAC T T C AACAAAT AT GCC HCCDR2 227 ATCGACCCCGTGTTCGGCAATACC HC CDR3 228 GT GCGT T GGAACAGCGGC T GGGGCAAT C T T 229 GCCAAAT GGAACAGCGGC T GGGGCAAT C T T 230 GCCCGTTGGAACAGCGGCTGGGGCAATCTT Light chain CDRs 16K21 LC CDR1 231 CAGACCATCGGCAGCGAC 232 CAGAGCATCGGCAGCGAC LCCDR2 233 AGAGCCTCT Parent mAb IgG chain SEQ ID NO Nucleic acid sequence LC CDR3 234 CAGCAGGGCTACAGCATGACCGACGTGGAAAATG TG 17124 LC CDR1 235 CCCAGCGTGTACAACAACAAGAAC LCCDR2 236 GAAGCCAGC 237 GATGCCAGC LC CDR3 238 CAGGGCGAGTTTAGCTGGTCCTCTGGCGATCTGA TTGCC 20E16 LC CDR1 239 CAGAGCATCGTGACCTAT LCCDR2 240 GGCGCCAGC LCCDR3 241 CAGAGCGGCGAT TAT TCTGCCGGCCT TACA Table 6. Amino acid sequences of mAb variable regions Parent mAb IgG chain SEQ ID NO Amino acid sequence 16K21 HC1 53 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAMSW VRQAPGKGLEWIGYIYS S DT TYYATWAKGRFTISRH NSKNTLYLQMNSLRAEDTAVYYCARDIGTAYYTFNI WGPGTLVTVSS HC2 54 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAMSW VRQAPGKGLEWVSYIYS S DT TYYATWAKGRFTISRH NSKNTLYLQMNSLRAEDTAVYYCARDIGTAYYTFNI WGPGTLVTVSS HC3 55 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAMSW VRQAPGKGLEWIGYIYS S DT TYYADSVKGRFTISRH NSKNTLYLQMNSLRAEDTAVYYCARDTGTAYYTFNT WGPGTLVTVSS HC4 56 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAMSW VRQAPGKGLEWVSYIYS S DT TYYADSVKGRFTISRH NSKNTLYLQMNSLRAEDTAVYYCARDIGTAYYTFNI WGPGTLVTVSS HC5 174 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAMSW VRQAPGKGLEWVSYIYS S DT TYYADSVKGRFTISRH NSKNTLYLQMNSLRAEDTAVYYCARDIGTAYYTFNI WGQGTLVTVSS HC6 175 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAMSW VRQAPGKGLEWIGYIYS S DT TYYADSVKGRFTISRH NSKNTLYLQMNSLRAEDTAVYYCARDIGTAYYTFNI WGQGTLVTVSS LC1 57 AY DMT Q S P S S L SASVGDRVTITCQASQTTGS DLNWY QQKPGKAPKLLIYRASTLASGVPSRFSGSGSGTDFT LTISSLQPEDFATYYCQQGYSMTDVENVFGGGTKVE IK LC2 58 DIQMTQS PSSLSASVGDRVTITCQASQTTGS DLNWY QQKPGKAPKLLIYRASTLASGVPSRFSGSGSGTDFT LTISSLQPEDFATYYCQQGYSMTDVENVFGGGTKVE IK LC3 166 DYQMTQSPSSLSASVGDRVTITCQASQTIGSDLNWY QQKPGKAPKLLIYRASTLASGVPSRFSGSGSGTDFT LTISSLQPEDFATYYCQQGYSMTDVENVFGGGTKVE IK LC4 59 DIQMTQS PSSLSASVGDRVTITCRASQTIGS DLNWY QQKPGKAPKLLIYRASTLASGVPSRFSGSGSGTDFT Parent mAb IgG chain SEQ ID NO Amino acid sequence LTISSLQPEDFATYYCQQGYSMTDVENVFGGGTKVE IK LC5 60 DIQMTQS PSSLSASVGDRVTITCQASQSIGS DLNWY QQKPGKAPKLLIYRASTLASGVPSRFSGSGSGTDFT LTISSLQPEDFATYYCQQGYSMTDVENVFGGGTKVE IK LC6 61 DIQMTQS PSSLSASVGDRVTITCRASQSIGS DLNWY QQKPGKAPKLLIYRASTLASGVPSRFSGSGSGTDFT LTISSLQPEDFATYYCQQGYSMTDVENVFGGGTKVE IK LC1-RESPECT-L 62 AY DMT Q S P S S L SASVGDRVTITCQASQTIGSDLNWY QQKPGKAPKLLIYRASTLASGVPSRFSGSGSGTDFT LTISSLQCEDVATYYCQQGYSMTDVENVFGGGTKVE IK LC2-RESPECT-L 63 DIQMTQS PSSLSASVGDRVTITCQASQTIGSDLNWY QQKPGKAPKLLIYRASTLASGVPSRFSGSGSGTDFT LTISSLQCEDVATYYCQQGYSMTDVENVFGGGTKVE IK LC3-RESPECT-L 176 DYQMTQSPSSLSASVGDRVTITCQASQTIGSDLNWY QQKPGKAPKLLIYRASTLASGVPSRFSGSGSGTDFT LTISSLQCEDVATYYCQQGYSMTDVENVFGGGTKVE IK LC4-RESPECT-L 64 DIQMTQS PSSLSASVGDRVTITCRASQTIGSDLNWY QQKPGKAPKLLIYRASTLASGVPSRFSGSGSGTDFT LTISSLQCEDVATYYCQQGYSMTDVENVFGGGTKVE IK LC5-RESPECT-L 65 DIQMTQS PSSLSASVGDRVTITCQASQSIGS DLNWY QQKPGKAPKLLIYRASTLASGVPSRFSGSGSGTDFT LTISSLQCEDVATYYCQQGYSMTDVENVFGGGTKVE IK LC6-RESPECT-L 66 DIQMTQS PSSLSASVGDRVTITCRASQSIGS DLNWY QQKPGKAPKLLIYRASTLASGVPSRFSGSGSGTDFT LTISSLQCEDVATYYCQQGYSMTDVENVFGGGTKVE IK 17124 HC1 67 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAMSW VRQAPGKGLEWIGIIYGSGS T FYASWAKGRFTISRD NSKNTLYLQMNSLRAEDTAVYYCARTMWTDSSVFLN IWGPGTLVTVSS HC2 68 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAMSW VRQAPGKGLEWVS11YGSGS T FYASWAKGRFTISRD NSKNTLYLQMNSLRAEDTAVYYCARTMWTDSSVFLN IWGPGTLVTVSS HC3 69 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAMSW VRQAPGKGLEWIGIIYGSGS T FYADSVKGRFTISRD NSKNTLYLQMNSLRAEDTAVYYCARTMWTDSSVFLN IWGPGTLVTVSS HC4 70 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAMSW VRQAPGKGLEWVS11YGSGS T FYADSVKGRFTISRD NSKNTLYLQMNSLRAEDTAVYYCARTMWTDSSVFLN IWGPGTLVTVSS HC5 177 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAMSW VRQAPGKGLEWVS11YGSGST FYADSVKGRFTISRD NSKNTLYLQMNSLRAEDTAVYYCARTMWTDSSVFLN IWGQGTLVTVSS Parent mAb IgG chain SEQ ID NO Amino acid sequence LC1 71 AQ VMT QS P S T LSASVGDRVTITCQAS PSVYNNKNLA WYQQKPGKAPKLLIYEASKVASGVPSRFSGSGSGTE FTLTISSLQPDDFATYYCQGEFSWSSGDLIAFGGGT KVEIK LC2 72 DIQMTQS PSTLSASVGDRVTITCQAS PSVYNNKNLA WYQQKPGKAPKLLIYEASKVASGVPSRFSGSGSGTE FTLTISSLQPDDFATYYCQGEFSWSSGDLIAFGGGT KVEIK LC3 167 DQQMTQS PSTLSASVGDRVTITCQAS PSVYNNKNLA WYQQKPGKAPKLLIYEASKVASGVPSRFSGSGSGTE FTLTISSLQPDDFATYYCQGEFSWSSGDLIAFGGGT KVEIK LC4 73 DIQMTQS PSTLSASVGDRVTITCRAS PSVYNNKNLA WYQQKPGKAPKLLIYEASKVASGVPSRFSGSGSGTE FTLTISSLQPDDFATYYCQGEFSWSSGDLIAFGGGT KVEIK LC5 74 DIQMTQS PSTLSASVGDRVTITCQAS PSVYNNKNLA WYQQKPGKAPKLLIYDASKVASGVPSRFSGSGSGTE FTLTISSLQPDDFATYYCQGEFSWSSGDLIAFGGGT KVEIK LC1-RESPECT-L 75 AQVMT Q S P S T L SASVGDRVTITCQAS PSVYNNKNLA WYQQKPGKAPKLLIYEASKVASGVPSRFSGSGSGTE FTLTISSLQCDDVATYYCQGEFSWSSGDLIAFGGGT KVEIK LC2-RESPECT-L 76 DIQMTQS PSTLSASVGDRVTITCQAS PSVYNNKNLA WYQQKPGKAPKLLIYEASKVASGVPSRFSGSGSGTE FTLTISSLQCDDVATYYCQGEFSWSSGDLIAFGGGT KVEIK LC3-RESPECT-L 187 DQQMT Q S P S T L SASVGDRVTITCQAS PSVYNNKNLA WYQQKPGKAPKLLIYEASKVASGVPSRFSGSGSGTE FTLTISSLQCDDVATYYCQGEFSWSSGDLIAFGGGT KVEIK LC4-RESPECT-L 77 DIQMTQS PSTLSASVGDRVTITCRAS PSVYNNKNLA WYQQKPGKAPKLLIYEASKVASGVPSRFSGSGSGTE FTLTISSLQCDDVATYYCQGEFSWSSGDLIAFGGGT KVEIK LC5-RESPECT-L 78 DIQMTQS PSTLSASVGDRVTITCQAS PSVYNNKNLA WYQQKPGKAPKLLIYDASKVASGVPSRFSGSGSGTE FTLTISSLQCDDVATYYCQGEFSWSSGDLIAFGGGT KVEIK 20E16 HC1 79 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGVSW VRQAPGKGLEWIGFIDPVFGNTVYASWVNGRFTISR DNSKNTLYLQMNSLRAEDTAVYYCVRWNSGWGNLWG PGTLVTVSS HC2 168 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGVSW VRQAPGKGLEWVS FIDPVFGNTVYASWVNGRFTISR DNSKNTLYLQMNSLRAEDTAVYYCVRWNSGWGNLWG PGTLVTVSS HC3 80 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGVSW VRQAPGKGLEWIGFIDPVFGNTVYADSVKGRFTISR DNSKNTLYLQMNSLRAEDTAVYYCVRWNSGWGNLWG PGTLVTVSS HC4 81 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYAMSW VRQAPGKGLEWIGFIDPVFGNTVYADSVKGRFTISR Parent mAb IgG chain SEQ ID NO Amino acid sequence DNSKNTLYLQMNSLRAEDTAVYYCVRWNSGWGNLWG PGTLVTVSS HC5 82 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGVSW VRQAPGKGLEWIGFIDPVFGNTVYADSVKGRFTISR DNSKNTLYLQMNSLRAEDTAVYYCAKWNSGWGNLWG PGTLVTVSS HC6 83 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGVSW VRQAPGKGLEWIGFIDPVFGNTVYADSVKGRFTISR DNSKNTLYLQMNSLRAEDTAVYYCARWNSGWGNLWG PGTLVTVSS LC1 84 AI VMT Q S P S S L SASVGDRVTITCQASQSI VT YL AWY QQKPGKAPKLLIYGASNLESGVPSRFSGSGSGTDFT FTISSLQPEDIATYYCQSGDYSAGLTFGGGTKVEIK LC2 85 DIQMTQS PSSLSASVGDRVTITCQASQSIVTYLAWY QQKPGKAPKLLIYGASNLESGVPSRFSGSGSGTDFT FTISSLQPEDIATYYCQSGDYSAGLTFGGGTKVEIK LC3 86 DIQMTQS PSSLSASVGDRVTITCQASQSIVTYLNWY QQKPGKAPKLLIYGASNLESGVPSRFSGSGSGTDFT FTISSLQPEDIATYYCQSGDYSAGLTFGGGTKVEIK LC4 87 DIQMTQS PSSLSASVGDRVTITCQASQSIVTYLAWY QQKPGKAPKLLIYGASNLETGVPSRFSGSGSGTDFT FTISSLQPEDIATYYCQSGDYSAGLTFGGGTKVEIK LC5 88 DIQMTQS PSSLSASVGDRVTITCQASQSIVTYLNWY QQKPGKAPKLLIYGASNLETGVPSRFSGSGSGTDFT FTISSLQPEDIATYYCQSGDYSAGLTFGGGTKVEIK LC1-RESPECT-L 89 AIVMT Q S P S S L SASVGDRVTITCQASQSIVTYLAWY QQKPGKAPKLLIYGASNLESGVPSRFSGSGSGTDFT FTISSLQCEDIATYYCQSGDYSAGLTFGGGTKVEIK LC2-RESPECT-L 90 DIQMTQS PSSLSASVGDRVTITCQASQSIVTYLAWY QQKPGKAPKLLIYGASNLESGVPSRFSGSGSGTDFT FTISSLQCEDIATYYCQSGDYSAGLTFGGGTKVEIK LC3-RESPECT-L 91 DIQMTQS PSSLSASVGDRVTITCQASQSIVTYLNWY QQKPGKAPKLLIYGASNLESGVPSRFSGSGSGTDFT FTISSLQCEDIATYYCQSGDYSAGLTFGGGTKVEIK LC4-RESPECT-L 92 DIQMTQS PSSLSASVGDRVTITCQASQSIVTYLAWY QQKPGKAPKLLIYGASNLETGVPSRFSGSGSGTDFT FTISSLQCEDIATYYCQSGDYSAGLTFGGGTKVEIK LC5-RESPECT-L 93 DIQMTQS PSSLSASVGDRVTITCQASQSIVTYLNWY QQKPGKAPKLLIYGASNLETGVPSRFSGSGSGTDFT FTISSLQCEDIATYYCQSGDYSAGLTFGGGTKVEIK Table 7. Nucleic acid sequences encoding mAb variable regions Parent mAb IgG chain SEQ ID NO Nucleic acid sequence 16K21 HC1 242 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTGG TTCAACCTGGCGGAAGCCTGAGACTGTCTTGTGC CGCCTCTGGCTTCAGCCTGAGCTACAATGCCATG AGCTGGGTTCGACAGGCCCCTGGCAAAGGACTGG AATGGATCGGCTACATCTACAGCAGCGACACCAC C TAC TACGCCACAT GGGCCAAGGGCAGAT T CACC ATCAGCCGGCACAACAGCAAGAACACCCTGTACC TGCAGATGAACAGCCTGAGAGCCGAGGACACCGC Parent mAb IgG chain SEQ ID NO Nucleic acid sequence CGTGTACTACTGTGCCAGAGATATCGGCACCGCC TAC TACACCT T CAACATC T GGGGCCC T GGCACAC TGGTTACAGTGTCTAGC HC2 243 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTGG TTCAACCTGGCGGAAGCCTGAGACTGTCTTGTGC CGCCTCTGGCTTCAGCCTGAGCTACAATGCCATG AGCTGGGTTCGACAGGCCCCTGGCAAAGGACTGG AATGGGTGAGCTACATCTACAGCAGCGACACCAC C TAC TACGCCACAT GGGCCAAGGGCAGAT T CACC ATCAGCCGGCACAACAGCAAGAACACCCTGTACC TGCAGATGAACAGCCTGAGAGCCGAGGACACCGC CGTGTACTACTGTGCCAGAGATATCGGCACCGCC T AC T AC ACCT T C AACATC T GGGGCCC T GGC ACAC TGGTTACAGTGTCTAGC HC3 244 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTGG TTCAACCTGGCGGAAGCCTGAGACTGTCTTGTGC CGCCTCTGGCTTCAGCCTGAGCTACAATGCCATG AGCTGGGTTCGACAGGCCCCTGGCAAAGGACTGG AATGGATCGGCTACATCTACAGCAGCGACACCAC CTACTACGCCGACAGCGTTAAGGGCAGATTCACC ATCAGCCGGCACAACAGCAAGAACACCCTGTACC TGCAGATGAACAGCCTGAGAGCCGAGGACACCGC CGTGTACTACTGTGCCAGAGATATCGGCACCGCC T AC T AC ACCT T CAACATC T GGGGCCC T GGC ACAC TGGTTACAGTGTCTAGC HC4 245 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTGG TTCAACCTGGCGGAAGCCTGAGACTGTCTTGTGC CGCCTCTGGCTTCAGCCTGAGCTACAATGCCATG AGCTGGGTTCGACAGGCCCCTGGCAAAGGACTGG AATGGGTGAGCTACATCTACAGCAGCGACACCAC CTACTACGCCGACAGCGTTAAGGGCAGATTCACC ATCAGCCGGCACAACAGCAAGAACACCCTGTACC TGCAGATGAACAGCCTGAGAGCCGAGGACACCGC CGTGTACTACTGTGCCAGAGATATCGGCACCGCC T AC T AC ACCT T CAACATC T GGGGCCC T GGC ACAC TGGTTACAGTGTCTAGC HC5 246 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTGG TTCAACCTGGCGGAAGCCTGAGACTGTCTTGTGC CGCCTCTGGCTTCAGCCTGAGCTACAATGCCATG AGCTGGGTTCGACAGGCCCCTGGCAAAGGACTGG AATGGGTGAGCTACATCTACAGCAGCGACACCAC CTACTACGCCGACAGCGTTAAGGGCAGATTCACC ATCAGCCGGCACAACAGCAAGAACACCCTGTACC TGCAGATGAACAGCCTGAGAGCCGAGGACACCGC CGTGTACTACTGTGCCAGAGATATCGGCACCGCC TACTACACCTTCAACATCTGGGGCCAGGGCACAC TGGTTACAGTGTCTAGC HC6 247 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTGG TTCAACCTGGCGGAAGCCTGAGACTGTCTTGTGC CGCCTCTGGCTT CAGCC T GAGCTACAAT GCCAT G Parent mAb IgG chain SEQ ID NO Nucleic acid sequence AGCTGGGTTCGACAGGCCCCTGGCAAAGGACTGG AATGGATCGGCTACATCTACAGCAGCGACACCAC CTACTACGCCGACAGCGTTAAGGGCAGATTCACC ATCAGCCGGCACAACAGCAAGAACACCCTGTACC TGCAGATGAACAGCCTGAGAGCCGAGGACACCGC CGTGTACTACTGTGCCAGAGATATCGGCACCGCC TACTACACCTTCAACATCTGGGGCCAGGGCACAC TGGTTACAGTGTCTAGC LC1 248 GCTTACGATATGACACAGAGCCCTAGCAGCCTGA GCGCCTCTGTGGGCGATAGAGTGACAATTACCTG TCAGGCCAGCCAGACCATCGGCAGCGACCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC T GC T GAT C T AC AGAGCCT C T ACAC TGGCC AGCGG CGTGCCAAGCAGATTTTCTGGCTCTGGCAGCGGC ACCGACTTCACCCTGACAATTAGTAGCCTGCAGC C TGAGGAC T T T GCCACCTAT TAC T GT CAGCAGGG CTACAGCATGACCGACGTGGAAAATGTGTTCGGC GGAGGCACCAAGGTGGAAATCAAG LC2 249 GACATCCAGATGACACAGAGCCCTAGCAGCCTGA GCGCCTCTGTGGGCGATAGAGTGACAATTACCTG TCAGGCCAGCCAGACCATCGGCAGCGACCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC T GC T GAT C T AC AGAGCCT C T ACAC TGGCC AGCGG CGTGCCAAGCAGATTTTCTGGCTCTGGCAGCGGC ACCGACTTCACCCTGACAATTAGTAGCCTGCAGC C TGAGGAC T T T GCCACCTAT TAC T GT CAGCAGGG CTACAGCATGACCGACGTGGAAAATGTGTTCGGC GGAGGCACCAAGGTGGAAATCAAG LC3 250 GACTACCAGATGACACAGAGCCCTAGCAGCCTGA GCGCCTCTGTGGGCGATAGAGTGACAATTACCTG TCAGGCCAGCCAGACCATCGGCAGCGACCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC T GC T GAT C T AC AGAGCCT C T ACAC TGGCC AGCGG CGTGCCAAGCAGATTTTCTGGCTCTGGCAGCGGC ACCGACTTCACCCTGACAATTAGTAGCCTGCAGC C TGAGGAC T T T GCCACCTAT TAC T GT CAGCAGGG CTACAGCATGACCGACGTGGAAAATGTGTTCGGC GGAGGCACCAAGGTGGAAATCAAG LC4 251 GACATCCAGATGACACAGAGCCCTAGCAGCCTGA GCGCCTCTGTGGGCGATAGAGTGACAATTACCTG TAGAGCCAGCCAGACCATCGGCAGCGACCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC T GC T GAT C T AC AGAGCCT C T ACAC TGGCC AGCGG CGTGCCAAGCAGATTTTCTGGCTCTGGCAGCGGC ACCGACTTCACCCTGACAATTAGTAGCCTGCAGC C TGAGGAC T T T GCCACCTAT TAC T GT CAGCAGGG CTACAGCATGACCGACGTGGAAAATGTGTTCGGC GGAGGCACCAAGGTGGAAATCAAG LC5 252 GACATCCAGATGACACAGAGCCCTAGCAGCCTGA GCGCCTCTGTGGGCGATAGAGTGACAATTACCTG TCAGGCCAGCCAGAGCATCGGCAGCGACCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC TGCTGATCTACAGAGCCTCTACACTGGCCAGCGG CGTGCCAAGCAGATTTTCTGGCTCTGGCAGCGGC Parent mAb IgG chain SEQ ID NO Nucleic acid sequence ACCGACTTCACCCTGACAATTAGTAGCCTGCAGC CTGAGGACTTTGCCACCTATTACTGTCAGCAGGG CTACAGCATGACCGACGTGGAAAATGTGTTCGGC GGAGGCACCAAGGTGGAAATCAAG LC6 253 GACATCCAGATGACACAGAGCCCTAGCAGCCTGA GCGCCTCTGTGGGCGATAGAGTGACAATTACCTG TAGAGCCAGCCAGAGCATCGGCAGCGACCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC T GC T GAT C T AC AGAGCCT C T ACAC TGGCC AGCGG CGTGCCAAGCAGATTTTCTGGCTCTGGCAGCGGC ACCGACTTCACCCTGACAATTAGTAGCCTGCAGC C TGAGGAC T T T GCCACCTAT TAC T GT CAGCAGGG CTACAGCATGACCGACGTGGAAAATGTGTTCGGC GGAGGCACCAAGGTGGAAATCAAG LC1-RESPECT- L 254 GCTTACGATATGACACAGAGCCCTAGCAGCCTGA GCGCCTCTGTGGGCGATAGAGTGACAATTACCTG TCAGGCCAGCCAGACCATCGGCAGCGACCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC T GC T GAT C T AC AGAGCCT C T ACAC TGGCC AGCGG CGTGCCAAGCAGATTTTCTGGCTCTGGCAGCGGC ACCGACTTCACCCTGACAATTAGTAGCCTGCAGT GCGAGGACGTGGCCACCTATTACTGTCAGCAGGG CTACAGCATGACCGACGTGGAAAATGTGTTCGGC GGAGGCACCAAGGTGGAAATCAAG LC2-RESPECT- L 255 GACATCCAGATGACACAGAGCCCTAGCAGCCTGA GCGCCTCTGTGGGCGATAGAGTGACAATTACCTG TCAGGCCAGCCAGACCATCGGCAGCGACCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC T GC T GAT C T AC AGAGCCT C T ACAC TGGCC AGCGG CGTGCCAAGCAGATTTTCTGGCTCTGGCAGCGGC ACCGACTTCACCCTGACAATTAGTAGCCTGCAGT GCGAGGACGTGGCCACCTATTACTGTCAGCAGGG CTACAGCATGACCGACGTGGAAAATGTGTTCGGC GGAGGCACCAAGGTGGAAATCAAG LC3-RESPECT- L 256 GACTACCAGATGACACAGAGCCCTAGCAGCCTGA GCGCCTCTGTGGGCGATAGAGTGACAATTACCTG TCAGGCCAGCCAGACCATCGGCAGCGACCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC T GC T GAT C T AC AGAGCCT C T ACAC TGGCC AGCGG CGTGCCAAGCAGATTTTCTGGCTCTGGCAGCGGC ACCGACTTCACCCTGACAATTAGTAGCCTGCAGT GCGAGGACGTGGCCACCTATTACTGTCAGCAGGG CTACAGCATGACCGACGTGGAAAATGTGTTCGGC GGAGGCACCAAGGTGGAAATCAAG LC4-RESPECT- L 257 GACATCCAGATGACACAGAGCCCTAGCAGCCTGA GCGCCTCTGTGGGCGATAGAGTGACAATTACCTG TAGAGCCAGCCAGACCATCGGCAGCGACCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC T GC T GAT C T AC AGAGCCT C T ACAC TGGCC AGCGG CGTGCCAAGCAGATTTTCTGGCTCTGGCAGCGGC ACCGACTTCACCCTGACAATTAGTAGCCTGCAGT GCGAGGACGTGGCCACCTATTACTGTCAGCAGGG CTACAGCATGACCGACGTGGAAAATGTGTTCGGC GGAGGCACCAAGGTGGAAATCAAG Parent mAb IgG chain SEQ ID NO Nucleic acid sequence LC5-RESPECT- L 258 GACATCCAGATGACACAGAGCCCTAGCAGCCTGA GCGCCTCTGTGGGCGATAGAGTGACAATTACCTG TCAGGCCAGCCAGAGCATCGGCAGCGACCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC T GC T GAT C T AC AGAGCCT C T ACAC TGGCC AGCGG CGTGCCAAGCAGATTTTCTGGCTCTGGCAGCGGC ACCGACTTCACCCTGACAATTAGTAGCCTGCAGT GCGAGGACGTGGCCACCTATTACTGTCAGCAGGG CTACAGCATGACCGACGTGGAAAATGTGTTCGGC GGAGGCACCAAGGTGGAAATCAAG LC6-RESPECT- L 259 GACATCCAGATGACACAGAGCCCTAGCAGCCTGA GCGCCTCTGTGGGCGATAGAGTGACAATTACCTG TAGAGCCAGCCAGAGCATCGGCAGCGACCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC T GC T GAT C T AC AGAGCCT C T ACAC TGGCC AGCGG CGTGCCAAGCAGATTTTCTGGCTCTGGCAGCGGC ACCGACTTCACCCTGACAATTAGTAGCCTGCAGT GCGAGGACGTGGCCACCTATTACTGTCAGCAGGG CTACAGCATGACCGACGTGGAAAATGTGTTCGGC GGAGGCACCAAGGTGGAAATCAAG 17124 HC1 260 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTGG TTCAACCTGGCGGAAGCCTGAGACTGTCTTGTGC CGCCTCTGGCATCGATCTGAGCAGACACGCCATG AGCTGGGTTCGACAGGCCCCTGGAAAAGGACTGG AATGGATCGGCATCATCTACGGCAGCGGCAGCAC CTTTTACGCCTCTTGGGCCAAGGGCAGATTCACC ATCAGCCGGGACAACAGCAAGAACACCCTGTACC TGCAGATGAACAGCCTGAGAGCCGAGGACACCGC CGTGTACTACTGTGCCAGAACCATGTGGACCGAC AGCAGCGTGTTCCTGAATATCTGGGGCCCTGGCA CACTGGTCACAGTGTCTAGC HC2 261 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTGG TTCAACCTGGCGGAAGCCTGAGACTGTCTTGTGC CGCCTCTGGCATCGATCTGAGCAGACACGCCATG AGCTGGGTTCGACAGGCCCCTGGAAAAGGACTGG AATGGGTGAGCATCATCTACGGCAGCGGCAGCAC CTTTTACGCCTCTTGGGCCAAGGGCAGATTCACC ATCAGCCGGGACAACAGCAAGAACACCCTGTACC TGCAGATGAACAGCCTGAGAGCCGAGGACACCGC CGTGTACTACTGTGCCAGAACCATGTGGACCGAC AGCAGCGTGTTCCTGAATATCTGGGGCCCTGGCA CACTGGTCACAGTGTCTAGC HC3 262 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTGG TTCAACCTGGCGGAAGCCTGAGACTGTCTTGTGC CGCCTCTGGCATCGATCTGAGCAGACACGCCATG AGCTGGGTTCGACAGGCCCCTGGAAAAGGACTGG AATGGATCGGCATCATCTACGGCAGCGGCAGCAC CTTTTACGCCGACAGCGTTAAGGGCAGATTCACC ATCAGCCGGGACAACAGCAAGAACACCCTGTACC TGCAGATGAACAGCCTGAGAGCCGAGGACACCGC CGTGTACTACTGTGCCAGAACCATGTGGACCGAC AGCAGCGTGTTCCTGAATATCTGGGGCCCTGGCA CACTGGTCACAGTGTCTAGC Parent mAb IgG chain SEQ ID NO Nucleic acid sequence HC4 263 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTGG TTCAACCTGGCGGAAGCCTGAGACTGTCTTGTGC CGCCTCTGGCATCGATCTGAGCAGACACGCCATG AGCTGGGTTCGACAGGCCCCTGGAAAAGGACTGG AATGGGTGAGCATCATCTACGGCAGCGGCAGCAC CTTTTACGCCGACAGCGTTAAGGGCAGATTCACC ATCAGCCGGGACAACAGCAAGAACACCCTGTACC TGCAGATGAACAGCCTGAGAGCCGAGGACACCGC CGTGTACTACTGTGCCAGAACCATGTGGACCGAC AGCAGCGTGTTCCTGAATATCTGGGGCCCTGGCA CACTGGTCACAGTGTCTAGC HC5 264 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTGG TTCAACCTGGCGGAAGCCTGAGACTGTCTTGTGC CGCCTCTGGCATCGATCTGAGCAGACACGCCATG AGCTGGGTTCGACAGGCCCCTGGAAAAGGACTGG AATGGGTGAGCATCATCTACGGCAGCGGCAGCAC CTTTTACGCCGACAGCGTTAAGGGCAGATTCACC ATCAGCCGGGACAACAGCAAGAACACCCTGTACC TGCAGATGAACAGCCTGAGAGCCGAGGACACCGC CGTGTACTACTGTGCCAGAACCATGTGGACCGAC AGCAGCGTGTTCCTGAATATCTGGGGCCAGGGCA CACTGGTCACAGTGTCTAGC LC1 265 GCT C AAGT GAT GAC AC AGAGCCC T AGC AC AC TGA GCGCCTCTGTGGGCGATAGAGTGACCATCACCTG TCAGGCTAGCCCCAGCGTGTACAACAACAAGAAC CTGGCCTGGTATCAGCAGAAGCCCGGAAAGGCCC C TAAGC T GCT GAT C TATGAAGCCAGCAAAGT GGC CAGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGAGTTCACCCTGACAATCAGTAGCC TGCAGCCCGACGACTTTGCCACATATTACTGCCA GGGCGAGTTTAGCTGGTCCTCTGGCGATCTGATT GCCTTCGGCGGAGGCACCAAGGTGGAAATCAAG LC2 266 GACAT CCAGAT GACACAGAGCCC TAGCACAC TGA GCGCCTCTGTGGGCGATAGAGTGACCATCACCTG TCAGGCTAGCCCCAGCGTGTACAACAACAAGAAC CTGGCCTGGTATCAGCAGAAGCCCGGAAAGGCCC C TAAGC T GCT GAT C TATGAAGCCAGCAAAGT GGC CAGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGAGTTCACCCTGACAATCAGTAGCC TGCAGCCCGACGACTTTGCCACATATTACTGCCA GGGCGAGTTTAGCTGGTCCTCTGGCGATCTGATT GCCTTCGGCGGAGGCACCAAGGTGGAAATCAAG LC3 267 GACCAACAGATGACACAGAGCCCTAGCACACTGA GCGCCTCTGTGGGCGATAGAGTGACCATCACCTG TCAGGCTAGCCCCAGCGTGTACAACAACAAGAAC CTGGCCTGGTATCAGCAGAAGCCCGGAAAGGCCC C TAAGC T GCT GAT C TATGAAGCCAGCAAAGT GGC CAGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGAGTTCACCCTGACAATCAGTAGCC TGCAGCCCGACGACTTTGCCACATATTACTGCCA GGGCGAGTTTAGCTGGTCCTCTGGCGATCTGATT GCCTTCGGCGGAGGCACCAAGGTGGAAATCAAG LC4 268 GACAT CCAGAT GACACAGAGCCC TAGCACAC TGA GCGCCTCTGTGGGCGATAGAGTGACCATCACCTG Parent mAb IgG chain SEQ ID NO Nucleic acid sequence TAGAGCTAGCCCCAGCGTGTACAACAACAAGAAC CTGGCCTGGTATCAGCAGAAGCCCGGAAAGGCCC C TAAGC T GCT GAT C TATGAAGCCAGCAAAGTGGC CAGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGAGTTCACCCTGACAATCAGTAGCC TGCAGCCCGACGACTTTGCCACATATTACTGCCA GGGCGAGTTTAGCTGGTCCTCTGGCGATCTGATT GCCTTCGGCGGAGGCACCAAGGTGGAAATCAAG LC5 269 GACAT CCAGAT GACACAGAGCCC TAGCACAC TGA GCGCCTCTGTGGGCGATAGAGTGACCATCACCTG TCAGGCTAGCCCCAGCGTGTACAACAACAAGAAC CTGGCCTGGTATCAGCAGAAGCCCGGAAAGGCCC C TAAGC T GCT GAT C TATGAT GCCAGCAAAGT GGC CAGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGAGTTCACCCTGACAATCAGTAGCC TGCAGCCCGACGACTTTGCCACATATTACTGCCA GGGCGAGTTTAGCTGGTCCTCTGGCGATCTGATT GCCTTCGGCGGAGGCACCAAGGTGGAAATCAAG LC1-RESPECT- L 270 GCT CAAGT GAT GACACAGAGCCC TAGCACAC TGA GCGCCTCTGTGGGCGATAGAGTGACCATCACCTG TCAGGCTAGCCCCAGCGTGTACAACAACAAGAAC CTGGCCTGGTATCAGCAGAAGCCCGGAAAGGCCC C TAAGC T GCT GAT C TATGAAGCCAGCAAAGTGGC CAGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGAGTTCACCCTGACAATCAGTAGCC TGCAGTGTGACGACGTGGCCACATATTACTGCCA GGGCGAGTTTAGCTGGTCCTCTGGCGATCTGATT GCCTTCGGCGGAGGCACCAAGGTGGAAATCAAG LC2-RESPECT- L 271 GACAT CCAGAT GACACAGAGCCC TAGCACAC TGA GCGCCTCTGTGGGCGATAGAGTGACCATCACCTG TCAGGCTAGCCCCAGCGTGTACAACAACAAGAAC CTGGCCTGGTATCAGCAGAAGCCCGGAAAGGCCC C TAAGC T GCT GAT C TATGAAGCCAGCAAAGT GGC CAGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGAGTTCACCCTGACAATCAGTAGCC TGCAGTGTGACGACGTGGCCACATATTACTGCCA GGGCGAGTTTAGCTGGTCCTCTGGCGATCTGATT GCCTTCGGCGGAGGCACCAAGGTGGAAATCAAG LC3-RESPECT- L 272 GACCAACAGATGACACAGAGCCCTAGCACACTGA GCGCCTCTGTGGGCGATAGAGTGACCATCACCTG TCAGGCTAGCCCCAGCGTGTACAACAACAAGAAC CTGGCCTGGTATCAGCAGAAGCCCGGAAAGGCCC C TAAGC T GCT GAT C TATGAAGCCAGCAAAGTGGC CAGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGAGTTCACCCTGACAATCAGTAGCC TGCAGTGTGACGACGTGGCCACATATTACTGCCA GGGCGAGTTTAGCTGGTCCTCTGGCGATCTGATT GCCTTCGGCGGAGGCACCAAGGTGGAAATCAAG LC4-RESPECT- L 273 GACAT CCAGAT GACACAGAGCCC TAGCACAC TGA GCGCCTCTGTGGGCGATAGAGTGACCATCACCTG TAGAGCTAGCCCCAGCGTGTACAACAACAAGAAC CTGGCCTGGTATCAGCAGAAGCCCGGAAAGGCCC CTAAGCTGCTGATCTATGAAGCCAGCAAAGTGGC CAGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC Parent mAb IgG chain SEQ ID NO Nucleic acid sequence AGCGGCACCGAGTTCACCCTGACAATCAGTAGCC TGCAGTGTGACGACGTGGCCACATATTACTGCCA GGGCGAGTTTAGCTGGTCCTCTGGCGATCTGATT GCCTTCGGCGGAGGCACCAAGGTGGAAATCAAG LC5-RESPECT- L 274 GACAT CCAGAT GACACAGAGCCC TAGCACAC TGA GCGCCTCTGTGGGCGATAGAGTGACCATCACCTG TCAGGCTAGCCCCAGCGTGTACAACAACAAGAAC CTGGCCTGGTATCAGCAGAAGCCCGGAAAGGCCC C TAAGC T GCT GAT C TATGAT GCCAGCAAAGT GGC CAGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGAGTTCACCCTGACAATCAGTAGCC TGCAGTGTGACGACGTGGCCACATATTACTGCCA GGGCGAGTTTAGCTGGTCCTCTGGCGATCTGATT GCCTTCGGCGGAGGCACCAAGGTGGAAATCAAG 20E16 HC1 275 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTGG TTCAACCTGGTGGCTCTCTGAGACTGTCTTGTGC CGCCTCTGGCCTGGACTTCAACAAATATGGCGTG TCCTGGGTCCGACAGGCCCCTGGAAAAGGACTGG AATGGATCGGCTTCATCGACCCCGTGTTCGGCAA TACCGTGTACGCCTCTTGGGTCAACGGCCGGTTC ACCATCAGCCGGGACAACAGCAAGAACACCCTGT ACCT GCAGAT GAACAGCC T GAGAGCCGAGGACAC CGCCGTGTATTACTGTGTGCGTTGGAACAGCGGC TGGGGCAATCTTTGGGGACCTGGCACACTGGTTA CAGTGTCCTCT HC2 276 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTGG TTCAACCTGGTGGCTCTCTGAGACTGTCTTGTGC CGCCTCTGGCCTGGACTTCAACAAATATGGCGTG TCCTGGGTCCGACAGGCCCCTGGAAAAGGACTGG AATGGGTGAGCTTCATCGACCCCGTGTTCGGCAA TACCGTGTACGCCTCTTGGGTCAACGGCCGGTTC ACCATCAGCCGGGACAACAGCAAGAACACCCTGT ACCT GCAGAT GAACAGCC T GAGAGCCGAGGACAC CGCCGTGTATTACTGTGTGCGTTGGAACAGCGGC TGGGGCAATCTTTGGGGACCTGGCACACTGGTTA CAGTGTCCTCT HC3 277 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTGG TTCAACCTGGTGGCTCTCTGAGACTGTCTTGTGC CGCCTCTGGCCTGGACTTCAACAAATATGGCGTG TCCTGGGTCCGACAGGCCCCTGGAAAAGGACTGG AATGGATCGGCTTCATCGACCCCGTGTTCGGCAA TACCGTGTACGCCGACAGCGTTAAGGGCCGGTTC ACCATCAGCCGGGACAACAGCAAGAACACCCTGT ACCT GCAGAT GAACAGCC T GAGAGCCGAGGACAC CGCCGTGTATTACTGTGTGCGTTGGAACAGCGGC TGGGGCAATCTTTGGGGACCTGGCACACTGGTTA CAGTGTCCTCT HC4 278 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTGG TTCAACCTGGTGGCTCTCTGAGACTGTCTTGTGC CGCCTCTGGCCTGGACTTCAACAAATATGCCATG TCCTGGGTCCGACAGGCCCCTGGAAAAGGACTGG AATGGATCGGCTTCATCGACCCCGTGTTCGGCAA TACCGTGTACGCCGACAGCGTTAAGGGCCGGTTC ACCATCAGCCGGGACAACAGCAAGAACACCCTGT Parent mAb IgG chain SEQ ID NO Nucleic acid sequence ACCT GCAGAT GAACAGCC T GAGAGCCGAGGACAC CGCCGTGTATTACTGTGTGCGTTGGAACAGCGGC TGGGGCAATCTTTGGGGACCTGGCACACTGGTTA CAGTGTCCTCT HC5 279 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTGG TTCAACCTGGTGGCTCTCTGAGACTGTCTTGTGC CGCCTCTGGCCTGGACTTCAACAAATATGGCGTG TCCTGGGTCCGACAGGCCCCTGGAAAAGGACTGG AATGGATCGGCTTCATCGACCCCGTGTTCGGCAA TACCGTGTACGCCGACAGCGTTAAGGGCCGGTTC ACCATCAGCCGGGACAACAGCAAGAACACCCTGT ACCT GCAGAT GAACAGCC T GAGAGCCGAGGACAC CGCCGTGTATTACTGTGCCAAATGGAACAGCGGC TGGGGCAATCTTTGGGGACCTGGCACACTGGTTA CAGTGTCCTCT HC6 280 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTGG TTCAACCTGGTGGCTCTCTGAGACTGTCTTGTGC CGCCTCTGGCCTGGACTTCAACAAATATGGCGTG TCCTGGGTCCGACAGGCCCCTGGAAAAGGACTGG AATGGATCGGCTTCATCGACCCCGTGTTCGGCAA TACCGTGTACGCCGACAGCGTTAAGGGCCGGTTC ACCATCAGCCGGGACAACAGCAAGAACACCCTGT ACCT GCAGAT GAACAGCC T GAGAGCCGAGGACAC CGCCGTGTATTACTGTGCCCGTTGGAACAGCGGC TGGGGCAATCTTTGGGGACCTGGCACACTGGTTA CAGTGTCCTCT LC1 281 GCTATCGTGATGACACAGAGCCCTAGCAGCCTGT CTGCCTCTGTGGGCGATAGAGTGACAATCACCTG TCAGGCCAGCCAGAGCATCGTGACCTATCTGGCC TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC TGCTGATCTACGGCGCCAGCAATCTGGAAAGCGG CGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGC ACCGACTTCACCTTTACAATCAGCAGCCTGCAGC CTGAGGATATCGCCACCTACTACTGCCAGAGCGG CGATTATTCTGCCGGCCTTACATTTGGCGGAGGC ACCAAGGTGGAAATCAAG LC2 282 GACATCCAGATGACACAGAGCCCTAGCAGCCTGT CTGCCTCTGTGGGCGATAGAGTGACAATCACCTG TCAGGCCAGCCAGAGCATCGTGACCTATCTGGCC TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC TGCTGATCTACGGCGCCAGCAATCTGGAAAGCGG CGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGC ACCGACTTCACCTTTACAATCAGCAGCCTGCAGC CTGAGGATATCGCCACCTACTACTGCCAGAGCGG CGATTATTCTGCCGGCCTTACATTTGGCGGAGGC ACCAAGGTGGAAATCAAG LC3 283 GACATCCAGATGACACAGAGCCCTAGCAGCCTGT CTGCCTCTGTGGGCGATAGAGTGACAATCACCTG TCAGGCCAGCCAGAGCATCGTGACCTATCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC TGCTGATCTACGGCGCCAGCAATCTGGAAAGCGG CGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGC ACCGACTTCACCTTTACAATCAGCAGCCTGCAGC CTGAGGATATCGCCACCTACTACTGCCAGAGCGG Parent mAb IgG chain SEQ ID NO Nucleic acid sequence CGATTATTCTGCCGGCCTTACATTTGGCGGAGGC ACCAAGGTGGAAATCAAG LC4 284 GACATCCAGATGACACAGAGCCCTAGCAGCCTGT CTGCCTCTGTGGGCGATAGAGTGACAATCACCTG TCAGGCCAGCCAGAGCATCGTGACCTATCTGGCC TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC TGCTGATCTACGGCGCCAGCAATCTGGAAACCGG CGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGC ACCGACTTCACCTTTACAATCAGCAGCCTGCAGC CTGAGGATATCGCCACCTACTACTGCCAGAGCGG CGATTATTCTGCCGGCCTTACATTTGGCGGAGGC ACCAAGGTGGAAATCAAG LC5 285 GACATCCAGATGACACAGAGCCCTAGCAGCCTGT CTGCCTCTGTGGGCGATAGAGTGACAATCACCTG TCAGGCCAGCCAGAGCATCGTGACCTATCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC TGCTGATCTACGGCGCCAGCAATCTGGAAACCGG CGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGC ACCGACTTCACCTTTACAATCAGCAGCCTGCAGC CTGAGGATATCGCCACCTACTACTGCCAGAGCGG CGATTATTCTGCCGGCCTTACATTTGGCGGAGGC ACCAAGGTGGAAATCAAG LC1-RESPECT- L 286 GCTATCGTGATGACACAGAGCCCTAGCAGCCTGT CTGCCTCTGTGGGCGATAGAGTGACAATCACCTG TCAGGCCAGCCAGAGCATCGTGACCTATCTGGCC TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC TGCTGATCTACGGCGCCAGCAATCTGGAAAGCGG CGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGC ACCGACTTCACCTTTACAATCAGCAGCCTGCAGT GCGAGGATATCGCCACCTACTACTGCCAGAGCGG CGATTATTCTGCCGGCCTTACATTTGGCGGAGGC ACCAAGGTGGAAATCAAG LC2-RESPECT- L 287 GACATCCAGATGACACAGAGCCCTAGCAGCCTGT CTGCCTCTGTGGGCGATAGAGTGACAATCACCTG TCAGGCCAGCCAGAGCATCGTGACCTATCTGGCC TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC TGCTGATCTACGGCGCCAGCAATCTGGAAAGCGG CGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGC ACCGACTTCACCTTTACAATCAGCAGCCTGCAGT GCGAGGATATCGCCACCTACTACTGCCAGAGCGG CGATTATTCTGCCGGCCTTACATTTGGCGGAGGC ACCAAGGTGGAAATCAAG LC3-RESPECT- L 288 GACATCCAGATGACACAGAGCCCTAGCAGCCTGT CTGCCTCTGTGGGCGATAGAGTGACAATCACCTG TCAGGCCAGCCAGAGCATCGTGACCTATCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC TGCTGATCTACGGCGCCAGCAATCTGGAAAGCGG CGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGC ACCGACTTCACCTTTACAATCAGCAGCCTGCAGT GCGAGGATATCGCCACCTACTACTGCCAGAGCGG CGATTATTCTGCCGGCCTTACATTTGGCGGAGGC ACCAAGGTGGAAATCAAG Parent mAh IgG chain SEQ ID NO Nucleic acid sequence LC4-RESPECT- L 289 GACATCCAGATGACACAGAGCCCTAGCAGCCTGT CTGCCTCTGTGGGCGATAGAGTGACAATCACCTG TCAGGCCAGCCAGAGCATCGTGACCTATCTGGCC TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC TGCTGATCTACGGCGCCAGCAATCTGGAAACCGG CGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGC ACCGACTTCACCTTTACAATCAGCAGCCTGCAGT GCGAGGATATCGCCACCTACTACTGCCAGAGCGG CGATTATTCTGCCGGCCTTACATTTGGCGGAGGC ACCAAGGTGGAAATCAAG LC5-RESPECT- L 290 GACATCCAGATGACACAGAGCCCTAGCAGCCTGT CTGCCTCTGTGGGCGATAGAGTGACAATCACCTG TCAGGCCAGCCAGAGCATCGTGACCTATCTGAAT TGGTATCAGCAGAAGCCTGGCAAGGCCCCTAAGC TGCTGATCTACGGCGCCAGCAATCTGGAAACCGG CGTGCCAAGCAGATTTTCTGGCAGCGGCTCTGGC ACCGACTTCACCTTTACAATCAGCAGCCTGCAGT GCGAGGATATCGCCACCTACTACTGCCAGAGCGG CGATTATTCTGCCGGCCTTACATTTGGCGGAGGC ACCAAGGTGGAAATCAAG Table 8. Amino acid sequences of full-length mAh Ig chains mAh IgG chain SEQ ID NO Amino acid sequence 16K21 HC1 94 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWIGYIYSSDTTYYATWAKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGPGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCWVDVSHED PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC2 95 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWVSYIYSSDTTYYATWAKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGPGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK mAh IgG chain SEQIDNO Amino acid sequence 16K21 HC3 96 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWIGYIYSSDTTYYADSVKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGPGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC4 97 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWVSYTYSSDTTYYADSVKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGPGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCWVDVSHED PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC5 178 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWVSYIYSSDTTYYADSVKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGQGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC6 179 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWIGYIYSSDTTYYADSVKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGQGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL mAh IgG chain SEQIDNO Amino acid sequence YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC1-14AAS 98 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWIGYIYSSDTTYYATWAKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGPGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAG GSSVFLFPPKPKDTLMTSRTPEVTCVWDVSQED PEVQFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC2-14AAS 99 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWVSYIYSSDTTYYATWAKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGPGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAG GSSVFLFPPKPKDTLMISRTPEVTCVWDVSQED PEVQFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC3-14AAS 100 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWIGYIYSSDTTYYADSVKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGPGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAG GSSVFLFPPKPKDTLMISRTPEVTCVWDVSQED PEVQFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDTAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC4-14AAS 101 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWVSYIYSSDTTYYADSVKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGPGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAG GSSVFLFPPKPKDTLMISRTPEVTCWVDVSQED PEVQFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK mAh IgG chain SEQIDNO Amino acid sequence AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC5-14AAS 180 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWVSYIYSSDTTYYADSVKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGQGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAG GSSVFLFPPKPKDTLMISRTPEVTCVWDVSQED PEVQFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDTAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC6-14AAS 181 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWIGYIYSSDTTYYADSVKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGQGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAG GSSVFLFPPKPKDTLMISRTPEVTCVWDVSQED PEVQFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC1-RH12 102 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWIGYIYSSDTTYYATWAKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGPGTLVTVSSASTKGPSVFPLAPSSKS KSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDATHTCPPCPAPEAAG GSSVFLFPPKPKDTLMISRTPEVTCVWDVSQED PEVQFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC2-RH12 103 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWVSYIYSSDTTYYATWAKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGPGTLVTVSSASTKGPSVFPLAPSSKS KSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDATHTCPPCPAPEAAG GSSVFLFPPKPKDTLMISRTPEVTCVWDVSQED mAh IgG chain SEQIDNO Amino acid sequence PEVQFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC3-RH12 104 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWIGYIYSSDTTYYADSVKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGPGTLVTVSSASTKGPSVFPLAPSSKS KSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDATHTCPPCPAPEAAG GSSVFLFPPKPKDTLMISRTPEVTCVWDVSQED PEVQFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC4-RH12 105 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWVSYIYSSDTTYYADSVKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGPGTLVTVSSASTKGPSVFPLAPSSKS KSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDATHTCPPCPAPEAAG GSSVFLFPPKPKDTLMISRTPEVTCVWDVSQED PEVQFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC5-RH12 182 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWVSYIYSSDTTYYADSVKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGQGTLVTVSSASTKGPSVFPLAPSSKS KSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDATHTCPPCPAPEAAG GSSVFLFPPKPKDTLMTSRTPEVTCVWDVSQED PEVQFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC6-RH12 183 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWIGYIYSSDTTYYADSVKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGQGTLVTVSSASTKGPSVFPLAPSSKS KSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV mAh IgG chain SEQIDNO Amino acid sequence NHKPSNTKVDKKVEPKSCDATHTCPPCPAPEAAG GSSVFLFPPKPKDTLMISRTPEVTCVWDVSQED PEVQFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 HC6-14AAS- A118C 380 EVQLVESGGGLVQPGGSLRLSCAASGFSLSYNAM SWVRQAPGKGLEWTGYTYSSDTTYYADSVKGRFT ISRHNSKNTLYLQMNSLRAEDTAVYYCARDIGTA YYTFNIWGQGTLVTVSSCSTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAG GSSVFLFPPKPKDTLMTSRTPEVTCVWDVSQED PEVQFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 16K21 LC1 106 AYDMTQSPSSLSASVGDRVTITCQASQTIGSDLN WYQQKPGKAPKLLIYRASTLASGVPSRFSGSGSG TDFTLTISSLQPEDFATYYCQQGYSMTDVENVFG GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASW CLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC 16K21 LC2 107 DIQMTQSPSSLSASVGDRVTITCQASQTIGSDLN WYQQKPGKAPKLLIYRASTLASGVPSRFSGSGSG TDFTLTISSLQPEDFATYYCQQGYSMTDVENVFG GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASW CLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC 16K21 LC3 169 DYQMTQSPSSLSASVGDRVTITCQASQTIGSDLN WYQQKPGKAPKLLIYRASTLASGVPSRFSGSGSG TDFTLTISSLQPEDFATYYCQQGYSMTDVENVFG GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASW CLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC 16K21 LC4 108 DIQMTQSPSSLSASVGDRVTITCRASQTIGSDLN WYQQKPGKAPKLLIYRASTLASGVPSRFSGSGSG TDFTLTISSLQPEDFATYYCQQGYSMTDVENVFG GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASW CLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC 16K21 LC5 109 DIQMTQSPSSLSASVGDRVTITCQASQSIGSDLN WYQQKPGKAPKLLIYRASTLASGVPSRFSGSGSG TDFTLTISSLQPEDFATYYCQQGYSMTDVENVFG GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASW mAh IgG chain SEQIDNO Amino acid sequence CLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC 16K21 LC6 110 DIQMTQSPSSLSASVGDRVTITCRASQSIGSDLN WYQQKPGKAPKLLIYRASTLASGVPSRFSGSGSG TDFTLTISSLQPEDFATYYCQQGYSMTDVENVFG GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASW CLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC 16K21 LC1-RESPECT- L 111 AYDMTQSPSSLSASVGDRVTITCQASQTIGSDLN WYQQKPGKAPKLLIYRASTLASGVPSRFSGSGSG TDFTLTISSLQCEDVATYYCQQGYSMTDVENVFG GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASW CLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC 16K21 LC2-RESPECT- L 112 DIQMTQSPSSLSASVGDRVTITCQASQTIGSDLN WYQQKPGKAPKLLIYRASTLASGVPSRFSGSGSG TDFTLTISSLQCEDVATYYCQQGYSMTDVENVFG GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASW CLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC 16K21 LC3-RESPECT- L 188 DYQMTQSPSSLSASVGDRVTITCQASQTIGSDLN WYQQKPGKAPKLLIYRASTLASGVPSRFSGSGSG TDFTLTISSLQCEDVATYYCQQGYSMTDVENVFG GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASW CLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC 16K21 LC4-RESPECT- L 113 DIQMTQSPSSLSASVGDRVTITCRASQTIGSDLN WYQQKPGKAPKLLIYRASTLASGVPSRFSGSGSG TDFTLTISSLQCEDVATYYCQQGYSMTDVENVFG GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASW CLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC 16K21 LC5-RESPECT- L 114 DIQMTQSPSSLSASVGDRVTITCQASQSIGSDLN WYQQKPGKAPKLLIYRASTLASGVPSRFSGSGSG TDFTLTISSLQCEDVATYYCQQGYSMTDVENVFG GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASW CLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC 16K21 LC6-RESPECT- L 115 DIQMTQSPSSLSASVGDRVTITCRASQSIGSDLN WYQQKPGKAPKLLIYRASTLASGVPSRFSGSGSG TDFTLTISSLQCEDVATYYCQQGYSMTDVENVFG GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASW CLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL SSPVTKSFNRGEC 17124 HC1 116 EVQLVESGGGLVQPGGSLRLSCAASGTDLSRHAM SWVRQAPGKGLEWIGIIYGSGSTFYASWAKGRFT mAh IgG chain SEQIDNO Amino acid sequence ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGPGTLVTVSSASTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHE DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW S VL TVLHQ DWLNGKEYKCKVSNKALPAPIEKTIS KAKGQPRE PQVYTLPPSRDELTKNQVSLT CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 HC2 117 EVQLVESGGGLVQPGGSLRLSCAASGTDLSRHAM SWVRQAPGKGLEWVSIIYGSGSTFYASWAKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGPGTLVTVSSASTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHE DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQ PRE PQVY TLPPSRDELTKNQVSL T CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 HC3 118 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAM SWVRQAPGKGLEWIGIIYGSGSTFYADSVKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGPGTLVTVSSASTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHE DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQ PRE PQVY TLPPSRDELTKNQVSL T CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 HC4 119 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAM SWVRQAPGKGLEWVSTTYGSGSTFYADSVKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGPGTLVTVSSASTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHE DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQ PRE PQVY TLPPSRDELTKNQVSL T CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK mAh IgG chain SEQIDNO Amino acid sequence 17124 HC5 184 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAM SWVRQAPGKGLEWVSIIYGSGSTFYADSVKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGQGTLVTVSSASTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHE DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQ PRE PQVY T LP PSRDE LTKNQVS LT CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 HC1-14AAS 120 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAM SWVRQAPGKGLEWIGTTYGSGSTFYASWAKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGPGTLVTVSSASTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAA GGSSVFLFPPKPKDTLMISRTPEVTCVWDVSQE DPEVQFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQ PRE PQVY TLPPSRDELTKNQVSL T CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 HC2-14AAS 121 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAM SWVRQAPGKGLEWVSIIYGSGSTFYASWAKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGPGTLVTVSSASTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAA GGSSVFLFPPKPKDTLMISRTPEVTCVWDVSQE DPEVQFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQ PRE PQVY TLPPSRDELTKNQVSL T CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 HC3-14AAS 122 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAM SWVRQAPGKGLEWIGIIYGSGSTFYADSVKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGPGTLVTVSSASTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAA GGSSVFLFPPKPKDTLMISRTPEVTCVWDVSQE DPEVQFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQ PRE PQVY T L P PSRDE L TKNQVS L T CLVKG mAh IgG chain SEQIDNO Amino acid sequence FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 HC4-14AAS 123 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAM SWVRQAPGKGLEWVSIIYGSGSTFYADSVKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGPGTLVTVSSASTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAA GGSSVFLFPPKPKDTLMISRTPEVTCVWDVSQE DPEVQFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPTEKTTS KAKGQ PRE PQVY T LP PSRDE LTKNQVS LT CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 HC5-14AAS 185 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAM SWVRQAPGKGLEWVSIIYGSGSTFYADSVKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGQGTLVTVSSASTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAA GGSSVFLFPPKPKDTLMISRTPEVTCVWDVSQE DPEVQFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQ PRE PQVY TLPPSRDELTKNQVSL T CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 HC1-RH12 124 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAM SWVRQAPGKGLEWIGIIYGSGSTFYASWAKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGPGTLVTVSSASTKGPSVFPLAPSSK SKSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDATHTCPPCPAPEAA GGSSVFLFPPKPKDTLMISRTPEVTCVWDVSQE DPEVQFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQ PRE PQVY TLPPSRDELTKNQVSL T CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 HC2-RH12 125 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAM SWVRQAPGKGLEWVSIIYGSGSTFYASWAKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGPGTLVTVSSASTKGPSVFPLAPSSK SKSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDATHTCPPCPAPEAA GGSSVFLFPPKPKDTLMISRTPEVTCVWDVSQE DPEVQFNWYVDGVEVHNAKTKPREEQYNSTYRW mAh IgG chain SEQIDNO Amino acid sequence SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQ PRE PQVY T LP PSRDE LTKNQVS LT CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 HC3-RH12 126 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAM SWVRQAPGKGLEWIGIIYGSGSTFYADSVKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGPGTLVTVSSASTKGPSVFPLAPSSK SKSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDATHTCPPCPAPEAA GGSSVFLFPPKPKDTLMISRTPEVTCVWDVSQE DPEVQFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQ PRE PQVY TLPPSRDELTKNQVSL T CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 HC4-RH12 127 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAM SWVRQAPGKGLEWVSIIYGSGSTFYADSVKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGPGTLVTVSSASTKGPSVFPLAPSSK SKSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDATHTCPPCPAPEAA GGSSVFLFPPKPKDTLMISRTPEVTCVWDVSQE DPEVQFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQ PRE PQVY TLPPSRDELTKNQVSL T CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 HC5-RH12 186 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAM SWVRQAPGKGLEWVSIIYGSGSTFYADSVKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGQGTLVTVSSASTKGPSVFPLAPSSK SKSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYTCN VNHKPSNTKVDKKVEPKSCDATHTCPPCPAPEAA GGSSVFLFPPKPKDTLMISRTPEVTCVWDVSQE DPEVQFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQ PRE PQVY TLPPSRDELTKNQVSL T CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 HC5-14AAS- A118C 381 EVQLVESGGGLVQPGGSLRLSCAASGIDLSRHAM SWVRQAPGKGLEWVSIIYGSGSTFYADSVKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARTMWTD SSVFLNIWGQGTLVTVSSCSTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAA mAh IgG chain SEQIDNO Amino acid sequence GGSSVFLFPPKPKDTLMISRTPEVTCVWDVSQE DPEVQFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQ PRE PQVY T LP PSRDE LTKNQVS LT CLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 17124 LC1 128 AQVMT Q S P S TL SASVGDRVTIT CQ ASPSVYNNKN LAWYQQKPGKAPKLLIYEASKVASGVPSRFSGSG SGTEFTLTTSSLQPDDFATYYCQGEFSWSSGDLT AFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA SWCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH QGLSSPVTKSFNRGEC 17124 LC2 129 DIQMTQS PSTLSASVGDRVTITCQASPSVYNNKN LAWYQQKPGKAPKLLIYEASKVASGVPSRFSGSG SGTEFTLTISSLQPDDFATYYCQGEFSWSSGDLI AFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA SWCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH QGLSSPVTKSFNRGEC 17124 LC3 170 DQQMT Q S P S TL SASVGDRVTITCQASPSVYNNKN LAWYQQKPGKAPKLLIYEASKVASGVPSRFSGSG SGTEFTLTISSLQPDDFATYYCQGEFSWSSGDLI AFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA SWCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH QGLSSPVTKSFNRGEC 17124 LC4 130 DIQMTQSPSTLSASVGDRVTITCRASPSVYNNKN LAWYQQKPGKAPKLLIYEASKVASGVPSRFSGSG SGTEFTLTISSLQPDDFATYYCQGEFSWSSGDLI AFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA SWCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH QGLSSPVTKSFNRGEC 17124 LC5 131 DIQMTQS PSTLSASVGDRVTITCQASPSVYNNKN LAWYQQKPGKAPKLLIYDASKVASGVPSRFSGSG SGTEFTLTISSLQPDDFATYYCQGEFSWSSGDLI AFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA SWCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH QGLSSPVTKSFNRGEC 17124 LC1-RESPECT- L 132 AQVMT Q S P S TL SASVGDRVTITCQASPSVYNNKN LAWYQQKPGKAPKLLIYEASKVASGVPSRFSGSG SGTEFTLTISSLQCDDVATYYCQGEFSWSSGDLI AFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA SWCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH QGLSSPVTKSFNRGEC 17124 LC2-RESPECT- L 133 DIQMTQS PSTLSASVGDRVTITCQASPSVYNNKN LAWYQQKPGKAPKLLIYEASKVASGVPSRFSGSG SGTEFTLTISSLQCDDVATYYCQGEFSWSSGDLI AFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA SWCLLNNFYPREAKVQWKVDNALQSGNSQESVT mAh IgG chain SEQIDNO Amino acid sequence EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH QGLSSPVTKSFNRGEC 17124 LC3-RESPECT- L 189 DQQMTQS PS TL SASVGDRVTIT CQ ASPSVYNNKN LAWYQQKPGKAPKLLIYEASKVASGVPSRFSGSG SGTEFTLTISSLQCDDVATYYCQGEFSWSSGDLI AFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA SWCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH QGLSSPVTKSFNRGEC 17124 LC4-RESPECT- L 134 DIQMTQSPSTLSASVGDRVTITCRASPSVYNNKN LAWYQQKPGKAPKLLIYEASKVASGVPSRFSGSG SGTEFTLTISSLQCDDVATYYCQGEFSWSSGDLI AFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA SWCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH QGLSSPVTKSFNRGEC 17124 LC5-RESPECT- L 135 DIQMTQS PSTLSASVGDRVTITCQASPSVYNNKN LAWYQQKPGKAPKLLIYDASKVASGVPSRFSGSG SGTEFTLTISSLQCDDVATYYCQGEFSWSSGDLI AFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA SWCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH QGLSSPVTKSFNRGEC 20E16 HC1 136 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWIGFIDPVFGNTVYASWVNGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCVRWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPTEKTTSKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC2 171 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWVS FIDPVFGNTVYASWVNGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCVRWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC3 137 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWIGFIDPVFGNTVYADSVKGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCVRWNSG mAh IgG chain SEQIDNO Amino acid sequence WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC4 138 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYAM SWVRQAPGKGLEWIGFT DPVFGNTVYADSVKGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCVRWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC5 139 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWIGFIDPVFGNTVYADSVKGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCAKWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC6 140 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWIGFIDPVFGNTVYADSVKGRF TTSRDNSKNTLYLQMNSLRAEDTAVYYCARWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK mAh IgG chain SEQIDNO Amino acid sequence 20E16 HC1-14AAS 141 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWIGFIDPVFGNTVYASWVNGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCVRWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGS SVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPE VQFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC2-14AAS 172 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWVS FT DPVFGNTVYASWVNGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCVRWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGS SVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPE VQFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC3-14AAS 142 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWIGFIDPVFGNTVYADSVKGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCVRWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGS SVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPE VQFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC4-14AAS 143 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYAM SWVRQAPGKGLEWIGFIDPVFGNTVYADSVKGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCVRWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGS SVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPE VQFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS mAh IgG chain SEQIDNO Amino acid sequence KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC5-14AAS 144 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWIGFIDPVFGNTVYADSVKGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCAKWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGS SVFLFPPKPKDTLMTSRTPEVTCVWDVSQEDPE VQFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC6-14AAS 145 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWIGFIDPVFGNTVYADSVKGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCARWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSTS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGS SVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPE VQFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC1-RH12 146 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWIGFIDPVFGNTVYASWVNGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCVRWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSKS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDATHTCPPCPAPEAAGGS SVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPE VQFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDTAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC2-RH12 173 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWVS FIDPVFGNTVYASWVNGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCVRWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSKS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDATHTCPPCPAPEAAGGS SVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPE VQFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK mAh IgG chain SEQIDNO Amino acid sequence GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC3-RH12 147 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWIGFIDPVFGNTVYADSVKGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCVRWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSKS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYTCNVNH KPSNTKVDKKVEPKSCDATHTCPPCPAPEAAGGS SVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPE VQFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDTAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC4-RH12 148 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYAM SWVRQAPGKGLEWIGFIDPVFGNTVYADSVKGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCVRWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSKS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDATHTCPPCPAPEAAGGS SVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPE VQFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC5-RH12 149 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWIGFIDPVFGNTVYADSVKGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCAKWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSKS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDATHTCPPCPAPEAAGGS SVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPE VQFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPTEKTTSKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 HC6-RH12 150 EVQLLESGGGLVQPGGSLRLSCAASGLDFNKYGV SWVRQAPGKGLEWIGFIDPVFGNTVYADSVKGRF TISRDNSKNTLYLQMNSLRAEDTAVYYCARWNSG WGNLWGPGTLVTVSSASTKGPSVFPLAPSSKSKS GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDATHTCPPCPAPEAAGGS SVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPE mAh IgG chain SEQIDNO Amino acid sequence VQFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 20E16 LC1 151 AIVMTQSPSSLSASVGDRVTITCQASQSIVTYLA WYQQKPGKAPKLLIYGASNLESGVPSRFSGSGSG TDFTFTISSLQPEDIATYYCQSGDYSAGLTFGGG TKVETKRTVAAPSVFTFPPSDEQLKSGTASWCL LNNFYPRE AKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC 20E16 LC2 152 DIQMTQSPSSLSASVGDRVTITCQASQSIVTYLA WYQQKPGKAPKLLIYGASNLESGVPSRFSGSGSG TDFTFTISSLQPEDIATYYCQSGDYSAGLTFGGG TKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC 20E16 LC3 153 DIQMTQSPSSLSASVGDRVTITCQASQSIVTYLN WYQQKPGKAPKLLIYGASNLESGVPSRFSGSGSG TDFTFTISSLQPEDIATYYCQSGDYSAGLTFGGG TKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC 20E16 LC4 154 DIQMTQSPSSLSASVGDRVTITCQASQSIVTYLA WYQQKPGKAPKLLIYGASNLETGVPSRFSGSGSG TDFTFTISSLQPEDIATYYCQSGDYSAGLTFGGG TKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC 20E16 LC5 155 DIQMTQSPSSLSASVGDRVTITCQASQSIVTYLN WYQQKPGKAPKLLIYGASNLETGVPSRFSGSGSG TDFTFTISSLQPEDIATYYCQSGDYSAGLTFGGG TKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC 20E16 LC1-RESPECT- L 156 AIVMTQSPSSLSASVGDRVTITCQASQSIVTYLA WYQQKPGKAPKLLIYGASNLESGVPSRFSGSGSG TDFTFTISSLQCEDIATYYCQSGDYSAGLTFGGG TKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC 20E16 LC2-RESPECT- L 157 DIQMTQSPSSLSASVGDRVTITCQASQSIVTYLA WYQQKPGKAPKLLIYGASNLESGVPSRFSGSGSG TDFTFTISSLQCEDIATYYCQSGDYSAGLTFGGG TKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCL LNNFY PREAKVQWKVDNALQ S GNSQESVTEQDSK mAh IgG chain SEQIDNO Amino acid sequence DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC 20E16 LC3-RESPECT- L 158 DIQMTQSPSSLSASVGDRVTITCQASQSIVTYLN WYQQKPGKAPKLLIYGASNLESGVPSRFSGSGSG TDFTFTISSLQCEDIATYYCQSGDYSAGLTFGGG TKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCL LNNFYPRE AKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC 20E16 LC4-RESPECT- L 159 DIQMTQSPSSLSASVGDRVTITCQASQSIVTYLA WYQQKPGKAPKLLIYGASNLETGVPSRFSGSGSG TDFTFTISSLQCEDIATYYCQSGDYSAGLTFGGG TKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCL LNNFYPRE AKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC 20E16 LC5-RESPECT- L 160 DIQMTQSPSSLSASVGDRVTITCQASQSIVTYLN WYQQKPGKAPKLLIYGASNLETGVPSRFSGSGSG TDFTFTISSLQCEDIATYYCQSGDYSAGLTFGGG TKVEIKRTVAAPSVFIFPPSDEQLKSGTASWCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC Table 9. Nucleic acid sequences of full-length mAh Ig chains mAh IgG chain SEQ ID NO Nucleic acid sequence 16K21 HC1 291 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA C T GGAAT GGAT CGGC TACATC TACAGCAGCGAC ACCACCTACTACGCCACATGGGCCAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CCTGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT T GAGCCCAAA TCTTGTGACAAAACTCACACATGCCCACCGTGC CCAGCACCTGAACTCCTGGGGGGACCGTCAGTC TTCCTCTTCCCCCCAAAACCCAAGGACACCCTC ATGATCTCCCGGACCCCTGAGGTCACATGCGTG GTGGTGGACGTGAGCCACGAAGACCCTGAGGTC mAb IgG chain SEQ ID NO Nucleic acid sequence AAGTTCAACTGGTACGTGGACGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCC T GCACCAGGAC T GGC T GAATGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCAGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GCAT GAGGC T CT GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC2 292 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA CTGGAATGGGTGAGCTACATCTACAGCAGCGAC ACCACCTACTACGCCACATGGGCCAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CCTGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT T GAGCCCAAA TCTTGTGACAAAACTCACACATGCCCACCGTGC CCAGCACCTGAACTCCTGGGGGGACCGTCAGTC TTCCTCTTCCCCCCAAAACCCAAGGACACCCTC ATGATCTCCCGGACCCCTGAGGTCACATGCGTG GTGGTGGACGTGAGCCACGAAGACCCTGAGGTC AAGTTCAACTGGTACGTGGACGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCC T GCACCAGGAC T GGC T GAATGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCAGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG mAb IgG chain SEQ ID NO Nucleic acid sequence TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GC AT GAGGC TC T GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC3 293 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA C T GGAAT GGAT CGGC TACATC TACAGCAGCGAC ACCACCTACTACGCCGACAGCGTTAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CCTGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT TGAGCCCAAA TCTTGTGACAAAACTCACACATGCCCACCGTGC CCAGCACCTGAACTCCTGGGGGGACCGTCAGTC TTCCTCTTCCCCCCAAAACCCAAGGACACCCTC ATGATCTCCCGGACCCCTGAGGTCACATGCGTG GTGGTGGACGTGAGCCACGAAGACCCTGAGGTC AAGTTCAACTGGTACGTGGACGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCC T GCACCAGGAC T GGC T GAATGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCAGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GCAT GAGGC TC T GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC4 294 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA CTGGAATGGGTGAGCTACATCTACAGCAGCGAC ACCACCTACTACGCCGACAGCGTTAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC mAb IgG chain SEQ ID NO Nucleic acid sequence CCTGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT T GAGCCCAAA TCTTGTGACAAAACTCACACATGCCCACCGTGC CCAGCACCTGAACTCCTGGGGGGACCGTCAGTC TTCCTCTTCCCCCCAAAACCCAAGGACACCCTC ATGATCTCCCGGACCCCTGAGGTCACATGCGTG GTGGTGGACGTGAGCCACGAAGACCCTGAGGTC AAGTTCAACTGGTACGTGGACGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCC T GCACCAGGAC T GGC T GAATGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCAGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GCAT GAGGC TC T GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC5 295 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA CTGGAATGGGTGAGCTACATCTACAGCAGCGAC ACCACCTACTACGCCGACAGCGTTAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CAGGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT T GAGCCCAAA T C T T GT GACAAAAC T CACACAT GC CCACCGT GC CCAGCACCTGAACTCCTGGGGGGACCGTCAGTC TTCCTCTTCCCCCCAAAACCCAAGGACACCCTC mAb IgG chain SEQ ID NO Nucleic acid sequence ATGATCTCCCGGACCCCTGAGGTCACATGCGTG GTGGTGGACGTGAGCCACGAAGACCCTGAGGTC AAGTTCAACTGGTACGTGGACGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCCTGCACCAGGACTGGCTGAATGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCAGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GCAT GAGGC TC T GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC6 296 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA C T GGAAT GGAT CGGC TACATC TACAGCAGCGAC ACCACCTACTACGCCGACAGCGTTAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CAGGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT TGAGCCCAAA TCTTGTGACAAAACTCACACATGCCCACCGTGC CCAGCACCTGAACTCCTGGGGGGACCGTCAGTC TTCCTCTTCCCCCCAAAACCCAAGGACACCCTC ATGATCTCCCGGACCCCTGAGGTCACATGCGTG GTGGTGGACGTGAGCCACGAAGACCCTGAGGTC AAGTTCAACTGGTACGTGGACGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCC T GCACCAGGAC T GGC T GAATGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCAGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG mAb IgG chain SEQ ID NO Nucleic acid sequence CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GC AT GAGGC TC T GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC1-14AAS 297 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA CTGGAATGGATCGGCTACATCTACAGCAGCGAC ACCACCTACTACGCCACATGGGCCAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CCTGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT T GAGCCCAAA TCTTGTGACAAAACTCACACATGCCCACCGTGC CCAGCACCTGAGGCCGCCGGGGGATCCTCAGTC TTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTC CAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCC T GCACCAGGAC T GGC T GAACGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCGGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GCAT GAGGC T CT GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC2-14AAS 298 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA C T GGAAT GGGT GAGC TACATC TACAGCAGCGAC ACCACCTACTACGCCACATGGGCCAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG mAb IgG chain SEQ ID NO Nucleic acid sequence GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CCTGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA C AGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT T GAGCCCAAA TCTTGTGACAAAACTCACACATGCCCACCGTGC CCAGCACCTGAGGCCGCCGGGGGATCCTCAGTC TTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTC CAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGT CC T GCACCAGGAC T GGC T GAACGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCGGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GCAT GAGGC TC T GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC3-14AAS 299 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA CTGGAATGGATCGGCTACATCTACAGCAGCGAC ACCACCTACTACGCCGACAGCGTTAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CCTGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGTTGAGCCCAAA TCTTGTGACAAAACTCACACATGCCCACCGTGC mAb IgG chain SEQ ID NO Nucleic acid sequence CCAGCACCTGAGGCCGCCGGGGGATCCTCAGTC TTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTC CAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGT CC T GCACCAGGAC T GGC T GAACGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCGGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GC AT GAGGC TC T GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC4-14AAS 300 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA C T GGAAT GGGT GAGC TACATC TACAGCAGCGAC ACCACCTACTACGCCGACAGCGTTAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CCTGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT T GAGCCCAAA TCTTGTGACAAAACTCACACATGCCCACCGTGC CCAGCACCTGAGGCCGCCGGGGGATCCTCAGTC TTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTC CAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCC T GCACCAGGAC T GGC T GAACGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCGGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC mAb IgG chain SEQ ID NO Nucleic acid sequence TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GC AT GAGGC TC T GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC5-14AAS 301 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA C T GGAAT GGGT GAGC TACATC TACAGCAGCGAC ACCACCTACTACGCCGACAGCGTTAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CAGGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT T GAGCCCAAA TCTTGTGACAAAACTCACACATGCCCACCGTGC CCAGCACCTGAGGCCGCCGGGGGATCCTCAGTC TTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTC CAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCC T GCACCAGGAC T GGC T GAACGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCGGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GCAT GAGGC T CT GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC6-14AAS 302 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA C T GGAAT GGAT CGGC TACATC TACAGCAGCGAC ACCACCTACTACGCCGACAGCGTTAAGGGCAGA mAb IgG chain SEQ ID NO Nucleic acid sequence TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CAGGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGTCCTCAGGACTCTACTCCCTCAGCAGCGTG GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT T GAGCCCAAA TCTTGTGACAAAACTCACACATGCCCACCGTGC CCAGCACCTGAGGCCGCCGGGGGATCCTCAGTC TTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTC CAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGT CC T GC ACC AGGAC T GGC T GAACGGC AAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCGGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GC AT GAGGC TC T GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC1-RH12 303 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA C T GGAAT GGAT CGGC TACATC TACAGCAGCGAC ACCACCTACTACGCCACATGGGCCAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CCTGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCAAATCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC mAb IgG chain SEQ ID NO Nucleic acid sequence AACACCAAGGTGGACAAGAAAGT T GAGCCCAAA TCTTGTGACGCCACTCACACATGCCCACCGTGC CCAGCACCTGAGGCCGCCGGGGGATCCTCAGTC TTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTC CAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCC T GCACCAGGAC T GGC T GAACGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCGGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GCAT GAGGC T CT GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC2-RH12 304 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA CTGGAATGGGTGAGCTACATCTACAGCAGCGAC ACCACCTACTACGCCACATGGGCCAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CCTGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCAAATCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT T GAGCCCAAA TCTTGTGACGCCACTCACACATGCCCACCGTGC CCAGCACCTGAGGCCGCCGGGGGATCCTCAGTC TTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTC CAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCC T GCACCAGGAC T GGC T GAACGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCGGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC mAb IgG chain SEQ ID NO Nucleic acid sequence CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GCAT GAGGC TC T GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC3-RH12 305 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA C T GGAAT GGAT CGGC TACATC TACAGCAGCGAC ACCACCTACTACGCCGACAGCGTTAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CCTGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCAAATCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT TGAGCCCAAA TCTTGTGACGCCACTCACACATGCCCACCGTGC CCAGCACCTGAGGCCGCCGGGGGATCCTCAGTC TTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTC CAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCC T GCACCAGGAC T GGC T GAACGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCGGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GCAT GAGGC T CT GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC4-RH12 306 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA mAb IgG chain SEQ ID NO Nucleic acid sequence C T GGAAT GGGT GAGC TACATC TACAGCAGCGAC ACCACCTACTACGCCGACAGCGTTAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CCTGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCAAATCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT T GAGCCCAAA TCTTGTGACGCCACTCACACATGCCCACCGTGC CCAGCACCTGAGGCCGCCGGGGGATCCTCAGTC TTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTC CAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCC T GCACCAGGAC T GGC T GAACGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCGGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GCAT GAGGC TC T GC ACAACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC5-RH12 307 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA CTGGAATGGGTGAGCTACATCTACAGCAGCGAC ACCACCTACTACGCCGACAGCGTTAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CAGGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCAAATCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGTCCTCAGGACTCTACTCCCTCAGCAGCGTG mAb IgG chain SEQ ID NO Nucleic acid sequence GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGTTGAGCCCAAA TCTTGTGACGCCACTCACACATGCCCACCGTGC CCAGCACCTGAGGCCGCCGGGGGATCCTCAGTC TTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTC CAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGT CC T GCACCAGGAC T GGC T GAACGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCGGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GCAT GAGGC TC T GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC6-RH12 308 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA C T GGAAT GGAT CGGC TACATC TACAGCAGCGAC ACCACCTACTACGCCGACAGCGTTAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CAGGGCACACTGGTTACAGTGTCTAGCGCATCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCAAATCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGTTGAGCCCAAA TCTTGTGACGCCACTCACACATGCCCACCGTGC CCAGCACCTGAGGCCGCCGGGGGATCCTCAGTC TTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTC CAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCC T GCACCAGGAC T GGC T GAACGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC mAb IgG chain SEQ ID NO Nucleic acid sequence CCGGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GC AT GAGGC TC T GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 HC6-14AAS- A118C 382 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCTTCAGCCTGAGCTACAATGCC ATGAGCTGGGTTCGACAGGCCCCTGGCAAAGGA CTGGAATGGATCGGCTACATCTACAGCAGCGAC ACCACCTACTACGCCGACAGCGTTAAGGGCAGA TTCACCATCAGCCGGCACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAGATATC GGCACCGCCTACTACACCTTCAACATCTGGGGC CAGGGCACACTGGTTACAGTGTCTAGCTGCTCC ACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGT CC T CAGGAC TCTACTCCCT CAGCAGCGT G GTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG ACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGT T GAGCCCAAA TCTTGTGACAAAACTCACACATGCCCACCGTGC CCAGCACCTGAGGCCGCCGGGGGATCCTCAGTC TTCCTGTTCCCCCCAAAACCCAAGGACACTCTC ATGATCTCCCGGACCCCTGAGGTCACGTGCGTG GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTC CAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCC T GCACCAGGAC T GGC T GAACGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCGGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACG CCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC TTATATTCAAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG AT GC AT GAGGC TC T GC AC AACC AC T ACACGC AG AAGAGCCTCTCCCTGTCTCCCGGGAAA 16K21 LC1 309 GC T TACGATAT GACACAGAGCCC TAGCAGCC T G AGCGCCTCTGTGGGCGATAGAGTGACAATTACC mAb IgG chain SEQ ID NO Nucleic acid sequence TGTCAGGCCAGCCAGACCATCGGCAGCGACCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGC TGCTGATCTACAGAGCCTCTACACTGGCC AGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGACTTCACCCTGACAATTAGTAGC C T GC AGCC T GAGGAC T T T GCC ACC T AT T AC T GT CAGCAGGGC TACAGCAT GACCGAC GT GGAAAAT GTGTTCGGCGGAGGCACCAAGGTGGAAATCAAG AGAACAGTGGCCGCTCCGAGCGTGTTCATCTTT CCACCAAGCGACGAGCAGCTGAAGTCTGGCACA GCCTCTGTCGTGTGCCTGCTGAACAACTTCTAC CCCAGAGAAGCCAAGGTGCAGTGGAAGGTGGAC AATGCCCTGCAGAGCGGCAATAGCCAAGAGAGC GTGACCGAGCAGGACAGCAAGGATAGCACCTAC AGCCTGTCCAGCACACTGACCCTGAGCAAGGCC GACTACGAGAAGCACAAAGTGTACGCCTGCGAA GTGACACACCAGGGCCTGTCTAGCCCTGTGACC AAGAGCTTCAACCGGGGCGAGTGT 16K21 LC2 310 GACATCCAGATGACACAGAGCCCTAGCAGCCTG AGCGCCTCTGTGGGCGATAGAGTGACAATTACC TGTCAGGCCAGCCAGACCATCGGCAGCGACCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCTGCTGATCTACAGAGCCTCTACACTGGCC AGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGACTTCACCCTGACAATTAGTAGC C T GC AGCC T GAGGAC T T T GCC ACC TAT T AC T GT CAGCAGGGC TACAGCAT GACCGAC GT GGAAAAT GTGTTCGGCGGAGGCACCAAGGTGGAAATCAAG AGAACAGTGGCCGCTCCGAGCGTGTTCATCTTT CCACCAAGCGACGAGCAGC TGAAG T C TGGCACA GCCTCTGTCGTGTGCCTGCTGAACAACTTCTAC CCCAGAGAAGCCAAGGTGCAGTGGAAGGTGGAC AATGCCCTGCAGAGCGGCAATAGCCAAGAGAGC GTGACCGAGCAGGACAGCAAGGATAGCACCTAC AGCCTGTCCAGCACACTGACCCTGAGCAAGGCC GACTACGAGAAGCACAAAGTGTACGCCTGCGAA GTGACACACCAGGGCCTGTCTAGCCCTGTGACC AAGAGCTTCAACCGGGGCGAGTGT 16K21 LC3 311 GACTACCAGATGACACAGAGCCCTAGCAGCCTG AGCGCCTCTGTGGGCGATAGAGTGACAATTACC TGTCAGGCCAGCCAGACCATCGGCAGCGACCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGC TGC T GAT CTACAGAGCC T C TACAC T GGCC AGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGACTTCACCCTGACAATTAGTAGC C T GC AGCC T GAGGAC T T T GCC ACC TAT T AC T GT CAGCAGGGC TACAGCAT GACCGAC GT GGAAAAT GTGTTCGGCGGAGGCACCAAGGTGGAAATCAAG AGAACAGTGGCCGCTCCGAGCGTGTTCATCTTT CCACCAAGCGACGAGCAGC TGAAG T C TGGCACA GCCTCTGTCGTGTGCCTGCTGAACAACTTCTAC CCCAGAGAAGCCAAGGTGCAGTGGAAGGTGGAC AATGCCCTGCAGAGCGGCAATAGCCAAGAGAGC GTGACCGAGCAGGACAGCAAGGATAGCACCTAC mAb IgG chain SEQ ID NO Nucleic acid sequence AGCCTGTCCAGCACACTGACCCTGAGCAAGGCC GACTACGAGAAGCACAAAGTGTACGCCTGCGAA GTGACACACCAGGGCCTGTCTAGCCCTGTGACC AAGAGCTTCAACCGGGGCGAGTGT 16K21 LC4 312 GACATCCAGATGACACAGAGCCCTAGCAGCCTG AGCGCCTCTGTGGGCGATAGAGTGACAATTACC TGTAGAGCCAGCCAGACCATCGGCAGCGACCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGC TGC T GAT CTACAGAGCC T C TACAC T GGCC AGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGACTTCACCCTGACAATTAGTAGC C T GC AGCC T GAGGAC T T T GCC ACC T AT T AC T GT CAGCAGGGC TACAGCAT GACCGAC GT GGAAAAT GTGTTCGGCGGAGGCACCAAGGTGGAAATCAAG AGAACAGTGGCCGCTCCGAGCGTGTTCATCTTT CCACCAAGCGACGAGCAGC TGAAG T C TGGCACA GCCTCTGTCGTGTGCCTGCTGAACAACTTCTAC CCCAGAGAAGCCAAGGTGCAGTGGAAGGTGGAC AATGCCCTGCAGAGCGGCAATAGCCAAGAGAGC GTGACCGAGCAGGACAGCAAGGATAGCACCTAC AGCCTGTCCAGCACACTGACCCTGAGCAAGGCC GACTACGAGAAGCACAAAGTGTACGCCTGCGAA GTGACACACCAGGGCCTGTCTAGCCCTGTGACC AAGAGCTTCAACCGGGGCGAGTGT 16K21 LC5 313 GACATCCAGATGACACAGAGCCCTAGCAGCCTG AGCGCCTCTGTGGGCGATAGAGTGACAATTACC TGTCAGGCCAGCCAGAGCATCGGCAGCGACCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGC TGCTGATCTACAGAGCCTCTACACTGGCC AGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGACTTCACCCTGACAATTAGTAGC C T GC AGCC T GAGGAC T T T GCC ACC TAT T AC T GT CAGCAGGGC TACAGCAT GACCGAC GT GGAAAAT GTGTTCGGCGGAGGCACCAAGGTGGAAATCAAG AGAACAGTGGCCGCTCCGAGCGTGTTCATCTTT CCACCAAGCGACGAGCAGC TGAAG T C TGGCACA GCCTCTGTCGTGTGCCTGCTGAACAACTTCTAC CCCAGAGAAGCCAAGGTGCAGTGGAAGGTGGAC AATGCCCTGCAGAGCGGCAATAGCCAAGAGAGC GTGACCGAGCAGGACAGCAAGGATAGCACCTAC AGCCTGTCCAGCACACTGACCCTGAGCAAGGCC GACTACGAGAAGCACAAAGTGTACGCCTGCGAA GTGACACACCAGGGCCTGTCTAGCCCTGTGACC AAGAGCTTCAACCGGGGCGAGTGT 16K21 LC6 314 GACATCCAGATGACACAGAGCCCTAGCAGCCTG AGCGCCTCTGTGGGCGATAGAGTGACAATTACC TGTAGAGCCAGCCAGAGCATCGGCAGCGACCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCTGCTGATCTACAGAGCCTCTACACTGGCC AGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGACTTCACCCTGACAATTAGTAGC C T GC AGCC T GAGGAC T T T GCC ACC TAT T AC T GT CAGCAGGGC TACAGCAT GACCGAC GT GGAAAAT GTGTTCGGCGGAGGCACCAAGGTGGAAATCAAG mAb IgG chain SEQ ID NO Nucleic acid sequence AGAACAGTGGCCGCTCCGAGCGTGTTCATCTTT CCACCAAGCGACGAGCAGCTGAAGTCTGGCACA GCCTCTGTCGTGTGCCTGCTGAACAACTTCTAC CCCAGAGAAGCCAAGGTGCAGTGGAAGGTGGAC AATGCCCTGCAGAGCGGCAATAGCCAAGAGAGC GTGACCGAGCAGGACAGCAAGGATAGCACCTAC AGCCTGTCCAGCACACTGACCCTGAGCAAGGCC GACTACGAGAAGCACAAAGTGTACGCCTGCGAA GTGACACACCAGGGCCTGTCTAGCCCTGTGACC AAGAGCTTCAACCGGGGCGAGTGT 16K21 LC1-RESPECT- L 315 GC T TACGATAT GACACAGAGCCC TAGCAGCC T G AGCGCCTCTGTGGGCGATAGAGTGACAATTACC TGTCAGGCCAGCCAGACCATCGGCAGCGACCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCT GC T GAT CTACAGAGCC T C TACAC T GGCC AGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGACTTCACCCTGACAATTAGTAGC CTGCAGTGCGAGGACGTGGCCACCTATTACTGT CAGCAGGGC TACAGCAT GACCGAC GT GGAAAAT GTGTTCGGCGGAGGCACCAAGGTGGAAATCAAG AGAACAGTGGCCGCTCCGAGCGTGTTCATCTTT CCACCAAGCGACGAGCAGCTGAAGTCTGGCACA GCCTCTGTCGTGTGCCTGCTGAACAACTTCTAC CCCAGAGAAGCCAAGGTGCAGTGGAAGGTGGAC AATGCCCTGCAGAGCGGCAATAGCCAAGAGAGC GTGACCGAGCAGGACAGCAAGGATAGCACCTAC AGCCTGTCCAGCACACTGACCCTGAGCAAGGCC GACTACGAGAAGCACAAAGTGTACGCCTGCGAA GTGACACACCAGGGCCTGTCTAGCCCTGTGACC AAGAGCTTCAACCGGGGCGAGTGT 16K21 LC2-RESPECT- L 316 GACATCCAGATGACACAGAGCCCTAGCAGCCTG AGCGCCTCTGTGGGCGATAGAGTGACAATTACC TGTCAGGCCAGCCAGACCATCGGCAGCGACCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCTGCTGATCTACAGAGCCTCTACACTGGCC AGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGACTTCACCCTGACAATTAGTAGC CTGCAGTGCGAGGACGTGGCCACCTATTACTGT CAGCAGGGC TACAGCAT GACCGAC GT GGAAAAT GTGTTCGGCGGAGGCACCAAGGTGGAAATCAAG AGAACAGTGGCCGCTCCGAGCGTGTTCATCTTT CCACCAAGCGACGAGCAGCTGAAGTCTGGCACA GCCTCTGTCGTGTGCCTGCTGAACAACTTCTAC CCCAGAGAAGCCAAGGTGCAGTGGAAGGTGGAC AATGCCCTGCAGAGCGGCAATAGCCAAGAGAGC GTGACCGAGCAGGACAGCAAGGATAGCACCTAC AGCCTGTCCAGCACACTGACCCTGAGCAAGGCC GACTACGAGAAGCACAAAGTGTACGCCTGCGAA GTGACACACCAGGGCCTGTCTAGCCCTGTGACC AAGAGCTTCAACCGGGGCGAGTGT 16K21 LC3-RESPECT- L 317 GACTACCAGATGACACAGAGCCCTAGCAGCCTG AGCGCCTCTGT GGGCGATAGAGT GACAAT TACC TGTCAGGCCAGCCAGACCATCGGCAGCGACCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT mAb IgG chain SEQ ID NO Nucleic acid sequence AAGC TGC T GAT CTACAGAGCC T C TACACT GGCC AGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGACTTCACCCTGACAATTAGTAGC CTGCAGTGCGAGGACGTGGCCACCTATTACTGT CAGCAGGGC TACAGCAT GACCGAC GT GGAAAAT GTGTTCGGCGGAGGCACCAAGGTGGAAATCAAG AGAACAGTGGCCGCTCCGAGCGTGTTCATCTTT CCACCAAGCGACGAGCAGCTGAAGTCTGGCACA GCCTCTGTCGTGTGCCTGCTGAACAACTTCTAC CCCAGAGAAGCCAAGGTGCAGTGGAAGGTGGAC AATGCCCTGCAGAGCGGCAATAGCCAAGAGAGC GTGACCGAGCAGGACAGCAAGGATAGCACCTAC AGCCTGTCCAGCACACTGACCCTGAGCAAGGCC GACTACGAGAAGCACAAAGTGTACGCCTGCGAA GTGACACACCAGGGCCTGTCTAGCCCTGTGACC AAGAGCTTCAACCGGGGCGAGTGT 16K21 LC4-RESPECT- L 318 GACATCCAGATGACACAGAGCCCTAGCAGCCTG AGCGCCTCTGTGGGCGATAGAGTGACAATTACC TGTAGAGCCAGCCAGACCATCGGCAGCGACCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCT GC T GAT CTACAGAGCC T C TACAC T GGCC AGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGACTTCACCCTGACAATTAGTAGC CTGCAGTGCGAGGACGTGGCCACCTATTACTGT CAGCAGGGC TACAGCAT GACCGAC GT GGAAAAT GTGTTCGGCGGAGGCACCAAGGTGGAAATCAAG AGAACAGTGGCCGCTCCGAGCGTGTTCATCTTT CCACCAAGCGACGAGCAGCTGAAGTCTGGCACA GCCTCTGTCGTGTGCCTGCTGAACAACTTCTAC CCCAGAGAAGCCAAGGTGCAGTGGAAGGTGGAC AATGCCCTGCAGAGCGGCAATAGCCAAGAGAGC GTGACCGAGCAGGACAGCAAGGATAGCACCTAC AGCCTGTCCAGCACACTGACCCTGAGCAAGGCC GACTACGAGAAGCACAAAGTGTACGCCTGCGAA GTGACACACCAGGGCCTGTCTAGCCCTGTGACC AAGAGCTTCAACCGGGGCGAGTGT 16K21 LC5-RESPECT- L 319 GACATCCAGATGACACAGAGCCCTAGCAGCCTG AGCGCCTCTGTGGGCGATAGAGTGACAATTACC TGTCAGGCCAGCCAGAGCATCGGCAGCGACCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCT GC T GAT CTACAGAGCC T C TACAC T GGCC AGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGACTTCACCCTGACAATTAGTAGC CTGCAGTGCGAGGACGTGGCCACCTATTACTGT CAGCAGGGC TACAGCAT GACCGAC GT GGAAAAT GTGTTCGGCGGAGGCACCAAGGTGGAAATCAAG AGAACAGTGGCCGCTCCGAGCGTGTTCATCTTT CCACCAAGCGACGAGCAGCTGAAGTCTGGCACA GCCTCTGTCGTGTGCCTGCTGAACAACTTCTAC CCCAGAGAAGCCAAGGTGCAGTGGAAGGTGGAC AATGCCCTGCAGAGCGGCAATAGCCAAGAGAGC GTGACCGAGCAGGACAGCAAGGATAGCACCTAC AGCCTGTCCAGCACACTGACCCTGAGCAAGGCC GACTACGAGAAGCACAAAGTGTACGCCTGCGAA mAb IgG chain SEQ ID NO Nucleic acid sequence GTGACACACCAGGGCCTGTCTAGCCCTGTGACC AAGAGCTTCAACCGGGGCGAGTGT 16K21 LC6-RESPECT- L 320 GACATCCAGATGACACAGAGCCCTAGCAGCCTG AGCGCCTCTGTGGGCGATAGAGTGACAATTACC TGTAGAGCCAGCCAGAGCATCGGCAGCGACCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCT GC T GAT CTACAGAGCC T C TACAC T GGCC AGCGGCGTGCCAAGCAGATTTTCTGGCTCTGGC AGCGGCACCGACTTCACCCTGACAATTAGTAGC CTGCAGTGCGAGGACGTGGCCACCTATTACTGT CAGCAGGGC TACAGCAT GACCGAC GT GGAAAAT GTGTTCGGCGGAGGCACCAAGGTGGAAATCAAG AGAACAGTGGCCGCTCCGAGCGTGTTCATCTTT CCACCAAGCGACGAGCAGCTGAAGTCTGGCACA GCCTCTGTCGTGTGCCTGCTGAACAACTTCTAC CCCAGAGAAGCCAAGGTGCAGTGGAAGGTGGAC AATGCCCTGCAGAGCGGCAATAGCCAAGAGAGC GTGACCGAGCAGGACAGCAAGGATAGCACCTAC AGCCTGTCCAGCACACTGACCCTGAGCAAGGCC GACTACGAGAAGCACAAAGTGTACGCCTGCGAA GTGACACACCAGGGCCTGTCTAGCCCTGTGACC AAGAGCTTCAACCGGGGCGAGTGT 17124 HC1 321 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCATCATCTACGGCAGCGGC AGCACCT T T TACGCCTCT TGGGCCAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCCTGGCACACTGGTCACAGTGTCTAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACAAAACTCACACATGCCCACCG TGCCCAGCACCTGAACTCCTGGGGGGACCGTCA GTCTTCCTCTTCCCCCCAAAACCCAAGGACACC CTCATGATCTCCCGGACCCCTGAGGTCACATGC GTGGTGGTGGACGTGAGCCACGAAGACCCTGAG GTCAAGTTCAACTGGTACGTGGACGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAATGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCAGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC mAb IgG chain SEQ ID NO Nucleic acid sequence ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGT GGC AGC AGGGGAACGTC T T C T CAT GC T CC GT GAT GC AT GAGGC T C T GCACAAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 HC2 322 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGGTGAGCATCATCTACGGCAGCGGC AGCACCT T T TACGCCTCT TGGGCCAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCCTGGCACACTGGTCACAGTGTCTAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACAAAACTCACACATGCCCACCG TGCCCAGCACCTGAACTCCTGGGGGGACCGTCA GTCTTCCTCTTCCCCCCAAAACCCAAGGACACC CTCATGATCTCCCGGACCCCTGAGGTCACATGC GTGGTGGTGGACGTGAGCCACGAAGACCCTGAG GTCAAGTTCAACTGGTACGTGGACGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAATGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCAGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCC GT GAT GC AT GAGGC T C T GC AC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 HC3 323 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA mAb IgG chain SEQ ID NO Nucleic acid sequence CTGGAATGGATCGGCATCATCTACGGCAGCGGC AGCACCT T T TACGCCGACAGCGT TAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCCTGGCACACTGGTCACAGTGTCTAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACAAAACTCACACATGCCCACCG TGCCCAGCACCTGAACTCCTGGGGGGACCGTCA GTCTTCCTCTTCCCCCCAAAACCCAAGGACACC CTCATGATCTCCCGGACCCCTGAGGTCACATGC GTGGTGGTGGACGTGAGCCACGAAGACCCTGAG GTCAAGTTCAACTGGTACGTGGACGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAATGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCAGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGT GGC AGC AGGGGAACGTC T T C T CAT GC T CC GT GAT GC AT GAGGC T C T GCAC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 HC4 324 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGGTGAGCATCATCTACGGCAGCGGC AGCACCT T T TACGCCGACAGCGT TAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCCTGGCACACTGGTCACAGTGTCTAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC mAb IgG chain SEQ ID NO Nucleic acid sequence GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACAAAACTCACACATGCCCACCG TGCCCAGCACCTGAACTCCTGGGGGGACCGTCA GTCTTCCTCTTCCCCCCAAAACCCAAGGACACC CTCATGATCTCCCGGACCCCTGAGGTCACATGC GTGGTGGTGGACGTGAGCCACGAAGACCCTGAG GTCAAGTTCAACTGGTACGTGGACGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAATGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCAGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGT GGC AGC AGGGGAACGTC T T C T CAT GC T CC GT GAT GC AT GAGGC T C T GC AC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 HC5 325 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGGTGAGCATCATCTACGGCAGCGGC AGCACCT T T TACGCCGACAGCGT TAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCAGGGCACAC T GGT CACAGT G T C TAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACAAAACTCACACATGCCCACCG TGCCCAGCACCTGAACTCCTGGGGGGACCGTCA GTCTTCCTCTTCCCCCCAAAACCCAAGGACACC CTCATGATCTCCCGGACCCCTGAGGTCACATGC GTGGTGGTGGACGTGAGCCACGAAGACCCTGAG GTCAAGTTCAACTGGTACGTGGACGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAATGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC mAb IgG chain SEQ ID NO Nucleic acid sequence CTCCCAGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCC GT GATGC AT GAGGC T C T GC AC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 HC1-14AAS 326 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCATCATCTACGGCAGCGGC AGCACCT T T TACGCCTCT TGGGCCAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCCTGGCACACTGGTCACAGTGTCTAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACAAAACTCACACATGCCCACCG TGCCCAGCACCTGAGGCCGCCGGGGGATCCTCA GTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGC GTGGTGGTGGACGTGAGCCAGGAAGACCCCGAG GTCCAGTTCAACTGGTACGTGGATGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCGGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCC GT GAT GC AT GAGGC T C T GC AC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 HC2-14AAS 327 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT mAb IgG chain SEQ ID NO Nucleic acid sequence GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGGTGAGCATCATCTACGGCAGCGGC AGCACC TTTTACGCCTCTT GGGCC AAGGGC AGA TTCACCATCAGCCGGGACAACAGCAAGAACACC CTGTACCTGCAGAT GAACAGC C T GAGAGC C GAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCCTGGCACACTGGTCACAGTGTCTAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACAAAACTCACACATGCCCACCG TGCCCAGCACCTGAGGCCGCCGGGGGATCCTCA GTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGC GTGGTGGTGGACGTGAGCCAGGAAGACCCCGAG GTCCAGTTCAACTGGTACGTGGATGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCGGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCC GT GATGC AT GAGGC T C T GC AC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 HC3-14AAS 328 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCATCATCTACGGCAGCGGC AGCACCT T T TACGCCGACAGCGT TAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCCTGGCACACTGGTCACAGTGTCTAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC mAb IgG chain SEQ ID NO Nucleic acid sequence CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACAAAACTCACACATGCCCACCG TGCCCAGCACCTGAGGCCGCCGGGGGATCCTCA GTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGC GTGGTGGTGGACGTGAGCCAGGAAGACCCCGAG GTCCAGTTCAACTGGTACGTGGATGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCGGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCC GT GATGC AT GAGGC T C T GC AC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 HC4-14AAS 329 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGGTGAGCATCATCTACGGCAGCGGC AGCACCT T T TACGCCGACAGCGT TAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCCTGGCACACTGGTCACAGTGTCTAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACAAAACTCACACATGCCCACCG TGCCCAGCACCTGAGGCCGCCGGGGGATCCTCA GTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGC GTGGTGGTGGACGTGAGCCAGGAAGACCCCGAG GTCCAGTTCAACTGGTACGTGGATGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC mAb IgG chain SEQ ID NO Nucleic acid sequence CTCACCGTCCTGCACCAGGACTGGCTGAACGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCGGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCC GT GAT GC AT GAGGC T C T GC AC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 HC5-14AAS 330 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGGTGAGCATCATCTACGGCAGCGGC AGCACCT T T TACGCCGACAGCGT TAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCAGGGCACAC T GGT CACAGT G T C TAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACAAAACTCACACATGCCCACCG TGCCCAGCACCTGAGGCCGCCGGGGGATCCTCA GTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGC GTGGTGGTGGACGTGAGCCAGGAAGACCCCGAG GTCCAGTTCAACTGGTACGTGGATGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCGGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGT GGCAGCAGGGGAACGTC T TCTCATGCTCC GT GATGC AT GAGGC T C T GC AC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA mAb IgG chain SEQ ID NO Nucleic acid sequence 17124 HC1-RH12 331 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCATCATCTACGGCAGCGGC AGCACC TTTTACGCCTCTT GGGCCAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCC T GGCACAC T GGT CACAGT G T C TAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCAAATCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACGCCACTCACACATGCCCACCG TGCCCAGCACCTGAGGCCGCCGGGGGATCCTCA GTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGC GTGGTGGTGGACGTGAGCCAGGAAGACCCCGAG GTCCAGTTCAACTGGTACGTGGATGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCGGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGTGGCAGCAGGGGAACGTC T TCTCATGCTCC GT GATGC AT GAGGC T C T GC AC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 HC2-RH12 332 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGGTGAGCATCATCTACGGCAGCGGC AGCACCT T T TACGCCTCT TGGGCCAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCCTGGCACACTGGTCACAGTGTCTAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCAAATCTGGGGGCACAGCG mAb IgG chain SEQ ID NO Nucleic acid sequence GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACGCCACTCACACATGCCCACCG TGCCCAGCACCTGAGGCCGCCGGGGGATCCTCA GTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGC GTGGTGGTGGACGTGAGCCAGGAAGACCCCGAG GTCCAGTTCAACTGGTACGTGGATGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCGGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCC GT GAT GC AT GAGGC T C T GC AC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 HC3-RH12 333 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCATCATCTACGGCAGCGGC AGCACCT T T TACGCCGACAGCGT TAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCCTGGCACACTGGTCACAGTGTCTAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCAAATCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACGCCACTCACACATGCCCACCG TGCCCAGCACCTGAGGCCGCCGGGGGATCCTCA GTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGC GTGGTGGTGGACGTGAGCCAGGAAGACCCCGAG GTCCAGTTCAACTGGTACGTGGATGGCGTGGAG mAb IgG chain SEQ ID NO Nucleic acid sequence GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCGGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGT GGC AGC AGGGGAACGTC T T C T CAT GC T CC GT GAT GC AT GAGGC T C T GC AC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 HC4-RH12 334 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGGTGAGCATCATCTACGGCAGCGGC AGCACCT T T TACGCCGACAGCGT TAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCCTGGCACACTGGTCACAGTGTCTAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCAAATCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACGCCACTCACACATGCCCACCG TGCCCAGCACCTGAGGCCGCCGGGGGATCCTCA GTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGC GTGGTGGTGGACGTGAGCCAGGAAGACCCCGAG GTCCAGTTCAACTGGTACGTGGATGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCGGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCC mAb IgG chain SEQ ID NO Nucleic acid sequence GT GATGC AT GAGGC T C T GC AC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 HC5-RH12 335 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGGTGAGCATCATCTACGGCAGCGGC AGCACCT T T TACGCCGACAGCGT TAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCAGGGCACAC T GGT CACAGT G T C TAGCGCA TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCAAATCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACGCCACTCACACATGCCCACCG TGCCCAGCACCTGAGGCCGCCGGGGGATCCTCA GTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGC GTGGTGGTGGACGTGAGCCAGGAAGACCCCGAG GTCCAGTTCAACTGGTACGTGGATGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCGGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCC GT GAT GC AT GAGGC T C T GC AC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 HC5-14AAS- A118C 383 GAAGTGCAACTGGTTGAGTCTGGCGGAGGACTG GTTCAACCTGGCGGAAGCCTGAGACTGTCTTGT GCCGCCTCTGGCATCGATCTGAGCAGACACGCC ATGAGCTGGGTTCGACAGGCCCCTGGAAAAGGA CTGGAATGGGTGAGCATCATCTACGGCAGCGGC AGCACCT T T TACGCCGACAGCGT TAAGGGCAGA TTCACCATCAGCCGGGACAACAGCAAGAACACC C T GTACC T GCAGAT GAACAGCC T GAGAGCCGAG GACACCGCCGTGTACTACTGTGCCAGAACCATG TGGACCGACAGCAGCGTGTTCCTGAATATCTGG GGCCAGGGCACAC T GGT CACAGT G T C TAGC TGC mAb IgG chain SEQ ID NO Nucleic acid sequence TCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACAAAACTCACACATGCCCACCG TGCCCAGCACCTGAGGCCGCCGGGGGATCCTCA GTCTTCCTGTTCCCCCCAAAACCCAAGGACACT CTCATGATCTCCCGGACCCCTGAGGTCACGTGC GTGGTGGTGGACGTGAGCCAGGAAGACCCCGAG GTCCAGTTCAACTGGTACGTGGATGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAACGGC AAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCGGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC TTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCTTATATTCAAAGCTCACCGTGGACAAGAGC AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCC GT GAT GC AT GAGGC T C T GC AC AAC C ACT AC ACG CAGAAGAGCCTCTCCCTGTCTCCCGGGAAA 17124 LC1 336 GCTCAAGTGATGACACAGAGCCC TAGCACAC T G AGCGCCTCTGTGGGCGATAGAGTGACCATCACC TGTCAGGCTAGCCCCAGCGTGTACAACAACAAG AACCTGGCCTGGTATCAGCAGAAGCCCGGAAAG GCCCCTAAGCTGCTGATCTATGAAGCCAGCAAA GTGGCCAGCGGCGTGCCAAGCAGATTTTCTGGC TCTGGCAGCGGCACCGAGTTCACCCTGACAATC AGTAGCCTGCAGCCCGACGACTTTGCCACATAT TACTGCCAGGGCGAGTTTAGCTGGTCCTCTGGC GATCTGATTGCCTTCGGCGGAGGCACCAAGGTG GAAATCAAGAGAACAGTGGCCGCTCCGAGCGTG TTCATCTTTCCACCAAGCGACGAGCAGCTGAAG TCTGGCACAGCCTCTGTCGTGTGCCTGCTGAAC AACTTCTACCCCAGAGAAGCCAAGGTGCAGTGG AAGGTGGACAATGCCCTGCAGAGCGGCAATAGC CAAGAGAGCGTGACCGAGCAGGACAGCAAGGAT AGCACC TACAGCC T GT CCAGCACAC T GACCC T G AGCAAGGCCGACTACGAGAAGCACAAAGTGTAC GCCTGCGAAGTGACACACCAGGGCCTGTCTAGC CCTGTGACCAAGAGCTTCAACCGGGGCGAGTGT 17124 LC2 337 GACATCCAGATGACACAGAGCCCTAGCACACTG AGCGCCTCTGT GGGCGATAGAGT GACCAT CACC TGTCAGGCTAGCCCCAGCGTGTACAACAACAAG AACCTGGCCTGGTATCAGCAGAAGCCCGGAAAG mAb IgG chain SEQ ID NO Nucleic acid sequence GCCCCTAAGCTGCTGATCTATGAAGCCAGCAAA GTGGCCAGCGGCGTGCCAAGCAGATTTTCTGGC TCTGGCAGCGGCACCGAGTTCACCCTGACAATC AGTAGCCTGCAGCCCGACGACTTTGCCACATAT TACTGCCAGGGCGAGTTTAGCTGGTCCTCTGGC GATCTGATTGCCTTCGGCGGAGGCACCAAGGTG GAAATCAAGAGAACAGTGGCCGCTCCGAGCGTG TTCATCTTTCCACCAAGCGACGAGCAGCTGAAG TCTGGCACAGCCTCTGTCGTGTGCCTGCTGAAC AACTTCTACCCCAGAGAAGCCAAGGTGCAGTGG AAGGTGGACAATGCCCTGCAGAGCGGCAATAGC CAAGAGAGCGTGACCGAGCAGGACAGCAAGGAT AGCACC TACAGCC T GT CCAGCACAC T GACCC T G AGCAAGGCCGACTACGAGAAGCACAAAGTGTAC GCCTGCGAAGTGACACACCAGGGCCTGTCTAGC CCTGTGACCAAGAGCTTCAACCGGGGCGAGTGT 17124 LC3 338 GACCAACAGAT GACACAGAGCCC TAGCACAC T G AGCGCCTCTGTGGGCGATAGAGTGACCATCACC TGTCAGGCTAGCCCCAGCGTGTACAACAACAAG AACCTGGCCTGGTATCAGCAGAAGCCCGGAAAG GCCCCTAAGCTGCTGATCTATGAAGCCAGCAAA GTGGCCAGCGGCGTGCCAAGCAGATTTTCTGGC TCTGGCAGCGGCACCGAGTTCACCCTGACAATC AGTAGCCTGCAGCCCGACGACTTTGCCACATAT TACTGCCAGGGCGAGTTTAGCTGGTCCTCTGGC GATCTGATTGCCTTCGGCGGAGGCACCAAGGTG GAAATCAAGAGAACAGTGGCCGCTCCGAGCGTG TTCATCTTTCCACCAAGCGACGAGCAGCTGAAG TCTGGCACAGCCTCTGTCGTGTGCCTGCTGAAC AACTTCTACCCCAGAGAAGCCAAGGTGCAGTGG AAGGTGGACAATGCCCTGCAGAGCGGCAATAGC CAAGAGAGCGTGACCGAGCAGGACAGCAAGGAT AGCACC TACAGCC T GT CCAGCACAC T GACCC T G AGCAAGGCCGACTACGAGAAGCACAAAGTGTAC GCCTGCGAAGTGACACACCAGGGCCTGTCTAGC CCTGTGACCAAGAGCTTCAACCGGGGCGAGTGT 17124 LC4 339 GACATCCAGATGACACAGAGCCCTAGCACACTG AGCGCCTCTGTGGGCGATAGAGTGACCATCACC TGTAGAGCTAGCCCCAGCGTGTACAACAACAAG AACCTGGCCTGGTATCAGCAGAAGCCCGGAAAG GCCCCTAAGCTGCTGATCTATGAAGCCAGCAAA GTGGCCAGCGGCGTGCCAAGCAGATTTTCTGGC TCTGGCAGCGGCACCGAGTTCACCCTGACAATC AGTAGCCTGCAGCCCGACGACTTTGCCACATAT TACTGCCAGGGCGAGTTTAGCTGGTCCTCTGGC GATCTGATTGCCTTCGGCGGAGGCACCAAGGTG GAAATCAAGAGAACAGTGGCCGCTCCGAGCGTG TTCATCTTTCCACCAAGCGACGAGCAGCTGAAG TCTGGCACAGCCTCTGTCGTGTGCCTGCTGAAC AACTTCTACCCCAGAGAAGCCAAGGTGCAGTGG AAGGTGGACAATGCCCTGCAGAGCGGCAATAGC CAAGAGAGCGTGACCGAGCAGGACAGCAAGGAT AGCACC TACAGCC T GT CCAGCACAC T GACCC T G AGCAAGGCCGACTACGAGAAGCACAAAGTGTAC mAb IgG chain SEQ ID NO Nucleic acid sequence GCCTGCGAAGTGACACACCAGGGCCTGTCTAGC CCTGTGACCAAGAGCTTCAACCGGGGCGAGTGT 17124 LC5 340 GACATCCAGATGACACAGAGCCCTAGCACACTG AGCGCCTCTGTGGGCGATAGAGTGACCATCACC TGTCAGGCTAGCCCCAGCGTGTACAACAACAAG AACCTGGCCTGGTATCAGCAGAAGCCCGGAAAG GCCCCTAAGCTGCTGATCTATGATGCCAGCAAA GTGGCCAGCGGCGTGCCAAGCAGATTTTCTGGC TCTGGCAGCGGCACCGAGTTCACCCTGACAATC AGTAGCCTGCAGCCCGACGACTTTGCCACATAT TACTGCCAGGGCGAGTTTAGCTGGTCCTCTGGC GATCTGATTGCCTTCGGCGGAGGCACCAAGGTG GAAATCAAGAGAACAGTGGCCGCTCCGAGCGTG TTCATCTTTCCACCAAGCGACGAGCAGCTGAAG TCTGGCACAGCCTCTGTCGTGTGCCTGCTGAAC AACTTCTACCCCAGAGAAGCCAAGGTGCAGTGG AAGGTGGACAATGCCCTGCAGAGCGGCAATAGC CAAGAGAGCGTGACCGAGCAGGACAGCAAGGAT AGCACC TACAGCC T GT CCAGCACAC T GACCC T G AGCAAGGCCGACTACGAGAAGCACAAAGTGTAC GCCTGCGAAGTGACACACCAGGGCCTGTCTAGC CCTGTGACCAAGAGCTTCAACCGGGGCGAGTGT 17124 LC1-RESPECT- L 341 GCTCAAGTGATGACACAGAGCCC TAGCACAC T G AGCGCCTCTGTGGGCGATAGAGTGACCATCACC TGTCAGGCTAGCCCCAGCGTGTACAACAACAAG AACCTGGCCTGGTATCAGCAGAAGCCCGGAAAG GCCCCTAAGCTGCTGATCTATGAAGCCAGCAAA GTGGCCAGCGGCGTGCCAAGCAGATTTTCTGGC TCTGGCAGCGGCACCGAGTTCACCCTGACAATC AGTAGCCTGCAGTGTGACGACGTGGCCACATAT TACTGCCAGGGCGAGTTTAGCTGGTCCTCTGGC GATCTGATTGCCTTCGGCGGAGGCACCAAGGTG GAAATCAAGAGAACAGTGGCCGCTCCGAGCGTG TTCATCTTTCCACCAAGCGACGAGCAGCTGAAG TCTGGCACAGCCTCTGTCGTGTGCCTGCTGAAC AACTTCTACCCCAGAGAAGCCAAGGTGCAGTGG AAGGTGGACAATGCCCTGCAGAGCGGCAATAGC CAAGAGAGCGTGACCGAGCAGGACAGCAAGGAT AGCACC TACAGCC T GT CCAGCACAC T GACCC T G AGCAAGGCCGACTACGAGAAGCACAAAGTGTAC GCCTGCGAAGTGACACACCAGGGCCTGTCTAGC CCTGTGACCAAGAGCTTCAACCGGGGCGAGTGT 17124 LC2-RESPECT- L 342 GACATCCAGATGACACAGAGCCCTAGCACACTG AGCGCCTCTGTGGGCGATAGAGTGACCATCACC TGTCAGGCTAGCCCCAGCGTGTACAACAACAAG AACCTGGCCTGGTATCAGCAGAAGCCCGGAAAG GCCCCTAAGCTGCTGATCTATGAAGCCAGCAAA GTGGCCAGCGGCGTGCCAAGCAGATTTTCTGGC TCTGGCAGCGGCACCGAGTTCACCCTGACAATC AGTAGCCTGCAGTGTGACGACGTGGCCACATAT TACTGCCAGGGCGAGTTTAGCTGGTCCTCTGGC GATCTGATTGCCTTCGGCGGAGGCACCAAGGTG GAAATCAAGAGAACAGTGGCCGCTCCGAGCGTG TTCATCTTTCCACCAAGCGACGAGCAGCTGAAG mAb IgG chain SEQ ID NO Nucleic acid sequence TCTGGCACAGCCTCTGTCGTGTGCCTGCTGAAC AACTTCTACCCCAGAGAAGCCAAGGTGCAGTGG AAGGTGGACAATGCCCTGCAGAGCGGCAATAGC CAAGAGAGCGTGACCGAGCAGGACAGCAAGGAT AGCACCTACAGCCTGTCCAGCACACTGACCCTG AGCAAGGCCGACTACGAGAAGCACAAAGTGTAC GCCT GCGAAGT GACACACCAGGGC CTGTCTAGC CCTGTGACCAAGAGCTTCAACCGGGGCGAGTGT 17124 LC3-RESPECT- L 343 GACCAACAGAT GACACAGAGCCC TAGCACAC T G AGCGCCTCTGTGGGCGATAGAGTGACCATCACC TGTCAGGCTAGCCCCAGCGTGTACAACAACAAG AACCTGGCCTGGTATCAGCAGAAGCCCGGAAAG GCCCCTAAGCTGCTGATCTATGAAGCCAGCAAA GTGGCCAGCGGCGTGCCAAGCAGATTTTCTGGC TCTGGCAGCGGCACCGAGTTCACCCTGACAATC AGTAGCCTGCAGTGTGACGACGTGGCCACATAT TACTGCCAGGGCGAGTTTAGCTGGTCCTCTGGC GATCTGATTGCCTTCGGCGGAGGCACCAAGGTG GAAATCAAGAGAACAGTGGCCGCTCCGAGCGTG TTCATCTTTCCACCAAGCGACGAGCAGCTGAAG TCTGGCACAGCCTCTGTCGTGTGCCTGCTGAAC AACTTCTACCCCAGAGAAGCCAAGGTGCAGTGG AAGGTGGACAATGCCCTGCAGAGCGGCAATAGC CAAGAGAGCGTGACCGAGCAGGACAGCAAGGAT AGCACC TACAGCC T GT CCAGCACAC T GACCC T G AGCAAGGCCGACTACGAGAAGCACAAAGTGTAC GCCTGCGAAGTGACACACCAGGGCCTGTCTAGC CCTGTGACCAAGAGCTTCAACCGGGGCGAGTGT 17124 LC4-RESPECT- L 344 GACATCCAGATGACACAGAGCCCTAGCACACTG AGCGCCTCTGTGGGCGATAGAGTGACCATCACC TGTAGAGCTAGCCCCAGCGTGTACAACAACAAG AACCTGGCCTGGTATCAGCAGAAGCCCGGAAAG GCCCCTAAGCTGCTGATCTATGAAGCCAGCAAA GTGGCCAGCGGCGTGCCAAGCAGATTTTCTGGC TCTGGCAGCGGCACCGAGTTCACCCTGACAATC AGTAGCCTGCAGTGTGACGACGTGGCCACATAT TACTGCCAGGGCGAGTTTAGCTGGTCCTCTGGC GATCTGATTGCCTTCGGCGGAGGCACCAAGGTG GAAATCAAGAGAACAGTGGCCGCTCCGAGCGTG TTCATCTTTCCACCAAGCGACGAGCAGCTGAAG TCTGGCACAGCCTCTGTCGTGTGCCTGCTGAAC AACTTCTACCCCAGAGAAGCCAAGGTGCAGTGG AAGGTGGACAATGCCCTGCAGAGCGGCAATAGC CAAGAGAGCGTGACCGAGCAGGACAGCAAGGAT AGCACC TACAGCC T GT CCAGCACAC T GACCC T G AGCAAGGCCGACTACGAGAAGCACAAAGTGTAC GCCTGCGAAGTGACACACCAGGGCCTGTCTAGC CCTGTGACCAAGAGCTTCAACCGGGGCGAGTGT 17124 LC5-RESPECT- L 345 GACATCCAGATGACACAGAGCCCTAGCACACTG AGCGCCTCTGTGGGCGATAGAGTGACCATCACC TGTCAGGCTAGCCCCAGCGTGTACAACAACAAG AACCTGGCCTGGTATCAGCAGAAGCCCGGAAAG GCCCCTAAGCTGCTGATCTATGATGCCAGCAAA GTGGCCAGCGGCGTGCCAAGCAGATTTTCTGGC mAb IgG chain SEQ ID NO Nucleic acid sequence TCTGGCAGCGGCACCGAGTTCACCCTGACAATC AGTAGCCTGCAGTGTGACGACGTGGCCACATAT TACTGCCAGGGCGAGTTTAGCTGGTCCTCTGGC GATCTGATTGCCTTCGGCGGAGGCACCAAGGTG GAAATCAAGAGAACAGTGGCCGCTCCGAGCGTG TTCATCTTTCCACCAAGCGACGAGCAGCTGAAG TCTGGCACAGCCTCTGTCGTGTGCCTGCTGAAC AACTTCTACCCCAGAGAAGCCAAGGTGCAGTGG AAGGTGGACAATGCCCTGCAGAGCGGCAATAGC CAAGAGAGCGTGACCGAGCAGGACAGCAAGGAT AGCACCTACAGCCTGTCCAGCACACTGACCCTG AGCAAGGCCGACTACGAGAAGCACAAAGTGTAC GCCT GCGAAGT GACACACCAGGGC CTGTCTAGC CCTGTGACCAAGAGCTTCAACCGGGGCGAGTGT 20E16 HC1 346 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCC T C T GGCC T GGAC T TCAAC AAAT AT GGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCTCTTGGGTCAACGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGTGCGTTGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCACCTCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACAAAACTCACACATGCCCACCGTGCCCAGCA CCTGAACTCCTGGGGGGACCGTCAGTCTTCCTC TTCCCCCCAAAACCCAAGGACACCCTCATGATC TCCCGGACCCCTGAGGTCACATGCGTGGTGGTG GACGTGAGCCACGAAGACCCTGAGGTCAAGTTC AACTGGTACGTGGACGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GC ACC AGGACT GGC T GAAT GGC AAGGAGT AC AAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT TCAAAGCTCACCGTGGACAAGAGCAGGTGGCAG CAGGGGAACGTCTTCTCATGCTCCGTGATGCAT mAb IgG chain SEQ ID NO Nucleic acid sequence GAGGCTCTGCACAACCACTACACGCAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC2 347 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCC T C T GGCC T GGAC T TCAAC AAAT AT GGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGGTGAGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCTCTTGGGTCAACGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGTGCGTTGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCACCTCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACAAAACTCACACATGCCCACCGTGCCCAGCA CCTGAACTCCTGGGGGGACCGTCAGTCTTCCTC TTCCCCCCAAAACCCAAGGACACCCTCATGATC TCCCGGACCCCTGAGGTCACATGCGTGGTGGTG GACGTGAGCCACGAAGACCCTGAGGTCAAGTTC AACTGGTACGTGGACGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GC ACC AGGACT GGC T GAAT GGC AAGGAGT AC AAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT TCAAAGCTCACCGTGGACAAGAGCAGGTGGCAG CAGGGGAACGTCTTCTCATGCTCCGTGATGCAT GAGGC T C T GCACAAC CACTACACG CAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC3 348 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCC T C T GGCC T GGAC T TCAAC AAAT AT GGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCGACAGCGTTAAGGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGTGCGTTGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG mAb IgG chain SEQ ID NO Nucleic acid sequence GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCACCTCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACAAAACTCACACATGCCCACCGTGCCCAGCA CCTGAACTCCTGGGGGGACCGTCAGTCTTCCTC TTCCCCCCAAAACCCAAGGACACCCTCATGATC TCCCGGACCCCTGAGGTCACATGCGTGGTGGTG GACGTGAGCCACGAAGACCCTGAGGTCAAGTTC AACTGGTACGTGGACGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GCACC AGGAC TGGC T GAAT GGC AAGGAGT AC AAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT TCAAAGCTCACCGTGGACAAGAGCAGGTGGCAG CAGGGGAACGT CT T C T CAT GC T CC GT GAT GCAT GAGGC T C T GCACAAC CACTACACG CAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC4 349 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCCTCTGGCCTGGACTTCAACAAATATGCC ATGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCGACAGCGTTAAGGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGTGCGTTGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCACCTCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACAAAACTCACACATGCCCACCGTGCCCAGCA CCTGAACTCCTGGGGGGACCGTCAGTCTTCCTC TTCCCCCCAAAACCCAAGGACACCCTCATGATC TCCCGGACCCCTGAGGTCACATGCGTGGTGGTG mAb IgG chain SEQ ID NO Nucleic acid sequence GACGTGAGCCACGAAGACCCTGAGGTCAAGTTC AACTGGTACGTGGACGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GCACC AGGACT GGC T GAAT GGC AAGGAGT AC AAGT GCAAGGTCTCCAACAAAGCCCTCCCAGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT T CAAAGC T CACCGT GGACAAGAGCAGGT GGCAG CAGGGGAACGTCTTCTCATGCTCCGTGATGCAT GAGGCTCTGCACAACCACTACACGCAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC5 350 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCC T C T GGCC T GGAC T TCAAC AAAT AT GGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCGACAGCGTTAAGGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGCCAAATGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCACCTCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACAAAACTCACACATGCCCACCGTGCCCAGCA CCTGAACTCCTGGGGGGACCGTCAGTCTTCCTC TTCCCCCCAAAACCCAAGGACACCCTCATGATC TCCCGGACCCCTGAGGTCACATGCGTGGTGGTG GACGTGAGCCACGAAGACCCTGAGGTCAAGTTC AACTGGTACGTGGACGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GCACC AGGACT GGC T GAAT GGC AAGGAGT AC AAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT mAb IgG chain SEQ ID NO Nucleic acid sequence TCAAAGCTCACCGTGGACAAGAGCAGGTGGCAG CAGGGGAACGT CT T CTCATGCTCCGTGATGCAT GAGGCTCTGCACAACCACTACACGCAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC6 351 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCCTCTGGCCTGGACTTCAACAAATATGGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCGACAGCGTTAAGGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGCCCGTTGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCACCTCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACAAAACTCACACATGCCCACCGTGCCCAGCA CCTGAACTCCTGGGGGGACCGTCAGTCTTCCTC TTCCCCCCAAAACCCAAGGACACCCTCATGATC TCCCGGACCCCTGAGGTCACATGCGTGGTGGTG GACGTGAGCCACGAAGACCCTGAGGTCAAGTTC AACTGGTACGTGGACGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GC ACC AGGACT GGC T GAAT GGC AAGGAGT AC AAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT TCAAAGCTCACCGTGGACAAGAGCAGGTGGCAG CAGGGGAACGTCTTCTCATGCTCCGTGATGCAT GAGGC T C T GCACAAC CACTACACG CAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC1-14AAS 352 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCCTCTGGCCTGGACTTCAACAAATATGGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCTCTTGGGTCAACGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGTGCGTTGG mAb IgG chain SEQ ID NO Nucleic acid sequence AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCACCTCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACAAAACTCACACATGCCCACCGTGCCCAGCA CCTGAGGCCGCCGGGGGATCCTCAGTCTTCCTG TTCCCCCCAAAACCCAAGGACACTCTCATGATC TCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTC AACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GCACCAGGACT GGC T GAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGCCCTCCCGGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT T CAAAGC T CACCGT GGACAAGAGCAGGT GGCAG CAGGGGAACGT CT T C T CAT GC T CC GT GAT GCAT GAGGCTCTGCACAACCACTACACGCAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC2-14AAS 353 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCC T C T GGCC T GGAC T TCAACAAAT AT GGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGGTGAGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCTCTTGGGTCAACGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGTGCGTTGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCACCTCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACAAAACTCACACATGCCCACCGTGCCCAGCA CCTGAGGCCGCCGGGGGATCCTCAGTCTTCCTG mAb IgG chain SEQ ID NO Nucleic acid sequence TTCCCCCCAAAACCCAAGGACACTCTCATGATC TCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTC AACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GOACCAGGACT GGC T GAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGCCCTCCCGGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT TCAAAGCTCACCGTGGACAAGAGCAGGTGGCAG CAGGGGAACGT CT T CTCATGCTCCGTGATGCAT GAGGCTCTGCACAACCACTACACG CAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC3-14AAS 354 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCCTCTGGCCTGGACTTCAACAAATATGGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCGACAGCGTTAAGGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGTGCGTTGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCACCTCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACAAAACTCACACATGCCCACCGTGCCCAGCA CCTGAGGCCGCCGGGGGATCCTCAGTCTTCCTG TTCCCCCCAAAACCCAAGGACACTCTCATGATC TCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTC AACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GCACCAGGACT GGC T GAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGCCCTCCCGGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG mAb IgG chain SEQ ID NO Nucleic acid sequence CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT TCAAAGCTCACCGTGGACAAGAGCAGGTGGCAG CAGGGGAACGT CT T CTCATGCTCCGTGATGCAT GAGGC T C T GCACAAC CACTACACG CAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC4-14AAS 355 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCCTCTGGCCTGGACTTCAACAAATATGCC ATGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCGACAGCGTTAAGGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGTGCGTTGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCACCTCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACAAAACTCACACATGCCCACCGTGCCCAGCA CCTGAGGCCGCCGGGGGATCCTCAGTCTTCCTG TTCCCCCCAAAACCCAAGGACACTCTCATGATC TCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTC AACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GCACCAGGACT GGC T GAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGCCCTCCCGGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT T CAAAGCTCACCGTGGACAAGAGCAGGTGGCAG CAGGGGAACGTCTTCTCATGCTCCGTGATGCAT GAGGCTCTGCACAACCACTACACG CAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC5-14AAS 356 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCCTCTGGCCTGGACTTCAACAAATATGGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCGACAGCGTTAAGGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC mAb IgG chain SEQ ID NO Nucleic acid sequence ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGCCAAATGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCACCTCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACAAAACTCACACATGCCCACCGTGCCCAGCA CCTGAGGCCGCCGGGGGATCCTCAGTCTTCCTG TTCCCCCCAAAACCCAAGGACACTCTCATGATC TCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTC AACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GCACCAGGACT GGC T GAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGCCCTCCCGGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT TCAAAGCTCACCGTGGACAAGAGCAGGTGGCAG CAGGGGAACGT CT T CTCATGCTCCGTGATGCAT GAGGC T C T GCACAAC CACTACACG CAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC6-14AAS 357 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCCTCTGGCCTGGACTTCAACAAATATGGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCGACAGCGTTAAGGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGCCCGTTGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCACCTCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT mAb IgG chain SEQ ID NO Nucleic acid sequence GACAAAACTCACACATGCCCACCGTGCCCAGCA CCTGAGGCCGCCGGGGGATCCTCAGTCTTCCTG TTCCCCCCAAAACCCAAGGACACTCTCATGATC TCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTC AACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC CTGCACCAGGACTGGCTGAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGCCCTCCCGGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT TCAAAGCTCACCGTGGACAAGAGCAGGTGGCAG CAGGGGAACGT CT T CTCATGCTCCGTGATGCAT GAGGC T C T GCACAAC CACTACACG CAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC1-RH12 358 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCCTCTGGCCTGGACTTCAACAAATATGGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCTCTTGGGTCAACGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGTGCGTTGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCAAATCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACGCCACTCACACATGCCCACCGTGCCCAGCA CCTGAGGCCGCCGGGGGATCCTCAGTCTTCCTG TTCCCCCCAAAACCCAAGGACACTCTCATGATC TCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTC AACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GCACCAGGACT GGC T GAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGCCCTCCCGGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC mAb IgG chain SEQ ID NO Nucleic acid sequence AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT T CAAAGC T CACCGT GGACAAGAGCAGGT GGCAG C AGGGGAACGT CT T C T C AT GC T CC GT GAT GC AT GAGGCTCTGCACAACCACTACACGCAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC2-RH12 359 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCC T C T GGCC T GGAC T TCAAC AAAT AT GGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGGTGAGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCTCTTGGGTCAACGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGTGCGTTGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCAAATCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACGCCACTCACACATGCCCACCGTGCCCAGCA CCTGAGGCCGCCGGGGGATCCTCAGTCTTCCTG TTCCCCCCAAAACCCAAGGACACTCTCATGATC TCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTC AACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GCACCAGGACT GGC T GAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGCCCTCCCGGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT T CAAAGC T CACCGT GGACAAGAGCAGGT GGCAG CAGGGGAACGTCTTCTCATGCTCCGTGATGCAT GAGGCTCTGCACAACCACTACACG CAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC3-RH12 360 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCC T C T GGCC T GGAC T TCAAC AAAT AT GGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC mAb IgG chain SEQ ID NO Nucleic acid sequence GGCAATACCGTGTACGCCGACAGCGTTAAGGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGTGCGTTGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCAAATCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACGCCAC T CACACAT GCCCACCG T GCCCAGCA CCTGAGGCCGCCGGGGGATCCTCAGTCTTCCTG TTCCCCCCAAAACCCAAGGACACTCTCATGATC TCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTC AACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GCACC AGGACT GGC T GAACGGC AAGGAGT AC AAGTGCAAGGTCTCCAACAAAGCCCTCCCGGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT TCAAAGCTCACCGTGGACAAGAGCAGGTGGCAG CAGGGGAACGT CT T C T CAT GC T CC GT GAT GCAT GAGGCTCTGCACAACCACTACACGCAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC4-RH12 361 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCCTCTGGCCTGGACTTCAACAAATATGCC ATGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCGACAGCGTTAAGGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGTGCGTTGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCAAATCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC mAb IgG chain SEQ ID NO Nucleic acid sequence ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACGCCAC T CACACAT GCCCACCG T GCCCAGCA CCTGAGGCCGCCGGGGGATCCTCAGTCTTCCTG TTCCCCCCAAAACCCAAGGACACTCTCATGATC TCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTC AACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GCACCAGGACT GGC T GAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGCCCTCCCGGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT T CAAAGC T CACCGT GGACAAGAGCAGGT GGCAG CAGGGGAACGTCTTCTCATGCTCCGTGATGCAT GAGGCTCTGCACAACCACTACACGCAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC5-RH12 362 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCC T C T GGCC T GGAC T TCAACAAAT AT GGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCGACAGCGTTAAGGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGCCAAATGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCAAATCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACGCCACTCACACATGCCCACCGTGCCCAGCA CCTGAGGCCGCCGGGGGATCCTCAGTCTTCCTG TTCCCCCCAAAACCCAAGGACACTCTCATGATC TCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTC AACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC CTGCACCAGGACTGGCTGAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGCCCTCCCGGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG mAb IgG chain SEQ ID NO Nucleic acid sequence CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT T CAAAGC T CACCGT GGACAAGAGCAGGT GGCAG CAGGGGAACGTCTTCTCATGCTCCGTGATGCAT GAGGCTCTGCACAACCACTACACGCAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 HC6-RH12 363 GAAGTTCAACTGCTGGAATCTGGCGGCGGACTG GTTCAACCTGGTGGCTCTCTGAGACTGTCTTGT GCCGCCTCTGGCCTGGACTTCAACAAATATGGC GTGTCCTGGGTCCGACAGGCCCCTGGAAAAGGA CTGGAATGGATCGGCTTCATCGACCCCGTGTTC GGCAATACCGTGTACGCCGACAGCGTTAAGGGC CGGTTCACCATCAGCCGGGACAACAGCAAGAAC ACCCTGTACCTGCAGATGAACAGCCTGAGAGCC GAGGACACCGCCGTGTATTACTGTGCCCGTTGG AACAGCGGCTGGGGCAATCTTTGGGGACCTGGC ACACTGGTTACAGTGTCCTCTGCATCCACCAAG GGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCAAATCTGGGGGCACAGCGGCCCTGGGC TGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACC AAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT GACGCCACTCACACATGCCCACCGTGCCCAGCA CCTGAGGCCGCCGGGGGATCCTCAGTCTTCCTG TTCCCCCCAAAACCCAAGGACACTCTCATGATC TCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTC AACTGGTACGTGGATGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTC C T GCACCAGGACT GGC T GAACGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGCCCTCCCGGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCTTATAT T CAAAGC T CACCGT GGACAAGAGCAGGT GGCAG CAGGGGAACGTCTTCTCATGCTCCGTGATGCAT GAGGCTCTGCACAACCACTACACG CAGAAGAGC CTCTCCCTGTCTCCCGGGAAA 20E16 LC1 364 GCTATCGTGATGACACAGAGCCCTAGCAGCCTG TCTGCCTCTGT GGGCGATAGAGT GACAAT CACC TGTCAGGCCAGCCAGAGCATCGTGACCTATCTG mAb IgG chain SEQ ID NO Nucleic acid sequence GCCTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCTGCTGATCTACGGCGCCAGCAATCTGGAA AGCGGCGTGCCAAGCAGATTTTCTGGCAGCGGC TCTGGCACCGACTTCACCTTTACAATCAGCAGC CTGCAGCCTGAGGATATCGCCACCTACTACTGC CAGAGCGGCGATTATTCTGCCGGCCTTACATTT GGCGGAGGCACCAAGGTGGAAATCAAGAGAACA GTGGCCGCTCCGAGCGTGTTCATCTTTCCACCA AGCGACGAGCAGC T GAAGT CT GGCACAGCC T C T GTCGTGTGCCTGCTGAACAACTTCTACCCCAGA GAAGCCAAGGTGCAGTGGAAGGTGGACAATGCC CTGCAGAGCGGCAATAGCCAAGAGAGCGTGACC GAGCAGGACAGCAAGGATAGCACCTACAGCCTG TCCAGCACACTGACCCTGAGCAAGGCCGACTAC GAGAAGCACAAAGTGTACGCCTGCGAAGTGACA CACCAGGGCCTGTCTAGCCCTGTGACCAAGAGC TTCAACCGGGGCGAGTGT 20E16 LC2 365 GACATCCAGATGACACAGAGCCCTAGCAGCCTG TCTGCCTCTGT GGGCGATAGAGT GACAAT CACC TGTCAGGCCAGCCAGAGCATCGTGACCTATCTG GCCTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCTGCTGATCTACGGCGCCAGCAATCTGGAA AGCGGCGTGCCAAGCAGATTTTCTGGCAGCGGC TCTGGCACCGACTTCACCTTTACAATCAGCAGC CTGCAGCCTGAGGATATCGCCACCTACTACTGC CAGAGCGGCGATTATTCTGCCGGCCTTACATTT GGCGGAGGCACCAAGGTGGAAATCAAGAGAACA GTGGCCGCTCCGAGCGTGTTCATCTTTCCACCA AGCGACGAGCAGC T GAAGT CT GGCACAGCC T C T GTCGTGTGCCTGCTGAACAACTTCTACCCCAGA GAAGCCAAGGTGCAGTGGAAGGTGGACAATGCC CTGCAGAGCGGCAATAGCCAAGAGAGCGTGACC GAGCAGGACAGCAAGGATAGCACCTACAGCCTG TCCAGCACACTGACCCTGAGCAAGGCCGACTAC GAGAAGCAC AAAGTGTACGCCTGCGAAGTGACA CACCAGGGCCTGTCTAGCCCTGTGACCAAGAGC TTCAACCGGGGCGAGTGT 20E16 LC3 366 GACATCCAGATGACACAGAGCCCTAGCAGCCTG TCTGCCTCTGT GGGCGATAGAGT GACAAT CACC TGTCAGGCCAGCCAGAGCATCGTGACCTATCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCTGCTGATCTACGGCGCCAGCAATCTGGAA AGCGGCGTGCCAAGCAGATTTTCTGGCAGCGGC TCTGGCACCGACTTCACCTTTACAATCAGCAGC CTGCAGCCTGAGGATATCGCCACCTACTACTGC CAGAGCGGCGATTATTCTGCCGGCCTTACATTT GGCGGAGGCACCAAGGTGGAAATCAAGAGAACA GTGGCCGCTCCGAGCGTGTTCATCTTTCCACCA AGCGACGAGCAGC T GAAGT CT GGCACAGCC T C T GTCGTGTGCCTGCTGAACAACTTCTACCCCAGA GAAGCCAAGGTGCAGTGGAAGGTGGACAATGCC CTGCAGAGCGGCAATAGCCAAGAGAGCGTGACC GAGCAGGACAGCAAGGATAGCACCTACAGCCTG TCCAGCACACTGACCCTGAGCAAGGCCGACTAC mAb IgG chain SEQ ID NO Nucleic acid sequence GAGAAGCACAAAGT GTACGCCTGCGAAGTGACA CACCAGGGCCTGTCTAGCCCTGTGACCAAGAGC TTCAACCGGGGCGAGTGT 20E16 LC4 367 GACATCCAGATGACACAGAGCCCTAGCAGCCTG TCTGCCTCTGT GGGCGATAGAGT GACAAT CACC TGTCAGGCCAGCCAGAGCATCGTGACCTATCTG GCCTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCTGCTGATCTACGGCGCCAGCAATCTGGAA ACCGGCGTGCCAAGCAGATTTTCTGGCAGCGGC TCTGGCACCGACTTCACCTTTACAATCAGCAGC CTGCAGCCTGAGGATATCGCCACCTACTACTGC CAGAGCGGCGATTATTCTGCCGGCCTTACATTT GGCGGAGGCACCAAGGTGGAAATCAAGAGAACA GTGGCCGCTCCGAGCGTGTTCATCTTTCCACCA AGCGACGAGCAGC T GAAGT CT GGCACAGCC T C T GTCGTGTGCCTGCTGAACAACTTCTACCCCAGA GAAGCCAAGGTGCAGTGGAAGGTGGACAATGCC CTGCAGAGCGGCAATAGCCAAGAGAGCGTGACC GAGCAGGACAGCAAGGATAGCACCTACAGCCTG TCCAGCACACTGACCCTGAGCAAGGCCGACTAC GAGAAGCACAAAGTGTACGCCTGCGAAGTGACA CACCAGGGCCTGTCTAGCCCTGTGACCAAGAGC TTCAACCGGGGCGAGTGT 20E16 LC5 368 GACATCCAGATGACACAGAGCCCTAGCAGCCTG TCTGCCTCTGT GGGCGATAGAGT GACAAT CACC TGTCAGGCCAGCCAGAGCATCGTGACCTATCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCTGCTGATCTACGGCGCCAGCAATCTGGAA ACCGGCGTGCCAAGCAGATTTTCTGGCAGCGGC TCTGGCACCGACTTCACCTTTACAATCAGCAGC CTGCAGCCTGAGGATATCGCCACCTACTACTGC CAGAGCGGCGATTATTCTGCCGGCCTTACATTT GGCGGAGGCACCAAGGTGGAAATCAAGAGAACA GTGGCCGCTCCGAGCGTGTTCATCTTTCCACCA AGCGACGAGCAGC T GAAGT CT GGCACAGCC T C T GTCGTGTGCCTGCTGAACAACTTCTACCCCAGA GAAGCCAAGGTGCAGTGGAAGGTGGACAATGCC CTGCAGAGCGGCAATAGCCAAGAGAGCGTGACC GAGCAGGACAGCAAGGATAGCACCTACAGCCTG TCCAGCACACTGACCCTGAGCAAGGCCGACTAC GAGAAGCACAAAGTGTACGCCTGCGAAGTGACA CACCAGGGCCTGTCTAGCCCTGTGACCAAGAGC TTCAACCGGGGCGAGTGT 20E16 LC1-RESPECT- L 369 GCTATCGTGATGACACAGAGCCCTAGCAGCCTG TCTGCCTCTGT GGGCGATAGAGT GACAAT CACC TGTCAGGCCAGCCAGAGCATCGTGACCTATCTG GCCTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCTGCTGATCTACGGCGCCAGCAATCTGGAA AGCGGCGTGCCAAGCAGATTTTCTGGCAGCGGC TCTGGCACCGACTTCACCTTTACAATCAGCAGC CTGCAGTGCGAGGATATCGCCACCTACTACTGC CAGAGCGGCGATTATTCTGCCGGCCTTACATTT GGCGGAGGCACCAAGGTGGAAATCAAGAGAACA GTGGCCGCTCCGAGCGTGTTCATCTTTCCACCA mAb IgG chain SEQ ID NO Nucleic acid sequence AGCGACGAGCAGCTGAAGTCTGGCACAGCCTCT GTCGTGTGCCTGCTGAACAACTTCTACCCCAGA GAAGCCAAGGTGCAGTGGAAGGTGGACAATGCC CTGCAGAGCGGCAATAGCCAAGAGAGCGTGACC GAGCAGGACAGCAAGGATAGCACCTACAGCCTG TCCAGCACACTGACCCTGAGCAAGGCCGACTAC GAGAAGCACAAAGTGTACGCCTGCGAAGTGACA CACCAGGGCCTGTCTAGCCCTGTGACCAAGAGC TTCAACCGGGGCGAGTGT 20E16 LC2-RESPECT- L 370 GACATCCAGATGACACAGAGCCCTAGCAGCCTG TCTGCCTCTGT GGGCGATAGAGT GACAAT CACC TGTCAGGCCAGCCAGAGCATCGTGACCTATCTG GCCTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCTGCTGATCTACGGCGCCAGCAATCTGGAA AGCGGCGTGCCAAGCAGATTTTCTGGCAGCGGC TCTGGCACCGACTTCACCTTTACAATCAGCAGC CTGCAGTGCGAGGATATCGCCACCTACTACTGC CAGAGCGGCGATTATTCTGCCGGCCTTACATTT GGCGGAGGCACCAAGGTGGAAATCAAGAGAACA GTGGCCGCTCCGAGCGTGTTCATCTTTCCACCA AGCGACGAGCAGC T GAAGT CT GGCACAGCC T C T GTCGTGTGCCTGCTGAACAACTTCTACCCCAGA GAAGCCAAGGTGCAGTGGAAGGTGGACAATGCC CTGCAGAGCGGCAATAGCCAAGAGAGCGTGACC GAGCAGGACAGCAAGGATAGCACCTACAGCCTG TCCAGCACACTGACCCTGAGCAAGGCCGACTAC GAGAAGCACAAAGTGTACGCCTGCGAAGTGACA CACCAGGGCCTGTCTAGCCCTGTGACCAAGAGC TTCAACCGGGGCGAGTGT 20E16 LC3-RESPECT- L 371 GACATCCAGATGACACAGAGCCCTAGCAGCCTG TCTGCCTCTGT GGGCGATAGAGT GACAAT CACC TGTCAGGCCAGCCAGAGCATCGTGACCTATCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCTGCTGATCTACGGCGCCAGCAATCTGGAA AGCGGCGTGCCAAGCAGATTTTCTGGCAGCGGC TCTGGCACCGACTTCACCTTTACAATCAGCAGC CTGCAGTGCGAGGATATCGCCACCTACTACTGC CAGAGCGGCGATTATTCTGCCGGCCTTACATTT GGCGGAGGCACCAAGGTGGAAATCAAGAGAACA GTGGCCGCTCCGAGCGTGTTCATCTTTCCACCA AGCGACGAGCAGC T GAAGT CT GGCACAGCC T C T GTCGTGTGCCTGCTGAACAACTTCTACCCCAGA GAAGCCAAGGTGCAGTGGAAGGTGGACAATGCC CTGCAGAGCGGCAATAGCCAAGAGAGCGTGACC GAGCAGGACAGCAAGGATAGCACCTACAGCCTG TCCAGCACACTGACCCTGAGCAAGGCCGACTAC GAGAAGCACAAAGTGTACGCCTGCGAAGTGACA CACCAGGGCCTGTCTAGCCCTGTGACCAAGAGC TTCAACCGGGGCGAGTGT 20E16 LC4-RESPECT- L 372 GACATCCAGATGACACAGAGCCCTAGCAGCCTG TCTGCCTCTGT GGGCGATAGAGT GACAAT CACC TGTCAGGCCAGCCAGAGCATCGTGACCTATCTG GCCTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCTGCTGATCTACGGCGCCAGCAATCTGGAA mAb IgG chain SEQ ID NO Nucleic acid sequence ACCGGCGTGCCAAGCAGATTTTCTGGCAGCGGC TCTGGCACCGACTTCACCTTTACAATCAGCAGC CTGCAGTGCGAGGATATCGCCACCTACTACTGC CAGAGCGGCGATTATTCTGCCGGCCTTACATTT GGCGGAGGCACCAAGGTGGAAATCAAGAGAACA GTGGCCGCTCCGAGCGTGTTCATCTTTCCACCA AGCGACGAGCAGC T GAAGT CT GGCACAGCC T C T GTCGTGTGCCTGCTGAACAACTTCTACCCCAGA GAAGCCAAGGTGCAGTGGAAGGTGGACAATGCC CTGCAGAGCGGCAATAGCCAAGAGAGCGTGACC GAGCAGGACAGCAAGGATAGCACCTACAGCCTG TCCAGCACACTGACCCTGAGCAAGGCCGACTAC GAGAAGCACAAAGTGTACGCCTGCGAAGTGACA CACCAGGGCCTGTCTAGCCCTGTGACCAAGAGC TTCAACCGGGGCGAGTGT 20E16 LC5-RESPECT- L 373 GACATCCAGATGACACAGAGCCCTAGCAGCCTG TCTGCCTCTGT GGGCGATAGAGT GACAAT CACC TGTCAGGCCAGCCAGAGCATCGTGACCTATCTG AATTGGTATCAGCAGAAGCCTGGCAAGGCCCCT AAGCTGCTGATCTACGGCGCCAGCAATCTGGAA ACCGGCGTGCCAAGCAGATTTTCTGGCAGCGGC TCTGGCACCGACTTCACCTTTACAATCAGCAGC CTGCAGTGCGAGGATATCGCCACCTACTACTGC CAGAGCGGCGATTATTCTGCCGGCCTTACATTT GGCGGAGGCACCAAGGTGGAAATCAAGAGAACA GTGGCCGCTCCGAGCGTGTTCATCTTTCCACCA AGCGACGAGCAGC T GAAGT CT GGCACAGCC T C T GTCGTGTGCCTGCTGAACAACTTCTACCCCAGA GAAGCCAAGGTGCAGTGGAAGGTGGACAATGCC CTGCAGAGCGGCAATAGCCAAGAGAGCGTGACC GAGCAGGACAGCAAGGATAGCACCTACAGCCTG TCCAGCACACTGACCCTGAGCAAGGCCGACTAC GAGAAGCACAAAGTGTACGCCTGCGAAGTGACA CACCAGGGCCTGTCTAGCCCTGTGACCAAGAGC TTCAACCGGGGCGAGTGT

[00214] In some embodiments, the sequences of the heavy chain variable domains, light chain variable domains, full-length heavy chains, and full-length light chains may be “mixed and matched” to create variants of the anti-TROP2 antibodies, e.g., 16K21,17124, or 20E16. Such “mixed and matched” anti-TROP2 antibodies can be tested using binding assays known in the art (e.g., ELISAs and other assays described in the Examples). For example, an amino acid sequence corresponding to a heavy chain variable domain from a particular set of heavy chain variable domains listed above in Table 6 for a specific antibody may be replaced with another amino acid sequence corresponding to a heavy chain variable domain option from the table. For example, the amino acid sequence of SEQ ID NO: 53 may be replaced with the amino acid sequence of SEQ ID NO: 54 to create a variant of 16K21. Similarly, the amino acid sequence of SEQ ID NO: 57 may be replaced with the amino acid sequence of SEQ ID NO: 62 to create another variant of 16K21 that comprises a RESPECT-L site. The same applies to the mixing and matching of light chain variable domains, full-length heavy chains, and full-length light chains. In various embodiments, the antibodies disclosed herein may comprise any set of heavy and light chain variable domains listed in the tables above (e.g., 16K21 heavy and light chain variable domains, 17124 heavy and light chain variable domains, or 20E16 heavy and light chain variable domains), or the set of six CDR sequences from the heavy and light chain set (e.g., three 16K21 heavy chain CDRs and three 16K21 light chain CDRs, three 17124 heavy chain CDRs and three 17124 light chain CDRs, or three 20E16 heavy chain CDRs and three 20E16 light chain CDRs). In some embodiments, the antibodies further comprise human heavy and light chain constant domains or fragments thereof. In various embodiments, the antibodies may comprise any set of full-length heavy chain and full-length light chain sequences listed in the tables above (e.g., 16K21 full-length heavy and light chains, 17124 full-length heavy and light chains, or 20E16 fulllength heavy and light chains). In some embodiments, the antibodies may comprise a human IgG heavy chain constant domain and a human kappa light chain constant domain. In some embodiments, the antibodies may comprise a human IgGl, IgG2, IgG3, or IgG4 heavy chain constant domain. In various embodiments, an antibody of the present invention comprises a human immunoglobulin G subtype 1 (IgGl) heavy chain constant domain with a human Ig kappa light chain constant domain. In some embodiments, the constant domain is a modified version of a human constant domain, e.g., comprising one or more of L234A, L235A, P238S, H268Q, and / or K274Q modifications of a human IgGl heavy chain constant domain.

[00215] In some embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises three heavy chain CDRs and three light chain CDRs as follows: heavy chain CDR1 (HCDR1) comprising SEQ ID NO: 18, heavy chain CDR2 (HCDR2) comprising SEQ ID NO: 20, heavy chain CDR3 (HCDR3) comprising SEQ ID NO: 21; light chain CDR1 (LCDR1) comprising SEQ ID NO: 22, light chain CDR2 (LCDR2) comprising SEQ ID NO: 24, and light chain CDR3 (LCDR3) comprising SEQ ID NO: 26, as defined by the Kabat numbering system.

[00216] In some embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises three heavy chain CDRs and three light chain CDRs as follows: HCDR1 comprising SEQ ID NO: 18, HCDR2 comprising SEQ ID NO: 20, HCDR3 comprising SEQ ID NO: 21; LCDR1 comprising SEQ ID NO: 23, LCDR2 comprising SEQ ID NO: 24, and LCDR3 comprising SEQ ID NO: 26, as defined by the Kabat numbering system.

[00217] In some embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises three heavy chain CDRs and three light chain CDRs as follows: HCDR1 comprising SEQ ID NO: 27, HCDR2 comprising SEQ ID NO: 28, HCDR3 comprising SEQ ID NO: 29; LCDR1 comprising SEQ ID NO: 30, LCDR2 comprising SEQ ID NO: 31, and LCDR3 comprising SEQ ID NO: 33, as defined by the IMGT numbering system.

[00218] In other embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises three heavy chain CDRs and three light chain CDRs as follows: HCDR1 comprising SEQ ID NO: 1, HCDR2 comprising SEQ ID NO: 3, HCDR3 comprising SEQ ID NO: 4; LCDR1 comprising SEQ ID NO: 5, LCDR2 comprising SEQ ID NO: 9, and LCDR3 comprising SEQ ID NO: 10, as defined by the Kabat numbering system.

[00219] In other embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises three heavy chain CDRs and three light chain CDRs as follows: HCDR1 comprising SEQ ID NO: 1, HCDR2 comprising SEQ ID NO: 3, HCDR3 comprising SEQ ID NO: 4; LCDR1 comprising SEQ ID NO: 8, LCDR2 comprising SEQ ID NO: 9, and LCDR3 comprising SEQ ID NO: 10, as defined by the Kabat numbering system.

[00220] In other embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises three heavy chain CDRs and three light chain CDRs as follows: HCDR1 comprising SEQ ID NO: 11, HCDR2 comprising SEQ ID NO: 12, HCDR3 comprising SEQ ID NO: 13; LCDR1 comprising SEQ ID NO: 14, LCDR2 comprising SEQ ID NO: 16, and LCDR3 comprising SEQ ID NO: 17, as defined by the IMGT numbering system.

[00221] In other embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises three heavy chain CDRs and three light chain CDRs as follows: HCDR1 comprising SEQ ID NO: 11, HCDR2 comprising SEQ ID NO: 12, HCDR3 comprising SEQ ID NO: 13; LCDR1 comprising SEQ ID NO: 15, LCDR2 comprising SEQ ID NO: 16, and LCDR3 comprising SEQ ID NO: 17, as defined by the IMGT numbering system.

[00222] In yet other embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises three heavy chain CDRs and three light chain CDRs as follows: HCDR1 comprising SEQ ID NO: 34, HCDR2 comprising SEQ ID NO: 37, HCDR3 comprising SEQ ID NO: 38; LCDR1 comprising SEQ ID NO: 39, LCDR2 comprising SEQ ID NO: 41, and LCDR3 comprising SEQ ID NO: 43, as defined by the Kabat numbering system.

[00223] In yet other embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises three heavy chain CDRs and three fight chain CDRs as follows: HCDR1 comprising SEQ ID NO: 34, HCDR2 comprising SEQ ID NO: 37, HCDR3 comprising SEQ ID NO: 38; LCDR1 comprising SEQ ID NO: 40, LCDR2 comprising SEQ ID NO: 42, and LCDR3 comprising SEQ ID NO: 43, as defined by the Kabat numbering system.

[00224] In yet other embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises three heavy chain CDRs and three light chain CDRs as follows: HCDR1 comprising SEQ ID NO: 44, HCDR2 comprising SEQ ID NO: 46, HCDR3 comprising SEQ ID NO: 47; LCDR1 comprising SEQ ID NO: 50, LCDR2 comprising SEQ ID NO: 51, and LCDR3 comprising SEQ ID NO: 52, as defined by the IMGT numbering system.

[00225] In yet other embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises three heavy chain CDRs and three light chain CDRs as follows: HCDR1 comprising SEQ ID NO: 44, HCDR2 comprising SEQ ID NO: 46, HCDR3 comprising SEQ ID NO: 48; LCDR1 comprising SEQ ID NO: 50, LCDR2 comprising SEQ ID NO: 51, and LCDR3 comprising SEQ ID NO: 52, as defined by the IMGT numbering system.

[00226] In some embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 69, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 72; or a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 69, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 76; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 69, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 73; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 69, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 77; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 70, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 72; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 70, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 76; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 70, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 73; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 70, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 77; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 177, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 72; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 177, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 76; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 177, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 73; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 177, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 77.

[00227] In some embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof comprises a heavy chain variable region amino acid sequence that is at least 95% identical to the above-mentioned heavy chain variable region amino acid sequences and a light chain variable region amino acid sequence that is at least 95% identical to the above-mentioned light chain variable region amino acid sequences. In some embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof comprises a heavy chain variable region amino acid sequence that is at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 69 or 70 and a light chain variable region amino acid sequence that is at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 72, 73, 76, or 77.

[00228] In other embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 58; or a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 63; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 61; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 56, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 58; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 56, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 63; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 56, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 61; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 56, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 58; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 63; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 61; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66. In some embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof comprises a heavy chain variable region amino acid sequence that is at least 95% identical to the above-mentioned heavy chain variable region amino acid sequences and a light chain variable region amino acid sequence that is at least 95% identical to the above-mentioned light chain variable region amino acid sequences. In some embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof comprises a heavy chain variable region amino acid sequence that is at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 55, 56, or 175 and a light chain variable region amino acid sequence that is at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 58, 61, 63, or 66.

[00229] In some embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 61; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66.

[00230] In some embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 58; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 63.

[00231] In some embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 61; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66.

[00232] In yet other embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof provided herein comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 80, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 85; or a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 80, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 90; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 80, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 88; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 80, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 93; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 82, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 85; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 82, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 90; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 82, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 88; or a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 82, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 93. In some embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof comprises a heavy chain variable region amino acid sequence that is at least 95% identical to the above-mentioned heavy chain variable region amino acid sequences and a light chain variable region amino acid sequence that is at least 95% identical to the above-mentioned light chain variable region amino acid sequences. In some embodiments, an anti-TROP2 antibody or antigen-binding fragment thereof comprises a heavy chain variable region amino acid sequence that is at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 80 or 82 and a light chain variable region amino acid sequence that is at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 85, 88, 90, or 93.

[00233] In various embodiments, any of the anti-TROP2 antibodies disclosed herein may comprise a human IgGl Fc domain. In some embodiments, an anti-TROP2 antibody comprises a human IgGl Fc domain that is modified to reduce binding to a FcyR as compared to an IgGl Fc-containing antibody with a wild-type IgGl Fc domain. In some embodiments, the anti-TROP2 antibodies comprise a mutated human IgGl Fc domain that comprises one or more (e.g., all of) L234A, L235A, P238S, H268Q, and K274Q modifications to a human IgGl heavy chain constant domain.

[00234] In various embodiments, the anti-TROP2 antibodies comprise a human Ig kappa light chain constant region. In various embodiments, the anti-TROP2 antibodies comprise a human Ig lambda light chain constant region.

[00235] In some embodiments, an anti-TROP2 antibody provided herein comprises a heavy chain comprising an amino acid sequence selected from SEQ ID NO: 118, 119, 122, 123,126, 127, 184, 185, 186, or 381, and a light chain comprising an amino acid sequence selected from SEQ ID NO: 129, 130, 133, or 134.

[00236] In some embodiments, an anti-TROP2 antibody provided herein comprises a heavy chain comprising an amino acid sequence selected from SEQ ID NO: 96, 97, 100, 101, 104, 105, 179, 181, 183, or 380, and a light chain comprising an amino acid sequence selected from SEQ ID NO: 107, 110, 112, or 115.

[00237] In some embodiments, an anti-TROP2 antibody provided herein comprises a heavy chain comprising an amino acid sequence selected from SEQ ID NO: 137, 139, 142, 144,147, or 149, and a light chain comprising an amino acid sequence selected from SEQ ID NO: 152,155, 157, or 160.

[00238] In some embodiments, an anti-TROP2 antibody comprises the heavy chain amino acid sequence of SEQ ID NO: 126 and the light chain amino acid sequence of SEQ ID NO: 129; or the heavy chain amino acid sequence of SEQ ID NO: 122 and the light chain amino acid sequence of SEQ ID NO: 133; or the heavy chain amino acid sequence of SEQ ID NO: 126 and the light chain amino acid sequence of SEQ ID NO: 130; or the heavy chain amino acid sequence of SEQ ID NO: 122 and the light chain amino acid sequence of SEQ ID NO: 134; or the heavy chain amino acid sequence of SEQ ID NO: 127 and the light chain amino acid sequence of SEQ ID NO: 129; or the heavy chain amino acid sequence of SEQ ID NO: 123 and the light chain amino acid sequence of SEQ ID NO: 133; or the heavy chain amino acid sequence of SEQ ID NO: 127 and the light chain amino acid sequence of SEQ ID NO: 130; or the heavy chain amino acid sequence of SEQ ID NO: 123 and the lig...

Claims

1. An anti-TR0P2 antibody or antigen-binding fragment thereof, wherein the antibody orantigen-binding fragment binds specifically to human TROP2, and wherein the antibody or antigenbinding fragment comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein(i) the HCDR1 comprises an amino acid sequence of SEQ ID NO: 1, the HCDR2 comprises an amino acid sequence selected from SEQ ID NO: 3, the HCDR3 comprises an amino acid sequence of SEQ ID NO: 4, the LCDR1 comprises an amino acid sequence selected from SEQ ID NO: 8, the LCDR2 comprises an amino acid sequence of SEQ ID NO: 9, and the LCDR3 comprises an amino acid sequence of SEQ ID NO: 10, as defined by the Kabat numbering system; or(ii) the HCDR1 comprises an amino acid sequence of SEQ ID NO: 11, the HCDR2 comprises an amino acid sequence of SEQ ID NO: 12, the HCDR3 comprises an amino acid sequence of SEQ ID NO: 13, the LCDR1 comprises an amino acid sequence selected from SEQ ID NO: 15, the LCDR2 comprises an amino acid sequence of SEQ ID NO: 16, and the LCDR3 comprises an amino acid sequence of SEQ ID NO: 17, as defined by the IMGT numbering system.

2. The anti-TROP2 antibody or antigen-binding fragment of claim 1, wherein the antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence selected from SEQ ID NO: 55 or 175, and a light chain variable region comprising an amino acid sequence selected from SEQ ID NO: 61 or 66.

3. The anti-TROP2 antibody or antigen-binding fragment of claim 1 or claim 2, wherein the antibody or antigen-binding fragment comprises(i) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66; or(ii) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66.

4. The anti-TROP2 antibody or antigen-binding fragment of any one of claims 1 to 3, wherein the antibody or antigen-binding fragment comprises a human IgGl heavy chain constant region.

5. The anti-TROP2 antibody or antigen-binding fragment of any one of claims 1 to 4, wherein the antibody or antigen-binding fragment comprises an IgGl Fc domain or an IgGl Fc domain mutated to reduce binding to a Fey receptor (FcyR) as compared to an IgGl Fc-containing antibodywith a wild type IgGl Fc domain, optionally wherein the mutated IgGl Fc domain comprises one or more of the mutations L234A, L235A, P238S, H268Q, and K274Q.

6. The anti-TROP2 antibody or antigen-binding fragment of any one of claims 1 to 5, wherein the antibody or antigen-binding fragment comprises a human Ig kappa light chain constant region.

7. The anti-TROP2 antibody or antigen-binding fragment of any one of claims 1 to 6, wherein the antibody or antigen-binding fragment comprises(i) a heavy chain comprising an amino acid sequence of SEQ ID NO: 181 and a light chain comprising an amino acid sequence of SEQ ID NO: 115;(ii) a heavy chain comprising an amino acid sequence of SEQ ID NO: 380 and a light chain comprising an amino acid sequence of SEQ ID NO: 115; or(iii) a heavy chain comprising an amino acid sequence of SEQ ID NO: 100 and a light chain comprising an amino acid sequence of SEQ ID NO: 115.

8. The anti-TROP2 antibody or antigen-binding fragment of any one of claims 1 to 7, wherein (a) the antibody or antigen-binding fragment comprises part of a bispecific or multi-specific binding construct; and / or(b) the antibody or antigen-binding fragment is linked to a therapeutic agent or detectable agent.

9. An antibody-drug conjugate of Formula (I):Ab-(L-D)p (I)wherein Ab is the anti-TROP2 antibody or antigen-binding fragment thereof of any one of claims 1 to 7;D is a cytotoxic agent;L is a cleavable linker that covalently attaches Ab to D; andp is an integer from 1 to 8.

10. The antibody-drug conjugate of claim 9, wherein the cytotoxic agent comprises an antitubulin agent, preferably wherein the anti-tubulin agent is eribulin or a salt thereof, preferably eribulin mesylate.

11. The antibody-drug conjugate of claim 9 or claim 10, wherein p is from 2 to 8, optionally wherein p is 2.

12. The antibody-drug conjugate of any one of claims 9 to 11, wherein cleavage of the conjugate releases the cytotoxic agent from the antibody and linker.

13. The antibody-drug conjugate of any one of claims 9 to 12, wherein the cleavable linker comprises a cleavable peptide moiety.

14. The antibody-drug conjugate of claim 13, wherein the cleavable peptide moiety is cleavable by an enzyme; optionally wherein the cleavable peptide moiety is cleavable by cathepsin or legumain; optionally wherein the cleavable peptide moiety is cleavable by cathepsin B.

15. The antibody-drug conjugate of claim 13 or claim 14, wherein the cleavable peptide moiety comprises an amino acid unit.

16. The antibody-drug conjugate of claim 15, wherein the amino acid unit comprises valinecitrulline (Val-Cit), valine-dimethylated lysine (Val-Lys(Me)2), alanine-dimethylated lysine (Ala-Lys(Me)2), valine-alanine (Val-Ala), asparagine (Asn), aspartic acid (Asp), or methylated aspartic acid (Asp(OMe)).

17. The antibody-drug conjugate of claim 16, wherein the amino acid unit comprises valinecitrulline (Val-Cit), valine-alanine (Val-Ala), or asparagine (Asn).

18. The antibody-drug conjugate of any one of claims 9 to 17, wherein the cleavable linker attaches to the antibody or antigen-binding fragment via a maleimide (Mal) moiety, optionally wherein the Mal moiety comprises a maleimidocaproyl (MC) moiety or a dithiomaleimide (DTM) moiety.

19. The antibody-drug conjugate of claim 18, wherein the Mal moiety is reactive with a cysteineresidue on the antibody or antigen-binding fragment.

20. The antibody-drug conjugate of claim 18 or claim 19, wherein the Mal moiety is joined to theantibody or antigen-binding fragment via a cysteine residue on the antibody or antigen-binding fragment.

21. The antibody-drug conjugate of any one of claims 18 to 20, wherein the cleavable linker comprises the Mal moiety and a cleavable peptide moiety.

22. The antibody-drug conjugate of claim 21, wherein the Mal moiety attaches the antibody or antigen-binding fragment to the cleavable peptide moiety in the linker.

23. The antibody-drug conjugate of any one of claims 18 to 22, wherein the cleavable linker comprises Mal-Val-Cit, Mal-Val-Lys(Me)2, Mal-Ala-Lys(Me)2, Mal-Val-Ala, Mal-Asn, Mal-Asp, or Mal-Asp(OMe).

24. The antibody-drug conjugate of any one of claims 9 to 21, wherein the cleavable linker comprises at least one spacer unit, wherein the spacer unit attaches to the antibody or antigen-binding fragment via the maleimide (Mal) moiety ("Mal-spacer unit").

25. The antibody-drug conjugate of claim 24, wherein the Mal-spacer unit comprises a polyethylene glycol (PEG) moiety, wherein the PEG moiety comprises -(PEG)m- and m is an integer from 1 to 10.

26. The antibody-drug conjugate of claim 25, wherein m is 2, 3, or 4.

27. The antibody-drug conjugate of claim 24, wherein the Mal-spacer unit comprises an alkylmoiety, wherein the alkyl moiety comprises -(CH2)n- and n is an integer from 1 to 10, optionally wherein n is 5.. . . . . .

28. The antibody-drug conjugate of claim 24, wherein the Mal-spacer unit comprises C2 029. The antibody-drug conjugate of claim 24, wherein the Mal-spacer unit comprises C2(PEG)mO                     , wherein m is an integer from 0 to 4.

30. The antibody-drug conjugate of claim 29, wherein m is 1,2, or 3.

31. The antibody-drug conjugate of claim 29 or claim 30, wherein the Mal-spacer unit comprisesHc2(peg)2 0                      0 .

32. The antibody-drug conjugate of any one of claims 24 to 31, wherein the cleavable linker comprises the Mal-spacer unit and the cleavable peptide moiety.

33. The antibody-drug conjugate of claim 32, wherein the Mal-spacer unit attaches the antibody or antigen-binding fragment to the cleavable peptide moiety in the linker.

34. The antibody-drug conjugate of claim 32 or claim 33, wherein the Mal-spacer unit comprises Mal-(PEG)2-Val-Cit, Mal-(PEG)3-Val-Cit, Mal-(PEG)4-Val-Cit, Mal-(PEG)2-Val-Lys(Me)2,Mal-(PEG)2-Ala-Lys(Me)2, Mal-(PEG)2-Val-Ala, Mal-(PEG)2-Asn, Mal-(PEG)2-Asp, Mal-(PEG)2-Asp(OMe), Mal-C2(PEG)m-Val-Cit, Mal-C2(PEG)m-Val-Lys(Me)2, Mal-C2(PEG)m-Val-Ala(Me)2, Mal-C2(PEG)m-Val-Ala, Mal-C2(PEG)m-Asn, Mal-C2(PEG)m-Asp, or Mal-C2(PEG)m-Asp(OMe); wherein m is an integer from 0 to 4.

35. The antibody-drug conjugate of claim 34, wherein m is 2.

36. The antibody-drug conjugate of any one of claims 12 to 35, wherein the cleavable moiety inthe linker is directly joined to the cytotoxic agent, or a spacer unit attaches the cleavable moiety in the linker to the cytotoxic agent.

37. The antibody-drug conjugate of claim 36, wherein the spacer unit attaching the cleavable moiety in the linker to the cytotoxic agent is self-immolative.

38. The antibody-drug conjugate of claim 36 or claim 37, wherein the spacer unit attaching the cleavable moiety in the linker to the cytotoxic agent comprises a p-aminobenzyloxycarbonyl (pABC).

39. The antibody-drug conjugate of claim 38, wherein the pABC attaches the cleavable moiety in the linker to the cytotoxic agent.

40. The antibody-drug conjugate of claim 39, wherein the cytotoxic agent is eribulin and the pABC covalently attaches to eribulin via a C-35 amine.

41. The antibody-drug conjugate of any one of claims 36 to 40, wherein the cleavable moiety comprises Val-Cit, Val-Ala, Val-Lys(Me)2, Ala-Lys(Me)2, Asn, Asp, or Asp(OMe).

42. The antibody-drug conjugate of claim 41, wherein the cleavable linker comprises Val-Cit-pABC, Val-Ala-pABC, Val-Lys(Me)2-pABC, or Ala-Lys(Me)2-pABC.

43. The antibody-drug conjugate of claim 24, wherein the cleavable linker comprises DTM-Asn, Mal-(PEG)2-Val-Cit-pABC, Mal-(PEG)3-Val-Cit-pABC, Mal-(PEG)4-Val-Cit-pABC, Mal-(PEG)2-Val-Lys(Me)2-pABC, Mal-(PEG)2-Ala-Lys(Me)2-pABC, Mal-(PEG)2-Val-Ala-pABC, Mal-(PEG)2-Asn, Mal-(PEG)2-Asp, Mal-(PEG)2-Asp(OMe), Mal-C2(PEG)m-Val-Cit-pABC, Mal-C2(PEG)m-Val-Lys(Me)2-pABC, Mal-C2(PEG)m-Val-Ala(Me)2-pABC, Mal-C2(PEG)m-Val-Ala-pABC, Mal-C2(PEG)m-Asn, Mal-C2(PEG)m-Asp, or Mal-C2(PEG)m-Asp(OMe); wherein m is an integer from Oto 4.

44. The antibody-drug conjugate of claim 43, wherein the cleavable linker comprises Mal-(PEG)2-Val-Cit-pABC, Mal-(PEG)2-Val-Ala-pABC, Mal-(PEG)2-Asn, MaJ-C2(PEG)m-Val-Cit-pABC, Mal-C2(PEG)m-Val-Ala-pABC, or Mal-C2(PEG)m-Asn; wherein m is an integer from 1 to 3.

45. The antibody-drug conjugate of claim 43 or claim 44, wherein m is 2.

46. The antibody-drug conjugate of any one of claims 9 to 45, wherein the antibody or antigenbinding fragment comprises three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system.

47. The antibody-drug conjugate of any one of claims 9 to 45, wherein the antibody or antigenbinding fragment comprises three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system.

48. The antibody-drug conjugate of claim 46 or claim 47, wherein the antibody or antigenbinding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66.

49. The antibody-drug conjugate of claim 46 or claim 47, wherein the antibody or antigenbinding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66.

50. The antibody-drug conjugate of claim 48, wherein the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 100 and a light chain comprising an amino acid sequence of SEQ ID NO: 115.

51. The antibody-drug conjugate of claim 49, wherein the antibody or antigen-binding fragmentcomprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 181 and a light chain comprising an amino acid sequence of SEQ ID NO: 115.

52. The antibody-drug conjugate of claim 49, wherein the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 380 and a light chain comprising an amino acid sequence of SEQ ID NO: 115.

53. An antibody-drug conjugate of Formula (I):Ab-(L-D),     (I)wherein Ab is an anti-TROP2 antibody or antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system;D is eribulin;L is a cleavable linker comprising Mal-(PEG)2-Val-Cit-pABC; andp is an integer from 1 to 8.

54. An antibody-drug conjugate of Formula (I):Ab-(L-D)p (I)wherein Ab is an anti-TROP2 antibody or antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system;D is eribulin;L is a cleavable linker comprising Mal-(PEG)2-Val-Cit-pABC; andp is an integer from 1 to 8.

55. An antibody-drug conjugate of Formula (I):Ab-(L-D)p (I)wherein Ab is an anti-TROP2 antibody or antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system;D is eribulin;L is a cleavable linker comprising Mal-(PEG)2-Val-Ala-pABC; andp is an integer from 1 to 8.

56. An antibody-drug conjugate of Formula (I):Ab-CL-D^ (I)wherein Ab is an anti-TROP2 antibody or antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system;D is eribulin;L is a cleavable linker comprising Mal-(PEG)2-Val-Ala-pABC; andp is an integer from 1 to 8.

57. An antibody-drug conjugate of Formula (I):Ab-(L-D)p (I)wherein Ab is an anti-TROP2 antibody or antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system;D is eribulin;L is a cleavable linker comprising Mal-(PEG)2-Asn; andp is an integer from 1 to 8.

58. An antibody-drug conjugate of Formula (I):Ab-(L-D)p (I)wherein Ab is an anti-TROP2 antibody or antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system;D is eribulin;L is a cleavable linker comprising Mal-(PEG)2-Asn; andp is an integer from 1 to 8.

59. An antibody-drug conjugate of Formula (I):Ab-(L-D)p (I)wherein Ab is an anti-TROP2 antibody or antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system;D is eribulin;L is a cleavable linker comprising Mal-C2(PEG)m-Val-Cit-pABC, wherein th is an integer from 0 to 4; andp is an integer from 1 to 8.

60. An antibody-drug conjugate of Formula (I):Ab-(L-D)^     (I)wherein Ab is an anti-TROP2 antibody or antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system;D is eribulin;L is a cleavable linker comprising Mal-C2(PEG)m-Val-Cit-pABC, wherein m is an integer from 0 to 4; andp is an integer from 1 to 8.

61. An antibody-drug conjugate of Formula (I):Ab-(L-D)p (I)wherein Ab is an anti-TROP2 antibody or antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system;D is eribulin;L is a cleavable linker comprising Mal-C2(PEG)m-Val-Ala-pABC, wherein m is an integer from 0 to 4; andp is an integer from 1 to 8.

62. An antibody-drug conjugate of Formula (I):Ab-(L-D)p (I)wherein Ab is an anti-TROP2 antibody or antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system;D is eribulin;L is a cleavable linker comprising Mal-C2(PEG)m-Val-Ala-pABC, wherein m is an integer from 0 to 4; andp is an integer from 1 to 8.

63. An antibody-drug conjugate of Formula (I):Ab-(L-D)p (I)wherein Ab is an anti-TR0P2 antibody or antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 3 (HCDR2), and SEQ ID NO: 4 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 8 (LCDR1), SEQ ID NO: 9 (LCDR2), and SEQ ID NO: 10 (LCDR3), as defined by the Kabat numbering system;D is eribulin;L is a cleavable linker comprising Mal-C2(PEG)m-Asn, wherein m is an integer from 0 to 4; andp is an integer from 1 to 8.

64. An antibody-drug conjugate of Formula (I):Ab-(L-D)p (I)wherein Ab is an anti-TROP2 antibody or antigen-binding fragment thereof comprising three HCDRs comprising amino acid sequences of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3); and three LCDRs comprising amino acid sequences of SEQ ID NO: 15 (LCDR1), SEQ ID NO: 16 (LCDR2), and SEQ ID NO: 17 (LCDR3), as defined by the IMGT numbering system;D is eribulin;L is a cleavable linker comprising Mal-C2(PEG)m-Asn, wherein m is an integer from 0 to 4; andp is an integer from 1 to 8.

65. The antibody-drug conjugate of any one of claims 53 to 64, wherein m is 2.

66. The antibody-drug conjugate of any one of claims 53 to 65, wherein the antibody or antigenbinding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 175, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66.

67. The antibody-drug conjugate of any one of claims 53 to 65, wherein the antibody or antigenbinding fragment comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 55, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 66.

68. The antibody-drug conjugate of claim 66, wherein the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 181 and a light chain comprising an amino acid sequence of SEQ ID NO: 115.

69. The antibody-drug conjugate of claim 66, wherein the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 380 and a light chain comprising an amino acid sequence of SEQ ID NO: 115.

70. The antibody-drug conjugate of claim 67, wherein the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 100 and a light chain comprising an amino acid sequence of SEQ ID NO: 115.

71. The antibody-drug conjugate of any one of claims 53 to 70, whereinp is 2.

72. The antibody-drug conjugate of any one of claims 9 to 71, whereinp is determined byhydrophobic interaction chromatography-high performance liquid chromatography (HIC-HPLC) or reverse-phase liquid chromatography-mass spectrometry (LC-MS).

73. The antibody-drug conjugate of any one of claims 9 to 72, wherein the cytotoxic agent is eribulin and the cleavable linker covalently attaches to the eribulin via a C-35 amine.

74. The antibody-drug conjugate of any one of claims 9 and 53 to 73, wherein the cleavable linker covalently attaches to the antibody or antigen-binding fragment via a cysteine or a lysine.

75. A composition comprising multiple copies of the antibody-drug conjugate of any one of claims 9 to 74, wherein the average p of the antibody-drug conjugates in the composition is about 1 to about 3.

76. The composition of claim 75, wherein the averagep is about 2.

77. One or more nucleic acid(s) encoding the antibody or antigen-binding fragment of any one of claims 1 to 7.

78. A host cell comprising the one or more nucleic acid(s) of claim 77.

79. A method of producing an antibody or antigen-biding fragment of any one of claims 1 to 7, comprising culturing the host cell of claim 78 under conditions sufficient to produce the antibody or antigen-binding fragment.

80. A method of producing the antibody-drug conjugate of any one of claims 9 to 74 or the composition of claim 75 or claim 76, comprising reacting an antibody or antigen-binding fragment of any one of claims 1 to 7 with a cleavable linker joined to eribulin under conditions that allow conjugation.

81. A compound of Formula (Ila):(Ila), wherein:D is a cytotoxic agent;Y is a cleavable moiety; andZ is absent or a spacer unit.

82. The compound of claim 81, wherein the cytotoxic agent comprises eribulin or a salt thereof.

83. The compound of claim 81 or claim 82, wherein the cleavable moiety comprises a cleavablepeptide moiety, optionally wherein the cleavable peptide moiety is cleavable by an enzyme; further optionally wherein the cleavable peptide moiety is cleavable by cathepsin or legumain, optionally wherein the cleavable peptide moiety is cleavable by cathepsin B.

84. The compound of claim 83, wherein the cleavable peptide moiety comprises an amino acid unit.

85. The compound of claim 84, wherein the amino acid unit comprises valine-citrulline (Val-Cit), valine-dimethylated lysine (Val-Lys(Me)2), alanine-dimethylated lysine (Ala-Lys(Me)2), valinealanine (Vai-Ala), asparagine (Asn), aspartic acid (Asp), or methylated aspartic acid (Asp(OMe)).

86. The compound of claim 85, wherein the amino acid unit comprises Val-Cit or Val-Ala.

87. The compound of claim 85, wherein the amino acid unit comprises Asn or Asp.

88. The compound of any one of claims 81 to 85 and 87, wherein Z is absent and the cleavable moiety is directly joined to the cytotoxic agent.

89. The compound of any one of claims 81 to 86, wherein Z is a spacer unit which attaches the cleavable moiety to the cytotoxic agent.

90. The compound of claim 89, wherein the spacer unit attaching the cleavable moiety to the cytotoxic agent is self-immolative.

91. The compound of claim 89 or claim 90, wherein the spacer unit attaching the cleavable moiety to the cytotoxic agent comprises a p-aminobenzyloxycarbonyl (pABC).

92. The compound of claim 91, wherein the cytotoxic agent is eribulin, and the pABC covalentlyattaches to eribulin via a C-35 amine.

93. The compound of claim 91 or claim 92, wherein -Y-Z- comprises Val-Cit-pABC, Val-Ala-pABC, Val-Lys(Me)2-pABC, or Ala-Lys(Me)2-pABC.

94. The compound of any one of claims 81 to 85, wherein -Y-Z- comprises Val-Cit-pABC, Val-Ala-pABC, or Asn.

95. A pharmaceutical composition comprising the antibody or antigen-binding fragment of any one of claims 1 to 8, the antibody-drug conjugate of any one of claims 9 to 74, the composition of claim 75 or claim 76, or the compound of any one of claims 81 to 94; and a pharmaceutically acceptable carrier.

96. A method of treating a patient having or at risk of having a cancer that expresses TROP2, comprising administering to the patient a therapeutically effective amount of the antibody or antigenbinding fragment of any one of claims 1 to 8, the antibody-drug conjugate of any one of claims 9 to 74, the composition of claim 75 or claim 76, the compound of any one of claims 81 to 94, or the pharmaceutical composition of claim 95.

97. The method of claim 96, wherein the TROP2-expressing cancer is a cholangiocarcinoma, bladder cancer, breast cancer, cervical carcinoma, colorectal cancer, esophageal cancer, gastric cancer, glioma, hepatocellular carcinoma, nasopharyngeal cancer, non-small cell lung cancer (NSCLC), pancreatic cancer, endometrial cancer, ovarian cancer, or skin cancer; optionally wherein the TROP2-expressing cancer is a cholangiocarcinoma, breast cancer, or NSCLC.

98. A method of reducing or inhibiting growth of a TR0P2-expressing tumor, comprising administering to the patient a therapeutically effective amount of the antibody or antigen-binding fragment of any one of claims 1 to 8, the antibody-drug conjugate of any one of claims 9 to 74, the composition of claim 75 or claim 76, the compound of any one of claims 81 to 94, or the pharmaceutical composition of claim 95.

99. The method of claim 98, wherein the tumor is a TROP2-expressing cholangiocarcinoma, bladder cancer, breast cancer, esophageal cancer, hepatocellular carcinoma, nasopharyngeal cancer, non-small cell lung cancer (NSCLC), pancreatic cancer, endometrial cancer, ovarian cancer, or skin cancer; optionally wherein the tumor is a cholangiocarcinoma.

100. Use of the antibody or antigen-binding fragment of any one of claims 1 to 8, the antibodydrug conjugate of any one of claims 9 to 75, the composition of claim 75 or claim 76, the compound of any one of claims 81 to 94, or the pharmaceutical composition of claim 95 in the manufacture of a medicament for the treatment of a TROP2-expressing cancer.

101. Use of an antibody or antigen-binding fragment of any one of claims 1 to 8, an antibody-drug conjugate of any one of claims 9 to 75, a composition of claim 75 or claim 76, a compound of any one of claims 81 to 95, or a pharmaceutical composition of claim 95 in the treatment of a TROP2-expressing cancer.

102. The use of claim 100 or claim 101, wherein the TROP2-expressing cancer is a cholangiocarcinoma, bladder cancer, breast cancer, esophageal cancer, hepatocellular carcinoma, nasopharyngeal cancer, non-small cell lung cancer (NSCLC), pancreatic cancer, endometrial cancer, ovarian cancer, or skin cancer; optionally wherein the TROP2-expressing cancer is a cholangiocarcinoma.

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