Compositions and methods comprising combinations of TSLP and interleukin 4 receptor alpha antibodies

Abstract

Described herein are antibodies, or antigen binding fragments thereof, that bind thymic stromal lymphopoietin (TSLP) and interleukin (IL)-4Rα in combination and methods of use thereof. In certain aspects, described herein are methods of inhibiting IL-4Rα and TSLP biological activity. In certain aspects, described herein are pharmaceutical compositions comprising the anti-TSLP and anti- IL-4Rα antibodies, or antigen binding fragments thereof. In certain aspects, the antibodies and methods described herein are used for treatment of an inflammatory disease or disorder associated with elevated levels of TSLP and / or IL-4.

Description

Goodwin Ref: PRG-061WOCOMPOSITIONS AND METHODS COMPRISING COMBINATIONS OF TSLP AND INTERLEUKIN 4 RECEPTOR ALPHA ANTIBODIESCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and benefit of U.S. Provisional Application Numbers 63 / 681,638 filed August 9, 2024, and 63 / 827,561 filed on June 20, 2025, the contents of each of which are incorporated by reference herein in their entirety.SEQUENCE LISTING

[0002] This application contains a Sequence Listing XML, which has been submitted electronically and is hereby incorporated by reference in its entirety. The XML copy of the Sequence Listing, created on July 22, 2025, is named PRG-061WO_SL.xml and is 531,531 bytes in size.BACKGROUND

[0003] Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine produced in response to pro-inflammatory stimuli. TSLP has been discovered to promote allergic inflammatory responses primarily through its activity on dendritic and mast cells. Human TSLP expression has been reported to be increased in asthmatic airways correlating to disease severity. In addition, TSLP protein levels are detectable in the concentrated bronchoalveolar lavage (BAL) fluid of asthma patients and other patients suffering from allergic disorders. In addition, TSLP has also been found to promote fibrosis.

[0004] TSLP binds to a heterodimeric receptor consisting of the TSLP receptor (TSLPR) and an IL-7 receptor a chain (IL-7Ra) in dendritic cells, thereby activating the dendritic cells. Upon activation, the dendritic cells express inflammatory chemokines such as thymus- and activation-regulated chemokine (TARC (CCL17)), macrophage-derived chemokine (MDC (CCL22)), and the like.

[0005] Activation of dendritic cells by TSLP through the TSLPR is associated with disease pathology, including allergic inflammatory diseases, such as asthma, and autoimmune disease, such as systemic sclerosis.

[0006] Interleukin 4 (IL-4) and interleukin 13 (IL-13) share a common receptor component, the Interleukin-4 Receptor Alpha (IL-4Ra) chain, that pairs with distinct subunits (Nelms, K., et al. (1999) Anmt. Rev. Immunol. 17:701 -738) and (Jensen, P.L. (2000) Stem Cells. 18:61-62). IL-4Ra pairs with the common yc chain to form a type I IL-4R complex that is found predominantly in hematopoietic cells and is exclusive for IL-4. IL-4Ra also pairs with the Interleukin- 13 Receptor Alpha 1 (IL-13Ral) subunit to form a type II IL-4R that binds both IL-41IPTS / 200090223.1Goodwin Ref: PRG-061WO and IL-13. The type II receptor is expressed on both hematopoietic and nonhematopoietic cells. IL-4 (also known as B cell stimulating factor or BSF-1) was originally characterized by its ability to stimulate the proliferation of B cells in response to low concentrations of antibodies directed to surface immunoglobulin. IL-4 has been shown to possess a broad spectrum of biological activities, including growth stimulation of T cells, mast cells, granulocytes, megakaryocytes and erythrocytes. IL-4 induces the expression of class II major histocompatibility complex molecules in resting B cells, and enhances the secretion of IgE and IgGl isotypes by stimulated B cells.

[0007] The biological and immunological functions of B -lymphocytes, monocytes, dendritic cells, and fibroblasts are all affected by IL-4 and IL-13. These cytokines interact with IL-4R to initiate the type 2 inflammatory pathway, which results in Th2 cell differentiation, inflammation, and mucus production. The type-2 inflammatory pathway is first activated in allergic illnesses by aberrant cytokine release resulting from an imbalance of Thl and Th2 differentiation. Th2 cells that have been activated release cytokines, including IL-4, IL-13, and IL-31, which prompt downstream B cells to undergo a change and produce IgE antibodies. Mast cells and basophils are then called upon to degranulate and release inflammatory substances. Simultaneously, the secreted IL-4 and IL- 13 continue to bind to their respective receptors, such as IL-4Ra, that repeatedly promotes TH2 differentiation and subsequent inflammation.

[0008] The important role of IL-4 and IL- 13 in the type-2 inflammation pathway identifies IL-4Ra as a potential target for individuals who exhibit aberrant type-2 inflammatory responses. Unlike medications that target IL-4 and IL- 13 exclusively, targeting IL-4Ra would target both IL-4 and IL-13.

[0009] Accordingly, there is a need in the art for antagonists to IL-4Ra and TSLP for preventing and treating diseases in which IL-4Ra and TSLP are involved in the disease pathology, such as inflammatory and fibrotic disorders. In addition, because targeting each of IL-4Ra and TSLP may lead to various clinical benefits in inflammatory conditions, there is a need in the art for improved therapeutics that target both TSLP and IL-4Ra, such as a combination of antibodies wherein, for example, one or more of the antibodies remains active for a longer period of time (i.e., has a longer half-life) as compared to another anti-TSLP antibody (e.g., tezepelumab) or anti-IL-4Ra antibody (e.g., dupilumab) when administered to a subject.2IPTS / 200090223.1Goodwin Ref: PRG-061WOSUMMARY

[0010] The present disclosure provides antibodies to TSLP, or antigen binding fragments thereof, such as recombinant human antibodies, and antibodies to interleukin-4 receptor alpha (IL-4Ra), or antigen binding fragments thereof, and methods of treating diseases in which TSLP and IL-4Ra are involved in disease pathology. The antibodies of the disclosure can include Fc modifications and exhibit longer half-lives than an otherwise identical antibody that does not include the Fc modification, for example, certain anti-TSLP or anti-IL-4Ra antibodies known in the art.

[0011] In one aspect, provided herein is an isolated antibody, or antigen binding fragment thereof, that binds TSLP, comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 27; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 19 and 22; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 30; (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CORED comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 310 and 324; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 351; or (iv) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 315 and 331; a CDR-L2 comprising the sequence set forth3IPTS / 200090223.1Goodwin Ref: PRG-061WO in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 355; and an isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra.

[0012] In some embodiments, the isolated antibody that binds IL-4Ra comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of an antibody selected from dupilumab, stapokibart, rademikibart, and Antibody 611.

[0013] In some embodiments, the isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0014] In another aspect, provided herein is an isolated antibody, or antigen binding fragment thereof, that binds TSLP; and an isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra, comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (i) a4IPTS / 200090223.1Goodwin Ref: PRG-061WOCDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0015] In some embodiments, the isolated antibody, or antigen binding fragment thereof, that binds TSLP comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 of an antibody selected from tezepelumab, hu23bl2, 43B1-H2L2, 43B1-H6L1, GR2002 (described in U.S. Patent Application Publication No. US 2024 / 0132581, which is incorporated herein by reference), TQC2731 (also known as BSL045B and bosakitug, described in U.S. Patent Application Publication No. US 2022 / 0289833, which is incorporated herein by reference), and solrikitug.

[0016] In some embodiments, the isolated antibody, or antigen binding fragment thereof, that binds TSLP comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds TSLP comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 27; (ii) a CDR-5IPTS / 200090223.1Goodwin Ref: PRG-061WOHl comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 19 and 22; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 30; (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 310 and 324; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 351; or (iv) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR- H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 315 and 331; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 355.

[0017] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 27; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0018] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10,6IPTS / 200090223.1Goodwin Ref: PRG-061WO11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 27; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0019] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 27; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0020] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 19 and 22; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 30; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set7IPTS / 200090223.1Goodwin Ref: PRG-061WO forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0021] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 19 and 22; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 30; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0022] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 19 and 22; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 30; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.8IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0023] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 310 and 324; a CDR- L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 351; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0024] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 310 and 324; a CDR- L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 351; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0025] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 310 and 324; a CDR- L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a9IPTS / 200090223.1Goodwin Ref: PRG-061WOCDR-L3 comprising the sequence set forth in SEQ ID NO: 351; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0026] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (iv) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 315 and 331; a CDR- L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 355; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0027] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (iv) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 315 and 331; a CDR- L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 355; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID10IPTS / 200090223.1Goodwin Ref: PRG-061WONO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0028] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (iv) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 315 and 331; a CDR- L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 355; and (b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0029] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 32-36. In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34.

[0030] In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 295-297.

[0031] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VL sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 37-45 and 361-396. In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VL sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41, 43, 374, and 380.

[0032] In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VL sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 298-300.

[0033] In some embodiments, (a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ11IPTS / 200090223.1Goodwin Ref: PRG-061WOID NO: 32; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 33; or (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and / or (iv) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 41; (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 43; (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 374; or (vii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 380; and / or (b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; (ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; or (iii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and / or (iv) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298; (v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:299; or (vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO:300.

[0034] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 41.

[0035] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 43.

[0036] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 374.

[0037] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 380.

[0038] In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.

[0039] In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.

[0040] In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.12IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0041] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 41; and the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.

[0042] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 41; and the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.

[0043] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 41; and the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.

[0044] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 43; and the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.

[0045] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 43; and the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.

[0046] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 43; and the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence13IPTS / 200090223.1Goodwin Ref: PRG-061WO comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.

[0047] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 374; and the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.

[0048] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 374; and the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.

[0049] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 374; and the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.

[0050] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 380; and the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.

[0051] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 380; and the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.

[0052] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO:14IPTS / 200090223.1Goodwin Ref: PRG-061WO34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 380; and the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.

[0053] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra is a humanized, human, or chimeric antibody.

[0054] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra is a humanized antibody.

[0055] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM.

[0056] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a human Fc region, and wherein the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgGl, IgG2, IgG3, and IgG4.

[0057] In some embodiments, the human Fc region of the antibody, or antigen binding fragment thereof, that binds TSLP and / or the human Fc region of the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a human IgGl Fc region.

[0058] In some embodiments, the human Fc region of the antibody, or antigen binding fragment thereof, that binds TSLP and / or the human Fc region of the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a human IgG4 Fc region.

[0059] In some embodiments, the human Fc region of the antibody, or antigen binding fragment thereof, that binds TSLP and / or the human Fc region of the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a human IgG2 Fc region.

[0060] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a heavy chain comprising a constant heavy chain sequence selected from an amino acid sequence set forth in any one of SEQ ID NOs: 47-270. In some embodiments, the heavy chain of the antibody, or antigen binding fragment thereof, that binds TSLP and / or the heavy chain of the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a constant heavy chain sequence selected from an amino acid sequence set forth in any one of SEQ ID NOs: 61 and 173.15IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0061] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a light chain comprising a constant light chain sequence set forth in SEQ ID NO: 46 or SEQ ID NO: 421.

[0062] In some embodiments, antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a light chain comprising a human lambda light chain constant region. In some embodiments, the human lambda light chain constant region comprises a sequence set forth in any one of SEQ ID NOs: 421-424. In some embodiments, the human lambda light chain constant region comprises a sequence set forth in SEQ ID NO: 421.

[0063] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a light chain comprising a human lambda light chain constant region and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a light chain comprising a human kappa light chain constant region.

[0064] In some embodiments, the light chain of the antibody, or antigen binding fragment thereof, that binds TSLP comprises a constant light chain sequence set forth in SEQ ID NO: 421.

[0065] In some embodiments, the light chain of the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a constant light chain sequence set forth in SEQ ID NO: 46.

[0066] In some embodiments, the antibody that binds IL-4Ra comprises a heavy chain sequence set forth in SEQ ID NO: 444 or 445 and a light chain sequence set forth in SEQ ID NO: 446. In some embodiments, the antibody that binds IL-4Ra comprises a heavy chain sequence set forth in SEQ ID NO: 444 and a light chain sequence set forth in SEQ ID NO: 446. The heavy chain sequence of SEQ ID NO: 444 contains a C-terminal lysine, which may be cleaved off during manufacture or after administration, resulting in the heavy chain sequence of SEQ ID NO: 445.

[0067] In some embodiments, the antibody that binds TSLP comprises a heavy chain sequence set forth in SEQ ID NO: 425 or 427 and a light chain sequence set forth in SEQ ID NO: 426. In some embodiments, the antibody that binds TSLP comprises a heavy chain sequence set forth in SEQ ID NO: 425 and a light chain sequence set forth in SEQ ID NO: 426. The heavy chain sequence of SEQ ID NO: 425 contains a C-terminal lysine, which may be cleaved off during manufacture or after administration, resulting in the heavy chain sequence of SEQ ID NO: 427.16IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0068] In some embodiments, the antibody that binds TSLP is Antibody 5 and the antibody that binds IL-4Ra is Construct 38 (mAb471).

[0069] In some embodiments, the antibody that binds TSLP is an antibody having a VH sequence and a VL sequence from the same row of TABLE 4 (i.e., a VH sequence and VL sequence from a single antibody in TABLE 4) and the antibody that binds IL-4Ra is Construct 38 (mAb471).

[0070] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP is an antibody having a VH sequence and a VL sequence from the same row of TABLE 13 (i.e., a VH sequence and VL sequence from a single antibody in TABLE 13) and the antibody that binds IL-4Ra is Construct 38 (mAb471).

[0071] In some embodiments, the antibody that binds TSLP is an antibody having a CDR- Hl, a CDR-H2, a CDR-H3, a CDR-L1, a CDR-L2, and a CDR-L3 from the same row of TABLE 3 (i.e., having six CDRs from a single antibody in TABLE 3) and the antibody that binds IL-4Ra is Construct 38 (mAb471).

[0072] In some embodiments, the antibody that binds TSLP is an antibody having a CDR- Hl, a CDR-H2, a CDR-H3, a CDR-L1, a CDR-L2, and a CDR-L3 from the same row of TABLE 12 (i.e., having six CDRs from a single antibody in TABLE 12) and the antibody that binds IL-4Ra is Construct 38 (mAb471).

[0073] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a heavy chain constant domain having a means for increasing the half-life of the antibody.

[0074] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more amino acid substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more amino acid substitutions.

[0075] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more amino acid substitutions result in a decrease in one or more of, ADCC activity, ADCP activity or CDC activity compared to an antibody comprising a wild-type Fc region.

[0076] In some embodiments, the one or more amino acid substitutions is selected from the group consisting of S228P, M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q,17IPTS / 200090223.1Goodwin Ref: PRG-061WOT307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W (or, e.g., L242A, L243A, L239A, L240A, M260Y, S262T, T264E, M257Y, S259T, or T261E using direct numbering); optionally, wherein the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L / N434S (LS), M252Y / S254T / T256E (YTE) using EU numbering or M257Y / S259T / T261E (YTE) using direct numbering or M260Y / S262T / T264E (YTE) using direct numbering, T250Q / M428L, T307A / E380A / N434A, T256D / T307Q (DQ), T256D / T307W (DW), M252Y / T256D (YD), T307Q / Q311V / A378V (QVV), T256D / H285D / T307R / Q311V / A378V (DDRVV), L309D / Q311H / N434S (DHS), S228P / L235E (SPLE), L234A / L235A (LALA) using EU numbering or L239A / L240A (LALA) using direct numbering or L242A / L243 A (LALA) using direct numbering, M428L / N434A (LA), L235A / G237A (LAGA), L234A / L235A / G237A (LALAGA), L234A / L235A / P329G (LALAPG), D265A / YTE, LALA / YTE, LAGA / YTE, LALAGA / YTE, LALAPG / YTE, N297A / LS, D265A / LS, LALA / LS, LALAGA / LS, LALAPG / LS, N297A / DHS, D265A / DHS, LALA / DHS, LAGA / DHS, LALAGA / DHS, LALAPG / DHS, SP / YTE, SPLE / YTE, SP / LS, SPLE / LS, SP / DHS, SPLE / DHS, N297A / LA, D265A / LA, LALA / LA, LAGA / LA, LALAGA / LA, LALAPG / LA, N297A / N434A, D265A / N434A, LALA / N434A, LAGA / N434A, LALAGA / N434A, LALAPG / N434A, N297A / N434W, D265A / N434W, LALA / N434W, LAGA / N434W, LALAGA / N434W, LALAPG / N434W, N297A / DQ, D265A / DQ, LALA / DQ, LAGA / DQ, LALAGA / DQ, LALAPG / DQ, N297A / DW, D265A / DW, LALA / DW, LAGA / DW, LALAGA / DW, LALAPG / DW, N297A / YD, D265A / YD, LALA / YD, LAGA / YD, LALAGA / YD, LALAPG / YD, T307Q / Q311V / A378V (QVV), N297A / QVV, D265A / QVV, LALA / QVV, LAGA / QVV, LALAGA / QVV, LALAPG / QVV, DDRVV, N297A / DDRVV, D265A / DDRVV, LALA / DDRVV, LAGA / DDRVV, LALAGA / DDRVV, and LALAPG / DDRVV. In some embodiments, the one or more amino acid substitutions is selected from the group consisting of LS, YTE, T250Q / M428L, T307A / E380A / N434A, DQ, DW, YD, QVV, DHS, LA, D265A / YTE, LALA / YTE, LAGA / YTE, LALAGA / YTE, LALAPG / YTE, N297A / LS, D265A / LS, LALA / LS, LALAGA / LS, LALAPG / LS, N297A / DHS, D265A / DHS, LALA / DHS, LAGA / DHS, LALAGA / DHS, LALAPG / DHS, SP / YTE, SPLE / YTE, SP / LS, SPLE / LS, SP / DHS, SPLE / DHS, N297A / LA, D265A / LA, LALA / LA, LAGA / LA, LALAGA / LA, LALAPG / LA, N297A / DQ, D265A / DQ, LALA / DQ, LAGA / DQ, LALAGA / DQ, LALAPG / DQ, N297A / DW, D265A / DW, LALA / DW, LAGA / DW, LALAGA / DW, LALAPG / DW, N297A / YD, D265A / YD, LALA / YD, LAGA / YD, LALAGA / YD, LALAPG / YD, N297A / QVV, D265A / QVV, LALA / QVV, LAGA / QVV, LALAGA / QVV, and LALAPG / QVV.18IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0077] In some embodiments, the Fc region of the antibody that binds TSLP and / or the antibody that binds IL-4Ra comprises LALA / YTE substitutions.

[0078] Although the EU numbering system is typically used to identify the positions of the various Fc mutations described herein, direct numbering can also be used. For example, in certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 260 / 262 / 264 or 257 / 259 / 261, respectively. In certain embodiments, an antibody described herein comprises an Fc region with LALA mutations at positions 242 / 243 or 239 / 240, respectively. In certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 260 / 262 / 264 or 257 / 259 / 261, respectively and with LALA mutations at positions 242 / 243 or 239 / 240, respectively. In certain embodiments, the TSLP antibody described herein comprises an Fc region comprising YTE mutations at positions 257 / 259 / 261, respectively, and LALA mutations at positions 239 / 240, respectively. In certain embodiments, the TSLP antibody described herein comprises the VH and VL of Antibody 5 and an Fc region comprising YTE mutations at positions 257 / 259 / 261, respectively and with LALA mutations at positions 239 / 240, respectively. In certain embodiments, the IL-4Ra antibody described herein comprises an Fc region comprising YTE mutations at positions 260 / 262 / 264, respectively, and LALA mutations at positions 242 / 243, respectively. In certain embodiments, the IL-4Ra antibody described herein comprises the VH and VL of Construct 38 (mAb471) and an Fc region comprising YTE mutations at positions 260 / 262 / 264, respectively and with LALA mutations at positions 242 / 243, respectively.

[0079] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34, a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 41, and a human IgGl Fc region comprising LALA and YTE mutations; and the antibody that binds IL- 4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300, and a human IgGl Fc region comprising LALA and YTE mutations. In some embodiments, the antibody that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34, a constant heavy chain sequence comprising the amino acid sequence set forth SEQ ID NO: 173 and / or a constant heavy chain sequence comprising the amino acid sequence set forth SEQ ID NO: 61, a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 41, and a constant light chain sequence comprising the amino acid sequence set forth in SEQ ID NO: 421; and the antibody that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297, a constant heavy chain19IPTS / 200090223.1Goodwin Ref: PRG-061WO sequence comprising the amino acid sequence set forth SEQ ID NO: 173 and / or a constant heavy chain sequence comprising the amino acid sequence set forth SEQ ID NO: 61, a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300, and a constant light chain sequence comprising the amino acid sequence set forth in SEQ ID NO: 46. In some embodiments, the antibody that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34, a constant heavy chain sequence comprising the amino acid sequence set forth SEQ ID NO: 173, a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 41, and a constant light chain sequence comprising the amino acid sequence set forth in SEQ ID NO: 421; and the antibody that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297, a constant heavy chain sequence comprising the amino acid sequence set forth SEQ ID NO: 173, a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300, and a constant light chain sequence comprising the amino acid sequence set forth in SEQ ID NO: 46. A C-terminal lysine is present in SEQ ID NO: 173, which may be cleaved off during manufacture or after administration, resulting in the sequence of SEQ ID NO: 61. Accordingly, a composition comprising an antibody that binds TSLP and / or an antibody that binds IL-4Ra comprising the constant heavy chain sequence of SEQ ID NO: 173 that is administered to a subject may comprise antibodies having the constant heavy chain sequence set forth in SEQ ID NO: 173 or SEQ ID NO: 61, or a mixture thereof (e.g., a mixture of antibodies containing either a constant heavy chain sequence of SEQ ID NO: 173 or a constant heavy chain sequence of SEQ ID NO: 61 and / or antibodies containing both constant heavy chain sequences (e.g., in an antibody containing two constant heavy chain sequences)).

[0080] In some embodiments, the antibody that binds TSLP comprises a heavy chain sequence comprising the amino acid sequence set forth SEQ ID NO: 425 and / or 427 and a light chain sequence comprising the amino acid sequence set forth in SEQ ID NO: 426; and the antibody that binds IL-4Ra comprises a heavy chain sequence comprising the amino acid sequence set forth SEQ ID NO: 444 and / or 445 and a light chain sequence comprising the amino acid sequence set forth in SEQ ID NO: 446. In some embodiments, the antibody that binds TSLP comprises a heavy chain sequence comprising the amino acid sequence set forth SEQ ID NO: 425 and a light chain sequence comprising the amino acid sequence set forth in SEQ ID NO: 426; and the antibody that binds IL-4Ra comprises a heavy chain sequence comprising the amino acid sequence set forth SEQ ID NO: 444 and a light chain sequence comprising the amino acid sequence set forth in SEQ ID NO: 446. The C-terminal lysine in SEQ ID NO: 425 and / or SEQ ID NO: 444 may not be present if cleavage occurs during manufacture or after20IPTS / 200090223.1Goodwin Ref: PRG-061WO administration (which would result in the heavy chain sequence of SEQ ID NO: 427 and / or SEQ ID NO: 445, respectively).

[0081] In some embodiments, the antibody that binds TSLP is Antibody 5 and the antibody that binds IL-4Ra is dupilumab, stapokibart, rademikibart, or Antibody 611.

[0082] In some embodiments, the antibody that binds TSLP is tezepelumab, GR2002, TQC2731, solrikitug, hu23bl2, 43B1-H2L2, or 43B1-H6L1 and the antibody that binds IL-4Ra is Construct 38.

[0083] In some embodiments, the Fc region of the antibody, or antigen binding fragment thereof, that binds TSLP and / or the Fc region of the antibody, or antigen binding fragment thereof, that binds IL-4Ra binds to Neonatal Fc receptor (FcRn).

[0084] In some embodiments, the Fc region of the antibody, or antigen binding fragment thereof, that binds TSLP and / or the Fc region of the antibody, or antigen binding fragment thereof, that binds IL-4Ra binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region.

[0085] In some embodiments, the Fc region of the antibody, or antigen binding fragment thereof, that binds TSLP and / or the Fc region of the antibody, or antigen binding fragment thereof, that binds IL-4Ra binds to FcRn with a KD of <1 x 10-7 M at pH 6.0.

[0086] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra is a monoclonal antibody.

[0087] In some embodiments, the antibody, or antigen binding fragment thereof, that binds TSLP binds a TSLP sequence set forth in the amino acid sequence of any one of SEQ ID NOs: 271-272.

[0088] In some embodiments, the antibody, or antigen binding fragment thereof, that binds IL-4Ra binds an IL-4Ra sequence set forth in the amino acid sequence of any one of SEQ ID NOs: 301-303.

[0089] In some embodiments, the isolated antibodies, or antigen binding fragments thereof, disclosed herein are for use in the treatment of an inflammatory disorder or disease.

[0090] In some embodiments, the isolated antibodies, or antigen binding fragments thereof, disclosed herein are for use in the treatment of atopic dermatitis (AD).

[0091] In some embodiments, the treatment reduces disease severity in a patient and wherein disease severity is assessed by an atopic dermatitis disease severity outcome measure.

[0092] In some embodiments, the isolated antibodies, or antigen binding fragments thereof, disclosed herein are for use in the treatment of asthma, chronic sinusitis with nasal polyps;21IPTS / 200090223.1Goodwin Ref: PRG-061WOChronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID), such as Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), or Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome / Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); an inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis; lupus; rheumatoid arthritis (RA); psoriasis; hidradenitis suppurativa; celiac disease; idiopathic pulmonary fibrosis; alopecia areata; or systemic sclerosis.

[0093] In one aspect, provided herein is an isolated polynucleotide or set of polynucleotides encoding any one of the isolated antibodies disclosed herein, a VH thereof, a VL thereof, a light chain thereof, a heavy chain thereof, or an antigen-binding portion thereof, and optionally, wherein the polynucleotide or set of polynucleotides comprises cDNA.

[0094] In one aspect, provided herein is a vector or set of vectors comprising the polynucleotide or set of polynucleotides disclosed herein.

[0095] In one aspect, provided herein is a host cell comprising the polynucleotide or set of polynucleotides disclosed herein or the vector or set of vectors disclosed herein.

[0096] In one aspect, provided herein is a method of producing one or more of the isolated antibodies, or antigen binding fragments thereof, disclosed herein the method comprising expressing one or more of the antibodies within the host cell disclosed herein and isolating the one or more expressed antibodies.

[0097] In one aspect, provided herein is a pharmaceutical composition comprising any of the isolated antibodies, or antigen binding fragments thereof, disclosed herein and a pharmaceutically acceptable excipient (i.e., a pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, that binds to TSLP and / or an antibody, or antigen binding fragment thereof, that binds to IL-4Ra).

[0098] In one aspect, provided herein is a kit comprising any of the isolated antibodies, or antigen binding fragments thereof, disclosed herein (e.g., a kit comprising an antibody, or antigen binding fragment thereof, that binds to TSLP and an antibody, or antigen binding fragment thereof, that binds to IL-4Ra) or the pharmaceutical composition disclosed herein and instructions for use.

[0099] In one aspect, provided herein is a method for treating an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the22IPTS / 200090223.1Goodwin Ref: PRG-061WO mammalian subject a therapeutically effective amount of any of the isolated antibodies, or antigen binding fragments thereof, disclosed herein; a therapeutically effective amount of the pharmaceutical composition disclosed herein; or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or antigen binding fragment thereof, that binds TSLP and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, that binds IL-4Ra and a pharmaceutically acceptable excipient.

[0100] In some embodiments, the mammalian subject is a human.

[0101] In some embodiments, the inflammatory disorder or disease is atopic dermatitis. In some embodiments, the inflammatory disorder or disease is asthma. In some embodiments, the inflammatory disorder or disease is chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID), such as Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), or Eosinophilic Gastroenteritis (EGE); Churg- Strauss syndrome / Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); an inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis; lupus; rheumatoid arthritis (RA); psoriasis; hidradenitis suppurativa; systemic sclerosis; idiopathic pulmonary fibrosis; alopecia areata; or celiac disease.

[0102] In one aspect, provided herein is a method for treating a pathology associated with elevated levels of TSLP, IL-13, IL-4, and / or IL-4Ra in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of any of the isolated antibodies, or antigen binding fragments thereof, disclosed herein, a pharmaceutical composition disclosed herein, or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or antigen binding fragment thereof, that binds TSLP and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, that binds IL-4Ra and a pharmaceutically acceptable excipient.

[0103] In one aspect, provided herein is a method of reducing biological activity of TSLP and / or IL-4Ra in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of any of the isolated antibodies, or antigen binding fragments thereof, disclosed herein, a pharmaceutical composition disclosed23IPTS / 200090223.1Goodwin Ref: PRG-061WO herein, or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or antigen binding fragment thereof, that binds TSLP and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, that binds IL-4Ra and a pharmaceutically acceptable excipient.

[0104] In some embodiments, the mammalian subject is a human.

[0105] In another aspect, provided herein is an isolated antibody, or antigen binding fragment thereof, that binds TSLP, comprising: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises: (i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 27; and an isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra, comprising: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR- H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR- Ll, CDR-L2, and CDR-L3, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: (iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293, wherein the isolated antibody, or antigen binding fragment thereof, that binds TSLP and / or the isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a heavy chain comprising a heavy chain constant region having a means for extending the half-life of the isolated antibody.24IPTS / 200090223.1Goodwin Ref: PRG-061WOBRIEF DESCRIPTION OF FIGURES

[0106] FIG. 1A - FIG. ID show the ability of exemplary anti-TSLP antibodies and a positive control antibody (antibody based on published sequences of tezepelumab) to inhibit TSLP binding. FIG. ID also includes an isotype control.

[0107] FIG. 2A -FIG. 2C show the ability of exemplary anti-TSLP antibodies and a positive control antibody (antibody based on published sequences of tezepelumab) to inhibit the STAT5- induced expression of luciferase. FIG. 2C also includes an isotype control.

[0001] FIG. 3A -FIG. 3C show the ability of exemplary anti-TSLP antibodies and a positive control antibody (antibody based on published sequences of tezepelumab) to inhibit the proliferation of Baf3 cells. FIG. 3C also includes an isotype control.

[0108] FIG. 4A - FIG. 4D show the ability of exemplary anti-TSLP antibodies and a positive control antibody (antibody based on published sequences of tezepelumab) to inhibit TSLP-induced TARC secretion.

[0109] FIG. 5 is a graph showing the serum concentration of Antibody 5 and a positive control antibody (antibody based on published sequences of tezepelumab) over time when injected intravenously (IV) or subcutaneously (SC) in vivo in non-human primates.

[0110] FIG. 6 is a schematic of TSLP with a positive control antibody (antibody based on published sequences of tezepelumab) and Antibody 5 epitope mapping regions shown in medium gray and black speckles, respectively, as measured by Hydrogen-Deuterium Exchange (HDX) mass spectrometry.

[0111] FIG. 7 is a schematic of TSLP with a positive control antibody (antibody based on published sequences of tezepelumab) and Antibody 5 epitope mapping regions shown in medium gray and black speckles, respectively, as measured by cross-linking mass spectrometry (XL-MS).

[0112] FIG. 8A and FIG. 8B show the ability of exemplary anti-IL4Ra antibodies and dupilumab to inhibit IL-4 and IL- 13 binding.

[0113] FIG. 9A and FIG. 9B show the ability of exemplary anti-IL4Ra antibodies and dupilumab to inhibit IL-4-induced and IL-13-induced STAT6 phosphorylation (pSTAT6).

[0114] FIG. 10A and FIG. 10B show the ability of exemplary anti-IL4Ra antibodies and dupilumab to inhibit IL-4- and / or IL-13-induced TARC secretion.

[0115] FIG. 11A and FIG. 11B show the ability of exemplary anti-IL4Ra antibodies and dupilumab to inhibit IL-4-induced and IL-13-induced proliferation of TF-1 cells.

[0116] FIG. 12A and FIG. 12B show the serum concentration of exemplary anti-IL4Ra antibodies (Construct 13 (mAb422), Construct 38 (mAb471), and dupilumab) over time after a25IPTS / 200090223.1Goodwin Ref: PRG-061WO single intravenous (FIG. 12A) or subcutaneous (FIG. 12B) administration of 25 mg / kg in nonhuman primates.

[0117] FIG. 13 is a heatmap depicting the changes in cytokine / chemokine levels of thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), interleukin (IL)-13, IL-5, interferon gamma (TFNy), tumor necrosis factor alpha (TNFa), IL-31, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in allogeneic lymphocyte reaction experiments performed on myeloid dendritic cells (mDCs) primed with recombinant human TSLP and allogeneic CD4-positive cells from four healthy volunteers treated with test article, Antibody 5, Construct 38, a combination of Antibody 5 and Construct 38, tezepelumab, or dupilumab, or unstimulated. Values are normalized to isotype control.DETAILED DESCRIPTIONDefinitions

[0118] Unless otherwise defined, all terms of art, notations and other scientific terminology used herein are intended to have the meanings commonly understood by those of skill in the art. In some cases, terms with commonly understood meanings are defined herein for clarity and / or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a difference over what is generally understood in the art. The techniques and procedures described or referenced herein are generally well understood and commonly employed using conventional methodologies by those skilled in the art, such as, for example, the widely utilized molecular cloning methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual 4th ed. (2012) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. As appropriate, procedures involving the use of commercially available kits and reagents are generally carried out in accordance with manufacturer-defined protocols and conditions unless otherwise noted.

[0119] As used herein, the singular forms “a,” “an,” and “the” include plural references unless indicated otherwise.

[0120] It is understood that aspects and embodiments of the invention described herein include “comprising,” “consisting,” and “consisting essentially of’ aspects and embodiments.

[0121] For all compositions described herein, and all methods using a composition described herein, the compositions can either comprise the listed components or steps, or can “consist essentially of’ the listed components or steps. When a composition is described as “consisting essentially of’ the listed components, the composition contains the components listed, and may26IPTS / 200090223.1Goodwin Ref: PRG-061WO contain other components which do not substantially affect the condition being treated, but do not contain any other components which substantially affect the condition being treated other than those components expressly listed; or, if the composition does contain extra components other than those listed which substantially affect the condition being treated, the composition does not contain a sufficient concentration or amount of the extra components to substantially affect the condition being treated. When a method is described as “consisting essentially of’ the listed steps, the method contains the steps listed, and may contain other steps that do not substantially affect the condition being treated, but the method does not contain any other steps which substantially affect the condition being treated other than those steps expressly listed. As a non-limiting specific example, when a composition is described as “consisting essentially of’ a component, the composition may additionally contain any amount of pharmaceutically acceptable carriers, vehicles, or diluents and other such components which do not substantially affect the condition being treated.

[0122] The term “vector,” as used herein, refers to a nucleic acid molecule capable of propagating another nucleic acid to which it is linked. The term includes the vector as a selfreplicating nucleic acid structure as well as the vector incorporated into the genome of a host cell into which it has been introduced. Certain vectors are capable of directing the expression of nucleic acids to which they are operatively linked. Such vectors are referred to herein as “expression vectors.”

[0123] The terms “host cell,” “host cell line,” and “host cell culture” are used interchangeably herein and refer to cells into which an exogenous nucleic acid has been introduced, and the progeny of such cells. Host cells include “transformants” (or “transformed cells”) and “transfectants” (or “transfected cells”), which each include the primary transformed or transfected cell and progeny derived therefrom. Such progeny may not be completely identical in nucleic acid content to a parent cell, and may contain mutations. A “recombinant host cell” or “host cell” refers to a cell that includes an exogenous polynucleotide, regardless of the method used for insertion, for example, direct uptake, transduction, f-mating, or other methods known in the art to create recombinant host cells.

[0124] As used herein, the term “eukaryote” refers to organisms belonging to the phylogenetic domain Eukarya such as animals (including but not limited to, mammals, insects, reptiles, birds, etc.), ciliates, plants (including but not limited to, monocots, dicots, algae, etc.), fungi, yeasts, flagellates, microsporidia, protists, etc.

[0125] As used herein, the term “prokaryote” refers to prokaryotic organisms. For example, a non-eukaryotic organism can belong to the Eubacteria (including but not limited to,27IPTS / 200090223.1Goodwin Ref: PRG-061WOEscherichia coli, Thermus thermophilus, Bacillus stearothermophilus, Pseudomonas fluorescens, Pseudomonas aeruginosa, Pseudomonas putida, etc.) phylogenetic domain, or the Archaea (including but not limited to, Methanococcus jannaschii, Methanobacterium thermoautotrophicum, Halobacterium such as Haloferax volcanii and Halobacterium species NRC-1, Archaeoglobus fulgidus, Pyrococcus furiosus, Pyrococcus horikoshii, Aeuropyrum pernix, etc.) phylogenetic domain.

[0126] An “effective amount” or “therapeutically effective amount” as used herein refers to an amount of therapeutic compound, such as an anti-TSLP antibody, or antigen binding fragment thereof, or an anti-IL-4Ra antibody, or antigen binding fragment thereof, administered to an individual, either as a single dose or as part of a series of doses, which is effective to produce or contribute to a desired therapeutic effect, either alone or in combination with another therapeutic modality. Examples of a desired therapeutic effect is reducing an aberrant immune response, slowing or delaying disease development; stabilization of disease; and amelioration of one or more symptoms. An effective amount may be given in one or more dosages.

[0127] The term “treating” (and variations thereof such as “treat” or “treatment”) refers to clinical intervention in an attempt to alter the natural course of a disease or condition in a subject in need thereof. Treatment can be performed during the course of clinical pathology. Desirable effects of treatment include preventing recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis.

[0128] The term “sufficient amount” means an amount sufficient to produce a desired effect, e.g., an amount sufficient to modulate an immune response in a subject.

[0129] As used herein, the term “subject,” “patient,” or “individual” means a mammalian subject. Exemplary subjects include humans, monkeys, dogs, cats, mice, rats, cows, horses, camels, goats, rabbits, and sheep. In certain embodiments, the subject is a human. In some embodiments the subject has a disease or condition that can be treated with an antibody, or antigen binding fragment thereof, provided herein. In some aspects, the disease or condition is atopic dermatitis. In some aspects, the disease or condition is asthma.

[0130] The term “in vitro" refers to processes that occur in a living cell growing separate from a living organism, e.g., growing in tissue culture.

[0131] The term “in vivo” refers to processes that occur in a living organism.

[0132] The term “package insert” is used to refer to instructions customarily included in commercial packages of therapeutic or diagnostic products (e.g., kits) that contain information28IPTS / 200090223.1Goodwin Ref: PRG-061WO about the indications, usage, dosage, administration, combination therapy, contraindications and / or warnings concerning the use of such therapeutic or diagnostic products.

[0133] The term “pharmaceutical composition” refers to a preparation which is in such form as to permit the biological activity of one or more active ingredient(s) contained therein to be effective in treating a subject.

[0134] As used herein, the term “pharmaceutically acceptable” refers to those compounds, materials, compositions and / or dosage forms, which are suitable for contact with the tissues of a subject, such as a mammal (e.g., a human) without excessive toxicity, irritation, allergic response and other problem complications commensurate with a reasonable benefit / risk ratio. Preferably, the term “pharmaceutically acceptable” means approved 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 mammals, and more particularly in humans.

[0135] The terms “co-administration,” “co-administer,” and “in combination with” include the administration of two or more therapeutic agents either simultaneously, concurrently or sequentially within no specific time limits. In one embodiment, the agents are present in the cell or in the subject's body at the same time or exert their biological or therapeutic effect at the same time. In one embodiment, the therapeutic agents are in the same composition or unit dosage form. In other embodiments, the therapeutic agents are in separate compositions or unit dosage forms. In certain embodiments, a first agent can be administered prior to the administration of a second therapeutic agent.

[0136] The terms “modulate” and “modulation” refer to reducing or inhibiting or, alternatively, activating or increasing, a recited variable.

[0137] The terms “increase” and “activate” refer to an increase of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20- fold, 50-fold, 100-fold, or greater in a recited variable.

[0138] The terms “reduce” and “inhibit” refer to a decrease of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or greater in a recited variable.

[0139] The term “about” indicates and encompasses an indicated value and a range above and below that value. In certain embodiments, the term “about” indicates the designated value ± 10%, ± 5%, or ± 1%. In certain embodiments, where applicable, the term “about” indicates the designated value(s) ± one standard deviation of that value(s).29IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0140] The term “agonize” refers to the activation of receptor signaling to induce a biological response associated with activation of the receptor. An “agonist” is an entity that binds to and agonizes a receptor.

[0141] The term “antagonize” refers to the inhibition of receptor signaling to inhibit a biological response associated with activation of the receptor. An “antagonist” is an entity that binds to and antagonizes a receptor.

[0142] For any of the structural and functional characteristics described herein, methods of determining these characteristics are known in the art.

[0143] The term “optionally” is meant, when used sequentially, to include from one to all of the enumerated combinations and contemplates all sub-combinations.

[0144] The term “amino acid” refers to, for example, the twenty common naturally occurring amino acids. Naturally occurring amino acids include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine (Cys; C), glutamic acid (Glu; E), glutamine (Gin; Q), Glycine (Gly; G), histidine (His; H), isoleucine (He; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; T), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Vai; V).

[0145] The term “affinity” refers to the strength of the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen or epitope). Unless indicated otherwise, as used herein, “affinity” refers to intrinsic binding affinity, which reflects a 1 : 1 interaction between members of a binding pair (e.g., antibody and antigen or epitope).

[0146] The term “kd” (sec-1), as used herein, refers to the dissociation rate constant of a particular antibody-antigen interaction. This value is also referred to as the koff value.

[0147] The term “ka” (M-l * sec- 1), as used herein, refers to the association rate constant of a particular antibody-antigen interaction. This value is also referred to as the kon value.

[0148] The term “KD” (M), as used herein, refers to the dissociation equilibrium constant of a particular antibody-antigen interaction. KD = kd / ka. In some embodiments, the affinity of an antibody is described in terms of the KD for an interaction between such antibody and its antigen. For clarity, as known in the art, a smaller KD value indicates a higher affinity interaction, while a larger KD value indicates a lower affinity interaction.

[0149] The term “KA” (M-l), as used herein, refers to the association equilibrium constant of a particular antibody-antigen interaction. KA = ka / kd.

[0150] As used herein, “administration” refers to providing or giving a subject a therapeutic agent (e.g., an anti-IL-4Ra antibody, or antigen binding fragment thereof, and / or an anti-TSLP30IPTS / 200090223.1Goodwin Ref: PRG-061WO antibody, or antigen binding fragment thereof, described herein) by any effective route. Exemplary routes of administration are described herein below.

[0151] As used herein, the term “polypeptide” describes a single polymer in which the monomers are amino acid residues which are covalently conjugated together through amide bonds. A polypeptide is intended to encompass any amino acid sequence, either naturally occurring, recombinant, or synthetically produced.

[0152] As used herein, the terms “nucleic acid” and “polynucleotide,” used interchangeably herein, refer to a polymeric form of nucleosides in any length. Typically, a polynucleotide is composed of nucleosides that are naturally found in DNA or RNA (e.g., adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine, deoxythymidine, deoxyguanosine, and deoxy cytidine) joined by phosphodiester bonds. The term encompasses molecules comprising nucleosides or nucleoside analogs containing chemically or biologically modified bases, modified backbones, etc., whether or not found in naturally occurring nucleic acids, and such molecules may be preferred for certain applications. Where this application refers to a polynucleotide it is understood that both DNA, RNA, and in each case both single- and doublestranded forms (and complements of each single-stranded molecule) are provided.

[0153] As used herein, the terms “conservative mutation,” “conservative substitution,” and “conservative amino acid substitution” refer to a substitution of one or more amino acids for one or more different amino acids that exhibit similar physicochemical properties, such as polarity, electrostatic charge, and steric volume. These properties are summarized for each of the twenty naturally occurring amino acids in TABLE 1 below.TABLE 1. Representative physicochemical properties of naturally occurring amino acids31IPTS / 200090223.1Goodwin Ref: PRG-061WOFrom this table it is appreciated that the conservative amino acid families include (i) G, A, V, L and I; (ii) D and E; (iii) C, S and T; (iv) H, K and R; (v) N and Q; and (vi) F, Y and W. A conservative mutation or substitution is therefore one that substitutes one amino acid for a member of the same amino acid family (e.g., a substitution of Ser for Thr or Lys for Arg).

[0154] The term “antibody” is used herein in its broadest sense and includes certain types of immunoglobulin molecules comprising one or more antigen-binding domains that specifically bind to an antigen or epitope. An antibody specifically includes intact antibodies (e.g., intact immunoglobulins), antibody fragments, and multi-specific antibodies.

[0155] An “anti-TSLP antibody,” “TSLP antibody,” or “TSLP specific antibody” is an antibody, as provided herein, which specifically binds to the antigen TSLP.

[0156] An “anti-IL-4Ra antibody,” “IL-4Ra antibody,” or “IL-4Ra specific antibody” is an antibody, as provided herein, which specifically binds to the antigen IL-4Ra.32IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0157] The term “epitope” means a portion of an antigen that specifically binds to an antibody.

[0158] The term “hypervariable region” or “HVR”, as used herein, refers to each of the regions of an antibody variable domain which are hypervariable in sequence and / or form structurally defined loops (“hypervariable loops”).

[0159] The term “antigen-binding domain” means the portion of an antibody that is capable of specifically binding to an antigen or epitope.

[0160] The term “chimeric antibody” refers to an antibody in which a portion of the heavy and / or light chain is derived from a particular source or species, while the remainder of the heavy and / or light chain is derived from a different source or species.

[0161] The term “human antibody” or “fully human antibody” refers to an antibody which possesses an amino acid sequence corresponding to that of an antibody produced by a human or a human cell, or derived from a non-human source that utilizes a human antibody repertoire or human antibody-encoding sequences (e.g., obtained from human sources or designed de novo). Human antibodies specifically exclude humanized antibodies.

[0162] The term “humanized antibody” refers to a protein having a sequence that differs from the sequence of an antibody derived from a non-human species by one or more amino acid substitutions, deletions, and / or additions, such that the humanized antibody is less likely to induce an immune response, and / or induces a less severe immune response, as compared to the non-human species antibody, when it is administered to a human subject.

[0163] The term “multispecific antibody” refers to an antibody that comprises two or more different antigen-binding domains that collectively specifically bind two or more different epitopes.

[0164] A “monospecific antibody” is an antibody that comprises one or more binding sites that specifically bind to a single epitope. An example of a monospecific antibody is a naturally occurring IgG molecule which, while divalent (z.e., having two antigen-binding domains), recognizes the same epitope at each of the two antigen-binding domains. The binding specificity may be present in any suitable valency.

[0165] The term “monoclonal antibody” refers to an antibody from a population of substantially homogeneous antibodies. A population of substantially homogeneous antibodies comprises antibodies that are substantially similar and that bind the same epitope(s), except for variants that may normally arise during production of the monoclonal antibody. Such variants are generally present in only minor amounts. A monoclonal antibody is typically obtained by a process that includes the selection of a single antibody from a plurality of antibodies. For33IPTS / 200090223.1Goodwin Ref: PRG-061WO example, the selection process can be the selection of a unique clone from a plurality of clones, such as a pool of hybridoma clones, phage clones, yeast clones, bacterial clones, or other recombinant DNA clones. The selected antibody can be further altered, for example, to improve affinity for the target (“affinity maturation”), to humanize the antibody, to improve its production in cell culture, and / or to reduce its immunogenicity in a subject.

[0166] The term “single-chain” refers to a molecule comprising amino acid monomers linearly linked by peptide bonds. In a particular such embodiment, the C-terminus of the Fab light chain is connected to the N-terminus of the Fab heavy chain in the single-chain Fab molecule. As described in more detail herein, an scFv has a variable domain of light chain (VL) connected from its C-terminus to the N-terminal end of a variable domain of heavy chain (VH) by a polypeptide chain. Alternately the scFv comprises a polypeptide chain wherein the C- terminal end of the VH is connected to the N-terminal end of VL by a polypeptide chain.

[0167] The “Fab fragment” (also referred to as fragment antigen-binding) contains the constant domain (CL) of the light chain and the first constant domain (CHI) of the heavy chain along with the variable domains VL and VH on the light and heavy chains, respectively. The variable domains comprise the complementarity determining loops (CDR, also referred to as hypervariable region (HVR)) that are involved in antigen-binding. Fab' fragments differ from Fab fragments by the addition of a few residues at the carboxy terminus of the heavy chain CHI domain including one or more cysteines from the antibody hinge region.

[0168] “F(ab’)2” fragments contain two Fab’ fragments joined, near the hinge region, by disulfide bonds. F(ab’)2 fragments may be generated, for example, by recombinant methods or by pepsin digestion of an intact antibody. The F(ab’) fragments can be dissociated, for example, by treatment with B-mercaptoethanol.

[0169] “Fv” fragments comprise a non-covalently-linked dimer of one heavy chain variable domain and one light chain variable domain.

[0170] “Single-chain Fv” or “sFv” or “scFv” includes the VH and VL domains of an antibody, wherein these domains are present in a single polypeptide chain. In one embodiment, the Fv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the scFv to form the desired structure for antigen-binding. For a review of scFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994). HER2 antibody scFv fragments are described in WO93 / 16185; U.S. Pat. No. 5,571,894; and U.S. Pat. No. 5,587,458.

[0171] “ scFv-Fc” fragments comprise an scFv attached to an Fc domain. For example, an Fc domain may be attached to the C-terminal of the scFv. The Fc domain may follow the VH or34IPTS / 200090223.1Goodwin Ref: PRG-061WOVL, depending on the orientation of the variable domains in the scFv (z.e., VH -VL or VL -VH). Any suitable Fc domain known in the art or described herein may be used. In some cases, the Fc domain comprises an IgG4 Fc domain.

[0172] The term “single domain antibody” or “sdAb” refers to a molecule in which one variable domain of an antibody specifically binds to an antigen without the presence of the other variable domain. Single domain antibodies, and fragments thereof, are described in Arabi Ghahroudi et al.. (1998) FEBS Letters 414:521-526 and Muyldermans et al. (2001) Trends in Biochem. Sci. 26:230-245, each of which is incorporated by reference in its entirety. Single domain antibodies are also known as sdAbs or nanobodies. SdAbs are fairly stable and easy to express as fusion partner with the Fc chain of an antibody (Harmsen MM, De Haard HJ (2007) “Properties, production, and applications of camelid single-domain antibody fragments” AppL Microbiol Biotechnol. 77(1): 13-22).

[0173] The terms “full length antibody,” “intact antibody,” and “whole antibody” are used herein interchangeably to refer to an antibody having a structure substantially similar to a naturally occurring antibody structure and having heavy chains that comprise an Fc region. For example, when used to refer to an IgG molecule, a “full length antibody” is an antibody that comprises two heavy chains and two light chains.

[0174] The term “antibody fragment” refers to an antibody that comprises a portion of an intact antibody, such as the antigen-binding or variable region of an intact antibody. Antibody fragments include, for example, Fv fragments, Fab fragments, F(ab’)2 fragments, Fab’ fragments, scFv (sFv) fragments, and scFv-Fc fragments.

[0175] The term “Fc domain” or “Fc region” herein is used to define a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions.

[0176] The term “substantially purified” refers to a construct described herein, or variant thereof that may be substantially or essentially free of components that normally accompany or interact with the protein as found in its naturally occurring environment, i.e. a native cell, or host cell in the case of recombinantly produced antibody that in certain embodiments, is substantially free of cellular material includes preparations of protein having less than about 30%, less than about 25%, less than about 20%, less than about 15%, less than about 10%, less than about 5%, less than about 4%, less than about 3%, less than about 2%, or less than about 1% (by dry weight) of contaminating protein.

[0177] The term percent “identity,” in the context of two or more nucleic acid or polypeptide sequences, refer to two or more sequences or subsequences that have a specified percentage of35IPTS / 200090223.1Goodwin Ref: PRG-061WO nucleotides or amino acid residues that are the same, when compared and aligned for maximum correspondence, as measured using one of the sequence comparison algorithms described below e.g., using publicly available computer software such as BLAST, BLASTP, BLASTN, BLAST- 2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, CLUSTAL OMEGA, or MUSCLE software or other algorithms available to persons of skill) or by visual inspection. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (ncbi.nlm.nih.gov). Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. Depending on the application, the percent “identity” can exist over a region of the sequence being compared, e.g., over a functional domain, or, alternatively, exist over the full length of the two sequences to be compared.

[0178] For sequence comparison, typically one sequence acts as a reference sequence to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters.

[0179] Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, (1981) Adv. AppL Math. 2:482, by the homology alignment algorithm of Needleman & Wunsch, (1970) J. Mol. Biol. 48:443, by the search for similarity method of Pearson & Lipman, (1988) Proc. Nat’l. Acad. Sci. USA 85:2444, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection (see generally Ausubel et al., supra).

[0180] One example of an algorithm that is suitable for determining percent sequence identity and sequence similarity is the BLAST algorithm, which is described in Altschul et al. (1990) J. Mol. Biol. 215:403-410. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (www.ncbi.nlm.nih.gov / ).

[0181] Ranges recited herein are understood to be shorthand for all of the values within the range, inclusive of the recited endpoints. For example, a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, and 50.36IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0182] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise.

[0183] The term "atopic dermatitis disease severity outcome measure" refers to a determination of certain signs, symptoms, features or parameters that have been associated with atopic dermatitis and that can be quantitatively or qualitatively assessed. Exemplary atopic dermatitis disease severity outcome measures include "Eczema Area and Severity Index" (EASI), "Severity Scoring of Atopic Dermatitis" (SCORAD), "Validated Investigator Global Assessment-Atopic Dermatitis" (vIGA-AD), "Investigator Global Assessment of Signs" (IGSA), Rajka / Langeland Atopic Dermatitis Severity Score, “Body Surface Area” (BSA), and Patient- Reported Outcomes including Pruritus Visual Analog Scale (an aspect of disease severity assessed as part of SCORAD), Sleep Loss Visual Analog Scale (an aspect of disease severity assessed as part of SCORAD), Atopic Dermatitis Symptom Diary (ADSD), Atopic Dermatitis Impact Questionnaire (ADIQ), Dermatology Life Quality Index (DLQI) (Finlay and Khan, Clin Exper Dermatol 1994; 19:210), 5-D Itch Scale (Elman et al., Br J Dermatol 2010;162(3):587- 593), Itch Numeric Rating Scale (LNRS) (see Naegeli et al., International Journal of Dermatology. 2015;54(6):715-722; and Newton L, el al., J. Patient Rep. Outcomes.2019;3(l):42), and the Patient-Oriented Eczema Measure (POEM) (www.nottingham.ac.uk / research / groups / cebd / resources / poem.aspx).Anti-TSLP and Anti-IL-4Ra AntibodiesAntibody Structure

[0184] The present application provides antibodies, or antigen binding fragments thereof, and compositions comprising an antibody which binds TSLP, or an antigen binding fragment thereof, and an antibody which binds IL-4 Receptor alpha (IL-4Ra), or an antigen binding fragment thereof. In certain embodiments, the anti-TSLP and / or anti-IL-4Ra antibody, or antigen binding fragment thereof, is an antibody comprising a modified Fc region.

[0185] The recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon and mu constant region genes, as well as the myriad immunoglobulin variable region genes. Light chains are classified as either kappa or lambda. There are four subtypes of human lambda light chain constant region ( i, 2, fa, fa), which are encoded by the genes IGLC1, IGCL2, IGLC3, and IGLC7. The “class” of an antibody or immunoglobulin refers to the type of constant domain or constant region possessed by its heavy chain. There are five major37IPTS / 200090223.1Goodwin Ref: PRG-061WO classes of antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgGl, IgG2, IgG3, IgG4, IgAl, and IgA2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called a, 5, a, y, and p, respectively.

[0186] An exemplary immunoglobulin (antibody) structural unit is composed of two pairs of polypeptide chains, each pair having one “light” (about 25 kD) and one “heavy” chain (about 50- 70 kD). The N-terminal domain of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The terms variable light chain (VL) and variable heavy chain (VH) refer to these light and heavy chain domains, respectively. The IgGl heavy chain comprises the VH, CHI, CH2, and CH3 domains, respectively from the N- to C-terminus. The light chain comprises the VL and CL domains from N- to C-terminus. The IgGl heavy chain comprises a hinge between the CHI and CH2 domains. In certain embodiments, the immunoglobulin constructs comprise at least one immunoglobulin domain from IgG, IgM, IgA, IgD, or IgE connected to a therapeutic polypeptide. In some embodiments, the immunoglobulin domain found in an antibody provided herein, is from or is derived from an immunoglobulin-based construct such as a diabody or a nanobody. In certain embodiments, the immunoglobulin constructs described herein comprise at least one immunoglobulin domain from a heavy chain antibody such as a camelid antibody. In certain embodiments, the immunoglobulin constructs provided herein comprise at least one immunoglobulin domain from a mammalian antibody such as a bovine antibody, a human antibody, a camelid antibody, a mouse antibody or any chimeric antibody.

[0187] In some embodiments, the antibodies provided herein comprise a heavy chain. In one embodiment, the heavy chain is an IgA. In one embodiment, the heavy chain is an IgD. In one embodiment, the heavy chain is an IgE. In one embodiment, the heavy chain is an IgG. In one embodiment, the heavy chain is an IgM. In one embodiment, the heavy chain is an IgGl. In one embodiment, the heavy chain is an IgG2. In one embodiment, the heavy chain is an IgG3. In one embodiment, the heavy chain is an IgG4. In one embodiment, the heavy chain is an IgAl. In one embodiment, the heavy chain is an IgA2.

[0188] In some embodiments, an antibody is an IgGl antibody. In some embodiments, an antibody is an IgG3 antibody. In some embodiments, an antibody is an IgG2 antibody. In some embodiments, an antibody is an IgG4 antibody.

[0189] Generally, native four-chain antibodies comprise six hypervariable regions (HVRs); three in the VH (Hl, H2, and H3), and three in the VL (LI, L2, and L3). HVRs generally comprise amino acid residues from the hypervariable loops and / or from the complementarity38IPTS / 200090223.1Goodwin Ref: PRG-061WO determining regions (CDRs), the latter being of highest sequence variability and / or involved in antigen recognition. With the exception of CDR1 in VH, CDRs generally comprise the amino acid residues that form the hypervariable loops. HVRs are also referred to as “complementarity determining regions” (CDRs), and these terms are used herein interchangeably in reference to portions of the variable region that form the antigen-binding regions. This particular region has been described by Kabat et al., U.S. Dept, of Health and Human Services, Sequences of Proteins of Immunological Interest (1983) and by Chothia c / a / . (1987) J Mol Biol 196:901-917, where the definitions include overlapping or subsets of amino acid residues when compared against each other. Nevertheless, application of either definition to refer to a CDR of an antibody or variants thereof is intended to be within the scope of the term as defined and used herein. The exact residue numbers which encompass a particular CDR will vary depending on the sequence and size of the CDR. Those skilled in the art can routinely determine which residues comprise a particular CDR given the variable region amino acid sequence of the antibody.

[0190] The amino acid sequence boundaries of a CDR can be determined by one of skill in the art using any of a number of known numbering schemes, including those described by Kabat et al., supra (“Kabat” numbering scheme); Al-Lazikani et al. (1997) J. Mol. Biol., 273:927-948 (“Chothia” numbering scheme); MacCallum et al. (1996) J. Mol. Biol. 262:732-745 (“Contact” numbering scheme); Lefranc et al. (2003) Dev. Comp. Immunol. 27:55-77 (“IMGT” numbering scheme); and Honegge and Pliickthun (2001) J. Mol. Biol. 309:657-70 (“AHo” numbering scheme); each of which is incorporated by reference in its entirety.

[0191] TABLE 2 provides the positions of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR- H2, and CDR-H3 as identified by the Kabat and Chothia schemes. For CDR-H1, residue numbering is provided using both the Kabat and Chothia numbering schemes.

[0192] CDRs may be assigned, for example, using antibody numbering software, such as Abnum, available at www.bioinf.org.uk / abs / abnum / , and described in Abhinandan and Martin, Immunology, 2008, 45:3832-3839, incorporated by reference in its entirety.TABLE 2. Residues in CDRs according to Kabat and Chothia numbering schemes* The C-terminus of CDR-H1, when numbered using the Kabat numbering convention, varies between H32 and H34, depending on the length of the CDR.39IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0193] The “EU numbering scheme” is generally used when referring to a residue in an antibody heavy chain constant region (e.g., as reported in Kabat et cd.. supra). Unless stated otherwise, the EU numbering scheme is used to refer to residues in antibody heavy chain constant regions described herein.

[0194] One example of an antigen-binding domain is an antigen-binding domain formed by a VH-VL dimer of an antibody. Another example of an antigen-binding domain is an antigenbinding domain formed by diversification of certain loops from the tenth fibronectin type III domain of an Adnectin. An antigen-binding domain can include CDRs 1, 2, and 3 from a heavy chain in that order; and CDRs 1, 2, and 3 from a light chain in that order.

[0195] Epitopes frequently consist of surface-accessible amino acid residues and / or sugar side chains and may have specific three-dimensional structural characteristics, as well as specific charge characteristics. Conformational and non-conformational epitopes are distinguished in that the binding to the former but not the latter may be lost in the presence of denaturing solvents. An epitope may comprise amino acid residues that are directly involved in the binding, and other amino acid residues, which are not directly involved in the binding. The epitope to which an antibody binds can be determined using known techniques for epitope determination such as, for example, testing for antibody binding to TSLP or IL-4Ra variants with different pointmutations, or to chimeric TSLP or IL4Ra variants.

[0196] To screen for antibodies which bind to an epitope on a target antigen bound by an antibody of interest (e.g., TSLP and / or IL-4Ra), a routine cross-blocking assay such as that described in Antibodies, A Laboratory Manual, Cold Spring Harbor Laboratory, Ed Harlow and David Lane (1988), can be performed. Alternatively, or additionally, epitope mapping can be performed by methods known in the art.

[0197] Anti-TSLP and anti- IL-4Ra antibodies can include those described herein such as the clones set forth in the drawings and / or tables. In some embodiments, the antibody comprises an alternative scaffold. In some embodiments, the antibody consists of an alternative scaffold. In some embodiments, the antibody consists essentially of an alternative scaffold. In some embodiments, the antibody comprises an antibody fragment. In some embodiments, the antibody consists of an antibody fragment. In some embodiments, the antibody consists essentially of an antibody fragment.

[0198] In some embodiments, the antibodies are monoclonal antibodies.

[0199] In some embodiments, the antibodies are polyclonal antibodies.40IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0200] In some embodiments, the antibodies are produced by hybridomas. In other embodiments, the antibodies are produced by recombinant cells engineered to express the desired variable and constant domains.

[0201] In some embodiments, the antibodies may be single chain antibodies or other antibody derivatives retaining the antigen specificity and the lower hinge region or a variant thereof.

[0202] In some embodiments, the antibodies may be polyfunctional antibodies, recombinant antibodies, fully human antibodies, humanized antibodies, or fragments or variants thereof. In particular embodiments, the antibody fragment or a derivative thereof is selected from a Fab fragment, a Fab '2 fragment, a CDR and scFv.Anti-TSLP Antibodies

[0203] The present application provides antibodies or antigen binding fragments thereof and compositions comprising an antibody, or an antigen binding fragment thereof, which binds TSLP. In some embodiments, an anti-TSLP antibody, or antigen binding fragment thereof, described herein is selected from tezepelumab, GR2002 (described in U.S. Patent Application Publication No. US 2024 / 0132581, which is incorporated herein by reference), TQC2731 (also known as BSI-045B and bosakitug, described in U.S. Patent Application Publication No. US 2022 / 0289833, which is incorporated herein by reference), solrikitug, hu23bl2 (described in U.S. Patent No. 8,232,372, which is incorporated herein by reference), 43B1-H2L2 (described in U.S. Patent Application Publication No. US 2022 / 0363781, which is incorporated herein by reference), and 43B1-H6L1 (also described in U.S. Patent Application Publication No. US 2022 / 0363781). In some embodiments, tezepelumab comprises a VH chain sequence having the amino acid sequence of SEQ ID NO: 34 and a VL chain sequence having the amino acid sequence of SEQ ID NO: 411. In some embodiments, TQC2731 comprises a VH chain sequence having the amino acid sequence of SEQ ID NO: 455 and a VL chain sequence having the amino acid sequence of SEQ ID NO: 456. In some embodiments, solrikitug comprises a VH chain sequence having the amino acid sequence of SEQ ID NO: 463 and a VL chain sequence having the amino acid sequence of SEQ ID NO: 464. In some embodiments, hu23bl2 comprises a VH chain sequence having the amino acid sequence of SEQ ID NO: 412 and a VL chain sequence having the amino acid sequence of SEQ ID NO: 413. In some embodiments, 43B1-H2L2 comprises a VH chain sequence having the amino acid sequence of SEQ ID NO: 414 and a VL chain sequence having the amino acid sequence of SEQ ID NO: 415. In some embodiments, 43B1-H6L1 comprises a VH chain sequence having the amino acid sequence of SEQ ID NO:41IPTS / 200090223.1Goodwin Ref: PRG-061WO416 and a VL chain sequence having the amino acid sequence of SEQ ID NO: 417 or a variant thereof comprising an Fc region with one or more amino acid substitutions as described herein. In some embodiments, tezepelumab comprises a heavy chain having the amino acid sequence of SEQ ID NO: 451 and a light chain sequence having the amino acid sequence of SEQ ID NO: 452 or a variant thereof comprising an Fc region with one or more amino acid substitutions as described herein. In some embodiments, TQC2731 comprises a heavy chain having the amino acid sequence of SEQ ID NO: 453 and a light chain sequence having the amino acid sequence of SEQ ID NO: 454 or a variant thereof comprising an Fc region with one or more amino acid substitutions as described herein. In some embodiments, solrikitug comprises a heavy chain having the amino acid sequence of SEQ ID NO: 465 and a light chain sequence having the amino acid sequence of SEQ ID NO: 466 or a variant thereof comprising an Fc region with one or more amino acid substitutions as described herein. In some embodiments, hu23bl2 comprises a heavy chain having the amino acid sequence of SEQ ID NO: 457 and a light chain sequence having the amino acid sequence of SEQ ID NO: 458 or a variant thereof comprising an Fc region with one or more amino acid substitutions as described herein. In some embodiments, 43B1-H2L2 comprises a heavy chain having the amino acid sequence of SEQ ID NO: 459 and a light chain sequence having the amino acid sequence of SEQ ID NO: 460 or a variant thereof comprising an Fc region with one or more amino acid substitutions as described herein. In some embodiments, 43B1-H6L1 comprises a heavy chain having the amino acid sequence of SEQ ID NO: 461 and a light chain sequence having the amino acid sequence of SEQ ID NO: 462 or a variant thereof comprising an Fc region with one or more amino acid substitutions as described herein. Additional anti-TSLP antibodies are described in PCT Application No. PCT / US2025 / 034623, which is incorporated herein by reference in its entirety. In some embodiments, an anti-TSLP antibody, or antigen binding fragment thereof, described herein is selected from an anti-TSLP antibody, or antigen binding fragment thereof, described therein. Further TSLP antibodies are described in U.S. Patent No. 8,232,372 and U.S. Patent Application Publication No. US 2022 / 0363781, each of which is incorporated herein by reference in its entirety.

[0204] Sequences of exemplary anti-TSLP antibodies, or antigen binding fragments thereof, are provided in TABLE 3, TABLE 4, TABLE 12, and TABLE 13.42IPTS / 200090223.1Goodwin Ref: PRG-061WOSequences of Exemplary Anti-TSLP Antibodies ABLE 3. Sequences of anti-TSLP antibody constructs - CDRs43IPTS / 200090223.1Goodwin Ref: PRG-061WO44IPTS / 200090223.1Goodwin Ref: PRG-061WO45IPTS / 200090223.1Goodwin Ref: PRG-061WO46IPTS / 200090223.1Goodwin Ref: PRG-061WO47IPTS / 200090223.1Goodwin Ref: PRG-061WO48IPTS / 200090223.1Goodwin Ref: PRG-061WO49IPTS / 200090223.1Goodwin Ref: PRG-061WO50IPTS / 200090223.1Goodwin Ref: PRG-061WO51IPTS / 200090223.1Goodwin Ref: PRG-061WO52IPTS / 200090223.1Goodwin Ref: PRG-061WO53IPTS / 200090223.1Goodwin Ref: PRG-061WOTABLE 4. Sequences of anti-TSLP antibody constructs - VH and VL54IPTS / 200090223.1Goodwin Ref: PRG-061WO55IPTS / 200090223.1Goodwin Ref: PRG-061WO56IPTS / 200090223.1Goodwin Ref: PRG-061WO57IPTS / 200090223.1Goodwin Ref: PRG-061WO58IPTS / 200090223.1Goodwin Ref: PRG-061WO59IPTS / 200090223.1Goodwin Ref: PRG-061WO60IPTS / 200090223.1Goodwin Ref: PRG-061WOAnti-TSLP VH Domains

[0205] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 32-36 and 420.

[0206] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VH sequence provided in any one of SEQ ID NOs: 32-36 and 420. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence provided in any one of SEQ ID NOs: 32-36 and 420, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.Anti-TSLP VL Domains

[0207] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 37-45, 361-397, and 471-484.61IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0208] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VL sequence provided in any one of SEQ ID NOs: 37-45, 361-397, and 471-484. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VL sequence provided in any one of SEQ ID NOs: 37-45, 361-397, and 471-484, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.Anti-TSLP VH-VL Combinations

[0209] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 32-36 and 420; and a VL sequence selected from any one of SEQ ID NOs: 37-45, 361-397, and 471-484.

[0210] In certain aspects, any one of SEQ ID NOs: 32-36 and 420 can be combined with any one of SEQ ID NOs: 37-45, 361-397, and 471-484.

[0211] In certain aspects, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence of a construct provided in TABLE 4 (e.g., a VH sequence and a VL sequence from the same row of TABLE 4). In certain aspects, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence of a construct provided in TABLE 13 (e.g., a VH sequence and a VL sequence from the same row of TABLE 13).

[0212] In certain aspects, an antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence of a construct provided in PCT Application No. PCT / US2025 / 034623, incorporated by reference herein in its entirety. In certain aspects, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence from Table 4 or Table 11 in PCT Application No. PCT / US2025 / 034623 (e.g., a VH sequence and a VL sequence from the same row of Table 4 or Table 11).

[0213] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%,62IPTS / 200090223.1Goodwin Ref: PRG-061WO96%, 97%, 98%, or 99% identity to a VH sequence provided in any one of SEQ ID NOs: 32-36 and 420; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VL sequence provided in any one of SEQ ID NOs: 37-45, 361- 397, and 471-484. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence provided in any one of SEQ ID NOs: 32-36 and 420, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions, and a VL sequence provided in any one of SEQ ID NOs: 37-45, 361-397, and 471- 484, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0214] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 32 and a VL sequence set forth in SEQ ID NO: 37.

[0215] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 33 and a VL sequence set forth in SEQ ID NO: 38.

[0216] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 420 and a VL sequence set forth in SEQ ID NO: 39.

[0217] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 33 and a VL sequence set forth in SEQ ID NO: 40.

[0218] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 34 and a VL sequence set forth in SEQ ID NO: 41.

[0219] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 35 and a VL sequence set forth in SEQ ID NO: 42.

[0220] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 34 and a VL sequence set forth in SEQ ID NO: 43.

[0221] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 32 and a VL sequence set forth in SEQ ID NO: 44.

[0222] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 36 and a VL sequence set forth in SEQ ID NO: 45.63IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0223] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 34 and a VL sequence set forth in SEQ ID NO: 374.

[0224] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 34 and a VL sequence set forth in SEQ ID NO: 380.

[0225] In certain embodiments of any of the antibodies, or antigen binding fragments thereof, described above, the antibody further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 47-270. In certain embodiments, the heavy chain comprises a human IgG sequence selected from SEQ ID NO: 61 and SEQ ID NO: 173.

[0226] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 34; a VL sequence set forth in SEQ ID NO: 41; and the antibody further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 47-270. In certain embodiments, the heavy chain comprises a human IgG sequence selected from SEQ ID NO: 61 and SEQ ID NO: 173. In certain embodiments of any of the antibodies described above, the antibody, or antigen binding fragment thereof, further comprises a constant light chain sequence comprising a sequence set forth in SEQ ID NO: 421.

[0227] Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 159- 270), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 47-158). Accordingly, any of the antibodies or antigen binding fragments thereof described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 159-270), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 47-158), or a mixture thereof (e.g., a mixture of the same heavy chain constant region sequence with and without a C- terminal lysine, such as a mixture of SEQ ID NO: 173 and SEQ ID NO: 61).

[0228] In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 34, a VL sequence set forth in SEQ ID NO: 41, a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions, and a human lambda light chain constant region (e.g., a lambda light chain constant region of subtype 1, 2, 3, or 7, such as a lambda light chain constant region set forth in any one of SEQ ID NOs: 421-424). In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 34, a VL sequence set forth in SEQ ID NO: 41, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ64IPTS / 200090223.1Goodwin Ref: PRG-061WOID NO: 421. In certain embodiments, the antibody comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VH sequence provided in SEQ ID NO: 34; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VL sequence provided in SEQ ID NO: 41, a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions, and a human lambda light chain constant region (e.g., a lambda light chain constant region of subtype 1, 2, 3, or 7, such as a lambda light chain constant region set forth in any one of SEQ ID NOs: 421-424). In certain embodiments, the antibody comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VH sequence provided in SEQ ID NO: 34; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VL sequence provided in SEQ ID NO: 41, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 421 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 421.

[0229] In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 34, a VL sequence set forth in SEQ ID NO: 41, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 421. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 34, a VL sequence set forth in SEQ ID NO: 41, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 421. In some embodiments, the antibody comprises a heavy chain sequence set forth in SEQ ID NO: 425 or 427 and a light chain sequence set forth in SEQ ID NO: 426. In some embodiments, the antibody comprises a heavy chain sequence set forth in SEQ ID NO: 425 and a light chain sequence set forth in SEQ ID NO: 426. The heavy chain sequence of SEQ ID NO: 425 contains a C-terminal lysine, which may be cleaved off during manufacture or after administration, resulting in an antibody containing the heavy chain sequence of SEQ ID NO: 427.

[0230] In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 34, a VL sequence set forth in SEQ ID NO: 43, a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions, and a human lambda light chain constant region (e.g., a lambda light chain constant region of subtype 1, 2, 3, or 7, such as a lambda light65IPTS / 200090223.1Goodwin Ref: PRG-061WO chain constant region set forth in any one of SEQ ID NOs: 421-424). In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 34, a VL sequence set forth in SEQ ID NO: 43, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 421. In certain embodiments, the antibody comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VH sequence provided in SEQ ID NO: 34; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VL sequence provided in SEQ ID NO: 43, a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions, and a human lambda light chain constant region (e.g., a lambda light chain constant region of subtype 1, 2, 3, or 7, such as a lambda light chain constant region set forth in any one of SEQ ID NOs: 421-424). In certain embodiments, the antibody comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VH sequence provided in SEQ ID NO: 34; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VL sequence provided in SEQ ID NO: 43, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 421 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 421.

[0231] In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 34, a VL sequence set forth in SEQ ID NO: 43, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 421. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 34, a VL sequence set forth in SEQ ID NO: 43, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 421. In some embodiments, the antibody comprises a heavy chain sequence set forth in SEQ ID NO: 428 and a light chain sequence set forth in SEQ ID NO: 429. The heavy chain sequence of SEQ ID NO: 428 contains a C-terminal lysine, which may be cleaved off during manufacture or after administration.66IPTS / 200090223.1Goodwin Ref: PRG-061WOAnti-TSLP CDRs

[0232] In some embodiments, disclosed herein is an antibody, or antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the CDRs of TABLE 3. In some embodiments, disclosed herein is an antibody, or antigen binding fragment thereof, comprising 6 of the Kabat CDRs of TABLE 3, 6 of the Chothia CDRs of TABLE 3, or 6 of the IMGT CDRs of TABLE 3. In some embodiments, the antibody, or antigen binding fragment thereof, comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of TABLE 3 (e.g., 6 CDRs from the same antibody).

[0233] In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the CDRs of TABLE 12. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 6 of the Kabat CDRs of TABLE 12, 6 of the Chothia CDRs of TABLE 12, or 6 of the IMGT CDRs of TABLE 12. In some embodiments, the antibody, or an antigen binding fragment thereof, comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of TABLE 12 e.g., 6 CDRs from the same antibody).

[0234] In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the CDRs of an antibody provided in PCT Application No. PCT / US2025 / 034623, incorporated by reference herein in its entirety, such as 1, 2, 3, 4, 5, or 6 of the CDRs in Table 3 or Table 10 in PCT Application No.PCT / US2025 / 034623. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the Kabat CDRs of an antibody, or an antigen binding fragment thereof, provided in PCT Application No. PCT / US2025 / 034623. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the Chothia CDRs of an antibody, or an antigen binding fragment thereof, provided in PCT Application No. PCT / US2025 / 034623. In some embodiments, disclosed herein is an antibody, or an antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of an antibody provided in PCT Application No. PCT / US2025 / 034623. In some embodiments, the antibody, or an antigen binding fragment thereof, comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of Table 3 or Table 10 in in PCT Application No. PCT / US2025 / 034623 (e.g., 6 CDRs from the same antibody).

[0235] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises one to three CDRs of a VH domain selected from any one of SEQ ID NOs: 32-67IPTS / 200090223.1Goodwin Ref: PRG-061WO36 and 420. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises two to three CDRs of a VH domain selected from any one of SEQ ID NOs: 32- 36 and 420. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises three CDRs of a VH domain selected from any one of SEQ ID NOs: 32-36 and 420. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs.

[0236] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-H1, CDR-H2, or CDR- H3 selected from SEQ ID NOs: 1-18. In some embodiments, the CDR-H1 is a CDR-H1 of a VH domain selected from any one of SEQ ID NOs: 32-36 and 420, with up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, the CDR-H2 is a CDR-H2 of a VH domain selected from any one of SEQ ID NOs: 32-36 and 420, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the CDR-H3 is a CDR-H3 of a VH domain selected from any one of SEQ ID NOs: 32-36 and 420, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0237] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises one to three CDRs of a VL domain selected from any one of SEQ ID NOs: 37- 45, 361-397, and 471-484. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises two to three CDRs of a VL domain selected from any one of SEQ ID NOs: 37-45, 361-397, and 471-484. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises three CDRs of a VL domain selected from any one of SEQ ID NOs: 37-45, 361-397, and 471-484. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs.

[0238] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-L1, CDR-L2, or CDR-68IPTS / 200090223.1Goodwin Ref: PRG-061WOL3 selected from SEQ ID NOs: 19-31, 304-360, 467-470, and 503 and the amino acid sequences DVS, DDS, EDS, DDT, DDK, DDL, and DDN. In some embodiments, the CDR-L1 is a CDR- L1 of a VL domain selected from any one of SEQ ID NOs: 37-45, 361-397, and 471-484, with up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, the CDR-L2 is a CDR-L2 of a VL domain selected from any one of SEQ ID NOs: 37-45, 361-397, and 471-484, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the CDR-L3 is a CDR-L3 of a VL domain selected from any one of SEQ ID NOs: 37-45, 361-397, and 471-484, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0239] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises one to three CDRs of a VH domain selected from any one of SEQ ID NOs: 32- 36 and 420 and one to three CDRs of a VL domain selected from any one of SEQ ID NOs: 37- 45, 361-397, and 471-484. In some embodiments, an antibody provided herein comprises two to three CDRs of a VH domain selected from any one of SEQ ID NOs: 32-36 and 420 and two to three CDRs of a VL domain selected from any one of SEQ ID NOs: 37-45, 361-397, and 471- 484. In some embodiments, an antibody provided herein comprises three CDRs of a VH domain selected from any one of SEQ ID NOs: 32-36 and 420 and three CDRs of a VL domain selected from any one of SEQ ID NOs: 37-45, 361-397, and 471-484. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs.

[0240] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from any one of SEQ ID NOs: 13-18. In some aspects, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H3 selected from any one of SEQ ID NOs: 13-18. In some embodiments, the CDR-H3 is a CDR-H3 selected from any one of SEQ ID NO: 13-18, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a69IPTS / 200090223.1Goodwin Ref: PRG-061WO sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0241] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 selected from any one of SEQ ID NOs: 1-9. In some aspects, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H1 selected from any one of SEQ ID NOs: 1-9. In some embodiments, the CDR-H1 is a CDR-H1 selected from any one of SEQ ID NO: 1-9, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0242] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H2 selected from any one of SEQ ID NOs: 10-12. In some aspects, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H2 selected from any one of SEQ ID NOs: 10-12. In some embodiments, the CDR-H2 is a CDR-H2 selected from any one of SEQ ID NOs: 10-12, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0243] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-L3 selected from any one of SEQ ID NOs: 27-31, 344-360, and 467- 470. In some aspects, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L3 selected from any one of SEQ ID NOs: 27-31, 344-360, and 467-470. In some embodiments, the CDR-L3 is a CDR-L3 selected from any one of SEQ ID NOs: 27-31, 344-360, and 467-470, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid70IPTS / 200090223.1Goodwin Ref: PRG-061WO substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0244] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-L2 selected from any one of SEQ ID NOs: 25-26, 336-343, and the amino acid sequences DDS, DVS, EDS, DDT, DDK, DDL, and DDN. In some aspects, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L2 selected from any one of SEQ ID NOs: 25-26, 336-343, and the amino acid sequences DDS, DVS, EDS, DDT, DDK, DDL, and DDN. In some embodiments, the CDR-L2 is a CDR-L2 selected from any one of SEQ ID NOs: 25-26, 336-343, and the amino acid sequences DDS, DVS, EDS, DDT, DDK, DDL, and DDN, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0245] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-L1 selected from any one of SEQ ID NOs: 19-24, 304-335, and 503. In some aspects, the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L1 selected from any one of SEQ ID NOs: 19-24, 304-335, and 503. In some embodiments, the CDR-L1 is a CDR-L1 selected from any one of SEQ ID NOs: 19-24, 304-335, and 503, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a71IPTS / 200090223.1Goodwin Ref: PRG-061WO sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0246] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from any one of SEQ ID NOs: 13-18, a CDR-H2 selected from any one of SEQ ID NOs: 10-12, a CDR-H1 selected from any one of SEQ ID NOs: 1-9, a CDR-L3 selected from any one of SEQ ID NOs: 27-31, 344-360, and 467-470, a CDR-L2 selected from any one of SEQ ID NOs: 25-26, 336-343, and the amino acid sequences DDS, DVS, EDS, DDT, DDK, DDL, and DDN, and a CDR-L1 selected from any one of SEQ ID NOs: 19-24, 304-335, and 503. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H3 selected from any one of SEQ ID NOs: 13-18, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H2 selected from any one of SEQ ID NOs: 10-12, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H1 selected from any one of SEQ ID NOs: 1-9, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR- L3 selected from any one of SEQ ID NOs: 27-31, 344-360, and 467-470, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR- L2 selected from any one of SEQ ID NOs: 25-26, 336-343, and the amino acid sequences DDS, DVS, EDS, DDT, DDK, DDL, and DDN, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L1 selected from any one of SEQ ID NOs: 19-24, 304-335, and 503. In some embodiments, the CDR-H3 is a CDR-H3 selected from any one of SEQ ID NOs: 13-18, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 selected from any one of SEQ ID NOs: 10-12, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 selected from any one of SEQ ID NOs: 1-9, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 selected from any one of SEQ ID NOs: 27-31, 344-360, and 467-470, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 selected from any one of SEQ ID NOs: 25-26, 336-343, and the amino acid sequences DDS, DVS, EDS, DDT, DDK, DDL, and DDN, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 selected from any one of SEQ ID NOs: 19-24, 304-335, and 503, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0247] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12;72IPTS / 200090223.1Goodwin Ref: PRG-061WO a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 27. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CORED selected from any one of SEQ ID NOs: 13 and 16, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H2 selected from any one of SEQ ID NOs: 10, 11, and 12, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H1 selected from any one of SEQ ID NOs: 3, 6, and 9, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L3 of SEQ ID NO: 27, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L2 set forth in SEQ ID NO: 26 or the amino acid sequence DDS, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L1 selected from any one of SEQ ID NOs: 21 and 24. In some embodiments, the CDR-H3 is a CDR-H3 selected from any one of SEQ ID NOs: 13 and 16, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 selected from any one of SEQ ID NOs: 10, 11, and 12, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 selected from any one of SEQ ID NOs: 3, 6, and 9, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 set forth in SEQ ID NO: 27 with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 set forth in SEQ ID NO: 26 or the amino acid sequence DDS, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 selected from any one of SEQ ID NOs: 21 and 24, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0248] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 27.

[0249] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L173IPTS / 200090223.1Goodwin Ref: PRG-061WO comprising the sequence set forth in any one of SEQ ID NOs: 19 and 22; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 30. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CORED selected from any one of SEQ ID NOs: 13 and 16, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H2 selected from any one of SEQ ID NOs: 10, 11, and 12, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H1 selected from any one of SEQ ID NOs: 3, 6, and 9, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L3 of SEQ ID NO: 30, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L2 set forth in SEQ ID NO: 25 or the amino acid sequence DVS, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L1 selected from any one of SEQ ID NOs: 19 and 22. In some embodiments, the CDR-H3 is a CDR-H3 selected from any one of SEQ ID NOs: 13 and 16, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 selected from any one of SEQ ID NOs: 10, 11, and 12, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 selected from any one of SEQ ID NOs: 3, 6, and 9, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of SEQ ID NO: 30 with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 set forth in SEQ ID NO: 25 or the amino acid sequence DVS, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 selected from any one of SEQ ID NOs: 19 and 22, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0250] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 19 and 22; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 30.

[0251] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 310 and 324; a CDR-L274IPTS / 200090223.1Goodwin Ref: PRG-061WO comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 351. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H3 selected from any one of SEQ ID NOs: 13 and 16, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR- H2 selected from any one of SEQ ID NOs: 10, 11, and 12, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H1 selected from any one of SEQ ID NOs: 3, 6, and 9, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L3 of SEQ ID NO: 351, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L2 set forth in SEQ ID NO: 26 or the amino acid sequence DDS, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR- L1 selected from any one of SEQ ID NOs: 310 and 324. In some embodiments, the CDR-H3 is a CDR-H3 selected from any one of SEQ ID NOs: 13 and 16, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 selected from any one of SEQ ID NOs: 10, 11, and 12, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 selected from any one of SEQ ID NOs: 3, 6, and 9, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of SEQ ID NO: 351 with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 set forth in SEQ ID NO: 26 or the amino acid sequence DDS, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 selected from any one of SEQ ID NOs: 310 and 324, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0252] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 310 and 324; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in any of SEQ ID NO: 351.

[0253] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 315 and 331; a CDR-L275IPTS / 200090223.1Goodwin Ref: PRG-061WO comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 355. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H3 selected from any one of SEQ ID NOs: 13 and 16, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR- H2 selected from any one of SEQ ID NOs: 10, 11, and 12, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H1 selected from any one of SEQ ID NOs: 3, 6, and 9, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L3 of SEQ ID NO: 355, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L2 set forth in SEQ ID NO: 26 or the amino acid sequence DDS, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR- L1 selected from any one of SEQ ID NOs: 315 and 331. In some embodiments, the CDR-H3 is a CDR-H3 selected from any one of SEQ ID NOs: 13 and 16, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 selected from any one of SEQ ID NOs: 10, 11, and 12, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 selected from any one of SEQ ID NOs: 3, 6, and 9, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of SEQ ID NO: 355 with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 set forth in SEQ ID NO: 26 or the amino acid sequence DDS, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 selected from any one of SEQ ID NOs: 315 and 331, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0254] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 315 and 331; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 355.

[0255] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1, 4, and 7, a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 11, and 12, a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 13 and 16, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ76IPTS / 200090223.1Goodwin Ref: PRG-061WOID NOs: 19 and 22, a CDR-L2 comprising an amino acid sequence set forth in of SEQ ID NO: 25 or the amino acid sequence DVS, and a CDR-L3 comprising an amino acid sequence set forth in SEQ ID NO: 27.

[0256] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 2, 5, and 8, a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 11, and 12, a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 13 and 16, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 19 and 22, a CDR-L2 comprising an amino acid sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS, and a CDR-L3 comprising an amino acid sequence set forth in SEQ ID NO: 28.

[0257] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 2, 5, and 8, a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 11, and 12, a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 14 and 17, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 20 and 23, a CDR-L2 comprising an amino acid sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS, and a CDR-L3 comprising an amino acid sequence set forth in SEQ ID NO: 28.

[0258] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 2, 5, and 8, a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 11, and 12, a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 13 and 16, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 21 and 24, a CDR-L2 comprising an amino acid sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS, and a CDR-L3 comprising an amino acid sequence set forth in SEQ ID NO: 28.

[0259] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 3, 6, and 9, a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 11, and 12, a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 15 and 18, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 21 and 24, a CDR-L2 comprising an amino acid sequence set forth in SEQ ID NO: 2577IPTS / 200090223.1Goodwin Ref: PRG-061WO or the amino acid sequence DVS, and a CDR-L3 comprising an amino acid sequence set forth in SEQ ID NO: 29.

[0260] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1, 4, and 7, a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 11, and 12, a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 13 and 16, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 19 and 22, a CDR-L2 comprising an amino acid sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS, and a CDR-L3 comprising an amino acid sequence set forth in SEQ ID NO: 31.

[0261] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 2, 5, and 8, a CDR-H2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 10, 11, and 12, a CDR-H3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 15 and 18, a CDR-L1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 21 and 24, a CDR-L2 comprising an amino acid sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS, and a CDR-L3 comprising an amino acid sequence set forth in SEQ ID NO: 28.

[0262] In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H3 of TABLE 3; the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR- H2 of TABLE 3, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H1 of TABLE 3, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L3 of TABLE 3, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L2 of TABLE 3, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L1 of TABLE 3. In some embodiments, the CDR-H3 is a CDR-H3 of TABLE 3, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 of TABLE 3, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 of TABLE 3, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of TABLE 3 with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 of TABLE 3, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 of TABLE 3, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.78IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0263] In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H3 of TABLE 12; the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR- H2 of TABLE 12, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H1 of TABLE 12, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L3 of TABLE 12, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L2 of TABLE 12, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L1 of TABLE 12. In some embodiments, the CDR-H3 is a CDR-H3 of TABLE 12, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 of TABLE 12, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 of TABLE 12, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of TABLE 12 with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 of TABLE 12, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 of TABLE 12, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0264] In certain embodiments of any of the antibodies, or antigen binding fragments thereof, described above, the antibody further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any of SEQ ID NOs: 47-270. In certain embodiments of any of the antibodies, or antigen binding fragments thereof, described above, the antibody further comprises a constant light chain sequence comprising a sequence set forth in SEQ ID NO: 421. In certain embodiments of any of the antibodies, or antigen binding fragments thereof, described above, the antibody comprises a heavy chain comprising a human IgG sequence selected from SEQ ID NO: 61 or SEQ ID NO: 173 and a constant light chain sequence comprising a sequence set forth in SEQ ID NO: 421. In certain embodiments of any of the antibodies, or antigen binding fragments thereof, described above, the antibody comprises a heavy chain comprising a human IgG sequence set forth in SEQ ID NO: 173 and a constant light chain sequence comprising a sequence set forth in SEQ ID NO: 421.

[0265] In some embodiments, the antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L379IPTS / 200090223.1Goodwin Ref: PRG-061WO comprising the sequence set forth in SEQ ID NO: 27. In certain embodiments, the antibody, or antigen binding fragment thereof, further comprises a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions. In certain embodiments, the antibody comprises a heavy chain comprising a heavy chain constant region selected from SEQ ID NO: 61 or SEQ ID NO: 173. In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a heavy chain comprising a heavy chain constant region set forth in SEQ ID NO: 173. In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a human lambda light chain constant region (e.g., a lambda light chain constant region of subtype 1, 2, 3, or 7, such as a lambda light chain constant region set forth in any one of SEQ ID NOs: 421-424). In some embodiments, the antibody, or antigen binding fragment thereof, comprises a constant light chain sequence comprising a sequence set forth in SEQ ID NO: 421.

[0266] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 19 and 22; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 30. In certain embodiments, the antibody, or antigen binding fragment thereof, further comprises a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions. In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a heavy chain comprising a heavy chain constant region selected from SEQ ID NO: 61 or SEQ ID NO: 173. In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a heavy chain comprising a heavy chain constant region set forth in SEQ ID NO: 173. In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a human lambda light chain constant region (e.g., a lambda light chain constant region of subtype 1, 2, 3, or 7, such as a lambda light chain constant region set forth in any one of SEQ ID NOs: 421-424). In some embodiments, the antibody, or antigen binding fragment thereof, comprises a constant light chain sequence comprising a sequence set forth in SEQ ID NO: 421.

[0267] Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 159- 270), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 40-158). Accordingly, any of the antibodies or antigen binding fragments thereof described above may comprise a human IgG80IPTS / 200090223.1Goodwin Ref: PRG-061WO sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 159-270), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 40-158), or a mixture thereof (e.g., a mixture of the same heavy chain constant sequence with and without a C-terminal lysine, such as a mixture of SEQ ID NO: 173 and SEQ ID NO: 61).

[0268] In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this disclosure are referred to herein as “variants” or “clones”. In some embodiments, such variants or clones are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants or clones are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.Anti-IL4Ra Antibodies

[0269] The present application provides antibodies, or antigen binding fragments thereof, and compositions comprising an antibody, or an antigen binding fragment thereof, which binds IL-4Ra. In some embodiments, an anti-IL-4Ra antibody, or antigen binding fragment thereof, described herein is selected from dupilumab, stapokibart, rademikibart, and Antibody 611. In some embodiments, dupilumab comprises a variable heavy (VH) chain sequence having the amino acid sequence of SEQ ID NO: 408 and a variable light (VL) chain sequence having the amino acid sequence of SEQ ID NO: 409. In some embodiments, dupilumab comprises a heavy chain having the amino acid sequence of SEQ ID NO: 449 and a light chain sequence having the amino acid sequence of SEQ ID NO: 450. In some embodiments, stapokibart comprises a heavy chain having the amino acid sequence of SEQ ID NO: 418 and a light chain sequence having the amino acid sequence of SEQ ID NO: 419, or a VH and / or VL therein (e.g., a VH having the sequence of SEQ ID NO: 447 and a VL having the sequence of SEQ ID NO: 448). In some embodiments, rademikibart comprises a VH chain sequence having the amino acid sequence of SEQ ID NO: 499 and a VL chain sequence having the amino acid sequence of SEQ ID NO: 500. In some embodiments, rademikibart comprises a heavy chain having the amino acid sequence of SEQ ID NO: 497 and a light chain sequence having the amino acid sequence of SEQ ID NO: 498. See also PCT Application No. PCT / US2024 / 016235 (corresponding to PCT Publication No. WO2024173847), which is incorporated herein by reference in its entirety. In some embodiments, an anti-IL-4Ra antibody, or an antigen binding fragment thereof, described herein is selected from an anti-IL-4Ra antibody described therein.81IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0270] Sequences of exemplary anti-IL-4Ra antibodies, or antigen binding fragments thereof, are provided in TABLE 5.TABLE 5. Sequences of IL-4Ra antibody constructs - VH, VL, and associated CDRs82IPTS / 200090223.1Goodwin Ref: PRG-061WOAnti- IL-4Ra VH Domains

[0271] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297.

[0272] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VH sequence selected from any one of SEQ ID NOs: 295- 297. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some83IPTS / 200090223.1Goodwin Ref: PRG-061WO embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.Anti- IL-4Ra VL Domains

[0273] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 298-300.

[0274] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VL sequence selected from any one of SEQ ID NOs: 298- 300. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VL sequence selected from any one of SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.Anti- IL-4Ra VH-VL Combinations

[0275] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence selected from any one of SEQ ID NOs: 295-297; and a VL sequence selected from any one of SEQ ID NO: 298-300.

[0276] In certain aspects, any one of SEQ ID NOs: 295-297 can be combined with any one of SEQ ID NOs: 298-300.

[0277] In certain aspects, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence of a construct provided in TABLE 5 or a VH sequence and a VL sequence of a construct provided in PCT Application No. PCT / US2024 / 016235 (corresponding to PCT Publication No. WO2024173847), incorporated by reference herein in its entirety. In certain aspects, an antibody, or antigen binding fragment 84IPTS / 200090223.1Goodwin Ref: PRG-061WO thereof, provided herein comprises a VH sequence and a VL sequence from Table 2 in PCT Application No. PCT / US2024 / 016235 (e.g., a VH sequence and a VL sequence from the same row of Table 2).

[0278] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VH sequence provided in any one of SEQ ID NOs: 295- 297; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VL sequence provided in any one of SEQ ID NOs: 298-300. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence provided in any one of SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions, and a VL sequence provided in any one of SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0279] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 295 and a VL sequence set forth in SEQ ID NO: 298.

[0280] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 296 and a VL sequence set forth in SEQ ID NO: 299.

[0281] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300.

[0282] In certain embodiments of any of the antibodies, or antigen binding fragments thereof, described above, the antibody further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 47-270. In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a heavy chain comprising a human IgG sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173. In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a heavy chain comprising a human IgG sequence set forth in SEQ ID NO: 173.85IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0283] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 295; a VL sequence set forth in SEQ ID NO: 298; and the antibody further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 47-270. In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a heavy chain comprising a human IgG sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173. In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a heavy chain comprising a human IgG sequence set forth in SEQ ID NO: 173. In certain embodiments of any of the antibodies, or antigen binding fragments thereof, described above, the antibody further comprises a constant light chain sequence comprising a sequence set forth in SEQ ID NO: 46.

[0284] In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 295, a VL sequence set forth in SEQ ID NO: 298, a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions, and a human kappa light chain constant region. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 295, a VL sequence set forth in SEQ ID NO: 298, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 46. In certain embodiments, the antibody comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VH sequence provided in SEQ ID NO: 295; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VL sequence provided in SEQ ID NO: 298, a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions, and a human kappa light chain constant region. In certain embodiments, the antibody comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VH sequence provided in SEQ ID NO: 295; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VL sequence provided in SEQ ID NO: 298, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 46 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 46.

[0285] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 295, a VL sequence set forth in SEQ ID NO: 298, a86IPTS / 200090223.1Goodwin Ref: PRG-061WO heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 46. In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 295, a VL sequence set forth in SEQ ID NO: 298, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 46.

[0286] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 296; and a VL sequence set forth in SEQ ID NO: 299; and the antibody further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any of SEQ ID NOs: 47-270. In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a heavy chain comprising a human IgG sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173. In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a heavy chain comprising a human IgG sequence set forth in SEQ ID NO: 173. In certain embodiments of any of the antibodies, or antigen binding fragments thereof, described above, the antibody further comprises a constant light chain sequence comprising a sequence set forth in SEQ ID NO: 46.

[0287] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 296, a VL sequence set forth in SEQ ID NO: 299, a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions, and a human kappa light chain constant region. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 296, a VL sequence set forth in SEQ ID NO: 299, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 46. In certain embodiments, the antibody comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VH sequence provided in SEQ ID NO: 296; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VL sequence provided in SEQ ID NO: 299, a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions, and a human kappa light chain constant region. In certain embodiments, the antibody comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VH sequence provided in SEQ ID NO: 296; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VL sequence provided in SEQ ID NO: 299, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173 or a sequence having at87IPTS / 200090223.1Goodwin Ref: PRG-061WO least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 46 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 46.

[0288] In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 296, a VL sequence set forth in SEQ ID NO: 299, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 46. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 296, a VL sequence set forth in SEQ ID NO:299, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 46.

[0289] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 297; and a VL sequence set forth in SEQ ID NO: 300; and the antibody further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any of SEQ ID NOs: 47-270. In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a heavy chain comprising a human IgG sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173. In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a heavy chain comprising a human IgG sequence set forth in SEQ ID NO: 173. In certain embodiments of any of the antibodies, or antigen binding fragments thereof, described above, the antibody further comprises a constant light chain sequence comprising a sequence set forth in SEQ ID NO: 46.

[0290] In certain embodiments, the antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 297, a VL sequence set forth in SEQ ID NO: 300, a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions, and a human kappa light chain constant region. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 297, a VL sequence set forth in SEQ ID NO: 300, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 46. In certain embodiments, the antibody comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VH sequence provided in SEQ ID NO: 297; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VL sequence provided in SEQ ID NO:300, a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions, and a human kappa light chain constant region. In certain embodiments, the88IPTS / 200090223.1Goodwin Ref: PRG-061WO antibody comprises a VH sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VH sequence provided in SEQ ID NO: 297; and a VL sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a VL sequence provided in SEQ ID NO: 300, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 46 or a sequence having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 46.

[0291] In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 297, a VL sequence set forth in SEQ ID NO: 300, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 61 or SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 46. In certain embodiments, the antibody comprises a VH sequence set forth in SEQ ID NO: 297, a VL sequence set forth in SEQ ID NO: 300, a heavy chain constant region comprising a sequence set forth in SEQ ID NO: 173, and a light chain constant region comprising a sequence set forth in SEQ ID NO: 46. In some embodiments, the antibody comprises a heavy chain sequence set forth in SEQ ID NO: 444 or 445 and a light chain sequence set forth in SEQ ID NO: 446. In some embodiments, the antibody comprises a heavy chain sequence set forth in SEQ ID NO: 444 and a light chain sequence set forth in SEQ ID NO: 446. The heavy chain sequence of SEQ ID NO: 444 contains a C-terminal lysine, which may be cleaved off during manufacture or after administration, resulting in an antibody containing the heavy chain sequence of SEQ ID NO: 445.

[0292] Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 159- 270), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 40-158). Accordingly, any of the antibodies or antigen binding fragments thereof described above may comprise a human IgG sequence containing a C-terminal lysine (e.g., any one of SEQ ID NOs: 159-270), a human IgG sequence lacking a C-terminal lysine (e.g., any one of SEQ ID NOs: 40-158), or a mixture thereof (e.g., a mixture of the same heavy chain constant region sequence with and without a C- terminal lysine, such as a mixture of SEQ ID NO: 173 and SEQ ID NO: 61).89IPTS / 200090223.1Goodwin Ref: PRG-061WOAnti- IL-4Ra CDRs

[0293] In some embodiments, disclosed herein is an antibody, or antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the CDRs of TABLE 5. In some embodiments, disclosed herein is an antibody, or antigen binding fragment thereof, comprising 6 of the Kabat CDRs of TABLE 5, 6 of the Chothia CDRs of TABLE 5, or 6 of the IMGT CDRs of TABLE 5. In some embodiments, the antibody, or an antigen binding fragment thereof, comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of TABLE5 (e.g., 6 CDRs from the same antibody).

[0294] In some embodiments, disclosed herein is an antibody, or antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the CDRs of an antibody provided in PCT Application No. PCT / US2024 / 016235 (corresponding to PCT Publication No. WO2024173847), incorporated by reference herein in its entirety. In some embodiments, disclosed herein is an antibody, or antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the Kabat CDRs of an antibody provided in PCT Application No. PCT / US2024 / 016235. In some embodiments, disclosed herein is an antibody, or antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or6 of the Chothia CDRs of an antibody provided in PCT Application No. PCT / US2024 / 016235. In some embodiments, disclosed herein is an antibody, or antigen binding fragment thereof, comprising 1, 2, 3, 4, 5, or 6 of the IMGT CDRs of an antibody provided in PCT Application No. PCT / US2024 / 016235. In some embodiments, the antibody, or an antigen binding fragment thereof, comprises 6 of the Kabat CDRs, 6 of the Chothia CDRs, or 6 of the IMGT CDRs from a single row of Table 2 of PCT Application No. PCT / US2024 / 016235 (e.g., 6 CDRs from the same antibody).

[0295] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises one to three CDRs of a VH domain selected from any one of SEQ ID NOs: 295-297. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises two to three CDRs of a VH domain selected from any one of SEQ ID NOs: 295-297. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises three CDRs of a VH domain selected from any one of SEQ ID NOs: 295-297. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs.

[0296] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-H1, CDR-H2, or CDR-90IPTS / 200090223.1Goodwin Ref: PRG-061WOH3 selected from SEQ ID NOs: 273-284. In some embodiments, the CDR-H1 is a CDR-H1 of a VH domain selected from any one of SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, the CDR-H2 is a CDR-H2 of a VH domain selected from any one of SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the CDR-H3 is a CDR-H3 of a VH domain selected from any one of SEQ ID NOs: 295-297, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0297] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises one to three CDRs of a VL domain selected from any one of SEQ ID NOs: 298-300. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises two to three CDRs of a VL domain selected from any one of SEQ ID NOs: 298-300. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises three CDRs of a VL domain selected from any one of SEQ ID NOs: 298-300. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs.

[0298] In some embodiments, the CDRs are CDRs having at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to a CDR-L1, CDR-L2, or CDR- L3 selected from SEQ ID NOs: 285-293, the amino acid sequence LG, and the amino acid sequence EG. In some embodiments, the CDR-L1 is a CDR-L1 of a VL domain selected from any one of SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, or 5 amino acid substitutions. In some embodiments, the CDR-L2 is a CDR-L2 of a VL domain selected from any one of SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some embodiments, the CDR-L3 is a CDR-L3 of a VL domain selected from any one of SEQ ID NOs: 298-300, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis,91IPTS / 200090223.1Goodwin Ref: PRG-061WO random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0299] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises one to three CDRs of a VH domain selected from any one of SEQ ID NOs: 295-297 and one to three CDRs of a VL domain selected from any one of SEQ ID NOs: 298- 300. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises two to three CDRs of a VH domain selected from any one of SEQ ID NOs: 295-297 and two to three CDRs of a VL domain selected from any one of SEQ ID NOs: 298-300. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises three CDRs of a VH domain selected from any one of SEQ ID NOs: 295-297 and three CDRs of a VL domain selected from any one of SEQ ID NO: 298-300. In some aspects, the CDRs are Kabat CDRs. In some aspects, the CDRs are Chothia CDRs. In some aspects, the CDRs are IMGT CDRs. In some aspects, the CDRs are AbM CDRs. In some aspects, the CDRs are Contact CDRs.

[0300] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from any one of SEQ ID NOs: 281-284. In some aspects, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H3 selected from any one of SEQ ID NOs: 281-284. In some embodiments, the CDR-H3 is a CDR-H3 selected from any one of SEQ ID NOs: 281-284, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0301] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 selected from any one of SEQ ID NOs: 273-275. In some aspects, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H1 selected from any one of SEQ ID NOs: 273-275. In some embodiments, the CDR-H1 is a CDR-H1 selected from any one of SEQ ID NOs: 273-275, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid92IPTS / 200090223.1Goodwin Ref: PRG-061WO substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0302] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H2 selected from any one of SEQ ID NOs: 276-280. In some aspects, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H2 selected from any one of SEQ ID NOs: 276-280. In some embodiments, the CDR-H2 is a CDR-H2 selected from any one of SEQ ID NOs: 276-280, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0303] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-L3 of SEQ ID NO: 293. In some aspects, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L3 of SEQ ID NO: 293. In some embodiments, the CDR-L3 is a CDR-L3 of SEQ ID NO: 293, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0304] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-L2 selected from any one of SEQ ID NOs: 290-292, the amino acid sequence LG, and the amino acid sequence EG. In some aspects, the CDR-L2 has at least about93IPTS / 200090223.1Goodwin Ref: PRG-061WO80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L2 selected from any one of SEQ ID NOs: 290-292, the amino acid sequence LG, and the amino acid sequence EG. In some embodiments, the CDR-L2 is a CDR-L2 selected from any one of SEQ ID NOs: 290-292, the amino acid sequence LG, and the amino acid sequence EG, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0305] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-L1 selected from any one of SEQ ID NOs: 285-289. In some aspects, the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L1 selected from any one of SEQ ID NOs: 285-289. In some embodiments, the CDR-L1 is a CDR-L1 selected from any one of SEQ ID NOs: 285-289, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this paragraph are referred to herein as “variants.” In some embodiments, such variants are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies.

[0306] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H3 selected from any one of SEQ ID NOs: 281-284, a CDR-H2 selected from any one of SEQ ID NOs: 276-280, a CDR-H1 selected from any one of SEQ ID NOs: 273-275, a CDR-L3 of SEQ ID NO: 293, a CDR-L2 selected from any one of SEQ ID NOs: 290-292, the amino acid sequence LG, and the amino acid sequence EG, and a CDR-L1 selected from any one of SEQ ID NOs: 285-289. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H3 selected from any one of SEQ ID NOs: 281-284, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H2 selected from any one of SEQ ID NOs: 276-280, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H1 selected from any one of SEQ ID NOs:94IPTS / 200090223.1Goodwin Ref: PRG-061WO273-275, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L3 of SEQ ID NO: 293, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L2 selected from any one of SEQ ID NOs: 290-292, the amino acid sequence LG, and the amino acid sequence EG, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L1 selected from any one of SEQ ID NOs: 285-289. In some embodiments, the CDR-H3 is a CDR-H3 selected from any one of SEQ ID NOs: 281-284, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 selected from any one of SEQ ID NOs: 276-280, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 selected from any one of SEQ ID NOs: 273-275, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of SEQ ID NO: 293, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 selected from any one of SEQ ID NOs: 290-292, the amino acid sequence LG, and the amino acid sequence EG, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 selected from any one of SEQ ID NOs: 285-289, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0307] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H3 set forth in any one of SEQ ID NOs: 281 and 282, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR- H2 set forth in any one of SEQ ID NOs: 276, 277, and 278, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H1 set forth in any one of SEQ ID NOs: 273, 274, and 275, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L3 of SEQ ID NO: 293, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L2 set forth in SEQ ID NO: 292 or the amino acid sequence LG, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L1 set forth in any one of SEQ ID NOs: 285 and 286. In some embodiments, the CDR-H3 is a CDR-H3 set forth in any one of SEQ ID NOs: 281 and 282, with up to 1, 2, 3,95IPTS / 200090223.1Goodwin Ref: PRG-061WO4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 set forth in any one of SEQ ID NOs: 276, 277, and 278, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR- H1 is a CDR-H1 set forth in any one of SEQ ID NOs: 273, 274, and 275, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of SEQ ID NO: 293 with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 set forth in SEQ ID NO: 292 or the amino acid sequence LG, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 set forth in any one of SEQ ID NOs: 285 and 286, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0308] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0309] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H3 set forth in any one of SEQ ID NOs: 283 and 284, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR- H2 set forth in any one of SEQ ID NOs: 279, 277, and 280, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H1 set forth in any one of SEQ ID NOs: 273, 274, and 275, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L3 set forth in SEQ ID NO: 293, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L2 set forth in SEQ ID NO: 291 or the amino acid sequence LG, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L1 set forth in any one of SEQ ID NOs: 287 and 288. In some embodiments, the CDR-H3 is a CDR-H3 set forth in any one of SEQ ID NOs: 283 and 284, with up to 1, 2, 3,96IPTS / 200090223.1Goodwin Ref: PRG-061WO4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 set forth in any one of SEQ ID NOs: 279, 277, and 280, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR- H1 is a CDR-H1 set forth in any one of SEQ ID NOs: 273, 274, and 275, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of SEQ ID NO: 293 with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 set forth in SEQ ID NO: 291 or the amino acid sequence LG, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 set forth in any one of SEQ ID NOs: 287 and 288, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0310] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NO: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0311] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H3 set forth in any one of SEQ ID NOs: 281 and 282, the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR- H2 set forth in any one of SEQ ID NOs: 279, 277, and 280, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H1 set forth in any one of SEQ ID NOs: 273, 274, and 275, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L3 of SEQ ID NO: 293, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L2 set forth in SEQ ID NO: 290 or the amino acid sequence EG, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L1 set forth in any one of SEQ ID NOs: 289 and 288. In some embodiments, the CDR-H3 is a CDR-H3 set forth in any one of SEQ ID NOs: 281 and 282, with up to 1, 2, 3,97IPTS / 200090223.1Goodwin Ref: PRG-061WO4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 set forth in any one of SEQ ID NOs: 279, 277, and 280, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR- H1 is a CDR-H1 set forth in any one of SEQ ID NOs: 273, 274, and 275, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of SEQ ID NO: 293 with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 set forth in SEQ ID NO: 290 or the amino acid sequence EG, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 set forth in any one of SEQ ID NOs: 289 and 288, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0312] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NO: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

[0313] In some embodiments, the CDR-H3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H3 of TABLE 5; the CDR-H2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR- H2 of TABLE 5, the CDR-H1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-H1 of TABLE 5, the CDR-L3 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L3 of TABLE 5, the CDR-L2 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L2 of TABLE 5, and the CDR-L1 has at least about 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a CDR-L1 of TABLE 5. In some embodiments, the CDR-H3 is a CDR-H3 of TABLE 5, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H2 is a CDR-H2 of TABLE 5, with up to 1, 2, 3, 4, 5, 6, 7, or 8 amino acid substitutions; the CDR-H1 is a CDR-H1 of TABLE 5, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L3 is a CDR-L3 of TABLE 5, with up to 1, 2, 3, 4, or 5 amino acid substitutions; the CDR-L2 is a CDR-L2 of TABLE 5, with up to 1, 2, 3, or 4 amino acid substitutions; and the CDR-L1 is a CDR-L1 of TABLE 5, with up to 1, 2, 3, 4, 5, or 6 amino acid substitutions.

[0314] In certain embodiments of any of the antibodies, or antigen binding fragments thereof, described above, the antibody further comprises a heavy chain comprising a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 47-270. In certain98IPTS / 200090223.1Goodwin Ref: PRG-061WO embodiments of any of the antibodies, or antigen binding fragments thereof, described above, the antibody further comprises a constant light chain sequence comprising a sequence set forth in SEQ ID NO: 46. In certain embodiments of any of the antibodies, or antigen binding fragments thereof, described above, the antibody further comprises a heavy chain comprising a human IgG sequence selected from SEQ ID NO: 61 and SEQ ID NO: 173 and a constant light chain sequence comprising a sequence set forth in SEQ ID NO: 46.

[0315] In some embodiments, the antibody, or antigen binding fragment thereof, comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. In certain embodiments, the antibody further comprises a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions. In certain embodiments, the antibody comprises a heavy chain comprising a heavy chain constant region selected from SEQ ID NO: 61 and SEQ ID NO: 173. In certain embodiments, the antibody comprises a heavy chain comprising a heavy chain constant region set forth in SEQ ID NO: 173. In certain embodiments, the antibody comprises a human kappa light chain constant region. In some embodiments, the antibody comprises a constant light chain sequence comprising a sequence set forth in SEQ ID NO: 46.

[0316] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NO: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. In certain embodiments, the antibody further comprises a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions. In certain embodiments, the antibody comprises a heavy chain comprising a heavy chain constant region selected from SEQ ID NO: 61 and SEQ ID NO: 173. In certain embodiments, the antibody comprises a heavy chain comprising a heavy chain constant region set forth in SEQ ID NO: 173. In certain embodiments, the antibody comprises a human kappa light chain constant region. In some embodiments, the antibody comprises a constant light chain sequence comprising a sequence set forth in SEQ ID NO: 46.99IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0317] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein comprises a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NO: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293. In certain embodiments, the antibody further comprises a heavy chain constant region (e.g., an IgGl constant region) comprising LALA / YTE substitutions. In certain embodiments, the antibody comprises a heavy chain comprising a heavy chain constant region selected from SEQ ID NO: 61 and SEQ ID NO: 173. In certain embodiments, the antibody comprises a heavy chain comprising a heavy chain constant region set forth in SEQ ID NO: 173. In certain embodiments, the antibody comprises a human kappa light chain constant region. In some embodiments, the antibody comprises a constant light chain sequence comprising a sequence set forth in SEQ ID NO: 46.

[0318] Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region (e.g., in a sequence encoding any one of SEQ ID NOs: 159- 270), it may be cleaved off during manufacture or after administration (resulting in, e.g., a constant heavy chain sequence of any one of SEQ ID NOs: 40-158). Accordingly, any of the antibodies or antigen binding fragments thereof described above may comprise a human IgG sequence containing a C-terminal lysine (e.g, any one of SEQ ID NOs: 159-270), a human IgG sequence lacking a C-terminal lysine (e.g, any one of SEQ ID NOs: 40-158), or a mixture thereof (e.g., a mixture of the same heavy chain constant region sequence with and without a C- terminal lysine, such as a mixture of SEQ ID NO: 173 and SEQ ID NO: 61).

[0319] In some aspects, the amino acid substitutions are conservative amino acid substitutions. In some embodiments, the antibodies described in this disclosure are referred to herein as “variants” or “clones”. In some embodiments, such variants or clones are derived from a sequence provided herein, for example, by affinity maturation, site directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such variants or clones are not derived from a sequence provided herein and may, for example, be isolated de novo according to the methods provided herein for obtaining antibodies100IPTS / 200090223.1Goodwin Ref: PRG-061WOFc Region

[0320] The structures of the Fc regions of various immunoglobulins, and the glycosylation sites contained therein, are known in the art. See Schroeder and Cavacini, J. (2010) Allergy Clin. Immunol. 125:S41-52, incorporated by reference in its entirety. The Fc region may be a naturally occurring Fc region, or an Fc region modified as described in the art or elsewhere in this disclosure.

[0321] Unless otherwise specified herein, numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al. , Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991. An “Fc polypeptide” of a dimeric Fc as used herein refers to one of the two polypeptides forming the dimeric Fc domain, i.e. a polypeptide comprising C-terminal constant regions of an immunoglobulin heavy chain, capable of stable self-association. For example, an Fc polypeptide of a dimeric IgG Fc comprises an IgG CH2 and an IgG CH3 constant domain sequence. An Fc can be of the class IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgGi, IgG2, IgGs, IgG4, IgAi, and IgA2.

[0322] The terms “Fc receptor” and “FcR” are used to describe a receptor that binds to the Fc region of an antibody. For example, an FcR can be a native sequence human FcR. Generally, an FcR is one which binds an IgG antibody (a gamma receptor) and includes receptors of the FcyRI, FcyRII, and FcyRIII subclasses, including allelic variants and alternatively spliced forms of these receptors. FcyRII receptors include FcyRIIA (an “activating receptor”) and FcyRIIB (an “inhibiting receptor”), which have similar amino acid sequences that differ primarily in the cytoplasmic domains thereof. Immunoglobulins of other isotypes can also be bound by certain FcRs (see, e.g., Janeway et al., Immuno Biology: the immune system in health and disease, (Elsevier Science Ltd., NY) (4th ed., 1999)). Activating receptor FcyRIIA contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. Inhibiting receptor FcyRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain (reviewed in Daeron, Annu. Rev. Immunol. 15:203-234 (1997)). FcRs are reviewed in Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991); Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J. Lab. Clin. Med. 126:330-41 (1995). Other FcRs, including those to be identified in the future, are encompassed by the term “FcR” herein. The term also includes the neonatal receptor, FcRn, which is responsible for the transfer of101IPTS / 200090223.1Goodwin Ref: PRG-061WO maternal IgGs to the fetus (Guyer et aL, J. Immunol. 117:587 (1976); and Kim et aL, J.Immunol. 24:249 (1994)).

[0323] Modifications in the CH2 domain can affect the binding of FcRs to the Fc. A number of amino acid modifications in the Fc region are known that can selectively alter the affinity of the Fc for different Fcgamma receptors. In some aspects, the Fc comprises one or more modifications designed to promote selective binding of Fc-gamma receptors.

[0324] Exemplary mutations that may alter the binding of FcRs to the Fc are listed below (in EU numbering format):S298A / E333A / K334A, S298A / E333A / K334A / K326A (Lu Y, Vernes JM, Chiang N, el al., J Immunol Methods . 2011 Feb 28;365(l-2): 132-41);F243L / R292P / Y300L / V305I / P396L, F243L / R292P / Y300L / L235V / P396L (Stavenhagen JB,Gorlatov S, Tuaillon N, et al., Cancer Res. 2007 Sep 15;67(18):8882-90; Nordstrom JL, Gorlatov S, Zhang W, et al., Breast Cancer Res. 2011 Nov 30; 13(6):R123);F243L (Stewart R, Thom G, Levens M, et al., Protein Eng Des Sei. 2011 Sep;24(9):671-8.), S298A / E333A / K334A (Shields RL, Namenuk AK, Hong K, et al., J Biol Chem. 2001 Mar 2;276(9):6591-604);S239D / I332E / A330L, S239D / I332E (Lazar GA, Dang W, Karki S, el al., Proc Natl Acad Sci U SA. 2006 Mar 14; 103(11):4005-10);S239D / S267E, S267E / L328F (Chu SY, Vostiar I, Karki S, et al, Mol Immunol. 2008 Sep;45(15):3926-33);S239D / D265S / S298A / I332E, S239E / S298A / K326A / A327H, G237F / S298A / A330L / I332E, S23 9D / I332E / S298A, S239D / K326E / A330L / I332E / S298A, G236A / S239D / D270L / I332E, S239E / S 267E / H268D, L234F / S267E / N325L, G237F / V266L / S267D and other mutations listed inWO201 1 / 120134 and WO2011 / 120135, herein incorporated by reference. Therapeutic Antibody Engineering (by William R. Strohl and Lila M. Strohl, Woodhead Publishing series in Biomedicine No 11, ISBN 1 907568 37 9, Oct 2012) lists mutations on page 283.

[0325] In some embodiments, an antibody, or antigen binding fragment thereof, described herein includes modifications intended to improve its ability to mediate effector function.“Effector functions” refer to those biological activities mediated by the Fc region of an antibody, which activities may vary depending on the antibody isotype. Examples of antibody effector functions include receptor ligand blocking, agonism or antagonism, Clq binding to activate complement dependent cytotoxicity (CDC), Fc receptor binding to activate antibody-dependent cellular cytotoxicity (ADCC), and antibody dependent cellular phagocytosis (ADCP). In some embodiments, the anti-TSLP antibody and / or anti-IL-4Ra antibody described herein includes102IPTS / 200090223.1Goodwin Ref: PRG-061WO modifications designed to improve its ability to mediate effector function. Such modifications that can have this effect are known in the art and include afucosylation, or engineering of the affinity of the Fc towards an activating receptor, mainly FCGR3a for ADCC, and towards Clq for CDC. The following TABLE 6 summarizes various designs reported in the literature for effector function engineering.

[0326] Methods of producing antibodies with little or no fucose on the Fc glycosylation site (Asn 297 EU numbering) without altering the amino acid sequence are well known in the art. The GlymaxX® technology (ProBioGen AG) is based on the introduction of a gene for an enzyme which deflects the cellular pathway of fucose biosynthesis into cells used for antibody production. This prevents the addition of the sugar “fucose” to the N-linked antibody carbohydrate part by antibody-producing cells (von Horsten et al. (2010) Glycobiology. 2010 Dec; 20 (12): 1607-18). Examples of cell lines capable of producing defucosylated antibody include CHO-DG44 with stable overexpression of the bacterial oxidoreductase GDP-6-deoxy-D- lyxo-4-hexylose reductase (RMD) (see von Horsten et al. (2010) supra) or Lecl3 CHO cells, which are deficient in protein fucosylation (see Ripka et al. (1986) Arch. Biochem. Biophys. 249:533-545; U.S. Pat. Pub. No. 2003 / 0157108; WO 2004 / 056312; each of which is incorporated by reference in its entirety), and knockout cell lines, such as alpha- 1,6- fucosyltransferase gene or FUT8 knockout CHO cells (see Yamane-Ohnuki et al. (2004) Biotech. Bioeng. 87: 614-622; Kanda c / a / . (2006) Biotechnol. Bioeng. 94:680-688; and WO 2003 / 085107; each of which is incorporated by reference in its entirety). Another approach to obtaining antibodies with lowered levels of fucosylation can be found in U.S. Patent No. 8,409,572, which teaches selecting cell lines for antibody production for their ability to yield lower levels of fucosylation on antibodies.

[0327] Antibodies can be fully afucosylated (meaning they contain no detectable fucose) or they can be partially afucosylated, meaning that the isolated antibody contains less than 95%, less than 85%, less than 75%, less than 65%, less than 55%, less than 45%, less than 35%, less than 25%, less than 15% or less than 5% of the amount of fucose normally detected for a similar antibody produced by a mammalian expression system.

[0328] In some aspects, the anti-IL-4Ra and / or anti-TSLP antibody provided herein comprises an Fc domain (e.g., an IgGl Fc domain) with reduced fucose content at position Asn 297 (EU numbering) compared to a naturally occurring Fc domain. Such Fc domains are known to have improved ADCC. See Shields et al., J. Biol. Chem., 2002, 277:26733-26740, incorporated by reference in its entirety. In some aspects, such antibodies do not comprise any103IPTS / 200090223.1Goodwin Ref: PRG-061WO fucose at position Asn 297. The amount of fucose may be determined using any suitable method, for example as described in WO 2008 / 077546, incorporated by reference in its entirety.

[0329] In some embodiments, the anti-IL-4Ra and / or anti-TSLP antibody described herein comprises an Fc region with one or more amino acid substitutions which improve ADCC, such as a substitution at one or more of positions 298, 333, and 334 of the Fc region. In some embodiments, the anti-IL-4Ra and / or anti-TSLP antibody provided herein comprises an Fc region with one or more amino acid substitutions at positions 239, 332, and 330, as described in Lazar et al., Proc. Natl. Acad. Set. USA, 2006,103:4005-4010, incorporated by reference in its entirety.

[0330] Other illustrative glycosylation variants which may be incorporated into the antibodies provided herein are described, for example, in U.S. Pat. Pub. Nos. 2003 / 0157108, 2004 / 0093621, 2003 / 0157108, 2003 / 0115614, 2002 / 0164328, 2004 / 0093621, 2004 / 0132140, 2004 / 0110704, 2004 / 0110282, 2004 / 0109865; International Pat. Pub. Nos. 2000 / 61739, 2001 / 29246, 2003 / 085119, 2003 / 084570, 2005 / 035586, 2005 / 035778; 2005 / 053742, 2002 / 031140; Okazaki et al., J. Mol. BioL, 2004, 336: 1239-1249; and Yamane-Ohnuki et al., Biotech. Bioeng., 2004, 87: 614-622; each of which is incorporated by reference in its entirety.

[0331] In some embodiments, an antibody provided herein comprises an Fc region with at least one galactose residue in the oligosaccharide attached to the Fc region. Such antibody variants may have improved CDC function. Examples of such antibody variants are described, for example, in WO 1997 / 30087; WO 1998 / 58964; and WO 1999 / 22764; each of which is incorporated by reference in its entirety.

[0332] In some embodiments, the effector function of the anti- IL-4Ra antibody, or antigen binding fragment thereof, described herein is antagonism and blocks IL-4Ra and IL-13Ral heterodimer formation, which reduces IL-4 and IL- 13 signaling. In some embodiments, the effector function of the anti-TSLP antibody, or antigen binding fragment thereof, described herein is antagonism and blocks TSLP from binding to a TSLP receptor.

[0333] Thus, in one embodiment, an antibody described herein can include a dimeric Fc that comprises one or more amino acid modifications as noted in TABLE 6 that may confer improved effector function. In another embodiment, the antibody can be afucosylated to improve effector function.104IPTS / 200090223.1Goodwin Ref: PRG-061WOTABLE 6. CH2 domains and effector function engineering

[0334] Fc modifications intended to reduce FcgR and / or complement binding and / or effector function are known in the art. Recent publications describe strategies that have been used to engineer antibodies with reduced or silenced effector activity (see Strohl, WR (2009), Curr Opin Biotech 20:685-691, and Strohl, WR and Strohl LM, “Antibody Fc engineering for optimal antibody performance” In Therapeutic Antibody Engineering, Cambridge: Woodhead Publishing (2012), pp 225-249). These strategies include reduction of effector function through modification of glycosylation, use of IgG2 / IgG4 scaffolds, or the introduction of mutations in the hinge or CH2 regions of the Fc. For example, U.S. Patent Publication No. 2011 / 0212087 (Strohl), International Patent Publication No. WO 2006 / 105338 (Xencor), U.S. Patent Publication No. 2012 / 0225058 (Xencor), U.S. Patent Publication No. 2012 / 0251531 (Genentech), and Strop et al. ((2012) J. Mol. Biol. 420: 204-219), each of which is incorporated by reference in its entirety, describe specific modifications designed to reduce FcgR or complement binding to the Fc.

[0335] Specific, non-limiting examples of amino acid modifications intended to reduce FcgR or complement binding to the Fc include those identified in the following TABLE 7:105IPTS / 200090223.1Goodwin Ref: PRG-061WOTABLE 7. Modifications designed to reduce FcgR or complement binding to the Fc

[0336] In some embodiments, an antibody, or an antigen binding fragment thereof, provided herein comprises one or more alterations that is designed to improve or diminish Clq binding and / or CDC. See U.S. Patent No. 6,194,551; WO 99 / 51642; and Idusogie et al., J. Immunol., 2000, 164:4178-4184; each of which is incorporated by reference in its entirety.

[0337] In certain embodiments, the heavy chain comprises a constant heavy chain sequence selected from a sequences set forth in any one of SEQ ID NOs: 47-270. In certain embodiments, the constant heavy chain sequence, (e.g., a constant heavy chain sequence selected from any one of SEQ ID NOs: 47-158) further comprises a C-terminal lysine (e.g., any one of SEQ ID NOs: 159-270). Although a C-terminal lysine may be present in the corresponding coding sequence of the constant heavy chain region, it may be cleaved off during manufacture or after106IPTS / 200090223.1Goodwin Ref: PRG-061WO administration. Accordingly, sequences of heavy chain constant regions with and without the C- terminal lysine are provided herein. Consequently, a composition resulting from the manufacture of an antibody comprising a C-terminal lysine in the corresponding coding sequence of the constant heavy chain region (e.g., an antibody with a coding sequence that encodes any one of SEQ ID NOs: 159-270) may comprise antibodies having a constant heavy chain sequence containing a C-terminal lysine (e.g., selected from SEQ ID NOs: 159-270), antibodies having a constant heavy chain sequence lacking a C-terminal lysine (e.g., the corresponding sequence of any one of SEQ ID NOs: 47-158), or a mixture thereof. For example, a composition comprising an antibody comprising the constant heavy chain sequence of SEQ ID NO: 173 that is administered to a subject may comprise antibodies having the constant heavy chain sequence set forth in SEQ ID NO: 173 or SEQ ID NO: 61, or a mixture thereof (e.g., a mixture of antibodies having either a constant heavy chain sequence of SEQ ID NO: 173 or a constant heavy chain sequence of SEQ ID NO: 61 and / or antibodies containing both constant heavy chain sequences (e.g, in a single antibody containing two constant heavy chain sequences)).

[0338] In certain embodiments, an anti-TSLP antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence provided in TABLE 4, together with a heavy chain constant region selected from a sequence set forth in any one of SEQ IDs NO: 47-270. In certain embodiments, an anti-TSLP antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence provided in TABLE 4, together with a heavy chain constant region selected from a sequence set forth in any one of SEQ ID NOs: 47-270 and a light chain constant region selected from any one of SEQ ID NOs: 421-424.

[0339] In certain embodiments, an anti-TSLP antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence provided in TABLE 13 (e.g, a VH sequence and a VL sequence from the same row of TABLE 13), together with a heavy chain constant region selected from a sequence set forth in any one of SEQ ID NOs: 47- 270. In certain embodiments, an anti-TSLP antibody, or an antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence provided in TABLE 13, together with a heavy chain constant region selected from a sequence set forth in any one of SEQ ID NOs: 47-270 and a light chain constant region selected from any one of SEQ ID NOs: 421-424.

[0340] In certain embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 34 and a VL sequence set forth in SEQ ID NO: 41; and the constant heavy chain comprises a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 47-270 (e.g., SEQ ID NO: 61 or SEQ ID NO:107IPTS / 200090223.1Goodwin Ref: PRG-061WO173). In certain embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 34 and a VL sequence set forth in SEQ ID NO: 43; and the constant heavy chain comprises a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 47-270 (e.g., SEQ ID NO: 61 or SEQ ID NO: 173). In certain embodiments, the antibody comprises a human lambda light chain constant region sequence (e.g., any one of SEQ ID NOs: 421-424).

[0341] In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 425 and / or SEQ ID NO: 427. In certain embodiments, the anti-TSLP antibody comprises a light chain comprising an amino acid sequence set forth in SEQ ID NO: 426. In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 425 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 426. The heavy chain sequence of SEQ ID NO: 425 contains a C-terminal lysine, which may be cleaved off during manufacture or after administration, resulting in an antibody containing the heavy chain sequence of SEQ ID NO: 427. In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 427 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 426.

[0342] In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 428. In certain embodiments, the anti-TSLP antibody comprises a light chain comprising an amino acid sequence set forth in SEQ ID NO: 429. In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 428 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 429.

[0343] In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 430. In certain embodiments, the anti-TSLP antibody comprises a light chain comprising an amino acid sequence set forth in SEQ ID NO: 431. In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 430 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 431.

[0344] In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 432. In certain embodiments, the anti-TSLP antibody comprises a light chain comprising an amino acid sequence set forth in SEQ ID NO: 433. In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an108IPTS / 200090223.1Goodwin Ref: PRG-061WO amino acid sequence set forth in SEQ ID NO: 432 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 433.

[0345] In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 434. In certain embodiments, the anti-TSLP antibody comprises a light chain comprising an amino acid sequence set forth in SEQ ID NO: 435. In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 434 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 435.

[0346] In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 436. In certain embodiments, the anti-TSLP antibody comprises a light chain comprising an amino acid sequence set forth in SEQ ID NO: 437. In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 436 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 437.

[0347] In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 438. In certain embodiments, the anti-TSLP antibody comprises a light chain comprising an amino acid sequence set forth in SEQ ID NO: 439. In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 438 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 439.

[0348] In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 440. In certain embodiments, the anti-TSLP antibody comprises a light chain comprising an amino acid sequence set forth in SEQ ID NO: 441. In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 440 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 441.

[0349] In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 442. In certain embodiments, the anti-TSLP antibody comprises a light chain comprising an amino acid sequence set forth in SEQ ID NO: 443. In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 442 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 443.

[0350] In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 485. In certain embodiments, the anti-TSLP109IPTS / 200090223.1Goodwin Ref: PRG-061WO antibody comprises a light chain comprising an amino acid sequence set forth in SEQ ID NO: 486. In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 485 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 486.

[0351] In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 487. In certain embodiments, the anti-TSLP antibody comprises a light chain comprising an amino acid sequence set forth in SEQ ID NO: 488. In certain embodiments, the anti-TSLP antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 487 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 488.

[0352] In certain embodiments, the Fc region of an anti-TSLP antibody, or antigen binding fragment thereof, comprises one or more amino acid substitutions, wherein the one or more amino acid substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc region without the one or more amino acid substitutions. In certain embodiments, the one or more amino acid substitutions results in increased antibody half-life at pH 6.0 compared to an antibody comprising a wild-type Fc region. In certain embodiments, the anti-TSLP antibody has an increased half-life that is about 10,000-fold, 1,000-fold, 500-fold, 100-fold, 50-fold, 20-fold, 10-fold, 9-fold, 8-fold, 7- fold, 6-fold, 5-fold, 4.5-fold, 4-fold, 3.5-fold, 3-fold, 2.5-fold, 2-fold, 1.95-fold, 1.9-fold, 1.85- fold, 1.8-fold, 1.75-fold, 1.7-fold, 1.65-fold, 1.6-fold, 1.55-fold, 1.50-fold, 1.45-fold, 1.4-fold, 1.35-fold, 1.3-fold, 1.25-fold, 1.2-fold, 1.15-fold, 1.1-fold, or 1.05-fold longer compared to an anti-TSLP antibody comprising a wild-type Fc region. In certain embodiments, the antibody has an increased half-life that is about 10,000-fold, 1,000-fold, 500-fold, 100-fold, 50-fold, 20-fold, 10-fold, 9-fold, 8-fold, 7-fold, 6-fold, 5-fold, 4.5-fold, 4-fold, 3.5-fold, 3-fold, 2.5-fold, 2-fold, 1.95-fold, 1.9-fold, 1.85-fold, 1.8-fold, 1.75-fold, 1.7-fold, 1.65-fold, 1.6-fold, 1.55-fold, 1.50- fold, 1.45-fold, 1.4-fold, 1.35-fold, 1.3-fold, 1.25-fold, 1.2-fold, 1.15-fold, 1.1-fold, or 1.05-fold longer compared to tezepelumab. In certain embodiments, the anti-TSLP antibody has an increased half-life that is about 2.5-fold, 2.4-fold, 2.3-fold, 2.2-fold, 2.1-fold, 2.0-fold, 1.9-fold, or 1.8-fold longer compared to tezepelumab.

[0353] In certain embodiments, an anti-IL-4Ra antibody, or antigen binding fragment thereof, provided herein comprises a VH sequence and a VL sequence provided in TABLE 5 (e.g., a VH sequence and a VL sequence from the same row of TABLE 5), together with a heavy chain constant region set forth in any one of SEQ ID NOs: 47-270 and a light chain constant region. In certain embodiments, an anti-IL-4Ra antibody, or antigen binding fragment110IPTS / 200090223.1Goodwin Ref: PRG-061WO thereof, provided herein comprises a VH sequence and a VL sequence provided in TABLE 5, together with a heavy chain constant region selected from a sequence set forth in any one of SEQ ID NOs: 47-270 and a light chain constant region set forth in SEQ ID NO: 46.

[0354] In certain embodiments, the anti-IL-4Ra antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 295 and a VL sequence set forth in SEQ ID NO: 298; and the constant heavy chain comprises a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 47-270 (e.g., SEQ ID NO: 61 or SEQ ID NO: 173). In certain embodiments, the anti-IL-4Ra antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 296 and a VL sequence set forth in SEQ ID NO: 299; and the constant heavy chain comprises a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 47-270 (e.g., SEQ ID NO: 61 or SEQ ID NO: 173). In certain embodiments, the anti-IL-4Ra antibody, or antigen binding fragment thereof, comprises a VH sequence set forth in SEQ ID NO: 297 and a VL sequence set forth in SEQ ID NO: 300; and the constant heavy chain comprises a human IgG sequence selected from a sequence set forth in any one of SEQ ID NOs: 47-270 (e.g., SEQ ID NO: 61 or SEQ ID NO: 173). In certain embodiments, the anti-IL-4Ra antibody, or antigen binding fragment thereof, comprises a light chain constant region set forth in SEQ ID NO: 46.

[0355] In certain embodiments, the anti- IL-4Ra antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 444 and / or SEQ ID NO: 445. In certain embodiments, the anti- IL-4Ra antibody comprises a light chain comprising an amino acid sequence set forth in SEQ ID NO: 446. In certain embodiments, the anti- IL-4Ra antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 444 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 446. The heavy chain sequence of SEQ ID NO: 444 contains a C-terminal lysine, which may be cleaved off during manufacture or after administration, resulting in an antibody containing the heavy chain sequence of SEQ ID NO: 445. In certain embodiments, the anti- IL-4Ra antibody comprises a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 445 and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 446.

[0356] In certain embodiments, the Fc region of an anti-IL-4Ra antibody, or antigen binding fragment thereof, comprises one or more amino acid substitutions, wherein the one or more amino acid substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc region without the one or more amino acid substitutions. In certain embodiments, the one or more amino acid substitutions results in increased antibody half-life at pH 6.0 compared to an antibody comprising a wild-type111IPTS / 200090223.1Goodwin Ref: PRG-061WOFc region. In certain embodiments, the anti-IL-4Ra antibody has an increased half-life that is about 10,000-fold, 1,000-fold, 500-fold, 100-fold, 50-fold, 20-fold, 10-fold, 9-fold, 8-fold, 7- fold, 6-fold, 5-fold, 4.5-fold, 4-fold, 3.5-fold, 3-fold, 2.5-fold, 2-fold, 1.95-fold, 1.9-fold, 1.85- fold, 1.8-fold, 1.75-fold, 1.7-fold, 1.65-fold, 1.6-fold, 1.55-fold, 1.50-fold, 1.45-fold, 1.4-fold, 1.35-fold, 1.3-fold, 1.25-fold, 1.2-fold, 1.15-fold, 1.1-fold, or 1.05-fold longer compared to an anti-IL-4Ra antibody comprising a wild-type Fc region. In certain embodiments, the anti-IL-4Ra antibody has an increased half-life that is about 10,000-fold, 1,000-fold, 500-fold, 100-fold, 50- fold, 20-fold, 10-fold, 9-fold, 8-fold, 7-fold, 6-fold, 5-fold, 4.5-fold, 4-fold, 3.5-fold, 3-fold, 2.5- fold, 2-fold, 1.95-fold, 1.9-fold, 1.85-fold, 1.8-fold, 1.75-fold, 1.7-fold, 1.65-fold, 1.6-fold, 1.55- fold, 1.50-fold, 1.45-fold, 1.4-fold, 1.35-fold, 1.3-fold, 1.25-fold, 1.2-fold, 1.15-fold, 1.1-fold, or 1.05-fold longer compared to dupilumab. In certain embodiments, the anti-IL-4Ra antibody has an increased half-life that is about 2.5-fold, 2.4-fold, 2.3-fold, 2.2-fold, 2.1-fold, 2.0-fold, 1.9- fold, or 1.8-fold longer compared to dupilumab.

[0357] In certain embodiments, the Fc region of an anti-TSLP antibody and / or an anti-IL- 4Ra antibody comprises one or more amino acid substitutions, wherein the one or more amino acid substitutions result in a decrease in one or more of ADCC activity, ADCP activity, or CDC activity compared with the Fc region without the one or more amino acid substitutions.

[0358] In certain embodiments, the one or more amino acid substitutions is selected from the group consisting of S228P (SP), M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W (or, e.g., L242A, L243A, L239A, L240A, M260Y, S262T, T264E, M257Y, S259T, or T261E using direct numbering). In certain embodiments, the one or more amino acid substitutions comprises a specific combination of amino acid substitutions selected from the group consisting of M428L / N434S (LS), M252Y / S254T / T256E (YTE) using EU numbering or M257Y / S259T / T261E (YTE) using direct numbering or M260Y / S262T / T264E (YTE) using direct numbering, T250Q / M428L, T307A / E380A / N434A, T256D / T307Q (DQ), T256D / T307W (DW), M252Y / T256D (YD), T307Q / Q311 V / A378V (QVV), T256D / H285D / T307R / Q311 V / A378V (DDRVV), L309D / Q311H / N434S (DHS), S228P / L235E (SPLE), L234A / L235A (LALA) using EU numbering or L239A / L240A (LALA) using direct numbering or L242A / L243 A (LALA) using direct numbering, M428L / N434A (LA), L235A / G237A (LAGA), L234A / L235A / G237A (LALAGA), L234A / L235A / P329G (LALAPG), D265A / YTE, LALA / YTE, LAGA / YTE, LALAGA / YTE, LALAPG / YTE, N297A / LS, D265A / LS, LALA / LS, LALAGA / LS, LALAPG / LS, N297A / DHS, D265A / DHS, LALA / DHS, LAGA / DHS, LALAGA / DHS,112IPTS / 200090223.1Goodwin Ref: PRG-061WOLALAPG / DHS, SP / YTE, SPLE / YTE, SP / LS, SPLE / LS, SP / DHS, SPLE / DHS, N297A / LA, D265A / LA, LALA / LA, LAGA / LA, LALAGA / LA, LALAPG / LA, N297A / N434A, D265A / N434A, LALA / N434A, LAGA / N434A, LALAGA / N434A, LALAPG / N434A, N297A / N434W, D265A / N434W, LALA / N434W, LAGA / N434W, LALAGA / N434W, LALAPG / N434W, N297A / DQ, D265A / DQ, LALA / DQ, LAGA / DQ, LALAGA / DQ, LALAPG / DQ, N297A / DW, D265A / DW, LALA / DW, LAGA / DW, LALAGA / DW, LALAPG / DW, N297A / YD, D265A / YD, LALA / YD, LAGA / YD, LALAGA / YD, LALAPG / YD, T307Q / Q311V / A378V (QVV), N297A / QVV, D265A / QVV, LALA / QVV, LAGA / QVV, LALAGA / QVV, LALAPG / QVV, DDRVV, N297A / DDRVV, D265A / DDRVV, LALA / DDRVV, LAGA / DDRVV, LALAGA / DDRVV, and LALAPG / DDRVV.

[0359] Although the EU numbering system is typically used to identify the positions of the various Fc mutations described herein, direct numbering can also be used. For example, in certain embodiments, an antibody described herein comprises an Fc region with YTE mutations at positions 257, 259, and 261 or 260, 262, and 264, respectively. In certain embodiments, an antibody described herein comprises an Fc region with LALA mutations at positions 239 and 240 or 242 and 243, respectively. In certain embodiments, an antibody (e.g., a TSLP antibody) described herein comprises an Fc region (e.g., a human IgGl Fc region) with YTE mutations at positions 257, 259, and 261, respectively, and with LALA mutations at positions 239 and 240, respectively. In certain embodiments, an antibody (e.g., an IL-4Ra antibody) described herein comprises an Fc region (e.g., a human IgGl Fc region) with YTE mutations at positions 260, 262, and 264 and with LALA mutations at positions 242 and 243, respectively. In certain embodiments, a TSLP antibody described herein comprises the VH and VL of Antibody 5 and an Fc region (e.g., a human IgGl Fc region) comprising YTE mutations at positions 257, 259, and 261 (M257Y / S259T / T261E), respectively, and with LALA mutations at positions 239 and 240 (L239A / L240A), respectively (e.g., as shown in the heavy chain sequences of SEQ ID NOs: 425 and 427). In certain embodiments, an IL-4Ra antibody described herein comprises the VH and VL of Construct 38 and an Fc region comprising YTE mutations at positions 260, 262, and 264 (M260Y / S262T / T264E), respectively and with LALA mutations at positions 242 and 243 (L242A / L243A), respectively (e.g., as shown in the heavy chain sequences of SEQ ID NOs: 444 and 445).

[0360] In certain embodiments the human Fc region comprises a human IgGl Fc region with LALA mutations. In certain embodiments, the human Fc region comprises a human IgGl Fc region with YTE mutations. In certain embodiments, the human Fc region comprises a human IgGl Fc region with LALA and YTE mutations. In certain embodiments, when direct numbering113IPTS / 200090223.1Goodwin Ref: PRG-061WO is used, “YTE” and “LALA” mutations can be located at different amino acid position numbers. For example, a human Fc region can comprise a human IgGl Fc region with LALA mutations at L239A / L240A and / or YTE mutations at M257Y / S259T / T261E. As another example, a human Fc region can comprise a human IgGl Fc region with LALA mutations at L242A / L243A and / or YTE mutations at M260Y / S262T / T264E.

[0361] In certain embodiments, the Fc region binds an Fey Receptor selected from the group consisting of: FcyRI, FcyRIIa, FcyRIIb, FcyRIIc, FcyRIIIa, and FcyRIIIb. In certain embodiments, the Fc region binds an Fey Receptor with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region.TSLP Binding

[0362] The affinity of an anti-TSLP antibody, or antigen binding fragment thereof, for TSLP can be represented by the dissociation equilibrium constant (KD). The kinetic components that contribute to the dissociation equilibrium constant are described in more detail below. Affinity can be measured by common methods known in the art, including those described herein, such as surface plasmon resonance (SPR) technology (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO®).

[0363] With regard to the binding of an antibody to a target molecule, the terms “bind,” “specific binding,” “specifically binds to,” “specific for,” “selectively binds,” and “selective for” a particular antigen (e.g., a polypeptide target) or an epitope on a particular antigen mean binding that is measurably different from a non-specific or non-selective interaction (e.g., with a non-target molecule). Specific binding can be measured, for example, by measuring binding to a target molecule (z.e., TSLP) and comparing it to binding to a non-target molecule. Specific binding can also be determined by competition with a control molecule that mimics the epitope recognized on the target molecule. In that case, specific binding is indicated if the binding of the antibody to the target molecule is competitively inhibited by the control molecule. In some embodiments, the affinity of an anti-TSLP antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 50% of the affinity for TSLP. In some embodiments, the affinity of an anti-TSLP antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 40% of the affinity for TSLP. In some embodiments, the affinity of an anti- TSLP antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 30% of the affinity for TSLP. In some embodiments, the affinity of an anti-TSLP antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 20% of the affinity114IPTS / 200090223.1Goodwin Ref: PRG-061WO for TSLP. In some embodiments, the affinity of an anti-TSLP antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 10% of the affinity for TSLP. In some embodiments, the affinity of an anti-TSLP antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 1% of the affinity for TSLP or. In some embodiments, the affinity of an anti-TSLP antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 0.1% of the affinity for TSLP.

[0364] In certain embodiments, the antibody, or antigen binding fragment thereof, binds a TSLP sequence set forth in SEQ ID NO: 365 or 366.

[0365] In certain embodiments, the antibody, or antigen binding fragment thereof, binds to a TSLP sequence set forth in SEQ ID NO: 365 or 366 with a KD of less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, or 9 x 10'9M, as measured by surface plasmon resonance (SPR). In certain embodiments, the antibody, or antigen binding fragment thereof, binds to a TSLP sequence set forth in SEQ ID NO: 365 or 366 with a KD of less than or equal to about 1 x 10'10M, as measured by surface plasmon resonance (SPR). In certain embodiments, the antibody, or antigen binding fragment thereof, binds to human TSLP with a KD of less than or equal to about 1 x 10'9M, as measured by surface plasmon resonance (SPR).

[0366] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein binds TSLP with a KD of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x 10'8M, as measured by ELISA or any other suitable method known in the art. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein binds TSLP with a KD of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x IO’9M, as measured by ELISA or any other suitable method known in the art.

[0367] In some embodiments, the KD of the antibody, or antigen binding fragment thereof, provided herein for the binding of TSLP is between about 0.001-0.01, 0.01-0.1, 0.01-0.05, 0.05- 0.1, 0.1-0.5, 0.5-1, 0.25-0.75, 0.25-0.5, 0.5-0.75, 0.75-1, 0.75-2, 1.1-1.2, 1.2-1.3, 1.3-1.4, 1.4- 1.5, 1.5-1.6, 1.6-1.7, 1.7-1.8, 1.8-1.9, 1.9-2, 1-2, 1-5, 2-7, 3-8, 3-5, 4-6, 5-7, 6-8, 7-9, 7-10, or 5- 10 x 10'8M, as measured by ELISA or any other suitable method known in the art. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein binds TSLP with a KD of less than or equal to about 1 x 10'8M, or less than or equal to about 1 x 10'9M as measured by ELISA or any other suitable method known in the art.115IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0368] In some embodiments, the antibody, or antigen binding fragment thereof, provided herein binds TSLP with a KD of less than or equal to about 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.98, 1.95, 1.9, 1.85, 1.8, 1.75, 1.7, 1.65, 1.6, 1.55, 1.50, 1.45, 1.4, 1.3, 1.2, 1.1, 1, 0.9, 0.85, 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.01, 0.005, 0.001, 0.0005, or 0.0001 x 10'8M, or less, as measured by ELISA or any other suitable method known in the art . In some embodiments, the antibody, or antigen binding fragment thereof, provided herein binds TSLP with a KD between 5-3, 4-2, 3-1, 1.9-1.8, 1.8-1.7, 1.7-1.6, 1.6-1.5, 1.9-1.5, 1.5-1, 1-0.8, 1-0.5, 0.9-0.6, 0.7-0.4, 0.6-0.2, 0.5-0.3, 0.3-0.2, 0.2-0.1, 0.1-0.01, 0.01-0.001, or 0.001-0.0001 x 10'8M as measured by ELISA or any other suitable method known in the art.

[0369] In some embodiments, the antibody, or antigen binding fragment thereof, provided herein binds FcRn with an affinity at pH 7.4 compared to pH 6.0 at a ratio (pH 7.4 / pH 6.0) of about 10,000, 1,000, 500, 100, 50, 20, 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.95, 1.9, 1.85, 1.8, 1.75, 1.7, 1.65, 1.6, 1.55, 1.50, 1.45, 1.4, 1.3, 1.2, 1.1, or 1.05, as measured by ELISA or any other suitable method known in the art. In some embodiments, the antibody, or antigen binding fragment thereof, provided herein binds FcRn with an affinity at pH 6.0 compared to pH 7.4 at a ratio (pH 6.0 / pH 7.4) of about 1-0.8, 1-0.5, 0.9-0.6, 0.7-0.4, 0.6-0.2, 0.5-0.3, 0.3-0.2, 0.2-0.1, 0.1-0.01, 0.01-0.001, or 0.001-0.0001 x 10'8M as measured by ELISA or any other suitable method known in the art.IL-4Ra Binding

[0370] The affinity of an anti- IL-4Ra antibody, or antigen binding fragment thereof, for IL- 4Ra can be represented by the dissociation equilibrium constant (KD). The kinetic components that contribute to the dissociation equilibrium constant are described in more detail below. Affinity can be measured by common methods known in the art, including those described herein, such as surface plasmon resonance (SPR) technology (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO®).

[0371] With regard to the binding of an antibody, or antigen binding fragment thereof, to a target molecule, the terms “bind,” “specific binding,” “specifically binds to,” “specific for,” “selectively binds,” and “selective for” a particular antigen (e.g., a polypeptide target) or an epitope on a particular antigen mean binding that is measurably different from a non-specific or non-selective interaction (e.g., with a non-target molecule). Specific binding can be measured, for example, by measuring binding to a target molecule (z.e., IL-4Ra) and comparing it to binding to a non-target molecule. Specific binding can also be determined by competition with a116IPTS / 200090223.1Goodwin Ref: PRG-061WO control molecule that mimics the epitope recognized on the target molecule. In that case, specific binding is indicated if the binding of the antibody to the target molecule is competitively inhibited by the control molecule. In some embodiments, the affinity of an anti-IL-4Ra antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 50% of the affinity for IL-4Ra. In some embodiments, the affinity of an anti-IL-4Ra antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 40% of the affinity for IL- 4Ra. In some embodiments, the affinity of an anti-IL-4Ra antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 30% of the affinity for IL-4Ra. In some embodiments, the affinity of an anti-IL-4Ra antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 20% of the affinity for IL-4Ra. In some embodiments, the affinity of an anti-IL-4Ra antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 10% of the affinity for IL-4Ra. In some embodiments, the affinity of an anti-IL-4Ra antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 1% of the affinity for IL-4Ra. In some embodiments, the affinity of an anti-IL-4Ra antibody, or antigen binding fragment thereof, for a non-target molecule is less than about 0.1% of the affinity for IL-4Ra.

[0372] In certain embodiments, the antibody, or antigen binding fragment thereof, binds an IL-4Ra sequence set forth in any one of SEQ ID NOs: 301-303.

[0373] In certain embodiments, the antibody, or antigen binding fragment thereof, binds to an IL-4Ra sequence set forth in any one of SEQ ID NOs: 301-303 with a KD of less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, or 9 x 10'9M, as measured by surface plasmon resonance (SPR). In certain embodiments, the antibody, or antigen binding fragment thereof, binds to an IL-4Ra sequence set forth in any one of SEQ ID NOs: 301-303 with a KD of less than or equal to about 1 x 10'10M, as measured by surface plasmon resonance (SPR). In certain embodiments, the antibody, or antigen binding fragment thereof, binds to human IL-4Ra with a KD of less than or equal to about 1 x 10'9M, as measured by surface plasmon resonance (SPR).

[0374] In some embodiments, an antibody, or antigen binding fragment thereof, provided herein binds IL-4Ra with a KD of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x 10'8M, as measured by ELISA or any other suitable method known in the art. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein binds IL-4Ra with a KD of less than or equal to about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2,117IPTS / 200090223.1Goodwin Ref: PRG-061WO1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 x IO’9M, as measured by ELISA or any other suitable method known in the art.

[0375] In some embodiments, the KD of the antibody, or antigen binding fragment thereof, provided herein for the binding of IL-4Ra is between about 0.001-0.01, 0.01-0.1, 0.01-0.05, 0.05-0.1, 0.1-0.5, 0.5-1, 0.25-0.75, 0.25-0.5, 0.5-0.75, 0.75-1, 0.75-2, 1.1-1.2, 1.2-1.3, 1.3-1.4,1.4-1.5, 1.5-1.6, 1.6-1.7, 1.7-1.8, 1.8-1.9, 1.9-2, 1-2, 1-5, 2-7, 3-8, 3-5, 4-6, 5-7, 6-8, 7-9, 7-10, or 5-10 x 10'8M, as measured by ELISA or any other suitable method known in the art. In some embodiments, an antibody, or antigen binding fragment thereof, provided herein binds IL-4Ra with a KD of less than or equal to about 1 x 10'8M, or less than or equal to about 1 x 10'9M as measured by ELISA or any other suitable method known in the art.

[0376] In some embodiments, the antibody, or antigen binding fragment thereof, provided herein binds IL-4Ra with a KD of less than or equal to about 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.98, 1.95, 1.9, 1.85, 1.8, 1.75, 1.7, 1.65, 1.6, 1.55, 1.50, 1.45, 1.4, 1.3, 1.2, 1.1, 1, 0.9, 0.85, 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.01, 0.005, 0.001, 0.0005, or 0.0001 x 10'8M, or less, as measured by ELISA or any other suitable method known in the art . In some embodiments, the antibody, or antigen binding fragment thereof, provided herein binds IL-4Ra with a KD between 5-3, 4-2, 3-1, 1.9-1.8, 1.8-1.7, 1.7-1.6, 1.6-1.5, 1.9-1.5,1.5-1, 1-0.8, 1-0.5, 0.9-0.6, 0.7-0.4, 0.6-0.2, 0.5-0.3, 0.3-0.2, 0.2-0.1, 0.1-0.01, 0.01-0.001, or 0.001-0.0001 x 10'8M as measured by ELISA or any other suitable method known in the art.

[0377] In some embodiments, the antibody, or antigen binding fragment thereof, provided herein binds FcRn with an affinity at pH 7.4 compared to pH 6.0 at a ratio (pH 7.4 / pH 6.0) of about 10,000, 1,000, 500, 100, 50, 20, 10, 9, 8, 7, 6, 5, 4.5, 4, 3.5, 3, 2.5, 2, 1.95, 1.9, 1.85, 1.8, 1.75, 1.7, 1.65, 1.6, 1.55, 1.50, 1.45, 1.4, 1.3, 1.2, 1.1, or 1.05, as measured by ELISA or any other suitable method known in the art. In some embodiments, the antibody, or antigen binding fragment thereof, provided herein binds FcRn with an affinity at pH 6.0 compared to pH 7.4 at a ratio (pH 6.0 / pH 7.4) of about 1-0.8, 1-0.5, 0.9-0.6, 0.7-0.4, 0.6-0.2, 0.5-0.3, 0.3-0.2, 0.2-0.1, 0.1-0.01, 0.01-0.001, or 0.001-0.0001 x 10'8M as measured by ELISA or any other suitable method known in the art.Combinations of Anti-TSLP Antibodies and Anti-IL-4Ra Antibodies

[0378] Any of the anti-TSLP antibodies, or antigen binding fragments thereof, described herein can be combined with any of the anti-IL-4Ra antibodies, or antigen binding fragments thereof, described herein (e.g., combined in a single composition or used in combination for118IPTS / 200090223.1Goodwin Ref: PRG-061WO treatment of a subject). In some embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, described herein, is selected from TABLE 3, TABLE 4, TABLE 12, or TABLE 13 and the anti-IL-4Ra antibody, or antigen fragment thereof, described herein is selected from TABLE 5.

[0379] In some embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, is Antibody 5 and the anti-IL-4Ra antibody, or antigen fragment thereof, described herein is selected from TABLE 5. In some embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, is Antibody 7 and the anti-IL-4Ra antibody, or antigen fragment thereof, described herein is selected from TABLE 5. In some embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, is Antibody 23 and the anti-IL-4Ra antibody, or antigen fragment thereof, described herein is selected from TABLE 5. In some embodiments, the anti- TSLP antibody, or antigen binding fragment thereof, is Antibody 29 and the anti-IL-4Ra antibody, or antigen fragment thereof, described herein is selected from TABLE 5. In some embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, is Antibody 38 and the anti-IL-4Ra antibody, or antigen fragment thereof, described herein is selected from TABLE 5. In some embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, is Antibody 39 and the anti-IL-4Ra antibody, or antigen fragment thereof, described herein is selected from TABLE 5. In some embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, is Antibody 31 and the anti-IL-4Ra antibody, or antigen fragment thereof, described herein is selected from TABLE 5. In some embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, is Antibody 36 and the anti-IL-4Ra antibody, or antigen fragment thereof, described herein is selected from TABLE 5. In some embodiments, the anti- TSLP antibody, or antigen binding fragment thereof, is Antibody 44 and the anti-IL-4Ra antibody, or antigen fragment thereof, described herein is selected from TABLE 5. In some embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, is Antibody 51 and the anti-IL-4Ra antibody, or antigen fragment thereof, described herein is selected from TABLE 5. In some embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, is Antibody 59 and the anti-IL-4Ra antibody, or antigen fragment thereof, described herein is selected from TABLE 5. In some embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, is tezepelumab and the anti-IL-4Ra antibody, or antigen fragment thereof, described herein is selected from TABLE 5.

[0380] In some embodiments, the anti-IL-4Ra antibody, or antigen binding fragment thereof, is Construct 38 (mAb471) and the anti-TSLP antibody, or antigen fragment thereof, described herein is selected from TABLE 4. In some embodiments, the anti-IL-4Ra antibody, or antigen119IPTS / 200090223.1Goodwin Ref: PRG-061WO binding fragment thereof, is Construct 38 (mAb471) and the anti-TSLP antibody, or antigen fragment thereof, described herein is selected from TABLE 13. In some embodiments, the anti- IL-4Ra antibody, or antigen binding fragment thereof, is Construct 13 (mAb422) and the anti- TSLP antibody, or antigen fragment thereof, described herein is selected from TABLE 4. In some embodiments, the anti-IL-4Ra antibody, or antigen binding fragment thereof, is Construct 13 (mAb422) and the anti-TSLP antibody, or antigen fragment thereof, described herein is selected from TABLE 13. In some embodiments, the anti-IL-4Ra antibody, or antigen binding fragment thereof, is Construct 24 (mAb432) and the anti-TSLP antibody, or antigen fragment thereof, described herein is selected from TABLE 4. In some embodiments, the anti-IL-4Ra antibody, or antigen binding fragment thereof, is Construct 24 (mAb432) and the anti-TSLP antibody, or antigen fragment thereof, described herein is selected from TABLE 13. In some embodiments, the anti-IL-4Ra antibody, or antigen binding fragment thereof, is dupilumab and the anti-TSLP antibody, or antigen fragment thereof, described herein is selected from TABLE 4. In some embodiments, the anti-IL-4Ra antibody, or antigen binding fragment thereof, is dupilumab and the anti-TSLP antibody, or antigen fragment thereof, described herein is selected from TABLE 13. In some embodiments, the anti-IL-4Ra antibody, or antigen binding fragment thereof, is stapokibart and the anti-TSLP antibody, or antigen fragment thereof, described herein is selected from TABLE 4. In some embodiments, the anti-IL-4Ra antibody, or antigen binding fragment thereof, is stapokibart and the anti-TSLP antibody, or antigen fragment thereof, described herein is selected from TABLE 13. In some embodiments, the anti-IL-4Ra antibody, or antigen binding fragment thereof, is rademikibart and the anti-TSLP antibody, or antigen fragment thereof, described herein is selected from TABLE 4. In some embodiments, the anti- IL-4Ra antibody, or antigen binding fragment thereof, is rademikibart and the anti-TSLP antibody, or antigen fragment thereof, described herein is selected from TABLE 13.

[0381] Exemplary combinations of anti-TSLP antibodies and anti-IL-4Ra antibodies are set forth in TABLE 8, below.TABLE 8. Combinations of anti-TSLP antibodies and anti-IL-4Ra antibodies120IPTS / 200090223.1Goodwin Ref: PRG-061WO121IPTS / 200090223.1Goodwin Ref: PRG-061WO122IPTS / 200090223.1Goodwin Ref: PRG-061WO123IPTS / 200090223.1Goodwin Ref: PRG-061WO124IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0382] In some embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, and the anti-IL-4Ra antibody, or antigen fragment thereof, are combined in a single composition (e.g., both antibodies, or antigen binding fragments thereof, are co-formulated in a single pharmaceutical composition with one or more pharmaceutically acceptable excipients). The composition can be administered to a subject (e.g., a mammalian subject, such as a human subject) for treatment of a disease or disorder in the subject, such as an inflammatory disorder or disease (e.g., atopic dermatitis, asthma, or COPD).

[0383] In some embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, and the anti-IL-4Ra antibody, or antigen fragment thereof, are in separate compositions (e.g., a first pharmaceutical composition containing an anti-TSLP antibody, or an antigen binding fragment thereof, and a pharmaceutically acceptable excipient and a second pharmaceutical composition containing an anti-IL-4Ra antibody, or an antigen binding fragment thereof, and a pharmaceutically acceptable excipient). These separate compositions can be co-administered to a subject (e.g., a mammalian subject, such as a human subject) for treatment of a disease or125IPTS / 200090223.1Goodwin Ref: PRG-061WO disorder in the subject, such as an inflammatory disorder or disease e.g., atopic dermatitis, asthma, or COPD). In some embodiments, the composition containing the anti-TSLP antibody, or an antigen binding fragment thereof, is administered at about the same time as the composition containing the anti-IL-4Ra antibody, or an antigen binding fragment thereof. In other embodiments, the composition containing the anti-TSLP antibody, or an antigen binding fragment thereof, and the composition containing the anti-IL-4Ra antibody, or an antigen binding fragment thereof are administered sequentially, such that the action of the two overlaps and their combined effect is such that the reduction in a symptom, or other parameter related to the disease or disorder is greater than what would be observed with one antibody, or antigen binding fragment thereof, delivered alone or in the absence of the other. In some embodiments, the anti-TSLP antibody, or antigen binding fragment thereof, is administered before the anti-IL- 4Ra antibody, or antigen binding fragment thereof, by intervals ranging from minutes, hours, days to weeks. In some embodiments, the anti-IL-4Ra antibody, or antigen binding fragment thereof, is administered before the anti-TSLP antibody, or antigen binding fragment thereof, by intervals ranging from minutes, hours, days to weeks.Pharmaceutical Compositions

[0384] The present application provides compositions comprising the antibodies or antigen binding fragments thereof described herein, including pharmaceutical compositions comprising any one or more of the antibodies, or antigen binding fragments thereof, described herein with one or more pharmaceutically acceptable excipients. In some embodiments the composition is sterile. The pharmaceutical compositions generally comprise an effective amount of a TSLP antibody, or an antigen binding fragment thereof, and / or an IL-4Ra antibody, or an antigen binding fragment thereof.

[0385] These compositions can comprise, in addition to one or more of the antibodies, or antigen binding fragments thereof, disclosed herein, a pharmaceutically acceptable excipient, carrier, buffer, stabilizer or other materials well known to those skilled in the art. Such materials should be non-toxic and should not interfere with the efficacy of the active ingredient. The precise nature of the carrier or other material can depend on the route of administration, e.g. oral, intravenous, cutaneous or subcutaneous, nasal, intramuscular, intraperitoneal routes.

[0386] Pharmaceutical compositions for oral administration can be in tablet, capsule, powder or liquid form. A tablet can include a solid carrier such as gelatin or an adjuvant. Liquid pharmaceutical compositions generally include a liquid carrier such as water, petroleum, animal126IPTS / 200090223.1Goodwin Ref: PRG-061WO or vegetable oils, mineral oil or synthetic oil. Physiological saline solution, dextrose or other saccharide solution or glycols such as ethylene glycol, propylene glycol or polyethylene glycol can be included.

[0387] For intravenous, cutaneous or subcutaneous injection, or injection at the site of affliction, the active ingredient will be in the form of a parenterally acceptable aqueous solution which is pyrogen-free and has suitable pH, isotonicity and stability. Those of relevant skill in the art are well able to prepare suitable solutions using, for example, isotonic vehicles such as Sodium Chloride Injection, Ringer's Injection, Lactated Ringer's Injection. Preservatives, stabilizers, buffers, antioxidants and / or other additives can be included, as required.

[0388] For the anti-TSLP antibody, or antigen binding fragment thereof, and / or the anti-IL- 4Ra antibody, or antigen binding fragment thereof, that are to be given to an individual, administration is preferably in a “therapeutically effective amount” or “prophylactically effective amount” (as the case can be, although prophylaxis can be considered therapy), this being sufficient to show benefit to the individual. The actual amount administered, and rate and timecourse of administration, will depend on a number of factors, e.g., the nature and severity of the disease being treated. Prescription of treatment, e.g. decisions on dosage etc., can be within the responsibility of general practitioners and other medical doctors, and typically takes account of the disorder to be treated, the condition of the individual patient, the site of delivery, the method of administration and other factors known to practitioners. Examples of the techniques and protocols mentioned above can be found in Remington's Pharmaceutical Sciences, 16th edition, Osol, A. (ed), 1980.

[0389] A composition comprising an antibody or combination of antibodies described herein can be administered alone or in combination with other treatments, either simultaneously or sequentially dependent upon the condition to be treated.MethodsMethods of Preparation

[0390] Antibodies, or antigen binding fragments thereof, described herein can be produced using recombinant methods and compositions, e.g., as described in U.S. Pat. No. 4,816,567. In one embodiment, isolated nucleic acid encoding an antibody, or antigen binding fragment thereof, described herein is provided. Such nucleic acid may encode an amino acid sequence comprising the VL and / or an amino acid sequence comprising the VH of the antibody (e.g., the light and / or heavy chains of the antibody) or an amino acid sequence comprising the VHH of a127IPTS / 200090223.1Goodwin Ref: PRG-061WO single domain antibody. In a further embodiment, one or more vectors (e.g., expression vectors) comprising such nucleic acid are provided. In one embodiment, the nucleic acid is provided in a multi ci str onic vector. In a further embodiment, a host cell comprising such nucleic acid is provided. In one such embodiment, a host cell comprises (e.g., has been transformed with): (1) a vector comprising a nucleic acid that encodes an amino acid sequence comprising the VL of the antibody and an amino acid sequence comprising the VH of the antigen-binding polypeptide construct, or (2) a first vector comprising a nucleic acid that encodes an amino acid sequence comprising the VL of the antigen-binding polypeptide construct and a second vector comprising a nucleic acid that encodes an amino acid sequence comprising the VH of the antigen-binding polypeptide construct. In one embodiment, the host cell is eukaryotic, e.g. a Chinese Hamster Ovary (CHO) cell, or human embryonic kidney (HEK) cell, or lymphoid cell (e.g., YO, NSO, Sp20 cell). In one embodiment, a method of making an antibody is provided, wherein the method comprises culturing a host cell comprising nucleic acid encoding the antibody, as provided above, under conditions suitable for expression of the antibody, and optionally recovering the antibody from the host cell (or host cell culture medium).

[0391] For recombinant production of the antibody, a nucleic acid encoding an antibody, e.g., as described above, is isolated and inserted into one or more vectors for further cloning and / or expression in a host cell. Such nucleic acid may be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the antibody).

[0392] When an antibody or variant thereof is recombinantly produced by the host cells, the protein in certain embodiments is present at about 30%, about 25%, about 20%, about 15%, about 10%, about 5%, about 4%, about 3%, about 2%, or about 1% or less of the dry weight of the cells. When the antibody or variant thereof is recombinantly produced by the host cells, the protein, in certain embodiments, is present in the culture medium at about 5 g / L, about 4 g / L, about 3 g / L, about 2 g / L, about 1 g / L, about 750 mg / L, about 500 mg / L, about 250 mg / L, about 100 mg / L, about 50 mg / L, about 10 mg / L, or about 1 mg / L or less of the dry weight of the cells. In certain embodiments, “substantially purified” antibody produced by the methods described herein, has a purity level of at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, specifically, a purity level of at least about 75%, 80%, 85%, and more specifically, a purity level of at least about 90%, a purity level of at least about 95%, a purity level of at least about 99% or greater as determined by appropriate methods such as SDS / PAGE analysis, RP-HPLC, SEC, and capillary electrophoresis.128IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0393] Suitable host cells for cloning or expression of antibody-encoding vectors include prokaryotic or eukaryotic cells described herein.

[0394] Recombinant host cells or host cells are cells that include an exogenous polynucleotide, regardless of the method used for insertion, for example, direct uptake, transduction, f-mating, or other methods known in the art to create recombinant host cells. The exogenous polynucleotide may be maintained as a nonintegrated vector, for example, a plasmid, or alternatively, may be integrated into the host genome. Host cells can include CHO, derivatives of CHO, NSO, Sp2O, CV-1, VERO-76, HeLa, HepG2, Per.C6, or BHK.

[0395] For example, antibody may be produced in bacteria, in particular when glycosylation and Fc effector function are not needed. For expression of antibody fragments and polypeptides in bacteria, see, e.g., U.S. Pat. Nos. 5,648,237, 5,789,199, and 5,840,523. (See also Charlton, Methods in Molecular Biology, Vol. 248 (B.K.C. Lo, ed., Humana Press, Totowa, N.J., 2003), pp. 245-254, describing expression of antibody fragments in E. coli.) After expression, the antibody may be isolated from the bacterial cell paste in a soluble fraction and can be further purified.

[0396] In addition to prokaryotes, eukaryotic microbes such as filamentous fungi or yeast are suitable cloning or expression hosts for antibody-encoding vectors, including fungi and yeast strains whose glycosylation pathways have been “humanized,” resulting in the production of an antibody with a partially or fully human glycosylation pattern. See Gemgross, Nat. Biotech. 22: 1409-1414 (2004), and Li el al., Nat. Biotech. 24:210-215 (2006).

[0397] Suitable host cells for the expression of glycosylated antibodies are also derived from multicellular organisms (invertebrates and vertebrates). Examples of invertebrate cells include plant and insect cells. Numerous baculoviral strains have been identified which may be used in conjunction with insect cells, particularly for transfection of Spodoptera frugiperda cells.

[0398] Plant cell cultures can also be utilized as hosts. See, e.g., U.S. Pat. Nos. 5,959,177, 6,040,498, 6,420,548, 7,125,978, and 6,417,429 (describing PLANTIBODIES™ technology for producing antibodies in transgenic plants).

[0399] Vertebrate cells may also be used as hosts. For example, mammalian cell lines that are adapted to grow in suspension may be useful. Other examples of useful mammalian host cell lines are monkey kidney CV1 line transformed by SV40 (COS-7); human embryonic kidney line (293 or 293T cells as described, e.g., in Graham et al., J. Gen Virol. 36:59 (1977)); baby hamster kidney cells (BHK); mouse sertoli cells (TM4 cells as described, e.g., in Mather, Biol. Reprod. 23:243-251 (1980)); monkey kidney cells (CV1); African green monkey kidney cells (VERO- 76); human cervical carcinoma cells (HELA); canine kidney cells (MDCK; buffalo rat liver cells129IPTS / 200090223.1Goodwin Ref: PRG-061WO(BRL 3 A); human lung cells (W138); human liver cells (Hep G2); mouse mammary tumor (MMT 060562); TRI cells, as described, e.g., in Mather et al., Annals N.Y. Acad. Sci. 383:44-68 (1982); MRC 5 cells; and FS4 cells. Other useful mammalian host cell lines include Chinese hamster ovary (CHO) cells, including DHFR- CHO cells (Urlaub el al.. Proc. Natl. Acad. Sci. USA 77:4216 (1980)); and myeloma cell lines such as Y0, NSO and Sp2 / 0. For a review of certain mammalian host cell lines suitable for antibody production, see, e.g., Yazaki and Wu, Methods in Molecular Biology, Vol. 248 (B.K.C. Lo, ed., Humana Press, Totowa, N.J.), pp. 255- 268 (2003).

[0400] In one embodiment, the antibodies described herein are produced in stable mammalian cells, by a method comprising: transfecting at least one stable mammalian cell with: nucleic acid encoding the antibody, in a predetermined ratio; and expressing the nucleic acid in the at least one mammalian cell. In some embodiments, the predetermined ratio of nucleic acid is determined in transient transfection experiments to determine the relative ratio of input nucleic acids that results in the highest percentage of the antibody in the expressed product.

[0401] In some embodiments, the method of producing an antibody in stable mammalian cells as described herein results in an expression product of the at least one stable mammalian cell comprising a larger percentage of the desired glycosylated antibody as compared to the monomeric heavy or light chain polypeptides, or other antibodies.

[0402] In some embodiments, the method of producing a glycosylated antibody in stable mammalian cells described herein comprises identifying and purifying the desired glycosylated antibody. In some embodiments, the said identification is by one or both of liquid chromatography and mass spectrometry.

[0403] If required, the antibodies can be purified or isolated after expression. Proteins may be isolated or purified in a variety of ways known to those skilled in the art. Standard purification methods include chromatographic techniques, including ion exchange, hydrophobic interaction, affinity, sizing or gel filtration, and reversed-phase, carried out at atmospheric pressure or at high pressure using systems such as FPLC and HPLC. Purification methods also include electrophoretic, immunological, precipitation, dialysis, and chromatofocusing techniques. Ultrafiltration and diafiltration techniques, in conjunction with protein concentration, are also useful. As is well known in the art, a variety of natural proteins bind Fc and antibodies, and these proteins can find use in the present invention for purification of antibodies. For example, the bacterial proteins A and G bind to the Fc region. Likewise, the bacterial protein L binds to the Fab region of some antibodies. Purification can often be enabled by a particular fusion partner. For example, antibodies may be purified using glutathione resin if a GST fusion130IPTS / 200090223.1Goodwin Ref: PRG-061WO is employed, Ni+2affinity chromatography if a His-tag is employed or immobilized anti-flag antibody if a flag-tag is used. For general guidance in suitable purification techniques, see, e.g. incorporated entirely by reference Protein Purification: Principles and Practice, 3rd Ed., Scopes, Springer- Verlag, NY, 1994, incorporated entirely by reference. The degree of purification necessary will vary depending on the use of the antibodies. In some instances, no purification is necessary.

[0404] In certain embodiments, the antibodies are purified using Anion Exchange Chromatography including, but not limited to, chromatography on Q-sepharose, DEAE sepharose, poros HQ, poros DEAF, Toy opearl Q, Toy opearl QAE, Toy opearl DEAE, Resource / Source Q and DEAE, Fractogel Q and DEAE columns.

[0405] In specific embodiments, the proteins described herein are purified using Cation Exchange Chromatography including, but not limited to, SP-sepharose, CM sepharose, poros HS, poros CM, Toyopearl SP, Toyopearl CM, Resource / Source S and CM, Fractogel S and CM columns and their equivalents and comparables.

[0406] In addition, antibodies described herein can be chemically synthesized using techniques known in the art (e.g., see Creighton, 1983, Proteins: Structures and Molecular Principles, W. H. Freeman & Co., N.Y and Hunkapiller et al., Nature, 310: 105-111 (1984)). For example, a polypeptide corresponding to a fragment of a polypeptide can be synthesized by use of a peptide synthesizer. Furthermore, if desired, nonclassical amino acids or chemical amino acid analogs can be introduced as a substitution or addition into the polypeptide sequence. Non- classical amino acids include, but are not limited to, to the D-isomers of the common amino acids, 2,4diaminobutyric acid, alpha-amino isobutyric acid, 4aminobutyric acid, Abu, 2-amino butyric acid, g-Abu, e-Ahx, 6amino hexanoic acid, Aib, 2-amino isobutyric acid, 3-amino propionic acid, ornithine, norleucine, norvaline, hydroxyproline, sarcosine, citrulline, homocitrulline, cysteic acid, t-butylglycine, t-butylalanine, phenylglycine, cyclohexylalanine, alanine, fluoro-amino acids, designer amino acids such as methyl amino acids, C-methyl amino acids, N-methyl amino acids, and amino acid analogs in general. Furthermore, the amino acid can be D (dextrorotary) or L (levorotary).Methods of Use

[0407] In an aspect, the present application provides methods of contacting TSLP with an anti-TSLP antibody, or antigen binding fragment thereof, such as a human or humanized antibody, which results in inhibition of TSLP binding to TSLPR.131IPTS / 200090223.1Goodwin Ref: PRG-061WO

[0408] In an aspect, the present application provides methods of using the isolated anti- TSLP antibodies, or antigen binding fragments thereof, described herein for treatment of a disorder or disease in a subject. In certain aspects, described herein is a method for treating a subject in need thereof with an anti-TSLP antibody, or antigen binding fragment thereof, the method comprising administering to the subject (e.g., a mammalian subject) a therapeutically effective amount of an anti-TSLP antibody, or antigen binding fragment thereof, or pharmaceutical composition comprising an anti-TSLP antibody, or antigen binding fragm...

Claims

1. Goodwin Ref: PRG-061WOCLAIMS1. An isolated antibody, or antigen binding fragment thereof, that binds TSLP, comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR- H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises:(i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CORED comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 27;(ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CORED comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 19 and 22; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 30;(iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CORED comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 310 and 324; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 351; or(iv) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CORED comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 315 and 331; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 355; and an isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra.

2. The isolated antibodies of claim 1, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-273IPTS / 200090223.1Goodwin Ref: PRG-061WOL2, and CDR-L3 of an antibody selected from dupilumab, stapokibart, rademikibart, and Antibody 611.

3. The isolated antibodies of claim 1, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:(i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293;(ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or(iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

4. An isolated antibody, or antigen binding fragment thereof, that binds TSLP; and an isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra, comprising: a) a variable heavy (VH) chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a variable light (VL) chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3; wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:(i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs:274IPTS / 200090223.1Goodwin Ref: PRG-061WO273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293;(ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293; or(iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

5. The isolated antibodies of claim 4, wherein the isolated antibody, or antigen binding fragment thereof, that binds TSLP comprises a CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR- L2, and CDR-L3 of an antibody selected from tezepelumab, GR2002, TQC2731, solrikitug, hu23bl2, 43B1-H2L2, and 43B1-H6L1.

6. The isolated antibodies of claim 4, wherein the isolated antibody, or antigen binding fragment thereof, that binds TSLP comprises: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the isolated antibody, or antigen binding fragment thereof, that binds TSLP comprises:(i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CORED comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 27;275IPTS / 200090223.1Goodwin Ref: PRG-061WO(ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CORED comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 19 and 22; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 30;(iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CORED comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 310 and 324; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 351; or(iv) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CORED comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 315 and 331; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 355.

7. The isolated antibodies of claim 4 or 6, wherein:(a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises:(i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 27; and(b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:(i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.276IPTS / 200090223.1Goodwin Ref: PRG-061WO8. The isolated antibodies of claim 4 or 6, wherein:(a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises:(i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 27; and(b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:(ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

9. The isolated antibodies of claim 4 or 6, wherein:(a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises:(i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 27; and(b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:(iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

10. The isolated antibodies of claim 4 or 6, wherein:(a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises:(ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6,277IPTS / 200090223.1Goodwin Ref: PRG-061WO and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 19 and 22; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 30; and(b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:(i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

11. The isolated antibodies of claim 4 or 6, wherein:(a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises:(ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 19 and 22; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 30; and(b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:(ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

12. The isolated antibodies of claim 4 or 6, wherein:(a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises:(ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 19 and 22; a CDR-L2 comprising278IPTS / 200090223.1Goodwin Ref: PRG-061WO the sequence set forth in SEQ ID NO: 25 or the amino acid sequence DVS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 30; and(b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:(iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs:273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs:279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

13. The isolated antibodies of claim 4 or 6, wherein:(a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises:(iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 310 and 324; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 351; and(b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:(i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273,274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

14. The isolated antibodies of claim 4 or 6, wherein:(a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises:(iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 310 and 324; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 351; and(b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:279IPTS / 200090223.1Goodwin Ref: PRG-061WO(ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

15. The isolated antibodies of claim 4 or 6, wherein:(a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises:(iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 310 and 324; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 351; and(b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:(iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs:273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

16. The isolated antibodies of claim 4 or 6, wherein:(a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises:(iv) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 315 and 331; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 355; and(b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:(i) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273,274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 276, 277, and 278; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and280IPTS / 200090223.1Goodwin Ref: PRG-061WO282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 285 and 286; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 292 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

17. The isolated antibodies of claim 4 or 6, wherein:(a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises:(iv) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 315 and 331; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 355; and(b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:(ii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 283 and 284; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 287 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 291 or the amino acid sequence LG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.

18. The isolated antibodies of claim 4 or 6, wherein:(a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises:(iv) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR- L1 comprising the sequence set forth in any one of SEQ ID NOs: 315 and 331; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 355; and(b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:(iii) a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293.281IPTS / 200090223.1Goodwin Ref: PRG-061WO19. The isolated antibodies of any one of claims 1-18, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a heavy chain variable domain (VH) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 32-36.

20. The isolated antibodies of claim 19, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34.

21. The isolated antibodies of any one of t claims 1-20, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 295-297.

22. The isolated antibodies of any one of claims 1-21, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a light chain variable domain (VL) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 37-45 and 361-396.

23. The isolated antibodies of claim 22, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a light chain variable domain (VL) sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 41, 43, 374, and 380.

24. The isolated antibodies of any one of claims 1-23, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VL sequence comprising the amino acid sequence set forth in any one of SEQ ID NOs: 298-300.

25. The isolated antibodies of any one of claims 19-24, wherein:(a) the antibody, or antigen binding fragment thereof, that binds TSLP comprises:(i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 32;(ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 33; or(iii) a VH sequence comprising the amino acid sequence set forth in SEQ IDNO: 34; and / or(iv) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 41;(v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 43;(vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID282IPTS / 200090223.1Goodwin Ref: PRG-061WONO: 374; or(vii) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 380; and / or(b) the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises:(i) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295;(ii) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; or(iv) a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and / or(v) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298;(vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299; or(vi) a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.

26. The isolated antibodies of claim 25, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34.

27. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 41.

28. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 43.

29. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 374.283IPTS / 200090223.1Goodwin Ref: PRG-061WO30. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 380.

31. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.

32. The isolated antibodies of claim 25 or 26, wherein the antibody that, or antigen binding fragment thereof, binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.

33. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.

34. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 41; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.

35. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 41; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.

36. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 41; and wherein the antibody, or antigen binding fragment thereof, that284IPTS / 200090223.1Goodwin Ref: PRG-061WO binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.

37. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 43; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.

38. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 43; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.

39. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 43; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.

40. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 374; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.

41. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 374; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in285IPTS / 200090223.1Goodwin Ref: PRG-061WOSEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.

42. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 374; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.

43. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 380; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 295; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 298.

44. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 380; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 296; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 299.

45. The isolated antibodies of claim 25 or 26, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 34; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 380; and wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH sequence comprising the amino acid sequence set forth in SEQ ID NO: 297; and a VL sequence comprising the amino acid sequence set forth in SEQ ID NO: 300.286IPTS / 200090223.1Goodwin Ref: PRG-061WO46. The isolated antibodies of any one of claims 1-45, wherein the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra is a humanized, human, or chimeric antibody.

47. The isolated antibodies of any one of claims 1-46, wherein the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra is a humanized antibody.

48. The isolated antibodies of any one of claims 1-47, wherein the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a heavy chain human constant region of a class selected from IgG, IgA, IgD, IgE, and IgM.

49. The isolated antibodies of any one of claims 1-48, wherein the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a human Fc region, and wherein the human Fc region comprises a human heavy chain constant region of the class IgG and a subclass selected from IgGl, IgG2, IgG3, and IgG4.

50. The isolated antibodies of claim 49, wherein the human Fc region of the antibody, or antigen binding fragment thereof, that binds TSLP and / or the human Fc region of the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a human IgGl Fc region.

51. The isolated antibodies of claim 49, wherein the human Fc region of the antibody, or antigen binding fragment thereof, that binds TSLP and / or the human Fc region of the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a human IgG4 Fc region.

52. The isolated antibodies of claim 49, wherein the human Fc region of the antibody, or antigen binding fragment thereof, that binds TSLP and / or the human Fc region of the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a human IgG2 Fc region.

53. The isolated antibodies of any one of claims 1-52, wherein the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a heavy chain comprising a constant heavy chain sequence selected from the amino acid sequences set forth in any one of SEQ ID NOs: 47-270.

54. The isolated antibodies of any one of claims 1-53, wherein the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment287IPTS / 200090223.1Goodwin Ref: PRG-061WO thereof, that binds IL-4Ra comprises a light chain comprising a constant light chain sequence set forth in SEQ ID NO: 46 or SEQ ID NO: 421.

55. The isolated antibodies of any one of claims 1-53, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a light chain comprising a human lambda light chain constant region and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a light chain comprising a human kappa light chain constant region.

56. The isolated antibodies of any one of claims 1-55, wherein the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more amino acid substitutions result in an increase in one or more of antibody half-life, ADCC activity, ADCP activity, or CDC activity compared with the Fc without the one or more amino acid substitutions.

57. The isolated antibodies of any one of claims 1-55, wherein the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises an Fc region comprising one or more amino acid substitutions, wherein the one or more amino acid substitutions result in a decrease in one or more of, ADCC activity, ADCP activity or CDC activity compared to an antibody comprising a wild-type Fc region.

58. The isolated antibodies of claim 56 or 57, wherein the one or more amino acid substitutions is selected from the group consisting of S228P, M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W; optionally, wherein the one or more amino acid substitutions comprises a plurality of amino acid substitutions selected from the group consisting of M428L / N434S (LS), M252Y / S254T / T256E (YTE), T250Q / M428L, T307A / E380A / N434A, T256D / T307Q (DQ), T256D / T307W (DW), M252Y / T256D (YD), T307Q / Q311V / A378V (QVV), T256D / H285D / T307R / Q311V / A378V (DDRVV), L309D / Q311H / N434S (DHS), S228P / L235E (SPLE), L234A / L235A (LALA), M428L / N434A (LA), L235A / G237A (LAGA), L234A / L235A / G237A (LALAGA), L234A / L235A / P329G (LALAPG), D265A / YTE, LALA / YTE, LAGA / YTE, LALAGA / YTE, LALAPG / YTE, N297A / LS, D265A / LS, LALA / LS, LALAGA / LS, LALAPG / LS, N297A / DHS, D265A / DHS, LALA / DHS, LAGA / DHS, LALAGA / DHS, LALAPG / DHS, SP / YTE, SPLE / YTE, SP / LS, SPLE / LS, SP / DHS, SPLE / DHS, N297A / LA, D265A / LA, LALA / LA,288IPTS / 200090223.1Goodwin Ref: PRG-061WOLAGA / LA, LALAGA / LA, LALAPG / LA, N297A / N434A, D265A / N434A, LALA / N434A, LAGA / N434A, LALAGA / N434A, LALAPG / N434A, N297A / N434W, D265A / N434W, LALA / N434W, LAGA / N434W, LALAGA / N434W, LALAPG / N434W, N297A / DQ, D265A / DQ, LALA / DQ, LAGA / DQ, LALAGA / DQ, LALAPG / DQ, N297A / DW, D265A / DW, LALA / DW, LAGA / DW, LALAGA / DW, LALAPG / DW, N297A / YD, D265A / YD, LALA / YD, LAGA / YD, LALAGA / YD, LALAPG / YD, T307Q / Q311V / A378V (QVV), N297A / QVV, D265A / QVV, LALA / QVV, LAGA / QVV, LALAGA / QVV, LALAPG / QVV, DDRVV, N297A / DDRVV, D265A / DDRVV, LALA / DDRVV, LAGA / DDRVV, LALAGA / DDRVV, and LALAPG / DDRVV.

59. The isolated antibodies of any one of claims 1-58, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 34, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 41, a constant heavy chain sequence set forth in SEQ ID NO: 173 or SEQ ID NO: 61, and a constant light chain sequence set forth in SEQ ID NO: 421.

60. The isolated antibodies of any one of claims 1-59, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 297, a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 300, a constant heavy chain sequence set forth in SEQ ID NO: 173 or SEQ ID NO: 61, and a constant light chain sequence set forth in SEQ ID NO: 46.

61. The isolated antibodies of any one of claims 1-60, wherein the Fc region of the antibody, or antigen binding fragment thereof, that binds TSLP and / or the Fc region of the antibody, or antigen binding fragment thereof, that binds IL-4Ra binds to Neonatal Fc receptor (FcRn).

62. The isolated antibodies of claim 61, wherein the Fc region of the antibody, or antigen binding fragment thereof, that binds TSLP and / or the Fc region of the antibody, or antigen binding fragment thereof, that binds IL-4Ra binds an FcRn with higher affinity at pH 6.0 compared to an antibody comprising a wild-type Fc region.

63. The isolated antibodies of claim 61 or 62, wherein the Fc region of the antibody, or antigen binding fragment thereof, that binds TSLP and / or the Fc region of the antibody, or antigen binding fragment thereof, that binds IL-4Ra binds to FcRn with a KD of <1 x 10'7M at pH 6.0.289IPTS / 200090223.1Goodwin Ref: PRG-061WO64. The isolated antibodies of any one of claims 1-63, wherein the antibody, or antigen binding fragment thereof, that binds TSLP and / or the antibody, or antigen binding fragment thereof, that binds IL-4Ra is a monoclonal antibody.

65. The isolated antibodies of any one of claims 1-64, wherein the antibody, or antigen binding fragment thereof, that binds TSLP binds a TSLP sequence set forth in the amino acid sequence of any one of SEQ ID NOs: 271-272.

66. The isolated antibodies of any one of claims 1-65, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra binds an IL-4Ra sequence set forth in the amino acid sequence of any one of SEQ ID NOs: 301-303.

67. The isolated antibodies of any one of claims 1-66 for use in the treatment of an inflammatory disorder or disease.

68. The isolated antibodies of claim 67, for use in the treatment of atopic dermatitis (AD).

69. The isolated antibodies of claim 68, wherein the treatment reduces disease severity in a patient and wherein disease severity is assessed by an atopic dermatitis disease severity outcome measure.

70. The isolated antibodies of claim 67, for use in the treatment of asthma, chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome / Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS); Allergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); Crohn’s disease; lupus; rheumatoid arthritis (RA); psoriasis; ulcerative colitis; hi dradenitis suppurativa; celiac disease; idiopathic pulmonary fibrosis; alopecia areata; or systemic sclerosis.

71. An isolated polynucleotide or set of polynucleotides encoding the isolated antibodies of any one of claims 1-66, a VH thereof, a VL thereof, a light chain thereof, a heavy chain thereof, or an antigen-binding portion thereof, and optionally, wherein the polynucleotide or set of polynucleotides comprises cDNA.290IPTS / 200090223.1Goodwin Ref: PRG-061WO'll. A vector or set of vectors comprising the polynucleotide or set of polynucleotides of claim 71.

73. A host cell comprising the polynucleotide or set of polynucleotides of claim 71 or the vector or set of vectors of claim 72.

74. A method of producing one or more of the isolated antibodies of any one claims 1-66, the method comprising expressing one or more of the antibodies within the host cell of claim 73 and isolating the one or more expressed antibodies.

75. A pharmaceutical composition comprising the isolated antibodies of any one of claims 1- 66 and a pharmaceutically acceptable excipient.

76. A kit comprising the isolated antibodies of any one of claims 1-66 or the pharmaceutical composition of claim 75 and instructions for use.

77. A method for treating an inflammatory disorder or disease in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the isolated antibodies of any one of claims 1-66; a therapeutically effective amount of the pharmaceutical composition of claim 75; or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or antigen binding fragment thereof, that binds TSLP and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, that binds IL-4Ra and a pharmaceutically acceptable excipient.

78. The method of claim 77, wherein the mammalian subject is a human.

79. The method of claim 77 or 78, wherein the inflammatory disorder or disease is atopic dermatitis.

80. The method of claim 77 or 78, wherein the inflammatory disorder or disease is asthma.

81. The method of claim 77 or 78, wherein the inflammatory disorder or disease is chronic sinusitis with nasal polyps; Chronic Rhinosinusitis without Nasal Polyps (CRSsNP); eosinophilic esophagitis (EoE); an Eosinophilic gastrointestinal disorder or disease (EGID) selected from the group consisting of Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), Eosinophilic Colitis (EoC), and Eosinophilic Gastroenteritis (EGE); Churg-Strauss syndrome / Eosinophilic granulomatosis with polyangiitis (EGPA); Prurigo Nodularis (PN); Chronic Spontaneous Urticaria (CSU); Chronic Pruritis of Unknown Origin (CPUO); Bullous Pemphigoid (BP); Cold Inducible Urticaria (ColdU); Allergic Fungal Rhinosinusitis (AFRS);291IPTS / 200090223.1Goodwin Ref: PRG-061WOAllergic Bronchopulmonary Aspergillosis (ABPA); Chronic Obstructive Pulmonary Disease (COPD); or celiac disease.

82. A method for treating a pathology associated with elevated levels of TSLP and / or IL-4 in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the isolated antibodies of any one of claims 1-66 or the pharmaceutical composition of claim 75, or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or antigen binding fragment thereof, that binds TSLP and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra and a pharmaceutically acceptable excipient.

83. A method of reducing biological activity of TSLP and / or IL-4Ra in a mammalian subject in need thereof, the method comprising administering to the mammalian subject a therapeutically effective amount of the isolated antibodies of any one of claims 1-66 , the pharmaceutical composition of claim 75, or a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or antigen binding fragment thereof, that binds TSLP and a pharmaceutically acceptable excipient and a therapeutically effective amount of a pharmaceutical composition comprising an isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra and a pharmaceutically acceptable excipient.

84. The method of any one of claims 77-83, wherein the mammalian subject is a human.

85. An isolated antibody, or antigen binding fragment thereof, that binds TSLP, comprising: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR- H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein the antibody, or antigen binding fragment thereof, that binds TSLP comprises: a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 3, 6, and 9; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 10, 11, and 12; a CORED comprising the sequence set forth in any one of SEQ ID NOs: 13 and 16; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 21 and 24; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 26 or the amino acid sequence DDS; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 27; and an isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra, comprising: a) a VH chain sequence having three heavy chain CDR sequences, CDR-H1, CDR-H2, and292IPTS / 200090223.1Goodwin Ref: PRG-061WOCDR-H3; and b) a VL chain sequence having three light chain CDR sequences, CDR-L1, CDR- L2, and CDR-L3, wherein the antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises: a CDR-H1 comprising the sequence set forth in any one of SEQ ID NOs: 273, 274, and 275; a CDR-H2 comprising the sequence set forth in any one of SEQ ID NOs: 279, 277, and 280; a CDR-H3 comprising the sequence set forth in any one of SEQ ID NOs: 281 and 282; a CDR-L1 comprising the sequence set forth in any one of SEQ ID NOs: 289 and 288; a CDR-L2 comprising the sequence set forth in SEQ ID NO: 290 or the amino acid sequence EG; and a CDR-L3 comprising the sequence set forth in SEQ ID NO: 293, wherein the isolated antibody, or antigen binding fragment thereof, that binds TSLP and / or the isolated antibody, or antigen binding fragment thereof, that binds IL-4Ra comprises a heavy chain comprising a heavy chain constant region having a means for extending the half-life of the isolated antibody.293IPTS / 200090223.1