Klk5 / 7 + th2 targeting antibodies and uses thereof

Abstract

Aspects of the application provide bispecific antibodies and methods of using the same for promoting barrier function and reducing inflammation, and treating conditions such as Netherton syndrome, eosinophilic esophagitis and atopic dermatitis. In some embodiments, the bispecific antibody comprises at least one antigen-specific binding site that specifically binds KLK5 and KLK7 and at least one antigen-specific binding site that specifically binds to a Th2 cytokine (e.g., IL-13) or receptor thereof.

Description

KLK5 / 7 + TH2 TARGETING ANTIBODIES AND USES THEREOF RELATED APPLICATIONS

[0001] This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application, U.S.S.N.63 / 578,959, filed August 25, 2023, and U.S. Provisional Application, U.S.S.N.63 / 549,274, filed February 2, 2024, the entire contents of each of which are incorporated herein by reference. REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0002] The contents of the electronic sequence listing (A140770003WO00-SEQ-LJG.xml; Size: 744,871 bytes; and Date of Creation: August 22, 2024) is herein incorporated by reference in its entirety. BACKGROUND

[0003] Skin contains tissue structure and cells, such as epithelial cells and immune cells, that together provide a functional and physical barrier that serves an important role in preventing allergen penetration into the body and responding to pathogens. Kallikrein (KLK) enzymes regulate desquamation and innate immunity to support skin homeostasis and wound healing. In a healthy skin, the outermost layer of the epidermis is regularly shed through a KLK driven proteolytic cascade resulting in the degradation of corneodesmosomes and desquamation. KLK5 is understood to be a main activator of this proteolytic cascade. Autoactivated KLK5 enzymatically converts proKLK7 and proKLK14 to active forms and stimulates a positive feedback loop that, via KLK14, leads to the production of more proKLK5. These KLK enzymes are kept in check by endogenous serine protease inhibitors, such as lymphoepithelial Kazal-type–related inhibitors. Dysregulation of KLKs, including KLK5 and KLK7, is associated with skin disorders, inflammatory diseases, and cancer. For example, hyperactive kallikrein 5 and 7 cause both genetic and spontaneous epidermal barrier disorders (e.g., Netherton syndrome, eosinophilic esophagitis, atopic dermatitis). SUMMARY

[0004] Certain aspects of the disclosure relate to a recognition that loss of balance between endogenous KLK proteases and associated protease inhibitors causes barrier dysfunction and 7107489induces inflammation (as illustrated in FIG.1), which can result in inflammatory conditions, such as Netherton syndrome, eosinophilic esophagitis and atopic dermatitis. Moreover, elevated activity of T helper 2 (Th2) cytokines (such as, for example, IL-13 and IL-4) can further drive inflammation and contribute to barrier dysfunction and related conditions (as illustrated in FIG.2). In some embodiments, compositions and methods provided herein are useful for inhibiting KLK5 / KLK7 and Th2 cytokine (e.g., IL-13, IL-4, IL-5, IL-6, IL-9, IL- 31, IL-17E (IL-25), OX40L, TSLP, etc.) signaling to improve barrier function and reduce inflammation, which ameliorates disease severity.

[0005] Further, aspects of the present disclosure provide multispecific antibodies comprising at least one antigen-specific binding site that specifically binds KLK5 and KLK7 and at least one antigen-specific binding site that specifically binds to a Th2 cytokine (e.g., IL-13, IL-4, IL-5, IL-6, IL-9, IL-31, IL-17E (IL-25), OX40L, TSLP, etc.) or receptor thereof. In certain embodiments, such multispecific antibodies are configured such that they comprise an arm that binds the active site of KLK5 and KLK7, and an arm that binds to a Th2 cytokine or a receptor thereof. In some embodiments, such multispecific antibodies (e.g., a bispecific antibody) are advantageous because they inhibit both KLK5 / 7 activity and Th2 cytokine activity in a single molecule. In some embodiments, with respect to KLK5 / 7 binding site within the multispecific antibody (e.g., bispecific antibody), such antibodies bind specifically to the active forms rather than the proforms of the enzymes.

[0006] In some embodiments, methods and related compositions, and antibody for use in methods are provided that are useful for inhibition of KLK5 and KLK7 along with Th2 cytokine activity for purposes of improving barrier function and reducing inflammation, which ameliorates disease severity. In particular, aspects of the disclosure provide bispecific antibodies in which one arm comprises an antigen-specific binding site of a dual inhibitor antibody targeting KLK5 and KLK7 (referred to as anti-KLK5 / KLK7 antibodies), which has high binding affinity and specificity to the active sites of both KLK5 and KLK7, and in which the other arm specifically binds to and inhibits activity of a Th2 cytokine (e.g., IL-13, IL-4, IL-5, IL-6, IL-9, IL-31, IL-17E (IL-25), OX40L, TSLP, etc.) or receptor thereof (referred to as an anti-KLK5 / KLK7 + Th2 targeting bispecific antibody). Accordingly, in some embodiments, the disclosure provides methods and related antibody compositions for treating conditions associated with KLK5 and KLK7 dysregulation and / or aberrant Th2 cytokine activity, such as Netherton Syndrome, atopic dermatitis (with and without filaggrin mutations), eosinophilic esophagitis, prurigo nodularis, chronic pruritus of unknown origin (CPUO), asthma (e.g., KLK5 related asthma), and ichthyosis vulgaris. 7107489

[0007] In certain embodiments, the present disclosure provides a bispecific antibody that comprises at least one antigen-specific binding site of a dual inhibitor antibody targeting KLK5 and KLK7, and at least one antigen-specific binding site that specifically binds to a Th2 cytokine (e.g., IL-13, IL-4, IL-5, IL-6, IL-9, IL-31, IL-17E (IL-25), OX40L, TSLP, etc.) or a receptor thereof and inhibits Th2 cytokine signaling. In some embodiments, the present disclosure provides a bispecific antibody that comprises at least one antigen-specific binding site of a dual inhibitor antibody targeting KLK5 and KLK7, and at least one antigen-specific binding site that specifically binds and inhibits IL-13 (referred to as an anti-KLK5 / KLK7 + IL-13 targeting bispecific antibody). In some embodiments, the present disclosure provides a bispecific antibody that comprises at least one antigen-specific binding site of a dual inhibitor antibody targeting KLK5 and KLK7, and at least one antigen-specific binding site that specifically binds and inhibits IL-4 (referred to as an anti-KLK5 / KLK7 + IL-4 targeting bispecific antibody). Accordingly, in some embodiments, the disclosure provides methods and related antibody compositions for treating conditions associated with KLK5 and KLK7 dysregulation, in which Th2 cytokines, such as IL-13, IL-4 and others, also play a role in pathogenesis, such as Netherton Syndrome, atopic dermatitis (with and without filaggrin mutations), eosinophilic esophagitis, prurigo nodularis, chronic pruritus of unknown origin (CPUO), asthma (e.g., KLK5 related asthma), and ichthyosis vulgaris.

[0008] In some aspects, the present disclosure provides a bispecific antibody comprising an antigen-specific binding site that specifically binds KLK5 and KLK7 and an antigen-specific binding site that specifically binds a Th2 cytokine or a receptor thereof.

[0009] In some embodiments, the antigen-specific binding site that specifically binds KLK5 and KLK7 binds to the active sites of KLK5 and KLK7 and inhibits activity of the enzymes. In some embodiments, the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 of any one of the antibodies listed in Table 1a and Table 1b. In some embodiments, the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 7, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 13, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 14. In some embodiments, 7107489the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 17, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 14. In some embodiments, the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 21, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 14. In some embodiments, the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 2, a HC CDR3 having the amino acid sequence of SEQ ID NO: 3, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 6. In some embodiments, the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 9, a HC CDR2 having the amino acid sequence of SEQ ID NO: 10, a HC CDR3 having the amino acid sequence of SEQ ID NO: 11, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 12. In some embodiments, the antigen- specific binding site that specifically binds KLK5 and KLK7 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 9, a HC CDR2 having the amino acid sequence of SEQ ID NO: 15, a HC CDR3 having the amino acid sequence of SEQ ID NO: 16, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 12. In some embodiments, the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 18, a HC CDR2 having the amino acid sequence of SEQ ID NO: 19, a HC CDR3 having the amino acid sequence of SEQ ID NO: 20, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 12. In some embodiments, the bispecific antibody comprises an antigen-specific binding site that specifically binds to KLK5 and KLK7 is of a VH and / or a VL of any one of the antibodies listed in Table 1a. In some embodiments, the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises a VH comprising the amino acid sequence of SEQ ID NO: 7 and a VL comprising 7107489the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises a VH comprising the amino acid sequence of SEQ ID NO: 13, and a VL comprising the amino acid sequence of SEQ ID NO: 14. In some embodiments, the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises a VH comprising the amino acid sequence of SEQ ID NO: 17, and a VL comprising the amino acid sequence of SEQ ID NO: 14. In some embodiments, the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises a VH comprising the amino acid sequence of SEQ ID NO: 21, and a VL comprising the amino acid sequence of SEQ ID NO: 14.

[0010] In some embodiments, the bispecific antibody comprises an antigen-specific binding site that specifically binds to the Th2 cytokine or a receptor thereof comprises a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 of any one of the antibodies listed in Table 2.

[0011] In some embodiments, the Th2 cytokine is IL-13. In some embodiments, the bispecific antibody comprises an antigen-specific binding site that specifically binds IL-13 or IL-13R. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 53, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 54. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 32, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 33. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL- 13R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 74, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 75. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL- 13R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 94, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 95. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL- 13R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 114, and a LC CDR1, LC CDR2 and LC 7107489CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 115. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL- 13R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 134, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 135. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL- 13R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 657, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 658. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL- 13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 55, a HC CDR2 having the amino acid sequence of SEQ ID NO: 56, a HC CDR3 having the amino acid sequence of SEQ ID NO: 57, a LC CDR1 having the amino acid sequence of SEQ ID NO: 58, a LC CDR2 having the amino acid sequence of SEQ ID NO: 59, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 60. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 61, a HC CDR2 having the amino acid sequence of SEQ ID NO: 62, a HC CDR3 having the amino acid sequence of SEQ ID NO: 63, a LC CDR1 having the amino acid sequence of SEQ ID NO: 64, a LC CDR2 having the amino acid sequence of SEQ ID NO: 65, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 66. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 67, a HC CDR2 having the amino acid sequence of SEQ ID NO: 68, a HC CDR3 having the amino acid sequence of SEQ ID NO: 69, a LC CDR1 having the amino acid sequence of SEQ ID NO: 70, a LC CDR2 having the amino acid sequence of SEQ ID NO: 71, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 72. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 34, a HC CDR2 having the amino acid sequence of SEQ ID NO: 35, a HC CDR3 having the amino acid sequence of SEQ ID NO: 36, a LC CDR1 having the amino acid sequence of SEQ ID NO: 37, a LC CDR2 having the amino acid sequence of SEQ ID NO: 38, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 39. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 41, a HC CDR3 having the amino acid 7107489sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 43, a LC CDR2 having the amino acid sequence of SEQ ID NO: 44, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 45. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 46, a HC CDR2 having the amino acid sequence of SEQ ID NO: 47, a HC CDR3 having the amino acid sequence of SEQ ID NO: 48, a LC CDR1 having the amino acid sequence of SEQ ID NO: 49, a LC CDR2 having the amino acid sequence of SEQ ID NO: 50, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 51. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 76, a HC CDR2 having the amino acid sequence of SEQ ID NO: 77, a HC CDR3 having the amino acid sequence of SEQ ID NO: 78, a LC CDR1 having the amino acid sequence of SEQ ID NO: 79, a LC CDR2 having the amino acid sequence of SEQ ID NO: 80, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 81. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 82, a HC CDR2 having the amino acid sequence of SEQ ID NO: 83, a HC CDR3 having the amino acid sequence of SEQ ID NO: 84, a LC CDR1 having the amino acid sequence of SEQ ID NO: 85, a LC CDR2 having the amino acid sequence of SEQ ID NO: 86, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 87. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 88, a HC CDR2 having the amino acid sequence of SEQ ID NO: 89, a HC CDR3 having the amino acid sequence of SEQ ID NO: 90, a LC CDR1 having the amino acid sequence of SEQ ID NO: 91, a LC CDR2 having the amino acid sequence of SEQ ID NO: 92, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 93. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 96, a HC CDR2 having the amino acid sequence of SEQ ID NO: 97, a HC CDR3 having the amino acid sequence of SEQ ID NO: 98, a LC CDR1 having the amino acid sequence of SEQ ID NO: 99, a LC CDR2 having the amino acid sequence of SEQ ID NO: 100, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 101. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 102, a HC CDR2 having the amino acid sequence of SEQ ID NO: 103, a HC CDR3 having the amino acid sequence of SEQ ID NO: 104, a LC CDR1 having the amino acid sequence of SEQ ID NO: 7107489105, a LC CDR2 having the amino acid sequence of SEQ ID NO: 106, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 107. In some embodiments, the antigen- specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 108, a HC CDR2 having the amino acid sequence of SEQ ID NO: 109, a HC CDR3 having the amino acid sequence of SEQ ID NO: 110, a LC CDR1 having the amino acid sequence of SEQ ID NO: 111, a LC CDR2 having the amino acid sequence of SEQ ID NO: 112, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 113. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 116, a HC CDR2 having the amino acid sequence of SEQ ID NO: 117, a HC CDR3 having the amino acid sequence of SEQ ID NO: 118, a LC CDR1 having the amino acid sequence of SEQ ID NO: 119, a LC CDR2 having the amino acid sequence of SEQ ID NO: 120, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 121. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 122, a HC CDR2 having the amino acid sequence of SEQ ID NO: 123, a HC CDR3 having the amino acid sequence of SEQ ID NO: 124, a LC CDR1 having the amino acid sequence of SEQ ID NO: 125, a LC CDR2 having the amino acid sequence of SEQ ID NO: 126, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 127. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 128, a HC CDR2 having the amino acid sequence of SEQ ID NO: 129, a HC CDR3 having the amino acid sequence of SEQ ID NO: 130, a LC CDR1 having the amino acid sequence of SEQ ID NO: 131, a LC CDR2 having the amino acid sequence of SEQ ID NO: 132, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 133. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 136, a HC CDR2 having the amino acid sequence of SEQ ID NO: 137, a HC CDR3 having the amino acid sequence of SEQ ID NO: 138, a LC CDR1 having the amino acid sequence of SEQ ID NO: 139, a LC CDR2 having the amino acid sequence of SEQ ID NO: 140, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 141. In some embodiments, the antigen- specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 142, a HC CDR2 having the amino acid sequence of SEQ ID NO: 143, a HC CDR3 having the amino acid sequence of SEQ ID NO: 144, a LC CDR1 having the amino acid sequence of SEQ ID NO: 145, a LC CDR2 having the amino 7107489acid sequence of SEQ ID NO: 146, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 147. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 148, a HC CDR2 having the amino acid sequence of SEQ ID NO: 149, a HC CDR3 having the amino acid sequence of SEQ ID NO: 150, a LC CDR1 having the amino acid sequence of SEQ ID NO: 151, a LC CDR2 having the amino acid sequence of SEQ ID NO: 152, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 153. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 655, a HC CDR2 having the amino acid sequence of SEQ ID NO: 41, a HC CDR3 having the amino acid sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 43, a LC CDR2 having the amino acid sequence of SEQ ID NO: 44, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 45. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 656, a HC CDR2 having the amino acid sequence of SEQ ID NO: 47, a HC CDR3 having the amino acid sequence of SEQ ID NO: 48, a LC CDR1 having the amino acid sequence of SEQ ID NO: 49, a LC CDR2 having the amino acid sequence of SEQ ID NO: 50, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 51. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a VH comprising the amino acid sequence of SEQ ID NO: 53 and a VL comprising the amino acid sequence of SEQ ID NO: 54. In some embodiments, the antigen- specific binding site that specifically binds IL-13 or IL-13R comprises a VH comprising the amino acid sequence of SEQ ID NO: 32, and a VL comprising the amino acid sequence of SEQ ID NO: 33. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a VH comprising the amino acid sequence of SEQ ID NO: 74, and a VL comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a VH comprising the amino acid sequence of SEQ ID NO: 94, and a VL comprising the amino acid sequence of SEQ ID NO: 95. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a VH comprising the amino acid sequence of SEQ ID NO: 114, and a VL comprising the amino acid sequence of SEQ ID NO: 115. In some embodiments, the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises a VH comprising the amino acid sequence of SEQ ID NO: 134, and a VL comprising the amino acid sequence of SEQ ID NO: 135. In some embodiments, the antigen- 7107489specific binding site that specifically binds IL-13 or IL-13R comprises a VH comprising the amino acid sequence of SEQ ID NO: 657, and a VL comprising the amino acid sequence of SEQ ID NO: 658.

[0012] In some embodiments, the bispecific antibody targets IL-4 or IL-4R. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 154, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 155. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 174, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 175. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 194, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 195. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 214, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 215. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 234, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 235. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 254, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 255. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 156, a HC CDR2 having the amino acid sequence of SEQ ID NO: 157, a HC CDR3 having the amino acid sequence of SEQ ID NO: 158, a LC CDR1 having the amino acid sequence of SEQ ID NO: 159, a LC CDR2 having the amino acid sequence of SEQ ID NO: 160, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 161. In some embodiments, the antigen- 7107489specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 162, a HC CDR2 having the amino acid sequence of SEQ ID NO: 163, a HC CDR3 having the amino acid sequence of SEQ ID NO: 164, a LC CDR1 having the amino acid sequence of SEQ ID NO: 165, a LC CDR2 having the amino acid sequence of LGS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 167. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 168, a HC CDR2 having the amino acid sequence of SEQ ID NO: 169, a HC CDR3 having the amino acid sequence of SEQ ID NO: 170, a LC CDR1 having the amino acid sequence of SEQ ID NO: 171, a LC CDR2 having the amino acid sequence of SEQ ID NO: 172, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 173. In some embodiments, the antigen- specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 176, a HC CDR2 having the amino acid sequence of SEQ ID NO: 177, a HC CDR3 having the amino acid sequence of SEQ ID NO: 178, a LC CDR1 having the amino acid sequence of SEQ ID NO: 179, a LC CDR2 having the amino acid sequence of SEQ ID NO: 180, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 181. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 182, a HC CDR2 having the amino acid sequence of SEQ ID NO: 183, a HC CDR3 having the amino acid sequence of SEQ ID NO: 184, a LC CDR1 having the amino acid sequence of SEQ ID NO: 185, a LC CDR2 having the amino acid sequence of AAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 187. In some embodiments, the antigen- specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 188, a HC CDR2 having the amino acid sequence of SEQ ID NO: 189, a HC CDR3 having the amino acid sequence of SEQ ID NO: 190, a LC CDR1 having the amino acid sequence of SEQ ID NO: 191, a LC CDR2 having the amino acid sequence of SEQ ID NO: 192, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 193. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 196, a HC CDR2 having the amino acid sequence of SEQ ID NO: 197, a HC CDR3 having the amino acid sequence of SEQ ID NO: 198, a LC CDR1 having the amino acid sequence of SEQ ID NO: 199, a LC CDR2 having the amino acid sequence of SEQ ID NO: 200, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 201. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 7107489having the amino acid sequence of SEQ ID NO: 202, a HC CDR2 having the amino acid sequence of SEQ ID NO: 203, a HC CDR3 having the amino acid sequence of SEQ ID NO: 204, a LC CDR1 having the amino acid sequence of SEQ ID NO: 205, a LC CDR2 having the amino acid sequence of SEQ ID NO: 206, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 207. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 208, a HC CDR2 having the amino acid sequence of SEQ ID NO: 209, a HC CDR3 having the amino acid sequence of SEQ ID NO: 210, a LC CDR1 having the amino acid sequence of SEQ ID NO: 211, a LC CDR2 having the amino acid sequence of GAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 213. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 216, a HC CDR2 having the amino acid sequence of SEQ ID NO: 217, a HC CDR3 having the amino acid sequence of SEQ ID NO: 218, a LC CDR1 having the amino acid sequence of SEQ ID NO: 219, a LC CDR2 having the amino acid sequence of SEQ ID NO: 220, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 221. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 222, a HC CDR2 having the amino acid sequence of SEQ ID NO: 223, a HC CDR3 having the amino acid sequence of SEQ ID NO: 224, a LC CDR1 having the amino acid sequence of SEQ ID NO: 225, a LC CDR2 having the amino acid sequence of YTS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 227. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 228, a HC CDR2 having the amino acid sequence of SEQ ID NO: 229, a HC CDR3 having the amino acid sequence of SEQ ID NO: 230, a LC CDR1 having the amino acid sequence of SEQ ID NO: 231, a LC CDR2 having the amino acid sequence of SEQ ID NO: 232, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 233. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 236, a HC CDR2 having the amino acid sequence of SEQ ID NO: 237, a HC CDR3 having the amino acid sequence of SEQ ID NO: 238, a LC CDR1 having the amino acid sequence of SEQ ID NO: 239, a LC CDR2 having the amino acid sequence of SEQ ID NO: 240, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 241. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 242, a HC CDR2 7107489having the amino acid sequence of SEQ ID NO: 243, a HC CDR3 having the amino acid sequence of SEQ ID NO: 244, a LC CDR1 having the amino acid sequence of SEQ ID NO: 245, a LC CDR2 having the amino acid sequence of SEQ ID NO: 246, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 247. In some embodiments, the antigen- specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 248, a HC CDR2 having the amino acid sequence of SEQ ID NO: 249, a HC CDR3 having the amino acid sequence of SEQ ID NO: 250, a LC CDR1 having the amino acid sequence of SEQ ID NO: 251, a LC CDR2 having the amino acid sequence of SEQ ID NO: 252, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 253. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 256, a HC CDR2 having the amino acid sequence of SEQ ID NO: 257, a HC CDR3 having the amino acid sequence of SEQ ID NO: 258, a LC CDR1 having the amino acid sequence of SEQ ID NO: 259, a LC CDR2 having the amino acid sequence of SEQ ID NO: 260, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 261. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 262, a HC CDR2 having the amino acid sequence of SEQ ID NO: 263, a HC CDR3 having the amino acid sequence of SEQ ID NO: 264, a LC CDR1 having the amino acid sequence of SEQ ID NO: 265, a LC CDR2 having the amino acid sequence of SEQ ID NO: 267, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 268. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 269, a HC CDR2 having the amino acid sequence of SEQ ID NO: 270, a HC CDR3 having the amino acid sequence of SEQ ID NO: 271, a LC CDR1 having the amino acid sequence of SEQ ID NO: 272, a LC CDR2 having the amino acid sequence of SAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 274. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a VH comprising the amino acid sequence of SEQ ID NO: 154 and a VL comprising the amino acid sequence of SEQ ID NO: 155. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a VH comprising the amino acid sequence of SEQ ID NO: 174, and a VL comprising the amino acid sequence of SEQ ID NO: 175. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a VH comprising the amino acid sequence of SEQ ID NO: 194, and a VL comprising the amino acid sequence of SEQ ID NO: 195. In some embodiments, the antigen- 7107489specific binding site that specifically binds IL-4 or IL-4R comprises a VH comprising the amino acid sequence of SEQ ID NO: 214, and a VL comprising the amino acid sequence of SEQ ID NO: 215. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a VH comprising the amino acid sequence of SEQ ID NO: 234, and a VL comprising the amino acid sequence of SEQ ID NO: 235. In some embodiments, the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises a VH comprising the amino acid sequence of SEQ ID NO: 254, and a VL comprising the amino acid sequence of SEQ ID NO: 255.

[0013] In some embodiments, the bispecific antibody targets IL-5 or IL-5R. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 275, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 276. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 295, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 296. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 315, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 316. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 335, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 336. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 355, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 356. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 375, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 376. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R 7107489comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 277, a HC CDR2 having the amino acid sequence of SEQ ID NO: 278, a HC CDR3 having the amino acid sequence of SEQ ID NO: 279, a LC CDR1 having the amino acid sequence of SEQ ID NO: 280, a LC CDR2 having the amino acid sequence of SEQ ID NO: 281, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 282. In some embodiments, the antigen- specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 283, a HC CDR2 having the amino acid sequence of SEQ ID NO: 284, a HC CDR3 having the amino acid sequence of SEQ ID NO: 285, a LC CDR1 having the amino acid sequence of SEQ ID NO: 286, a LC CDR2 having the amino acid sequence of SEQ ID NO: 287, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 288. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 289, a HC CDR2 having the amino acid sequence of SEQ ID NO: 290, a HC CDR3 having the amino acid sequence of SEQ ID NO: 291, a LC CDR1 having the amino acid sequence of SEQ ID NO: 292, a LC CDR2 having the amino acid sequence of SEQ ID NO: 293, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 294. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 297, a HC CDR2 having the amino acid sequence of SEQ ID NO: 298, a HC CDR3 having the amino acid sequence of SEQ ID NO: 299, a LC CDR1 having the amino acid sequence of SEQ ID NO: 300, a LC CDR2 having the amino acid sequence of SEQ ID NO: 301, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 302. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 303, a HC CDR2 having the amino acid sequence of SEQ ID NO: 304, a HC CDR3 having the amino acid sequence of SEQ ID NO: 305, a LC CDR1 having the amino acid sequence of SEQ ID NO: 306, a LC CDR2 having the amino acid sequence of GAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 308. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 309, a HC CDR2 having the amino acid sequence of SEQ ID NO: 310, a HC CDR3 having the amino acid sequence of SEQ ID NO: 311, a LC CDR1 having the amino acid sequence of SEQ ID NO: 312, a LC CDR2 having the amino acid sequence of SEQ ID NO: 313, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 314. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of 7107489SEQ ID NO: 317, a HC CDR2 having the amino acid sequence of SEQ ID NO: 318, a HC CDR3 having the amino acid sequence of SEQ ID NO: 319, a LC CDR1 having the amino acid sequence of SEQ ID NO: 320, a LC CDR2 having the amino acid sequence of SEQ ID NO: 321, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 322. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 323, a HC CDR2 having the amino acid sequence of SEQ ID NO: 324, a HC CDR3 having the amino acid sequence of SEQ ID NO: 325, a LC CDR1 having the amino acid sequence of SEQ ID NO: 326, a LC CDR2 having the amino acid sequence of GAN, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 328. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 329, a HC CDR2 having the amino acid sequence of SEQ ID NO: 330, a HC CDR3 having the amino acid sequence of SEQ ID NO: 331, a LC CDR1 having the amino acid sequence of SEQ ID NO: 332, a LC CDR2 having the amino acid sequence of SEQ ID NO: 333, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 334. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 337, a HC CDR2 having the amino acid sequence of SEQ ID NO: 338, a HC CDR3 having the amino acid sequence of SEQ ID NO: 339, a LC CDR1 having the amino acid sequence of SEQ ID NO: 340, a LC CDR2 having the amino acid sequence of SEQ ID NO: 341, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 342. In some embodiments, the antigen- specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 343, a HC CDR2 having the amino acid sequence of SEQ ID NO: 344, a HC CDR3 having the amino acid sequence of SEQ ID NO: 345, a LC CDR1 having the amino acid sequence of SEQ ID NO: 346, a LC CDR2 having the amino acid sequence of G, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 348. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 349, a HC CDR2 having the amino acid sequence of SEQ ID NO: 350, a HC CDR3 having the amino acid sequence of SEQ ID NO: 351, a LC CDR1 having the amino acid sequence of SEQ ID NO: 352, a LC CDR2 having the amino acid sequence of SEQ ID NO: 353, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 354. In some embodiments, the antigen- specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 357, a HC CDR2 having the amino acid sequence of 7107489SEQ ID NO: 358, a HC CDR3 having the amino acid sequence of SEQ ID NO: 359, a LC CDR1 having the amino acid sequence of SEQ ID NO: 360, a LC CDR2 having the amino acid sequence of SEQ ID NO: 361, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 362. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 363, a HC CDR2 having the amino acid sequence of SEQ ID NO: 364, a HC CDR3 having the amino acid sequence of SEQ ID NO: 365, a LC CDR1 having the amino acid sequence of SEQ ID NO: 366, a LC CDR2 having the amino acid sequence of RAD, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 368. In some embodiments, the antigen- specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 369, a HC CDR2 having the amino acid sequence of SEQ ID NO: 370, a HC CDR3 having the amino acid sequence of SEQ ID NO: 371, a LC CDR1 having the amino acid sequence of SEQ ID NO: 372, a LC CDR2 having the amino acid sequence of SEQ ID NO: 373, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 374. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 377, a HC CDR2 having the amino acid sequence of SEQ ID NO: 378, a HC CDR3 having the amino acid sequence of SEQ ID NO: 379, a LC CDR1 having the amino acid sequence of SEQ ID NO: 380, a LC CDR2 having the amino acid sequence of SEQ ID NO: 381, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 382. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 383, a HC CDR2 having the amino acid sequence of SEQ ID NO: 384, a HC CDR3 having the amino acid sequence of SEQ ID NO: 385, a LC CDR1 having the amino acid sequence of SEQ ID NO: 386, a LC CDR2 having the amino acid sequence of AAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 388. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 389, a HC CDR2 having the amino acid sequence of SEQ ID NO: 390, a HC CDR3 having the amino acid sequence of SEQ ID NO: 391, a LC CDR1 having the amino acid sequence of SEQ ID NO: 392, a LC CDR2 having the amino acid sequence of SEQ ID NO: 393, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 394. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a VH comprising the amino acid sequence of SEQ ID NO: 275 and a VL comprising the amino acid sequence of SEQ ID NO: 276. In some embodiments, the antigen-specific binding site that specifically 7107489binds IL-5 or IL-5R comprises a VH comprising the amino acid sequence of SEQ ID NO: 295, and a VL comprising the amino acid sequence of SEQ ID NO: 296. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a VH comprising the amino acid sequence of SEQ ID NO: 315, and a VL comprising the amino acid sequence of SEQ ID NO: 316. In some embodiments, the antigen- specific binding site that specifically binds IL-5 or IL-5R comprises a VH comprising the amino acid sequence of SEQ ID NO: 335, and a VL comprising the amino acid sequence of SEQ ID NO: 336. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a VH comprising the amino acid sequence of SEQ ID NO: 355, and a VL comprising the amino acid sequence of SEQ ID NO: 356. In some embodiments, the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises a VH comprising the amino acid sequence of SEQ ID NO: 375, and a VL comprising the amino acid sequence of SEQ ID NO: 376.

[0014] In some embodiments, the bispecific antibody targets IL-9 or IL-9R. In some embodiments, the antigen-specific binding site that specifically binds IL-9 or IL-9R comprises a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 395, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 396. In some embodiments, the antigen-specific binding site that specifically binds IL-9 or IL-9R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 397, a HC CDR2 having the amino acid sequence of SEQ ID NO: 398, a HC CDR3 having the amino acid sequence of SEQ ID NO: 399, a LC CDR1 having the amino acid sequence of SEQ ID NO: 400, a LC CDR2 having the amino acid sequence of SEQ ID NO: 401, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 402. In some embodiments, the antigen- specific binding site that specifically binds IL-9 or IL-9R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 403, a HC CDR2 having the amino acid sequence of SEQ ID NO: 404, a HC CDR3 having the amino acid sequence of SEQ ID NO: 405, a LC CDR1 having the amino acid sequence of SEQ ID NO: 406, a LC CDR2 having the amino acid sequence of GTS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 408. In some embodiments, the antigen-specific binding site that specifically binds IL-9 or IL-9R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 409, a HC CDR2 having the amino acid sequence of SEQ ID NO: 410, a HC CDR3 having the amino acid sequence of SEQ ID NO: 411, a LC CDR1 having the amino acid sequence of SEQ ID NO: 412, a LC CDR2 having the amino acid sequence of SEQ ID NO: 413, and a LC CDR3 7107489having the amino acid sequence of SEQ ID NO: 414. In some embodiments, the antigen- specific binding site that specifically binds IL-9 or IL-9R comprises a VH comprising the amino acid sequence of SEQ ID NO: 395 and a VL comprising the amino acid sequence of SEQ ID NO: 396. In some embodiments, the bispecific antibody targets OX40L or OX40. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 415, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 416. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 435, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 436. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 819, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 820. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 839, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 840. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 859, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 860. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 417, a HC CDR2 having the amino acid sequence of SEQ ID NO: 418, a HC CDR3 having the amino acid sequence of SEQ ID NO: 419, a LC CDR1 having the amino acid sequence of SEQ ID NO: 420, a LC CDR2 having the amino acid sequence of SEQ ID NO: 421, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 422. In some embodiments, the antigen- specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 423, a HC CDR2 having the amino acid sequence of SEQ ID NO: 424, a HC CDR3 having the amino acid sequence of SEQ ID NO: 425, a LC CDR1 having the amino acid sequence of SEQ ID NO: 426, a LC CDR2 having the amino 7107489acid sequence of GAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 428. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 429, a HC CDR2 having the amino acid sequence of SEQ ID NO: 430, a HC CDR3 having the amino acid sequence of SEQ ID NO: 431, a LC CDR1 having the amino acid sequence of SEQ ID NO: 432, a LC CDR2 having the amino acid sequence of SEQ ID NO: 433, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 434. In some embodiments, the antigen- specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 437, a HC CDR2 having the amino acid sequence of SEQ ID NO: 438, a HC CDR3 having the amino acid sequence of SEQ ID NO: 439, a LC CDR1 having the amino acid sequence of SEQ ID NO: 440, a LC CDR2 having the amino acid sequence of SEQ ID NO: 441, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 442. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 443, a HC CDR2 having the amino acid sequence of SEQ ID NO: 444, a HC CDR3 having the amino acid sequence of SEQ ID NO: 445, a LC CDR1 having the amino acid sequence of SEQ ID NO: 446, a LC CDR2 having the amino acid sequence of AAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 448. In some embodiments, the antigen- specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 449, a HC CDR2 having the amino acid sequence of SEQ ID NO: 450, a HC CDR3 having the amino acid sequence of SEQ ID NO: 451, a LC CDR1 having the amino acid sequence of SEQ ID NO: 452, a LC CDR2 having the amino acid sequence of SEQ ID NO: 453, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 454. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 821, a HC CDR2 having the amino acid sequence of SEQ ID NO: 822, a HC CDR3 having the amino acid sequence of SEQ ID NO: 823, a LC CDR1 having the amino acid sequence of SEQ ID NO: 824, a LC CDR2 having the amino acid sequence of SEQ ID NO: 825, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 826. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 827, a HC CDR2 having the amino acid sequence of SEQ ID NO: 828, a HC CDR3 having the amino acid sequence of SEQ ID NO: 829, a LC CDR1 having the amino acid sequence of SEQ ID NO: 830, a LC CDR2 having the amino acid sequence of ATS, and a LC CDR3 having the amino acid sequence of SEQ ID 7107489NO: 832. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 833, a HC CDR2 having the amino acid sequence of SEQ ID NO: 834, a HC CDR3 having the amino acid sequence of SEQ ID NO: 835, a LC CDR1 having the amino acid sequence of SEQ ID NO: 836, a LC CDR2 having the amino acid sequence of SEQ ID NO: 837, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 838. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 841, a HC CDR2 having the amino acid sequence of SEQ ID NO: 842, a HC CDR3 having the amino acid sequence of SEQ ID NO: 843, a LC CDR1 having the amino acid sequence of SEQ ID NO: 844, a LC CDR2 having the amino acid sequence of SEQ ID NO: 845, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 846. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 847, a HC CDR2 having the amino acid sequence of SEQ ID NO: 848, a HC CDR3 having the amino acid sequence of SEQ ID NO: 849, a LC CDR1 having the amino acid sequence of SEQ ID NO: 850, a LC CDR2 having the amino acid sequence of AAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 852. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 853, a HC CDR2 having the amino acid sequence of SEQ ID NO: 854, a HC CDR3 having the amino acid sequence of SEQ ID NO: 855, a LC CDR1 having the amino acid sequence of SEQ ID NO: 856, a LC CDR2 having the amino acid sequence of SEQ ID NO: 857, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 858. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 861, a HC CDR2 having the amino acid sequence of SEQ ID NO: 862, a HC CDR3 having the amino acid sequence of SEQ ID NO: 863, a LC CDR1 having the amino acid sequence of SEQ ID NO: 864, a LC CDR2 having the amino acid sequence of SEQ ID NO: 865, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 866. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 867, a HC CDR2 having the amino acid sequence of SEQ ID NO: 868, a HC CDR3 having the amino acid sequence of SEQ ID NO: 869, a LC CDR1 having the amino acid sequence of SEQ ID NO: 870, a LC CDR2 having the amino acid sequence of RAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 872. In some embodiments, the antigen-specific binding site 7107489that specifically binds OX40L or OX40 comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 873, a HC CDR2 having the amino acid sequence of SEQ ID NO: 874, a HC CDR3 having the amino acid sequence of SEQ ID NO: 875, a LC CDR1 having the amino acid sequence of SEQ ID NO: 876, a LC CDR2 having the amino acid sequence of SEQ ID NO: 878, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 872. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a VH comprising the amino acid sequence of SEQ ID NO: 415 and a VL comprising the amino acid sequence of SEQ ID NO: 416. In some embodiments, the antigen- specific binding site that specifically binds OX40L or OX40 comprises a VH comprising the amino acid sequence of SEQ ID NO: 435, and a VL comprising the amino acid sequence of SEQ ID NO: 436. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a VH comprising the amino acid sequence of SEQ ID NO: 819, and a VL comprising the amino acid sequence of SEQ ID NO: 820. In some embodiments, the antigen-specific binding site that specifically binds OX40L or OX40 comprises a VH comprising the amino acid sequence of SEQ ID NO: 839, and a VL comprising the amino acid sequence of SEQ ID NO: 840. In some embodiments, the antigen- specific binding site that specifically binds OX40L or OX40 comprises a VH comprising the amino acid sequence of SEQ ID NO: 859, and a VL comprising the amino acid sequence of SEQ ID NO: 860.

[0015] In some embodiments, the bispecific antibody targets IL-25 or IL-25R. In some embodiments, the antigen-specific binding site that specifically binds IL-25 or IL-25R comprises a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 455, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 456. In some embodiments, the antigen-specific binding site that specifically binds IL-25 or IL-25R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 719, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 720. In some embodiments, the antigen-specific binding site that specifically binds IL-25 or IL-25R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 457, a HC CDR2 having the amino acid sequence of SEQ ID NO: 458, a HC CDR3 having the amino acid sequence of SEQ ID NO: 459, a LC CDR1 having the amino acid sequence of SEQ ID NO: 460, a LC CDR2 having the amino acid sequence of SEQ ID NO: 461, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 462. In some embodiments, the antigen- 7107489specific binding site that specifically binds IL-25 or IL-25R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 463, a HC CDR2 having the amino acid sequence of SEQ ID NO: 464, a HC CDR3 having the amino acid sequence of SEQ ID NO: 465, a LC CDR1 having the amino acid sequence of SEQ ID NO: 466, a LC CDR2 having the amino acid sequence of DAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 468. In some embodiments, the antigen-specific binding site that specifically binds IL-25 or IL- 25R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 469, a HC CDR2 having the amino acid sequence of SEQ ID NO: 470, a HC CDR3 having the amino acid sequence of SEQ ID NO: 471, a LC CDR1 having the amino acid sequence of SEQ ID NO: 472, a LC CDR2 having the amino acid sequence of SEQ ID NO: 473, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 474. In some embodiments, the antigen- specific binding site that specifically binds IL-25 or IL-25R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 721, a HC CDR2 having the amino acid sequence of SEQ ID NO: 722, a HC CDR3 having the amino acid sequence of SEQ ID NO: 723, a LC CDR1 having the amino acid sequence of SEQ ID NO: 724, a LC CDR2 having the amino acid sequence of SEQ ID NO: 725, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 726. In some embodiments, the antigen-specific binding site that specifically binds IL-25 or IL-25R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 727, a HC CDR2 having the amino acid sequence of SEQ ID NO: 728, a HC CDR3 having the amino acid sequence of SEQ ID NO: 729, a LC CDR1 having the amino acid sequence of SEQ ID NO: 730, a LC CDR2 having the amino acid sequence of RTS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 732. In some embodiments, the antigen- specific binding site that specifically binds IL-25 or IL-25R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 733, a HC CDR2 having the amino acid sequence of SEQ ID NO: 734, a HC CDR3 having the amino acid sequence of SEQ ID NO: 735, a LC CDR1 having the amino acid sequence of SEQ ID NO: 736, a LC CDR2 having the amino acid sequence of SEQ ID NO: 737, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 738. In some embodiments, the antigen-specific binding site that specifically binds IL-25 or IL-25R comprises a VH comprising the amino acid sequence of SEQ ID NO: 455 and a VL comprising the amino acid sequence of SEQ ID NO: 456. In some embodiments, the antigen-specific binding site that specifically binds IL-25 or IL-25R comprises a VH comprising the amino acid sequence of SEQ ID NO: 719, and a VL comprising the amino acid sequence of SEQ ID NO: 720.

[0016] In some embodiments, the bispecific antibody targets IL-31 or IL-31R. In 7107489some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 475, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 476. In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 495, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 496. In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 739, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 740. In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 759, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 760. In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 477, a HC CDR2 having the amino acid sequence of SEQ ID NO: 478, a HC CDR3 having the amino acid sequence of SEQ ID NO: 479, a LC CDR1 having the amino acid sequence of SEQ ID NO: 480, a LC CDR2 having the amino acid sequence of SEQ ID NO: 481, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 482. In some embodiments, the antigen- specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 483, a HC CDR2 having the amino acid sequence of SEQ ID NO: 484, a HC CDR3 having the amino acid sequence of SEQ ID NO: 485, a LC CDR1 having the amino acid sequence of SEQ ID NO: 486, a LC CDR2 having the amino acid sequence of SEQ ID NO: 487, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 488. In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 489, a HC CDR2 having the amino acid sequence of SEQ ID NO: 490, a HC CDR3 having the amino acid sequence of SEQ ID NO: 491, a LC CDR1 having the amino acid sequence of SEQ ID NO: 492, a LC CDR2 having the amino acid sequence of SEQ ID NO: 493, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 494. In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1 7107489having the amino acid sequence of SEQ ID NO: 497, a HC CDR2 having the amino acid sequence of SEQ ID NO: 498, a HC CDR3 having the amino acid sequence of SEQ ID NO: 499, a LC CDR1 having the amino acid sequence of SEQ ID NO: 500, a LC CDR2 having the amino acid sequence of SEQ ID NO: 501, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 502. In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 503, a HC CDR2 having the amino acid sequence of SEQ ID NO: 504, a HC CDR3 having the amino acid sequence of SEQ ID NO: 505, a LC CDR1 having the amino acid sequence of SEQ ID NO: 506, a LC CDR2 having the amino acid sequence of NIN, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 508. In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 509, a HC CDR2 having the amino acid sequence of SEQ ID NO: 510, a HC CDR3 having the amino acid sequence of SEQ ID NO: 511, a LC CDR1 having the amino acid sequence of SEQ ID NO: 512, a LC CDR2 having the amino acid sequence of SEQ ID NO: 513, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 514 In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 741, a HC CDR2 having the amino acid sequence of SEQ ID NO: 742, a HC CDR3 having the amino acid sequence of SEQ ID NO: 743, a LC CDR1 having the amino acid sequence of SEQ ID NO: 744, a LC CDR2 having the amino acid sequence of SEQ ID NO: 745, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 746. In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 747, a HC CDR2 having the amino acid sequence of SEQ ID NO: 748, a HC CDR3 having the amino acid sequence of SEQ ID NO: 749, a LC CDR1 having the amino acid sequence of SEQ ID NO: 750, a LC CDR2 having the amino acid sequence of QAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 752. In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 753, a HC CDR2 having the amino acid sequence of SEQ ID NO: 754, a HC CDR3 having the amino acid sequence of SEQ ID NO: 755, a LC CDR1 having the amino acid sequence of SEQ ID NO: 756, a LC CDR2 having the amino acid sequence of SEQ ID NO: 757, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 758. In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 761, a HC CDR2 7107489having the amino acid sequence of SEQ ID NO: 762, a HC CDR3 having the amino acid sequence of SEQ ID NO: 763, a LC CDR1 having the amino acid sequence of SEQ ID NO: 764, a LC CDR2 having the amino acid sequence of SEQ ID NO: 765, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 766. In some embodiments, the antigen- specific binding site that specifically binds IL-31 or IL-31R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 767, a HC CDR2 having the amino acid sequence of SEQ ID NO: 768, a HC CDR3 having the amino acid sequence of SEQ ID NO: 770, a LC CDR1 having the amino acid sequence of SEQ ID NO: 346, a LC CDR2 having the amino acid sequence of NAK, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 772. In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL- 31R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 773, a HC CDR2 having the amino acid sequence of SEQ ID NO: 774, a HC CDR3 having the amino acid sequence of SEQ ID NO: 775, a LC CDR1 having the amino acid sequence of SEQ ID NO: 776, a LC CDR2 having the amino acid sequence of SEQ ID NO: 777, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 778. In some embodiments, the antigen- specific binding site that specifically binds IL-31 or IL-31R comprises a VH comprising the amino acid sequence of SEQ ID NO: 475 and a VL comprising the amino acid sequence of SEQ ID NO: 476. In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a VH comprising the amino acid sequence of SEQ ID NO: 495, and a VL comprising the amino acid sequence of SEQ ID NO: 496. In some embodiments, the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises a VH comprising the amino acid sequence of SEQ ID NO: 739, and a VL comprising the amino acid sequence of SEQ ID NO: 740. In some embodiments, the antigen- specific binding site that specifically binds IL-31 or IL-31R comprises a VH comprising the amino acid sequence of SEQ ID NO: 759, and a VL comprising the amino acid sequence of SEQ ID NO: 760.

[0017] In some embodiments, the bispecific antibody targets IL-36 or IL-36R. In some embodiments, the antigen-specific binding site that specifically binds IL-36 or IL-36R comprises a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 575, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 576. In some embodiments, the antigen-specific binding site that specifically binds IL-36 or IL-36R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 595, and a LC CDR1, LC CDR2 and LC CDR3 of a 7107489light chain variable domain having the amino acid sequence of SEQ ID NO: 596. In some embodiments, the antigen-specific binding site that specifically binds IL-36 or IL-36R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 779, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 780. In some embodiments, the antigen-specific binding site that specifically binds IL-36 or IL-36R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 577, a HC CDR2 having the amino acid sequence of SEQ ID NO: 578, a HC CDR3 having the amino acid sequence of SEQ ID NO: 579, a LC CDR1 having the amino acid sequence of SEQ ID NO: 580, a LC CDR2 having the amino acid sequence of SEQ ID NO: 581, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 582. In some embodiments, the antigen- specific binding site that specifically binds IL-36 or IL-36R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 583, a HC CDR2 having the amino acid sequence of SEQ ID NO: 584, a HC CDR3 having the amino acid sequence of SEQ ID NO: 585, a LC CDR1 having the amino acid sequence of SEQ ID NO: 586, a LC CDR2 having the amino acid sequence of RTS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 588. In some embodiments, the antigen-specific binding site that specifically binds IL-36 or IL- 36R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 589, a HC CDR2 having the amino acid sequence of SEQ ID NO: 590, a HC CDR3 having the amino acid sequence of SEQ ID NO: 591, a LC CDR1 having the amino acid sequence of SEQ ID NO: 592, a LC CDR2 having the amino acid sequence of SEQ ID NO: 593, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 594. In some embodiments, the antigen- specific binding site that specifically binds IL-36 or IL-36R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 597, a HC CDR2 having the amino acid sequence of SEQ ID NO: 598, a HC CDR3 having the amino acid sequence of SEQ ID NO: 599, a LC CDR1 having the amino acid sequence of SEQ ID NO: 600, a LC CDR2 having the amino acid sequence of SEQ ID NO: 601, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 602. In some embodiments, the antigen-specific binding site that specifically binds IL-36 or IL-36R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 603, a HC CDR2 having the amino acid sequence of SEQ ID NO: 604, a HC CDR3 having the amino acid sequence of SEQ ID NO: 605, a LC CDR1 having the amino acid sequence of SEQ ID NO: 606, a LC CDR2 having the amino acid sequence of QMS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 608. In some embodiments, the antigen- specific binding site that specifically binds IL-36 or IL-36R comprises a HC CDR1 having 7107489the amino acid sequence of SEQ ID NO: 609, a HC CDR2 having the amino acid sequence of SEQ ID NO: 610, a HC CDR3 having the amino acid sequence of SEQ ID NO: 611, a LC CDR1 having the amino acid sequence of SEQ ID NO: 612, a LC CDR2 having the amino acid sequence of SEQ ID NO: 613, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 614. In some embodiments, the antigen-specific binding site that specifically binds IL-36 or IL-36R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 781, a HC CDR2 having the amino acid sequence of SEQ ID NO: 782, a HC CDR3 having the amino acid sequence of SEQ ID NO: 783, a LC CDR1 having the amino acid sequence of SEQ ID NO: 784, a LC CDR2 having the amino acid sequence of SEQ ID NO: 785, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 786. In some embodiments, the antigen-specific binding site that specifically binds IL-36 or IL-36R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 787, a HC CDR2 having the amino acid sequence of SEQ ID NO: 788, a HC CDR3 having the amino acid sequence of SEQ ID NO: 789, a LC CDR1 having the amino acid sequence of SEQ ID NO: 790, a LC CDR2 having the amino acid sequence of STS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 792. In some embodiments, the antigen-specific binding site that specifically binds IL- 36 or IL-36R comprises a VH comprising the amino acid sequence of SEQ ID NO: 575 and a VL comprising the amino acid sequence of SEQ ID NO: 576. In some embodiments, the antigen-specific binding site that specifically binds IL-36 or IL-36R comprises a VH comprising the amino acid sequence of SEQ ID NO: 595, and a VL comprising the amino acid sequence of SEQ ID NO: 596. In some embodiments, the antigen-specific binding site that specifically binds IL-36 or IL-36R comprises a VH comprising the amino acid sequence of SEQ ID NO: 779, and a VL comprising the amino acid sequence of SEQ ID NO: 780.

[0018] In some embodiments, the bispecific antibody targets TSLP or TSLPR. In some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 615, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 616. In some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 635, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 636. In some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having 7107489the amino acid sequence of SEQ ID NO: 879, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 880. In some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 899, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 900. In some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 617, a HC CDR2 having the amino acid sequence of SEQ ID NO: 618, a HC CDR3 having the amino acid sequence of SEQ ID NO: 619, a LC CDR1 having the amino acid sequence of SEQ ID NO: 620, a LC CDR2 having the amino acid sequence of SEQ ID NO: 621, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 622. In some embodiments, the antigen- specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 623, a HC CDR2 having the amino acid sequence of SEQ ID NO: 624, a HC CDR3 having the amino acid sequence of SEQ ID NO: 625, a LC CDR1 having the amino acid sequence of SEQ ID NO: 626, a LC CDR2 having the amino acid sequence of DDS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 628. In some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 629, a HC CDR2 having the amino acid sequence of SEQ ID NO: 630, a HC CDR3 having the amino acid sequence of SEQ ID NO: 631, a LC CDR1 having the amino acid sequence of SEQ ID NO: 632, a LC CDR2 having the amino acid sequence of SEQ ID NO: 633, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 634. In some embodiments, the antigen- specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 637, a HC CDR2 having the amino acid sequence of SEQ ID NO: 638, a HC CDR3 having the amino acid sequence of SEQ ID NO: 639, a LC CDR1 having the amino acid sequence of SEQ ID NO: 640, a LC CDR2 having the amino acid sequence of SEQ ID NO: 641, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 642. In some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 643, a HC CDR2 having the amino acid sequence of SEQ ID NO: 644, a HC CDR3 having the amino acid sequence of SEQ ID NO: 645, a LC CDR1 having the amino acid sequence of SEQ ID NO: 646, a LC CDR2 having the amino acid sequence of GDN, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 648. In some embodiments, the antigen- 7107489specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 649, a HC CDR2 having the amino acid sequence of SEQ ID NO: 650, a HC CDR3 having the amino acid sequence of SEQ ID NO: 651, a LC CDR1 having the amino acid sequence of SEQ ID NO: 652, a LC CDR2 having the amino acid sequence of SEQ ID NO: 653, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 654. some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 881, a HC CDR2 having the amino acid sequence of SEQ ID NO: 882, a HC CDR3 having the amino acid sequence of SEQ ID NO: 883, a LC CDR1 having the amino acid sequence of SEQ ID NO: 884, a LC CDR2 having the amino acid sequence of SEQ ID NO: 885, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 886. some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 887, a HC CDR2 having the amino acid sequence of SEQ ID NO: 888, a HC CDR3 having the amino acid sequence of SEQ ID NO: 889, a LC CDR1 having the amino acid sequence of SEQ ID NO: 890, a LC CDR2 having the amino acid sequence of FAR, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 892. some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 893, a HC CDR2 having the amino acid sequence of SEQ ID NO: 894, a HC CDR3 having the amino acid sequence of SEQ ID NO: 895, a LC CDR1 having the amino acid sequence of SEQ ID NO: 896, a LC CDR2 having the amino acid sequence of SEQ ID NO: 897, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 898. some embodiments, the antigen- specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 901, a HC CDR2 having the amino acid sequence of SEQ ID NO: 902, a HC CDR3 having the amino acid sequence of SEQ ID NO: 903, a LC CDR1 having the amino acid sequence of SEQ ID NO: 904, a LC CDR2 having the amino acid sequence of SEQ ID NO: 905, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 906. some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 907, a HC CDR2 having the amino acid sequence of SEQ ID NO: 908, a HC CDR3 having the amino acid sequence of SEQ ID NO: 909, a LC CDR1 having the amino acid sequence of SEQ ID NO: 910, a LC CDR2 having the amino acid sequence of FAK, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 912. some embodiments, the antigen- specific binding site that specifically binds TSLP or TSLPR comprises a HC CDR1 having 7107489the amino acid sequence of SEQ ID NO: 913, a HC CDR2 having the amino acid sequence of SEQ ID NO: 914, a HC CDR3 having the amino acid sequence of SEQ ID NO: 915, a LC CDR1 having the amino acid sequence of SEQ ID NO: 916, a LC CDR2 having the amino acid sequence of SEQ ID NO: 917, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 918. n some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a VH comprising the amino acid sequence of SEQ ID NO: 615 and a VL comprising the amino acid sequence of SEQ ID NO: 616. some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a VH comprising the amino acid sequence of SEQ ID NO: 635, and a VL comprising the amino acid sequence of SEQ ID NO: 636. some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a VH comprising the amino acid sequence of SEQ ID NO: 879, and a VL comprising the amino acid sequence of SEQ ID NO: 880. some embodiments, the antigen-specific binding site that specifically binds TSLP or TSLPR comprises a VH comprising the amino acid sequence of SEQ ID NO: 899, and a VL comprising the amino acid sequence of SEQ ID NO: 900.

[0019] In some embodiments, the bispecific antibody targets IL-33 or IL-33R. In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 677, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 678. In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 697, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 698. In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 717, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 718. In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 799, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 800. In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 659, a HC CDR2 7107489having the amino acid sequence of SEQ ID NO: 660, a HC CDR3 having the amino acid sequence of SEQ ID NO: 661, a LC CDR1 having the amino acid sequence of SEQ ID NO: 662, a LC CDR2 having the amino acid sequence of SEQ ID NO: 663, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 664. In some embodiments, the antigen- specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 665, a HC CDR2 having the amino acid sequence of SEQ ID NO: 666, a HC CDR3 having the amino acid sequence of SEQ ID NO: 667, a LC CDR1 having the amino acid sequence of SEQ ID NO: 668, a LC CDR2 having the amino acid sequence of RDT, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 670, In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL- 33R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 671, a HC CDR2 having the amino acid sequence of SEQ ID NO: 672, a HC CDR3 having the amino acid sequence of SEQ ID NO: 673, a LC CDR1 having the amino acid sequence of SEQ ID NO: 674, a LC CDR2 having the amino acid sequence of SEQ ID NO: 675, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 676. In some embodiments, the antigen- specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 679, a HC CDR2 having the amino acid sequence of SEQ ID NO: 680, a HC CDR3 having the amino acid sequence of SEQ ID NO: 681, a LC CDR1 having the amino acid sequence of SEQ ID NO: 682, a LC CDR2 having the amino acid sequence of SEQ ID NO: 683, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 684. In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 685, a HC CDR2 having the amino acid sequence of SEQ ID NO: 686, a HC CDR3 having the amino acid sequence of SEQ ID NO: 687, a LC CDR1 having the amino acid sequence of SEQ ID NO: 688, a LC CDR2 having the amino acid sequence of AAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 690. In some embodiments, the antigen- specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 691, a HC CDR2 having the amino acid sequence of SEQ ID NO: 692, a HC CDR3 having the amino acid sequence of SEQ ID NO: 693, a LC CDR1 having the amino acid sequence of SEQ ID NO: 694, a LC CDR2 having the amino acid sequence of SEQ ID NO: 695, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 696. In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 699, a HC CDR2 having the amino acid sequence of SEQ ID NO: 700, a HC CDR3 having the 7107489amino acid sequence of SEQ ID NO: 701, a LC CDR1 having the amino acid sequence of SEQ ID NO: 702, a LC CDR2 having the amino acid sequence of SEQ ID NO: 703, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 704. In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 705, a HC CDR2 having the amino acid sequence of SEQ ID NO: 706, a HC CDR3 having the amino acid sequence of SEQ ID NO: 707, a LC CDR1 having the amino acid sequence of SEQ ID NO: 708, a LC CDR2 having the amino acid sequence of WAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 710. In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 711, a HC CDR2 having the amino acid sequence of SEQ ID NO: 712, a HC CDR3 having the amino acid sequence of SEQ ID NO: 713, a LC CDR1 having the amino acid sequence of SEQ ID NO: 714, a LC CDR2 having the amino acid sequence of SEQ ID NO: 715, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 716. In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 801, a HC CDR2 having the amino acid sequence of SEQ ID NO: 802, a HC CDR3 having the amino acid sequence of SEQ ID NO: 803, a LC CDR1 having the amino acid sequence of SEQ ID NO: 804, a LC CDR2 having the amino acid sequence of SEQ ID NO: 805, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 806. In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 807, a HC CDR2 having the amino acid sequence of SEQ ID NO: 808, a HC CDR3 having the amino acid sequence of SEQ ID NO: 809, a LC CDR1 having the amino acid sequence of SEQ ID NO: 810, a LC CDR2 having the amino acid sequence of FTN, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 812. In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 813, a HC CDR2 having the amino acid sequence of SEQ ID NO: 814, a HC CDR3 having the amino acid sequence of SEQ ID NO: 815, a LC CDR1 having the amino acid sequence of SEQ ID NO: 816, a LC CDR2 having the amino acid sequence of SEQ ID NO: 817, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 818. In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises a VH comprising the amino acid sequence of SEQ ID NO: 677 and a VL comprising the amino acid sequence of SEQ ID NO: 678. In some embodiments, the antigen-specific binding site that specifically binds IL-33 or IL-33R 7107489comprises a VH comprising the amino acid sequence of SEQ ID NO: 799, and a VL comprising the amino acid sequence of SEQ ID NO: 800.

[0020] In some embodiments, the antigen-specific binding site that specifically binds a Th2 cytokine or a receptor thereof comprises VH and / or a VL of any one of the antibodies in Table 2.

[0021] In some embodiments, the bispecific antibody retains the binding affinity to KLK5 and KLK7 of no more than 20% difference relative to an anti-KLK5 / KLK7 antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody. In some embodiments, the bispecific antibody retains the binding affinity of no more than 20% difference to a Th2 target relative to a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody. In some embodiments, the bispecific antibody retains at least 80% of inhibitory activity to KLK5 and KLK7 relative to an anti-KLK5 / KLK7 antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody. In some embodiments, the bispecific antibody retains at least 80% of inhibitory activity to a Th2 signaling relative to a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody.

[0022] The present disclosure provides a composition comprising the bispecific antibody described herein and an acceptable carrier.

[0023] In some aspects, the present disclosure provides a method comprising administering the bispecific antibody of the antibody or the composition described herein to a subject. In some embodiments, the subject has a skin barrier defect. In some aspects, the present disclosure provides a method of treating a skin barrier defect, the method comprising administering to a subject an effective amount of the bispecific antibody or the composition described herein. In some embodiments, the skin barrier defect is associated with Netherton syndrome, atopic dermatitis, eosinophilic esophagitis, prurigo nodularis, chronic pruritus of unknown origin (CPUO), dry skin, asthma (KLK5 specifically), ichthyosis vulgaris, or itch or chronic itch. In some embodiments, the subject has atopic dermatitis.

[0024] In some embodiments, the administration reduces ear thickness by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody. In some embodiments, the administration reduces ear thickness by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody. In some embodiments, the administration reduces skin erythema / hemorrhage by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs 7107489and / or VH / VL as the bispecific antibody. In some embodiments, the administration reduces skin erythema / hemorrhage by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody. In some embodiments, the administration reduces skin erythema / hemorrhage by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody. In some embodiments, the administration reduces skin excoriation / erosion by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody. In some embodiments, the administration reduces skin scaling / dryness by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody. In some embodiments, the administration reduces skin scaling / dryness by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody. In some embodiments, the administration reduces skin edema by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody. In some embodiments, the administration reduces skin edema by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody.

[0025] The foregoing and other aspects, implementations, acts, functionalities, features and embodiments of the present teachings can be more fully understood from the following description in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate certain embodiments, and together with the written description, serve to provide non-limiting examples of certain aspects of the compositions and methods disclosed herein.

[0027] FIG.1 is a diagram showing aberrant protease activation (e.g., aberrant KLK5, KLK7, and KLK14) activation leading to skin barrier defect associated diseases.

[0028] FIG.2 is a graph showing that, in conditions related to epidermal barrier dysfunction, elevated KLK5 / KLK7 activity leads to Th2 cell activation, which further increases KLK5 / KLK7 activity.

[0029] FIGs.3A-3B are graphs showing that inhibiting KLK5 / KLK7 and Th2 7107489signaling has beneficial effects beyond targeting either pathway alone in Nc / Nga model for atopic dermatitis. FIG.3A shows that mice treated with KLK5 / KLK7-Dual-Ab4 in combination with an anti-IL-4R antibody have further reduced ear thickness compared to mice treated with KLK5 / KLK7-Dual-Ab4 or the anti-IL-4R antibody alone. FIG.3B shows mice treated with KLK5 / KLK7-Dual-Ab4 in combination with an anti-IL-4R antibody have reduced clinical skin score compared to treating with KLK5 / KLK7-Dual-Ab4 or the anti-IL- 4R antibody alone.

[0030] FIGs.4A-4I relate to binding affinity of an exemplary anti-KLK5 / KLK7 + IL-13 bispecific antibody (referred to as K13-0004). FIGs 4A-4C show KD values of binding to KLK5 (FIG.4A), KLK7 (FIG.4B), and IL-13 (FIG.4C). FIGs.4D-4H show the inhibition of KLK5 (FIG.4D; comparison to an exemplary anti-KLK5 / KLK7 dual antibody in FIG. 4E), KLK7 (FIG.4F; comparison to an exemplary anti-KLK5 / KLK7 dual antibody in FIG. 4G), IL-13 (FIG.4H), and the extracellular matrix protein (ECM) periostin (FIG.4I).

[0031] FIGs.5A-5D relate to the abrogation of KLK5- and KLK7-mediated disruption of primary human keratinocyte barrier disruption. FIGs.5A shows the trans- epithelial resistance (TEER) follow treatment with an anti-KLK5 / KLK7 + IL-13 bispecific antibody K13-0004 at varying concentrations (FIG.5A) or KLK5 / KLK7-dual-Ab4 at varying concentrations (FIG.5B). FIGs.5C-5D show the migration of FITC-Dextran dye following treatment with anti-KLK5 / KLK7 + IL-13 bispecific antibody K13-0004 at varying concentrations (FIG.5C) or KLK5 / KLK7-dual-Ab4 at varying concentrations (FIG.5D). DETAILED DESCRIPTION

[0032] The present disclosure, at least in part, is based on the development of dual inhibitor antibodies and variants thereof targeting KLK5 and KLK7. These dual inhibitor antibodies target KLK5 and KLK7 via a common distinct antigen-specific binding site. Such dual inhibitor antibodies have high binding affinity and specificity to KLK5 and KLK7 (anti- KLK5 / KLK7 antibodies). In some embodiments, bispecific antibodies are provided in which one arm comprises an antigen-specific binding site of a dual inhibitor antibody targeting KLK5 and KLK7 and in which the other arm specifically binds to and inhibits activity of a Th2 cytokine, such as IL-13, IL-4, IL-5, IL-6, IL-9, IL-31, IL-17E (IL-25), OX40L, TSLP, etc., or a receptor thereof. Also provided are methods of using the anti- KLK5 / KLK7 + Th2 bi specific antibodies and their variants in research, diagnostic / detection, 7107489and therapeutic applications, and anti-KLK5 / KLK7 + Th2 bispecific antibodies for use in such methods.

[0033] The foregoing and other aspects, implementations, acts, functionalities, features and embodiments of the present teachings can be more fully understood from the following description in conjunction with the accompanying drawings. I. Definitions

[0034] Administering: As used herein, the terms “administering” or “administration” means to provide an antibody or a composition thereof to a subject in a manner that is physiologically and / or pharmacologically useful (e.g., to treat a condition in the subject).

[0035] Affinity Matured Antibody: The term “Affinity Matured Antibody” is used herein to refer to an antibody with one or more alterations in one or more CDRs, which result in an improvement in the affinity (e.g., KD, kd or ka) of the antibody for a target antigen compared to a parent antibody, which does not possess the alteration(s). Exemplary affinity matured antibodies may have nanomolar or even picomolar affinities for the target antigen in some embodiments. A variety of procedures for producing affinity matured antibodies are available, including the screening of a combinatory antibody library that has been prepared using bio-display. For example, Marks et al., BioTechnology, 10: 779-783 (1992) describes affinity maturation by VH and VL domain shuffling. Random mutagenesis of CDR and / or framework residues is described by Barbas et al., Proc. Nat. Acad. Sci. USA, 91: 3809-3813 (1994); Schier et al., Gene, 169: 147-155 (1995); Yelton et al., J. Immunol., 155: 1994-2004 (1995); Jackson et al., J. Immunol., 154(7): 3310-3319 (1995); and Hawkins et al, J. Mol. Biol., 226: 889-896 (1992). Selective mutation at selective mutagenesis positions and at contact or hypermutation positions with an activity-enhancing amino acid residue is described in U.S. Pat. No.6,914,128 B1.

[0036] Antibody: As used herein, the term “antibody” refers to a polypeptide that comprises at least one immunoglobulin variable domain, which comprises at least one distinct antigen-specific binding site, or a portion of an immunoglobulin variable domain (such as a paratope or portion thereof) that comprises at least one distinct antigen-specific binding site. In some embodiments, an antibody comprises at least one distinct antigen- specific binding site that specifically binds to the active site of an enzyme. In some embodiments, an antibody is a Th2 targeting antibody that comprises at least one antigen- specific binding site that specifically binds to a Th2 cytokine or a receptor thereof. In some embodiments, an antibody is a full-length antibody. In some embodiments, an antibody is a 7107489chimeric antibody. In some embodiments, an antibody is a humanized antibody. However, in some embodiments, an antibody is a Fab fragment, a F(ab')2 fragment, a Fv fragment or a scFv fragment. In some embodiments, an antibody is a multi-specific antibody (e.g., a bispecific antibody). In some embodiments, an antibody is a nanobody derived from a camelid antibody or a nanobody derived from shark antibody. In some embodiments, an antibody is a diabody. In some embodiments, an antibody comprises a framework having a human germline sequence. In another embodiment, an antibody comprises a heavy chain constant domain selected from the group consisting of IgG, IgG1, IgG2, IgG2A, IgG2B, IgG2C, IgG3, IgG4, IgA1, IgA2, IgD, IgM, and IgE constant domains. In some embodiments, an antibody comprises a heavy (H) chain variable region or domain (abbreviated herein as VH), and / or a light (L) chain variable region or domain (abbreviated herein as VL). In some embodiments, an antibody comprises a constant domain. An immunoglobulin constant domain refers to a heavy or light chain constant domain. Human IgG heavy chain and light chain constant domain amino acid sequences and their functional variations are known. In some embodiments, a heavy chain constant domain of an immunoglobulin comprises an Fc region. With respect to the heavy chain, in some embodiments, the heavy chain of an antibody described herein can be an alpha (α), delta (∆), epsilon (ε), gamma (γ) or mu (µ) heavy chain. In some embodiments, the heavy chain of an antibody described herein can comprise a human alpha (α), delta (∆), epsilon (ε), gamma (γ) or mu (µ) heavy chain. In some embodiments, an antibody described herein comprises a human gamma 1 CH1, CH2, and / or CH3 domain. In some embodiments, the amino acid sequence of the antibody comprises the amino acid sequence of a human gamma (γ) heavy chain constant region, such as any known in the art. Non-limiting examples of human constant region sequences have been described in the art, e.g., see U.S. Pat. No.5,693,780 and Kabat E A et al., (1991) supra. In some embodiments, an antibody comprises a heavy chain that comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or at least 99% identical to any of the heavy chain constant regions provided herein. In some embodiments, an antibody comprises a light chain that comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or at least 99% identical to any of the light chain constant regions provided herein. In some embodiments, an antibody is modified, e.g., modified via glycosylation, phosphorylation, sumoylation, and / or methylation. In some embodiments, an antibody is a glycosylated antibody, which is conjugated to one or more sugar or carbohydrate molecules. In some embodiments, the one 7107489or more sugar or carbohydrate molecule are conjugated to the antibody via N-glycosylation, O-glycosylation, C-glycosylation, glypiation (GPI anchor attachment), and / or phosphoglycosylation. In some embodiments, the one or more sugar or carbohydrate molecule are monosaccharides, disaccharides, oligosaccharides, or glycans. In some embodiments, the one or more sugar or carbohydrate molecule is a branched oligosaccharide or a branched glycan. In some embodiments, the one or more sugar or carbohydrate molecule includes a mannose unit, a glucose unit, an N-acetylglucosamine unit, or a phospholipid unit. In some embodiments, an antibody is a construct that comprises a polypeptide comprising one or more antigen binding fragments of the disclosure linked to a linker polypeptide or an immunoglobulin constant domain. Linker polypeptides comprise two or more amino acid residues joined by peptide bonds and are used to link one or more antigen binding portions. Examples of linker polypeptides have been reported (see e.g., Holliger, P., et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448; Poljak, R. J., et al. (1994) Structure 2:1121-1123). Still further, an antibody may be part of a larger immunoadhesion molecule, formed by covalent or noncovalent association of the antibody or antibody portion with one or more other proteins or peptides. Examples of such immunoadhesion molecules include use of the streptavidin core region to make a tetrameric scFv molecule (Kipriyanov, S. M., et al. (1995) Human Antibodies and Hybridomas 6:93-101) and use of a cysteine residue, a marker peptide and a C-terminal polyhistidine tag to make bivalent and biotinylated scFv molecules (Kipriyanov, S. M., et al. (1994) Mol. Immunol.31:1047-1058).

[0037] Approximately: As used herein, the term “approximately” or “about,” as applied to one or more values of interest, refers to a value that is similar to a stated reference value. In certain embodiments, the term “approximately” or “about” refers to a range of values that fall within 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value).

[0038] Bispecific Antibody: As used herein, the term “bispecific antibody” refers to an antibody that comprises two distinct antigen-specific binding sites or two linked (covalently or non-covalently) antibodies that, combined, comprise two distinct antigen- specific binding sites. Non-limiting examples of bispecific antibody formats or architectures are provided in Labrijn, AF, et al., Bispecific antibodies: a mechanistic review of the pipeline, Nature Reviews Drug Discovery volume 18, pages 585–608 (2019) and Brinkmann U and Kontermann EE, The making of bispecific antibodies, MAbs.2017 Feb / Mar;9(2):182-212, 7107489the entire contents of each of which are incorporated herein by reference in their entireties.

[0039] CDR: As used herein, the term "CDR" refers to the complementarity determining region within antibody variable sequences. A typical antibody molecule comprises a heavy chain variable region or heavy chain variable domain (VH) and a light chain variable region or light chain variable domain (VL), which are usually involved in antigen binding. The VH and VL regions can be further subdivided into regions of hypervariability, also known as “complementarity determining regions” (“CDR”), interspersed with regions that are more conserved, which are known as “framework regions” (“FR”). Each VH and VL is typically composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The extent of the framework region and CDRs can be precisely identified using methodology known in the art, for example, by the Kabat definition, the IMGT definition, the Chothia definition, the AbM definition, and / or the contact definition, all of which are well known in the art. See, e.g., Kabat, E.A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242; IMGT®, the international ImMunoGeneTics information system® http: / / www.imgt.org, Lefranc, M.-P. et al., Nucleic Acids Res., 27:209-212 (1999); Ruiz, M. et al., Nucleic Acids Res., 28:219-221 (2000); Lefranc, M.-P., Nucleic Acids Res., 29:207- 209 (2001); Lefranc, M.-P., Nucleic Acids Res., 31:307-310 (2003); Lefranc, M.-P. et al., In Silico Biol., 5, 0006 (2004) [[Epub]], 5:45-60 (2005); Lefranc, M.-P. et al., Nucleic Acids Res., 33:D593-597 (2005); Lefranc, M.-P. et al., Nucleic Acids Res., 37:D1006-1012 (2009); Lefranc, M.-P. et al., Nucleic Acids Res., 43:D413-422 (2015); Chothia et al., (1989) Nature 342:877; Chothia, C. et al. (1987) J. Mol. Biol.196:901-917, Al-lazikani et al (1997) J. Molec. Biol.273:927-948; and Almagro, J. Mol. Recognit.17:132-143 (2004). ee also hgmp.mrc.ac.uk and bioinf.org.uk / abs. As used herein, a CDR may refer to the CDR defined by any method known in the art. Two antibodies having the same CDR means that the two antibodies have the same amino acid sequence of that CDR as determined by the same method, for example, the IMGT definition.

[0040] In certain embodiments, there are three CDRs in each of the variable regions of a heavy chain and a light chain, which are designated CDR1, CDR2 and CDR3, for each of the variable regions. The term "CDR set" as used herein refers to a group of three CDRs that occur in a single variable region capable of binding the antigen. The exact boundaries of these CDRs have been defined differently according to different systems. The system described by Kabat (Kabat et al., Sequences of Proteins of Immunological Interest (National 7107489Institutes of Health, Bethesda, Md. (1987) and (1991)) not only provides an unambiguous residue numbering system applicable to any variable region of an antibody, but also provides precise residue boundaries defining the three CDRs. These CDRs may be referred to as Kabat CDRs. Sub-portions of CDRs may be designated as L1, L2 and L3 or H1, H2 and H3 where the "L" and the "H" designate the light chain and the heavy chains regions, respectively. These regions may be referred to as Chothia CDRs, which have boundaries that overlap with Kabat CDRs. Other boundaries defining CDRs overlapping with the Kabat CDRs have been described by Padlan (FASEB J.9:133-139 (1995)) and MacCallum (J Mol Biol 262(5):732- 45 (1996)). Still other CDR boundary definitions may not strictly follow one of the above systems, but will nonetheless overlap with the Kabat CDRs, although they may be shortened or lengthened in light of prediction or experimental findings that particular residues or groups of residues or even entire CDRs do not significantly impact antigen binding. The methods used herein may utilize CDRs defined according to any of these systems, although preferred embodiments use Kabat or Chothia defined CDRs.

[0041] CDR-grafted antibody: As used herein, the term "CDR-grafted antibody" refers to antibodies which comprise heavy and light chain variable region sequences from one species but in which the sequences of one or more of the CDR regions of VH and / or VL are replaced with CDR sequences of another species, such as antibodies having murine heavy and light chain variable regions in which one or more of the murine CDRs (e.g., CDR3) has been replaced with human CDR sequences.

[0042] Chimeric antibody: As used herein, the term "chimeric antibody" refers to antibodies which comprise heavy and light chain variable region sequences from one species and constant region sequences from another species, such as antibodies having murine heavy and light chain variable regions linked to human constant regions.

[0043] Complementary: As used herein, the term “complementary” refers to the capacity for precise pairing between two nucleotides or two sets of nucleotides. In particular, complementary is a term that characterizes an extent of hydrogen bond pairing that brings about binding between two nucleotides or two sets of nucleotides. For example, if a base at one position of an oligonucleotide is capable of hydrogen bonding with a base at the corresponding position of a target nucleic acid (e.g., an mRNA), then the bases are considered to be complementary to each other at that position. Base pairings may include both canonical Watson-Crick base pairing and non-Watson-Crick base pairing (e.g., Wobble base pairing and Hoogsteen base pairing). For example, in some embodiments, for complementary base pairings, adenosine-type bases (A) are complementary to thymidine- 7107489type bases (T) or uracil-type bases (U), that cytosine-type bases (C) are complementary to guanosine-type bases (G), and that universal bases such as 3-nitropyrrole or 5-nitroindole can hybridize to and are considered complementary to any A, C, U, or T. Inosine (I) has also been considered in the art to be a universal base and is considered complementary to any A, C, U or T.

[0044] Conservative amino acid substitution: As used herein, a “conservative amino acid substitution” refers to an amino acid substitution that does not alter the relative charge or size characteristics of the protein in which the amino acid substitution is made. Variants can be prepared according to methods for altering polypeptide sequence known to one of ordinary skill in the art such as are found in references which compile such methods, e.g. Molecular Cloning: A Laboratory Manual, J. Sambrook, et al., eds., Fourth Edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2012, or Current Protocols in Molecular Biology, F.M. Ausubel, et al., eds., John Wiley & Sons, Inc., New York. Conservative substitutions of amino acids include substitutions made amongst amino acids within the following groups: (a) M, I, L, V; (b) F, Y, W; (c) K, R, H; (d) A, G; (e) S, T; (f) Q, N; and (g) E, D.

[0045] Cross-reactive: As used herein, the term “cross-reactive,” refers to a property of the agent being capable of specifically binding to more than one antigen of a similar type or class (e.g., antigens of multiple homologs, paralogs, or orthologs) with similar affinity or avidity. For example, in some embodiments, an antibody that is cross-reactive against human and non-human primate antigens of a similar type or class (e.g., a human KLK5 and non- human primate KLK5, a human KLK7 and non-human primate KLK7) is capable of binding to the human antigen and non-human primate antigens with a similar affinity or avidity. In some embodiments, an antibody is cross-reactive against a human antigen and a rodent antigen of a similar type or class. In some embodiments, an antibody is cross-reactive against a rodent antigen and a non-human primate antigen of a similar type or class. In some embodiments, an antibody is cross-reactive against a human antigen, a non-human primate antigen, and a rodent antigen of a similar type or class.

[0046] Dual Inhibitor Antibody: As used herein, the term “dual inhibitor antibody” refers to an antibody that targets at least two (e.g., two, three) different antigens via a common distinct antigen-specific binding site and inhibits activity of those antigens. In some embodiments, a dual inhibitor antibody targets at least two different proteins (e.g., expressed from two different genes (e.g., endogenous genes, e.g., homologues, paralogues) via a common distinct antigen-specific binding site and inhibits activity of the at least two 7107489different proteins (e.g., enzymes, such as proteases). In some embodiments, a dual inhibitor antibody targets at least two different proteases (e.g., expressed by two different endogenous genes, e.g., KLK5 and KLK7) via a common distinct antigen-specific binding site and inhibits activity of the at least two different proteases. In some embodiments, the common distinct antigen-specific binding site binds to a similar (e.g., homologous) domain shared between or among the at least two different antigens. For example, in some embodiments, the common distinct antigen-specific binding site binds to a similar (e.g., homologous) catalytic domain or substrate binding site shared between or among the at least two different enzymes, e.g., proteases. In some embodiments, the common distinct antigen-specific binding site of a dual inhibitor antibody comprises amino acids of one or more complementarity determining regions of the antibody. In some embodiments, the common distinct antigen-specific binding site of a dual inhibitor antibody is within a heavy chain variable region and / or a light chain variable region of the antibody. In some embodiments, the common distinct antigen-specific binding site of a dual inhibitor antibody comprises one or more complementarity determining regions of a heavy chain variable region and / or a light chain variable region of the antibody. In some embodiments, the common distinct antigen- specific binding site of a dual inhibitor antibody comprises HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 of a heavy chain variable region and a light chain variable region of the antibody. In some embodiments a dual inhibitor antibody specifically binds to two different proteins expressed from two different genes (e.g., KLK5 and KLK7).

[0047] Effective Amount: As used herein, “an effective amount” refers to the amount of each active agent (e.g., anti-KLK5 / KLK7 + Th2 cytokine targeting bispecific antibody) required to confer a desired effect (e.g., a therapeutic effect on the subject), either alone or in combination with one or more other active agents. In some embodiments, the therapeutic “effect is reduced KLK5 and / or KLK7 activity and / or reduced Th2 cytokine activity and / or alleviated disease (e.g., Netherton syndrome, eosinophilic esophagitis and atopic dermatitis) or related symptoms, e.g., improved barrier function.

[0048] Framework: As used herein, the term "framework" or "framework sequence" refers to the remaining sequences of a variable region minus the CDRs. Because the exact definition of a CDR sequence can be determined by different systems, the meaning of a framework sequence is subject to correspondingly different interpretations. The six CDRs (CDR-L1, CDR-L2, and CDR-L3 of light chain and CDR-H1, CDR-H2, and CDR-H3 of heavy chain) also divide the framework regions on the light chain and the heavy chain into 7107489four sub-regions (FR1, FR2, FR3 and FR4) on each chain, in which CDR1 is positioned between FR1 and FR2, CDR2 between FR2 and FR3, and CDR3 between FR3 and FR4. Without specifying the particular sub-regions as FR1, FR2, FR3 or FR4, a framework region, as referred to by others, represents the combined FRs within the variable region of a single, naturally occurring immunoglobulin chain. As used herein, a FR represents one of the four sub-regions, and FRs represents two or more of the four sub-regions constituting a framework region. Human heavy chain and light chain acceptor sequences are known in the art. In one embodiment, the acceptor sequences known in the art may be used in the antibodies disclosed herein.

[0049] Human antibody: The term "human antibody", as used herein, is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences. The human antibodies of the disclosure may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs and in particular CDR3. However, the term "human antibody", as used herein, is not intended to include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences.

[0050] Humanized antibody: As used herein, the term "humanized antibody" refers to antibodies which comprise heavy and light chain variable region sequences from a non- human species (e.g., a mouse) but in which at least a portion of the VH and / or VL sequence has been altered to be more "human-like", i.e., more similar to human germline variable sequences. One type of humanized antibody is a CDR-grafted antibody, in which human CDR sequences are introduced into non-human VH and VL sequences to replace the corresponding nonhuman CDR sequences. In one embodiment, humanized antibodies are provided. Such antibodies may be generated by obtaining murine monoclonal antibodies using traditional hybridoma technology followed by humanization using in vitro genetic engineering, such as those disclosed in Kasaian et al PCT publication No. WO 2005 / 123126 A2.

[0051] Humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat, or rabbit having the desired specificity, affinity, and capacity. In some embodiments, Fv framework region (FR) residues of the human immunoglobulin are replaced by 7107489corresponding non-human residues. Furthermore, the humanized antibody may comprise residues that are found neither in the recipient antibody nor in the imported CDR or framework sequences, but are included to further refine and optimize antibody performance. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin. Antibodies may have Fc regions modified as described in WO 99 / 58572. Other forms of humanized antibodies have one or more CDRs (one, two, three, four, five, six) which are altered with respect to the original antibody, which are also termed one or more CDRs derived from one or more CDRs from the original antibody. Humanized antibodies may also involve affinity maturation.

[0052] In some embodiments, humanization is achieved by grafting the CDRs (e.g., as shown in Tables 1a, or 1b) into the human variable domains (e.g., IGKV1-NL1*01 and IGHV1-3*01 human variable domain). In some embodiments, an antibody of the present disclosure is a humanized variant comprising one or more amino acid substitutions (e.g., in the VH framework region) as compared with any one of the VHs listed in Tables 1a, or 1b and / or one or more amino acid substitutions (e.g., in the VL framework region) as compared with any one of the VLs listed in Tables 1a, or 1b.

[0053] Isolated antibody: An "isolated antibody", as used herein, is intended to refer to an antibody that is substantially free of other antibodies having different antigenic specificities. An isolated antibody may, however, have cross-reactivity to other antigens, in some embodiments. Moreover, an isolated antibody may be substantially free of other cellular material and / or chemicals.

[0054] Kabat numbering: As used herein, the terms "Kabat numbering", "Kabat definitions" and "Kabat labeling" are used interchangeably herein. These terms, which are recognized in the art, refer to a system of numbering amino acid residues which are more variable (i.e. hypervariable) than other amino acid residues in the heavy and light chain variable regions of an antibody, or an antigen binding portion thereof (Kabat et al. (1971) Ann. NY Acad, Sci.190:382-391 and, Kabat, E. A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No.91-3242). For the heavy chain variable region, the hypervariable region ranges from amino acid positions 31 to 35 for CDR1, amino acid positions 50 to 65 for 7107489CDR2, and amino acid positions 95 to 102 for CDR3. For the light chain variable region, the hypervariable region ranges from amino acid positions 24 to 34 for CDR1, amino acid positions 50 to 56 for CDR2, and amino acid positions 89 to 97 for CDR3.

[0055] Multi-Specific Antigen Binding Molecule: As used herein, the term “multi- specific antigen binding molecule” refers to a molecule that comprises two or more antigen- specific binding sites. In some embodiments, a multi-specific antigen binding molecule is a multi-specific antibody (e.g., a bispecific antibody).

[0056] Multi-Specific Antibody: As used herein, the term “multi-specific antibody” refers to an antibody that comprises at least two distinct antigen-specific binding sites or at least two linked (covalently or non-covalently) antibodies that, combined, comprise at least two distinct antigen-specific binding sites. In some embodiments, a multi-specific antibody is a bispecific antibody. Non-limiting examples of multi-specific specific antibody formats or architectures are provided in Sawant MS, et al., Toward Drug-Like Multispecific Antibodies by Design, Int J Mol Sci.2020 Oct 12;21(20):7496; Klein C, et al., The use of CrossMAb technology for the generation of bi- and multispecific antibodies, MAbs 2016 Aug-Sep;8(6):1010-20; and Brinkmann U and Kontermann EE, The making of bispecific antibodies, MAbs.2017 Feb / Mar;9(2):182-212, the entire contents of each of which are incorporated herein by reference in their entireties.

[0057] Recombinant antibody: As used herein, the term "recombinant antibody", as used herein, is intended to include all antibodies that are prepared, expressed, created or isolated by recombinant means, such as antibodies expressed using a recombinant expression vector transfected into a host cell (described in more details in this disclosure), including, for example, antibodies isolated from a recombinant, combinatorial human antibody library (Hoogenboom H. R., (1997) TIB Tech.15:62-70; Azzazy H., and Highsmith W. E., (2002) Clin. Biochem.35:425-445; Gavilondo J. V., and Larrick J. W. (2002) BioTechniques 29:128- 145; Hoogenboom H., and Chames P. (2000) Immunology Today 21:371-378), antibodies isolated from an animal (e.g., a mouse) that is transgenic for human immunoglobulin genes (see e.g., Taylor, L. D., et al. (1992) Nucl. Acids Res.20:6287-6295; Kellermann S-A., and Green L. L. (2002) Current Opinion in Biotechnology 13:593-597; Little M. et al (2000) Immunology Today 21:364-370) or antibodies prepared, expressed, created or isolated by any other means that involves splicing of human immunoglobulin gene sequences to other DNA sequences. In some embodiments, recombinant human antibodies are provided herein. In certain embodiments, such recombinant human antibodies have variable and constant regions derived from human germline immunoglobulin sequences. In certain embodiments, however, 7107489such recombinant human antibodies are subjected to in vitro mutagenesis (or, when an animal transgenic for human Ig sequences is used, in vivo somatic mutagenesis) and thus the amino acid sequences of the VH and VL regions of the recombinant antibodies are sequences that, while derived from and related to human germline VH and VH sequences, may not naturally exist within the human antibody germline repertoire in vivo. One embodiment of the disclosure provides fully human antibodies, e.g., capable of binding human KLK5 or KLK7, which can be generated using appropriate techniques, such as, but not limited to, using human Ig phage libraries such as those disclosed in Jermutus et al., PCT publication No. WO 2005 / 007699 A2.

[0058] Selective: As used herein, the term “selective” or “selectively” refers to the ability of a molecule to produce an effect (e.g., inhibit, antagonize, agonize, etc) in relation to its target molecule compared to a reference molecule. For example, a molecule that selectively inhibits its target molecule means that this molecule is capable of inhibiting its target molecule to a degree that is distinguishable from a reference molecule in an inhibition assay or other inhibitory context. For example, with respect to an inhibitor, the term, “selectively inhibits”, refers to the ability of the inhibitor to inhibit its target molecule with a degree that is distinguishable from a reference molecule that is not substantially inhibited in an inhibition assay, e.g., to an extent that permit selective inhibition of the target molecule, as described herein. Once the reaction is terminated, the signal produced by inhibiting the target molecule can be measured. The half maximal inhibitor concentration for the target molecule and the reference molecule can be calculated.

[0059] Specifically binds: As used herein, the term “specifically binds” refers to the ability of a molecule to bind to a binding partner with a degree of affinity or avidity that enables the molecule to be used to distinguish the binding partner from an appropriate control in a binding assay or other binding context. With respect to an antibody, the term, “specifically binds”, refers to the ability of the antibody to bind to a specific antigen with a degree of affinity or avidity, compared with an appropriate reference antigen or antigens, which enables the antibody to be used to distinguish the specific antigen from others, as described herein. In some embodiments, an antibody specifically binds to a target if the antibody has a KDfor binding the target of at least about 10-4M, 10-5M, 10-6M, 10-7M, 10-8M, 10-9M, 10-10M, 10-11M, 10-12M, 10-13M, or less. In some embodiments, an antibody specifically binds KLK5 or KLK7. In some embodiments, an antibody specifically binds a Th2 cytokine (e.g., IL-13, IL-4, IL-5, IL-6, IL-9, IL-31, IL-17E (IL-25), OX40L, TSLP, etc.), or a receptor thereof. In some embodiments, a bispecific antibody comprises an antigen 7107489binding site that specifically binds KLK5 and KLK7, and an antigen binding site that specifically binds a Th2 cytokine (e.g., IL-13, IL-4, IL-5, IL-6, IL-9, IL-31, IL-17E (IL-25), OX40L, TSLP, etc.), or a receptor thereof.

[0060] Subject: As used herein, the term “subject” refers to a mammal. In some embodiments, a subject is non-human primate, or rodent. In some embodiments, a subject is a human. In some embodiments, a subject is a patient, e.g., a human patient that has or is suspected of having a disease.

[0061] Th2 targeting antibody: As used herein, the term “Th2 targeting antibody” refers to an antibody that binds to a Th2 cytokine or a receptor thereof. In some embodiments, a Th2 targeting antibody inhibits Th2 cytokine mediated signaling. In some embodiments, a Th2 targeting antibody suppresses Th2 cytokine mediated inflammation.

[0062] Treatment: As used herein, the term “treating” or “treatment” refers to the application or administration of a composition including one or more active agents (e.g., anti- KLK5 / KLK7 + Th2 bispecific antibodies) to a subject, who has a target disease or disorder, a symptom of the disease / disorder, or a predisposition toward the disease / disorder, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect the disorder, the symptom of the disease, or the predisposition toward the disease or disorder. Alleviating a target disease / disorder includes delaying or preventing the development or progression of the disease, or reducing disease severity. It will be understood that references to treating or treatment may also refer to antibodies, including KLK5 / KLK7 + Th2 bispecific antibodies for use in such methods. II. Antibodies (a) KLK5 and KLK7 Targeting

[0063] In some embodiments, a dual inhibitor antibody targeting KLK5 and KLK7 (referred to as an anti-KLK5 / KLK7 antibody) is an antibody specific for both Kallikrein-5 (KLK5) and KLK7 via a common, specific antigen binding site. Dual inhibitor KLK5 / KLK7 antibodies are described in PCT / US2024 / 019231, the entire contents of which is incorporated herein by reference. Provided herein, in some aspects, are antibodies that bind to KLK5 (e.g., human KLK5, or mouse KLK5) and KLK7 (e.g., human KLK7, or mouse KLK7) with high specificity and affinity via a common antigen binding site. In some embodiments, the anti- KLK5 / KLK7 antibody described herein specifically binds to an epitope of KLK5 that is exposed or becomes exposed to an antibody, and an epitope of KLK7 that is exposed or becomes exposed to an antibody. In some embodiments, an anti-KLK5 / KLK7 antibody 7107489described herein binds to the active site of KLK5 and KLK7. In some embodiments, anti- KLK5 / KLK7 antibodies provided herein bind specifically to KLK5 and KLK7 from human, non-human primates, mouse, rat, etc. In some embodiments, anti-KLK5 / KLK7 antibodies provided herein specifically bind to human KLK5. In some embodiments, anti-KLK5 / LKL7 antibodies provided herein specifically bind to mouse KLK5. In some embodiments, anti- KLK5 / KLK7 antibodies provided herein specifically bind to human KLK7. In some embodiments, anti-KLK5 / LKL7 antibodies provided herein specifically bind to mouse KLK7. In some embodiments, multispecific antibodies are provided herein comprising an arm having an antigen-specific binding site of a dual inhibitor antibody targeting KLK5 and KLK7 and an arm having an antigen-specific binding site that specifically binds to a Th2 cytokine (e.g., IL-13, IL-4, IL-5, IL-6, IL-9, IL-31, IL-17E (IL-25), OX40L, TSLP, etc.) or a receptor thereof. For example, in some embodiments, bispecific antibodies are provided herein comprising an arm having an antigen-specific binding site of a dual inhibitor antibody targeting KLK5 and KLK and an arm having an antigen-specific binding site that specifically binds to a Th2 cytokine(e.g., IL-13, IL-4, IL-5, IL-6, IL-9, IL-31, IL-17E (IL-25), OX40L, TSLP, etc.)

[0064] In some embodiments, an anti-KLK5 / KLK7 antibody is not a bispecific antibody or bispecific antigen binding molecule in which KLK5 binding is conferred by one binding site within the antibody and KLK7 binding conferred by another binding site within the antibody.

[0065] In some embodiments, an anti-KLK5 / KLK7 antibody described herein may be characterized by reference to certain functional properties. In some embodiments, an anti- KLK5 / KLK7 antibody described herein binds specifically to KLK5 and KLK7. In some embodiments, an anti-KLK5 / KLK7 antibody binds specifically to the active form of KLK5 and KLK7. In some embodiments, an anti-KLK5 / KLK7 antibody does not bind the inactive form (the pro-form) of KLK5 and KLK7. In some embodiments, the antibody specifically binds to the active form of KLK5 and the active form of KLK7, but does not specifically bind the inactive form of KLK5 or the inactive form of KLK7. In some embodiments, the antibody detectably binds to the active form of KLK5 and the active form of KLK7, but under the same or comparable conditions does not detectably bind to the inactive form of KLK5 or the inactive form of KLK7. In some embodiments, an anti-KLK5 / KLK7 antibody inhibits KLK5 and KLK7 protease activity. In some embodiments, an anti-KLK5 / KLK7 antibody is not cleaved by KLK5 or KLK7 when bound to KLK5 or KLK7. In some embodiments, an anti- KLK5 / KLK7 antibody competes with SPINK5 and / or leupeptin for binding of the active site 7107489of KLK5 and KLK7. In some embodiments, an anti-KLK5 / KLK7 antibody reduces hyperkeratosis and desquamation. In some embodiments, an anti-KLK5 / KLK7 antibody reduces stratum corneum thickness. In some embodiments, an anti-KLK5 / KLK7 antibody reduces inflammation and epidermal effects.

[0066] Kallikrein-5, also known as stratum corneum tryptic enzyme (SCTE), is a serine protease expressed in the epidermis encoded by the KLK5 gene. The KLK5 gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome. Its expression is up-regulated by estrogens and progestins. KLK5 is expressed in the stratum granulosum and stratum corneum. In some embodiments, KLK5 regulates epidermal desquamation. In some embodiments, KLK5 regulates epidermal desquamation in conjunction with another member of the Kallikrein family proteases (e.g., KLK7 and / or KLK14). In some embodiments, KLK5 degrades proteins which form the epidermis (e.g., stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, or stratum basale). In some embodiments, KLK5 degrades proteins which form the stratum corneum and / or stratum granulosum (e.g., Corneodesmosin (CDSN), desmoglein 1 (DSG1), and desmocollin 1 (DSC1), etc.). In the epidermis (e.g., stratum granulosum and stratum corneum) KLK5 is expressed in an inactive form (sometimes referred to as the proform or pro-form), proKLK5, and can autoactivate itself. When activated, KLK5 can, through a proteolytic cleavage, convert both proKLK7 and proKLK14 to active forms. Active KLK14 is then able to activate newly produced proKLK5, thus creating a positive feedback loop (see, e.g., Nauroy et al., Kallikreins: Essential epidermal messengers for regulation of the skin microenvironment during homeostasis, repair and disease, Matrix Biol Plus.2019;6- 7:100019). KLK7 and KLK14 also degrade proteins which form the stratum corneum and / or stratum granulosum (e.g., Corneodesmosin (CDSN), desmoglein 1 (DSG1), and desmocollin 1 (DSC1), etc). Structural proteins, such as CDSN, DSG1, DSC1, are adhesive proteins of the extracellular part of the corneodesmosomes, the junctional structures that mediate corneocyte cohesion. The degradation of these proteins at the epidermis surface leads to desquamation, which may lead to skin barrier defects (e.g., stratum corneum detachment, decreased permeability barrier, allergy and inflammation, etc.). KLK5 and KLK7 have been implicated in this process (see, e.g., Caubet et al., Degradation of Corneodesmosome Proteins by Two Serine Proteases of the Kallikrein Family, SCTE / KLK5 / hK5 and SCCE / KLK7 / hK7, Journal of Investigative Dermatology, Volume 122, Issue 5, May 2004, Pages 1235-1244). Inhibition of KLK5 and / or KLK7 promotes improved skin barrier integrity and reduced inflammation (e.g., Chavarria-Smith et al., Dual antibody inhibition of KLK5 and KLK7 for Netherton 7107489syndrome and atopic dermatitis, SCIENCE TRANSLATIONAL MEDICINE, 14 Dec 2022, Vol 14, Issue 675).

[0067] Kallikrein-7 is a serine protease that in humans is encoded by the KLK7 gene. KLK7 is characterized as stratum corneum chymotryptic enzyme (SCCE). [It is the seventh member of the human kallikrein family, which includes fifteen homologous serine proteases located on chromosome 19. KLK7 is secreted as an inactive zymogen (e.g., in the stratum granulosum layer of the epidermis), requiring proteolytic cleavage to be activated. In some embodiments, KLK5 or matriptase activates KLK7. Once active, KLK7 is able to cleave proteins which form the stratum corneum and / or stratum granulosum (e.g., Corneodesmosin (CDSN), desmoglein 1 (DSG1), and desmocollin 1 (DSC1), etc) (see, e.g., Caubet et al. (May 2004). Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE / KLK5 / hK5 and SCCE / KLK7 / hK7. The Journal of Investigative Dermatology. 122 (5): 1235–1244). These proteins constitute the extracellular component of corneodesmosomes, intercellular cohesive structures which link the intermediate filaments of adjacent cells in the stratum corneum. In some embodiments, proteolysis of corneodesmosomes leads to desquamation of the epidermis (i.e., the shedding of corneocytes from the outer layer of the epidermis). In some embodiments, the combined role of KLK5 and KLK7 suggests that KLK skin cascade is responsible for coordinating desquamation. KLK7 is a chymotrypsin-like serine protease, which cleaves proteins at the residues tyrosine, phenylalanine or leucine. In some embodiments, dysregulation of KLK7 has been linked to several skin disorders including atopic dermatitis, psoriasis and Netherton syndrome. These diseases are characterized by excessively dry, scaly and inflamed skin, due to a disruption of skin homeostasis and correct barrier function.

[0068] In some embodiments, an anti-KLK5 / KLK7 antibody described herein specifically binds to an epitope on human KLK5. Exemplary amino acid sequences of human KLK5 are set forth in NCBI Accession Numbers NP_001070959.1, NP_001070960.1, or NP_036559.1, and UniProt Accession Numbers: Q8IU55, Q6S9W8, M0QXX2, Q9P0G3, A0A2I2MP48, or A0A2I2MP49, the entire sequences of which are incorporated herein by reference.

[0069] In some embodiments, an anti-KLK5 / KLK7 antibody described herein specifically binds to an epitope on mouse KLK5. Exemplary amino acid sequences of mouse KLK5 are set forth in NCBI Accession Numbers NP_081082.1, XP_006541213.1, XP_006541214.1, XP_006541215.1, XP_036009294.1, or XP_036009295.1, and UniProt 7107489Accession Numbers P15945, or Q9D140, the entire sequences of which are incorporated herein by reference.

[0070] In some embodiments, an anti-KLK5 / KLK7 antibody described herein specifically binds to an epitope on human KLK7 via the same antigen binding site that binds to KLK5 (e.g., human KLK5 or mouse KLK5). Exemplary amino acid sequences of human KLK7 are set forth in NCBI Accession Numbers NP_001193982.1, NP_001230055.1, NP_005037.1, NP_644806.1, and UniProt Accession Numbers: M0QYU8, Q6DTY1, X2J289, X2J4X7, A0A024R4H6, P49862, A0A2H4GDB2, and A0A2H4GDB6, the entire sequences of which are incorporated herein by reference.

[0071] In some embodiments, an anti-KLK5 / KLK7 antibody described herein specifically binds to an epitope on mouse KLK7 via the same antigen binding site that binds to KLK5 (e.g., human KLK5 or mouse KLK5). Exemplary amino acid sequences of mouse KLK7 are set forth in NCBI Accession Numbers NP_036002.1, and UniProt Accession Numbers Q91VE3, the entire sequences of which are incorporated herein by reference.

[0072] In some embodiments, an anti-KLK5 / KLK7 antibody described herein specifically binds to an epitope on KLK5 (e.g., active site of the enzyme, also known as the catalytic domain / pocket of human KLK5 or mouse KLK5) and an epitope on KLK7 (e.g., the catalytic domain / pocket of human KLK7 or mouse KLK7). In some embodiments, an anti- KLK5 / KLK7 antibody described herein prevents KLK5 (e.g., human or mouse KLK5) and KLK7 (e.g., human or mouse KLK7) from cleaving its substrates. In some embodiments, an anti-KLK5 antibody described herein binds to a fragment of KLK5 (e.g., human or mouse KLK5) and a fragment of KLK7 (e.g., human or mouse KLK7). The fragment of KLK5 and / or KLK7 (e.g., human or mouse) may be between about 5 and about 425 amino acids, between about 10 and about 400 amino acids, between about 50 and about 350 amino acids, between about 100 and about 300 amino acids, between about 150 and about 250 amino acids, between about 200 and about 300 amino acids, between about 75 and about 150 amino acids, between about 25 and about 100 amino acids, between about 10 and about 30 amino acids in length. Not wishing to be bound to any particular theory, and in some embodiments, a heavy chain (HC) complementarity-determining region 3 (CDR3) of any one of the anti- KLK5 / KLK7 antibodies described herein inhibits KLK5 (e.g., human or mouse KLK5) and KLK7 (e.g., human or mouse KLK7) by binding to the catalytic domain / pocket of KLK5.

[0073] In some embodiments, an anti-KLK5 / KLK7 antibody described herein inhibits KLK5 protease activity, KLK7 protease activity, or both KLK5 and KLK7 protease activity. In some embodiments the anti-KLK5 / KLK7 antibody inhibits KLK5 cleavage of BOC-Val- 7107489Pro-Arg-AMC with an IC50 of less than 30 nM, less than 25 nM, less than 20 nM, less than 15 nM, less than 10 nM, less than 5 nM, less than 3 nM, less than 2.5 nM, less than 2 nM, or less than 1.5 nM, less than 1nM, less than 0.5nM, less than 0.3nM, less than 0.25nM, less than 0.2 nM or less than 0.1 nM. In some embodiments, the anti-KLK5 / KLK7 antibody inhibits KLK5 (e.g., human KLK5 or mouse KLK5) cleavage of BOC-Val-Pro-Arg-AMC with an IC50 in the range of 0.1 nM to 30 nM, 0.1 nM to 20 nM, 0.1 nM to 10 nM, 0.1 nM to 5 nM, 0.1 nM to 2.5 nM, 0.1 nM to 2 nM, 0.1 nM to 1 nM, 0.1 nM to 0.5 nM, 0.1 nM to 0.25 nM, 0.1 nM to 50 nM, 0.1 nM to 40 nM, 0.1 nM to 30 nM, 0.1 nM to 20 nM, 0.1 nM to 10 nM, 0.1 nM to 5 nM, 0.1 nM to 2.5 nM, 0.1 nM to 2 nM, 0.1 nM to 1 nM, 0.1 nM to 0.9 nM, 0.1 nM to 0.8 nM, 0.1 nM to 0.7 nM, 0.1 nM to 0.6 nM, 0.1 nM to 0.5 nM, 0.1 nM to 0.4 nM, 0.1 nM to 0.3 nM, 0.1 nM to 0.25 nM, 0.1 nM to 0.2 nM, 0.1 nM to 0.15 nM, 0.15 nM to 0.2 nM, 0.15 nM to 0.25 nM, 0.15 nM to 0.3 nM, 0.15 nM to 0.4 nM, 0.15 nM to 0.5 nM, 0.15 nM to 1 nM, 0.2 nM to 30 nM, 0.2 nM to 20 nM, 0.2 nM to 10 nM, 0.2 nM to 5 nM, 0.2 nM to 2.5 nM, 0.2 nM to 2 nM, 0.2 nM to 1 nM, 0.2 nM to 0.5 nM, 0.2 nM to 0.2 nM, 0.2 nM to 50 nM, 0.2 nM to 40 nM, 0.2 nM to 30 nM, 0.2 nM to 20 nM, 0.2 nM to 10 nM, 0.2 nM to 5 nM, 0.2 nM to 2.5 nM, 0.2 nM to 2 nM, 0.2 nM to 1 nM, 0.2 nM to 0.9 nM, 0.2 nM to 0.8 nM, 0.2 nM to 0.7 nM, 0.2 nM to 0.6 nM, 0.2 nM to 0.5 nM, 0.2 nM to 0.4 nM, 0.2 nM to 0.3 nM, 0.2 nM to 0.25 nM, 1 nM to 30 nM, 1 nM to 20 nM, 1 nM to 10 nM, 1 nM to 5 nM, 1 nM to 2.5 nM, 1 nM to 2 nM, 1 nM to 3 nM, 1 nM to 5.5 nM, 1.5 nM to 2 nM, 1.5 nM to 3 nM, 1.5 nM to 5.5 nM, 2 nM to 5 nM, 2 nM to 4 nM, 2 nM to 5.5 nM, 3 nM to 5.5 nM, 4 nM to 5.5 nM, 3 nM to 30 nM, 3 nM to 20 nM, 3 nM to 10 nM, 3 nM to 5 nM, 3 nM to 2.5 nM, 3 nM to 4 nM, 3 nM to 5.5 nM, 5 nM to 30 nM, 5 nM to 20 nM, 5 nM to 10 nM, 5 nM to 9 nM, 5 nM to 8 nM, 5 nM to 7 nM, 5 nM to 6 nM, 5 nM to 5.5 nM, 10 nM to 30 nM, 10 nM to 25 nM, 10 nM to 20 nM, 10 nM to 18 nM, 10 nM to 15 nM, 10 nM to 12 nM, 12 nM to 20 nM, 12 nM to 25 nM, 12 nM to 16 nM, 12 nM to 18 nM, 12 nM to 20 nM, 12 nM to 24 nM, 12 nM to 28 nM, 12 nM to 30 nM, 15 nM to 30 nM, 15 nM to 25 nM, 15 nM to 20 nM, 15 nM to 18 nM, 18 nM to 30 nM, 18 nM to 25 nM, 18 nM to 20 nM, 20 nM to 30 nM, 20 nM to 25 nM, 20 nM to 22 nM, 20 nM to 24 nM, 20 nM to 26 nM, 20 nM to 28 nM, 22 nM to 30 nM, 22 nM to 25 nM, 22 nM to 28 nM, 24 nM to 30 nM, 24 nM to 25 nM, 24 nM to 26 nM, or 24 nM to 28 nM. In some embodiments the anti-KLK5 / KLK7 antibody inhibits KLK7 cleavage of KHLF-AMC with an IC50 of less than 6 nM, less than 5 nM, less than 4 nM, less than 3 nM, less than 2.5 nM, less than 2 nM, or less than 1.5 nM, less than 1 nM, less than 0.5 nM, less than 0.4nM, less than 0.3nM, less than 0.2nM, less than 0.16 nM, less than 0.1 nM or less than 0.05 nM. In some embodiments the anti-KLK5 / KLK7 antibody inhibits KLK7 7107489cleavage of KHLF-AMC with an IC50 in the range of 0.1 nM to 30 nM, 0.1 nM to 20 nM, 0.1 nM to 10 nM, 0.1 nM to 5 nM, 0.1 nM to 2.5 nM, 0.1 nM to 2 nM, 0.1 nM to 1 nM, 0.1 nM to 0.5 nM, 0.1 nM to 0.25 nM, 0.1 nM to 50 nM, 0.1 nM to 40 nM, 0.1 nM to 30 nM, 0.1 nM to 20 nM, 0.1 nM to 10 nM, 0.1 nM to 5 nM, 0.1 nM to 2.5 nM, 0.1 nM to 2 nM, 0.1 nM to 1 nM, 0.1 nM to 0.9 nM, 0.1 nM to 0.8 nM, 0.1 nM to 0.7 nM, 0.1 nM to 0.6 nM, 0.1 nM to 0.5 nM, 0.1 nM to 0.4 nM, 0.1 nM to 0.3 nM, 0.1 nM to 0.25 nM, 0.1 nM to 0.2 nM, 0.1 nM to 0.15 nM, 0.15 nM to 0.2 nM, 0.15 nM to 0.25 nM, 0.15 nM to 0.3 nM, 0.15 nM to 0.4 nM, 0.15 nM to 0.5 nM, 0.15 nM to 1 nM, 0.2 nM to 30 nM, 0.2 nM to 20 nM, 0.2 nM to 10 nM, 0.2 nM to 5 nM, 0.2 nM to 2.5 nM, 0.2 nM to 2 nM, 0.2 nM to 1 nM, 0.2 nM to 0.5 nM, 0.2 nM to 0.2 nM, 0.2 nM to 50 nM, 0.2 nM to 40 nM, 0.2 nM to 30 nM, 0.2 nM to 20 nM, 0.2 nM to 10 nM, 0.2 nM to 5 nM, 0.2 nM to 2.5 nM, 0.2 nM to 2 nM, 0.2 nM to 1 nM, 0.2 nM to 0.9 nM, 0.2 nM to 0.8 nM, 0.2 nM to 0.7 nM, 0.2 nM to 0.6 nM, 0.2 nM to 0.5 nM, 0.2 nM to 0.4 nM, 0.2 nM to 0.3 nM, 0.2 nM to 0.25 nM, 1 nM to 30 nM, 1 nM to 20 nM, 1 nM to 10 nM, 1 nM to 5 nM, 1 nM to 2.5 nM, 1 nM to 2 nM, 1 nM to 3 nM, 1 nM to 5.5 nM, 1.5 nM to 2 nM, 1.5 nM to 3 nM, 1.5 nM to 5.5 nM, 2 nM to 5 nM, 2 nM to 4 nM, 2 nM to 5.5 nM, 3 nM to 5.5 nM, 4 nM to 5.5 nM, 3 nM to 30 nM, 3 nM to 20 nM, 3 nM to 10 nM, 3 nM to 5 nM, 3 nM to 2.5 nM, 3 nM to 4 nM, 3 nM to 5.5 nM, 5 nM to 30 nM, 5 nM to 20 nM, 5 nM to 10 nM, 5 nM to 9 nM, 5 nM to 8 nM, 5 nM to 7 nM, 5 nM to 6 nM, 5 nM to 5.5 nM, 10 nM to 30 nM, 10 nM to 25 nM, 10 nM to 20 nM, 10 nM to 18 nM, 10 nM to 15 nM, 10 nM to 12 nM, 12 nM to 20 nM, 12 nM to 25 nM, 12 nM to 16 nM, 12 nM to 18 nM, 12 nM to 20 nM, 12 nM to 24 nM, 12 nM to 28 nM, 12 nM to 30 nM, 15 nM to 30 nM, 15 nM to 25 nM, 15 nM to 20 nM, 15 nM to 18 nM, 18 nM to 30 nM, 18 nM to 25 nM, 18 nM to 20 nM, 20 nM to 30 nM, 20 nM to 25 nM, 20 nM to 22 nM, 20 nM to 24 nM, 20 nM to 26 nM, 20 nM to 28 nM, 22 nM to 30 nM, 22 nM to 25 nM, 22 nM to 28 nM, 24 nM to 30 nM, 24 nM to 25 nM, 24 nM to 26 nM, or 24 nM to 28 nM.

[0074] In some embodiments, an anti-KLK5 / KLK7 antibody described herein binds specifically to the active form of KLK5, KLK7 or KLK5 and KLK7. In some embodiments, the anti-KLK5 / KLK7 antibody described herein does not bind to the inactive form of KLK5, KLK7, or KLK5 and KLK7. In some embodiments, an anti-KLK5 / KLK7 antibody described herein binds specifically to the active site of KLK5, KLK7 or KLK5 and KLK7. In some embodiments, the anti-KLK5 / KLK7 antibody described herein specifically binds to the active form of KLK5, the active form of KLK7, or the active form of KLK5 and the active form of KLK7, but does not specifically bind to the inactive form of KLK5, the inactive form of KLK7, or the inactive form of KLK5 and the inactive form of KLK7. In some embodiments, 7107489the anti-KLK5 / KLK7 antibody described herein detectably binds the active form of KLK5, the active form of KLK7, or the active form of KLK5 and the active form of KLK7, but under the same or comparable conditions does not detectably bind the inactive form of KLK5, the inactive form of KLK7, or the inactive form of KLK5 and the inactive form of KLK7. The active site of KLK5 and / or KLK7 is the site at which the KLK5 and / or KLK7 substrate molecules bind to undergo cleavage. The active site may also be known as the catalytic domain, or catalytic triad. In some embodiments, the active site (i.e., catalytic domain or catalytic triad) of KLK5 or KLK7 consists of amino acids Ser195, His57, and Asp102 of KLK5 or KLK7 (see, e.g., Goettig et al., Natural and synthetic inhibitors of kallikrein-related peptidases (KLKs), Biochimie.2010 Nov; 92(11): 1546–1567).

[0075] In some embodiments, antibodies described herein are optimized versions (e.g., affinity matured) of the parental antibody. In some embodiments, an antibody described herein specifically binds a KLK5 (e.g., a human or mouse KLK5) and a KLK7 (e.g., a human or mouse KLK7) with binding affinity (e.g., as indicated by KD) of at least about 10-4M, at least about 10-5M, at least about 10-6M, at least about 10-7M, at least about 10-8M, at least about 10-9M, at least about 10-10M, at least about 10-11M, at least about 10-12M, at least about 10-13M, or less. In some embodiments, an antibody described herein specifically binds a KLK5 (e.g., a human or mouse KLK5) ) and a KLK7 (e.g., a human or mouse KLK7) with binding affinity (e.g., as indicated by KD) of between 1x10-10M and 5x10-9M, between 1x10- 10 M and 1x10-9M, between 5x10-10and 1x10-9M, between 5x10-11and 1x10-10M, between 1x10-11and 5x10-10M, or between 5x10-13and 1x10-12M. For example, an antibody of the present disclosure can bind to a KLK5 protein (e.g., human or mouse KLK5) ) and a KLK7 (e.g., a human or mouse KLK7) with an affinity between 1 pM and 500 nM, e.g., between 50 pM and 100 nM, between 500 pM and 50 nM, between 1 pM and 100 pM, between 10 pM and 100 pM, between 50 pM and 100 pM, between 100 pM and 500 pM, between 500 pM and 1 nM, between 1 nM and 5 nM, between 1 nM and 10 nM, between 5 nM and 25 nM, between 10 nM and 50 nM between 50 nM and 100 nM, between 100 nM and 500 nM. The disclosure also includes antibodies that compete with any of the antibodies described herein for binding to a KLK5 protein (e.g., human or mouse KLK5) ) and a KLK7 (e.g., a human or mouse KLK7) and that have an affinity of 100 nM or lower (e.g., 80 nM or lower, 50 nM or lower, 20 nM or lower, 10 nM or lower, 1 nM or lower, 500 pM or lower, 50 pM or lower, or 5 pM or lower). The affinity and binding kinetics of an antibody can be tested using any suitable method including but not limited to biosensor technology (e.g., OCTET or 7107489BIACORE). In some embodiments, antibodies described herein bind to KLK5 and KLK7 with a KD of sub-nanomolar range.

[0076] Binding affinity (or binding specificity) can be determined by a variety of methods including equilibrium dialysis, equilibrium binding, gel filtration, ELISA, surface plasmon resonance (SPR), florescent activated cell sorting (FACS) or spectroscopy (e.g., using a fluorescence assay). Exemplary conditions for evaluating binding affinity are in HBS- P buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.005% (v / v) surfactant P20) and PBS buffer (10mM PO4-3, 137mM NaCl, and 2.7mM KCl). These techniques can be used to measure the concentration of bound proteins as a function of target protein concentration. The concentration of bound protein ([[Bound]]) is generally related to the concentration of free target protein ([[Free]]) by the following equation: [[Bound]] = [[Free]] / (Kd+[[Free]])

[0077] It is not always necessary to make an exact determination of KA, though, since sometimes it is sufficient to obtain a quantitative measurement of affinity, e.g., determined using a method such as ELISA or FACS analysis, is proportional to KA, and thus can be used for comparisons, such as determining whether a higher affinity is, e.g., 2-fold higher, to obtain a qualitative measurement of affinity, or to obtain an inference of affinity, e.g., by activity in a functional assay, e.g., an in vitro or in vivo assay.

[0078] Exemplary anti-KLK5 / KLK7 antibody sequences (e.g., the heavy chain (HC) and light chain (LC) sequences, heavy chain variable domain (VH) and light chain variable domain (VL), CDR sequences are provided in Tables 1a and 1b. Table 1a. Examples of anti-KLK5 / KLK7 antibodies7107489

[0079] In some embodiments, certain amino acid positions in an antibody described herein (e.g., amino acids in the VH / VL regions and / or CDR regions) are substitutable and the substitution results in an antibody with substantially similar binding and biological activities (e.g., substantially similar binding affinity, binding specificity, protease activity inhibitory activity, anti-inflammatory activity, or a combination thereof) as the reference antibody. In order to identify a substitutable position of an antibody, the amino acid sequence of that antibody is compared to the sequences of other antibodies belonging to the same group as that antibody. If the identity of that amino acid varies between the different related antibodies of a group at any particular position, that position is a substitutable position of the antibody. In other words, a substitutable position is a position in which the identity of the amino acid varies between the related antibodies. Positions that contain a constant amino acid are not substitutable positions.

[0080] In some embodiments, the above method may be employed to provide a consensus antibody sequence. In such a consensus sequence, a non-substitutable position is 7107489indicated by the amino acid present at that position, and a substitutable position is indicated as an "X".

[0081] Depending on how the antibodies are to be employed, X may be a) any amino acid, b) any amino acid present at that position in any of the related antibodies in the group or a conservatively substituted variant thereof or c) any amino acid present at that position in any of the related antibodies in the group. Any antibody having a sequence that is encompassed by the consensus should bind to the same antigen as any of the related antibodies.

[0082] In some embodiments, the method described above may be employed in methods of designing and making a variant of a parental antibody that at least maintains (e.g., maintains or increases) the antigen binding activity of the parental antibody. Because antibodies containing substitutions at substitutable positions have already been produced and tested, substitutions at those positions can be made in the knowledge that they should not significantly decrease the binding activity of the antibody. In general, an antibody variant of a parental antibody has an antigen binding affinity that is at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or at least 100% (e.g., at least 150%, at least 200%, at least 500%, at least 1000%, usually up to at least 10,000%) of the binding affinity of the parental antibody to a particular antigen.

[0083] In some embodiments, a substitutable position of a parental antibody may be substituted by a) any of the 20 naturally occurring amino acids to produce random substitutions, b) an amino acid having biochemical properties similar to the amino acid already present at the substitutable position to produce conservative substitutions, c) an amino acid that is present at the same position in a related antibody to produce a directed substitution, or d) an amino acid that is present at the same position in a similar human antibody to produce a humanizing substitution. A substitution may be made at any part of an antibody variable region, including any framework region or CDR. In certain embodiments, a single substitutable amino acid may be substituted. However, in other embodiments, a plurality of substitutable amino acids (e.g., up to about 5 or 10 or more) may be substituted. In particular embodiments, the type of substitution that can be made at each substitutable position may be indicated by the types of amino acids present at that position in the related antibodies. For example, if unrelated amino acids (e.g., Ala, Gly, Cys, Glu and Thr) are present at a certain position of a group of related antibodies, then any amino acid could be substituted at that position without significantly reducing binding activity of the antibody. 7107489Exemplary amino acids substitutions of an anti-KLK5 / KLK7 antibody described herein are set forth in Table 1b: Table 1b. Exemplary Anti-KLK5 / KLK7 Antibody Amino Acid Substitutions

[0084] In some embodiments, an antibody of the present disclosure comprises a HC CDR1 comprising the amino acid sequence of GSISSX1DYYWX2 (SEQ ID NO: 28), in which X1 is S, D or L., X2 is G or V; a HC CDR2 comprising the amino acid sequence of SIX3YX4X5X6TYYX7PSLKS (SEQ ID NO: 29), in which X3is Y or D, X4is S, F or Y, X5is G or A, X6is S or D, or X7is N or S; a HC CDR3 comprising the amino acid sequence of ARGRPLGYGAX8HX9YYGMDV (SEQ ID NO: 30), in which X8 is R or K, or X9 is Y or D; a LC CDR1 comprising the amino acid sequence of SEQ ID NO: 4; a LC CDR2 comprising the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 comprising the amino acid sequence of QQSPX10FPPLT (SEQ ID NO: 31), in which X10 is P or Y.

[0085] In some embodiments, an antibody of the present disclosure comprises one or more of the HC CDRs (e.g., HC CDR1, HC CDR2, or HC CDR3) amino acid sequences from any one of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b. In some embodiments, an antibody of the present disclosure comprises the HC CDR3 amino acid sequences from any one of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b. In some embodiments, an antibody of the present disclosure comprises the HC CDR1, HC CDR2, and HC CDR3 as provided for any one of the antibodies elected from Tables 1a and 71074891b. In some embodiments, an antibody of the present disclosure comprises the LC CDR3 amino acid sequences from any one of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b. In some embodiments, an antibody of the present disclosure comprises one or more of the LC CDRs (e.g., LC CDR1, LC CDR2, or LC CDR3) amino acid sequences from any one of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b. In some embodiments, an antibody of the present disclosure comprises the LC CDR1, LC CDR2, and LC CDR3 s provided for any one of the anti-KLK5 antibodies selected from Tables 1a and 1b.

[0086] In some embodiments, an antibody of the present disclosure comprises the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 as provided for any one of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b. In some embodiments, antibody heavy and / or light chain CDR3 domains may play a particularly important role in the binding specificity / affinity of an antibody for an antigen. Accordingly, an antibody of the disclosure may include at least the heavy and / or light chain CDR3s of any one of the anti- KLK5 / KLK7 antibodies selected from Tables 1a and 1b.

[0087] Also within the scope of the present disclosure are variants of any of the exemplary anti-KLK5 / KLK7 antibodies as disclosed herein. A variant may contain one or more amino acid residue variations in the VH and / or VL, or in one or more of the HC CDRs and / or one or more of the LC CDRs as relative to the reference antibody, while retaining substantially similar binding and biological activities (e.g., substantially similar binding affinity, binding specificity, protease activity inhibitory activity, anti-inflammatory activity, or a combination thereof) as the reference antibody.

[0088] In some embodiments, an antibody of the disclosure has one or more CDRs (e.g., HC CDR or LC CDR) sequences substantially similar to any of the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 sequences from one of the anti- KLK5 / KLK7 antibodies selected from Tables 1a and 1b. In some embodiments, the position of one or more CDRs along the VH (e.g., HC CDR1, HC CDR2, or HC CDR3) and / or VL (e.g., LC CDR1, LC CDR2, or LC CDR3) region of an antibody described herein can vary by one, two, three, four, five, or six amino acid positions so long as specific binding to KLK5 (e.g., human or mouse KLK5) and KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived). For example, in some embodiments, the position defining a CDR of any antibody described herein can vary by shifting the N-terminal and / or C-terminal boundary of the CDR by one, 7107489two, three, four, five, or six amino acids, relative to the CDR position of any one of the antibodies described herein, so long as specific binding to KLK5 (e.g., human or mouse KLK5) and KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived). In another embodiment, the length of one or more CDRs along the VH (e.g., HC CDR1, HC CDR2, or HC CDR3) and / or VL (e.g., LC CDR1, LC CDR2, or LC CDR3) region of an antibody described herein can vary (e.g., be shorter or longer) by one, two, three, four, five, or more amino acids, so long as immunospecific binding to KLK5 (e.g., human or mouse KLK5) and KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived).

[0089] Accordingly, in some embodiments, a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein may be one, two, three, four, five or more amino acids shorter than one or more of the CDRs described herein (e.g., CDRS from any of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b) so long as specific binding to KLK5 (e.g., human or mouse KLK5) and KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein may be one, two, three, four, five or more amino acids longer than one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b) so long as specific binding to KLK5 (e.g., human or mouse KLK5) and KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, the amino portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be extended by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b) so long as specific binding to KLK5 (e.g., human or mouse KLK5) and KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some 7107489embodiments, the carboxy portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be extended by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b) so long as specific binding to KLK5 (e.g., human or mouse KLK5) and KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, the amino portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be shortened by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b) so long as specific binding to KLK5 (e.g., human or mouse KLK5) and KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, the carboxy portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be shortened by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b) so long as specific binding to KLK5 (e.g., human or mouse KLK5) and KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). Any method can be used to ascertain whether specific binding to KLK5 (e.g., human or mouse KLK5) and KLK7 (e.g., human or mouse KLK7) is maintained, for example, using binding assays and conditions described in the art.

[0090] In some examples, an antibody of the disclosure has one or more CDR (e.g., HC CDR or LC CDR) sequences substantially similar to any one of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b. For example, an antibody described herein may include one or more CDR sequence(s) from any of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b containing up to 5, 4, 3, 2, or 1 amino acid residue variations as compared to the corresponding CDR region in any one of the CDRs provided herein (e.g., CDRs from any of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b) so long as specific binding to KLK5 (e.g., human or mouse KLK5) and KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, 7107489at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, any of the amino acid variations in any of the CDRs provided herein may be conservative variations. Conservative variations can be introduced into the CDRs at positions where the residues are not likely to be involved in interacting with a KLK5 (e.g., human or mouse KLK5) and / or a KLK7 (e.g., human or mouse KLK7), for example, as determined based on a crystal structure. Some aspects of the disclosure provide antibodies that comprise one or more of the heavy chain variable (VH) and / or light chain variable (VL) domains provided herein. In some embodiments, any of the VH domains provided herein include one or more of the HC CDR sequences (e.g., HC CDR1, HC CDR2, and HC CDR3) provided herein, for example, any of the HC CDR sequences provided in any one of the anti-KLK5 / KLK7 selected from Tables 1a and 1b. In some embodiments, any of the VL domains provided herein include one or more of the LC CDR sequences (e.g., LC CDR1, LC CDR2, and LC CDR3) provided herein, for example, any of the LC CDR sequences provided in any one of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b.

[0091] In some embodiments, an antibody of the disclosure includes any antibody that includes a heavy chain variable domain and / or a light chain variable domain of any one of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b, and variants thereof. In some embodiments, an antibody of the disclosure includes any antibody that includes the heavy chain variable and light chain variable pairs of any anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b.

[0092] Aspects of the disclosure provide antibodies having a heavy chain variable (VH) and / or a light chain variable (VL) domain amino acid sequence homologous to any of those described herein. In some embodiments, an antibody comprises a heavy chain variable sequence or a light chain variable sequence that is at least 75% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the heavy chain variable sequence and / or any light chain variable sequence of any one of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b. In some embodiments, the homologous heavy chain variable and / or a light chain variable amino acid sequences do not vary within any of the CDR sequences provided herein. For example, in some embodiments, the degree of sequence variation (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) may occur within a heavy chain variable and / or a light chain variable 7107489sequence excluding any of the CDR sequences provided herein. In some embodiments, an antibody provided herein comprise a heavy chain variable sequence and a light chain variable sequence that comprises a framework sequence that is at least 75% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the framework sequence of any anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b.

[0093] In some embodiments, an antibody of the present disclosure is a humanized antibody (e.g., a humanized variant containing one or more CDRs of Tables 1a and 1b). In some embodiments, an antibody of the present disclosure comprises a HC CDR1, a HC CDR2, a HC CDR3, a LC CDR1, a LC CDR2, and a LC CDR3 that are the same as the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 shown in Tables 1a and 1b, and comprises a humanized heavy chain variable region and / or a humanized light chain variable region.

[0094] In some embodiments, an antibody of the present disclosure is a humanized antibody comprising a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH of any of the anti-KLK5 / KLK7 antibodies listed in Tables 1a and 1b. Alternatively or in addition, the antibody of the present disclosure is a humanized antibody comprising a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL of any one of the anti-KLK5 / KLK7 antibodies listed in Tables 1a and 1b.

[0095] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 7. Alternatively or in addition, the anti- KLK5 / KLK7 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 8.

[0096] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 2, a HC CDR3 having the amino acid sequence of SEQ ID NO: 3, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 6. 7107489

[0097] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 3. “Collectively,” as used anywhere in the present disclosure, means that the total number of amino acid variations in all of the three heavy chain CDRs is within the defined range. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0098] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0099] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 2; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or in addition, the anti- 7107489KLK5 / KLK7 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 6. [000100] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 7. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 8. [000101] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 7. Alternatively or in addition, the anti- KLK5 / KLK7 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 8. [000102] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the VH as set forth in SEQ ID NO: 7. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the VL as set forth in SEQ ID NO: 8. [000103] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 13. Alternatively or in addition, the anti- KLK5 / KLK7 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 14. [000104] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 9, a HC CDR2 7107489having the amino acid sequence of SEQ ID NO: 10, a HC CDR3 having the amino acid sequence of SEQ ID NO: 11, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 12. [000105] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 9, HC CDR2 having the amino acid sequence of SEQ ID NO: 10, and HC CDR3 having the amino acid sequence of SEQ ID NO: 11. “Collectively,” as used anywhere in the present disclosure, means that the total number of amino acid variations in all of the three heavy chain CDRs is within the defined range. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 12. [000106] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 9, HC CDR2 having the amino acid sequence of SEQ ID NO: 10, and HC CDR3 having the amino acid sequence of SEQ ID NO: 11. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 12. [000107] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 9; a HC CDR2 having no more than 3 amino acid variations (e.g., no more 7107489than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 10; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 11. Alternatively or in addition, the anti- KLK5 / KLK7 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 12. [000108] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 13. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 14. [000109] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 13. Alternatively or in addition, the anti- KLK5 / KLK7 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 14. [000110] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the VH as set forth in SEQ ID NO: 13. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the VL as set forth in SEQ ID NO: 14. [000111] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having 7107489the amino acid sequence of SEQ ID NO: 17. Alternatively or in addition, the anti- KLK5 / KLK7 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 14. [000112] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 9, a HC CDR2 having the amino acid sequence of SEQ ID NO: 15, a HC CDR3 having the amino acid sequence of SEQ ID NO: 16, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 12. [000113] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 9, HC CDR2 having the amino acid sequence of SEQ ID NO: 15, and HC CDR3 having the amino acid sequence of SEQ ID NO: 16. “Collectively,” as used anywhere in the present disclosure, means that the total number of amino acid variations in all of the three heavy chain CDRs is within the defined range. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 12. [000114] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 9, HC CDR2 having the amino acid sequence of SEQ ID NO: 15, and HC CDR3 having the amino acid sequence of SEQ ID NO: 16. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the 7107489amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 12. [000115] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 9; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 15; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 16. Alternatively or in addition, the anti- KLK5 / KLK7 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 12. [000116] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 17. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 14. [000117] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 17. Alternatively or in addition, the anti- KLK5 / KLK7 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 14. [000118] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the VH as set forth in SEQ ID NO: 17. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the 7107489present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the VL as set forth in SEQ ID NO: 14. [000119] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 21. Alternatively or in addition, the anti- KLK5 / KLK7 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 14. [000120] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 18, a HC CDR2 having the amino acid sequence of SEQ ID NO: 19, a HC CDR3 having the amino acid sequence of SEQ ID NO: 20, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 12. [000121] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 18, HC CDR2 having the amino acid sequence of SEQ ID NO: 19, and HC CDR3 having the amino acid sequence of SEQ ID NO: 20. “Collectively,” as used anywhere in the present disclosure, means that the total number of amino acid variations in all of the three heavy chain CDRs is within the defined range. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 12. [000122] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 18, HC CDR2 having the amino acid sequence of SEQ ID NO: 19, and HC CDR3 having the amino acid sequence of SEQ ID 7107489NO: 20. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 12. [000123] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 18; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 19; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 20. Alternatively or in addition, the anti- KLK5 / KLK7 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 12. [000124] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 21. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 14. [000125] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 21. Alternatively or in addition, the anti- KLK5 / KLK7 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 14. 7107489[000126] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the VH as set forth in SEQ ID NO: 21. Alternatively or in addition, the anti-KLK5 / KLK7 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to the VL as set forth in SEQ ID NO: 14. [000127] The antibodies described herein can be in any antibody form, including, but not limited to, intact (i.e., full-length) antibodies, antigen-binding fragments thereof (such as Fab, F(ab'), F(ab')2, Fv), single chain antibodies, bi-specific antibodies, or nanobodies. In some embodiments, the anti-KLK5 / KLK7 antibody described herein is a scFv. In some embodiments, the anti-KLK5 / KLK7 antibody described herein is a scFv-Fab (e.g., scFv fused to a portion of a constant region). [000128] In some embodiments, an anti-KLK5 / KLK7 antibody of the present disclosure is a chimeric antibody, which can include a heavy constant region and a light constant region from a human antibody. Chimeric antibodies refer to antibodies having a variable region or part of variable region from a first species and a constant region from a second species. Typically, in these chimeric antibodies, the variable region of both light and heavy chains mimics the variable regions of antibodies derived from one species of mammals (e.g., a non- human mammal such as mouse, rabbit, and rat), while the constant portions are homologous to the sequences in antibodies derived from another mammal such as human. In some embodiments, amino acid modifications can be made in the variable region and / or the constant region. [000129] In some embodiments, an antibody of the present disclosure comprises a VL domain and / or VH domain of any one of the anti-KLK5 / KLK7 antibodies selected from Tables 1a and 1b, and comprises a constant region comprising the amino acid sequences of the constant regions of an IgG, IgE, IgM, IgD, IgA or IgY immunoglobulin molecule, any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2), or any subclass (e.g., IgG2a and IgG2b) of immunoglobulin molecule. Non-limiting examples of human constant regions are described in the art, e.g., see Kabat E A et al., (1991) supra. [000130] In some embodiments, the light chain of any of the anti-KLK5 / KLK7 antibodies described herein may further comprise a light chain constant region (CL), which 7107489can be any CL known in the art. In some examples, the CL is a kappa light chain. In other examples, the CL is a lambda light chain. In some embodiments, the CL is a kappa light chain. [000131] Other antibody heavy and light chain constant regions are well known in the art, e.g., those provided in the IMGT database (www.imgt.org) or at www.vbase2.org / vbstat.php., both of which are incorporated by reference herein. [000132] In some embodiments, conservative mutations can be introduced into antibody sequences (e.g., CDRs or framework sequences) at positions where the residues are not likely to be involved in interacting with a target antigen (e.g., human or mouse KLK5 and / or human or mouse KLK7), for example, as determined based on a crystal structure. In some embodiments, one, two or more mutations (e.g., amino acid substitutions) are introduced into the Fc region of an anti-KLK5 / KLK7 antibody described herein (e.g., in a CH2 domain (residues 231-340 of human IgG1) and / or CH3 domain (residues 341-447 of human IgG1) and / or the hinge region, with numbering according to the Kabat numbering system (e.g., the EU index in Kabat)) to alter one or more functional properties of the antibody, such as serum half-life, complement fixation, Fc receptor binding and / or antigen-dependent cellular cytotoxicity. [000133] In some embodiments, one, two or more mutations (e.g., amino acid substitutions) are introduced into the hinge region of the Fc region (CH1 domain) such that the number of cysteine residues in the hinge region are altered (e.g., increased or decreased) as described in, e.g., U.S. Pat. No.5,677,425. The number of cysteine residues in the hinge region of the CH1 domain can be altered to, e.g., facilitate assembly of the light and heavy chains, or to alter (e.g., increase or decrease) the stability of the antibody or to facilitate linker conjugation. [000134] In some embodiments, one, two or more mutations (e.g., amino acid substitutions) are introduced into the Fc region of an antibody described herein (e.g., in a CH2 domain (residues 231-340 of human IgG1) and / or CH3 domain (residues 341-447 of human IgG1) and / or the hinge region, with numbering according to the Kabat numbering system (e.g., the EU index in Kabat)) to increase or decrease the affinity of the antibody for an Fc receptor (e.g., an activated Fc receptor) on the surface of an effector cell. Mutations in the Fc region of an antibody that decrease or increase the affinity of an antibody for an Fc receptor and techniques for introducing such mutations into the Fc receptor or fragment thereof are known to one of skill in the art. Examples of mutations in the Fc receptor of an antibody that can be made to alter the affinity of the antibody for an Fc receptor are described 7107489in, e.g., Smith P et al., (2012) PNAS 109: 6181-6186, U.S. Pat. No.6,737,056, and International Publication Nos. WO 02 / 060919; WO 98 / 23289; and WO 97 / 34631, which are incorporated herein by reference. [000135] In some embodiments, one, two or more amino acid mutations (i.e., substitutions, insertions or deletions) are introduced into an IgG constant domain, or FcRn- binding fragment thereof (preferably an Fc or hinge-Fc domain fragment) to alter (e.g., decrease or increase) half-life of the antibody in vivo. See, e.g., International Publication Nos. WO 02 / 060919; WO 98 / 23289; and WO 97 / 34631; and U.S. Pat. Nos.5,869,046, 6,121,022, 6,277,375 and 6,165,745 for examples of mutations that will alter (e.g., decrease or increase) the half-life of an antibody in vivo. [000136] In some embodiments, one, two or more amino acid mutations (i.e., substitutions, insertions or deletions) are introduced into an IgG constant domain, or FcRn- binding fragment thereof (preferably an Fc or hinge-Fc domain fragment) to decrease the half-life of the anti-KLK5 / KLK7 antibody in vivo. In some embodiments, one, two or more amino acid mutations (i.e., substitutions, insertions or deletions) are introduced into an IgG constant domain, or FcRn-binding fragment thereof (preferably an Fc or hinge-Fc domain fragment) to increase the half-life of the antibody in vivo. In some embodiments, the antibodies can have one or more amino acid mutations (e.g., substitutions) in the second constant (CH2) domain (residues 231-340 of human IgG1) and / or the third constant (CH3) domain (residues 341-447 of human IgG1), with numbering according to the EU index in Kabat (Kabat E A et al., (1991) supra). In some embodiments, the constant region of the IgG1 of an antibody described herein comprises a methionine (M) to tyrosine (Y) substitution in position 252, a serine (S) to threonine (T) substitution in position 254, and a threonine (T) to glutamic acid (E) substitution in position 256, numbered according to the EU index as in Kabat. See U.S. Pat. No.7,658,921, which is incorporated herein by reference. This type of mutant IgG, referred to as "YTE mutant" has been shown to display fourfold increased half- life as compared to wild-type versions of the same antibody (see Dall'Acqua W F et al., (2006) J Biol Chem 281: 23514-24). In some embodiments, an antibody comprises an IgG constant domain comprising one, two, three or more amino acid substitutions of amino acid residues at positions 251-257, 285-290, 308-314, 385-389, and 428-436, numbered according to the EU index as in Kabat. [000137] In some embodiments, an antibody comprises an Fc region that has been engineered for half-life extension purposes, e.g., by introducing M428L and / or N434A substitutions. Non-limiting examples of such Fc variants affecting half-life in circulation are 7107489provided in Saunders KO, Conceptual Approaches to Modulating Antibody Effector Functions and Circulation Half-Life, Front Immunol.2019; 10: 1296, the contents of which are incorporated herein by reference. [000138] In some embodiments, one, two or more amino acid substitutions are introduced into an IgG constant domain Fc region to alter the effector function(s) of the anti- KLK5 / KLK7 antibody, e.g., by introducing Leu234Ala and Leu235Ala mutations (commonly called LALA mutations). The effector ligand to which affinity is altered can be, for example, an Fc receptor or the C1 component of complement. This approach is described in further detail in U.S. Pat. Nos.5,624,821 and 5,648,260. In some embodiments, the deletion or inactivation (through point mutations or other means) of a constant region domain can reduce Fc receptor binding of the circulating antibody thereby increasing tumor localization. See, e.g., U.S. Pat. Nos.5,585,097 and 8,591,886 for a description of mutations that delete or inactivate the constant domain and thereby increase tumor localization. In some embodiments, one or more amino acid substitutions may be introduced into the Fc region of an antibody described herein to remove potential glycosylation sites on Fc region, which may reduce Fc receptor binding (see, e.g., Shields R L et al., (2001) J Biol Chem 276: 6591-604). [000139] In some embodiments, one or more amino in the constant region of an anti- KLK5 / KLK7 antibody described herein can be replaced with a different amino acid residue such that the antibody has altered Clq binding and / or reduced or abolished complement dependent cytotoxicity (CDC). This approach is described in further detail in U.S. Pat. No. 6,194,551 (Idusogie et al). In some embodiments, one or more amino acid residues in the N- terminal region of the CH2 domain of an antibody described herein are altered to thereby alter the ability of the antibody to fix complement. This approach is described further in International Publication No. WO 94 / 29351. In some embodiments, the Fc region of an antibody described herein is modified to increase the ability of the antibody to mediate antibody dependent cellular cytotoxicity (ADCC) and / or to increase the affinity of the antibody for an Fcγ receptor. This approach is described further in International Publication No. WO 00 / 42072. [000140] In some embodiments, an antibody comprises an Fc variant comprising amino acid substitutions L234A, L235E, and P329G, wherein numbering is according to the EU index. In some embodiments, the antibody comprising the Fc variant exhibits reduced affinity to one or more or each of FcyRJ, FcyRIIA, FcyRIIIA, and Clq as compared to an antibody comprising the wild- type human Fc region. Examples of such Fc variants are provided in International Patent Application Publication No.: WO 2021 / 055669 entitled, FC 7107489VARIANTS WITH REDUCED EFFECTOR FUNCTION, published on March 25, 2021; and US Patent Application Publication No.: US 2021-0087271 entitled, FC VARIANTS WITH REDUCED EFFECTOR FUNCTION, published on March 25, 2021, the contents of which are incorporated herein by reference. [000141] In some embodiments, the heavy and / or light chain variable domain(s) sequence(s) of the antibodies provided herein can be used to generate, for example, CDR- grafted, chimeric, humanized, or composite human antibodies or antigen-binding fragments, as described elsewhere herein. As understood by one of ordinary skill in the art, any variant, CDR-grafted, chimeric, humanized, or composite antibodies derived from any of the antibodies provided herein may be useful in the compositions and methods described herein and will maintain the ability to specifically bind KLK5 and KLK7, such that the variant, CDR-grafted, chimeric, humanized, or composite antibody has at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% or more binding to KLK5 and KLK7 relative to the original antibody from which it is derived. [000142] In some embodiments, the antibodies provided herein comprise mutations that confer desirable properties to the antibodies. For example, to avoid potential complications due to Fab-arm exchange, which is known to occur with native IgG4 mAbs, the antibodies provided herein may comprise a stabilizing ‘Adair’ mutation (Angal S., et al., “A single amino acid substitution abolishes the heterogeneity of chimeric mouse / human (IgG4) antibody,” Mol Immunol 30, 105-108; 1993), where serine 228 (EU numbering; residue 241 Kabat numbering) is converted to proline resulting in an IgG1-like hinge sequence. Accordingly, any of the antibodies may include a stabilizing ‘Adair’ mutation. [000143] In some embodiments, an antibody is modified, e.g., modified via glycosylation, phosphorylation, sumoylation, and / or methylation. In some embodiments, an antibody is a glycosylated antibody, which is conjugated to one or more sugar or carbohydrate molecules. In some embodiments, the one or more sugar or carbohydrate molecule are conjugated to the antibody via N-glycosylation, O-glycosylation, C- glycosylation, glypiation (GPI anchor attachment), and / or phosphoglycosylation. In some embodiments, the one or more sugar or carbohydrate molecules are monosaccharides, disaccharides, oligosaccharides, or glycans. In some embodiments, the one or more sugar or carbohydrate molecule is a branched oligosaccharide or a branched glycan. In some embodiments, the one or more sugar or carbohydrate molecule includes a mannose unit, a glucose unit, an N-acetylglucosamine unit, an N-acetylgalactosamine unit, a galactose unit, a fucose unit, or a phospholipid unit. In some embodiments, there are about 1-10, about 1-5, 7107489about 5-10, about 1-4, about 1-3, or about 2 sugar molecules. In some embodiments, a glycosylated antibody is fully or partially glycosylated. In some embodiments, an antibody is glycosylated by chemical reactions or by enzymatic means. In some embodiments, an antibody is glycosylated in vitro or inside a cell, which may optionally be deficient in an enzyme in the N- or O- glycosylation pathway, e.g., a glycosyltransferase. In some embodiments, an antibody is functionalized with sugar or carbohydrate molecules as described in International Patent Application Publication WO2014065661, published on May 1, 2014, entitled, “Modified antibody, antibody-conjugate and process for the preparation thereof”. [000144] In some embodiments, any one of the anti-KLK5 / KLK7 antibodies described herein may comprise a signal peptide in the heavy and / or light chain sequence (e.g., a N- terminal signal peptide). In some embodiments, the anti-KLK5 / KLK7 antibody described herein comprises any one of the VH and VL sequences, any one of the IgG heavy chain and light chain sequences, or any one of the F(ab') heavy chain and light chain sequences described herein, and further comprises a signal peptide (e.g., a N-terminal signal peptide). (b) Th2 Targeting [000145] Conditions associated with barrier dysfunction is characterized by barrier disruption and T helper 2 (Th2)-driven inflammation, e.g., inflammation mediated by Th2 cytokines and receptors thereof such as IL-13, IL-13 receptor (IL-13R), IL-4, IL-4R, IL-5, IL-5R, IL-6, IL-6R, IL-9, IL-9R, IL-31, IL-31R, IL-17E (IL-25), IL-17ER (IL-25R), IL-33, IL-33R, IL-36, IL-36R, OX40L, OX40, TSLP, TSLPR, etc. In some cases, unregulated KLK activity in the epidermis results in and / or is associated with Th2 cell activation, leading to secretion of Th2 cytokines. Elevated Th2 cytokines may further contribute to KLK overactivation (FIG.2). Therapeutic antibodies have been developed to suppress Th2 cytokine mediated inflammation by targeting Th2 cytokines and / or their respective receptors (referred to as Th2-targeting antibodies), for example, anti-IL-13 antibody, anti-IL-4R antibody, etc. [000146] In some embodiments, antibodies provided herein comprise at least one antigen-specific binding site that specifically binds to a Th2 cytokine or a receptor thereof. In some embodiments, such Th2 cytokines or receptors include but are not limited to IL-13, IL-13 receptor (IL-13R), IL-4, IL-4R, IL-5, IL-5R, IL-6, IL-6R, IL-9, IL-9R, IL-31, IL-31R, IL-17E (IL-25), IL-17ER (IL-25R), IL-33, IL-33R, IL-36, IL-36R, OX40L, OX40, TSLP, and TSLPR. Antibodies targeting Th2 cytokines or receptors thereof include, but are not 7107489limited to, anti-IL-13 antibodies, anti-IL-13R antibodies, anti-IL-4 antibodies, anti-IL-4R antibodies, anti-IL-5 antibodies, anti-IL-5R antibodies, anti-IL-6 antibodies, anti-IL-6R antibodies, anti-IL-9 antibodies, anti-IL-9R antibodies, anti-IL-31 antibodies, anti-IL-31R antibodies, anti-IL-17E antibodies, anti-IL-17ER antibodies, anti-IL-31 antibodies, anti-IL- 31R antibodies, anti-IL-36 antibodies, anti-IL-36R antibodies, anti-OX40L antibodies, anti_OX40 antibodies, anti-TSLP antibodies, or anti-TSLPR antibodies. Any suitable Th2 targeting antibodies can be used in the methods and compositions, including but are not limited to those described in Table 2. Table 2: Examples of Th2 targeting Antibodies7107489710748971074897107489710748971074897107489710748971074897107489Anti-TSLP Antibodies / Anti-TSLPR Antibodies71074897107489[000147] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-13 or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-13 or IL-13R derived from any known anti- IL-13 or a receptor thereof, e.g., anti-IL-13 / anti-IL-13R antibodies described in WO2005062972, which is published on 07 / 14 / 2005, and which is entitled “Treatment of cancer with novel anti-il 13 monoclonal antibodies”; WO 2005062967, which is published on 07 / 14 / 2005, and which is entitled “Novel anti-il 13 antibodies and uses thereof”; WO 2008140455, which is published on 05 / 15 / 2007, and which is entitled “Treatment of radiation and chemo-therapy induced fibrosis using novel anti-il 13 monoclonal antibodies”; WO2023245187, which is published on 12 / 21 / 2023, and which is entitled “Antibodies that bind interleukin 13 and methods of use”; US6703488, which published on 03 / 09 / 2004, and which is entitled, Antibody / Receptor Targeting Moiety For Enhanced Delivery Of Armed Ligand; US2005058645, which published on 03 / 17 / 2005, and which is entitled, Monoclonal Antibody Against Interleukin-13 Receptor Alpha 1 (IL-13Ralpha1); US2005154192, which published on 07 / 14 / 2005, and which is entitled, Anti-IL13 Receptor Alpha1 Neutralizing Antibody; US2006099652, which published on 05 / 11 / 2006, and which is entitled, IL 13 Receptor Alpha 2 Antibody And Methods Of Use; US2006140948, which published on 06 / 29 / 2006, and which is entitled, Fully Human Monoclonal Antibodies To IL-13; US2006263356, which published on 11 / 23 / 2006, and which is entitled, Antibodies Against IL-13 Receptor Alpha1 And Uses Thereof; US2007048785, which published on 03 / 01 / 2007, and which is entitled, Anti-IL-13 Antibodies And Complexes; US2007128192, which 7107489published on 06 / 07 / 2007, and which is entitled, Human Antibody Molecules For IL-13; WO07080174, which published on 07 / 19 / 2007, and which is entitled, Immunoglobulins; US2007258979, which published on 11 / 08 / 2007, and which is entitled, Chimeric And Humanised Monoclonal Antibodies Against Interleukin-13; US2008008648, which published on 01 / 10 / 2008, and which is entitled, Treatment Of Cancer With A Novel Anti- IL13 Monoclonal Antibody; US2008044420, which published on 02 / 21 / 2008, and which is entitled, Anti-IL-13 Antibodies, Compositions, Methods And Uses; US2008166343, which published on 07 / 10 / 2008, and which is entitled, High Affinity Antibody Antagonists Of Interleukin-13 Receptor Alpha 1; US2008171014, which published on 07 / 17 / 2008, and which is entitled, Interleukin-13 Binding Proteins; US2008248048, which published on 10 / 09 / 2008, and which is entitled, Interleukin-13 Antibody Composition; US2008267959, which published on 10 / 30 / 2008, and which is entitled, Anti-IL13 Human Antibodies; US2009060906, which published on 03 / 05 / 2009, and which is entitled, Anti-IL-13 Antibody Formulations And Uses Thereof; US2009148905, which published on 06 / 11 / 2009, and which is entitled, Antigen-Binding Constructs; US2009285799, which published on 11 / 19 / 2009, and which is entitled, Antibody Antagonists Of Interleukin-13 Receptor Alpha1; WO09138413, which published on 11 / 19 / 2009, and which is entitled, Single Domain Antibodies That Bind IL-13; US2010226923, which published on 09 / 09 / 2010, and which is entitled, Antibodies That Bind IL-4 And / Or IL-13 And Their Uses; US2010260773, which published on 10 / 14 / 2010, and which is entitled, Antibody Molecules Having Binding Specificity For Human IL-13; US2011052597, which published on 03 / 03 / 2011, and which is entitled, Anti- IL-13R Alpha1 Antibodies And Their Uses Thereof; US2011206687, which published on 08 / 25 / 2011, and which is entitled, Isolation And Purification Of Anti-IL-13 Antibodies Using Protein A Affinity Chromatography; US2012045438, which published on 02 / 23 / 2012, and which is entitled, Engineered Anti-IL-13 Antibodies, Compositions, Methods And Uses; US2012093830, which published on 04 / 19 / 2012, and which is entitled, Single Domain Antibodies That Bind IL-13; WO13103783, which published on 07 / 11 / 2013, and which is entitled, Murine IL-13 Antibodies; US2014341913, which published on 11 / 20 / 2014, and which is entitled, Methods And Compositions For Treating Asthma Using Anti-IL-13 Antibodies; US2014348855, which published on 11 / 27 / 2014, and which is entitled, Antibody Formulations; US2015225479, which published on 08 / 13 / 2015, and which is entitled, Anti- IL-4 / Anti-IL-13 Bispecific Antibody / Polyglutamate Formulations; US2015266962, which published on 09 / 24 / 2015, and which is entitled, Anti-IL-13 Receptor Alpha 2 Antibodies And Antibody-Drug Conjugates; US2016075777, which published on 03 / 17 / 2016, and which is 7107489entitled, Anti-IL-4 / Anti-IL-13 Bispecific Antibody Formulations; US2016319012, which published on 11 / 03 / 2016, and which is entitled, Methods And Compositions Comprising Purified Recombinant Polypeptides; US2017145089, which published on 05 / 25 / 2017, and which is entitled, Anti-IL4-Il 13 Bispecific Antibodies; WO17191627, which published on 11 / 09 / 2017, and which is entitled, Antibodies To Interleukin 13 Receptor Alpha-1 (IL-13R Alpha 1) And Uses Thereof; US2017334985, which published on 11 / 23 / 2017, and which is entitled, Anti-IL-13 / Il-17 Bispecific Antibodies And Uses Thereof; WO19096219, which published on 05 / 23 / 2019, and which is entitled, Humanized Anti-IL-13 Antibody And Preparation Method And Use Thereof; US2019247303, which published on 08 / 15 / 2019, and which is entitled, Inhalable Powder Composition Comprising IL-13 Antibody; US2019309059, which published on 10 / 10 / 2019, and which is entitled, IL-13 Antibody And Preparation Method And Use Thereof; US2020165347, which published on 05 / 28 / 2020, and which is entitled, Method Of Treatment Using IL-13R Antibody; US2021277131, which published on 09 / 09 / 2021, and which is entitled, Treatment Employing Anti-Il-L3R Antibody Or Binding Fragment Thereof; US2021380674, which published on 12 / 09 / 2021, and which is entitled, Methods Of Treatment Of Diseases In Which IL-13 Activity Is Detrimental Using Anti-IL-13 Antibodies; US2022033508, which published on 02 / 03 / 2022, and which is entitled, Anti-IL13R Alpha2 Antibodies; WO22174808, which published on 08 / 25 / 2022, and which is entitled, Antibody Against IL-13Ra2 And Use Thereof; US2022305104, which published on 09 / 29 / 2022, and which is entitled, Methods Of Treating Atopic Dermatitis; US2023002484, which published on 01 / 05 / 2023, and which is entitled, Treatment Of Atopic Dermatitis Employing Anti-IL-13Ra1 Antibody Or Binding Fragment Thereof; WO23287590, which published on 01 / 19 / 2023, and which is entitled, IL-13 Antibodies For The Treatment Of Atopic Dermatitis; WO23019260, which published on 02 / 16 / 2023, and which is entitled, IL-13 Antibodies For The Treatment Of Atopic Dermatitis; WO23023497, which published on 02 / 23 / 2023, and which is entitled, Anti-IL-13 Antibody Formulation; US2023084464, which published on 03 / 16 / 2023, and which is entitled, Antibody With Binding Specificity For Human IL-13; US2023087378, which published on 03 / 23 / 2023, and which is entitled, Multi-Specific Antibody With Binding Specificity For Human IL-13 And Il-17; WO23075700, which published on 05 / 04 / 2023, and which is entitled, Anti-IL-13R Antibody Formulation; WO23075702, which published on 05 / 04 / 2023, and which is entitled, Anti-IL-13R Antibody Formulation; US2023183364, which published on 06 / 15 / 2023, and which is entitled, Anti-IL13R-Alpha2 Antibodies, Antigen-Binding Fragments And Uses Thereof; WO23163659, which published on 08 / 31 / 2023, and which is entitled, Glycosylated 7107489Form Of Anti-IL13R Antibody; US2023357381, which published on 11 / 09 / 2023, and which is entitled, Multispecific Antibodies Targeting IL-13 And Il-18; WO23215769, which published on 11 / 09 / 2023, and which is entitled, IL-13 Antibodies For The Treatment Of Atopic Dermatitis; WO23245187, which published on 12 / 21 / 2023, and which is entitled, Antibodies That Bind Interleukin 13 And Methods Of Use; WO24043837, which published on 02 / 29 / 2024, and which is entitled, High Concentration Anti-IL13R Antibody Formulation; US2024117030, which published on 04 / 11 / 2024, and which is entitled, Multispecific Antibodies And Uses Thereof; US2024158521, which published on 05 / 16 / 2024, and which is entitled, Dna-Encoded Bispecific Antibodies Targeting IL13Ra2 And Methods Of Use In Cancer Therapeutics; WO08140455, which published on 11 / 20 / 2008, and which is entitled, Treatment Of Radiation And Chemo-Therapy Induced Fibrosis Using Novel Anti-IL 13 Monoclonal Antibodies; and WO24099310, which published on 05 / 16 / 2024, and which is entitled, Anti-IL-13 Long-Acting Nanobody Sequence And Use Thereof, the contents describing an anti-IL-13 antibody in each of which are incorporated herein by reference. [000148] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-4 or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-4 or IL-4R derived from any known anti-IL- 4 or a receptor thereof, e.g., anti-IL-4 / anti-IL-4R antibodies described in: US5552304, which published on 09 / 03 / 1996, and which is entitled, cDNA Clones Coding For Human Protein Exhibiting A Broad Cellular Activity Spectrum (Human Interleukin-4); US5676940, which published on 10 / 14 / 1997, and which is entitled, Method Of Reducing Immunoglobulin E Responses; US5985280, which published on 11 / 16 / 1999, and which is entitled, Diagnosis And / Or Therapy Of Tumours Using Monoclonal Antibodies Specific For The Human IL-4 Receptor; US6358509, which published on 03 / 19 / 2002, and which is entitled, Antibody Antagonists Of Human Interleukin-4; US5863537, which published on 01 / 26 / 1999, and which is entitled, Humanized Monoclonal Antibodies Against Human Interleukin-4; WO9414975, which published on 07 / 07 / 1994, and which is entitled, Monoclonal Antibodies Against The Human Interleukin-4 Receptor And Hybridomas Producing The Same; US5928904, which published on 07 / 27 / 1999, and which is entitled, DNA Encoding Recombinant IL4 Antibodies Useful In Treatment Of IL4 Mediated Disorders; US5597710, which published on 01 / 28 / 1997, and which is entitled, Humanized Monoclonal Antibodies Against Human Interleukin-4; US5783181, which published on 07 / 21 / 1998, and which is entitled, Therapeutic Uses Of Fusion Proteins Between Mutant Il 4 / IL13 Antagonists And Immunoglobulins; US2002002132, which published on 01 / 03 / 2002, and which is entitled, 7107489Use Of Interleukin-4 Antagonists And Compositions Thereof; US2007274996, which published on 11 / 29 / 2007, and which is entitled, Antibodies That Bind Interleukin-4 Receptor; US2008241160, which published on 10 / 02 / 2008, and which is entitled, Human Monoclonal Antibodies Against Human IL-4; US2010297110, which published on 11 / 25 / 2010, and which is entitled, Antibody Specific For Human IL-4 For The Treatment Of Cancer; US2008160035, which published on 07 / 03 / 2008, and which is entitled, High Affinity Human Antibodies To Human IL-4 Receptor; US2010226923, which published on 09 / 09 / 2010, and which is entitled, Antibodies That Bind IL-4 And / Or IL-13 And Their Uses; US2012097565, which published on 04 / 26 / 2012, and which is entitled, Stabilized Formulations Containing Anti-Interleukin-4 Receptor (IL-4R) Antibodies; US2014056920, which published on 02 / 27 / 2014, and which is entitled, Methods For Treating Or Preventing Asthma By Administering An IL-4R Antagonist; US2014072583, which published on 03 / 13 / 2014, and which is entitled, Methods For Treating Atopic Dermatitis By Administering An IL-4R Antagonist; US2016207995, which published on 07 / 21 / 2016, and which is entitled, Anti-IL-4 Antibodies And Bispecific Antibodies And Uses Thereof; US2016075777, which published on 03 / 17 / 2016, and which is entitled, Anti-IL-4 / Anti-IL-13 Bispecific Antibody Formulations; US2014356372, which published on 12 / 04 / 2014, and which is entitled, Methods For Treating Allergy And Enhancing Allergen-Specific Immunotherapy By Administering An IL-4R Inhibitor; US2015017176, which published on 01 / 15 / 2015, and which is entitled, Methods For Treating Eosinophilic Esophagitis By Administering An IL- 4R Inhibitor; US2015225479, which published on 08 / 13 / 2015, and which is entitled, Anti-IL- 4 / Anti-IL-13 Bispecific Antibody / Polyglutamate Formulations; US2017145089, which published on 05 / 25 / 2017, and which is entitled, Anti-IL4-Il 13 Bispecific Antibodies; US2017281769, which published on 10 / 05 / 2017, and which is entitled, Stable Anti-IL-4Ra Formulation; US2018346580, which published on 12 / 06 / 2018, and which is entitled, Antibodies To Canine Interleukin-4 Receptor Alpha; US2019177408, which published on 06 / 13 / 2019, and which is entitled, Antibody For Binding To Interleukin 4 Receptor; US2022081485, which published on 03 / 17 / 2022, and which is entitled, Anti-IL-4R Antibody And Use Thereof; WO19148405, which published on 08 / 08 / 2019, and which is entitled, IL- 4R Antibody And Use Thereof; US2022073631, which published on 03 / 10 / 2022, and which is entitled, Monoclonal Antibody Against Human Interleukin-4 Receptor Alpha And Use Thereof; US2021238294, which published on 08 / 05 / 2021, and which is entitled, Human IL- 4R Binding Antibody, Antigen Binding Fragment Thereof, And Medical Use Thereof; US2021206861, which published on 07 / 08 / 2021, and which is entitled, Antibodies Binding 7107489To Human IL-4R, Preparation Method Therefor And Use Thereof; US2021403580, which published on 12 / 30 / 2021, and which is entitled, Human Antibody Having High Affinity To Human IL-4 Receptor Alpha, And Use Thereof; US2023295312, which published on 09 / 21 / 2023, and which is entitled, Antibody Against Human IL-4Ra And Use Thereof; US2022162328, which published on 05 / 26 / 2022, and which is entitled, Interleukin-4 Receptor Antibody And Application Thereof; US2022348666, which published on 11 / 03 / 2022, and which is entitled, Liquid Composition Comprising Antibody Of Human Interleukin-4 Receptor Alpha; US2022411519, which published on 12 / 29 / 2022, and which is entitled, Anti-IL-4R Single-Domain Antibody And Use Thereof; US2023053131, which published on 02 / 16 / 2023, and which is entitled, Antibodies To Canine Interleukin-4 Receptor Alpha; US2023088052, which published on 03 / 23 / 2023, and which is entitled, Pharmaceutical Composition Containing Anti-IL-4R Antibody And Use Thereof; US2023105029, which published on 04 / 06 / 2023, and which is entitled, Antibodies Binding IL4R And Uses Thereof; US2024067738, which published on 02 / 29 / 2024, and which is entitled, Anti-IL4 Receptor Antibodies For Veterinary Use; US2023203172, which published on 06 / 29 / 2023, and which is entitled, Anti-Human Interleukin-4 Receptor Alpha Antibody And Preparation Method And Application Thereof; US2023167180, which published on 06 / 01 / 2023, and which is entitled, Antibody Binding With Specific Epitope In Human IL-4R Alpha And Applications Of Antibody; WO21254221, which published on 12 / 23 / 2021, and which is entitled, Stable Liquid Preparation Of Anti-IL-4R Monoclonal Antibodies; US2023279124, which published on 09 / 07 / 2023, and which is entitled, Fusion Protein Comprising Ige Fc Receptor Alpha Subunit Extracellular Domain And Anti-IL-4R Antibody, And Use Thereof; US2023357415, which published on 11 / 09 / 2023, and which is entitled, Bispecific Antibody Simultaneously Binding To Interleukin-4 Receptor Alpha Subunit And Interleukin-5 Receptor Alpha Subunit, And Use Thereof; US2023374144, which published on 11 / 23 / 2023, and which is entitled, Antibodies Specifically Recognizing Interleukin-4 Receptor Alpha And Uses Thereof; US2023279123, which published on 09 / 07 / 2023, and which is entitled, Humanized Anti-IL-4Ra Single Domain Antibody And Application Thereof; US2024075158, which published on 03 / 07 / 2024, and which is entitled, Complex Of Anti-IL-4R Antibody Or Antigen-Binding Fragment Thereof And Medical Use Thereof; WO23011502, which published on 02 / 09 / 2023, and which is entitled, Stable Formulation Comprising Anti-IL-4R Antibody; US2023064378, which published on 03 / 02 / 2023, and which is entitled, Human Interleukin-4 Receptor Alpha Antibodies; WO23025217, which published on 03 / 02 / 2023, and which is entitled, Pharmaceutical Composition Of Anti-IL4R 7107489Antibody And Use Thereof; WO23191665, which published on 10 / 05 / 2023, and which is entitled, Antibodies To Human IL-4R Having Reduced Immunogenicity And Application Thereof; US2024024472, which published on 01 / 25 / 2024, and which is entitled, Anti- Interleukin-4 Receptor (IL-4R) Antibody Formulations; US2024100176, which published on 03 / 28 / 2024, and which is entitled, Human Interleukin-4 Receptor Alpha Antibody Glucocorticoid Conjugates; and WO24061279, which published on 03 / 28 / 2024, and which is entitled, Recombinant Bispecific Antibodies Targeting TSLP And IL4R, the contents describing an anti-IL-4 or anti-IL-4R antibody in each of which are incorporated herein by reference. [000149] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for OX40L or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for OX40L or OX40 derived from any known anti- OX40L or a receptor thereof, e.g., anti-OX40L / anti-OX40 antibodies described in: US2006002929, which published on 01 / 05 / 2006, and which is entitled, Monoclonal Antibodies; US7291331, which published on 11 / 06 / 2007, and which is entitled, Methods Of Treating OX40 Medicated Recall Immune Responses; US2009053230, which published on 02 / 26 / 2009, and which is entitled, Anti-OX40L Antibodies And Methods Using Same; US7501496, which published on 03 / 10 / 2009, and which is entitled, Anti-OX40L Antibodies; US2010098712, which published on 04 / 22 / 2010, and which is entitled, Pharmaceutical Formulation Of An Antibody Against OX40L; US2010136030, which published on 06 / 03 / 2010, and which is entitled, Antagonist OX40 Antibodies And Their Use In The Treatment Of Inflammatory And Autoimmune Diseases; US2010196359, which published on 08 / 05 / 2010, and which is entitled, Human Monoclonal Antibody Human Cd134 (OX40) And Methods Of Making And Using Same; US2010254978, which published on 10 / 07 / 2010, and which is entitled, Antibody Molecules Having Specificity For Human OX40; US2013018175, which published on 01 / 17 / 2013, and which is entitled, Single Variable Domain Antibodies Against OX40L, Constructs And Therapeutic Use; US2013183315, which published on 07 / 18 / 2013, and which is entitled, Antibodies That Bind To OX40 And Their Uses; US2013243772, which published on 09 / 19 / 2013, and which is entitled, Antibody Molecules Having Specificity For Human OX40; US2013280275, which published on 10 / 24 / 2013, and which is entitled, Anti-OX40 Antibodies And Methods Of Using The Same; US2014377284, which published on 12 / 25 / 2014, and which is entitled, Humanized Anti- Cd134 (OX40) Antibodies And Uses Thereof; US2015307617, which published on 10 / 29 / 2015, and which is entitled, Anti-OX40 Antibodies And Methods Of Use; 7107489WO16002820, which published on 01 / 07 / 2016, and which is entitled, Novel Anti-Human OX40 Ligand Antibody, And Anti-Influenza Drug Comprising Same; US2016137740, which published on 05 / 19 / 2016, and which is entitled, Humanized Anti-OX40 Antibodies And Uses Thereof; US2016347847, which published on 12 / 01 / 2016, and which is entitled, Anti-OX40 Antibodies And Methods Of Use Thereof; US2016347849, which published on 12 / 01 / 2016, and which is entitled, Antibodies Against OX40 And Uses Thereof; US2016368997, which published on 12 / 22 / 2016, and which is entitled, Antibodies, Uses And Methods; WO17096281, which published on 06 / 08 / 2017, and which is entitled, Anti-OX40 Antibodies And Methods Of Use Thereof; WO17134292, which published on 08 / 10 / 2017, and which is entitled, Anti-OX40 Antagonistic Antibodies For The Treatment Of Atopic Dermatitis; US2017349661, which published on 12 / 07 / 2017, and which is entitled, Antagonistic Anti- OX40L Antibodies And Methods Of Their Use; US2018171023, which published on 06 / 21 / 2018, and which is entitled, Anti-OX40 Antibodies And Their Uses; US2021206864, which published on 07 / 08 / 2021, and which is entitled, Anti-OX40 Antagonistic Antibodies And Dosage For The Treatment Of OX40-Mediated Disorders; US2021214453, which published on 07 / 15 / 2021, and which is entitled, Anti-OX40 Antagonistic Antibodies For The Treatment Of Autoimmune Diseases; WO22042692, which published on 03 / 03 / 2022, and which is entitled, Anti-OX40 Antibody Having Low Toxicity, And Pharmaceutical Composition And Use Thereof; US2023151105, which published on 05 / 18 / 2023, and which is entitled, Anti-OX40 Antibody And Uses Thereof; WO23109901, which published on 06 / 22 / 2023, and which is entitled, Anti-OX40 Antibodies And Methods Of Use; WO23109976, which published on 06 / 22 / 2023, and which is entitled, Antibody Against OX40 And Medical Use Thereof; US2024182594, which published on 06 / 06 / 2024, and which is entitled, Uses Of Antagonist, Non-Depleting OX40 Antibodies; US2024209104, which published on 06 / 27 / 2024, and which is entitled, Anti-OX40 Antibody, And Pharmaceutical Composition And Application Thereof; US2024209107, which published on 06 / 27 / 2024, and which is entitled, Cd28 / OX40 Bispecific Antibodies; and US2024270859, which published on 08 / 15 / 2024, and which is entitled, Anti-OX40L Antibody, Anti- OX40L / Anti-TNFa Bispecific Antibody, And Uses Thereof, the contents describing an anti- OX40L or anti-OX40 antibody in each of which are incorporated herein by reference. [000150] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for TSLP or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for TSLP or TSLPR derived from any known anti- TSLP or a receptor thereof, e.g., anti-TSLP / anti-TSLPR antibodies described in: 7107489US2009186022, which published on 07 / 23 / 2009, and which is entitled, Organic Compounds; US2010166766, which published on 07 / 01 / 2010, and which is entitled, Engineered Anti- TSLP Antibody; US2011020369, which published on 01 / 27 / 2011, and which is entitled, Engineered Anti-TSLPR Antibodies; US2012020988, which published on 01 / 26 / 2012, and which is entitled, Antibodies Specifically Binding To Human TSLPR And Methods Of Use; US2012219565, which published on 08 / 30 / 2012, and which is entitled, Engineered Anti- TSLP Antibody; US2014227250, which published on 08 / 14 / 2014, and which is entitled, Stable Formulations Of Antibodies To TSLP; US2016046720, which published on 02 / 18 / 2016, and which is entitled, Novel Anti-Human TSLP Receptor Antibody; US2017066823, which published on 03 / 09 / 2017, and which is entitled, Thymic Stromal Lymphopoietin (TSLP)-Binding Molecules And Methods Of Using The Molecules; US2018296669, which published on 10 / 18 / 2018, and which is entitled, Treatment Of Asthma With Anti-TSLP Antibody; US2019111129, which published on 04 / 18 / 2019, and which is entitled, Pharmaceutical Composition Comprising Anti-Human TSLP Receptor Antibody; US2021121406, which published on 04 / 29 / 2021, and which is entitled, Dry Powder Formulations Of Thymic Stromal Lymphopoietin (TSLP)-Binding Antibodies And Methods Of Use Thereof; WO21155634, which published on 08 / 12 / 2021, and which is entitled, Anti- Human-TSLP Antibody And Use Thereof; WO22184074, which published on 09 / 09 / 2022, and which is entitled, Pharmaceutical Composition Containing Anti-TSLP Antibody; US2022289833, which published on 09 / 15 / 2022, and which is entitled, Antibodies Binding TSLP And Uses Thereof; US2022340654, which published on 10 / 27 / 2022, and which is entitled, Antibody Capable Of Binding To Thymic Stromal Lymphopoietin And Use Thereof; US2022363781, which published on 11 / 17 / 2022, and which is entitled, Anti-TSLP Antibody And Uses Thereof; WO22253147, which published on 12 / 08 / 2022, and which is entitled, Anti-Thymic Stromal Lymphopoietin (TSLP) Antibody And Use Thereof; WO23028612, which published on 03 / 02 / 2023, and which is entitled, Anti-TSLPR (Crlf2) Antibodies; US2023073888, which published on 03 / 09 / 2023, and which is entitled, Treatment Of Atopic Dermatitis With Anti-TSLP Antibody; WO23029281, which published on 03 / 09 / 2023, and which is entitled, Anti-Human TSLP Monoclonal Antibody And Use Thereof; US2023078678, which published on 03 / 16 / 2023, and which is entitled, Formulations Of Human Anti-TSLP Antibodies And Methods Of Treating Atopic Dermatitis; US2023081261, which published on 03 / 16 / 2023, and which is entitled, Formulations Of Human Anti-TSLP Antibodies And Methods Of Using The Same; US2023082287, which published on 03 / 16 / 2023, and which is entitled, Methods Of Treating An Inflammatory Or Obstructive 7107489Airway Disease Using Anti-TSLP Antibody; WO23070948, which published on 05 / 04 / 2023, and which is entitled, Preparation Method For Concentrated Solution Containing Anti- Human Thymic Stromal Lymphopoietin (TSLP) Monoclonal Antibody, And Liquid Preparation; WO23098491, which published on 06 / 08 / 2023, and which is entitled, Anti- TSLP Monoclonal Antibody, Antigen-Binding Fragment Thereof And Use Thereof; WO23116925, which published on 06 / 29 / 2023, and which is entitled, Novel Anti-TSLP Antibodies; WO23142309, which published on 08 / 03 / 2023, and which is entitled, Anti-TSLP Nanobody And Use Thereof; US2024016931, which published on 01 / 18 / 2024, and which is entitled, Anti-TSLP Antibody Pharmaceutical Composition And Use Thereof; WO24061279, which published on 03 / 28 / 2024, and which is entitled, Recombinant Bispecific Antibodies Targeting TSLP And Il4R; US2024117030, which published on 04 / 11 / 2024, and which is entitled, Multispecific Antibodies And Uses Thereof; US2024132581, which published on 04 / 25 / 2024, and which is entitled, Antibodies Against Human TSLP And Use Thereof; WO24092064, which published on 05 / 02 / 2024, and which is entitled, Anti-TSLP Antibody Compositions And Uses Thereof; US2024173405, which published on 05 / 30 / 2024, and which is entitled, Pharmaceutical Compositions Comprising Anti-Human TSLP Receptor Antibodies And Methods Of Using The Same; US2024182558, which published on 06 / 06 / 2024, and which is entitled, Modified Anti-TSLP Antibodies; US2024190951, which published on 06 / 13 / 2024, and which is entitled, Anti-TSLP Antibody Compositions And Uses Thereof; WO24146630, which published on 07 / 11 / 2024, and which is entitled, Method For Treating Asthma By Using TSLP Antibody; WO24152881, which published on 07 / 25 / 2024, and which is entitled, Anti-TSLP Antibody And Use Thereof; and WO24163978, which published on 08 / 08 / 2024, and which is entitled, Treatment Of Chronic Rhinosinusitis With Anti-TSLP Antibody, the contents describing an anti-TSLP or anti- TSLPR antibody in each of which are incorporated herein by reference. [000151] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-5 or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-5 or IL-5R derived from any known anti-IL- 5 or a receptor thereof, e.g., anti-IL-5 / anti-IL-5R antibodies described in: US5683892, which published on 11 / 04 / 1997, and which is entitled, DNA Encoding Recombinant IL-5 Antagonists Useful In Treatment Of IL-5 Mediated Disorders; US5976821, which published on 11 / 02 / 1999, and which is entitled, Monoclonal Antibodies Specific For Human Interleukin-5; US5998586, which published on 12 / 07 / 1999, and which is entitled, Interleukin-5 Specific Recombinant Antibodies; US6018032, which published on 710748901 / 25 / 2000, and which is entitled, Antibody Against Human Interleukin-5-Receptor Alpha Chain; US6056957, which published on 05 / 02 / 2000, and which is entitled, Humanized Monoclonal Antibodies Against Human Interleukin-5; US6451982, which published on 09 / 17 / 2002, and which is entitled, Design, Cloning And Expression Of Humanized Monoclonal Antibodies Against Human Interleukin-5; US2003194404, which published on 10 / 16 / 2003, and which is entitled, Human Monoclonal Antibodies To Interleukin-5 And Methods And Compositions Comprising Same; US6720155, which published on 04 / 13 / 2004, and which is entitled, Monoclonal Antibody Inhibitor Of Gm-Csf, Il-3, IL-5 And Other Cytokines, And Uses Thereof; US2005226867, which published on 10 / 13 / 2005, and which is entitled, IL-5R-Specific Antibody Composition; US2009252723, which published on 10 / 08 / 2009, and which is entitled, Remedy For Endometriosis; US2010086547, which published on 04 / 08 / 2010, and which is entitled, Methods For Administering Anti-IL-5 Antibodies; US2010291073, which published on 11 / 18 / 2010, and which is entitled, Methods Of Reducing Eosinophil Levels; US2011020339, which published on 01 / 27 / 2011, and which is entitled, Methods Of Treatment; US2015118249, which published on 04 / 30 / 2015, and which is entitled, Stable, Aqueous Antibody Formulations; US2018155434, which published on 06 / 07 / 2018, and which is entitled, Therapeutic Agent And Therapeutic Method For Pulmonary Hypertension; US2018186873, which published on 07 / 05 / 2018, and which is entitled, Anti-IL-5 Antibodies; US2018251539, which published on 09 / 06 / 2018, and which is entitled, Biopharmaceutical Compositions; US2020262909, which published on 08 / 20 / 2020, and which is entitled, IL-5 Antibody, Antigen Binding Fragment Thereof, And Medical Application Therefor; US2020291121, which published on 09 / 17 / 2020, and which is entitled, Anti-IL-5Ralpha Monoclonal Antibody; US2020399382, which published on 12 / 24 / 2020, and which is entitled, Combined Antagonists Against IL-5 / IL-5R And Either Il-4 / Il-4R Or Il- 13 / Il-13R; US2021171621, which published on 06 / 10 / 2021, and which is entitled, Monoclonal Antibody Binding To Human IL-5, Preparation Method Therefor And Use Thereof; WO21249373, which published on 12 / 16 / 2021, and which is entitled, Stable High- Concentration Anti-Human IL-5 Monoclonal Antibody Liquid Preparation; US2022010008, which published on 01 / 13 / 2022, and which is entitled, Anti-Human Interleukin 5(IL-5) Monoclonal Antibody And Use Thereof; US2022144937, which published on 05 / 12 / 2022, and which is entitled, Pharmaceutical Composition Containing Antibody Against IL-5 And Use Thereof; US2022193238, which published on 06 / 23 / 2022, and which is entitled, Anti- IL5R Antibody Formulations; US2023357415, which published on 11 / 09 / 2023, and which is entitled, Bispecific Antibody Simultaneously Binding To Interleukin-4 Receptor Alpha 7107489Subunit And Interleukin-5 Receptor Alpha Subunit, And Use Thereof; US2023399395, which published on 12 / 14 / 2023, and which is entitled, Anti-IL5 Nanoantibody And Use Thereof; US2023416380, which published on 12 / 28 / 2023, and which is entitled, Antibody Binding Human IL-5R Alpha And Use Thereof; and US2024115698, which published on 04 / 11 / 2024, and which is entitled, Anti-IL-5 Antibody Formulation, Preparation Method Therefor And Use Thereof, the contents describing an anti-IL-5 or anti-IL-5R antibody in each of which are incorporated herein by reference. [000152] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-9 or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-9 or IL-9R derived from any known anti-IL- 9 or a receptor thereof, e.g., anti-IL-9 / anti-IL-9R antibodies described in: US5789237, which published on 08 / 04 / 1998, and which is entitled, Nucleic Acid Sequences Coding For Or Complementary To Nucleic Acid Sequences Coding For Interleukin 9 Receptor; US5908839, which published on 06 / 01 / 1999, and which is entitled, Asthma Associated Factors As Targets For Treating Atopic Allergies Including Asthma And Related Disorders; US2003219439, which published on 11 / 27 / 2003, and which is entitled, Recombinant Anti-Interleukin-9 Antibodies; US2005002934, which published on 01 / 06 / 2005, and which is entitled, Recombinant IL-9 Antibodies And Uses Thereof; US2005260204, which published on 11 / 24 / 2005, and which is entitled, Anti-IL-9 Antibody Formulations And Uses Thereof; WO23246570, which published on 12 / 28 / 2023, and which is entitled, Interleukin-9 Antibody And Use Thereof; and US2024109960, which published on 04 / 04 / 2024, and which is entitled, Anti-IL-9 Antibodies And Methods Of Use Thereof, the contents describing an anti- IL-9 or anti-IL-9R antibody in each of which are incorporated herein by reference. [000153] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-25 or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-25 or IL-25R derived from any known anti- IL-25 or a receptor thereof, e.g., anti-IL-25 / anti-IL-25R antibodies described in: US2010028343, which published on 02 / 04 / 2010, and which is entitled, ILL17 Homologous Polypeptides And Therapeutic Uses Thereof; US2010129380, which published on 05 / 27 / 2010, and which is entitled, Antibodies Against IL-25; US7771719, which published on 08 / 10 / 2010, and which is entitled, Pharmaceutical Compositions, Kits, And Therapeutic Uses Of Antagonist Antibodies To IL-17E; US2011250195, which published on 10 / 13 / 2011, and which is entitled, Antibodies Against IL-25; US2011318353, which published on 12 / 29 / 2011, and which is entitled, Humanized IL-25 Antibodies; US2016083466, which 7107489published on 03 / 24 / 2016, and which is entitled, Anti-IL-25 Antibodies And Uses Thereof; US2020291105, which published on 09 / 17 / 2020, and which is entitled, Neutralizing Monoclonal Antibodies To IL-25 And Uses Thereof; US2021332123, which published on 10 / 28 / 2021, and which is entitled, Anti-IL-25 Antibodies And Use Thereof; and WO23060144, which published on 04 / 13 / 2023, and which is entitled, Monoclonal Antibodies To IL-25 And Uses Thereof, the contents describing an anti-IL-25 or anti-IL-25R antibody in each of which are incorporated herein by reference. [000154] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-31 or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-31 or IL-31R derived from any known anti- IL-31 or a receptor thereof, e.g., anti-IL-31 / anti-IL-31R antibodies described in: US2006275296, which published on 12 / 07 / 2006, and which is entitled, IL-31 Monoclonal Antibodies And Methods Of Use; US2007160610, which published on 07 / 12 / 2007, and which is entitled, Methods Of Treating Pain And Inflammation In Neuronal Tissue Using IL- 31 Antagonists; US2009208494, which published on 08 / 20 / 2009, and which is entitled, Humanized Antibody Molecules Specific For IL-31; US2013022616, which published on 01 / 24 / 2013, and which is entitled, Interleukin-31 Monoclonal Antibody; and US2024043547, which published on 02 / 08 / 2024, and which is entitled, Antibody Variable Domains That Bind IL-31, the contents describing an anti-IL-31 or anti-IL-31R antibody in each of which are incorporated herein by reference. [000155] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-33 or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-33 or IL-33R derived from any known anti- IL-33 or a receptor thereof, e.g., anti-IL-33 / anti-IL-33R antibodies described in: US2003124624, which published on 07 / 03 / 2003, and which is entitled, Monoclonal Antibody And Method And Kit For Immunoassay Of Soluble Human ST2; US2012213774, which published on 08 / 23 / 2012, and which is entitled, Antibodies Against Human IL33R And Uses Thereof; US2014004107, which published on 01 / 02 / 2014, and which is entitled, ST2 Antigen Binding Proteins; US2014271658, which published on 09 / 18 / 2014, and which is entitled, Anti-IL-33 Antibodies And Uses Thereof; US2016168242, which published on 06 / 16 / 2016, and which is entitled, Anti-Interleukin-33 Antibodies And Uses Thereof; US2016289322, which published on 10 / 06 / 2016, and which is entitled, Human Anti-IL-33 Neutralizing Monoclonal Antibody; US2016333090, which published on 11 / 17 / 2016, and which is entitled, Antibodies Directed Against Interleukin-33 (IL-33); US2018037644, which 7107489published on 02 / 08 / 2018, and which is entitled, Anti-IL-33 Antibodies, Compositions, Methods And Uses Thereof; US2018118821, which published on 05 / 03 / 2018, and which is entitled, Anti-IL-33 Antibodies And Uses Thereof; US2019202907, which published on 07 / 04 / 2019, and which is entitled, Method Of Treating Systemic Fibrotic Disorders Using An IL-33 / Tnf Bispecific Antibody; US2019225682, which published on 07 / 25 / 2019, and which is entitled, Method Of Treating Localized Fibrotic Disorders Using An IL-33 / Tnf Bispecific Antibody; WO20061571, which published on 03 / 26 / 2020, and which is entitled, Anti-IL-33 Antibody For Use In Treating Eosinophilic Asthma; US2020190182, which published on 06 / 18 / 2020, and which is entitled, IL-33 Antagonist-Containing Therapeutic Agent For Endometriosis; US2020297845, which published on 09 / 24 / 2020, and which is entitled, Stabilized Formulations Containing Anti-IL-33 Antibodies; WO21017071, which published on 02 / 04 / 2021, and which is entitled, Anti-Human ST2 Antibody And Use Thereof; US2021284725, which published on 09 / 16 / 2021, and which is entitled, Anti-Interleukin-33 Antibodies And Uses Thereof; US2022041709, which published on 02 / 10 / 2022, and which is entitled, Human Anti-IL-33 Monoclonal Antibody-Containing Pharmaceutical Composition; WO22039455, which published on 02 / 24 / 2022, and which is entitled, Antibody Or Antigen- Binding Fragment Thereof That Specifically Binds To IL-33; WO23025932, which published on 03 / 02 / 2023, and which is entitled, Treatment Of Chronic Obstructive Pulmonary Disease With An Anti-Interleukin-33 Antibody; WO23029280, which published on 03 / 09 / 2023, and which is entitled, Anti-Human Interleukin-33 Monoclonal Antibody And Use Thereof; WO23077685, which published on 05 / 11 / 2023, and which is entitled, Method For Preparing Concentrated Solution Comprising Monoclonal Antibody Against Human Interleukin-33 And Liquid Preparation; WO23086807, which published on 05 / 19 / 2023, and which is entitled, Anti-Interleukin-33 Antibodies And Uses Thereof; US2023174638, which published on 06 / 08 / 2023, and which is entitled, Formulations Of Anti-IL-33 Antibodies; US2023220086, which published on 07 / 13 / 2023, and which is entitled, Anti-ST2 Antibody And Application Thereof; US2023399394, which published on 12 / 14 / 2023, and which is entitled, Antibody Binding To Human IL-33, Preparation Method Therefor, And Use Thereof; and WO24042212, which published on 02 / 29 / 2024, and which is entitled, Treatment Of Asthma With An Anti-Interleukin-33 Antibody, the contents describing an anti-IL-33 or anti-IL33R antibody in each of which are incorporated herein by reference. [000156] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-6 or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-6 or IL-6R derived from any known anti-IL- 71074896 or a receptor thereof, e.g., anti-IL-6 / anti-IL-6R antibodies described in: US2002037523, which published on 03 / 28 / 2002, and which is entitled, IL-6-Like Polynucleotides, Polypeptides, And Antibodies; US2002187150, which published on 12 / 12 / 2002, and which is entitled, Preventive And / Or Therapeutic Agent For Systemic Lupus Erythematosus Comprising Anti-IL-6 Receptor Antibody As An Active Ingredient; US2006134113, which published on 06 / 22 / 2006, and which is entitled, Preventive Or Therapeutic Agent For Sensitized T Cell-Mediated Diseases Comprising IL-6 Antagonist As An Active Ingredient; US2006188502, which published on 08 / 24 / 2006, and which is entitled, Anti-IL-6 Antibodies, Compositions, Methods And Uses; US2006240012, which published on 10 / 26 / 2006, and which is entitled, Human Antihuman Interleukin-6 Antibody And Fragment Of Antibody; US2006251653, which published on 11 / 09 / 2006, and which is entitled, Methods For Treating Interleukin-6 Related Diseases; US2006257407, which published on 11 / 16 / 2006, and which is entitled, Anti-IL-6 Antibodies, Compositions, Methods And Uses; US2007036785, which published on 02 / 15 / 2007, and which is entitled, Pharmaceutical Composition For Treatment Of Diseases Caused By IL-6 Production; US2007154481, which published on 07 / 05 / 2007, and which is entitled, Antibody Molecules Having Specificity For Human IL-6; US2007178098, which published on 08 / 02 / 2007, and which is entitled, Interleukin-6 Antagonists; US2007280945, which published on 12 / 06 / 2007, and which is entitled, High Affinity Antibodies To Human IL-6 Receptor; US2008075726, which published on 03 / 27 / 2008, and which is entitled, Anti-IL-6 Monoclonal Antibodies And Uses Thereof; US2008145367, which published on 06 / 19 / 2008, and which is entitled, Methods Of Treating Osteoarthritis With IL-6 Antagonists; US2008188401, which published on 08 / 07 / 2008, and which is entitled, Compounds; US2009028784, which published on 01 / 29 / 2009, and which is entitled, Antibodies To IL-6 And Use Thereof; US2009220499, which published on 09 / 03 / 2009, and which is entitled, Agents For Suppressing Damage To Transplanted Islets After Islet Transplantation; US2009220500, which published on 09 / 03 / 2009, and which is entitled, Agents For Treating Cardiopathy; US2009297436, which published on 12 / 03 / 2009, and which is entitled, Antibodies To IL-6 And Use Thereof; US2009297513, which published on 12 / 03 / 2009, and which is entitled, Antibodies To IL-6 And Use Thereof; US2009317402, which published on 12 / 24 / 2009, and which is entitled, Antibodies To IL-6 And Their Uses; US2010098709, which published on 04 / 22 / 2010, and which is entitled, Antibodies Specific For The Complex Of Interleukin-6 And The Interleukin-6 Receptor; US2010129357, which published on 05 / 27 / 2010, and which is entitled, Antibodies To IL-6 And Use Thereof; US2010138945, which published on 06 / 03 / 2010, and which is entitled, 7107489Humanized Anti-IL-6 Antibodies; US2010150829, which published on 06 / 17 / 2010, and which is entitled, Antibodies To IL-6 And Use Thereof; US2010158859, which published on 06 / 24 / 2010, and which is entitled, Antagonists Of IL-6 To Prevent Or Treat Cachexia, Weakness, Fatigue, And / Or Fever; US2010247523, which published on 09 / 30 / 2010, and which is entitled, Subtypes Of Humanized Antibody Against Interleukin-6 Receptor; US2010290993, which published on 11 / 18 / 2010, and which is entitled, Antibodies To IL-6 And Use Thereof; US2011002936, which published on 01 / 06 / 2011, and which is entitled, Anti-IL-6 / IL-6R Antibodies And Methods Of Use Thereof; US2011059080, which published on 03 / 10 / 2011, and which is entitled, Use Of An Anti-IL6 Antibody To Decrease Hepcidin In Cancer Patients; US2011098450, which published on 04 / 28 / 2011, and which is entitled, Antibody Molecules; US2011171241, which published on 07 / 14 / 2011, and which is entitled, Stabilized Formulations Containing Anti-Interleukin-6 (IL-6) Antibodies; US2011293622, which published on 12 / 01 / 2011, and which is entitled, Antibodies To IL-6 And Use Thereof; US2012009177, which published on 01 / 12 / 2012, and which is entitled, Gene Expression Markers For Predicting Response To Interleukin-6 Receptor-Inhibiting Monoclonal Antibody Drug Treatment; US2012014955, which published on 01 / 19 / 2012, and which is entitled, Antagonists Of IL-6 To Raise Albumin And / Or Lower Crp; US2012034212, which published on 02 / 09 / 2012, and which is entitled, Human Anti-IL-6 Antibodies With Extended In Vivo Half-Life And Their Use In Treatment Of Oncology, Autoimmune Diseases And Inflammatory Diseases; US2012077731, which published on 03 / 29 / 2012, and which is entitled, Amino Acid Sequences Directed Against IL-6R And Polypeptides Comprising The Same For The Treatment Of IL-6R Related Diseases And Disorders; US2012121594, which published on 05 / 17 / 2012, and which is entitled, Anti-IL-6 Antibodies For The Treatment Of Arthritis; US2012128626, which published on 05 / 24 / 2012, and which is entitled, Anti-IL-6 Antibodies For The Treatment Of Anemia; US2012142900, which published on 06 / 07 / 2012, and which is entitled, Antibodies To IL-6 And Use Thereof; US2012189629, which published on 07 / 26 / 2012, and which is entitled, Anti-IL-6 Antibodies For The Treatment Of Oral Mucositis; US2012225060, which published on 09 / 06 / 2012, and which is entitled, Anti- IL-6 Receptor Antibodies And Methods Of Use; US2012301460, which published on 11 / 29 / 2012, and which is entitled, Subcutaneously Administered Anti-IL-6 Receptor Antibody; US2013017575, which published on 01 / 17 / 2013, and which is entitled, Nucleic Acids Encoding Anti-IL-6 Antibodies Of Defined Epitopic Specificity; US2013028860, which published on 01 / 31 / 2013, and which is entitled, Antagonists Of IL-6 To Prevent Or Treat Cachexia, Weakness, Fatigue And / Or Fever; US2013034554, which published on 710748902 / 07 / 2013, and which is entitled, Antibodies To IL-6 And Use Thereof; US2013224201, which published on 08 / 29 / 2013, and which is entitled, Antibodies To IL-6 And Use Thereof; US2014079702, which published on 03 / 20 / 2014, and which is entitled, Antagonists Of IL-6 To Raise Albumin And / Or Lower Crp; US2014112935, which published on 04 / 24 / 2014, and which is entitled, Antibodies To Interleukin-6 And Use Thereof; US2014127209, which published on 05 / 08 / 2014, and which is entitled, Antibody Derivatives; US2014363430, which published on 12 / 11 / 2014, and which is entitled, Activatable Antibodies That Bind Interleukin-6 Receptor And Methods Of Use Thereof; US2015125450, which published on 05 / 07 / 2015, and which is entitled, Bispecific Antibodies That Neutralize Both Tnf-Alpha And IL-6: Novel Therapeutic Agent For Autoimmune Disease; US2015132224, which published on 05 / 14 / 2015, and which is entitled, Antibodies To IL-6 And Use Thereof; US2015197567, which published on 07 / 16 / 2015, and which is entitled, Antibodies To IL-6 And Use Thereof; US2015259413, which published on 09 / 17 / 2015, and which is entitled, Antibodies To IL-6 And Use Thereof; US2015273058, which published on 10 / 01 / 2015, and which is entitled, Antagonists Of IL-6 To Prevent Or Treat Cachexia, Weakness, Fatigue, And / Or Fever; US2015274822, which published on 10 / 01 / 2015, and which is entitled, Antagonists Of IL-6 To Raise Albumin And / Or Lower Crp; US2015274823, which published on 10 / 01 / 2015, and which is entitled, Antibodies To IL-6 And Use Thereof; US2015337036, which published on 11 / 26 / 2015, and which is entitled, Antibodies To IL-6 And Use Thereof; US2015344558, which published on 12 / 03 / 2015, and which is entitled, Anti-IL-6 Antibodies For The Treatment Of Arthritis; US2015368337, which published on 12 / 24 / 2015, and which is entitled, Anti-IL-6 Antibodies For The Treatment Of Oral Mucositis; US2016130340, which published on 05 / 12 / 2016, and which is entitled, Dosing Regimens Using Anti-IL-6 Antibodies For The Treatment Of Rheumatoid And Psoriatic Arthritis; US2016326252, which published on 11 / 10 / 2016, and which is entitled, Treatment Of IL-6R Related Diseases; US2016340423, which published on 11 / 24 / 2016, and which is entitled, Anti-IL-6 Antibodies For The Treatment Of Anemia; US2017115307, which published on 04 / 27 / 2017, and which is entitled, Antibodies To IL-6 And Use Thereof; US2017166646, which published on 06 / 15 / 2017, and which is entitled, Compositions Comprising IL6R Antibodies For The Treatment Of Uveitis And Macular Edema And Methods Of Using Same; US2017291950, which published on 10 / 12 / 2017, and which is entitled, Method For Treating Multiloculated Hydrocephalus By Administering An Anti-IL6 Receptor Antibody; US2018022801, which published on 01 / 25 / 2018, and which is entitled, Antibodies To IL-6 And Use Thereof; US2018066046, which published on 03 / 08 / 2018, and which is entitled, Anti-IL-6 AntibodiesFor The Treatment Of Arthritis; US2018092999, which published on 04 / 05 / 2018, and which is entitled, Antibodies To IL-6 And Use Thereof; US2018100013, which published on 04 / 12 / 2018, and which is entitled, Antibodies To IL-6 And Use Thereof; US2018186874, which published on 07 / 05 / 2018, and which is entitled, Antibodies To IL-6 And Use Thereof; US2018201668, which published on 07 / 19 / 2018, and which is entitled, In Vivo Imaging Using Anti-IL-6 Antibodies; US2018201675, which published on 07 / 19 / 2018, and which is entitled, Antibodies To IL-6 And Use Thereof; US2018371079, which published on 12 / 27 / 2018, and which is entitled, Antibodies To IL-6 And Use Thereof; US2019023780, which published on 01 / 24 / 2019, and which is entitled, Anti-IL-6 Antibodies For The Treatment Of Oral Mucositis; US2019083665, which published on 03 / 21 / 2019, and which is entitled, Antibodies To IL-6 And Use Thereof; US2019192692, which published on 06 / 27 / 2019, and which is entitled, Dna Monoclonal Antibodies Targeting IL-6 And Cd126; US2019194312, which published on 06 / 27 / 2019, and which is entitled, IL-6 Antibodies; US2019194313, which published on 06 / 27 / 2019, and which is entitled, Antibody Or An Antigen-Binding Fragment Thereof Capable Of Binding To A Human Receptor Of Interleukin-6; US2019218300, which published on 07 / 18 / 2019, and which is entitled, Liquid Pharmaceutical Composition; US2019270806, which published on 09 / 05 / 2019, and which is entitled, IL-6 Antibodies And Fusion Constructs And Conjugates Thereof; US2019315854, which published on 10 / 17 / 2019, and which is entitled, Antibodies, Composition And Kits Comprising Same, And Methods Of Use Thereof; US2020040074, which published on 02 / 06 / 2020, and which is entitled, Antibodies To IL-6 And Use Thereof; US2020087391, which published on 03 / 19 / 2020, and which is entitled, Antibodies To IL-6 And Use Thereof; US2020108140, which published on 04 / 09 / 2020, and which is entitled, Antibodies To IL-6 And Use Thereof; US2020140539, which published on 05 / 07 / 2020, and which is entitled, Anti-IL-6 Antibodies For The Treatment Of Anemia; US2020165295, which published on 05 / 28 / 2020, and which is entitled, Method For Purifying Anti-IL-6 Receptor Antibodies; US2020299391, which published on 09 / 24 / 2020, and which is entitled, Anti-IL-6 Receptor Antibody-Containing Medicinal Composition For Preventing Post-Surgical Adhesion; US2020339693, which published on 10 / 29 / 2020, and which is entitled, Compositions And Methods For Treating Juvenile Idiopathic Arthritis; US2020369774, which published on 11 / 26 / 2020, and which is entitled, IL-6R Antibody And Antigen Binding Fragment Thereof And Medical Use; US2021070853, which published on 03 / 11 / 2021, and which is entitled, Use Of Anti-IL-6 Antibody, E.G., Clazakizumab For Desensitization Of Solid Organ Transplant Recipients And / Or For Preventing, Stabilizing Or Reducing Antibody MediatedRejection (Abmr); US2021246201, which published on 08 / 12 / 2021, and which is entitled, Antibodies To IL-6 And Use Thereof; US2021284743, which published on 09 / 16 / 2021, and which is entitled, Compositions Of IL-6 / IL-6R Antibodies And Methods Of Use Thereof; US2021332126, which published on 10 / 28 / 2021, and which is entitled, Anti-IL-6 Antibodies For The Treatment Of Oral Mucositis; US2021395357, which published on 12 / 23 / 2021, and which is entitled, Humanized Monoclonal Antibodies Against Interleukin-6, Encoding Genes And Uses Thereof; US2022040301, which published on 02 / 10 / 2022, and which is entitled, Anti-IL-6 Antibody Formulation; US2022071901, which published on 03 / 10 / 2022, and which is entitled, A Liquid Formulation Of Humanized Antibody For Treating IL-6-Mediated Diseases; US2022220210, which published on 07 / 14 / 2022, and which is entitled, Anti-IL-6 Receptor Antibody-Containing Inhibitor For Inhibiting Deterioration Of Bbb Function; US2022396615, which published on 12 / 15 / 2022, and which is entitled, Anti-Human IL6 Monoclonal Antibodies, Preparation Method Therefor And Use Thereof; US2023167182, which published on 06 / 01 / 2023, and which is entitled, Antibodies Binding IL6R And Uses Thereof; US2023174640, which published on 06 / 08 / 2023, and which is entitled, Use Of Anti-IL-6 Antibody, E.G., Clazakizumab For Treatment / Prevention Of Ards Associated With Coronavirus (Covid-19) Infection; US2023174657, which published on 06 / 08 / 2023, and which is entitled, Compositions Comprising An Antibody Against Interleukin-6 Receptor For The Treatment Of Rheumatoid Arthritis And Methods Of Using Same; US2024209076, which published on 06 / 27 / 2024, and which is entitled, Use Of IL-6 Antibodies And Vegf Traps, And Fusion Constructs And Conjugates Thereof; US5559012, which published on 09 / 24 / 1996, and which is entitled, Therapeutic, IL-6 Antibody Kits, And Process For Their Preparation; US5618700, which published on 04 / 08 / 1997, and which is entitled, IL-6 Specific Monoclonal Antibodies, Hybridomas Therefor And Methods Of Making And Using Same; US5795965, which published on 08 / 18 / 1998, and which is entitled, Reshaped Human To Human Interleukin-6 Receptor; US5856135, which published on 01 / 05 / 1999, and which is entitled, Reshaped Human Antibody To Human Interleukin-6; US5888510, which published on 03 / 30 / 1999, and which is entitled, Chronic Rheumatoid Arthritis Therapy Containing IL-6 Antagonist As Effective Component; US6261560, which published on 07 / 17 / 2001, and which is entitled, Method For Inhibiting Muscle Protein Proteolysis With Antibodies To Interleukin-6 Receptor; US6723319, which published on 04 / 20 / 2004, and which is entitled, Method Of Treating Inflammatory Intestinal Diseases Containing As The Ingredient IL-6 Receptors Antibodies; US8440196, which published on 05 / 14 / 2013, and which is entitled, Treatment For Pancreatitis Using IL-6 Receptor Antagonist Antibodies; 7107489US8632778, which published on 01 / 21 / 2014, and which is entitled, Stabilized Anti- Interleukin-6 Receptor Antibody-Containing Preparations; WO08144763, which published on 11 / 27 / 2008, and which is entitled, Antibodies To IL-6 And Use Thereof; WO09109584, which published on 09 / 11 / 2009, and which is entitled, Antibody Binding Only To IL6-SIL6R Complex; WO10065072, which published on 06 / 10 / 2010, and which is entitled, Antagonists Of IL-6 To Raise Albumin And / Or Lower Crp; WO10065078, which published on 06 / 10 / 2010, and which is entitled, Antagonists Of IL-6 To Prevent Or Treat Cachexia, Weakness, Fatigue And / Or Fever; WO11066369, which published on 06 / 03 / 2011, and which is entitled, Antagonists Of IL-6 To Raise Albumin And / Or Lower Crp; WO11066371, which published on 06 / 03 / 2011, and which is entitled, Antibodies To IL-6 And Use Thereof; WO12071554, which published on 05 / 31 / 2012, and which is entitled, Anti-IL-6 Antibodies For The Treatment Of Oral Mucositis; WO12071561, which published on 05 / 31 / 2012, and which is entitled, Anti-IL-6 Antibodies For The Treatment Of Anemia; WO15116852, which published on 08 / 06 / 2015, and which is entitled, Methods For Treating Rheumatoid Arthritis By Administering An IL-6R Antibody; WO18029182, which published on 02 / 15 / 2018, and which is entitled, IL-6R Single Variable Domain Antibodies For Treatment Of IL-6R Related Diseases; WO21164107, which published on 08 / 26 / 2021, and which is entitled, Novel Application Of IL-6 Receptor Antibodies; WO22037606, which published on 02 / 24 / 2022, and which is entitled, Liquid Formulations Comprising High Concentrations Humanized Antibodies For Treating IL-6 Related Diseases; WO22179432, which published on 09 / 01 / 2022, and which is entitled, Antibody Fusion Proteins Targeting IL-6 Receptor And Angiogenic Factors; WO23020563, which published on 02 / 23 / 2023, and which is entitled, Liquid Formulations Comprising High Concentrations Humanized Antibodies For Treating IL-6 Related Diseases; WO23217933, which published on 11 / 16 / 2023, and which is entitled, Antibody That Binds To Vegf-A And IL6 And Methods Of Use; WO24036385, which published on 02 / 22 / 2024, and which is entitled, Treatment Of Myocarditis By Administration Of Anti-Interleukin-6 Antibodies; WO24093652, which published on 05 / 10 / 2024, and which is entitled, Application Of Nanobody Targeting On IL-6R; WO24170583, which published on 08 / 22 / 2024, and which is entitled, Antibodies Binding To Human Interleukin-6 Receptor; and WO9509873, which published on 04 / 13 / 1995, and which is entitled, A Monoclonal Anti- Human IL-6 Receptor Antibody, the contents describing an anti-IL-6 or anti-IL-6R antibody in each of which are incorporated herein by reference. [000157] In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of a VH of any one of the anti-IL-13 antibodies or anti-IL-13R antibodies 7107489in Table 2, and a LC CDR1, LC CDR2, and LC CDR3 of a VL of any one of the anti-IL-13 antibodies or anti-IL-13R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a VH of any one of the anti-IL-13 antibodies in Table 2, and a VL of any one of the anti-IL-13 antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Anrukinzumab, and a LC CDR1, LC CDR2, and LC CDR3 of Anrukinzumab. In some embodiments, a Th2 targeting antibody comprises a VH of Anrukinzumab, and a VL of Anrukinzumab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of lebrikizumab, and a LC CDR1, LC CDR2, and LC CDR3 of Lebrikizumab. In some embodiments, a Th2 targeting antibody comprises a VH of Lebrikizumab, and a VL of Lebrikizumab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Tralokinumab, and a LC CDR1, LC CDR2, and LC CDR3 of Tralokinumab. In some embodiments, a Th2 targeting antibody comprises a VH of Tralokinumab, and a VL of Tralokinumab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Eblasakimab, and a LC CDR1, LC CDR2, and LC CDR3 of Eblasakimab. In some embodiments, a Th2 targeting antibody comprises a VH of Eblasakimab, and a VL of Eblasakimab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Cendakimab, and a LC CDR1, LC CDR2, and LC CDR3 of Cendakimab. In some embodiments, a Th2 targeting antibody comprises a VH of Cendakimab, and a VL of Cendakimab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Dectrekumab, and a LC CDR1, LC CDR2, and LC CDR3 of Dectrekumab. In some embodiments, a Th2 targeting antibody comprises a VH of Dectrekumab, and a VL of Dectrekumab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of APG777, and a LC CDR1, LC CDR2, and LC CDR3 of APG777. In some embodiments, a Th2 targeting antibody comprises a VH of APG777, and a VL of APG777. [000158] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-4 or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of a VH of any one of the anti-IL-4 antibodies or anti-IL-4R antibodies in Table 2, and a LC CDR1, LC CDR2, and LC CDR3 of a VL of any one of the anti-IL-4 antibodies or anti-IL4R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a VH of any one of the anti-IL-4 antibodies or anti-IL-4R antibodies in Table 2, and a VL of any one of the anti-IL-4 antibodies or anti-IL-4R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a HC 7107489CDR1, HC CDR2, HC CDR3 of Dupilumab, and a LC CDR1, LC CDR2, and LC CDR3 of Dupilumab. In some embodiments, a Th2 targeting antibody comprises a VH of Dupilumab, and a VL of Dupilumab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Pascolizumab, and a LC CDR1, LC CDR2, and LC CDR3 of Pascolizumab. In some embodiments, a Th2 targeting antibody comprises a VH of Pascolizumab, and a VL of Pascolizumab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of AMG 317, and a LC CDR1, LC CDR2, and LC CDR3 of AMG 317. In some embodiments, a Th2 targeting antibody comprises a VH of AMG 317, and a VL of AMG 317. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Stapokibart, and a LC CDR1, LC CDR2, and LC CDR3 of Stapokibart. In some embodiments, a Th2 targeting antibody comprises a VH of Stapokibart, and a VL of Stapokibart. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Rademikibart, and a LC CDR1, LC CDR2, and LC CDR3 of Rademikibart. In some embodiments, a Th2 targeting antibody comprises a VH of Rademikibart, and a VL of Rademikibart. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Manfidokimab, and a LC CDR1, LC CDR2, and LC CDR3 of Manfidokimab. In some embodiments, a Th2 targeting antibody comprises a VH of Manfidokimab, and a VL of Manfidokimab. [000159] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-5 or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of a VH of any one of the anti-IL-5 antibodies or anti-IL-5R antibodies in Table 2, and a LC CDR1, LC CDR2, and LC CDR3 of a VL of any one of the anti-IL-5 antibodies or anti-IL5R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a VH of any one of the anti-IL-5 antibodies or anti-IL-5R antibodies in Table 2, and a VL of any one of the anti-IL-5 antibodies or anti-IL-5R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Benralizumab, and a LC CDR1, LC CDR2, and LC CDR3 of Benralizumab. In some embodiments, a Th2 targeting antibody comprises a VH of Benralizumab, and a VL of Benralizumab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Mepolizumab, and a LC CDR1, LC CDR2, and LC CDR3 of Mepolizumab. In some embodiments, a Th2 targeting antibody comprises a VH of Mepolizumab, and a VL of Mepolizumab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Reslizumab, and a LC CDR1, LC CDR2, and LC CDR3 of Reslizumab. In some embodiments, a Th2 targeting antibody 7107489comprises a VH of Reslizumab, and a VL of Reslizumab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Depemokimab, and a LC CDR1, LC CDR2, and LC CDR3 of Depemokimab. In some embodiments, a Th2 targeting antibody comprises a VH of Depemokimab, and a VL of Depemokimab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Clone 601 described by WO2019120,060 or WO2021249,373, and a LC CDR1, LC CDR2, and LC CDR3 of Clone 601 described by WO2019120,060 or WO2021249,373. In some embodiments, a Th2 targeting antibody comprises a VH of Clone 601 described by WO2019120,060 or WO2021249,373, and a VL of Clone 601 described by WO2019120,060 or WO2021249,373. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Trabikibart, and a LC CDR1, LC CDR2, and LC CDR3 of Trabikibart. In some embodiments, a Th2 targeting antibody comprises a VH of Trabikibart, and a VL of Trabikibart. [000160] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-9 or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of a VH of any one of the anti-IL-9 antibodies or anti-IL-9R antibodies in Table 2, and a LC CDR1, LC CDR2, and LC CDR3 of a VL of any one of the anti-IL-9 antibodies or anti-IL-9R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a VH of any one of the anti-IL-9 antibodies or anti-IL-9R antibodies in Table 2, and a VL of any one of the anti-IL-9 antibodies or anti-IL-9R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Enokizumab, and a LC CDR1, LC CDR2, and LC CDR3 of Enokizumab. In some embodiments, a Th2 targeting antibody comprises a VH of Enokizumab, and a VL of Enokizumab. [000161] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for OX40 or a ligand thereof. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of a VH of any one of the anti-OX40 antibodies or anti-OX40L antibodies in Table 2, and a LC CDR1, LC CDR2, and LC CDR3 of a VL of any one of the anti-OX40 antibodies or anti-OX40L antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a VH of any one of the anti-OX40 antibodies or anti-OX40L antibodies in Table 2, and a VL of any one of the anti-OX40 antibodies or anti-OX40L antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Rocatinlimab, and a LC CDR1, LC CDR2, and LC CDR3 of Rocatinlimab. In some embodiments, a Th2 targeting antibody 7107489comprises a VH of Rocatinlimab, and a VL of Rocatinlimab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Oxelumab, and a LC CDR1, LC CDR2, and LC CDR3 of Oxelumab. In some embodiments, a Th2 targeting antibody comprises a VH of Oxelumab, and a VL of Oxelumab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Telazorlimab, and a LC CDR1, LC CDR2, and LC CDR3 of Telazorlimab. In some embodiments, a Th2 targeting antibody comprises a VH of Telazorlimab, and a VL of Telazorlimab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Amlitelimab, and a LC CDR1, LC CDR2, and LC CDR3 of Amlitelimab. In some embodiments, a Th2 targeting antibody comprises a VH of Amlitelimab, and a VL of Amlitelimab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of IMG-007, and a LC CDR1, LC CDR2, and LC CDR3 of IMG-007. In some embodiments, a Th2 targeting antibody comprises a VH of IMG-007, and a VL of IMG-007. [000162] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-25 (also known as IL-17E) or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of a VH of any one of the anti-IL-25 antibodies or anti-IL-25R antibodies in Table 2, and a LC CDR1, LC CDR2, and LC CDR3 of a VL of any one of the anti-IL-25 antibodies or anti-IL-25R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a VH of any one of the anti-IL-25 antibodies or anti-IL-25R antibodies in Table 2, and a VL of any one of the anti- IL-25 antibodies or anti-IL-25R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Brodalumab, and a LC CDR1, LC CDR2, and LC CDR3 of Brodalumab. In some embodiments, a Th2 targeting antibody comprises a VH of Brodalumab, and a VL of Brodalumab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of LNR125, and a LC CDR1, LC CDR2, and LC CDR3 of LNR125. In some embodiments, a Th2 targeting antibody comprises a VH of LNR125, and a VL of LNR125. [000163] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-31 or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of a VH of any one of the anti-IL-31 antibodies or anti-IL-31R antibodies in Table 2, and a LC CDR1, LC CDR2, and LC CDR3 of a VL of any one of the anti-IL-31 antibodies or anti-IL-31R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a VH of any one of the anti-IL-31 antibodies or anti-IL-31R antibodies in Table 2, and a VL of any one of the anti-IL-31 7107489antibodies or anti-IL-31R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Nemolizumab, and a LC CDR1, LC CDR2, and LC CDR3 of Nemolizumab. In some embodiments, a Th2 targeting antibody comprises a VH of Nemolizumab, and a VL of Nemolizumab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Vixarelimab, and a LC CDR1, LC CDR2, and LC CDR3 of Vixarelimab. In some embodiments, a Th2 targeting antibody comprises a VH of Vixarelimab, and a VL of Vixarelimab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of NM26-2198, and a LC CDR1, LC CDR2, and LC CDR3 of NM26-2198. In some embodiments, a Th2 targeting antibody comprises a VH of NM26-2198, and a VL of NM26-2198. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of BMS-981164, and a LC CDR1, LC CDR2, and LC CDR3 of BMS-981164. In some embodiments, a Th2 targeting antibody comprises a VH of BMS-981164, and a VL of BMS-981164. [000164] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-36 or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of a VH of any one of the anti-IL-36 antibodies or anti-IL-36R antibodies in Table 2, and a LC CDR1, LC CDR2, and LC CDR3 of a VL of any one of the anti-IL-36 antibodies or anti-IL-36R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a VH of any one of the anti-IL-36 antibodies or anti-IL-36R antibodies in Table 2, and a VL of any one of the anti-IL-36 antibodies or anti-IL-36R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Spesolimab, and a LC CDR1, LC CDR2, and LC CDR3 of Spesolimab. In some embodiments, a Th2 targeting antibody comprises a VH of Spesolimab, and a VL of Spesolimab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Imsidolimab, and a LC CDR1, LC CDR2, and LC CDR3 of Imsidolimab. In some embodiments, a Th2 targeting antibody comprises a VH of Imsidolimab, and a VL of Imsidolimab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of HB0034, and a LC CDR1, LC CDR2, and LC CDR3 of HB0034. In some embodiments, a Th2 targeting antibody comprises a VH of HB0034, and a VL of HB0034. [000165] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for Thymic stromal lymphopoietin (TSLP) or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of a VH of any one of the anti-TSLP antibodies or anti-TSLPR antibodies in Table 2, and a LC 7107489CDR1, LC CDR2, and LC CDR3 of a VL of any one of the anti-TSLP antibodies or anti- TSLPR antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a VH of any one of the anti-TSLP antibodies or anti-TSLPR antibodies in Table 2, and a VL of any one of the anti-TSLP antibodies or anti-TSLPR antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Tezepelumab, and a LC CDR1, LC CDR2, and LC CDR3 of Tezepelumab. In some embodiments, a Th2 targeting antibody comprises a VH of Tezepelumab, and a VL of Tezepelumab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Ecleralimab, and a LC CDR1, LC CDR2, and LC CDR3 of Ecleralimab. In some embodiments, a Th2 targeting antibody comprises a VH of Ecleralimab, and a VL of Ecleralimab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of BSI-045B, and a LC CDR1, LC CDR2, and LC CDR3 of BSI-045B. In some embodiments, a Th2 targeting antibody comprises a VH of BSI-045B, and a VL of BSI-045B. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of CM326, and a LC CDR1, LC CDR2, and LC CDR3 of CM326. In some embodiments, a Th2 targeting antibody comprises a VH of CM326, and a VL of CM326. [000166] In some embodiments, a Th2 targeting antibody comprises an antigen-specific binding site for IL-33 or a receptor thereof. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of a VH of any one of the anti-IL-33 antibodies or anti-IL-33R antibodies in Table 2, and a LC CDR1, LC CDR2, and LC CDR3 of a VL of any one of the anti-IL-33 antibodies or anti-IL-33R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a VH of any one of the anti-IL-33 antibodies or anti-IL-33R antibodies in Table 2, and a VL of any one of the anti-IL-33 antibodies or anti-IL-33R antibodies in Table 2. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Tozorakimab, and a LC CDR1, LC CDR2, and LC CDR3 of Tozorakimab. In some embodiments, a Th2 targeting antibody comprises a VH of Tozorakimab , and a VL of Tozorakimab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Itepekimab, and a LC CDR1, LC CDR2, and LC CDR3 of Itepekimab. In some embodiments, a Th2 targeting antibody comprises a VH of Itepekimab, and a VL of Itepekimab. In some embodiments, a Th2 targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of Etokimab, and a LC CDR1, LC CDR2, and LC CDR3 of Etokimab. In some embodiments, a Th2 targeting antibody comprises a VH of Etokimab, and a VL of Etokimab. In some embodiments, a Th2 7107489targeting antibody comprises a HC CDR1, HC CDR2, HC CDR3 of PF-07264660, and a LC CDR1, LC CDR2, and LC CDR3 of PF-07264660. In some embodiments, a Th2 targeting antibody comprises a VH of PF-07264660, and a VL of PF-07264660. (c) Multispecific Antibodies [000167] In some embodiments, an antibody provided here is a multi-specific antibody (e.g., a bispecific antibody). For example, in some embodiments, one or more anti- KLK5 / KLK7 antibodies may be combined with one or more different anti-KLK5 / KLK7 antibody to produce a multi-specific or a bispecific anti-KLK5 / KLK7 antibody. For example, one or more anti-KLK5 / KLK7 antibody as described herein (Table 1a and Table 1b), can be combined with one or more different anti-KLK5 / KLK7 antibody described herein (Table 1a and Table 1b) to produce a multi-specific antibody. [000168] In some embodiments, one or more anti-KLK5 / KLK7 antibodies may be combined with any other appropriate therapeutic antibodies to produce a multi-specific or a bispecific anti-KLK5 / KLK7 / additional target antibody. For example, an anti-KLK5 / KLK7 antibody as described herein (Table 1a and Table 1b), can be combined with any appropriate antibody (e.g., Th2 targeting antibodies as described in Table 2) to produce a bispecific antibody. Such additional therapeutic antibody include but are not limited to: anti-IL4R antibodies (e.g., dupilumab), anti-IL-13 antibodies, TNF inhibitors (e.g., anti-TNF antibody), IL-12 / 23 antibodies, IL-17 antibodies, adalimumab, infliximab, golimumab, ustekinumab, secukinumab, ixekizumab, brodalumab, abatacept, tidrakizumab- asmn, risankisumab-rzaa, and guselkumab. [000169] In some aspects, the present disclosure provides a bispecific antibody comprising at least one antigen-specific binding site that specifically binds KLK5 and KLK7 and at least one antigen-specific binding site that specifically binds to a T helper cell 2 (Th2) cytokine (i.e., cytokines produced by Th2 cell) or receptor thereof. In some embodiments, Th2 cytokines include but are not limited to IL-13, IL-4, IL-5, IL-9, IL-31, IL-17E (IL-25), IL-33, OX40, IL-36, JAG1, and TSLP. In some embodiments, at least one antigen-specific binding site that specifically binds to a T helper cell 2 (Th2) cytokine or receptor thereof does not target IL-13, IL-17, IL-5 or IL-4. In some embodiments the at least one antigen-specific binding site that specifically binds to a T helper cell 2 (Th2) cytokine or receptor thereof binds to IL-9, IL-31, IL-33, OX40, IL-36, JAG1, and TSLP . [000170] Table 6 below sets forth possible arm configurations for an anti-KLK5 / KLK7 + Th2 targeting bispecific antibody. In some embodiments, an anti-KLK5 / KLK7 + Th2 7107489targeting bispecific antibody comprises one arm comprising CDRs and / or VH and / or VL, the sequences of which are derived from or correspond to or are the same as the sequences of the CDRs and / or VH and / or VL of an antibody listed in the left column of Table 6, and a second arm comprising CDRs and / or VH / VL, the sequences of which are derived from or correspond to or are the same as the sequences of CDRs and / or VH and / or VL of an antibody listed in the corresponding row in the right column of Table 6 or of another suitable antibody disclosed herein. The CDRs and VH / VL of the respective antibodies are listed in Tables 1a and 2. Table 6: Anti-KLK5 / KLK7 + Th2 Bispecific Antibody Arm Configurations71074897107489710748971074897107489[000171] In some embodiments, an anti-KLK5 / KLK7 + Th2 targeting bispecific antibody comprises one arm comprising CDRs and / or VH / VL pair, the sequences of which are derived from or correspond to or are the same as the sequences of the CDRs and / or VH / VL of an anti-KLK5 / KLK7 antibody listed in Table 1a, and a second arm comprising CDRs and / or VH / VL, the sequences of which are derived from or correspond to or are the same as the sequences of CDRs and / or VH / VL of an anti-IL-13 or anti-IL-13R antibody listed in Table 2, Table 6, or elsewhere herein. In some embodiments, an anti-KLK5 / KLK7 + Th2 bispecific antibody may include one arm comprising an antigen-specific binding site targeting KLK5 and KLK7, and a second arm comprising an antigen specific binding site that does not target IL-13 or IL-13R. 7107489[000172] In some embodiments, an anti-KLK5 / KLK7 + Th2 targeting bispecific antibody comprises one arm comprising CDRs and / or VH / VL pair, the sequences of which are derived from or correspond to or are the same as the sequences of the CDRs and / or VH / VL of an anti-KLK5 / KLK7 antibody listed in Table 1a, and a second arm comprising CDRs and / or VH / VL, the sequences of which are derived from or correspond to or are the same as the sequences of CDRs and / or VH / VL of an anti-IL-4 or anti-IL4R antibody listed in Table 2, Table 6, or elsewhere herein. In some embodiments, an anti-KLK5 / KLK7 + Th2 bispecific antibody may include one arm comprising an antigen-specific binding site targeting KLK5 and KLK7, and a second arm comprising an antigen specific binding site that does not target IL-4 or IL-4R. [000173] In some embodiments, an anti-KLK5 / KLK7 + Th2 targeting bispecific antibody comprises one arm comprising CDRs and / or VH / VL pair, the sequences of which are derived from or correspond to or are the same as the sequences of the CDRs and / or VH / VL of an anti-KLK5 / KLK7 antibody listed in Table 1a, and a second arm comprising CDRs and / or VH / VL, the sequences of which are derived from or correspond to or are the same as the sequences of CDRs and / or VH / VL of an anti-IL-5 or anti-IL-5R antibody listed in Table 2, Table 6, or elsewhere herein. In some embodiments, an anti-KLK5 / KLK7 + Th2 bispecific antibody may include one arm comprising an antigen-specific binding site targeting KLK5 and KLK7, and a second arm comprising an antigen specific binding site that does not target IL-5 or IL-5R. [000174] In some embodiments, an anti-KLK5 / KLK7 + Th2 targeting bispecific antibody comprises one arm comprising CDRs and / or VH / VL pair, the sequences of which are derived from or correspond to or are the same as the sequences of the CDRs and / or VH / VL of an anti-KLK5 / KLK7 antibody listed in Table 1a, and a second arm comprising CDRs and / or VH / VL, the sequences of which are derived from or correspond to or are the same as the sequences of CDRs and / or VH / VL of an anti-IL-25 or anti-IL-25R antibody listed in Table 2, Table 6, or elsewhere herein. In some embodiments, an anti-KLK5 / KLK7 + Th2 bispecific antibody may include one arm comprising an antigen-specific binding site targeting KLK5 and KLK7, and a second arm comprising an antigen specific binding site that does not target IL-25 or IL-25R. [000175] In some embodiments, an anti-KLK5 / KLK7 + Th2 targeting bispecific antibody comprises one arm comprising CDRs and / or VH / VL pair, the sequences of which are derived from or correspond to or are the same as the sequences of the CDRs and / or VH / VL of an anti-KLK5 / KLK7 antibody listed in Table 1a, and a second arm comprising 7107489CDRs and / or VH / VL, the sequences of which are derived from or correspond to or are the same as the sequences of CDRs and / or VH / VL of an anti-IL-9 or anti-IL9R antibody listed in Table 2, Table 6, or elsewhere herein. In some embodiments, an anti-KLK5 / KLK7 + Th2 bispecific antibody may include one arm comprising an antigen-specific binding site targeting KLK5 and KLK7, and a second arm comprising an antigen specific binding site that does not target IL-9 or IL-9R. [000176] In some embodiments, an anti-KLK5 / KLK7 + Th2 targeting bispecific antibody comprises one arm comprising CDRs and / or VH / VL pair, the sequences of which are derived from or correspond to or are the same as the sequences of the CDRs and / or VH / VL of an anti-KLK5 / KLK7 antibody listed in Table 1a, and a second arm comprising CDRs and / or VH / VL, the sequences of which are derived from or correspond to or are the same as the sequences of CDRs and / or VH / VL of an anti-OX40L or anti-OX40 antibody listed in Table 2, Table 6, or elsewhere herein. In some embodiments, an anti-KLK5 / KLK7 + Th2 bispecific antibody may include one arm comprising an antigen-specific binding site targeting KLK5 and KLK7, and a second arm comprising an antigen specific binding site that does not target OX40L or OX40. [000177] In some embodiments, an anti-KLK5 / KLK7 + Th2 targeting bispecific antibody comprises one arm comprising CDRs and / or VH / VL pair, the sequences of which are derived from or correspond to or are the same as the sequences of the CDRs and / or VH / VL of an anti-KLK5 / KLK7 antibody listed in Table 1a, and a second arm comprising CDRs and / or VH / VL, the sequences of which are derived from or correspond to or are the same as the sequences of CDRs and / or VH / VL of an anti-IL-31 or anti-IL-31R antibody listed in Table 2, Table 6, or elsewhere herein. In some embodiments, an anti-KLK5 / KLK7 + Th2 bispecific antibody may include one arm comprising an antigen-specific binding site targeting KLK5 and KLK7, and a second arm comprising an antigen specific binding site that does not target IL-31 or IL-31R. [000178] In some embodiments, an anti-KLK5 / KLK7 + Th2 targeting bispecific antibody comprises one arm comprising CDRs and / or VH / VL pair, the sequences of which are derived from or correspond to or are the same as the sequences of the CDRs and / or VH / VL of an anti-KLK5 / KLK7 antibody listed in Table 1a, and a second arm comprising CDRs and / or VH / VL, the sequences of which are derived from or correspond to or are the same as the sequences of CDRs and / or VH / VL of an anti-TSLP or anti-TSLPR antibody listed in Table 2, Table 6, or elsewhere herein. In some embodiments, an anti-KLK5 / KLK7 + Th2 bispecific antibody may include one arm comprising an antigen-specific binding site 7107489targeting KLK5 and KLK7, and a second arm comprising an antigen specific binding site that does not target TSLPR or TSLPR. [000179] In some em...

Claims

CLAIMS What is claimed is:

1. A bispecific antibody comprising an antigen-specific binding site that specifically binds KLK5 and KLK7 and an antigen-specific binding site that specifically binds a Th2 cytokine or a receptor thereof.

2. The bispecific antibody of claim 1, wherein the antigen-specific binding site that specifically binds KLK5 and KLK7 binds to the active sites of KLK5 and KLK7 and inhibits activity of the enzymes.

3. The bispecific antibody of claim 1 or 2, wherein the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 of any one of the antibodies listed in Table 1a and Table 1b.

4. The bispecific antibody of any one of claims 1-3, wherein the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises: (a) a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 7, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 8; (b) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 13, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 14; (c) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 17, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 14; or (d) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 21, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO:

14.

5. The bispecific antibody of any one of claims 1-4, wherein the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises: 7107489(a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 2, a HC CDR3 having the amino acid sequence of SEQ ID NO: 3, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 6: (b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 9, a HC CDR2 having the amino acid sequence of SEQ ID NO: 10, a HC CDR3 having the amino acid sequence of SEQ ID NO: 11, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 12; (c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 9, a HC CDR2 having the amino acid sequence of SEQ ID NO: 15, a HC CDR3 having the amino acid sequence of SEQ ID NO: 16, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 12; or (d) a HC CDR1 having the amino acid sequence of SEQ ID NO: 18, a HC CDR2 having the amino acid sequence of SEQ ID NO: 19, a HC CDR3 having the amino acid sequence of SEQ ID NO: 20, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO:

12.

6. The bispecific antibody of any one of claims 1-5, wherein the antigen-specific binding site that specifically binds to KLK5 and KLK7 is of a VH and / or a VL of any one of the antibodies listed in Table 1a.

7. The bispecific antibody of any one of claims 1-6, wherein the antigen-specific binding site that specifically binds KLK5 and KLK7 comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 7 and a VL comprising the amino acid sequence of SEQ ID NO: 8; (b) a VH comprising the amino acid sequence of SEQ ID NO: 13, and a VL comprising the amino acid sequence of SEQ ID NO: 14; (c) a VH comprising the amino acid sequence of SEQ ID NO: 17, and a VL comprising the amino acid sequence of SEQ ID NO: 14; or 7107489(d) a VH comprising the amino acid sequence of SEQ ID NO: 21, and a VL comprising the amino acid sequence of SEQ ID NO:

14.

8. The bispecific antibody of any one of claims 1-7, wherein the antigen-specific binding site that specifically binds to the Th2 cytokine or a receptor thereof comprises a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 of any one of the antibodies listed in Table 2.

9. The bispecific antibody of any one of claims 1-8, wherein the Th2 cytokine is IL-13.

10. The bispecific antibody of claim 9, wherein the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises: (a) a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 53, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 54; (b) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 32, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 33; (c) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 74, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 75; (d) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 94, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 95; (e) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 114, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 115; (f) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 134, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 135; or (g) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 657, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO:

658. 710748911. The bispecific antibody of claim 9 or 10, wherein the antigen-specific binding site that specifically binds Il-13 or IL-13R comprises: (a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 55, a HC CDR2 having the amino acid sequence of SEQ ID NO: 56, a HC CDR3 having the amino acid sequence of SEQ ID NO: 57, a LC CDR1 having the amino acid sequence of SEQ ID NO: 58, a LC CDR2 having the amino acid sequence of SEQ ID NO: 59, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 60; (b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 61, a HC CDR2 having the amino acid sequence of SEQ ID NO: 62, a HC CDR3 having the amino acid sequence of SEQ ID NO: 63, a LC CDR1 having the amino acid sequence of SEQ ID NO: 64, a LC CDR2 having the amino acid sequence of SEQ ID NO: 65, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 66; (c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 67, a HC CDR2 having the amino acid sequence of SEQ ID NO: 68, a HC CDR3 having the amino acid sequence of SEQ ID NO: 69, a LC CDR1 having the amino acid sequence of SEQ ID NO: 70, a LC CDR2 having the amino acid sequence of SEQ ID NO: 71, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 72; (d) a HC CDR1 having the amino acid sequence of SEQ ID NO: 34, a HC CDR2 having the amino acid sequence of SEQ ID NO: 35, a HC CDR3 having the amino acid sequence of SEQ ID NO: 36, a LC CDR1 having the amino acid sequence of SEQ ID NO: 37, a LC CDR2 having the amino acid sequence of SEQ ID NO: 38, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 39; (e) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 41, a HC CDR3 having the amino acid sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 43, a LC CDR2 having the amino acid sequence of SEQ ID NO: 44, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 45; (f) a HC CDR1 having the amino acid sequence of SEQ ID NO: 46, a HC CDR2 having the amino acid sequence of SEQ ID NO: 47, a HC CDR3 having the amino acid sequence of SEQ ID NO: 48, a LC CDR1 having the amino acid sequence of SEQ ID NO: 49, a LC CDR2 having the amino acid sequence of SEQ ID NO: 50, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 51; (g) a HC CDR1 having the amino acid sequence of SEQ ID NO: 76, a HC CDR2 having the amino acid sequence of SEQ ID NO: 77, a HC CDR3 having the amino acid 7107489sequence of SEQ ID NO: 78, a LC CDR1 having the amino acid sequence of SEQ ID NO: 79, a LC CDR2 having the amino acid sequence of SEQ ID NO: 80, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 81; (h) a HC CDR1 having the amino acid sequence of SEQ ID NO: 82, a HC CDR2 having the amino acid sequence of SEQ ID NO: 83, a HC CDR3 having the amino acid sequence of SEQ ID NO: 84, a LC CDR1 having the amino acid sequence of SEQ ID NO: 85, a LC CDR2 having the amino acid sequence of SEQ ID NO: 86, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 87; (i) a HC CDR1 having the amino acid sequence of SEQ ID NO: 88, a HC CDR2 having the amino acid sequence of SEQ ID NO: 89, a HC CDR3 having the amino acid sequence of SEQ ID NO: 90, a LC CDR1 having the amino acid sequence of SEQ ID NO: 91, a LC CDR2 having the amino acid sequence of SEQ ID NO: 92, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 93; (j) a HC CDR1 having the amino acid sequence of SEQ ID NO: 96, a HC CDR2 having the amino acid sequence of SEQ ID NO: 97, a HC CDR3 having the amino acid sequence of SEQ ID NO: 98, a LC CDR1 having the amino acid sequence of SEQ ID NO: 99, a LC CDR2 having the amino acid sequence of SEQ ID NO: 100, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 101; (k) a HC CDR1 having the amino acid sequence of SEQ ID NO: 102, a HC CDR2 having the amino acid sequence of SEQ ID NO: 103, a HC CDR3 having the amino acid sequence of SEQ ID NO: 104, a LC CDR1 having the amino acid sequence of SEQ ID NO: 105, a LC CDR2 having the amino acid sequence of SEQ ID NO: 106, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 107; (l) a HC CDR1 having the amino acid sequence of SEQ ID NO: 108, a HC CDR2 having the amino acid sequence of SEQ ID NO: 109, a HC CDR3 having the amino acid sequence of SEQ ID NO: 110, a LC CDR1 having the amino acid sequence of SEQ ID NO: 111, a LC CDR2 having the amino acid sequence of SEQ ID NO: 112, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 113; (m) a HC CDR1 having the amino acid sequence of SEQ ID NO: 116, a HC CDR2 having the amino acid sequence of SEQ ID NO: 117, a HC CDR3 having the amino acid sequence of SEQ ID NO: 118, a LC CDR1 having the amino acid sequence of SEQ ID NO: 119, a LC CDR2 having the amino acid sequence of SEQ ID NO: 120, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 121; 7107489(n) a HC CDR1 having the amino acid sequence of SEQ ID NO: 122, a HC CDR2 having the amino acid sequence of SEQ ID NO: 123, a HC CDR3 having the amino acid sequence of SEQ ID NO: 124, a LC CDR1 having the amino acid sequence of SEQ ID NO: 125, a LC CDR2 having the amino acid sequence of SEQ ID NO: 126, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 127; (o) a HC CDR1 having the amino acid sequence of SEQ ID NO: 128, a HC CDR2 having the amino acid sequence of SEQ ID NO: 129, a HC CDR3 having the amino acid sequence of SEQ ID NO: 130, a LC CDR1 having the amino acid sequence of SEQ ID NO: 131, a LC CDR2 having the amino acid sequence of SEQ ID NO: 132, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 133; (p) a HC CDR1 having the amino acid sequence of SEQ ID NO: 136, a HC CDR2 having the amino acid sequence of SEQ ID NO: 137, a HC CDR3 having the amino acid sequence of SEQ ID NO: 138, a LC CDR1 having the amino acid sequence of SEQ ID NO: 139, a LC CDR2 having the amino acid sequence of SEQ ID NO: 140, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 141; (q) a HC CDR1 having the amino acid sequence of SEQ ID NO: 142, a HC CDR2 having the amino acid sequence of SEQ ID NO: 143, a HC CDR3 having the amino acid sequence of SEQ ID NO: 144, a LC CDR1 having the amino acid sequence of SEQ ID NO: 145, a LC CDR2 having the amino acid sequence of SEQ ID NO: 146, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 147; (r) a HC CDR1 having the amino acid sequence of SEQ ID NO: 148, a HC CDR2 having the amino acid sequence of SEQ ID NO: 149, a HC CDR3 having the amino acid sequence of SEQ ID NO: 150, a LC CDR1 having the amino acid sequence of SEQ ID NO: 151, a LC CDR2 having the amino acid sequence of SEQ ID NO: 152, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 153; (s) a HC CDR1 having the amino acid sequence of SEQ ID NO: 655, a HC CDR2 having the amino acid sequence of SEQ ID NO: 41, a HC CDR3 having the amino acid sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 43, a LC CDR2 having the amino acid sequence of SEQ ID NO: 44, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 45; or (t) a HC CDR1 having the amino acid sequence of SEQ ID NO: 656, a HC CDR2 having the amino acid sequence of SEQ ID NO: 47, a HC CDR3 having the amino acid sequence of SEQ ID NO: 48, a LC CDR1 having the amino acid sequence of SEQ ID NO: 710748949, a LC CDR2 having the amino acid sequence of SEQ ID NO: 50, and a LC CDR3 having the amino acid sequence of SEQ ID NO:

51.

12. The bispecific antibody of any one of claims 9-11, wherein the antigen-specific binding site that specifically binds IL-13 or IL-13R comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 53 and a VL comprising the amino acid sequence of SEQ ID NO: 54; (b) a VH comprising the amino acid sequence of SEQ ID NO: 32, and a VL comprising the amino acid sequence of SEQ ID NO: 33; (c) a VH comprising the amino acid sequence of SEQ ID NO: 74, and a VL comprising the amino acid sequence of SEQ ID NO: 75; (d) a VH comprising the amino acid sequence of SEQ ID NO: 94, and a VL comprising the amino acid sequence of SEQ ID NO: 95; (e) a VH comprising the amino acid sequence of SEQ ID NO: 114, and a VL comprising the amino acid sequence of SEQ ID NO: 115; (f) a VH comprising the amino acid sequence of SEQ ID NO: 134, and a VL comprising the amino acid sequence of SEQ ID NO: 135; or (g) a VH comprising the amino acid sequence of SEQ ID NO: 657, and a VL comprising the amino acid sequence of SEQ ID NO:

658.

13. The bispecific antibody of any one of claims 1-8, wherein the Th2 cytokine is IL-4.

14. The bispecific antibody of claim 13, wherein the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises: (a) a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 154, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 155; (b) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 174, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 175; (c) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 194, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 195; 7107489(d) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 214, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 215; (e) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 234, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 235; or (f) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 254, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO:

255.

15. The bispecific antibody of claim 13 or 14, wherein the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises: (a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 156, a HC CDR2 having the amino acid sequence of SEQ ID NO: 157, a HC CDR3 having the amino acid sequence of SEQ ID NO: 158, a LC CDR1 having the amino acid sequence of SEQ ID NO: 159, a LC CDR2 having the amino acid sequence of SEQ ID NO: 160, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 161; (b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 162, a HC CDR2 having the amino acid sequence of SEQ ID NO: 163, a HC CDR3 having the amino acid sequence of SEQ ID NO: 164, a LC CDR1 having the amino acid sequence of SEQ ID NO: 165, a LC CDR2 having the amino acid sequence of LGS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 167; (c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 168, a HC CDR2 having the amino acid sequence of SEQ ID NO: 169, a HC CDR3 having the amino acid sequence of SEQ ID NO: 170, a LC CDR1 having the amino acid sequence of SEQ ID NO: 171, a LC CDR2 having the amino acid sequence of SEQ ID NO: 172, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 173; (d) a HC CDR1 having the amino acid sequence of SEQ ID NO: 176, a HC CDR2 having the amino acid sequence of SEQ ID NO: 177, a HC CDR3 having the amino acid sequence of SEQ ID NO: 178, a LC CDR1 having the amino acid sequence of SEQ ID NO: 179, a LC CDR2 having the amino acid sequence of SEQ ID NO: 180, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 181; (e) a HC CDR1 having the amino acid sequence of SEQ ID NO: 182, a HC CDR2 having the amino acid sequence of SEQ ID NO: 183, a HC CDR3 having the amino acid 7107489sequence of SEQ ID NO: 184, a LC CDR1 having the amino acid sequence of SEQ ID NO: 185, a LC CDR2 having the amino acid sequence of AAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 187; (f) a HC CDR1 having the amino acid sequence of SEQ ID NO: 188, a HC CDR2 having the amino acid sequence of SEQ ID NO: 189, a HC CDR3 having the amino acid sequence of SEQ ID NO: 190, a LC CDR1 having the amino acid sequence of SEQ ID NO: 191, a LC CDR2 having the amino acid sequence of SEQ ID NO: 192, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 193; (g) a HC CDR1 having the amino acid sequence of SEQ ID NO: 196, a HC CDR2 having the amino acid sequence of SEQ ID NO: 197, a HC CDR3 having the amino acid sequence of SEQ ID NO: 198, a LC CDR1 having the amino acid sequence of SEQ ID NO: 199, a LC CDR2 having the amino acid sequence of SEQ ID NO: 200, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 201; (h) a HC CDR1 having the amino acid sequence of SEQ ID NO: 202, a HC CDR2 having the amino acid sequence of SEQ ID NO: 203, a HC CDR3 having the amino acid sequence of SEQ ID NO: 204, a LC CDR1 having the amino acid sequence of SEQ ID NO: 205, a LC CDR2 having the amino acid sequence of SEQ ID NO: 206, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 207; (i) a HC CDR1 having the amino acid sequence of SEQ ID NO: 208, a HC CDR2 having the amino acid sequence of SEQ ID NO: 209, a HC CDR3 having the amino acid sequence of SEQ ID NO: 210, a LC CDR1 having the amino acid sequence of SEQ ID NO: 211, a LC CDR2 having the amino acid sequence of GAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 213; (j) a HC CDR1 having the amino acid sequence of SEQ ID NO: 216, a HC CDR2 having the amino acid sequence of SEQ ID NO: 217, a HC CDR3 having the amino acid sequence of SEQ ID NO: 218, a LC CDR1 having the amino acid sequence of SEQ ID NO: 219, a LC CDR2 having the amino acid sequence of SEQ ID NO: 220, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 221; (k) a HC CDR1 having the amino acid sequence of SEQ ID NO: 222, a HC CDR2 having the amino acid sequence of SEQ ID NO: 223, a HC CDR3 having the amino acid sequence of SEQ ID NO: 224, a LC CDR1 having the amino acid sequence of SEQ ID NO: 225, a LC CDR2 having the amino acid sequence of YTS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 227; 7107489(l) a HC CDR1 having the amino acid sequence of SEQ ID NO: 228, a HC CDR2 having the amino acid sequence of SEQ ID NO: 229, a HC CDR3 having the amino acid sequence of SEQ ID NO: 230, a LC CDR1 having the amino acid sequence of SEQ ID NO: 231, a LC CDR2 having the amino acid sequence of SEQ ID NO: 232, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 233; (m) a HC CDR1 having the amino acid sequence of SEQ ID NO: 236, a HC CDR2 having the amino acid sequence of SEQ ID NO: 237, a HC CDR3 having the amino acid sequence of SEQ ID NO: 238, a LC CDR1 having the amino acid sequence of SEQ ID NO: 239, a LC CDR2 having the amino acid sequence of SEQ ID NO: 240, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 241; (n) a HC CDR1 having the amino acid sequence of SEQ ID NO: 242, a HC CDR2 having the amino acid sequence of SEQ ID NO: 243, a HC CDR3 having the amino acid sequence of SEQ ID NO: 244, a LC CDR1 having the amino acid sequence of SEQ ID NO: 245, a LC CDR2 having the amino acid sequence of SEQ ID NO: 246, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 247; (o) a HC CDR1 having the amino acid sequence of SEQ ID NO: 248, a HC CDR2 having the amino acid sequence of SEQ ID NO: 249, a HC CDR3 having the amino acid sequence of SEQ ID NO: 250, a LC CDR1 having the amino acid sequence of SEQ ID NO: 251, a LC CDR2 having the amino acid sequence of SEQ ID NO: 252, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 253; (p) a HC CDR1 having the amino acid sequence of SEQ ID NO: 256, a HC CDR2 having the amino acid sequence of SEQ ID NO: 257, a HC CDR3 having the amino acid sequence of SEQ ID NO: 258, a LC CDR1 having the amino acid sequence of SEQ ID NO: 259, a LC CDR2 having the amino acid sequence of SEQ ID NO: 260, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 261; (q) a HC CDR1 having the amino acid sequence of SEQ ID NO: 262, a HC CDR2 having the amino acid sequence of SEQ ID NO: 263, a HC CDR3 having the amino acid sequence of SEQ ID NO: 264, a LC CDR1 having the amino acid sequence of SEQ ID NO: 265, a LC CDR2 having the amino acid sequence of SEQ ID NO: 267, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 268; or (r) a HC CDR1 having the amino acid sequence of SEQ ID NO: 269, a HC CDR2 having the amino acid sequence of SEQ ID NO: 270, a HC CDR3 having the amino acid sequence of SEQ ID NO: 271, a LC CDR1 having the amino acid sequence of SEQ ID NO: 7107489272, a LC CDR2 having the amino acid sequence of SAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO:

274.

16. The bispecific antibody of any one of claims 13-15, wherein the antigen-specific binding site that specifically binds IL-4 or IL-4R comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 154 and a VL comprising the amino acid sequence of SEQ ID NO: 155; (b) a VH comprising the amino acid sequence of SEQ ID NO: 174, and a VL comprising the amino acid sequence of SEQ ID NO: 175; (c) a VH comprising the amino acid sequence of SEQ ID NO: 194, and a VL comprising the amino acid sequence of SEQ ID NO: 195; (d) a VH comprising the amino acid sequence of SEQ ID NO: 214, and a VL comprising the amino acid sequence of SEQ ID NO: 215; (e) a VH comprising the amino acid sequence of SEQ ID NO: 234, and a VL comprising the amino acid sequence of SEQ ID NO: 235; or (f) a VH comprising the amino acid sequence of SEQ ID NO: 254, and a VL comprising the amino acid sequence of SEQ ID NO:

255.

17. The bispecific antibody of any one of claims 1-8, wherein the Th2 cytokine is IL-5.

18. The bispecific antibody of claim 17, wherein the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises: (a) a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 275, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 276; (b) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 295, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 296; (c) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 315, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 316; (d) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 335, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 336; 7107489(e) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 355, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 356; or (f) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 375, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO:

376.

19. The bispecific antibody of claim 17 or 18, wherein the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises: (a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 277, a HC CDR2 having the amino acid sequence of SEQ ID NO: 278, a HC CDR3 having the amino acid sequence of SEQ ID NO: 279, a LC CDR1 having the amino acid sequence of SEQ ID NO: 280, a LC CDR2 having the amino acid sequence of SEQ ID NO: 281, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 282; (b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 283, a HC CDR2 having the amino acid sequence of SEQ ID NO: 284, a HC CDR3 having the amino acid sequence of SEQ ID NO: 285, a LC CDR1 having the amino acid sequence of SEQ ID NO: 286, a LC CDR2 having the amino acid sequence of SEQ ID NO: 287, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 288; (c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 289, a HC CDR2 having the amino acid sequence of SEQ ID NO: 290, a HC CDR3 having the amino acid sequence of SEQ ID NO: 291, a LC CDR1 having the amino acid sequence of SEQ ID NO: 292, a LC CDR2 having the amino acid sequence of SEQ ID NO: 293, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 294; (d) a HC CDR1 having the amino acid sequence of SEQ ID NO: 297, a HC CDR2 having the amino acid sequence of SEQ ID NO: 298, a HC CDR3 having the amino acid sequence of SEQ ID NO: 299, a LC CDR1 having the amino acid sequence of SEQ ID NO: 300, a LC CDR2 having the amino acid sequence of SEQ ID NO: 301, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 302; (e) a HC CDR1 having the amino acid sequence of SEQ ID NO: 303, a HC CDR2 having the amino acid sequence of SEQ ID NO: 304, a HC CDR3 having the amino acid sequence of SEQ ID NO: 305, a LC CDR1 having the amino acid sequence of SEQ ID NO: 306, a LC CDR2 having the amino acid sequence of GAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 308; 7107489(f) a HC CDR1 having the amino acid sequence of SEQ ID NO: 309, a HC CDR2 having the amino acid sequence of SEQ ID NO: 310, a HC CDR3 having the amino acid sequence of SEQ ID NO: 311, a LC CDR1 having the amino acid sequence of SEQ ID NO: 312, a LC CDR2 having the amino acid sequence of SEQ ID NO: 313, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 314; (g) a HC CDR1 having the amino acid sequence of SEQ ID NO: 317, a HC CDR2 having the amino acid sequence of SEQ ID NO: 318, a HC CDR3 having the amino acid sequence of SEQ ID NO: 319, a LC CDR1 having the amino acid sequence of SEQ ID NO: 320, a LC CDR2 having the amino acid sequence of SEQ ID NO: 321, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 322; (h) a HC CDR1 having the amino acid sequence of SEQ ID NO: 323, a HC CDR2 having the amino acid sequence of SEQ ID NO: 324, a HC CDR3 having the amino acid sequence of SEQ ID NO: 325, a LC CDR1 having the amino acid sequence of SEQ ID NO: 326, a LC CDR2 having the amino acid sequence of GAN, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 328; (i) a HC CDR1 having the amino acid sequence of SEQ ID NO: 329, a HC CDR2 having the amino acid sequence of SEQ ID NO: 330, a HC CDR3 having the amino acid sequence of SEQ ID NO: 331, a LC CDR1 having the amino acid sequence of SEQ ID NO: 332, a LC CDR2 having the amino acid sequence of SEQ ID NO: 333, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 334; (j) a HC CDR1 having the amino acid sequence of SEQ ID NO: 337, a HC CDR2 having the amino acid sequence of SEQ ID NO: 338, a HC CDR3 having the amino acid sequence of SEQ ID NO: 339, a LC CDR1 having the amino acid sequence of SEQ ID NO: 340, a LC CDR2 having the amino acid sequence of SEQ ID NO: 341, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 342; (k) a HC CDR1 having the amino acid sequence of SEQ ID NO: 343, a HC CDR2 having the amino acid sequence of SEQ ID NO: 344, a HC CDR3 having the amino acid sequence of SEQ ID NO: 345, a LC CDR1 having the amino acid sequence of SEQ ID NO: 346, a LC CDR2 having the amino acid sequence of G, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 348; (l) a HC CDR1 having the amino acid sequence of SEQ ID NO: 349, a HC CDR2 having the amino acid sequence of SEQ ID NO: 350, a HC CDR3 having the amino acid sequence of SEQ ID NO: 351, a LC CDR1 having the amino acid sequence of SEQ ID NO: 7107489352, a LC CDR2 having the amino acid sequence of SEQ ID NO: 353, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 354; (m) a HC CDR1 having the amino acid sequence of SEQ ID NO: 357, a HC CDR2 having the amino acid sequence of SEQ ID NO: 358, a HC CDR3 having the amino acid sequence of SEQ ID NO: 359, a LC CDR1 having the amino acid sequence of SEQ ID NO: 360, a LC CDR2 having the amino acid sequence of SEQ ID NO: 361, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 362; (n) a HC CDR1 having the amino acid sequence of SEQ ID NO: 363, a HC CDR2 having the amino acid sequence of SEQ ID NO: 364, a HC CDR3 having the amino acid sequence of SEQ ID NO: 365, a LC CDR1 having the amino acid sequence of SEQ ID NO: 366, a LC CDR2 having the amino acid sequence of RAD, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 368; (o) a HC CDR1 having the amino acid sequence of SEQ ID NO: 369, a HC CDR2 having the amino acid sequence of SEQ ID NO: 370, a HC CDR3 having the amino acid sequence of SEQ ID NO: 371, a LC CDR1 having the amino acid sequence of SEQ ID NO: 372, a LC CDR2 having the amino acid sequence of SEQ ID NO: 373, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 374; (p) a HC CDR1 having the amino acid sequence of SEQ ID NO: 377, a HC CDR2 having the amino acid sequence of SEQ ID NO: 378, a HC CDR3 having the amino acid sequence of SEQ ID NO: 379, a LC CDR1 having the amino acid sequence of SEQ ID NO: 380, a LC CDR2 having the amino acid sequence of SEQ ID NO: 381, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 382; (q) a HC CDR1 having the amino acid sequence of SEQ ID NO: 383, a HC CDR2 having the amino acid sequence of SEQ ID NO: 384, a HC CDR3 having the amino acid sequence of SEQ ID NO: 385, a LC CDR1 having the amino acid sequence of SEQ ID NO: 386, a LC CDR2 having the amino acid sequence of AAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 388; or (r) a HC CDR1 having the amino acid sequence of SEQ ID NO: 389, a HC CDR2 having the amino acid sequence of SEQ ID NO: 390, a HC CDR3 having the amino acid sequence of SEQ ID NO: 391, a LC CDR1 having the amino acid sequence of SEQ ID NO: 392, a LC CDR2 having the amino acid sequence of SEQ ID NO: 393, and a LC CDR3 having the amino acid sequence of SEQ ID NO:

394. 710748920. The bispecific antibody of any one of claims 17-19, wherein the antigen-specific binding site that specifically binds IL-5 or IL-5R comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 275 and a VL comprising the amino acid sequence of SEQ ID NO: 276; (b) a VH comprising the amino acid sequence of SEQ ID NO: 295, and a VL comprising the amino acid sequence of SEQ ID NO: 296; (c) a VH comprising the amino acid sequence of SEQ ID NO: 315, and a VL comprising the amino acid sequence of SEQ ID NO: 316; (d) a VH comprising the amino acid sequence of SEQ ID NO: 335, and a VL comprising the amino acid sequence of SEQ ID NO: 336; (e) a VH comprising the amino acid sequence of SEQ ID NO: 355, and a VL comprising the amino acid sequence of SEQ ID NO: 356; or (f) a VH comprising the amino acid sequence of SEQ ID NO: 375, and a VL comprising the amino acid sequence of SEQ ID NO:

376.

21. The bispecific antibody of any one of claims 1-8, wherein the Th2 cytokine is IL-9.

22. The bispecific antibody of claim 21, wherein the antigen-specific binding site that specifically binds IL-9 or IL-9R comprises: (a) a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 395, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO:

396.

23. The bispecific antibody of claim 21 or 22, wherein the antigen-specific binding site that specifically binds IL-9 or IL-9R comprises: (a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 397, a HC CDR2 having the amino acid sequence of SEQ ID NO: 398, a HC CDR3 having the amino acid sequence of SEQ ID NO: 399, a LC CDR1 having the amino acid sequence of SEQ ID NO: 400, a LC CDR2 having the amino acid sequence of SEQ ID NO: 401, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 402: (b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 403, a HC CDR2 having the amino acid sequence of SEQ ID NO: 404, a HC CDR3 having the amino acid sequence of SEQ ID NO: 405, a LC CDR1 having the amino acid sequence of SEQ ID NO: 7107489406, a LC CDR2 having the amino acid sequence of GTS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 408; or (c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 409, a HC CDR2 having the amino acid sequence of SEQ ID NO: 410, a HC CDR3 having the amino acid sequence of SEQ ID NO: 411, a LC CDR1 having the amino acid sequence of SEQ ID NO: 412, a LC CDR2 having the amino acid sequence of SEQ ID NO: 413, and a LC CDR3 having the amino acid sequence of SEQ ID NO:

414.

24. The bispecific antibody of any one of claims 21-23, wherein the antigen-specific binding site that specifically binds IL-9 or IL-9R comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 395 and a VL comprising the amino acid sequence of SEQ ID NO:

396.

25. The bispecific antibody of any one of claims 1-8, wherein the Th2 cytokine is OX40L.

26. The bispecific antibody of claim 25, wherein the antigen-specific binding site that specifically binds OX40L or OX40 comprises: (a) a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 415, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 416; (b) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 435, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 436; (c) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 819, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 820; (d) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 839, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 840; or (e) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 859, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO:

860. 710748927. The bispecific antibody of claim 25 or 26, wherein the antigen-specific binding site that specifically binds OX40L or OX40 comprises: (a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 417, a HC CDR2 having the amino acid sequence of SEQ ID NO: 418, a HC CDR3 having the amino acid sequence of SEQ ID NO: 419, a LC CDR1 having the amino acid sequence of SEQ ID NO: 420, a LC CDR2 having the amino acid sequence of SEQ ID NO: 421, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 422: (b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 423, a HC CDR2 having the amino acid sequence of SEQ ID NO: 424, a HC CDR3 having the amino acid sequence of SEQ ID NO: 425, a LC CDR1 having the amino acid sequence of SEQ ID NO: 426, a LC CDR2 having the amino acid sequence of GAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 428; (c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 429, a HC CDR2 having the amino acid sequence of SEQ ID NO: 430, a HC CDR3 having the amino acid sequence of SEQ ID NO: 431, a LC CDR1 having the amino acid sequence of SEQ ID NO: 432, a LC CDR2 having the amino acid sequence of SEQ ID NO: 433, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 434; (d) a HC CDR1 having the amino acid sequence of SEQ ID NO: 437, a HC CDR2 having the amino acid sequence of SEQ ID NO: 438, a HC CDR3 having the amino acid sequence of SEQ ID NO: 439, a LC CDR1 having the amino acid sequence of SEQ ID NO: 440, a LC CDR2 having the amino acid sequence of SEQ ID NO: 441, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 442; (e) a HC CDR1 having the amino acid sequence of SEQ ID NO: 443, a HC CDR2 having the amino acid sequence of SEQ ID NO: 444, a HC CDR3 having the amino acid sequence of SEQ ID NO: 445, a LC CDR1 having the amino acid sequence of SEQ ID NO: 446, a LC CDR2 having the amino acid sequence of AAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 448; (f) a HC CDR1 having the amino acid sequence of SEQ ID NO: 449, a HC CDR2 having the amino acid sequence of SEQ ID NO: 450, a HC CDR3 having the amino acid sequence of SEQ ID NO: 451, a LC CDR1 having the amino acid sequence of SEQ ID NO: 452, a LC CDR2 having the amino acid sequence of SEQ ID NO: 453, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 454; (g) a HC CDR1 having the amino acid sequence of SEQ ID NO: 821, a HC CDR2 having the amino acid sequence of SEQ ID NO: 822, a HC CDR3 having the amino acid 7107489sequence of SEQ ID NO: 823, a LC CDR1 having the amino acid sequence of SEQ ID NO: 824, a LC CDR2 having the amino acid sequence of SEQ ID NO: 825, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 826; (h) a HC CDR1 having the amino acid sequence of SEQ ID NO: 827, a HC CDR2 having the amino acid sequence of SEQ ID NO: 828, a HC CDR3 having the amino acid sequence of SEQ ID NO: 829, a LC CDR1 having the amino acid sequence of SEQ ID NO: 830, a LC CDR2 having the amino acid sequence of ATS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 832; (i) a HC CDR1 having the amino acid sequence of SEQ ID NO: 833, a HC CDR2 having the amino acid sequence of SEQ ID NO: 834, a HC CDR3 having the amino acid sequence of SEQ ID NO: 835, a LC CDR1 having the amino acid sequence of SEQ ID NO: 836, a LC CDR2 having the amino acid sequence of SEQ ID NO: 837, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 838; (j) a HC CDR1 having the amino acid sequence of SEQ ID NO: 841, a HC CDR2 having the amino acid sequence of SEQ ID NO: 842, a HC CDR3 having the amino acid sequence of SEQ ID NO: 843, a LC CDR1 having the amino acid sequence of SEQ ID NO: 844, a LC CDR2 having the amino acid sequence of SEQ ID NO: 845, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 846; (k) a HC CDR1 having the amino acid sequence of SEQ ID NO: 847, a HC CDR2 having the amino acid sequence of SEQ ID NO: 848, a HC CDR3 having the amino acid sequence of SEQ ID NO: 849, a LC CDR1 having the amino acid sequence of SEQ ID NO: 850, a LC CDR2 having the amino acid sequence of AAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 852; (l) a HC CDR1 having the amino acid sequence of SEQ ID NO: 853, a HC CDR2 having the amino acid sequence of SEQ ID NO: 854, a HC CDR3 having the amino acid sequence of SEQ ID NO: 855, a LC CDR1 having the amino acid sequence of SEQ ID NO: 856, a LC CDR2 having the amino acid sequence of SEQ ID NO: 857, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 858; (m) a HC CDR1 having the amino acid sequence of SEQ ID NO: 861, a HC CDR2 having the amino acid sequence of SEQ ID NO: 862, a HC CDR3 having the amino acid sequence of SEQ ID NO: 863, a LC CDR1 having the amino acid sequence of SEQ ID NO: 864, a LC CDR2 having the amino acid sequence of SEQ ID NO: 865, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 866; 7107489(n) a HC CDR1 having the amino acid sequence of SEQ ID NO: 867, a HC CDR2 having the amino acid sequence of SEQ ID NO: 868, a HC CDR3 having the amino acid sequence of SEQ ID NO: 869, a LC CDR1 having the amino acid sequence of SEQ ID NO: 870, a LC CDR2 having the amino acid sequence of RAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 872; or (o) a HC CDR1 having the amino acid sequence of SEQ ID NO: 873, a HC CDR2 having the amino acid sequence of SEQ ID NO: 874, a HC CDR3 having the amino acid sequence of SEQ ID NO: 875, a LC CDR1 having the amino acid sequence of SEQ ID NO: 876, a LC CDR2 having the amino acid sequence of SEQ ID NO: 878, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 872; 28. The bispecific antibody of any one of claims 25-27, wherein the antigen-specific binding site that specifically binds OX40L or OX40 comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 415 and a VL comprising the amino acid sequence of SEQ ID NO: 416; (b) a VH comprising the amino acid sequence of SEQ ID NO: 435, and a VL comprising the amino acid sequence of SEQ ID NO: 436; (c) a VH comprising the amino acid sequence of SEQ ID NO: 819, and a VL comprising the amino acid sequence of SEQ ID NO: 820; (d) a VH comprising the amino acid sequence of SEQ ID NO: 839, and a VL comprising the amino acid sequence of SEQ ID NO: 840; or (e) a VH comprising the amino acid sequence of SEQ ID NO: 859, and a VL comprising the amino acid sequence of SEQ ID NO:

860.

29. The bispecific antibody of any one of claims 1-8, wherein the Th2 cytokine is IL-25.

30. The bispecific antibody of claim 29, wherein the antigen-specific binding site that specifically binds IL-25 or IL-25R comprises: (a) a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 455, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 456; or (b) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 719, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 720; 710748931. The bispecific antibody of claim 29 or 30, wherein the antigen-specific binding site that specifically binds IL-25 or IL-25R comprises: (a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 457, a HC CDR2 having the amino acid sequence of SEQ ID NO: 458, a HC CDR3 having the amino acid sequence of SEQ ID NO: 459, a LC CDR1 having the amino acid sequence of SEQ ID NO: 460, a LC CDR2 having the amino acid sequence of SEQ ID NO: 461, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 462: (b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 463, a HC CDR2 having the amino acid sequence of SEQ ID NO: 464, a HC CDR3 having the amino acid sequence of SEQ ID NO: 465, a LC CDR1 having the amino acid sequence of SEQ ID NO: 466, a LC CDR2 having the amino acid sequence of DAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 468; (c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 469, a HC CDR2 having the amino acid sequence of SEQ ID NO: 470, a HC CDR3 having the amino acid sequence of SEQ ID NO: 471, a LC CDR1 having the amino acid sequence of SEQ ID NO: 472, a LC CDR2 having the amino acid sequence of SEQ ID NO: 473, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 474; (d) a HC CDR1 having the amino acid sequence of SEQ ID NO: 721, a HC CDR2 having the amino acid sequence of SEQ ID NO: 722, a HC CDR3 having the amino acid sequence of SEQ ID NO: 723, a LC CDR1 having the amino acid sequence of SEQ ID NO: 724, a LC CDR2 having the amino acid sequence of SEQ ID NO: 725, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 726; (e) a HC CDR1 having the amino acid sequence of SEQ ID NO: 727, a HC CDR2 having the amino acid sequence of SEQ ID NO: 728, a HC CDR3 having the amino acid sequence of SEQ ID NO: 729, a LC CDR1 having the amino acid sequence of SEQ ID NO: 730, a LC CDR2 having the amino acid sequence of RTS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 732; or (f) a HC CDR1 having the amino acid sequence of SEQ ID NO: 733, a HC CDR2 having the amino acid sequence of SEQ ID NO: 734, a HC CDR3 having the amino acid sequence of SEQ ID NO: 735, a LC CDR1 having the amino acid sequence of SEQ ID NO: 736, a LC CDR2 having the amino acid sequence of SEQ ID NO: 737, and a LC CDR3 having the amino acid sequence of SEQ ID NO:

738. 710748932. The bispecific antibody of any one of claims 29-31, wherein the antigen-specific binding site that specifically binds IL-25 or IL-25R comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 455 and a VL comprising the amino acid sequence of SEQ ID NO: 456; or (b) a VH comprising the amino acid sequence of SEQ ID NO: 719, and a VL comprising the amino acid sequence of SEQ ID NO:

720.

33. The bispecific antibody of any one of claims 1-8, wherein the Th2 cytokine is IL-31.

34. The bispecific antibody of claim 33, wherein the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises: (a) a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 475, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 476; (b) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 495, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 496; (c) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 739, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 740; or (d) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 759, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO:

760.

35. The bispecific antibody of claim 33 or 34, wherein the antigen-specific binding site that specifically binds IL-31 or IL-31R comprises: (a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 477, a HC CDR2 having the amino acid sequence of SEQ ID NO: 478, a HC CDR3 having the amino acid sequence of SEQ ID NO: 479, a LC CDR1 having the amino acid sequence of SEQ ID NO: 480, a LC CDR2 having the amino acid sequence of SEQ ID NO: 481, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 482, (b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 483, a HC CDR2 having the amino acid sequence of SEQ ID NO: 484, a HC CDR3 having the amino acid sequence of SEQ ID NO: 485, a LC CDR1 having the amino acid sequence of SEQ ID NO: 7107489486, a LC CDR2 having the amino acid sequence of SEQ ID NO: 487, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 488; (c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 489, a HC CDR2 having the amino acid sequence of SEQ ID NO: 490, a HC CDR3 having the amino acid sequence of SEQ ID NO: 491, a LC CDR1 having the amino acid sequence of SEQ ID NO: 492, a LC CDR2 having the amino acid sequence of SEQ ID NO: 493, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 494; (d) a HC CDR1 having the amino acid sequence of SEQ ID NO: 497, a HC CDR2 having the amino acid sequence of SEQ ID NO: 498, a HC CDR3 having the amino acid sequence of SEQ ID NO: 499, a LC CDR1 having the amino acid sequence of SEQ ID NO: 500, a LC CDR2 having the amino acid sequence of SEQ ID NO: 501, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 502; (e) a HC CDR1 having the amino acid sequence of SEQ ID NO: 503, a HC CDR2 having the amino acid sequence of SEQ ID NO: 504, a HC CDR3 having the amino acid sequence of SEQ ID NO: 505, a LC CDR1 having the amino acid sequence of SEQ ID NO: 506, a LC CDR2 having the amino acid sequence of NIN, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 508; (f) a HC CDR1 having the amino acid sequence of SEQ ID NO: 509, a HC CDR2 having the amino acid sequence of SEQ ID NO: 510, a HC CDR3 having the amino acid sequence of SEQ ID NO: 511, a LC CDR1 having the amino acid sequence of SEQ ID NO: 512, a LC CDR2 having the amino acid sequence of SEQ ID NO: 513, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 514; (g) a HC CDR1 having the amino acid sequence of SEQ ID NO: 741, a HC CDR2 having the amino acid sequence of SEQ ID NO: 742, a HC CDR3 having the amino acid sequence of SEQ ID NO: 743, a LC CDR1 having the amino acid sequence of SEQ ID NO: 744, a LC CDR2 having the amino acid sequence of SEQ ID NO: 745, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 746; (h) a HC CDR1 having the amino acid sequence of SEQ ID NO: 747, a HC CDR2 having the amino acid sequence of SEQ ID NO: 748, a HC CDR3 having the amino acid sequence of SEQ ID NO: 749, a LC CDR1 having the amino acid sequence of SEQ ID NO: 750, a LC CDR2 having the amino acid sequence of QAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 752; (i) a HC CDR1 having the amino acid sequence of SEQ ID NO: 753, a HC CDR2 having the amino acid sequence of SEQ ID NO: 754, a HC CDR3 having the amino acid 7107489sequence of SEQ ID NO: 755, a LC CDR1 having the amino acid sequence of SEQ ID NO: 756, a LC CDR2 having the amino acid sequence of SEQ ID NO: 757, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 758; (j) a HC CDR1 having the amino acid sequence of SEQ ID NO: 761, a HC CDR2 having the amino acid sequence of SEQ ID NO: 762, a HC CDR3 having the amino acid sequence of SEQ ID NO: 763, a LC CDR1 having the amino acid sequence of SEQ ID NO: 764, a LC CDR2 having the amino acid sequence of SEQ ID NO: 765, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 766; (k) a HC CDR1 having the amino acid sequence of SEQ ID NO: 767, a HC CDR2 having the amino acid sequence of SEQ ID NO: 768, a HC CDR3 having the amino acid sequence of SEQ ID NO: 770, a LC CDR1 having the amino acid sequence of SEQ ID NO: 346, a LC CDR2 having the amino acid sequence of NAK, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 772; or (l) a HC CDR1 having the amino acid sequence of SEQ ID NO: 773, a HC CDR2 having the amino acid sequence of SEQ ID NO: 774, a HC CDR3 having the amino acid sequence of SEQ ID NO: 775, a LC CDR1 having the amino acid sequence of SEQ ID NO: 776, a LC CDR2 having the amino acid sequence of SEQ ID NO: 777, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 778; 36. The bispecific antibody of any one of claims 33-35, wherein the antigen-specific binding site that specifically binds IL-31 or IL31R comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 475 and a VL comprising the amino acid sequence of SEQ ID NO: 476; (b) a VH comprising the amino acid sequence of SEQ ID NO: 495, and a VL comprising the amino acid sequence of SEQ ID NO: 496; (c) a VH comprising the amino acid sequence of SEQ ID NO: 739, and a VL comprising the amino acid sequence of SEQ ID NO: 740; or (d) a VH comprising the amino acid sequence of SEQ ID NO: 759, and a VL comprising the amino acid sequence of SEQ ID NO:

760.

37. The bispecific antibody of any one of claims 1-8, wherein the Th2 cytokine is IL-36.

38. The bispecific antibody of claim 37, wherein the antigen-specific binding site that specifically binds IL-36 or IL-36R comprises: 7107489(a) a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 575, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 576; (b) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 595, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 596; or (c) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 779, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO:

780.

39. The bispecific antibody of claim 37 or 38, wherein the antigen-specific binding site that specifically binds IL-36 or IL-36R comprises: (a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 577, a HC CDR2 having the amino acid sequence of SEQ ID NO: 578, a HC CDR3 having the amino acid sequence of SEQ ID NO: 579, a LC CDR1 having the amino acid sequence of SEQ ID NO: 580, a LC CDR2 having the amino acid sequence of SEQ ID NO: 581, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 582; (b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 583, a HC CDR2 having the amino acid sequence of SEQ ID NO: 584, a HC CDR3 having the amino acid sequence of SEQ ID NO: 585, a LC CDR1 having the amino acid sequence of SEQ ID NO: 586, a LC CDR2 having the amino acid sequence of RTS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 588; (c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 589, a HC CDR2 having the amino acid sequence of SEQ ID NO: 590, a HC CDR3 having the amino acid sequence of SEQ ID NO: 591, a LC CDR1 having the amino acid sequence of SEQ ID NO: 592, a LC CDR2 having the amino acid sequence of SEQ ID NO: 593, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 594; (d) a HC CDR1 having the amino acid sequence of SEQ ID NO: 597, a HC CDR2 having the amino acid sequence of SEQ ID NO: 598, a HC CDR3 having the amino acid sequence of SEQ ID NO: 599, a LC CDR1 having the amino acid sequence of SEQ ID NO: 600, a LC CDR2 having the amino acid sequence of SEQ ID NO: 601, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 602; (e) a HC CDR1 having the amino acid sequence of SEQ ID NO: 603, a HC CDR2 having the amino acid sequence of SEQ ID NO: 604, a HC CDR3 having the amino acid 7107489sequence of SEQ ID NO: 605, a LC CDR1 having the amino acid sequence of SEQ ID NO: 606, a LC CDR2 having the amino acid sequence of QMS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 608; (f) a HC CDR1 having the amino acid sequence of SEQ ID NO: 609, a HC CDR2 having the amino acid sequence of SEQ ID NO: 610, a HC CDR3 having the amino acid sequence of SEQ ID NO: 611, a LC CDR1 having the amino acid sequence of SEQ ID NO: 612, a LC CDR2 having the amino acid sequence of SEQ ID NO: 613, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 614; (g) a HC CDR1 having the amino acid sequence of SEQ ID NO: 781, a HC CDR2 having the amino acid sequence of SEQ ID NO: 782, a HC CDR3 having the amino acid sequence of SEQ ID NO: 783, a LC CDR1 having the amino acid sequence of SEQ ID NO: 784, a LC CDR2 having the amino acid sequence of SEQ ID NO: 785, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 786; or (h) a HC CDR1 having the amino acid sequence of SEQ ID NO: 787, a HC CDR2 having the amino acid sequence of SEQ ID NO: 788, a HC CDR3 having the amino acid sequence of SEQ ID NO: 789, a LC CDR1 having the amino acid sequence of SEQ ID NO: 790, a LC CDR2 having the amino acid sequence of STS, and a LC CDR3 having the amino acid sequence of SEQ ID NO:

792.

40. The bispecific antibody of any one of claims 37-39, wherein the antigen-specific binding site that specifically binds IL-36 or IL-36R comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 575 and a VL comprising the amino acid sequence of SEQ ID NO: 576; (b) a VH comprising the amino acid sequence of SEQ ID NO: 595, and a VL comprising the amino acid sequence of SEQ ID NO: 596; or (c) a VH comprising the amino acid sequence of SEQ ID NO: 779, and a VL comprising the amino acid sequence of SEQ ID NO:

780.

41. The bispecific antibody of any one of claims 1-8, wherein the Th2 cytokine is TSLP.

42. The bispecific antibody of claim 41, wherein the antigen-specific binding site that specifically binds TSLP or TSLPR comprises: 7107489(a) a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 615, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 616; (b) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 635, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 636; (c) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 879, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 880; or (d) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 899, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO:

900.

43. The bispecific antibody of claim 41 or 42, wherein the antigen-specific binding site that specifically binds TSLP or TSLPR comprises: (a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 617, a HC CDR2 having the amino acid sequence of SEQ ID NO: 618, a HC CDR3 having the amino acid sequence of SEQ ID NO: 619, a LC CDR1 having the amino acid sequence of SEQ ID NO: 620, a LC CDR2 having the amino acid sequence of SEQ ID NO: 621, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 622: (b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 623, a HC CDR2 having the amino acid sequence of SEQ ID NO: 624, a HC CDR3 having the amino acid sequence of SEQ ID NO: 625, a LC CDR1 having the amino acid sequence of SEQ ID NO: 626, a LC CDR2 having the amino acid sequence of DDS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 628; (c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 629, a HC CDR2 having the amino acid sequence of SEQ ID NO: 630, a HC CDR3 having the amino acid sequence of SEQ ID NO: 631, a LC CDR1 having the amino acid sequence of SEQ ID NO: 632, a LC CDR2 having the amino acid sequence of SEQ ID NO: 633, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 634; or (d) a HC CDR1 having the amino acid sequence of SEQ ID NO: 637, a HC CDR2 having the amino acid sequence of SEQ ID NO: 638, a HC CDR3 having the amino acid sequence of SEQ ID NO: 639, a LC CDR1 having the amino acid sequence of SEQ ID NO: 7107489640, a LC CDR2 having the amino acid sequence of SEQ ID NO: 641, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 642; (e) a HC CDR1 having the amino acid sequence of SEQ ID NO: 643, a HC CDR2 having the amino acid sequence of SEQ ID NO: 644, a HC CDR3 having the amino acid sequence of SEQ ID NO: 645, a LC CDR1 having the amino acid sequence of SEQ ID NO: 646, a LC CDR2 having the amino acid sequence of GDN, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 648; (f) a HC CDR1 having the amino acid sequence of SEQ ID NO: 649, a HC CDR2 having the amino acid sequence of SEQ ID NO: 650, a HC CDR3 having the amino acid sequence of SEQ ID NO: 651, a LC CDR1 having the amino acid sequence of SEQ ID NO: 652, a LC CDR2 having the amino acid sequence of SEQ ID NO: 653, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 654; (g) a HC CDR1 having the amino acid sequence of SEQ ID NO: 881, a HC CDR2 having the amino acid sequence of SEQ ID NO: 882, a HC CDR3 having the amino acid sequence of SEQ ID NO: 883, a LC CDR1 having the amino acid sequence of SEQ ID NO: 884, a LC CDR2 having the amino acid sequence of SEQ ID NO: 885, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 886; (h) a HC CDR1 having the amino acid sequence of SEQ ID NO: 887, a HC CDR2 having the amino acid sequence of SEQ ID NO: 888, a HC CDR3 having the amino acid sequence of SEQ ID NO: 889, a LC CDR1 having the amino acid sequence of SEQ ID NO: 890, a LC CDR2 having the amino acid sequence of FAR, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 892; (i) a HC CDR1 having the amino acid sequence of SEQ ID NO: 893, a HC CDR2 having the amino acid sequence of SEQ ID NO: 894, a HC CDR3 having the amino acid sequence of SEQ ID NO: 895, a LC CDR1 having the amino acid sequence of SEQ ID NO: 896, a LC CDR2 having the amino acid sequence of SEQ ID NO: 897, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 898; (j) a HC CDR1 having the amino acid sequence of SEQ ID NO: 901, a HC CDR2 having the amino acid sequence of SEQ ID NO: 902, a HC CDR3 having the amino acid sequence of SEQ ID NO: 903, a LC CDR1 having the amino acid sequence of SEQ ID NO: 904, a LC CDR2 having the amino acid sequence of SEQ ID NO: 905, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 906; (k) a HC CDR1 having the amino acid sequence of SEQ ID NO: 907, a HC CDR2 having the amino acid sequence of SEQ ID NO: 908, a HC CDR3 having the amino acid 7107489sequence of SEQ ID NO: 909, a LC CDR1 having the amino acid sequence of SEQ ID NO: 910, a LC CDR2 having the amino acid sequence of FAK, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 912; or (l) a HC CDR1 having the amino acid sequence of SEQ ID NO: 913, a HC CDR2 having the amino acid sequence of SEQ ID NO: 914, a HC CDR3 having the amino acid sequence of SEQ ID NO: 915, a LC CDR1 having the amino acid sequence of SEQ ID NO: 916, a LC CDR2 having the amino acid sequence of SEQ ID NO: 917, and a LC CDR3 having the amino acid sequence of SEQ ID NO:

918.

44. The bispecific antibody of any one of claims 41-43, wherein the antigen-specific binding site that specifically binds TSLP or TSLPR comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 615 and a VL comprising the amino acid sequence of SEQ ID NO: 616; (b) a VH comprising the amino acid sequence of SEQ ID NO: 635, and a VL comprising the amino acid sequence of SEQ ID NO: 636; (c) a VH comprising the amino acid sequence of SEQ ID NO: 879, and a VL comprising the amino acid sequence of SEQ ID NO: 880; or (d) a VH comprising the amino acid sequence of SEQ ID NO: 899, and a VL comprising the amino acid sequence of SEQ ID NO:

900.

45. The bispecific antibody of any one of claims 1-8, wherein the Th2 cytokine is IL-33.

46. The bispecific antibody of claim 45, wherein the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises: (a) a HC CDR1, a HC CDR2, a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 677, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 678; (b) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 697, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 698; (c) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 717, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 718; or 7107489(d) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 799, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO:

800.

47. The bispecific antibody of claim 45 or 46, wherein the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises: (a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 659, a HC CDR2 having the amino acid sequence of SEQ ID NO: 660, a HC CDR3 having the amino acid sequence of SEQ ID NO: 661, a LC CDR1 having the amino acid sequence of SEQ ID NO: 662, a LC CDR2 having the amino acid sequence of SEQ ID NO: 663, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 664; (b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 665, a HC CDR2 having the amino acid sequence of SEQ ID NO: 666, a HC CDR3 having the amino acid sequence of SEQ ID NO: 667, a LC CDR1 having the amino acid sequence of SEQ ID NO: 668, a LC CDR2 having the amino acid sequence of RDT, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 670; (c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 671, a HC CDR2 having the amino acid sequence of SEQ ID NO: 672, a HC CDR3 having the amino acid sequence of SEQ ID NO: 673, a LC CDR1 having the amino acid sequence of SEQ ID NO: 674, a LC CDR2 having the amino acid sequence of SEQ ID NO: 675, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 676; (d) a HC CDR1 having the amino acid sequence of SEQ ID NO: 679, a HC CDR2 having the amino acid sequence of SEQ ID NO: 680, a HC CDR3 having the amino acid sequence of SEQ ID NO: 681, a LC CDR1 having the amino acid sequence of SEQ ID NO: 682, a LC CDR2 having the amino acid sequence of SEQ ID NO: 683, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 684; (e) a HC CDR1 having the amino acid sequence of SEQ ID NO: 685, a HC CDR2 having the amino acid sequence of SEQ ID NO: 686, a HC CDR3 having the amino acid sequence of SEQ ID NO: 687, a LC CDR1 having the amino acid sequence of SEQ ID NO: 688, a LC CDR2 having the amino acid sequence of AAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 690; (f) a HC CDR1 having the amino acid sequence of SEQ ID NO: 691, a HC CDR2 having the amino acid sequence of SEQ ID NO: 692, a HC CDR3 having the amino acid sequence of SEQ ID NO: 693, a LC CDR1 having the amino acid sequence of SEQ ID NO: 7107489694, a LC CDR2 having the amino acid sequence of SEQ ID NO: 695, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 696; (g) a HC CDR1 having the amino acid sequence of SEQ ID NO: 699, a HC CDR2 having the amino acid sequence of SEQ ID NO: 700, a HC CDR3 having the amino acid sequence of SEQ ID NO: 701, a LC CDR1 having the amino acid sequence of SEQ ID NO: 702, a LC CDR2 having the amino acid sequence of SEQ ID NO: 703, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 704; (h) a HC CDR1 having the amino acid sequence of SEQ ID NO: 705, a HC CDR2 having the amino acid sequence of SEQ ID NO: 706, a HC CDR3 having the amino acid sequence of SEQ ID NO: 707, a LC CDR1 having the amino acid sequence of SEQ ID NO: 708, a LC CDR2 having the amino acid sequence of WAS, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 710; (i) a HC CDR1 having the amino acid sequence of SEQ ID NO: 711, a HC CDR2 having the amino acid sequence of SEQ ID NO: 712, a HC CDR3 having the amino acid sequence of SEQ ID NO: 713, a LC CDR1 having the amino acid sequence of SEQ ID NO: 714, a LC CDR2 having the amino acid sequence of SEQ ID NO: 715, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 716; (j) a HC CDR1 having the amino acid sequence of SEQ ID NO: 801, a HC CDR2 having the amino acid sequence of SEQ ID NO: 802, a HC CDR3 having the amino acid sequence of SEQ ID NO: 803, a LC CDR1 having the amino acid sequence of SEQ ID NO: 804, a LC CDR2 having the amino acid sequence of SEQ ID NO: 805, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 806; (k) a HC CDR1 having the amino acid sequence of SEQ ID NO: 807, a HC CDR2 having the amino acid sequence of SEQ ID NO: 808, a HC CDR3 having the amino acid sequence of SEQ ID NO: 809, a LC CDR1 having the amino acid sequence of SEQ ID NO: 810, a LC CDR2 having the amino acid sequence of FTN, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 812; or (l) a HC CDR1 having the amino acid sequence of SEQ ID NO: 813, a HC CDR2 having the amino acid sequence of SEQ ID NO: 814, a HC CDR3 having the amino acid sequence of SEQ ID NO: 815, a LC CDR1 having the amino acid sequence of SEQ ID NO: 816, a LC CDR2 having the amino acid sequence of SEQ ID NO: 817, and a LC CDR3 having the amino acid sequence of SEQ ID NO:

818. 710748948. The bispecific antibody of any one of claims 45-47, wherein the antigen-specific binding site that specifically binds IL-33 or IL-33R comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 677 and a VL comprising the amino acid sequence of SEQ ID NO: 678; or (b) a VH comprising the amino acid sequence of SEQ ID NO: 799, and a VL comprising the amino acid sequence of SEQ ID NO:

800.

49. The bispecific antibody of any one of claims 1 to 5, wherein the antigen-specific binding site that specifically binds to the Th2 cytokine or a receptor thereof is of a VH and / or a VL of any one of the antibodies in Table 2.

50. The bispecific antibody of any one of claims 1-49, wherein the bispecific antibody retains the binding affinity to KLK5 and KLK7 of no more than 20% difference relative to an anti-KLK5 / KLK7 antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody.

51. The bispecific antibody of any one of claims 1-50, wherein the bispecific antibody retains the binding affinity of no more than 20% difference to a Th2 target relative to a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody.

52. The bispecific antibody of any one of claims 1-51, wherein the bispecific antibody retains at least 80% of inhibitory activity to KLK5 and KLK7 relative to an anti-KLK5 / KLK7 antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody.

53. The bispecific antibody of any one of claims 1-52, wherein the bispecific antibody retains at least 80% of inhibitory activity to a Th2 signaling relative to a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody.

54. A composition comprising the bispecific antibody of any one of claims 1-53 and an acceptable carrier.

55. A method comprising administering the bispecific antibody of any one of claims 1-53 or the composition of claim 54 to a subject.

56. The method of claim 55, wherein the subject has a skin barrier defect. 710748957. A method of treating a skin barrier defect, the method comprising administering to a subject an effective amount of the bispecific antibody of any one of claims 1-53 or the composition of claim 54.

58. The method of claim 56 or 57, wherein the skin barrier defect is associated with Netherton syndrome, atopic dermatitis, eosinophilic esophagitis, prurigo nodularis, chronic pruritus of unknown origin (CPUO), dry skin, asthma (KLK5 specifically), ichthyosis vulgaris, or itch or chronic itch.

59. The method of any one of claims 55-58, wherein the subject has atopic dermatitis.

60. The method of claim 55-59, wherein the administration reduces ear thickness by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody.

61. The method of any one of claims 55-60, wherein the administration reduces ear thickness by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody.

62. The method of any one of claims 55-61, wherein the administration reduces skin erythema / hemorrhage by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody.

63. The method of any one of claims 55-62, wherein the administration reduces skin erythema / hemorrhage by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody.

64. The method of any one of claims 55-63, wherein the administration reduces skin erythema / hemorrhage by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody. 710748965. The method of any one of claims 55-64, wherein the administration reduces skin excoriation / erosion by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody.

66. The method of any one of claims 55-65, wherein the administration reduces skin scaling / dryness by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody.

67. The method of any one of claims 55-66, wherein the administration reduces skin scaling / dryness by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody.

68. The method of any one of claims 55-67, wherein the administration reduces skin edema by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody.

69. The method of any one of claims 55-68, wherein the administration reduces skin edema by more than 30% relative to a subject administered a Th2 targeting antibody that comprises the same CDRs and / or VH / VL as the bispecific antibody. 7107489

Images