Kallikrein antibodies and uses thereof

HK40137788APending Publication Date: 2026-09-18TRIVENI BIO INC
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Patent Information

Application Number
HK62026125698
Authority / Receiving Office
HK · HK
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-03-07
Filing Date
2026-07-03
Publication Date
2026-09-18
Estimated Expiration
2044-03-07

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Abstract

Aspects of the application provide anti-KLK5 antibodies, anti-KLK7 antibodies, and anti-KLK5 / KLK7 antibodies (e.g., 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.
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Description

Abstract This application provides various aspects of anti-KLK5 antibodies, anti-KLK7 antibodies, and anti-KLK5 / KLK7 antibodies (e.g., bispecific antibodies), as well as methods of using these antibodies to promote barrier function, reduce inflammation, and treat conditions such as Natherton syndrome, eosinophilic esophagitis, and atopic dermatitis.

Claims

CLAIMSWhat is claimed is:

1. An antibody specifically binds to KLK5, the antibody comprising(a) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 3, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 11;(b) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 10, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 11.;(c) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 14, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 11;(d) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 16, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 11;(e) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 18, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 11;(f) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 24, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 29;(g) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 28, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 29;(h) 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: 37.(i) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 36, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 29;(j) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 42, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 43;(k) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 46, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 43;(l) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 49, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 43;(m) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 51, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 43;(n) a HC CDR1, HC CDR2 and 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: 43;(o) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 58, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 59; or(p) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 64, and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 65.

2. The antibody of claim 1, wherein the antibody comprises:(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: 9, 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: 7, a HC CDR2 having the amino acid sequence of SEQ ID NO: 8, a HC CDR3 having the amino acid sequence of SEQ ID NO: 9, 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;(c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 12, a HC CDR2 having the amino acid sequence of SEQ ID NO: 13, a HC CDR3 having the amino acid sequence of SEQ ID NO: 9, 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;(d) a HC CDR1 having the amino acid sequence of SEQ ID NO: 15, a HC CDR2 having the amino acid sequence of SEQ ID NO: 13, a HC CDR3 having the amino acid sequence of SEQ ID NO: 9, 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;(e) a HC CDR1 having the amino acid sequence of SEQ ID NO: 12, a HC CDR2 having the amino acid sequence of SEQ ID NO: 13, a HC CDR3 having the amino acid sequence of SEQ ID NO: 17, 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;(f) a HC CDR1 having the amino acid sequence of SEQ ID NO: 19, a HC CDR2 having the amino acid sequence of SEQ ID NO: 20, a HC CDR3 having the amino acid sequence of SEQ ID NO: 21, a LC CDR1 having the amino acid sequence of SEQ ID NO: 22, a LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 34;(g) a HC CDR1 having the amino acid sequence of SEQ ID NO: 25, a HC CDR2 having the amino acid sequence of SEQ ID NO: 26, a HC CDR3 having the amino acid sequence of SEQ ID NO: 27, a LC CDR1 having the amino acid sequence of SEQ ID NO: 22, a LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 34;(h) a HC CDR1 having the amino acid sequence of SEQ ID NO: 30, a HC CDR2 having the amino acid sequence of SEQ ID NO: 26, a HC CDR3 having the amino acid sequence of SEQ ID NO: 31, a LC CDR1 having the amino acid sequence of SEQ ID NO: 22, a LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 35;(i) a HC CDR1 having the amino acid sequence of SEQ ID NO: 30, a HC CDR2 having the amino acid sequence of SEQ ID NO: 26, a HC CDR3 having the amino acid sequence of SEQ ID NO: 33, a LC CDR1 having the amino acid sequence of SEQ ID NO:22, a LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 34;(j) a HC CDR1 having the amino acid sequence of SEQ ID NO: 38, a HC CDR2 having the amino acid sequence of SEQ ID NO: 39, a HC CDR3 having the amino acid sequence of SEQ ID NO: 40, 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: 41;(k) a HC CDR1 having the amino acid sequence of SEQ ID NO: 44, a HC CDR2 having the amino acid sequence of SEQ ID NO: 45, a HC CDR3 having the amino acid sequence of SEQ ID NO: 40, 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: 41;(l) a HC CDR1 having the amino acid sequence of SEQ ID NO: 47, a HC CDR2 having the amino acid sequence of SEQ ID NO: 48, a HC CDR3 having the amino acid sequence of SEQ ID NO: 40, 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: 41;(m) a HC CDR1 having the amino acid sequence of SEQ ID NO: 47, a HC CDR2 having the amino acid sequence of SEQ ID NO: 48, a HC CDR3 having the amino acid sequence of SEQ ID NO: 50, 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: 41;(n) a HC CDR1 having the amino acid sequence of SEQ ID NO: 44, a HC CDR2 having the amino acid sequence of SEQ ID NO: 45, a HC CDR3 having the amino acid sequence of SEQ ID NO: 52, 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: 41;(o) a HC CDR1 having the amino acid sequence of SEQ ID NO: 54, a HC CDR2 having the amino acid sequence of SEQ ID NO: 55, a HC CDR3 having the amino acid sequence of SEQ ID NO: 56, 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: 57; or(p) a HC CDR1 having the amino acid sequence of SEQ ID NO: 60, a HC CDR2 having the amino acid sequence of SEQ ID NO: 61, a HC CDR3 having the amino acidsequence of SEQ ID NO: 62, 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: 63.

3. The antibody of claim 1 or 2, wherein the antibody comprises:(a) a VH comprising the amino acid sequence of SEQ ID NO: 3 and a VL comprising the amino acid sequence of SEQ ID NO: 11;(b) a VH comprising the amino acid sequence of SEQ ID NO: 10, and a VL comprising the amino acid sequence of SEQ ID NO: 11.;(c) a VH comprising the amino acid sequence of SEQ ID NO: 14, and a LC CDR1, LC CDR2 and a VL comprising the amino acid sequence of SEQ ID NO: 11;(d) a VH comprising the amino acid sequence of SEQ ID NO: 16, and a VL comprising the amino acid sequence of SEQ ID NO: 11;(e) a VH comprising the amino acid sequence of SEQ ID NO: 18, and a VL comprising the amino acid sequence of SEQ ID NO: 11;(f) a VH comprising the amino acid sequence of SEQ ID NO: 24, and a VL comprising the amino acid sequence of SEQ ID NO: 29;(g) a VH comprising the amino acid sequence of SEQ ID NO: 28, and a VL comprising the amino acid sequence of SEQ ID NO: 29;(h) a VH comprising the amino acid sequence of SEQ ID NO: 32, and a VL comprising the amino acid sequence of SEQ ID NO: 37.(i) a VH comprising the amino acid sequence of SEQ ID NO: 36, and a VL comprising the amino acid sequence of SEQ ID NO: 29;(j) a VH comprising the amino acid sequence of SEQ ID NO: 42, and a VL comprising the amino acid sequence of SEQ ID NO: 43;(k) a VH comprising the amino acid sequence of SEQ ID NO: 46, and a VL comprising the amino acid sequence of SEQ ID NO: 43;(l) a VH comprising the amino acid sequence of SEQ ID NO: 49, and a VL comprising the amino acid sequence of SEQ ID NO: 43;(m) a VH comprising the amino acid sequence of SEQ ID NO: 51, and a VL comprising the amino acid sequence of SEQ ID NO: 43;(n) a VH comprising the amino acid sequence of SEQ ID NO: 53, and a VH comprising the amino acid sequence of SEQ ID NO: 43;(o) a VH comprising the amino acid sequence of SEQ ID NO: 58, and a VH comprising the amino acid sequence of SEQ ID NO: 59; or(p) a VH comprising the amino acid sequence of SEQ ID NO: 64, and a VH comprising the amino acid sequence of SEQ ID NO: 65.

4. An antibody specifically binds to KLK7, the antibody comprising:(a) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 72 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 73;(b) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 199 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 200;(c) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 77 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 78;(d) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 80 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 78;(e) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 80 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 82;(f) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 84 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 78;(g) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 87 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 88;(h) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 285 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 82;(i) comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 98 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 97;(j) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 153 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 97;(k) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 103 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 104;(l) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 107 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 108;(m) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 111 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 97;(n) comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 115 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 116;(o) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 121 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 122;(p) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 127 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 128;(q) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 133 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 134;(r) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 139 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 140.(s) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 145 and a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 146; or(t) a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 151 and a LC CDR1, LC CDR2 andLC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 152.

5. The antibody of claim 4, wherein the antibody comprises:(a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 66, a HC CDR2 having the amino acid sequence of SEQ ID NO: 67, a HC CDR3 having the amino acid sequence of SEQ ID NO: 68, a LC CDR1 having the amino acid sequence of SEQ ID NO: 69, a LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 71;(b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 74, a HC CDR2 having the amino acid sequence of SEQ ID NO: 67, a HC CDR3 having the amino acid sequence of SEQ ID NO: 75, a LC CDR1 having the amino acid sequence of SEQ ID NO: 69, a LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 198;(c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 284, a HC CDR2 having the amino acid sequence of SEQ ID NO: 201, a HC CDR3 having the amino acid sequence of SEQ ID NO: 68, a LC CDR1 having the amino acid sequence of SEQ ID NO: 69, a LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 76;(d) a HC CDR1 having the amino acid sequence of SEQ ID NO: 284, a HC CDR2 having the amino acid sequence of SEQ ID NO: 79, a HC CDR3 having the amino acid sequence of SEQ ID NO: 68, a LC CDR1 having the amino acid sequence of SEQ ID NO: 69, a LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 76;(e) a HC CDR1 having the amino acid sequence of SEQ ID NO: 284, a HC CDR2 having the amino acid sequence of SEQ ID NO: 79, a HC CDR3 having the amino acid sequence of SEQ ID NO: 68, a LC CDR1 having the amino acid sequence of SEQ ID NO: 69, a LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 81;(f) a HC CDR1 having the amino acid sequence of SEQ ID NO: 284, a HC CDR2 having the amino acid sequence of SEQ ID NO: 79, a HC CDR3 having the amino acid sequence of SEQ ID NO: 83, a LC CDR1 having the amino acid sequence of SEQ ID NO: 69, a LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 76;(g) a HC CDR1 having the amino acid sequence of SEQ ID NO: 284, a HC CDR2 having the amino acid sequence of SEQ ID NO: 79, a HC CDR3 having the amino acid sequence of SEQ ID NO: 85, a LC CDR1 having the amino acid sequence of SEQ ID NO: 69, a LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 86;(h) a HC CDR1 having the amino acid sequence of SEQ ID NO: 284, a HC CDR2 having the amino acid sequence of SEQ ID NO: 79, a HC CDR3 having the amino acid sequence of SEQ ID NO: 89, a LC CDR1 having the amino acid sequence of SEQ ID NO: 69, a LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 81;(i) a HC CDR1 having the amino acid sequence of SEQ ID NO: 90, a HC CDR2 having the amino acid sequence of SEQ ID NO: 91, a HC CDR3 having the amino acid sequence of SEQ ID NO: 92, a LC CDR1 having the amino acid sequence of SEQ ID NO: 93, a LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 95;(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: 109, a HC CDR3 having the amino acid sequence of SEQ ID NO: 92, a LC CDR1 having the amino acid sequence of SEQ ID NO: 93, a LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 95;(k) a HC CDR1 having the amino acid sequence of SEQ ID NO: 99, a HC CDR2 having the amino acid sequence of SEQ ID NO: 100, a HC CDR3 having the amino acid sequence of SEQ ID NO: 101, a LC CDR1 having the amino acid sequence of SEQ ID NO: 93, a LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 102;(l) a HC CDR1 having the amino acid sequence of SEQ ID NO: 99, a HC CDR2 having the amino acid sequence of SEQ ID NO: 100, a HC CDR3 having the amino acid sequence of SEQ ID NO: 105, a LC CDR1 having the amino acid sequence of SEQ ID NO: 93, a LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 106;(m) 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: 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:93, a LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 95;(n) a HC CDR1 having the amino acid sequence of SEQ ID NO: 66, a HC CDR2 having the amino acid sequence of SEQ ID NO: 112, a HC CDR3 having the amino acid sequence of SEQ ID NO: 113, 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: 114;(o) a HC CDR1 having the amino acid sequence of SEQ ID NO: 117, a HC CDR2 having the amino acid sequence of SEQ ID NO: 118, a HC CDR3 having the amino acid sequence of SEQ ID NO: 119, 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: 120;(p) a HC CDR1 having the amino acid sequence of SEQ ID NO: 123, a HC CDR2 having the amino acid sequence of SEQ ID NO: 124, a HC CDR3 having the amino acid sequence of SEQ ID NO: 125, 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: 126;(q) a HC CDR1 having the amino acid sequence of SEQ ID NO: 19, a HC CDR2 having the amino acid sequence of SEQ ID NO: 20, a HC CDR3 having the amino acid sequence of SEQ ID NO: 129, a LC CDR1 having the amino acid sequence of SEQ ID NO: 130, a LC CDR2 having the amino acid sequence of SEQ ID NO: 131, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 132;(r) a HC CDR1 having the amino acid sequence of SEQ ID NO: 135, a HC CDR2 having the amino acid sequence of SEQ ID NO: 136, a HC CDR3 having the amino acid sequence of SEQ ID NO: 137, a LC CDR1 having the amino acid sequence of SEQ ID NO: 130, a LC CDR2 having the amino acid sequence of SEQ ID NO: 131, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 138;(s) a HC CDR1 having the amino acid sequence of SEQ ID NO: 38, a HC CDR2 having the amino acid sequence of SEQ ID NO: 141, a HC CDR3 having the amino acid sequence of SEQ ID NO: 142, a LC CDR1 having the amino acid sequence of SEQ ID NO: 23, a LC CDR2 having the amino acid sequence of SEQ ID NO: 144, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 145; or(t) a HC CDR1 having the amino acid sequence of SEQ ID NO: 147, a HC CDR2 having the amino acid sequence of SEQ ID NO: 148, a HC CDR3 having the amino acidsequence of SEQ ID NO: 149, a LC CDR1 having the amino acid sequence of SEQ ID NO: 143, a LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 150.

6. The antibody of claim 4 or 5, wherein the antibody comprises:(a) a VH comprising the amino acid sequence of SEQ ID NO: 72 and a VL comprising the amino acid sequence of SEQ ID NO: 73;(b) a VH comprising the amino acid sequence of SEQ ID NO: 199 and a VL comprising the amino acid sequence of SEQ ID NO: 200;(c) a VH comprising the amino acid sequence of SEQ ID NO: 77 and a VL comprising the amino acid sequence of SEQ ID NO: 78;(d) a VH comprising the amino acid sequence of SEQ ID NO: 80 and a VL comprising the amino acid sequence of SEQ ID NO: 78;(e) a VH comprising the amino acid sequence of SEQ ID NO: 80 and a VL comprising the amino acid sequence of SEQ ID NO: 82;(f) a VH comprising the amino acid sequence of SEQ ID NO: 84 and a VL comprising the amino acid sequence of SEQ ID NO: 78;(g) a VH comprising the amino acid sequence of SEQ ID NO: 87 and a VL comprising the amino acid sequence of SEQ ID NO: 88;(h) a VH comprising the amino acid sequence of SEQ ID NO: 285 and a VL comprising the amino acid sequence of SEQ ID NO: 82;(i) a VH comprising the amino acid sequence of SEQ ID NO: 98 and a VL comprising the amino acid sequence of SEQ ID NO: 97;(j) a VH comprising the amino acid sequence of SEQ ID NO: 153 and a VL comprising the amino acid sequence of SEQ ID NO: 97;(k) a VH comprising the amino acid sequence of SEQ ID NO: 103 and a VL comprising the amino acid sequence of SEQ ID NO: 104;(l) a VH comprising the amino acid sequence of SEQ ID NO: 107 and a VL comprising the amino acid sequence of SEQ ID NO: 108;(m) a VH comprising the amino acid sequence of SEQ ID NO: 111 and a VL comprising the amino acid sequence of SEQ ID NO: 97;(n) a VH comprising the amino acid sequence of SEQ ID NO: 115 and a VL comprising the amino acid sequence of SEQ ID NO: 116;(o) a VH comprising the amino acid sequence of SEQ ID NO: 121 and a VL comprising the amino acid sequence of SEQ ID NO: 122;(p) a VH comprising the amino acid sequence of SEQ ID NO: 127 and a VL comprising the amino acid sequence of SEQ ID NO: 128;(q) a VH comprising the amino acid sequence of SEQ ID NO: 133 and a VL comprising the amino acid sequence of SEQ ID NO: 134;(r) a VH comprising the amino acid sequence of SEQ ID NO: 139 and a VL comprising the amino acid sequence of SEQ ID NO: 140;(s) a VH comprising the amino acid sequence of SEQ ID NO: 145 and a VL comprising the amino acid sequence of SEQ ID NO: 146; or(t) a VH comprising the amino acid sequence of SEQ ID NO: 151 and a VL comprising the amino acid sequence of SEQ ID NO: 152.

7. A bispecific antibody comprising a first antigen specific binding site from an anti- KLK5 antibody selected from Table la and Table lb, and second antigen specific binding site from an anti-KLK7 antibody selected from Table 2a and Table 2b.

8. The bispecific antibody of claim 7, wherein the bispecific antibody comprises pairs of anti-KLK5 antibodies and anti-KLK7 antibodies as listed in Table 4.

9. The bispecific antibody of claim 7 or 8, wherein the bispecific antibody comprises a HC CDR1, a HC CDR2, a HC CDR3, a LC CDR1, a LC CDR2, and a LC CDR3 of an anti- KLK5 antibody selected from Table la and Table lb, and a HC CDR1, a HC CDR2, a HC CDR3, a LC CDR1, a LC CDR2, and a LC CDR3 of an anti-KLK7 antibody selected from Table 2a and Table 2b.

10. The bispecific antibody of any one of claims 7-9, wherein the bispecific antibody binds to the active site of KLK5.

11. The bispecific antibody of any one of claims 7-10, wherein the bispecific antibody binds to the active site of KLK7.

12. The bispecific antibody of any one of claims 7-11, wherein the bispecific antibody competes with SPINK5 and / or leupeptin for binding of the KLK5 active site.

13. The bispecific antibody of any one of claims 7-12, wherein the bispecific antibody competes with SPINK5 and / or leupeptin for binding of the KLK7 active site.

14. The bispecific antibody of any one of claims 7-13, wherein the bispecific antibody binds to the active form of KLK5 but not the inactive form of KLK5.

15. The bispecific antibody of any one of claims 7-14, wherein the bispecific antibody binds to the active form of KLK7 but not the inactive form of KLK7.

16. The bispecific antibody of any one of claims 7-15, wherein the bispecific antibody inhibits the protease activity of KLK5.17 The bispecific antibody of any one of claims 7-16, wherein the bispecific antibody inhibits the protease activity of KLK7.18 The bispecific antibody of any one of claims 7-17, wherein the bispecific antibody is not cleaved in the heavy chain by KLK5 on binding to KLK5.

19. The bispecific antibody of any one of claims 7-18, wherein the bispecific antibody is not cleaved in the heavy chain by KLK7 on binding to KLK7.

20. The bispecific antibody of any one of claims 7-19, wherein the bispecific antibody comprises:(a) a first arm comprising:(i) a HC CDR1, a HC CDR2, and a HC CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 28, and(ii) a LC CDR1, a LC CDR2, and a LC CDR3 of a light chain variable region(VL) comprising the amino sequence of SEQ ID NO: 29; and(b) a second arm comprising:(i) a HC CDR1, a HC CDR2, and a HC CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 285, and(ii) a LC CDR1, a LC CDR2, and a LC CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 82.

21. The bispecific antibody of any one of claims 7-20, wherein the bispecific antibody comprises:(a) a first arm comprising a HC CDR1 comprising the amino acid sequence of SEQ ID NO: 25, a HC CDR2 comprising the amino acid sequence of SEQ ID NO: 26, a HC CDR3 comprising the amino acid sequence of SEQ ID NO: 27, a LC CDR1 comprising the amino acid sequence of SEQ ID NO: 22, a LC CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and a LC CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and(b) a second arm comprising a HC CDR1 comprising the amino acid sequence of SEQ ID NO: 284, a HC CDR2 comprising the amino acid sequence of SEQ ID NO: 79, a HC CDR3 comprising the amino acid sequence of SEQ ID NO: 89, a LC CDR1 comprising the amino acid sequence of SEQ ID NO: 69, a LC CDR2 comprising the amino acid sequence of SEQ ID NO: 70, and a LC CDR3 comprising the amino acid sequence of SEQ ID NO: 81.

22. The bispecific antibody of any one of claims 7-21, wherein the bispecific antibody comprises:(a) a first arm comprising a VH comprising the amino acid of SEQ ID NO: 28 and a VL comprising the amino acid sequence of SEQ ID NO: 29; and(b) a second arm comprising a VH comprising the amino acid sequence of SEQ ID NO: 285 and a VL comprising the amino acid sequence of SEQ ID NO: 82.

23. A composition comprising the antibody of any one of claims 1-6, or the bispecific antibody of any one of claims 7-22, and optionally an acceptable carrier.

24. A nucleic acid encoding the antibody of any one of claims 1-6, or the bispecific antibody of any one of claims 7-22.

25. A method of treating a skin barrier defect, the method comprising administering to a subject an effective amount of the antibody of any one of claims 1-6, or the bispecific antibody of any one of claims 7-22.

26. The antibody of any one of claims 1-6, the bispecific antibody of any one of claims 7- 22, or the composition of claim 10 for use in a method of treating a skin barrier defect.

27. The method of claim 26, wherein the skin barrier defect 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.

28. The antibody, bispecific antibody, or composition for use according to claim 27, wherein the skin barrier defect 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.