Kallikrein antibodies and their use

Abstract

Aspects of this application provide anti-KLK5 antibodies, anti-KLK7 antibodies, and anti-KLK5 / KLK7 antibodies (e.g., bispecific antibodies), as well as methods of using them to promote barrier function, reduce inflammation, and treat conditions such as Netherton syndrome, eosinophilic esophagitis, and atopic dermatitis. Certain aspects of this disclosure relate to the recognition that a loss of balance between endogenous KLK proteases and associated protease inhibitors can lead to barrier dysfunction and induce inflammation (see, for example, Figure 1), which can result in inflammatory conditions, such as Netherton syndrome, eosinophilic esophagitis, and atopic dermatitis.

Description

[Technical Field]

[0001] Related applications This application claims priority under 35 United States Code § 119(e) to U.S. Provisional Patent Application, USSN 63 / 489,419 (filed on 9 March 2023) and U.S. Provisional Patent Application, USSN 63 / 562,304 (filed on 7 March 2024), the entire contents of which are incorporated herein by reference.

[0002] Reference to electronic sequence listings The contents of the electronic sequence listing (A14070000WO00-SEQ-LJG.xml; size: 279,377 bytes; and creation date: March 8, 2024) are incorporated herein by reference in their entirety. [Background technology]

[0003] Kallikrein (KLK) enzymes regulate desquamation and innate immunity, supporting skin homeostasis and wound healing. In 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 the major activator of this proteolytic cascade. Self-activated KLK5 enzymatically converts pro-KLK7 and pro-KLK14 into their active forms, stimulating a positive feedback loop that leads to the production of more pro-KLK5 via KLK14. These KLK enzymes are suppressed by endogenous serine protease inhibitors, such as lymphoepithelial Cazal-type-associated inhibitors. Dysregulation of KLK, including KLK5 and KLK7, is associated with skin disorders, inflammatory diseases, and cancer. For example, hyperactive kallikrein 5 and 7 can cause both hereditary and spontaneous epidermal barrier disorders (e.g., Netherton syndrome, eosinophilic esophagitis, atopic dermatitis). [Overview of the project] [Means for solving the problem]

[0004] Certain aspects of this disclosure relate to the recognition that a loss of balance between endogenous KLK proteases and associated protease inhibitors can cause barrier dysfunction and induce inflammation (see, for example, Figure 1), which can lead to inflammatory conditions such as Netherton syndrome, eosinophilic esophagitis, and atopic dermatitis. Some embodiments provide methods and related compositions useful for inhibiting KLK5 and / or KLK7 for the purpose of restoring disease severity, improving barrier function, and reducing inflammation. Aspects of this disclosure provide anti-KLK5 antibodies that have high binding affinity and specificity to KLK5 and inhibit KLK5 activity. Further aspects of this disclosure provide anti-KLK7 antibodies that have high binding affinity and specificity to KLK7 and inhibit KLK7 activity. Further aspects of the present disclosure provide anti-KLK5 / KLK7 antibodies (e.g., bispecific antibodies targeting KLK5 and KLK7) that have high binding affinity and specificity to both KLK5 and KLK7 and inhibit the activity of KLK5 and KLK7. Accordingly, in some embodiments, the present disclosure provides methods, antibodies for use in methods, and related antibody compositions for treating conditions associated with KLK5 and KLK7 dysregulation, such as Netherton syndrome, atopic dermatitis (with and without filaggrin mutations), eosinophilic esophagitis, prurigo nodosa, chronic pruritus of unknown cause (CPUO), asthma (e.g., KLK5-associated asthma), and ichthyosis vulgaris.

[0005] The preceding and other aspects, embodiments, actions, functions, features, and embodiments of this instruction can be better understood from the following description in conjunction with the accompanying drawings.

[0006] The accompanying drawings, incorporated herein and constituting part thereof, illustrate certain embodiments and, together with the written description, are useful in providing non-limiting examples of certain aspects of the compositions and methods disclosed herein. [Brief explanation of the drawing]

[0007] [Figure 1]This chart shows abnormal protease activation (e.g., abnormal KLK5, KLK7, and KLK14) that can lead to skin barrier deficiency-related diseases.

[0008] [Figure 2A] The relative response curves for anti-KLK5 antibodies (Figures 2A-2D) that bind to either the active form of human KLK5 (hKLK5) or the proform of hKLK5, and anti-KLK7 antibodies (Figures 2F-2I) that bind to either the active form of human KLK7 (hKLK7) or the proform of hKLK7 are shown. The anti-KLK5 antibodies KLK5-L1-Ab2 (Figure 2A), KLK5-L2-Ab3 (Figure 2B), KLK5-L3-Ab5 (Figure 2C), and KLK5-L2-Ab4 (Figure 2D) bind only to the active form of hKLK5, while the anti-KLK7 antibodies KLK7-L2-Ab4 (Figure 2F), KLK7-L2-Ab5 (Figure 2G), KLK7-L5-Ab2 (Figure 2H), and KLK7-L1-Ab7 (Figure 2I) bind only to the active form of hKLK7. The anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2×KLK7-L1-Ab8 has been shown to bind only to the active forms of hKLK5 (Figure 2E) and hKLK7 (Figure 2J). [Figure 2B] The relative response curves for anti-KLK5 antibodies (Figures 2A-2D) that bind to either the active form of human KLK5 (hKLK5) or the proform of hKLK5, and anti-KLK7 antibodies (Figures 2F-2I) that bind to either the active form of human KLK7 (hKLK7) or the proform of hKLK7 are shown. The anti-KLK5 antibodies KLK5-L1-Ab2 (Figure 2A), KLK5-L2-Ab3 (Figure 2B), KLK5-L3-Ab5 (Figure 2C), and KLK5-L2-Ab4 (Figure 2D) bind only to the active form of hKLK5, while the anti-KLK7 antibodies KLK7-L2-Ab4 (Figure 2F), KLK7-L2-Ab5 (Figure 2G), KLK7-L5-Ab2 (Figure 2H), and KLK7-L1-Ab7 (Figure 2I) bind only to the active form of hKLK7. The anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2×KLK7-L1-Ab8 has been shown to bind only to the active forms of hKLK5 (Figure 2E) and hKLK7 (Figure 2J). [Figure 2C]The relative response curves for anti-KLK5 antibodies (Figures 2A-2D) that bind to either the active form of human KLK5 (hKLK5) or the proform of hKLK5, and anti-KLK7 antibodies (Figures 2F-2I) that bind to either the active form of human KLK7 (hKLK7) or the proform of hKLK7 are shown. The anti-KLK5 antibodies KLK5-L1-Ab2 (Figure 2A), KLK5-L2-Ab3 (Figure 2B), KLK5-L3-Ab5 (Figure 2C), and KLK5-L2-Ab4 (Figure 2D) bind only to the active form of hKLK5, while the anti-KLK7 antibodies KLK7-L2-Ab4 (Figure 2F), KLK7-L2-Ab5 (Figure 2G), KLK7-L5-Ab2 (Figure 2H), and KLK7-L1-Ab7 (Figure 2I) bind only to the active form of hKLK7. The anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2×KLK7-L1-Ab8 has been shown to bind only to the active forms of hKLK5 (Figure 2E) and hKLK7 (Figure 2J). [Figure 2D] The relative response curves for anti-KLK5 antibodies (Figures 2A-2D) that bind to either the active form of human KLK5 (hKLK5) or the proform of hKLK5, and anti-KLK7 antibodies (Figures 2F-2I) that bind to either the active form of human KLK7 (hKLK7) or the proform of hKLK7 are shown. The anti-KLK5 antibodies KLK5-L1-Ab2 (Figure 2A), KLK5-L2-Ab3 (Figure 2B), KLK5-L3-Ab5 (Figure 2C), and KLK5-L2-Ab4 (Figure 2D) bind only to the active form of hKLK5, while the anti-KLK7 antibodies KLK7-L2-Ab4 (Figure 2F), KLK7-L2-Ab5 (Figure 2G), KLK7-L5-Ab2 (Figure 2H), and KLK7-L1-Ab7 (Figure 2I) bind only to the active form of hKLK7. The anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2×KLK7-L1-Ab8 has been shown to bind only to the active forms of hKLK5 (Figure 2E) and hKLK7 (Figure 2J). [Figure 2E]The relative response curves for anti-KLK5 antibodies (Figures 2A-2D) that bind to either the active form of human KLK5 (hKLK5) or the proform of hKLK5, and anti-KLK7 antibodies (Figures 2F-2I) that bind to either the active form of human KLK7 (hKLK7) or the proform of hKLK7 are shown. The anti-KLK5 antibodies KLK5-L1-Ab2 (Figure 2A), KLK5-L2-Ab3 (Figure 2B), KLK5-L3-Ab5 (Figure 2C), and KLK5-L2-Ab4 (Figure 2D) bind only to the active form of hKLK5, while the anti-KLK7 antibodies KLK7-L2-Ab4 (Figure 2F), KLK7-L2-Ab5 (Figure 2G), KLK7-L5-Ab2 (Figure 2H), and KLK7-L1-Ab7 (Figure 2I) bind only to the active form of hKLK7. The anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2×KLK7-L1-Ab8 has been shown to bind only to the active forms of hKLK5 (Figure 2E) and hKLK7 (Figure 2J). [Figure 2F] The relative response curves for anti-KLK5 antibodies (Figures 2A-2D) that bind to either the active form of human KLK5 (hKLK5) or the proform of hKLK5, and anti-KLK7 antibodies (Figures 2F-2I) that bind to either the active form of human KLK7 (hKLK7) or the proform of hKLK7 are shown. The anti-KLK5 antibodies KLK5-L1-Ab2 (Figure 2A), KLK5-L2-Ab3 (Figure 2B), KLK5-L3-Ab5 (Figure 2C), and KLK5-L2-Ab4 (Figure 2D) bind only to the active form of hKLK5, while the anti-KLK7 antibodies KLK7-L2-Ab4 (Figure 2F), KLK7-L2-Ab5 (Figure 2G), KLK7-L5-Ab2 (Figure 2H), and KLK7-L1-Ab7 (Figure 2I) bind only to the active form of hKLK7. The anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2×KLK7-L1-Ab8 has been shown to bind only to the active forms of hKLK5 (Figure 2E) and hKLK7 (Figure 2J). [Figure 2G]The relative response curves for anti-KLK5 antibodies (Figures 2A-2D) that bind to either the active form of human KLK5 (hKLK5) or the proform of hKLK5, and anti-KLK7 antibodies (Figures 2F-2I) that bind to either the active form of human KLK7 (hKLK7) or the proform of hKLK7 are shown. The anti-KLK5 antibodies KLK5-L1-Ab2 (Figure 2A), KLK5-L2-Ab3 (Figure 2B), KLK5-L3-Ab5 (Figure 2C), and KLK5-L2-Ab4 (Figure 2D) bind only to the active form of hKLK5, while the anti-KLK7 antibodies KLK7-L2-Ab4 (Figure 2F), KLK7-L2-Ab5 (Figure 2G), KLK7-L5-Ab2 (Figure 2H), and KLK7-L1-Ab7 (Figure 2I) bind only to the active form of hKLK7. The anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2×KLK7-L1-Ab8 has been shown to bind only to the active forms of hKLK5 (Figure 2E) and hKLK7 (Figure 2J). [Figure 2H] The relative response curves for anti-KLK5 antibodies (Figures 2A-2D) that bind to either the active form of human KLK5 (hKLK5) or the proform of hKLK5, and anti-KLK7 antibodies (Figures 2F-2I) that bind to either the active form of human KLK7 (hKLK7) or the proform of hKLK7 are shown. The anti-KLK5 antibodies KLK5-L1-Ab2 (Figure 2A), KLK5-L2-Ab3 (Figure 2B), KLK5-L3-Ab5 (Figure 2C), and KLK5-L2-Ab4 (Figure 2D) bind only to the active form of hKLK5, while the anti-KLK7 antibodies KLK7-L2-Ab4 (Figure 2F), KLK7-L2-Ab5 (Figure 2G), KLK7-L5-Ab2 (Figure 2H), and KLK7-L1-Ab7 (Figure 2I) bind only to the active form of hKLK7. The anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2×KLK7-L1-Ab8 has been shown to bind only to the active forms of hKLK5 (Figure 2E) and hKLK7 (Figure 2J). [Figure 2I]The relative response curves for anti-KLK5 antibodies (Figures 2A-2D) that bind to either the active form of human KLK5 (hKLK5) or the proform of hKLK5, and anti-KLK7 antibodies (Figures 2F-2I) that bind to either the active form of human KLK7 (hKLK7) or the proform of hKLK7 are shown. The anti-KLK5 antibodies KLK5-L1-Ab2 (Figure 2A), KLK5-L2-Ab3 (Figure 2B), KLK5-L3-Ab5 (Figure 2C), and KLK5-L2-Ab4 (Figure 2D) bind only to the active form of hKLK5, while the anti-KLK7 antibodies KLK7-L2-Ab4 (Figure 2F), KLK7-L2-Ab5 (Figure 2G), KLK7-L5-Ab2 (Figure 2H), and KLK7-L1-Ab7 (Figure 2I) bind only to the active form of hKLK7. The anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2×KLK7-L1-Ab8 has been shown to bind only to the active forms of hKLK5 (Figure 2E) and hKLK7 (Figure 2J). [Figure 2J] The relative response curves for anti-KLK5 antibodies (Figures 2A-2D) that bind to either the active form of human KLK5 (hKLK5) or the proform of hKLK5, and anti-KLK7 antibodies (Figures 2F-2I) that bind to either the active form of human KLK7 (hKLK7) or the proform of hKLK7 are shown. The anti-KLK5 antibodies KLK5-L1-Ab2 (Figure 2A), KLK5-L2-Ab3 (Figure 2B), KLK5-L3-Ab5 (Figure 2C), and KLK5-L2-Ab4 (Figure 2D) bind only to the active form of hKLK5, while the anti-KLK7 antibodies KLK7-L2-Ab4 (Figure 2F), KLK7-L2-Ab5 (Figure 2G), KLK7-L5-Ab2 (Figure 2H), and KLK7-L1-Ab7 (Figure 2I) bind only to the active form of hKLK7. The anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2×KLK7-L1-Ab8 has been shown to bind only to the active forms of hKLK5 (Figure 2E) and hKLK7 (Figure 2J).

[0009] [Figure 3A]These are SDS-PAGE results showing antibodies alone or after incubation with either hKLK5 (Figure 3A) or hKLK7 (Figure 3B). The anti-KLK5 antibody KLK5-L2-Ab2 is resistant to cleavage by hKLK5, but KLK5-L3-Ab7 and KLK-L1-Ab5 undergo heavy chain cleavage by hKLK5. [Figure 3B] These are SDS-PAGE results showing antibodies alone or after incubation with either hKLK5 (Figure 3A) or hKLK7 (Figure 3B). The anti-KLK7 antibodies KLK7-L1-Ab8, KLK7-L2-Ab3, KLK7-L3-Ab2, KLK7-L4-Ab2, and KLK7-L5-Ab2 are resistant to cleavage by hKLK7.

[0010] [Figure 4A] This shows the binding activity of the anti-KLK5 antibody to KLK1 compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK5 family members or related proteases. [Figure 4B] This shows the binding activity of the anti-KLK5 antibody to KLK2 compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK5 family members or related proteases. [Figure 4C] This shows the binding activity of the anti-KLK5 antibody to KLK4 compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK5 family members or related proteases. [Figure 4D] This shows the binding activity of the anti-KLK5 antibody to KLK6 compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK5 family members or related proteases. [Figure 4E]This shows the binding activity of the anti-KLK5 antibody to KLK12 compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK5 family members or related proteases. [Figure 4F] This shows the binding activity of the anti-KLK5 antibody to KLK14 compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK5 family members or related proteases. [Figure 4G] This shows the binding activity of the anti-KLK5 antibody to plasma KLK compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK5 family members or related proteases. [Figure 4H] This shows the binding activity of the anti-KLK5 antibody to trypsin compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK5 family members or related proteases. [Figure 4I] This shows the binding activity of anti-KLK5 antibodies to chymotrypsin compared to isotype controls. Since the test antibody's relative activity is not higher than that of the isotype controls, it does not specifically inhibit non-KLK5 family members or related proteases. [Figure 4J] This shows the binding activity of the anti-KLK5 antibody to urokinase compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK5 family members or related proteases. [Figure 4K] In follow-up studies, the anti-KLK5 antibody again demonstrated binding activity to KLK6 compared to the isotype control. Because the test antibody's relative activity was not higher than that of the isotype control, it did not specifically inhibit non-KLK5 family members or related proteases.

[0011] [Figure 5A]This shows the binding activity of the anti-KLK7 antibody to KLK1 compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK7 family members or related proteases. [Figure 5B] This shows the binding activity of the anti-KLK7 antibody to KLK2 compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK7 family members or related proteases. [Figure 5C] This shows the binding activity of the anti-KLK7 antibody to KLK4 compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK7 family members or related proteases. [Figure 5D] This shows the binding activity of the anti-KLK7 antibody to KLK6 compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK7 family members or related proteases. [Figure 5E] This shows the binding activity of the anti-KLK7 antibody to KLK12 compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK7 family members or related proteases. [Figure 5F] This shows the binding activity of the anti-KLK7 antibody to KLK14 compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK7 family members or related proteases. [Figure 5G] This shows the binding activity of the anti-KLK7 antibody to plasma KLK compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK7 family members or related proteases. [Figure 5H] This shows the binding activity of the anti-KLK7 antibody to trypsin compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK7 family members or related proteases. [Figure 5I] This shows the binding activity of the anti-KLK7 antibody to chymotrypsin compared to the isotype control. Since the test antibody does not have higher relative activity than the isotype control, it does not specifically inhibit non-KLK7 family members or related proteases. [Figure 5J] This shows the binding activity of the anti-KLK7 antibody to urokinase compared to the isotype control. The test antibody does not specifically inhibit non-KLK7 family members or related proteases because its relative activity is not higher than that of the isotype control.

[0012] [Figure 6] This shows the binding activity of anti-KLK5 / anti-KLK7 bispecific antibodies to various concentrations of KLK13 compared to isotype controls.

[0013] [Figure 7] Figures A and B show the relative response of the anti-KLK5 antibody KLK5-L1-Ab5 binding in the presence of hKLK5 alone, or in the presence of the serine protease inhibitors PMSF (Figure 7A), leupeptin, or SPINK5 (Figure 7B).

[0014] [Figure 8A] The relative response of anti-KLK5 antibody KLK5-L2-Ab2 binding is shown in the presence of hKLK5 alone, or in the presence of the serine protease inhibitors PMSF (Figure 8A), leupeptin, or SPINK5 (Figure 8B). [Figure 8B] The relative response of anti-KLK5 antibody KLK5-L2-Ab2 binding is shown in the presence of hKLK5 alone, or in the presence of the serine protease inhibitors PMSF (Figure 8A), leupeptin, or SPINK5 (Figure 8B).

[0015] [Figure 9]Figures A and B show the relative response of the anti-KLK5 antibody KLK5-L3-Ab7 binding in the presence of hKLK5 alone, or in the presence of the serine protease inhibitors PMSF (Figure 9A), leupeptin, or SPINK5 (Figure 9B).

[0016] [Figure 10] Figures A and B show the relative response of the anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2 × KLK7-L1-Ab8 binding in the presence of hKLK5 alone or the serine protease inhibitors PMSF (Figure 10A), leupeptin, or SPINK5 (Figure 10B).

[0017] [Figure 11A] This shows the relative response of the anti-KLK7 antibody KLK7-L1-Ab8 binding to hKLK7 alone or in the presence of the serine protease inhibitors PMSF or SPINK5. [Figure 11B] This shows the relative response of the anti-KLK7 antibody KLK7-L2-Ab3 binding to hKLK7 alone, or in the presence of the serine protease inhibitor PMSF or SPINK5. [Figure 11C] This shows the relative response of the anti-KLK7 antibody KLK7-L3-Ab2 binding to hKLK7 alone, or in the presence of the serine protease inhibitor PMSF or SPINK5. [Figure 11D] This shows the relative response of the anti-KLK7 antibody KLK7-L4-Ab2 binding to hKLK7 alone, or in the presence of the serine protease inhibitor PMSF or SPINK5. [Figure 11E] This shows the relative response of the anti-KLK7 antibody KLK7-L5-Ab2 binding to hKLK7 alone or in the presence of the serine protease inhibitor PMSF or SPINK5. [Figure 11F] This shows the relative response of the anti-KLK7 antibody KLK7-L1-Ab8 binding to hKLK7 alone or in the presence of the serine protease inhibitors PMSF or SPINK5. [Figure 11G]This study shows the relative response of the anti-KLK7 / anti-KLK5 bispecific antibody KLK5-L2-Ab2 × KLK7-L1-Ab8 binding to hKLK7 alone or in the presence of the serine protease inhibitor PMSF or SPINK5.

[0018] [Figure 12A] The competitive binding of KLK5 (Figures 12A-12D) and KLK7 (Figures 12E-12F) between anti-KLK5 or anti-KLK7 antibodies and SPINK5, which binds to the active sites of KLK5 and KLK7, is shown. When anti-KLK5 antibodies KLK5-L1-Ab5 (Figure 12A), KLK5-L2-Ab2 (Figure 12B), or KLK5-L3-Ab7 (Figure 12C) are conjugated to the chip and KLK5 is added, the binding curve increases. Adding a second anti-KLK5 antibody ("mAb#2") or SPINK5 does not increase binding. When anti-KLK7 antibody KLK7-L1-Ab5 (Figure 12E) is conjugated to the chip and KLK7 is added, the binding curve increases. Adding an isotype control or SPINK5 does not increase binding. Alternatively, if SPINK5 is bound to the chip and either KLK5 (Figure 12D) or KLK7 (Figure 12F) is added, the binding curve increases. The reason why the binding does not increase when an anti-KLK5 antibody (Figure 12D) or anti-KLK7 antibody (Figure 12F) is added is that SPINK5 is already bound to the active site of KLK5 or KLK7. [Figure 12B]The competitive binding of KLK5 (Figures 12A-12D) and KLK7 (Figures 12E-12F) between anti-KLK5 or anti-KLK7 antibodies and SPINK5, which binds to the active sites of KLK5 and KLK7, is shown. When anti-KLK5 antibodies KLK5-L1-Ab5 (Figure 12A), KLK5-L2-Ab (Figure 12B), or KLK5-L3-Ab7 (Figure 12C) are conjugated to the chip and KLK5 is added, the binding curve increases. Adding a second anti-KLK5 antibody ("mAb#2") or SPINK5 does not increase binding. When anti-KLK7 antibody KLK7-L1-Ab5 (Figure 12E) is conjugated to the chip and KLK7 is added, the binding curve increases. Adding an isotype control or SPINK5 does not increase binding. Alternatively, if SPINK5 is bound to the chip and either KLK5 (Figure 12D) or KLK7 (Figure 12F) is added, the binding curve increases. The reason why the binding does not increase when an anti-KLK5 antibody (Figure 12D) or anti-KLK7 antibody (Figure 12F) is added is that SPINK5 is already bound to the active site of KLK5 or KLK7. [Figure 12C] The competitive binding of KLK5 (Figures 12A-12D) and KLK7 (Figures 12E-12F) between anti-KLK5 or anti-KLK7 antibodies and SPINK5, which binds to the active sites of KLK5 and KLK7, is shown. When anti-KLK5 antibodies KLK5-L1-Ab5 (Figure 12A), KLK5-L2-Ab (Figure 12B), or KLK5-L3-Ab7 (Figure 12C) are conjugated to the chip and KLK5 is added, the binding curve increases. Adding a second anti-KLK5 antibody ("mAb#2") or SPINK5 does not increase binding. When anti-KLK7 antibody KLK7-L1-Ab5 (Figure 12E) is conjugated to the chip and KLK7 is added, the binding curve increases. Adding an isotype control or SPINK5 does not increase binding. Alternatively, if SPINK5 is bound to the chip and either KLK5 (Figure 12D) or KLK7 (Figure 12F) is added, the binding curve increases. The reason why the binding does not increase when an anti-KLK5 antibody (Figure 12D) or anti-KLK7 antibody (Figure 12F) is added is that SPINK5 is already bound to the active site of KLK5 or KLK7. [Figure 12D]The competitive binding of KLK5 (Figures 12A-12D) and KLK7 (Figures 12E-12F) between anti-KLK5 or anti-KLK7 antibodies and SPINK5, which binds to the active sites of KLK5 and KLK7, is shown. When anti-KLK5 antibodies KLK5-L1-Ab5 (Figure 12A), KLK5-L2-Ab (Figure 12B), or KLK5-L3-Ab7 (Figure 12C) are conjugated to the chip and KLK5 is added, the binding curve increases. Adding a second anti-KLK5 antibody ("mAb#2") or SPINK5 does not increase binding. When anti-KLK7 antibody KLK7-L1-Ab5 (Figure 12E) is conjugated to the chip and KLK7 is added, the binding curve increases. Adding an isotype control or SPINK5 does not increase binding. Alternatively, if SPINK5 is bound to the chip and either KLK5 (Figure 12D) or KLK7 (Figure 12F) is added, the binding curve increases. The reason why the binding does not increase when an anti-KLK5 antibody (Figure 12D) or anti-KLK7 antibody (Figure 12F) is added is that SPINK5 is already bound to the active site of KLK5 or KLK7. [Figure 12E] The competitive binding of KLK5 (Figures 12A-12D) and KLK7 (Figures 12E-12F) between anti-KLK5 or anti-KLK7 antibodies and SPINK5, which binds to the active sites of KLK5 and KLK7, is shown. When anti-KLK5 antibodies KLK5-L1-Ab5 (Figure 12A), KLK5-L2-Ab (Figure 12B), or KLK5-L3-Ab7 (Figure 12C) are conjugated to the chip and KLK5 is added, the binding curve increases. Adding a second anti-KLK5 antibody ("mAb#2") or SPINK5 does not increase binding. When anti-KLK7 antibody KLK7-L1-Ab5 (Figure 12E) is conjugated to the chip and KLK7 is added, the binding curve increases. Adding an isotype control or SPINK5 does not increase binding. Alternatively, if SPINK5 is bound to the chip and either KLK5 (Figure 12D) or KLK7 (Figure 12F) is added, the binding curve increases. The reason why the binding does not increase when an anti-KLK5 antibody (Figure 12D) or anti-KLK7 antibody (Figure 12F) is added is that SPINK5 is already bound to the active site of KLK5 or KLK7. [Figure 12F]The competitive binding of KLK5 (Figures 12A-12D) and KLK7 (Figures 12E-12F) between anti-KLK5 or anti-KLK7 antibodies and SPINK5, which binds to the active sites of KLK5 and KLK7, is shown. When anti-KLK5 antibodies KLK5-L1-Ab5 (Figure 12A), KLK5-L2-Ab (Figure 12B), or KLK5-L3-Ab7 (Figure 12C) are conjugated to the chip and KLK5 is added, the binding curve increases. Adding a second anti-KLK5 antibody ("mAb#2") or SPINK5 does not increase binding. When anti-KLK7 antibody KLK7-L1-Ab5 (Figure 12E) is conjugated to the chip and KLK7 is added, the binding curve increases. Adding an isotype control or SPINK5 does not increase binding. Alternatively, if SPINK5 is bound to the chip and either KLK5 (Figure 12D) or KLK7 (Figure 12F) is added, the binding curve increases. The reason why the binding does not increase when an anti-KLK5 antibody (Figure 12D) or anti-KLK7 antibody (Figure 12F) is added is that SPINK5 is already bound to the active site of KLK5 or KLK7.

[0019] [Figure 13] This study demonstrates the effect of treatment with either the anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2×KLK7-L1-Ab8 or comparative antibody #1 at 30 mg / kg on stratum corneum thickness in the MC903 atopic dermatitis mouse model. Treatment with the KLK5-L2-Ab2×KLK7-L1-Ab8 antibody significantly reduced thickness. ***p<0.001;**p<0.01;*p<0.05, one-way ANOVA with Dunnett's multiple comparisons.

[0020] [Figure 14A] This shows the therapeutic efficacy of the anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2×KLK7-L1-Ab8 compared to topical tacrolimus ointment and comparative antibody #1 in a mouse model of Nc / Nga atopic dermatitis, regarding disease presentation. This was measured by clinical ear thickness. ***p<0.001;**p<0.01;*p<0.05, one-way ANOVA with Dunnett's multiple comparisons. [Figure 14B]This shows the therapeutic efficacy of the anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2×KLK7-L1-Ab8 compared to topical tacrolimus ointment and comparative antibody #1 in a mouse model of Nc / Nga atopic dermatitis, regarding disease presentation. This was measured by epidermal area. ***p<0.001;**p<0.01;*p<0.05, one-way ANOVA with Dunnett's multiple comparisons. [Figure 14C] This shows the therapeutic efficacy of the anti-KLK5 / anti-KLK7 bispecific antibody KLK5-L2-Ab2×KLK7-L1-Ab8 compared to topical tacrolimus ointment and comparative antibody #1 in a mouse model of Nc / Nga atopic dermatitis, regarding disease presentation. This was measured by itching. ***p<0.001;**p<0.01;*p<0.05, calculated using one-way ANOVA with Dunnett's multiple comparisons. [Modes for carrying out the invention]

[0021] This disclosure is at least in part based on the development of inhibitory anti-KLK5 antibodies and variants thereof that have high binding affinity and specificity to KLK5. Also provided are methods for using anti-KLK5 antibodies and variants thereof in research, diagnostic / detection, and therapeutic applications, as well as anti-KLK5 antibodies for use in such applications. This disclosure is further in part based on the development of inhibitory anti-KLK7 antibodies and variants thereof that have high binding affinity and specificity to KLK7. Also provided are methods for using anti-KLK7 antibodies and variants thereof in research, diagnostic / detection, and therapeutic applications, as well as anti-KLK7 antibodies for use in such applications. This disclosure is further in part based on the development of inhibitory anti-KLK5 / KLK7 antibodies (e.g., multispecific antibodies, e.g., bispecific antibodies) and variants thereof that have high binding affinity and specificity to both KLK5 and KLK7. Also provided are methods for using anti-KLK5 / KLK7 antibodies and variants thereof in research, diagnostic / detection, and therapeutic applications.

[0022] The preceding and other aspects, embodiments, actions, functions, features, and embodiments of this instruction can be better understood from the following description in conjunction with the accompanying drawings.

[0023] I. Definition To administer: As used herein, the terms “to administer” or “to administer” mean to provide an antibody or a composition thereof to a subject in a physiologically and / or pharmacologically useful manner (for example, to treat a condition of the subject).

[0024] Affinity-matured antibodies: In this specification, “affinity-matured antibodies” are used to refer to antibodies in which one or more modifications have been made to one or more CDRs that result in improved affinity (e.g., KD, kd, or ka) for a target antigen compared to an unmodified parent antibody. Exemplary affinity-matured antibodies may, in some embodiments, have nanomolar or even picomolar affinity for a target antigen. Various procedures are available for generating affinity-matured antibodies, including screening of combination antibody libraries prepared using biodisplay. For example, Marks et al., BioTechnology, 10:779-783 (1992) describe affinity maturation by shuffling of VH and VL domains. Random mutagenesis of CDRs and / or framework residues has been 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 mutagenesis sites and selective mutations at contact sites with activity-enhancing amino acid residues or at hypermutagenic sites have been described in U.S. Patent No. 6,914,128B1.

[0025] Antibody: As used herein, the term “antibody” refers to a polypeptide comprising at least one immunoglobulin variable domain containing at least one distinct antigen-specific binding site, or a portion of an immunoglobulin variable domain (a paratope or a portion thereof) containing at least one distinct antigen-specific binding site. In some embodiments, the antibody comprises at least one distinct antigen-specific binding site that specifically binds to the active site of an enzyme. In some embodiments, the antibody is a full-length antibody. In some embodiments, the antibody is a chimeric antibody. In some embodiments, the antibody is a humanized antibody. However, in some embodiments, the antibody is a Fab fragment, an F(ab')2 fragment, an Fv fragment, or an scFv fragment. In some embodiments, the antibody is a multispecific antibody (e.g., a bispecific antibody). In some embodiments, the antibody is a nanobody derived from a camelid antibody or a nanobody derived from a shark antibody. In some embodiments, the antibody is a diabody. In some embodiments, the antibody comprises a framework having a human germline sequence. In another embodiment, the 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, the antibody comprises a heavy (H) chain variable region (abbreviated herein as VH) and / or a light (L) chain variable region (abbreviated herein as VL). In some embodiments, the antibody comprises a constant domain, e.g., an Fc region. The immunoglobulin constant domain refers to either a heavy chain constant domain or a light chain constant domain. The amino acid sequences of the constant domains of human IgG heavy and light chains and their functional variations are known. With respect to the heavy chain, in some embodiments, the heavy chain of the antibody described herein may be an alpha (α), delta (Δ), epsilon (ε), gamma (γ), or mu (μ) heavy chain. In some embodiments, the heavy chains of the antibodies described herein may include human alpha (α), delta (Δ), epsilon (ε), gamma (γ), or mu (μ) heavy chains. In certain embodiments, the antibodies described herein include the CH1, CH2, and / or CH3 domains of human gamma 1. In some embodiments, V HThe amino acid sequence of the domain includes the amino acid sequence of the human gamma (γ) heavy chain constant region, such as any known in the art. Non-limiting examples of human constant region sequences are described in the art; see, for example, U.S. Patent No. 5,693,780 and Kabat EA et al., (1991) cited above. In some embodiments, V HThe domains include an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or at least 99% identical to any of the variable chain constant regions provided herein. In some embodiments, the antibody is modified, for example, by glycosylation, phosphorylation, SUMOylation, and / or methylation. In some embodiments, the antibody is a glycosylated antibody conjugated to one or more sugar or carbohydrate molecules. In some embodiments, one or more sugar or carbohydrate molecules are conjugated to the antibody via N-glycosylation, O-glycosylation, C-glycosylation, glyciation (GPI anchor attachment), and / or phosphoglycosylation. In some embodiments, one or more sugar or carbohydrate molecules are monosaccharides, disaccharides, oligosaccharides, or glycans. In some embodiments, one or more sugar or carbohydrate molecules are branched oligosaccharides or branched glycans. In some embodiments, one or more sugar or carbohydrate molecules include mannose units, glucose units, N-acetylglucosamine units, or phospholipid units. In some embodiments, the antibody is a construct comprising a polypeptide containing one or more antigen-binding fragments of the present disclosure linked to a linker polypeptide or an immunoglobulin constant domain. The linker polypeptide contains two or more amino acid residues joined by a peptide bond and is used to link one or more antigen-binding moieties. Examples of linker polypeptides have been reported (see, for example, Holliger, P., et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448; Poljak, RJ, et al. (1994) Structure 2:1121-11233). Furthermore, the antibody may be part of a larger immunoadhesion molecule formed by the covalent or non-covalent association of the antibody or antibody moiety with one or more other proteins or peptides.Examples of such immunoadhesion molecules include the use of streptavidin core regions to construct tetrameric scFv molecules (Kipriyanov, SM, et al. (1995) Human Antibodies and Hybridomas 6:93-101), and the use of cysteine ​​residues, marker peptides, and C-terminal polyhistidine tags to construct divalent biotinylated scFv molecules (Kipriyanov, SM, et al. (1994) Mol.Immunol.31:1047-1058).

[0026] Approximately: As used herein, the terms “approximately” or “about” refer to values ​​similar to the described reference values ​​when applied to the values ​​of one or more subjects. In certain embodiments, unless otherwise stated or evident from the content (except where such numbers may exceed 100% of the possible values), the terms “approximately” or “about” refer to a range of values ​​that fall within 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, and 1% or less in either direction (above or below) the described reference values.

[0027] Bispecific antibodies: As used herein, the term “bispecific antibodies” refers to an antibody containing two distinct antigen-specific binding sites, or, in combination, two antibodies (covalently or noncovalently) linked, each containing two distinct antigen-specific binding sites. Non-limiting examples of the format or structure of bispecific antibodies 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, the full contents of each of these are incorporated herein by reference.

[0028] CDR: As used herein, the term “CDR” refers to the complementarity-determining region within the antibody variable sequence. A typical antibody molecule contains a heavy chain variable region (VH) and a light chain variable region (VL), which are usually involved in antigen binding. The VH and VL regions can be further subdivided into hypervariable regions also known as “complementarity-determining regions” (“CDR”) and more conserved regions known as “framework regions” (“FR”). Each VH and VL typically consists of three CDRs and four FRs, arranged from the amino terminus to the carboxyl terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The extent of the framework regions and CDRs can be precisely identified using methodologies known in the art, such as the Kabat definition, IMGT definition, Chothia definition, AbM definition, and / or contact definition, all of which are well known in the art.For example, Kabat, EA, et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, USDepartment of Health and Human Services, NIH Publication No. 91-3242; IMGT (registered trademark), the international ImMunoGeneTics information system (registered trademark) 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. See al(1997)J.Molec.Biol.273:927-948; and Almagro,J.Mol.Recognit.17:132-143(2004). See also hgmp.mrc.ac.uk and bioinf.org.uk / abs. As used herein, CDR may mean CDR as defined by any method known in the art.Two antibodies having the same CDR means that the amino acid sequences of the CDRs of the two antibodies are the same, as determined by the same method, for example, the IMGT definition.

[0029] In certain embodiments, three CDRs are present in each of the variable regions of the heavy and light chains, and these are designated as CDR1, CDR2, and CDR3 with respect to each variable region. As used herein, the term “CDR set” refers to a group of three CDRs occurring in a single variable region capable of binding to an antigen. The exact boundaries of these CDRs are defined differently depending on the system. The system described by Kabat (Kabat et al., Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987) and (1991)) not only provides a clear residue numbering system applicable to any variable region of an antibody, but also provides precise residue boundaries that define three CDRs. These CDRs are sometimes called Kabat CDRs. The sub-parts of the CDRs may be designated as L1, L2, and L3, or H1, H2, and H3, where "L" and "H" represent the light chain region and heavy chain region, respectively. These regions are sometimes called Chothia CDRs and have boundaries that overlap with Kabat CDRs. Other boundaries that define CDRs that overlap with Kabat CDRs are described by Padlan (FASEB J.9:133-139 (1995)) and MacCallum (J Mol Biol This is described in 262(5):732-45(1996). Furthermore, other CDR boundary definitions may not strictly adhere to one of the above systems and, although they overlap with Kabat CDRs, they may be shortened or extended in consideration of predictions or experimental results that certain residues or groups of residues, or even the entire CDR, do not significantly affect antigen binding. The methods used herein may utilize CDRs defined according to any of these systems, but preferred embodiments use Kabat or Chothia-defined CDRs.

[0030] CDR-transplanted antibody: As used herein, the term "CDR-transplanted antibody" refers to an antibody that contains heavy chain variable region sequences and light chain variable region sequences derived from one species, but in which one or more sequences of the VH and / or VL CDR regions are replaced with CDR sequences from another species. For example, in an antibody having mouse heavy chain variable region and light chain variable region, one or more mouse CDRs (e.g., CDR3) are replaced with human CDR sequences.

[0031] Chimeric antibody: As used herein, the term "chimeric antibody" refers to an antibody that contains a heavy chain variable region sequence and a light chain variable region sequence derived from one species and a constant region sequence derived from another species, such as an antibody in which the mouse heavy chain variable region and light chain variable region are linked to the human constant region.

[0032] Complementary: As used herein, the term “complementary” refers to the ability of two nucleotides or two sets of nucleotides to form a precise pairing. Specifically, complementarity is a term that characterizes the degree of hydrogen bond pairing that results in a bond between two nucleotides or two sets of nucleotides. For example, if a base at one position of an oligonucleotide can form a hydrogen bond with a base at a corresponding position in a target nucleic acid (e.g., mRNA), then those bases are considered complementary to each other at that position. Base pairings can include both canonical Watson-Crick base pairings and non-Watson-Crick base pairings (e.g., Wobble base pairings and Hoogsteen base pairings). For example, in some embodiments, in the case of complementary base pairing, an adenosine-type base (A) is complementary to a thymidine-type base (T) or a uracil-type base (U), a cytosine-type base (C) is complementary to a guanosine-type base (G), and universal bases such as 3-nitropyrrole or 5-nitroindole can hybridize to any A, C, U, or T and are considered complementary to them. Inosine (I) is also considered a universal base in the art and is considered complementary to any of A, C, U, or T.

[0033] Conservative amino acid substitutions: As used herein, “conservative amino acid substitutions” refer to amino acid substitutions that do not alter the relative charge or size properties of the protein being substituted. Variants can be prepared according to methods of modifying polypeptide sequences known to those skilled in the art, for example, according to references that summarize 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 according to methods found in Current Protocols in Molecular Biology, FMAusubel, et al., eds., John Wiley & Sons, Inc., New York. Conservative amino acid substitutions include substitutions made between amino acids in 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.

[0034] Cross-reactivity: As used herein, the term “cross-reactivity” refers to the property of a drug to specifically bind to multiple antigens of similar type or class (e.g., multiple homologous, paralogous, or orthologous antigens) with similar affinity or binding strength. For example, in some embodiments, an antibody that cross-reactive to human and non-human primate antigens of similar type or class (e.g., human KLK5 and non-human primate KLK5, human KLK7 and non-human primate KLK7) can bind to human and non-human primate antigens with similar affinity or binding strength. In some embodiments, the antibody cross-reactive to human and rodent antigens of similar type or class. In some embodiments, the antibody cross-reactive to rodent antigens and non-human primate antigens of similar type or class. In some embodiments, the antibody cross-reactive to human, non-human primate, and rodent antigens of similar type or class.

[0035] Effective dose: As used herein, “effective dose” refers to the amount of each activator (e.g., anti-KLK5 antibody, anti-KLK7 antibody, anti-KLK5 / KLK7 antibody) required to deliver the desired effect (e.g., therapeutic effect on a subject), either alone or in combination with one or more other activators. In some embodiments, the therapeutic effect is a reduction in KLK5 and / or KLK7 activity and / or relief of a disease (e.g., Netherton syndrome, eosinophilic esophagitis, and atopic dermatitis) or related symptoms, such as an improvement in barrier function.

[0036] Framework: As used herein, the terms “framework” or “framework sequence” refer to the sequence remaining after removing the CDRs from the variable region. Since the precise definition of a CDR sequence can be determined by various systems, the meaning of the framework sequence is also subject to different interpretations accordingly. The six CDRs (CDR-L1, CDR-L2, and CDR-L3 of the light chain, and CDR-H1, CDR-H2, and CDR-H3 of the heavy chain) divide the framework regions of the light and heavy chains into four sub-regions (FR1, FR2, FR3, and FR4) on each chain, with CDR1 located between FR1 and FR2, CDR2 between FR2 and FR3, and CDR3 between FR3 and FR4. When a framework region is referred to by others without specifying a particular sub-region as FR1, FR2, FR3, or FR4, it represents a combination of FRs within the variable region of a single naturally occurring immunoglobulin chain. As used herein, FR represents one of four subregions, and multiple FRs represent two or more of the four subregions that constitute a framework region. Human heavy and light chain acceptor sequences are known in the art. In one embodiment, acceptor sequences known in the art may be used in the antibodies disclosed herein.

[0037] Human Antibodies: As used herein, the term “human antibody” is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences. The human antibodies of this disclosure may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-directed mutagenesis in vitro, or by somatic mutation in vivo) in the CDR, specifically CDR3. However, as used herein, the term “human antibody” is not intended to include antibodies in which a CDR sequence derived from the germline of another mammalian species, such as mouse, has been transplanted into a human framework sequence.

[0038] Humanized antibody: As used herein, the term "humanized antibody" includes heavy chain variable region sequences and light chain variable region sequences derived from non-human species (e.g., mouse), but V H and / or V L This refers to antibodies in which at least a portion of the sequence has been modified to be more "human-like," that is, to more closely resemble human germline variable sequences. One type of humanized antibody is a CDR-transplant antibody in which a human CDR sequence is introduced into non-human VH and VL sequences to replace the corresponding non-human CDR sequence. In one embodiment, a humanized antibody is provided. Such an antibody may be produced by obtaining a mouse monoclonal antibody using conventional hybridoma technology and then humanizing it using in vitro genetic engineering, such as that disclosed in PCT publication number WO2005 / 123126 A2 by Kasaian et al.

[0039] A humanized antibody is a human immunoglobulin (recipient antibody) in which residues from the recipient's complementarity-determining region (CDR) are replaced with residues from the CDR of a non-human species (donor antibody), such as mouse, rat, or rabbit, having the desired specificity, affinity, and capabilities. In some embodiments, Fv framework region (FR) residues of the human immunoglobulin are replaced with corresponding non-human residues. Furthermore, the humanized antibody may include residues not found in the recipient antibody or the transferred CDR or framework sequence, but included to further improve and optimize the antibody's performance. Generally, a humanized antibody may include substantially all of at least one, typically two, variable domains, where all or substantially all of the CDR region corresponds to that of a non-human immunoglobulin, and all or substantially all of the FR region corresponds to that of the human immunoglobulin consensus sequence. The humanized antibody also includes, optimally, at least a portion of the immunoglobulin constant region or domain (Fc), typically at least a portion of the constant region or domain (Fc) of the human immunoglobulin. Antibodies may have modified Fc regions as described in WO99 / 58572. Other forms of humanized antibodies have one or more modified CDRs (1, 2, 3, 4, 5, 6) relative to the original antibody, also called one or more CDRs derived from one or more CDRs of the original antibody. Humanized antibodies may also undergo affinity maturation.

[0040] In some embodiments, humanization involves using a CDR (e.g., one shown in Table 1a, 1b, 2a, or 2b) to create a human variable domain (e.g., IGKV1-NL1). * 01 and IGHV1-3 * This is achieved by transplanting (01 human variable domain). In some embodiments, the antibodies of this disclosure are humanized variants comprising one or more amino acid substitutions (e.g., in the VH framework region) compared to any one of the VHs listed in Table 1a, 1b, 2a, or 2b, and / or comprising one or more amino acid substitutions (e.g., in the VL framework region) compared to any one of the VLs listed in Table 1a, 1b, 2a, or 2b.

[0041] Isolated Antibodies: As used herein, “isolated antibodies” is intended to refer to antibodies that substantially contain other antibodies with different antigen specificities (for example, an isolated antibody that specifically binds to KLK5 substantially contains antibodies that specifically bind to antigens other than KLK5, an isolated antibody that specifically binds to KLK7 substantially contains antibodies that specifically bind to antigens other than KLK7, and an isolated antibody that specifically binds to both KLK5 and KLK7 substantially contains antibodies that specifically bind to antigens other than KLK5 and KLK7). However, isolated antibodies may cross-reactive to other antigens in some embodiments. Furthermore, isolated antibodies may substantially contain other cellular material and / or chemical substances.

[0042] Kabat Numbering: As used herein, the terms “Kabat Numbering,” “Kabat Definition,” and “Kabat Labeling” are interchangeable. These terms, as recognized in the art, refer to a system for numbering amino acid residues that are more variable than other amino acid residues (i.e., hypervariable) in the heavy chain variable region and light chain variable region of an antibody, or in their antigen-binding regions (Kabat et al. (1971) Ann. NY Acad, Sci. 190:382-391 and Kabat, EA, et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, USD Department of Health and Human Services, NIH Publication No. 91-3242). In the heavy chain variable region, the hypervariable region ranges from amino acid positions 31-35 in CDR1, from amino acid positions 50-65 in CDR2, and from amino acid positions 95-102 in CDR3. In the case of the light chain variable region, the hypervariable region is located at amino acid positions 24-34 in CDR1, amino acid positions 50-56 in CDR2, and amino acid positions 89-97 in CDR3.

[0043] Multispecific antigen-binding molecule: As used herein, the term “multispecific antigen-binding molecule” refers to a molecule containing two or more antigen-specific binding sites. In some embodiments, the multispecific antigen-binding molecule is a multispecific antibody (e.g., a bispecific antibody).

[0044] Multispecific antibody: As used herein, the term “multispecific antibody” refers to an antibody comprising at least two distinct antigen-specific binding sites, or, in combination, at least two (covalently or noncovalently) linked antibodies comprising at least two distinct antigen-specific binding sites. In some embodiments, a multispecific antibody is a bispecific antibody. Non-limiting examples of the format or structure of multispecific antibodies 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 full contents of each of these are incorporated herein by reference.

[0045] Recombinant Antibody: As used herein, the term "recombinant antibody" is intended to include all antibodies prepared, expressed, created, or isolated by recombinant means, such as an antibody expressed using a recombinant expression vector transfected into a host cell (described in more detail in the present disclosure), which includes, for example, an antibody 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), an antibody isolated from an animal (e.g., mouse) into which a human immunoglobulin gene has been transfected (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 an antibody prepared, expressed, created, or isolated by any other method involving splicing a human immunoglobulin gene sequence to another DNA sequence. 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. However, in certain embodiments, such recombinant human antibodies are subjected to in vitro mutagenesis (or, if an animal into which a human Ig sequence has been transfected is used, in vivo somatic mutagenesis), and thus, the amino acid sequences of the V H region and V L region are the human germline V H sequences and V LThese are sequences that originate from and are associated with other sequences, but may not naturally exist within the in vivo human antibody germline repertoire. One embodiment of the present disclosure provides, for example, a fully human antibody capable of binding to human KLK5 or KLK7, which can be generated using a suitable technique, such as, but not limited to, a human Ig phage library disclosed in PCT publication number WO2005 / 007699 A2 by Jermutus et al.

[0046] Selective: As used herein, the terms “selective” or “selectively” refer to the ability of a molecule to produce an effect (e.g., inhibition, antagonism, agonization, etc.) on its target molecule compared to a reference molecule. For example, a molecule that selectively inhibits its target molecule means that this molecule can inhibit the target molecule to a degree that is distinguishable from the reference molecule in an inhibition assay or other inhibition situation. For example, with respect to an inhibitor, the term “selectively inhibits” refers to the ability of the inhibitor to inhibit the target molecule to a degree that is distinguishable from a reference molecule that does not substantially inhibit it in an inhibition assay, to the extent that it enables selective inhibition of the target molecule, as described herein. After the reaction is complete, the signal produced by the inhibition of the target molecule can be measured. The maximum half-molecule inhibitor concentrations for the target molecule and the reference molecule can be calculated.

[0047] Specific binding: As used herein, the term “specifically binding” refers to the ability of a molecule to bind to a binding partner with an affinity or binding strength sufficient to enable the use of the molecule to distinguish the binding partner from a suitable control in a binding assay or other binding context. With respect to an antibody, the term “specifically binding” refers to the ability of an antibody to bind to a specific antigen with an affinity or binding strength sufficient to enable the use of the antibody to distinguish a particular antigen from others, as described herein, compared to a suitable reference antigen(s). In some embodiments, the antibody has K for binding to a target. D However, at least about 10 -4 M, 10 -5 M, 10 -6M, 10 -7 M, 10 -8 M, 10 -9 M, 10 -10 M, 10 -11 M, 10 -12 M, 10 -13 If the antibody is M or less, it binds specifically to the target. In some embodiments, the antibody binds specifically to KLK5 or KLK7.

[0048] Subject: As used herein, the term "subject" refers to mammals. In some embodiments, the subject is a non-human primate or rodent. In some embodiments, the subject is a human. In some embodiments, the subject is a patient who has or is suspected of having a disease, e.g., a human patient.

[0049] Treatment: As used herein, the terms “to treat” or “treatment” mean the application or administration of a composition comprising one or more activators (e.g., anti-KLK5 antibody, anti-KLK7 antibody, anti-KLK5 / KLK7 antibody) to a subject with a target disease or disorder, symptoms of a disease / disorder, or predisposition to a disease / disorder, with the aim of treating, curing, alleviating, reducing, modifying, resuscitating, improving, or influencing the disorder, symptoms of a disease, or predisposition to a disease or disorder. Alleviation of a target disease / disorder includes delaying or preventing the onset or progression of the disease, or reducing the severity of the disease. It will be understood that “to treat” or “treatment” may also refer to antibodies.

[0050] II. Anti-KLK5 antibody, anti-KLK7 antibody, and anti-KLK5 / KLK7 antibody (a) Anti-KLK5 antibody In some embodiments, an antibody targeting KLK5 (referred to as an anti-KLK5 antibody) is an antibody specific to kallikrein-5 (KLK5). In some embodiments, antibodies are provided herein that bind to KLK5 (e.g., human KLK5 or mouse KLK5) with high specificity and affinity. In some embodiments, the anti-KLK5 antibody described herein specifically binds to the KLK5 epitope that is or will be exposed to the antibody. In some embodiments, the anti-KLK5 antibody provided herein specifically binds to KLK5 derived from humans, non-human primates, mice, rats, etc. In some embodiments, the anti-KLK5 antibody provided herein specifically binds to human KLK5. In some embodiments, the anti-KLK5 antibody provided herein specifically binds to mouse KLK5.

[0051] Kallikrein-5, also known as stratum corneum trypsinase (SCTE), is a serine protease expressed in the epidermis and encoded by the KLK5 gene. The KLK5 gene is one of 15 kallikrein subfamily members located in a cluster on the chromosome. Its expression is upregulated by estrogen and progestin. KLK5 is expressed in the stratum granulosum and stratum corneum. In some embodiments, KLK5 controls epidermal desquamation. In some embodiments, KLK5 controls epidermal desquamation in conjunction with other members of the kallikrein family proteases (e.g., KLK7 and / or KLK14). In some embodiments, KLK5 degrades proteins that make up the epidermis (e.g., stratum corneum, stratum clearusa, stratum granulosum, stratum spinosum, or stratum basale). In some embodiments, KLK5 degrades proteins that form the stratum corneum and / or granular layer (e.g., cornodesmosine (CDSN), desmoglein 1 (DSG1), and desmocolin 1 (DSC1)). In the epidermis (e.g., granular layer and stratum corneum), KLK5 is expressed as pro-KLK5, an inactive form (sometimes called proform or pro-form), which can self-activate itself. Once activated, KLK5 can convert both pro-KLK7 and pro-KLK14 to their active forms via proteolytic cleavage. Subsequently, active KLK14 can activate newly generated pro-KLK5, thus forming a positive feedback loop (see, for example, 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 that form the stratum corneum and / or granular layer (e.g., cornodesmosine (CDSN), desmoglein 1 (DSG1), and desmocolin 1 (DSC1)).Structural proteins such as CDSN, DSG1, and DSC1 are adhesion proteins in the extracellular portion of corneodesmosomes, which are junctional structures that mediate the adhesion of keratinocytes. Degradation of these proteins on the epidermal surface leads to desquamation, which can result in skin barrier defects (e.g., stratum corneum exfoliation, reduced permeability barrier, allergies, and inflammation). KLK5 and KLK7 are involved in this process (see, for example, 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 syndrome and atopic dermatitis, SCIENCE TRANSLATIONAL MEDICINE, 14 Dec 2022, Vol 14, Issue 675).

[0052] In some embodiments, the anti-KLK5 antibodies described herein specifically bind to epitopes on human KLK5. Exemplary amino acid sequences of human KLK5 are described 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, and these entire sequences are incorporated herein by reference.

[0053] In some embodiments, the anti-KLK5 antibodies described herein specifically bind to epitopes on mouse KLK5. Exemplary amino acid sequences of mouse KLK5 are described 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 accession number P15945, or Q9D140, and these entire sequences are incorporated herein by reference.

[0054] In some embodiments, the anti-KLK5 antibodies described herein specifically bind to an epitope on KLK5 (e.g., a catalytic domain / pocket of human or mouse KLK5). In some embodiments, the anti-KLK5 antibodies described herein prevent KLK5 (e.g., human or mouse KLK5) from cleaving its substrate. In some embodiments, the anti-KLK5 antibodies described herein bind to a fragment of KLK5 (e.g., human or mouse KLK5). The fragment of KLK5 (e.g., human or mouse) may be about 5 to 425 amino acids, about 10 to 400 amino acids, about 50 to 350 amino acids, about 100 to 300 amino acids, about 150 to 250 amino acids, about 200 to 300 amino acids, about 75 to 150 amino acids, about 25 to 100 amino acids, or about 10 to 30 amino acids in length. Without intending to be bound by any particular theory, in some embodiments, any one of the heavy chain (HC) complementarity-determining regions 3 (CDR3) of the anti-KLK5 antibodies described herein inhibits KLK5 (e.g., human or mouse KLK5) by binding to the catalytic domain / pocket of KLK5.

[0055] In some embodiments, the anti-KLK5 antibodies described herein inhibit KLK5 protease activity. In some embodiments, the anti-KLK5 antibodies inhibit KLK5 cleavage of BOC-Val-Pro-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 1 nM, less than 0.5 nM, less than 0.3 nM, less than 0.25 nM, less than 0.2 nM, less than 0.1 nM, or less than 0.05 nM.

[0056] In some embodiments, the anti-KLK5 antibody described herein specifically binds to the active form of KLK5. In some embodiments, the anti-KLK5 antibody described herein does not bind to the inactive form of KLK5. In some embodiments, the anti-KLK5 antibody described herein specifically binds to the active site of KLK5. The active site of KLK5 is the site on which a KLK5 substrate molecule binds and is cleaved. The active site may also be known as the catalytic domain or catalytic triresidue. In some embodiments, the active site of KLK5 (i.e., the catalytic domain or catalytic triresidue) consists of the amino acids Ser195, His57, and Asp102 of KLK5 (see, for example, Goettig et al., Natural and synthetic inhibitors of kallikrein-related peptidases (KLKs), Biochimie. 2010 Nov;92(11):1546-1567).

[0057] In some embodiments, the antibodies described herein are optimized versions (e.g., affinity-mature) of the parent antibody. In some embodiments, the antibodies described herein are KLK5 (e.g., human or mouse KLK5) with at least about 10 -4 M, 10 -5 M, 10 -6 M, 10 -7 M, 10 -8 M, 10 -9 M, 10 -10 M, 10 -11 M, 10 -12 M, 10 -13M, or lower binding affinity (e.g., K D It specifically binds to (as shown by). In some embodiments, the antibodies described herein bind to KLK5 (e.g., human or mouse KLK5) at a rate of 1 × 10⁻¹⁶ -10 M~5×10 -9 M, 1×10 -10 M~1×10 -9 M, 5×10 -10 ~1 × 10 -9 M, 5×10 -11 ~1 × 10 -10 M, 1×10 -11 ~5×10 -10 M, or 5×10 -13 ~1 × 10 -12 Binding affinity of M (e.g., K D The antibodies bind specifically to the KLK5 protein (e.g., human or mouse KLK5) with affinities of 1 pM to 500 nM, e.g., 50 pM to 100 nM, 500 pM to 50 nM, 1 pM to 100 pM, 10 pM to 100 pM, 50 pM to 100 pM, 100 pM to 500 pM, 500 pM to 1 nM, 1 nM to 5 nM, 1 nM to 10 nM, 5 nM to 25 nM, 10 nM to 50 nM, 50 nM to 100 nM, and 100 nM to 500 nM. This disclosure also includes antibodies that compete with any of the antibodies described herein for binding to the KLK5 protein (e.g., human or mouse KLK5) and have an affinity of 100 nM or less (e.g., 80 nM or less, 50 nM or less, 20 nM or less, 10 nM or less, 1 nM or less, 500 pM or less, 50 pM or less, or 5 pM or less). The affinity and binding reaction rate of the antibodies can be tested using any suitable method, including but not limited to biosensor technologies (e.g., OCTET or BIACORE). In some embodiments, the antibodies described herein have a sub-nanomolecular K D Then it connects to KLK5.

[0058] 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), fluorescence-activated cell sorting (FACS), or spectroscopy (e.g., using fluorescence assays). Exemplary conditions for evaluating binding affinity are HBS-P buffer (10 mM HEPES pH 7.4, 150 mM NaCl, 0.005% (v / v) surfactant P2O) and PBS buffer (10 mM PO4-3, 137 mM NaCl, and 2.7 mM KCl). Using these techniques, the concentration of the binding protein can be measured as a function of the target protein concentration. Generally, the concentration of the binding protein ([[binding]]) is given by the following formula: [[Bound]]=[[Free]] / (Kd+[[Free]]) This is related to the concentration of free target protein (free).

[0059] K A While it is not always necessary to make an accurate determination, obtaining a quantitative measure of affinity determined using methods such as ELISA or FACS analysis is useful, as it indicates that K A Since it is proportional to the activity, it may be sufficient, and therefore can be used for comparisons to determine whether a higher affinity is, for example, twice as high, to obtain a qualitative measurement of affinity, or to infer affinity by activity in a functional assay (e.g., an in vitro or in vivo assay).

[0060] Exemplary anti-KLK5 antibody sequences (e.g., heavy chain (HC) sequence and light chain (LC) sequence, heavy chain variable domain (VH) and light chain variable domain (VL), and CDR sequence) are provided in Tables 1a and 1b. [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6]

[0061] In some embodiments, certain amino acid positions in the antibodies described herein (e.g., amino acids in the VH / VL region and / or CDR region) are substitutable, and this substitution results in an antibody having substantially similar binding and biological activity (e.g., substantially similar binding affinity, binding specificity, protease inhibitory activity, anti-inflammatory activity, or a combination thereof) to the reference antibody. To identify substitutable positions in 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 among related antibodies of different groups at any particular position, that position is a substitutable position in the antibody. In other words, a substitutable position is a position where the identity of the amino acid varies among related antibodies. Positions containing constant amino acids are not substitutable positions.

[0062] In some embodiments, the above method may be used to provide a consensus antibody sequence. In such a consensus sequence, non-substitutable positions are indicated by the amino acids present at those positions, and substitutable positions are indicated by "X".

[0063] Depending on how the antibody is adopted, X may be a) any amino acid, b) any amino acid present at that position in any of the related antibodies within that group, or a conservatively substituted variant thereof, or c) any amino acid present at that position in any of the related antibodies within that group. Any antibody having a sequence encompassed by consensus should bind to the same antigen as any of the related antibodies.

[0064] In some embodiments, the methods described above may be employed in a method for designing and producing variants of a parent antibody that at least maintain (e.g., maintain or increase) the antigen-binding activity of the parent antibody. Antibodies containing substitutions at substitutable positions can be produced and tested, and therefore substitutions at those positions should not significantly reduce the antibody's binding activity. Generally, antibody variants of a parent antibody have an antigen-binding affinity of 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%, and typically up to at least 10,000%) of the parent antibody's binding affinity to a particular antigen.

[0065] In some embodiments, the substitutable positions of the parent antibody may be substituted by: a) any of 20 naturally occurring amino acids to produce a random substitution; b) an amino acid with biochemical properties similar to an amino acid already present at the substitutable position to produce a conservative substitution; c) an amino acid present at the same position in the related antibody to produce a designated substitution; or d) an amino acid present at the same position in a similar human antibody to produce a humanization substitution. Substitutions may occur in any portion of the antibody variable region, including any framework region or CDR. In certain embodiments, a single substitutable amino acid may be substituted. However, in other embodiments, multiple substitutable amino acids (e.g., up to about 5 or 10 or more) may be substituted. In certain embodiments, the type of substitution that can be performed at each substitutable position may be indicated by the type of amino acid present at that position in the related antibody. For example, if an unrelated amino acid (e.g., Ala, Gly, Cys, Glu, and Thr) is present at a particular position in the group of related antibodies, any amino acid can be substituted at that position without significantly reducing the antibody's binding activity. Exemplary amino acid substitutions of anti-KLK5 antibodies described herein are shown in Table 1b: [Table 1-7] [Table 1-8]

[0066] In some embodiments, the antibodies of the present disclosure include HC CDR1 comprising the amino acid sequence FTFX1X2YX3MN, where X1 is S, G, E, or N, X2 is S, H, or D, or X3 is S or A; HC CDR2 comprising the amino acid sequence YISSSSSX4IX5YADSVKG, where X4 is T, F, or Y, X5 is Y or D; HC CDR3 comprising the amino acid sequence ARDLTX6X7QSESYYYYGMDV, where X6 is S or D, or X7 is M or R; LC CDR1 comprising the amino acid sequence of SEQ ID NO: 4; LC CDR2 comprising the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 comprising the amino acid sequence of SEQ ID NO: 6.

[0067] In some embodiments, the antibodies of the present disclosure include: HC CDR1 comprising the amino acid sequence GSIX1SSSYYWX2, where X1 is S or P, or X2 is G, A, or S; HC CDR2 comprising the amino acid sequence X3IX4YSGSTYYNPSLKS, where X3 is S or N, or X4 is S or Y; HC CDR3 comprising the amino acid sequence ARGEYDRSX5X6X7X8GX9DV, where X5 is Y or A, X6 is Y or L, X7 is Y or F, X8 is Y or W, or X9 is M or L; LC CDR1 comprising the amino acid sequence of SEQ ID NO: 22; LC CDR2 comprising the amino acid sequence of SEQ ID NO: 23; and / or LC CDR3 comprising the amino acid sequence QQAFSSPX9, where X9 is T or S.

[0068] In some embodiments, the antibody of this disclosure is HC CDR1 comprising the amino acid sequence X1TFX2X3YX4X5X6, where X1 is Y or G, X2 is T, S or N, X3 is G or N, X4 is Y, S, H or V, X5 is M or I, or X6 is H or S; X7IX8PX9X 10 GX 11 AX 12 HC CDR2 containing the amino acid sequence YAQKFQG, where X7 is G or L, X8 is I or F, X9 is I, P or T, X 10 X is either S or F. 11 is T or Y, or X 12 is N, H, or V; ARX 13 X 14 ASGYYDRASEYX 15 X 16 GX 17 HC CDR3 containing the amino acid sequence of DV, where X 13 X is G, Q, or A. 14 X is either S or E. 15 X is either Y or R. 16 is Y or D, or X 17 is M or L; LC CDR1 containing the amino acid sequence of SEQ ID NO: 4; LC CDR2 containing the amino acid sequence of SEQ ID NO: 5; and / or QQVX 18 SFPX 19 LC CDR3 containing the amino acid sequence of T, where X 18 is S or I, or X 19 This includes the condition that it is either Y or Q.

[0069] In some embodiments, the antibody of this disclosure comprises one or more HC CDR (e.g., HC CDR1, HC CDR2, or HC CDR3) amino acid sequences from any one of the anti-KLK5 antibodies selected from Tables 1a and 1b. In some embodiments, the antibody of this disclosure comprises an HC CDR3 amino acid sequence from any one of the anti-KLK5 antibodies selected from Tables 1a and 1b. In some embodiments, the antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 provided for any one of the antibodies selected from Tables 1a and 1b. In some embodiments, the antibody of this disclosure comprises an LC CDR3 amino acid sequence from any one of the anti-KLK5 antibodies selected from Tables 1a and 1b. In some embodiments, the antibody of this disclosure comprises one or more LC CDR (e.g., LC CDR1, LC CDR2, or LC CDR3) amino acid sequences from any one of the anti-KLK5 antibodies selected from Tables 1a and 1b. In some embodiments, the antibodies of this disclosure include LC CDR1, LC CDR2, and LC CDR3, which are provided for any one of the anti-KLK5 antibodies selected from Tables 1a and 1b.

[0070] In some embodiments, the antibodies of this disclosure include HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 provided for any one of the anti-KLK5 antibodies selected from Tables 1a and 1b. In some embodiments, the heavy chain CDR3 domain and / or light chain CDR3 domain of the antibody may play a particularly important role in the antibody's binding specificity / affinity to the antigen. Therefore, the antibodies of this disclosure may include at least the heavy chain CDR3 and / or light chain CDR3 of any one of the anti-KLK5 antibodies selected from Tables 1a and 1b.

[0071] Any variant of the exemplary anti-KLK5 antibody disclosed herein is also within the scope of this disclosure. The variant may contain one or more amino acid residue mutations in the VH and / or VL, or in one or more of the HC CDRs and / or one or more of the LC CDRs, compared to the reference antibody, but retain substantially similar binding activity and biological activity (e.g., substantially similar binding affinity, binding specificity, protease inhibitory activity, anti-inflammatory activity, or a combination thereof) to the reference antibody.

[0072] In some embodiments, the antibodies of this disclosure have one or more CDR (e.g., HC CDR or LC CDR) sequences substantially similar to any of HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 from one of the anti-KLK5 antibodies selected from Tables 1a and 1b. In some embodiments, the positions 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) regions of the antibodies described herein can be mutated by 1, 2, 3, 4, 5, or 6 amino acid positions, as long as specific binding to KLK5 (e.g., human or mouse KLK5) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% of the binding of the original antibody from which it is derived). For example, in some embodiments, the position defining the CDR of any antibody described herein can be mutated by shifting the N-terminal and / or C-terminal boundary of the CDR by 1, 2, 3, 4, 5, or 6 amino acids relative to any one CDR position of the antibody described herein, insofar as specific binding of KLK5 (e.g., human or mouse KLK5) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% of the binding of the original antibody from which it originates). 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) regions of the antibodies described herein may be mutated (e.g., shortened or lengthened) by only 1, 2, 3, 4, 5, or more amino acids, as long as immunospecific binding to KLK5 (e.g., human or mouse KLK5) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% of the binding of the original antibody from which it is derived).

[0073] Therefore, in some embodiments, the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein may be 1, 2, 3, 4, or 5 amino acids shorter than one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK5 antibodies selected from Tables 1a and 1b), as long as specific binding to KLK5 (e.g., human or mouse KLK5) is maintained (e.g., substantially maintained by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% compared to the binding of the original antibody from which it is derived). In some embodiments, the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein may be 1, 2, 3, 4, or 5 amino acids or longer than one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK5 antibodies selected from Tables 1a and 1b), provided that specific binding to KLK5 (e.g., human or mouse KLK5) is maintained (e.g., substantially maintained by, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% compared to the binding of the original antibody from which it is derived). In some embodiments, the amino portions of HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be extended by 1, 2, 3, 4, or 5 amino acids or more compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK5 antibodies selected from Tables 1a and 1b), provided that specific binding to KLK5 (e.g., human or mouse KLK5) is maintained (e.g., substantially maintained by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% compared to the binding of the original antibody from which it is derived).In some embodiments, the carboxyl portions of HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be extended by 1, 2, 3, 4, or 5 amino acids or more compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK5 antibodies selected from Tables 1a and 1b), provided that specific binding to KLK5 (e.g., human or mouse KLK5) is maintained (e.g., substantially maintained by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% compared to the binding of the original antibody from which it is derived). In some embodiments, the amino portion of HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be shortened by 1, 2, 3, 4, or 5 amino acids or more compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK5 antibodies selected from Tables 1a and 1b), insofar as specific binding to KLK5 (e.g., human or mouse KLK5) is maintained (e.g., substantially maintained by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% compared to the binding of the original antibody from which it is derived). In some embodiments, the carboxyl portions of HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be shortened by 1, 2, 3, 4, or 5 amino acids or more compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK5 antibodies selected from Tables 1a and 1b), insofar as specific binding to KLK5 (e.g., human or mouse KLK5) is maintained (e.g., substantially maintained by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% compared to the binding of the original antibody from which it is derived).To confirm whether or not immunospecific binding to KLK5 (e.g., human or mouse KLK5) is maintained, any method can be used, such as using the binding assays and conditions described in the Art.

[0074] In some examples, the antibodies of this disclosure have one or more CDR (e.g., HC CDR or LC CDR) sequences substantially similar to any one of the anti-KLK5 antibodies selected from Tables 1a and 1b. For example, the antibodies described herein may include one or more CDR sequences from any of the anti-KLK5 antibodies selected from Tables 1a and 1b, containing up to 5, 4, 3, 2, or 1 amino acid residue mutations compared to the corresponding CDR region of any one of the CDRs provided herein (e.g., CDRs from any of the anti-KLK5 antibodies selected from Tables 1a and 1b), insofar as specific binding to KLK5 (e.g., human or mouse KLK5) is maintained (e.g., substantially maintained by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% compared to the binding of the original antibody from which it is derived). In some embodiments, any amino acid mutations in any of the CDRs provided herein may be conservative mutations. Conservative mutations can be introduced into a CDR at a position where the residue is unlikely to be involved in interaction with KLK5 (e.g., human or mouse KLK5), for example, when determined based on the crystal structure. Some aspects of this disclosure provide antibodies comprising one or more heavy chain variable (VH) domains and / or light chain variable (VL) domains provided herein. In some embodiments, any VH domain provided herein comprises one or more of the HC CDR sequences provided herein (e.g., HC CDR1, HC CDR2, and HC CDR3), which are, for example, any of the HC CDR sequences provided for any one of the anti-KLK5 selected from Tables 1a and 1b. In some embodiments, any VL domain provided herein comprises one or more of the LC CDR sequences provided herein (e.g., LC CDR1, LC CDR2, and LC CDR3), which are, for example, any of the LC CDR sequences provided for any one of the anti-KLK5 antibodies selected from Tables 1a and 1b.

[0075] In some embodiments, the antibodies of the Disclosure include any antibody comprising a heavy chain variable domain and / or light chain variable domain of any one anti-KLK5 antibody selected from Tables 1a and 1b, as well as variants thereof. In some embodiments, the antibodies of the Disclosure include any antibody comprising a pair of heavy chain variable and light chain variable regions of any anti-KLK5 antibody selected from Tables 1a and 1b.

[0076] Aspects of this disclosure provide antibodies comprising heavy chain variable (VH) domain amino acid sequences and / or light chain variable (VL) domain amino acid sequences homologous to any of the amino acid sequences described herein. In some embodiments, the antibody comprises a heavy chain variable sequence or a light chain variable sequence that is at least 75% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to any one of the heavy chain variable sequences and / or light chain variable sequences of an anti-KLK5 antibody selected from Tables 1a and 1b. In some embodiments, the homologous heavy chain variable amino acid sequences and / or light chain variable amino acid sequences do not mutate within any of the CDR sequences provided herein. For example, in some embodiments, the degree of sequence mutation (e.g., 75%, 80%, 85%, 90%, 95%, 98%, or 99%) may occur within the heavy chain variable sequence and / or light chain variable sequence, excluding any of the CDR sequences provided herein. In some embodiments, the antibodies provided herein include heavy-chain and light-chain variable sequences that include a framework sequence which is at least 75%, 80%, 85%, 90%, 95%, 98%, or 99% identical to the framework sequence of any anti-KLK5 antibody selected from Tables 1a and 1b.

[0077] In some embodiments, the antibody of the Disclosure is a humanized antibody (e.g., a humanized variant containing one or more CDRs from Tables 1a and 1b). In some embodiments, the antibody of the Disclosure comprises HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3, which are the same as HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 shown in Tables 1a and 1b, and includes a humanized heavy chain variable region and / or a humanized light chain variable region.

[0078] In some embodiments, the antibody of the Disclosure is a humanized antibody comprising a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH of any of the anti-KLK5 antibodies listed in Tables 1a and 1b. Alternatively or additionally, the antibody of the Disclosure is a humanized antibody comprising a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to any one VL of any of the anti-KLK5 antibodies listed in Tables 1a and 1b.

[0079] In some embodiments, the anti-KLK5 antibody of this disclosure comprises heavy chain variable domains HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises light chain variable domains LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 11.

[0080] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 2, HC CDR3 having the amino acid sequence of SEQ ID NO: 9, 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.

[0081] In some embodiments, the anti-KLK5 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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: 9. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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.

[0082] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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: 9. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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.

[0083] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 1; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO: 2; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO: 9. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0084] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 11.

[0085] In some embodiments, the anti-KLK5 antibody of this disclosure includes a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 3. Alternatively or additionally, the anti-KLK5 antibody of this disclosure includes a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 11.

[0086] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 3. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 11.

[0087] In some embodiments, the anti-KLK5 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 10. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 11.

[0088] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 7, HC CDR2 having the amino acid sequence of SEQ ID NO: 8, HC CDR3 having the amino acid sequence of SEQ ID NO: 9, 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.

[0089] In some embodiments, the anti-KLK5 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 7, HC CDR2 having the amino acid sequence of SEQ ID NO: 8, and HC CDR3 having the amino acid sequence of SEQ ID NO: 9. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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.

[0090] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 7, HC CDR2 having the amino acid sequence of SEQ ID NO: 8, and HC CDR3 having the amino acid sequence of SEQ ID NO: 9. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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.

[0091] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 7; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO: 8; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO: 9. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0092] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 10. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 11.

[0093] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 10. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 11.

[0094] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 10. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 11.

[0095] In some embodiments, the anti-KLK5 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 14. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 11.

[0096] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 12, HC CDR2 having the amino acid sequence of SEQ ID NO: 13, HC CDR3 having the amino acid sequence of SEQ ID NO: 9, 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.

[0097] In some embodiments, the anti-KLK5 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 12, HC CDR2 having the amino acid sequence of SEQ ID NO: 13, and HC CDR3 having the amino acid sequence of SEQ ID NO: 9. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 12, HC CDR2 having the amino acid sequence of SEQ ID NO: 13, and HC CDR3 having the amino acid sequence of SEQ ID NO: 9. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 12; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 13; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 9. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0100] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 14. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 11.

[0101] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 14. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 11.

[0102] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 14. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 11.

[0103] In some embodiments, the anti-KLK5 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 16. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 11.

[0104] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 15, HC CDR2 having the amino acid sequence of SEQ ID NO: 13, HC CDR3 having the amino acid sequence of SEQ ID NO: 9, 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.

[0105] In some embodiments, the anti-KLK5 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 15, HC CDR2 having the amino acid sequence of SEQ ID NO: 13, and HC CDR3 having the amino acid sequence of SEQ ID NO: 9. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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.

[0106] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 15, HC CDR2 having the amino acid sequence of SEQ ID NO: 13, and HC CDR3 having the amino acid sequence of SEQ ID NO: 9. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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.

[0107] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 15; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO: 13; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO: 9. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0108] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 16. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 11.

[0109] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 16. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 11.

[0110] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 16. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 11.

[0111] In some embodiments, the anti-KLK5 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 18. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 11.

[0112] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 12, HC CDR2 having the amino acid sequence of SEQ ID NO: 13, HC CDR3 having the amino acid sequence of SEQ ID NO: 17, 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.

[0113] In some embodiments, the anti-KLK5 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 12, HC CDR2 having the amino acid sequence of SEQ ID NO: 13, and HC CDR3 having the amino acid sequence of SEQ ID NO: 17. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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.

[0114] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 12, HC CDR2 having the amino acid sequence of SEQ ID NO: 13, and HC CDR3 having the amino acid sequence of SEQ ID NO: 17. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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.

[0115] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 12; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 13; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 17. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0116] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 18. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 11.

[0117] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 18. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 11.

[0118] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 18. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 11.

[0119] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises heavy chain variable domains HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 24. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises light chain variable domains LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 29.

[0120] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 19, HC CDR2 having the amino acid sequence of SEQ ID NO: 20, HC CDR3 having the amino acid sequence of SEQ ID NO: 21, LC CDR1 having the amino acid sequence of SEQ ID NO: 22, LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and LC CDR3 having the amino acid sequence of SEQ ID NO: 34.

[0121] In some embodiments, the anti-KLK5 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 19, HC CDR2 having the amino acid sequence of SEQ ID NO: 20, and HC CDR3 having the amino acid sequence of SEQ ID NO: 21. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 22, LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and LC CDR3 having the amino acid sequence of SEQ ID NO: 34.

[0122] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 19, HC CDR2 having the amino acid sequence of SEQ ID NO: 20, and HC CDR3 having the amino acid sequence of SEQ ID NO: 21. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 22, LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and LC CDR3 having the amino acid sequence of SEQ ID NO: 34.

[0123] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 19; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 20; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 21. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 22; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 23; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 34.

[0124] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 24. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 29.

[0125] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 24. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 29.

[0126] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 24. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 29.

[0127] In some embodiments, the anti-KLK5 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 28. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 29.

[0128] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 25, HC CDR2 having the amino acid sequence of SEQ ID NO: 26, HC CDR3 having the amino acid sequence of SEQ ID NO: 27, LC CDR1 having the amino acid sequence of SEQ ID NO: 22, LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and LC CDR3 having the amino acid sequence of SEQ ID NO: 34.

[0129] In some embodiments, the anti-KLK5 antibodies of the Disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 25, HC CDR2 having the amino acid sequence of SEQ ID NO: 26, and HC CDR3 having the amino acid sequence of SEQ ID NO: 27. As used anywhere in the Disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of the Disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 22, LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and LC CDR3 having the amino acid sequence of SEQ ID NO: 34.

[0130] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 25, HC CDR2 having the amino acid sequence of SEQ ID NO: 26, and HC CDR3 having the amino acid sequence of SEQ ID NO: 27. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 22, LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and LC CDR3 having the amino acid sequence of SEQ ID NO: 34.

[0131] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 25; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 26; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 27. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 22; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 23; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 34.

[0132] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 28. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 29.

[0133] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 28. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 29.

[0134] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 28. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 29.

[0135] In some embodiments, the anti-KLK5 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 32. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 37.

[0136] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 30, HC CDR2 having the amino acid sequence of SEQ ID NO: 26, HC CDR3 having the amino acid sequence of SEQ ID NO: 31, LC CDR1 having the amino acid sequence of SEQ ID NO: 22, LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and LC CDR3 having the amino acid sequence of SEQ ID NO: 35.

[0137] In some embodiments, the anti-KLK5 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 30, HC CDR2 having the amino acid sequence of SEQ ID NO: 26, and HC CDR3 having the amino acid sequence of SEQ ID NO: 31. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 22, LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and LC CDR3 having the amino acid sequence of SEQ ID NO: 35.

[0138] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 30, HC CDR2 having the amino acid sequence of SEQ ID NO: 26, and HC CDR3 having the amino acid sequence of SEQ ID NO: 31. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 22, LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and LC CDR3 having the amino acid sequence of SEQ ID NO: 35.

[0139] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 30; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 26; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 31. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 22; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 23; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 35.

[0140] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises, alternatively or additionally, a VH comprising the amino acid sequence of SEQ ID NO: 32, or a VL comprising the amino acid sequence of SEQ ID NO: 37.

[0141] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 32. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 37.

[0142] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 32. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 37.

[0143] In some embodiments, the anti-KLK5 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 36. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 29.

[0144] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 30, HC CDR2 having the amino acid sequence of SEQ ID NO: 26, HC CDR3 having the amino acid sequence of SEQ ID NO: 33, LC CDR1 having the amino acid sequence of SEQ ID NO: 22, LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and LC CDR3 having the amino acid sequence of SEQ ID NO: 34.

[0145] In some embodiments, the anti-KLK5 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 30, HC CDR2 having the amino acid sequence of SEQ ID NO: 26, and HC CDR3 having the amino acid sequence of SEQ ID NO: 33. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 22, LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and LC CDR3 having the amino acid sequence of SEQ ID NO: 34.

[0146] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 30, HC CDR2 having the amino acid sequence of SEQ ID NO: 26, and HC CDR3 having the amino acid sequence of SEQ ID NO: 33. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 22, LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and LC CDR3 having the amino acid sequence of SEQ ID NO: 34.

[0147] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 30; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 26; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 33. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 22; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 23; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 34.

[0148] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 36. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 29.

[0149] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 36. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 29.

[0150] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 36. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 29.

[0151] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 42. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 43.

[0152] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 38, HC CDR2 having the amino acid sequence of SEQ ID NO: 39, HC CDR3 having the amino acid sequence of SEQ ID NO: 40, 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: 41.

[0153] In some embodiments, the anti-KLK5 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 38, HC CDR2 having the amino acid sequence of SEQ ID NO: 39, and HC CDR3 having the amino acid sequence of SEQ ID NO: 40. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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: 41.

[0154] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 38, HC CDR2 having the amino acid sequence of SEQ ID NO: 39, and HC CDR3 having the amino acid sequence of SEQ ID NO: 40. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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: 41.

[0155] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 38; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 39; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 40. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO: 41.

[0156] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 42. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 43.

[0157] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 42. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 43.

[0158] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 42. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 43.

[0159] In some embodiments, the anti-KLK5 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 46. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 43.

[0160] In some embodiments, the antibodies of this disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 44, HC CDR2 having the amino acid sequence of SEQ ID NO: 45, HC CDR3 having the amino acid sequence of SEQ ID NO: 40, 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: 41.

[0161] In some embodiments, the anti-KLK5 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 44, HC CDR2 having the amino acid sequence of SEQ ID NO: 45, and HC CDR3 having the amino acid sequence of SEQ ID NO: 40. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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: 41.

[0162] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 44, HC CDR2 having the amino acid sequence of SEQ ID NO: 45, and HC CDR3 having the amino acid sequence of SEQ ID NO: 40. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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: 41.

[0163] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 44; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO: 45; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO: 40. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO: 41.

[0164] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 46. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 43.

[0165] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 46. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 43.

[0166] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 46. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 43.

[0167] In some embodiments, the anti-KLK5 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 49. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 43.

[0168] In some embodiments, the antibodies of this disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 47, HC CDR2 having the amino acid sequence of SEQ ID NO: 48, HC CDR3 having the amino acid sequence of SEQ ID NO: 40, 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: 41.

[0169] In some embodiments, the anti-KLK5 antibodies of the Disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 47, HC CDR2 having the amino acid sequence of SEQ ID NO: 48, and HC CDR3 having the amino acid sequence of SEQ ID NO: 40. As used anywhere in the Disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of the Disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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: 41.

[0170] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 47, HC CDR2 having the amino acid sequence of SEQ ID NO: 48, and HC CDR3 having the amino acid sequence of SEQ ID NO: 40. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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: 41.

[0171] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 47; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO: 48; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO: 40. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO: 41.

[0172] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 49. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 43.

[0173] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 49. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 43.

[0174] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 49. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 43.

[0175] In some embodiments, the anti-KLK5 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 51. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 43.

[0176] In some embodiments, the antibodies of this disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 47, HC CDR2 having the amino acid sequence of SEQ ID NO: 48, HC CDR3 having the amino acid sequence of SEQ ID NO: 50, 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: 41.

[0177] In some embodiments, the anti-KLK5 antibodies of the Disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 47, HC CDR2 having the amino acid sequence of SEQ ID NO: 48, and HC CDR3 having the amino acid sequence of SEQ ID NO: 50. As used anywhere in the Disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of the Disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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: 41.

[0178] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 47, HC CDR2 having the amino acid sequence of SEQ ID NO: 48, and HC CDR3 having the amino acid sequence of SEQ ID NO: 50. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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: 41.

[0179] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 47; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO: 48; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO: 50. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO: 41.

[0180] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 51. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 43.

[0181] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 51. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 43.

[0182] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 51. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 43.

[0183] In some embodiments, the anti-KLK5 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 53. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 43.

[0184] In some embodiments, the antibodies of this disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 44, HC CDR2 having the amino acid sequence of SEQ ID NO: 45, HC CDR3 having the amino acid sequence of SEQ ID NO: 52, 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: 41.

[0185] In some embodiments, the anti-KLK5 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 44, HC CDR2 having the amino acid sequence of SEQ ID NO: 45, and HC CDR3 having the amino acid sequence of SEQ ID NO: 52. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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: 41.

[0186] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 44, HC CDR2 having the amino acid sequence of SEQ ID NO: 45, and HC CDR3 having the amino acid sequence of SEQ ID NO: 52. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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: 41.

[0187] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 44; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO: 45; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO: 52. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO: 41.

[0188] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 53. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 43.

[0189] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 53. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 43.

[0190] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 53. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 43.

[0191] In some embodiments, the anti-KLK5 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 58. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 59.

[0192] In some embodiments, the antibodies of this disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 54, HC CDR2 having the amino acid sequence of SEQ ID NO: 55, HC CDR3 having the amino acid sequence of SEQ ID NO: 56, 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: 57.

[0193] In some embodiments, the anti-KLK5 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 54, HC CDR2 having the amino acid sequence of SEQ ID NO: 55, and HC CDR3 having the amino acid sequence of SEQ ID NO: 56. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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: 57.

[0194] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 54, HC CDR2 having the amino acid sequence of SEQ ID NO: 55, and HC CDR3 having the amino acid sequence of SEQ ID NO: 56. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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: 57.

[0195] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 54; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 55; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 56. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO: 57.

[0196] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 58. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 59.

[0197] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 58. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 59.

[0198] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 58. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 59.

[0199] In some embodiments, the anti-KLK5 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 64. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 65.

[0200] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 60, HC CDR2 having the amino acid sequence of SEQ ID NO: 61, HC CDR3 having the amino acid sequence of SEQ ID NO: 62, 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: 63.

[0201] In some embodiments, the anti-KLK5 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 60, HC CDR2 having the amino acid sequence of SEQ ID NO: 61, and HC CDR3 having the amino acid sequence of SEQ ID NO: 62. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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: 63.

[0202] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 60, HC CDR2 having the amino acid sequence of SEQ ID NO: 61, and HC CDR3 having the amino acid sequence of SEQ ID NO: 62. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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: 63.

[0203] In some embodiments, the anti-KLK5 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 60; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 61; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 62. Alternatively or additionally, the anti-KLK5 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 63.

[0204] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 64. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 65.

[0205] In some embodiments, the anti-KLK5 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 64. Alternatively or additionally, the anti-KLK5 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 65.

[0206] In some embodiments, the anti-KLK5 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 64. Alternatively or additionally, the anti-KLK5 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 65.

[0207] The antibodies described herein may be in any antibody form, including but not limited to intact (i.e., full-length) antibodies, their antigen-binding fragments (Fab, F(ab'), F(ab')2, Fv, etc.), single-chain antibodies, bispecific antibodies, or nanobodies. In some embodiments, the anti-KLK5 antibody described herein is scFv. In some embodiments, the anti-KLK5 antibody described herein is scFv-Fab (e.g., scFv fused to a portion of the constant region).

[0208] In some embodiments, the anti-KLK5 antibody of this disclosure is a chimeric antibody, which may include a heavy chain constant region and a light chain constant region derived from a human antibody. A chimeric antibody refers to an antibody having a variable region or a portion of a variable region derived from a first species and a constant region derived from a second species. Typically, in these chimeric antibodies, both the light chain and heavy chain variable regions mimic the variable regions of an antibody derived from one species of mammal (e.g., a non-human mammal such as a mouse, rabbit, and rat), while the constant region is homologous to the sequence in an antibody derived from another mammal, such as a human. In some embodiments, amino acid modifications may occur in the variable region and / or the constant region.

[0209] In some embodiments, the antibodies of the present disclosure comprise any one VL domain and / or VH domain of anti-KLK5 antibodies selected from Tables 1a and 1b, and comprise a constant region comprising the amino acid sequence of a constant region of an IgG, IgE, IgM, IgD, IgA or IgY immunoglobulin molecule, of any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2), or of any subclass (e.g., IgG2a and IgG2b). Non-limiting examples of human constant regions are described in the art, see, e.g., Kabat E A et al., (1991) supra.

[0210] In some embodiments, any light chain of the anti-KLK5 antibodies described herein may further comprise a light chain constant region (CL), which can 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.

[0211] Other antibody heavy chain constant regions and light chain constant regions are well known in the art and include, for example, those provided in the IMGT database (www.imgt.org) or www.vbase2.org / vbstat.php, both of which are incorporated herein by reference.

[0212] In some embodiments, conservative mutations may be introduced into the antibody sequence (e.g., CDR or framework sequence) at a position where, if determined based on, for example, the residue is unlikely to be involved in interaction with the target antigen (e.g., human or mouse KLK5). In some embodiments, one, two or more mutations (e.g., amino acid substitutions) may be introduced into the Fc region of the anti-KLK5 antibody described herein (numbered according to the Kabat numbering system (e.g., EU index in Kabat), for example, the CH2 domain (residues 231-340 of human IgG1) and / or the CH3 domain (residues 341-447 of human IgG1) and / or the hinge region) to modify one or more functional properties of the antibody, such as serum half-life, complement fixation, Fc receptor binding and / or antigen-dependent cytotoxicity.

[0213] In some embodiments, one, two, or more mutations (e.g., amino acid substitutions) are introduced into the hinge region of the Fc domain (CH1 domain) to modify (e.g., increase or decrease) the number of cysteine ​​residues in the hinge region, as described, for example, in U.S. Patent No. 5,677,425. Modifying the number of cysteine ​​residues in the hinge region of the CH1 domain can, for example, facilitate the assembly of light and heavy chains, or modify (e.g., increase or decrease) the stability of the antibody, or facilitate linker conjugation.

[0214] In some embodiments, one, two, or more mutations (e.g., amino acid substitutions) are introduced into the Fc region of the antibodies described herein (numbered according to the Kabat numbering system (e.g., the EU index in Kabat), for example, the CH2 domain (residues 231-340 of human IgG1) and / or the CH3 domain (residues 341-447 of human IgG1) and / or the hinge region) to increase or decrease the affinity of the antibody to Fc receptors (e.g., activated Fc receptors) on the surface of effector cells. Mutations in the Fc region of antibodies that decrease or increase the affinity of an antibody to Fc receptors, and techniques for introducing such mutations into Fc receptors or fragments thereof, are known to those skilled in the art. Examples of antibody mutations at the Fc receptor that can be used to alter the affinity of an antibody to the Fc receptor are described, for example, in Smith P et al., (2012) PNAS 109:6181-6186, U.S. Patent No. 6,737,056, and International Publication Nos. WO02 / 060919; WO98 / 23289; and WO97 / 34631, which are incorporated herein by reference.

[0215] In some embodiments, one, two, or more amino acid mutations (i.e., substitutions, insertions, or deletions) are introduced into the IgG constant domain or its FcRn binding fragment (preferably an Fc or hinge-Fc domain fragment) to modify (e.g., decrease or increase) the in vivo half-life of the antibody. See, for example, International Publication Nos. WO02 / 060919; WO98 / 23289; and WO97 / 34631; and U.S. Patents 5,869,046, 6,121,022, 6,277,375, and 6,165,745 for examples of mutations that modify (e.g., decrease or increase) the in vivo half-life of the antibody.

[0216] In some embodiments, one, two, or more amino acid mutations (i.e., substitutions, insertions, or deletions) are introduced into the IgG constant domain or its FcRn binding fragment (preferably an Fc or hinge-Fc domain fragment) to reduce the half-life of the anti-KLK5 antibody in vivo. In some embodiments, one, two, or more amino acid mutations (i.e., substitutions, insertions, or deletions) are introduced into the IgG constant domain or its FcRn binding fragment (preferably an Fc or hinge-Fc domain fragment) to increase the half-life of the antibody in vivo. In some embodiments, the antibody may have one or more amino acid mutations (e.g., substitutions) in a second constant (CH2) domain (residues 231-340 of human IgG1) and / or a third constant (CH3) domain (residues 341-447 of human IgG1), numbered according to the EU index in Kabat (Kabat EA et al., (1991), cited above). In some embodiments, the constant region of IgG1 of the antibodies described herein, numbered according to the EU index as set forth in Kabat, includes a methionine (M) to tyrosine (Y) substitution at position 252, a serine (S) to threonine (T) substitution at position 254, and a threonine (T) to glutamic acid (E) substitution at position 256. See U.S. Patent No. 7,658,921, which is incorporated herein by reference. This type of mutant IgG is called a “YTE mutant” and has been shown to exhibit a four-fold increased half-life compared to the wild-type version of the same antibody (see Dall'Acqua WF et al., (2006) J Biol Chem 281:23514-24). In some embodiments, the antibody includes an IgG constant domain that contains 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 found in Kabat.

[0217] In some embodiments, the antibody includes an Fc region that has been modified, for example, by introducing substitutions of M428L and / or N434A, for the purpose of extending the half-life. Non-limiting examples of such Fc variants that affect the circulating half-life are provided in Saunders KO, Conceptual Approaches to Modulating Antibody Effector Functions and Circulation Half-Life, Front Immunol. 2019;10:1296, which is incorporated herein by reference.

[0218] In some embodiments, the effector function(s) of an anti-KLK5 antibody is modified by introducing one, two, or more amino acid substitutions into the IgG constant domain Fc region, for example, by introducing Leu234Ala and Leu235Ala mutations (commonly referred to as LALA mutations). The effector ligand whose affinity is modified may be, for example, the Fc receptor or the C1 component of complement. This technique is described in U.S. Patents 5,624,821 and 5,648,260. In some embodiments, deletion or inactivation of the constant domain (via point mutation or other means) can reduce the binding of the circulating antibody to the Fc receptor, thereby increasing tumor localization. For a description of mutations that delete or inactivate the constant domain and thereby increase tumor localization, see, for example, U.S. Patents 5,585,097 and 8,591,886. In some embodiments, one or more amino acid substitutions may be introduced into the Fc region of the antibodies described herein to remove potential glycosylation sites on the Fc region, thereby reducing Fc receptor binding (see, for example, Shields RL et al., (2001) J Biol Chem 276:6591-604).

[0219] In some embodiments, one or more amino acids in the constant region of the anti-KLK5 antibody described herein can be replaced with different amino acid residues, thereby giving the antibody modified C1q binding and / or reduced or ineffective complement-dependent cell-mediated cytotoxicity (CDC). This technique is described in detail in U.S. Patent 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 the antibody described herein are modified, thereby altering the antibody's ability to immobilize complement. This technique is further described in International Publication No. WO94 / 29351. In some embodiments, the Fc region of the antibody described herein is modified to increase the antibody's ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) and / or increase the antibody's affinity for the Fcγ receptor. This technique is further described in International Publication No. WO00 / 42072.

[0220] In some embodiments, the antibody comprises an Fc variant containing amino acid substitutions L234A, L235E, and P329G, in which case the numbering follows the EU index. In some embodiments, the antibody comprising the Fc variant exhibits reduced affinity for one or more or each of FcyRJ, FcyRIIA, FcyRIIIA, and Clq compared to the antibody comprising the wild-type human Fc region. Examples of such Fc variants are provided in International Patent Application Publication No. WO2021 / 055669, title, FC VARIANTS WITH REDUCED EFFECTOR FUNCTION, published March 25, 2021; and U.S. Patent Application Publication No. US2021-0087271, title, FC VARIANTS WITH REDUCED EFFECTOR FUNCTION, published March 25, 2021, the contents of which are incorporated herein by reference.

[0221] In some embodiments, as described elsewhere herein, variable domain(s) sequences(options) of the heavy and / or light chains of the antibodies provided herein can be used to generate, for example, CDR-implanted, chimeric, humanized, or compound human antibodies or antigen-binding fragments. As will be understood by those skilled in the art, any variant, CDR-implanted, chimeric, humanized, or compound antibody derived from any of the antibodies provided herein may be useful in the compositions and methods described herein, and the variant, CDR-implanted, chimeric, humanized, or compound antibody will maintain the ability to specifically bind to KLK5 such that it has at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% or more binding to KLK5 compared to the original antibody from which it is derived.

[0222] In some embodiments, the antibodies provided herein include mutations that confer desirable properties to the antibody. For example, to avoid potential complications from Fab-arm exchange, which are known to occur with natural IgG4 mAbs, the antibodies provided herein may include 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), in which serine 228 (EU numbering; residue 241 Kabat numbering) is converted to proline, resulting in an IgG1-like hinge sequence. Thus, any of the antibodies may include a stabilizing "Adair" mutation.

[0223] In some embodiments, the antibody is modified, for example, by glycosylation, phosphorylation, SUMOylation, and / or methylation. In some embodiments, the antibody is a glycosylated antibody conjugated to one or more sugar or carbohydrate molecules. In some embodiments, one or more sugar or carbohydrate molecules are conjugated to the antibody via N-glycosylation, O-glycosylation, C-glycosylation, glyciation (GPI anchor attachment), and / or phosphoglycosylation. In some embodiments, one or more sugar or carbohydrate molecules are monosaccharides, disaccharides, oligosaccharides, or glycans. In some embodiments, one or more sugar or carbohydrate molecules are branched oligosaccharides or branched glycans. In some embodiments, one or more sugar or carbohydrate molecules include mannose units, glucose units, N-acetylglucosamine units, N-acetylgalactosamine units, galactose units, fucose units, or phospholipid units. In some embodiments, there are about 1–10, about 1–5, about 5–10, about 1–4, about 1–3, or about 2 sugar molecules. In some embodiments, the glycosylated antibody is completely or partially glycosylated. In some embodiments, the antibody is glycosylated by chemical reaction or enzymatic means. In some embodiments, the antibody is glycosylated in vitro or intracellularly, which may optionally be deficient in enzymes of the N- or O-glycosylation pathway, such as glycosyltransferase. In some embodiments, the antibody is functionalized with sugar molecules or carbohydrate molecules, as described in International Patent Application Publication No. WO2014065661, published May 1, 2014, titled "Modified antibody, antibody-conjugate and process for the preparation thereof".

[0224] In some embodiments, any one of the anti-KLK5 antibodies described herein may include a signal peptide in the heavy chain sequence and / or light chain sequence (e.g., an N-terminal signal peptide). In some embodiments, the anti-KLK5 antibody described herein comprises either a VH sequence or a VL sequence, either an IgG heavy chain sequence or a light chain sequence, or either an F(ab') heavy chain sequence or a light chain sequence described herein, and further comprises a signal peptide (e.g., an N-terminal signal peptide).

[0225] (b) Anti-KLK7 antibody In some embodiments, an antibody targeting KLK7 (referred to as an anti-KLK7 antibody) is an antibody specific to kallikrein-(KLK7). In some embodiments, antibodies are provided herein that bind to KLK7 (e.g., human KLK7 or mouse KLK7) with high specificity and affinity. In some embodiments, the antibodies described herein bind specifically to the KLK7 epitope that is exposed to or will be exposed to the antibody. In some embodiments, the anti-KLK7 antibodies provided herein bind specifically to KLK7 derived from humans, non-human primates, mice, rats, etc. In some embodiments, the anti-KLK7 antibodies provided herein bind specifically to human KLK7. In some embodiments, the anti-KLK7 antibodies provided herein bind specifically to mouse KLK7.

[0226] Kallikrein-7 is a serine protease encoded by the KLK7 gene in humans. KLK7 is characterized as a stratum corneum chymotriptic enzyme (SCCE). It is the seventh member of the human kallikrein family, which includes 15 homologous serine proteases located on chromosome 19.

[0227] KLK7 is secreted as an inactive zymogen (for example, in the granular layer of the epidermis) and requires proteolytic cleavage to be activated. In some embodiments, KLK5 or matryptase activates KLK7. Once activated, KLK7 can cleave proteins that form the stratum corneum and / or granular layer (e.g., corneodesmosine (CDSN), desmoglein 1 (DSG1), and desmocolin 1 (DSC1)) (see, for example, 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 components of corneodesmosomes, which are intercellular adhesion structures that connect intermediate filaments of adjacent cells within the stratum corneum. In some embodiments, proteolysis of keratinodesmosomes leads to epidermal desquamation (i.e., the shedding of keratinocytes from the outer layer of the epidermis). In some embodiments, the combined roles of KLK5 and KLK7 suggest that the KLK skin cascade is responsible for regulating desquamation. KLK7 is a chymotrypsin-like serine protease that cleaves proteins at tyrosine, phenylalanine, or leucine residues. In some embodiments, dysregulation of KLK7 is 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 breakdown of skin homeostasis and normal barrier function.

[0228] In some embodiments, the anti-KLK7 antibodies described herein specifically bind to epitopes on human KLK7. Exemplary amino acid sequences of human KLK7 are described 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 entirety of which are incorporated herein by reference.

[0229] In some embodiments, the anti-KLK7 antibodies described herein specifically bind to epitopes on mouse KLK7. Exemplary amino acid sequences of mouse KLK7 are described in NCBI accession number NP_036002.1 and UniProt accession number Q91VE3, and these entire sequences are incorporated herein by reference.

[0230] In some embodiments, the anti-KLK7 antibodies described herein specifically bind to an epitope on KLK7 (e.g., a catalytic domain / pocket of human or mouse KLK7). In some embodiments, the anti-KLK7 antibodies described herein prevent KLK7 (e.g., human or mouse KLK7) from cleaving its substrate. In some embodiments, the anti-KLK7 antibodies described herein bind to a fragment of KLK7 (e.g., human or mouse KLK7). The fragment of KLK7 (e.g., human or mouse) may be about 5 to 425 amino acids, about 10 to 400 amino acids, about 50 to 350 amino acids, about 100 to 300 amino acids, about 150 to 250 amino acids, about 200 to 300 amino acids, about 75 to 150 amino acids, about 25 to 100 amino acids, or about 10 to 30 amino acids in length. Without intending to be bound by any particular theory, in some embodiments, any one of the heavy chain (HC) complementarity-determining regions 3 (CDR3) of the anti-KLK7 antibodies described herein inhibits KLK7 (e.g., human or mouse KLK7) by binding to the catalytic domain / pocket of KLK7.

[0231] In some embodiments, the anti-KLK7 antibodies described herein inhibit KLK7 protease activity. In some embodiments, the anti-KLK7 antibody inhibits the cleavage of KHLF-AMC by KLK7 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 0.4 nM, less than 0.3 nM, less than 0.2 nM, less than 0.16 nM, less than 0.1 nM or less than 0.05 nM.

[0232] In some embodiments, the anti-KLK7 antibodies described herein specifically bind to the active form of KLK7. In some embodiments, the anti-KLK7 antibodies described herein do not bind to the inactive form of KLK7. In some embodiments, the anti-KLK7 antibodies described herein specifically bind to the active site of KLK7. The active site of KLK7 is the site to which a KLK7 substrate molecule binds and undergoes cleavage. The active site may also be known as the catalytic domain or catalytic triad. In some embodiments, the active site of KLK7 (i.e., the catalytic domain or catalytic triad) consists of amino acids Ser195, His57, and Asp102 of KLK7 (see, e.g., Goettig et al., Natural and synthetic inhibitors of kallikrein-related peptidases (KLKs), Biochimie. 2010 Nov;92(11):1546-1567).

[0233] In some embodiments, the antibodies described herein are optimized versions (e.g., affinity matured versions) of the parental antibody. In some embodiments, the antibodies described herein bind to KLK7 (e.g., human or mouse KLK7) with at least 10 -4 M, 10 -5 M, 10 -6 M, 10 -7 M, 10 -8 M, 10 -9 M, 10 -10 M, 10 -11 M, 10 -12 M, 10 -13With a binding affinity of less than M (e.g., as shown by K D ), it binds specifically. In some embodiments, the antibodies described herein bind to KLK7 (e.g., human or mouse KLK7) with a binding affinity of 1×10 -10 M to 5×10 -9 M, 1×10 -10 M to 1×10 -9 M, 5×10 -10 to 1×10 -9 M, 5×10 -11 to 1×10 -10 M, 1×( -11 to 5×10 -10 M, or 5×10 -13 to 1×10 -12 M (e.g., as shown by K D ), and binds specifically. For example, the antibodies of the present disclosure can bind to the KLK7 protein (e.g., human or mouse KLK7) with an affinity of 1 pM to 500 nM, such as 50 pM to 100 nM, 500 pM to 50 nM, 1 pM to 100 pM, 10 pM to 100 pM, 50 pM to 100 pM, 100 pM to 500 pM, 500 pM to 1 nM, 1 nM to 5 nM, 1 nM to 10 nM, 5 nM to 25 nM, 10 nM to 50 nM, 50 nM to 100 nM, 100 nM to 500 nM. The present disclosure also includes antibodies that compete with any of the antibodies described herein for binding to the KLK7 protein (e.g., human or mouse KLK7) and have an affinity of 100 nM or less (e.g., 80 nM or less, 50 nM or less, 20 nM or less, 10 nM or less, 1 nM or less, 500 pM or less, 50 pM or less, or 5 pM or less). The affinity and binding reaction rate of the antibodies can be tested using any suitable method, including but not limited to biosensor technology (e.g., OCTET or BIACORE). In some embodiments, the antibodies described herein bind to KLK7 with a K D in the subnanomolar range.

[0234] ​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), fluorescence-activated cell sorting (FACS), or spectroscopy (e.g., using fluorescence assays). Exemplary conditions for evaluating binding affinity are HBS-P buffer (10 mM HEPES pH 7.4, 150 mM NaCl, 0.005% (v / v) surfactant P2O) and PBS buffer (10 mM PO4-3, 137 mM NaCl, and 2.7 mM KCl). Using these techniques, the concentration of the binding protein can be measured as a function of the target protein concentration. Generally, the concentration of the binding protein ([[binding]]) is given by the following formula: [[Bound]]=[[Free]] / (Kd+[[Free]]) This is related to the concentration of free target protein (free).

[0235] K A While it is not always necessary to make an accurate determination, obtaining a quantitative measure of affinity determined using methods such as ELISA or FACS analysis is useful, as it indicates that K A Since it is proportional to the activity, it may be sufficient, and therefore can be used for comparisons to determine whether a higher affinity is, for example, twice as high, to obtain a qualitative measurement of affinity, or to infer affinity by activity in a functional assay (e.g., an in vitro or in vivo assay).

[0236] Exemplary anti-KLK7 antibody sequences (e.g., heavy chain (HC) sequence and light chain (LC) sequence, heavy chain variable domain (VH) and light chain variable domain (VL), and CDR sequence) are provided in Table 2a. [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4] [Table 2-5] [Table 2-6] [Table 2-7]

[0237] In some embodiments, certain amino acid positions in the antibodies described herein (e.g., amino acids in the VH / VL region and / or CDR region) are substitutable, and this substitution results in an antibody having substantially similar binding and biological activity (e.g., substantially similar binding affinity, binding specificity, protease inhibitory activity, anti-inflammatory activity, or a combination thereof) to the reference antibody. To identify substitutable positions in 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 among related antibodies of different groups at any particular position, that position is a substitutable position in the antibody. In other words, a substitutable position is a position where the identity of the amino acid varies among related antibodies. Positions containing constant amino acids are not substitutable positions.

[0238] In some embodiments, the above method may be used to provide a consensus antibody sequence. In such a consensus sequence, non-substitutable positions are indicated by the amino acids present at those positions, and substitutable positions are indicated by "X".

[0239] Depending on how the antibody is adopted, X may be a) any amino acid, b) any amino acid present at that position in any of the related antibodies within that group, or a conservatively substituted variant thereof, or c) any amino acid present at that position in any of the related antibodies within that group. Any antibody having a sequence encompassed by consensus should bind to the same antigen as any of the related antibodies.

[0240] In some embodiments, the methods described above may be employed in a method for designing and producing variants of a parent antibody that at least maintain (i.e., maintain or increase) the antigen-binding activity of the parent antibody. Antibodies containing substitutions at substitutable positions can be produced and tested, and therefore substitutions at those positions should not significantly reduce the antibody's binding activity. Generally, antibody variants of a parent antibody have an antigen-binding affinity of 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%, and usually up to at least 10,000%) of the parent antibody's binding affinity to a particular antigen.

[0241] In some embodiments, the substitutable positions of the parent antibody may be substituted by: a) any of 20 naturally occurring amino acids to produce a random substitution; b) an amino acid with biochemical properties similar to an amino acid already present at the substitutable position to produce a conservative substitution; c) an amino acid present at the same position in the related antibody to produce a designated substitution; or d) an amino acid present at the same position in a similar human antibody to produce a humanization substitution. Substitutions may occur in any portion of the antibody variable region, including any framework region or CDR. In certain embodiments, a single substitutable amino acid may be substituted. However, in other embodiments, multiple substitutable amino acids (e.g., up to about 5 or 10 or more) may be substituted. In certain embodiments, the type of substitution that can be performed at each substitutable position may be indicated by the type of amino acid present at that position in the related antibody. For example, if an unrelated amino acid (e.g., Ala, Gly, Cys, Glu, and Thr) is present at a particular position in the group of related antibodies, any amino acid can be substituted at that position without significantly reducing the antibody's binding activity. Exemplary amino acid substitutions of anti-KLK7 antibodies described herein are shown in Table 2b:

Table 2-8

Table 2-9

Table 2-10

[0242] In some embodiments, the antibody of the present disclosure comprises an HC CDR1 having the amino acid sequence of X1TFX2X3X4X5IX6, where X1 is G or Y, X2 is S, G, or T, X3 is N, P or S, X4 is Y or E, X5 is A or G, or X6 is S or H; an HC CDR2 having the amino acid sequence of X7ISAX8SGDTNYAQX9LQG, where X7 is W or S, X8 is Y or S, or X9 is K or E; ARX 10 AGYGARX 11 an HC CDR3 comprising WYFDL, where X 10 is A, G, or S, or X 11 is H, W, S or D; an LC CDR1 having the amino acid sequence of SEQ ID NO: 69; an LC CDR2 having the amino acid sequence of SEQ ID NO: 70; and / or an LC CDR3 having the amino acid sequence of DX 12 X 13 YSTPPIT, where X 12 is Q or G, or X 13 is S, F, W, or R.

[0243] In some embodiments, the antibodies of this disclosure include: HC CDR1 containing the amino acid sequence GSISSGGYX1WX2, where X1 is Y or S, or X2 is S, H, or N; HC CDR2 containing the amino acid sequence X3IYX4SGX5TYYNPSLKS, where X3 is S or Y, X4 is Y or R, or X5 is S or Y; HC CDR3 containing the amino acid sequence ARAKX6LTX7X8RYX9DY, where X6 is Q or A, X7 is T or L, X8 is H, T, or S, or X9 is F or V; LC CDR1 containing the amino acid sequence of SEQ ID NO: 93; LC CDR2 containing the amino acid sequence of SEQ ID NO: 94; and / or QQAX9X 10 LC CDR3 containing the amino acid sequence of LPFT, where X9 is S or R, or X 10 This includes the condition that it is either D or Q.

[0244] In some embodiments, the antibodies of the present disclosure include HC CDR1 comprising the amino acid sequence GTFX1X2X3AIX4, where X1 is S or N, X2 is N or S, X3 is Y or H, or X4 is S or T; HC CDR2 comprising the amino acid sequence X5IIPIFGX6ANYAQKFQG, where X5 is G or A, or X6 is T, V, or F; HC CDR3 comprising the amino acid sequence ARGAPNYYGX7X8SSRGIAFDI, where X7 is S or A, or X8 is S, Q, or A; LC CDR1 comprising the amino acid sequence of SEQ ID NO: 4; LC CDR2 comprising the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 comprising the amino acid sequence VQANAFPYX9, where X9 is T, K, or S.

[0245] In some embodiments, the antibodies of the present disclosure include: HC CDR1 comprising the amino acid sequence GSISSSX1YX2WX3, where X1 is S or P, X2 is Y or N, or X3 is G or V; HC CDR2 comprising the amino acid sequence SIX4X5SGSTYYNPSLKS, where X4 is S or L, or X5 is Y or H; HC CDR3 comprising the amino acid sequence ARGX6PTYX7GAASHYYYYMDV, where X6 is A or V, X7 is F or W; LC CDR1 comprising the amino acid sequence of SEQ ID NO: 130; LC CDR2 comprising the amino acid sequence of SEQ ID NO: 131; and / or LC CDR3 comprising the amino acid sequence EQYGSX8SPLT, where X8 is Y or E.

[0246] In some embodiments, the antibodies of the present disclosure include: HC CDR1 comprising the amino acid sequence YTFX1GYX2MH, where X1 is T or A, or X2 is Y or D; HC CDR2 comprising the amino acid sequence SINPX3SGX4TNYAQKFQG, where X3 is S or T, or X4 is G or R; HC CDR3 comprising the amino acid sequence ARGGPSTWYGGSAYX5YYGX6DV, where X5 is Y or T, or X6 is M or A; LC CDR1 comprising the amino acid sequence of SEQ ID NO: 143; LC CDR2 comprising the amino acid sequence of SEQ ID NO: 23; and / or LC CDR3 comprising the amino acid sequence QQYAX7LWT, where X7 is N or P.

[0247] In some embodiments, the antibody of this disclosure comprises one or more HC CDR (e.g., HC CDR1, HC CDR2, or HC CDR3) amino acid sequences from any one of the anti-KLK7 antibodies selected from Tables 2a and 2b. In some embodiments, the antibody of this disclosure comprises an HC CDR3 amino acid sequence from any one of the anti-KLK7 antibodies selected from Tables 2a and 2b. In some embodiments, the antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 provided for any one of the (elected) antibodies selected from Tables 2a and 2b. In some embodiments, the antibody of this disclosure comprises an LC CDR3 amino acid sequence from any one of the anti-KLK7 antibodies selected from Tables 2a and 2b. In some embodiments, the antibody of this disclosure comprises one or more LC CDR (e.g., LC CDR1, LC CDR2, or LC CDR3) amino acid sequences from any one of the anti-KLK7 antibodies selected from Tables 2a and 2b. In some embodiments, the antibodies of this disclosure include LC CDR1, LC CDR2, and LC CDR3, which are provided for any one of the anti-KLK7 antibodies selected from Tables 2a and 2b.

[0248] In some embodiments, the antibodies of this disclosure include HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 provided for any one of the anti-KLK7 antibodies selected from Tables 2a and 2b. In some embodiments, the heavy chain CDR3 domain and / or light chain CDR3 domain of the antibody may play a particularly important role in the antibody's binding specificity / affinity to the antigen. Therefore, the antibodies of this disclosure may include at least the heavy chain CDR3 and / or light chain CDR3 of any one of the anti-KLK7 antibodies selected from Tables 2a and 2b.

[0249] Any variant of the exemplary anti-KLK7 antibody disclosed herein is also within the scope of this disclosure. The variant may contain one or more amino acid residue mutations in the VH and / or VL, or in one or more of the HC CDRs and / or one or more of the LC CDRs, compared to the reference antibody, but retain substantially similar binding activity and biological activity (e.g., substantially similar binding affinity, binding specificity, protease inhibitory activity, anti-inflammatory activity, or a combination thereof) to the reference antibody.

[0250] In some embodiments, the antibodies of this disclosure have one or more CDR (e.g., HC CDR or LC CDR) sequences substantially similar to any of HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 from one of the anti-KLK7 antibodies selected from Tables 2a and 2b. In some embodiments, the positions 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) regions of the antibodies described herein can be mutated by 1, 2, 3, 4, 5, or 6 amino acid positions, as long as specific binding to 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%, or at least 95% of the binding of the original antibody from which it is derived). For example, in some embodiments, the position defining the CDR of any antibody described herein can be mutated by shifting the N-terminal and / or C-terminal boundary of the CDR by 1, 2, 3, 4, 5, or 6 amino acids relative to any one CDR position of the antibody described herein, insofar as specific binding of 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%, or at least 95% of the binding of the original antibody from which it originates). 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) regions of the antibodies described herein may be mutated (e.g., shortened or lengthened) by only 1, 2, 3, 4, 5, or more amino acids, as long as immunospecific binding to 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%, or at least 95% of the binding of the original antibody from which it is derived).

[0251] Therefore, in some embodiments, the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein may be 1, 2, 3, 4, or 5 amino acids shorter than one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK7 antibodies selected from Tables 2a and 2b), as long as specific binding to KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained by, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% compared to the binding of the original antibody from which it is derived). In some embodiments, the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein may be 1, 2, 3, 4, or 5 amino acids or longer than one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK7 antibodies selected from Tables 2a and 2b), provided that specific binding to KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained by, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% compared to the binding of the original antibody from which it is derived). In some embodiments, the amino portion of HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be extended by 1, 2, 3, 4, or 5 amino acids or more compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK7 antibodies selected from Tables 2a and 2b), provided that specific binding to KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% compared to the binding of the original antibody from which it is derived).In some embodiments, the carboxyl portions of HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be extended by 1, 2, 3, 4, or 5 amino acids or more compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK7 antibodies selected from Tables 2a and 2b), provided that specific binding to KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% compared to the binding of the original antibody from which it is derived). In some embodiments, the amino portion of HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be shortened by 1, 2, 3, 4, or 5 amino acids or more compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK7 antibodies selected from Tables 2a and 2b), insofar as specific binding to KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% compared to the binding of the original antibody from which it is derived). In some embodiments, the carboxyl portion of HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be shortened by 1, 2, 3, 4, or 5 amino acids or more compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-KLK7 antibodies selected from Tables 2a and 2b), insofar as specific binding to KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% compared to the binding of the original antibody from which it is derived).To confirm whether or not immunospecific binding to KLK7 (e.g., human or mouse KLK7) is maintained, any method can be used, such as using the binding assays and conditions described in the Art.

[0252] In some examples, the antibodies of this disclosure have one or more CDR (e.g., HC CDR or LC CDR) sequences substantially similar to any one of the anti-KLK7 antibodies selected from Tables 2a and 2b. For example, the antibodies described herein may include one or more CDR sequences from any of the anti-KLK7 antibodies selected from Tables 2a and 2b, containing up to 5, 4, 3, 2, or 1 amino acid residue mutations compared to the corresponding CDR region of any one of the CDRs provided herein (e.g., CDRs from any of the anti-KLK7 antibodies selected from Tables 2a and 2b), insofar as specific binding to KLK7 (e.g., human or mouse KLK7) is maintained (e.g., substantially maintained by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% compared to the binding of the original antibody from which it is derived). In some embodiments, any amino acid mutations in any of the CDRs provided herein may be conservative mutations. Conservative mutations can be introduced into a CDR at a position where the residue is unlikely to be involved in interaction with KLK7 (e.g., human or mouse KLK7), for example, when determined based on the crystal structure. Some aspects of this disclosure provide antibodies comprising one or more heavy chain variable (VH) domains and / or light chain variable (VL) domains provided herein. In some embodiments, any VH domain provided herein comprises one or more of the HC CDR sequences provided herein (e.g., HC CDR1, HC CDR2, and HC CDR3), which are, for example, any of the HC CDR sequences provided for any one of the anti-KLK7 selected from Tables 2a and 2b. In some embodiments, any VL domain provided herein comprises one or more of the LC CDR sequences provided herein (e.g., LC CDR1, LC CDR2, and LC CDR3), which are, for example, any of the LC CDR sequences provided for any one of the anti-KLK7 antibodies selected from Tables 2a and 2b.

[0253] In some embodiments, the antibodies of the Disclosure include any antibody comprising a heavy chain variable domain and / or light chain variable domain of any one anti-KLK7 antibody selected from Tables 2a and 2b, as well as variants thereof. In some embodiments, the antibodies of the Disclosure include any antibody comprising a pair of heavy chain variable and light chain variable regions of any anti-KLK7 antibody selected from Tables 2a and 2b.

[0254] Aspects of this disclosure provide antibodies comprising heavy chain variable (VH) domain amino acid sequences and / or light chain variable (VL) domain amino acid sequences homologous to any of the amino acid sequences described herein. In some embodiments, the antibody comprises a heavy chain variable sequence or a light chain variable sequence that is at least 75% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to any one of the heavy chain variable sequences and / or light chain variable sequences of an anti-KLK7 antibody selected from Tables 2a and 2b. In some embodiments, the homologous heavy chain variable amino acid sequences and / or light chain variable amino acid sequences do not mutate within any of the CDR sequences provided herein. For example, in some embodiments, the degree of sequence mutation (e.g., 75%, 80%, 85%, 90%, 95%, 98%, or 99%) may occur within the heavy chain variable sequence and / or light chain variable sequence excluding any of the CDR sequences provided herein. In some embodiments, the antibodies provided herein include heavy-chain and light-chain variable sequences that include a framework sequence which is at least 75%, 80%, 85%, 90%, 95%, 98%, or 99% identical to the framework sequence of any anti-KLK7 antibody selected from Tables 2a and 2b.

[0255] In some embodiments, the antibody of the Disclosure is a humanized antibody (e.g., a humanized variant containing one or more CDRs from Tables 2a and 2b). In some embodiments, the antibody of the Disclosure comprises HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3, which are the same as HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 shown in Tables 2a and 2b, and includes a humanized heavy chain variable region and / or a humanized light chain variable region.

[0256] In some embodiments, the antibody of the Disclosure is a humanized antibody comprising a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH of any of the anti-KLK7 antibodies listed in Tables 2a and 2b. Alternatively or additionally, the antibody of the Disclosure is a humanized antibody comprising a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to any one of the anti-KLK7 antibodies listed in Tables 2a and 2b.

[0257] In some embodiments, the anti-KLK7 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 72. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 73.

[0258] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 66, HC CDR2 having the amino acid sequence of SEQ ID NO: 67, HC CDR3 having the amino acid sequence of SEQ ID NO: 68, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 71.

[0259] In some embodiments, the anti-KLK7 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 66, HC CDR2 having the amino acid sequence of SEQ ID NO: 67, and HC CDR3 having the amino acid sequence of SEQ ID NO: 68. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 71.

[0260] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 66, HC CDR2 having the amino acid sequence of SEQ ID NO: 67, and HC CDR3 having the amino acid sequence of SEQ ID NO: 68. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 71.

[0261] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 66; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 67; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 68. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 69; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 70; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 71.

[0262] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 72. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 73.

[0263] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 72. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 73.

[0264] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 72. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 73.

[0265] In some embodiments, the anti-KLK7 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 199. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 200.

[0266] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 74, HC CDR2 having the amino acid sequence of SEQ ID NO: 67, HC CDR3 having the amino acid sequence of SEQ ID NO: 75, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 198.

[0267] In some embodiments, the anti-KLK7 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 74, HC CDR2 having the amino acid sequence of SEQ ID NO: 67, and HC CDR3 having the amino acid sequence of SEQ ID NO: 75. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 198.

[0268] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 74, HC CDR2 having the amino acid sequence of SEQ ID NO: 67, and HC CDR3 having the amino acid sequence of SEQ ID NO: 75. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 198.

[0269] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 74; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO: 67; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO: 75. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 69; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 70; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 198.

[0270] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 199. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 200.

[0271] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 199. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 200.

[0272] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 199. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 200.

[0273] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 77. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 78.

[0274] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 201, HC CDR3 having the amino acid sequence of SEQ ID NO: 68, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 76.

[0275] In some embodiments, the anti-KLK7 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 201, and HC CDR3 having the amino acid sequence of SEQ ID NO: 68. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 76.

[0276] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 201, and HC CDR3 having the amino acid sequence of SEQ ID NO: 68. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 76.

[0277] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 284; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 201; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 68. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 69; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 70; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 76.

[0278] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 77. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 78.

[0279] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 77. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 78.

[0280] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 77. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 78.

[0281] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 80. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 78.

[0282] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, HC CDR3 having the amino acid sequence of SEQ ID NO: 68, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 76.

[0283] In some embodiments, the anti-KLK7 antibodies of the Disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, and HC CDR3 having the amino acid sequence of SEQ ID NO: 68. As used anywhere in the Disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of the Disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 76.

[0284] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, and HC CDR3 having the amino acid sequence of SEQ ID NO: 68. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 76.

[0285] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 284; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 79; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 68. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 69; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 70; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 76.

[0286] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 80. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 78.

[0287] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 80. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 78.

[0288] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 80. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 78.

[0289] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 80. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 82.

[0290] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, HC CDR3 having the amino acid sequence of SEQ ID NO: 68, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 81.

[0291] In some embodiments, the anti-KLK7 antibodies of the Disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, and HC CDR3 having the amino acid sequence of SEQ ID NO: 68. As used anywhere in the Disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of the Disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 81.

[0292] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, and HC CDR3 having the amino acid sequence of SEQ ID NO: 68. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 81.

[0293] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 284; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 79; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 68. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 69; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 70; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 81.

[0294] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 80. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 82.

[0295] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 80. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 82.

[0296] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 80. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 82.

[0297] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 84. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 78.

[0298] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, HC CDR3 having the amino acid sequence of SEQ ID NO: 83, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 76.

[0299] In some embodiments, the anti-KLK7 antibodies of the Disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, and HC CDR3 having the amino acid sequence of SEQ ID NO: 83. As used anywhere in the Disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of the Disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 76.

[0300] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, and HC CDR3 having the amino acid sequence of SEQ ID NO: 83. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 76.

[0301] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 284; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 79; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 83. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 69; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 70; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 76.

[0302] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 84. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 78.

[0303] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 84. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 78.

[0304] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 84. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 78.

[0305] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 87. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 88.

[0306] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, HC CDR3 having the amino acid sequence of SEQ ID NO: 85, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 86.

[0307] In some embodiments, the anti-KLK7 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, and HC CDR3 having the amino acid sequence of SEQ ID NO: 85. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 86.

[0308] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, and HC CDR3 having the amino acid sequence of SEQ ID NO: 85. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 86.

[0309] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 284; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 79; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 85. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 69; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 70; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 86.

[0310] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which comprises the amino acid sequence of SEQ ID NO: 87. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which comprises the amino acid sequence of SEQ ID NO: 88.

[0311] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 87. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 88.

[0312] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 87. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 88.

[0313] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 285. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 82.

[0314] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, HC CDR3 having the amino acid sequence of SEQ ID NO: 89, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 81.

[0315] In some embodiments, the anti-KLK7 antibodies of the Disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, and HC CDR3 having the amino acid sequence of SEQ ID NO: 89. As used anywhere in the Disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of the Disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 81.

[0316] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, and HC CDR3 having the amino acid sequence of SEQ ID NO: 89. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 81.

[0317] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 284; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 79; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 89. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 69; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 70; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 81.

[0318] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 285. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 82.

[0319] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 285. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 82.

[0320] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 285. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 82.

[0321] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 98. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 97.

[0322] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 90, HC CDR2 having the amino acid sequence of SEQ ID NO: 91, HC CDR3 having the amino acid sequence of SEQ ID NO: 92, LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 95.

[0323] In some embodiments, the anti-KLK7 antibodies of the Disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 90, HC CDR2 having the amino acid sequence of SEQ ID NO: 91, and HC CDR3 having the amino acid sequence of SEQ ID NO: 92. As used anywhere in the Disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of the Disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 95.

[0324] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 90, HC CDR2 having the amino acid sequence of SEQ ID NO: 91, and HC CDR3 having the amino acid sequence of SEQ ID NO: 92. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 95.

[0325] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 90; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO: 91; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO: 92. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 93; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 94; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 95.

[0326] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 98. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 97.

[0327] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 98. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 97.

[0328] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 98. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 97.

[0329] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises heavy chain variable domains HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 153. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises light chain variable domains LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 97.

[0330] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 96, HC CDR2 having the amino acid sequence of SEQ ID NO: 109, HC CDR3 having the amino acid sequence of SEQ ID NO: 92, LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 95.

[0331] In some embodiments, the anti-KLK7 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 96, HC CDR2 having the amino acid sequence of SEQ ID NO: 109, and HC CDR3 having the amino acid sequence of SEQ ID NO: 92. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 95.

[0332] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 96, HC CDR2 having the amino acid sequence of SEQ ID NO: 109, and HC CDR3 having the amino acid sequence of SEQ ID NO: 92. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 95.

[0333] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 96; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 109; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 92. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 93; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 94; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 95.

[0334] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 153. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 97.

[0335] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 153. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 97.

[0336] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 153. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 97.

[0337] In some embodiments, the anti-KLK7 antibody of this disclosure comprises heavy chain variable domains HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 103. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises light chain variable domains LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 104.

[0338] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 99, HC CDR2 having the amino acid sequence of SEQ ID NO: 100, HC CDR3 having the amino acid sequence of SEQ ID NO: 101, LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 102.

[0339] In some embodiments, the anti-KLK7 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 99, HC CDR2 having the amino acid sequence of SEQ ID NO: 100, and HC CDR3 having the amino acid sequence of SEQ ID NO: 101. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 102.

[0340] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 99, HC CDR2 having the amino acid sequence of SEQ ID NO: 100, and HC CDR3 having the amino acid sequence of SEQ ID NO: 101. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 102.

[0341] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 99; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 100; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 101. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 93; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 94; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 102.

[0342] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 103. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 104.

[0343] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 103. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 104.

[0344] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 103. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 104.

[0345] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises heavy chain variable domains HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 107. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises light chain variable domains LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 108.

[0346] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 99, HC CDR2 having the amino acid sequence of SEQ ID NO: 100, HC CDR3 having the amino acid sequence of SEQ ID NO: 105, LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 106.

[0347] In some embodiments, the anti-KLK7 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 99, HC CDR2 having the amino acid sequence of SEQ ID NO: 100, and HC CDR3 having the amino acid sequence of SEQ ID NO: 105. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 106.

[0348] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 99, HC CDR2 having the amino acid sequence of SEQ ID NO: 100, and HC CDR3 having the amino acid sequence of SEQ ID NO: 105. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 106.

[0349] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 99; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 100; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 105. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 93; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 94; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 106.

[0350] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 107. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 108.

[0351] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 107. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 108.

[0352] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 107. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 108.

[0353] In some embodiments, the anti-KLK7 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 111. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 97.

[0354] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 96, HC CDR2 having the amino acid sequence of SEQ ID NO: 109, HC CDR3 having the amino acid sequence of SEQ ID NO: 110, LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 95.

[0355] In some embodiments, the anti-KLK7 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 96, HC CDR2 having the amino acid sequence of SEQ ID NO: 109, and HC CDR3 having the amino acid sequence of SEQ ID NO: 110. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 95.

[0356] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 96, HC CDR2 having the amino acid sequence of SEQ ID NO: 109, and HC CDR3 having the amino acid sequence of SEQ ID NO: 110. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 95.

[0357] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 96; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 109; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 110. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 93; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 94; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 95.

[0358] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 111. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 97.

[0359] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 111. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 97.

[0360] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 111. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 97.

[0361] In some embodiments, the anti-KLK7 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 115. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 116.

[0362] In some embodiments, the antibodies of this disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 66, HC CDR2 having the amino acid sequence of SEQ ID NO: 112, HC CDR3 having the amino acid sequence of SEQ ID NO: 113, 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: 114.

[0363] In some embodiments, the anti-KLK7 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 66, HC CDR2 having the amino acid sequence of SEQ ID NO: 112, and HC CDR3 having the amino acid sequence of SEQ ID NO: 113. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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: 114.

[0364] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 66, HC CDR2 having the amino acid sequence of SEQ ID NO: 112, and HC CDR3 having the amino acid sequence of SEQ ID NO: 113. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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: 114.

[0365] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 66; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 112; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 113. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO: 114.

[0366] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 115. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 116.

[0367] In some embodiments, the anti-KLK7 antibody of this disclosure includes a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 115. Alternatively or additionally, the anti-KLK7 antibody of this disclosure includes a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 116.

[0368] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 115. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 116.

[0369] In some embodiments, the anti-KLK7 antibody of this disclosure comprises HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 121. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 122.

[0370] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 117, HC CDR2 having the amino acid sequence of SEQ ID NO: 118, HC CDR3 having the amino acid sequence of SEQ ID NO: 119, 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: 120.

[0371] In some embodiments, the anti-KLK7 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 117, HC CDR2 having the amino acid sequence of SEQ ID NO: 118, and HC CDR3 having the amino acid sequence of SEQ ID NO: 119. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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: 120.

[0372] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 117, HC CDR2 having the amino acid sequence of SEQ ID NO: 118, and HC CDR3 having the amino acid sequence of SEQ ID NO: 119. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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: 120.

[0373] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 117; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 118; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 119. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO. 120.

[0374] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 121. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 122.

[0375] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 121. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 122.

[0376] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 121. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 122.

[0377] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises heavy chain variable domains HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 127. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises light chain variable domains LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 128.

[0378] In some embodiments, the antibodies of this disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 123, HC CDR2 having the amino acid sequence of SEQ ID NO: 124, HC CDR3 having the amino acid sequence of SEQ ID NO: 125, 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: 126.

[0379] In some embodiments, the anti-KLK7 antibodies of this disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 123, HC CDR2 having the amino acid sequence of SEQ ID NO: 124, and HC CDR3 having the amino acid sequence of SEQ ID NO: 125. As used anywhere in this disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to 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: 126.

[0380] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 123, HC CDR2 having the amino acid sequence of SEQ ID NO: 124, and HC CDR3 having the amino acid sequence of SEQ ID NO: 125. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to 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: 126.

[0381] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 123; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 124; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 125. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 4; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of SEQ ID NO: 126.

[0382] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises VH, which contains the amino acid sequence of SEQ ID NO: 127. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises VL, which contains the amino acid sequence of SEQ ID NO: 128.

[0383] In some embodiments, the anti-KLK7 antibody of this disclosure comprises a VH containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VH described in SEQ ID NO. 127. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises a VL containing 20 or fewer amino acid mutations (e.g., 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to the VL described in SEQ ID NO. 128.

[0384] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises a VH having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH described in SEQ ID NO: 127. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises a VL having an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL described in SEQ ID NO: 128.

[0385] In some embodiments, the anti-KLK7 antibody of this disclosure comprises heavy chain variable domains HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 133. Alternatively or additionally, the anti-KLK7 antibody of this disclosure comprises light chain variable domains LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 134.

[0386] In some embodiments, the antibodies of the present disclosure include HC CDR1 having the amino acid sequence of SEQ ID NO: 19, HC CDR2 having the amino acid sequence of SEQ ID NO: 20, HC CDR3 having the amino acid sequence of SEQ ID NO: 129, LC CDR1 having the amino acid sequence of SEQ ID NO: 130, LC CDR2 having the amino acid sequence of SEQ ID NO: 131, and LC CDR3 having the amino acid sequence of SEQ ID NO: 132.

[0387] In some embodiments, the anti-KLK7 antibodies of the Disclosure comprise HC CDR1, HC CDR2, and HC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 19, HC CDR2 having the amino acid sequence of SEQ ID NO: 20, and HC CDR3 having the amino acid sequence of SEQ ID NO: 129. As used anywhere in the Disclosure, “collectively” means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or additionally, the anti-KLK7 antibodies of the Disclosure comprise LC CDR1, LC CDR2, and LC CDR3, which collectively contain 5 or fewer amino acid mutations (e.g., 5, 4, 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 130, LC CDR2 having the amino acid sequence of SEQ ID NO: 131, and LC CDR3 having the amino acid sequence of SEQ ID NO: 132.

[0388] In some embodiments, the anti-KLK7 antibody of the present disclosure comprises HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 19, HC CDR2 having the amino acid sequence of SEQ ID NO: 20, and HC CDR3 having the amino acid sequence of SEQ ID NO: 129. Alternatively or additionally, the anti-KLK7 antibody of the present disclosure comprises LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 130, LC CDR2 having the amino acid sequence of SEQ ID NO: 131, and LC CDR3 having the amino acid sequence of SEQ ID NO: 132.

[0389] In some embodiments, the anti-KLK7 antibody of the present disclosure includes HC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO. 19; HC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR2 having the amino acid sequence of SEQ ID NO. 20; and / or HC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to HC CDR3 having the amino acid sequence of SEQ ID NO. 129. Alternatively or additionally, the anti-KLK7 antibodies of this disclosure include LC CDR1 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO. 130; LC CDR2 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR2 having the amino acid sequence of SEQ ID NO. 131; and / or LC CDR3 having 3 or fewer amino acid mutations (e.g., 3, 2, or 1 or fewer amino acid mutations) compared to LC CDR3 having the amino acid sequence of S...

Claims

1. An antibody that specifically binds to KLK5, (a) HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 3, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 11; (b) HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 10, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 11; (c) HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 14, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 11; (d) HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 16, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 11; (e) HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 18, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 11; (f) HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 24, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 29; (g) HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 28, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 29; (h) HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 32, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 37; (i) HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 36, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 29; (j) HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 42, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 43; (k) HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 46, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 43; (l) HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 49, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 43; (m) HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 51, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 43; (n) HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 53, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 43; (o) HC CDR1, HC CDR2 and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 58, and LC CDR1, LC CDR2 and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO: 59; or (p) The antibody comprising HC CDR1, HC CDR2, and HC CDR3 heavy chain variable domains having the amino acid sequence of SEQ ID NO: 64, and LC CDR1, LC CDR2, and LC CDR3 light chain variable domains having the amino acid sequence of SEQ ID NO:

65.

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

63.

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

65.

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

152.

5. The aforementioned antibody (a) HC CDR1 having the amino acid sequence of SEQ ID NO: 66, HC CDR2 having the amino acid sequence of SEQ ID NO: 67, HC CDR3 having the amino acid sequence of SEQ ID NO: 68, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 71; (b) HC CDR1 having the amino acid sequence of SEQ ID NO: 74, HC CDR2 having the amino acid sequence of SEQ ID NO: 67, HC CDR3 having the amino acid sequence of SEQ ID NO: 75, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 198; (c) HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 201, HC CDR3 having the amino acid sequence of SEQ ID NO: 68, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 76; (d) HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, HC CDR3 having the amino acid sequence of SEQ ID NO: 68, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 76; (e) HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, HC CDR3 having the amino acid sequence of SEQ ID NO: 68, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 81; (f) HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, HC CDR3 having the amino acid sequence of SEQ ID NO: 83, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 76; (g) HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, HC CDR3 having the amino acid sequence of SEQ ID NO: 85, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 86; (h) HC CDR1 having the amino acid sequence of SEQ ID NO: 284, HC CDR2 having the amino acid sequence of SEQ ID NO: 79, HC CDR3 having the amino acid sequence of SEQ ID NO: 89, LC CDR1 having the amino acid sequence of SEQ ID NO: 69, LC CDR2 having the amino acid sequence of SEQ ID NO: 70, and LC CDR3 having the amino acid sequence of SEQ ID NO: 81; (i) HC CDR1 having the amino acid sequence of SEQ ID NO: 90, HC CDR2 having the amino acid sequence of SEQ ID NO: 91, HC CDR3 having the amino acid sequence of SEQ ID NO: 92, LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 95; (j) HC CDR1 having the amino acid sequence of SEQ ID NO: 96, HC CDR2 having the amino acid sequence of SEQ ID NO: 109, HC CDR3 having the amino acid sequence of SEQ ID NO: 92, LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 95; (k) HC CDR1 having the amino acid sequence of SEQ ID NO: 99, HC CDR2 having the amino acid sequence of SEQ ID NO: 100, HC CDR3 having the amino acid sequence of SEQ ID NO: 101, LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 102; (l) HC CDR1 having the amino acid sequence of SEQ ID NO: 99, HC CDR2 having the amino acid sequence of SEQ ID NO: 100, HC CDR3 having the amino acid sequence of SEQ ID NO: 105, LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 106; (m) HC CDR1 having the amino acid sequence of SEQ ID NO: 96, HC CDR2 having the amino acid sequence of SEQ ID NO: 109, HC CDR3 having the amino acid sequence of SEQ ID NO: 110, LC CDR1 having the amino acid sequence of SEQ ID NO: 93, LC CDR2 having the amino acid sequence of SEQ ID NO: 94, and LC CDR3 having the amino acid sequence of SEQ ID NO: 95; (n) HC CDR1 having the amino acid sequence of SEQ ID NO: 66, HC CDR2 having the amino acid sequence of SEQ ID NO: 112, HC CDR3 having the amino acid sequence of SEQ ID NO: 113, 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: 114; (o) HC CDR1 having the amino acid sequence of SEQ ID NO: 117, HC CDR2 having the amino acid sequence of SEQ ID NO: 118, HC CDR3 having the amino acid sequence of SEQ ID NO: 119, 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: 120; (p) HC CDR1 having the amino acid sequence of SEQ ID NO: 123, HC CDR2 having the amino acid sequence of SEQ ID NO: 124, HC CDR3 having the amino acid sequence of SEQ ID NO: 125, 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: 126; (q) HC CDR1 having the amino acid sequence of SEQ ID NO: 19, HC CDR2 having the amino acid sequence of SEQ ID NO: 20, HC CDR3 having the amino acid sequence of SEQ ID NO: 129, LC CDR1 having the amino acid sequence of SEQ ID NO: 130, LC CDR2 having the amino acid sequence of SEQ ID NO: 131, and LC CDR3 having the amino acid sequence of SEQ ID NO: 132; (r) HC CDR1 having the amino acid sequence of SEQ ID NO: 135, HC CDR2 having the amino acid sequence of SEQ ID NO: 136, HC CDR3 having the amino acid sequence of SEQ ID NO: 137, LC CDR1 having the amino acid sequence of SEQ ID NO: 130, LC CDR2 having the amino acid sequence of SEQ ID NO: 131, and LC CDR3 having the amino acid sequence of SEQ ID NO: 138; (s) HC CDR1 having the amino acid sequence of SEQ ID NO: 38, HC CDR2 having the amino acid sequence of SEQ ID NO: 141, HC CDR3 having the amino acid sequence of SEQ ID NO: 142, LC CDR1 having the amino acid sequence of SEQ ID NO: 23, LC CDR2 having the amino acid sequence of SEQ ID NO: 144, and LC CDR3 having the amino acid sequence of SEQ ID NO: 145; or (t) The antibody according to claim 4, comprising HC CDR1 having the amino acid sequence of SEQ ID NO: 147, HC CDR2 having the amino acid sequence of SEQ ID NO: 148, HC CDR3 having the amino acid sequence of SEQ ID NO: 149, LC CDR1 having the amino acid sequence of SEQ ID NO: 143, LC CDR2 having the amino acid sequence of SEQ ID NO: 23, and LC CDR3 having the amino acid sequence of SEQ ID NO:

150.

6. The aforementioned antibody (a) VH containing the amino acid sequence of SEQ ID NO: 72 and VL containing the amino acid sequence of SEQ ID NO: 73; (b) VH containing the amino acid sequence of SEQ ID NO: 199 and VL containing the amino acid sequence of SEQ ID NO: 200; (c) VH containing the amino acid sequence of SEQ ID NO: 77 and VL containing the amino acid sequence of SEQ ID NO: 78; (d) VH containing the amino acid sequence of SEQ ID NO: 80 and VL containing the amino acid sequence of SEQ ID NO: 78; (e) VH containing the amino acid sequence of SEQ ID NO: 80 and VL containing the amino acid sequence of SEQ ID NO: 82; (f) VH containing the amino acid sequence of SEQ ID NO: 84 and VL containing the amino acid sequence of SEQ ID NO: 78; (g) VH containing the amino acid sequence of SEQ ID NO: 87 and VL containing the amino acid sequence of SEQ ID NO: 88; (h) VH containing the amino acid sequence of SEQ ID NO: 285 and VL containing the amino acid sequence of SEQ ID NO: 82; (i) VH containing the amino acid sequence of SEQ ID NO: 98 and VL containing the amino acid sequence of SEQ ID NO: 97; (j) VH containing the amino acid sequence of SEQ ID NO: 153 and VL containing the amino acid sequence of SEQ ID NO: 97; (k) VH containing the amino acid sequence of SEQ ID NO: 103 and VL containing the amino acid sequence of SEQ ID NO: 104; (l) VH containing the amino acid sequence of SEQ ID NO: 107 and VL containing the amino acid sequence of SEQ ID NO: 108; (m) VH containing the amino acid sequence of SEQ ID NO: 111 and VL containing the amino acid sequence of SEQ ID NO: 97; (n) VH containing the amino acid sequence of SEQ ID NO: 115 and VL containing the amino acid sequence of SEQ ID NO: 116; (o) VH containing the amino acid sequence of SEQ ID NO: 121 and VL containing the amino acid sequence of SEQ ID NO: 122; (p) VH containing the amino acid sequence of SEQ ID NO: 127 and VL containing the amino acid sequence of SEQ ID NO: 128; (q) VH containing the amino acid sequence of SEQ ID NO: 133 and VL containing the amino acid sequence of SEQ ID NO: 134; (r) VH containing the amino acid sequence of SEQ ID NO: 139 and VL containing the amino acid sequence of SEQ ID NO: 140; (s) VH containing the amino acid sequence of SEQ ID NO: 145 and VL containing the amino acid sequence of SEQ ID NO: 146; (t) The antibody according to claim 4 or 5, comprising VH containing the amino acid sequence of SEQ ID NO: 151 and VL containing 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 Tables 1a and 1b, and a second antigen-specific binding site from an anti-KLK7 antibody selected from Tables 2a and 2b.

8. The bispecific antibody according to claim 7, wherein the bispecific antibody comprises a pair of anti-KLK5 antibody and anti-KLK7 antibody as listed in Table 4.

9. The bispecific antibody according to claim 7 or 8, wherein the bispecific antibody comprises HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 of anti-KLK5 antibodies selected from Tables 1a and 1b, and HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 of anti-KLK7 antibodies selected from Tables 2a and 2b.

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

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

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

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

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

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

16. The bispecific antibody according to any one of claims 7 to 15, wherein the bispecific antibody inhibits the protease activity of KLK5.

17. The bispecific antibody according to any one of claims 7 to 16, wherein the bispecific antibody inhibits the protease activity of KLK7.

18. The bispecific antibody according to any one of claims 7 to 17, wherein the bispecific antibody is not cleaved in the heavy chain by KLK5 upon binding to KLK5.

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

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

82.

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

81.

22. The aforementioned bispecific antibody (a) A first arm comprising VH containing the amino acid sequence of SEQ ID NO: 28 and VL containing the amino acid sequence of SEQ ID NO: 29; and (b) A bispecific antibody according to any one of claims 7 to 21, comprising a second arm comprising VH containing the amino acid sequence of SEQ ID NO: 285 and VL containing the amino acid sequence of SEQ ID NO:

82.

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

24. A nucleic acid encoding an antibody according to any one of claims 1 to 6, or a bispecific antibody according to any one of claims 7 to 22.

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

26. An antibody according to any one of claims 1 to 6, a bispecific antibody according to any one of claims 7 to 22, or a composition according to claim 10, for use in a method for treating skin barrier defects.

27. The method according to claim 26, wherein the skin barrier defect is associated with Netherton syndrome, atopic dermatitis, eosinophilic esophagitis, prurigo nodularis, chronic pruritus of unknown cause (CPUO), dry skin, asthma (especially KLK5), ichthyosis vulgaris, or itching or chronic itching.

28. An antibody, bispecific antibody, or composition for use according to claim 27, wherein the skin barrier defect is associated with Netherton syndrome, atopic dermatitis, eosinophilic esophagitis, prurigo nodosa, chronic pruritus of unknown cause (CPUO), dry skin, asthma (especially KLK5), ichthyosis vulgaris, or itching or chronic itching.

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