IP Library › Granted Patent US 12,312,415
Granted Patent B2
US 12,312,415 · App. 18/389,748 · Granted May 27, 2025

Anti-KLK7 antibodies, anti-KLK5 antibodies, multispecific anti-KLK5/KLK7 antibodies, and methods of use

Inventors: James Thomas Koerber (San Mateo, CA); Wyne Pun Lee (Millbrae, CA); Tangsheng Yi (Belmont, CA); Juan Zhang (Palo Alto, CA); Cary Dean Austin (San Carlos, CA); Cecilia P.C. Chiu (Redwood City, CA); Joseph Edward Chavarria-Smith (San Francisco, CA); Jawahar Sudhamsu (San Francisco, CA)
Assignee: Genentech, Inc.
C07K16/40A61K39/3955A61P17/00A61K2039/507C07K2317/24C07K2317/31C07K2317/565C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 12,312,415
App. No.
18/389,748
Granted
May 27, 2025
Kind
B2
Abstract

The invention provides anti-KLK7 antibodies, anti-KLK5 antibodies, anti-KLK5/KLK7 multispecific antibodies, and methods of using the same.

Claims (60)

1. An antibody that binds to human KLK5, wherein the antibody comprises:

a) a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 68, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 70, and (c) CDR-H3 comprising an amino acid sequence selected from SEQ ID NOs: 71 and 72, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 73, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 74, and (f) CDR-L3 comprising an amino acid sequence selected from SEQ ID NOs: 75-78; or

b) a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 68, (b) CDR-H2 comprising an amino acid sequence selected from SEQ ID NOs: 69 and 70, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 72, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 73, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 74, and (f) CDR-L3 comprising an amino acid sequence selected from SEQ ID NOs: 75-78; or

c) a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 68, (b) CDR-H2 comprising an amino acid sequence selected from SEQ ID NOs: 69 and 70, and (c) CDR-H3 comprising an amino acid sequence selected from SEQ ID NOs: 71 and 72, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 73, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 74, and (f) CDR-L3 comprising an amino acid sequence selected from SEQ ID NOs: 75-78.

2. A pharmaceutical composition comprising the antibody of claim 1 .

3. The pharmaceutical composition of claim 2 , further comprising an additional therapeutic agent, wherein the additional therapeutic agent is an antibody that binds to human KLK7, wherein the antibody comprises a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12.

4. The antibody of claim 1 , wherein the antibody comprises a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 68, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 69, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 71, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 73, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 74, and (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 75.

5. The antibody of claim 1 , which is a monoclonal antibody.

6. The antibody of claim 4 , which is a monoclonal antibody.

7. The antibody of claim 1 , which is a humanized, or chimeric antibody.

8. The antibody of claim 4 , which is a humanized, or chimeric antibody.

9. The antibody of claim 1 , which is an antibody fragment that binds human KLK5.

10. The antibody of claim 4 , which is an antibody fragment that binds human KLK5.

11. The antibody of claim 1 , wherein the antibody binds human KLK5 with a KD of less than 1 nM as measured by surface plasmon resonance.

12. The antibody of claim 4 , wherein the antibody binds human KLK5 with a KD of less than 1 nM as measured by surface plasmon resonance.

13. The antibody of claim 1 , wherein the heavy chain variable region comprises an FR1 comprising the amino acid sequence of SEQ ID NO: 171, an FR2 comprising the amino acid sequence of SEQ ID NO: 172 or 173, an FR3 comprising the amino acid sequence of SEQ ID NO: 174, and/or an FR4 comprising the amino acid sequence of SEQ ID NO: 175.

14. The antibody of claim 4 , wherein the heavy chain variable region comprises an FR1 comprising the amino acid sequence of SEQ ID NO: 171, an FR2 comprising the amino acid sequence of SEQ ID NO: 172 or 173, an FR3 comprising the amino acid sequence of SEQ ID NO: 174, and/or an FR4 comprising the amino acid sequence of SEQ ID NO: 175.

15. The antibody of claim 1 , wherein the light chain variable region comprises an FR1 comprising the amino acid sequence of SEQ ID NO: 176, an FR2 comprising the amino acid sequence of SEQ ID NO: 177 or 178, an FR3 comprising the amino acid sequence of SEQ ID NO: 179, and/or an FR4 comprising the amino acid sequence of SEQ ID NO: 180.

16. The antibody of claim 4 , wherein the light chain variable region comprises an FR1 comprising the amino acid sequence of SEQ ID NO: 176, an FR2 comprising the amino acid sequence of SEQ ID NO: 177 or 178, an FR3 comprising the amino acid sequence of SEQ ID NO: 179, and/or an FR4 comprising the amino acid sequence of SEQ ID NO: 180.

17. The antibody of claim 1 , comprising:

a) a VH sequence having at least 95% sequence identity to an amino acid sequence selected from the amino acid sequence of SEQ ID NOs: 79, or 81-87;

b) a VL sequence having at least 95% sequence identity to an amino acid sequence selected from the amino acid sequence of SEQ ID NOs: 80 or 88-94; or

c) a VH sequence as defined in (a) and a VL sequence as defined in (b).

18. The antibody of claim 4 , comprising:

a) a VH sequence having at least 95% sequence identity to an amino acid sequence selected from the amino acid sequence of SEQ ID NO: 79, or 81-87;

b) a VL sequence having at least 95% sequence identity to an amino acid sequence selected from the amino acid sequence of SEQ ID NO: 80 and 88-94; or

c) a VH sequence as defined in (a) and a VL sequence as defined in (b).

19. The antibody of claim 1 , comprising:

a) a VH sequence comprising an amino acid sequence selected from the amino acid sequence of SEQ ID NOs: 84-87;

b) a VL sequence comprising an amino acid sequence selected from the amino acid sequence of SEQ ID NOs: 91-94; or

c) a VH sequence as defined in (a) and a VL sequence as defined in (b).

20. The antibody of claim 1 , wherein the antibody comprises a heavy chain constant region and a light chain constant region, wherein the heavy chain constant region comprises a S183K substitution (EU numbering) and/or an S183E substitution (EU numbering); and/or the light chain constant region comprises a V133K substitution (EU numbering) and/or a V133E substitution (EU numbering).

21. The antibody of claim 4 , wherein the antibody comprises a heavy chain constant region and a light chain constant region, wherein the heavy chain constant region comprises a S183K substitution (EU numbering) and/or an S183E substitution (EU numbering); and/or the light chain constant region comprises a V133K substitution (EU numbering) and/or a V133E substitution (EU numbering).

22. The antibody of claim 1 , which is a full length IgG1 antibody.

23. The antibody of claim 4 , which is a full length IgG1 antibody.

24. The antibody of claim 22 , wherein the antibody comprises a N297G substitution (EU numbering).

25. The antibody of claim 23 , wherein the antibody comprises a N297G substitution (EU numbering).

26. The antibody of claim 22 , wherein the antibody comprises a M428L substitution (EU numbering) and/or an N434S substitution (EU numbering).

27. The antibody of claim 23 , wherein the antibody comprises a M428L substitution (EU numbering) and/or an N434S substitution (EU numbering).

28. The antibody of claim 1 , wherein the antibody inhibits human KLK5 protease activity with an IC50 of less than 5 nM.

29. The antibody of claim 4 , wherein the antibody inhibits human KLK5 protease activity with an IC50 of less than 5 nM.

30. The antibody of claim 1 , wherein the antibody binds human KLK5 with a KD of less than 60 pM, as measured by surface plasmon resonance; and wherein the antibody inhibits human KLK5 protease activity with an IC50 of less than 5 nM.

31. The antibody of claim 4 , wherein the antibody binds human KLK5 with a KD of less than 60 pM, as measured by surface plasmon resonance; and wherein the antibody inhibits human KLK5 protease activity with an IC50 of less than 5 nM.

32. The antibody of claim 28 , wherein inhibition of human KLK5 protease activity is inhibition of human KLK5-mediated cleavage of the substrate Boc-Val-Pro-Arg-AMC.

33. The antibody of claim 29 , wherein inhibition of human KLK5 protease activity is inhibition of human KLK5-mediated cleavage of the substrate Boc-Val-Pro-Arg-AMC.

34. The antibody of claim 30 , wherein inhibition of human KLK5 protease activity is inhibition of human KLK5-mediated cleavage of the substrate Boc-Val-Pro-Arg-AMC.

35. The antibody of claim 31 , wherein inhibition of human KLK5 protease activity is inhibition of human KLK5-mediated cleavage of the substrate Boc-Val-Pro-Arg-AMC.

36. The antibody of claim 1 , wherein the antibody is a multispecific antibody.

37. The antibody of claim 4 , wherein the antibody is a multispecific antibody.

38. The antibody of claim 20 , wherein the antibody is a bispecific antibody.

39. The antibody of claim 21 , wherein the antibody is a bispecific antibody.

40. The antibody of claim 36 , wherein the antibody is a bispecific antibody.

41. The antibody of claim 37 , wherein the antibody is a bispecific antibody.

42. A pharmaceutical composition comprising the antibody of claim 4 .

43. The antibody of claim 38 , wherein said antibody comprises a binding moiety that binds to human KLK7, wherein the antibody comprises a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12.

44. The antibody of claim 39 , wherein said antibody comprises a binding moiety that binds to human KLK7, wherein the antibody comprises a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12.

45. The antibody of claim 40 , wherein said antibody comprises a binding moiety that binds to human KLK7, wherein the antibody comprises a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12.

46. The antibody of claim 41 , wherein said antibody comprises a binding moiety that binds to human KLK7, wherein the antibody comprises a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12.

47. The pharmaceutical composition of claim 42 , further comprising an additional therapeutic agent.

48. The pharmaceutical composition of claim 47 , wherein the additional therapeutic agent is an antibody that binds to human KLK7, wherein the antibody comprises a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12.

Continuity (3)
Division 17024094 · Sep 17, 2020
Provisional Application 62901990 · Sep 18, 2019
Related Publication 20240150491A1 · May 9, 2024
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