IP Library › Granted Patent US 12,312,414
Granted Patent B2
US 12,312,414 · App. 17/024,094 · 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 12,312,414
App. No.
17/024,094
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 (65)

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: 107, (b) CDR-H2 comprising an amino acid sequence selected from SEQ ID NOs: 40 and 41, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 42, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising an amino acid sequence selected from SEQ ID NOs: 43 and 44, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and (f) CDR-L3 comprising an amino acid sequence selected from SEQ ID NOs: 46-49; or

b) a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising an amino acid sequence selected from SEQ ID NOs: 39 and 107, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 41, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 42, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising an amino acid sequence selected from SEQ ID NOs: 43 and 44, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and (f) CDR-L3 comprising an amino acid sequence selected from SEQ ID NOs: 46-49; or

c) a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising an amino acid sequence selected from SEQ ID NOs: 39 and 107, (b) CDR-H2 comprising an amino acid sequence selected from SEQ ID NOs: 40 and 41, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 42, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising the amino acid sequence of SEQ ID NOs: 44, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and (f) CDR-L3 comprising an amino acid sequence selected from SEQ ID NOs: 46-49; or

d) a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising an amino acid sequence selected from SEQ ID NOs: 39 and 107, (b) CDR-H2 comprising an amino acid sequence selected from SEQ ID NOs: 40 and 41, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 42, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising an amino acid sequence selected from SEQ ID NOs: 43 and 44, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and (f) CDR-L3 comprising an amino acid sequence selected from SEQ ID NOs: 47-49.

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

3. The pharmaceutical composition of claim 2 , further comprising an additional therapeutic agent.

4. The pharmaceutical composition of claim 3 , 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.

5. 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: 39, (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 41, and (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 42, and a light chain variable domain (VL) comprising (d) CDR-L1 comprising the amino acid sequence of SEQ ID NOs: 43, (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 47.

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

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

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

9. The antibody of claim 5 , which is a humanized, or chimeric antibody.

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

11. The antibody of claim 5 , which is an antibody fragment that binds human KLK5.

12. 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.

13. The antibody of claim 5 , wherein the antibody binds human KLK5 with a KD of less than 1 nM as measured by surface plasmon resonance.

14. The antibody of claim 1 , wherein the heavy chain variable region comprises an FR1 comprising the amino acid sequence of SEQ ID NO: 161, an FR2 comprising the amino acid sequence of SEQ ID NO: 162 or 163, an FR3 comprising the amino acid sequence of SEQ ID NO: 164, and/or an FR4 comprising the amino acid sequence of SEQ ID NO: 165.

15. The antibody of claim 5 , wherein the heavy chain variable region comprises an FR1 comprising the amino acid sequence of SEQ ID NO: 161, an FR2 comprising the amino acid sequence of SEQ ID NO: 162 or 163, an FR3 comprising the amino acid sequence of SEQ ID NO: 164, and/or an FR4 comprising the amino acid sequence of SEQ ID NO: 165.

16. The antibody of claim 1 , wherein the light chain variable region comprises an FR1 comprising the amino acid sequence of SEQ ID NO: 166, an FR2 comprising the amino acid sequence of SEQ ID NO: 167 or 168, an FR3 comprising the amino acid sequence of SEQ ID NO: 169, and/or an FR4 comprising the amino acid sequence of SEQ ID NO: 170.

17. The antibody of claim 5 , wherein the light chain variable region comprises an FR1 comprising the amino acid sequence of SEQ ID NO: 166, an FR2 comprising the amino acid sequence of SEQ ID NO: 167 or 168, an FR3 comprising the amino acid sequence of SEQ ID NO: 169, and/or an FR4 comprising the amino acid sequence of SEQ ID NO: 170.

18. The antibody of claim 1 , comprising:

a) a VH sequence having at least 95% sequence identity to an amino acid sequence selected from SEQ ID NOs: 50, 52, 53, 105, and 106;

b) a VL sequence having at least 95% sequence identity to an amino acid sequence selected from SEQ ID NOs: 51 and 54-67; or

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

19. The antibody of claim 5 , comprising:

a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 52 or 53;

b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 55 or 62; or

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

20. The antibody of claim 1 , comprising:

a) a VH sequence comprising an amino acid sequence selected from SEQ ID NOs: 50, 52, 53, 105, and 106;

b) a VL sequence comprising an amino acid sequence selected from SEQ ID NOs: 51 and 54-67; or

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

21. The antibody of claim 5 , comprising:

a) a VH sequence comprising the amino acid sequence of SEQ ID NO: 52 or 53;

b) a VL sequence comprising the amino acid sequence of SEQ ID NO: 55 or 62; or

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

22. The antibody of claim 1 , comprising a VH sequence of SEQ ID NO: 52 and a VL sequence of SEQ ID NO: 55.

23. The antibody of claim 1 , comprising a VH sequence of SEQ ID NO: 53 and a VL sequence of SEQ ID NO: 62.

24. An antibody that specifically binds to human KLK5 comprising a VH sequence of SEQ ID NO: 52 and a VL sequence of SEQ ID NO: 55; or a VH sequence of SEQ ID NO: 53 and a VL sequence of SEQ ID NO: 62.

25. 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).

26. The antibody of claim 5 , 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).

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

28. The antibody of claim 5 , which is a full length IgG1 antibody.

29. The antibody of claim 27 , wherein the antibody comprises a N297G substitution (EU numbering).

30. The antibody of claim 28 , wherein the antibody comprises a N297G substitution (EU numbering).

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

32. The antibody of claim 28 , wherein the antibody comprises a M428L substitution (EU numbering) and/or an N434S substitution (EU numbering).

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

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

35. 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.

36. The antibody of claim 5 , 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.

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

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

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

40. The antibody of claim 36 , wherein inhibition of human KLK5 protease activity is inhibition of human KLK5-mediated cleavage of the substrate Boc-Val-Pro-Arg-AMC.

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

42. The antibody of claim 5 , wherein the antibody is a multispecific antibody.

43. The antibody of claim 25 , wherein the antibody is a bispecific antibody.

44. The antibody of claim 26 , wherein the antibody is a bispecific antibody.

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

46. The antibody of claim 42 , wherein the antibody is a bispecific antibody.

47. A pharmaceutical composition comprising the antibody of claim 5 .

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

49. The pharmaceutical composition of claim 48 , 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.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 16, 2020
From: GENENTECH, INC.
To: F. HOFFMANN-LA ROCHE AG
Reel/Frame 054377/0225 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 16, 2020
From: KOERBER, JAMES THOMAS; LEE, WYNE PUN; YI, TANGSHENG; ZHANG, JUAN; AUSTIN, CARY DEAN; CHIU, CECILIA P.C.; CHAVARRIA-SMITH, JOSEPH EDWARD; SUDHAMSU, JAWAHAR
To: GENENTECH, INC.
Reel/Frame 054433/0691 →
Continuity (2)
Provisional Application 62901990 · Sep 18, 2019
Related Publication 20210130492A1 · May 6, 2021
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