Granted Patent B2

US 11,434,304 · App. 16/656,401 · Granted Sep 6, 2022

Inventors: Kathleen Ann Elias (South San Francisco, CA); Gregory Landes (San Bruno, CA); Shweta Singh (South San Francisco, CA); Wouter Korver (South San Francisco, CA); Andrew Walling Drake (South San Francisco, CA); Mary Haak-Frendscho (San Francisco, CA); Gyorgy Pal Snell (South San Francisco, CA); Vinay Bhaskar (South San Francisco, CA)

Assignee: Takeda Pharmaceutical Company Limited

C07K16/40A61K47/6871C07K16/2896C12N9/99A61K2039/505C07K2317/24C07K2317/30C07K2317/33C07K2317/34C07K2317/52C07K2317/56C07K2317/565C07K2317/732C07K2317/734C07K2317/76C07K2317/92

Abstract

Claims (102)

1. An isolated nucleic acid encoding the heavy chain of an isolated antibody, wherein the isolated antibody specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2 comprising a heavy chain variable region comprising:

i) a first CDR consisting of SEQ ID NO:3;

ii) a second CDR consisting of SEQ ID NO:4; and

iii) a third CDR consisting of SEQ ID NO:5; and

wherein the heavy chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:9.

2. An isolated nucleic acid encoding the light chain of an isolated antibody, wherein the isolated antibody specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2 comprising a light chain variable region comprising:

i) a first CDR consisting of SEQ ID NO:6;

ii) a second CDR consisting of SEQ ID NO:7; and

iii) a third CDR consisting of SEQ ID NO:8,

wherein the light chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:10.

3. An isolated nucleic acid composition comprising:

a) a first nucleic acid encoding a heavy chain variable region comprising:

i) a first CDR consisting of SEQ ID NO:3;

ii) a second CDR consisting of SEQ ID NO:4; and

iii) a third CDR consisting of SEQ ID NO:5; and

b) a second nucleic acid encoding a light chain variable region comprising:

i) a first CDR consisting of SEQ ID NO:6;

ii) a second CDR consisting of SEQ ID NO:7; and

iii) a third CDR consisting of SEQ ID NO:8,

wherein the heavy chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:9 and the light chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:10.

4. The isolated nucleic acid of claim 1 , wherein the heavy chain variable region comprises an amino acid sequence having an identity of at least 99% to SEQ ID NO:9.

5. The isolated nucleic acid of claim 2 , wherein the light chain variable region comprises an amino acid sequence having an identity of at least 99% to SEQ ID NO:10.

6. The isolated nucleic acid composition of claim 3 , wherein the heavy chain variable region comprises an amino acid sequence having an identity of at least 99% to SEQ ID NO:9 and the light chain variable region comprises an amino acid sequence having an identity of at least 99% to SEQ ID NO:10.

7. An isolated nucleic acid composition encoding an antibody,

wherein the antibody specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2, and wherein the antibody interacts with at least K121, F135, Q139, D141, E239, W241, C275, K276, F284, P291 and E292 of SEQ ID NO:1, based on human sequence numbering;

wherein the isolated nucleic acid composition comprises:

a) a first nucleic acid encoding a heavy chain variable region of the antibody comprising:

i) a first CDR consisting of SEQ ID NO:3;

ii) a second CDR consisting of SEQ ID NO:4; and

iii) a third CDR consisting of SEQ ID NO:5; and

b) a second nucleic acid encoding a light chain variable region of the antibody comprising:

i) a first CDR consisting of SEQ ID NO:6;

ii) a second CDR consisting of SEQ ID NO:7; and

iii) a third CDR consisting of SEQ ID NO:8.

8. An isolated nucleic acid encoding the heavy chain of an isolated antibody, wherein the isolated antibody specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2 comprising a heavy chain variable region comprising:

i) a first CDR consisting of SEQ ID NO:13;

ii) a second CDR consisting of SEQ ID NO:14; and

iii) a third CDR consisting of SEQ ID NO:15; and

wherein the heavy chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:11.

9. An isolated nucleic acid encoding the light chain of an isolated antibody, wherein the isolated antibody specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2 comprising a light chain variable region comprising:

i) a first CDR consisting of SEQ ID NO:16;

ii) a second CDR consisting of SEQ ID NO:17; and

iii) a third CDR consisting of SEQ ID NO:18,

wherein the light chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:12.

10. An isolated nucleic acid composition comprising:

a) a first nucleic acid encoding a heavy chain variable region comprising:

i) a first CDR consisting of SEQ ID NO:13;

ii) a second CDR consisting of SEQ ID NO:14; and

iii) a third CDR consisting of SEQ ID NO:15; and

b) a second nucleic acid encoding a light chain variable region comprising:

i) a first CDR consisting of SEQ ID NO:16;

ii) a second CDR consisting of SEQ ID NO:17; and

iii) a third CDR consisting of SEQ ID NO:18,

wherein the heavy chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:11 and the light chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:12.

11. The isolated nucleic acid of claim 8 , wherein the heavy chain variable region comprises an amino acid sequence having an identity of at least 99% to SEQ ID NO:11.

12. The isolated nucleic acid of claim 8 , wherein the light chain variable region comprises an amino acid sequence having an identity of at least 99% to SEQ ID NO:12.

13. The isolated nucleic acid composition of claim 10 , wherein the heavy chain variable region comprises an amino acid sequence having an identity of at least 99% to SEQ ID NO:11 and the light chain variable region comprises an amino acid sequence having an identity of at least 99% to SEQ ID NO:12.

14. An isolated nucleic acid composition encoding an antibody,

wherein the isolated antibody specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2, and wherein the antibody interacts with at least G91, E103, E104, D105, Q107, M110, K111, T114, Q115, T148, V192, R194, R195, F196, A199, H228, N229, Q231, E233 and K234 of SEQ ID NO:1, based on human sequence numbering;

wherein the isolated nucleic acid composition comprises:

a) a first nucleic acid encoding a heavy chain variable region comprising:

i) a first CDR consisting of SEQ ID NO:13;

ii) a second CDR consisting of SEQ ID NO:14; and

iii) a third CDR consisting of SEQ ID NO:15; and

b) a second nucleic acid encoding a light chain variable region comprising:

i) a first CDR consisting of SEQ ID NO:16;

ii) a second CDR consisting of SEQ ID NO:17; and

iii) a third CDR consisting of SEQ ID NO:18.

15. An expression vector comprising:

a) a first isolated nucleic acid encoding the heavy chain of an isolated antibody, wherein the isolated antibody specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2 comprising a heavy chain variable region comprising:

i) a first CDR consisting of SEQ ID NO:3;

ii) a second CDR consisting of SEQ ID NO:4; and

iii) a third CDR consisting of SEQ ID NO:5; and

wherein the heavy chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:9; and

b) a second isolated nucleic acid encoding the light chain of an isolated antibody, wherein the isolated antibody specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2 comprising a light chain variable region comprising:

i) a first CDR consisting of SEQ ID NO:6;

ii) a second CDR consisting of SEQ ID NO:7; and

iii) a third CDR consisting of SEQ ID NO:8,

wherein the light chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:10.

16. A host cell comprising the expression vector of claim 15 .

17. A host cell comprising the isolated nucleic acid composition of claim 3 .

18. A host cell comprising the isolated nucleic acid composition of claim 7 .

19. An expression vector comprising:

a) a first isolated nucleic acid encoding the heavy chain of an isolated antibody, wherein the isolated antibody specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2 comprising a heavy chain variable region comprising:

i) a first CDR consisting of SEQ ID NO:13;

ii) a second CDR consisting of SEQ ID NO:14; and

iii) a third CDR consisting of SEQ ID NO:15; and

wherein the heavy chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:11; and

b) a second isolated nucleic acid encoding the light chain of an isolated antibody, wherein the isolated antibody specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2 comprising a light chain variable region comprising:

i) a first CDR consisting of SEQ ID NO:16;

ii) a second CDR consisting of SEQ ID NO:17; and

iii) a third CDR consisting of SEQ ID NO:18,

wherein the light chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:12.

20. A host cell comprising the expression vector of claim 19 .

21. A host cell comprising the isolated nucleic acid composition of claim 10 .

22. A host cell comprising the isolated nucleic acid composition of claim 14 .

23. A method of producing an antibody that specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2 comprising culturing the host cell of claim 16 under conditions wherein said antibody is produced.

24. A method of producing an antibody that specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2 comprising culturing the host cell of claim 17 under conditions wherein said antibody is produced.

25. A method of producing an antibody that specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2 comprising culturing the host cell of claim 18 under conditions wherein said antibody is produced.

26. A method of producing an antibody that specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2 comprising culturing the host cell of claim 20 under conditions wherein said antibody is produced.

27. A method of producing an antibody that specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:2 comprising culturing the host cell of claim 21 under conditions wherein said antibody is produced.

28. A method of producing an antibody that specifically binds human CD38 as set forth in SEQ ID NO:1 and cynomolgus CD38 as set forth in SEQ ID NO:comr comprising culturing the host cell of claim 22 under conditions wherein said antibody is produced.

Assignments (4)

Continuity (9)