IP Library › Granted Patent US 12,344,677
Granted Patent B2
US 12,344,677 · App. 17/476,856 · Granted Jul 1, 2025

Anti-PSMA antibodies, bispecific antigen-binding molecules that bind PSMA and CD3, and uses thereof

Inventors: Jessica R. Kirshner (New York, NY); Alison Crawford (Dobbs Ferry, NY); Gavin Thurston (Briarcliff Manor, NY); Eric Smith (New York, NY); Lauric Haber (Rye Brook, NY); Drew Dudgeon (Union, NJ); Ashique Rafique (Yonkers, NY)
Assignee: Regeneron Pharmaceuticals, Inc.
C07K16/3069A61P35/00C07K16/2809A61K39/39558A61K2039/505C07K2317/24C07K2317/31C07K2317/33C07K2317/56C07K2317/565C07K2317/73C07K2317/732C07K2317/734C07K2317/76C07K2317/92C07K2317/94
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Quick Facts
Patent No.
US 12,344,677
App. No.
17/476,856
Granted
Jul 1, 2025
Kind
B2
Abstract

The present invention provides antibodies that bind to prostate-specific membrane antigen (PSMA), bispecific antibodies that bind to PSMA and CD3, and methods of using the same. According to certain embodiments, the antibodies of the invention bind human PSMA with high affinity and bind CD3 to induce human T cell proliferation. The invention includes antibodies that bind PSMA and CD3 and induce T cell-mediated killing of PSMA-expressing tumor cells. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding molecule that specifically binds human PSMA. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of prostate tumors expressing PSMA. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and/or therapeutically beneficial. For example, the antibodies of the invention are useful for the treatment of various cancers.

Claims (34)

1. A method for treating a human prostate specific membrane antigen (PSMA)-expressing cancer in a human subject, the method comprising administering a bispecific antigen-binding molecule comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding domain that specifically binds human PSMA,

wherein the first antigen-binding domain that specifically binds human CD3 comprises heavy chain complementarity determining regions A1-HCDR1, A1-HCDR2 and A1-HCDR3 contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1514, or SEQ ID NO: 1618, and light chain complementarity determining regions LCDR1, LCDR2 and LCDR3 contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 1386, and

wherein the second antigen-binding domain that specifically binds human PSMA comprises heavy chain complementarity determining regions A2-HCDR1, A2-HCDR2 and A2-HCDR3 contained within a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 66, and light chain complementarity determining regions LCDR1, LCDR2 and LCDR3 contained within a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 1386.

2. The method of claim 1 , wherein A1-HCDR1, A1-HCDR2 and A1-HCDR3 comprise the amino acid sequences, respectively, of SEQ ID NOs: 1516, 1518 and 1520.

3. The method of claim 1 , wherein A1-HCDR1, A1-HCDR2 and A1-HCDR3 comprise the amino acid sequences, respectively, of SEQ ID NOs: 1620, 1622 and 1624.

4. The method of claim 1 , wherein A2-HCDR1, A2-HCDR2 and A2-HCDR3 comprise the amino acid sequences, respectively, of SEQ ID NOS: 68, 70 and 72.

5. The method of claim 2 , wherein A2-HCDR1, A2-HCDR2 and A2-HCDR3 comprise the amino acid sequences, respectively, of SEQ ID NOs: 68, 70 and 72.

6. The method of claim 3 , wherein A2-HCDR1, A2-HCDR2 and A2-HCDR3 comprise the amino acid sequences, respectively, of SEQ ID NOs: 68, 70 and 72.

7. The method of claim 1 , wherein LCDR1, LCDR2 and LCDR3 comprise the amino acid sequences, respectively, of SEQ ID NOs: 1388, 1390 and 1392.

8. The method of claim 2 , wherein LCDR1, LCDR2 and LCDR3 comprise the amino acid sequences, respectively, of SEQ ID NOs: 1388, 1390 and 1392.

9. The method of claim 3 , wherein LCDR1, LCDR2 and LCDR3 comprise the amino acid sequences, respectively, of SEQ ID NOs: 1388, 1390 and 1392.

10. The method of claim 4 , wherein LCDR1, LCDR2 and LCDR3 comprise the amino acid sequences, respectively, of SEQ ID NOs: 1388, 1390 and 1392.

11. The method of claim 5 , wherein LCDR1, LCDR2 and LCDR3 comprise the amino acid sequences, respectively, of SEQ ID NOs: 1388, 1390 and 1392.

12. The method of claim 6 , wherein LCDR1, LCDR2 and LCDR3 comprise the amino acid sequences, respectively, of SEQ ID NOs: 1388, 1390 and 1392.

13. The method of claim 1 , wherein the first antigen-binding domain that specifically binds human CD3 comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 1514 or SEQ ID NO: 1618, and a LCVR comprising the amino acid sequence of SEQ ID NO: 1386, and wherein the second antigen-binding domain that specifically binds human PSMA comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 66, and a LCVR comprising the amino acid sequence of SEQ ID NO: 1386.

14. The method of claim 13 , wherein the first antigen-binding domain that specifically binds human CD3 comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 1514.

15. The method of claim 13 , wherein the first antigen-binding domain that specifically binds human CD3 comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 1618.

16. A method for treating a human prostate specific membrane antigen (PSMA)-expressing cancer in a human subject, the method comprising administering an isolated bispecific antibody comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding domain that specifically binds human PSMA,

wherein the first antigen-binding domain that specifically binds human CD3 comprises heavy chain complementarity determining regions A1-HCDR1, A1-HCDR2 and A1-HCDR3 comprising the amino acid sequences, respectively, of SEQ ID NOs: 1516, 1518 and 1520, and light chain complementarity determining regions LCDR1, LCDR2 and LCDR3 comprising the amino acid sequences, respectively, of SEQ ID NOs: 1388, 1390 and 1392, and

wherein the second antigen-binding domain that specifically binds human PSMA comprises heavy chain complementarity determining regions A2-HCDR1, A2-HCDR2 and A2-HCDR3 comprising the amino acid sequences, respectively, of SEQ ID NOs: 68, 70 and 72, and light chain complementarity determining regions LCDR1, LCDR2 and LCDR3 comprising the amino acid sequences, respectively, of SEQ ID NOs: 1388, 1390 and 1392.

17. The method of claim 16 , wherein the first antigen-binding domain comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 1514 and a LCVR comprising the amino acid sequence of SEQ ID NO: 1386, and the second antigen-binding domain comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 66 and a LCVR comprising the amino acid sequence of SEQ ID NO: 1386.

18. The method of claim 16 , wherein the cancer is selected from the group consisting of prostate cancer, kidney cancer, bladder cancer, colorectal cancer, and gastric cancer.

19. The method of claim 18 , wherein the cancer is prostate cancer.

20. The method of claim 19 , wherein the prostate cancer is castrate-resistant prostate cancer.

21. A method for treating a human prostate specific membrane antigen (PSMA)-expressing cancer in a human subject, the method comprising administering an isolated bispecific antibody comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding domain that specifically binds human PSMA,

wherein the first antigen-binding domain that specifically binds human CD3 comprises heavy chain complementarity determining regions A1-HCDR1, A1-HCDR2 and A1-HCDR3 comprising the amino acid sequences, respectively, of SEQ ID NOs: 1620, 1622 and 1624, and light chain complementarity determining regions LCDR1, LCDR2 and LCDR3 comprising the amino acid sequences, respectively, of SEQ ID NOs: 1388, 1390 and 1392, and

wherein the second antigen-binding domain that specifically binds human PSMA comprises heavy chain complementarity determining regions A2-HCDR1, A2-HCDR2 and A2-HCDR3 comprising the amino acid sequences, respectively, of SEQ ID NOs: 68, 70 and 72, and light chain complementarity determining regions LCDR1, LCDR2 and LCDR3 comprising the amino acid sequences, respectively, of SEQ ID NOs: 1388, 1390 and 1392.

22. The method of claim 21 , wherein the first antigen-binding domain comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 1618 and a LCVR comprising the amino acid sequence of SEQ ID NO: 1386, and the second antigen-binding domain comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 66 and a LCVR comprising the amino acid sequence of SEQ ID NO: 1386.

23. The method of claim 21 , wherein the cancer is selected from the group consisting of prostate cancer, kidney cancer, bladder cancer, colorectal cancer, and gastric cancer.

24. The method of claim 23 , wherein the cancer is prostate cancer.

25. The method of claim 24 , wherein the prostate cancer is castrate-resistant prostate cancer.

26. The method of claim 1 , wherein the human PSMA comprises the amino acid sequence of SEQ ID NO: 1651.

27. The method of claim 16 , wherein the human PSMA comprises the amino acid sequence of SEQ ID NO: 1651.

28. The method of claim 21 , wherein the human PSMA comprises the amino acid sequence of SEQ ID NO: 1651.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 7, 2024
From: KIRSHNER, JESSICA R.; CRAWFORD, ALISON; THURSTON, GAVIN; SMITH, ERIC; HABER, LAURIC; DUDGEON, DREW; RAFIQUE, ASHIQUE
To: REGENERON PHARMACEUTICALS, INC.
Reel/Frame 067660/0106 →
Continuity (6)
Division 16205917 · Nov 30, 2018
Division 15223434 · Jul 29, 2016
Provisional Application 62351823 · Jun 17, 2016
Provisional Application 62222590 · Sep 23, 2015
Provisional Application 62199823 · Jul 31, 2015
Related Publication 20210403595A1 · Dec 30, 2021
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