Granted Patent B2

US 12,378,326 · App. 18/440,860 · Granted Aug 5, 2025

Inventors: John R. Desjarlais (Pasadena, CA); Gregory Moore (Azusa, CA); Michael Hedvat (Encino, CA); Juan Diaz (Anaheim Hills, CA); Veronica Gusti Zeng (Duarte, CA); Matthew Adam Dragovich (Rancho Cucamonga, CA); Joseph Erhardt (Sellersville, PA); Theresa McDevitt (Warminster, PA); Fouad Moussa (Allentown, PA); Pankaj Seth (Norristown, PA); Fei Shen (Collegeville, PA); Adam Zwolak (Bala Cynwyd, PA)

Assignee: Xencor, Inc.

C07K16/468C07K16/2818C07K16/3069C07K2317/31C07K2317/565C07K2317/622

Abstract

Claims (41)

1. A bispecific antibody comprising a first antigen binding domain (ABD) that binds PSMA and a second ABD that binds CD28, wherein the first ABD that binds PSMA comprises a VH of SEQ ID NO: 214 and a VL of SEQ ID NO: 218, and the second ABD that binds CD28 comprises a VH of SEQ ID NO: 396 and a VL of SEQ ID NO: 400.

2. The bispecific antibody of claim 1 , wherein the first ABD or second ABD is an scFv.

3. The bispecific antibody of claim 2 , wherein the scFv comprises an scFv linker selected from GKPGSGKPGSGKPGSGKPGS (SEQ ID NO: 443), GGSEGKSSGSGSESKSTGGS (SEQ ID NO: 456), and GGGSGGSGGCPPCGGSGG (SEQ ID NO: 457).

4. The bispecific antibody of claim 3 , wherein the second ABD is the scFv, and the scFv linker is SEQ ID NO:457.

5. The bispecific antibody of claim 1 , wherein the bispecific antibody further comprises a first Fc domain and a second Fc domain.

6. The bispecific antibody of claim 5 , wherein the first Fc domain and the second Fc domain are each variant human IgG1, IgG2, or IgG4 Fc domains.

7. The bispecific antibody of claim 6 , wherein one of the first and second Fc domains comprises heterodimerization variant T366W, and the other of the first and second Fc domains comprises heterodimerization variants T366S/L368A/Y407V, wherein numbering is according to EU numbering.

8. The bispecific antibody of claim 6 , wherein the first and the second Fc domains each comprise ablation variants L234A/L235A/D265S, wherein numbering is according to EU numbering.

9. The bispecific antibody of claim 6 , wherein the first or the second Fc domain comprises purification variants H435R/Y436F, wherein numbering is according to EU numbering.

10. The bispecific antibody of claim 6 , wherein the first Fc domain comprises amino acid substitutions L234A/L235A/D265S/T366W, and the second Fc domain comprises amino acid substitutions L234A/L235A/D265S/T366S/L368A/Y407V/H435R/Y436F, wherein numbering is according to EU numbering.

11. The bispecific antibody of claim 1 , wherein the bispecific antibody comprises a first monomer that is at least 95% identical to SEQ ID NO: 342, a second monomer that is at least 95% identical to SEQ ID NO: 343, and a light chain that is at least 95% identical to SEQ ID NO: 344.

12. A pharmaceutical composition comprising the bispecific antibody of claim 1 and a pharmaceutically acceptable carrier.

13. A composition comprising one or more nucleic acids encoding the bispecific antibody of claim 1 .

14. A composition comprising one or more expression vectors, wherein each of the one or more expression vectors comprises a nucleic acid of the one or more nucleic acids of claim 13 .

15. A host cell comprising the composition of claim 14 .

16. A method of making a bispecific antibody comprising culturing the host cell of claim 15 under conditions wherein the bispecific antibody is expressed and recovering the bispecific antibody.

17. A method of treating prostate cancer in a patient in need thereof, comprising administering to the patient the bispecific antibody of claim 1 .

18. The method of claim 17 , wherein the prostate cancer is castration-resistant prostate cancer.

19. A method of enhancing T cell proliferation in the presence of PSMA-expressing cells, comprising contacting the cells with the bispecific antibody of claim 1 .

20. A method of inhibiting the growth or proliferation of PSMA-expressing cells, comprising contacting the cells with the bispecific antibody of claim 1 .

21. A bispecific anti-PSMA×anti-CD28 antibody comprising:

a) a first monomer having an amino acid sequence of SEQ ID NO: 342;

b) a second monomer having an amino acid sequence of SEQ ID NO: 343; and

c) a light chain having an amino acid sequence of SEQ ID NO: 344.

22. A pharmaceutical composition comprising the bispecific antibody of claim 21 and a pharmaceutically acceptable carrier.

23. A nucleic acid composition comprising:

a) a first nucleic acid encoding a first monomer;

b) a second nucleic acid encoding a second monomer; and

c) a third nucleic acid encoding a light chain,

wherein the first monomer, second monomer, and light chain are the first monomer, second monomer, and light chain of claim 21 , respectively.

24. An expression vector composition comprising:

a) a first expression vector comprising a first nucleic acid encoding a first monomer;

b) a second expression vector comprising a second nucleic acid encoding a second monomer; and

c) a third expression vector comprising a third nucleic acid encoding a light chain,

wherein the first monomer, second monomer, and light chain are the first monomer, second monomer, and light chain of claim 21 , respectively.

25. A host cell comprising the expression vector composition of claim 24 .

26. A method of making a bispecific antibody comprising culturing the host cell of claim 25 under conditions wherein the bispecific antibody is expressed and recovering the bispecific antibody.

27. A method of treating prostate cancer in a patient in need thereof, comprising administering to the patient the bispecific antibody of claim 21 .

28. The method of claim 27 , wherein the prostate cancer is castration-resistant prostate cancer.

29. A method of enhancing T cell proliferation in the presence of PSMA-expressing cells, comprising contacting the cells with the bispecific antibody of claim 21 .

30. A method of inhibiting the growth or proliferation of PSMA-expressing cells, comprising contacting the cells with the bispecific antibody of claim 21 .

Assignments (3)

Continuity (4)

References Cited (243)