IP Library › Granted Patent US 12,297,270
Granted Patent B2
US 12,297,270 · App. 18/517,327 · Granted May 13, 2025

Bispecific antigen-binding molecules and methods of use

Inventors: Diego Ellerman (San Francisco, CA); Teemu T. Junttila (San Mateo, CA); Twyla Noelle Lombana (San Francisco, CA); Dionysos Slaga (Richmond, CA); Christoph Spiess (Mountain View, CA)
Assignee: Genentech, Inc.
C07K16/2809A61K9/0019A61K39/3955A61K47/65A61P35/00A61P35/02C07K16/1063C07K16/2803C07K16/2818C07K16/32C07K16/468
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Quick Facts
Patent No.
US 12,297,270
App. No.
18/517,327
Granted
May 13, 2025
Kind
B2
Abstract

The present invention provides bispecific antigen-binding molecules having a monovalent arm specific to a first target antigen (e.g., a T cell antigen, such as CD3) and a bivalent arm specific for a second target antigen (e.g., a tumor antigen, such as HER2). Bispecific antigen-binding molecules are useful in the treatment of disorders, such as cancer (e.g., HER2-positive cancer). The invention also features methods of producing bispecific antigen-binding molecules, methods of treating disorders using bispecific antigen-binding molecules, and compositions including bispecific antigen-binding molecules.

Claims (192)

1. One or more isolated nucleic acids encoding a bispecific antigen-binding molecule that specifically binds CD3 and HER2 comprising a monovalent arm and a bivalent arm, wherein:

(a) the monovalent arm comprises a Fab A that specifically binds CD3, wherein the C-terminus of the Fab A is fused to an N-terminus of a first Fc subunit, and wherein the Fab A comprises the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6;

(b) the bivalent arm comprises a Fab B1 and a Fab B2 that each specifically binds HER2, wherein the C-terminus of the Fab B2 is fused to the N-terminus of the Fab B1 , and the C-terminus of the Fab B1 is fused to an N-terminus of a second Fc subunit, wherein the Fab B1 and the Fab B2 each comprise the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 11,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 37,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26; and

(c) the first Fc subunit is associated with the second Fc subunit to form an Fc domain.

2. The one or more isolated nucleic acids of claim 1 , wherein:

(a) the Fab A comprises a VH A region and a VL A region, wherein the VH A region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 7, and the VL A region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 8;

(b) the Fab B1 comprises a VH B1 region and a VL B1 region, wherein the VH B1 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 41, and the VL B1 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 49; and

(c) the Fab B2 comprises a VH B2 region and a VL B2 region, wherein the VH B2 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 41, and the VL B2 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 49.

3. The one or more isolated nucleic acids of claim 2 , wherein:

(a) the VH A region comprises the amino acid sequence of SEQ ID NO: 7, and the VL A region comprises the amino acid sequence of SEQ ID NO: 8;

(b) the VH B1 region comprises the amino acid sequence of SEQ ID NO: 41, and the VL B1 region comprises the amino acid sequence of SEQ ID NO: 49; and

(c) the VH B2 region comprises the amino acid sequence of SEQ ID NO: 41, and the VL B2 region comprises the amino acid sequence of SEQ ID NO: 49.

4. One or more vectors comprising the one or more isolated nucleic acids of claim 1 .

5. One or more host cells comprising the one or more isolated nucleic acids of claim 1 .

6. The one or more host cells of claim 5 , wherein the one or more host cells comprise one or more mammalian cells or one or more prokaryotic cells.

7. The one or more host cells of claim 6 , wherein:

(a) the one or more host cells comprise one or more mammalian cells, and wherein the one or more mammalian cells comprise one or more Chinese hamster ovary (CHO) cells; or

(b) the one or more host cells comprise one or more prokaryotic cells, and wherein the one or more prokaryotic cells comprise one or more E. coli cells.

8. A method of producing a bispecific antigen-binding molecule that specifically binds CD3 and HER2 comprising a monovalent arm and a bivalent arm, wherein:

(a) the monovalent arm comprises a Fab A that specifically binds CD3, wherein the C-terminus of the Fab A is fused to an N-terminus of a first Fc subunit, and wherein the Fab A comprises the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6;

(b) the bivalent arm comprises a Fab B1 and a Fab B2 that each specifically binds HER2, wherein the C-terminus of the Fab B2 is fused to the N-terminus of the Fab B1 , and the C-terminus of the Fab B1 is fused to an N-terminus of a second Fc subunit, wherein the Fab B1 and the Fab B2 each comprise the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 11,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 37,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26; and

(c) the first Fc subunit is associated with the second Fc subunit to form an Fc domain,

wherein the method comprises culturing the one or more host cells of claim 5 in a culture medium.

9. The method of claim 8 , wherein the method further comprises recovering the bispecific antigen-binding molecule from the one or more host cells or the culture medium.

10. One or more isolated nucleic acids encoding a bispecific antigen-binding molecule that specifically binds CD3 and HER2 comprising a monovalent arm and a bivalent arm, wherein:

(a) the monovalent arm comprises a Fab A that specifically binds CD3, wherein the C-terminus of the Fab A is fused to an N-terminus of a first Fc subunit, and wherein the Fab A comprises the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6;

(b) the bivalent arm comprises a Fab B1 and a Fab B2 that each specifically binds HER2, wherein the C-terminus of the Fab B2 is fused to the N-terminus of the Fab B1 , and the C-terminus of the Fab B1 is fused to an N-terminus of a second Fc subunit, wherein the Fab B1 and the Fab B2 each comprise the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 11,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 19,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 20,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 21,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 22, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26; and

(c) the first Fc subunit is associated with the second Fc subunit to form an Fc domain.

11. The one or more isolated nucleic acids of claim 10 , wherein:

(a) the Fab A comprises a VH A region and a VL A region, wherein the VH A region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 7, and the VL A region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 8;

(b) the Fab B1 comprises a VH B1 region and a VL B1 region, wherein the VH B1 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 24, and the VL B1 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 27; and

(c) the Fab B2 comprises a VH B2 region and a VL B2 region, wherein the VH B2 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 24, and the VL B2 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 27.

12. The one or more isolated nucleic acids of claim 11 , wherein:

(a) the VH A region comprises the amino acid sequence of SEQ ID NO: 7, and the VL A region comprises the amino acid sequence of SEQ ID NO: 8;

(b) the VH B1 region comprises the amino acid sequence of SEQ ID NO: 24, and the VL B1 region comprises the amino acid sequence of SEQ ID NO: 27; and

(c) the VH B2 region comprises the amino acid sequence of SEQ ID NO: 24, and the VL B2 region comprises the amino acid sequence of SEQ ID NO: 27.

13. One or more vectors comprising the one or more isolated nucleic acids of claim 10 .

14. One or more host cells comprising the one or more isolated nucleic acids of claim 10 .

15. The one or more host cells of claim 14 , wherein the one or more host cells comprise one or more mammalian cells or one or more prokaryotic cells.

16. The one or more host cells of claim 15 , wherein:

(a) the one or more host cells comprise one or more mammalian cells, and wherein the one or more mammalian cells comprise one or more CHO cells; or

(b) the one or more host cells comprise one or more prokaryotic cells, and wherein the one or more prokaryotic cells comprise one or more E. coli cells.

17. A method of producing a bispecific antigen-binding molecule that specifically binds CD3 and HER2 comprising a monovalent arm and a bivalent arm, wherein:

(a) the monovalent arm comprises a Fab A that specifically binds CD3, wherein the C-terminus of the Fab A is fused to an N-terminus of a first Fc subunit, and wherein the Fab A comprises the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6;

(b) the bivalent arm comprises a Fab B1 and a Fab B2 that each specifically binds HER2, wherein the C-terminus of the Fab B2 is fused to the N-terminus of the Fab B1 , and the C-terminus of the Fab B1 is fused to an N-terminus of a second Fc subunit, wherein the Fab B1 and the Fab B2 each comprise the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 11,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 19,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 20,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 21,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 22, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26; and

(c) the first Fc subunit is associated with the second Fc subunit to form an Fc domain,

wherein the method comprises culturing the one or more host cells of claim 14 in a culture medium.

18. The method of claim 17 , wherein the method further comprises recovering the bispecific antigen-binding molecule from the one or more host cells or the culture medium.

19. One or more isolated nucleic acids encoding a bispecific antigen-binding molecule that specifically binds CD3 and HER2 comprising a monovalent arm and a bivalent arm, wherein:

(a) the monovalent arm comprises a Fab A that specifically binds CD3, wherein the C-terminus of the Fab A is fused to an N-terminus of a first Fc subunit, and wherein the Fab A comprises the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6;

(b) the bivalent arm comprises a Fab B1 and a Fab B2 that each specifically binds HER2, wherein the C-terminus of the Fab B2 is fused to the N-terminus of the Fab B1 , and the C-terminus of the Fab B1 is fused to an N-terminus of a second Fc subunit, wherein the Fab B1 and the Fab B2 each comprise the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 11,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 19,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 32,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 21,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 22, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 23; and

(c) the first Fc subunit is associated with the second Fc subunit to form an Fc domain.

20. The one or more isolated nucleic acids of claim 19 , wherein:

(a) the Fab A comprises a VH A region and a VL A region, wherein the VH A region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 7, and the VL A region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 8;

(b) the Fab B1 comprises a VH B1 region and a VL B1 region, wherein the VH B1 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 33, and the VL B1 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 25; and

(c) the Fab B2 comprises a VH B2 region and a VL B2 region, wherein the VH B2 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 33, and the VL B2 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 25.

21. The one or more isolated nucleic acids of claim 20 , wherein:

(a) the VH A region comprises the amino acid sequence of SEQ ID NO: 7, and the VL A region comprises the amino acid sequence of SEQ ID NO: 8;

(b) the VH B1 region comprises the amino acid sequence of SEQ ID NO: 33, and the VL B1 region comprises the amino acid sequence of SEQ ID NO: 25; and

(c) the VH B2 region comprises the amino acid sequence of SEQ ID NO: 33, and the VL B2 region comprises the amino acid sequence of SEQ ID NO: 25.

22. One or more vectors comprising the one or more isolated nucleic acids of claim 19 .

23. One or more host cells comprising the one or more isolated nucleic acids of claim 19 .

24. The one or more host cells of claim 23 , wherein the one or more host cells comprise one or more mammalian cells or one or more prokaryotic cells.

25. The one or more host cells of claim 24 , wherein:

(a) the one or more host cells comprise one or more mammalian cells, and wherein the one or more mammalian cells comprise one or more CHO cells; or

(b) the one or more host cells comprise one or more prokaryotic cells, and wherein the one or more prokaryotic cells comprise one or more E. coli cells.

26. A method of producing a bispecific antigen-binding molecule that specifically binds CD3 and HER2 comprising a monovalent arm and a bivalent arm, wherein:

(a) the monovalent arm comprises a Fab A that specifically binds CD3, wherein the C-terminus of the Fab A is fused to an N-terminus of a first Fc subunit, and wherein the Fab A comprises the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6;

(b) the bivalent arm comprises a Fab B1 and a Fab B2 that each specifically binds HER2, wherein the C-terminus of the Fab B2 is fused to the N-terminus of the Fab B1 , and the C-terminus of the Fab B1 is fused to an N-terminus of a second Fc subunit, wherein the Fab B1 and the Fab B2 each comprise the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 11,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 19,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 32,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 21,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 22, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 23; and

(c) the first Fc subunit is associated with the second Fc subunit to form an Fc domain,

wherein the method comprises culturing the one or more host cells of claim 23 in a culture medium.

27. The method of claim 26 , wherein the method further comprises recovering the bispecific antigen-binding molecule from the one or more host cells or the culture medium.

28. One or more isolated nucleic acids encoding a bispecific antigen-binding molecule that specifically binds CD3 and HER2 comprising a monovalent arm and a bivalent arm, wherein:

(a) the monovalent arm comprises a Fab A that specifically binds CD3, wherein the C-terminus of the Fab A is fused to an N-terminus of a first Fc subunit, and wherein the Fab A comprises the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6;

(b) the bivalent arm comprises a Fab B1 and a Fab B2 that each specifically binds HER2, wherein the C-terminus of the Fab B2 is fused to the N-terminus of the Fab B1 , and the C-terminus of the Fab B1 is fused to an N-terminus of a second Fc subunit, wherein the Fab B1 and the Fab B2 each comprise the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 11,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 43,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 21,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26; and

(c) the first Fc subunit is associated with the second Fc subunit to form an Fc domain.

29. The one or more isolated nucleic acids of claim 28 , wherein:

(a) the Fab A comprises a VH A region and a VL A region, wherein the VH A region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 7, and the VL A region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 8;

(b) the Fab B1 comprises a VH B1 region and a VL B1 region, wherein the VH B1 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 44, and the VL B1 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 48; and

(c) the Fab B2 comprises a VH B2 region and a VL B2 region, wherein the VH B2 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 44, and the VL B2 region comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 48.

30. The one or more isolated nucleic acids of claim 29 , wherein:

(a) the VH A region comprises the amino acid sequence of SEQ ID NO: 7, and the VL A region comprises the amino acid sequence of SEQ ID NO: 8;

(b) the VH B1 region comprises the amino acid sequence of SEQ ID NO: 44, and the VL B1 region comprises the amino acid sequence of SEQ ID NO: 48; and

(c) the VH B2 region comprises the amino acid sequence of SEQ ID NO: 44, and the VL B2 region comprises the amino acid sequence of SEQ ID NO: 48.

31. One or more vectors comprising the one or more isolated nucleic acids of claim 28 .

32. One or more host cells comprising the one or more isolated nucleic acids of claim 28 .

33. The one or more host cells of claim 32 , wherein the one or more host cells comprise one or more mammalian cells or one or more prokaryotic cells.

34. The one or more host cells of claim 33 , wherein:

(a) the one or more host cells comprise one or more mammalian cells, and wherein the one or more mammalian cells comprise one or more CHO cells; or

(b) the one or more host cells comprise one or more prokaryotic cells, and wherein the one or more prokaryotic cells comprise one or more E. coli cells.

35. A method of producing a bispecific antigen-binding molecule that specifically binds CD3 and HER2 comprising a monovalent arm and a bivalent arm, wherein:

(a) the monovalent arm comprises a Fab A that specifically binds CD3, wherein the C-terminus of the Fab A is fused to an N-terminus of a first Fc subunit, and wherein the Fab A comprises the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6;

(b) the bivalent arm comprises a Fab B1 and a Fab B2 that each specifically binds HER2, wherein the C-terminus of the Fab B2 is fused to the N-terminus of the Fab B1 , and the C-terminus of the Fab B1 is fused to an N-terminus of a second Fc subunit, wherein the Fab B1 and the Fab B2 each comprise the following HVRs:

(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 11,

(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36,

(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 43,

(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 21,

(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and

(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26; and

(c) the first Fc subunit is associated with the second Fc subunit to form an Fc domain,

wherein the method comprises culturing the one or more host cells of claim 32 in a culture medium.

36. The method of claim 35 , wherein the method further comprises recovering the bispecific antigen-binding molecule from the one or more host cells or the culture medium.

Continuity (3)
Division 16271410 · Feb 8, 2019
Provisional Application 62628088 · Feb 8, 2018
Related Publication 20240092906A1 · Mar 21, 2024
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