FcgammaRIIB-Specific Antibodies and Methods of Use Thereof

• US 20200131265A1
• Filed: 06/11/2019
• Published: 04/30/2020
• Est. Priority Date: 08/14/2002
• Status: Abandoned Application

• Current Assignee: MacroGenics, Inc.
• Original Assignee: MacroGenics, Inc.
• Inventors: Koenig, Scott, Veri, Maria Concetta
• Application Number:
  US16/437,571
• Publication Number:
  US 20200131265A1
• Time in Patent Office: Days
• CPC Class Codes: C07K 16/283 against Fc-receptors, e.g. CD16, CD32, CD64 CD23 C07K16/2851
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/75 Agonist effect on antigen
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The present invention relates to antibodies or fragments thereof that specifically bind FcγRIIB, particularly human FcγRIIB, with greater affinity than said antibodies or fragments thereof bind FcγRIIA, particularly human FcγRIIA. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention.

Claims

1-19. -19. (canceled)

20. A bispecific antibody comprising a first heavy chain-light chain pair that binds the extracellular domain of endogenously expressed Fcγ

RIIB, and a second heavy chain-light chain pair that binds IgE or Fcε

RI, wherein said first heavy chain-light chain pair;

(A) specifically binds to the extracellular domain of said endogenously expressed Fcγ

RIIB with at least 10 times greater affinity than said first heavy chain-light chain pair binds an Fcγ

RIIA that comprises the amino acid sequence of SEQ ID NO;

7; and

(B) specifically binds to the extracellular domain of said endogenously expressed Fcγ

RIIB with at least 10 times greater affinity than said first heavy chain-light chain pair binds an Fcγ

RIIA that comprises the amino acid sequence of SEQ ID NO;

9.

21. The bispecific antibody of claim 20, wherein binding of said first heavy chain-light chain pair to said Fcγ

RIIB blocks binding of aggregated IgG to said Fcγ

RIIB.

22. The bispecific antibody of claim 20, wherein said first heavy chain-light chain pair:

(A) specifically binds to the extracellular domain of said endogenously expressed Fcγ

RIIB with at least 10 times greater affinity than said first heavy chain-light chain pair binds an Fcγ

RIIA that comprises the amino acid sequence of SEQ ID NO;

7; and

(B) specifically binds to the extracellular domain of said endogenously expressed Fcγ

RIIB with at least 10 times greater affinity than said first heavy chain-light chain pair binds an Fcγ

RIIA that comprises the amino acid sequence of SEQ ID NO;

9.

23. The bispecific antibody of claim 20, wherein said first heavy chain-light chain pair comprises CDRs that are at least 90% identical to the amino acid sequence of the CDRs of the mouse monoclonal antibody 2B6 or 3H7.

24. The bispecific antibody of claim 20, wherein said first heavy chain-light chain pair comprises CDRs that are at least 95% identical to the amino acid sequence of the CDRs of the mouse monoclonal antibody 2B6 or 3H7.

25. A pharmaceutical composition comprising the bispecific antibody of claim 20 and a pharmaceutically acceptable carrier.

26. A pharmaceutical composition comprising the bispecific antibody of claim 23 and a pharmaceutically acceptable carrier.

27. A bispecific antibody comprising a first heavy chain-light chain pair that binds the extracellular domain of endogenously expressed Fcγ

RIIB, wherein said first heavy chain-light chain pair;

(A) specifically binds to the extracellular domain of said endogenously expressed Fcγ

RIIB with at least 10 times greater affinity than said first heavy chain-light chain pair binds an Fcγ

RIIA that comprises the amino acid sequence of SEQ ID NO;

7;

(B) specifically binds to the extracellular domain of said endogenously expressed Fcγ

RIIB with at least 10 times greater affinity than said first heavy chain-light chain pair binds an Fcγ

RIIA that comprises the amino acid sequence of SEQ ID NO;

9; and

(C) comprises CDRs that are at least 90% identical to the amino acid sequence of the CDRs of the mouse monoclonal antibody 2B6 or 3H7.

28. The bispecific antibody of claim 27, wherein binding of said first heavy chain-light chain pair to said Fcγ

RIIB blocks binding of aggregated IgG to said Fcγ

RIIB.

29. The bispecific antibody of claim 27, wherein said first heavy chain-light chain pair:

(A) specifically binds to the extracellular domain of said endogenously expressed Fcγ

RIIB with at least 10 times greater affinity than said first heavy chain-light chain pair binds an Fcγ

RIIA that comprises the amino acid sequence of SEQ ID NO;

7; and

(B) specifically binds to the extracellular domain of said endogenously expressed Fcγ

RIIB with at least 10 times greater affinity than said first heavy chain-light chain pair binds an Fcγ

RIIA that comprises the amino acid sequence of SEQ ID NO;

9.

30. The bispecific antibody of claim 27, wherein said first heavy chain-light chain pair comprises CDRs that are at least 95% identical to the amino acid sequence of the CDRs of the mouse monoclonal antibody 2B6 or 3H7.

31. The bispecific antibody of claim 27, wherein said bispecific antibody further comprises a second heavy chain-light chain pair that binds a cancer antigen.

32. The bispecific antibody of claim 31, wherein said cancer antigen is Her2/neu.

33. The bispecific antibody of claim 27, wherein said bispecific antibody further comprises a second heavy chain-light chain pair that binds IgE or Fcε

RI.

34. A pharmaceutical composition comprising the bispecific antibody of claim 27 and a pharmaceutically acceptable carrier.

35. A pharmaceutical composition comprising the bispecific antibody of claim 31 and a pharmaceutically acceptable carrier.

36. A pharmaceutical composition comprising the bispecific antibody of claim 33 and a pharmaceutically acceptable carrier.