Antibody Specific for GPC3 and Methods of Use Thereof

Patent metadata

Field	Value
Publication number	US-2022251237-A1
Application number	US-202017629297-A
Country	US
Kind code	A1
Filing date	Jul 31, 2020
Priority date	Aug 1, 2019
Publication date	Aug 11, 2022
Grant date	—

Abstract

The present disclosure provides antibodies specific for glypican-3 (GPC3). Nucleic acids that encode one or both of the variable chain polypeptides of an antibody of the present disclosure are also provided, as are cells that include such nucleic acids. Also provided are compositions that include the antibodies of the present disclosure, including in some instances, pharmaceutical compositions. Methods of making and using the antibodies of the present disclosure are also provided. In certain aspects, provided are methods that include administering to an individual having a cell proliferative disorder a therapeutically effective amount of an antibody of the present disclosure, where the antibody is administered to the individual to enhance an immune response, e.g., a T cell response, to abnormally proliferating cells of the cell proliferative disorder. The antibodies are useful in various diagnostic, and monitoring applications, which are also provided.

First claim

What is claimed is:

1 . An antibody that specifically binds to GPC3, and competes for binding to GPC3 with a second antibody comprising:
a variable heavy chain (V H ) polypeptide comprising:
a V H CDR1 comprising the amino acid sequence GYTFTSYFLH (SEQ ID NO:2) or the amino acid sequence GYTFTSYYMH (SEQ ID NO:3),
a V H CDR2 comprising the amino acid sequence IIDPPTGRTTYAQKFQG (SEQ ID NO:4), and
a V H CDR3 comprising the amino acid sequence GNYGGRYFDY (SEQ ID NO:5); and
a variable light chain (V L ) polypeptide comprising:
a V L CDR1 comprising the amino acid sequence RASQSISSYLN (SEQ ID NO:6),
a V L CDR2 comprising the amino acid sequence AASSLQS (SEQ ID NO:7), and
a V L CDR3 comprising the amino acid sequence QQSYSTPLT (SEQ ID NO:8).

2 . The antibody of claim 1 , wherein the antibody that specifically binds to GPC3 comprises:
a variable heavy chain (V H ) polypeptide comprising:
a V H CDR1 comprising the amino acid sequence GYTFTSYFLH (SEQ ID NO:2) or the amino acid sequence GYTFTSYYMH (SEQ ID NO:3),
a V H CDR2 comprising the amino acid sequence IIDPPTGRTTYAQKFQG (SEQ ID NO:4), and
a V H CDR3 comprising the amino acid sequence GNYGGRYFDY (SEQ ID NO:5); and
a variable light chain (V L ) polypeptide comprising:
a V L CDR1 comprising the amino acid sequence RASQSISSYLN (SEQ ID NO:6),
a V L CDR2 comprising the amino acid sequence AASSLQS (SEQ ID NO:7), and
a V L CDR3 comprising the amino acid sequence QQSYSTPLT (SEQ ID NO:8).

3 . The antibody of claim 1 or claim 2 , wherein the V H polypeptide comprises an amino acid sequence having at least 70% identity to the amino acid sequence set forth in SEQ ID NO:9.

4 . The antibody of any one of claims 1 - 3 , wherein the V L polypeptide comprises an amino acid sequence having at least 70% identity to the amino acid sequence set forth in SEQ ID NO:10.

5 . The antibody of any one of claims 1 - 4 , wherein the antibody is a humanized antibody.

6 . The antibody of any one of claims 1 - 5 , wherein the antibody is a chimeric antibody.

7 . The antibody of any one of claims 1 - 6 , wherein the antibody is selected from the group consisting of: an IgG, Fv, single chain antibody, scFv, Fab, F(ab′)2, or Fab′.

8 . The antibody of any one of claims 1 - 6 , wherein the antibody is an IgG.

9 . The antibody of claim 8 , wherein the antibody is an IgG1.

10 . The antibody of any one of claims 1 - 6 , wherein the antibody is a Fab.

11 . The antibody of any one of claims 1 - 6 , wherein the antibody is a single chain antibody.

12 . The antibody of claim 11 , wherein the antibody is an scFv.

13 . The antibody of any one of claims 1 - 12 , wherein the antibody is a bispecific antibody comprising a first antigen-binding domain that specifically binds GPC3, and wherein the first antigen binding domain comprises a V H polypeptide and a V L polypeptide as defined in any one of claims 1 to 4 .

14 . The antibody of any one of claims 1 - 13 , wherein the antibody is detectably labeled.

15 . The antibody of any one of claims 1 - 14 , wherein the antibody comprises a covalently linked non-peptide synthetic polymer.

16 . The antibody of claim 15 , wherein the synthetic polymer is poly(ethylene glycol) polymer.

17 . The antibody of any one of claims 1 - 16 , wherein the antibody comprises a covalently linked lipid or fatty acid moiety.

18 . The antibody of any one of claims 1 - 14 , wherein the antibody comprises a covalently linked polysaccharide or carbohydrate moiety.

19 . The antibody of any one of claims 1 - 18 , wherein the antibody comprises a contrast agent.

20 . The antibody of any one of claims 1 - 19 , wherein the antibody comprises an affinity domain.

21 . The antibody of any one of claims 1 - 20 , wherein the antibody is immobilized on a solid support.

22 . The antibody of any one of claims 1 - 21 , wherein the antibody comprises a covalently linked cytotoxin.

23 . The antibody of any one of claims 1 - 22 , wherein the antibody comprises a constant region amino acid sequence comprising an amino acid sequence of a sulfatase motif.

24 . The antibody of any one of claims 1 - 22 , wherein the antibody comprises a constant region amino acid sequence comprising an amino acid sequence of a sulfatase motif, and wherein the sulfatase motif is modified to comprise a 2-formylglycine (FGly) moiety.

25 . The antibody of claim 24 , wherein the antibody comprises a heterologous moiety covalently linked to the antibody via the FGly moiety.

26 . The antibody of claim 25 , wherein the heterologous moiety is selected from a drug, a toxin, a detectable label, a water-soluble polymer, and a synthetic peptide.

27 . A nucleic acid encoding a variable heavy chain (V H ) polypeptide, a variable light chain (V L ) polypeptide, or both, of the antibody of any one of claims 1 to 13 .

28 . The nucleic acid of claim 27 , wherein the antibody is a single chain antibody, and wherein the nucleic acid encodes the single chain antibody.

29 . The nucleic acid of claim 8 , wherein the single chain antibody is an scFv.

30 . A recombinant expression vector comprising the nucleic acid of any one of claims 27 - 29 , wherein the nucleic acid is operably linked to a transcriptional control element that is active in a eukaryotic cell.

31 . A cell comprising the nucleic acid of any one of claims 27 to 29 or the expression vector of claim 30 .

32 . The cell of claim 31 , wherein the nucleic acid encodes the V H polypeptide of the antibody and the V L polypeptide of the antibody.

33 . The cell of claim 32 , wherein the antibody is a single chain antibody, and wherein the nucleic acid encodes the single chain antibody.

34 . The cell of claim 33 , wherein the single chain antibody is an scFv.

35 . A cell comprising:
a first nucleic acid encoding a variable heavy chain (V H ) polypeptide of the antibody of any one of claims 1 to 13 ; and a second nucleic acid encoding a variable light chain (V L ) polypeptide of the antibody.

36 . The cell of claim 35 comprising:
a first expression vector comprising the first nucleic acid; and
a second expression vector comprising the second nucleic acid.

37 . A conjugate, comprising:
the antibody of any one of claims 1 - 13 ; and an agent conjugated to the antibody.

38 . The conjugate of claim 37 , wherein the agent is selected from the group consisting of: a half-life extending moiety, a labeling agent, and a therapeutic agent.

39 . A fusion protein, comprising:
a variable heavy chain (V H ) polypeptide, a variable light chain (V L ) polypeptide, or both, of the antibody of any one of claims 1 - 13 ; fused to a heterologous amino acid sequence.

40 . A pharmaceutical composition comprising:
a) the antibody of any one of claims 1 - 13 ; and b) a pharmaceutically acceptable carrier.

41 . A pharmaceutical composition comprising:
a) the conjugate of any one of claims 37 - 38 ; and b) a pharmaceutically acceptable carrier.

42 . A pharmaceutical composition comprising:
a) the fusion protein of claim 40 ; and

Assignees

• Scherer Technologies Llc R P

Inventors

• Rabuka David
• Drake Penelope M
• Kim Yun Cheol
• Barfield Robyn M
• Bauzon Maxine

Classifications

• C07K16/28

  against receptors, cell surface antigens or cell surface determinants · CPC title

• C07K16/18

  against material from animals or humans · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/55

  Fab or Fab' · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title