# US 12,595,314 B2 · Antibody specific for GPC3 and methods of use thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 12,595,314 B2
- Document ID: US12595314B2
- Status: Granted
- Kind: B2
- Application number: 17/629,297
- Filed: 2020-07-31
- Published: 2022-08-11
- Granted: 2026-04-07
- Earliest claimed: 2019-08-01
- Assignees: R.P. Scherer Technologies, LLC
- Applicants: R.P. Scherer Technologies, LLC
- Inventors: David Rabuka; Penelope M. Drake; Yun Cheol Kim; Robyn M. Barfield; Maxine Bauzon
- Web page: https://patentgrep.com/patent/US12595314B2

## CPC

- C07K 16/303: {Liver or Pancreas}
- A61P 35/00: Antineoplastic agents
- C07K 16/18: against material from animals or humans
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/565: Complementarity determining region [CDR]
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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.

## Claims

### Claim 1

An antibody that specifically binds to Glypican-3 (GPC3), the antibody comprising:
a variable heavy chain (VH) polypeptide comprising:
a VH CDR1 comprising the amino acid sequence GYTFTSYFLH (SEQ ID NO:2),
a VH CDR2 comprising the amino acid sequence IIDPPTGRTTYAQKFQG (SEQ ID NO:4), and
a VH CDR3 comprising the amino acid sequence GNYGGRYFDY (SEQ ID NO:5); and
a variable light chain (VL) polypeptide comprising:
a VL CDR1 comprising the amino acid sequence RASQSISSYLN (SEQ ID NO:6),
a VL CDR2 comprising the amino acid sequence AASSLQS (SEQ ID NO:7), and
a VL CDR3 comprising the amino acid sequence QQSYSTPLT (SEQ ID NO:8).

### Claim 2 (depends on 1)

The antibody of claim 1, wherein the VH polypeptide comprises an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:9.

### Claim 3 (depends on 2)

The antibody of claim 2, wherein the VL polypeptide comprises an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:10.

### Claim 4 (depends on 1)

The antibody of claim 1, wherein the antibody is a humanized antibody.

### Claim 5 (depends on 1)

The antibody of claim 1, wherein the antibody is a chimeric antibody.

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 1)

The antibody of claim 1, wherein the antibody is an IgG.

### Claim 8 (depends on 7)

The antibody of claim 7, wherein the antibody is an IgG1.

### Claim 9 (depends on 1)

The antibody of claim 1, wherein the antibody is a Fab.

### Claim 10 (depends on 1)

The antibody of claim 1, wherein the antibody is a single chain antibody.

### Claim 11 (depends on 10)

The antibody of claim 10, wherein the antibody is an scFv.

### Claim 12 (depends on 1)

The antibody of claim 1, 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 the VH polypeptide and the VL polypeptide as defined in claim 1.

### Claim 13 (depends on 1)

The antibody of claim 1, wherein the antibody is detectably labeled.

### Claim 14 (depends on 1)

The antibody of claim 1, wherein the antibody comprises a covalently linked non-peptide synthetic polymer.

### Claim 15 (depends on 14)

The antibody of claim 14, wherein the synthetic polymer is poly(ethylene glycol) polymer.

### Claim 16 (depends on 1)

The antibody of claim 1, wherein the antibody comprises a covalently linked lipid or fatty acid moiety.

### Claim 17 (depends on 1)

The antibody of claim 1, wherein the antibody comprises a covalently linked polysaccharide or carbohydrate moiety.

### Claim 18 (depends on 1)

The antibody of claim 1, wherein the antibody comprises a contrast agent.

### Claim 19 (depends on 1)

The antibody of claim 1, wherein the antibody comprises an affinity domain.

### Claim 20 (depends on 1)

The antibody of claim 1, wherein the antibody is immobilized on a solid support.

### Claim 21 (depends on 1)

The antibody of claim 1, wherein the antibody comprises a covalently linked cytotoxin.

### Claim 22 (depends on 1)

The antibody of claim 1, wherein the antibody comprises a constant region amino acid sequence comprising an amino acid sequence of a sulfatase motif.

### Claim 23 (depends on 1)

The antibody of claim 1, 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.

### Claim 24 (depends on 23)

The antibody of claim 23, wherein the antibody comprises a heterologous moiety covalently linked to the antibody via the FGly moiety.

### Claim 25 (depends on 24)

The antibody of claim 24, wherein the heterologous moiety is selected from a drug, a toxin, a detectable label, a water-soluble polymer, and a synthetic peptide.

### Claim 26 (depends on 1)

A conjugate, comprising:
the antibody of claim 1; and
an agent conjugated to the antibody.

### Claim 27 (depends on 26)

The conjugate of claim 26, wherein the agent is selected from the group consisting of: a half-life extending moiety, a labeling agent, and a therapeutic agent.

### Claim 28 (depends on 1)

A fusion protein, comprising:
the VH polypeptide, and the VL-polypeptide, of the antibody of claim 1 fused to a heterologous amino acid sequence.

### Claim 29 (depends on 1)

A pharmaceutical composition comprising:
a) the antibody of claim 1; and
b) a pharmaceutically acceptable carrier.

### Claim 30 (depends on 26)

A pharmaceutical composition comprising:
a) the conjugate of claim 26; and
b) a pharmaceutically acceptable carrier.

### Claim 31 (depends on 28)

A pharmaceutical composition comprising:
a) the fusion protein of claim 28; and
b) a pharmaceutically acceptable carrier.

### Claim 32 (depends on 29)

The pharmaceutical composition of claim 29, further comprising a T cell activator.

### Claim 33 (depends on 32)

The pharmaceutical composition of claim 32, wherein the T cell activator is selected from the group consisting of: an immune checkpoint inhibitor, a cytokine, and an antagonist of an inhibitory immune receptor.

### Claim 34 (depends on 29)

The pharmaceutical composition of claim 29, wherein the antibody is encapsulated in a liposome.

### Claim 35 (depends on 29)

A method of treating a cell proliferative disorder in a subject having the cell proliferative disorder, the method comprising:
administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 29,
wherein the cell proliferative disorder is associated with or caused by a GPC3-positive cell.

### Claim 36 (depends on 35)

The method of claim 35, wherein the cell proliferative disorder is a cancer and the GPC3-positive cell is a cancerous GPC3-positive cell.

### Claim 37 (depends on 35)

The method of claim 35, wherein the GPC3-positive cell is an autoreactive GPC3-positive cell.