# US 11,078,286 B2 · Monoclonal antibodies specific for fibroblast growth factor receptor 4 (FGFR4) and methods of their use

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- Number: US 11,078,286 B2
- Document ID: US11078286B2
- Status: Granted
- Kind: B2
- Application number: 15/761,398
- Filed: 2016-09-19
- Published: 2018-11-08
- Granted: 2021-08-03
- Earliest claimed: 2015-09-20
- Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services
- Applicants: The U.S.A., as represented by the Secretary, Department of Health and Human Services
- Inventors: Javed Khan; Sivasubramanian Baskar; Rimas J. Orentas; Dimiter S. Dimitrov; Zhongyu Zhu; Tai Chi Cheuk
- Web page: https://patentgrep.com/patent/US11078286B2

## CPC

- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 39/0011: {Cancer antigens}
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 47/6803: {Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates}
- A61K 47/68031: {the drug being an auristatin}
- A61K 47/6911: {the form being a liposome}
- A61P 35/00: Antineoplastic agents
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/5156: {expressing foreign proteins}
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/77: Internalization into the cell
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

Monoclonal antibodies selected from immunized mice, immunized rabbits and a human scFv library that specifically bind fibroblast growth factor receptor 4 (FGFR4) are described. Chimeric antigen receptors, antibody-drug conjugates, immunoconjugates, bispecific antibodies and immunoliposomes comprising the disclosed FGFR4-specific antibodies are also described. The antibody compositions can be used to diagnose or treat a FGFR4-positive cancer, such as rhabdomyosarcoma, lung cancer, liver cancer, breast cancer, pancreatic cancer or prostate cancer.

## Claims

### Claim 1

An isolated monoclonal antibody that specifically binds fibroblast growth factor receptor 4 (FGFR4), or an antigen-binding fragment thereof, comprising a variable heavy (VH) domain and a variable light (VL) domain, wherein:
the amino acid sequence of the VH domain of the antibody comprises the complementarity determining region 1 (CDR1), CDR2 and CDR3 sequences of SEQ ID NO: 3, wherein the CDR1, CDR2, and CDR3 sequences respectively comprise residues 26-33, 52-59, and 98-111 of SEQ ID NO:3; and
the amino acid sequence of the VL domain of the antibody comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 4, wherein the CDR1, CDR2, and CDR3 sequences respectively comprise residues 27-32, 50-52, and 88-98 of SEQ ID NO:4.

### Claim 2 (depends on 1)

The monoclonal antibody or antigen-binding fragment of claim 1, wherein:
the amino acid sequence of the VH domain is at least 90% identical to SEQ ID NO: 3 and the amino acid sequence of the VL domain is at least 90% identical to SEQ ID NO: 4.

### Claim 3 (depends on 1)

The monoclonal antibody or antigen-binding fragment of claim 1, wherein:
the amino acid sequence of the VH domain comprises SEQ ID NO: 3 and the amino acid sequence of the VL domain comprises SEQ ID NO: 4.

### Claim 4 (depends on 1)

The antigen-binding fragment of claim 1, wherein the antigen-binding fragment is an Fab fragment, an Fab′ fragment, an F(ab)′2 fragment, a single chain variable fragment (scFv) or a disulfide stabilized variable fragment (dsFv).

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 1)

The monoclonal antibody or antigen-binding fragment of claim 1, which is a fully human antibody or antigen-binding fragment.

### Claim 7 (depends on 1)

The monoclonal antibody or antigen-binding fragment of claim 1, which is a chimeric, synthetic, or humanized antibody or antigen-binding fragment.

### Claim 8 (depends on 1)

A composition comprising the monoclonal antibody or antigen-binding fragment of claim 1 and a pharmaceutically acceptable carrier.

### Claim 9 (depends on 4)

The antigen-binding fragment of claim 4, wherein the fragment is a scFv comprising the amino acid sequence of SEQ ID NO: 38.