# US 5,707,632 A · Receptors for fibroblast growth factors

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- Number: US 5,707,632 A
- Document ID: US5707632A
- Status: Granted
- Kind: A
- Application number: 08/458,938
- Filed: 1995-06-02
- Granted: 1998-01-13
- Earliest claimed: 1989-07-06
- Assignees: The Regents of the University of CA
- Inventors: Lewis T. Williams; Daniel E. Johnson; Pauline E. Lee
- Web page: https://patentgrep.com/patent/US5707632A

## CPC

- C07K 14/71: for growth factors; for growth regulators
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- G01N 33/74: involving hormones {or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- G01N 2333/50: Fibroblast growth factors [FGF]
- G01N 2333/71: for growth factors; for growth regulators
- G01N 2500/00: Screening for compounds of potential therapeutic value
- 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
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- 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)

## Abstract

A fibroblast growth factor (FGF) receptor including a basic fibroblast growth factor receptor has been purified. Various forms have been identified including soluble forms lacking any transmembrane segment. DNA sequences encoding full-length fibroblast growth factor receptors and polypeptides comprising a portion of an FGF-R ligand-binding domain have been isolated and sequenced. These DNAs include DNAs encoding for a basic FGF-R and a human FGF-R and are operably linked to control sequences and expressed in a culture of a compatible host transformed, transfected or electrophoresed by a cloning vehicle containing the DNA sequence. The invention also comprises antibodies to the receptor, methods of synthesizing the growth factor receptor proteins, methods for providing analogs of the fibroblast growth factor receptors. Methods for evaluating compositions which promote or inhibit fibroblastic growth factors and compositions which are agonistic or antagonistic to fibroblast growth factor receptors are also provided. Diagnostic and therapeutic uses are described.

## Claims

### Claim 1

A method for producing an antibody against a fibroblast growth factor receptor fragment, said method comprising steps of:
immunizing lymphocytes of an animal with a polypeptide epitope homologous to a sequence of at least six contiguous amino acids described in FIG. 7; and
screening antibodies produced by the lymphocytes for binding to a fibroblast growth factor receptor or fragment thereof comprising the epitope.

### Claim 2 (depends on 1)

A method of claim 1, wherein said epitope is selected from the group of protein segments consisting of a signal segment, an IgI segment, an acidic segment, an IgII segment, an IgIII segment, and an IgIIIT segment.

### Claim 3 (depends on 1)

The method of claim 1, further comprising immortalizing the immunized lymphocytes to produce hybridomas, wherein the hybridomas are screened for production of a monoclonal antibody binding to the fibroblast growth factor receptor or fragment thereof.

### Claim 4 (depends on 3)

The method of claim 3, wherein the lymphocytes are immunized with an isolated extracellular domain of a human fibroblast growth factor receptor comprising the polypeptide epitope.

### Claim 5 (depends on 3)

The method of claim 3, wherein the lymphocytes are immunized with a human fibroblast growth factor receptor shown in FIG. 7 comprising the polypeptide epitope.

### Claim 6 (depends on 4)

The method of claim 4, wherein the polypeptide epitope is a sequence of at least seven contiguous amino acids of the fibroblast growth factor receptor designated h3 and the antibodies are screened for binding to h3 or a fragment thereof comprising the epitope.

### Claim 7 (depends on 3)

The method of claim 3, wherein the hybridomas are screened for production of a monoclonal antibody binding to an isolated extracellular domain of a fibroblast growth factor receptor shown in FIG. 7 comprising the epitope.

### Claim 8 (depends on 7)

The method of claim 7 wherein the fibroblast growth factor receptor is human.

### Claim 9 (depends on 8)

The method of claim 8, wherein the extracellular domain is an IgII domain.

### Claim 10 (depends on 8)

The method of claim 8, wherein the extracellular domain is an IgIII domain.

### Claim 11 (depends on 3)

The method of claim 3, further comprising mixing the monoclonal antibody with a carrier.

### Claim 12 (depends on 3)

The method of claim 3, further comprising the step of screening the antibody for capacity to block binding of fibroblast growth factor to the fibroblast growth factor receptor or fragment comprising the polypeptide epitope.

### Claim 13

A monoclonal antibody that binds to any one of the fibroblast growth factor receptor sequences shown in FIG. 7 and blocks binding of fibroblast growth factor to said fibroblast growth factor receptor sequences.

### Claim 14 (depends on 13)

The monoclonal antibody of claim 13 that binds to the fibroblast growth factor receptor designated h3.
