# US 8,784,809 B2 · Vascular endothelial growth factor 2

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- Number: US 8,784,809 B2
- Document ID: US8784809B2
- Status: Granted
- Kind: B2
- Application number: 13/749,157
- Filed: 2013-01-24
- Published: 2013-11-21
- Granted: 2014-07-22
- Earliest claimed: 2001-04-13
- Assignees: Human Genome Sciences, Inc.
- Applicants: Human Genome Sciences, Inc.
- Inventors: Craig Rosen; Vivian Albert; Steven M. Ruben; Ruth Wager
- Web page: https://patentgrep.com/patent/US8784809B2

## CPC

- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- C07K 16/22: against growth factors {; against growth regulators}
- A61P 3/02: Nutrients, e.g. vitamins, minerals
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 13/08: of the prostate
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 17/06: Antipsoriatics
- A61P 19/00: Drugs for skeletal disorders
- A61P 27/02: Ophthalmic agents
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/18: for HIV
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- A61P 41/00: Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/52: Cytokines; Lymphokines; Interferons
- C07K 16/24: against cytokines, lymphokines or interferons
- G01N 33/575: for cancer
- G01N 33/74: involving hormones {or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors}
- A01K 2217/05: Animals comprising random inserted nucleic acids (transgenic)
- A01K 2217/075: inducing loss of function, i.e. knock out
- 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)
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/622: Single chain antibody (scFv)
- C12N 2799/026: where the vector is derived from a baculovirus
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- Y10S 435/81: Packaged device or kit
- 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)
- 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)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

Disclosed are human VEGF-2 antibodies, antibody fragments, or variants thereof. Also provided are processes for producing such antibodies. The present invention relates to methods and compositions for preventing, treating or ameliorating a disease or disorder comprising administering to an animal, preferably a human, an effective amount of one or more VEGF-2 antibodies or fragments or variants thereof.

## Claims

### Claim 1

A method of treating or ameliorating an inflammatory disease or disorder mediated by human VEGF-2 in a human subject comprising administering to the subject an isolated antibody or antigen binding fragment thereof that specifically binds to a human VEGF-2 polypeptide in an amount effective to treat or ameliorate to the inflammatory disease or disorder in the subject, wherein the isolated antibody or antigen binding fragment thereof inhibits binding of human VEGF-2 to flk-1 or Flt-4 and wherein the isolated antibody or antigen binding fragment thereof comprises:
(a) an amino acid sequence that is at least 96% identical to the amino acid sequence of the VH domain of the antibody expressed by the hybridoma cell line deposited under ATCC Deposit No. PTA-4095, with the proviso that the amino acid sequence of the isolated antibody or antigen binding fragment thereof includes the amino acid sequences of the VHCDR1, VHCDR2, and VHCDR3 regions of the antibody expressed by the hybridoma deposited under ATCC Deposit No. PTA-4095, and
an amino acid sequence that is at least 96% identical to the amino acid sequence of the VL domain of the antibody expressed by the hybridoma cell line deposited under ATCC Deposit No. PTA-4095, with the proviso that the amino acid sequence of the isolated antibody or antigen binding fragment thereof includes the amino acid sequences of the VLCDR1, VLCDR2, and VLCDR3 regions of the antibody expressed by the hybridoma deposited under ATCC Deposit No. PTA-4095; or
(b) an amino acid sequence that is at least 96% identical to the amino acid sequence of the VH domain of SEQ ID NO: 79, with the proviso that the amino acid sequence of the isolated antibody or antigen binding fragment thereof includes a VHCDR1consisting of the amino acid sequence of amino acid residues 26-35 of SEQ ID NO: 79; a VHCDR2 consisting of the amino acid sequence of amino acid residues 50-66 of SEQ ID NO: 79; and a VHCDR3 consisting of the amino acid sequence of amino acid residues 99-107 of SEQ ID NO: 79; and
an amino acid sequence that is at least 96% identical to the amino acid sequence of the VL domain of SEQ ID NO: 79, with the proviso that the amino acid sequence of the isolated antibody or antigen binding fragment thereof includes a VLCDR1 consisting of the amino acid sequence of amino acid residues 158-170 of SEQ ID NO: 79; a VLCDR2 consisting of the amino acid sequence of amino acid residues 186-192 of SEQ ID NO: 79; and a VLCDR3 consisting of the amino acid sequence of amino acid residues 225-236 of SEQ ID NO: 79.

### Claim 2 (depends on 1)

The method of claim 1, wherein the isolated antibody or antigen binding fragment thereof is administered at a dosage of 0.1 mg/kg to 100 mg/kg of the human's body weight.

### Claim 3 (depends on 1)

The method of claim 1, wherein the isolated antibody or antigen binding fragment thereof is administered in a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient.

### Claim 4 (depends on 1)

The method of claim 1, wherein the isolated antibody is a monoclonal antibody.

### Claim 5 (depends on 1)

The method of claim 1, wherein the isolated antibody is a polyclonal antibody.

### Claim 6 (depends on 1)

The method of claim 1, wherein the isolated antibody is a human antibody or humanized antibody.

### Claim 7 (depends on 1)

The method of claim 1, wherein the antigen binding fragment is selected from the group consisting of Fab, Fab′, F(ab′)2, Fv, single-chain Fv and disulfide-linked Fv.

### Claim 8 (depends on 1)

The method of claim 1, wherein the isolated antibody or antigen-binding fragment thereof binds to least one VEGF-2 polypeptide selected from the group consisting of:
(a) a VEGF-2 polypeptide comprising amino acids 1-419 of SEQ ID NO:18;
(b) a VEGF-2 polypeptide comprising amino acids 32-419 of SEQ ID NO:18;
(c) a VEGF-2 polypeptide comprising amino acids 103-227 of SEQ ID NO:18;
(d) a VEGF-2 polypeptide comprising amino acids 112-227 of SEQ ID NO:18;
(e) a dimeric VEGF-2 polypeptide consisting of two polypeptides each consisting of amino acids 103-227 of SEQ ID NO:18;
(f) a dimeric VEGF-2 polypeptide consisting of two polypeptides each consisting of amino acids 112-227 of SEQ ID NO:18;
(g) the amino acid sequence of the full-length VEGF-2 polypeptide encoded by cDNA contained in ATCC Deposit Number 97149;
(h) the amino acid sequence of the pro-protein VEGF-2 polypeptide encoded by cDNA contained in ATCC Deposit Number 97149;
(i) the amino acid sequence of the secreted VEGF-2 polypeptide encoded by cDNA contained in ATCC Deposit Number 97149;
(j) the amino acid sequence of the full-length VEGF-2 polypeptide encoded by cDNA contained in ATCC Deposit Number 75698;
(k) the amino acid sequence of the pro-protein VEGF-2 polypeptide encoded by cDNA contained in ATCC Deposit Number 75698;
(l) the amino acid sequence of the secreted VEGF-2 polypeptide encoded by cDNA contained in ATCC Deposit Number 75698; and
(m) the amino acid sequence of the secreted form of the VEGF-2 polypeptide of SEQ ID NO:18.

### Claim 9 (depends on 1)

The method of claim 1, wherein the isolated antibody or antigen binding fragment thereof comprises
(a) an amino acid sequence that is at least 96% identical to the amino acid sequence of the VH domain of the antibody expressed by the hybridoma cell line deposited under ATCC Deposit No. PTA-4095, with the proviso that the amino acid sequence of the isolated antibody or antigen binding fragment thereof includes the amino acid sequences of the VHCDR1, VHCDR2, and VHCDR3 regions of the antibody expressed by the hybridoma deposited under ATCC Deposit No. PTA-4095; and
(b) an amino acid sequence that is at least 96% identical to the amino acid sequence of the VL domain of the antibody expressed by the hybridoma cell line deposited under ATCC Deposit No. PTA-4095, with the proviso that the amino acid sequence of the isolated antibody or antigen binding fragment thereof includes the amino acid sequences of the VLCDR1, VLCDR2, and VLCDR3 regions of the antibody expressed by the hybridoma deposited under ATCC Deposit No. PTA-4095.

### Claim 10 (depends on 1)

The method of claim 1, wherein the isolated antibody or antigen binding fragment thereof comprises
(i) an amino acid sequence that is at least 96% identical to the amino acid sequence of the VH domain of SEQ ID NO: 79, with the proviso that the amino acid sequence of the isolated antibody or antigen binding fragment thereof includes a VHCDR1 consisting of the amino acid sequence of amino acid residues 26-35 of SEQ ID NO: 79; a VHCDR2 consisting of the amino acid sequence of amino acid residues 50-66 of SEQ ID NO: 79; and a VHCDR3 consisting of the amino acid sequence of amino acid residues 99-107 of SEQ ID NO: 79; and
(ii) an amino acid sequence that is at least 96% identical to the amino acid sequence of the VL domain of SEQ ID NO: 79, with the proviso that the amino acid sequence of the isolated antibody or antigen binding fragment thereof includes a VLCDR1 consisting of the amino acid sequence of amino acid residues 158-170 of SEQ ID NO: 79; a VLCDR2 consisting of the amino acid sequence of amino acid residues 186-192 of SEQ ID NO: 79; and a VLCDR3 consisting of the amino acid sequence of amino acid residues 225-236 of SEQ ID NO: 79.

### Claim 11 (depends on 1)

The method of claim 1, wherein the isolated antibody or antigen-binding fragment thereof comprises
(i) the amino acid sequence of the VH domain of the antibody expressed by the hybridoma cell line deposited under ATCC Deposit No. PTA-4095;
(ii) the amino acid sequence of the VL domain of the antibody expressed by the hybridoma cell line deposited under ATCC Deposit No. PTA-4095; or
(iii) the amino acid sequence of the VH domain of the antibody expressed by the hybridoma cell line deposited under ATCC Deposit No. PTA-4095; and the amino acid sequence of the VL domain of the antibody expressed by the hybridoma cell line deposited under ATCC Deposit No. PTA-4095.

### Claim 12 (depends on 1)

The method of claim 1, wherein the isolated antibody or antigen binding fragment thereof comprises:
(i) the amino acid sequence of the VH domain of SEQ ID NO: 79;
(ii) the amino acid sequence of the VL domain of SEQ ID NO: 79; or
(iii) the amino acid sequence of the VH domain of SEQ ID NO: 79; and the amino acid sequence of the VL domain of SEQ ID NO: 79.

### Claim 13 (depends on 1)

The method of claim 1, wherein the isolated antibody or antigen-binding fragment thereof is administered intravenously.