# US 7,740,841 B1 · Therapeutic method for reducing angiogenesis

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- Number: US 7,740,841 B1
- Document ID: US7740841B1
- Status: Granted
- Kind: B1
- Application number: 09/539,692
- Filed: 2000-03-31
- Granted: 2010-06-22
- Earliest claimed: 2000-01-28
- Assignees: Sunnybrook Health Science Center
- Inventors: Robert Kerbel
- Web page: https://patentgrep.com/patent/US7740841B1

## CPC

- G01N 33/5011: {for testing antineoplastic activity}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- A61K 2039/505: {comprising antibodies}
- 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)
- 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

A method of controlling or treating an angiogenic dependent condition in a mammal, preferably in a human by administering an anti-angiogenic molecule such as an angiogenesis growth factor antagonist, and a chemotherapeutic agent in amounts and frequencies effective, in combination, to produce a regression or arrest of said condition while minimizing or preventing significant toxicity of the chemotherapeutic agent. Also a kit for controlling or treating an angiogenic dependent condition in a mammal, preferably in a human, comprising an anti-angiogenic molecule, such as an angiogenesis growth factor antagonist, and a chemotherapeutic agent in amounts effective, in combination, to produce a regression or arrest of said condition while minimizing or preventing significant toxicity of the chemotherapeutic agent.

## Claims

### Claim 1

A method of treating a solid tumor in a human patient by inhibiting angiogenesis, comprising:
administering to the human patient comprising a solid tumor selected from the group consisting of breast carcinoma, lung carcinoma, prostate carcinoma, colon carcinoma, ovarian carcinoma, neuroblastoma, central nervous system tumor, glioblastoma multiforme and melanoma:
(a) an antibody or binding fragment thereof that (i) specifically binds to a flk-1/KDR receptor and (ii) inhibits angiogenesis; and
(b) a chemotherapeutic agent having anti-angiogenic activity selected from the group consisting of vincristine, vinblastine, vinorelbine, vindesine, paclitaxel, docetaxel, 5 FU, cisplatin, carboplatin, irinotecan, topotecan and cyclophosphamide,
in amounts and frequencies effective, in combination, to inhibit formation of blood vessels supplying the solid tumor while minimizing or preventing toxicity of the chemotherapeutic agent, wherein the chemotherapeutic agent is administered at a dose intensity of less than about 10% of the dose intensity of the chemotherapeutic agent when used in a conventional chemotherapeutic regimen,
wherein said administering is continued over a period of time from about 10 days to about 6 months, and
wherein synergistic tumor inhibition is obtained.

### Claim 2 (depends on 1)

The method of claim 1, wherein:
the chemotherapeutic agent is selected from the group consisting of vincristine, vinblastine, vinorelbine, and vindesine;
the solid tumor is selected from the group consisting of neuroblastoma and neuroepithelioma; and
said administering is continued for a period of about 6 months.

### Claim 3 (depends on 2)

The method of claim 2, wherein the chemotherapeutic agent is vinblastine.

### Claim 4 (depends on 1)

The method of claim 1, wherein:
said administering is continued for a period of about 6 months.

### Claim 5 (depends on 4)

The method of claim 4, wherein the chemotherapeutic agent is vinblastine.