# US 2014/0193397 A1 · Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy

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- Number: US 2014/0193397 A1
- Document ID: US20140193397A1
- Status: Published application
- Kind: A1
- Application number: 13/802,333
- Filed: 2013-03-13
- Published: 2014-07-10
- Earliest claimed: 2010-07-19
- Assignees: Genentech, Inc.; Hoffmann-La Roche Inc.
- Inventors: Herbert Andres; Sanne Lysbet De Haas; Rebecca Elliott; Johann Karl; Yu-Ju Gloria Meng; Gregory D. Plowman; Stefan Scherer; Norbert Wild
- Web page: https://patentgrep.com/patent/US20140193397A1

## CPC

- C07K 16/22: against growth factors {; against growth regulators}
- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/70: Carbohydrates; Sugars; Derivatives thereof (sorbitol A61K31/047)
- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K 33/00: Medicinal preparations containing inorganic active ingredients
- A61K 33/24: Heavy metals; Compounds thereof
- A61K 33/243: Platinum; Compounds thereof
- A61K 38/43: Enzymes; Proenzymes; Derivatives thereof
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/12: of the kidneys
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- G01N 33/57555: of the prostate
- G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells}
- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 33/74: involving hormones {or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors}
- G01N 2333/475: Assays involving growth factors
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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)
- 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
- 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)

## Abstract

The invention provides methods for identifying patient who may benefit from treatment with an anti-cancer therapy comprising a VEGF antagonist. The invention also provides methods for monitoring a patients' response to the anti-cancer therapy. The invention also provides kits and articles of manufacture for use in the methods.

## Claims

### Claim 1

A method of identifying a patient who may benefit from treatment with an anti-cancer therapy comprising a VEGF antagonist, the method comprising:
determining an expression level of VEGF121 in a sample obtained from the patient, wherein a level of VEGF121 in the sample obtained from the patient at or above a reference level indicates that the patient may benefit from treatment with the anti-cancer therapy, and;
informing the identified patient that they may benefit from anti-cancer therapy comprising a VEGF antagonist.

### Claim 2

A method of predicting responsiveness of a patient suffering from cancer to treatment with an anti-cancer therapy comprising a VEGF-A antagonist, the method comprising:
determining an expression level of VEGF121 in a sample obtained from the patient, wherein a level of VEGF121 in the sample obtained from the patient at or above a reference level indicates that the patient is more likely to be responsive to treatment with the anti-cancer therapy, and;
informing the patient that they have an increased likelihood of being responsive to anti-cancer therapy comprising a VEGF-A antagonist.

### Claim 3

A method for determining the likelihood that a patient with cancer will exhibit benefit from anti-cancer therapy comprising a VEGF-A antagonist, the method comprising:
determining an expression level of VEGF121 in a sample obtained from the patient, wherein a level of VEGF121 in the sample obtained from the patient at or above a reference level indicates that the patient has increased likelihood of benefit from the anti-cancer therapy, and;
informing the patient that they have an increased likelihood of exhibiting benefit from anti-cancer therapy comprising a VEGF-A antagonist.

### Claim 4

A method for optimizing the therapeutic efficacy of an anti-cancer therapy comprising a VEGF-A antagonist, the method comprising:
determining an expression level of VEGF121 in a sample obtained from the patient, wherein a level of VEGF121 in the sample obtained from the patient at or above a reference level indicates that the patient has increased likelihood of benefit from the anti-cancer therapy, and;
providing a recommendation to the patient that they receive an anti-cancer therapy comprising a VEGF-A antagonist.

### Claim 5

A method for treating cancer in a patient, the method comprising
determining that a sample obtained from the patient has a level of VEGF121 at or above the level of VEGF121 in a reference sample and
administering an effective amount of an anti-cancer therapy comprising a VEGF-A antagonist to said patient, whereby the cancer is treated.

### Claim 6 (depends on 1, 2, 3, 4, 5)

The method of any one of claims 1 to 5, wherein the cancer is selected from the group consisting of: colorectal cancer, glioblastoma, renal cancer, ovarian cancer, breast cancer, pancreatic cancer, gastric cancer, and lung cancer.

### Claim 7 (depends on 1, 2, 3, 4, 5)

The method of any one of claims 1 to 5, wherein the sample obtained from the patient is a member selected from the group consisting of: whole blood, plasma, serum, and combinations thereof.

### Claim 8 (depends on 1, 2, 3, 4, 5)

The method of any one of claims 1 to 5, wherein the level of VEGF121 is a protein level.

### Claim 9 (depends on 8)

The method of claim 8, wherein the protein level is determined by measuring plasma protein level.

### Claim 10 (depends on 9)

The method of claim 9, wherein a plasma level of unmodified VEGF in the sample obtained from the patient that is at or above the level of VEGF121 in a reference sample, indicates that the patient may benefit from the anti-cancer therapy, is more likely to be responsive to the anti-cancer therapy, or has increased likelihood of benefit from the anti-cancer therapy.

### Claim 11 (depends on 1, 2, 3, 4)

The method of any one of claims 1 to 4, further comprising administering an effective amount of an anti-cancer therapy comprising a VEGF-A antagonist to said patient.

### Claim 12 (depends on 11)

The method of claim 11, wherein the VEGF-A antagonist is an antibody.

### Claim 13 (depends on 12)

The method of claim 12, wherein the antibody is bevacizumab.

### Claim 14 (depends on 11)

The method of claim 11, further comprising administering an effective amount of a second anti-cancer therapy selected from the group consisting of: a cytotoxic agent, a chemotherapeutic agent, a growth inhibitory agent, and anti-angiogenic agents, and combinations thereof.

### Claim 15 (depends on 14)

The method of claim 14, wherein the second anti-cancer therapy and the VEGF-A antagonist are administered concurrently.

### Claim 16 (depends on 14)

The method of claim 14, wherein the second anti-cancer therapy and the VEGF-A antagonist are administered sequentially.

### Claim 17 (depends on 14)

The method of claim 14, further comprising administering an effective amount of a third anti-cancer therapy selected from the group consisting of: a cytotoxic agent, a chemotherapeutic agent, a growth inhibitory agent, and anti-angiogenic agents, and combinations thereof.

### Claim 18 (depends on 17)

The method of claim 17, wherein the third anti-cancer therapy, the second anti-cancer therapy and the VEGF-A antagonist are administered concurrently.

### Claim 19 (depends on 17)

The method of claim 17, wherein the third anti-cancer therapy, the second anti-cancer therapy and the VEGF-A antagonist are administered sequentially.

### Claim 20 (depends on 5)

The method of claim 5, wherein the VEGF-A antagonist is an antibody.

### Claim 21 (depends on 20)

The method of claim 20, wherein the antibody is bevacizumab.

### Claim 22 (depends on 5)

The method of claim 5, wherein the anti-cancer therapy further comprises administering an effective amount of a second anti-cancer therapy selected from the group consisting of: a cytotoxic agent, a chemotherapeutic agent, a growth inhibitory agent, and anti-angiogenic agents, and combinations thereof.

### Claim 23 (depends on 19)

The method of claim 19, wherein the second anti-cancer therapy and the VEGF-A antagonist are administered concurrently.

### Claim 24 (depends on 19)

The method of claim 19, wherein the second anti-cancer therapy and the VEGF-A antagonist are administered sequentially.

### Claim 25 (depends on 19)

The method of claim 19, wherein the anti-cancer therapy further comprises administering an effective amount of a third anti-cancer therapy selected from the group consisting of: a cytotoxic agent, a chemotherapeutic agent, a growth inhibitory agent, and anti-angiogenic agents, and combinations thereof.

### Claim 26 (depends on 25)

The method of claim 25, wherein the third anti-cancer therapy, the second anti-cancer therapy and the VEGF-A antagonist are administered concurrently.

### Claim 27 (depends on 25)

The method of claim 25, wherein the third anti-cancer therapy, the second anti-cancer therapy and the VEGF-A antagonist are administered sequentially.

### Claim 28

A kit for determining whether a patient may benefit from treatment with an anti-cancer therapy comprising a VEGF-A antagonist, the kit comprising
a set of compounds capable of specifically binding to VEGF121 and
instructions for using said compounds to determine the level of VEGF121 to predict responsiveness of a patient to treatment with an anti-cancer therapy comprising a VEGF-A antagonist, wherein a level of VEGF121 at or above the level of VEGF121 in a reference sample indicates that the patient may benefit from treatment with an anti-cancer therapy comprising a VEGF-A antagonist.

### Claim 29 (depends on 28)

The kit of claim 28, wherein the compounds are proteins.

### Claim 30 (depends on 29)

The kit of claim 29, wherein the proteins are antibodies.

### Claim 31

A set of compounds for detecting levels of VEGF121, the set comprising
at least one compound capable of specifically binding to VEGF121.

### Claim 32 (depends on 31)

The set of compounds of claim 31, wherein the compounds are proteins.

### Claim 33 (depends on 32)

The set of compounds of claim 32, wherein the proteins are antibodies.