# US 11,439,683 B2 · Anti-angiogenic therapy of metastatic colorectal cancer

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- Number: US 11,439,683 B2
- Document ID: US11439683B2
- Status: Granted
- Kind: B2
- Application number: 16/690,459
- Filed: 2019-11-21
- Published: 2020-04-30
- Granted: 2022-09-13
- Earliest claimed: 2014-09-16
- Assignees: Regeneron Pharmaceuticals, Inc.
- Applicants: Regeneron Pharmaceuticals, Inc.
- Inventors: Tasha Nicholle Sims; Bo Gao; Israel Lowy
- Web page: https://patentgrep.com/patent/US11439683B2

## CPC

- A61K 38/179: {for growth factors; for growth regulators}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- G01N 33/57535: of the large intestine, e.g. colon, rectum or anus
- 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
- 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 present invention provides methods for treating metastatic cancer comprising identifying subjects who will respond favorably to anti-VEGF therapy. According to certain aspects of the invention, subjects are identified based on their expression level of one or more predictive biomarkers. Favorable response to anti-VEGF therapy is indicated by high expression levels of certain biomarkers or by low expression levels of certain biomarkers. An exemplary predictive biomarker is VEGF-A. Also disclosed herein are prognostic biomarkers useful for identifying cancer-bearing subjects who are expected to have better relative survival outcomes.

## Claims

### Claim 1

A method for treating metastatic colorectal cancer (mCRC) in a patient comprising administering a VEGF Trap that comprises Ig-like domain 2 of VEGFR1, Ig-like domain 3 of VEGFR2, and a multimerizing domain, to the patient,
wherein the patient has been identified as likely to respond favorably to VEGF Trap therapy by a method comprising obtaining a sample from the patient and measuring in the sample the level of VEGF-A; wherein an elevated level of expression of VEGF-A identifies the patient as a patient who is likely to respond favorably to VEGF Trap therapy, and
wherein the elevated expression of VEGF-A is determined based on a comparison to the lower level of VEGF-A in subjects with mCRC.

### Claim 2 (depends on 1)

The method of claim 1, wherein the sample is blood, serum or plasma.

### Claim 3 (depends on 1)

The method of claim 1, wherein the VEGF Trap is ziv-aflibercept.

### Claim 4 (depends on 3)

The method of claim 3, wherein the expression level of VEGF-A is measured using an ELISA.

### Claim 5 (depends on 3)

The method of claim 3 wherein the VEGF Trap therapy, further comprises:
administering to the subject a chemotherapeutic regimen comprising irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI).

### Claim 6 (depends on 1)

The method of claim 1 wherein an elevated plasma level of expression of VEGF-A is determined to be at or above 88 pg/mL prior to treatment.

### Claim 7 (depends on 6)

The method of claim 6, wherein the level of expression of VEGF-A is in a range of 88-1140 pg/mL.

### Claim 8 (depends on 6)

The method of claim 6, wherein the VEGF-A level of expression is 142 pg/mL or higher.