Methods of determining patient response by measurement of HER-3 and P95

• US 9,766,242 B2
• Filed: 07/17/2015
• Issued: 09/19/2017
• Est. Priority Date: 01/15/2009
• Status: Active Grant

• Current Assignee: Laboratory Corporation Of America Holdings
• Original Assignee: Laboratory Corporation Of America Holdings
• Inventors: Bates, Michael, Cook, Jennifer W., Diedrich, Gundo, Goodman, Laurie, Mukherjee, Ali, Parry, Gordon, Sperinde, Jeff, Williams, Stephen J.
• Primary Examiner(s): Sang, Hong
• Application Number:
  US14/802,170
• Publication Number:
  US 20160061839A1
• Time in Patent Office: 795 Days
• Field of Search: None
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: G01N 2333/47 Assays involving proteins of known structure or function as defined in the subgroups
• CPC Class Codes: G01N 2333/71 for growth factors; for growth regulators
• CPC Class Codes: G01N 2800/00 Detection or diagnosis of diseases
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 2800/54 Determining the risk of relapse
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: G01N 33/57415 of breast

Abstract

The invention provides methods of measuring and/or quantifying the presence and/or amount of Her-3 and/or Her-3 in a complex and the presence and/or amount of p95 in a sample. The invention also provides antibodies specific for Her-3.

Claims

1. A method for quantifying Her-3 and p95 levels in a sample from a subject that has a cancer, comprising:

(a) obtaining a sample from the subject'"'"'s cancer;

(b) measuring the amount of Her-3 and p95 in the sample using a Her-3 antibody and a p95 antibody that specifically binds to a p95 protein having a first amino acid corresponding to methionine 611 of human Her-2 protein; and

(c) quantifying the amount of Her-3 and p95 in the subject'"'"'s sample,

wherein the Her 3 antibody is at least one of;

a monoclonal antibody comprising (a) a light chain variable region comprising CDR1, CDR2 and CDR3 having sequences as set forth in SEQ ID NOs;

13, 14 and 15, respectively, and (b) a heavy chain variable region comprising CDR1, CDR2 and CDR3 having sequences as set forth in SEQ ID NOs;

16, 17 and 18, respectively;

a monoclonal antibody comprising (a) a light chain variable region comprising CDR1, CDR2 and CDR3 having sequences as set forth in SEQ ID NOs;

19, 20 and 21, respectively, and (b) a heavy chain variable region comprising CDR1, CDR2 and CDR3 having sequences as set forth in SEQ ID NOs;

22, 23 and 24, respectively,

an antibody comprising amino acid sequences set forth in SEQ ID NOs;

9 and 11 for the light and heavy chains, respectively, or

an antibody comprising amino acid sequences set forth in SEQ ID NOs;

10 and 12 for the light and heavy chains, respectively.

2. The method of claim 1, further comprising determining whether the amount of Her-3 in the subject'"'"'s sample is above a Her-3 cutoff and whether the p95 in the subject'"'"'s sample is above a p95 cutoff.

3. The method of claim 1, wherein measuring the amount of Her-3 in the sample comprises the steps of:

a) contacting the sample with the Her-3 antibody, the Her-3 antibody having a molecular tag attached thereto via a cleavable linker;

b) contacting the sample with a cleaving agent;

c) cleaving the cleavable linker of the Her-3 antibody, thereby releasing the molecular tag; and

d) quantitating the released molecular tag to determine the amount of Her-3 protein in the sample.

4. The method of claim 1, wherein measuring the amount of Her-3 in the sample comprises the steps of:

a) contacting the sample with the Her-3 antibody;

b) contacting the Her-3 antibody with a tagged antibody, wherein the tagged antibody comprises a molecular tag attached thereto via a cleavable linker, and wherein the tagged antibody specifically binds to the Her-3 antibody;

c) cleaving the cleavable linker of the tagged antibody, thereby releasing the molecular tag; and

d) quantitating the released molecular tag to determine the amount of Her-3 protein in the sample.

5. The method of claim 1, wherein measuring the amount of p95 in the sample comprises the steps of:

a) contacting the sample with the p95 antibody;

b) contacting the p95 antibody with a tagged antibody, wherein the tagged antibody comprises a molecular tag attached thereto via a cleavable linker, and wherein the tagged antibody specifically binds to the p95 antibody;

c) cleaving the cleavable linker of the tagged antibody, thereby releasing the molecular tag; and

d) quantitating the released molecular tag to determine the amount of p95 protein in the sample.

6. The method of claim 1, wherein the subject'"'"'s cancer comprises breast cancer, colorectal cancer, ovarian cancer, non-small cell lung cancer or gastric cancer.

7. The method of claim 1, wherein the subject'"'"'s cancer comprises metastatic breast cancer.

8. The method of claim 1, wherein the subject'"'"'s cancer comprises early stage breast cancer.

9. The method of claim 1, wherein the subject'"'"'s cancer comprises a Her-2 positive cancer.

10. The method of claim 1, wherein measuring the amount of Her-3 in the subject'"'"'s sample comprises measuring at least one of total Her-3 protein, Her-3 homodimers or Her-3/Her-2 heterodimers.

11. The method of claim 1, further comprising measuring and quantifying the amount of Her-2 in the subject'"'"'s sample.

12. The method of claim 11, wherein the amount of Her-2 is measured and quantified using a fluorescence-based immunoassay.

13. The method of claim 12, wherein measuring the amount of Her-2 in the sample comprises the steps of:

a) contacting the sample with a Her-2 antibody, the Her-2 antibody having a molecular tag attached thereto via a cleavable linker;

b) contacting the sample with a cleaving agent;

c) cleaving the cleavable linker of the Her-2 antibody, thereby releasing the molecular tag; and

d) quantitating the released molecular tag to determine the amount of Her-2 protein in the sample.

14. The method of claim 11, further comprising determining whether the amount of Her-2 in the subject'"'"'s sample is above a Her-2 cutoff.