HER-3 antibodies and methods of use

• US 9,110,066 B2
• Filed: 11/07/2012
• Issued: 08/18/2015
• 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:
  US13/670,508
• Publication Number:
  US 20130071859A1
• Time in Patent Office: 1,014 Days
• Field of Search: None
• US Class Current: 1/1
• 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 in a sample. The invention also provides antibodies specific for Her-3.

Claims

1. A monoclonal Her-3 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, or a monoclonal Her-3 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.

3. A method of measuring and/or quantifying the presence and/or amount of Her-3 or Her-3 in a complex in a sample from a subject, the method comprising providing a sample and determining the presence and/or quantity of Her-3 and/or Her-3 in a complex in the sample using the monoclonal Her-3 antibody of claim 1, and wherein the method comprises mixing contacting the sample with the monoclonal Her-3 antibody and determining the presence and/or quantity of the monoclonal Her-3 antibody bound to Her-3 and/or Her-3 in a complex.

4. The method of claim 3, wherein the method comprises measuring and/or quantifying the presence and/or amount of total Her-3.

5. The method of claim 3, wherein the method comprises the steps of:

(a) contacting the sample with (i) a first Her-3 antibody having a cleaving agent with an effective proximity and (ii) a second Her-3 antibody having one or more molecular tags attached thereto via a cleavable linkage, wherein binding of the first Her-3 antibody and the second Her-3 antibody within the effective proximity cleaves the cleavable linkage and releases the molecular tags; and

(b) detecting the released molecular tags to determine the presence and/or quantity of Her-3 and/or Her-3 in a complex,

wherein at least one of the first Her-3 antibody and the second Her-3 antibody is the monoclonal Her-3 antibody of claim 1.

6. The method of claim 3, wherein the method comprises the steps of:

(a) contacting the sample with the monoclonal Her-3 antibody of claim 1, wherein the monoclonal Her-3 antibody has one or more molecular tags attached thereto via a cleavable linkage;

(b) contacting the sample with a cleaving agent;

(c) cleaving the cleavable linkage thereby releasing the one or more molecular tags; and

(d) quantitating the released molecular tags to determine the presence and/or amount of Her-3 in the sample.

7. The method of claim 6, wherein the cleaving agent is capable of cleaving the cleavable linkage upon contacting the sample.

8. The method of claim 3, wherein the method comprises measuring and/or quantifying the presence and/or amount of Her-3 by immunohistochemistry.

9. The method of claim 3, wherein the sample is a formalin-fixed, paraffin-embedded (FFPE) sample or a solubilized FFPE sample.

10. The method of claim 3, wherein the sample is a tumor sample.

11. The method of claim 3, wherein the sample is a breast cancer sample, a colorectal cancer sample, an ovarian cancer sample, a non-small cell lung cancer sample, or a gastric cancer sample.

12. The method of claim 3, wherein the sample is a breast cancer sample.

13. The method of claim 3, wherein the sample is an early stage breast cancer sample or a metastatic breast cancer sample.

14. The method of claim 3, wherein the sample is a Her-2 positive breast cancer sample.

27. The method of claim 3, wherein the method comprises measuring and/or quantifying the presence and/or amount of Her-3 homodimers.

29. The method of claim 3, wherein the method comprises measuring and/or quantifying the presence and/or amount of Her-3 heterodimers.

31. The method of claim 3, wherein the sample is fresh or frozen tissue.

33. The method of claim 5, further comprising activating the cleaving agent to cleave the cleavable linkage.

2. A monoclonal Her-3 antibody comprising the amino acid sequences set forth in SEQ ID NOs:

9 and 11 for the light and heavy chains, respectively, or a monoclonal Her-3 antibody comprising the amino acid sequences set forth in SEQ ID NOs;

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

15. A method of measuring and/or quantifying the presence and/or amount of Her-3 or Her-3 in a complex in a sample from a subject, the method comprising providing a sample and determining the presence and/or quantity of Her-3 and/or Her-3 in a complex in the sample using the monoclonal Her-3 antibody of claim 2, and wherein the method comprises contacting the sample with the monoclonal Her-3 antibody and determining the presence and/or quantity of the monoclonal Her-3 antibody bound to Her-3 and/or Her-3 in a complex.

16. The method of claim 15, wherein the method comprises measuring and/or quantifying the presence and/or amount of total Her 3.

17. The method of claim 15, wherein the method comprises the steps of:

(a) contacting the sample with (i) a first Her-3 antibody having a cleaving agent with an effective proximity and (ii) a second Her-3 antibody having one or more molecular tags attached thereto via a cleavable linkage, wherein binding of the first Her-3 antibody and the second Her-3 antibody within the effective proximity cleaves the cleavable linkage and releases the molecular tags; and

(b) detecting the released molecular tags to determine the presence and/or quantity of Her-3 and/or Her-3 in a complex,

wherein at least one of the first Her-3 antibody and the second Her-3 antibody is the monoclonal Her-3 antibody of claim 2.

18. The method of claim 15, wherein the method comprises the steps of:

(a) contacting the sample with the monoclonal Her-3 antibody of claim 2, wherein the monoclonal Her-3 antibody has one or more molecular tags attached thereto via a cleavable linkage;

(b) contacting the sample with a cleaving agent;

(c) cleaving the cleavable linkage thereby releasing the one or more molecular tags; and

(d) quantitating the released molecular tags to determine the presence and/or amount of Her-3 in the sample.

19. The method of claim 18, wherein the cleaving agent is capable of cleaving the cleavable linkage upon contacting the sample.

20. The method of claim 15, wherein the method comprises measuring and/or quantifying the presence and/or amount of Her-3 by immunohistochemistry.

21. The method of claim 15, wherein the sample is a formalin-fixed, paraffin-embedded (FFPE) sample or a solubilized FFPE sample.

22. The method of claim 15, wherein the sample is a tumor sample.

23. The method of claim 15, wherein the sample is a breast cancer sample, a colorectal cancer sample, an ovarian cancer sample, a non-small cell lung cancer sample, or a gastric cancer sample.

24. The method of claim 15, wherein the sample is a breast cancer sample.

25. The method of claim 15, wherein the sample is an early stage breast cancer sample or a metastatic breast cancer sample.

26. The method of claim 15, wherein the sample is a Her-2 positive breast cancer sample.

28. The method of claim 15, wherein the method comprises measuring and/or quantifying the presence and/or amount of Her-3 homodimers.

30. The method of claim 15, wherein the method comprises measuring and/or quantifying the presence and/or amount of Her-3 heterodimers.

32. The method of claim 15, wherein the sample is fresh or frozen tissue.

34. The method of claim 17, further comprising activating the cleaving agent to cleave the cleavable linkage.