HER-3 antibodies and methods of use
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.
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.
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.
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.
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.
27. The method of claim 3 , wherein the method comprises measuring and/or quantifying the presence and/or amount of Her-3 homodimers.
28. The method of claim 15 , 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.
30. The method of claim 15 , 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.
32. The method of claim 15 , 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.
34. The method of claim 17 , further comprising activating the cleaving agent to cleave the cleavable linkage.