Anti-HER2 antibodies and immunoconjugates
The invention provides anti-HER2 antibodies and immunoconjugates and methods of using the same.
1. A method of detecting human HER2 in a biological sample comprising contacting the biological sample with an anti-HER2 antibody under conditions permissive for binding of the anti-HER2 antibody to a naturally occurring human HER2, and detecting whether a complex is formed between the anti-HER2 antibody and a naturally occurring human HER2 in the biological sample, wherein the anti-HER2 antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:15; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:16; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:17; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:12; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:13; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:14.
2. A method for detecting a HER2-positive cancer comprising (i) administering a labeled anti-HER2 antibody to a subject having or suspected of having a HER2-positive cancer, wherein the labeled anti-HER2 antibody comprises a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:15; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:16; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:17; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:12; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:13; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:14 and (ii) detecting the labeled anti-HER2 antibody in the subject, wherein detection of the labeled anti-HER2 antibody indicates a HER2-positive cancer in the subject.
3. The method of claim 1 , wherein the anti-HER2 antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 11.
4. The method of claim 1 , wherein the anti-HER2 antibody comprises a light chain variable region comprising the sequence of SEQ ID NO: 10.
5. The method of claim 1 , wherein the anti-HER2 antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 11 and a light chain variable region comprising the sequence of SEQ ID NO: 10.
6. The method of claim 1 , wherein the anti-HER2 antibody is an IgG1, IgG2a or IgG2b antibody.
7. The method of claim 1 , wherein the anti-HER2 antibody comprises a κ light chain.
8. The method of claim 7 , wherein the antibody is an IgG1, IgG2a or IgG2b antibody.
9. The method of claim 1 , wherein the anti-HER2 antibody comprises a heavy chain comprising at least one mutation in the heavy chain constant region selected from A118C and S400C.
10. The method of claim 1 , wherein the anti-HER2 antibody comprises a light chain comprising at least one mutation in the light chain constant region selected from K149C and V205C.
11. The method of claim 1 , wherein the anti-HER2 antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 19 or SEQ ID NO: 24.
12. The method of claim 1 , wherein the anti-HER2 antibody comprises a light chain comprising the sequence of SEQ ID NO: 18 or SEQ ID NO: 23.
13. The method of claim 1 , wherein the anti-HER2 antibody comprises:
a) a heavy chain comprising the sequence of SEQ ID NO: 19 and a light chain comprising the sequence of SEQ ID NO: 18; or
b) a heavy chain comprising the sequence of SEQ ID NO: 19 and a light chain comprising the sequence of SEQ ID NO: 23; or
c) a heavy chain comprising the sequence of SEQ ID NO: 24 and a light chain comprising the sequence of SEQ ID NO: 18.
14. The method of claim 2 , wherein the anti-HER2 antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 11.
15. The method of claim 2 , wherein the anti-HER2 antibody comprises a light chain variable region comprising the sequence of SEQ ID NO: 10.
16. The method of claim 2 , wherein the anti-HER2 antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 11 and a light chain variable region comprising the sequence of SEQ ID NO: 10.
17. The method of claim 2 , wherein the anti-HER2 antibody is an IgG1, IgG2a or IgG2b antibody.
18. The method of claim 2 , wherein the anti-HER2 antibody comprises a κ light chain.
19. The method of claim 18 , wherein the antibody is an IgG1, IgG2a or IgG2b antibody.
20. The method of claim 2 , wherein the anti-HER2 antibody comprises a heavy chain comprising at least one mutation in the heavy chain constant region selected from A118C and S400C.
21. The method of claim 2 , wherein the anti-HER2 antibody comprises a light chain comprising at least one mutation in the light chain constant region selected from K149C and V205C.
22. The method of claim 2 , wherein the anti-HER2 antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 19 or SEQ ID NO: 24.
23. The method of claim 2 , wherein the anti-HER2 antibody comprises a light chain comprising the sequence of SEQ ID NO: 18 or SEQ ID NO: 23.
24. The method of claim 2 , wherein the anti-HER2 antibody comprises:
a) a heavy chain comprising the sequence of SEQ ID NO: 19 and a light chain comprising the sequence of SEQ ID NO: 18; or
b) a heavy chain comprising the sequence of SEQ ID NO: 19 and a light chain comprising the sequence of SEQ ID NO: 23; or
c) a heavy chain comprising the sequence of SEQ ID NO: 24 and a light chain comprising the sequence of SEQ ID NO: 18.
25. The method of claim 2 , wherein the labeled anti-HER2 antibody comprises an anti-HER2 antibody conjugated to a positron emitter.
26. The method of claim 25 , wherein the positron emitter is 89 Zr.