Antibodies immunoreactive with heregulin-coupled HER3
Antibodies which specifically bind heregulin-coupled HER3, at a site distinct from the heregulin binding site, are described. These antibodies are particularly useful in treating cancer.
1. A method to treat HER3-expressing cancer in a subject which method comprises administering to a subject in need of such treatment an effective amount of antibodies or fragments which bind to HER3 not complexed to heregulin, and which bind to HER3:heregulin complex with greater affinity as compared to binding uncomplexed HER3.
2. The method of claim 1 wherein the antibodies or fragments contain a heavy chain that comprises CDR1:GYTFTDYVIS (SEQ ID NO:4), CDR2:IYPGSGRY (SEQ ID NO:5) and CDR3:TRSLQRLRYFDV (SEQ ID NO:6).
3. The method of claim 2 wherein the antibodies or fragments further contain a light chain that comprises CDR1:RASQSISDYLH (SEQ ID NO:10), CDR2:YGSQSIS (SEQ ID NO:11) and CDR3:QQSNSWPLT (SEQ ID NO:12).
4. The method of claim 1 wherein the subject is human and said antibodies or fragments are human or humanized.
5. The method of claim 2 wherein the subject is human and said antibodies or fragments are human or humanized.
6. The method of claim 3 wherein the subject is human and said antibodies or fragments are human or humanized.
7. A method to treat HER3-expressing cancer in a subject which method comprises administering to a subject in need of such treatment an effective amount of a conjugate of a monoclonal antibody or fragment thereof which binds to HER3 not complexed to heregulin, and binds to HER3:heregulin complex with greater affinity as compared to binding uncomplexed HER3, said antibody or fragment coupled to a cytotoxic or chemotherapeutic agent.
8. The method of claim 7 wherein the antibody or fragment contains a heavy chain that comprises CDR1:GYTFTDYVIS (SEQ ID NO:4), CDR2:IYPGSGRY (SEQ ID NO:5) and CDR3:TRSLQRLRYFDV (SEQ ID NO:6).
9. The method of claim 8 wherein the antibody or fragment further contains a light chain that comprises CDR1:RASQSISDYLH (SEQ ID NO:10), CDR2:YGSQSIS (SEQ ID NO:11) and CDR3:QQSNSWPLT (SEQ ID NO:12).
10. The method of claim 7 wherein the subject is human and said antibody or fragment is human or humanized.
11. The method of claim 8 wherein the subject is human and said antibody or fragment is human or humanized.
12. The method of claim 9 wherein the subject is human and said antibody or fragment is human or humanized.