Antibodies immunoreactive with heregulin-coupled HER3
Recombinant materials and methods for producing antibodies that specifically bind heregulin-coupled HER3, at a site distinct from the heregulin binding site, are described. These antibodies are particularly useful in treating cancer that expresses HER3.
1. A recombinant expression system which comprises one or more nucleotide sequences that encode 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 one or more nucleotide sequences operably linked to control sequences for expression;
wherein the encoded monoclonal antibody or fragment comprises a heavy chain that comprises CDR1:GYTFTDYVIS (SEQ ID NO:4), CDR2:IYPGSGRY (SEQ ID NO:5) and CDR3:TRSLQRLRYFDV (SEQ ID NO:6); and
comprises a light chain that comprises CDR1:RASQSISDYLH (SEQ ID NO:10), CDR2:YGSQSIS (SEQ ID NO:11) and CDR3:QQSNSWPLT (SEQ ID NO:12).
2. Recombinant host cells that contain the expression system of claim 1 .
3. A method to produce monoclonal antibodies including fragments thereof which bind to HER3 but which bind to HER3:heregulin complex with greater affinity as compared to binding uncomplexed HER3
which method comprises culturing the cells of claim 2 and recovering said antibodies.
4. The recombinant expression system of claim 1 wherein the encoded monoclonal antibody or fragment comprises a heavy chain that comprises SEQ ID NO:2; and
a light chain that comprises SEQ ID NO:8.
5. Recombinant host cells that contain the expression system of claim 4 .
6. A method to produce monoclonal antibodies including fragments thereof which bind to HER3 but which bind to HER3:heregulin complex with greater affinity as compared to binding uncomplexed HER3
which method comprises culturing the cells of claim 5 and recovering said antibodies.