Antibodies specific for heregulin 2-.alpha.
AssigneeGenentech, Inc.
InventorsRichard L. Vandlen, William E. Holmes
Life of this patent
Estimating the term…
Abstract
Novel polypeptides with binding affinity for the p185.sup.HER2 receptor, designated heregulin 2-.alpha. and heregulin 2-.beta., have been identified and purified from human tissue. The cDNA encoding the novel heregulin 2-.alpha. has been isolated from human tissue and sequenced. Provided herein is nucleic acid sequence of the heregulin 2-.alpha. useful in the production of heregulin 2-.alpha. by recombinant means. Further provided an amino acid sequence of heregulin 2-.alpha. and heregulin 2-.beta.. Heregulins and their antibodies are useful as therapeutic agents and in diagnostic methods.
Claims27
An isolated antibody that specifically binds to human heregulin 2-.alpha., said heregulin 2-.alpha. comprising:
- (a) a polypeptide having the amino acid sequence of mature heregulin 2-.alpha. in SEQ ID NO:11 or (b) a polypeptide encoded by nucleic acid which hybridizes under high stringency conditions with the complement of the nucleic acid of SEQ ID NO:10, wherein the polypeptide is able to stimulate tyrosine phosphorylation of p185.sup.HER2 in MDA-MB-453 cells.
An isolated antibody which binds heregulin 2-.alpha., said heregulin 2-.alpha. comprising an amino acid sequence in SEQ ID NO:11 or a naturally occurring variant thereof which is encoded by nucleic acid which hybridizes under high stringency conditions with the complement of the nucleic acid of SEQ ID NO:10, wherein the antibody prevents heregulin 2-.alpha. from activating p185.sup.HER2.
An isolated antibody which binds an epitope in the growth factor domain (GFD) of heregulin 2-.alpha., said heregulin 2-.alpha. comprising an amino acid sequence in SEQ ID NO:11.
An isolated antibody which binds mature heregulin 2-.alpha., said heregulin 2-.alpha. comprising an amino sequence as in SEQ ID NO:11 or an alternative splice variant thereof which is encoded by nucleic acid which hybridizes under high stringency conditions with the complement of the nucleic acid of SEQ ID NO:10.
An isolated antibody which binds mature heregulin 2-.alpha., said heregulin 2-.alpha. comprising an amino acid sequence as in SEQ ID NO:11 or a naturally occurring variant thereof which is encoded by nucleic acid which hybridizes under high stringency conditions with the complement of the nucleic acid of SEQ ID NO:10, wherein the antibody antagonizes growth stimulation of SKBR3 or MCF7 cells by heregulin 2-.alpha..
An isolated antibody which binds to a polypeptide, said polypeptide comprising the amino acid sequence -Ala-Glu-Lys-Glu-Lys-Thr-Phe-Cys-Val-Asn-Gly-Gly-Glu-Cys-Phe-Met-Val-Lys-A sp-Leu-Ser-Asn-Pro- (SEQ ID NO:18), wherein said polypeptide is able to stimulate tyrosine phosphorylation of p185.sup.HER2 in MDA-MB-453 cells.
Dependencies are inferred from the claim text.