Berlex Laboratories, Inc.

Schering Aktiengesellschaft

Triton Biosciences Inc.

Bayer Schering Pharma Ag

John J Monahan

Susan G Stuart

Ronald P Mischak

Elaina Mann

Laura K Shawver

John W Brandis

David J Larocca

Miriam E Hancock

Terence K Brunck

Miriam E C Hancock

Beatrice Claudia Langton

Miriam Ec Hancock

Peter Bluford

Lorrine A Chao

Disclosed are methods and compositions for identifying malignant tumors that overexpress the c-erbB-2 oncogene. Assays useful for diagnosis and prognosis of neoplastic disease are provided which detect the external domain of c-erbB-2, the glycoprotein gp75 and quantitate the level of gp75 in the biological fluids of mammals carrying a tumor burden. Further disclosed are recombinant, synthetically and otherwise biologically produced novel proteins and polypeptides which are encoded by the external domain DNA sequence of the c-erbB-2 oncogene (the gp75 gene) or fragments thereof. Such gp75 proteins and polypeptides are useful as vaccines, therapeutically in the treatment of cancer either alone or in combination with chemotherapeutic agents. Also disclosed are antibodies to such gp75 proteins and polypeptides which are useful diagnostically and therapeutically. Still further disclosed are test kits embodying the assays of this invention.

C-erbB-2 external domain: GP75

This invention is directed toward novel synergistic combinations of ligand-mimicking agents specific to the c-erbB-2 protein and anti-neoplastic drugs or agents, which can be used to treat a mammalian host, usually a human, suspected of having cancer or tumor cells by administering the combination in a therapeutically- or synergistically-effective amount. The drug combinations cytotoxic to tumor cells comprise an anti-neoplastic agent and a molecule, that is not conjugated to the anti-neoplastic agent, that binds the tumor cells and induces an increase in the phosphorylation of c-erbB-2 protein when placed in contact with the tumor cells. Alternatively, the drug combination cytotoxic to tumor cells may comprise an anti-neoplastic agent and a molecule, that is not conjugated to the anti-neoplastic agent, that binds the tumor cells and causes down modulation or internalization of c-erbB-2 protein. The anti-neoplastic drug is preferably an alkylating agent, most preferably cisplatin. This combination is particularly effective for inhibiting the growth of breast and ovarian tumor cells. Methods for killing target tumor cells are contemplated by contacting the target cells with the novel drug combinations, methods for treating mammals by administering therapeutic amounts of the drug combinations are also contemplated.

Use of ligand-mimicking agents and anti-neoplastic drugs in cancer therapy

Anti-neoplastic drugs in cancer therapy

The mRNA coded by the 'anti-sense' strand of the complementary DNA produced by HTLV-I infection contains significant open reading frames. Cells infected by HTLV-I virus produce mRNA that is anti-sense to the viral RNA genome. Infected cells may produce proteins from the newly discovered mRNA. The production of the anti-sense in mRNA initiates from a newly discovered transcriptional promoter located within 1.8 kb from the 3' terminus of the viral genome. The mRNA, protein, and antibodies directed thereto can be used in the prevention, diagnosis, and treatment of HTLV-I infections.

HTLV-I anti-sense RNA and encoded proteins

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Orinda, CA, United States of America

John J Monahan