Amgen Inc.

Raymond A Koski

Scott Michael Silbiger

The present invention relates in general to metalloproteinase inhibitors and to polynucleotides encoding such inhibitors. In particular, the invention relates to novel mammalian inhibitors of metalloproteinase, which are designated as type three or TIMP-3, to fragments, derivatives, and analogs thereof, and to polynucleotides encoding the same. Novel methods of producing such compositions and novel methods of using such compositions are also provided.

Tissue inhibitor of metalloproteinase type three (TIMP-3) composition and methods

The present invention reveals a class of novel inhibitors of metalloproteinase. For convenience, these polypeptides are referred to as &ldquo;TIMP-3&rdquo;, as these polypeptides represent a new class of members of the tissue inhibitors of metalloproteinases. Also provided are DNA sequences coding for all or part of the TIMP-3s, vectors containing such DNA sequences, and host cells transformed or transfected with such vectors. In addition, methods of producing recombinant TIMP-3s, methods of treating disorders, pharmaceutical compositions including TIMP-3s and antibodies selectively binding TIMP-3s are provided.

Anti-p185 antibodies which are useful in the detection of HER-2/neu oncogene overexpression in biological samples are described. The antibodies are accurate and reliable in immunocytochemical or immunohistochemical assays of cell and tissue samples. Also described are methods for detecting HER-2/neu oncogene expression in a biological sample using the antibodies of the invention and a diagnostic kit comprising the antibodies. The reagents provide an accurate means of identifying certain cancer patients who have the greatest probability of relapse and/or the least likelihood of survival.

Methods and compositions for determining HER-2/neu expression

Anti-p185.sup.HER-2/neu antibodies which are useful in the detection of HER-2/neu oncogene overexpression in biological samples are described. The antibodies are accurate and reliable in immunocytochemical or immunohistochemical assays of cell and tissue samples. Also described are methods for detecting HER-2/neu oncogene expression in a biological sample using the antibodies of the invention and a diagnostic kit comprising the antibodies. The reagents provide an accurate means of identifying certain cancer patients who have the greatest probability of relapse and/or the least likelihood of survival.

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Raymond A Koski