Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2007-05-29
2007-05-29
Huff, Sheela J. (Department: 1643)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C530S350000, C530S300000, C530S324000
Reexamination Certificate
active
10296733
ABSTRACT:
Thrombospondin-1 (TSP-1) is a potent inhibitor of tumor growth and angiogenesis. To elucidate the molecular mechanisms that are involved in the inhibition of tumor growth by the type 1 repeats (TSRs), recombinant versions of these motifs have been produced and have been assayed for their ability to inhibit the growth of experimental B16F10 and Lewis lung carcinomas. Recombinant proteins that contain all three TSRs (3TSR) or the second TSR with (TSR2+RFK) or without (TSR2) the transforming growth factor beta (TGFβ) activating sequence (RFK) have been expressed inDrosophilaS2 cells. A recombinant protein containing all three type 1 repeats of TSP-2 and a recombinant protein containing the second TSR with the RFK sequence altered to QFK have also been produced. The data indicate that the TSRs inhibit tumor growth by inhibition of angiogenesis and regulation of tumor cell growth and apoptosis. The regulation of tumor cell growth and apoptosis is RFK-dependent while the inhibition of angiogenesis is not. The invention relates to polypeptides based on the amino acid sequence of human TSP-1 type 1 repeats. The polypeptides, variants, fragments and mutants thereof can be made by recombinant methods or can be made by chemical synthesis. The polypeptides can be formulated into pharmaceutical compositions and used in methods of therapy to reduce tumor growth.
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Beth Israel Deaconess Medical Center Inc.
Hamilton Brook Smith & Reynolds P.C.
Huff Sheela J.
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