Modified PF4 compositions and methods of use
AssigneeRepligen Corporation
InventorTheodore Maione
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Abstract
The subject invention pertains to the use of modified PF4 and recombinant PF4(rPF4) as well as modified analogs (mutants) of PF4, and peptide fragments thereof, to inhibit angiogenesis. The modified PF4, analogs, and certain fragments are shown to have utility for treating angiogenic diseases and for the inhibition of endothelial cell proliferation. Also, the subject invention concerns modification of PF4 which facilitate the targeting of the biological activity of PF4 to specific locations.
Claims18
A substantially pure polypeptide conjugate free of other platelet proteins comprising:
- (a) a mutant polypeptide of native PF4, comprising the sequence Gln-Glu-Ile-Ile-Gln-Glu-Leu-Leu-Glu-Ser wherein said mutant polypeptide has angiogenic inhibitory activity;
- and
- (b) an entity which is conjugated to said mutant polypeptide,
- wherein said conjugate retains angiogenic inhibitory activity.
A pharmaceutical composition for the treatment of angiogenic diseases, said composition comprising a substantially pure polypeptide conjugate free of other platelet proteins, wherein said polypeptide conjugate comprises:
- (a) a mutant polypeptide of native PF4, comprising the sequence Gln-Glu-Ile-Ile-Gln-Glu-Leu-Leu-Glu-Ser, wherein said mutant polypeptide has angiogenic inhibitory activity;
- and
- (b) an entity which is conjugated to said mutant polypeptide,
- wherein said conjugate retains angiogenic inhibitory activity.
A method for delivering angiogenic inhibitory activity to cells in need of treatment, said method comprising the administration of a composition comprising a substantially pure polypeptide conjugate free of other platelet proteins comprising:
- (a) a mutant polypeptide of native PF4, comprising the sequence Gln-Glu-Ile-Ile-Gln-Glu-Leu-Leu-Glu-Ser, wherein said mutant polypeptide has angiogenic inhibitory activity;
- and
- (b) an entity which is conjugated to said mutant polypeptide,
- wherein said conjugate retains angiogenic inhibitory activity, and wherein said conjugated entity is a monoclonal antibody, polyclonal antibody, or antigenic determinant which specifically interacts with said cells in need of treatment.
A substantially pure polypeptide conjugate free of other platelet proteins comprising
- (a) a mutant polypeptide of native PF4 selected from the group consisting of PF4-241, C-13-241, and C-41-241;
- and
- (b) an entity which is conjugated to said mutant polypeptide, wherein said conjugated entity is selected from the group consisting of monoclonal antibodies, polyclonal antibodies, fluorescein-isothiocyanate, fluorophores, toxins, cell receptor molecules, non-proteinaceous biological effector molecules, chelators, and carrier proteins.
Dependencies are inferred from the claim text.