Elastin-based compositions
AssigneeUniversity of Utah Research Foundation
InventorsMark T. Keating, Dean Y. Li
Life of this patent
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Abstract
The present invention provides screening methods that use organisms or cells that lack function in one or both elastin genes. These methods are useful in identifying drugs for the prevention and treatment of obstructive vascular diseases, such as atherosclerosis, vascular restenosis and transplant arteriopathy. Further, the invention provides pharmaceutical compositions containing elastin-based compositions that are particularly potent regulators of proliferation, differentiation, and migration of smooth muscle cells in vitro and in vivo. These pharmaceutical compositions and related methods are useful in the prevention and treatment of disorders characterized by diminished capacity to regulate smooth muscle cell function.
Claims35
A pharmaceutical composition that provides an elastin-based composition for localized delivery in vivo, said elastin-based composition consisting of a polypeptide, wherein said polypeptide consists of (i) an amino acid sequence at least 95% identical to SEQ ID NO:
- 3, (ii) an amino acid sequence represented by SEQ ID NO:
- 2, or (iii) a peptide fragment of six repeats of the hexameric sequence represented by SEQ ID NO:
- 1, wherein said elastin-based composition is attached to a biocompatible support or dissolved in a biocompatible matrix and has one or more biological activities selected from the group consisting of:
- a) inhibiting the proliferation of smooth muscle cells in vivo;
- b) stimulating the differentiation of smooth muscle cells in vivo;
- c) regulating the migration of smooth muscle cells in vivo;
- and
- d) binding to smooth muscle cells, and
- wherein said elastin-based composition has an IC50/EC50 for at least one of said biological activities that is less than or equal to 10−3.
A pharmaceutical composition that provides an elastin-based composition, said elastin-based composition consisting of a polypeptide, wherein said polypeptide consists of (i) an amino acid sequence identical to SEQ ID NO:
- 3, (ii) an amino acid sequence identical to SEQ ID NO:
- 2, or (iii) a peptide fragment of six repeats of the hexameric sequence represented by SEQ ID NO:
- 1, wherein said elastin-based composition is attached to a biocompatible support or dissolved in a biocompatible matrix and has one or more biological activities selected from the group consisting of:
- a) inhibiting the proliferation of smooth muscle cells;
- b) stimulating the differentiation of smooth muscle cells;
- c) regulating the migration of smooth muscle cells;
- and
- d) binding to smooth muscle cells, and
- wherein said elastin-based composition has an IC50/EC50 for at least one of said biological activities that is less than or equal to 10−3.
Dependencies are inferred from the claim text.