Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 8 to 10 amino acid residues in defined sequence
Reexamination Certificate
1998-06-11
2002-12-31
Romeo, David S. (Department: 1647)
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
8 to 10 amino acid residues in defined sequence
C530S324000, C530S325000, C530S326000, C530S327000, C435S325000
Reexamination Certificate
active
06500920
ABSTRACT:
BACKGROUND OF THE INVENTION
Transforming growth factor &bgr; (TGF-&bgr;) is a family of 25-kDa structurally homologous dimeric proteins containing one interchain disulfide bond and four intrachain disulfide bonds. The TGF-&bgr; family is composed of three-known members (TGF-&bgr;
1
, TGF-&bgr;
2
, and TGF-&bgr;
3
) in mammalian species. TGF-&bgr; is a bifunctional growth regulator: it is a growth inhibitor for epithelial cells, endothelial cells, T-cells, and other cell types and a mitogen for mesenchymal cells. TGF-&bgr; also has other biological activities, including stimulation of collagen, fibronectin, and plasminogen activator inhibitor 1 (PAI-1) synthesis, stimulation of angiogenesis, and induction of differentiation in several cell lineages.
TGF-&bgr; has been implicated in the pathogenesis of various diseases such as intimal hyperplasia following angioplasty, tissue fibrosis, and glomerulonephritis. Neutralizing antibodies to TGF-&bgr; have been used experimentally to reduce scarring of wounds, to prevent lung injury in adult respiratory distress syndrome (ARDS), and to block restenosis following angioplasty in animal models. These promising results warrant the development of TGF-&bgr; antagonists (inhibitor) that might be useful in inhibiting, ameliorating or reversing the effects of TGF-&bgr; and treating diseases.
SUMMARY OF THE INVENTION
A method of inhibiting, ameliorating or reversing the effects of TGF-&bgr; in biological systems, comprising the step of exposing said biological systems with a binding agent, said binding agent is a peptide which substantially resembles a segment of the TGF-&bgr; molecules.
The binding agent is a peptide which substantially resembles an active site of the TGF-&bgr; molecules, hereinafter referred to as active site peptide.
The binding agent may be in the form of a peptide or other chemical agents which substantially resembles an active site of the TGF-&bgr; molecule, the binding agents occupy the TGF-&bgr; cellular receptors making the TGF-&bgr; cellular receptors unavailable for the binding of TGF-&bgr; molecules.
The biological systems may be either in-vitro or in-vivo.
Most preferably, the binding agent of TGF-&bgr; substantially corresponds to a peptide having an amino acid sequence substantially extending from residue 41 to residue 65 of TGF-&bgr; amino acid sequence. Most preferably, said binding agents correspond to an amino acid sequence motif preferably represented by WSXD (SEQ ID NO:10) and/or RSXD (SEQ ID NO:11), wherein X represents any amino acid.
Yet another object of the present invention is to provide an active site of TGF-&bgr; molecules. And to provide an amino acid sequence which substantially represents an active site of TGF-&bgr; molecules.
Yet another object of the present invention is to provide an agonist of TGF-&bgr; molecules, comprising a carrier molecule have a plurality of said binding agent. Furthermore, a method of producing an agonist of TGF-&bgr; molecules, comprising the step of conjugating a plurality of said binding agents to a carrier molecule.
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Romeo David S.
St. Louis University
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