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Last Updated: April 23, 2024

Claims for Patent: 5,211,657


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Summary for Patent: 5,211,657
Title: Laminin a chain deduced amino acid sequence, expression vectors and active synthetic peptides
Abstract:The present invention relates to peptides and derivatives thereof having laminin-like activity. The invention further relates to pharmaceutical compositions containing these peptides, to antibodies effective against these peptides, and to vectors containing a DNA sequence of cDNA coding for the A chain of laminin. The peptides of the invention may be used to treat diseases such as cancer.
Inventor(s): Yamada; Yoshihiko (Silver Spring, MD), Sasaki; Makoto (Beppu, JP), Kleinman; Hynda K. (Bethesda, MD), Martin; George R. (Bethesda, MD)
Assignee: The United States Government as represented by the Secretary of the (Washington, DC)
Application Number:07/267,564
Patent Claims:1. Peptides and derivatives thereof having laminin A-like activity selected from the group consisting of:

(i) KCQAGTFALRGDNPQG,

(ii) CSKCQAGTFALR,

(iii) XFALRGDNPQG,

(iv) XSRARKQAASIKVAVSADR,

(v) XRKQAASIKVAVS,

(vi) XIKVAVSADR,

(vii) XSRNLSEIKLLISRARK

(viii) GLWNYIEREGKC,

(ix) KPLKTLEENLSRNLSEI,

(x ) DRLKPLKTLEENLSRNLSEI,

(xi) XGQIKKSPAVKVTHFKG,

(xii) XGQIKKSPAVKVT, and

(xiii) CIRAYQPQTSSTNYNTLTIL

wherein the X group is an amino acid which is not present in the A chain but is used in coupling the peptide to other materials.

2. The peptides of claim 1 wherein the peptides and derivatives thereof comprise protein polymers or cycled peptides.

3. A pharmaceutical composition comprising a therapeutically effective amount of a peptide of claim 1 and a pharmaceutically acceptable carrier therefor.

4. A pharmaceutical composition comprising 50 ng to 5 ug peptide per cm.sup.2 of polymer surface of the polymer of claim 2.

5. A substrate active in promoting epithelial, endothelial or neural cell adhesion, migration, growth, collagenase IV production, neurite outgrowth, tumor formation and heparin binding, comprising the peptides of claim 1 and the expressed material from vectors containing a DNA sequence of cDNA coding for the A chain of laminin or a segment of DNA coding for a portion of the A chain, wherein the DNA sequence is in association with an expression regulatory sequence.

6. A method of stimulating cancer, which comprises administering to an animal a therapeutically effective amount of a peptide of claim 1.

7. The method of claim 6, wherein the animal is a mammal.

8. The method of claim 6, which comprises administering to the animal 0.01 gm to 0.1 gm/gm body weight of the peptide.

9. The method of claim 6, wherein the mode of administration is intravenous, intraperitoneally or via slow release pellet or pump.

10. A prosthetic device having a biologically active surface which exhibits cell attachment activity and growth activity, said surface having linked thereto a peptide of claim 1 or the expressed protein of a vector containing a DNA sequence of cDNA coding for the A chain of laminin or a segment of DNA coding for a portion of the A chain.

11. The prosthetic device of claim 10, wherein said surface comprises a portion of a vascular graft.

12. The prosthetic device of claim 10, wherein said surface comprises synthetic resin fiber.

13. The prosthetic device of claim 10, wherein said surface comprises a portion of a percutaneous device.

14. A method for promoting increased adhesion of epithelial or endothelial cells to vascular prostheses and other artificial organs comprising coating of the prostheses or organ with a protein selected from the group consisting of a peptide of claim 1 or expressed proteins of a vector containing a DNA sequence of cDNA coding for the A chain of laminin or a segment of DNA coding for a portion of the A chain.

15. An anti-adhesion factor for laminin-responsive cells comprising an antibody effective against a peptide of claim 1 or effective against an expressed protein of a vector containing a DNA sequence of cDNA coding for the A chain of laminin or a segment of DNA coding for a portion of the A chain.

16. A method for promoting the migration and growth of epithelial cells and nerves in a wound comprising administering to the wound a therapeutically effective amount of a protein selected from the group consisting of a peptide of claim 1 and the expressed protein of a vector containing a DNA sequence of cDNA coding for the A chain of laminin or a segment of DNA coding for a portion of the A chain.

17. A method for isolating a laminin cell surface receptor from detergent extracts of cells or cell membranes bound to a laminin affinity column, comprising adding to said cells or cell membranes a peptide of claim 1.

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