Claims for Patent: 5,061,786

Summary for Patent: 5,061,786

Title:	Biologically active polypeptides based on transforming growth factor-.beta.
Abstract:	A polypeptide is provided that excludes (a) a full-length mature TGF-.beta. molecule or precursor TGF-.beta. molecule or deletion variants of mature or precursor TGF-.beta. molecules in which from about 1 to 10 amino acid residues have been deleted, (b) a polypeptide of the sequence: Cys-Val-Arg-Gln-Leu-Tyr-Ile-Asp-Phe-Arg-Lys-Asp-Leu-Gly-Trp-Lys, and (c) a polypeptide of the sequence: Arg Asn-Leu-Glu-Glu-Asn-Cys-Cys-Val-Arg-Pro-Leu-Tyr-Ile-Asp-Phe-Arg-Gln-Asp-Le u, said polypeptide comprising an amino acid sequence that is based on conserved sequences in the family of TGF-.beta. molecules. Such polypeptides are particularly useful therapeutically as immunosuppressive agents when coupled to carrier proteins or crosslinked to form polymers.
Inventor(s):	Burnier; John P. (Pacifica, CA), Cianciolo; George J. (San Carlos, CA)
Assignee:	Genentech, Inc. (South San Francisco, CA)
Application Number:	07/356,964
Patent Claims:	1. A polypeptide comprising an amino acid sequence of the formula: wherein: X is Cys or a crosslinker moiety or a polypeptide that has at its C-terminus a Cys, and that, if greater than 15 residues, does not have the sequence of mature or precursor TGF-.beta. at a homologous location in the mature or precursor TGF-.beta. molecule; A is Val or Leu; B is Pro or Gln; H is Arg or Lys; and I is Lys, Arg, or Gln; or a physiologically acceptable salt or ester thereof; provided, however, that the polypeptide excludes (a) a full-length mature TGF-.beta. molecule or precursor TGF-.beta. molecule or deletion variants of mature or precursor TGF-.beta. molecules in which from about 1 to 10 amino acid residues have been deleted, (b) a polypeptide of the sequency:Cys-Val-Arg-Gln-Leu-Tyr-Ile-Asp-Phe-Arg-Lys-Asp-Leu-Gly-Trp-Lys, and (c) a polypeptide of the sequence: Arg-Asn-Leu-Glu-Glu-Asn-Cys-Cys-Val-Arg-Pro-Leu-Tyr-Ile-Asp-Phe-Arg-Gln-As p-Leu. 2. The polypeptide of claim 1 comprising an amino acid sequence of the formula: 3. The polypeptide of claim 2 comprising an amino acid sequence of the formula: wherein: B is Pro or Gln; and I is Lys or Gln. 4. The polypeptide of claim 3 wherein B is Gln and I is Lys. 5. The polypeptide of claim 3 wherein B is Pro and I is Gln. 6. The polypeptide of claim 1 comprising an amino acid sequence of the formula: 7. The polypeptide of claim 1 that is coupled to a carrier protein, sugar group, or lipid. 8. The polypeptide of claim 7 wherein the carrier protein comprises bovine serum albumin, human serum albumin, an immunoglobulin, or a hormone. 9. The polypeptide of claim 8 wherein the carrier protein comprises human serum albumin. 10. The polypeptide of claim 1 that is coupled to a protein to be rendered non-immunogenic or tolerogenic. 11. A polypeptide polymer comprising at least two of the polypeptides of claim 1 crosslinked to each other. 12. The polypeptide polymer of claim 11 wherein two of the polypeptides are crosslinked through the cysteine residue in the given polypeptide sequence. 13. The polypeptide polymer of claim 12 wherein each polypeptide comprises an amino acid sequence of the formula: 14. The polypeptide polymer of claim 13 wherein each polypeptide comprises an amino acid sequence of the formula: wherein: B is Pro or Gln; and I is Lys or Gln. 15. The polypeptide polymer of claim 14 wherein B is Gln and I is Lys. 16. The polypeptide polymer of claim 14 wherein B is Pro and I is Gln. 17. The polypeptide polymer of claim 14 wherein each polypeptide comprises an amino acid sequence of the formula:

Details for Patent 5,061,786

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Grifols Therapeutics Llc	ALBUKED, PLASBUMIN-20, PLASBUMIN-25, PLASBUMIN-5	albumin (human)	For Injection	101138	10/21/1942		2040-01-28
Baxalta Us Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	03/03/1954		2040-01-28
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	07/23/1976		2040-01-28
Grifols Biologicals Llc	ALBUTEIN	albumin (human)	Injection	102478	08/15/1978		2040-01-28
Instituto Grifols, S.a.	HUMAN ALBUMIN GRIFOLS	albumin (human)	Injection	103352	02/17/1995		2040-01-28
Instituto Grifols, S.a.	HUMAN ALBUMIN GRIFOLS	albumin (human)	Injection	103352	06/11/2003		2040-01-28
Csl Behring Llc	ALBUMINAR, ALBUMINAR-20, ALBUMINAR-25, ALBUMINAR-5	albumin (human)	Injection	103955	03/17/2000		2040-01-28