Claims for Patent: 4,962,091

Summary for Patent: 4,962,091

Title:	Controlled release of macromolecular polypeptides
Abstract:	An active agent delivery system for the controlled administration of macromolecular polypeptides which comprises a micro-suspension of water-soluble components in a polylactide matrix.
Inventor(s):	Eppstein; Deborah A. (Palo Alto, CA), Schryver; Brian B. (Redwood City, CA)
Assignee:	Syntex (U.S.A.) Inc. (Palo Alto, CA)
Application Number:	06/866,625
Patent Claims:	1. A composition for the controlled administration of a biologically active macromolecular polypeptide comprising (a) a polylactide matrix in which is incorporated a micro-suspension of not more than about 30 percent by weight based on weight of the system of (b) particles of at least one biologically active macromolecular polypeptide having a molecular weight not less than about 1000 daltons, wherein substantially all of the particles of polypeptide have a diameter of 10.mu. or less and are uniformly and discreetly dispersed throughout the matrix, and wherein the polypeptide retains at least about 50 percent of the biological activity which it possessed prior to manufacture of the composition. 2. The system of claim 1 in which the polypeptide and other water soluble components comprise about 20 percent by weight, or less, of the matrix. 3. The system of claim 1 in which the polypeptide has a molecular weight greater than about 2,500. 4. The system of claim 3 in which the polypeptide has a molecular weight greater than about 6,000. 5. The system of claim 4 in which the polypeptide has a molecular weight greater than about 10,000. 6. The system of claim 5 in which the polypeptide is selected from the group consisting of cytokines, lymphokines, monokines and interferons. 7. The system of claim 6 in which the polypeptide is interleukin-2 or an analog thereof. 8. The system of claim 6 in which the polypeptide is an interferon. 9. The system of claim 8 which includes a pharmaceutically acceptable stabilizer for the interferon. 10. The system of claim 9 in which the interferon is a beta interferon. 11. The system of claim 10 in which the beta interferon and other water-soluble components comprise about 20 percent by weight, or less, of the matrix. 12. The system of claim 11 in which the beta interferon and other water-soluble components comprise about 10 percent by weight, or less, of the matrix. 13. The system of claim 12 in which the beta interferon and other water-soluble components comprise about 5 percent by weight, or less, of the matrix. 14. The system of claim 13 in which the stabilizer comprises either or both of human serum albumin and dextrose. 15. The system of claim 1 in which the polylactide is a poly(lactide-co-glycolide) copolymer having a molar ratio of lactide to glycolide units of between about 100:0 and 30:70. 16. The system of claim 15 in which the copolymer has a molar ratio of lactide to glycolide units of between 75:25 and 40:60. 17. The system of claim 16 in which the copolymer has a molar ratio of lactide to glycolide units of about 50:50. 18. The system of claim 17 in which the polypeptide is a recombinant human beta interferon, and in which the beta interferon and other water soluble components comprise 10 percent by weight, or less, of the matrix. 19. The system of claim 18 in which the beta interferon and other water soluble components comprise 5 percent by weight, or less, of the matrix. 20. The system of claim 1 which is formed from one or more layers of a spray-cast film. 21. The system of claim 20 which incorporates a biocompatible inert reinforcement material. 22. The system of claim 1 which contains more than one species of biologically active macromolecular polypeptide. 23. The system of claim 1 in which the polypeptide is a hormone. 24. The system of claim 23 in which the hormone is calcitonin or an analog thereof. 25. The system of claim 23 in which the hormone is parathyroid hormone or an analog thereof. 26. The system of claim 23 in which the hormone is epidermal growth factor or an analog thereof. 27. The system of claim 1 in which the polypeptide is an immunomodulator. 28. The system of claim 27 in which the polypeptide is an immune stimulator. 29. The system of claim 27 in which the polypeptide is an immune depressant. 30. The system of claim 1 in which the polypeptide is an enzyme. 31. The system of claim 30 in which the enzyme is superoxide dismutase. 32. The system of claim 30 in which the enzyme is a plasminogen activator. 33. The system of claim 32 in which the enzyme is tissue plasminogen activator. 34. The system of claim 1 in which the polypeptide is a growth promotant or growth inhibitory factor. 35. The system of claim 34 in which the polypeptide is transforming growth factor-.beta.. 36. The system of claim 34 in which the polypeptide is a growth hormone or growth hormone releasing factor. 37. The system of claim 36 in which the polypeptide is bovine growth hormone. 38. The system of claim 1 in which the polypeptide is a blood coagulation factor. 39. The system of claim 1 in which the polypeptide is a vaccine antigen. 40. The system of claim 1 in which the polypeptide is an antibody. 41. The system of claim 1 in which the polypeptide is a protease inhibitor. 42. A composition according to claim 1 further comprising one or more other water soluble, pharmaceutically acceptable components, particles of which have a diameter of about 10.mu. or less, selected from the group consisting of other active agents, proteins, other polypeptides, stabilizers, carbohydrates, surfactants and plasticizers, wherein the macromolecular agent and other water soluble components together comprise about 30 percent by weight of the system.

Details for Patent 4,962,091

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2039-03-29