Claims for Patent: 8,623,830

Summary for Patent: 8,623,830

Title:	Compositions containing .alpha.-1-antitrypsin and methods for use
Abstract:	Methods and compositions for treating patients (e.g., patients who are insulin resistant, patients who have diabetes, or are at risk for developing diabetes) are disclosed herein. The methods can include administration of an a1 antitrypsin (AAT) polypeptide or an agent, such as a nucleic acid molecule or organic compound, that promotes the expression or activity of a1-antitrypsin.
Inventor(s):	Flier; Jeffrey (Newton, MA), Koulmanda; Maria (Brookline, MA), Strom; Terry B. (Brookline, MA)
Assignee:	Beth Israel Deaconess Medical Center, Inc. (Boston, MA) The General Hospital Corporation (Boston, MA)
Application Number:	12/441,064
Patent Claims:	1. A method of treating a patient who has been diagnosed as having Type 2 diabetes, the method consisting essentially of: (a) identifying a patient who has been diagnosed as having Type 2 diabetes; and (b) administering to the patient a therapeutically effective amount of an .alpha.1-antitrypsin polypeptide or a nucleic acid molecule that encodes the .alpha.1-antitrypsin polypeptide, wherein the .alpha.1-antitrypsin polypeptide has at least 95% identity to a sequence of a wild type .alpha.1-antitrypsin polypeptide. 2. The method of claim 1, wherein the patient is a human patient. 3. The method of claim 2, wherein the human patient is a child or adolescent. 4. The method of claim 1, wherein the patient has been diagnosed as having Type 2 diabetes on the basis of one or more of the following findings: (a) hyperglycemia in conjunction with a normal or elevated level of insulin; (b) hyperglycemia in conjunction with evidence of pancreatic .beta. cell maintenance; (c) hyperglycemia in conjunction with a blunted blood glucose response to insulin; and (d) hyperglycemia and a family history of Type 2 diabetes. 5. The method of claim 4, wherein the normal or elevated level of insulin is reflected by a normal or elevated level of C-peptide. 6. The method of claim 4, wherein the patient is a human patient. 7. The method of claim 6, wherein the human patient is an adult. 8. A method of treating a patient who has been diagnosed as being at greater than average risk for developing Type 2 diabetes, the method comprising: (a) identifying a patient who has been diagnosed as being at greater than average risk for developing Type 2 diabetes; and (b) administering to the patient a therapeutically effective amount of an .alpha.1-antitrypsin polypeptide or a nucleic acid molecule that encodes the .alpha.1-antitrypsin polypeptide, wherein the .alpha.1-antitrypsin polypeptide has at least 95% identity to a sequence of a wild type .alpha.1-antitrypsin polypeptide. 9. The method of claim 8, wherein the patient has been diagnosed as being at risk for developing Type 2 diabetes on the basis of one or more of the following findings: (a) impaired glucose tolerance with or without features of metabolic syndrome; (b) normal or impaired glucose tolerance with hyperinsulinemia; and (c) impaired glucose tolerance and a family history of Type 2 diabetes. 10. The method of claim 9, wherein the features of metabolic syndrome include abdominal obesity, atherogenic dyslipidemia, a prothrombotic state, elevated blood pressure, or elevated levels of inflammatory cytokines. 11. The method of claim 9, wherein the hyperinsulinemia is reflected by an elevated level of C-peptide. 12. The method of claim 9, wherein the patient who has been diagnosed as being at risk for developing Type 2 diabetes is a female patient who has had gestational diabetes. 13. The method of claim 8, wherein the patient is a human patient. 14. The method of claim 13, wherein the human patient is an adult. 15. A method of treating a patient who has been diagnosed as having Type 2 diabetes, the method consisting of: (a) identifying a patient who has been diagnosed as having Type 2 diabetes; and (b) administering to the patient a therapeutically effective amount of an .alpha.1-antitrypsin polypeptide or a nucleic acid molecule that encodes the .alpha.1-antitrypsin polypeptide, wherein the .alpha.1-antitrypsin polypeptide has at least 95% identity to a sequence of a wild type .alpha.1-antitrypsin polypeptide. 16. The method of claim 15, wherein the patient is a human patient. 17. The method of claim 16, wherein the human patient is a child or adolescent. 18. The method of claim 15, wherein the patient has been diagnosed as having Type 2 diabetes on the basis of one or more of the following findings: (a) hyperglycemia in conjunction with a normal or elevated level of insulin; (b) hyperglycemia in conjunction with evidence of pancreatic 0 cell maintenance; (c) hyperglycemia in conjunction with a blunted blood glucose response to insulin; and (d) hyperglycemia and a family history of Type 2 diabetes. 19. The method of claim 18, wherein the normal or elevated level of insulin is reflected by a normal or elevated level of C-peptide. 20. The method of claim 18, wherein the patient is a human patient. 21. The method of claim 20, wherein the human patient is an adult. 22. The method of claim 1, wherein the patient is administered a therapeutically effective amount of an .alpha.1-antitrypsin polypeptide that has at least 99% identity to a sequence of a wild type .alpha.1-antitrypsin polypeptide. 23. The method of claim 1, wherein the .alpha.1-antitrypsin polypeptide is joined to a portion of an immunoglobulin or an albumin. 24. The method of claim 23, wherein the portion of the immunoglobulin is an Fc region of an IgG molecule. 25. The method of claim 8, wherein the patient is administered a therapeutically effective amount of an .alpha.1-antitrypsin polypeptide that has at least 99% identity to a sequence of a wild type .alpha.1-antitrypsin polypeptide. 26. The method of claim 8, wherein the .alpha.1-antitrypsin polypeptide is joined to a portion of an immunoglobulin or an albumin. 27. The method of claim 26, wherein the portion of the immunoglobulin is an Fc region of an IgG molecule. 28. The method of claim 15, wherein the patient is administered a therapeutically effective amount of an .alpha.1-antitrypsin polypeptide that has at least 99% identity to a sequence of a wild type .alpha.1-antitrypsin polypeptide. 29. The method of claim 15, wherein the .alpha.1-antitrypsin polypeptide is joined to a portion of an immunoglobulin or an albumin. 30. The method of claim 15, wherein the portion of the immunoglobulin is an Fc region of an IgG molecule. 31. The method of any of claims 1, 8, and 15, wherein the .alpha.1-antitrypsin polypeptide is a full-length .alpha.1-antitrypsin polypeptide. 32. The method of claim 31, wherein the full-length .alpha.1-antitrypsin polypeptide is a human .alpha.1-antitrypsin polypeptide. 33. The method of claim 8, wherein the method further comprises administering an agent that selectively inhibits TNF.alpha. or a moiety within the TNF.alpha. signaling pathway. 34. The method of claim 33, wherein the agent that inhibits TNF.alpha. is an anti-TNF.alpha. antibody. 35. The method of claim 34, wherein the anti-TNF.alpha. antibody is a human, humanized, chimeric or single chain antibody. 36. The method of claim 34, wherein the anti-TNF.alpha. antibody is a monoclonal antibody. 37. The method of claim 34, wherein the anti-TNF.alpha. antibody is adalimumab or infliximab. 38. The method of claim 33, wherein the agent that selectively inhibits a moiety within the TNF.alpha. signaling pathway is a soluble receptor antagonist. 39. The method of claim 38, wherein the soluble receptor antagonist comprises an immunoglobulin-like molecule. 40. The method of claim 38, wherein the soluble receptor antagonist is etanercept. 41. The method of claim 38, wherein the soluble receptor antagonist comprises polyethylene glycol. 42. The method of claim 41, wherein the soluble receptor antagonist is PEG-sTNF-RI (p55). 43. The method of claim 33, wherein the agent that selectively inhibits TNF.alpha. is an RNA molecule that mediates RNAi. 44. The method of claim 43, wherein the RNA molecule that mediates RNAi is an siRNA or an shRNA. 45. The method of claim 33, wherein the agent that selectively inhibits TNF.alpha. is a small organic or inorganic compound. 46. The method of claim 45, wherein the small organic or inorganic compound is LMP420. 47. The method of claim 8, wherein the method further comprises administering an antagonist of an inflammatory cytokine. 48. The method of claim 47, wherein the inflammatory cytokine is IL-1 or IL-6. 49. The method of claim 48, wherein the inflammatory cytokine is IL-1. 50. The method of claim 49, wherein the antagonist is anakinra. 51. The method of claim 8, wherein the method further comprises administering an agonist of a glucagon-like peptide (GLP) receptor or an agonist of an exendin receptor. 52. The method of claim 51, wherein the GLP receptor is GLP-1. 53. The method of claim 51, wherein the agonist of the GLP receptor or the agonist of the exendin receptor is exendin-3, exendin-4, or GLP-1(7-36)-amide. 54. The method of claim 8, wherein the method further comprises administering a CD3 antagonist. 55. The method of claim 54, wherein the CD3 antagonist is an anti-CD3 antibody.

Details for Patent 8,623,830

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2026-09-12
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2026-09-12
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2026-09-12