Claims for Patent: 6,169,068

Summary for Patent: 6,169,068

Title:	Pulmonary administration of soluble complement receptor-1 (sCR1) and its derivatives
Abstract:	A method is disclosed for treating diseases or disorders involving complement by pulmonary administration of complement inhibitory proteins such as soluble complement receptor type 1 (sCR1). The present invention relates to the direct treatment of certain complement related disorders by administering complement inhibitory proteins via the pulmonary route, in particular, by direct delivery to the lungs by aerosolization of a complement inhibitory protein and subsequent inhalation.
Inventor(s):	Levin; James L. (Wellesley, MA), Regal; Jean F. (Duluth, MN), Toth; Carol A. (Sharon, MA)
Assignee:	Avant Immunotherpeutics, Inc. (Needham, MA) Regents of the University of Minnesota (Minneapolis, MN)
Application Number:	08/602,761
Patent Claims:	1. A method for administering a soluble complement receptor type 1 (sCR1) agent to a subject comprising; a) providing a sCR1 polypeptide or fragment, derivative, or analog thereof and a pharmaceutically acceptable dispersant in a formulation suitable for pulmonary delivery, wherein said sCR1 polypeptide or fragment, derivative, or analog thereof retains at least one complement-binding activity of an erythrocyte CR1 allotype; and b) administering said formulation to said subject via the pulmonary route. 2. The method according to claim 1 in which the dispersant is a surfactant. 3. The method according to claim 2 in which the surfactant is selected from the group consisting of polyoxyethylene fatty acid esters, polyoxyethylene fatty acid alcohols, and polyoxyethylene sorbitan fatty acid esters. 4. The method according to claim 3 in which the surfactant is polyoxyethylene sorbitan monooleate. 5. The method according to claim 2 in which the concentration of the surfactant is about 0.001% to about 4% by weight of the formulation. 6. The method according to claim 1 in which said formulation is a dry powder aerosol formulation in which the sCR1 polypeptide, fragment, derivative, or analog is present as a finely divided powder. 7. The method according to claim 6 in which the sCR1 polypeptide, fragment, derivative, or analog is lyophilized. 8. The method according to claim 6 wherein the formulation further comprises a bulking agent. 9. The method according to claim 8 in which the bulking agent is selected from the group consisting of lactose, sorbitol, sucrose and mannitol. 10. The method according to claim 1 in which said formulation is a liquid aerosol formulation comprising a pharmaceutically acceptable diluent. 11. The method according to claim 10 in which the diluent is selected from the group consisting of sterile water, saline, buffered saline and dextrose solution. 12. The method according to claim 11 in which the diluent is phosphate buffered saline in the pH 7.0 to 8.0 range. 13. A method for treating a disease or disorder involving complement comprising administering to a subject suffering from said disease or disorder, via the pulmonary route, a soluble complement receptor 1 (sCR1) polypeptide or fragment, derivative, or analog thereof in an amount effective to inhibit complement activity, wherein said sCR1 polypeptide or fragment, derivative or analog thereof retains at least one complement-binding activity of an erythrocyte CR1 allotype. 14. The method according to claim 13 in which the administered sCR1 is the same as that expressed by the Chinese Hamster Ovary cell DUX B11 carrying plasmid pBSCR1c/pTCSgpt as deposited with the ATCC and assigned accession number CRL 10052. 15. The method according to claim 13 in which the disease or disorder involving complement is selected from the group consisting of neurological disorders, disorders of inappropriate or undesirable complement activation, inflammatory disorders, post-ischemic reperfusion conditions, infectious disease, sepsis, immune complex disorders and autoimmune disease. 16. The method according to claim 13 in which the disease or disorder involving complement is a disorder of inappropriate or undesirable complement activation selected from the group consisting of hemodialysis complications, hyperacute allograft rejection, xenograft rejection and interleukin-2 induced toxicity during interleukin-2 therapy. 17. The method according to claim 13 in which the disease or disorder involving complement is a post-ischemic reperfusion condition selected from the group consisting of myocardial infarction, balloon angioplasty, post-pump syndrome in cardiopulmonary bypass or renal bypass, hemodialysis and renal ischemia. 18. A method for treating a lung disease or lung disorder involving complement comprising administering to a subject suffering from said lung disease or lung disorder, via the pulmonary route, a soluble complement receptor 1 (sCR1) polypeptide or fragment, derivative, or analog thereof in an amount effective to inhibit complement activity, wherein said sCR1 polypeptide or fragment, derivative or analog thereof retains at least one complement-binding activity of an erythrocyte CR1 allotype. 19. The method according to claim 18 in which the administered sCR1 is the same as that expressed by the Chinese Hamster Ovary cell DUX B11 carrying plasmid pBSCR1c/pTCSgpt as deposited with the ATCC and assigned accession number CRL 10052. 20. The method according to claim 18 in which the lung disease or lung disorder involving complement is selected from the group consisting of dyspnea, hemoptysis, asthma, chronic obstructive pulmonary disease (COPD), emphysema, pulmonary embolisms, and pulmonary infarcts. 21. The method according to claim 18 in which the lung disease or lung disorder involving complement is selected from the group consisting of pneumonia, fibrinogenic dust diseases, pulmonary fibrosis, organic dust diseases, exposure to irritant gasses and chemicals, hypersensitivity pneumonia, parasitic disease, Goodpasture's Syndrome, adult respiratory distress syndrome (ARDS) and pulmonary vasculitis. 22. The method acccording to claim 21 in which the fibrinogenic dust disease results from exposure to dust or minerals selected from the group consisting of silicon, coal dust, beryllium, and asbestos. 23. The method according to claim 21 in which the exposure to irritant gasses or chemicals is exposure to a gas or chemical selected from the group consisting of chlorine, phosgene, sulfur dioxide, hydrogen sulfide, nitrogen dioxide, ammonia and hydrochloric acid. 24. The method according to claim 18 in which the lung disease or lung disorder involving complement is bronchoconstriction. 25. The method according to claim 18 in which the lung disease or lung disorder involving complement results from a thermal injury to the lung. 26. The method according to claim 18 in which the lung disease or lung disorder involving complement results from a smoke inhalation injury to the lung. 27. A method for treating bronchoconstriction comprising administering to a subject suffering bronchoconstriction, via the pulmonary route, an aerosol formulation consisting essentially of a soluble complement receptor 1 (sCR1) polypeptide or fragment, derivative, or analog thereof and a pharmaceutically acceptable dispersant in an amount effective to inhibit complement activity, wherein said sCR1 polypeptide or fragment, derivative or analog thereof retains at least one complement-binding activity of an erythrocyte CR1 allotype. 28. The method according to claim 27 in which the administered sCR1 is the same as that expressed by the Chinese Hamster Ovary cell DUX B11 carrying plasmid pBSCR1c/pTCSgpt as deposited with the ATCC and assigned accession number CRL 10052. 29. The method according to claim 27 in which the bronchoconstriction results from smoke inhalation. 30. A method for treating anaphylaxis, idiopathic anaphylaxis, or an anaphylactoid reaction comprising administering to a subject experiencing anaphylaxis or an anaphylactoid reaction, via the pulmonary route, an aerosol formulation consisting essentially of a soluble complement receptor 1 (sCR1) polypeptide or fragment, derivative, or analog thereof and a pharmaceutically acceptable dispersant in an amount effective to inhibit complement activity, wherein said sCR1 polypeptide or fragment, derivative or analog thereof retains at least one complement-binding activity of an erythrocyte CR1 allotype. 31. The method according to claim 30 in which the administered sCR1 is the same as that expressed by the Chinese Hamster Ovary cell DUX B11 carrying plasmid pBSCR1c/pTCSgpt as deposited with the ATCC and assigned accession number CRL 10052.

Details for Patent 6,169,068

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2013-02-12