Claims for Patent: 4,534,972

Summary for Patent: 4,534,972

Title:	Protein compositions substantially free from infectious agents
Abstract:	Compositions containing therapeutically or immunologically active proteins are rendered substantially free from infectious agents such as viable viruses and bacteria without substantial loss of therapeutic or immunologic activity by mixing the protein composition with a complex formed from source of transition metal ions, such as copper ions, and an angularly-fused, polynuclear heterocyclic arene having two nitrogen atoms in a \"cis-ortho\" relationship, such as phenanthroline, and a reducing agent such as a thiol in amounts and at a temperature and for a time sufficient to inactivate substantially all of the viruses and bacteria contained therein. Compositions containing therapeutically active proteins substantially free from viral and bacterial infectivity, which have heretofore been unattainable, can be prepared by the method of the invention.
Inventor(s):	Lembach; Kenneth J. (Danville, CA)
Assignee:	Miles Laboratories, Inc. (Elkhart, IN)
Application Number:	06/480,056
Patent Claims:	1. A method for rending a composition, which contains a therapeutically or immunologically active protein, selected from the group consisting of blood plasma proteins, virus vaccines, bacterial vaccines, and non-infectious antigens dissolved in an aqueous medium, substantially free from infectious agents selected from viable viruses and bacteria without substantial loss of therapeutic or immunologic activity, which comprises (a) mixing an aqueous solution of the protein composition with an effective amount of a complex formed from mixing an angularly-fused, polynuclear heterocyclic arene have two nitrogen atoms in a "cis-ortho" relationship and a source of transition metal ions capable of complexing with said arene and a thiol in effective amounts to inactivate substantially all of the infectious agents contained in said composition and which does not result in substantial loss of therapeutic or immunological activity and (b) holding the mixture for a time and at a temperature sufficient to render said infectious agents substantially non-infective in the protein composition without substantial loss of therapeutic or immunologic activity therein. 2. The method of claim 1 wherein the mixture is held in step (b) at a temperature of about 2.degree.-60.degree. C. for a period of at least about 0.25 hours. 3. The method of claim 1 wherein the mixture is held in step (b) at a temperature of about 20.degree.-37.degree. C. for a period of about 0.5-3 hours. 4. The method of claim 1 wherein the mixture is held for a time and at a temperature to inactivate at least about 99% of the viruses and bacteria in the protein composition. 5. The method of claim 1 wherein the pH in step (b) is physiologically compatible. 6. The method of claim 1 wherein the pH is about 4-10. 7. The method of claim 1 wherein the amount of complex in step (a) is about 0.001-0.1 mM in an about 0.5-2% (weight/volume) aqueous solution of the protein composition. 8. The method of claim 1 wherein the amount of reducing agent is about 0.1-5 mM in an about 0.5-2% (weight/volume) aqueous solution of the protein composition. 9. The method of claim 1 wherein the complex is a copper/1,10-phenanthroline complex. 10. The method of claim 1 wherein the reducing agent is 3-mercaptopropionic acid. 11. The method of claim 1 wherein the protein composition comprises an component derived from blood plasma. 12. The method of claim 1 wherein the protein composition comprises a viral vaccine. 13. The method of claim 1 wherein the protein composition comprises non-infectious antigen. 14. The method of claim 1 wherein the protein composition comprises a protein selected from the group consisting of blood plasma, partially fractionated blood plasma, plasminogen, albumin, antihemophilic factor (Factor VIII), Factor IX concentrate containing Factors II, VII, IX and X, and the individual factors, Plasma Protein Fraction (human), fibronectin (cold insoluble globulin), Factor XIII, IgG, IgA, IgD, IgE, IgM, high molecular weight kininogen (90,000-106,000), an immune globulin, intravenous (modified, either chemically or enzymatically or by fractional separation, immune serum globulin, anti-inhibitor coagulant complex, antithrombin III, alpha-1-proteinase inhibitor, plasma growth hormone, somatomedin, prealbumin, plasminogen-streptokinase complex, ceruloplasmin, transferrin, haptoglobin, and prekallikrein and mixtures thereof. 15. The substantially non-infective protein composition produced by the method of claim 12. 16. The substantially non-infective protein composition produced by the method of claim 13. 17. The substantially non-infective protein composition produced by the method of claim 14. 18. The substantially non-infective protein composition produced by the method of claim 15.

Details for Patent 4,534,972

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Grifols Therapeutics Llc	PLASMANATE	plasma protein fraction (human)	Injection	101140	October 02, 1958	4,534,972	2040-01-28
Takeda Pharmaceuticals U.s.a., Inc.	AUTOPLEX, FEIBA NF, FEIBA VH	anti-inhibitor coagulant complex	For Injection	101447	December 21, 1979	4,534,972	2040-01-28
Takeda Pharmaceuticals U.s.a., Inc.	AUTOPLEX, FEIBA NF, FEIBA VH	anti-inhibitor coagulant complex	For Injection	101447	July 31, 2000	4,534,972	2040-01-28
Takeda Pharmaceuticals U.s.a., Inc.	AUTOPLEX, FEIBA NF, FEIBA VH	anti-inhibitor coagulant complex	For Injection	101447	August 11, 2005	4,534,972	2040-01-28
Octapharma Pharmazeutika Produktionsges.m.b.h.	OCTAGAM	immune globulin intravenous (human)	Injection	125062	May 21, 2004	4,534,972	2040-01-28