Claims for Patent: 4,440,679

Summary for Patent: 4,440,679

Title:	Pasteurized therapeutically active protein compositions
Abstract:	Compositions containing thermally sensitive, therapeutically active proteins are pasteurized without substantial loss of therapeutic activity by mixing the protein composition with a pasteurization-stabilizing amount of a polyol prior to pasteurization. Pasteurized compositions containing therapeutically active proteins, which have heretofore been unattainable, can be prepared by the method of the invention.
Inventor(s):	Fernandes; Peter M. (Concord, CA), Lundblad; John L. (El Cerrito, CA)
Assignee:	Cutter Laboratories, Inc. (Berkeley, CA)
Application Number:	06/451,645
Patent Claims:	1. A method of pasteurizing a composition comprising a thermally sensitive, therapeutically active protein selected from the group consisting of antihemophilic factor (Factor VIII), fibronectin, plasminogen, antithrombin III, fibrinogen, alpha-1-antitrypsin, and prekallikrein, which comprises: (a) mixing the protein composition with a compound selected from the group consisting of sugars and reduced sugars in an aqueous medium said compound being present in the mixture in an amount of about 30% to saturation, on a weight to volume basis, and (b) heating the mixture at a temperature of about 60.degree.-75.degree. C. and a pH of about 5.5-8.0 for a time sufficient to pasteurize the protein composition and render it substantially free of infective hepatitis. 2. The method of claim 1 wherein the molecular weight of the compound is about 5000 or less. 3. The method of claim 1 wherein the mixture is heated in Step b at a temperature of about 62.degree.-65.degree. C. 4. The method of claim 1 wherein the mixture is heated for a period of about 10 hours. 5. The method of claim 1 which further includes the step of removing the compound from the mixture of Step b. 6. The method of claim 5 wherein the compound is removed from the mixture of Step b by subjecting the mixture to diafiltration or dialysis. 7. The method of claim 5 which further includes the step of removing water from the mixture of Step b. 8. The method of claim 7 wherein water is removed from the mixture of Step b by subjecting the mixture to ultrafiltration or freeze-drying. 9. The method of claim 1 wherein about 1-1000 parts of compound are mixed with 1 part of total protein. 10. A composition comprising a protein selected from the group consisting of antihemophilic factor (Factor VIII), fibronectin, fibrinogen, alpha-1-antitrypsin and prekallikrein produced by the method of claim 1. 11. A pharmaceutical preparation comprising a composition of claim 10. 12. A method of pasteurizing an antihemophilic factor concentrate, which comprises: (a) mixing the concentrate with a compound selected from the group consisting of sugars and reduced sugars in an aqueous medium, said compound being present in the mixture in an amount of about 30% to saturation, on a weight to volume basis and (b) heating the mixture at a temperature of about 60.degree.-75.degree. C. and a pH of about 5.5-8.0 for a time sufficient to pasteurize the antihemophilic factor concentrate and render it substantially free of infective hepatitis. 13. The method of claim 12 wherein about 1-1000 parts of compound are mixed with 1 part of total protein. 14. The method of claim 12 wherein about 1-500 parts of the aqueous solution are mixed with one part of concentrate. 15. The method of claim 12 wherein the mixture is heated in Step b at a temperature of about 62.degree.-65.degree. C. 16. The method of claim 12 wherein the mixture is heated for a period of about 10 hours. 17. The method of claim 12 which further includes the step of removing the compound from the mixture of Step b. 18. The method of claim 17 wherein the compound is removed from the mixture of Step b by subjecting the mixture to diafiltration or dialysis. 19. The method of claim 16 which further includes the step of removing water from the mixture of Step b. 20. The method of claim 19 wherein water is removed from the mixture of Step b by subjecting the mixture to ultrafiltration or freeze-drying. 21. A pasteurized antihemophilic factor concentrate produced by the method of claim 12. 22. A pharmaceutical preparation comprising the pasteurized antihemophilic factor concentrate of claim 21. 23. A method for pasteurizing a composition containing a thermally sensitive, therapeutically active protein selected from the group consisting of antihemophilic factor (Factor VIII), fibronectin, plasminogen, albumin, an immune serum globulin, a modified immune serum globulin, antithrombin III, Plasma Protein Fraction (human), fibrinogen, alpha-1-antitrypsin, human blood plasma, partially fractionated human blood plasma and prekallikrein, which comprises: (a) mixing the protein composition with an aqueous medium containing a heat stabilizing compound consisting essentially of non-heat treated sugars and reduced sugars, said compound being present in the mixture in an amount of about 30% to saturation, on a weight to volume basis and (b) heating the mixture at a temperature of about 60.degree.-75.degree. C. and a pH of about 5.5-8.0 for a time sufficient to pasteurize the protein composition and render it substantially free of infective hepatitis. 24. The method of claim 23 wherein about 1-500 parts of the aqueous medium are mixed with one part of protein composition. 25. The method of claim 23 wherein the mixture is heated in Step b at a temperature of about 62.degree.-65.degree. C. for a period of about 10 hours.

Details for Patent 4,440,679

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	4,440,679	2002-12-20