Claims for Patent: 4,970,156

Summary for Patent: 4,970,156

Title:	Immobilization of active protein by cross-linking to inactive protein
Abstract:	A solution of an active protein substance and an inactive protein substance is reacted with a cross-linking agent, optionally in the presence of an inert carrier, under cross-linking conditions to produce articles comprising both active and inactive protein substances. The active protein substance comprises up to about 20 percent, e.g. from 1 to 20 percent by weight, based on the final weight of the total protein substance, whereas the cross-linking agent comprises from 0.5 to 8 percent by weight, based on the weight of the total treated mixture. The obtained articles are in the form of a solution or a suspension in aqueous medium, in the form of a film, in the form of a membrane, in the form of a fabric, in the form of a porous material, or in the form of a mass, such as granules, pills or tablets.
Inventor(s):	Avrameas; Statis (La Celle Saint Cloud, FR), Broun; Georges (Rouen, FR), Selegny; Eric (Rouen, FR), Thomas; Daniel (Rouen, FR)
Assignee:	Agence Nationale de Valorisation de la Recherche (FR)
Application Number:	06/775,956
Patent Claims:	1. A product which consists essentially of immobilized active protein in the form of a compound in which the active protein is homogeneously distributed and correlated with and thus chemically bound to inactive protein through glutaraldehyde-based bridges, the weight ratio of active protein to inactive protein in the compound being at most 1 to 4 and the proportion of glutarladehyde bridges in said compound being sufficient to immobilize the active protein. 2. A product according to claim 1 wherein the active protein is a member selected from the group consisting of antigen, allergen, antibody, hormone, enzyme and proteinic part of a virus or of a cell. 3. A product according to claim 1 wherein the active protein is a member selected from the group consisting of oxidase, hydroxylase, isomerase, transferase, lyase and oxidoreductase. 4. A product according to claim 1 wherein the active protein is a member selected from the group consisting of pepsin, subtilisin, trypsin, chymotrypsin and papain. 5. A product according to claim 1 wherein the active protein is a member selected from the group consisting of glucose-oxidase, carbonic anhydrase, lipolytic hydrolase, amylolytic hydrolase, urease, asparaginase, uricase, peroxidase, catalase, phenylalanine-hydroxylase, galactose phosphate uridyl transferase, pronase, collagenase, keratinase, elastase, urate oxidase, tyrosine decarboxylase, hexokinase, phosphatase, L-amino-acid-oxidase, xanthine oxidase, decarboxylase, ribonuclease, .alpha.-amylase and .beta.-galactosidase. 6. A product according to claim 1 wherein the active protein substantially retains both its activity and specificity. 7. A shaped solid product having useful mechanical strength and consisting essentially of immobilized active protein according to claim 1. 8. A product according to claim 1 wherein the inactive protein is a member selected from the group consisting of albumin, plasma protein, ovalbumin, fibrinogen, gelatin and hemoglobin. 9. A product according to claim 1 wherein the inactive protein is that found in microbes. 10. A product according to claim 1 wherein the inactive protein is albumin. 11. A product according to claim 2 wherein the inactive protein is a member selected from the group consisting of albumin, plasma protein, ovalbumin, fibrinogen, gelatin, hemoglobin and inactive protein found in microbes. 12. A product according to claim 3 wherein the inactive protein is a member selected from the group consisting of albumin, plasma protein, ovalbumin, fibrinogen, gelatin, hemoglobin and inactive protein found in microbes. 13. A product according to claim 4 wherein the inactive protein is a member selected from the group consisting of albumin, plasma protein, ovalbumin, fibrinogen, gelatin, hemoglobin and inactive protein found in microbes. 14. A product according to claim 5 wherein the inactive protein is a member selected from the group consisting of albumin, plasma protein, ovalbumin, fibrinogen, gelatin, hemoglobin and inactive protein found in microbes. 15. A product according to claim 7 wherein the inactive protein is a member selected from the group consisting of albumin, plasma protein, ovalbumin, fibrinogen, gelatin, hemoglobin and inactive protein found in microbes. 16. A product according to claim 1 wherein the inactive protein is gelatin. 17. A product according to claim 1 wherein the active protein is an antigen. 18. A product according to claim 1 wherein the active protein is an antibody. 19. A product according to claim 1 wherein the active protein is an allergen. 20. A product according to claim 1 wherein the active protein is a part of a virus. 21. A product according to claim 6 wherein the inactive protein is that of a microbe. 22. A product according to claim 1 wherein the active protein and the inactive protein are derived from a single impure source. 23. A product according to claim 22 wherein the single impure source is a microbe source. 24. A self-sustaining flexible sheet or film of immobilized active protein according to claim 1 which is free from a separate or distinct carrier. 25. A sheet or film of immobilized active protein according to claim 1 in combination and integral with an inert non-proteinic carrier which imparts form and strength thereto. 26. A sheet or film according to claim 25 wherein the immobilized active protein is diffused throughout the carrier, which is macroporgus. 27. A sheet or film of immobilized active protein according to claim 25 wherein the carrier is of a material selected from the group consisting of cellulose, regenerated cellulose, amylose, an alginate, a polysilane, polyvinyl alcohol, aminated paper, a polyacrylamide, silicone sheet, activated carbon and silk. 28. Open-cell foam or sponge which consists essentially of immobilized active protein according to claim 1. 29. A product according to claim 1 wherein the active protein is hydrolytic enzyme. 30. A product according to claim 1 wherein the active protein is proteolytic hydrolase. 31. A product according to claim 2 wherein the active protein substantially retains both its activity and specificity, and the inactive protein is a member selected from the group consisting of albumin, plasma protein, ovalbumin, fibrinogen, gelatin and hemoglobin. 32. A product according to claim 1 which, when free from a separate or distinct carrier, is capable of being in a shaped self-supporting form selected from the group consisting of flexible sheet, flexible film, open-cell foam and sponge. 33. A product according to claim 32 which is free from a separate or distinct carrier. 34. A product according to claim 33 which is in one of the stated shaped self-supporting forms. 35. A product according to claim 1 which consists essentially of self-supporting solid.

Details for Patent 4,970,156

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2007-11-13
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2007-11-13