Claims for Patent: 6,232,088

Summary for Patent: 6,232,088

Title:	Treatment and prevention of immune rejection reactions
Abstract:	Provided, among other things, is a method of preventing or ameliorating transplantation rejection reactions comprising treating the donor tissue with a rejection reaction preventing or ameliorating effective amount of a hydrolase that is effective reduce the amount of one or more cell surface adhesion molecules.
Inventor(s):	Franklin; Richard L. (London, GB), St. Pierre; Yves (Laval, CA)
Assignee:	Phairson Medical, Inc. (Wilmington, DE)
Application Number:	09/220,731
Patent Claims:	1. A method of ameliorating transplantation rejection reactions comprising treating, extra-corporeally, donor tissue with a rejection reaction ameliorating effective amount of a hydrolase enzyme. 2. The method of claim 1, wherein the hydrolase is a trypsin from cod. 3. The method of claim 1, wherein the hydrolase is: a krill-derived enzyme having N-terminal sequence I-V-G-G-X-E-V-T-P-H-A-Y-P-W-Q-V-G-L-F-I-D-D-M-Y-F (SEQ ID NO. 20); or a Panaeus vanameii 1 enzyme having N-terminal sequence I-V-G-G-V-E-A-T-P-H-S-W-P-H-Q-A-A-L-F-1-D-D-M-Y-F (SEQ ID NO:3); or a Panaeus vanameii 2 enzyme having N-terminal sequence I-V-G-G-V-E-A-T-P-H-S-X-P-H-Q-A-A-L-F-I (SEQ ID NO:4); or a Panaeus monodon tryptic enzyme having N-terminal sequence I-V-G-G-T-A-V-T-P-G-E-F-P-Y-Q-L-S-F-Q-D-S-I-E-G-V (SEQ ID NO:5); or a Panaeus monodon chymotryptic-1 enzyme having N-terminal sequence I-V-G-G-V-E-A-V-P-G-V-W-P-Y-Q-A-A-L-F-I-I-D-M-Y-F (SEQ ID NO:6); or a Panaeus monodon chymotryptic-2 enzyme having N-terminal sequence I-V-G-G-V-E-A-V-P-H-S-W-P-Y-Q-A-A-L-F-I-I-D-M-Y-F (SEQ ID NO:7); or a Uca pugilator enzyme I enzyme having N-terminal sequence I-V-G-G-V-E-A-V-P-N-S-W-P-H-Q-A-A-L-F-I-D-D-M-Y-F (SEQ ID NO:8); or a Uca pugilator enzyme II enzyme having N-terminal sequence I-V-G;-G-Q-D-A-T-P-G-Q-F-P-Y-Q-L-S-F-Q-D (SEQ ID NO:9); or a Kamchatka crab IA enzyme having N-terminal sequence I-V-G-G-Q-E-A-S-P-G-S-W-P-X-Q-V-G-L-F-F (SEQ ID NO:11); or a Kamchatka crab IIA enzyme having N-terminal sequence I-V-G-G-T-E-V-T-P-G-E-I-P-Y-Q-L-S-L-Q-D (SEQ ID NO:12); or a Kamchatka crab IIB enzyme having N-terminal sequence I-V-G-G-T-E-V-T-P-G-E-I-P-Y-Q-L-S-F-Q-D (SEQ ID NO:13); or a Kamchatka crab IIC enzyme having N-terminal sequence I-V-G-G-S-E-A-T-S-G-Q-F-P-Y-Q-X-S-F-Q-D (SEQ ID NO:14); or is crayfish enzyme having N-terminal sequence I-V-G-G-T-D-A-T-L-G-E-F-P-Y-Q-L-S-F-Q-N (SEQ ID NO:14); or is salmon and comprises sequence I-V-G-G-Y-E-C-K-A-Y-S-Q-A-Y-Q-V-S-L-N-S-G-Y-H-Y-C (SEQ ID NO:17). 4. A method of ameliorating transplantation rejection reactions comprising treating, extra-corporeally, a donor source of immune cells with a rejection ameliorating effective amount of a hydrolase enzyme. 5. The method of claim 4, further comprising treating donor tissue ex vivo. 6. The method of claim 4, wherein the hydrolase is a trypsin from cod. 7. The method of claim 4, wherein the hydrolase is: a krill-derived enzyme having N-terminal sequence I-V-G-G-X-E-V-T-P-H-A-Y-P-W-Q-V-G-L-F-I-D-D-M-Y-F (SEQ ID NO.20); or a Panaeus vanameii 1 enzyme having N-terminal sequence I-V-G-G-V-E-A-T-P-H-S-W-P-H-Q-A-A-L-F-I-D-D-M-Y-F (SEQ ID NO:3); or a Panaeus vanameii 2 enzyme having N-terminal sequence I-V-G-G-V-E-A-T-P-H-S-X-P-H-Q-A-A-L-F-I (SEQ ID NO-4); or a Panaeus monodon tryptic enzyme having N-terminal sequence I-V-G-G-T-A-V-T-P-G-E-F-P-Y-Q-L-S-F-Q-D-S-I-E-G-V (SEQ ID NO: 5); or a Panaeus monodon chymotryptic-1 enzyme having N-terminal sequence I-V-G-G-V-E-A-V-P-G-V-W-P-Y-Q-A-A-L-F-I-I-D-M-Y-F (SEQ ID NO:6); or a Panaeus monodon chymotryptic-2 enzyme having N-terminal sequence I-V-G-G-V-E-A-V-P-H-S-W-P-Y-Q-A-A-L-F-I-I-D-M-Y-F (SEQ ID NO:7); or a Uca pugilator enzyme I enzyme having N-terminal sequence I-V-G-G-V-E-A-V-P-N-S-W-P-H-Q-A-A-L-F-I-D-D-M-Y-F (SEQ ID NO:8); or a Uca pugilator enzyme II enzyme having N-terminal sequence I-V-G-G-Q-D-A-T-P-G-Q-F-P-Y-Q-L-S-F-Q-D (SEQ ED NO:9); or a Kamchatka crab IA enzyme having N-terminal sequence I-V-G-G-Q-E-A-S-P-G-S-W-P-X-Q-V-G-L-F-F (SEQ ID NO:11); or a Kamchatka crab IIA enzyme having N-terminal sequence I-V-G-G-T-E-V-T-P-G-E-I-P-Y-Q-L-S-L-Q-D (SEQ ID NO:12); or a Kamchatka crab IIB enzyme having N-terminal sequence I-V-G-G-T-E-V-T-P-G-E-I-P-Y-Q-L-S-F-Q-D (SEQ ID NO:13); or a Kamchatka crab IIC enzyme having N-terminal sequence I-V-G-G-S-E-A-T-S-G-Q-F-P-Y-Q-X-S-F-Q-D (SEQ ID NO:14); or is crayfish enzyme having N-terminal sequence I-V-G-G-T-D-A-T-L-G-E-F-P-Y-Q-L-S-F-Q-N (SEQ ID NO:14); or is salmon and comprises sequence I-V-G-G-Y-E-C-K-A-Y-S-Q-A-Y-Q-V-S-L-N-S-G-Y-H-Y-C (SEQ ID NO:17). 8. The method of claim 1, wherein the enzyme removes, destroyes, inactivates or disables one or more of CD4, CD8, CD28 and ICAM-1 (CD54). 9. The method of claim 1, wherein the enzyme removes, destroyes, inactivates or disables two or more of CD4, CD8, CD28 and ICAM-1 (CD54). 10. The method of claim 1, wherein the enzyme removes, destroyes, inactivates or disables three or more of CD4, CD8, CD28 and ICAM-1 (CD54). 11. The method of claim 1, wherein the enzyme removes, destroyes, inactivates or disables four or more of CD4, CD8, CD28 and ICAM-1 (CD54). 12. The method of claim 1, wherein the enzyme is a krill derived multifunctional enzyme, wherein the multifunctional enzyme has at least two of a chymotrypsin, trypsin, collagenase, elastase or exo peptidase activity, a molecular weight of 26,000-32,000 Daltons as determined by SDS PAGE, and an N-terminal sequence comprising: I-V-G-G-X-E-V-T-P-H-A-Y-P-W-Q-V-G-L-F-I-D-D-M-Y-F (SEQ ID NO:20) wherein X is an amino acid. 13. The method of claim 12, wherein the composition consists essentially of, with respect to proteases, said multifunctional enzyme. 14. The method of claim 12, wherein said multifunctional enzyme has endo and exo peptidase activity. 15. The method of claim 12, wherein said multifunctional enzyme has at least three of said activities. 16. The method of claim 1, wherein the composition comprises an enzyme which is a multifunctional enzyme that has at least two of a chymotrypsin, trypsin, collagenase, elastase or exo peptidase activity and comprises an amino acid sequence that has at least 95% identity to a reference sequence, wherein the reference sequence is (i) the amino acid 64-300 sequence of SEQ ID NO:21, or (i) a sequence which is that of the amino acid 64-300 sequence of SEQ ID NO:21 except that it has one or more of the amino acid substitutions found in the amino acid 1-185 sequence of SEQ ID NO:22, or one or more of the amino acid substitutions found in the amino acid 72-178 sequence of SEQ ID NOS:23 or 24, or one or more of the amino acid substitutions found in the amino acid 1-211 sequence of SEQ ID NO:25, or one or more of the amino acid substitutions found in the amino acid 66-302 sequence of SEQ ID NO:26, or has asparagine or lysine at a residue corresponding to residue 68 of SEQ ID NO:21. 17. The method of claim 16, wherein the multifunctional enzyme comprises an amino acid sequence that matches a reference sequence. 18. The method of claim 4, wherein the enzyme removes, destroyes, inactivates or disables one or more of CD4, CD8, CD28 and ICAM-1 (CD54). 19. The method of claim 4, wherein the enzyme removes, destroyes, inactivates or disables two or more of CD4, CD8, CD28 and ICAM-1 (CD54). 20. The method of claim 4, wherein the enzyme removes, destroyes, inactivates or disables three or more of CD4, CD8, CD28 and ICAM-1 (CD54). 21. The method of claim 4, wherein the enzyme removes, destroyes, inactivates or disables four or more of CD4, CD8, CD28 and ICAM-1 (CD54). 22. The method of claim 4, wherein the composition comprises an enzyme which is a krill derived multifunctional enzyme, wherein the multifunctional enzyme has at least two of a chymotrypsin, trypsin, collagenase, elastase or exo peptidase activity, a molecular weight of 26,000-32,000 Daltons as determined by SDS PAGE, and an N-terminal sequence comprising: I-V-G-G-X-E-V-T-P-H-A-Y-P-W-Q-V-G-L-F-I-D-D-M-Y-F (SEQ ID NO:20) wherein X is an amino acid. 23. The method of claim 22, wherein said multifunctional enzyme has endo and exo peptidase activity. 24. The method of claim 22, wherein said multifunctional enzyme has at least three of said activities. 25. The method of claim 22, further comprising treating the donor tissue ex vivo. 26. The method of claim 22, wherein said multifunctional enzyme has endo and exo peptidase activity. 27. The method of claim 22, wherein said multifunctional enzyme has at least three of said activities. 28. The method of claim 4, wherein the composition comprises an enzyme which is a multifunctional enzyme that has at least two of a chymotrypsin, trypsin, collagenase, elastase or exo peptidase activity and comprises an amino acid sequence that has at least 95% identity to a reference sequence, wherein the reference sequence is (i) the amino acid 64-300 sequence of SEQ ID NO:21, or (i) a sequence which is that of the amino acid 64-300 sequence of SEQ ID NO:21 except that it has one or more of the amino acid substitutions found in the amino acid 1-185 sequence of SEQ ID NO:22, or one or more of the amino acid substitutions found in the amino acid 72-178 sequence of SEQ ID NOS:23 or 24, or one or more of the amino acid substitutions found in the amino acid 1-211 sequence of SEQ ID NO:25, or one or more of the amino acid substitutions found in the amino acid 66-302 sequence of SEQ ID NO:26, or has asparagine or lysine at a residue corresponding to residue 68 of SEQ ID NO:21. 29. The method of claim 28, further comprising treating the donor tissue ex vivo. 30. The method of claim 28, wherein the multifunctional enzyme comprises an amino acid sequence that matches a reference sequence. 31. The method of claim 30, further comprising treating the donor tissue ex vivo.

Details for Patent 6,232,088

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2015-02-08