Patent EA-004956-B1 (EA)
Title: Hapten-carrier conjugates, antibody and process for producing thereof, functional fragment of the antibody, a kit for determining the presence of nicotine in a sample, a vaccine composition and method of preventing or treating nicotine addiction
Inventor: ENNIFAR SOFIANE
IPC: A61K47/48
Filed: 1999-12-01
Abstract: 1. A hapten-carrier conjugate of the following formula: wherein m is 1 to 2500, n is 0 to 12, y is 1 to 12, X is selected from the group consisting of NH-CO, CO-NH, CO-NH-NH, NH-NH-CO, NH-CO-NH, CO-NH-NH-CO, and S-S; Y is selected from the group consisting of NH-CO, CO-NH, CO-NH-NH, NH-NH-CO, NH-CO-NH, CO-NH-NH-CO, and S-S, and the -(CH2)n-X-(CH2)y-Y-moiety is bonded to the 3', 4' or 5' position of nicotine. 2. The conjugate of claim 1, wherein m is 11 to 17, n is 1, y is 2, X is NH-CO, Y is CO-NH, wherein the -(CH2)n-X-(CH2)y-Y- is bonded to the 3' position of nicotine. 3. The conjugate of claim 1, wherein m is 11 to 17, n is 1, y is 2, X is NH-CO, Y is CO-NH, wherein the -(CH2)n-X-(CH2)y-Y- is bonded to the 4' position of nicotine. 4. The conjugate of claim 1, wherein m is 11 to 17, n is 1, y is 2, X is NH-CO, Y is CO-NH, wherein the- (CH2)n-X-(CH2)y-Y- is bonded to the 5' position of nicotine. 5. The conjugate of claim 1, wherein m is selected from the group consisting of 1 to 20 and 1 to 200. 6. The conjugate of any one of claims 1 to 5, wherein the carrier protein is exoprotein A. 7. A hapten-carrier conjugate of the following formula: wherein m is 11 to 17, n is 1, y is 2, X is NH-CO, Y is CO-NH, the carrier protein is exoprotein A, the -(CH2)n-X-(CH2)y-Y- is bonded to the 3' position. 8. A hapten-carrier conjugate of the following formula: wherein n is 0 to 12, j is 1 to 1000, k is 1 to 20, and E is an amino acid-containing matrix. 9. The hapten-carrier conjugate of claim 8, wherein the matrix is poly-L-glutamic acid. 10. The hapten-carrier conjugate of any one of claims 1 to 9, wherein said conjugate is made using trans-4'-carboxy-(-)-cotinine as the starting material. 11. An antibody produced in response to the hapten-carrier conjugate of any one of claims 1 to 10. 12. The antibody of claim 11, which is a monoclonal antibody. 13. The antibody of claim 11, which is a polyclonal antibody. 14. A functional fragment of the antibody of claim 11. 15. A kit for determining the presence of nicotine in a sample, comprising an antibody or a functional fragment thereof of any one of claims 11 to 14. 16. A process for producing an antibody, comprising immunizing a host mammal with the hapten-carrier conjugate of any one of claims 1 to 10. 17. The process of claim 16 wherein the antibody is monoclonal. 18. A vaccine composition comprising at least one conjugate of any one of claims 1 to 10. 20. A vaccine composition consisting essentially of a hapten-carrier conjugate of any one of claims 1 to 10. 21. A vaccine composition consisting of a hapten-carrier conjugate of any one of claims 1 to 10. 22. A vaccine composition consisting of a hapten-carrier conjugate of any one of claims 1 to 10 and at least one adjuvant. 23. A vaccine composition consisting of a hapten-carrier conjugate of any one of claims 1 to 10, at least one adjuvant, and at least one excipient. 24. A vaccine composition consisting of a hapten-carrier conjugate of any one of claims 1 to 10, at least one adjuvant, at least one excipient, and at least one auxiliary agent. 25. A method of preventing or treating nicotine comprising administering a therapeutically effective amount of the hapten-carrier conjugate of any one of claims 1 to 10. 26. A method of preventing or treating nicotine addiction comprising administering a therapeutically effective amount of the antibody or the functional fragment thereof of any one of claims 11 to 14. 27. A method of preventing or treating nicotine addiction comprising administering a therapeutically effective amount of the hapten carrier conjugate of any one of claims 1 to 10 and further comprising administering a compound that is useful in the treatment of nicotine addiction.