Synthetic immunogen

• US 5,080,896 A
• Filed: 05/06/1988
• Issued: 01/14/1992
• Est. Priority Date: 02/14/1985
• Status: Expired due to Term

• Current Assignee: Intervet International BV (Merck & Co., Inc.)
• Original Assignee: Akzo Nobel N.V. (Nouryon BV)
• Inventors: Visser, Nicolaas, Boon, Petrus J.
• Primary Examiner(s): Russel, Jefrey E.
• Assistant Examiner(s): Kim, Kay
• Application Number:
  US07/191,801
• Time in Patent Office: 1,348 Days
• Field of Search: 424/88, 424/89, 424/90, 424/91, 424/92, 424/460, 424/468, 424/450, 436/829, 530/330, 530/322, 530/403, 530/404, 530/405, 530/406
• US Class Current: 424/193.1
• CPC Class Codes: A61K 2039/6018 Lipids, e.g. in lipopeptides
• CPC Class Codes: A61K 2039/627 characterised by the linker
• CPC Class Codes: A61K 39/385 Haptens or antigens, bound to carriers
• CPC Class Codes: A61K 47/55 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence

Abstract

The present invention concerns novel immunogens. These immunogens comprise novel compounds which consist of an antigen or antigenic determinant couple dot an amphiphilic adjuvant molecule and optionally also free amphiphilic adjuvant molecules. An advantageous features of these novel immunogens is the presence of both an excellent immunogen activity as well as a pronounced adjuvant activity in a single complex.

Claims

1. Compound containing an amphiphilic adjuvant molecule, comprising at least one amphiphilic glycoside and at least one antigen or antigenic determinant, which are covalently coupled to one another.

2. Compound according to claim 1, characterized in that the antigen or antigenic determinant and the amphiphilic adjuvant molecule are linked to one another by at least one linker.

3. Compound according to claim 1, comprising a saponin as the amphiphilic adjuvant.

4. Compound according to claim 2, characterized in that it contains a saponin as the amphiphilic adjuvant.

5. Immunogen comprising at least one type of antigens or antigenic determinants derived from a microorganism or a hormone coupled to a carrier, wherein the carrier is a micelle comprising at least one type of amphiphilic adjuvant molecules, of which at least a portion are covalently coupled to the antigens or antigenic determinants.

6. Immunogen according to claim 5, wherein the antigens or antigenic determinants are coupled to the amphiphilic adjuvant molecule by means of at least one linker.

7. Immunogen according to claim 5, comprising at least one saponin as an amphiphilic adjuvant.

8. Immunogen according to claim 5, comprising more than one type of antigens or antigenic determinants, which are characteristic of more than one type of pathogen against which immunization is desired.

9. Immunogen according to claim 5 that has been stabilized by having at least a portion of the antigenic determinants or antigens, or at least a portion of the amphiphilic adjuvant molecule, or a portion of each, linked to one another.

10. Immunogen according to claim 5, characterized in that it is encapsulated.

11. An immunogen according to claim 5, comprising at least one type of amphiphilic adjuvant selected from the group consisting of avridine (N,N-dioctadecyl-N'"'"',N'"'"'-bis(2-hydroxyethyl)-propanediamine);

4-aminomethyl-1-(2,3-(di-n-decyloxy)-n-propyl)-4-phenylpiperidine;

dimethyl-dioctadecylammonium bromide;

laurylmuramyl-dipeptide;

lauryltetrapeptide (N² -[N-(N-lauryl-L-alanyl)-gamma-D-glutamyl]-N⁶ -(glycyl)-D,D-L,L-2,6-diaminepimelamic acid;

L-tyrosine and alkyl derivatives thereof.

12. An immunogen according to claim 5, comprising at least one type of amphiphilic adjuvant selected from the group consisting of maltose tetrapalmitate, pluronic polyols, L-tyrosineazobenzene-p-arsonate, sorbitanmonooleate, trehalose, retinoic acid, D,L-α

-tocopherol, lipid A, a saponin, a carbomer and derivatives thereof.

13. Immunogen according to claim 6, characterized in that it contains saponins as amphiphilic adjuvants.

14. Immunogen according to claim 13, comprising more than one type of antigen or antigenic determinant characteristic of more than one type of pathogen against which immunization is desired.

15. Immunogen according to claim 13, that has been stabilized by having at least a portion of the antigenic determinant or determinant or antigen, or at least a portion of the amphiphilic adjuvant molecule, or a portion of each, linked to one another.

16. Immunogen according to claim 6, comprising more than one type of antigen or antigenic determinant characteristic of more than one type of pathogen against which immunization is desired.

17. Immunogen according to claim 16, that has been stabilized by having at least a portion of the antigenic determinant or antigen, or at least a portion of the amphiphilic adjuvant molecule, or a portion of each, linked to one another.

18. Immunogen according to claim 6, that has been stabilized by having at least a portion of the antigenic determinant or antigen, or at least a portion of the amphiphilic adjuvant molecule, or a portion of each, linked to one another.

19. Immunogen according to claim 6, which is encapsulated.

20. Immunogen according to claim 7, comprising more than one type of antigen or antigenic determinant characteristic of more than one type of pathogen against which immunization is desired.

21. Immunogen according to claim 20, that has been stabilized by having at least a portion of the antigenic determinant or antigen, or at least a portion of the amphiphilic adjuvant molecule, or a portion of each, linked to one another.

22. Immunogen according to claim 7 that has been stabilized by having at least a portion of the antigenic determinants that are characteristic of more than one type of pathogen against which immunization is desired.

23. Immunogen according to claim 7, characterized in that it is encapsulated.

24. Immunogen according to claim 8, that has been stabilized by having at least a portion of the antigenic determinant or antigen, or at least a portion of the amphiphilic adjuvant molecule, or a portion of each, linked to one another.

25. Immunogen according to claim 8, characterized in that it is encapsulated.

26. Pharmaceutical preparation having an immunizing action, comprising an effective amount of at least one immunogen as defined in claim 5.

27. Pharmaceutic preparation according to claim 26, comprising two or more different types of said immunogens.

28. Pharmaceutical preparation according to claim 26, comprising a plurality of said immunogens in a delayed-release dosage form.

29. Pharmaceutical preparation according to claim 28, characterized in that it contains an effective amount of two or more different types of the said immunogens.

30. Pharmaceutical preparation having an immunizing action, characterized in that it contains an effective amount of at least one immunogen as defined in claim 6.

31. Pharmaceutical preparation according to claim 30, characterized in that it contains two or more different types of the said immunogens.

32. Pharmaceutical preparation according to claim 30, characterized in that it contains a plurality of the said immunogens in a delayed-release dosage form.

33. Pharmaceutical preparation according to claim 32, characterized in that it contains two or more different types of the said immunogens.

34. Pharmaceutical preparation having an immunizing action, characterized in that it contains an effective amount of at least one immunogen as defined in claim 7.

35. Pharmaceutical preparation according to claim 34, characterized in that it contains two or more different types of the said immunogens.

36. Pharmaceutical preparation according to claim 34, characterized in that it contains a plurality of the said immunogens in a delayed-release dosage form.

37. Pharmaceutical preparation according to claim 36, characterized in that it contains two or more different types of the said immunogens.

38. Pharmaceutical preparation having an immunizing action, characterized in that it contains an effective amount of at least one immunogen as defined in claim 8.

39. Pharmaceutical preparation according to claim 38, characterized in that it contains two or more different types of the said immunogens.

40. Pharmaceutical preparation according to claim 38, characterized in that it contains a plurality of the said immunogens in a delayed-release dosage form.

41. Pharmaceutical preparation according to claim 40, characterized in that it contains two or more different types of the said immunogens.

42. Immunogen according to claim 9, characterized in that it is encapsulated.

43. Pharmaceutical preparation having an immunizing action, characterized in that it contains an effective amount of at least one immunogen as defined in claim 9.

44. Pharmaceutical preparation according to claim 43, characterized in that it contains two or more different types of the said immunogens.

45. Pharmaceutical preparation according to claim 43, characterized in that it contains a plurality of the said immunogens in a delayed-release dosage form.

46. Pharmaceutical preparation according to claim 45, characterized in that it contains two or more different types of the said immunogens.

47. Pharmaceutical preparation having an immunizing action, characterized in that it contains an effective amount of at least one immunogen as defined in claim 10.

48. Pharmaceutical preparation according to claim 47, characterized in that it contains two or more different types of the said immunogens.

49. Pharmaceutical preparation according to claim 47, characterized in that it contains a plurality of the said immunogens in a delayed-release dosage form.

50. Pharmaceutical preparation according to claim 49, characterized in that it contains two or more different types of the said immunogens.