Multiple antigen peptide system

• US 5,229,490 A
• Filed: 12/20/1990
• Issued: 07/20/1993
• Est. Priority Date: 05/06/1987
• Status: Expired due to Fees

• Current Assignee: Rockefeller University
• Original Assignee: Rockefeller University
• Inventors: Tam, James P.
• Primary Examiner(s): Nucker, Christine M.
• Assistant Examiner(s): KIM, KAY KWANG AE
• Application Number:
  US07/631,185
• Time in Patent Office: 943 Days
• Field of Search: 530/323, 530/324, 530/326, 530/327, 530/345, 530/405, 530/325, 530/328, 530/409, 530/403, 514/13, 514/12, 514/14, 514/15, 514/21, 424/88, 424/92, 424/89, 930/30, 930/210, 930/221
• US Class Current: 530/324
• CPC Class Codes: C07K 14/001 by chemical synthesis
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/445 Plasmodium
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C08G 83/003 Dendrimers
• CPC Class Codes: C12N 2730/10122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: Y10S 930/221 Retrovirus related, or human immunodeficiency virus related, or simian immunodeficiency virus related
• CPC Class Codes: Y10S 977/754 Dendrimer, i.e. serially branching or "tree-like" structure

Abstract

Multiple antigen peptide systems are described in which a large number of antigens are bound to the functional groups of a dendritic core molecule providing a high concentration of antigen in a low molecular volume. The products are useful for producing chemically defined univalent or multivalent vaccines and in diagnostic tests.

Claims

1. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues to which a plurality of antigenic molecules are joined by covalent bonds.

3. The antigenic product of claim 1 wherein the core molecule is lysine.

4. The antigenic product of claims 1, 2 or 3 wherein the antigenic molecules are identical.

5. The antigenic product of claims 1, 2 or 3 wherein the antigenic molecules are different.

6. The antigenic product of claims 1, 2 or 3 wherein the antigenic molecules are a combination of T-cell and B-cell antigens.

33. An antigenic product of claim 1 or 2 in which the antigenic molecule is a peptide.

2. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues the core molecule of which contains at least two amino groups to which polyamide branches are joined through peptide bonds, said branches having terminal functional groups which are covalently bonded to antigenic molecules.

7. (Phe-Glu-Pro-Ser-Glu-Ala-Glu-Ile-Ser-His-Thr-Gln-Lys-Ala)₈ -Lys₄ -Lys₂ -Lys-Gly-OH.

8. ((Asn-Ala-Asn-Pro)₄)₈ Lys₄ -Lys₂ -Lys.

9. (Ile-Glu-Asp-Asn-Glu-Tyr-Thr-Ala-Arg-Gln-Gly)₈ -Lys₄ -Lys₂ -Lys-Gly-OH.

10. (Tyr-Ile-Gln-His-Lys-Leu-Gln-Gln-Glu-Ile-Arg-His-Ser-Pro)₈ -Lys₄ -Lys₃ -Lys-Gly-OH.

11. (Asp-Gly-Ile-Ser-Ala-Ala-Lys-Asp-Val)₈ -Lys₄ -Lys₂ -Lys-Gly-OH.

12. An antigenic product comprising a dendritic hompolymer containing up to 10 monomeric residues to which a malarial antigenic peptide is joined by a covalent bond.

14. The antigenic product of claim 12 or 13 wherein the antigenic peptide is selected from the group consisting of:

H-(ASN-Ala-ASN-Pro)_n -OH wherein n is 3,

H-(Gly-Asp-Arg-Ala-Asp-Gly-Gln-Pro-Ala)_n -OH wherein n is 2,

Glu-Gln-Asn-Val-Glu-His-Asp-Ala,

Asn-Ala-Glu-Asn-Lys-Glu-Glu-Leu-Thr-Ser-Ser-Asp-Pro-Glu-Gly-Gln-Ile-Met.

13. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues the core molecule of which contains at least two amino groups to which polyamide branches are joined through peptide bonds, said branches having terminal functional groups to which a malarial antigenic peptide is joined by covalent bonds.

15. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues to which an hepatitis antigenic peptide is joined by a covalent bond.

17. The antigenic product of claim 15 or 16 wherein the antigenic peptide is selected from the group consisting of:

Met-Gln-Trp-Asr-Ser-Thr-Ala-Phe-His-Gln-Thr-Leu-Gln-Asp-Pro-Arg-Val-Arg-Gly-Leu-Try-Leu-Tyr-Leu-Pro-Ala-Gly-Gly,

Asp-Pro-Arg-Val-Arg-Gly-Leu-Tyr-Phe-Pro-Ala-Gly-Gly-Ser-Ser-Ser-Gly-Thr-Val and

Cys-Thr-Lys-Pro-Thr-Asp-Gly-Asn-Cys-Thr-Cys.

16. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues the core molecule of which contains at least two amino groups to which polyamide branches are joined through peptide bonds, said branches having terminal functional groups to which an hepatitis antigenic peptide is joined by a covalent bond.

18. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues to which a streptococcus antigenic peptide is joined by a covalent bond.

20. The antigenic product of claim 18 or 19 wherein the antigenic peptide is:

Asn-Phe-Ser-Thr-Ala-Asp-Ser-Ala-Lys-Ile-Lys-Thr-Leu-Glu-Ala-Glu-Lys-Ala-Asp-Leu-Gly-Lys-Ala-Leu-Gly-Ala.

19. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues the core molecule of which contains at least two amino groups to which polyamide branches are joined through peptide bonds, said branches having terminal functional groups to which a streptococcus antigenic peptide is joined by a covalent bond.

21. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues to which a polivirus antigenic peptide is joined by a covalent bond.

23. The antigenic product of claim 21 or 22 wherein the antigenic peptide is selected from the group consisting of:

Tyr-Ser-Thr-Leu-Ryr-Arg-Trp-Leu-Asp-Aso-Ser-Phe and

Asn-Ala-Pro-Ser-Lys-Thr-Lys-Leu-Glu-Pro-Ser-Ala-Phe.

22. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues the core molecule of which contains at least two amino groups to which polyamide branches are joined through peptide bonds, said branches having terminal functional groups to which a poliovirus antigenic peptide is joined by a covalent bond.

24. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues to which a foot and mouth disease antigenic peptide is joined by a covalent bond.

26. The antigenic product of claim 24 or 25 wherein the antigenic peptide is selected from the group consisting of:

Gly-Ser-Gly-Val-Arg-Gly-Asp-Ser-Gly-Ser-Leu-Ala-Leu-Arg-Val-Ala-Arg-Gln-Leu-Pro and

Arg-His-Lys-Gln-Lys-Ile-Val-Ala-Pro-Val-Lys-Gln-Thr-Leu.

25. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues the core molecule of which contains at least two amino groups to which polyamide brances are joined through peptide bonds, said branches having terminal functional groups to which a foot and mouth disease antigenic peptide is joined by a covalent bond.

27. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues to which an influenza virus antigenic peptide is joined by a covalent bond.

29. The antigenic product of claim 27 or 28 wherein the antigenic peptide is selected from the group consisting of:

Gly-Lue-Phe-Gly-Ala-Ile-Ala-Gly-Phe-Ile-Glu and

Arg-Ser-Lys-Ala-Phe-Ser-Asn-Cys-Tyr-Pro-Tyr-Asp-Val-Pro-Asp-Tyr-Ala-Ser.

28. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues the core molecule of which contains at least two amino groups to which polyamide branches are joined through peptide bonds, said branches having terminal functional groups to which an influenza virus antigenic peptide is joined by a covalent bond.

30. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues to which HIV antigenic peptide is joined by a covalent bond.

32. The antigenic product of claim 30 or 31 wherein the antigenic peptide is:

Arg-Ile-Leu-Ala-Val-Glu-Arg-Tyr-Leu-Lys-Asp-Gln-Gln-Leu-Leu-Gly-Ile-Trp-Gly-Cys-Ser.

31. An antigenic product comprising a dendritic homopolymer containing up to 10 monomeric residues the core molecule of which contains at least two amino groups to which polyamide branches are joined through peptide bonds, said branches having terminal functional groups to which HIV antigenic peptide is joined by a covalent bond.