Covalent polar lipid-peptide conjugates for immunological targeting

• US 5,256,641 A
• Filed: 07/09/1992
• Issued: 10/26/1993
• Est. Priority Date: 11/01/1990
• Status: Expired due to Fees

• Current Assignee: State of Oregon
• Original Assignee: State of Oregon
• Inventors: Stowell, Michael H. B., Yatvin, Milton B., Malkovsky, Miroslav
• Primary Examiner(s): Rollins, John W.
• Application Number:
  US07/911,209
• Time in Patent Office: 474 Days
• Field of Search: 514/2, 514/78, 514/557, 514/885, 530/300, 530/329, 530/331
• US Class Current: 514/2.3
• CPC Class Codes: A61K 47/543 Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
• CPC Class Codes: A61K 47/544 Phospholipids
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids

Abstract

This invention relates to methods of facilitating the entry of peptides into cells and targeting such peptides to specific organelles within the cell. The invention provides methods for delivering and specific targeting of antigenically-active peptides to cells for the specific production of immunological reactivity against such peptides, as well as compositions and pharmaceutical compositions of matter comprising such peptides. This invention thereby provides improved methods for vaccine production and in vivo vaccination against pathogenic microorganisms. Methods for alleviating autoimmune disease and ameliorating tissue and organ transplant rejection using such conjugates are also provided.

Claims

1. A composition of matter comprising a peptide, a polar lipid carrier, two linker functional groups and a spacer, wherein the spacer has a first end and a second end and wherein the polar lipid is attached to the first end of the spacer through a first linker functional group and the peptide is attached to the second end of the spacer through a second linker functional group.

2. The compostion of matter of claim 1 wherein the peptide is an antigenically active peptide.

3. A composition of matter according to claim 1 wherein the spacer allows the peptide to act without being released at an intracellular site and wherein the first linker functional group attached to the first end of the spacer is strong and the second linker functional group attached to the second end of the spacer is weak.

4. A composition of matter according to claim 1 wherein the spacer allows the peptide to facilitate hydrolytic release of the peptide at an intracellular site and wherein the first linker functional group attached to the first end of the spacer is strong and the second linker functional group attached to the second end of the spacer is weak.

5. A composition of matter according to claim 1 wherein the spacer allows the spacer to facilitate enzymatic release of the peptide at an intracellular site and wherein the first linker functional group attached to the first end of the spacer is strong and the second linker functional group attached to the second end of the spacer is weak.

6. A composition of matter according to claim 1 wherein the polar lipid is sphingosine, ceramide, phosphatidyl choline, phosphatidyl glycerol, phosphatidyl ethanolamine, phosphatidyl inositol, phosphatidyl serine, cardiolipin and phosphatidic acid.

12. A method of immunizing an animal against a pathogenic microorganism, comprising the step of inoculating the animal with the composition of matter of claim 2 in a pharmaceutically acceptable carrier and in an amount sufficient to elicit an immunological response in the animal.

13. The method of claim 12 wherein the animal is a human.

16. A method of alleviating an autoimmune disease in an animal, comprising the step of inoculating the animal with the composition of matter of claim 2 in a pharmaceutically acceptable carrier and in an amount sufficient to inhibit the autoimmune response in the animal.

17. The method of claim 16 wherein the animal is a human.

20. A method of preventing tissue or organ transplant rejection in an animal, comprising the step of inoculating the animal with the composition of matter of claim 2 in a pharmaceutically acceptable carrier and in an amount sufficient to inhibit transplant rejection in the animal.

21. The method of claim 20 wherein the animal is a human.

7. A composition of matter comprising a peptide having a first functional linker group, and a polar lipid carrier having a second functional linker group, wherein the peptide is covalently linked to the polar lipid carrier by a chemical bond between the first and second functional linker groups.

8. A composition of matter according to claim 7 wherein the first functional linker group is a hydroxyl group, a primary or secondary amino group, a phosphate group or substituted derivatives thereof or a carboxylic acid group.

9. A composition of matter according to claim 7 wherein the second functional linker group is a hydroxyl group, a primary or secondary amino group, a phosphate group or substituted derivatives thereof or a carboxylic acid group.

10. A composition of matter according to claim 7 wherein the polar lipid is sphingosine, ceramide, phosphatidyl choline, phosphatidyl glycerol, phosphatidyl ethanolamine, phosphatidyl inositol, phosphatidyl serine, cardiolipin and phosphatidic acid.

11. The composition of matter of claim 7 wherein the peptide is an antigenically active peptide.

14. A method of immunizing an animal against a pathogenic microorganism, comprising the step of inoculating the animal with the composition of matter of claim 11 in a pharmaceutically acceptable carrier and in an amount sufficient to elicit an immunological response in the animal.

15. The method of claim 14 wherein the animal is a human.

18. A method of alleviating an autoimmune disease in an animal, comprising the step of inoculating the animal with the composition of matter of claim 11 in a pharmaceutically acceptable carrier and in an amount sufficient to inhibit the autoimmune response in the animal.

19. The method of claim 18 wherein the animal is a human.

22. A method of preventing tissue or organ transplant rejection in an animal, comprising the step of inoculating the animal with the composition of matter of claim 11 in a pharmaceutically acceptable carrier and in an amount sufficient to inhibit transplant rejection in the animal.

23. The method of claim 22 wherein the animal is a human.