IP Library Granted Patent US 8,492,347
Granted Patent B2
US 8,492,347 · App. 12/682,759 · Granted Jul 23, 2013

Peptide for induction of immune tolerance as treatment for systemic lupus erythematosus

Inventors: Bevra H. Hahn (Encino, CA); Fanny M. Ebling (Encino, CA); Antonio La Cava (Santa Monica, CA); Ram Raj Singh (Los Angeles, CA); Ram Pyare Singh (Los Angeles, CA)
Assignee: The Regents of the University of California
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Quick Facts
Patent No.
US 8,492,347
App. No.
12/682,759
Granted
Jul 23, 2013
Kind
B2
Abstract

The present invention relates to D-amino acid peptides and their use in methods for the diagnosis and/or treatment of immune disorders such as systemic lupus erythematosus.

Claims (27)

1. A composition comprising a peptide having the sequence: FIEWNKLRFRQGLEW (SEQ ID NO: 1), wherein at least one amino acid moiety is a D-amino acid.

2. The composition of claim 1 , wherein 14 amino acid moieties are D-amino acids.

3. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier used in orally administered medications.

4. The composition of claim 1 , wherein the D-amino acid peptide is coupled to a heterologous amino acid sequence.

5. A method of binding a D-amino acid peptide having the sequence: FIEWNKLRFRQGLEW (SEQ ID NO: 1) to a T lymphocyte, the method comprising:

combining the peptide with the T lymphocyte; and

allowing the peptide to bind the T lymphocyte so that the peptide is bound to the T lymphocyte.

6. The method of claim 5 , wherein the method is used to identify the T lymphocyte as a CD4+CD25− helper T lymphocyte.

7. The method of claim 5 , wherein the binding of the peptide to the T lymphocyte comprises an assay for screening the presence or susceptibility of a mammal to an immunological disorder, the assay comprising:

labeling the peptide with a detectable label;

incubating the labelled peptide with the T cells so that the labelled peptide is bound to the T cells; and

observing the amount of peptide bound cells, wherein the extent of the binding of the peptide to the T cells is correlated to the presence or susceptibility to the disorder.

8. The method of claim 7 , wherein the disorder comprises the production of autoantibodies.

9. The method of claim 5 , wherein the method is performed in vitro.

10. A method of inhibiting the production of autoantibodies that bind double stranded DNA in a mammal, the method comprising administering to the mammal an isolated D-amino acid peptide comprising the sequence: FIEWNKLRFRQGLEW (SEQ ID NO: 1), wherein the isolated peptide:

binds to Major Histocompatibility Complex polypeptides expressed by T cells in the mammal; and

inhibits the production of autoantibodies that bind double stranded DNA in the mammal.

11. The method of claim 10 , wherein the mammal suffers from an autoimmune disorder comprising systemic lupus erythematosus (SLE).

12. The method of claim 10 , wherein the mammal suffers from an autoimmune disorder comprising nephritis.

13. The method of claim 10 , wherein the D-amino acid peptide is coupled to a heterologous amino acid sequence.

14. The method of claim 13 , wherein the heterologous amino acid sequence comprises a constant region from an immunoglobulin.

15. The method of claim 10 , wherein the D-amino acid peptide is administered orally.

16. The method of claim 15 , wherein the D-amino acid peptide is combined with a pharmaceutically acceptable carrier comprising a composition that inhibits acidic or enzymatic degradation of the peptide.

17. The method of claim 10 , wherein the administration of the D-amino acid peptide results in an induction of CD4+CD25+Foxp3+ T cells or CD8+Foxp3+ T cells in the mammal.

18. The method of claim 10 , wherein the administration of the D-amino acid peptide reduces the number of the mammal's splenic B cells that make antibodies that bind double stranded DNA by at least about 50%.

19. The method of claim 10 , wherein the administration of the D-amino acid peptide results in a decrease in the concentration of proteins present in the urine of the mammal.

20. A kit, comprising a container and, within the container, an isolated D-amino acid peptide comprising the sequence: FIEWNKLRFRQGLEW (SEQ ID NO: 1), wherein the peptide is capable of binding a T lymphocyte.

Assignments (1)
CONFIRMATORY LICENSE Recorded Jan 29, 2013
From: UNIVERSITY OF CALIFORNIA LOS ANGELES
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 029717/0613 →
Continuity (2)
Provisional Application 60999289 · Oct 17, 2007
Related Publication 20100234302A1 · Sep 16, 2010