Immunomodulating compositions and methods for use in the treatment of human autoimmune diseases

• US 20060240032A1
• Filed: 03/30/2006
• Published: 10/26/2006
• Est. Priority Date: 03/31/2005
• Status: Abandoned Application

• Current Assignee: Avi Biopharma, Inc.
• Original Assignee: Avi Biopharma, Inc.
• Inventors: Iversen, Patrick L., Hinrichs, David J., Mourich, Dan V.
• Application Number:
  US11/395,663
• Publication Number:
  US 20060240032A1
• Time in Patent Office: Days
• US Class Current: 424/185.100
• CPC Class Codes: A61K 2039/64 characterised by the architecture of the carrier-antigen complex, e.g. repetition of carrier-antigen units
• CPC Class Codes: A61K 2039/645 Dendrimers; Multiple antigen peptides
• CPC Class Codes: A61K 39/0008 Antigens related to auto-immune diseases; Preparations to induce self-tolerance

Abstract

A composition and method for treating an autoimmune condition are disclosed. The composition includes of an immunomodulating compound composed of a central amino acid core having a plurality of chemical attachment groups, and a plurality of antigenic peptides which are (i) associated with an auto-immune disorder and (ii) attached to the core groups with the same N-terminus to C-terminus orientation. The compound is carried in a pharmaceutically acceptable carrier. An exemplary compound has an octomeric polylysine core and eight antigenic peptides, such as the peptides identified by SEQ ID NOS: 1-11, attached thereto. The compound is effective in treating an autoimmune disorder, by administering to a subject in need of the treatment, a pharmaceutically effective amount of the compound.

Claims

1. A composition for use in treating an autoimmune disorder, comprising

(a) an immunomodulating compound composed of a central amino acid core having a plurality of chemical attachment groups, and a plurality of antigenic peptides which are (i) associated with an auto-immune disorder and (ii) attached to said groups with the same N-terminus to C-terminus orientation, and

(b) a pharmaceutically acceptable carrier.

2. The composition of claim 1, wherein each of said antigenic peptides is attached to said amino acid core through a spacer containing a linear chain of at least about 5 atoms in length.

3. The composition of claim 1, wherein said central amino acid core is a branched polylysine core having between 4-16 attachment sites, and the compound includes between 4-16 antigenic peptides.

4. The composition of claim 3, wherein said core is composed of a polylysine octamer, and said compound includes up to eight antigenic peptides, each coupled to said octamer through the peptide'"'"'s C terminus.

5. The composition of claim 3, wherein each of said antigenic peptides is attached to said polylysine core through a spacer containing a linear chain of at least about 5 atoms in length.

6. The composition of claim 5, wherein said spacer is composed of a linear chain of at least two amino acids.

7. The composition of claim 5, wherein said spacer has the sequence identified by SEQ ID NO:

12.

8. The composition of claim 3, wherein said antigenic peptide is selected from the group consisting of SEQ ID NOS:

1-11.

9. The composition of claim 1, wherein said carrier is buffered physiological saline.

10. The composition of claim 1, wherein central amino acid core is a branched polylysine octamer having eight amine attachment sites, and said antigenic peptides are attached at the C termini to said sites, each through a spacer composed of a linear chain of at least five amino acids, and the antigenic peptides are selected from the group consisting of SEQ ID NOS:

1-11.

11. The composition of claim 10, wherein said compound includes eight antigenic peptides having selected from the group consisting of SEQ ID NOS:

1-11, and each peptide is linked to a polylysine amine attachment group through a spacer having the sequence identified by SEQ ID NO;

12.

12. A method of treating an autoimmune disorder in a mammalian subject in need of such treatment comprising

administering to said subject, in a pharmaceutically effective amount, a composition containing (a) an immunomodulating compound composed of a central amino acid core having a plurality of chemical attachment groups, and a plurality of antigenic peptides which are (i) associated with an auto-immune disorder and (ii) attached to said groups with the same N-terminus to C-terminus orientation, and (b) a pharmaceutically acceptable carrier.

13. The method of claim 12, wherein said administering includes administering a compound whose central amino acid core is a branched polylysine core having between 4-16 attachment sites, and which has between 4-16 antigenic peptides, each attached at their C termini through a spacer containing a linear chain composed of at least five amino acids.

14. The method of claim 13, for use in treating multiple sclerosis, wherein the compound administered contains, as the antigenic peptides, a peptide selected from the group consisting of SEQ ID NOS:

1, 7, or 8.

15. The method of claim 13, for use in treating early-onset diabetes, wherein the compound administered contains, as the antigenic peptides, a peptide selected from the group consisting of SEQ ID NOS:

2, 9, 10, or 11.

16. The method of claim 13, for use in treating Pemphigus vulgaris, wherein the compound administered contains, as the antigenic peptides, a peptide selected from the group consisting of SEQ ID NOS:

3-5.

17. The method of claim 13, for use in treating Celiac disease, wherein the compound administered contains, as the antigenic peptides, the peptide identified as SEQ ID NO:

6.