Methods and materials for treating autoimmune and/or complement mediated diseases and conditions

• US 20110104156A1
• Filed: 12/23/2010
• Published: 05/05/2011
• Est. Priority Date: 09/11/2003
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Tuzun, Erdem, Christadoss, Premkumar
• Granted Patent: US 8,501,705 B2
• Time in Patent Office: Days
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 16/18 against material from animals or humans

Abstract

Disclosed are methods for treating an autoimmune and/or complement mediated disease or condition in a subject. The methods include administering to the subject a compound which inhibits the subject'"'"'s classical complement pathway. The methods include administering to the subject a compound which inhibits the subject'"'"'s classical complement pathway. Compositions which include inhibitors of C1q, C1r, C1s, C2 or C4 and a pharmaceutically acceptable excipient are also described.

Claims

1. A method for treating an autoimmune and/or complement mediated disease or condition in a subject, said method comprising the step of:

administering to the subject a compound which inhibits the subject'"'"'s classical complement pathway.

2. A method according to claim 1, wherein the compound inhibits the subject'"'"'s classical complement pathway by inhibiting C1q, C1r, C1s, C2, C4, or the interaction between C2 and C4.

3. A method according to claim 2, wherein said compound that inhibits the interaction between C2 and C4 has a sequence shown in SEQ ID:

22.

4. A method according to claim 2, wherein inhibitor of C1q is a C1q inhibiting peptide selected from the group consisting of SEQ ID nos:

1-18.

5. A method according to claim 2, wherein inhibitor of C1q is CINRYZE, which is FDA-approved plasma-derived C1 esterase inhibitor used for hereditary angioedema.

6. A method according to claim 2, wherein inhibitor of C1r and C1s is a peptide that inhibits C1r or Cis, said peptide has a sequence selected from the group consisting of SEQ ID nos:

35-37.

7. A method according to claim 1, wherein the compound is an inhibitor of C2.

8. A method according to claim 7, wherein the inhibitor of C2 is an anti-C2 antibody selected from the group consisting of an anti-C2 monoclonal antibody, an anti-C2 polyclonal antibody and a chimeric humanized anti-C2 antibody.

9. A method according to claim 1, wherein the autoimmune and/or complement mediated disease or condition is selected from the group consisting of myasthenia gravis, pemphigus, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, autoimmune glomerulonephritis, Type I diabetes, atherosclerosis, rheumatoid arthritis, Hashimoto'"'"'s disease, Graves disease, dermatomyositis, autoimmune vitiligo, psoriasis, Guillain-Barre syndrome, Kawasaki syndrome, kidney reperfusion injury and hyperacute graft rejection in a subject.

10. A method according to claim 7, wherein the inhibitor of C2 is a C2 small interfering RNA.

11. A method according to claim 10, wherein the small interfering RNA is a human C2 small interfering RNA.

12. The method of claim 11, wherein the sequence of said human C2 small interfering RNA is a sequence having at least 90% identity to a sequence selected from the group consisting of SEQ ID nos:

24-25, SEQ ID nos;

27-28, SEQ ID nos;

30-31 and SEQ ID nos;

33-34.

13. A composition for treating an autoimmune and/or complement mediated disease or condition in a subject, said composition comprising:

an inhibitor of C2.

14. The composition of claim 13, wherein the inhibitor of C2 is selected from the group consisting of:

an anti-C2 monoclonal antibody, an anti-C2 polyclonal antibody, a chimeric humanized anti-C2 antibody and a C2 small interfering RNA.

15. The composition of claim 14, wherein said C2 small interfering RNA is a human C2 small interfering RNA.

16. The composition of claim 15, wherein the sequence of said human C2 small interfering RNA is a sequence having at least 90% identity to a sequence selected from the group consisting of SEQ ID nos:

24-25, SEQ ID nos;

27-28, SEQ ID nos;

30-31 and SEQ ID nos;

33-34.

17. A kit for treating an autoimmune and/or complement mediated disease or condition in a subject, comprising the composition of claim 16.

18. A method for treating myasthenia gravis in a subject, said method comprising the step of:

administering to the subject a compound which inhibits the subject'"'"'s classical complement pathway.

19. A method according to claim 18, wherein the compound inhibits the subject'"'"'s classical complement pathway by inhibiting C1q, C2, or C4.

20. A method according to claim 19, wherein the inhibitor of C2 is an anti-C2 antibody, selecting from the group consisting of:

an anti-C2 monoclonal antibody, an anti-C2 polyclonal antibody and a chimeric humanized anti-C2 antibody.

21. A method according to claim 19, wherein the inhibitor of C2 is a C2 small interfering RNA.

22. The method of claim 21, wherein the sequence of said C2 small interfering RNA is a sequence having at least 90% identity to a sequence selected from the group consisting of SEQ ID nos:

24-25, SEQ ID nos;

27-28, SEQ ID nos;

30-31 and SEQ ID nos;

33-34.

23. A method according to claim 18, wherein the inhibitor of C2 is a C2 and receptor inhibiting peptide selected from the group consisting of SEQ ID nos:

19-21.