ANNEXIN II COMPOSITIONS FOR TREATING OR MONITORING INFLAMMATION OR IMMUNE-MEDIATED DISORDERS

• US 20100098715A1
• Filed: 12/22/2009
• Published: 04/22/2010
• Est. Priority Date: 07/14/2008
• Status: Abandoned Application

• Current Assignee: University of Hong Kong (Government of Hong Kong Special Administrative Region)
• Original Assignee: University of Hong Kong (Government of Hong Kong Special Administrative Region)
• Inventors: Chan, Daniel Tak Mao, Yung, Susan Sou Ying
• Application Number:
  US12/645,036
• Publication Number:
  US 20100098715A1
• Time in Patent Office: Days
• US Class Current: 514/1.1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/711 Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 38/02 Peptides of undefined number of amino acids; Derivatives thereof
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: G01N 2333/4718 Lipocortins
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9

Abstract

Methods and compositions for treating, detecting, diagnosing or assisting in the diagnosis of an inflammatory or immunological disorder are provided. The authors have made the novel discovery that anti-dsDNA antibodies are reactive to cell surface annexin II and through this interaction, anti-dsDNA antibodies are bound and then internalized and translocated into the cytoplasm and/or nucleus where they mediate altered cellular functions. Compositions that inhibit or interfere with the interaction of annexin II with anti-dsDNA antibodies can be used to treat one or more symptoms or pathological processes of an inflammatory or immunological disorder, preferably an auto-immune disorder. Methods for monitoring the progression or severity of an inflammatory or immunological disorder are also provided. In certain embodiments, levels of annexin II and/or anti-dsDNA antibodies, including anti-dsDNA antibodies that can bind to annexin II, are assessed and compared to a reference level of annexin II and/or anti-dsDNA antibodies that corresponds to a specific stage or severity of the disorder.

Claims

1-15. -15. (canceled)

16. A method for treating an inflammatory or immunological disease or disorder characterized by the presence of anti-dsDNA antibodies comprising,

administering a composition comprising an effective amount of a ligand for annexin II to a subject in need thereof to inhibit or reduce internalization of anti-DNA antibodies in cells expressing annexin II on their surface.

18. The method of claim 16, wherein the inflammatory or immunological disease or disorder characterized by the presence of anti-dsDNA antibodies is an autoimmune disease.

19. The method of claim 18, wherein the inflammatory or immunological disease or disorder characterized by the presence of anti-dsDNA antibodies is systemic lupus erythematosus.

20. The method of claim 16, wherein the inflammatory or immunological disease or disorder characterized by the presence of anti-dsDNA antibodies is a kidney disease or disorder.

21. The method of claim 20, wherein the immunological disease or disorder characterized by the presence of anti-dsDNA antibodies is lupus nephritis.

22. The method of claim 16, wherein the ligand is a polypeptide.

23. The method of claim 22, wherein the polypeptide is an antibody or annexin II binding fragment thereof.

17. (canceled)

24. A method for treating an inflammatory or immunological disease or disorder characterized by the presence of anti-dsDNA antibodies comprising, administering a composition to a subject in need thereof comprising an effective amount of an inhibitory nucleic acid to downregulate cellular expression of annexin II to inhibit or reduce internalization of anti-DNA antibodies in cells expressing annexin II on their surface.

25. The method of claim 24, wherein the inflammatory or immunological disease or disorder characterized by the presence of anti-dsDNA antibodies is an autoimmune disease.

26. The method of claim 25, wherein the inflammatory or immunological disease or disorder characterized by the presence of anti-dsDNA antibodies is systemic lupus erythematosus.

27. The method of claim 24, wherein the inflammatory or immunological disease or disorder characterized by the presence of anti-dsDNA antibodies is a kidney disease or disorder.

28. The method of claim 27, wherein the immunological disease or disorder characterized by the presence of anti-dsDNA antibodies is lupus nephritis.

29. The method of claim 24, wherein the inhibitory nucleic acid is selected from the group consisting of dsRNA, siRNA, microRNA, antisense DNA or combinations thereof.

30. The method of claim 29, wherein the dsRNA is at least about 21 nucleotides.