METHODS AND COMPOSITIONS FOR TREATING DEGOS' DISEASE

• US 20130064820A1
• Filed: 03/01/2011
• Published: 03/14/2013
• Est. Priority Date: 03/01/2010
• Status: Active Grant

• Current Assignee: Alexion Pharmaceuticals Incorporated (Astrazeneca PLC)
• Original Assignee: Alexion Pharmaceuticals Incorporated (Astrazeneca PLC)
• Inventors: Magro, Cynthia
• Granted Patent: US 8,999,340 B2
• Time in Patent Office: Days
• US Class Current: 424/135.1
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• 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 31/245 Amino benzoic acid types, e.g. procaine, novocaine salicylic acid esters A61K31/60
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/1725 Complement proteins, e.g. anaphylatoxin, C3a or C5a
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 : Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The present disclosure relates to, inter alia, compositions containing an inhibitor of human complement and/or an inhibitor of interferon alpha, and the use of the compositions in methods for treating or preventing Degos'"'"' disease in a subject. In some embodiments, the inhibitor is an antibody, or antigen-binding fragment thereof, that binds to a human complement component C5 protein or to a biologically-active fragment of C5 such as C5a or C5b. In some embodiments, the inhibitor is an antibody, or an antigen-binding fragment thereof, that binds to interferon alpha or to an interferon alpha receptor.

Claims

1. A method for treating a patient afflicted with Degos'"'"' disease, the method comprising administering to a patient afflicted with Degos'"'"' disease a complement inhibitor in an amount sufficient to treat the disease or lessen the severity of one or more symptoms of the disease.

2. The method of claim 1, wherein the complement inhibitor is chronically administered to the patient.

3. The method of claim 1, further comprising identifying a patient as being, or likely to be, afflicted with Degos'"'"' disease.

4. The method of claim 1, wherein the Degos'"'"' disease is associated with a B19 parvoviral infection or human immunodeficiency virus infection.

5. The method of claim 1, wherein the Degos'"'"' disease is idiopathic.

6. The method of claim 1, wherein the Degos'"'"' disease pathologically affects the gastrointestinal tract, the central nervous system, or the cardiovascular system.

9. The method of claim 1, wherein the Degos'"'"' disease is multiorgan, systemic Degos'"'"' disease.

10. The method of claim 1, wherein the Degos'"'"' disease is refractory to at least one therapy selected from the group consisting of an anti-inflammatory agent, an anticoagulant, an antithrombotic, and intravenous immunoglobulin.

14. The method of claim 1, wherein the complement inhibitor is selected from the group consisting of soluble CR1, LEX-CR1, MCP, DAF, CD59, Factor H, cobra venom factor, FUT-175, complestatin, and K76 COOH.

19. The method of claim 1, wherein the complement inhibitor is an antibody or an antigen-binding fragment thereof that binds to a human complement component protein.

20. The method of claim 19, wherein the antibody or antigen-binding fragment thereof binds to a human complement component C5 protein.

22. The method of claim 20, wherein the antibody inhibits the cleavage of complement component C5 into fragments C5a and C5b.

26. The method of claim 19, wherein the antibody or antigen-binding fragment thereof is selected from the group consisting of a humanized antibody, a recombinant antibody, a diabody, a chimerized or chimeric antibody, a deimmunized human antibody, a fully human antibody, a single chain antibody, an Fv fragment, an Fd fragment, an Fab fragment, an Fab′

fragment, and an F(ab′

)₂ fragment.

27. The method of claim 1, wherein the complement inhibitor is eculizumab.

28. The method of claim 1, wherein the complement inhibitor is pexelizumab.

53. The method of claim 1, further comprising administering to the patient an inhibitor of interferon alpha.

54. The method of claim 53, wherein the inhibitor of interferon alpha is an antibody or an antigen-binding fragment thereof that binds to interferon alpha or an interferon alpha receptor.

7-8. -8. (canceled)

11-13. -13. (canceled)

15-18. -18. (canceled)

21. (canceled)

23-25. -25. (canceled)

29-34. -34. (canceled)

35. A method for treating a patient afflicted with Degos'"'"' disease, the method comprising administering to a patient afflicted with Degos'"'"' disease an inhibitor of interferon alpha in an amount sufficient to treat the disease or lessen the severity of one or more symptoms of the disease.

43. The method of claim 35, wherein the inhibitor of interferon alpha is an antibody or an antigen-binding fragment thereof that binds to interferon alpha or an interferon alpha receptor.

36-42. -42. (canceled)

44-52. -52. (canceled)

55. A pharmaceutical composition or package comprising:

(i) a complement inhibitor and (ii) an inhibitor of interferon alpha.