METHODS AND COMPOSITIONS FOR IMMUNOTHERAPY AND DETECTION OF INFLAMMATORY AND IMMUNE-DYSREGULATORY DISEASE, INFECTIOUS DISEASE, PATHOLOGIC ANGIOGENESIS AND CANCER

• US 20120230953A1
• Filed: 04/09/2012
• Published: 09/13/2012
• Est. Priority Date: 12/08/2004
• Status: Abandoned Application

• Current Assignee: Immunomedics, Inc.
• Original Assignee: Immunomedics, Inc.
• Inventors: GOLDENBERG, David M., HANSEN, Hans J.
• Application Number:
  US13/442,504
• Publication Number:
  US 20120230953A1
• Time in Patent Office: Days
• US Class Current: 424/85.4
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 38/2013 IL-2
• CPC Class Codes: A61K 38/4866 Protein C (3.4.21.69)
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/40 bacterial
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• 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: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07K 16/1203 : from Gram-negative bacteria
• CPC Class Codes: C07K 16/24 : against cytokines, lymphokines or interferons
• CPC Class Codes: C07K 16/241 : Tumor Necrosis Factors
• CPC Class Codes: C07K 16/248 : IL-6
• CPC Class Codes: C07K 16/2803 : against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2896 : against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/30 : from tumour cells
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 : multispecific
• CPC Class Codes: C07K 2317/734 : Complement-dependent cytotoxicity [CDC]

Abstract

Methods and compositions for immunotherapy of inflammatory and immune-dysregulatory diseases are disclosed, using multispecific antagonists that target at least two different markers. The different targets are proinflammatory effectors of the innate immune system. The multispecific antagonists can be used to treat sepsis or septic shock.

Claims

1-18. -18. (canceled)

19. A method of treating sepsis or septic shock, comprising administering to a patient that has been diagnosed with sepsis or septic shock a therapeutic composition comprising a therapeutically effective amount of a multispecific antagonist that reacts specifically with at least two different targets on a cell, wherein a first target is MIF and a second target is selected from the group consisting of a second proinflammatory effector cytokine, a proinflammatory effector chemokine, a proinflammatory effector receptor, a coagulation factor, a complement factor, or a complement regulatory protein.

20. A method according to claim 19, wherein said multispecific antagonist is a combination of two separate antibodies.

21. A method according to claim 19, wherein said multispecific antagonist is a multispecific antibody.

22. A method according to claim 19, wherein said multispecific antagonist is a fusion protein.

23. A method according to claim 19, wherein said multispecific antagonist comprises a therapeutic agent.

24. A method according to claim 19, wherein said therapeutic composition additionally comprises a further therapeutic agent.

25. A method according to claim 19, wherein said method of treating additionally comprises administration of activated protein C.

26. A method according to claim 19, wherein said second target is a second proinflammatory effector cytokine.

27. A method according to claim 26, wherein said second target is selected from the group consisting of HMGB-I, TNF-α

, IL-1. and IL-6.

28. A method according to claim 19, wherein said second target is a proinflammatory effector chemokine.

29. A method according to claim 28, wherein said second target is selected from the group consisting of MCP-19, RANIES, MIP-1A, and MIP-1B.

30. A method according to claim 19, wherein said second target is a proinflammatory effector receptor.

31. A method according to claim 30, wherein said second target is selected from the group consisting of IL-6R IL-13R, and IL-15R.

32. A method according to claim 19, wherein said second target is a coagulation factor.

33. A method according to claim 32, wherein said second target is selected from the group consisting of TF and thrombin.

34. A method according to claim 19, wherein said second target is a complement factor.

35. A method according to claim 34, wherein said second target is selected from the group consisting of C3, C5, C3a, and C5a.

36. A method according to claim 19, wherein said second target is a complement regulatory protein.

37. A method according to claim 36, wherein said a second target is selected from the group consisting of CD46. CD55, CD59 and mCRP.

38. A method according to claim 24, wherein the further therapeutic agent is an agent for treating an autoimmune disease.

39. A method according to claim 24, wherein the further therapeutic agent is an immunomodulator.

40. A method according to claim 39, wherein the immunomodulator is a cytokine, a stem cell growth factor, a lymphotoxin, a hematopoietic factor, a colony stimulating factor (CSF), an interferon (IFN), a stem cell growth factor, erythropoietin, or thrombopoietin.

41. A method according to claim 24, wherein the further therapeutic agent is a drug or toxin.

42. A method according to claim 24, wherein the further therapeutic agent is an RNase.

43. A method according to claim 24, wherein the further therapeutic agent is an agent used in GVHD or organ transplantation.