Compounds for neutralizing the effects of secreted pla2iia

Abstract

A compound comprising at least a structural entity which binds secretory phospholipase A2 IIA (sPLA2 IIA) or parts of it and more preferably human sPLA2 IIA and which a.) blocks at least one or more sPLA2 IIA function on cell surfaces or in a solution, preferably blood or other body fluids or from tissues, most preferably in vivo, b.) and/or depletes sPLA2 IIA from a solution, preferably blood or other body fluids or from tissues, most preferably in vivo.

1 - 26 . (canceled)  
     
     
         27 : A compound comprising a structural entity which binds or inhibits secretory phospholipase A2 IIA (sPLA2 IIA) or parts of it, wherein the compound 
 a) blocks and/or neutralizes at least one function of the sPLA2 IIA, on a cell surface or in a solution, and/or    b) depletes sPLA2 IIA from a solution.    
     
     
         28 : The compound of  claim 27  wherein the sPLA2 IIA is human sPLA2 IIA and the compound blocks and/or neutralizes the at least one function of the sPLA2 IIA in a body fluid or tissue.  
     
     
         29 : The compound according to  claim 27  being a polypeptide and the structural entity being a binding site to sPLA2 IIA.  
     
     
         30 : The compound according to  claim 27  being an antibody and the structural entity being an antigen-binding site to sPLA2 IIA.  
     
     
         31 : The compound according to  claim 30 , wherein the antibody is a monoclonal antibody.  
     
     
         32 : The compound according to  claim 31 , wherein the monoclonal antibody is obtainable by immunizing a vertebrate.  
     
     
         33 : The compound according to  claim 31 , wherein the monoclonal antibody is obtainable by immunizing a transgenic vertebrate.  
     
     
         34 : The compound according to  claim 31 , wherein the monoclonal antibody is obtainable by immunizing a humanized (with a humanized immune system) vertebrate.  
     
     
         35 : The compound according to  claim 27 , wherein the monoclonal antibody is obtainable by immunizing an immune defective mouse repopulated with vital immune cells.  
     
     
         36 : The compound according to  claim 30 , wherein the antibody is a recombinant antibody.  
     
     
         37 : The compound according to  claim 36 , wherein the antibody is a humanized or human antibody.  
     
     
         38 : A host cell producing the compound according to  claim 36 .  
     
     
         39 : A recombinant vector comprising a nucleotide sequence encoding the compound according to  claim 36 , operably linked to a regulating sequence capable of expressing the antibody in a host cell.  
     
     
         40 : A secretory protein comprising the compound according to  claim 36 .  
     
     
         41 : A host cell containing the vector according to  claim 39 .  
     
     
         42 : A prokaryotic or eukaryotic cell line producing the recombinant antibody according to  claim 36 .  
     
     
         43 : A non-human eukaryotic organism producing the recombinant compound according to  claim 36 .  
     
     
         44 : A method of producing a recombinant molecule capable of binding sPLA2 IIA, comprising the steps of culturing the host cell of claim  12  to produce the compound and isolating the produced compound.  
     
     
         45 : A method of using the compound of  claim 27  comprising administering a therapeutically effective amount of the compound to a patient having an increased IL-6, CRP, and/or sPLA2 level to inhibit an immunologic, inflammatory, and/or pathophysiological response.  
     
     
         46 : A pharmaceutical composition for reducing the sPLA2 IIA concentration and/or blocking, neutralizing sPLA2 IIA, containing a therapeutically effective amount of the compound according to  claim 27  and a pharmaceutically acceptable carrier.  
     
     
         47 : A method of treatment for reducing inflammatory immune and/or pathophysiological responses, the method comprising reducing the sPLA2 IIA concentration and/or neutralizing sPLA2 IIA by administering to a patient in need of the treatment a therapeutically effective amount of the pharmaceutical composition according to  claim 46 .  
     
     
         48 : A method of treatment for reducing cell and/or endothel injury and/or destruction, the method comprising reducing the sPLA2 IIA concentration and/or neutralizing sPLA2 IIA by administering to a patient in need of the treatment a therapeutically effective amount of the pharmaceutical composition according to  claim 46 .  
     
     
         49 : A method of treatment for reducing acute endothelial injury and/or destruction associated with stroke, cardiac infarction, avoidance of sudden cardiac death, burnt offering, for severe surgery or other injury with severe wound areas, diabetic shock, acute liver failure, pancreatitis, neurodegenerative diseases, or irradiation-induced leukemia, the method comprising reducing the sPLA2 IIA concentration and/or neutralizing sPLA2 IIA by administering to a patient in need of the treatment a therapeutically effective amount of the pharmaceutical composition according to  claim 46 .  
     
     
         50 : A method of treatment for reducing long term endothelial injury and/or destruction associated with medium CRP-amounts, atherosclerosis, unstable angina, diabetes type I or type II, overweight and/or obesity, alcoholism, Hormone Replacement Therapy (HRT), old age, or smoking, the method comprising administering to a patient in need of the treatment a therapeutically effective amount of the pharmaceutical composition according to  claim 46 .  
     
     
         51 : A method of treatment for preventing allograft transplant rejection or xeno-transplant rejection, the method comprising administering to a patient in need of the treatment a therapeutically effective amount of the pharmaceutical composition according to  claim 46 .  
     
     
         52 : A method of treatment for induction of allo-transplant or xeno-transplant tolerance or inhibition of T cell activation, the method comprising administering to a patient in need of the treatment a therapeutically effective amount of the pharmaceutical composition according to  claim 46 .  
     
     
         53 : A method of treatment or prevention of an autoimmune disease, the method comprising administering to a patient in need of the treatment a therapeutically effective amount of the pharmaceutical composition according to  claim 46 .  
     
     
         54 : A method of treatment or prevention of an autoimmune disease selected from the group consisting of SLE, osteo arthritis, rheumatoid arthritis, multiple sclerosis, myasthenia gravis, Graves' disease, psoriasis vulgaris, dilated cardiomyopathy, diabetes mellitus, Bechterew, inflammatory bile disease, ulcerative colitis, Crohn's disease, idiopathic thrombocytopenia purpura (ITP), aplastic anemia, idiopathic dilated cardiomyopathy (IDM), autoimmune thyroiditis, Goodpastures' disease, and arterial and venous chronic inflammation, the method comprising administering to a patient in need of the treatment a therapeutically effective amount of the pharmaceutical composition according to  claim 46 .  
     
     
         55 : A method of treatment of an HIV-infected patient, the method comprising administering to a patient in need of the treatment a therapeutically effective amount of the pharmaceutical composition according to  claim 46 .  
     
     
         56 : A medicament useful to inhibit an immunologic, inflammatory, and/or pathophysiological response comprising the compound of  claim 27  in combination with an additional therapeutically active agent.  
     
     
         57 : The medicament of  claim 56  wherein the additional therapeutically active agent is an anti-inflammatory substance.  
     
     
         58 : The medicament of  claim 56  wherein the additional therapeutically active agent is selected from the group consisting of an anti-IL-6-molecule, anti-IL-1β-molecule, anti-CRP-molecule, complement blocker, and a combination thereof.