Stable Therapeutic Proteins

Abstract

The invention relates to storable medicaments produced from pharmaceutical active ingredient preparations which are virus safe. Said medicaments contain at least one intact therapeutic protein obtained from plasma or by means of genetic engineering, as an active pharmaceutical substance. Said active ingredient preparations contain active enzymes, especially proteases, which are either free or bound to the substrates thereof and act against the therapeutic protein(s) present.

1 - 24 . (canceled) 
     
     
         25 . A method for preparing a storable parenteral drug composition comprising contacting a protease inhibitor with a blood or tissue sample, wherein the blood or tissue sample includes a therapeutic protein selected from the group consisting of fibrinogen, Factor VIII, Factor V, Factor XIII and clotting Factors II, VII, IX and X of the prothrombin complex. 
     
     
         26 . The method of  claim 25 , further comprising a virus inactivating step, wherein a virucidal chemical is contacted to the sample. 
     
     
         27 . The method of  claim 25 , further comprising filtering the sample through a nanofilter. 
     
     
         28 . The method of  claim 27 , wherein the nanofilter comprises pores with a diameter selected from the group consisting of about 15 nm, about 20 nm, about 35 nm and about 75 nm. 
     
     
         29 . The method of  claim 27 , wherein the sample is filtered at a temperature of between about 20° C. and 40° C. 
     
     
         30 . The method of  claim 27 , further comprising a second step of filtering the sample through a second nanofilter. 
     
     
         31 . The method of  claim 25 , wherein the protease inhibitor is an atoxic, virus-safe, high-molecular weight protease inhibitor that inhibits the activation of a zymogen by a proteases or protease cascade as well as the proteolytic effect of the protease formed from the zymogen and acting against the therapeutic protein present in the sample. 
     
     
         32 . The method of  claim 25 , wherein the protease inhibitor comprises antithrombin III. 
     
     
         33 . The method of  claim 25 , wherein the protease inhibitor comprises C 1 -inhibitor. 
     
     
         34 . The method of  claim 25 , wherein the protease inhibitor comprises r-hirudin. 
     
     
         35 . The method of  claim 25 , wherein the protease inhibitor forms a complex with an enzyme-activating ion, wherein the ability of the enzyme-activating ion to activate an enzyme is reduced. 
     
     
         36 . The method of  claim 25 , wherein the protease inhibitor is selected from the group consisting of an inorganic ion, organic ion, inorganic zwitterion and organic zwitterion. 
     
     
         37 . The method of  claim 25 , wherein the protease inhibitor is selected from the group consisting of an atoxic reducing agent and an oxidizing agent. 
     
     
         38 . The method of  claim 25 , wherein the protease inhibitor is contacted with the sample at a temperature of 10° C. or lower. 
     
     
         39 . The method of  claim 25 , wherein the protease inhibitor is an atoxic, chaotropic agent, wherein the chaotropic agent dissociates an enzyme-substrate bond or reduces formation of an enzyme-substrate bond. 
     
     
         40 . A storable, parenteral drug composition prepared by a process comprising contacting a protease inhibitor with a blood or tissue sample, wherein the blood or tissue sample includes a therapeutic protein selected from the group consisting of fibrinogen, Factor VIII, Factor V, Factor XIII and clotting Factors II, VII, and X of the prothrombin complex. 
     
     
         41 . The storable, parenteral drug composition of  claim 40 , wherein the process further comprises a virus inactivating step, wherein a virucidal chemical is contacted to the sample. 
     
     
         42 . The storable, parenteral drug composition of  claim 40 , wherein the process further comprising filtering the sample through a nanofilter. 
     
     
         43 . The storable, parenteral drug composition of  claim 40 , wherein the drug composition does not contain any free active enzymes that act against the therapeutic protein, enzymes that are bound to their substrates that act against the therapeutic protein, or any active protease or protease cascade which activate a zymogen of the enzymes that act against the therapeutic protein. 
     
     
         44 . The storable, parenteral drug composition of  claim 40 , wherein the drug composition does not contain any high-molecular cofactors or profactors which directly or indirectly promote the effects of an enzyme that acts against the therapeutic protein. 
     
     
         45 . The storable, parenteral drug composition of  claim 40 , wherein the protease inhibitor comprises an agent selected from the group consisting of antithrombin III, C 1 -inhibitor, r-hirudin, inorganic ion, organic ion, inorganic zwitterion, organic zwitterion, atoxic reducing agent, oxidizing agent, and chaotropic agent. 
     
     
         46 . The storable, parenteral drug composition of  claim 45 , wherein the chaotropic agent is atoxic and dissociates an enzyme-substrate bond or reduces formation of an enzyme-substrate bond. 
     
     
         47 . The storable, parenteral drug composition of  claim 40 , wherein wherein the protease inhibitor forms a complex with an enzyme-activating ion, wherein the ability of the enzyme-activating ion to activate an enzyme is reduced.