Compositions and methods to increase production

Abstract

Disclosed herein are methods for increasing protein yield and cellular productivity. Chemical agents facilitate host cell production of biological molecules to increase product yield.

1 . A method for producing therapeutic, prophylactic or diagnostic biological molecules from a host cell system comprising contacting a host cell system with at least one chemical agent selected from Table 1. 
     
     
         2 . The method according to  claim 1  wherein the host cell system is a cell culture or an embryonated egg. 
     
     
         3 . The method according to  claim 2 , wherein the cell culture is selected from the group consisting of MDCK, Vero, BHK or CHO cells. 
     
     
         4 . The method according to  claim 1  wherein the chemical agent is a statin or analog thereof having a final concentration of 0.001 μM to 10 μM. 
     
     
         5 . The method according to  claim 1 , wherein the chemical agent comprises a concentration of 0.05 μM or less and a structure as follows: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The method according to  claim 1 , wherein the host cell system is infected with a virus. 
     
     
         7 . The method according to  claim 6  wherein the chemical agent is added concurrently with virus inoculation of a host cell. 
     
     
         8 . The method according to  claim 7 , wherein the virus used for inoculation is influenza. 
     
     
         9 . The method according to  claim 8  wherein the biological molecule produced by the host cell system is selected from an influenza virus particle, a split influenza virion or an influenza virus glycoprotein. 
     
     
         10 . The method according to  claim 9  wherein the influenza virus glycoprotein is hemagglutinin. 
     
     
         11 . The method according to  claim 1 , wherein the yield of the biological molecule produced is increased at least 1.5-fold compared to a control, as measured by ELISA. 
     
     
         12 . The method according to  claim 1 , wherein an analog is selected from the group consisting of fluvastatin, pitavastatin, atorvastatin, cerivastatin, lovastatin, mevastatin, pravastatin or isomers thereof. 
     
     
         13 . The method according to  claim 1 , wherein the chemical agent is fluvastatin or pitavastatin or isomers thereof. 
     
     
         14 . A method for producing a therapeutic, prophylactic or diagnostic influenza protein in a cell culture, comprising contacting the cell culture with at least one statin compound or analog thereof at a concentration of 0.05 μM or less. 
     
     
         15 . A method for producing a therapeutic, prophylactic or diagnostic protein in a cell culture, characterized in that the production is conducted in the presence of at least one statin or derivative thereof other than simvastatin, wherein the therapeutic, prophylatic or diagnostic protein is produced at least 2-fold higher relative to a control, as measured by ELISA.