Reactively modified therapeutic compounds having an extended lifetime in vivo

Abstract

First and second compounds are provided, where the first compound is administered to a mammalian host into blood for covalent bonding to blood components, where the components have an extended lifetime in the blood stream. The first compound comprises an active functionality and an agent of interest or a first binding entity. A second compound may be subsequently administered to the patient, which comprises a second binding entity, complementary to the first binding entity and an agent of interest. By virtue of binding to long-lived blood components, the half-life of the agent of interest is greatly extended in vivo.

What is claimed is:  
     
         1 . A method for extending the lifetime of a biologically active agent of interest, said method comprising: 
 administering to the vascular system of a mammalian host a first compound, said first compound comprising (i) a reactive functional group which reacts with proteins to form stable covalent bonds and (ii) either a biologically active agent of interest or a first binding entity which is a member of a specific binding pair consisting of said first binding member and a complementary second binding member, whereby said reactive functional group reacts with at least one of mobile protein and cellular components of the vascular system to produce modified vascular components;    wherein when said first compound comprises said first binding entity, the additional step of administering a second compound comprising said second binding entity and a biologically active agent of interest,    wherein said biologically active agent of interest is added in an amount to achieve its biological function over an extended period of time.    
     
     
         2 . A method according to  claim 1 , wherein said first compound comprises said biologically active agent of interest.  
     
     
         3 . A method according to  claim 1 , wherein said agent of interest is an immunoglobulin or binding fragment thereof.  
     
     
         4 . A method according to  claim 1 , wherein said agent of interest is a synthetic peptide.  
     
     
         5 . A method according to  claim 1 , wherein said protein is a glycoprotein.  
     
     
         6 . A method according to  claim 1 , wherein said agent of interest is a naturally occurring compound.  
     
     
         7 . A method according to  claim 1 , wherein said agent of interest is a synthetic organic compound of less than about 5 kDa.  
     
     
         8 . A method according to  claim 1 , wherein said agent of interest is an immunogen.  
     
     
         9 . A method according to  claim 1 , wherein said reactive functional group is a carboxylate ester which reacts with amines in an aqueous medium to form amides.  
     
     
         10 . A method for extending the lifetime in a mammalian host of an immunogen for enhancing the immune response, said method comprising: 
 administering to the vascular system of a mammalian host a first compound, said first compound comprising (i) a reactive functional group which reacts with proteins to form stable covalent bonds and (ii) a first binding entity which is a member of a specific binding pair consisting of said first binding member and a complementary second binding member, whereby said reactive functional group reacts with at least one of mobile protein or cellular components of the vascular system to produce modified vascular components;    adminstering a second compound comprising said second binding entity and an immunogen;    whereby said host mounts an immune response to said immunogen with the production of antibodies.    
     
     
         11 . A blood composition comprising conjugates of immunoglobulins and serum albumin covalently bonded to a biologically active agent as the major protein conjugates in said blood composition, said conjugates resulting from the addition of a first compound, said first compound comprising a reactive functional group which reacts with proteins to form stable covalent bonds and either a biologically active agent of interest or a first binding entity which is a member of a specific binding pair consisting of said first binding member and a complementary second binding member, to blood in vivo.  
     
     
         12 . A blood composition according to  claim 11 , wherein said biologically active agent is biotin.