Stabilized antibody compositions

Abstract

The invention provides novel compositions of antibodies based on liquid vehicles selected from semifluorinated alkanes. The use of these vehicles provides for improved stability and shelf-life of antibodies and their derivatives. The compositions are useful for topical administration or for parenteral injection.

1 . Composition comprising an antigen-binding polypeptide or protein and a liquid vehicle, wherein the liquid vehicle comprises a semifluorinated alkane of the formula
   RFRH   
       wherein RF is a linear perfluorinated hydrocarbon segment with 4 to 12 carbon atoms, and wherein RH is a linear alkyl group with 4 to 8 carbon atoms; and wherein the antigen-binding polypeptide or protein is incorporated in the composition such as to form a dispersion or suspension. 
     
     
         2 . The method according to  claim 10 , wherein the antigen-binding polypeptide or protein is selected from a monoclonal antibody, polyclonal antibody, an antibody fragment, a fusion protein comprising an antibody fragment, an antibody-drug conjugate, or any combination thereof. 
     
     
         3 . The method according to  claim 2 , wherein the antibody fragment is a fragment antigen-binding (Fab), a single-chain variable fragment (scFv), a single-domain antibody, a minibody, or a diabody. 
     
     
         4 . The method according to  claim 2 , wherein the monoclonal antibody is a chimeric, humanized, or human antibody. 
     
     
         5 . The method according to  claim 10 , wherein the antigen-binding polypeptide or protein has a molecular mass of at least 90 kDa. 
     
     
         6 . The method according to  claim 10 , wherein the semifluorinated alkane is selected from F4H5, F4H6, F4H8, F6H4, F6H6, F6H8, and F6H10. 
     
     
         7 . The method according to  claim 10 , wherein the composition is substantially free of water. 
     
     
         8 . The method according to  claim 10 , wherein the composition retains at least 85% of its initial antigen-binding activity during storage of 6 months at a temperature of between RT to 40° C. 
     
     
         9 . The method according to  claim 10 , wherein the antigen-binding polypeptide or protein is at a concentration of at least 0.5 mg/mL. 
     
     
         10 . A method for treating or preventing a disease or condition in a patient in need thereof, comprising the step of administering to the patient an effective amount of a composition comprising an antigen-binding polypeptide or protein and a liquid vehicle, wherein the liquid vehicle comprises a semifluorinated alkane of the formula
   RFRH   wherein RF is a linear perfluorinated hydrocarbon segment with 4 to 12 carbon atoms, and wherein RH is a linear alkyl group with 4 to 8 carbon atoms; and wherein the antigen-binding polypeptide or protein is incorporated in the composition such as to form a dispersion or suspension.   
     
     
         11 . The method according to  claim 10 , wherein the composition is administered by subcutaneous, dermal, intramuscular, or locoregional injection. 
     
     
         12 . A method of stabilizing an antigen-binding polypeptide or protein, comprising the step of mixing the antigen-binding polypeptide or protein with a liquid vehicle comprising a semifluorinated alkane of the formula
   RFRH   wherein RF is a linear perfluorinated hydrocarbon segment with 4 to 12 carbon atoms, and wherein RH is a linear alkyl group with 4 to 8 carbon atoms, such as to form a suspension or a dispersion.   
     
     
         13 . The method of  claim 12 , wherein the antigen-binding polypeptide or protein retains at least 85% of initial antigen-binding activity during storage of 6 months at a temperature between RT to 40° C. 
     
     
         14 . The method according to  claim 10 , wherein the disease or condition is cancer or an autoimmune disease. 
     
     
         15 . The method according to  claim 10 , wherein the antigen-binding polypeptide or protein is an angiogenesis inhibitor, an anti-proliferative agent or a TNF inhibitor. 
     
     
         16 . The method according to  claim 12 , wherein the semifluorinated alkane is selected from F4H5, F4H6, F4H8, F6H4, F6H6, F6H8, and F6H10. 
     
     
         17 . The method according to  claim 12 , wherein the composition is substantially free of water. 
     
     
         18 . The method according to  claim 12 , wherein the antigen-binding polypeptide or protein is a monoclonal antibody, a polyclonal antibody, an antibody fragment, a fusion protein comprising an antibody fragment, an antibody-drug conjugate, or any combination thereof. 
     
     
         19 . The method of  claim 18 , wherein the semifluorinated alkane is selected from F4H5, F4H6, F4H8, F6H4, F6H6, F6H8, and F6H10. 
     
     
         20 . The method of  claim 12 , wherein the antigen-binding polypeptide or protein is at a concentration of at least 0.5 mg/mL.