Functional heavy chain antibodies, fragments thereof, library thereof and methods of production thereof

Abstract

The present invention relates to functional heavy chain antibodies, functional single domain heavy chain antibodies, functional VH domains, or functional fragments thereof comprising an amino acid which is neither a charged amino acid nor a C at position 45, and comprising an amino acid at position 103 independently chosen from the group consisting of R, G, K, S, Q, L, and P, and optionally an amino acid at position 108 independently chosen from the group consisting of Q, L and R, said positions determined according to the Kabat numbering.

1 .- 19 . (canceled) 
     
     
         20 . An isolated functional immunoglobulin V-domain from the H-chain of a functional heavy chain antibody (VHH) or from the H-chain of a four-chain antibody (VH),
 wherein the immunoglobulin V-domain selectively binds human serum albumin, and   wherein the amino acid at position 103 is arginine (R) or wherein the amino acid at position 103 is replaced with arginine (R), said position determined according to the Kabat numbering.   
     
     
         21 . The isolated functional immunoglobulin V-domain of  claim 20 , wherein the immunoglobulin V-domain is not stabilized by a disulfide bridge formed between CDR3 and either CDR1 or CDR2. 
     
     
         22 . An isolated fusion polypeptide comprising the isolated functional immunoglobulin V-domain of  claim 20 , wherein the polypeptide is a dimer, trimer or multimer. 
     
     
         23 . A pharmaceutical composition comprising the isolated functional immunoglobulin V-domain according to  claim 20 , optionally in combination with a suitable excipient. 
     
     
         24 . A pharmaceutical composition comprising the isolated functional immunoglobulin V-domain according to  claim 21 , optionally in combination with a suitable excipient. 
     
     
         25 . A pharmaceutical composition comprising the isolated fusion polypeptide according to  claim 22 , optionally in combination with a suitable excipient.