STABLE AND SOLUBLE ANTIBODIES INHIBITING TNF ALPHA

摘要

The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNFα, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNFα, and low immunogenicity. Said antibodies are designed for the diagnosis and/or treatment of TNFα-related disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of said antibodies in medicine are also disclosed.

主权项

1. A method for the production of an antibody which specifically binds TNFα, said antibody comprising a light chain variable domain (VL) comprising the sequence of SEQ ID NO:1 and a heavy chain variable domain (VH) comprising the sequence of SEQ ID NO:2, or an antigen-binding derivative thereof, wherein said derivative has at maximum up to five amino acid changes as compared to SEQ ID NO: 1 and/or at maximum up to nine amino acid changes as compared to SEQ ID NO: 2, wherein said changes occur at amino acid positions in framework regions of said VL comprising the sequence of SEQ ID NO: 1 and said VH comprising the sequence of SEQ ID NO: 2, and wherein said derivative does not comprise the entire sequences of SEQ ID NO: 3 and SEQ ID NO: 4, the method comprising the steps of:
culturing a host cell under conditions that allow the synthesis of said antibody, and recovering it from said culture.