TNF alpha-binding polypeptide compositions and methods

摘要

A TNF alpha-binding polypeptide composition comprises at least one of a modified heavy chain variable region polypeptide or a modified light chain variable region polypeptide that is capable of specifically binding to human TNF alpha. The modified heavy chain variable region polypeptide and the modified light chain variable region polypeptide each are homologous to respective heavy chain or light chain variable regions of a non-human monoclonal antibody that specifically binds to human TNF alpha. The amino acid residue sequence of at least one of the modified heavy chain variable region polypeptide and the modified light chain variable region polypeptide differs from the amino acid residue sequence of the respective non-human monoclonal antibody heavy chain variable regions or light chain variable regions by at least one amino acid residue substitution, deletion or addition. The polypeptide compositions of the invention are less immunogenic to a human than an antibody comprising the same human constant regions and having heavy chain and light chain variable regions identical to the respective heavy chain and light chain variable regions of said non-human monoclonal antibody.