Patent ID: 8147830
Filing Date: 2012-04-03
Classification: A61K,A61P,C07K

Abstract:
1. A method of therapeutic treatment of a tumor necrosis factor α-mediated (TNF-α-mediated) disorder in a mammal comprising administering to the mammal an effective amount of a conjugate consisting essentially of an antibody fragment covalently modified by one or two nonproteinaceous polymer molecules at a free sulfhydryl group of a cysteine residue within the hinge region of the antibody fragment, wherein said antibody fragment is engineered to both (1) provide an unpaired cysteine within the hinge region, so as to provide said free sulfhydryl group, and (2) to avoid disulfide bridge formation between said cysteine and an amino acid in the opposite chain of said antibody fragment, wherein (a) the average actual molecular weight of each nonproteinaceous polymer molecule is at least 20 kD, (b) the conjugate binds the same antigen as the parental molecule that is not covalently modified by one or two nonproteinaceous polymer molecules, wherein the antibody fragment comprises an antigen binding site that binds to a human tumor necrosis factor-α (TNF-α) polypeptide, and wherein the TNF-α-mediated disorder is selected from the group consisting of Crohn's disease and rheumatoid arthritis.