Patent ID: 7244823
Filing Date: 2007-07-17
Classification: A61K,C07K

Abstract:
1. A variant Tumor necrosis factor α (TNF-alpha) protein comprising an amino acid sequence that has at least one amino acid substitution in the Large Domain and at least one amino acid substitution in a domain selected from the group consisting of the DE Loop and the Small Domain as compared to the wild type TNF-alpha sequence of amino acids 1-157 of SEQ ID NO:2, wherein the Large Domain substitution is at a position selected from the group consisting of 21, 30, 31, 32, 33, 35, 65, 66, 67, 111, 112, 115, 140, 143, 144, 145 and 146, wherein the Small Domain substitution at a position selected from the group consisting of 75 and 97, wherein the DE Loop substitution at a position selected from the group consisting of 84, 86, 87 and 91, and wherein said variant TNF-alpha protein is capable of interacting with the wild type TNF-alpha to form mixed trimers having at least a 50% decrease in receptor activation as compared to a homotrimer of wild-type TNF-alpha proteins as determined by a caspase assay.