Patent ID: 9676841
Date: 2017-06-13
CPC Classifications: A61K,A61P,C07K

Claim:
1. A modified immunoglobulin formulation comprising a modified or isolated immunoglobulin having reduced propensity for aggregation comprising at least one aggregation reducing mutation at a residue in a conserved domain of the immunoglobulin that (i) has a Spatial-Aggregation-Propensity (5 Å radius sphere) of at least 0.15, or (ii) has an Spatial-Aggregation-Propensity (5 Å radius sphere) of greater than 0.0 and is within 5 Å of a residue having a Spatial-Aggregation-Propensity (5 Å radius sphere) of at least 0.15, wherein the at least one aggregation reducing mutation is a substitution with an amino acid residue that lowers the Spatial-Aggregation-Propensity (5 Å radius sphere) of the residue as compared to the unmutated immunoglobulin and the propensity for aggregation that is reduced is aggregation between immunoglobulin molecules in a concentrated, liquid solution, wherein the at least one aggregation reducing mutation is not at residue 234 (hinge) or 235 (hinge), wherein the modified or isolated immunoglobulin is at a concentration of at least 75 mg/ml, wherein at least eighty percent of the modified or isolated immunoglobulin is non-aggregated monomer, and wherein the modified or isolated immunoglobulin comprises a substitution at 282 (C H2 ).