IMMUNOGLOBULINS WITH REDUCED AGGREGATION

摘要

The present disclosure relates to immunoglobulins with reduced aggregation and compositions, methods of generating such immunoglobulins with computational tools and methods of using such immunoglobulins particularly in the treatment and prevention of disease.

主权项

1. 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 residue 234 (hinge) or 235 (hinge).