| abstract |
A modified immunoglobulin formulation comprising a modified immunoglobulin having a reduced propensity to aggregation comprising a reduction aggregation mutation in a residue selected from the group consisting of residues of an aggregation motif 1: 174 (CH1), 175 ( CH1) and 181 (CH1); an aggregation reason 2: 226 (hinge), 227 (hinge), 228 (hinge), 229 (hinge), 230 (hinge), 231 (hinge) and 232 (hinge); an aggregation motif 4: 252 (CH2) and 253 (CH2); a reason for aggregation 5: 282 (CH2); a reason for aggregation 6: 291 (CH2); a reason for aggregation 7: 296 (CH2); an aggregation reason 8: 308 (CH2) and 309 (CH2); an aggregation reason 9: 328 (CH2), 329 (CH2), 330 (CH2) and 331 (CH2); an aggregation reason 10: 395 (CH3), 396 (CH3), 397 (CH3), 398 (CH3) and 404 (CH3); a reason for aggregation 11: 443 (CH3), where the aggregation-reducing mutation is a substitution with an amino acid residue that is less hydrophobic than the rest in the unmodified immunoglobulin and the aggregation propensity that is reduced is the aggregation between immunoglobulin molecules in a concentrated liquid solution, where the unmodified immunoglobulin encompasses the constant domain sequences of: (a) SEQ ID NOs: 1, 5, 9 and 13, (b) SEQ ID NOs: 2, 6, 10 and 14, (c) SEQ ID NOs: 3, 7, 11 and 15, or (d) SEQ ID NOs: 4, 8, 12 and 16, wherein the immunoglobulin further comprises a binding affinity for a target antigen and the binding affinity for the target antigen is at least seventy percent, at least eighty percent, at least ninety percent or at least one hundred percent of the binding affinity of the non-mutated immunoglobulin for the target antigen , and wherein the immunoglobulin is at a concentration of at least 75 mg / ml, at least os 100 mg / ml, at least 125 mg / ml, or at least 150 mg / ml. |