Molecules with extended half-lives, compositions and uses thereof
AssigneesMedImmune, LLC, Board of Regents, The University of Texas System
InventorsWilliam Dall'Acqua, Leslie S. Johnson, Elizabeth Sally Ward
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Abstract
The present invention provides molecules, including IgGs, non-IgG immunoglobulins, proteins and non-protein agents, that have increased in vivo half-lives due to the presence of an IgG constant domain, or a portion thereof that binds the FcRn, having one or more amino acid modifications that increase the affinity of the constant domain or fragment for FcRn. Such proteins and molecules with increased half-lives have the advantage that smaller amounts and or less frequent dosing is required in the therapeutic, prophylactic or diagnostic use of such molecules.
Claims28
A modified IgG comprising an IgG constant domain, wherein the IgG constant domain comprises a human IgG CH3 domain in which there is an amino acid substitution at amino acid residues 433, 434 and 436 relative to a corresponding IgG comprising a wild-type human IgG CH3 domain, numbered according to the EU numbering index of Kabat, wherein the modified IgG has an increased half-life compared to the half-life of the corresponding IgG comprising the wild-type human IgG CH3 domain, and wherein the substitution at amino acid residue 433 is a substitution with a lysine, the substitution at amino acid residue 434 is a substitution with a phenylalanine, and the substitution at amino acid residue 436 is a substitution with a histidine.
Dependencies are inferred from the claim text.