Molecules with extended half-lives, compositions and uses thereof
AssigneesMedImmine, 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.
Claims26
A modified IgG comprising a human IgG constant domain, wherein the human constant domain comprises an amino acid substitution at amino acid residue 428 relative to a wild-type human IgG constant 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 an IgG having the wild-type human IgG constant domain.
A modified IgG comprising an IgG constant domain, wherein the IgG constant domain comprises a human CH3 domain in which there is an amino acid substitution at amino acid residue 428, numbered according to the EU numbering index of Kabat, wherein the modified IgG has an increased half-life compared to the half-life of an IgG comprising a corresponding IgG constant domain comprising a wild-txpe human CH3domain.
Dependencies are inferred from the claim text.