Molecules with extended half-lives, compositions and uses thereof
AssigneesMedImmune, LLC, Board of Regents, The Texas University System
InventorsWilliam Dall'Acqua, Leslie S. Johnson, Elizabeth Sally Ward Ober
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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.
Claims20
A fusion protein comprising a non-IgG polypeptide covalently linked to a modified human IgG constant domain, or a fragment thereof that binds to FeRn, said modified human IgG constant domain or fragment comprising one or more amino acid modifications relative to a wild-type human IgG constant domain, wherein the one or more modifications are at one or more of positions 251-256, 285-290, 308-314, 385-389, and 428-436, numbered according to the EU numbering index of Kabat, and wherein at least one of the one or more modifications is an insertion, deletion or substitution, and wherein said fusion protein has a longer half life than the non-IgG polypeptide alone.
A molecule comprising a non-protein agent conjugated to a modified human IgG constant domain, or a fragment thereof that binds to FcRn, said modified human IgG constant domain or fragment comprising one or more amino acid modifications relative to a wild-type human IgG constant domain, wherein the one or more modifications are at one or more of positions 251-256, 285-290, 308-314, 385-389, and 428-436, numbered according to the EU numbering index of Kabat, and wherein at least one of the one or more modifications is an insertion, deletion or substitution, and wherein said molecule has a longer half life than the non-protein agent alone.
Dependencies are inferred from the claim text.