Molecules with altered neonate Fc receptor binding having enhanced therapeutic and diagnostic properties
AssigneeMedImmune, LLC
InventorsPing Tsui, Martin Borrok, William Dall'acqua, Yanli Wu, Nurten Beyaz-Kavuncu
Life of this patent
Estimating the term…
Abstract
The present invention provides molecules, including proteins, more particularly, immunoglobulins whose in vivo half-lives are altered (increased or decreased) by the presence of an IgG constant domain, or FcRn binding fragment thereof (e.g., an Fc region or hinge-Fe region) (e.g., from a human IgG, e.g., human IgG1), that have modifications of one or more of amino acid residues in at least the CH3 domain.
Claims20
A nucleic acid comprising a nucleotide sequence encoding a modified human or humanized IgG1 comprising an Fc region wherein
- (i) positions 432 and 437 are each substituted with cysteine,
- (ii) position 433 is substituted with serine;
- (iii) position 434 is substituted with tryptophan or tyrosine;
- (iv) position 435 is histidine;
- (v) position 436 is substituted with leucine;
- numbered according to the EU numbering index of Kabat, relative to a human wild-type Fc region;
- and wherein the modified human or humanized IgG1 has an increased half-life compared to the half-life of an IgG1 having the human wild-type Fc region.
A nucleic acid comprising a nucleotide sequence encoding a polypeptide comprising an FcRn-binding portion of an Fc region of a human IgG1 molecule, wherein positions 432 and 437 of said FcRn-binding portion are each substituted with cysteine, position 433 is substituted with serine;
- position 434 is substituted with tryptophan or tyrosine;
- position 435 is histidine;
- and position 436 is substituted with leucine;
- numbered according to the EU numbering index of Kabat, relative to a wild-type human FcRn-binding portion.
A nucleic acid comprising a nucleotide sequence encoding a fusion protein comprising a non-IgG polypeptide covalently linked to at least an FcRn-binding portion of an Fc region of a human IgG1 molecule, wherein positions 432 and 437 of said FcRn-binding portion are each substituted with cysteine, position 433 is substituted with serine;
- position 434 is substituted with tryptophan or tyrosine;
- position 435 is histidine;
- and position 436 is substituted with leucine;
- numbered according to the EU numbering index of Kabat, relative to a wild-type human Fc region;
- and wherein said fusion protein has a longer in vivo half life than the non-IgG polypeptide.
Dependencies are inferred from the claim text.