Polypeptide variants with altered effector function
AssigneeGenentech, Inc.
InventorsCamellia Adams, Samantha Lien, Henry Lowman, Jonathan Marvin, Yu-Ju Meng
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Abstract
The invention provides polypeptides having IgG Fc regions with amino acid modifications that result in the polypeptides exhibiting altered Fc effector functions.
Claims80
An isolated polypeptide comprising a variant IgG Fc region comprising at least an amino acid substitution at Asn 434 to Trp (N434W).
The polypeptide of claim I wherein the polypeptide has a longer serum half life in primate serum than a polypeptide with native sequence Fc region.
An isolated antibody comprising a variant IgG Fc region comprising at least an amino acid substitution at Asn 434 to Trp (N434W).
The antibody of claiml6, wherein the antibody binds human CD11a and comprises a VL sequence of SEQ ID NO.13 or the full length L chain of SEQ ID NO.15, with VH sequence of SEQ ID NO.14.
An isolated polypeptide comprising a variant IgG Fc region comprising at least an amino acid substitution at Asn 434 to Tyr (N434Y) wherein the polypeptide does not further have an amino acid substitution selected from the group consisting of H433R, H433S, Y436H, Y436R, Y436T.
An isolated polypeptide comprising a variant IgG Fc region comprising at least an amino acid substitution at Asn 434 to Phe (N434F) wherein the polypeptide does not further have an amino acid substitution of H433K, Y436H,-M252Y, S254T, or T256E.
An isolated polypeptide comprising a variant IgG Fc region comprising at least an amino acid substitution at Asn 434 to His (N434H).
An isolated polypeptide comprising a variant IgG Fc region comprising at least an amino acid substitution at Lys 334 to Leucine (K334L).
A humanized CD20 binding antibody having the L chain sequence of SEQ ID NO.39 and the H chain sequence of SEQ ID NO.40 except that N434 in the Fc region is substituted with W, Y, F or A.
A method of screening for a polypeptide with high affinity binding to FcRn at pH 6.0 and with weaker binding affinity at pH 7.4 than at pH 6.0 as compared to a polypeptide with native sequence IgG Fc, the method comprising expressing a candidate polypeptide on phage, providing human FcRn immobilized on a solid matrix, allowing phage particles to bind to the human FcRn on the matrix, removing unbound phage particles by multiple rounds of washes each round with increasing stringency, and eluting the remaining bound phage at pH 7.4.
An isolated anti-HER2 antibody comprising VL sequence of SEQ ID NO.5, VH sequence of SEQ ID NO.6, and a variant IgG Fc region comprising at least an amino acid substitution at Asn 434 to Ala (N434A).
Dependencies are inferred from the claim text.