摘要 |
Disclosed are processes for producing a variant polypeptide (e.g. antibod ies) having modified binding characteristics for human Fc gamma receptor IIA (CD32A) leading to increased inhibition of proinflammatory mediators while retaining binding to a target antigen via its Fv portion, which processes co mprise altering the polypeptides by substitution of at least two amino acid residues at EU position 325, 326 or 328 of a human IgG CH2 region for a sequ ence selected from SAAF, SKAF, NAAF and NKAF. Also disclosed are molecules, particularly polypeptides, more particularly immunoglobulins (e.g. antibodie s) that include a variant CDR3 region, wherein the variant CDR3 region inclu des at least one amino acid modified relative to a wild-type CDR3 region. Th e polypeptides that can be generated according to the methods of the inventi on are highly variable, and they can include antibodies and fusion proteins that contain an Fc region or a biologically active portion thereof. |