Stable IgG4 antibodies
AssigneeGenmab A/S
InventorsJan Van De Winkel, Tom Vink, Janine Schuurman, Paul Parren, Rob Aalberse, Marijn Van Der Neut Kolfschoten
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Abstract
The present invention relates to novel stabilized IgG4 antibodies, to methods of producing such antibodies and to uses of such antibodies as a medicament. In a main aspect, the invention relates to a stabilized IgG4 antibody, comprising a heavy chain and a light chain, wherein said heavy chain comprises a human IgG4 constant region having a substitution of the Arg residue at position (409), the Phe residue at position (405) or the Lys residue at position (370).
Claims11
A stabilized homodimeric IgG4 antibody, comprising two heavy chains and two light chains, wherein the two heavy chains and the two light chains each comprise a variable region and a constant region,
- wherein the constant region in the two heavy chains is a human IgG4 constant region having a substitution of the Lys residue at EU index position 370 with a Thr residue, and optionally one or more additional amino acid substitutions to reduce Fab arm exchange, selected from:
- a Lys, Thr, Met, or Leu residue at EU index position 409, and an Ala or Leu residue at EU index position 405, and/or to reduce effector function, selected from:
- an Ala at EU index position 234, an Ala at EU index position 236, an Ala at EU index position 237, an Ala at EU index position 297, an Ala or Val at EU index position 318, an Ala at EU index position 320, and an Ala or Gln at EU index position 322;
- and
- wherein the antibody has a Cys-Pro-Ser-Cys sequence (SEQ ID NO:
- 51) in the hinge region at EU index positions 226-229.
Dependencies are inferred from the claim text.