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US 9,085,625 B2Granted
Antibody variants having modifications in the constant region
AssigneeGenmab A/S
InventorsAran Frank Labrijn, Stefan Loverix, Paul Parren, Jau Van De Winkel, Janine Schuurman, Lgnace Laster
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Abstract
The present invention relates to positions in the constant region of antibodies, in particular the CH3 region of IgG4, which affect the strength of CH3-CH3 interactions. Mutations that either stabilize or destabilize this interaction are disclosed.
Claims19
An isolated, stabilized IgG4 antibody, comprising a heavy chain and a light chain, wherein said heavy chain comprises a human IgG4 constant region comprising the sequence set forth in SEQ ID NO:2 but wherein
- (A) Lys(K) in position 250 has been replaced by Gln(Q) or Glu(E), and
- (B) the constant region comprises less than 10 total substitutions, deletions and/or insertions at amino acid positions corresponding to positions 99-118, 119-220, and/or 221-327 of the sequence as set forth in SEQ ID NO:2.
Dependencies are inferred from the claim text.