Method of preparing ph-dependent antibodies
Assigneeargenx BV
InventorsChristophe Blanchetot, Erik Hofman, Johannes de Haard, Jacobus Cornelis Rasser
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Abstract
Methods for preparing engineered antibodies exhibiting improved pH-dependent antigen binding are disclosed. The methods are based on introduction of histidine residues at a subset of defined amino acid positions within the antibody CDRs. The set of amino acid positions selected for histidine substitution is derived from a heat-map of histidine occurrence within the CDRs of functional antibodies from a natural antibody repertoire. The methods provide a simpler and less time-consuming approach to the identification of pH-dependent antibody variants.
Claims14
1-42. (canceled)
An engineered antibody which exhibits pH dependent binding to its antigen wherein at least one amino acid in the CDRs of the engineered antibody is a histidine residue, characterized in that at least one amino acid residue selected from the following hot-spot list is a histidine residue:
- VH CDR1
- H31, H32, H33, H35
- VH CDR2
- H50, H52, H52a, H53, H56, H58, H59, H62, H63
- VH CDR3
- H95, H96, H97, H98, H99, H100, H100a, H100b, H100c,
- H100d, H100e, H100f, H100h, H100i, H100j, H100l,
- H101, H102
- VL CDR1
- L27, L27d, L29, L30, L31, L32, L34
- VL CDR2
- L51, L52, L53, L54, L55
- VL CDR3
- L89, L90, L91, L92, L93, L94, L95a, L95b, L95c, L96
- FR
- L49, L87
- and at least one amino acid residue selected from the following cold-spot list is not a histidine residue:
- VH CDR1
- H34, H35a, H35b, H35c
- VH CDR2
- H51, H52b, H52c, H54, H55, H57, H60, H61, H64, H65
- VH CDR3
- H100g, H100k, H100m, H100n
- VL CDR1
- L24, L25, L26, L27a, L27b, L27c, L27e, L28, L33
- VL CDR2
- L50, L51a, L51b, L51c, L51d, L56
- VL CDR3
- L95, L95d, L95e, L95f, L97
Dependencies are inferred from the claim text.