Anti-cd19 antibodies with reduced immunogenicity
AssigneeCancer Research Technology Limited
InventorsMichael Super, Jonathan Davis, Pascal Andre Stein
Life of this patent
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Abstract
Anti-CD19 B4 antibodies with modified variable regions are disclosed. The modified anti-CD19 variable region polypeptides have alterations to one or more framework regions or complementarity determining regions of the heavy chain variable region or light chain variable region, thereby to reduce a T-cell response.
Claims19
1-22. (canceled)
A pharmaceutical composition comprising:
- i) in a pharmacologically effective amount an antibody or polypeptide comprising an anti-CD19 antibody variable domain comprising
- a) a heavy chain variable region that is at least 90% identical to SEQ ID NO:
- 13 and has an amino acid substitution at one or more residues corresponding to Gln5, Arg19, Leu20, Arg40, Gln43, Lys65, Ser85, Ser88, and Val93;
- and/or
- b) a light chain variable region that is at least 90% identical to SEQ ID NO:
- 25 and has an amino acid substitution at one or more residues corresponding to Ile10, Met11, Val19, Ser51, and Leu53;
- and
- ii) a pharmaceutically acceptable diluent, carrier, or excipient.
A method of treating a patient having Castleman's disease, rheumatoid arthritis, Crohn's disease, or multiple myeloma, the method comprising the step of administering to the patient a therapeutically effective amount of an anti-CD 19 antibody comprising a variable domain comprising:
- a) a heavy chain variable region that is at least 90% identical to SEQ ID NO:
- 13 and has an amino acid substitution at one or more residues corresponding to Gln5, Arg19, Leu20, Arg40, Gln43, Lys65, Ser85, Ser88, and Val93;
- and/or
- b) a light chain variable region that is at least 90% identical to SEQ ID NO:
- 25 and has an amino acid substitution at one or more residues corresponding to Ile10, Met11, Val19, Ser51, and Leu53.
A host cell expressing an antibody or polypeptide comprising an anti-CD19 antibody variable domain comprising
- a) a heavy chain variable region that is at least 90% identical to SEQ ID NO:
- 13 and has an amino acid substitution at one or more residues corresponding to Gln5, Arg19, Leu20, Arg40, Gln43, Lys65, Ser85, Ser88, and Val93;
- and/or
- b) a light chain variable region that is at least 90% identical to SEQ ID NO:
- 25 and has an amino acid substitution at one or more residues corresponding to Ile10, Met11, Val19, Ser51, and Leu53.
Dependencies are inferred from the claim text.