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US 10,519,249 B2Granted
Covalently linked polypeptide toxin-antibody conjugates
AssigneeHoffmann-La Roche Inc.
InventorsUlrich Brinkmann, Eike Hoffmann, Stefan Dengl, Klaus Mayer
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Abstract
Herein is reported a conjugate of a haptenylated polypeptide toxin and an anti-hapten antibody, wherein a disulfide bond is formed between a cysteine residue either before or after the lysine residue that is used for hapten-conjugation and a cysteine residue in the CDR2 of the antibody, whereby the CDR2 is determined according to Kabat.
Claims8
A conjugate comprising a haptenylated polypeptide toxin and an anti-hapten antibody,
- wherein the polypeptide toxin is conjugated to the hapten at a lysine residue within the 10 N-terminal amino acid residues of the toxin,
- wherein the haptenylated polypeptide toxin is conjugated to the anti-hapten antibody by a disulfide bond,
- wherein the disulfide bond is formed between
- i) a cysteine residue of the haptenylated polypeptide toxin that is one or two residues either before or after the lysine residue that is used for hapten-conjugation, and
- ii) a cysteine residue in the heavy chain CDR2 of the antibody at position 52b or 53, wherein the CDR2 is determined according to Kabat,
- wherein the anti-hapten antibody is a humanized antibody, a chimeric antibody with murine CDR sequences, or a murine antibody.
3 more elements
Dependencies are inferred from the claim text.