Anti-biotin antibodies and methods of use
US-9765153-B2 · Sep 19, 2017 · US
US10519249B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-10519249-B2 |
| Application number | US-201615200629-A |
| Country | US |
| Kind code | B2 |
| Filing date | Jul 1, 2016 |
| Priority date | Jan 3, 2014 |
| Publication date | Dec 31, 2019 |
| Grant date | Dec 31, 2019 |
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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.
Opening claim text (preview).
What is claimed is: 1. 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. 2. The conjugate according to claim 1 , wherein the alpha carbon atom of the cysteine residue in the heavy chain CDR2 of the antibody is about 10 to 11 Angstrom apart from the atom of lysine residue of the polypeptide toxin to which the hapten is conjugated. 3. The conjugate according to claim 1 , wherein the cysteine residue on the polypeptide toxin is two residues before or after the lysine residue. 4. The conjugate according to claim 1 , wherein the polypeptide toxin comprises exactly one lysine residue in its amino acid sequence. 5. The conjugate according to claim 1 , wherein the antibody is a bispecific antibody comprising a first binding specificity to a non-hapten antigen and a second binding specificity to a hapten. 6. The conjugate according to claim 1 , wherein the disulfide bond is formed without the addition of redox active agents. 7. The conjugate according to claim 1 , wherein the hapten is biotin, theophylline, digoxigenin, carborane, fluorescein, or bromodeoxyuridine. 8. A pharmaceutical formulation comprising the conjugate according to claim 1 and a pharmaceutically acceptable carrier.
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