Covalently linked polypeptide toxin-antibody conjugates

US10519249B2 · US · B2

Patent metadata
FieldValue
Publication numberUS-10519249-B2
Application numberUS-201615200629-A
CountryUS
Kind codeB2
Filing dateJul 1, 2016
Priority dateJan 3, 2014
Publication dateDec 31, 2019
Grant dateDec 31, 2019

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  1. Title

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  2. Abstract

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  3. Assignees and inventors

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  4. Key dates

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  5. First independent claim

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  6. CPC / IPC classifications

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  7. Citations and related patents

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Abstract

Official abstract text for this publication.

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.

First claim

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.

Assignees

Inventors

Classifications

  • Antineoplastic agents · CPC title

  • variable (Fv) region, i.e. VH and/or VL · CPC title

  • multispecific · CPC title

  • Complementarity determining region [CDR] · CPC title

  • Bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin A · CPC title

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What does patent US10519249B2 cover?
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.
Who is the assignee on this patent?
Hoffmann La Roche
What technology area does this patent fall under?
Primary CPC classification A61K47/6829. Mapped technology areas include Human Necessities.
When was this patent published?
Publication date Tue Dec 31 2019 00:00:00 GMT+0000 (Coordinated Universal Time) (B2). Legal status and post-grant events are not shown on this page.
What related patents are in patentsdb?
We list 10 related publications on this page (citations in our corpus or others sharing the same primary CPC).