Covalently linked helicar-anti-helicar antibody conjugates and uses thereof

Patent metadata

Field	Value
Publication number	US-10407511-B2
Application number	US-201615200584-A
Country	US
Kind code	B2
Filing date	Jul 1, 2016
Priority date	Jan 3, 2014
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

Abstract

Herein is reported a conjugate comprising a helicar motif amino acid sequence containing compound and an antibody that specifically binds to the helicar motif amino acid sequence characterized by a covalent bond between the helicar motif amino acid sequence containing compound and an amino acid residue in the CDR2 of the anti-helicar antibody, whereby the CDR2 is determined according to Kabat.

First claim

What is claimed is:

1. A conjugate comprising
i) a compound comprising a helicar motif amino acid sequence selected from the group consisting of SEQ ID NO: 02 and SEQ ID NO: 03, and
ii) an anti-helicar motif amino acid sequence antibody, wherein the antibody comprises hypervariable loops as in the variable domain of SEQ ID NO: 04 for the heavy chain and as in the variable domain of SEQ ID NO: 06 for the light chain variable domain.

2. The conjugate according to claim 1 , wherein the helicar motif amino acid sequence containing compound is a polypeptide comprising the helicar motif amino acid sequence either fused to one of its termini or within the polypeptide sequence.

3. The conjugate according to claim 1 , wherein the antibody is a bispecific antibody comprising a first binding specificity to a non-helicar motif amino acid sequence antigen and a second binding specificity to the helicar motif amino acid sequence.

4. The conjugate according to claim 1 , wherein the disulfide bond is formed between the cysteine residues without the addition of a redox active agent.

5. An anti-helicar motif amino acid sequence antibody, wherein the antibody comprises hypervariable loops as in the variable domain of SEQ ID NO: 04 for the heavy chain and as in any of the variable domains of SEQ ID NO: 05, or SEQ ID NO: 06, or SEQ ID NO: 07 for the light chain variable domain.

6. A pharmaceutical formulation comprising the conjugate according to claim 1 and a pharmaceutically acceptable carrier.

7. A bispecific anti-helicar antibody for targeted delivery of a helicar motif amino acid sequence containing compound to a target cell, wherein the bispecific antibody comprises a first binding site that specifically binds to the helicar motif amino acid sequence containing compound and a second binding specificity that specifically binds to a cell surface marker of the target cell, wherein the first binding site comprises hypervariable loops as in the variable domain of SEQ ID NO: 04 for the heavy chain and as in any of the variable domains of SEQ ID NO: 05, or SEQ ID NO: 06, or SEQ ID NO: 07 for the light chain variable domain.

8. The antibody of claim 5 , wherein the antibody is humanized.

9. The bispecific anti-helicar antibody of claim 7 , wherein the antibody is humanized.

Assignees

• Hoffmann La Roche

Inventors

• Brinkmann Ulrich
• Georges Guy
• Hoffmann Eike
• Tiefenthaler Georg
• Moessner Ekkehard
• Dengl Stefan
• Gaertner Achim

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2319/75

  containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones · CPC title

• C07K2319/73

  containing coiled-coiled motif (leucine zippers) · CPC title

• C07K16/26

  against hormones {; against hormone releasing or inhibiting factors} · CPC title

• A61K47/6879

  the immunoglobulin having two or more different antigen-binding sites, e.g. bispecific or multispecific immunoglobulin · CPC title