Process for the modulation of the antagonistic activity of a monoclonal antibody

Patent metadata

Field	Value
Publication number	US-9676839-B2
Application number	US-200913131907-A
Country	US
Kind code	B2
Filing date	Dec 2, 2009
Priority date	Dec 2, 2008
Publication date	Jun 13, 2017
Grant date	Jun 13, 2017

Abstract

The present disclosure relates to the antibody engineering field and, more particularly, to a process for the screening of antibodies and/or the modulation of the agonistic/antagonistic activity of antibodies. More particularly, the disclosure concerns a process of improving the antagonistic activity of a monoclonal antibody directed against a specific target molecule, or a divalent functional fragment or derivative thereof, the antibody being capable of inhibiting one or more of the biological activities of the target molecule, wherein the process comprises a stage of reconfiguration of the hinge region consisting of a modification of the amino acid sequence of the hinge region by the deletion, the addition or the substitution of at least one amino acid. The disclosure also relates to polypeptides useful for such a modulation method and the obtained antibodies.

First claim

The invention claimed is:

1. A process of improving a monoclonal antibody's ability to inhibit the binding of a transmembrane receptor to its ligand, wherein said antibody comprises a hinge region, or of a divalent functional fragment of said antibody comprising a hinge region, wherein said process comprises:
modifying an antibody that is capable of inhibiting the binding of a transmembrane receptor to its ligand by deleting, adding, or substituting at least one amino acid in the amino acid sequence of said hinge region of said antibody;
selecting the modified antibody wherein the modification improves the antibody's ability to inhibit the binding of the transmembrane receptor to its ligand over a modified antibody wherein the modification does not improve the antibody's ability to inhibit the binding of the transmembrane receptor to its ligand;
wherein the hinge that comprises a modification that improves the antibody's ability to inhibit the binding of the transmembrane receptor to its ligand;
comprises SEQ ID No. 6.

2. The process according to claim 1 , wherein said monoclonal antibody is a divalent antibody.

3. The process according to claim 1 , wherein said monoclonal antibody is a chimeric antibody.

4. The process according to claim 1 , wherein said monoclonal antibody is a humanized antibody.

5. The process according to claim 1 , wherein said monoclonal antibody is a human antibody.

6. The process according to claim 1 , wherein said monoclonal antibody is an IgG1 antibody.

7. The process of claim 1 , wherein said transmembrane receptor is selected from tyrosine kinase receptors, tetraspanin, and G-protein coupled receptors (GPCRs).

Assignees

• Goetsch Liliane
• Wurch Thierry
• Pf Medicament

Inventors

• Goetsch Liliane
• Wurch Thierry

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K16/00 Primary

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K16/2863

  against receptors for growth factors, growth regulators · CPC title