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Antibodies that bind IL-4 and/or IL-13 and their uses

A technology of IL-4 and antibodies, applied in the direction of antibodies, antibody medical ingredients, medical preparations of non-active ingredients, etc., can solve the problem of no specific effect

Active Publication Date: 2010-09-08
SANOFI AVENTIS SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

On the other hand, in contrast to IL-4, it has no specific effect on resting or activated T cells (Zurawuki, G. et al., Immunol. Today, 1994, 15, 19-26)

Method used

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  • Antibodies that bind IL-4 and/or IL-13 and their uses
  • Antibodies that bind IL-4 and/or IL-13 and their uses
  • Antibodies that bind IL-4 and/or IL-13 and their uses

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0288] Example 1: Sequencing of the Fv domain of mouse anti-human IL-13 monoclonal antibody clone B-B13

[0289] The reagent used in the following method was mouse anti-IL-13 monoclonal antibody clone B-B13 purchased from Cell Sciences, Inc. (Canton, MA, USA). Cell Sciences is the US distributor for Diaclone (Besancon, France), maker of antibody B-B13.

[0290] The amino acid sequence of anti-IL-13 monoclonal antibody clone B-B13 was determined using a combination of Edman N-terminal sequencing and mass spectrometry. Antibodies are processed in various ways as described below to produce polypeptides or peptide fragments which are then fractionated in various ways to prepare samples for subsequent Edman N-terminal sequencing and liquid chromatography / mass spectrometry / mass spectrometry (LC-MS / MS ) analysis, which is matched against peptides in related protein sequence databases.

[0291] SDS-Page of antibodies, with or without pyrogluamino-treatment to separate heavy and ligh...

Embodiment 2

[0297] Example 2: Fv domain sequencing of mouse anti-human IL-4 monoclonal antibody clone 8D4-8

[0298] Reagents Mouse anti-IL-4 monoclonal antibody clone 8D4-8 was purchased from Biozol diagnostica Vertrieb GmbH (Eching, Germany). Biozol is the German distributor of BioLegend (San Diego, CA, USA), which produces the 8D4-8 antibody.

[0299] The amino acid sequence of the mouse anti-IL-4 monoclonal antibody (clone 8D4-8) was determined using a combination of Edman sequencing and mass spectrometry (Pham et al., 2006, Anal. Biochem. 352:77-86; Roberts et al., 2005 , Anal. Chem. 67:3613-25). Briefly, antibodies are first separated into light and heavy chains, and then each chain is cleaved with sequence-specific proteases or chemicals. The resulting peptides were separated by reverse phase chromatography and analyzed by matrix-assisted laser desorption / ionization mass spectrometry (MALDI) and / or LC-MS / MS. The unique peptides as well as the complete heavy and light chains are ...

Embodiment 3

[0300] Example 3: Humanization of the Fv domain of mouse anti-human IL-13 monoclonal antibody clone B-B13

[0301] The humanization protocol described here was used to achieve humanization of the B-B13 clone. Six humanized versions were suggested, including mutations in the CDRs to address problematic residues (deamidation sites, solvent-exposed methionines, acid-labile positions).

[0302] The VL&VH sequence of B-B13 was blasted with the protein database (PDB) version in July 2007. Most similar light and heavy chain amino acid sequences were retrieved. The most homologous of the variable light chains was found to be 1EGJ. The most homologous of the variable heavy chains was found to be 1FNS. The 1EGJ & 1FNS structures were used to construct homology models of the variable domains, which were then energy minimized using standard procedures implemented in the Molecular Operating Environment (MOE). MOE is a comprehensive set of computer-aided drug design software provided by...

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Abstract

The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and / or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis.

Description

field of invention [0001] The present invention relates to novel anti-IL-4 antibodies, anti-IL-13 antibodies and bispecific anti-IL-4 / anti-IL-13 antibodies and their role in inappropriate IL-4 and / or IL-13 activity or metabolism. Use in the improvement, treatment and prevention of diseases or disorders in mammals including humans. Antibodies of interest may block binding and / or signaling of ligands such as IL-4 or IL-13 to receptors or receptor complexes such as IL-4Rα, IL-13Rα1 and IL-13Rα2. The invention also discloses prophylactic, immunotherapeutic and diagnostic compositions containing antibodies of interest and their use in methods of preventing or treating diseases in mammals, including humans, caused by lymphoid and non-lymphoid cells, including Inappropriate metabolism and / or activity of monocytes, fibroblasts and endothelial cells. These diseases include autoimmune deficiencies as well as diseases caused by or characterized by inflammation, such as allergic asthma ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/46C07K16/24A61K39/395A61P35/00A61P37/08A61P11/06
CPCC07K2317/31A61K47/48546C07K16/468C07K2317/64C07K16/244C07K16/247C07K2317/76A61K39/00A61P11/00A61P11/06A61P29/00A61P35/00A61P37/00A61P37/02A61P37/08A61P43/00Y02A50/30A61K47/6845A61K39/39533C12N15/63
Inventor E·劳V·米科尔D·李J·克鲁伊普M·戴维森
Owner SANOFI AVENTIS SA
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