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Lyon, France

Boshuizen R.S.,Pepscan | Boshuizen R.S.,Astellas Pharma Europe B.V. | Marsden C.,Astrazeneca | Turkstra J.,Pepscan | And 6 more authors.
mAbs | Year: 2014

Background: Development of functional monoclonal antibodies against intractable GPCR targets. Results: Identification of structured peptides mimicking the ligand binding site, their use in panning to enrich for a population of binders, and the subsequent challenge of this population with receptor overexpressing cells leads to functional monoclonal antibodies. Conclusion: The combination of techniques provides a successful strategic approach for the development of functional monoclonal antibodies against CXCR2 in a relatively small campaign. Significance: The presented combination of techniques might be applicable for other, notoriously difficult, GPCR targets. Summary: The CXC chemokine receptor-2 (CXCR2) is a member of the large 'family A' of G-protein-coupled-receptors and is overexpressed in various types of cancer cells. CXCR2 is activated by binding of a number of ligands, including interleukin 8 (IL-8) and growth-related protein α (Gro-α). Monoclonal antibodies capable of blocking the ligand-receptor interaction are therefore of therapeutic interest; however, the development of biological active antibodies against highly structured GPCR proteins is challenging. Here we present a combination of techniques that improve the discovery of functional monoclonal antibodies against the native CXCR2 receptor. The IL-8 binding site of CXCR2 was identified by screening peptide libraries with the IL-8 ligand, and then reconstructed as soluble synthetic peptides. These peptides were used as antigens to probe an antibody fragment phage display library to obtain subpopulations binding to the IL-8 binding site of CXCR2. Further enrichment of the phage population was achieved by an additional selection round with CXCR2 overexpressing cells as a different antigen source. The scFvs from the CXCR2 specific phage clones were sequenced and converted into monoclonal antibodies. The obtained antibodies bound specifically to CXCR2 expressing cells and inhibited the IL-8 and Gro-α induced β-arrestin recruitment with IC50 values of 0.3 and 0.2 nM, respectively, and were significantly more potent than the murine monoclonal antibodies (18 and 19 nM, respectively) obtained by the classical hybridoma technique, elicited with the same peptide antigen. According to epitope mapping studies, the antibody efficacy is largely defined by N-terminal epitopes comprising the IL-8 and Gro-α binding sites. The presented strategic combination of in vitro techniques, including the use of different antigen sources, is a powerful alternative for the development of functional monoclonal antibodies by the classical hybridoma technique, and might be applicable to other GPCR targets. © 2014 Taylor & Francis Group, LLC. Source


Trademark
Valneva Inc. | Date: 2013-05-31

Chemicals for use in industry, science and agriculture, except fungicides, herbicides, insecticides and parasiticides; molecules from biotechnologies, namely, proteins in raw material for industrial use, scientific or medical research; cells and cell lines for use in scientific, laboratory, or medical research; nucleic acids for laboratory use; proteins in raw material form for scientific and medical research; recombinant proteins in raw material form for scientific and medical research; Biomedical compounds, namely, peptide substrates and peptide antigens used in analyzing and detecting certain toxins for clinical or medical laboratory use; Biochemical preparations derived from blood serum used as growth promoters in tissue cultures and microbiological media; Biochemicals, namely, antibodies and fragments thereof for in vitro scientific or research use; Chemicals for use in biotechnological product development; Cultures of microorganisms other than for medical and veterinary use; Biological preparations and bacteriological preparations for use in cell cultures other than for medical or veterinary use. Pharmaceuticals for human and veterinary use for the treatment of autoimmune diseases, inflammation, cancer, infectious diseases, diseases of the central nervous system, cardiovascular diseases, neurodegenerative and chronic diseases; antibodies and fragments thereof for use in disease testing; cell cultures, microorganisms and viruses for medical and veterinary use; diagnostic agents for medical, pharmaceutical and veterinary use; cells for medical or clinical use; culture media for cultivating microorganism cells for medical and veterinary use; adjuvants for medical or and veterinary use; pharmaceutical and veterinary preparations for medical, pharmaceutical and veterinary use, namely, preparations of encapsulated cells which release antibodies, living cells and microorganisms, vaccines, viral vectors, proteins, peptides, enzymes, nucleic acids or pharmaceutically active compounds for the treatment of cancer, auto-immune disorders, infectious diseases, inflammatory diseases, neurological and genetic disorders, bowel diseases, and digestion problems. Scientific research services for medical purposes in the fields of autoimmune diseases, inflammation, cancer, infectious diseases, diseases of the central nervous system, cardiovascular diseases, neurodegenerative and chronic diseases; scientific research for medical, pharmaceutical and veterinary purposes in the fields of autoimmune diseases, inflammation, cancer, infectious diseases, diseases of the central nervous system, cardiovascular diseases, neurodegenerative and chronic diseases; scientific research, in particular, in the fields of biology, cellular and molecular biology, biotechnology, bacteriology, immunology, genetics, medicine, pharmacology, virology, chemistry; scientific research relating to vaccines, antibiotics and immunological products for human and veterinary use; research and development of new products for others; testing, analysis, and evaluation of the goods of others to assure compliance with industry standards in the scientific, medical and veterinary fields; development and design of laboratory instruments for scientific and industrial research, in particular, to obtain and prepare cells, cell lines, viruses, proteins, animal and human materials; development of vaccines, antibiotics and immunological products for human and veterinary use; scientific and technological services, namely, diagnostic and prognostic analyses in the fields of cells, cell lines, animal and human materials, microorganisms, molecules for scientific purposes; scientific research, namely, preparation of scientific experts opinions reports.


Patent
Valneva Inc. | Date: 2012-06-27

The invention relates to high throughput screening methods for identifying, isolating and retrieving cells secreting antibodies of interest, e.g., having functional activity and/or multi-antigen specificities. It further provides methods for the cloning of said antibodies VH/VL sequences and the generation of recombinant monoclonal antibodies derived thereof having the features of interest.


Trademark
Valneva Inc. | Date: 2015-07-21

Chemical products, namely, fungicides, herbicides, insecticides and parasiticides for use in industry, science as well as in agriculture; molecules from bio technologies, namely, proteins in raw material for scientific and medical research; cells for scientific, laboratory or medical research; cell lines for scientific and medical research; nucleic acids for laboratory use; proteins for industrial use; recombinant proteins for industrial use; biomedical compounds, namely, peptides substrates; peptide antigens used in analyzing and detecting certain toxins for research, clinical, medical laboratory use; Biochemical preparations derived from blood serum for use in scientific and medical research; Bio chemicals, namely, antibodies and fragments thereof for in vitro scientific or research use, Chemicals for use in biotechnological product development; cultures of microorganisms other than for medical and veterinary use; viruses, cells, biological, bacteriological or viral preparations, other than for nucleic acids for scientific, laboratory, or medical research. Pharmaceutical products for human and veterinary use for the treatment of auto immune diseases, inflammation, cancer, infectious diseases, diseases of the central nervous system, cardiovascular diseases, neurodegenerative and chronic diseases; medical, biological, biotechnological, protein, virological, immunological, bacteriological, chemical, enzymatic and pharmaceutical preparations for medical and veterinary use; medical, biological, biotechnological, protein, virological, immunological, bacteriological, chemical, enzymatic and pharmaceutical products, namely, preparation of encapsulated cells which release antibodies for medical and veterinary use; diagnostic products, namely, diagnostic preparations for use in human, veterinary medicine and pharmaceutical use; cell, microorganism or virus cultures for medical and veterinary use; adjuvants for medical or veterinary use; antibiotics, vaccines, viruses, viral vectors, nucleic acids, proteins, recombinant proteins, peptides, peptide antigens, blood serum, antibodies and fragments thereof, and cells for medical, pharmaceutical and veterinary use; viral substances, immunological substances, bacterial substances, enzyme substances used for human and veterinary medicine; diagnostic kits consisting primarily of antibodies and fragments thereof for use in disease testing; diagnostic kits primarily of antibodies and antibody fragments for use in disease testing. Scientific research services for medical purposes in the fields of auto immune diseases, inflammation, cancer, infectious diseases, diseases, diseases of the central nervous system, cardiovascular diseases, neurodegenerative and chronic diseases; scientific research for medical, pharmaceutical and veterinary purposes in the fields of auto immune diseases, inflammation, cancer, infectious diseases, diseases of the central nervous systems, cardiovascular diseases, neurodegenerative and chronic diseases; scientific and industrial research, in particular in the fields of biology, cellular and molecular biology, biotechnology, bacteriology, immunology, genetics, gene study, medicine, pharmacology, virology, chemistry; scientific research relating to vaccines, antibiotics and immunological products for human and veterinary use; research and development of new products for others; testing and evaluations of the goods of others to assure compliance with industry standards in the scientific, medical and veterinary fields; research and development of new products for human and veterinary use; scientific research, namely, preparation of scientific experts opinion reports in the scientific, medical and veterinary fields; development and design of laboratory instruments for scientific and industrial research, in particular to obtain and prepare cells, cell lines, viruses, proteins, animal and human materials; development of vaccines, antibiotics and immunological products for human and veterinary use; scientific and technological services, namely, diagnostic and prognostic analyses in the fields of cells, cell lines, animal and human materials, microorganisms, molecules for scientific purposes; scientific research, namely, preparation of scientific expert opinions reports.


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