Neutralizing antibodies and methods of use thereof

Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Monoclonal antibody or fragment thereof

Reexamination Certificate

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C424S143100, C424S141100, C424S133100, C424S142100, C530S388100, C530S388200, C530S388220, C530S387300, C530S388850

Reexamination Certificate

active

07744884

ABSTRACT:
This invention provides monoclonal antibodies that recognize the Toll-like Receptor 4/MD-2 receptor complex, and monoclonal antibodies that recognize the TLR4/MD2 complex as well as TLR4 when not complexed with MD-2. The invention further provides methods of using the monoclonal antibodies as therapeutics. This invention also provides soluble chimeric proteins, methods of expressing and purifying soluble chimeric proteins, and methods of using soluble chimeric proteins as therapeutics, in screening assays and in the production of antibodies.

REFERENCES:
patent: 7271248 (2007-09-01), Hardiman et al.
patent: 2002/0192217 (2002-12-01), Calandra et al.
patent: WO 03/013440 (2003-02-01), None
patent: WO 2005/047330 (2005-05-01), None
O'Neill 2003. Curr. Opin in Pharm 3:396-403.
Abdollahi-Roodsaz et al 2007. Arthritis and Rheumatism 56:2957-2967.
Raschi et al 2008. Lupus 17:937-942.
Akashi et al., “Cutting edge: Cell surface expression and lipopolysaccharide signaling via the Toll-like receptor 4-MD-2 complex on mouse peritoneal macrophages,” J. Immunol., vol. 164(7): 3471-3475 (2000).
Akashi et al., “Lipopolysaccharide interaction with cell surface Toll-like receptor 4-MD-2: Higher affinity than that with MD-2 or CD14,” J. Exp. Med., vol. 198(7): 1035-1042 (2003).
Backhed et al, “TLR4-dependent recognition of lipopolysaccharide by epithelial cells requires sCD14,” Cellular Microbiology, vol. 4(8): 493-501 (2002).
Buell et al., “Blockade of human P2X7 receptor function with a monoclonal antibody.” Blood 92: 3521-3528 (1998).
Devaney et al., “Neutrophil elastase up-regulates interleukin via toll-like receptor 4,” FEBS Letters, vol. 544 (1-3): 129-132 (2003).
GenBank Accession No. AAH20690. I “Lymphocyte antigen 96 [Homo sapiens]” 2006.
GenBank Accession No. BAA78717.1 “MD-2 [Homo sapiens]” 1999.
GenBank Accession No. CAH72619.1 “toll-like receptor 4 [Homo sapiens]” 2009.
GenBank Accession No. CAH72620 “toll-like receptor 4 [Homo sapiens]” 2005.
GenBank Accession No. NP—056179, “MD-2 protein [Homo sapiens]” 2009.
GenBank Accession No. Q9Y6Y9, “RecName: Full=Lymphocyte antigen 96; AltName: Full=Protein MD-2; AltName: Full=ESPO-1; Flags: Precursor” 2009.
Ishida et al., “Hypoxia diminishes Toll-like Receptor 4 expression through reactive oxygen species generated by mitochondria in endothelial cells,” J. Immunol., vol. 169(4): 2069-2075 (2002).
Johnson et al., “Activation of mammalian Toll-like receptors by endogenous agonists” Crit. Rev. Immunol., 23(1-2):15-44 (2003).
Jones and Bendig, “Rapid PCR-cloning of full-length mouse immunoglobulin variable regions.” Biotechnology (N. Y.), 9: 88-89 (1991).
Kammann et al., “Rapid insertional mutagenesisof DNA by polymerase chain reaction (PCR),” Nucleic Acids Res. vol. 17: 5404 (1989).
Kawasaki et al., “Identification of mouse MD-2 residues important for forming the cell surface TLR4- MD-2 complex recognized by anti-TLR4-MD2 antibodies, and for conferring LPS and taxol responsiveness on mouse TLR4 by alanine-scanning mutagenesis,” J. Immunol., vol. 170(1): 413-420 (2003).
Kirkland et al., “Analysis of Lipopolysaccharide Binding by CD14,” J. Biol. Chem., vol. 268(33): 24818-24823(1993).
Kolbinger et al., “Humanization of a mouse anti-human IgE antibody: a potential therapeutic for IgE-mediated allergies” Protein Eng. 6, 971-980, 1993).
Lakhani et al., “Toll-like receptor signaling in sepsis” Curr. Opin. Pediatr. 15: 278-282 (2003).
Lenhardt et al., “Activation of innate immunity in the CNS triggers neurodegeneration through a Toll like receptor 4-dependent pathway,” PNAS, vol. 100(14): 8514-8519 (2003).
Miyake, “Endotoxin recognition molecules MD-2 and Toll-like Receptor 4 as potential targets for therapeutic intervention of endotoxin shock,” Current Drug Targets: Inflammation and Allergy, vol. 3(3): 291-297 (2004).
Miyake, “Innate recognition of lipopolysaccharide by CD14 and toll-like receptor 4-MD-2: unique roles for MD-2,” International Immunopharmacology, vol. 3(1): 1199-128 (2003).
Nijhuis et al, “Endothelial cells are main producers of Interleukin 8 through Toll-like receptor 2 and 4 signaling during bacterial infection in leukopenic cancer patients,” Clinical aid Diagnostic Laboratory Immunology, vol. 10(4): 558-563 (2003).
O'Neill, “Therapeutic targeting of Toll-like receptors for inflammatory and infectious diseases” Curr. Opin. Pharmacol. 3: 396-403 (2003).
Ohashi et al., “Cutting Edge: Heat Shock Protein 60 is a Putative Endogenous Ligand of the Toll-Like Receptor-4 Complex,” J. Immunol., vol. 164: 558-561 (2000).
Okamura et al., “The Extra Domain A of Fibronectin Activates Toll-like Receptor 4,” J. Biol. Chem. vol. 276(13): 10229-10233 (2001).
Pasterkamp et al., “Role of Toll-like Receptor 4 in the initiation and progression of atherosclerotic disease,” Eur. J. Clin. Invest., vol. 34(5): 328-334 (2004).
Pivarcsi et al., “Expression and Function of Toll-like Receptors 2 and 4 in Human Keratinocytes,” International Immunology, vol. 15(6): 721-730 (2003).
Pugin et al., “Soluble MD-2 activity in plasma from patients with severe sepsis and septic shock,” Blood, vol. 104(13): 4071-4079 (2004).
Sato et al., “Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth,” Cancer Res. vol. 53: 851-856 (1993).
Shimazu et al., “MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4,” J. Exp. Med., vol. 189(11): 1777-1782 (1999).
Takeda et al., “Toll-like receptors” Annu. Rev. Immunol., 21: 335-76 (2003).
Yang et al., “Cellular events mediated by lipopolysaccharide-stimulated Toll-like receptor 4,” J. Biol. Chem., vol. 275(27): 20861-20866 (2000).

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