Monoclonal antibody against LPS core

US5858728A · kind A · utility

Assignee

• The Common Services Agency · GB

Inventors

• Hermann Gram · Weil am Rhein, DE
• Franco E. Di Padova · Birsfelden, CH
• George Robin Barclay · Gorebridge, GB
• Ian Raymond Poxton · Gorebridge, GB

Key dates

• Filing date: May 9, 1996
• Grant date: Jan 12, 1999
• Expiry date: May 9, 2016

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2400/50
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

The invention provides monoclonal antibodies (Mabs) which are cross-protective against endotoxemia caused by at least two different Gram-negative bacterial strains having different core structures; and methods of production of these antibodies. By use of the Kohler/Milstein procedure involving immunization of mice with a number of different rough strains of heat-killed Gram-negative bacteria, followed by fusion and proper screening of the resulting hybridomas, such murine MAbs are obtained. The murine MAbs may be chimerized or humanized by known methods. For example, a chimeric MAb of IgG isotype is provided in which the hypervariable regions of the heavy chain have the amino acid sequences: Asp Tyr Tyr Met Thr; Leu Ile Arg Asn Lys Arg Asn Gly Asp Thr Ala Glu Tyr Ser Ala Ser Val Lys; and Gln Gly Arg Gly Tyr Thr Leu Asp Tyr; the hypervariable regions of the light chain have the amino acid sequences: Arg Ala Ser Gln Asn Ile Asn Ile Trp Leu Ser; Lys Ala Ser Asn Leu His Thr; and Leu Gln Gly Gln Ser Tyr Pro Arg Thr; the framework regions in the variable domains are murine and the constant domains are human.