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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.

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First Claim