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ANTIBODY DESIGN USING ANTI-LIPID ANTIBODY CRYSTAL STRUCTURES

  • US 20130261287A1
  • Filed: 03/11/2013
  • Published: 10/03/2013
  • Est. Priority Date: 12/05/2008
  • Status: Abandoned Application
First Claim
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1. A method of designing an optimized antibody to a lipid, comprising:

  • a. providing an amino acid sequence of at least one variable region of a heavy or light chain of a first anti-lipid antibody, optionally a humanized antibody, wherein the anti-lipid antibody is specific for a first lipid, optionally a sphingolipid or a lysolipid, and wherein optionally at least one complementarity-determining region within the variable region is identified;

    b. replacing one or more amino acids within the at least one variable region with a different amino acid to yield a variant amino acid sequence, wherein the amino acid replacement(s) is(are) within a complementarity-determining region;

    c. preparing a second anti-lipid antibody containing the variant amino acid sequence, wherein the amino acid sequences of the first and second anti-lipid antibodies differ only in the variant amino acid sequence;

    d. determining one or more activity criteria of the second antibody, optionally by molecular modeling, ELISA, or surface plasmon resonance, wherein at least one of the activity criteria is optionally binding affinity for the first lipid, binding affinity for a second lipid, or specificity for the first lipid or specificity for a second lipid, wherein the first and second lipids are different lipid species; and

    e. selecting an optimized antibody based on one or more of the activity criteria, wherein the optimized antibody is the second antibody,wherein the method is optionally performed in silico.

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