Abstract:
Compositions and methods for making and using humanized anti-LPA monoclonal antibodies, and fragments and derivatives thereof, are described.
Abstract:
The present invention provides crystalline forms of an anti-lipid antibody or fragment thereof, which may further comprise a lipid ligand of said antibody and/or salts, metals, or co-factors. Methods for making such crystals and co-crystals are provided. The lipid may be a bioactive lipid, including sphingolipids such as S1P. X-ray coordinates of such a crystal are provided, as are methods of using this information in antibody design or optimization. Methods for designing a humanized antibody to a lipid are provided. These methods may be performed in silico and may be intended to enhance binding affinity of an antibody to its original target lipid, and/or to alter binding specificity. Antibodies produced by these methods are also provided.
Abstract:
Compositions and methods for producing monoclonal antibodies and their derivatives reactive against bioactive lipid targets are described. These compositions include derivatized lipids, each of which comprises a bioactive lipid that having a polar head group and at least one hydrocarbon chain (e.g., a lysolipid such as lysophosphatidic acid or sphingosine-1 -phosphate) in which a carbon atom has been derivatized with a pendant reactive group; immunogens made by linking a derivatized lipid to a carrier moiety (e.g., a carrier protein, polyethylene glycol, colloidal gold, alginate, or a silicone bead); monoclonal antibodies and derivatives produced by immunizing an animal with such an immunogen; and therapeutic and diagnostic compositions containing such antibodies and antibody derivatives. Methods for making such derivatized lipids, immunogens, and monoclonal antibodies and derivatives, methods for detecting such antibodies once generated, and therapeutic and diagnostic methods for using such antibodies and derivatives, are also described.
Abstract:
Compositions and methods for producing monoclonal antibodies and their derivatives reactive against bioactive lipid targets are described. These compositions include derivatized lipids, each of which comprises a bioactive lipid that having a polar head group and at least one hydrocarbon chain (e.g., a lysolipid such as lysophosphatidic acid) in which a carbon atom has been derivatized with a pendant reactive group; immunogens made by linking a derivatized lipid to a carrier moiety (e.g., a earner protein, polyethylene glycol); monoclonal antibodies and derivatives produced by immunizing an animal with such an immunogen; and therapeutic and diagnostic compositions containing such antibodies and antibody derivatives. Methods for making such derivatized lipids, immunogens, and monoclonal antibodies and derivatives, and detecting or using such antibodies once generated, are also described.
Abstract:
Methods are provided for stem cell therapy using inhibitors of lysophosphatidic acid (LPA). Inhibition of LPA may be direct or indirect; particularly preferred direct inhibitors of LPA are antibodies to LPA, including humanized monoclonal antibodies to LPA. Such inhibitors are used in combination with stem cells for the treatment of injuries, diseases, or conditions amenable to treatment by stem cell therapy.
Abstract:
Methods for administering combinations of compositions comprising anti-S1P antibodies or antibody fragments and modulators of sphingolipid metabolic pathway enzymes are described. Such methods allow aberrant or undesirable levels of S1P to be reduced in patients known or suspected to have a disease or disorder correlated with aberrant S1P levels, and thus will be useful in treating such diseases and disorders.
Abstract:
The present invention provides crystalline forms of an anti-lipid antibody or fragment thereof, which may further comprise a lipid ligand of said antibody and/or salts, metals, or co-factors. Methods for making such crystals and co-crystals are provided. The lipid may be a bioactive lipid, including sphingolipids such as S1P. X-ray coordinates of such a crystal are provided, as are methods of using this information in antibody design or optimization. Methods for designing a humanized antibody to a lipid are provided. These methods may be performed in silico and may be intended to enhance binding affinity of an antibody to its original target lipid, and/or to alter binding specificity. Antibodies produced by these methods are also provided.
Abstract:
Methods are provided for increasing neuronal differentiation of neuronal stem cells using antibodies that bind lysophosphatidic acid (LPA). Particularly preferred antibodies to LPA are monoclonal antibodies, including humanized monoclonal antibodies to LPA. Such antibodies, and derivatives and variants thereof, can be used in increasing neuronal differentiation, and in treatment and/or prevention of injuries, diseases, or conditions associated with insufficient neuronal differentiation and/or with elevated LPA levels in neural tissues.
Abstract:
Compositions and methods for making and using humanized anti-LPA monoclonal antibodies, and fragments and derivatives thereof, are described.
Abstract:
The present invention relates to compositions that comprise an anti-SIP monoclonal antibody, antibody fragment, or derivative in a carrier, particularly a buffered, hypertonic aqueous solution, as well as to kits containing such compositions, and methods for using such compositions for treatment of diseases and conditions associated with SlP.