Compositions and methods including a recombinant human mab that promotes cns remyelination

Abstract

Antibodies, and particularly human antibodies, are disclosed that demonstrate activity in the treatment of demyelinating diseases as well as other diseases of the central nervous system that are of viral, bacterial or idiopathic origin, including neural dysfunction caused by spinal cord injury. Neuromodulatory agents are set forth that include and comprise a material selected from the group consisting of an antibody capable of binding structures or cells in the central nervous system, a peptide analog, a hapten, active fragments thereof, agonists thereof, mimics thereof, monomers thereof and combinations thereof. Methods are described for treating demyelinating diseases, and diseases of the central nervous system of humans and domestic animals, using polyclonal IgM antibodies and human monoclonal antibodies sHIgm22(LYM 22), sHIgm46(LYM46) ebvHIgM MSI19D10, CB2bG8, AKJR4, CB2iE12, CB2iE7, MSI19E5 and MSI10E10, active fragments thereof and the like. The invention also extends to the use of human antibodies, fragments, peptide derivatives and like materials, and their use in above referenced therapeutic applications, and to pharmaceutical compositions containing them, that may be administered in desirably low doses to treat conditions involving demyelination and to promote remyelination.

1 . A pharmaceutical composition comprising a human monoclonal antibody selected from the group consisting of mAb sHIgM22 (LYM 22), sHIgM46 (LYM46), ebvHIgM MSI19D10, Cb2BG8, MSI10E10, mixtures thereof, monomers thereof, active fragments thereof, binding partners thereto, and recombinant antibodies derived therefrom and a pharmaceutically acceptable carrier, vehicle or diluent, wherein said composition is prepared for delivery in a dose range that corresponds or is equivalent to from about 500 ng to about 600 μg or to a range of from about 1.25 μg/kg to about 2.5 μg/kg. 
     
     
         2 . The pharmaceutical composition of  claim 1  wherein said dose is on the order of 500 ng. 
     
     
         3 . The pharmaceutical composition of  claim 1  wherein said dose is on the order of 600 μg. 
     
     
         4 . The pharmaceutical composition of  claim 1  wherein said dose corresponds to a range of from about 1.25 μg/kg to about 2.5 μg/kg. 
     
     
         5 . The pharmaceutical composition of  claim 2  wherein said dose corresponds to about 2.5 μg/kg. 
     
     
         6 . The pharmaceutical composition of  claim 3  wherein said dose corresponds to a range of about 1.25 μg/kg. 
     
     
         7 . The pharmaceutical composition comprising of  claim 1  wherein said human recombinant antibody corresponds to or is derived from mAb SHIgM22 (LYM22). 
     
     
         8 . The pharmaceutical composition comprising of  claim 1  wherein said human recombinant antibody corresponds to or is derived from mAb SHIgM46 (LYM46). 
     
     
         9 . The pharmaceutical composition of  claim 1  wherein said composition further includes up to about 2 mg of a steroid. 
     
     
         10 . The pharmaceutical composition of  claim 9  wherein said composition includes from about 1 to about 2 mg of said steroid. 
     
     
         11 . The pharmaceutical composition of  claim 9  wherein said steroid comprises methylprednisolone. 
     
     
         12 . A method of stimulating remyelination of central nervous system axons in a mammal which comprises administering to said mammal an effective amount of a monoclonal antibody, or mixtures, monomers, active fragments thereof, or recombinant antibodies derived therefrom, characterized by their ability to bind structures and cells within the central nervous system, including oligodendrocytes, comprising administering a composition of  claim 1 . 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 12  which comprises administration of a human monoclonal antibody selected from the group consisting of mAb sHIgM22 (LYM 22), ebvHIgM MSI19D10, sHIgM46 (LYM46), ebvHIgM CB2b-G8, MSI10E10, mixtures thereof, monomers thereof, active fragments thereof, binding partners thereto, and recombinant antibodies derived therefrom. 
     
     
         15 . A method of treating or preventing a demyelinating disease of the central nervous system in a mammal which comprises administering to said mammal an effective amount of a monoclonal antibody, or mixtures, monomers, active fragments thereof, or recombinant antibodies derived therefrom, characterized by their ability to bind to structures and cells in the central nervous system, including oligodendrocytes, and to stimulate remyelination of axons of the central nervous system, comprising administering a composition of  claim 1 . 
     
     
         16 . The method of  claim 15  which comprises administration of a human monoclonal antibody selected from the group consisting of mAb sHIgM22 (LYM 22), ebvHIgM MSI19D10, sHIgM46 (LYM46), ebvHIgM CB2b-G8, MSI10E10, mixtures thereof, monomers thereof, active fragments thereof, binding partners thereto, and recombinant antibodies derived therefrom. 
     
     
         17 . The method of  claim 12  wherein said mammal is a human being having multiple sclerosis, or a human or domestic animal with a demyelinating disease, or a disease or other injury or dysfunction of the central nervous system. 
     
     
         18 . The method of  claim 12  wherein the method of administration is selected from intravenous, intraperitoneal, intrathecal, subcutaneous, sublingual, intramuscular, rectal, respiratory and nasopharyngeal administration. 
     
     
         19 . The method of  claim 15  wherein said mammal is a human being having multiple sclerosis, or a human or domestic animal with a demyelinating disease, or a disease or other injury or dysfunction of the central nervous system. 
     
     
         20 . The method of  claim 15  wherein the method of administration is selected from intravenous, intraperitoneal, intrathecal, subcutaneous, sublingual, intramuscular, rectal, respiratory and nasopharyngeal administration.