Mayo Foundation for Medical Education and Research

Larry R Pease

Moses Rodriguez

David J Miller

Suresh Radhakrishnan

Bogoljub Ciric

Hirohito Kita

Arthur E Warrington

Virginia Van Keulen

Daren Ure

Loc T Nguyen

Bogolub Ciric

Koji Iijima

Materials and methods for identifying and using MHC molecule variants for activating self-reactive T cells in a peptide-specific manner, and their use to focus autoimmune cellular responses against diseases such as cancers and persisting viral infections, are described.

Enhancing T cell activation using altered MHC-peptide ligands

Materials and methods for using multivalent molecules (e.g., antibodies) to modulate cellular function. A molecule can be targeted to a particular type of cell, either through direct binding to an epitope on the surface of the cell, or through a linker that recognizes both the multivalent molecule and a marker on the cell surface.

IgM-mediated receptor clustering and cell modulation

Materials and methods for identifying and using MEW molecule variants for activating self-reactive T cells in a peptide-specific manner, and their use to focus autoimmune cellular responses against diseases such as cancers and persisting viral infections, are described.

Antibodies, particularly human antibodies, are disclosed having activity in treatment of demyelinating diseases and diseases of the central nervous system. Neuromodulatory agents are provided comprising a material selected from the group consisting of an antibody capable of binding structures or cells in the central nervous system, a peptide analog, and active fragments, monomers and combinations thereof having one or more of the following characteristics: capable of inducing remyelination; binding to neural tissue; promoting Casignaling with oligodendrocytes; and promoting cellular proliferation of glial cells. Amino acid and DNA sequences of exemplary antibodies are disclosed. Methods are described for treating demyelinating diseases, and diseases of the central nervous system, using polyclonal IgM antibodies and human monoclonal antibodies sHIgm22(LYM 22), sHIgm46(LYM46) ebvHIgM MSI19D10, CB2bG8, AKJR4, CB2iE12, CB2iE7, MSI19E5 and MSI10E10, and active fragments thereof. The invention extends to the use of antibodies and fragments in diagnostic and therapeutic applications, including screening assays.

Human IgM antibodies, and diagnostic and therapeutic uses thereof particularly in the central nervous system

An antibody capable of potentiating immune responses and modifying existing states of immune responsiveness is described, as is the sequence of the antibody. Also described are compositions containing the antibody, as well as methods for using the antibody and the compositions to enhance immune responses, to enhance DC function, to modify an existing state of immune responsiveness, to immunize individuals, or to treat or inhibit conditions such as allergic asthma.

Isolated antibody

Materials and methods for using multivalent molecules (e.g., antibodies) to modulate cellular function. A molecule can be targeted to a particular type of cell, either through direct binding to an epitope on the surface of the cell, or through a linker that recognizes both the multivalent molecule and a marker on the cell surface. The invention provides a chimeric polypeptide comprising a first amino acid sequence and a second amino acid sequence, wherein the first amino acid sequence comprises an WIC Class I peptide sequence, and where the second amino acid sequence comprises an epitope to which a multivalent molecule binds, including wherein the multivalent molecule is an IgM antibody, including antibody hIgM22. The invention provides a linker molecule for targeting IgM antibody, including antibody hIgM22, to a cell in the oligodendrocyte lineage.

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. The neuromodulatory agent has one or more of the following characteristics: it is capable of inducing remyelination; binding to neural tissue; promoting Casignaling with oligodendrocytes; and promoting cellular proliferation of glial cells. Amino acid and DNA sequences of exemplary antibodies are disclosed. 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 diagnostic and therapeutic applications, including screening assays for the discovery of additional antibodies that bind to cells of the nervous system, particularly oligodendrocytes.

Recombinantly produced antibody

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. The neuromodulatory agent has one or more of the following characteristics: it is capable of inducing remyelination; binding to neural tissue; promoting Casignaling with oligodendrocytes; and promoting cellular proliferation of glial cells. Amino acid and DNA sequences of exemplary antibodies are disclosed. 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 diagnostic and therapeutic applications, including screening assays for the discovery of additional antibodies that bind to cells of the nervous system, particularly oligodendrocytes.

Methods of promoting remyelination of central nervous system axons by administrating sHIgM22

A molecule capable of potentiating immune responses and modifying existing states of immune responsiveness is described. Also described are compositions containing the molecule, as well as methods for using the molecule and the compositions to enhance immune responses, to enhance DC function, to modify an existing state of immune responsiveness, to immunize individuals, or to treat or inhibit conditions such as allergic asthma.

Methods and molecules for modulating an immune response

A molecule capable of potentiating immune responses is described, as well as methods for using the molecule to enhance immune responses and enhance dendritic cell function. Also described are compositions containing the molecule and methods for using the compositions to treat or immunize individuals.

Growing community of inventors

Rochester, MN, United States of America

Larry R Pease