Mucosal vascular addressins and uses thereof

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/12 (2006.01) A61K 38/17 (2006.01) A61K 39/395 (2006.01) C07K 14/705 (2006.01) C07K 16/28 (2006.01) C07K 19/00 (2006.01) C12N 15/62 (2006.01) G01N 33/566 (2006.01) G01N 33/68 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2212702

The present invention relates to isolated and/or recombinant nucleic acids which encode primate MAdCAMs, and to proteins or polypeptides referred to herein as isolated and/or recombinant primate MAdCAMs. The invention further relates to recombinant nucleic acid constructs, comprising a nucleic acid which encodes a primate MAdCAM of the present invention, a portion thereof, or a variant; to host cells comprising such constructs, useful for the production of recombinant proteins; the use of nucleic acids and/or proteins in assays to identify inhibitors (e.g., antagonists) of primate MAdCAM function; and to antibodies reactive with primate MAdCAM, which are useful in in vitro methods, diagnostic and/or therapeutic applications. The invention also relates to the treatment of individuals, particularly humans, suffering from a disease (e.g., inflammatory bowel disease) associated with leukocyte recruitment to the gastrointestinal tract or other tissues, for example, as a result of binding of leukocytes to cells expressing the molecule MAdCAM (gut-associated endothelium), comprising administering to the individual an effective amount of an agent, such as an antibody which inhibits the binding of leukocytes to MAdCAM.

La présente invention se rapporte à des acides nucléiques isolés et/ou recombinés qui codent des molécules d'adhésion cellulaire de l'adressine de muqueuses (MAdCAM) chez le primate, ainsi qu'à des protéines ou polypeptides auxquels il est ici fait référence en tant que molécules MAdCAM de primate, isolées et/ou recombinées. L'invention se rapporte en outre à des constructions d'acides nucléiques recombinés, comprenant un acide nucléique codant une molécule MAdCAM de la présente invention, une portion de cette molécule ou une variante; à des cellules hôtes comprenant de telles constructions, utiles pour la production de protéines recombinées; à l'utilisation d'acides nucléiques et/ou de protéines dans des dosages afin d'identifier des inhibiteurs (par exemple des antagonistes) de la fonction de la molécule MAdCAM chez le primate; ainsi qu'à des anticorps réagissant avec MAdCAM, et qui sont utiles dans des procédés in vitro, dans des applications diagnostiques et/ou thérapeutiques. L'invention se rapporte également au traitement d'individus, notamment des humains, souffrant d'une maladie (par exemple une maladie intestinale inflammatoire) associée au recrutement des leucocytes dans le tractus gastro-intestinal ou d'autres tissus, par exemple, en tant que conséquence de la liaison des leucocytes à des cellules exprimant MAdCAM (endothélium associé aux intestins), ce traitement consistant à administrer à l'individu une dose efficace d'un agent tel qu'un anticorps inhibant la liaison des leucocytes à MAdCAM.

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