Millennium Pharmaceuticals Limited

Douglas J Ringler

Walter Newman

Paul D Ponath

Shixin Qin

Charles R Mackay

Mary M Bendig

S Tarran Jones

José W Saldanha

Dominic Picarella

Michael J Briskin

José Saldanha

The invention relates to isolated and/or recombinant nucleic acids which encode a human chemotactic cytokine designated human eotaxin, and to isolated and/or recombinant human eotaxin proteins or polypeptides, including synthetic polypeptides. The invention further relates to recombinant nucleic acid constructs, comprising a nucleic acid which encodes a human eotaxin, a portion thereof, or a variant; to host cells comprising such constructs, useful for the production of recombinant human eotaxin; and to antibodies reactive with human eotaxin, useful in in vitro methods, diagnosis and/or therapy. Also provided are methods of use of the eotaxin proteins, e.g., in the recruitment of eosinophils to a particular site or in the treatment of allergic conditions. Human eotaxins can be used to identify inhibitors (e.g., antagonists) or promoters (agonists) of human eotaxin, which can be used to selectively modulate leukocyte function, in inflammatory and autoimmune diseases, or in infections.

Method of diagnosis of inflammatory disease using eotaxin antibodies

The present invention relates to fusion proteins comprising a naturally occurring primate MAdCAM, wherein said naturally occurring primate MAdCAM binds &#x3b1;4&#x3b2;7 integrin and has at least about 75% amino acid similarity to an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4 and SEQ ID NO:6.

Mucosal vascular addressing and uses thereof

Antibodies to human eotaxin

The present invention relates to isolated nucleic acids encoding humanized immunoglobulins having binding specificity for &#x3b1;4&#x3b2;7 integrin, isolated nucleic acids encoding a humanized immunoglobulin heavy chain and isolated nucleic acids encoding a humanized light chain having binding specificity for &#x3b1;4&#x3b2;7 integrin. The invention also relates to expression vectors and host cells comprising a nucleotide sequence which encodes a humanized immunoglobulin or antigen-binding fragment thereof having binding specificity for &#x3b1;4&#x3b2;7. The invention further relates to methods of preparing a humanized immunoglobulin, humanized immunoglobulin heavy chain and humanized immunoglobulin light chain that has binding specificity for &#x3b1;4&#x3b2;7 integrin.

Humanized immunoglobulin reactive with &#x3b1;4&#x3b2;7 integrin

Human chemotactic cytokine

The present invention relates to isolated and/or recombinant nucleic acids which encode a human chemotactic cytokine designated human eotaxin, and to proteins or polypeptides referred to herein as isolated and/or recombinant human eotaxin, including synthetic polypeptides. The invention further relates to recombinant nucleic acid constructs, comprising a nucleic acid which encodes a human eotaxin of the present invention, a portion thereof, or a variant; to host cells comprising such constructs, useful for the production of recombinant human eotaxin; and to antibodies reactive with human eotaxin, which are useful in in vitro methods, diagnostic and/or therapeutic applications. Also provided are methods of use of the proteins of the present invention, for example in the recruitment of eosinophils to a particular site or in the treatment of allergic conditions. Human eotaxins can be used in assays to identify inhibitors (e.g., antagonists) or promoters (agonists) of human eotaxin function. Agents which inhibit or promote eotaxin function can be administered to an individual, providing a new approach to selective modulation of leukocyte function, which is useful in a variety of inflammatory and autoimmune diseases, or in the treatment of infections.

The present invention relates to humanized immunoglobulins having binding specificity for &#x3b1;4&#x3b2;7 integrin, comprising an antigen binding region of nonhuman origin (e.g., rodent) and at least a portion of an immunoglobulin of human origin (e.g., a human framework region, a human constant region). In one embodiment, the humanized immunoglobulin can compete with murine Act-1 for binding to human &#x3b1;4&#x3b2;7 integrin. In a preferred embodiment, the antigen binding region of the humanized immunoglobulin comprises each of the complementarity determining regions of the light and heavy chains of the murine Act-1 antibody.

The invention relates to the treatment of individuals suffering from a disease associated with leukocyte recruitment to the gastrointestinal tract or other tissues as a result of binding of leukocytes to gut-associated endothelium expressing the molecule MAdCAM (such as inflammatory bowel disease), comprising administering to the individual an effective amount of an antibody which inhibits the binding of leukocytes to endothelial MAdCAM.

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Revere, MA, United States of America

Douglas J Ringler