Millennium Pharmaceuticals Limited

Michael J Briskin

Lijun Wu

Alyson M Wilbanks

Kristine E Murphy

Walter Newman

Douglas J Ringler

Dominic Picarella

Lily Zou

The present invention relates to isolated antibodies and antigen-binding fragments thereof that bind naturally occurring human MAdCAM, wherein said naturally occurring human MAdCAM comprises a polypeptide with at least 90% sequence identity to SEQ ID NO:2 or SEQ ID NO:4, said naturally occurring human MAdCAM binds &#x3b1;4&#x3b2;7, and wherein said isolated antibodies and antigen-binding fragments thereof inhibit binding of said naturally occurring human MAdCAM to human &#x3b1;4&#x3b2;7, and wherein said antibody inhibits adhesion of RPMI 8866 cells to cells that express said human MAdCAM.

Mucosal vascular addressins and uses thereof

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

The present invention relates to isolated and/or recombinant nucleic acids which encode naturally occurring primate MAdCAMs, wherein said nucleic acid encodes the polypeptide shown in FIG.(SEQ ID NO:2), the polypeptide shown in FIG.(SEQ ID NO:4), or the polypeptide shown in FIG.(SEQ ID NO:6). The invention further relates to recombinant nucleic acid constructs, comprising a nucleic acid which encodes a naturally occurring primate MAdCAM, wherein said nucleic acid encodes a polypeptide having an amino acid sequence as set forth in FIG.(SEQ ID NO:2), FIG.(SEQ ID NO:4), or FIG.(SEQ ID NO:6); 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.

Mucosal vascular addressins

The invention relates to an antibody or antigen-binding fragment thereof which binds to the CXC chemokine receptor Bonzo (also referred to as STRL33, TYMSTR, HBMBU14 and CXCR6) and blocks the binding of a ligand (e.g., SExCkine (also referred to as chemokine alpha-5 and CXCL16) to the receptor. The invention also relates to a method of identifying agents (molecules, compounds) which can bind to Bonzo and inhibit the binding of a ligand (e.g., SExCkine) and/or modulate a function of Bonzo. The invention relates to an antibody or antigen-binding fragment thereof which binds to the CXC chemokine SExCkine (also referred to as chemokine alpha-5) and inhibit binding of SExCkine to receptor (e.g., Bonzo). The invention also relates to targeting molecules which contain a first binding moiety which binds to mammalian Bonzo and a second binding moiety which binds to a molecule expressed on the surface of a target cell. The invention also relates to a method of promoting and/or effectuating the interaction of a Bonzocell and a target cell. The invention further relates to a method of modulating a function of Bonzo, and to the use of the antibodies, antigen-binding fragments, targeting molecules and agents identified by the method of the invention in research, therapeutic, prophylactic and diagnostic methods.

Antibodies for 'Bonzo' chemokine receptor and therapeutic uses thereof

The invention relates to an antibody or antigen-binding fragment thereof which binds to the CXC chemokine receptor Bonzo (also referred to as STRL33, TYMSTR, HBMBU14 and CXCR6) and blocks the binding of a ligand (e.g., SExCkine (also referred to as chemokine alpha-5 and CXCL16) to the receptor. The invention also relates to a method of identifying agents (molecules, compounds) which can bind to Bonzo and inhibit the binding of a ligand (e.g., SExCkine) and/or modulate a function of Bonzo. The invention further relates to a method of modulating a function of Bonzo, and to the use of the antibodies, antigen-binding fragments, targeting molecules and agents identified by the method of the invention in research, therapeutic, prophylactic and diagnostic methods.

Antibodies and ligands for 'Bonzo' chemokine receptor

Methods of modulating LERK-2-mediated cell adhesion, as well as methods of modulating angiogenesis and inflammation are described. Also described are agents such as antibodies which can modulate LERK-2-mediated cell adhesion, as well as methods of treating angiogenic diseases and inflammatory diseases.

Inhibition of LERK-2-mediated cell adhesion

The present invention relates to an isolated or recombinant nucleic acid which encodes a mammalian hyaluronan synthase (e.g. human). The present invention also relates to a host cell comprising the nucleic acid encoding mammalian hyaluronan synthase. The present invention also relates to a method for producing a mammalian hyaluronan synthase comprising introducing into a host cell a nucleic acid construct comprising a nucleic acid which encodes a mammalian hyaluronan synthase, whereby a recombinant host cell is produced having said coding sequence operably linked to at least one expression control sequence; and maintaining the host cells produced in a suitable medium under conditions whereby the nucleic acid is expressed. The present invention also relates to an antibody or functional portion thereof which binds mammalian hyaluronan synthase. The present invention also relates to a method of detecting mammalian hyaluronan synthase in a sample comprising contacting a sample with an antibody which binds hyaluronan synthase under conditions suitable for specific binding of said antibody to the mammalian hyaluronan synthase; and detecting antibody-mammalian hyaluronan synthase. The invention further relates to a method of using hyaluronan synthase to make hyaluronan.

Mammalian hyaluronan synthases, nucleic acids and uses thereof

The invention relates to a method of detecting and/or identifying agents (molecules, compounds) which can bind to Bonzo and inhibit the binding of a ligand and/or modulate a function of Bonzo.

Growing community of inventors

Lexington, MA, United States of America

Michael J Briskin