University of California

Genentech, Inc.

Mark S Singer

Steven D Rosen

Laurence A Lasky

Yasuyuki Imai

Ted A Yednock

Scott E Stachel

Joyce Geoffroy

Kun Huang

The present invention provides novel assays for determining the ability of a test compound to inhibit intercellular adhesion mediated by a selectin receptor, such as the LHR. The assay involves coating a surface of a solid substrate with an antibody which specifically binds a selectin ligand. Preferred are antibodies against GlyCAM-1 which is a natural biological ligand for L-Selectin and also binds to P-Selectin and E-Selectin. A compound such as GlyCAM-1 is then bound to the antibodies. The test compound mixture putatively containing a selectin ligand is then brought into contact with a chimeric molecule. The test mixture might include any compound which might block or hinder binding between a selectin receptor and the ligand bound to the antibody. The chimeric molecule is comprised of an immunoglobulin bound to a selectin receptor and is introduced under conditions such that the selectin receptor portion of the chimeric molecule will bind to the selectin ligand bound to the antibodies on the surface if such binding is not blocked by the test compound. Bound chimeric molecules can be detected in a variety of ways such as by a conjugate compound of an anti-immunoglobulin antibody bound to enzyme such as alkaline phosphatase for the generation of color. Any test compounds which bind to the selectin receptor and block finding can be isolated, analyzed and identified.

Assays for inhibitors of leukocyte adhesion

DNA isolates coding for the lymphocyte homing receptor and methods of obtaining such DNA are provided, together with expression systems for recombinant production of the lymphocyte homing receptor useful in therapeutic or diagnostic compositions.

Soluble lymphocyte homing receptors

The invention relates to glycoprotein ligands of selectins. The invention further relates to methods and means for preparing and to nucleic acids encoding these ligands. The invention further concerns a method of treating a symptom or condition associated with excessive binding of circulating leukocytes to endothelial cells by administering to a patient in need of such treatment a glycoprotein ligand of a selectin.

Method for purification of L-selectin ligands

Selectin ligands

The present invention provides novel assays for determining the ability of a test compound to inhibit intercellular adhesion mediated by a selectin receptor, such as the LHR. The assays involve contacting the test compound with the receptor and an isolated receptor-binding agent. The receptor-binding agent is a sulfated polysaccharide, a sulfated glycolipid, or a compound comprising the extracellular region of an endothelial cell surface glycoprotein. Also provided are compositions comprising a compound comprising the extracellular region of an endothelial cell surface protein, which is specifically recognized by lymphocyte homing receptors.

DNA sequence encoding a selectin ligand

The present invention provides pharmaceutical compositions and methods for treating demyelinating diseases. The compositions comprise a blocking agent which inhibits LHR-mediated binding of leukocytes to myelin.

Compositions and methods for inhibiting leukocyte adhesion to CNS myelin

Lymphocyte homing receptors

DNA isolates coding for a lymphocyte homing receptor and methods of obtaining such DNA are provided, together with expression systems for recombinant production of the lymphocyte homing receptor useful in therapeutic or diagnostic compositions.

Growing community of inventors

Berkeley, CA, United States of America

Mark S Singer