Merck Serono S. A.

Bar-ilan University

University of Geneva

Geneva University Hospitals

Universitè De Genève

Laboratoires Serono S.a.

Beat Albert Imhof

Michel Aurrand-Lions

Hanoch Senderowitz

Arie Lev Gruzman

Paul Bradfield

Tamar Getter

Thomas Matthes

Pierre-Yves Dietrich

Mirna Tenan

Bernhard M Wehrle-Haller

Provided herein are novel barbituric acid derivatives, their synthesis and use thereof in blocking leukocyte transmigration. The novel barbituric acid derivatives are useful for the treatment of disorders associated with leukocyte transmigration, such as for example inflammatory diseases and disorders, autoimmune diseases and disorders, and cancers.

Barbituric acid derivatives, their preparation and use thereof as leukocyte transmigration inhibitors and for treating inflammatory diseases, autoimmune diseases and cancer

The invention relates to new polypeptides in isolated form belonging to a subfamily of the human immunoglobulin superfamily, which polypeptide shows at least 70% sequence homology with the amino acid sequence of the murine Confluency Regulated Adhesion Molecules 1 or 2 (CRAM-1 or CRAM-2) as depicted in FIG., upper and second row, respectively, and antibodies thereto as well as their use in treatment of inflammation and tumors.

Vascular adhesion molecules and modulation of their function

The present invention relates to a method for providing molecules that are capable of inhibiting angiogenesis, comprising the steps of providing a range of molecules; testing whether these molecules can prevent interaction between JAM-B and JAM-C; testing the positive molecules for their ability to block angiogenesis in vivo; and selecting molecules that are positive in the angiogenesis test as angiogenesis inhibiting molecules. The method may further comprise the step of isolating or producing the angiogenesis inhibiting molecules. The invention further relates to the angiogenesis inhibiting molecules thus provided and produced, to their use in the treatment of cancer, to therapeutical compositions comprising them. In a particular embodiment the invention relates to monoclonal antibodies, in particular Mab H33, to soluble JAM-C and JAM-B and to small molecules.

Angiogenesis inhibiting molecules, their selection, production and their use in the treatment of cancer

The present invention relates to the use of a compound that specifically binds to JAM-C or JAM-B for the treatment of gliomas. More specifically the invention relates to the use of an antagonist of JAM-B or JAM-C for the treatment of glioma, in particular astrocytoma.

Junctional adhesion molecule-C (JAM-C) binding compounds and methods of their use

The present invention relates to angiogenesis inhibiting molecules that are the monoclonal antibody H33 or fragments or derivatives thereof, to their use in the treatment of cancer, in particular the treatment of solid tumors and to therapeutic and diagnostic compositions comprising them. The invention relates in particular to humanized derivatives of H33 of human monoclonal antibodies having the specificity of H33.

Angiogenesis inhibiting molecules and their use in the treatment and diagnosis of cancer

Confluence regulated adhesion molecules useful in modulating vascular permeability

The present invention relates to a method for providing molecules that are capable of inhibiting angiogenesis, comprising the steps of providing a range of molecules; testing whether these molecules can prevent interaction between JAM-B and JAM-C; testing the positive molecules for their ability to block angiogenesis in vivo; and selecting molecules that are positive in the angiogenesis test as angiogenesis inhibiting molecules. The method may further comprise the step of isolating or producing the angiogenesis inhibiting molecules. The invention further relates to the angiogenesis inhibiting molecules thus provided and produced, to their use in the treatment of cancer, to therapeutical compositions comprising them. In a particular embodiment the invention relates to monoclonal antibodies, in particular MAb H33, to soluble JAM-C and JAM-B and to small molecules.

The invention relates to new polypeptide in isolated form belonging to a subfamily of the human Immunoglobulin Superfamily, which polypeptide shows at least 70% sequence homology with the amino acid sequence of the murine Confluency Regulated Adhesion Molecules 1 or 2 (CRAM-1 or CRAM-2) as depicted in FIG.upper and second row, respectively, and antibodies thereto as well as their use in treatment of inflammation and tumors.

Mono-leucine dependent basolateral sorting signal consisting of the amino acid sequence XhXhpp, wherein: Xrepresents a polar amino acid residue or alanine, hrepresents any hydrophobic amino acid residue, Xrepresents any amino a residue, hrepresents any hydrophobic amino acid residue, except leucine and isoleucine L represents a leucine residue, prepresents any polar amino acid residue, and prepresents any polar amino acid.

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Conches, Switzerland

Beat Albert Imhof