Cornell University

Genzyme Corporation

T.a.c. Thrombosis and Coagulation Aktiebolag

T.a.c. Thrombosis and Coagulation Ab

Björn Dahlbäck

William R Dackowski

Timothy Hla

Johan Stenflo

Robert Wydro

Ake Lundwall

Lars Bo Nielsen

Edward Cohen

Hideru Obinata

Christina Christoffersen

Sylvain Galvani

Victoria Blaho

Apolipoprotein M forms a complex with sphingosine-1-phosphate (S1P) and is the carrier of S1P in high density lipoprotein particles and mediates its endothelial protective effect. Increasing the concentration of the apoM/S1P complex by administering it, either alone or in HDL particles, can prevent or treat diseases caused by endothelial cell injury, including inflammatory diseases, sepsis, atherosclerosis and acute lung injury, ischemic heart disease, stroke, vital organ failure after ischemic stress.

Endothelium protective materials and methods of use

Methods are disclosed for determining, in a sample derived from a human, the functional activity of a component of the human blood coagulation system, which activity can be correlated to conversion of a substrate specific for activated Protein C (APC), by measuring in an assay medium containing the sample and a substrate for APC, the conversion of the substrate by APC and correlating the conversion to the functional activity of the component. When the component is anticoagulant Factor V, at least one of exogenous APC, Protein S or an inhibitor of Protein S activity is added to the medium. When the component is Protein C, APC, or Protein S, exogenous anticoagulant Factor V or an inhibitor of anticoagulant activity of Factor V is added to the medium. Methods are also disclosed for diagnosing a blood coagulation/anticoagulation disorder or for determining a predisposition thereto in a human by determining anticoagulant Factor V activity in an assay medium containing a sample derived from the human.

Assays for determining anticoagulant cofactor activity

The present invention relates to an assay for free protein S comprising the addition of a ligand specific for free protein S to a biological fluid sample to form a protein S/ligand complex, and subsequent determination of the amount of the complex formed in the sample. The ligand specific for free protein S is comprised of the C4b binding protein (C4BP), or part thereof, or a compound comprising an amino acid residue sequence that binds specifically to the binding site for C4BP in protein S. The present invention further relates to antibodies specific for free protein S, which can be used as ligands in the assay of the invention, and with protein S related polypeptides, which can be used to produce such antibodies. In addition, the present invention is related to diagnostic test systems, suitable in kit form, comprising the present ligand and at least one further reagent required in the assay for free protein S.

Methods and reagents for determining protein S

Disclosed are a transformed mammalian cell that produces biologically active Protein S, and a vector for effecting the transformation of the cell. produces biologically active human Protein S, and the vector used to effect the transgenesis of the cell. The vector disclosed includes DNA encoding mature human Protein S, under the transcriptional control of a eukaryotic metallothionein gene, and also includes the transforming region of the bovine papilloma virus genome, and a fragment of SV40 DNA.

Vector containing DNA encoding mature human protein S

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Malmö, Sweden

Björn Dahlbäck