Abstract: The present invention provides an in vitro method for the assessment of functional protein S levels in a sample. The present invention also provides kits for use in the determination of functional protein S levels in a sample. Also provided is a method of treatment based on the determination of functional protein S levels, followed by administration of a therapeutic agent.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The present invention is concerned with a variant blood coagulation component, which is substantially homologous in amino acid sequence to a wild-type blood coagulation component capable of exhibiting anticoagulant activity in the protein C-anticoagulant system of blood and selected from protein C (PC) and activated protein C (APC), said variant component being capable of exhibiting an anticoagulant activity, that is enhanced in comparison with the anticoagulant activity expressed by the corresponding wild-type blood coagulation component, and said variant component differing from the respective wild-type component, in that it contains in comparison with said wild-type component at least one amino acid residue modification in its N-terminal amino acid residue sequence that constitutes the Gla-domain of protein C and at least one amino acid residue modification in the serine-protease domain of protein C.

Abstract: The present invention is concerned with a variant blood coagulation component, which is substantially homologous in amino acid sequences to a wild-type blood coagulation component capable of exhibiting anticoagulant activity in the protein C-anticoagulant system of blood and selected from protein C (PC) and activated protein C (APC), said variant component being capable of exhibiting an anticoagulant activity, that is enhanced in comparison with anticoagulant activity expressed by the corresponding wild-type blood coagulation component, said variant component differing from the respective wild-type component, in that it contains in comparison with said wild-type component at least one amino acid residue modification in it N-terminal amino acid residue sequence that constitutes the Gla-domain of protein C.

Abstract: 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.

Abstract: The present invention is concerned with an assay for free protein S comprising 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 said 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.

Abstract: Particle-based methods, compositions, and kits are provided for the detection of the free form of a member of a binding pair which may be found free or in a bound state in a sample. Inhibition and direct assay formats are provided. In one embodiment, the invention provides diagnostic tools for the diagnosis of thrombophilia through the detection of free protein S.

Abstract: The present invention is concerned with an assay for free protein S comprising 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 said 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 is further concerned with 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.

Abstract: The present invention is directed to a method of detecting APC resistance and a kit for use with the method.

Abstract: 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.