73 results about "Tissue factor pathway inhibitor" patented technology

The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, and / or treat a blood coagulation disorder in a subject.

The invention relates to antibodies that specifically bind to tissue factor pathway inhibitor (TFPI) and that reduce the clotting time of blood. Such antibodies have utility in the treatment of subjects with a coagulopathy.

In a process for preparing Tissue Factor Pathway Inhibitor (TFPI) by the genetically engineered technique by the use of a transformed animal cell wherein a DNA encoding human TFPI is introduced, the improvement which comprises culturing said transformed animal cell in a culture medium supplemented with a sulfated polysaccharide to protect an intact TFPI produced by said transformed animal cell from cleavage by proteases present in the culture medium.

The present invention relates to methods for the identification of compounds that increase or decrease the inhibitory effect of TFPI on tissue factor activity and / or Factor Xa activity and / or thrombin formation. The invention also relates to methods for the identification of compounds that increase or decrease the co-factor activity of Protein S in TFPI-mediated inhibition of tissue factor and / or Factor Xa activity. This invention also relates to a pharmaceutical composition comprising the compounds identifiable by such methods. The invention also relates to methods for the regulation of tissue factor activity by influencing the interaction between Protein S and Tissue Factor Pathway Inhibitor.

Methods for prophylactically or therapeutically treating a patient at risk of developing or diagnosed as having a severe bacterial infection involving administration of tissue factor pathway inhibitor (TFPI) or a TFPI analog to patients suffering from or at risk of developing this condition. The methods involve the use of continuous intravenous infusion of TFPI or a TFPI analog at low doses to avoid adverse side effects.

The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, treat a blood coagulation disorder in a subject, purify TFPI, and identify a TFPI-binding compound.

The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, treat a blood coagulation disorder in a subject, purify TFPI, and identify a TFPI-binding compound.

The invention relates to antibodies that specifically bind to tissue factor pathway inhibitor (TFPI) and that reduce the clotting time of blood. Such antibodies have utility in the treatment of subjects with a coagulopathy.

The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, and / or treat a blood coagulation disorder in a subject.

Ixolaris, a novel protein with anticoagulant activity is described. Ixolaris can be isolated from the salivary glands of ticks or made by recombinant methods using various DNA expression techniques.

Isolated monoclonal antibodies that bind human tissue factor pathway inhibitor (TFPI) and the isolated nucleic acid molecules encoding them are provided. Pharmaceutical compositions comprising the anti-TFPI monoclonal antibodies and methods of treating deficiencies or defects in coagulation by administration of the antibodies are also provided. Methods of producing the antibodies are also provided.

The present invention provides methods of treating hemorrhagic fevers where selective inhibitors of fVIIa / TF are used as a treatment for hemorrhagic fevers and have therapeutic effects which include ameliorating and / or preventing coagulopathy and inflammatory responses. These inhibitors include certain proteins which are part of a family termed Nematode-Extracted Anticoagulant Proteins (“NAPs”). Other inhibitors include Tissue Factor Pathway Inhibitor (“TFPI”) and TFPI analogs.

Isolated monoclonal antibodies that bind to specific epitopes of human tissue factor pathway inhibitor (TFPI) and the isolated nucleic acid molecules encoding them are provided. Pharmaceutical compositions comprising the anti-TFPI monoclonal antibodies and methods of treating deficiencies or defects in coagulation by administration of the antibodies are also provided.

The invention relates to the field of microbiology, in particular to a tissue factor pathway inhibitor (TFPI), a preparation method thereof and application thereof. A TFPI-1 is represented by the amino acid sequence SEQ ID No.1 in the sequence list; and a TFPI-2 is represented by the amino acid sequence SEQ ID No.2 in the sequence list. The preparation method comprises: converting colibacillus BL21 (DE3) by plasmids pE15TFPI1 and pE15TFP2 to obtain BL21 / pE15TFPI1 and BL21 / pE15TFPI2 respectively; inducing the obtained products with isopropyl-beta-D-thiogalactoside; and purifying recombinant proteins through affinity chromatography to obtain TFPI-1 and TFPI-2. The TFPI has a high-efficiency sterilization effect and therefore can resist to bacterial infection and be used for disease prevention and treatment. The TFPI provided by the invention can effectively crack many pathogenic bacteria so as to inhibit bacterial infection.

This invention provides for the prevention and treatment of tumor growth, metastasis, and cancer-mediated thrombosis through the administration, in combination, of a short or long acting GPIIb / IIIa antagonist (A) and anticoagulant (B) that might include the following: UFH or low molecular weight heparin, (LMWH), ultra LMWH, pentasaccharide or direct anti-Xa or direct anti-IX / IXa, direct anti-IIa (thrombin) or tissue factor pathway inhibitor (TFPI) by any means that produces contact of the agents with their site of action wherein at least one of the components of each of these combinations is given in reduced amount. This combined formulation could be used as a stand-alone regimen or in conjunction with other therapies (chemotherapy, radiotherapy, angiogenesis inhibitors, . . . ), and pre- & post-tumor surgery in the prevention and treatment of cancer associated metastasis, angiogenesis, tumor growth, and thrombosis.

The application discloses a combination of two monospecific TFPI antibodies, wherein one antibody is capable of specifically binding TFPI (1-181) and the other antibody is capable of specifically binding TFPI (182-276), as well as bispecific anti-TFPI antibodies derived from two such monospecific antibodies. Both the combination of the two monospecific antibodies and the bispecific antibody strongly enhance thrombin generation by neutralising full length TFPIα, even where the concentration of TFPI is abnormally elevated.

The invention relates to antibodies that are capable of specifically binding tissue factor pathway inhibitor (TFPI), neutralising free TFPI and reducing the clotting time of blood. Furthermore, the invention relates to polynucleotides that encode such antibodies and to cells that comprise the polynucleotides or that express the antibodies of the invention. Such antibodies have utility in the treatment of subjects with a coagulopathy, alone as well as in combination with a second agent.

Methods for prophylactically or therapeutically treating severe pneumonia involve administration of tissue factor pathway inhibitor (TFPI) or a TFPI analog to patients suffering from or at risk of developing this condition. The methods involve the use of continuous intravenous infusion of TFPI or a TFPI analog, preferably at low doses to avoid adverse side effects.

The invention provides a thromboplastin reagent comprising: tissue factor, a phospholipid and a polyphosphate that acts as a blocker of tissue factor pathway inhibitor (TFPI). Also provided are a composition for promoting clotting comprising polyphosphate, and a reagent for a clotting assay also comprising polyphosphate together with an activator of clotting. Methods for stopping or slowing wound bleeding and fibrinolysis using compositions comprising polyphosphate are also disclosed.

Methods for prophylactically or therapeutically treating severe pneumonia involve administration of tissue factor pathway inhibitor (TFPI) or a TFPI analog to patients suffering from or at risk of developing this condition. The methods involve the use of continuous intravenous infusion of TFPI or a TFPI analog, preferably at low doses to avoid adverse side effects.

The invention relates to antibodies that are capable of specifically binding tissue factor pathway inhibitor (TFPI), neutralizing free TFPI and reducing the clotting time of blood. Furthermore, the invention relates to polynucleotides that encode such antibodies and to cells that comprise the polynucleotides or that express the antibodies of the invention. Such antibodies have utility in the treatment of subjects with a coagulopathy, alone as well as in combination with a second agent.

The invention relates to antibodies that specifically bind to tissue factor pathway inhibitor (TFPI) and that reduce clotting time in (a) human FVIII-deficient plasma and / or (b) human whole blood. Such antibodies have utility in the treatment of bleeding disorders and in the stimulation of blood clotting.

The invention relates to the field of medicament, in particular to an in-vitro microplate-based screening method of tissue factor (TF) pathway inhibitors, and is characterized in that the invention comprises the following steps: incubating cells and the medicament to be measured together; getting cell lysis solution after freeze thaw, blowing and beating; putting the cell lysis solution on the microplate for incubation; adding human prothrombin complex solution for incubation; adding chromogenic substrate solution in the reactant liquor for incubation; measuring the value of absorbance with a micro-plate reader of 405nm. The invention also discloses some tissue factor pathway inhibitors screened out by using the method, such as hydroxygenkwanin, ruscogenin, quercetinic acid, ginsenoside Rb1, ginsenoside or diosgenin and so on.

The present invention provides methods of treating hemorrhagic fevers where selective inhibitors of fVIIa / TF are used as a treatment for hemorrhagic fevers and have therapeutic effects which include ameliorating and / or preventing coagulopathy and inflammatory responses. These inhibitors include certain proteins which are part of a family termed Nematode-Extracted Anticoagulant Proteins ("NAPs"). Other inhibitors include Tissue Factor Pathway Inhibitor ("TFPI") and TFPI analogs.

The application discloses a combination of two monospecific TFPI antibodies, wherein one antibody is capable of specifically binding TFPI (1-181) and the other antibody is capable of specifically binding TFPI (182-276), as well as bispecific anti-TFPI antibodies derived from two such monospecific antibodies. Both the combination of the two monospecific antibodies and the bispecific antibody strongly enhance thrombin generation by neutralising full length TFPI[alpha], even where the concentration of TFPI is abnormally elevated.

The present invention provides compositions and methods for modulating TFPI protein plasma concentration and TFPI protein function. Such modulation can be used to treat blood disorders such as bleeding disorders and clotting disorders.