43 results about "Factor XIa" patented technology

The present disclosure provides antibodies that bind to catalytic domains of Factor XI (FXI) and methods of use thereof. According to certain embodiments, the antibody is an antagonist antibody that inhibits blood clot formation achieved through an intrinsic pathway without affecting hemostasis, as shown by the effect of the antagonist antibody on extension of aPTT without affecting PT. As such, these antagonist antibodies can be used in therapeutic regimens for the treatment of blood clotting diseases or disorders or with clot formation as risk factors, such as, but not limited to, atrial fibrillation. In certain embodiments, the present disclosure comprises antibodies that bind to FXI and mediate clot formation or thrombosis. The antibodies of the present disclosure may be fully human, non-naturally occurring antibodies.

Novel binding molecules comprising humanized antibodies, fragments, variants, and derivatives thereof, as well as compositions, methods, and kits comprising the same, are described, wherein the binding molecules specifically bind to FX1 and FX1a. The binding molecules are capable of binding to the factor X1A2 domain and forming immune complexes, thereby disrupting the contact activation molecule complex without affecting the activity or activation of hemostatic factor XI. The binding molecules disclosed herein are suitable for safely inhibiting thrombosis and inflammation without impairing hemostasis. Thus, the binding molecules, compositions, methods, and kits provided herein are intended for treating diseases and conditions, particularly those associated with thrombosis and inflammation. In addition, polynucleotides encoding the binding molecules disclosed herein, vectors comprising the polynucleotides, and host cells for producing the polynucleotides are also provided.

The present disclosure describes cyclic peptide inhibitors of Factor XI (FXI), preferably FXIa. Also described are pharmaceutical compositions comprising the cyclic peptides and their use in treating conditions, diseases and / or disorders responsive to FXI, preferably FXIa inhibition, including thrombosis or thrombo-inflammatory conditions.

The present invention provides novel antigen-binding peptides, such as antibodies or antibody fragments, that specifically bind to selective FXIa inhibitors and / or dual inhibitors of FXIa and plasma kallikrein.The present invention further relates to a method of reducing the antithrombotic effect of FXIa inhibitors by administering to a subject a pharma- ceutical effective amount of the antigen-binding peptides disclosed herein.In addition, the present invention provides detection reagents and methods for detecting FXIa inhibitor levels in biological samples. TIFF2024505390000129.tif113125

The present invention provides a compound of Formula I and pharmaceutical compositions comprising one or more compounds of Formula I compounds, and methods for using the compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein.

The present disclosure provides methods for using antibodies that bind to Factor XI (FXI) for the purpose of preventing or treating clot formation or thrombogenesis after a surgical procedure. According to certain embodiments, the antibodies are antagonist antibodies that inhibit blood clot formation via the intrinsic pathway without affecting hemostasis, as shown by their effect on prolonging aPTT without affecting PT. As such, these antagonist antibodies may be used to treat or prevent clot formation in a subject requiring such treatment, such as, but not limited to, post-surgery.

The present invention provides compounds of Formula (I):or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective Factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

The present invention relates to methods of preventing, treating or managing, reducing the risk of stroke or thromboembolism in a subject afflicted with end stage renal disease comprising administering a pharmaceutical composition comprising a monoclonal antibody or an antigen binding fragment thereof that bind to human Factor XI and / or activated Factor XI (“Factor XIa”).

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XI activation inhibitors.

RNA interference (RNAi) agents for inhibiting the expression of Factor XI (FXI) are provided, as are pharmaceutical compositions comprising one or more FXI RNAi agents together with one or more excipients capable of delivering the RNAi agent(s) to a liver cell in vivo. Delivery of the FXI RNAi agent(s) to liver cells in vivo provides for inhibition of FXI gene expression and can provide for treatment of myocardial infarction, atrial fibrillation (AFib), deep vein thrombosis, pulmonary embolism, ischemic stroke, transient ischemic attack, retinal artery occlusion, mesenteric ischemia, renal vein thrombosis, cerebral venous sinus thrombosis, venous thromboembolism due to deep vein thrombosis, and peripheral artery disease, as well as diseases and disorders associated with angioedema, thrombosis, and / or coagulation.

Disclosed is a method for removing factor XI (FXI) during plasma protein purification, more specifically a method for removing FXI including dialyzing and concentrating a plasma protein fraction II paste containing FXI and a plasma protein, and then removing the FXI using ceramic-based cation exchange resin. The method for removing factor XI (FXI) can improve removal efficiency of impurities and thrombogenic substances, thereby producing stable plasma proteins with improved quality.

The present disclosure provides antibodies that bind to the A2 domain of Factor XI (FXI) and methods of using the same. According to certain embodiments, the antibodies are antagonist antibodies that inhibit blood clot formation via the intrinsic pathway without affecting hemostasis, as shown by their effect on prolonging aPTT without affecting PT. As such, these antagonist antibodies may be used to treat blood clotting diseases or disorders or treatment regimens that have clot formation as a risk factor, such as, but not limited to atrial fibrillation. In certain embodiments, the disclosure includes antibodies that bind FXI and mediate clot formation or thrombogenesis. The antibodies of the disclosure may be fully human, non-naturally occurring antibodies.

The present invention provides compounds useful for the treatment or prevention of diseases or conditions involving (a) thromboembolic disorders, (b) inflammatory disorders, or (c) plasma kallikrein activity. [Solution] A compound of formula (I), or its tautomers, stereoisomers, isotope substitutions, or pharmaceutically acceptable salts or solvates is provided. TIFF2026062690000101.tif47128

The present invention provides compounds and compositions that inhibit Factor XIa or kallikrein and methods of using these compounds and composition.

The present disclosure is in the field of coagulation diagnostics and relates to a method for excluding anticoagulants from the group of factor XIa inhibitors in a patient sample.

The present invention provides compounds of Formula (I):or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

The present invention provides a heparin-insensitive assay for measuring the quantity of Factor XIa in a sample. The present invention provides a method for measuring the concentration of Factor XIa in a plasma sample by using enzymatic heparin degradation as sample pretreatment step.

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XI activation inhibitors.

This disclosure relates to dosage regimens for combination therapies comprising anti-Factor XI and / or activated Factor XI (Factor XIa) antibodies, or antigen-binding fragments thereof, e.g., for use in the treatment of thromboembolic disorders or related conditions.

The present invention is directed to 3-(1H-imidazol-2-yl)-2,3,8,8a-tetrahydroindolizin-5(1H)-one derivatives, stereoisomers, isotopologues, and pharmaceutically acceptable salts thereof, pharmaceutical compositions containing said compounds and the use of said compounds in the treatment and / or prophylaxis of thromboembolic disorders, inflammatory disorders and diseases or conditions in which plasma kallikrein activity is implicated.

RNA interference (RNAi) agents for inhibiting the expression of Factor XI (FXI) are provided, as are pharmaceutical compositions comprising one or more FXI RNAi agents together with one or more excipients capable of delivering the RNAi agent(s) to a liver cell in vivo. Delivery of the FXI RNAi agent(s) to liver cells in vivo provides for inhibition of FXI gene expression and can provide for treatment of myocardial infarction, atrial fibrillation (AFib), deep vein thrombosis, pulmonary embolism, ischemic stroke, transient ischemic attack, retinal artery occlusion, mesenteric ischemia, renal vein thrombosis, cerebral venous sinus thrombosis, venous thromboembolism due to deep vein thrombosis, and peripheral artery disease, as well as diseases and disorders associated with angioedema, thrombosis, and / or coagulation.

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XI activation inhibitors.

The present invention is directed to Factor XIa inhibitors, tautomers, stereoisomers, isotopologues, and pharmaceutically acceptable salts and solvates thereof, pharmaceutical compositions containing said compounds and the use of said compounds in the treatment and / or prophylaxis of thromboembolic disorders, inflammatory disorders, and diseases or conditions in which plasma kallikrein activity is implicated.

The present invention is directed to 5-oxo-1,2,3,5,8,8a-hexahydroindolizine-3-carboxamide derivatives, stereoisomers, isotopologues, and pharmaceutically acceptable salts thereofThe present invention is also directed to pharmaceutical compositions containing such compounds and the use of such compounds in the treatment and / or prophylaxis of thromboembolic disorders, inflammatory disorders and diseases or conditions in which plasma kallikrein activity is implicated.

A Factor XIa inhibitor having therapeutic properties useful in methods for treating or preventing ischemic stroke.

The present disclosure belongs to the field of biomedicines, and specifically relates to a nucleic acid capable of inhibiting the expression of a coagulation factor XI (factor XI), a pharmaceutical composition containing the nucleic acid, and an siRNA conjugate. Specifically, provided in the present disclosure is a double-stranded oligonucleotide capable of inhibiting the expression of FXI. The double-stranded oligonucleotide comprises a sense strand and an antisense strand, wherein the sense strand and the antisense strand are at least partially reverse-complementary to form a double-stranded region, the antisense strand is at least partially complementary to a segment of nucleotides within FXI-transcribed mRNA, the length of the sense strand does not exceed 21 nucleotides, the length of the antisense strand does not exceed 23 nucleotides, and the antisense strand comprises a sequence of at least 17 contiguous nucleotides that differs from any one of the nucleotide sequences as set forth in SEQ ID NOs: 175-347 and 706-714 by no more than 4, 3, 2, or 1 nucleotides. The oligonucleotide prepared in the present disclosure has a good inhibitory effect on the expression of the coagulation factor XI both in vitro and in vivo.

Methods for treating cancer using combination therapy with an anti-coagulant and a B-Raf inhibitor and / or a mitogen-activated protein kinase (MEK) inhibitor are disclosed. The anti-coagulant may be a direct inhibitor of thrombin or an indirect inhibitor of thrombin, such as an inhibitor of factor Xa, factor XIa, or other coagulation factors.

The present invention provides compounds of formula (I): or stereoisomers, tautomers or pharmaceutically acceptable salts thereof, wherein all variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. The present invention also relates to pharmaceutical compositions comprising these compounds and methods of using these compositions to treat thromboembolic and / or inflammatory conditions.