Abstract: The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor IX variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia B. In some embodiments, the present disclosure provides methods for dosing a hemophilia B patient with a polynucleotide, e.g., a codon-altered polynucleotide, encoding a Factor IX polypeptide.

Abstract: 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, an identify a TFPI-binding compound.

Abstract: The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A.

Abstract: The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A.

Abstract: The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor IX variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia B. In some embodiments, the present disclosure provides methods for dosing a hemophilia B patient with a polynucleotide, e.g., a codon-altered polynucleotide, encoding a Factor IX polypeptide.

Abstract: The present disclosure provides, among other things, a recombinant adeno-associated virus (rAAV) vector comprising an AAV8 capsid and a codon-optimized SERPING1 sequence encoding a human C1-esterase inhibitor. The disclosure also provides a method of treating a subject having Hereditary angioedema (HAE), comprising administering to the subject in need thereof a recombinant adeno-associated virus (rAAV) vector comprising an AAV8 capsid, and codon-optimized SERPING1 sequences encoding a human C1-esterase inhibitor.

Abstract: The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A.

Abstract: The disclosure provides a method for treating sickle cell disease with A Disintegrin And Metalloproteinase with Thrombospondin type 1 motif, member-13 (ADAMTS13). The disclosure provides a method for increasing ADAMTS13-mediated von Willebrand factor (VWF) cleavage in a subject suffering from sickle cell disease by administering ADAMTS13. The disclosure also provides a method of treating a vaso-occlusive crisis (VOC) in a subject suffering from sickle cell disease by administering ADAMTS13 after the onset of the VOC. The disclosure also provides a method of preventing a VOC in a subject suffering from sickle cell disease by administering ADAMTS13 prior to the onset of the VOC. The disclosure also provides a method of determining the efficacy of a treatment for a VOC in a mouse model.

Abstract: The present invention pertains to the specific detection of MIF, in particular oxMIF, in tissues. A detection method is provided which uses immunohistochemistry and wherein specific anti-oxMIF antibodies are used.

Abstract: The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A.

Abstract: The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A.

Abstract: The disclosure provides compositions and methods for treating, ameliorating, and/or preventing a vaso-occlusive crisis (VOC) in a subject suffering from sickle cell disease (SCD). The disclosure also provides compositions and methods for treating, ameliorating, and/or preventing lung injury in a subject suffering from or at risk of suffering from acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). The disclosure provides A Disintegrin And Metalloproteinase with Thrombospondin type 1 motif, member-13 (ADAMTS13) or a composition comprising ADAMTS13 for treating, ameliorating, and/or preventing the VOC, or for treating, ameliorating, and/or preventing lung injury in a subject suffering from or at risk of suffering from ALI and/or ARDS.

Abstract: This invention relates to a pharmaceutical composition having thrombolytic activity comprising ADAMTS13, and to methods for treating or preventing a disorder associated with the formation and/or the presence of one or more thrombus and to methods of disintegrating one or more thrombus in a patient in need thereof.

Abstract: The disclosure provides compositions and methods for treating, ameliorating, and/or preventing a vaso-occlusive crisis (VOC) in a subject suffering from sickle cell disease (SCD). The disclosure also provides compositions and methods for treating, ameliorating, and/or preventing lung injury in a subject suffering from or at risk of suffering from acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). The disclosure provides A Disintegrin And Metalloproteinase with Thrombospondin type 1 motif, member-13 (ADAMTS13) or a composition comprising ADAMTS13 for treating, ameliorating, and/or preventing the VOC, or for treating, ameliorating, and/or preventing lung injury in a subject suffering from or at risk of suffering from ALI and/or ARDS.

Abstract: Disclosed herein are compositions and methods for improving hemostasis in the treatment of bleeding disorders and reversal of anticoagulant activity. Effective ratios of prothrombin (FII) and activated factor X (FXa) for the treatment of bleeding disorders that are as efficacious as FEIBA®, but require a lower concentration of FII are described herein.

Abstract: This invention relates to a pharmaceutical composition having thrombolytic activity comprising ADAMTS13, and to methods for treating or preventing a disorder associated with the formation and/or the presence of one or more thrombus and to methods of disintegrating one or more thrombus in a patient in need thereof. Furthermore, the invention relates to the use of a pharmaceutically effective amount of ADAMTS13 for the preparation of a pharmaceutical composition for treating or preventing a disorder associated with the formation or the presence of one or more thrombus and for disintegrating one or more thrombus in a patient in need thereof.

Abstract: The present invention pertains to anti-MIF antibodies, in particular their use in combination with glucocorticoids, in the treatment of glucocorticoid receptive diseases.

Abstract: 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.

Abstract: Codon-altered polynucleotides encoding Factor IX variants for expression in mammalian cells are provided, including sequences with high nucleotide sequence identity to the CS02, CS03, CSO4, CS05, and CS06 sequences. Mammalian gene therapy vectors, such as adeno-associated viral vectors, and methods for treating hemophilia B using those vectors are also provided.

Abstract: Provided herein are methods for recanalization of occluded blood vessels in a subject having an infarction. The method includes a step of administering to the subject a therapeutically effective amount of isolated ADAMTS13 protein at particular dosages and ranges of times after detection of the infarction. As described herein, ADAMTS13 advantageously recanalizes occluded blood vessels and reduces infarction size, even when administered a prolonged period after stable occlusion. Accordingly, such methods and compositions are useful for the treatment of infractions caused by blood vessel occlusion.