The present invention relates to a tumor vascular disrupting agent polypeptide, gene, expression vector, and use thereof. The tumor vascular disrupting agent polypeptide has the amino acid sequence as shown by SEQ ID NO: 1. The polypeptide comprises a truncated tissue factor (tTF) and a tumor-targeting molecule (pHLIP); the factor and the molecule are connected by 5 amino acids, thereby ensuring the function of each not being affected by the other; the fusion protein can be positioned to the surface of a tumor vascular endothelial cell by means of the pHLIP, and provides the blood coagulation feature of the tTF in a tumor vessel and forms a thrombus, thereby disrupting the blood supply to the tumor area and treating tumor. The polypeptide of the present invention is significant to the treatment of tumor, and can be used in medicines for treating tumors.

Provided is a method for purifying α-thrombin and for quantifying α-thrombin and its degradation polypeptides in a liquid proteinatious solution. The method employs a one-step anion exchange chromatography method. The method allows purification and/or quantification of a homogenous post-translationally modified α-thrombin. The method can also be used for purification and/or quantification of β-thrombin.

Provided is a method for purifying α-thrombin and for quantifying α-thrombin and its degradation polypeptides in a liquid proteinatious solution. The method employs a one-step anion exchange chromatography method. The method allows purification and/or quantification of a homogenous post-translationally modified α-thrombin. The method can also be used for purification and/or quantification of β-thrombin.

The present invention relates to nucleic acid regulatory elements that are able to enhance liver-specific expression of genes, methods employing these regulatory elements and uses of these elements. Expression cassettes and vectors containing these nucleic acid regulatory elements are also disclosed. The present invention is particularly useful for applications using gene therapy, more particularly liver-directed gene therapy, and for vaccination purposes.

The present invention relates to variants of factor IX (F.IX) or activated factor IX (F.IXa), wherein the variant is characterized in that it has clotting activity in absence of its cofactor. The present invention furthermore relates to variants of factor IX (F.IX) or activated factor IX (F.IXa), wherein the variant is characterized in that it has increased F.IX clotting activity compared to wildtype. The present invention furthermore relates to the use of these variants for the treatment and/or prophylaxis of bleeding disorders, in particular hemophilia A and/or hemophilia B or hemophilia caused or complicated by inhibitory antibodies to F.VIII. The present invention also relates to further variants of factor IX (F.IX) which have desired properties and can, thus be tailored for respective specific therapeutic applications.

The present invention relates to variants of factor IX (F.IX) or activated factor IX (F.IXa), wherein the variant is characterized in that it has clotting activity in absence of its cofactor. The present invention furthermore relates to variants of factor IX (F.IX) or activated factor IX (F.IXa), wherein the variant is characterized in that it has increased F.IX clotting activity compared to wildtype. The present invention furthermore relates to the use of these variants for the treatment and/or prophylaxis of bleeding disorders, in particular hemophilia A and/or hemophilia B or hemophilia caused or complicated by inhibitory antibodies to F.VIII. The present invention also relates to further variants of factor IX (F.IX) which have desired properties and can, thus be tailored for respective specific therapeutic applications.

In various embodiments, disclosed herein are methods of assessing therapeutic efficacy of an anticoagulant. Preferably, the method comprising providing a blood sample; perfusing the blood sample over a surface coated with collagen or immobilized rTF; measuring platelet aggregation and fibrin deposition on the surface coated with collagen or immobilized rTF; and assessing therapeutic efficacy of the anticoagulant based on the volume of platelet aggregates and/or deposited fibrin.

In various embodiments, disclosed herein are methods of assessing therapeutic efficacy of an anticoagulant. Preferably, the method comprising providing a blood sample; perfusing the blood sample over a surface coated with collagen or immobilized rTF; measuring platelet aggregation and fibrin deposition on the surface coated with collagen or immobilized rTF; and assessing therapeutic efficacy of the anticoagulant based on the volume of platelet aggregates and/or deposited fibrin.

A fusion protein of hFGF21 or its analogs having improved pharmaceutical properties, and use of the fusion protein in preparing medicines for treating diseases, such as diabetes, obesity, non-alcoholic fatty liver disease, dyslipidemia, and/or metabolic syndrome.

The present invention relates to a nucleic acid molecule encoding human albumin for increasing the levels and/or activity of a protein or polypeptide encoded by a transgene, comprising a sequence defined by SEQ ID NO: 14 or a sequence having at least 80% sequence identity to said sequence, its use in nucleic acid expression cassettes and vectors containing liver-specific regulatory elements and codon-optimized factor IX, factor VIII, factor VII or factor VIIa transgenes, methods employing these expression cassettes and vectors and uses thereof. The present invention is particularly useful for applications using liver-directed gene therapy, in particular for the treatment of hemophilia A, hemophilia B or factor VII deficiency.