The present invention provides a novel antithrombotic antibody, the antibody uses FIXa as a target and has unique properties, and specifically targets the binding site of coagulation factor FIXa and FVIIIa, reduces the formation of a FVIIa-FIXa complex, blocks the conversion of FX to FXa, and thereby exerts an antithrombotic effect. The antibody of the present invention has suitable antithrombotic properties, and has a large effective therapeutic concentration window, but does not increase the risk of bleeding in addition, the antibody can meet the needs for suitable antithrombotic performance in clinical application and for effective avoidance of problems regarding bleeding caused by excessive effects. The present invention also discloses a method for screening drugs by using an FIXa-FVIIIa binding site as a target.

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.

Embodiments of the disclosure concern methods of determining the effectiveness of immune cells, such as T cells, with particular chimeric antigen receptors. In specific embodiments, a synapse between the CAR and the tumor antigen is measured for structure, signaling, and functionality by imaging. As such, the quality of the synapse is determined and positively correlates with effectiveness of the particular CAR immune cells.

The present disclosure provides methods and compositions for diagnosing and treating subject having a bleeding disorder. The disclosed methods comprise contacting a sample, e.g., a blood or plasma sample obtained from the patient, with an activation mixture comprising an activated coagulation factor and a phospholipid mixture, wherein the activation mixture is dried onto a solid substrate. Also provided is a global hemostasis test based on the integration of clotting time (Ct) and pharmacokinetics data. The methods and compositions presented can be applied to point-of-care diagnostic systems.

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 polynucleotides comprising a Factor IX nucleotide sequence, wherein the Factor IX nucleotide sequence comprises a coding sequence that encodes a Factor IX protein or fragment thereof and wherein a portion of the coding sequence is not wild type. The present invention further relates to viral particles comprising a recombinant genome comprising the polynucleotide of the invention, compositions comprising the polynucleotides or viral particles, and methods and uses of the polynucleotides, viral particles or compositions.

This invention relates to recombinant aptamer 9.3t-resistant Factor IX proteins, as well as methods of making the same and methods of using the same in methods comprising non-hemophilic subjects, including methods of modeling Factor IX replacement therapy in a non-hemophilic subject and methods of identifying genetic background effects of a non-hemophilic subject on an exogenous Factor IX replacement protein. The invention also pertains to methods of modeling gene and/or protein replacement therapy in a protein non-deficient subject and methods of identifying genetic background effects of a protein non-deficient subject on an exogenous replacement protein, as well as methods of selecting aptamer-resistant recombinant proteins and selecting aptamer-sensitive protein non-deficient subjects for use in such methods as disclosed herein.

The present invention provides methods for detecting a complex with low affinity, under conditions in which the binding equilibrium of the complex is substantially maintained, and methods for measuring the concentration and/or amount of the complex. The invention also provides methods for evaluating the kinetics of a complex and methods for deciding on a therapeutic method that uses a pharmaceutical agent, based on the concentration and/or amount of the complex determined by the above-mentioned measurement method.