The disclosure provides compositions and methods for counteracting the effects of direct activated Factor XI (FXIa) inhibitors in a subject by administering a variant of FXIa.

The invention relates to therapeutic fusion proteins in which a coagulation factor is fused to a half-life enhancing polypeptide, and in which both are connected by a linker peptide that is proteolytically cleavable. The cleavage of such linkers liberates the coagulation factor from activity-compromising steric hindrance caused by the half-life enhancing polypeptide and thereby allows the generation of fusion proteins may show relatively high molar specific activity when tested in coagulation-related assays. Furthermore, the fact that the linker is cleavable can enhance the rates of inactivation and/or elimination after proteolytic cleavage of the peptide linker compared to the rates measured for corresponding therapeutic fusion proteins linked by the non-cleavable linker having the amino acid sequence GGGGGGV.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

The invention relates to a method for preparing an irradiated platelet lysate, comprising the steps of providing a starting platelet lysate having platelet factors including growth factors and plasma proteins including coagulation factors and proteins other than the coagulation factors. Double irradiation of the starting platelet lysate, using UVC radiation and ionizing radiation. The double irradiation with UVC radiation and ionizing radiation being arranged to retain at least 75% of the total protein concentration of the starting platelet lysate, while reducing, by at least 40%, the concentration of at least one of the coagulation factors including fibrinogen, factor II, factor VII, factor IX, factor X and factor XI of the starting platelet lysate.

Products, compositions, and their uses are provided. In particular, nucleic acid products that modulate, in particular interfere with or inhibit, Factor XI (FXI) gene expression are provided. The products can be oligomeric compounds that comprise at least a first region of linked nucleosides having at least a first nucleobase sequence that is at least partially complementary to at least a portion of RNA transcribed from an FXI gene, wherein said first nucleobase sequence is selected from the following sequences, or a portion thereof: SEQ ID NOs 1 to 250.

A high-activity blood coagulation factor XI mutant Ala570Thr (A570T), having nucleotide sequences as shown in SEQ ID NOs: 1-4 and an amino acid sequence as shown in SEQ ID NO: 5, is provided. The mutant is resistant to a physiological inhibitor thereof after being activated from a zymogen state to an active enzyme. Therefore, the mutant has a very high blood coagulation activity and a stronger catalytic ability for a non-physiological substrate; and the mutant is applied to the treatment of hemorrhagic diseases, and has good prospects in terms of gene therapy, gene editing and recombinant protein replacement treatments.