The disclosure relates to the recombinant Gla domain proteins and their use targeting phosphatidylserine (PtdS) moieties on the surface of cells, particularly those expressing elevated levels of PtdS, such as cells undergoing apoptosis.

The disclosure relates to the recombinant Gla domain proteins and their use targeting phosphatidylserine (PtdS) moieties on the surface of cells, particularly those expressing elevated levels of PtdS, such as cells undergoing apoptosis. These proteins can be linked to both diagnostic and therapeutic payloads, thereby permitting identification and treatment of cells expression elevated PtdS.

The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

The present invention relates to a method of modifying at least one gene in a cell via CRISPR/Cas, wherein the at least one gene has at least three alleles. The present invention further relates to cells obtainable by the method of the invention. Additionally, the present invention provides a method of producing a protein in a cell obtainable by the method of modifying at least one gene of the invention. Moreover, the invention relates to proteins obtainable by the method of producing a protein and use thereof, for example in therapy.

Short-acting Factor VII peptides are disclosed. A shortened half-life is desirable for treatment of acute bleeding and similar disorders. Modification of the sialylation and/or glycosylation of Factor VII and variants thereof produced peptides useful in treating conditions of acute bleeding.

The invention relates to a method of controlling a polypeptide modification reaction, in particular but not exclusively, a method of controlling the activation of human factor VII (FVII) to produce human factor VII(a) (FVII(a)). The invention also relates to polypeptides obtainable by the polypeptide modification reaction and to pharmaceutical compositions comprising said polypeptides.

The present invention relates to a method and compositions for the treatment of haemorrhagic diseases.

Disclosed are methods and compositions related to chimeric antigen receptors (CARs) that recognize Tissue Factor (TF). Specifically, disclosed are CARs that comprise fVII or a functional fragment thereof. Also disclosed are immune effector cells comprising the CARs disclosed herein.

A process for producing blood coagulation Factor VII in large scale in 3 human cell lines (HepG2, Sk-Hep, HKB-11) and to select the best recombinant protein producer is described. The murine line BHK-21 was used as control. The data allowed for the assertion that the system used to modify cell lines was efficient, so that all the cells were satisfactorily modified, and produced the protein of interest in a stable form. In addition, when comparing the murine line BHK-21 with the human cells (HepG2, Sk-Hep-1 and HKB-11), the latter proved to be able to produce rFVII more efficiently, which allows us to conclude that human cell lines are a great alternative to produce recombinant blood coagulation factors in large scale.

Disclosed herein are methods and compositions related to coagulation factor complexes comprising a coagulation factor; a fusion protein; and a modifying molecule, wherein the modifying molecule is coupled to the coagulation factor in such a way as to allow binding by the fusion protein, thereby creating a modified coagulation factor; wherein the modilied coagulation factor and the fusion protein interact in at least two independent sites.