The present invention relates to mutated factor (FX) polypeptides and uses thereof for the treatment of haemophilia. In particular, the present invention relates to a mutated factor X (FX) polypeptide wherein the heavy chain comprises at least one mutation selected from the group consisting of: —the mutation which consists of the substitution of the glutamic acid residue (E) at position 255 of Seq. ID No. 1 by a glutamine residue (Q), an asparagine residue (N), a serine residue (S), an alanine residue (A), or a tyrosine residue (Y); —the mutation which consists of the substitution of the glutamic acid residue (E) at position 256 of Seq. ID No. 1 by a glutamine residue (Q); and —the mutation which consists of the substitution of the glutamic acid residue (E) at position 258 of Seq. ID No. 1 by a glutamine residue (Q);

The invention relates to a method for purifying biologically active GLA-domain coagulation proteins, comprising the following steps: a) bringing a sample that contains one or more GLA-domain coagulation proteins and may contain biologically inactive molecules of GLA-domain protein(s), into contact with an affinity support on which nucleic aptamers that bind specifically to at least one biologically active GLA-domain coagulation protein are immobilized, in order to form complexes between (i) said nucleic aptamers and (ii) said GLA-domain coagulation protein(s), b) releasing the GLA-domain coagulation protein(s) from the complexes formed in step a), and c) recovering said biologically active GLA-domain coagulation protein(s) in a purified form.

The invention relates to a method for purifying biologically active GLA-domain coagulation proteins, comprising the following steps: a) bringing a sample that contains one or more GLA-domain coagulation proteins and may contain biologically inactive molecules of GLA-domain protein(s), into contact with an affinity support on which nucleic aptamers that bind specifically to at least one biologically active GLA-domain coagulation protein are immobilized, in order to form complexes between (i) said nucleic aptamers and (ii) said GLA-domain coagulation protein(s), b) releasing the GLA-domain coagulation protein(s) from the complexes formed in step a), and c) recovering said biologically active GLA-domain coagulation protein(s) in a purified form.

The present disclosure relates to a class of engineered polypeptides having a binding affinity for interleukin-17A (IL-17A), and provides an IL-17A binding polypeptide comprising the sequence EX.sub.2DX.sub.4AX.sub.6X.sub.7EIX.sub.10X.sub.11 LPNL X.sub.16X.sub.17X.sub.18QX.sub.20X.sub.21AFIX.sub.25 X.sub.26LX.sub.28X.sub.29. Also disclosed is the use of such an interleukin-17A binding polypeptide as a diagnostic, prognostic and/or therapeutic agent.

The present disclosure relates to a class of engineered polypeptides having a binding affinity for interleukin-17A (IL-17A), and provides an IL-17A binding polypeptide comprising the sequence EX.sub.2DX.sub.4AX.sub.6X.sub.7EIX.sub.10X.sub.11 LPNL X.sub.16X.sub.17X.sub.18QX.sub.20X.sub.21AFIX.sub.25 X.sub.26LX.sub.28X.sub.29. Also disclosed is the use of such an interleukin-17A binding polypeptide as a diagnostic, prognostic and/or therapeutic agent.

The present invention provides a recombinant adeno-associated virus (rAAV) vector for treating a blood coagulation-related disease to provide a novel gene therapy means for hemophilia. The virus vector comprises a virus genome comprising a liver-specific promoter sequence and a polynucleotide sequence encoding a genome editing means operably linked to the promoter sequence, wherein the genome editing means is (a) a means comprising CRISPR/Cas9 composed of a Cas9 protein and a guide RNA (gRNA) and a repair gene, or (b) a means comprising CRISPR/Cas9 composed of a Cas9 protein and a gRNA, and the gRNA comprises a nucleotide region complementary to a part of a region related to expression of a disease-related protein on the genome of a patient and a region that interacts with the Cas9 protein.

Methods of isolating highly sialylated recombinant vitamin K dependent proteins, particularly Factor IX, by chromatographic methods are described. The highly sialylated recombinant proteins are characterized. The improved Factor IX has at least 62% N-glycosylation with 3 or 4 sialic acid residues and improved bioavailability and pharmokinetic properties.

Methods of isolating highly sialylated recombinant vitamin K dependent proteins, particularly Factor IX, by chromatographic methods are described. The highly sialylated recombinant proteins are characterized. The improved Factor IX has at least 62% N-glycosylation with 3 or 4 sialic acid residues and improved bioavailability and pharmokinetic properties.

Efficient sequence specific gene silencing is possible through the use of siRNA technology. Be selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods compositions, and kits generated through rational design of siRNAs are disclosed, including those directed to the nucleotide sequences for F12.

Antibodies and antigen-binding antibody fragments that bind to GPIIb/IIIa and chimeric polypeptides comprising these binding molecules are disclosed. Some of these antibodies and antigen-binding antibody fragments preferentially bind GPIIb/IIIa on activated platelets while others do not show a preference for binding GPIIb/IIIa on resting versus activated platelets. Some of these antibodies and antibody fragments do not inhibit the interaction of GPIIb/IIIa with fibrinogen, while some others do. The disclosed antibodies do not induce platelet activation. Some of these antibodies and antigen-binding antibody fragments are useful in targeting therapeutic agents such as clotting factors to platelets while others are useful in reducing platelet aggregation and/or thrombus formation.