The present invention is a novel blood or plasma panel with utility in assessing chronic liver disease severity in a point-of-care setting. The scoring system exhibits 97.2% correlation to previously assigned Child Pugh scores and does not require clinical assessment beyond laboratory testing.

Polypeptides comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to the carboxy terminus but not to the amino terminus of a coagulation factor and polynucleotides encoding the same are disclosed. Pharmaceutical compositions comprising the polypeptides and polynucleotides of the invention and methods of using and producing same are also disclosed.

Polypeptides comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to the carboxy terminus but not to the amino terminus of a coagulation factor and polynucleotides encoding the same are disclosed. Pharmaceutical compositions comprising the polypeptides and polynucleotides of the invention and methods of using and producing same are also disclosed.

Methods of isolating highly sialylated recombinant vitamin K dependent proteins, particularly Factor IX, by chromatographic methods am 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 am 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.

Provided herein are multi-chain chimeric polypeptides that include: (a) a first chimeric polypeptide including a first target-binding domain, a soluble tissue factor domain, and a first domain of a pair of affinity domains; and (b) a second chimeric polypeptide including a second domain of a pair of affinity domains and a second target-binding domain, where the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains. Also provided here are methods of using these multi-chain chimeric polypeptides and nucleic acids encoding these multi-chain chimeric polypeptides.

Provided herein are multi-chain chimeric polypeptides that include: (a) a first chimeric polypeptide including a first target-binding domain, a soluble tissue factor domain, and a first domain of a pair of affinity domains; and (b) a second chimeric polypeptide including a second domain of a pair of affinity domains and a second target-binding domain, where the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains. Also provided here are methods of using these multi-chain chimeric polypeptides and nucleic acids encoding these multi-chain chimeric polypeptides.

The invention relates to a glycosylated polypeptide comprising an amino acid sequence being identical or homologous to at least a fragment of a mammalian, preferably a human protein, wherein said glycosylated polypeptide contains one or more sialylated O-glycans and wherein the glycosylated polypeptide shows an increased binding affinity to one or more SIGLECs, selected from SIG-5, SIG-7, SIG-8, and SIG-9 compared to the mammalian protein or fragment thereof. The invention further relates to composition comprising a first and a second polypeptide, wherein the first polypeptide is a glycosylated polypeptide containing one or more sialylated O-glycans and the second polypeptide contains an amino acid sequence homologous or identical to a second mammalian, in particular human protein, wherein compared to the second polypeptide the composition has an increased binding affinity to a SIGLEC selected from to one or more SIGLECs, selected from SIG-5, SIG-7, SIG-8, and SIG-9.

The invention relates to a glycosylated polypeptide comprising an amino acid sequence being identical or homologous to at least a fragment of a mammalian, preferably a human protein, wherein said glycosylated polypeptide contains one or more sialylated O-glycans and wherein the glycosylated polypeptide shows an increased binding affinity to one or more SIGLECs, selected from SIG-5, SIG-7, SIG-8, and SIG-9 compared to the mammalian protein or fragment thereof. The invention further relates to composition comprising a first and a second polypeptide, wherein the first polypeptide is a glycosylated polypeptide containing one or more sialylated O-glycans and the second polypeptide contains an amino acid sequence homologous or identical to a second mammalian, in particular human protein, wherein compared to the second polypeptide the composition has an increased binding affinity to a SIGLEC selected from to one or more SIGLECs, selected from SIG-5, SIG-7, SIG-8, and SIG-9.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized coagulation factor XII (F12) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized F12 locus express a human coagulation factor XII protein or a chimeric coagulation factor XII protein, fragments of which are from human coagulation factor XII. Methods are provided for using such non-human animals comprising a humanized F12 locus to assess in vivo efficacy of human-coagulation-factor-XII-targeting reagents such as nuclease agents designed to target human F12. A short isoform of F12 that is produced locally in the brain, and methods of using the short isoform, are also provide.