35 results about "Factor IX" patented technology

The present invention provides codon optimized Factor IX sequences, vectors and host cells comprising codon optimized Factor IX sequences, polypeptides encoded by codon optimized Factor IX sequences, and methods of producing such polypeptides. The present invention also provides methods of treating bleeding disorders such as hemophilia comprising administering to the subject a codon optimized Factor IX nucleic acid sequence or the polypeptide encoded thereby.

The present invention provides codon optimized Factor IX sequences, vectors and host cells comprising codon optimized Factor IX sequences, polypeptides encoded by codon optimized Factor IX sequences, and methods of producing such polypeptides. The present invention also provides methods of treating bleeding disorders such as hemophilia comprising administering to the subject a codon optimized Factor IX nucleic acid sequence or the polypeptide encoded thereby.

Compositions and methods for expressing Factor IX in a host cell or a population of host cells are provided. Also provided are engineered host cells expressing Factor IX.

To provide a method for treating reversible hemophilic arthropathy of a joint in a human having hemophilia.SOLUTION: Uses of a chimeric protein or composition comprising a coagulation factor and an Fc region are provided. The coagulation factor is selected from the group consisting of Factor VII (FVII), Factor VIIa (FVIIa), Factor VIII (FVIII), Factor IX (FIX), Factor X (FX), von Willebrand Factor (VWF), an antigen-binding portion thereof that specifically binds to FIX and FX, or any combination thereof.SELECTED DRAWING: None

Disclosed are a modified FIX (Factor IX) polypeptide comprising a leucine, cysteine, aspartic acid, glutamic acid, histidine, lysine, asparagine, glutamine or tyrosine in position 338; pharmaceutical preparations containing said modified FIX polypeptide; a nucleotide sequence coding for the modified FIX polypeptide; and a method for producing the modified FIX polypeptide.

This invention relates to Factor IX variant polypeptides for administration to soft tissues.

To provide nucleic acid sequences, expression vectors (e.g., vector genomes) and plasmids, compositions and viral vectors in which the nucleic acid encodes Factor IX (e.g. human Factor IX).SOLUTION: A nucleic acid sequence encodes human Factor IX protein, where the nucleic acid has a reduced number of CpG di-nucleotides compared to a wild-type sequence encoding human Factor IX.SELECTED DRAWING: None

To provide compositions and methods for expressing Factor IX in a host cell or a population of host cells, and engineered host cells expressing Factor IX.SOLUTION: A method for introducing Factor IX nucleic acid into a cell or a population of cells includes administering i) a nucleic acid construct including a Factor IX protein coding sequence, ii) an RNA guide DNA binder, iii) a contiguous nucleotide selected from a specific sequence group, and guide RNA(gRNA) selected from a specific sequence, by which the Factor IX nucleic acid is introduced into the cell or the population of cells.SELECTED DRAWING: None

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.

The application provides a completely humanized anti-human blood coagulation factor IX monoclonal antibody or an antigen binding fragment thereof and application thereof. The antibody provided by the application has high affinity to human blood coagulation factor IX and significant inhibitory activity, and belongs to a neutralizing antibody, and has a good treatment prospect for thrombus diseases. The functional antibody is directly screened from blood plasma of hemophilia B patients by a mass spectrometry + de novo sequencing technology, and has the advantages of complete human origin, high safety and the like.

Compositions and methods for expressing Factor IX in a host cell or a population of host cells are provided. Also provided are engineered host cells expressing Factor IX.

To provide a method of preventing or treating hemophilia.SOLUTION: The present disclosure provides lentiviral vectors comprising a nucleic acid sequence encoding a polypeptide with factor IX (FIX) activity, and methods of using such lentiviral vectors. The liver-targeted lentiviral vectors disclosed herein can be used for gene therapy, where the lentiviral gene delivery enables stable integration of a transgene expression cassette into the genome of targeted cells (e.g., hepatocytes) of pediatric (e.g., neonatal) or adult subjects, achieving an improvement in FIX expression at low lentiviral vector doses. The present disclosure also provides methods of treating bleeding disorders such as hemophilia (e.g., hemophilia B) comprising administering to a subject in need thereof a liver-targeted lentiviral vector comprising a nucleic acid sequence encoding a polypeptide with a FIX activity sequence at low dosages.SELECTED DRAWING: None

Disclosed are a modified FIX (factor IX) polypeptide comprising a leucine, cysteine, aspartic acid, glutamic acid, histidine, lysine, asparagine, glutamine or tyrosine in position 338; pharmaceutical preparations containing said modified FIX polypeptide; a nucleotide sequence coding for the modified FIX polypeptide; and a method for producing the modified FIX polypeptide.

The invention relates to synthetic liver-specific promoters and expression constructs for producing polypeptides and functional nucleic acids in the liver of a subject. The invention further relates to optimized polynucleotide sequences encoding Factor IX proteins, vector comprising the same, and methods of using these compositions to treat a bleeding disorder.

A method and kit are provided for monitoring anticoagulant therapy based on measuring the simultaneous influence of factors II and X only, in a test sample (i.e., test plasma or whole blood) of an anticoagulated patient, by creating a corrected sample that circumvents measuring also the influence of fibrinogen, factor V, and factor VII on the clotting process in the corrected sample. One or more coagulation reagents that activate factor VII or factor X, but not factor IX, are added to the corrected sample, and the blood clotting ability of the corrected plasma sample is subsequently determined by measuring blood clotting time. Alternatively, a reagent plasma with added factor VII is mixed into the reagent activator, such as thromboplastin, that is subsequently added to a sample of test plasma or whole blood to correct the test sample and measure the simultaneous influence of only factors II and X.

A chorionic gonadotropin carboxy terminal peptide (CTP)-modified Factor IX, Factor VII or Factor VIIa coagulation factor having three CTPs attached to the carboxy terminus of said coagulation factor for use in increasing patient compliance in coagulation factor therapy in a human subject or for use in treating hemophilia A in a human subject.

This invention relates to the intranasal administration of blood coagulation factors.

The invention provides a completely humanized anti-human coagulation factor IX monoclonal antibody or an antigen binding fragment thereof and application thereof. The antibody provided by the invention has high affinity and remarkable inhibitory activity on the human coagulation factor IX, belongs to a neutralizing antibody, and has a good treatment prospect on thrombosis diseases. The functional antibody is directly screened from the blood plasma of the hemophilia B patient through the'mass spectrum + de novo sequencing 'technology, and the method has the advantages of being completely humanized, high in safety and the like.

A method and kit are provided for monitoring anticoagulant therapy based on measuring the simultaneous influence of factors II and X only, in a test sample (i.e., test plasma or whole blood) of an anticoagulated patient, by creating a corrected sample that circumvents measuring also the influence of fibrinogen, factor V, and factor VII on the clotting process in the corrected sample. One or more coagulation reagents that activate factor VII or factor X, but not factor IX, are added to the corrected sample, and the blood clotting ability of the corrected plasma sample is subsequently determined by measuring blood clotting time. Alternatively, a reagent plasma with added factor VII is mixed into the reagent activator, such as thromboplastin, that is subsequently added to a sample of test plasma or whole blood to correct the test sample and measure the simultaneous influence of only factors II and X.

The present disclosure provides methods and compositions for culturing, engineering B-lineage cell populations that produce Factor IX (FIX), and administering engineered B-lineage cell populations.

This invention provides Factor IX variants, molecules comprising the variants, nucleic acids encoding the variants, compositions comprising the variants or the nucleic acids encoding the variants, and their use in methods for the modulation of hemostasis, for example in the prophylaxis or treatment of hemophilia B. The Factor IX variants have improved biological properties relative to other Factor IX variants and / or relative to wild-type Factor IX.

The present invention relates to a combination comprising transgenic factor VII and multispecific antibodies against factors IX and X for simultaneous or separate administration.

The present invention provides a pharmaceutical composition for treating bleeding disorders such as hemophilia (e.g., hemophilia B). [Solution] A pharmaceutical composition comprising a lentiviral vector for use in a method to reduce transduction into macrophages in a target that requires it, wherein the lentiviral vector comprises a specific nucleotide sequence encoding a polypeptide having factor IX (FIX) activity and a lipid coat containing the CD47 protein, and the method comprises 2 × 10 9 The pharmaceutical composition comprises administering a lentiviral vector to a subject in a dose of less than transduction units / kg (TU / kg), wherein the lentiviral vector is packaged in HEK293T cells overexpressing CD47 and contains a higher level of surface CD47 protein on its lipid coating than a control lentiviral vector produced in unmodified HEK293T cells.

The invention relates to commercially viable methods for producing biologically active vitamin K dependent proteins, particularly Factor IX. Factor IX is produced at a level of at least about 15 mg / L and is at least 25% biologically active. The method relies upon co-expression of one or more of paired basic amino acid converting enzyme (PACE), vitamin K dependent epoxide reductase (VKOR) and vitamin K dependent γ-glutamyl carboxylase (VKGC) at a preferred ratio so that the vitamin K dependent protein is efficiently produced and processed by a recombinant cell.

The present invention provides Factor IX fusion proteins with higher specific activity and a longer useful clotting function relative to wild type or non-modified Factor IX protein.

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.

The present invention relates to Factor IX variant polypeptides for administration to soft tissue.

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.

A pharmaceutical composition comprising: a. transgenic Factor VII and b. a multispecific antibody directed against Factor IX and Factor X. The patent application contains 10 more claims.

Factor IX / IXa variants and methods of use thereof are disclosed.