104results about "Factor VII" patented technology

The invention relates generally to compositions and methods for purifying the desired species from a mixture of desired heterodimer and contaminating homodimer immunoglobulin variants by modifying the isoelectric point(s) of the individual chains.

The present invention relates to engineered liver-specific core promoters, synthetic promoters (which contains the engineered core promoters and enhancers), expression vectors (which contains the synthetic promoter), as well as methods of using the promoter or the expression vector thereof to address the need in the field, including treatment of various genetic diseases or conditions associated with the liver. In some embodiments, the liver-specific promoter includes continuous or discontinuous genome sequences from SERPINA1 genome.

Compositions and methods for treating Factor X deficiency are disclosed. The compositions and methods include the use of a a FVIII mimetic bispecific antibody that binds Factor IXa and Factor X.

This disclosure generally relates to super minimal transposon inverted repeat sequence (ITR) polynucleotides, compositions comprising the polynucleotides and methods of using compositions comprising the polynucleotides for the ex vivo and in vivo delivery of nucleic acids to cells, in particular, in vivo delivery of therapeutic genes to treat genetic disorders or diseases.

Variants of coagulation factor VIII (FVIII) and expression cassettes encoding the FVIII variants thereof are described. A variant FVIII includes a glycoepitope of the FVIII protein including an N2118Q mutation. The N2118Q mutation can be combined with other mutations including a BDD-FVIII, N6, V3, RH, furin-cleavage site deletion. X10, K12, and / or F309S mutation to form additional FVIII variants. The FVIII variants with the N2118Q mutation and expression cassettes thereof can result in reduced immunogenicity of the resulting protein. When combined with other FVIII mutations, higher gene expression, increased secretion, increased stability, and higher FVIII functional activity can be achieved by the expressed FVIII variants. The variant FVIII and expression cassettes described here can be useful in protein replacement therapy and / or gene therapy for the treatment of hemophilia A.

Compositions and regimens useful in treating Wilson's Disease are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human ATP7B.

Lentiviral vector (LV) formulations, and pharmaceutical compositions comprising such LV formulations, with improved stability and suitable for systemic administration are provided. Methods for treating disorders, especially blood disorders, using systemic administration of LV formulations are also provided.

The present invention provides a chimeric protein comprising a first polypeptide which comprises a FVIII protein and a first Ig constant region or a portion thereof and a second polypeptide which comprises a VWF protein comprising the D′ domain and D3 domain of VWF, a XTEN sequence having less than 288 amino acids in length, and a second Ig constant region or a portion thereof, wherein the first polypeptide and the second polypeptide are associated with each other. The invention also includes nucleotides, vectors, host cells, methods of using the chimeric proteins.

The invention provides a preparation method of a recombinant human blood coagulation factor VIII and a product of the recombinant human blood coagulation factor VIII. The preparation method comprises the step of culturing a mammalian cell strain for expressing the recombinant human blood coagulation factor VIII in a serum-free culture medium of a compound containing copper ions and methionine sulfoximine. By adopting the preparation method provided by the invention, the purity of the recombinant human blood coagulation factor VIII product can be further improved on the basis of keeping the high activity and high yield of the recombinant human blood coagulation factor VIII product obtained by culture.

The invention discloses a human blood coagulation factor VIII and a preparation method thereof, and the preparation method comprises the following steps: S1, carrying out refrigerated centrifugation on cryoprecipitate to obtain an extracting solution; s2, mixing the extracting solution and the heparin sodium solution to obtain a dissolving solution; s3, adjusting the pH value of the dissolving solution to 6.2-6.4 by using hydrochloric acid, and controlling the temperature to be 20-30 DEG C to obtain an acid precipitate; s4, mixing the acid precipitate with polyethylene glycol to obtain a polyethylene glycol precipitate; s5, adding the carboxylated ferroferric oxide nano-particles into the polyethylene glycol precipitate, incubating, and carrying out magnetic separation to obtain a first separation solution; s6, performing centrifugal separation on the first separation liquid to obtain a second separation liquid; s7, clarifying and filtering the second separation liquid, and adjusting the pH value to 6.4-7.4 to obtain a clarified liquid; and S8, adding a stabilizer and an inactivator into the clear liquid, and carrying out water bath heat preservation to obtain a human blood coagulation factor VIII stock solution. The method has the effect of improving the recovery activity and purity of the human blood coagulation factor VIII.

This disclosure generally relates to super minimal transposon inverted repeat sequence (ITR) polynucleotides, compositions comprising the polynucleotides and methods of using compositions comprising the polynucleotides for the ex vivo and in vivo delivery of nucleic acids to cells, in particular, in vivo delivery of therapeutic genes to treat genetic disorders or diseases.

The present invention refers to nucleotide sequences used for driving the expression of a therapeutic gene, preferably FVIII and / or its variants specifically in endothelial cells and / or hematopoietic, preferably myeloid cells. The sequences are useful for gene and / or cell therapy, preferably for treating hemophilia, more preferably type A hemophilia.

Modified human factor VIII polypeptides with enhanced factor VIII activity are described. In some embodiments, the modified human factor VIII polypeptides comprise one or more amino acid substitutions at positions A20, T21, F57, L69, I80, L178, R199, H212, I215, R269, I310, L318, S332, R378, I610 and / or I661. Such polypeptides and viral vectors encoding such polypeptides may be used for treatment of FVIII deficiencies, such as hemophilia A.

Provided are splice-modulating antisense oligonucleotides (ASOs) that target a terminal stem loop structure at the 3' end of intron 15 (TSL-3-15) of a Factor VIII (F8) pre-mRNA. Also provided are compositions comprising the splice-modulating ASOs. In some embodiments, the compositions are formulated for administration to a subject. Methods of treating Hemophilia A (HA) in a subject in need thereof are also provided. In certain embodiments, the subject exhibits aberrant splicing of Factor VIII (F8) exon 16, and the methods comprise administering to the subject a therapeutically effective amount of a composition of the present disclosure.

A serum albumin variant or functional fragment thereof comprising one or more amino acid substitutions selected from the group consisting of: (i) glycine, isoleucine, lysine, methionine, phenylalanine, tryptophan, tyrosine, valine, and leucine substituting glutamine at position (522); (ii) valine substituting alanine at position (552); and (iii) alanine, glutamic acid, histidine, serine, lysine, and arginine substituting glycine at position (572).

The present invention relates to a solid oral pharmaceutical composition comprising (i) a core comprising a peptide or protein drug, and (ii) a first coating, wherein the first coating comprises a copolymer (A) in combination with a copolymer (B) and / or a copolymer (C) and / or a copolymer (D).

Various aspects of the invention relate to recombinant polypeptides that specifically bind human von Willebrand Factor. Such recombinant polypeptides typically include a modified extracellular domain of platelet glycoprotein lbα that typically comprises at least one mutation selected from G233T, D235V, and K237V, and such recombinant polypeptides optionally include an oligomerization domain.

The invention relates to isolated single-domain antibodies (sdAb) directed against von Willebrand Factor (VWF) D′D3 domain and chimeric polypeptides comprising thereof such as blood clotting factors and their uses in therapy such as in the prevention and treatment of hemostatic disorders. The invention also relates to a method of extending or increasing half-life of a therapeutic polypeptide comprising a step of adding to the polypeptide sequence of said therapeutic polypeptide at least one sdAb directed against VWF D′D3 domain.

Described herein are methods, compositions, and systems derived from uncultivated microorganisms useful supplementing liver enzyme deficiencies.

The present invention provides a formulation of a Factor VIII polypeptide, e.g., FVIII-Fc, and methods of using the same. The FVIII polypeptide can be a recombinant FVIII protein, a short-acting FVIII protein, or a long-acting FVIII protein. The pharmaceutical formulation comprising a FVIII polypeptide can be used for individual prophylaxis, weekly prophylaxis, episodic (on-demand) treatment, or perioperative management of hemophilia.

The utility model belongs to the technical field of plasma product equipment, and particularly relates to a drainage cut-off device for a siphonage method. Comprising a driving device and siphons, the driving device comprises a rear mounting plate frame, a pressing plate mounting box, a pressing plate positioning block, a movable pressing plate set, a cam shaft, a fixed cut-off plate, a front mounting plate, a cut-off door, a movable cut-off plate, a lock rod, an electric push rod, a servo motor and a gear set. The drainage cut-off device for the siphoning method is compact and small in structure, can be used for rapidly and simply achieving automatic siphoning drainage cut-off operation, fully liberates manpower, is used for achieving automation of the siphoning method cryoprecipitation blood coagulation factor preparation process and avoiding direct contact between an operator and a blood bag in the siphoning operation process, and improves the operation efficiency. The isolation effect is enhanced, and the production safety is improved.

- 46 - A b s t r a c t The invention relates to a fusion protein comprising: a Factor VIII (FVIII) heavy chain; an FVIII light chain; a fragment of von Willebrand Factor (VWF); and at least two copies of an extension peptide (EP); wherein the EP has at least 90 % amino acid 5 sequence identity to SEQ ID NO: 1 and contains a cluster of O-glycosylation sites, wherein the cluster contains at least two O-glycosylated amino acids. The complex shows improved pharmacokinetic properties in comparison to FVIII. The invention further relates to a polynucleotide encoding the fusion protein as well as a vector and host cell comprising the polynucleotide.10

Disclosed herein are nucleic acid compositions and methods of use. The nucleic acid compositions may have a therapeutic nucleic acid sequence operably linked to a nuclear targeting sequence that increases expression of the therapeutic nucleic acid in a cell by at least 1.25 fold; at least 80% sequence identity to SEQ ID NO: 6; or a first regulatory element comprising a promoter sequence operably linked to a hemoglobin subunit gamma intron (hBGi) sequence, and a second regulatory element comprising a woodchuck hepatitis posttranscriptional regulatory element (WPRE) sequence. The nucleic acid compositions with these features may enhance therapeutic nucleic acid transfection and expression. Also disclosed herein are transgenes optimized for gene therapy applications, including novel FVIII transgene sequences, in which the B domain may be non-naturally occurring the A1 and / or A3 domain may include at least one amino acid substitution.

The present disclosure relates to novel polynucleotide sequences, constructs, and cell hosts for expressing the novel polynucleotide sequences, constructs, and compositions comprising the novel polynucleotide sequences, constructs. The disclosure further relates to methods for using the novel polynucleotide sequences, constructs, cellular hosts, and compositions. In some embodiments, the first polynucleotide encodes a polypeptide capable of having natural killer (NK) cell inhibitory activity; and the second polynucleotide encodes a polypeptide capable of inducing an immune response or encoding a naturally endogenously produced protein.

The present invention relates to an integration-defective lentiviral vector (IDLV) comprising a nucleic acid, the said nucleic acid comprising, between a 5′ LTR sequence and a 3′ LTR sequence, at least one nucleus export signaling sequence; at least one nucleic acid sequence of interest; and at least one nuclease site. The invention further relates to an isolated cell comprising said IDLV, a pharmaceutical composition comprising said IDLV or said isolated cell, and their pharmaceutical use in the treatment of a disease selected from the group consisting of immune diseases, viral infections, tumors and blood diseases; and / or a disease caused by the lack of a protein or by the presence of an aberrant non-functional one in an individual in need thereof.

This application relates to the fields of genetics, gene therapy and molecular biology. More specifically, the present invention relates to a codon-optimized nucleic acid encoding FVIII-BDD (B-domain deleted coagulation factor VIII) protein, an expression cassette and vector based thereon, a host cell for producing FVIII-BDD, and various uses of said vector.

The invention includes compositions comprising at least one chimeric alloantigen receptor (CALLAR) specific for an alloantibody, vectors comprising the same, compositions comprising CALLAR vectors packaged in viral particles, and recombinant T cells comprising the CALLAR. The invention also includes methods of making a genetically modified T cell expressing a CALLAR, wherein the expressed CALLAR comprises a Factor VIII or fragment thereof extracellular domain.