380results about "Factor VII" patented technology

The present invention relates to methods of preparing a therapeutic exosome using a protein newly-identified to be enriched on the surface of exosomes. Specifically, the present invention provides methods of using the proteins for affinity purification of exosomes. It also provides methods of localizing a therapeutic peptide on exosomes, and targeting exosomes to a specific organ, tissue or cell by using the proteins. The methods involve generation of surface-engineered exosomes that include one or more of the exosome proteins at higher density, or a variant or a fragment of the exosome protein.

The present invention provides methods of administering Factor VIII (processed FVIII, single chain FVIII, or a combination thereof); methods of administering chimeric and hybrid polypeptides comprising Factor VIII; chimeric and hybrid polypeptides comprising Factor VIII; polynucleotides encoding such chimeric and hybrid polypeptides; cells comprising such polynucleotides; and methods of producing such chimeric and hybrid polypeptides using such cells.

Provided is a recombinant human serum albumin-collagen binding domain (CBD) fusion protein for tumor-specific targeting matrix and its use in specific targeted treatment of a solid tumor. HSA and the CBD generate gene fusion in the form of different molecular structures, and can be expressed in a constructed recombinant engineered host. A pharmaceutical recombinant fusion protein is obtained through large-scale fermentation. The recombinant fusion protein shows tumor-specific targeting of solid tumors and can be used as a starting material of a broad-spectrum matrix carrier. The recombinant fusion protein is coupled with any tumor treatment drug, small-molecule compound, or cytotoxic protein to form an innovative pharmaceutical composition. The pharmaceutical composition of the recombinant fusion protein is also long-acting, can prolong a half-life of the conjugate drug in vivo, and has a significantly better clinical curative efficacy on anti-tumor than that of a monomer drug.

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 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.

To provide non-viral DNA vectors for expressing FVIII therapeutic agents and uses thereof.SOLUTION: The application describes a ceDNA vector having a linear and continuous structure for the delivery and expression of a transgene. The ceDNA vector comprises an expression cassette franked by two ITR sequences, where the expression cassette encodes a transgene encoding FVIII protein. Some ceDNA vectors further comprise a cis-regulatory element including a regulatory switch. Further provided herein are methods and cell lines for reliable gene expression of FVIII protein in vitro, ex vivo and in vivo using the ceDNA vectors.SELECTED DRAWING: None

Described herein are particles comprising a first compartment, a second compartment, and a compound of Formula (I), as well as compositions and methods of making and using the same. The particles may comprise a cell capable of expressing a therapeutic agent useful for the treatment of a disease, disorder, or condition described herein.

The present invention relates to methods of preparing a therapeutic exosome using a protein newly-identified to be enriched on the surface of exosomes. Specifically, the present invention provides methods of using the proteins for affinity purification of exosomes. It also provides methods of localizing a therapeutic peptide on exosomes, and targeting exosomes to a specific organ, tissue or cell by using the proteins. The methods involve generation of surface-engineered exosomes that include one or more of the exosome proteins at higher density, or a variant or a fragment of the exosome protein.

The present disclosure provides a method of treating hemophilia A in a human subject in need thereof comprising administering to the subject a chimeric protein comprising (i) a factor VIII (FVIII) protein and (ii) a von Willebrand factor (VWF) fragment comprising a D′ domain of VWF and a D3 domain of VWF.

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

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.

The present invention relates to a fusion protein comprising a main protein and one or more extension peptides, wherein the amino acid sequence of the main protein is identical or similar to the amino acid sequence of a mammalian protein or a fragment thereof, and the extension peptides comprise a cluster of O-glycosylated amino acids. The extension peptide is identical to a non-repeated sequence of a mammalian protein and / or is identical or similar to SEQ ID NO:1. The main protein is preferably VWF. The fusion protein has an increased half-life compared to the main protein and can be used to increase the half-life of a binding partner, such as FVIII. The invention further relates to complexes formed by the fusion proteins, polynucleotides encoding the fusion proteins, and vectors and host cells containing the polynucleotides. [Selected Figure] Figure 1

To provide FVIII drugs with increased in vivo half-life while retaining sufficient biological activity, and prevention methods for hemophilia subjects.SOLUTION: The invention provides a conjugate comprising recombinant FVIII (rFVIII) and a zwitterionic polymer, where the polymer comprises one or more monomer units and where at least one monomer unit comprises a zwitterionic group. Optionally, the zwitterionic group comprises phosphorylcholine. In some conjugates, the polymer is covalently bonded to at least one of an amino group, a hydroxyl group, a sulfhydryl group and a carboxyl group of rFVIII.SELECTED DRAWING: Figure 2

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 invention provides a dual-signal peptide, the dual-signal peptide comprises a first signal peptide and a second signal peptide, the first signal peptide comprises an exogenous signal peptide, the second signal peptide comprises an endogenous signal peptide of a blood coagulation factor VIII, and the first signal peptide and the second signal peptide are connected in series. According to the dual-signal peptide, the secretion effect and the blood coagulation activity of the blood coagulation factor VIII are substantially improved, the production of FVIII can be greatly improved, the industrial production efficiency of FVIII is improved, the application of FVIII in hemophilia treatment drugs is further promoted, and the treatment cost is reduced.

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.

Among other aspects, the present invention relates to cell culture conditions for producing high molecular weight vWF, in particular, highly multimericWF with a high specific activity and ADAMTS13 with a high specific activity. The cell culture conditions of the present invention can include, for example, a cell culture medium with an increased copper concentration and / or cell culture supernatant with a low ammonium (NH4+) concentration. The present invention also provides methods for cultivating cells in the cell culture conditions to express high molecular weight vWF and rA13 having high specific activities.

Methods and assays for determining the activation level of the plasma kallikrein (pKal) system and the uses thereof for assessing the activity of pKal modulators on the pKal system.

The present specification discloses methods of inactivating a lipid-coat containing virus and proteins essentially free of a lipid-coat containing virus obtained from such methods.

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.

To provide methods of inducing immune tolerance in a human with hemophilia.SOLUTION: The present disclosure provides methods inducing immune tolerance in a human, comprising a step of administering to the human an effective amount of a composition or a chimeric protein comprising a clotting factor and an Fc region.SELECTED DRAWING: None

The application describes ceDNA vectors having linear and continuous structure for delivery and expression of a transgene. ceDNA vectors comprise an expression cassette flanked by two ITR sequences, where the expression cassette encodes a transgene encoding FVIII protein. Some ceDNA vectors further comprise cis-regulatory elements, including regulatory switches. Further provided herein are methods and cell lines for reliable gene expression of FVIII protein in vitro, ex vivo and in vivo using the ceDNA vectors. Provided herein are method and compositions comprising ceDNA vectors useful for the expression of FVIII protein in a cell, tissue or subject, and methods of treatment of diseases with said ceDNA vectors expressing FVIII protein. Such FVIII protein can be expressed for treating disease, e.g., 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 present invention relates to means and method for AAV based gene therapies in humans. In particular, the present invention relates to the treatment of human patients that may be suspected to have antibodies directed against the AAV intended for use in said treatment.

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.