|| List of recent Factor Viii-related patents
| Coagulation factor viii with reduced immunogenicity|
B. Modification of said epitope(s) by eliminating at least one hydrophobic aminoacid residues in position p1 and/or p7, substituting at least one hydrophobic aminoacid residue in position p1 and/or p7 with a non-hydrophobic residue, or adding a non-hydrophobic residue in position p1 and/or p7..
|Treatment and prevention of radiation injury using mfg-e8|
Methods and compositions are disclosed for treating and preventing radiation injury using milk fat globule epidermal growth factor-factor viii (mfg-e8).. .
The Feinstein Institute For Medical Research
|Assays to monitor bleeding disorders|
The present invention provides methods of dosing factor viii or factor ix chimeric and hybrid polypeptides. The present invention further provides high-sensitivity methods of quantifying an amount of activated fix protein in a test sample.
Biogen Idec Hemophilia Inc.
|Adeno-associated virus factor viii vectors|
The invention provides improved adeno-associated virus (aav) factor viii (fviii) vectors, including aav fviii vectors that produce a functional factor viii polypeptide and aav fviii vectors with high expression activity.. .
Biomarin Pharmaceutical Inc.
|Compositions and methods for enhancing coagulation factor viii function|
factor viii variants and methods of use thereof are disclosed.. .
The Children's Hospital Of Philadelphia
|Unit dosage forms of pharmaceutical compositions comprising a polymer-factor viii polypeptide conjugate|
Conjugates of a factor viii moiety and one or more water-soluble polymers are provided. Typically, the water-soluble polymer is poly(ethylene glycol) or a derivative thereof.
|Factor viii compositions and methods of making and using same|
The present invention relates to compositions comprising factor viii coagulation factors linked to extended recombinant polypeptide (xten), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of making and using such compositions in treatment of factor viii-related diseases, disorders, and conditions.. .
Amunix Operating Inc.
|Recombinant factor viii having enhanced stability following mutation at the a1-c2 domain interface|
The invention relates to a recombinant factor viii that includes one or more mutations at an interface of a1 and c2 domains of recombinant factor viii. The one or more mutations include substitution of one or more amino acid residues with either a cysteine or an amino acid residue having a higher hydrophobicity.
University Of Rochester
|Novel albumin-free factor viii formulations|
A factor viii composition formulated without albumin, comprising the following formulation excipients in addition to factor viii: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mm to 5 mm calcium salt; 100 mm to 300 mm nacl; and a buffering agent for maintaining a ph of approximately between 6 and 8. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mm to 5 mm calcium salt; 100 mm to 300 mm nacl; and a buffering agent for maintaining a ph of approximately between 6 and 8.
University Of Connecticut
|Chimeric factor viii polypeptides and uses thereof|
The present invention provides a vwf fragment comprising the d′ domain and d3 domain of vwf, a chimeric protein comprising the vwf fragment and a heterologous moiety, or a chimeric protein comprising the vwf fragment and a fviii protein and methods of using the same. A polypeptide chain comprising a vwf fragment of the invention binds to or is associated with a polypeptide chain comprising a fviii protein and the polypeptide chain comprising the vwf fragment can prevent or inhibit binding of endogenous vwf to the fviii protein.
Biogen Idec Ma Inc.
Combined use of a sulfated glycosaminoglycan and a hyaluronidase for improving the bioavailability of factor viii
The present invention relates to pharmaceutical preparations comprising factor viii, a sulfated glycosaminoglycan and a hyaluronidase for the non-intravenous administration in the therapy and prophylactic treatment of bleeding disorders. The invention further relates to the combined use of a factor viii, a sulfated glycosaminoglycan and a hyaluronidase for the treatment and prevention of bleeding disorders, and to a method for increasing the bioavailability after non-intravenous administration of factor viii by co-adminstration of a sulfated glycosaminoglycan and a hyaluronidase..
Csl Behring Gmbh
Recombinant expression vector system for variants of coagulation factor viii and von willebrand factor
Disclosed is an expression vector system for variants of coagulation factor viii (fviii) and von willebrand factor (vwf). In detail, mutant vwf the size of which is significantly reduced by deleting exons but which has remarkably increased fviii stabilizing and activating efficiency, and an expression vector system useful for the treatment of hemophilia which is capable of expressing the same along with fviii are disclosed.
Korea University Industrial & Academic Collaborative Foundation
Compositions and methods for immune tolerance induction
Methods and compositions to reduce immunogenicity of proteins are disclosed. Compositions comprising therapeutic proteins (such as factor viii or any other protein or peptide) complexed with liposomes comprising ps and pc (ps liposomes), or comprising ps, pi and pc and, optionally, cholesterol (ps/pi liposomes) may be used..
The Research Foundation For The State University Of New York
Methods of reducing immunogenicity against factor viii in individuals undergoing factor viii therapy
The present disclosure provides methods of administering chimeric and hybrid factor viii (fviii) polypeptides comprising fviii and fc to subjects at risk of developing inhibitory fviii immune responses, including anti-fviii antibodies and/or cell-mediated immunity. The administration is sufficient to promote coagulation and to induce immune tolerance to fviii.
Puget Sound Blood Center
Multi-specific antigen-binding molecules and uses thereof
Various bispecific antibodies that specifically bind to both blood coagulation factor ix/activated blood coagulation factor ix and blood coagulation factor x and functionally substitute for the cofactor function of blood coagulation factor viii, that is, the function to promote activation of blood coagulation factor x by activated blood coagulation factor ix, were produced. From these antibodies, multispecific antigen-binding molecules having a high activity of functionally substituting for blood coagulation factor viii were successfully discovered..
Chugai Seiyaku Kabushiki Kaisha
Method of producing factor viii proteins by recombinant methods
Provided herein are methods and compositions for producing factor viii proteins. Such methods include introducing into a cell a nucleic acid molecule encoding a factor viii protein operably linked to a promoter, wherein the promoter is characterized by the ability to produce commercially viable factor viii protein; and incubating the cell under conditions for producing commercially viable factor viii protein.
Von willebrand factor variants having improved factor viii binding affinity
The present invention relates to a polypeptide comprising a modified von willebrand factor (vwf) having a higher factor viii binding affinity than non-modified vwf, its pharmaceutical use and method of its preparation.. .
Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients
The present invention is based, at least in part, on the identification of a pharmaceutical container formed, at least in part, of a glass composition which exhibits a reduced propensity to delaminate, i.e., a reduced propensity to shed glass particulates. As a result, the presently claimed containers are particularly suited for storage of pharmaceutical compositions and, specifically, a pharmaceutical solution comprising a pharmaceutically active ingredient, for example, victoza (liraglutide), tresiba (insulin degludec), ryzodeg (insulin degludec/insulin aspart), ideglira (liraglutide and insulin degludec), novoseven (recombinant human coagulation factor viia), novoseven rt (recombinant human coagulation factor viia), or turoctocog alfa (third-generation recombinant coagulation factor viii)..
Use of sulfated glycosaminoglycans for improving the bioavailability of factor viii
The present invention relates to pharmaceutical preparations comprising one or more factor viii and a sulfated glycosaminoglycan for increasing the bioavailability of factor viii upon non-intravenous administration. The invention further relates to the combined use of factor viii and a sulfated glycosaminoglycan for the treatment and prevention of bleeding disorders, whereby the bioavailability of factor viii is increased, and to a method for increasing the bioavailability after non-intravenous administration of factor viii by coadminstration of a sulfated glycosaminoglycan..
Method for production of factor viii
The present invention relates to methods of producing a factor viii polypeptide in mammalian cell cultures.. .
Factor viii polypeptide formulations
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.
Factor viii chimeric and hybrid polypeptides, and methods of use thereof
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. .
Modified coagulation factors with prolonged in vivo half-life
The present invention relates to nucleic acid sequences coding for modified coagulation factors, preferably coagulation factor viii, and their derivatives; recombinant expression vectors containing such nucleic acid sequences; host cells transformed with such recombinant expression vectors; and recombinant polypeptides and derivatives coded for by said nucleic acid sequences, whereby said recombinant polypeptides and derivatives have biological activities and prolonged in vivo half-lives compared to the unmodified wild-type proteins. The invention also relates to corresponding sequences that result in improved in vitro stability.
Methods for treating bleeding disorders
Disclosed are methods for treating bleeding disorders, such as hemophilia, in subjects in need thereof by administering an antibody that specifically binds cd73. The methods reduce production of adenosine, increase platelet activation and/or enhance the level of coagulation on the platelet surface to reduce and/or stop bleeding.
Methods of using adenosine receptor antagonists for treating bleeding disorders
Methods of treating bleeding disorders, such as bleeding diseases such as hemophilia, by administering adenosine 2a receptor and/or adenosine 2b receptor antagonists to subjects in need thereof are disclosed. In some embodiments, the methods further include administration of the antagonist with one or more of factor viii, factor ix and factor xi to treat the bleeding disorder..
Method for improving the stability of purified factor viii after reconstitution
The present invention relates to a method for increasing the stability of a factor viii molecule after purification, lyophilization and reconstitution, comprising preventing proteolytic cleavage of the factor viii molecule into a first fragment comprising essentially the a1 domain and the a2 domain and a second fragment comprising essentially the a3 domain, the c1 domain and the c2 domain throughout manufacturing of the factor viii molecule. The invention further pertains to a method for improving the bioavailability of factor viii after intravenous and non-intravenous injection..
Conjugated factor viii molecules
The present invention relates to b-domain truncated factor viii molecules with a modified circulatory half life, said molecule being covalently conjugated with a hydrophilic polymer. The invention furthermore relates to methods for obtaining such molecules as well as use of such molecules..
Kit for measuring the thrombin generation in a sample of a patient's blood or plasma
The invention provides a kit for measuring the thrombin generation in a sample of a patient's blood or plasma, or in a sample of clotting factors. The kit contains lyophilized tissue factor/phospholipid-complex and a lyophilized mixture containing a thrombin-substrate and cacl2.
Binding molecules for human factor viii and factor viii-like proteins
It is an object of the present invention to provide novel binding molecules for factor viii and factor viii-like proteins. Preferred binding molecules of the present invention exhibit not only distinct characteristics for binding of the target factor viii polypeptides but also specific and desirable characteristics for release (elution) of the target polypeptides.
Modified factor viii and factor ix genes and vectors for gene therapy
The present invention relates to a modified and optimized factor viii or factor ix nucleic acid for inclusion in a chimeric virus vector. Use of such vector can be used for treatment of hemophilia..
Method of administering porcine b-domainless fviii
The present invention provides a method of administering porcine b-domainless factor viii (obi-1) to a patient having factor viii deficiency to provide more rapid and effective protection against bleeding episodes, compared to formerly available methods, or to provide more effective protection to such patients during non-bleeding periods. This invention is based on the discovery that the recombinant b-domainless porcine fviii, termed obi-1, has greater bioavailability compared to the natural porcine fviii partially purified from porcine plasma, termed hyate:c.
Method of purifying therapeutic proteins
The present invention relates generally to a method of reducing the level of plasminogen and/or tissue plasminogen activator and/or other protease(s) in a solution comprising fibrinogen and/or factor viii and/or von willebrand factor (vwf), the method comprising: (i) passing a feedstock comprising fibrinogen and/or factor viii and/or vwf through a hydrophobic charge-induction chromatographic resin under conditions selected such that the plasminogen and/or tissue plasminogen activator and/or other protease(s) is bound to the resin; and (ii) recovering the solution comprising fibrinogen and/or factor viii and/or vwf which passes through the resin; wherein the concentration of the plasminogen and/or tissue plasminogen activator and/or protease(s) in the recovered solution is reduced by at least 50% compared to the feedstock. Also provided are solutions and pharmaceutical formulations comprising the fibrinogen and/or factor viii and/or vwf recovered by such methods, and uses thereof..
Manufacturing and purification processes of complex protein found in fraction iv to make a separated apo, transferrin, and alpha 1 anti strepsin (a1at) or a combined transferrin/apo/human albumin/a1at and all new found proteins
A method of introducing healthy good human cells to eat up bad damaged cells, comprising administering an effective amount of a healthy good protein containing transferrin, alpha 1-antitrypsin, apolipoprotein a and human albumin. The method further comprises administering an effective amount of a protein containing apoa1/2/4, or administering an effective amount of a protein containing factor ii, factor vii, factor ix and factor x in prothrombin complex concentrate.
Von willebrand factor or factor viii and von willebrand factor for the treatment of coagulopathy induced by inhibitors of thrombocytes
The present invention relates to a von willebrand factor for use in the treatment and/or prevention of a bleeding event associated with a thrombopathy induced by substances inhibiting thrombocytes. Furthermore, the present invention relates to a method of treating and/or preventing a disorder related to a bleeding event associated with a thrombopathy induced by substances inhibiting thrombocytes comprising administering a pharmaceutically effective amount of a von-willebrand-factor (vwf) to a patient in need thereof.
Mfg-e8 and uses thereof
Methods of treating cerebral ischemia using milk fat globule epidermal growth factor-factor viii (mfg-e8) are disclosed, as are recombinant human mfg-e8 and its uses in pharmaceutical compositions, products and methods for treating inflammation and organ injury after ischemia/reperfusion, sepsis, and lung injury.. .