 Patent Application Title |
Patent App Num. |
Date |
 Factor viii t cell epitope variants having reduced immunogenicity | 20130123181 | 20130516 |
 Provided herein are methods and compositions for preventing or reducing an initial immune response to factor VIII in patients suffering from hemophilia A, and for reducing the intensity of the immune response in patients having pre-formed inhibitor antibodies against factor VIII.
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| Factor viii b cell epitope variants having reduced immunogenicity | 20130116182 | 20130509 |
 Provided herein are methods and compositions for preventing or reducing an initial immune response to factor VIII in patients suffering from hemophilia A, and for reducing the intensity of the immune response in patients having pre-formed inhibitor antibodies against factor VIII.
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| Recombinant factor viii having increased stability | 20130085110 | 20130404 |
 The present invention relates to a recombinant factor VIII that includes one or more mutations that result in enhanced stability of both factor VIII and factor VIIIa. Methods of making and using the recombinant factor VIII, and pharmaceutical compositions containing the same are also disclosed. The present invention further relates to an isolated nucleic acid molecule that encodes the recombinant factor VIII, as well as DNA expression systems and host cells containing the isolated nucleic acid molecule.
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| Factor viii molecules with reduced vwf binding | 20130040888 | 20130214 |
 The present invention relates to a recombinant Factor VIII molecule, wherein said molecule has reduced vWF binding capacity, and wherein said molecule is covalently conjugated with at least one side group.
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| Factor viii fusion protein | 20130040889 | 20130214 |
 The present invention relates to modified coagulation factors. In particular, the present invention relates to conjugated Factor VIII molecules fused to a polypeptide such as e.g. an antibody binding protein or a Fc domain.
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| Factor viii compositions and methods of making and using same | 20130017997 | 20130117 |
| 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.
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| Modified factor viii and factor ix genes and vectors for gene therapy | 20130004462 | 20130103 |
| 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.
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| Conjugated proteins | 20130004524 | 20130103 |
| The present invention relates to modified therapeutic proteins, such as e.g. coagula-tion factors. In particular, the present invention relates to conjugated Factor VIII molecules such as e.g. FVII, FVIII, or FIX comprising a hydrophobic side group.
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| Modified factor viii | 20130005656 | 20130103 |
| Methods of treating patients with Factor VIII deficiency by administration of modified porcine factor VIII are disclosed. The particular modified porcine factor VIII is one in which most of the B domain has been removed through genetic engineering. This modified factor VIII is particularly useful for treatment of hemophiliacs, especially those undergoing bleeding episodes.
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| Modified recombinant factor viii and von willebrand factor and methods of use | 20120322737 | 20121220 |
| The present invention provides novel methods of increasing the survival of a coagulation protein by inhibiting the interaction with a clearance receptor. The invention also provides methods of preparing compositions that inhibit coagulation protein clearance receptors. Conjugated coagulation proteins, including compositions and formulations thereof, are also provided by the present invention.
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| Conjugated fviii variants | 20120322738 | 20121220 |
| The present invention relates to conjugated Factor VIII variants. The present invention in particular relates to conjugated FVIII variants comprising different polymeric groups as well as use thereof.
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| Compositions and methods for enhancing coagulation factor viii function | 20120308641 | 20121206 |
| Factor VIII variants and methods of use thereof are disclosed.
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| Compositions and methods of treatment of black hemophiliac patients | 20120297494 | 20121122 |
| It has been determined that most mutations in factor VIII occur in multiple haplotypes, not primarily in one haplo-type. The frequencies of mild, moderate, and severe hemophilia did not differ significantly according to the background haplo-type. The odds of having inhibitor were significantly higher among patients in the H3+H4 haplotype groups as compared to H1+H2 haplotype groups. This association appears to be independent of the mutation. The results indicate that white hemophiliacs should be treated with Kogenate®. However, it would clearly be of benefit to assess the haplotype of black hemophiliacs prior to prescribing the recombinant FVIII to be used for treatment. It is not essential to determine the actual mutations responsible for the hemophilia prior to prescribing the recombinant FVIII. Also described are transgenic human... |
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| Nucleic ac1d and amino ac1d sequences encoding high-level expressor factor viii polypeptides and methods of use | 20120270266 | 20121025 |
| Methods and compositions are provided that allow for high-level expression of a factor VIII polypeptide. More specifically, methods and compositions are provided comprising nucleic acid and amino acid sequences comprising a modified factor VIII that result in high-level expression of the polypeptide. The methods and compositions of the invention find use in the treatment of factor VIII deficiency including, for example, hemophilia A.
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| Method of administering porcine b-domainless fviii | 20120270788 | 20121025 |
| 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. Therefore, the inventive method employs lower unit doses of OBI-1, including, alternatively, omission of antibody-neutralizing dosage, or has longer intervals between the administration, compared to HYATE:C, to provide equivalent protection in patients having fVIII deficiency. The invention further provides pharmaceutical compositions and kits containing OBI-1 in combination with... |
| Polymer factor viii moiety conjugates | 20120244597 | 20120927 |
| 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. Also provided are compositions comprising the conjugates, methods of making the conjugates, and methods of administering compositions comprising the conjugates to a patient.
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| Polymer-factor viii moiety conjugates | 20120245289 | 20120927 |
| 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. Also provided are compositions comprising the conjugates, methods of making the conjugates, and methods of administering compositions comprising the conjugates to a patient.
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| Factor viii polymer conjugates | 20120232252 | 20120913 |
| The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.
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| Stable formulation of factor viii | 20120225819 | 20120906 |
| The invention relates inter alia to a composition which is storage-stable at 25° C. for a minimum of 18 weeks comprising a therapeutically effective amount of Factor VIII and an aqueous medium having a Factor VIII potency after 18 weeks of storage at 25° C. of at least 90% of the Factor VIII potency of a Control Composition.
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| Factor viii compositions and methods of making and using same | 20120178691 | 20120712 |
| 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.
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| Dosage forms of polymer-factor viii moiety conjugates | 20120178692 | 20120712 |
| 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. Also provided are compositions comprising the conjugates, methods of making the conjugates, and methods of administering compositions comprising the conjugates to a patient.
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| Factor viii variants and methods of use | 20120142593 | 20120607 |
| A Factor VIII fusion protein or a Factor VIII fusion heterodimer comprising Factor VIII in which an amino acid sequence of a modulator is present in the B-domain, or an amino acid sequence of a modulator replaces some or all of the amino acid sequence of the B-domain is disclosed. Nucleic acids encoding the inventive fusion proteins and fusion heterodimers are also disclosed, as are methods for producing the fusion proteins and fusion heterodimers, pharmaceutical compositions, and methods of treating deficiencies in coagulation with the inventive fusion molecules.
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| Polymer-von willebrand factor-conjugates | 20120135462 | 20120531 |
| The present invention relates to a proteinaceous construct (also designated as polymer-VWF-conjugate) comprising plasmatic and/or recombinant von Willebrand factor (VWF), said VWF being bound to at least one physiologically acceptable polymer molecule, as well as to a complex between said proteinaceous construct and at least one factor VIII (FVIII) protein. The physiologically acceptable polymer molecule can be, for instance, polyethylene glycol (PEG) or polysialic acid (PSA). Further the present invention relates to methods for prolonging the in vivo-half-life of VWF or FVIII in the blood of a mammal having a bleeding disorder associated with functional defects of or deficiencies of at least one of FVIII or VWF.
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| Peptide | 20120121625 | 20120517 |
| The present invention provides peptides at least partly derivable from FVIII which are capable of binding to an MHC class II molecule without further antigen processing and being recognised by a factor VIII specific T cell. In particular, the present invention provides a peptide comprising or consisting of the sequence EDNIMVTFRNQASR. The present invention also relates to the use of such a peptide for the prevention or suppression of inhibitor antibody formation in haemophilia A and/or acquired haemophilia.
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| Targeted delivery of factor viii proteins to platelets | 20120093840 | 20120419 |
| The invention described herein relates to novel molecules and polypeptides comprising at least one amino acid sequence having significant identity with (homology to) human Factor VIII or biologically active portion(s) thereof, related molecules (such as nucleic acids encoding such polypeptides), compositions (such as pharmaceutical formulations) comprising such polypeptides, and methods of making and using such polypeptides.
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| Novel albumin-free factor viii formulations | 20120083446 | 20120405 |
| An albumin-free Factor VIII formulation comprising, 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 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. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from... |
| Genetic factors associated with inhibitor development in hemophilia a | 20120065077 | 20120315 |
| The present invention provides methods for predicting the risk of an individual developing antibodies to factor VIII by identifying a single nucleotide polymorphism of an immune response or immune modifier gene. The invention further provides oligonucleotides, diagnostic kits, microarrays, and isolated nucleic acids comprising single nucleotide polymorphisms of immune response or immune modifier genes.
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| Recombinant factor viii having enhanced stability following mutation at the a1-c2 domain interface | 20120065136 | 20120315 |
| 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. This results in enhanced stability of factor VIII. Methods for making the recombinant factor VIII, pharmaceutical compositions containing the recombinant factor VIII, and use of the recombinant factor VIII for treating hemophilia A are also disclosed.
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| Binding molecules for human factor viii and factor viii-like proteins | 20120045819 | 20120223 |
| 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. Especially preferred binding molecules according to the invention are short polypeptide sequences, characterized by a stable loop structure.
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| Method of producing factor viii proteins by recombinant methods | 20120028900 | 20120202 |
| 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. Also provided are nucleic acid molecules which encode a Factor VIII protein operably linked to a Chinese hamster elongation factor 1-α (CHEF1) promoter, which may be used in the methods provided herein.
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| Transgenic animal expressing b cell antigen receptor | 20110010786 | 20110113 |
| The invention relates to a non-human transgenic mammal containing in its genome a DNA construct expressing a B cell antigen receptor specific for factor VIII of the coagulation pathway.
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| Method for purifying factor viii and von willebrand factor | 20100305305 | 20101202 |
| The purification method includes, starting from a solution selected from (i) a solution containing a mixture of FVIII and FvW, (ii) a solution containing FvW, (iii) a solution derived from a secretion of a non-human animal and (iv) a solution derived from a FVIII-containing plant extract, a step of absorption of FVIII or FvW on an ion-exchange chromatography filter-type membrane.
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| Binding molecules for human factor viii and factor viii-like proteins | 20100292440 | 20101118 |
| 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. Especially preferred binding molecules according to the invention are short polypeptide sequences, characterized by a stable loop structure.
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| Use of vwf stabilized fviii preparations and of vwf preparations without fviii for extravascular administration in the therapy and prophylactic treatment of bleeding disorders | 20100286047 | 20101111 |
| The present invention relates to the use of von Willebrand Factor (VWF) preparations or of a VWF preparation in combination with coagulation Factor VIII (FVIII) for extravascular administration in the therapy and prophylactic treatment of bleeding disorders.
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| Ligands for use in therapeutic compositions for the treatment of hemostasis disorders | 20100285021 | 20101111 |
| The invention, in general, features a method of treatment and/or prevention of a thrombotic pathological condition, in a mammal, which includes administering to the mammal in need of such treatment a therapeutically effective amount of a composition including an antibody directed against the C1 domain of Factor VIII, which is a partially inhibitory antibody of Factor VIII.
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| Modified factor viii and factor ix genes and vectors for gene therapy | 20100284971 | 20101111 |
| 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.
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| Variable antibodies | 20100272715 | 20101028 |
| The present invention discloses inhibitory antibodies against Factor VIII with modified glycosylation, either by enzymatic deglycosylation or by site directed mutagenesis. Said antibodies with modified glycosylation have equal affinity for FVIII but show different inhibiting properties. The use of one or a mixture of said antibodies allow modulation of the inhibition of factor VIII to levels between 40 and 95%. The present invention further discloses pharmaceutical compositions comprising inhibitory antibodies against Factor VIII with modified glycosylation, combinations of these antibodies and methods for treating haemostasis disorders using said antibodies and antibody mixtures.
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| Variable antibodies | 20100266586 | 20101021 |
| The present invention discloses inhibitory antibodies against Factor VIII with modified glycosylation, either by enzymatic deglycosylation or by site directed mutagenesis. Said antibodies with modified glycosylation have equal affinity for FVIII but show different inhibiting properties. The use of one or a mixture of said antibodies allow modulation of the inhibition of factor VIII to levels between 40 and 95%. The present invention further discloses pharmaceutical compositions comprising inhibitory antibodies against Factor VIII with modified glycosylation, combinations of these antibodies and methods for treating haemostasis disorders using said antibodies and antibody mixtures.
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| Factor viii: remodeling and glycoconjugation of factor viii | 20100261872 | 20101014 |
| The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.
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| Allelic variants of human factor viii | 20100256062 | 20101007 |
| Disclosed are compositions and methods related to Factor VIII.
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| Suppression of immune response to factor viii in hemophilia a patients | 20100233119 | 20100916 |
| This invention relates to methods and compositions for suppressing an immune response to Factor VIII in subjects suffering from hemophilia A and having preformed inhibitor antibodies against Factor VIII, and compositions and methods that advantageously render subjects amenable to standard treatments for hemophilia A, including Factor VIII replacement therapy.
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| Purification of factor viii using a mixed-mode or multimodal resin | 20100204452 | 20100812 |
| A method for purifying a recombinant protein using a multimodal or mixed mode resin containing ligands which comprise a hydrophobic part and a negatively charged part is described. The invention is advantageous in that it is a single step chromatographic process which does not require adjustment of pH or conductivity during loading step and results in high yield and potency. The process is used for the purification of recombinant compositions of coagulation factor, particularly recombinant Factor VIII.
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| Demannosylated recombinant factor viii [[vii]] for the treatment of patients with haemophilia a | 20100197578 | 20100805 |
| There is provided in accordance with the practice of this invention a demannosylated Factor VIII, the immunogenicity of which is substantially decreased or abolished in Human. The modified factor VIII is disclosed together with the modified amino acid sequence, changed by at least one substitution. The modified factor VIII is useful for hemophiliacs, either to avoid or prevent the action of inhibitory anti-FVIII antibodies.
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| Recombinant expression vector system for variants of coagulation factor viii and von willebrand factor | 20100183556 | 20100722 |
| 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. Use of the mutant vWF with a reduced size enables effective expression of FVIII in a viral vector and significantly enhanced FVIII activity. Further, the viral vector may be effectively used to treat hemophilia through gene therapy.
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| Factor viii polymer conjugates | 20100173831 | 20100708 |
| The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.
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| Factor viii polymer conjugates | 20100173830 | 20100708 |
| The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.
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| Recombinant human blood coagulation factor viii protein, composition, use of a recombinant factor viii protein, use of a composition, method of obtaining a recombinant human blood coagulation factor viii protein and use thereof | 20100172891 | 20100708 |
| The present invention refers to a recombinant human blood coagulation factor VIII protein and a composition containing it. The present invention also refers to the use of the protein or composition of the invention for manufacturing a medicine for treating hemophilia A. Additionally, the present invention refers to the method of obtaining a recombinant human blood coagulation factor VIII protein. A further object of the present invention is a recombinant protein obtained by the method described herein, and its use in the preparation of a medicine for the treatment of hemophilia A.
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| Pegylated factor viii | 20100168391 | 20100701 |
| The invention is a proteinaceous construct comprising a Factor VIII molecule having at least a portion of the B domain intact, which is conjugated to a water-soluble polymer such as polyethylene glycol having a molecular weight of greater than 10,000 Daltons. The construct has a biological activity of at least 80% of the biological activity of native Factor VIII, and the in vivo half-life of the construct is increased by at least 1.5 fold as compared to the in vivo half-life of native factor FVIII.
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| Factor viii formulations | 20100168018 | 20100701 |
| A Factor VIII (FVIII) composition formulated such that NaCl is not present in the final formulation or is present in trace amounts, which allows for a concomitant reduction in the lyophilization cycle time and increased stability of the lyophilized FVIII.
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| Application of anti-apoptotic gene expression in mammalian cells for perfusion culture | 20100167396 | 20100701 |
| The present invention relates to preventing or delaying programmed cell death by expressing one or more anti-apoptotic polypeptides in a cell expressing recombinant Factor VIII such that programmed cell death in the cell is prevented or delayed. The present invention also relates to increasing production of recombinant Factor VIII by expressing one or more anti-apoptotic polypeptides in a cell such that production of recombinant Factor VIII by the cell is increased. Recombinant cells useful for producing Factor VIII.
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| Factor viii compositions and methods | 20100167392 | 20100701 |
| The present invention provides methods of increasing the half-life and/or specific activity of factor VIII. More specifically, the invention provides methods of increasing the half-life and/or specific activity of factor VIII by substituting one or more amino acids in the A2 domain. It further provides methods for producing such factor VIII mutants. The invention also provides polynucleotides encoding the mutant factor VIII, and methods of treating hemophilia using the polypeptides and polynucleotides of the invention.
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| Polymer-factor viii moiety conjugates | 20100130427 | 20100527 |
| 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. Also provided are compositions comprising the conjugates, methods of making the conjugates, and methods of administering compositions comprising the conjugates to a patient.
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| Polymer factor viii moiety conjugates | 20100125049 | 20100520 |
| 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. Also provided are compositions comprising the conjugates, methods of making the conjugates, and methods of administering compositions comprising the conjugates to a patient.
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| Polymer factor viii moiety conjugates | 20100120689 | 20100513 |
| 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. Also provided are compositions comprising the conjugates, methods of making the conjugates, and methods of administering compositions comprising the conjugates to a patient.
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| Modified coagulation factors with prolonged in vivo half-life | 20100120664 | 20100513 |
| 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. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such nucleic acid sequences.
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| Factor viii polypeptide titers in cell cultures | 20100120094 | 20100513 |
| The invention relates to a method for the production of a Factor VIII polypeptide, the method comprising the steps of a) culturing a mammalian cell expressing a Factor VIII polypeptide under conditions for expression of said Factor VIII polypeptide, said culturing conditions involving a cell culture medium comprising a C2-domain ligand, and b) isolating the expressed Factor VIII polypeptide from the mammalian cell by suitable means.
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| Factor viii polymer conjugates | 20100113364 | 20100506 |
| The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.
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| Factor viii polymer conjugates | 20100113365 | 20100506 |
| The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.
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| Process for producing and purifying factor viii and its derivatives | 20100112641 | 20100506 |
| Disclosed is a method for producing proteins having factor VIII procoagulant activity in serum-free medium by in vitro culturing of mammalian cells, wherein the serum-free medium contains an inhibitor against the protease released from cultured cells. In accordance with this invention, the inhibitor can protect the cleavage of a target protein during cultivation and increase homogeneity of a target molecule, wherein the inhibitor can be a dextran sulfate. This invention also relates to a method of purifying target molecules from the culture medium containing both a target molecule and selected inhibitors by affinity chromatography.
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| Minimized small peptides with high affinity for factor viii and factor viii-like proteins | 20100099113 | 20100422 |
| The present invention relates to the composition of small molecules and their use in the field of protein isolation, purification, stabilizing and/or enhancing its activity. In particular, the present invention relates to the synthesis and optimization of compounds comprising small peptides and peptide derivatives with affinity to coagulation Factor VIII and/or Factor VIII-like polypeptides and/or domains thereof. These compounds are useful for labeling, detecting, identifying, isolating and preferably for purifying, stabilizing and enhancing the activity of Factor VIII, Factor VIII-like polypeptides or domains thereof from physiological and non-physiological solutions comprising same. Further, these compounds may be used as ligands, which bind Factor VIII, Factor VIII-like polypeptides or domains thereof in methods of the present invention.
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| Modified factor viii | 20090325881 | 20091231 |
| Methods of treating patients with Factor VIII deficiency by administration of modified porcine factor VIII are disclosed. The particular modified porcine factor VIII is one in which most of the B domain has been removed through genetic engineering. This modified factor VIII is particularly useful for treatment of hemophiliacs, especially those undergoing bleeding episodes.
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| Inhibition of the anti-fviii immune response | 20090317373 | 20091224 |
| The invention relates to a compound capable of inhibiting the endocytosis of FVIII (factor VIII) by immune system cells capable of endocytosing the antigen and to the therapeutic use of such a compound for the manufacture of a medicament for use in the treatment of hemophiliacs in order to reduce the immunogenicity of FVIII and/or increase the half-life of FVIII.
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| Expression of soluble factor viii proteins in bacteria | 20090305349 | 20091210 |
| The present invention provides enhanced methods of producing soluble Factor VIII proteins in microorganisms that have an oxidizing environment.
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| Blood coagulation factor viii activation-enhancing antibodies | 20090297503 | 20091203 |
| For the first time, the present invention provides antibodies that enhance the generation of activated blood coagulation factor VIII. The antibodies enhance the cleavage of blood coagulation factor VIII at the Arg of position 372 and suppress the cleavage at the Arg of position 336 by recognizing and binding to the A2 domain of blood coagulation Factor VIII. Such antibodies are expected to be useful in preventing or treating diseases that develop or progress due to decrease or loss of the blood coagulation factor VIII activity, for example, hemophilia A, acquired hemophilia, and von Willebrand's disease.
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| Milk fat globule epidermal growth factor-factor viii and sepsis | 20090297498 | 20091203 |
| Provided are methods of treating a mammal undergoing sepsis or at risk for sepsis. Also provided are methods of preventing or treating a physiologic effect of sepsis in a mammal. Additionally provided is the use of milk fat globule epidermal growth factor-factor VIII (MFG-E8) for the manufacture of a medicament for preventing or treating a physiologic effect of sepsis in a mammal, and the use of milk fat globule epidermal growth factor-factor VIII (MFG-E8) for the treatment of a mammal having sepsis or at risk for sepsis.
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| Affinity adsorbents for factor viii and von willebrand's factor | 20090275141 | 20091105 |
| For the separation, removal, isolation, purification, characterisation, identification or quantification of Factor VIII, von Willebrand's Factor or a protein that is a analogue of either, an affinity adsorbent is used that is a compound of formula (II) wherein one X is N and the other is N, C—Cl or C—CN; A is a support matrix, optionally linked to the triazine ring by a spacer; Y is O, S or NR2; Z is O, S or N—R3; R2 and R3 are each H, C1-6 alkyl, Cu, hydroxyalkyl, benzyl or phenylethyl; B and W are each an optionally substituted hydrocarbon linkage containing from 1 to 10 carbon atoms; D is H, OH or a primary amino, secondary amino, tertiary amino, quaternary ammonium, imidazole, guanidino or amidino group; or... |
| Affinity adsorbents for factor viii and von willebrand's factor | 20090275141 | 20091105 |
| For the separation, removal, isolation, purification, characterisation, identification or quantification of Factor VIII, von Willebrand's Factor or a protein that is a analogue of either, an affinity adsorbent is used that is a compound of formula (II) wherein one X is N and the other is N, C—Cl or C—CN; A is a support matrix, optionally linked to the triazine ring by a spacer; Y is O, S or NR2; Z is O, S or N—R3; R2 and R3 are each H, C1-6 alkyl, Cu, hydroxyalkyl, benzyl or phenylethyl; B and W are each an optionally substituted hydrocarbon linkage containing from 1 to 10 carbon atoms; D is H, OH or a primary amino, secondary amino, tertiary amino, quaternary ammonium, imidazole, guanidino or amidino group; or... |
| Crystal structure of human factor viii and uses thereof | 20090271163 | 20091029 |
| The present invention provides crystals of human Factor VIII, in particular, a B-domain deleted human Factor VIII, and its three-dimensional structure. The present invention also provides the structural information of Factor VIII, and methods for identifying compounds that modulate Factor VIII activity, for determining structures of Factor VIII homologs or analogs, and for designing drug candidates for the treatment of hemophilia based on the structural information.
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| Methods of administering porcine b-domainless fviii | 20090270329 | 20091029 |
| 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. Therefore, the inventive method employs lower unit doses of OBI-1, including, alternatively, omission of antibody-neutralizing dosage, or has longer intervals between the administration, compared to HYATE:C, to provide equivalent protection in patients having fVIII deficiency. The invention further provides pharmaceutical compositions and kits containing OBI-1 in combination with... |
| Methods of administering porcine b-domainless fviii | 20090270329 | 20091029 |
| 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. Therefore, the inventive method employs lower unit doses of OBI-1, including, alternatively, omission of antibody-neutralizing dosage, or has longer intervals between the administration, compared to HYATE:C, to provide equivalent protection in patients having fVIII deficiency. The invention further provides pharmaceutical compositions and kits containing OBI-1 in combination with... |
| Crystal structure of human factor viii and uses thereof | 20090271163 | 20091029 |
| The present invention provides crystals of human Factor VIII, in particular, a B-domain deleted human Factor VIII, and its three-dimensional structure. The present invention also provides the structural information of Factor VIII, and methods for identifying compounds that modulate Factor VIII activity, for determining structures of Factor VIII homologs or analogs, and for designing drug candidates for the treatment of hemophilia based on the structural information.
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| Anti-idiotypic antibodies neutralizing the inhibitory activity of an inhibitory antibody directed against the c1 domain of factor viii | 20090263380 | 20091022 |
| The present invention is related to a monoclonal anti-idiotypic antibody directed against a Factor VIII inhibitor antibody binding to the C1 domain of Factor VIII, as well as to a cell line producing this monoclonal anti-idiotypic antibody, to the use of this monoclonal anti-idiotypic antibody as medicament, and more particularly to the use thereof for manufacturing a medicament intended for the treatment of haemophilia A.
... |
| Use of blood coagulation factor xiii for treating hemophilia a | 20090264347 | 20091022 |
| A patient having hemophilia A is treated by administering factor XIII generally in conjunction with factor VIII or desmopressin.
... |
| Modified recombinant factor viii and von willebrand factor and methods of use | 20090247459 | 20091001 |
| The present invention provides novel methods of increasing the survival of a coagulation protein by inhibiting the interaction with a clearance receptor. The invention also provides methods of preparing compositions that inhibit coagulation protein clearance receptors. Conjugated coagulation proteins, including compositions and formulations thereof, are also provided by the present invention.
... |
| Transgenic non-human animals expressing human blood clotting factors and uses thereof | 20090235369 | 20090917 |
| The present invention relates, in general, to development of non-human transgenic animals expressing a human blood clotting factor, such as Factor VIII, Factor VII, Factor IX and von Willebrand factor. The invention further provides methods of detecting immunogenic events against human blood clotting factor using the transgenic animals described.
... |
| Transgenic non-human animals expressing human blood clotting factors and uses thereof | 20090235369 | 20090917 |
| The present invention relates, in general, to development of non-human transgenic animals expressing a human blood clotting factor, such as Factor VIII, Factor VII, Factor IX and von Willebrand factor. The invention further provides methods of detecting immunogenic events against human blood clotting factor using the transgenic animals described.
... |
| Small peptidic and peptido-mimetic affinity ligands for factor viii and factor viii-like proteins | 20090215025 | 20090827 |
| The present invention pertains to compounds that show a high affinity to Factor VIII and Factor VIII-like proteins, and their uses. The compounds are characterized by the general Formula B-Q-X, wherein B represents a dipeptide, tripeptide, or a peptidomimetic; Q represents a spacer and X represents an anchoring molecule; Q and X are optional. These compounds can be used for coating a solid support material. The resulting coated solid support material can be used for purifying Factor VIII by means of affinity chromatography methods. In addition, the compounds of the present invention may be used for stabilizing Factor VIII and for enhancing its activity. The present invention thus pertains also to methods for manufacturing a stabilized Factor VIII containing medicament of increased activity. The inventive compounds... |
| Highly sensitive immunoassays and antibodies for detection of blood factor viii | 20090215070 | 20090827 |
| Disclosed are antibodies that selectively bind to blood coagulation factor FVIII, and highly sensitive immunological assays comprising these antibodies. Preferred assays can detect FVIII at about 3500-fold below the normal physiological levels, and have a wide array of applications including accurate monitoring of FVIII concentration in pharmaceutical products for treatment of blood coagulation disorders, and determination of FVIII levels in plasma of human patients, including those with blood coagulation disorders such as hemophilia.
... |
| Small peptidic and peptido-mimetic affinity ligands for factor viii and factor viii-like proteins | 20090215025 | 20090827 |
| The present invention pertains to compounds that show a high affinity to Factor VIII and Factor VIII-like proteins, and their uses. The compounds are characterized by the general Formula B-Q-X, wherein B represents a dipeptide, tripeptide, or a peptidomimetic; Q represents a spacer and X represents an anchoring molecule; Q and X are optional. These compounds can be used for coating a solid support material. The resulting coated solid support material can be used for purifying Factor VIII by means of affinity chromatography methods. In addition, the compounds of the present invention may be used for stabilizing Factor VIII and for enhancing its activity. The present invention thus pertains also to methods for manufacturing a stabilized Factor VIII containing medicament of increased activity. The inventive compounds... |
| Highly sensitive immunoassays and antibodies for detection of blood factor viii | 20090215070 | 20090827 |
| Disclosed are antibodies that selectively bind to blood coagulation factor FVIII, and highly sensitive immunological assays comprising these antibodies. Preferred assays can detect FVIII at about 3500-fold below the normal physiological levels, and have a wide array of applications including accurate monitoring of FVIII concentration in pharmaceutical products for treatment of blood coagulation disorders, and determination of FVIII levels in plasma of human patients, including those with blood coagulation disorders such as hemophilia.
... |
| Small peptidic and peptido-mimetic affinity ligands for factor viii and factor viii-like proteins | 20090215025 | 20090827 |
| The present invention pertains to compounds that show a high affinity to Factor VIII and Factor VIII-like proteins, and their uses. The compounds are characterized by the general Formula B-Q-X, wherein B represents a dipeptide, tripeptide, or a peptidomimetic; Q represents a spacer and X represents an anchoring molecule; Q and X are optional. These compounds can be used for coating a solid support material. The resulting coated solid support material can be used for purifying Factor VIII by means of affinity chromatography methods. In addition, the compounds of the present invention may be used for stabilizing Factor VIII and for enhancing its activity. The present invention thus pertains also to methods for manufacturing a stabilized Factor VIII containing medicament of increased activity. The inventive compounds... |
| Highly sensitive immunoassays and antibodies for detection of blood factor viii | 20090215070 | 20090827 |
| Disclosed are antibodies that selectively bind to blood coagulation factor FVIII, and highly sensitive immunological assays comprising these antibodies. Preferred assays can detect FVIII at about 3500-fold below the normal physiological levels, and have a wide array of applications including accurate monitoring of FVIII concentration in pharmaceutical products for treatment of blood coagulation disorders, and determination of FVIII levels in plasma of human patients, including those with blood coagulation disorders such as hemophilia.
... |
| Small peptidic and peptido-mimetic affinity ligands for factor viii and factor viii-like proteins | 20090215025 | 20090827 |
| The present invention pertains to compounds that show a high affinity to Factor VIII and Factor VIII-like proteins, and their uses. The compounds are characterized by the general Formula B-Q-X, wherein B represents a dipeptide, tripeptide, or a peptidomimetic; Q represents a spacer and X represents an anchoring molecule; Q and X are optional. These compounds can be used for coating a solid support material. The resulting coated solid support material can be used for purifying Factor VIII by means of affinity chromatography methods. In addition, the compounds of the present invention may be used for stabilizing Factor VIII and for enhancing its activity. The present invention thus pertains also to methods for manufacturing a stabilized Factor VIII containing medicament of increased activity. The inventive compounds... |
| Highly sensitive immunoassays and antibodies for detection of blood factor viii | 20090215070 | 20090827 |
| Disclosed are antibodies that selectively bind to blood coagulation factor FVIII, and highly sensitive immunological assays comprising these antibodies. Preferred assays can detect FVIII at about 3500-fold below the normal physiological levels, and have a wide array of applications including accurate monitoring of FVIII concentration in pharmaceutical products for treatment of blood coagulation disorders, and determination of FVIII levels in plasma of human patients, including those with blood coagulation disorders such as hemophilia.
... |
| Small peptidic and peptido-mimetic affinity ligands for factor viii and factor viii-like proteins | 20090215025 | 20090827 |
| The present invention pertains to compounds that show a high affinity to Factor VIII and Factor VIII-like proteins, and their uses. The compounds are characterized by the general Formula B-Q-X, wherein B represents a dipeptide, tripeptide, or a peptidomimetic; Q represents a spacer and X represents an anchoring molecule; Q and X are optional. These compounds can be used for coating a solid support material. The resulting coated solid support material can be used for purifying Factor VIII by means of affinity chromatography methods. In addition, the compounds of the present invention may be used for stabilizing Factor VIII and for enhancing its activity. The present invention thus pertains also to methods for manufacturing a stabilized Factor VIII containing medicament of increased activity. The inventive compounds... |
| Highly sensitive immunoassays and antibodies for detection of blood factor viii | 20090215070 | 20090827 |
| Disclosed are antibodies that selectively bind to blood coagulation factor FVIII, and highly sensitive immunological assays comprising these antibodies. Preferred assays can detect FVIII at about 3500-fold below the normal physiological levels, and have a wide array of applications including accurate monitoring of FVIII concentration in pharmaceutical products for treatment of blood coagulation disorders, and determination of FVIII levels in plasma of human patients, including those with blood coagulation disorders such as hemophilia.
... |
| Catalytic anti-factor viii allo-antibodies | 20090208512 | 20090820 |
| The present invention relates to a method of determining the presence of catalytic anti-Factor VIII allo-antibodies capable of degrading Factor VIII in a mammal, and of characterising the cleavage sites in said Factor VIII molecule by said catalytic anti-Factor VIII allo-antibodies. It also relates to an anti-Factor VIII allo-antibody-catalysed Factor VIII degradation inhibitor; and to a pharmaceutical composition comprising said catalytic anti-Factor VIII allo-antibodies which are capable of degrading Factor VIII and which originate from said method of determination; and further to a pharmaceutical composition comprising said anti-Factor VIII allo-antibody-catalysed Factor VIII degradation inhibitor. Finally, the present invention relates to the application in therapeutics of said anti-Factor VIII allo-antibody-catalysed Factor VIII degradation inhibitor, of a pharmaceutical composition comprising said catalytic anti-Factor VIII allo-antibodies which are capable... |
| Catalytic anti-factor viii allo-antibodies | 20090208512 | 20090820 |
| The present invention relates to a method of determining the presence of catalytic anti-Factor VIII allo-antibodies capable of degrading Factor VIII in a mammal, and of characterising the cleavage sites in said Factor VIII molecule by said catalytic anti-Factor VIII allo-antibodies. It also relates to an anti-Factor VIII allo-antibody-catalysed Factor VIII degradation inhibitor; and to a pharmaceutical composition comprising said catalytic anti-Factor VIII allo-antibodies which are capable of degrading Factor VIII and which originate from said method of determination; and further to a pharmaceutical composition comprising said anti-Factor VIII allo-antibody-catalysed Factor VIII degradation inhibitor. Finally, the present invention relates to the application in therapeutics of said anti-Factor VIII allo-antibody-catalysed Factor VIII degradation inhibitor, of a pharmaceutical composition comprising said catalytic anti-Factor VIII allo-antibodies which are capable... |
| Method of producing factor viii proteins by recombinant methods | 20090203077 | 20090813 |
| 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. Also provided are nucleic acid molecules which encode a Factor VIII protein operably linked to a Chinese hamster elongation factor 1-α (CHEF1) promoter, which may be used in the methods provided herein.
... |
| Coagulation factor x polypeptides with modified activation properties | 20090175828 | 20090709 |
| The present invention relates to modified cDNA sequences coding for factor X polypeptides, in particular human factor X and its derivatives which can bypass the need for either factor VIIIa/factor IXa or factor VIIa/tissue factor for activation. The invention relates further to recombinant expression vectors containing such modified cDNA sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives which do have biological activities of the unmodified wild type protein but having altered activation properties, and processes for the manufacture of such recombinant proteins and their derivatives. The invention also covers a transfer vector for use in human gene therapy, which comprises such modified DNA sequences.
... |
| Modified cdna for high expression levels of factor viii and its derivatives | 20080312143 | 20081218 |
| The present invention relates to modified DNA sequences coding for biologically active recombinant human factor VIII and its derivatives, recombinant expression vectors containing such DNA sequences, host cells transformed with such recombinant expression vectors, and processes for the manufacture of the recombinant human factor VIII and its derivatives. The invention also covers a transfer vector for use in human gene therapy which comprises such modified DNA sequences. The present invention relates to modified DNA sequences coding for biologically active recombinant human factor VIII and its derivatives, recombinant expression vectors containing such DNA sequences, host cells transformed with such recombinant expression vectors, and processes for the manufacture of the recombinant human factor VIII and its derivatives. The invention also covers a transfer vector for use in human... |
| Salvia hispanica i (chia) in the management and treatment of cardiovascular disease, diabetes and associated risk factors | 20080305190 | 20081211 |
| Described is use of Salvia hispanica L. (Chia) for controlling, in one embodiment reducing, blood glucose levels, preferably post-prandial blood glucose levels. This is useful in both non-diabetic and diabetic individuals, but especially in diabetic individuals. Also described is the use of chia in reducing postprandial blood glucose, insulin sensitivity, blood pressure, and oxidative stress in such individuals. The present invention further found that Chia can be used to improve endothelial function, coagulation, fibrinolysis and iron status. The present invention further encompasses the use of Chia in the treatment and/or management of diabetes and/or the treatment and management of diabetes associated conditions or risk factors, such as one or more of the following: blood pressure and blood glucose levels, post-prandial glycemia, inflammatory factors (C-reactive protein), coagulation... |
| Compositions and methods for enhancing factor viii heavy chain secretion | 20080300174 | 20081204 |
| FVIII heavy chain mutants are provided which exhibit enhanced secretion from transfected cells and robust anti-coagulation activity.
... |
| Von willebrand factor-and factor viii-polymer conjugates having a releasable linkage | 20080234193 | 20080925 |
| The present invention provides von Willebrand Factor-polymer conjugates and Factor VIII-polymer conjugates, each having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided.
... |
| Antagonists of factor viii interaction with low-density lipoprotein receptor related protein | 20080219983 | 20080911 |
| The present invention concerns the use of peptides derived from and antibodies generated against Factor VIII and the inhibition of Factor VIII interaction with LRP. Furthermore, the present invention concerns a method to inhibit LRP interaction with Factor VIII as well as a method to decrease Factor VIII degradation and/or prolong Factor VIII half-life in a biological fluid and/or a method to treat patients suffering from a blood coagulation disorder, especially Haemophilia A. The present invention also concerns a pharmaceutical composition useful for the decrease of Factor VIII degradation in a biological fluid, the inhibition of Factor VIII interaction with LRP, and/or the prolongation of Factor VIII half-life in a biological fluid for treatment of a blood coagulation disorder, especially Haemophilia A.
... |
| Fviii-independent fix-mutant proteins for hemophilia a treatment | 20080214461 | 20080904 |
| The present invention relates to recombinant blood coagulation factor IX (rFIX) mutants having factor VIII (FVIII) independent factor X (FX) activation potential. Five full length FIX proteins with combinations of mutations of amino acids important for functional activity of FIX and FIX wild type were cloned and expressed in HEK 293 cells. The proteins were tested by an activated partial thromboplastin time (aPTT) assay in FVIII-depleted plasma as well as in FVIII-inhibited patient plasma. In FVIII-depleted plasma functional activity of the FIX mutants was calculated as increased FVIII equivalent activity. The mutant proteins had increased FVIII equivalent activity. In FVIII-inhibited patient plasma the FEIBA equivalent activity was calculated for analysis of FVIII independent FX activation potential. The proteins had also increased FEIBA equivalent activity. Furthermore, the... |
| Novel anti-factor viii antibodies | 20080206254 | 20080828 |
| The present invention relates to new antibodies and fragments and derivatives thereof, which are particularly suited for the characterization of the structure and function of Factor VIII (FVIII) of the coagulation pathway, for the design of therapeutic strategies for eradication of FVIII inhibitors and for the use as a medicament The invention also relates to cell lines producing the specific antibodies. The present invention furthermore relates to pharmaceutical compositions comprising the antibodies, fragments and/or derivatives of the Invention and to methods of preventing and treating cardiovascular disorders by using the antibodies or fragments and derivatives thereof or pharmaceutical compositions thereof.
... |
| Novel albumin-free factor viii formulations | 20080176791 | 20080724 |
| 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... |
| Anti-idiotypic antibodies neutralizing the inhibitory activity of an inhibitory antibody directed against the c1 domain of factor viii | 20080160015 | 20080703 |
| The present invention is related to a monoclonal anti-idiotypic antibody directed against a Factor VIII inhibitor antibody binding to the C1 domain of Factor VIII, as well as to a cell line producing this monoclonal anti-idiotypic antibody, to the use of this monoclonal anti-idiotypic antibody as medicament, and more particularly to the use thereof for manufacturing a medicament intended for the treatment of haemophilia A.
... |
| Double specific antibodies substituting for functional proteins | 20080075712 | 20080327 |
| The present inventors succeeded in separating bispecific antibodies that functionally substitute for ligands of type I interferon receptors comprising two types of molecules: AR1 chain and AR2 chain. Furthermore, the present inventors succeeded in producing bispecific antibodies that substitute for the enzyme reaction-accelerating function of blood coagulation factor VIII/activated blood coagulation factor VIII, which bind to both blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X.
... |
| Adeno-associated virus (aav) serotype 8 sequences, vectors containing same, and uses therefor | 20080075737 | 20080327 |
| Sequences of a serotype 8 adeno-associated virus and vectors and host cells containing these sequences are provided. Also described are methods of using such host cells and vectors in production of rAAV particles. rAAV8-mediated delivery of therapeutic and immunogenic genes, including Factor VIII, is also provided.
... |
| Combined use of factor vii polypeptides and factor viii polypeptides | 20080076702 | 20080327 |
| The invention concerns a pharmaceutical preparation comprising a factor VII or factor VII-related polypeptide and a factor VIII or factor VIII-related polypeptide. The invention also concerns use of a factor VII or factor VII-related polypeptide and a factor VIII or factor VIII-related polypeptide for manufacture of a medicament for pharmaceutical use as well as methods for prevention or treatment of bleeding episodes in subjects.
... |
| Method of producing factor viii proteins by recombinant methods | 20080070251 | 20080320 |
| 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. Also provided are nucleic acid molecules which encode a Factor VIII protein operably linked to a Chinese hamster elongation factor 1-α (CHEF1) promoter, which may be used in the methods provided herein.
... |
| Factor viii: remodeling and glycoconjugation of factor viii | 20080070275 | 20080320 |
| The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.
... |
| Polymer-factor viii moiety conjugates | 20080058504 | 20080306 |
| 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. Also provided are compositions comprising the conjugates, methods of making the conjugates, and methods of administering compositions comprising the conjugates to a patient.
... |
| Agent for stimulating the production of a blood coagulation factor viii | 20080044430 | 20080221 |
| The inventive agent comprises polyclongal immunoglobulins of IgG class whose molecular mass is equal to 150 kD and which are obtainable in the form of a humoral immune response to an endothelial and mesenchymal stem cells complex.
... |
| Virally-safe factor viii with a low content of higher multimers | 20070275880 | 20071129 |
| La present invention pertains to a composition of plasma-derived virally-safe factor VIII, obtained after nanometric filtration, said composition comprising von Willebrand factor (vWF) at a rate of 15% or less of decamers and higher multimers. Such compositions have a reduction factor of the virus titre higher than 4 log and are thus suitable for treatment of hemophilia.
... |
| Stabilized proteins with engineered disulfide bonds | 20070276128 | 20071129 |
| The present invention relates to methods of introducing one or more cysteine residues into a polypeptide which permit the stabilization of the polypeptide by formation of at least one bond, preferably a disulfide bond, between different domains of the polypeptide. The invention also relates to polypeptides containing such introduced cysteine residue(s), nucleic acids encoding such polypeptides and pharmaceutical compositions comprising such polypeptides or nucleic acids. The invention also relates to vectors, viral particles and host cells containing such nucleic acids, and methods of using them to produce the polypeptides of the invention. Exemplified polypeptides include plasma proteins, including hepatocyte growth factor activator and plasma hyaluronin binding protein, as well as blood coagulation factors, such as Factor VIII, Factor V, Factor XII and prothrombin.
... |
| Recombinant factor viii having increased specific activity | 20070265199 | 20071115 |
| The present invention relates to recombinant factor VIII having a specific activity that is higher than that of the corresponding wild-type factor VIII. The present invention also relates to methods of making and using the recombinant factor VIII. The present invention also relates to an isolated nucleic acid molecule that encodes the recombinant factor VIII, as well as DNA expression systems and host cells containing the isolated nucleic acid molecule.
... |
| Pegylated factor viii | 20070244301 | 20071018 |
| The invention is a proteinaceous construct comprising a Factor VIII molecule having at least a portion of the B domain intact, which is conjugated to a water-soluble polymer such as polyethylene glycol having a molecular weight of greater than 10,000 Daltons. The construct has a biological activity of at least 80% of the biological activity of native Factor VIII, and the in vivo half-life of the construct is increased by at least 1.5 fold as compared to the in vivo half-life of native factor FVIII.
... |
| Factor viii compositions and methods | 20070232788 | 20071004 |
| The present invention provides methods of increasing the half-life and/or specific activity of factor VIII. More specifically, the invention provides methods of increasing the half-life and/or specific activity of factor VIII by substituting one or more amino acids in the A2 domain. It further provides methods for producing such factor VIII mutants. The invention also provides polynucleotides encoding the mutant factor VIII, and methods of treating hemophilia using the polypeptides and polynucleotides of the invention.
... |
| Factor viii compositions and methods | 20070232789 | 20071004 |
| The present invention provides methods of increasing the half-life and/or specific activity of factor VIII. More specifically, the invention provides methods of increasing the half-life and/or specific activity of factor VIII by substituting one or more amino acids in the A2 domain. It further provides methods for producing such factor VIII mutants. The invention also provides polynucleotides encoding the mutant factor VIII, and methods of treating hemophilia using the polypeptides and polynucleotides of the invention.
... |
| Factor viii separation | 20070215475 | 20070920 |
| The claims describe methods for isolating functionally active Factor VIII using a membrane-based separation system containing a separation membrane to create a first and second interstitial volume between at least two restriction membranes. One or more stabilizing agents are added to the sample and/or an interstitial volume. A solvent in the first interstitial volume maintains FVIII in a desired charge state. Applying a potential between the first and second interstitial volumes separates FVIII on one side of the separation membrane from unwanted molecules on the other side of the separation membrane. These methods may also be used as a substitute for one or more steps in a conventional purification scheme for the separation of native or recombinant FVIII.
... |
| Lentiviral vectors featuring liver specific transcriptional enhancer and methods of using same | 20070178592 | 20070802 |
| Recombinant lentiviruses and transfer vectors for transgene delivery as well as methods for gene therapy using such vectors are disclosed. The invention provides a third generation lentiviral packaging system and a set of vectors for producing recombinant lentiviruses, as well as novel tissue specific enhancer and promoter elements useful for optimizing liver specific transgene delivery. The transgene is preferably a blood clotting factor such as human factor IX (hFIX) or human factor VIII (hFVIII) and can be used for treatment of hemophilia.
... |
| Method of administering porcine b-domainless fviii | 20070173446 | 20070726 |
| 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. Therefore, the inventive method employs lower unit doses of OBI-1, including, alternatively, omission of antibody-neutralizing dosage, or has longer intervals between the administration, compared to HYATE:C, to provide equivalent protection in patients having fVIII deficiency. The invention further provides pharmaceutical compositions and kits containing OBI-1 in combination with... |
| Pharmaceutical composition comprising proteins and/or polypeptides and colloidal particles | 20070167359 | 20070719 |
| A pharmaceutical composition for parenteral administration comprising a therapeutically effective amount of a protein or polypeptide and colloidal particles. The particles comprise approximately 1-20 mole percent of an amphipathic lipid derivatized with a biocompatible hydrophilic polymer. The protein or polypeptide is selected from the group consisting of (a) proteins or polypeptides capable of externally binding said colloidal particles; (b) proteins or polypeptides capable of binding polymers of the polyalkylether, polylactic and polyglycolic acid families; and (c) proteins or polypeptides that include a consensus sequence of S/T-X/I/V-I/V/Q/S-S/T-X-X-X-E, where X may be any amino acid, and S,T,L,I,V,E and Q have their standard meanings. The protein or polypeptide is not Factor VIII (FVIII) and is not encapsulated in the colloidal particles.
... |
| Compositions and methods for less immunogenic protein-lipid complexes | 20070141135 | 20070621 |
| The present invention provides compositions and methods for reducing the immunogenicity and increasing the circulating half-life of therapeutic proteins such as Factor VIII. The compositions comprise lipidic structures such as liposomes, micelles and cochleates comprising a negatively charged lipid and polyethylene glycol derivatized phospatidyl ethanolamine.
... |
| Modified factor viii | 20070135342 | 20070614 |
| Modified porcine factor VIII is disclosed in which most of the B domain has been removed through genetic engineering. This modified factor VIII is particularly useful for treatment of hemophiliacs, especially those undergoing bleeding episodes.
... |
| Anti-idiotypic antibody neutralizing the inhibitor activity of a factor viii inhibitor antibody | 20070065425 | 20070322 |
| The present invention is related to a monoclonal anti-idiotypic antibody directed against a Factor VIII inhibitor antibody binding to the domain A2 of Factor VIII, and to a cell line producing this monoclonal anti-idiotypic antibody, to the use of this monoclonal anti-idiotypic antibody as drug, and more particularly, to its use for the manufacturing of a drug to be used for the treatment of haemophilia A.
... |
| Super-size adeno-associated viral vector harboring a recombinant genome larger than 5.7 kb | 20070042462 | 20070222 |
| Prior art teaches an effective packaging capacity for adeno-associated virus and adeno-associated viral vectors of 4.1 kb to 4.9 kb as well as a packaging limit of 5.2 kb to 5.6 kb. However, the inventor discovered that this packaging limit as well as that effective packaging capacity does not apply to all AAV serotypes: Whereas it is true that efficient packaging of AAV serotype 2 is limited to less than 5 kb, the inventor discovered that one can efficiently package more than 6 kb of genetic information into AAV capsids of other AAV serotypes, particularly into capsids of AAV serotype 5 and—to a lesser extent—into capsids of AAV serotype 7. This discovery will be useful in the context of gene therapy where large transgenes will have... |
| Bispecific antibody substituting for functional proteins | 20070041978 | 20070222 |
| The present inventors succeeded in constructing bispecific antibodies, which bind to both the blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X, and functionally substitute for blood coagulation factor VIII/activated blood coagulation factor VIII which enhances the enzymatic reaction.
... |
| Use of blood coagulation factor xiii for treating hemophilia a | 20070021340 | 20070125 |
| A patient having hemophilia A is treated by administering factor XIII generally in conjunction with factor VIII or desmopressin.
... |
| Production of human proteins in transgenic animal saliva | 20070011752 | 20070111 |
| The invention relates to the production of proteins, peptides and other substances of interest in the saliva of transgenic animals, particularly in mammals that produce large quantities of saliva, particularly monogastric ruminants, and ovine, caprine and bovine mammals. Preferred embodiments of the invention relate in particular to the production of foreign and modified proteins in the saliva of these transgenic animals, including particularly human serum albumin, human Protein C, human Factor IX, human factor VII, human Factor VIII and human von Willebrand factor, among others. Also provided are methods of expressing and producing proteins using such nucleic acid constructs. The invention relates as well to methods, devices, genetic constructs and to transgenic constructs for making the proteins and other substances of interest, to novel saliva and... |
| Variable antibodies | 20060292149 | 20061228 |
| The present invention discloses inhibitory antibodies against Factor VIII with modified glycosylation, either by enzymatic deglycosylation or by site directed mutagenesis. Said antibodies with modified glycosylation have equal affinity for FVIII but show different inhibiting properties. The use of one or a mixture of said antibodies allow modulation of the inhibition of factor VII to levels between 40 and 95%. The present invention further disclosed pharmaceutical compositions comprising inhibitory antibodies against Factor VIII with modified glycosylation, combinations of these antibodies and methods for treating haemostasis disorders using said antibodies and antibody mixtures.
... |
| Inactivation resistant factor viii | 20060293238 | 20061228 |
| The present invention provides novel purified and isolated nucleic acid sequences encoding procoagulant-active FVIII proteins. The nucleic acid sequences of the present invention encode amino acid sequences corresponding to known human FVIII sequences, wherein residue Phe309 is mutated. The nucleic acid sequences of the present invention also encode amino acid sequences corresponding to known human FVIII sequences, wherein the APC cleavage sites, Arg336 and Ile562, are mutated. The nucleic acid sequences of the present invention further encode amino acid sequences corresponding to known human FVIII sequences, wherein the B-domain is deleted, the von Willebrand factor binding site is deleted, a thrombin cleavage site is mutated, an amino acid sequence spacer is inserted between the A2- and A3-domains. Methods of producing the FVIII proteins of the invention,... |
| Crystal of a truncated protein construct containing a coagulation factor viii c2 domain in the presence or absence of a bound ligand and methods of use thereof | 20060293505 | 20061228 |
| A detailed three-dimensional structure for the C-terminal C2 domain of blood coagulation factor VIII is disclosed. The novel truncated factor VIII constructs which were designed so as to omit a significant portion of the flexible full length protein are also part of the present invention. In addition, the crystals of the protein, both in the presence and absence of bound ligands are also included. Furthermore, methods of identifying antagonists of the human factor VIII protein which can be used to inhibit coagulation or to stabilize and activate factor VIII mutants are also disclosed. Furthermore, methods of identifying variations of the C2 domain sequence and structure that can be incorporated into intact factor VIII for the purpose Of administration to hemophiliac patients who are immunoreactive against wild... |
| Vectors | 20060281180 | 20061214 |
| Provided is a lentiviral vector capable of delivering a nucleotide of interest (NOI) to a desired target site and wherein the NOI encodes the Factor VIII and the Factor VIII is expressed following delivery of the NOI to the desired target site.
... |
| Combined use of factor vii polypeptides and factor viii polypeptides | 20060276398 | 20061207 |
| The invention concerns a pharmaceutical preparation comprising a factor VII or factor VII-related polypeptide and a factor VIII or factor VIII-related polypeptide. The invention also concerns use of a factor VII or factor VII-related polypeptide and a factor VIII or factor VIII-related polypeptide for manufacture of a medicament for pharmaceutical use as well as methods for prevention or treatment of bleeding episodes in subjects.
... |
| Anti-idiotypic antibodies against factor viii inhibitor and uses thereof | 20060239998 | 20061026 |
| The present invention discloses anti-idiotypic antibodies and fragments thereof against inhibitory Factor VIII anti-bodies, said inhibitory antibodies having an affinity for the C2 domain of Factor VIII. The anti-idiotypic antibodies of the present invention are able to completely neutralise in vitro and in an in vivo mouse model the inhibitory activity of FVIII inhibitors. The anti idiotypic antibodies of the present invention can be applied for the prevention, treatment or reduction of bleeding disorders of hemophilia patients with inhibitory antibody against the C2 domain of Factor VIII.
... |
| Agent neutralizint tissue factor inhibitor and agent neutralizing activated blood coagulation factor viii preparation | 20060233786 | 20061019 |
| Formulations for neutralizing the anticoagulant action of a human tissue factor inhibitor, comprising a blood coagulation factor complex product or an activated blood coagulation factor VII product as an active ingredient; and formulations for neutralizing the blood coagulation-promoting action of an activated blood coagulation factor VII product, comprising a human tissue factor inhibitor as an active ingredient.
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| Novel albumin-free factor viii formulations | 20060205661 | 20060914 |
| 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... |
| Binding molecules for human factor viii and factor viii-like proteins | 20060193829 | 20060831 |
| 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. Especially preferred binding molecules according to the invention are short polypeptide sequences, characterized by a stable loop structure.
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| Polymer-von willebrand factor-conjugates | 20060160948 | 20060720 |
| The present invention relates to a proteinaceous construct (also designated as polymer-VWF-conjugate) comprising plasmatic and/or recombinant von Willebrand factor (VWF), said VWF being bound to at least one physiologically acceptable polymer molecule, as well as to a complex between said proteinaceous construct and at least one factor VIII (FVIII) protein. The physiologically acceptable polymer molecule can be, for instance, polyethylene glycol (PEG) or polysialic acid (PSA). Further the present invention relates to methods for prolonging the in vivo-half-life of VWF or FVIII in the blood of a mammal having a bleeding disorder associated with functional defects of or deficiencies of at least one of FVIII or VWF.
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| Factor viii polypeptide having factor viii:c activity | 20060160994 | 20060720 |
| Factor VIII polypeptides having FVIII:C activity that contain modifications in the A3 and/or C1 and/or C2 domains of the sequence of the light chain of Factor VIII, characterized by the binding affinity to low density lipoprotein receptor protein, and methods for producing the same.
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| Protein complexes having factor viii:c activity and production thereof | 20060122376 | 20060608 |
| Recombinant protein complexes having human Factor VIII:C activity are expressed in a eukaryotic host cell by transforming the host cell with first and second expression cassettes encoding a first polypeptide substantially homologous to human Factor VIII:C A domain and a second polypeptide substantially homologous to human Factor VIII:C C domain, respectively. In the present invention, the first polypeptide may be extended having at its C-terminal a human Factor VIII:C B domain N-terminal peptide, a polypeptide spacer of 3-40 amino acids, and a human Factor VIII:C B domain C-terminal peptide. Expression of the second polypeptide is improved by employing an .alpha.sub.1-antitrypsin signal sequence.
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| Ligands for use in therapeutic compositions for the treatment of hemostasis disorders | 20060115474 | 20060601 |
| The invention, in general, features a method of treatment and/or prevention of a thrombotic pathological condition, in a mammal, which includes administering to the mammal in need of such treatment a therapeutically effective amount of a composition including an antibody directed against the C1 domain of Factor VIII, which is a partially inhibitory antibody of Factor VIII.
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| Site-directed modification of fviii | 20060115876 | 20060601 |
| This invention relates to Factor VIII muteins that are covalently bound, at a predefined site that is not an N-terminal amine, to one or more biocompatible polymers such as polyethylene glycol. The mutein conjugates retain FVIII procoagulant activity and have improved pharmacokinetic properties.
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| Plant bioreactors | 20060107353 | 20060518 |
| A plant expressing a cytokine and an autoantigen is disclosed. An example of a cytokine is a contra-inflammatory cytokine, for example IL-4 and IL-10, and an example of autoantigen is GAD. A novel method for the production of transgenic proteins of interest suitable for oral administration is also disclosed. Further, non-food crop plants expressing one or more proteins of interest are disclosed, as is a method involving the preparation of a protein of interest suitable for oral administration within a non-food crop plant comprising, transforming the non-food crop plant with a suitable vector containing a gene of interest and appropriate regulatory regions to ensure expression of the gene of interest within the non-food crop plant, such that the non-food crop plant is characterized as being non-toxic,... |
| Recombinant expression of factor viii in human cells | 20060099685 | 20060511 |
| The invention discloses a process for recombinant production of blood coagulation Factor VIII in an immortalized human embryonic retina cell, said cell expressing at least an adenoviral E1A protein and comprising a nucleic acid sequence encoding said Factor VIII, said nucleic acid sequence being under control of a heterologous promoter, said process comprising culturing said cell and expressing the Factor VIII in said cell, and harvesting the expressed Factor VIII. Cells that can be used in the process of the invention are also provided.
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