Factor Viii Or Derivative Affecting Or Utilizing Patents (Class 514/14.1)
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Publication number: 20130085110Abstract: 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.Type: ApplicationFiled: November 30, 2012Publication date: April 4, 2013Applicant: UNIVERSITY OF ROCHESTERInventor: University of Rochester
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Publication number: 20130084277Abstract: The present invention provides pharmaceutical formulations for sustained release, and methods for delivering a treatment regimen with a combination of sustained release and long half-life formulations. The invention provides improved pharmacokinetics for peptide and small molecule drugs.Type: ApplicationFiled: August 24, 2012Publication date: April 4, 2013Applicant: PhaseBio Pharmaceuticals, Inc.Inventors: Susan Arnold, Christopher Prior
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Publication number: 20130072434Abstract: The present invention provides novel purified and isolated nucleic acid sequences encoding procoagulant-active FVIII proteins. The nucleic acid sequences may encode amino acid sequences corresponding to known human FVIII sequences, wherein residue Phe309 is mutated. The nucleic acid sequences also may 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.Type: ApplicationFiled: July 5, 2012Publication date: March 21, 2013Applicant: UNIVERSITY OF MICHIGANInventors: Randal J. Kaufman, Steven W. Pipe
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Publication number: 20130071383Abstract: A method of selectively introducing a substituent into a protein proximal to a binding site on the protein for a homing peptide, comprising: (a) contacting the protein with a compound comprising a homing peptide having the ability to bind to the binding site of the protein; and (b) allowing a moiety on the protein proximal to the binding site to react with the compound comprising the homing peptide, thereby to transfer the substituent G onto the protein.Type: ApplicationFiled: April 12, 2011Publication date: March 21, 2013Applicant: NOVO NORDISK A/SInventors: Mikael Kofod-Hansen, Henning Ralf Stennicke, Soeren Oestergaard, Henrik Oestergaard
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Publication number: 20130040889Abstract: 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.Type: ApplicationFiled: February 10, 2011Publication date: February 14, 2013Applicant: Novo Nordisk A/SInventors: Gert Bolt, Kristian Kjaergaard, Peder Lisby Noerby
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Publication number: 20130040888Abstract: 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.Type: ApplicationFiled: February 2, 2011Publication date: February 14, 2013Applicant: Novo Nordisk A/SInventors: Bernd Peschke, Mikael Kofod-Hansen, Jens Buchardt, Henning Ralf Stennicke, Henrik Oestergaard, Marianne Kjalke, Eva H. Norling Olsen, Jens Jacob Hansen
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Publication number: 20130035288Abstract: Aspects of the invention include methods for enhancing blood coagulation in a subject. In practicing methods according to certain embodiments, an amount of a non-anticoagulant sulfated polysaccharide (NASP) in combination with a gastrointestinal epithelial barrier permeation enhancer is orally administered to a subject in a manner sufficient to enhance blood coagulation in the subject. Compositions and kits for practicing methods of the invention are also described.Type: ApplicationFiled: July 18, 2012Publication date: February 7, 2013Inventors: Peter Turecek, Susanne Vejda
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Patent number: 8357779Abstract: 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.Type: GrantFiled: November 28, 2011Date of Patent: January 22, 2013Assignees: Baxter International Inc., Baxter Healthcare S.A.Inventors: Friedrich Scheiflinger, Peter Turecek, Juergen Siekmann
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Publication number: 20130017997Abstract: 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.Type: ApplicationFiled: February 2, 2012Publication date: January 17, 2013Applicant: Amunix Operating Inc.Inventors: Volker Schellenberger, Pei-Yun Chang, Fatbardha Varfaj, John Kulman, Tongyao Liu, Garabet G. Toby, Haiyan Jiang, Robert Peters, Deping Wang, Baisong Mei, Joshua Silverman, Chia-Wei Wang, Benjamin Spink, Nathan Geething
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Publication number: 20130012442Abstract: 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.Type: ApplicationFiled: September 14, 2012Publication date: January 10, 2013Applicants: NEKTAR THERAPEUTICS, Baxter Healthcare SA, Baxter International Inc.Inventors: Mary J. Bossard, Gayle Stephenson, Zhihao Fang, Harold Zappe, Stacy Mitchell, Ping Zhang, Friedrich Scheiflinger, Peter Turecek, Juergen Siekmann, Katalin Varadi, Herbert Gritsch
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Patent number: 8349800Abstract: 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.Type: GrantFiled: February 10, 2012Date of Patent: January 8, 2013Assignees: Nektar Therapeutics, Baxter International Inc., Baxter Healthcare S.A.Inventors: Mary J. Bossard, Gayle Stephenson, Zhihao Fang, Harold Zappe, Stacy Mitchell, Ping Zhang, Friedrich Scheiflinger, Peter Turecek, Juergen Siekmann, Katalin Varadi, Herbert Gritsch
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Publication number: 20130005657Abstract: The field of the invention is the treatment of acquired bleeding, a clinical condition associated with severe traumatic, peri- or post-operative bleeding. A novel treatment is proposed in which synergistic pro-coagulatory properties of Prothrombin Complex Concentrates (PCC) together with medicaments comprising FVIII and/or vWF are exploited.Type: ApplicationFiled: September 12, 2012Publication date: January 3, 2013Inventor: Gerhard DICKNEITE
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Publication number: 20130005656Abstract: 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.Type: ApplicationFiled: March 27, 2012Publication date: January 3, 2013Applicant: Emory UniversityInventor: John S. Lollar
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Publication number: 20130007926Abstract: Protein replacement therapy for patients with hemophilia or other inherited protein deficiencies is often complicated by pathogenic antibody responses, including antibodies that neutralize the therapeutic protein or that predispose to potentially life-threatening anaphylactic reactions by formation of IgE. Using murine hemophilia B as a model, we have developed a prophylactic protocol against such responses that is non-invasive and does not include immune suppression or genetic manipulation of the patient's cells. Oral delivery of coagulation factor IX (F. IX) expressed in chloroplasts, bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies in protein replacement therapy. Inhibitor titers were mostly undetectable and up to 100-fold lower in treated mice when compared to controls. Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after 4 to 6 exposures to intravenous F. IX protein. While only 20-25% of control animals survived after 6-8 F.Type: ApplicationFiled: November 9, 2010Publication date: January 3, 2013Inventors: Henry Daniell, Roland Herzog
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Publication number: 20120329709Abstract: The present invention provides methods and materials by which glycosylation of glycoproteins can be regulated. Methods include the monitoring and regulation of parameters such that a glycoprotein having a desired product quality is obtained.Type: ApplicationFiled: May 25, 2010Publication date: December 27, 2012Inventors: Brian Edward Collins, Tiffany Guo, Lakshmanan Thiruneelakantapillai, Kevin Millea, Dorota A. Bulik
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Patent number: 8338571Abstract: 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.Type: GrantFiled: July 25, 2008Date of Patent: December 25, 2012Assignee: University of RochesterInventors: Philip J. Fay, Hironao Wakabayashi
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Publication number: 20120322738Abstract: 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.Type: ApplicationFiled: February 7, 2011Publication date: December 20, 2012Applicant: Novo Nordisk A/SInventors: Carsten Behrens, Jens Buchardt, Magali Zundel
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Publication number: 20120316116Abstract: The present invention provides methods of treating coagulation disease, including hemophilia and von Willebrand disease by administering recombinant von Willebrand Factor alone or in combination with Factor VIII.Type: ApplicationFiled: June 11, 2012Publication date: December 13, 2012Applicants: Baxter Healthcare S.A., Baxter International Inc.Inventors: Friedrich Scheiflinger, Peter Turecek, Bruce Ewenstein, Wing Yen Wong, Tobias M. Suiter
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Publication number: 20120308641Abstract: Factor VIII variants and methods of use thereof are disclosed.Type: ApplicationFiled: April 2, 2012Publication date: December 6, 2012Inventors: Valder Arruda, Rodney M. Camire, Nicholas Iacobelli
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Publication number: 20120297494Abstract: 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 FVIII animal models.Type: ApplicationFiled: October 16, 2009Publication date: November 22, 2012Inventor: Tommy Eugene Howard
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Publication number: 20120289468Abstract: The present invention relates to methods, compositions and kits for preparing FVIII and employing same. Also provided are vWF polypeptides and nucleic acid molecules encoding same.Type: ApplicationFiled: November 12, 2010Publication date: November 15, 2012Applicant: GRIFOLS THERAPEUTICS INC.Inventor: Thomas Barnett
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Patent number: 8309086Abstract: 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.Type: GrantFiled: May 13, 2010Date of Patent: November 13, 2012Assignee: Life Sciences Research Partners VZWInventors: Marc G. Jacquemin, Jean-Marie R. Saint-Remy
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Publication number: 20120270788Abstract: 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.Type: ApplicationFiled: January 23, 2012Publication date: October 25, 2012Applicant: Emory UniversityInventors: John S. Lollar, Garrett E. Bergman
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Patent number: 8282923Abstract: 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.Type: GrantFiled: March 29, 2010Date of Patent: October 9, 2012Assignee: Life Sciences Research PartnersInventors: Jean-Marie Saint-Remy, Marc Jacquemin
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Patent number: 8277805Abstract: 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.Type: GrantFiled: March 26, 2010Date of Patent: October 2, 2012Assignee: Life Sciences Research PartnersInventors: Jean-Marie Saint-Remy, Marc Jacquemin
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Publication number: 20120230947Abstract: The present invention provides unstructured recombinant polymers (URPs) and proteins containing one or more of the URPs. The present invention also provides microproteins, toxins and other related proteinaceous entities, as well as genetic packages displaying these entities. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.Type: ApplicationFiled: April 4, 2012Publication date: September 13, 2012Applicant: AMUNIX OPERATING INC.Inventors: VOLKER SCHELLENBERGER, WILLEM P. STEMMER, CHIA-WEI WANG, MICHAEL D. SCHOLLE, MIKHAIL POPKOV, NATHANIEL C. GORDON, ANDREAS CRAMERI
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Publication number: 20120225819Abstract: 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.Type: ApplicationFiled: March 1, 2012Publication date: September 6, 2012Inventors: Jan Jezek, Barry Kingston Derham
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Patent number: 8252287Abstract: 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.Type: GrantFiled: March 2, 2009Date of Patent: August 28, 2012Assignees: Chugai Seiyaku Kabushiki Kaisha, Nara Medical UniversityInventors: Masahiro Takeyama, Keiji Nogami, Midori Shima, Tsukasa Suzuki
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Publication number: 20120190623Abstract: 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.Type: ApplicationFiled: January 27, 2011Publication date: July 26, 2012Applicant: UNIVERSITY OF MICHIGANInventors: Randal J. Kaufman, Steven W. Pipe
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Publication number: 20120189574Abstract: Methods of modulating mobilization of cells from the bone marrow are provided. In a specific embodiment there is provided a method of increasing mobilization of hematopoietic precursors from the bone marrow to the peripheral blood in a subject in need thereof, the method comprising: (a) administering to the subject an agent which downregulates an activity or expression of a coagulation factor or an effector thereof; and (b) harvesting the hematopoietic precursors from the peripheral blood.Type: ApplicationFiled: September 5, 2010Publication date: July 26, 2012Applicants: TEL HASHOMER MEDICAL RESEARCH INFRASTRUCTURE AND SERVICES LTD., YEDA RESEARCH AND DEVELOPMENT CO. LTD.Inventors: Anna Aronovich, Dalit Tchorsh-Yutsis, Gideon Rechavi, Yair Reisner
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Publication number: 20120178692Abstract: 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.Type: ApplicationFiled: March 27, 2012Publication date: July 12, 2012Applicant: NEKTAR THERAPEUTICSInventors: Mary J. Bossard, Michael D. Bentley, Ping Zhang
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Publication number: 20120178691Abstract: 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.Type: ApplicationFiled: March 16, 2012Publication date: July 12, 2012Applicant: Amunix Operating Inc.Inventors: Volker Schellenberger, Pei-Yun Chang, Fatbardha Varfaj, Joshua Silverman, Chia-Wei Wang, Benjamin Spink, Nathan Geething
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Patent number: 8207117Abstract: The invention concerns glycosylated proteins having human factor VIII activity. In a preferred embodiment, the protein is glycosylated with oligosaccharides that include an alpha-(2,6)-linked sialic acid and a bisecting GlcNAc linked to a core beta-mannose.Type: GrantFiled: November 8, 2010Date of Patent: June 26, 2012Assignee: Bayer Healthcare LLCInventors: Myung-Sam Cho, Sham-Yuen Chan
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Publication number: 20120148557Abstract: The present invention relates to pharmaceutical preparations comprising albumin-fused coagulation factors for the non-intravenous administration in the therapy and prophylactic treatment of bleeding disorders and to a method for increasing the in-vivo recovery after non-intravenous administration of a coagulation factor by fusing it to albumin.Type: ApplicationFiled: August 18, 2010Publication date: June 14, 2012Inventor: Ulrich Kronthaler
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Publication number: 20120148529Abstract: The present invention relates to the use of inclusion bodies as vehicles for therapeutic protein delivery. This method is applicable to the delivery of therapeutic proteins to intracellular locations. In addition, the invention also relates to the administration of a cell or a pharmaceutical composition comprising inclusion bodies formed by therapeutic proteins. These inclusion bodies formed by therapeutic proteins could be used for the treatment of different diseases.Type: ApplicationFiled: May 12, 2010Publication date: June 14, 2012Applicants: Centro de Invesigacion Biomedica en Red en Bioiagenieria, Biomateriales, y Nanomedicina (Cibe, Universitat Autonoma de Barcelona et al.Inventors: Elena Garcia-Fruitos, Esther Vazquez Gomez, Jose Luis Corchero, Antonio Pedro Villa Verde Corrales
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Publication number: 20120142594Abstract: 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.Type: ApplicationFiled: February 10, 2012Publication date: June 7, 2012Applicants: Baxter International Inc., NEKTAR THERAPEUTICSInventors: Mary J. Bossard, Gayle Stephenson, Zhihao Fang, Harold Zappe, Stacy Mitchell, Ping Zhang, Friedrich Scheiflinger, Peter Turecek, Juergen Siekmann, Katalin Varadi, Herbert Gritsch
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Publication number: 20120142593Abstract: 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.Type: ApplicationFiled: March 24, 2010Publication date: June 7, 2012Applicant: BAYER HEALTHCARE LLCInventors: Xiao-Yan Zhao, Peter John Kretschmer, Thomas Eugene Thompson, Douglas W. Schneider, John Edward Murphy
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Publication number: 20120134977Abstract: The present invention provides albumin-binding probes capable of reversibly linking to short-lived amino-containing drugs and non-covalently associating with albumin in-vivo, thereby converting said drugs into inactive reactivable prodrugs having prolonged lifetime in-vivo. The invention further provides conjugates of said probes with amino-containing drugs, as well as pharmaceutical compositions and uses thereof.Type: ApplicationFiled: June 1, 2010Publication date: May 31, 2012Applicant: YEDA RESEARCH AND DEVELOPMENT CO. LTD.Inventors: Yoram Shechter, Matityahu Fridkin
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Publication number: 20120129777Abstract: Methods for treating bleeding disorders using non-anticoagulant sulfated polysaccharides (NASPs) as procoagulants are disclosed. NASPs can be administered as single agents, or in combination with one another, or, with other medications (such as factors VII, VIII and IX) to promote hemostasis. In particular, the use of NASPs in treatment of bleeding disorders, including congenital coagulation disorders, acquired coagulation disorders, and trauma induced hemorrhagic conditions is described.Type: ApplicationFiled: May 19, 2011Publication date: May 24, 2012Inventor: Kirk W. Johnson
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Patent number: 8183344Abstract: 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.Type: GrantFiled: June 16, 2006Date of Patent: May 22, 2012Assignee: University of MichiganInventors: Randal J. Kaufman, Steven W. Pipe
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Patent number: 8183345Abstract: The present invention relates to a recombinant factor VIII that is characterized by one or more mutations within a region surrounding an activated protein C cleavage site, which one or more mutations result in a reduced rate of inactivation by activated protein C. Isolated nucleic acid molecules, recombinant expression vectors, and host cells suitable for expression of the recombinant factor VIII are also disclosed. The recombinant factor VIII can be used for the treatment of clotting disorders, such as hemophilia A.Type: GrantFiled: July 25, 2008Date of Patent: May 22, 2012Assignee: University of RochesterInventors: Philip J. Fay, Hironao Wakabayashi, Fatbardha Varfaj
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Publication number: 20120121613Abstract: The invention is directed to a procoagulant conjugate having an endopeptidase-activatable procoagulant protein moiety and one or more bioprotective moieties, which are conjugated to one another by a linker that is cleaved by an endopeptidase in situ to release the bioprotective moiety. The invention is also directed to therapeutic uses of the procoagulant conjugate and methods of making the conjugate.Type: ApplicationFiled: January 19, 2010Publication date: May 17, 2012Applicant: BAYER HEALTHCARE LLCInventors: Liang Tang, Jun Wang, Baisong Mei, John E. Murphy
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Patent number: 8173597Abstract: 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.Type: GrantFiled: November 7, 2008Date of Patent: May 8, 2012Assignees: Baxter International Inc., Baxter Healthcare S.A.Inventors: Hans-Peter Schwarz, Peter Turecek
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Publication number: 20120083446Abstract: 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 the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent.Type: ApplicationFiled: September 30, 2011Publication date: April 5, 2012Applicants: University of Connecticut, Baxter International Inc.Inventors: Marc Besman, Erik Bjornson, Feroz Jameel, Ramesh Kashi, Michael Pikal, Serguei Tchessalov, John Carpenter
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Publication number: 20120076779Abstract: The present invention provides, among other aspects, storage stabile aqueous formulations of labile proteins at a mildly acidic to neutral pH. The present invention also provides methods for stabilizing a labile therapeutic protein composition at a mildly acidic to neutral pH. Advantageously, the methods and formulations provided herein allow stabile aqueous compositions of labile proteins at mildly acidic to neutral pH useful for parenteral administration.Type: ApplicationFiled: September 16, 2011Publication date: March 29, 2012Applicants: Baxter Healthcare S.A., Baxter International Inc.Inventors: Harald Arno Butterweck, Theresa Friederike Bauer, Lucia Hofbauer, Wolfgang Teschner, Oliver Zoechling, Hans-Peter Schwarz, Christa Mayer, Meinhard Hasslacher
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Publication number: 20120065136Abstract: 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.Type: ApplicationFiled: September 13, 2011Publication date: March 15, 2012Applicant: UNIVERSITY OF ROCHESTERInventors: Philip J. FAY, Hironao WAKABAYASHI
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Publication number: 20120058180Abstract: This disclosure describes liver-specific nanocapsules for specifically targeting liver cells. This disclosure also provides methods of using such liver-specific nanocapsules to deliver one or more cargo moieties to the liver cells.Type: ApplicationFiled: August 30, 2011Publication date: March 8, 2012Inventors: Betsy T. Kren, Clifford J. Steer, Gretchen M. Unger
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Publication number: 20120052055Abstract: Invented is a method of treating thrombocytopenia in a human, in need thereof which comprises the in vivo administration of a therapeutically effective amount of a peptide or a non-peptide TPO receptor agonist and an anti-clotting agent or agents, and optional further active ingredients, to such human.Type: ApplicationFiled: May 6, 2010Publication date: March 1, 2012Applicant: Glaxosmithkline LLCInventors: Connie L. Erickson-Miller, Michael Arning
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Publication number: 20120035110Abstract: Among other aspects, the present invention relates to cell culture conditions for producing high molecular weight vWF, in particular, highly multimericWF with a high specific activity and ADAMTS13 with a high specific activity. The cell culture conditions of the present invention can include, for example, a cell culture medium with an increased copper concentration and/or cell culture supernatant with a low ammonium (NH4+) concentration. The present invention also provides methods for cultivating cells in the cell culture conditions to express high molecular weight vWF and rA13 having high specific activities.Type: ApplicationFiled: July 8, 2011Publication date: February 9, 2012Applicants: Baxter Healthcare S.A., Baxter International Inc.Inventors: LEOPOLD GRILLBERGER, MANFRED REITER, WOLFGANG MUNDT
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Patent number: 8110190Abstract: 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.Type: GrantFiled: August 23, 2007Date of Patent: February 7, 2012Inventors: Jean-Guy Gilles, Marc G. Jacquemin, Jean-Marie Saint-Remy, Christian Behrens