Stabilized Enzymes Or Enzymes Complexed With Nonenzyme (e.g., Liposomes, Etc.) Patents (Class 424/94.3)
  • Patent number: 11505525
    Abstract: Disclosed are general and “substantially pure” branched discrete polyethylene glycol constructs useful in attaching to a variety of biologically active groups, for example, preferential locators, as well as biologics like enzymes, for use in diagnostics, e.g. imaging, therapeutics, theranostics, and moieties specific for other applications. In its simplest intermediate state, a branched discrete polyethylene glycol construct is terminated at one end by a chemically reactive moiety, “A”, a group that is reactive with a biologic material that creates “A”, which is a biologically reactive group, connected through to a branched core (BC) which has attached at least two dPEG-containing chains, indicated by the solid line, , having terminal groups, which can be charged, non-reactive or reactable moieties and containing between about 2 and 64 dPEG residues.
    Type: Grant
    Filed: June 23, 2017
    Date of Patent: November 22, 2022
    Assignees: Quanta BioDesign, Ltd., University of Washington
    Inventors: Paul D. Davis, D. Scott Wilbur
  • Patent number: 11504389
    Abstract: The present disclosure is in the field of diagnostics and therapeutics for Alzheimer's Disease.
    Type: Grant
    Filed: December 1, 2017
    Date of Patent: November 22, 2022
    Assignees: Sangamo Therapeutics, Inc., The General Hospital Corporation
    Inventors: Annemarie Ledeboer, Bryan Zeitler, H. Steve Zhang, Sarah DeVos, Bradley T. Hyman, Susanne Wegmann
  • Patent number: 11505560
    Abstract: Disclosed are heterobifunctional compounds that effectuate selective degradation of a target protein, and which include a targeting ligand that binds a target protein and at least one other protein, a ligand that binds an E3 ubiquitin ligase or a component of E3 ubiquitin ligase, and a specificity modulating linker that links the first ligand and the second ligand. Pharmaceutical compositions containing the compounds, and methods of using and making the compounds are also disclosed.
    Type: Grant
    Filed: October 19, 2018
    Date of Patent: November 22, 2022
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Radoslaw P. Nowak, Eric S. Fischer, Nathanael S. Gray, Tinghu Zhang, Zhixiang He, Brian Groendyke
  • Patent number: 11491199
    Abstract: Biocomposites comprising sulfated carboxymethyl cellulose and Azadirachta indica leaf extracts are provided. The sulfated carboxymethyl cellulose is made using an improved, environmentally friendly technique. Methods of using the biocomposites as anticoagulants are also provided.
    Type: Grant
    Filed: June 9, 2021
    Date of Patent: November 8, 2022
    Assignee: KING ABDULAZIZ UNIVERSITY
    Inventors: Khalid A. Alamry, Ajahar Khan, Mahmoud A. Hussein, Abdullah M. Asiri
  • Patent number: 11484499
    Abstract: The present invention provides a pharmaceutical composition for subcutaneous administration comprising a blood factor and a colloidal particle comprising about 0.5 to 20 mole percent of an amphipathic lipid derivatized with a biocompatible hydrophilic polymer, wherein the blood factor is not encapsulated in said colloidal particle.
    Type: Grant
    Filed: August 1, 2018
    Date of Patent: November 1, 2022
    Assignee: Cantab Biopharmaceuticals Patents Limited
    Inventor: William Henry
  • Patent number: 11471516
    Abstract: The present invention provides an effective and less invasive approach for direct delivery of therapeutic agents to the central nervous system (CNS). In some embodiments, the present invention provides methods including a step of administering intrathecally to a subject suffering from or susceptible to a lysosomal storage disease associated with reduced level or activity of a lysosomal enzyme, a composition comprising a replacement enzyme for the lysosomal enzyme.
    Type: Grant
    Filed: September 17, 2019
    Date of Patent: October 18, 2022
    Assignee: Shire Human Genetic Therapies, Inc.
    Inventors: Pericles Calias, Jing Pan, Jan Powell, Lawrence Charnas, Thomas McCauley, Teresa Leah Wright, Richard Pfeifer, Zahra Shahrokh
  • Patent number: 11434484
    Abstract: The invention described herein provides compositions and reagents for assembling a tripartite complex at a specific location of a target DNA. The invention also provides methods for using the complex to, for example, label a specific genomic locus, to regulate the expression of a target gene, or to create a gene regulatory network.
    Type: Grant
    Filed: September 13, 2017
    Date of Patent: September 6, 2022
    Assignee: The Jackson Laboratory
    Inventors: Haoyi Wang, Albert Cheng, Nathaniel Jillette
  • Patent number: 11358992
    Abstract: The present invention relates to a novel cell-penetrating recombinant fusion protein including a peptide domain consisting of the amino acid sequence of SEQ ID NO: 1 and a peptide domain consisting of the amino acid sequence of SEQ ID NO: 2. The novel cell-penetrating cereblon recombinant fusion protein according to the present invention may be usefully employed in the prevention or treatment of cereblon-related diseases.
    Type: Grant
    Filed: April 30, 2021
    Date of Patent: June 14, 2022
    Assignee: UPPTHERA
    Inventors: SooHee Ryu, Hwa Jin Lee, Seong Hoon Kim, Hyeong Seok Lee
  • Patent number: 11338019
    Abstract: The present application relates to dual anti-angiogenic and anti-inflammatory effects of recombinant thrombomodulin domain 1 (TMD1). Specifically, an isolated recombinant polypeptide comprising an amino acid sequence that is at least 80% identical to TMD1 for use in treating an eye disease and/or an eye disorder associated with pathological ocular angiogenesis (POA) in a subject in need thereof is disclosed. The length of the recombinant polypeptide is no more than 200 amino acid residues. The eye disease and/or the eye disorder may be at least one selected from the group consisting of retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. Use of TMD1 in the manufacture of a medicament for treating an eye disease and/or an eye disorder associated with vascular endothelial growth factor (VEGF)-induced ocular angiogenesis and/or hypoxia-inducible factor-1? (HIF-1?)-VEGF pathway is also disclosed.
    Type: Grant
    Filed: May 24, 2020
    Date of Patent: May 24, 2022
    Inventors: Yi-Hsun Huang, Hua-Lin Wu
  • Patent number: 11331640
    Abstract: A microcapsule includes a core/shell structure, in which the shell includes a water-soluble polymer and the core includes an organic peroxide. The water-soluble polymer is preferably at least one water-soluble polymer selected from the group consisting of polyvinyl alcohol, gelatin, poly(meth)acrylic acid derivatives, polyvinyl pyrrolidone, and polyethylene oxide. The polyvinyl alcohol is preferably partially saponified polyvinyl alcohol having a degree of saponification of 80% by mole or more and 99.5% by mole or less and an average degree of polymerization of 1,500 or more and 3,500 or less.
    Type: Grant
    Filed: February 4, 2020
    Date of Patent: May 17, 2022
    Assignee: Shin-Etsu Chemical Co., Ltd.
    Inventors: Hiroaki Saito, Toshihiko Kawakubo
  • Patent number: 11319533
    Abstract: The present invention relates to a CRISPR nanocomplex for nonviral genome editing, a method for preparing the same, and the like. The CRISPR nanocomplex for nonviral genome editing of the present invention has a size of several nanometers to several microns, enables intracellular delivery without external physical stimulation, and can be utilized for genome editing through nonviral routes with respect to target genes of cells. As a result, when used for preparation of animal model, microbiological engineering, cell engineering for disease treatment, or formulations for biological administration, the CRISPR Nanocomplex shows high intracellular delivery and gene editing efficiency, and can minimize problems, such as nonspecific editing, gene mutation, and induction of cytotoxicity and biotoxicity.
    Type: Grant
    Filed: November 27, 2017
    Date of Patent: May 3, 2022
    Assignee: KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY
    Inventors: Hyun Jung Chung, Yoo Kyung Kang
  • Patent number: 11208452
    Abstract: The present invention relates to novel insulins or insulins analogues that are extended with predominantly sequences of polar amino acid residues in order to improve the half-life and stability of the drug substance. The invention also provides pharmaceutical compositions comprising such drug substances, and relates to the use of such drug substances for the treatment or prevention of medical conditions relating to diabetes.
    Type: Grant
    Filed: June 2, 2016
    Date of Patent: December 28, 2021
    Assignee: Novo Nordisk A/S
    Inventors: Thomas Boerglum Kjeldsen, Thomas Hoeg-Jensen, Tine Nygaard Vinther, Frantisek Hubalek, Ingrid Pettersson
  • Patent number: 11091534
    Abstract: The present invention provides a chimeric protein comprising a VWF protein comprising the D? domain and D3 domain of VWF, one or more XTEN sequence, and a FVIII protein, wherein the VWF fragment, the XTEN sequence, or the FVIII protein are linked to or associated with each other. The chimeric protein can further comprise one or more Ig constant region or a portion thereof (e.g., an Fc region). A polypeptide chain comprising a VWF fragment of the invention binds to or is associated with a polypeptide chain comprising a FVIII protein linked to an XTEN sequence and the polypeptide chain comprising the VWF fragment can prevent or inhibit binding of endogenous VWF to the FVIII protein linked to the XTEN sequence. By preventing or inhibiting binding of endogenous VWF to the FVIII protein, which is a half-life limiting factor for FVIII, the VWF fragment can induce extension of half-life of the chimeric protein comprising a FVIII protein.
    Type: Grant
    Filed: October 8, 2018
    Date of Patent: August 17, 2021
    Assignee: Bioverativ Therapeutics Inc.
    Inventors: Ekta Seth Chhabra, Tongyao Liu, Pei-yun Chang, Robert T. Peters, John Kulman, Haiyan Jiang
  • Patent number: 11065231
    Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hppel-Lindau, cereblon, ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
    Type: Grant
    Filed: November 16, 2018
    Date of Patent: July 20, 2021
    Assignee: ARVINAS OPERATIONS, INC.
    Inventors: Andrew P. Crew, Erika Araujo
  • Patent number: 11052135
    Abstract: The present invention provides, among other things, compositions and methods for CNS delivery of Idursulfase-beta, a human recombinant iduronate-2-sulfatase protein, for effective treatment of Hunter Syndrome. The compositions and methods provided by the present invention effectively reduce symptoms not only in brain and spinal cord but also in peripheral tissues including heart, liver, spleen, lung, and kidney.
    Type: Grant
    Filed: December 21, 2016
    Date of Patent: July 6, 2021
    Assignees: GREEN CROSS CORPORATION, MEDIGENEBIO CORPORATION
    Inventors: Torayuki Okuyama, Thong-Gyu Jin, Han-Yeul Byun, Jin-Wook Seo, Byoung-Ju Lee, Yong-Chul Kim, In-Young Jang, Kyuhyun Lee
  • Patent number: 11046946
    Abstract: Disclosed is a conjugate of a protein having substantial L-asparagine amino hydrolase activity and polyethylene glycol. In particular, the polyethylene glycol has a molecular weight of about 5000 Da and the protein is an L-asparaginase from Erwinia. The conjugate of the invention has shown superior properties such as maintenance of a high level of in vitro activity and an unexpected increase in half-life in vivo. Also disclosed are methods of producing the conjugate and use of the conjugate in therapy. In particular, a method is disclosed for use of the conjugate in the treatment of cancer, particularly Acute Lymphoblastic Leukemia (ALL). More specifically, a method is disclosed for use of the conjugate as a second line therapy for patients who have developed hypersensitivity or have had a disease relapse after treatment with other L-asparaginase preparations.
    Type: Grant
    Filed: May 18, 2020
    Date of Patent: June 29, 2021
    Assignee: JAZZ PHARMACEUTICALS II SAS
    Inventor: Thierry Abribat
  • Patent number: 11020461
    Abstract: Provided are methods of treating metachromatic leukodystrophy comprising administering to a subject in need of treatment a therapeutically effective amount of recombinant arylsulfatase A enzyme.
    Type: Grant
    Filed: February 17, 2017
    Date of Patent: June 1, 2021
    Assignee: Takeda Pharmaceutical Company Limited
    Inventors: Margaret Wasilewski, Anna Wijatyk
  • Patent number: 10961522
    Abstract: Recombinant human alpha glucosidase (rhGAA) composition derived from CHO cells that contains a more optimized glycan composition consisting of a higher amount of rhGAA containing N-glycans carrying mannose-6-phosphate (M6P) or bis-M6P than conventional rhGAAs, along with low amount of non-phosphorylated high mannose glycans, and low amount of terminal galactose on complex oligosaccharides. Compositions containing the rhGAA, and methods of use are described.
    Type: Grant
    Filed: January 18, 2019
    Date of Patent: March 30, 2021
    Assignee: Amicus Therapeutics, Inc.
    Inventors: Russell Gotschall, Hung V. Do
  • Patent number: 10940185
    Abstract: [Problem] To provide a pharmaceutical composition containing a fusion protein comprising an antibody and a lysosomal enzyme as an active ingredient, which is stable enough to permit its distribution to the market. [Solution] A lyophilized formulation containing; a fusion protein comprising an antibody and a lysosomal enzyme as an active ingredient, and further containing a neutral salt, a disaccharide, a nonionic surfactant, and a buffer. Such a lyophilized formulation includes, for example, as an active ingredient, a fusion protein comprising an anti-transferrin receptor antibody and human iduronate-2-sulfatase, and further containing sodium chloride as the neutral salt, sucrose as the disaccharide, poloxamer as the nonionic surfactant, and phosphate buffer as the buffer.
    Type: Grant
    Filed: December 28, 2017
    Date of Patent: March 9, 2021
    Assignee: JCR Pharmaceuticals Co., Ltd.
    Inventors: Hidehito Yasukawa, Yuka Yamaguchi, Shinji Okabe
  • Patent number: 10898476
    Abstract: Provided herewith are bioactive agents that increase the intracellular concentration and/or activity of one or more heat shock proteins, including Hsp70, for use in the treatment of a disease associated with dysregulation of cholesterol homeostasis.
    Type: Grant
    Filed: April 10, 2017
    Date of Patent: January 26, 2021
    Assignee: Orphazyme A/S
    Inventors: Thomas Kirkegaard Jensen, Elina Ikonen, Burcin Gungor
  • Patent number: 10889819
    Abstract: The present invention relates to a visceral adipose tissue macrophage-targeted non-viral gene/carrier complex for preventing and treating obesity-induced type II diabetes. More specifically, the gene/carrier complex according to the present invention delivers a therapeutic gene in a stable manner in a case of being injected into the body with the visceral adipose tissue macrophages being targeted, and thus exhibits an excellent inhibitory effect against TACE, which allows the gene/carrier complex to be applied for prevention or treatment of obesity-induced type II diabetes.
    Type: Grant
    Filed: March 29, 2019
    Date of Patent: January 12, 2021
    Inventors: Yong-Hee Kim, Yoon Sung Song, Seok-Beom Yong
  • Patent number: 10842878
    Abstract: The present application provides bifunctional compounds of Formula (I): or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for Bruton's tyrosine kinase (BTK). The present application also relates to methods for the targeted degradation of BTK through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to BTK which can be utilized in the treatment of disorders modulated by BTK.
    Type: Grant
    Filed: November 22, 2017
    Date of Patent: November 24, 2020
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, Dennis Dobrovolsky, Hai-Tsang Huang
  • Patent number: 10836804
    Abstract: This disclosure concerns compositions and methods for increasing the expression of a polynucleotide of interest. Some embodiments concern novel transactivation polypeptides and variants thereof that have been identified in plants, and methods of using the same. Particular embodiments concern the use of at least one DNA-binding polypeptide in a fusion protein to target at least one transactivation polypeptide or variant thereof to a specific binding site on a nucleic acid comprising the polynucleotide of interest, such that its expression may be increased.
    Type: Grant
    Filed: May 2, 2019
    Date of Patent: November 17, 2020
    Assignee: Dow Agrosciences LLC
    Inventors: Joseph Petolino, Jianquan Li, Steven L. Evans, Ryan C. Blue
  • Patent number: 10822617
    Abstract: Disclosed are compositions comprising: a sequence encoding a fusion protein, the sequence comprising a sequence encoding a first RNA-binding polypeptide and a sequence encoding a second RNA-binding polypeptide, wherein neither the first RNA-binding polypeptide nor the second RNA-binding polypeptide comprises a significant DNA-nuclease activity, wherein the first RNA-binding polypeptide and the second RNA-binding polypeptide are not identical, and wherein the second RNA-binding polypeptide comprises an RNA-nuclease activity. Methods of making and methods of using compositions of the disclosure are also provided. For example, compositions of the disclosure may be used in the treatment of a disease or disorder in a subject. Exemplary disease or disorders of the disclosure include genetic and epigenetic diseases or disorders.
    Type: Grant
    Filed: December 20, 2019
    Date of Patent: November 3, 2020
    Assignee: Locana, Inc.
    Inventors: David A. Nelles, Ranjan Batra, Eugene Yeo
  • Patent number: 10660944
    Abstract: The present invention provides, among oilier things, compositions and methods for CNS delivery of lysosomal enzymes (e.g., recombinant human arylsulfatase A (rhASA)) for effective treatment of lysosomal storage diseases (e.g. Metachromatic Leukodystrophy Disease), In some embodiments, the present invention includes a stable formulation for intrathecal administration comprising an ASA protein and a poloxamer, wherein less than 3% of the ASA protein exists in aggregated form.
    Type: Grant
    Filed: June 5, 2018
    Date of Patent: May 26, 2020
    Assignee: Shire Human Genetic Therapies, Inc.
    Inventors: Nazila Salamat-Miller, Katherine Taylor, Paul Campolieto, Zahra Shahrokh, Jing Pan, Lawrence Charnas, Teresa Leah Wright, Pericles Calias, Keethkumar Jain, Sujit Basu
  • Patent number: 10639273
    Abstract: In accordance with one aspect of the invention, injectable particles are provided which comprise (a) a first group of injectable particles comprising first polymeric particles loaded with a first therapeutic agent and (b) a second group of injectable particles comprising second polymeric particles loaded with a second therapeutic agent. The first and second polymeric particles may be the same or different, and the first and second therapeutic agents may be the same or different. Other aspects of the invention pertain to methods of making such particles, to kits that comprise such particles, and to methods of treatment that employ such injectable particles.
    Type: Grant
    Filed: December 22, 2008
    Date of Patent: May 5, 2020
    Assignee: Boston Scientific Scimed, Inc.
    Inventors: Sonali Puri, Robert E. Richard, John E. O'gara
  • Patent number: 10633687
    Abstract: This invention provides a substrate solution for measuring lipase activity, a reagent for measuring lipase activity, and an emulsion solution excellent in storage stability. This invention also provides a method for measuring lipase activity in a sample that enables accurate measurement over a long period of time. This invention further provides a method for improving storage stability of a substrate solution for measuring lipase activity and an emulsion solution. To this end, a substrate solution for measuring lipase activity comprising the emulsion solution comprising micelle particles of 1,2-o-dilauryl-rac-glycero-3-glutaric acid (6?-methylresorufin) ester and side-chain-type nonreactive polyether-modified-type modified silicone oil is used.
    Type: Grant
    Filed: June 17, 2016
    Date of Patent: April 28, 2020
    Assignee: Shino-Test Corporation
    Inventors: Naomi Iizuka, Atsushi Hikichi
  • Patent number: 10632209
    Abstract: Provided herein are small molecules that bind to ASH1L and inhibit ASH1L activity, and methods of use thereof for the treatment of disease, including acute leukemia, solid cancers and other diseases dependent on activity of ASH1L.
    Type: Grant
    Filed: November 9, 2018
    Date of Patent: April 28, 2020
    Assignee: The Regents of the University of Michigan
    Inventors: Jolanta Grembecka, Szymon Klossowski, Jing Deng, Tomasz Cierpicki, Hao Li, Hongzhi Miao, Trupta Purohit, EunGi Kim
  • Patent number: 10612011
    Abstract: Engineered transcriptional activator-like effectors (TALEs) are versatile tools for genome manipulation with applications in research and clinical contexts. One current drawback of TALEs is that the 5? nucleotide of the target is specific for thymine (T). TALE domains with alternative 5? nucleotide specificities could expand the scope of DNA target sequences that can be bound by TALEs. This disclosure provides methods and strategies for the continuous evolution of proteins comprising DNA-binding domains, e.g., TALE domains. In some aspects, this disclosure provides methods and strategies for evolving such proteins under positive selection for a desired DNA-binding activity and/or under negative selection against one or more undesired (e.g., off-target) DNA-binding activities. Some aspects of this disclosure provide engineered TALE domains and TALEs comprising such engineered domains, e.g.
    Type: Grant
    Filed: July 28, 2016
    Date of Patent: April 7, 2020
    Assignee: President and Fellows of Harvard College
    Inventors: David R. Liu, Basil Hubbard, Ahmed Hussein Badran
  • Patent number: 10604726
    Abstract: A cleaning composition is provided including an alkalinity source, builder, surfactant, water, a reducing agent and amylase in the ratio of from about 1:1 to about 1:3 wherein the total amount of amylase in the composition is equal to or less than about 1.0 weight percent; and wherein the composition is substantially free of polyols, alkanolamine, phosphates, and boric acid. A method of presoaking soiled substrates is further provided. The method including the steps of providing presoak solution to a soiled substrate at a temperature of between about 65.5° C. up to about 80° C., the presoak solution including the provided composition; draining the presoak solution from the substrate; providing a detergent to a soiled substrate including the composition of the present invention; and removing or draining the detergent; and rinsing the substrate with water.
    Type: Grant
    Filed: December 13, 2017
    Date of Patent: March 31, 2020
    Assignee: Ecolab USA Inc.
    Inventors: Michael S. Rischmiller, Kim R. Solomon, Sara Peters, Steven E. Lentsch
  • Patent number: 10518233
    Abstract: A liquid enzyme formulation, an enzyme granule formulation, methods for manufacturing enzyme granules using a fluid bed dryer, wherein the enzyme granules are thermostable without the need for a thermostable coating is provided. The enzyme granules are phytase granules used in the manufacturing of an animal feed, wherein the phytase granule is thermostable without the need for a thermostable coating and the phytase retains about 63% to about 134% of its activity after pelleting at 80° C.
    Type: Grant
    Filed: March 10, 2014
    Date of Patent: December 31, 2019
    Assignee: BASF Enzymes LLC
    Inventors: Yun Han, Michael Pratt, Yi Wu
  • Patent number: 10512676
    Abstract: Provided are pharmaceutical formulations comprising a recombinant acid ?-glucosidase, wherein the recombinant acid ?-glucosidase is expressed in Chinese hamster ovary (CHO) cells and comprises an increased content of N-glycan units bearing one or two mannose-6-phosphate residues when compared to a content of N-glycan units bearing one or two mannose-6-phosphate residues of alglucosidase alfa; at least one buffer selected from the group consisting of a citrate, a phosphate and combinations thereof; and at least one excipient selected from the group consisting of mannitol, polysorbate 80, and combinations thereof, wherein the formulation has a pH of from about 5.0 to about 7.0. Also provided are methods of treating Pompe disease using these pharmaceutical formulations.
    Type: Grant
    Filed: March 30, 2017
    Date of Patent: December 24, 2019
    Assignee: Amicus Therapeutics, Inc.
    Inventors: Hing Char, Sergey Tesler, Wendy Sunderland, Enrique Diloné, Russell Gotschall, Hung Do
  • Patent number: 10442812
    Abstract: Disclosed are new small molecules having a 4-methylpyrrrolo[1,2-a]pyrimidine-8-carboxamide core structure and the uses thereof for modulating glucocerebrosidase activity. Also disclosed are pharmaceutical compositions comprising the small molecules which may be administered in methods of treating diseases or disorders associated with glucocerebrosidase activity, including neurological diseases and disorders such as Gaucher's disease and Parkinson's disease. The small molecules may contain a fluorophore or may be conjugated to a fluorophore in order to prepare a fluorescent probe for use in high throughput screening methods to identify new modulators of glucocerebrosidase activity via fluorescence polarization.
    Type: Grant
    Filed: January 18, 2019
    Date of Patent: October 15, 2019
    Assignee: Northwestern University
    Inventors: Dimitri Krainc, Richard B. Silverman, Jianbin Zheng
  • Patent number: 10398782
    Abstract: The invention relates to MIC-1 compounds. More specifically it relates to compounds comprising a MIC-1 polypeptide with an N-terminal amino acid extension and a protractor wherein the amino acid extension comprises 3 to 36 amino acid residues and where the MIC-1 polypeptide and the N-terminal amino acid extension together have a calculated pI lower than 6.5. The compounds of the invention have MIC-1 activity. The invention also relates to pharmaceutical compositions comprising such compounds and pharmaceutically acceptable excipients, as well as the medical use of the compounds.
    Type: Grant
    Filed: May 23, 2018
    Date of Patent: September 3, 2019
    Assignee: Novo Nordisk A/S
    Inventors: Xiang Gao, Xujia Zhang, Hongtao Guan, Henning Thoegersen, Kristian Sass-Oerum, Lars Fogh Iversen, Per Noergaard, Sebastian Beck Joergensen, Kristian Tage Hansen, Yi Wang, Kilian Waldemar Conde Frieboes, Birgit Wieczorek
  • Patent number: 10231952
    Abstract: Described herein are methods of decreasing the proliferation of prostate cancer cells in a mammalian subject by administering to a subject in need thereof a composition comprising an AVPR antagonist in amount effective to decrease proliferation of the cancer cells. Also provided are methods of inducing prostate cancer cell death (or decreasing invasion migration of the prostate cancer cells) in a mammalian subject by administering to a subject in need thereof a composition comprising an AVPR antagonist.
    Type: Grant
    Filed: July 28, 2015
    Date of Patent: March 19, 2019
    Assignee: UNIVERSITY OF MIAMI
    Inventor: Kerry L. Burnstein
  • Patent number: 10227352
    Abstract: Disclosed are new small molecules having a 4-methylpyrrrolo[1,2-a]pyrimidine-8-carboxamide core structure and the uses thereof for modulating glucocerebrosidase activity. Also disclosed are pharmaceutical compositions comprising the small molecules which may be administered in methods of treating diseases or disorders associated with glucocerebrosidase activity, including neurological diseases and disorders such as Gaucher's disease and Parkinson's disease. The small molecules may contain a fluorophore or may be conjugated to a fluorophore in order to prepare a fluorescent probe for use in high throughput screening methods to identify new modulators of glucocerebrosidase activity via fluorescence polarization.
    Type: Grant
    Filed: June 28, 2018
    Date of Patent: March 12, 2019
    Assignee: Northwestern University
    Inventors: Dimitri Krainc, Richard B. Silverman, Jianbin Zheng
  • Patent number: 10221408
    Abstract: Provided herein are phenylalanine ammonia-lyase (PAL) variants produced by prokaryotes, wherein such prokaryotic PAL variant has a greater phenylalanine-converting activity and/or a reduced immunogenicity as compared to a wild-type PAL. Further provided are compositions of prokaryotic PAL and biologically active fragments, mutants, variants or analogs thereof, as well as methods for the production, purification, formulation, and use of such compositions for industrial and therapeutic purposes, e.g., treating hyperphenylalaninemia, including phenylketonuria, and other disorders, including cancer.
    Type: Grant
    Filed: April 15, 2016
    Date of Patent: March 5, 2019
    Assignee: BIOMARIN PHARMACEUTICAL INC.
    Inventors: Augustus O. Okhamafe, Sean M. Bell, G. Nick Zecherle, Kris Antonsen, Yanhong Zhang, Kieu Ly Tran, Paul A. Fitzpatrick, Emil D. Kakkis, Michel Claude Vellard, Daniel J. Wendt, Mubarack Muthalif
  • Patent number: 10113163
    Abstract: The disclosure provides adenosine deaminases that are capable of deaminating adenosine in DNA. The disclosure also provides fusion proteins comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA. In some embodiments, the fusion proteins further comprise a nuclear localization sequence (NLS), and/or an inhibitor of base repair, such as, a nuclease dead inosine specific nuclease (dISN).
    Type: Grant
    Filed: October 23, 2017
    Date of Patent: October 30, 2018
    Assignee: President and Fellows of Harvard College
    Inventors: David R. Liu, Nicole Gaudelli
  • Patent number: 10072060
    Abstract: Isolated non-naturally occurring, mutant-human islet amyloid polypeptides (hIAPP) are disclosed. These polypeptides can be formulated or co-formulated at physiological pH, which enable the polypeptides of the instant disclosure to be delivered to a subject having an amyloid-based disease in a single injection with an insulin agent. Methods and compositions for treating amyloid-based disease in a subject in need thereof, by administering an effective amount of an isolated, mutant-hIAPP polypeptide, including formulations or co-formulations thereof are also disclosed.
    Type: Grant
    Filed: May 1, 2015
    Date of Patent: September 11, 2018
    Assignee: The Research Foundation for The State University of New York
    Inventors: Daniel Raleigh, Hui Wang, Ping Cao, Andisheh Abedini
  • Patent number: 10046036
    Abstract: The invention provides reagents and methods for enzyme replacement therapy using chemically modified species of human cystathionine ?-synthase (CBS) to treat homocystinuria and other related diseases and disorders.
    Type: Grant
    Filed: August 12, 2016
    Date of Patent: August 14, 2018
    Assignee: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE
    Inventors: Jan P Kraus, Tomas Majtan, Erez Bublil
  • Patent number: 9957315
    Abstract: Described herein are methods for purifying recombinant, cell culture derived alpha1-protease inhibitor and removing a colored species that co-purifies with the recA1PI protein. Also described are methods for reducing the iron in cell culture derived alpha1-protease inhibitor.
    Type: Grant
    Filed: April 26, 2016
    Date of Patent: May 1, 2018
    Assignee: GRIFOLS, S.A.
    Inventors: David Ownby, Thomas P. Zimmerman, Jennifer A. Hunt, Charles Miller, Senthil Ranganathan, Tonny Dessources
  • Patent number: 9944912
    Abstract: Engineered CRISPR-Cas9 nucleases with altered and improved PAM specificities and their use in genomic engineering, epigenomic engineering, and genome targeting.
    Type: Grant
    Filed: March 3, 2016
    Date of Patent: April 17, 2018
    Assignee: The General Hospital Corporation
    Inventors: J. Keith Joung, Benjamin Kleinstiver
  • Patent number: 9932566
    Abstract: This invention discloses reagents and methods for increasing specificity and efficiency of RNA-guided genome editing.
    Type: Grant
    Filed: August 6, 2015
    Date of Patent: April 3, 2018
    Assignee: AGILENT TECHNOLOGIES, INC.
    Inventors: Andrew Kennedy, Daniel E. Ryan
  • Patent number: 9926545
    Abstract: Engineered CRISPR-Cas9 nucleases with altered and improved PAM specificities and their use in genomic engineering, epigenomic engineering, and genome targeting.
    Type: Grant
    Filed: July 12, 2016
    Date of Patent: March 27, 2018
    Assignee: The General Hospital Corporation
    Inventors: J. Keith Joung, Benjamin Kleinstiver
  • Patent number: 9868943
    Abstract: Virion-associated peptidoglycan hydrolases have a potential as antimicrobial agents due to their ability to lyse Gram positive bacteria on contact. Fusion proteins HydH5SH3b and HydH5Lyso comprising full-length peptidoglycan hydrolase HydH5 from the Staphylococcus aureus bacteriophage vB_SauS-phi-IPLA88 in combination with the SH3b cell wall-binding domain from lysostaphin or full length lysostaphin, respectively, exhibited high lytic activity against live S. aureus cells. CHAPSH3b, a HydH5 CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) domain from truncated HydH5 in combination with the SH3b domain of lysostaphin, exhibited the highest lytic activity against live S. aureus cells. HydH5 and its derivative fusions lysed bovine and human S. aureus, methicillin-resistant S. aureus (MRSA) N315 strain, and human S. epidermidis strains in zymogram, plate lysis and turbidity reduction assays.
    Type: Grant
    Filed: February 12, 2015
    Date of Patent: January 16, 2018
    Assignee: The United States of America, as represented by The Secretary of Agriculture
    Inventors: David M. Donovan, Lorena Rodriguez Rubio, Beatriz Martinez Fernandez, Ana Rodriguez, Pilar Garcia Suarez
  • Patent number: 9789167
    Abstract: The invention relates to the field of microbiology, specifically to a combination of a source of a first enzymatic active domain and a source of a second enzymatic active domain and to a composition comprising said combination. The invention further relates to a composition comprising said combination for use as a medicament, to the use of said composition as an antimicrobial agent and to a method for controlling microbial contamination in a food- or feed product, on and/or in food- or feed processing equipment, on and/or in food- or feed containers.
    Type: Grant
    Filed: May 7, 2013
    Date of Patent: October 17, 2017
    Assignee: MICREOS HUMAN HEALTH B.V.
    Inventors: Martin Johannes Loessner, Fritz Eichenseher
  • Patent number: 9731024
    Abstract: The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.
    Type: Grant
    Filed: July 17, 2014
    Date of Patent: August 15, 2017
    Assignees: Baxalta Incorporated, Baxalta GmbH
    Inventors: Juergen Siekmann, Stefan Haider, Hanspeter Rottensteiner, Peter Turecek
  • Patent number: 9708595
    Abstract: Multimeric protein structures comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety are disclosed herein, as well a process for preparing same, and methods of treating Fabry disease via administration of a multimeric protein structure. The disclosed multimeric protein structures exhibit an improved performance, in terms of enhanced activity and/or a longer lasting activity under both lysosomal conditions and in a serum environment.
    Type: Grant
    Filed: November 10, 2015
    Date of Patent: July 18, 2017
    Assignee: Protalix Ltd.
    Inventors: Avidor Shulman, Ilya Ruderfer, Tehila Ben Moshe, Talia Shekhter, Yaniv Azulay, Yoseph Shaaltiel, Tali Kizhner
  • Patent number: 9682129
    Abstract: The present invention provides a method of treating cognitive impairment of Hunter syndrome. Among other things, the present invention provides a method comprising a step of administering intrathecally to a subject in need of treatment a recombinant iduronate-2-sulfatase (I2S) enzyme at a therapeutically effective dose and an administration interval for a treatment period sufficient to improve, stabilize or reduce declining of one or more cognitive, adaptive, motor, and/or executive functions relative to a control.
    Type: Grant
    Filed: December 21, 2012
    Date of Patent: June 20, 2017
    Assignee: Shire Human Genetic Therapies, Inc.
    Inventors: Ann Barbier, Thomas McCauley, Charles W. Richard, III
  • Patent number: 9675678
    Abstract: Provided herein are improved compositions and methods for enzyme replacement therapy using modified human cystathionine beta synthase (CBS) in the treatment of homocystinuria and related diseases and disorders.
    Type: Grant
    Filed: November 9, 2015
    Date of Patent: June 13, 2017
    Assignee: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE
    Inventors: Jan P Kraus, Tomas Majtan, Erez Bublil