Abstract: Disclosed herein are novel compounds, pharmaceutical compositions comprising such compounds and related methods of their use. The compounds described herein are useful, e.g., as liposomal delivery vehicles to facilitate the delivery of encapsulated polynucleotides to target cells and subsequent transfection of said target cells, and in certain embodiments are characterized as having one or more properties that afford such compounds advantages relative to other similarly classified lipids.
Type:
Grant
Filed:
March 29, 2013
Date of Patent:
January 17, 2017
Assignee:
Shire Human Genetic Therapies, Inc.
Inventors:
Frank DeRosa, Braydon Charles Guild, Michael Heartlein
Abstract: The present invention provides, among other things, methods of treating phenylketonuria (PKU), including administering to a subject in need of treatment a composition comprising an mRNA encoding phenylalanine hydroxylase (PAH) at an effective dose and an administration interval such that at least one symptom or feature of PKU is reduced in intensity, severity, or frequency or has delayed in onset. In some embodiments, the mRNA is encapsulated in a liposome comprising one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.
Type:
Grant
Filed:
October 22, 2014
Date of Patent:
December 20, 2016
Assignee:
Shire Human Genetic Therapies, Inc.
Inventors:
Frank DeRosa, Michael Heartlein, Anusha Dias
Abstract: The invention provides methods of treating ?-galactosidase A deficiency. Dosage forms, methods of administration, and methods of analyzing human ?-galactosidase A are also included.
Type:
Grant
Filed:
January 14, 2016
Date of Patent:
December 20, 2016
Assignee:
SHIRE HUMAN GENETIC THERAPIES, INC.
Inventors:
Douglas A. Treco, Kenneth Loveday, Marianne Borowski
Abstract: The present invention provides, among other things, improved methods for purifying I2S protein produced recombinantly for enzyme replacement therapy. The present invention is, in part, based on the surprising discovery that recombinant I2S protein can be purified from unprocessed biological materials, such as, I2S-containing cell culture medium, using a process involving as few as four chromatography columns.
Abstract: Described herein are isolated nucleic acid molecules comprising nucleotide sequence encoding mannose receptor, C type 1 (MRC1) wherein the 5? region of the nucleotide sequence encoding MRC1 is codon optimized; cells comprising such nucleic acid molecules; and methods of detecting antibody production, e.g., neutralizing antibody production, in a subject being treated for Gaucher disease using such cells.
Type:
Grant
Filed:
July 19, 2011
Date of Patent:
September 27, 2016
Assignee:
SHIRE HUMAN GENETIC THERAPIES, INC.
Inventors:
Juan Ruiz, Marcia Sellos-Moura, Michael F. Concino, Pan Luying, Paolo Martini, Bettina Strack-Logue, Scott Alderucci
Abstract: Disclosed herein are methods and kits which are useful for detecting presence of an enzyme in a test sample based upon the intrinsic enzymatic activity of such test sample. The present invention provides the ability to evaluate cell culture conditions and optimize the desired glycoform content of recombinantly prepared enzymes.
Abstract: The invention provides methods of treating ?-galactosidase A deficiency. Dosage forms, methods of administration, and methods of analyzing human ?-galactosidase A are also included.
Type:
Application
Filed:
January 14, 2016
Publication date:
June 30, 2016
Applicant:
SHIRE HUMAN GENETIC THERAPIES, INC.
Inventors:
Douglas A. TRECO, Kenneth LOVEDAY, Marianne BOROWSKI
Abstract: Disclosed are compositions and methods for producing therapeutic fusion proteins in vivo. The compositions and methods disclosed herein are capable of ameliorating diseases by providing therapeutic protein delivery.
Abstract: The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising a heparan N-sulfatase (HNS) protein, salt, and a polysorbate surfactant for the treatment of Sanfilippo Syndrome Type A.
Type:
Grant
Filed:
June 25, 2011
Date of Patent:
April 26, 2016
Assignee:
Shire Human Genetic Therapies, Inc.
Inventors:
Farah Natoli, Gaozhong Zhu, Jennifer Terew, Yuan Jiang, Jamie Tsung, Zahra Shahrokh, Brian Vernaglia, Jing Pan, Richard Pfeifer, Pericles Calias
Abstract: Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.
Type:
Grant
Filed:
June 18, 2014
Date of Patent:
April 12, 2016
Assignee:
Shire Human Genetic Therapies, Inc.
Inventors:
Braydon Charles Guild, Frank DeRosa, Michael Heartlein
Abstract: The present invention provides, among other things, methods and compositions for treating muscular dystrophy, in particular, Duchenne muscular dystrophy (DMD). In some embodiments, a method according to the present invention includes administering to an individual who is suffering from or susceptible to DMD an effective amount of a recombinant follistatin protein such that at least one symptom or feature of DMD is reduced in intensity, severity, or frequency, or has delayed onset.
Abstract: The present invention provides, among other things, methods for the characterization of recombinant Heparan N-Sulfatase (HNS) during manufacture. The present invention uses capillary zone electrophoresis to determine the charge profile, isoform distribution, and/or glycan profile of recombinant HNS; and represents a quality feature for the batch consistency, storage stability, biological half-life, pharmacokinetic, pharmacodynamic and biological activity of the enzyme. In particular, such characterization methods may be beneficial to optimize conditions and ensure consistency for the manufacture of HNS for the treatment of a patient diagnosed with Sanfilippo syndrome using enzyme replacement therapy.
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:
June 25, 2011
Date of Patent:
March 15, 2016
Assignee:
Shire Human Genetic Therapies, Inc.
Inventors:
Pericles Calias, Jing Pan, Jan Powell, Lawrence Charnas, Thomas McCauley, Teresa Leah Wright, Richard Pfeifer, Zahra Shahrokh
Abstract: The invention provides methods of treating ?-galactosidase A deficiency. Dosage forms, methods of administration, and methods of analyzing human ?-galactosidase A are also included.
Type:
Grant
Filed:
April 15, 2010
Date of Patent:
February 23, 2016
Assignee:
SHIRE HUMAN GENETIC THERAPIES, INC.
Inventors:
Douglas A. Treco, Kenneth Loveday, Marianne Borowski
Abstract: The present invention provides, among other things, compositions and methods for treatment of Friedrich's Ataxia based on effective targeting of a therapeutic moiety to mitochondria that can substitute for natural FXN protein activity or rescue one or more phenotypes or symptoms associated with frataxin-deficiency. In some embodiments, the present invention provides a targeted therapeutic comprising a therapeutic moiety, which is a polypeptide having an N-terminus and a C-terminus, a mitochondrial targeting sequence associated with the therapeutic moiety at the N-terminus, and a mitochondrial membrane-penetrating peptide associated with the therapeutic moiety at the C-terminus, wherein the therapeutic moiety is targeted to mitochondria upon cellular entry.
Type:
Grant
Filed:
June 15, 2012
Date of Patent:
February 16, 2016
Assignee:
Shire Human Genetic Therapies, Inc.
Inventors:
Dennis Keefe, Michael Concino, Michael Heartlein, Serene Josiah, Bettina Strack-Logue
Abstract: The present invention provides, among other things, methods of quantitating mRNA capping efficiency, particularly mRNA synthesized in vitro. In some embodiments, methods according to the present invention comprise providing an mRNA sample containing capped and uncapped mRNA, providing a cap specific binding substance under conditions that permit the formation of a complex between the cap specific binding substance and the capped mRNA, and quantitatively determining the amount of the complex as compared to a control, thereby quantifying mRNA capping efficiency.
Type:
Application
Filed:
March 14, 2014
Publication date:
January 7, 2016
Applicant:
Shire Human Genetic Therapies, Inc.
Inventors:
Michael Heartlein, Frank DeRosa, Anusha Dias
Abstract: The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an iduronate-2-sulfatase (I2S) protein, salt, and a polysorbate surfactant for the treatment of Hunters Syndrome.
Type:
Grant
Filed:
August 23, 2013
Date of Patent:
December 29, 2015
Assignee:
Shire Human Genetic Therapies, Inc.
Inventors:
Gaozhong Zhu, Kris Lowe, Zahra Shahrokh, James Christian, Rick Fahrner, Jing Pan, Teresa Leah Wright, Pericles Calias
Abstract: Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.
Type:
Application
Filed:
December 6, 2013
Publication date:
December 24, 2015
Applicant:
Shire Human Genetics Therapies, Inc.
Inventors:
Braydon Charles Guild, Frank DeRosa, Michael Heartlein
Abstract: The present invention provides, among other things, methods and compositions for treating muscular dystrophy, in particular, Duchenne muscular dystrophy (DMD). In some embodiments, a method according to the present invention includes administering to an individual who is suffering from or susceptible to DMD an effective amount of an anti-Flt-1 antibody, or antigen binding fragment thereof, such that at least one symptom or feature of DMD is reduced in intensity, severity, or frequency, or has delayed onset.
Type:
Application
Filed:
January 28, 2014
Publication date:
December 17, 2015
Applicants:
Shire Human Genetic Therapies, Inc., Regents of the University of Minnesota
Inventors:
Serene Josiah, Thomas M. Luby, Atsushi Asakura, Dennis Keefe, Lawrence Charnas
Abstract: Disclosed herein are novel peptide linkers and polypeptide compositions comprising the linkers (e.g., chimeric polypeptides) and methods of using the polypeptide compositions. The compositions and methods are particularly useful for targeting/delivering a polypeptide or protein of interest (e.g., a therapeutic polypeptide) to a cell, tissue or organ of interest in order to treat various diseases or disorders (e.g., lysosomal storage disorders).