Abstract: Provided herein are methods of processing a fluid that include the use of one or both of a circuit system including a tangential flow filtration (TFF) unit and a circuit system including a tangential flow virus filtration (TFVF) unit. Also provided are integrated and continuous processes for manufacturing a therapeutic protein drug substance that include a step of processing a fluid including the recombinant therapeutic protein using any of the methods provided herein.
Type:
Grant
Filed:
February 19, 2021
Date of Patent:
January 30, 2024
Assignee:
Genzyme Corporation
Inventors:
Tarl Vetter, Michael Coolbaugh, Veena Warikoo, Konstantin Konstantinov
Abstract: The present disclosure provides a method that aims to maintain a favorable benefit-risk balance for patients with hemophilia A or B with or without inhibitors treated with fitusiran.
Type:
Application
Filed:
December 6, 2021
Publication date:
January 25, 2024
Applicant:
Genzyme Corporation
Inventors:
Stacey Poloskey, Shauna Andersson, Pratik R. Bhagunde, Yue Cui, Sajida Iqbal, Baisong Mei
Abstract: Engineered antibodies that are stable and can be conjugated to a ligand or drug at a ligand/drug to antibody ratio of above 3, making these conjugates suitable for treatment of a variety of indications, are provided. Methods of producing these engineered antibodies are also provided.
Type:
Grant
Filed:
February 26, 2021
Date of Patent:
January 23, 2024
Assignee:
GENZYME CORPORATION
Inventors:
Qun Zhou, Sunghae Park, Huawei Qiu, Marie-Priscille Brun, Francis Duffieux
Abstract: Tropomyosin-related kinase inhibitors (Trk inhibitors) are small molecule compounds useful in the treatment of disease. Trk inhibitors can be used as pharmaceutical agents and in pharmaceutical compositions. Trk inhibitors are useful in the treatment of inflammatory diseases, autoimmune disease, defects of bone metabolism and/or cancer, and are particularly useful in the treatment of osteoarthritis (OA), pain, and pain associated with OA. Trk inhibitors are also useful for inhibiting tropomyosin-related kinase A (TrkA), tropomyosin-related kinase B (TrkB), tropomyosin-related kinase C (TrkC), and/or c-FMS (the cellular receptor for colony stimulating factor-1 (CSF-1)).
Type:
Grant
Filed:
August 8, 2022
Date of Patent:
January 23, 2024
Assignee:
GENZYME CORPORATION
Inventors:
John L. Kane, Jr., Gloria Matthews, Markus Metz, Michael Kothe, Jinyu Liu, Andrew Scholte
Abstract: The present provides methods for treating spinal muscular atrophy using a self-complementary recombinant adeno-associated virus (rAAV) viral particle comprising a transgene expressing SMN. In one aspect, the viral particles are administered in the spinal column or cisterna magna in a human subject; for example, a pediatric human subject. Viral particles comprising AAV9 capsids are contemplated.
Type:
Application
Filed:
April 21, 2023
Publication date:
January 4, 2024
Applicant:
Genzyme Corporation
Inventors:
Marco A. Passini, Lamya S. Shihabuddin, Catherine R. O'Riordan, Seng H. Cheng
Abstract: The present disclosure relates to pharmaceutical compositions, including dosage forms, such as tablets or capsules, comprising venglustat, in free base, or pharmaceutically acceptable salt form, a diluent/filler and a lubricant, optionally in combination with one or more additional therapeutic agents, to processes for manufacture thereof, and to methods of use in the treatment or prevention of disease.
Type:
Grant
Filed:
July 23, 2021
Date of Patent:
January 2, 2024
Assignee:
GENZYME CORPORATION
Inventors:
Audrey Jeanjean, Danielle Combessis, David Rigal, Chris Ho, Pankaj Taneja
Abstract: The present disclosure provides anti-complement factor Bb antibodies, and compositions comprising the antibodies. The anti-Bb antibodies are useful for treating complement-mediated disorders. The present disclosure provides methods of treating complement-mediated disorders.
Type:
Grant
Filed:
January 19, 2021
Date of Patent:
December 26, 2023
Assignee:
Genzyme Corporation
Inventors:
Sandip Panicker, Graham Parry, Karen Sue Christopherson, Tony SangYoung Byun
Abstract: Provided herein are methods for the purification of recombinant adeno-associated virus (rAAV) vectors that can be used for gene transfer and specifically for gene therapy or vaccination. Recombinant AAV vectors of the invention are substantially free of in-process impurities, including production components such as cellular nucleic acids, cellular proteins, helper virus, and media components.
Type:
Grant
Filed:
September 28, 2020
Date of Patent:
December 12, 2023
Assignee:
Genzyme Corporation
Inventors:
Paulene McLean Quigley Sheldon, Peter S. Gagnon, Gina Nichols, Barbara A. Thorne
Abstract: Provided herein are methods of reducing bioburden of (e.g., sterilizing) a chromatography resin that include exposing a container including a composition including a chromatography resin and at least one antioxidant agent and/or chelator to a dose of gamma-irradiation sufficient to reduce the bioburden of the container and the chromatography resin, where the at least one antioxidant agent and/or chelator are present in an amount sufficient to ameliorate the loss of binding capacity of the chromatography resin after/upon exposure to the dose of gamma-irradiation. Also provided are reduced bioburden chromatography columns including the reduced bioburden chromatography resin, compositions including a chromatography resin and at least one chelator and/or antioxidant agent, methods of performing reduced bioburden column chromatography using one of these reduced bioburden chromatography columns, and integrated, closed, and continuous processes for reduced bioburden manufacturing of a purified recombinant protein.
Abstract: A modified IgG antibody binds and neutralizes TGF?1 selectively and with high affinity and avidity. The modified IgG antibody comprises four polypeptide chains and may comprise modifications to the elbow regions of the polypeptide chains. The modified IgG antibody may comprise the same VH and VL domains or CDR regions as metelimumab. The modified IgG anti-body is useful in therapeutic and diagnostic applications.
Abstract: The present invention provides methods for improved label-free absolute quantification of relatively low abundant polypeptides by liquid chromatography/mass spectrometry analysis of peptide products obtained from simple or complex polypeptide mixtures. The methods for absolute quantification include MS signals from a set of qualified ions of peptide products of a relatively high abundant polypeptide to improve quantification of a relatively low abundant polypeptide.
Abstract: Disclosed here are compositions comprising recombinant acid sphingomyelinase (rASM) having desired purity, specific activity, and/or rASM isoforms. Also provided are methods for making and purifying such compositions, comprising chromatography steps. Further provided are methods of modulating rASM specific activity in a composition, and methods of modulating rASM isoforms in a composition. The methods disclosed here can be particularly useful for manufacturing pharmaceutical compositions comprising rASM for treating acid sphingomyelinase deficiency (ASMD).
Type:
Application
Filed:
March 20, 2023
Publication date:
November 16, 2023
Applicant:
Genzyme Corporation
Inventors:
Thomas M. Wasylenko, Kevin Brower, Xiaoying Jin
Abstract: The invention relates to iRNA, e.g., double-stranded ribonucleic acid (dsRNA), compositions targeting the Serpinc1 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of Serpinc1 and methods of treating subjects having a bleeding disorder, such as a hemophilia.
Type:
Application
Filed:
January 17, 2023
Publication date:
November 16, 2023
Applicant:
Genzyme Corporation
Inventors:
Akin Akinc, Alfica Sehgal, Ivanka Toudjarska, Donald Foster, Stuart Milstein, Brian Bettencourt, Martin A. Maier, Klaus Charisse, Satyanarayana Kuchimanchi, Kallanthottathil G. Rajeev, Muthiah Manoharan
Abstract: The invention provides a crystalline imidazo[4,5-b]pyridine compound, pharmaceutical compositions, methods of inhibiting tropomyosin-related kinase and/or c-FMS, and methods of treating medical diseases and conditions, such as pain.
Abstract: Provided are binding polypeptides (e.g., antibodies), and effector moiety conjugates thereof, comprising a CH1 domain (e.g., a human IgG1 CH1 domain), wherein the CH1 domain has an engineered N-linked glycosylation site at amino acid position 114, according to Kabat numbering. Also provided are nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.
Type:
Grant
Filed:
October 17, 2019
Date of Patent:
November 7, 2023
Assignee:
GENZYME CORPORATION
Inventors:
Clark Pan, Huawei Qiu, Pradeep Dhal, Bo Chen, Diego Gianolio
Abstract: The present disclosure relates to antisense oligonucleotides (AONs) for modulating the expression of glycogen synthase. AONs of the present disclosure may be useful in treating diseases associated with the modulation of the expression of the enzyme glycogen synthase, such as Pompe disease. Also provided by the present disclosure are compositions comprising AONs, as well as methods of down regulating mRNA coding for glycogen synthase, methods for reducing glycogen synthase in skeletal and cardiac muscle, and methods for treating Pompe disease.
Type:
Grant
Filed:
May 5, 2020
Date of Patent:
October 31, 2023
Assignee:
GENZYME CORPORATION
Inventors:
Carol A. Nelson, Bruce M. Wentworth, Ronald K. Scheule, Timothy E. Weeden, Nicholas P. Clayton
Abstract: Pharmaceutical formulations with a tropomyosin-related kinase inhibitor (“Trk inhibitor”) are disclosed. The pharmaceutical formulations comprise 3-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-amine in microcrystalline suspension formulations in its monohydrate form, which shows improved characteristics over the anhydrate form, and in extended release formulations. The extended release pharmaceutical formulations comprise 3-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-amine-loaded microspheres.
Type:
Grant
Filed:
August 20, 2021
Date of Patent:
October 24, 2023
Assignee:
Genzyme Corporation
Inventors:
Harvey Lieberman, Donglai Yang, C. Michael Philbrook, Michael Santos, Chris Ho
Abstract: Methods for quantifying the amount of drug present in a crosslinked hyaluronic acid-linker-peptide (xHA-L-P) prodrug composition are provided. Disclosed are steps of contacting a sample of the xHA-L-P prodrug formulation with a hyaluronoglucosidase to generate oligomeric hyaluronic acid-linker-peptide drug (oHA-L-P), contacting the oHA-L-P with a second enzyme to generate peptide digest products of the drug, and detecting the peptide digest products to determine the amount of the drug present in the xHA-L-P prodrug formulation.
Abstract: Provided herein are RNAi molecules including a first strand containing a guide sequence and a second strand comprising a non-guide sequence where the non-guide sequence contains a bulge opposite the seed region of the guide sequences; e.g., opposite the cleavage sequence. In some aspects, the invention provides RNAi for treating Huntington's disease. Further provided herein are expression cassettes, vectors (e.g., rAAV, recombinant adenoviral, recombinant lentiviral, and recombinant HSV vectors), cells, viral particles, and pharmaceutical compositions containing the RNAi. Yet further provided herein are methods and kits related to the use of the RNAi, for example, to treat Huntington's disease.
Type:
Grant
Filed:
July 28, 2020
Date of Patent:
October 10, 2023
Assignee:
Genzyme Corporation
Inventors:
Lisa M. Stanek, Adam Palermo, Brenda Richards, Sergio Pablo Sardi, Catherine O′Riordan, Antonius Song