Abstract: Provided herein are integrated continuous biomanufacturing processes for producing a therapeutic protein drug substance. Also provided are systems that are capable of continuously producing a therapeutic protein drug substance.
Type:
Application
Filed:
June 22, 2020
Publication date:
October 8, 2020
Applicant:
Genzyme Corporation
Inventors:
Konstantin Konstantinov, Rahul Godawat, Veena Warikoo, Sujit Jain
Abstract: Methods of making ligand-decorated polymer conjugates of therapeutic glycoproteins are described. Improved targeting of glycoproteins to specific tissues is achieved by masking the natural carbohydrate and other surface determinants with high molecular weight polymers, such as, e.g., PEG, polysialic acid, etc., which in turn are decorated with target-specific ligands. In some embodiments, acid-labile linkages in such conjugates or rapidly degradable masking groups allow for the intracellular release of the polymer from the glycoprotein, for example, under conditions found in lysosomes.
Abstract: The present invention relates to treatment of relapsing and progressive forms of multiple sclerosis using a humanized anti-human CD52 IgG1 monoclonal antibody.
Abstract: The present invention relates to antibody molecules, in particular antibody molecules that bind Transforming Growth Factor beta (TGF?), and uses thereof. More particularly, the invention relates to antibody molecules that bind and preferably neutralise TGF?1, TGF?2 and TGF?3, so-called “pan-specific” antibody molecules, and uses of such antibody molecules. Preferred embodiments within the present invention are antibody molecules, whether whole antibody (e.g. IgG, such as IgG1 or IgG4) or antibody fragments (e.g. scFv, Fab, dAb).
Type:
Grant
Filed:
November 21, 2018
Date of Patent:
September 22, 2020
Assignees:
Genzyme Corporation, Optein, Inc.
Inventors:
Steven R. Ledbetter, Celia Patricia Hart, Robert G. Holgate, Lutz U. Jermutus, Catriona L. Buchanan, Alexander R. Duncan, Donna K. Finch
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:
September 10, 2019
Date of Patent:
September 1, 2020
Assignee:
Genzyme Corporation
Inventors:
Lisa M. Stanek, Adam Palermo, Brenda Richards, Sergio Pablo Sardi, Catherine O'Riordan, Antonius Song
Abstract: The invention relates to quinazoline derivatives of formula (I), wherein m is an integer from 1 to 3; R1 represents halogeno or C1-3alkyl; X1 represents —O—; R2 is selected from one of the following three groups: 1) C1-5alkylR3 (wherein R3 is piperidin-4-yl which may bear one or two substituents selected from hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy; 2) C2-5alkenylR3 (wherein R3 is as defined hereinbefore); 3) C2-5alkynylR3 (wherein R3 is as defined hereinbefore); and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.
Type:
Application
Filed:
September 25, 2019
Publication date:
August 20, 2020
Applicant:
Genzyme Corporation
Inventors:
Andrew Peter Thomas, Elaine Sophie Elizabeth Stokes, Laurent Francois Andre Hennequin
Abstract: This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention provides a method to deliver a transgene to a subject's spinal cord by administering a recombinant neurotropic viral vector containing the transgene. The viral vector delivers the transgene to a region of the deep cerebellar nuclei region of the brain. Also provided are compositions and methods to deliver a transgene to a subject's spinal cord by administering a recombinant neurotropic viral vector containing the transgene to the motor cortex region of the subject's brain.
Type:
Grant
Filed:
November 2, 2007
Date of Patent:
August 18, 2020
Assignee:
GENZYME CORPORATION
Inventors:
James Dodge, Lamya Shihabuddin, Marco Passini, Seng H. Cheng, Catherine O'Riordan
Abstract: The invention relates, in part, to antibodies with increased ADCC activity. Methods of producing such antibodies are also provided. The antibodies of the invention are produced in mammary epithelial cells, such as those in a non-human transgenic animal engineered to express and secrete the antibody in its milk. The antibodies or compositions comprising the antibodies can be used to treat disease in which ADCC activity provides a benefit. In one embodiment, therefore, the antibodies or compositions comprising the antibodies can be used to treat cancer, lymphoproliferative disease or autoimmune disease.
Type:
Application
Filed:
February 21, 2020
Publication date:
August 13, 2020
Applicants:
LFB USA, Inc., Genzyme Corporation
Inventors:
Daniel Schindler, Harry M. Meade, Timothy Edmunds, John McPherson
Abstract: Provided herein are methods of perfusion culturing an adherent mammalian cell using a shake flask and a plurality of microcarriers, and various methods that utilize these culturing methods.
Type:
Application
Filed:
March 2, 2020
Publication date:
August 13, 2020
Applicant:
Genzyme Corporation
Inventors:
Jianguo Yang, Yang Yang, Jennifer Tengtrakool, Weichang Zhou
Abstract: Antibodies or antigen-binding fragments thereof are engineered to bind Transforming Growth Factor-? (TGF?). TGF?-isoform selective antibodies or antigen-binding fragments thereof may selectively bind human TGF?1, compared to human TGF?2 and human TGF?3, or may selectively bind human TGF?3, compared to human TGF?1 and human TGF?2. The design of the antibodies or antigen-binding fragments thereof is facilitated by a co-crystal structure of a recombinant Fab fragment of GC1008 bound to TGF?2 and by another co-crystal structure of the scFv version of GC1008 bound to TGF?1.
Type:
Grant
Filed:
August 7, 2017
Date of Patent:
August 4, 2020
Assignee:
GENZYME CORPORATION
Inventors:
Ronnie Wei, Aaron Moulin, Magali Mathieu, Clark Pan, Sunghae Park, Huawei Qiu
Abstract: Provided herein are integrated continuous biomanufacturing processes for producing a therapeutic protein drug substance. Also provided are systems that are capable of continuously producing a therapeutic protein drug substance.
Type:
Grant
Filed:
April 21, 2017
Date of Patent:
July 14, 2020
Assignee:
Genzyme Corporation
Inventors:
Konstantin Konstantinov, Rahul Godawat, Veena Warikoo, Sujit Jain
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:
June 12, 2018
Date of Patent:
June 30, 2020
Assignee:
Genzyme Corporation
Inventors:
Paulene Mclean Quigley Sheldon, Peter S. Gagnon, Gina Nichols, Barbara A. Thorne
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 25, 2018
Date of Patent:
June 16, 2020
Assignee:
Genzyme Corporation
Inventors:
Carol A. Nelson, Bruce M. Wentworth, Ronald K. Scheule, Timothy E. Weeden, Nicholas P. Clayton
Abstract: A method for identifying a patient that is at risk for developing a thyroid disorder that occurs subsequent to treatment with a regimen that depletes lymphocytes, comprising determining whether antibodies directed against thyroid peroxidase or thyroid microsomes are present in the patient, wherein if the antibodies are present in the patient then the patient is at increased risk for developing a thyroid disorder. A particular embodiment is a method for identifying a patient with multiple sclerosis that is at risk for developing a thyroid disorder that occurs subsequent to treatment with a regimen that depletes CD52-positive cells, comprising determining whether antibodies directed against thyroid peroxidase or thyroid microsomes are present in the patient, wherein if the antibodies are present in the patient then the patient is at risk for developing the thyroid disorder.
Abstract: Disclosed herein are methods that have been developed to control the formation of disulfide bonds between polypeptides of a multimeric protein produced by a bioprocess. Also disclosed are protein solution parameters that allow for controlling the formation of disulfide bonds. In one example, the methods disclosed herein can be used to control the proportion of half antibody molecules in an antibody solution.
Type:
Grant
Filed:
March 25, 2015
Date of Patent:
May 12, 2020
Assignee:
GENZYME CORPORATION
Inventors:
Kevin P. Brower, Chris Hwang, Rao Koduri, Konstantin B. Konstantinov, Veena Warikoo, Marcella Yu, Jin Yin
Abstract: Compositions and methods for treating macular degeneration are disclosed. The methods utilize IL17 inhibitors, such as IL17 receptors, as well as fusion proteins including an IL17 receptor fused with a multimerization domain, and recombinant viral vectors encoding such fusions.
Type:
Grant
Filed:
April 17, 2014
Date of Patent:
May 5, 2020
Assignees:
GENZYME CORPORATION, THE UNITED STATES OF AMERICA AS REPRESENTED BY THE
Inventors:
Samuel Wadsworth, Abraham Scaria, Chi-Chao Chan
Abstract: The present invention relates to methods for purifying or enriching a biomolecule using multimodal resins and an elution buffer containing a Good's buffer.
Type:
Application
Filed:
December 23, 2019
Publication date:
April 30, 2020
Applicant:
Genzyme Corporation
Inventors:
Rahul Godawat, Daniel Cummings, Veena Warikoo
Abstract: An scFv-Fc dimer binds and neutralizes TGF?1 selectively and with high affinity and avidity. The scFv region may comprise the same VH and VL domains or CDR regions as metelimumab. The unique combination of their smaller size, high selectivity, potency against TGF?1, and long in vivo half-life makes the scFv-Fc dimers ideal candidates for therapeutic applications.
Abstract: Disclosed herein is a method of treating a patient suffering a myocardial infarction, particularly an acute myocardial infarction, or of reducing an adverse consequence of a myocardial infarction in a patient comprising administering an antagonist of TGF-? to the patient during the acute stage of the myocardial infarction.
Type:
Grant
Filed:
December 12, 2016
Date of Patent:
April 28, 2020
Assignee:
GENZYME CORPORATION
Inventors:
Geoffrey Y. Akita, Scott Lonning, Richard C Gregory, Jr., Amelia B Kudej
Abstract: The disclosure pertains to methods and compositions for treating disorders affecting the central nervous system (CNS). These disorders include neurometabolic disorders such as lysosomal storage diseases that affect the central nervous system, e.g., Niemann-Pick A disease. They also include disorders such as Alzheimer's disease. The disclosed methods involve contacting an axonal ending of a neuron with a composition containing high titer AAV carrying a therapeutic transgene so that the AAV vector is axonally transported in a retrograde fashion and transgene product is expressed distally to the administration site.