WO2013013017A3 - Compositions and methods for modifying the glycosylation of lysosomal storage disorder therapeutics - Google Patents

Compositions and methods for modifying the glycosylation of lysosomal storage disorder therapeutics Download PDF

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Publication number
WO2013013017A3
WO2013013017A3 PCT/US2012/047354 US2012047354W WO2013013017A3 WO 2013013017 A3 WO2013013017 A3 WO 2013013017A3 US 2012047354 W US2012047354 W US 2012047354W WO 2013013017 A3 WO2013013017 A3 WO 2013013017A3
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WO
WIPO (PCT)
Prior art keywords
methods
modifying
compositions
glycosylation
lysosomal storage
Prior art date
Application number
PCT/US2012/047354
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French (fr)
Other versions
WO2013013017A2 (en
Inventor
Anthony Rossomando
Brian Bettencourt
Original Assignee
Alnylam Pharmaceuticals, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Alnylam Pharmaceuticals, Inc. filed Critical Alnylam Pharmaceuticals, Inc.
Publication of WO2013013017A2 publication Critical patent/WO2013013017A2/en
Publication of WO2013013017A3 publication Critical patent/WO2013013017A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C07K14/8114—Kunitz type inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C07K14/8121—Serpins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2405—Glucanases
    • C12N9/2408—Glucanases acting on alpha -1,4-glucosidic bonds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2465—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1) acting on alpha-galactose-glycoside bonds, e.g. alpha-galactosidase (3.2.1.22)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00—Preparation of peptides or proteins
    • C12P21/005—Glycopeptides, glycoproteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering N.A.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Saccharide Compounds (AREA)
  • Peptides Or Proteins (AREA)

Abstract

The invention generally relates to compositions and methods for producing lysosomal proteins that have altered glycan structure, such that the protein can be delivered efficiently into the lysosomes of target cells (e.g., via mannose-6-phosphate mediated endocytosis). The lysosomal proteins are produced by modifying the glycosylation pathways and/or lysosomal targeting in a host cell using an RNA effector molecule, such as an siRNA. Glycan-modified lysosomal proteins produced using the methods described herein have improved properties.
PCT/US2012/047354 2011-07-21 2012-07-19 Compositions and methods for modifying the glycosylation of lysosomal storage disorder therapeutics WO2013013017A2 (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201161510437P 2011-07-21 2011-07-21
US61/510,437 2011-07-21
US201161532999P 2011-09-09 2011-09-09
US61/532,999 2011-09-09
US201261617322P 2012-03-29 2012-03-29
US61/617,322 2012-03-29

Publications (2)

Publication Number Publication Date
WO2013013017A2 WO2013013017A2 (en) 2013-01-24
WO2013013017A3 true WO2013013017A3 (en) 2013-04-18

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2012/047354 WO2013013017A2 (en) 2011-07-21 2012-07-19 Compositions and methods for modifying the glycosylation of lysosomal storage disorder therapeutics

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WO (1) WO2013013017A2 (en)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111529708A (en) * 2013-03-15 2020-08-14 夏尔维洛药品公司 C1-INH compositions and methods for the prevention and treatment of disorders associated with a deficiency in C1 esterase inhibitors
US20150104445A1 (en) * 2013-10-10 2015-04-16 Viropharma Holdings Limited Methods of inhibiting the alternative pathway of complement immune system activation and compositions used therein
WO2015095568A1 (en) * 2013-12-18 2015-06-25 Kelvin Lee Reduction of lipase activity in product formulations
PT3201320T (en) * 2014-09-30 2024-01-12 Amicus Therapeutics Inc Highly potent acid alpha-glucosidase with enhanced carbohydrates
TW202248420A (en) * 2014-09-30 2022-12-16 美商阿米庫斯醫療股份有限公司 Highly potent modified acid alpha-glucosidase and method of making and using it
WO2017029148A1 (en) * 2015-08-14 2017-02-23 Cancer Research Technology Limited Insulin-like growth factor 2 (igf2) binding agents
KR102510941B1 (en) 2015-12-30 2023-03-20 아미쿠스 세라퓨틱스, 인코포레이티드 Enriched acid alpha-glucosidase for the treatment of Pompe disease
KR102343162B1 (en) 2016-03-30 2021-12-23 아미쿠스 세라퓨틱스, 인코포레이티드 Selection method for high M6P recombinant protein
KR102618519B1 (en) * 2016-03-30 2023-12-28 아미쿠스 세라퓨틱스, 인코포레이티드 Formulations comprising recombinant acid alpha-glucosidase
TWI813388B (en) * 2016-03-30 2023-08-21 美商阿米庫斯醫療股份有限公司 Formulations comprising recombinant acid alpha-glucosidase
SG11201901494UA (en) 2016-09-12 2019-03-28 Genethon Acid-alpha glucosidase variants and uses thereof
EP3293203A1 (en) * 2016-09-12 2018-03-14 Genethon Acid-alpha glucosidase variants and uses thereof
CA3043768A1 (en) 2016-11-29 2018-06-07 PureTech Health LLC Exosomes for delivery of therapeutic agents

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5641670A (en) * 1991-11-05 1997-06-24 Transkaryotic Therapies, Inc. Protein production and protein delivery
US20060188975A1 (en) * 2003-08-21 2006-08-24 Mani Ramaswami Genetically modified somatic cells for sustained secretion of lysosomal proenzymes deficient in lysosomal storage disorders
WO2011005786A2 (en) * 2009-07-06 2011-01-13 Alnylam Pharmaceuticals, Inc. Compositions and methods for enhancing production of a biological product

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5641670A (en) * 1991-11-05 1997-06-24 Transkaryotic Therapies, Inc. Protein production and protein delivery
US20060188975A1 (en) * 2003-08-21 2006-08-24 Mani Ramaswami Genetically modified somatic cells for sustained secretion of lysosomal proenzymes deficient in lysosomal storage disorders
WO2011005786A2 (en) * 2009-07-06 2011-01-13 Alnylam Pharmaceuticals, Inc. Compositions and methods for enhancing production of a biological product

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
FREEZE, H.: "Towards a therapy for phosphomannomutase 2 defeciency, the defect in CDG-la patients.", BIOCHIM BIOPHYS ACTA, vol. 1792, no. 9, September 2009 (2009-09-01), pages 835 - 840 *

Also Published As

Publication number Publication date
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