WO2009131740A3 - Neutralizing proprotein convertase subtilisin kexin type 9 (pcsk9) variants and uses thereof - Google Patents

Neutralizing proprotein convertase subtilisin kexin type 9 (pcsk9) variants and uses thereof Download PDF

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Publication number
WO2009131740A3
WO2009131740A3 PCT/US2009/034775 US2009034775W WO2009131740A3 WO 2009131740 A3 WO2009131740 A3 WO 2009131740A3 US 2009034775 W US2009034775 W US 2009034775W WO 2009131740 A3 WO2009131740 A3 WO 2009131740A3
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Prior art keywords
variants
neutralizing
pcsk9
proprotein convertase
convertase subtilisin
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Ceased
Application number
PCT/US2009/034775
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French (fr)
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WO2009131740A2 (en
Inventor
Simon Mark Jackson
Derek Evan Piper
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Amgen Inc
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Amgen Inc
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Priority to EP09735447.6A priority Critical patent/EP2296694B1/en
Priority to MX2010011499A priority patent/MX2010011499A/en
Priority to AU2009238550A priority patent/AU2009238550B2/en
Priority to CA2720681A priority patent/CA2720681C/en
Priority to JP2011506310A priority patent/JP5806110B2/en
Priority to US12/989,404 priority patent/US9994923B2/en
Publication of WO2009131740A2 publication Critical patent/WO2009131740A2/en
Publication of WO2009131740A3 publication Critical patent/WO2009131740A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21061—Kexin (3.4.21.61), i.e. proprotein convertase subtilisin/kexin type 9
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/482—Serine endopeptidases (3.4.21)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/6454—Dibasic site splicing serine proteases, e.g. kexin (3.4.21.61); furin (3.4.21.75) and other proprotein convertases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Emergency Medicine (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Neutralizing PCSK9 variants that interact with low density lipoprotein receptor (LDLR) are described. Methods and compositions for treating disorders by administering a pharmaceutically effective amount of a neutralizing PCSK9 variant are described.
PCT/US2009/034775 2008-04-23 2009-02-20 Neutralizing proprotein convertase subtilisin kexin type 9 (pcsk9) variants and uses thereof Ceased WO2009131740A2 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP09735447.6A EP2296694B1 (en) 2008-04-23 2009-02-20 Neutralizing proprotein convertase subtilisin kexin type 9 (pcsk9) variants and uses thereof
MX2010011499A MX2010011499A (en) 2008-04-23 2009-02-20 Neutralizing proprotein convertase subtilisin kexin type 9 (pcsk9) variants and uses thereof.
AU2009238550A AU2009238550B2 (en) 2008-04-23 2009-02-20 Neutralizing proprotein convertase subtilisin kexin type 9 ( PCSK9) variants and uses thereof
CA2720681A CA2720681C (en) 2008-04-23 2009-02-20 Neutralizing proprotein convertase subtilisin kexin type 9 (pcsk9) variants and uses thereof
JP2011506310A JP5806110B2 (en) 2008-04-23 2009-02-20 Neutralized proprotein convertase subtilisin kexin type 9 (PCSK9) variants and uses thereof
US12/989,404 US9994923B2 (en) 2008-04-23 2009-02-20 Neutralizing proprotein convertase subtilisin kexin type 9 (PCSK9) variants and uses thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US12530408P 2008-04-23 2008-04-23
US61/125,304 2008-04-23

Publications (2)

Publication Number Publication Date
WO2009131740A2 WO2009131740A2 (en) 2009-10-29
WO2009131740A3 true WO2009131740A3 (en) 2010-01-07

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PCT/US2009/034775 Ceased WO2009131740A2 (en) 2008-04-23 2009-02-20 Neutralizing proprotein convertase subtilisin kexin type 9 (pcsk9) variants and uses thereof

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Country Link
US (1) US9994923B2 (en)
EP (1) EP2296694B1 (en)
JP (1) JP5806110B2 (en)
AU (1) AU2009238550B2 (en)
CA (1) CA2720681C (en)
MX (1) MX2010011499A (en)
WO (1) WO2009131740A2 (en)

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USRE50880E1 (en) 2022-08-01 2026-05-05 Kymab Limited Anti-human OX40L antibodies and methods of treatment

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JOP20080381B1 (en) 2007-08-23 2023-03-28 Amgen Inc Antigen Binding Proteins to Proprotein Convertase subtillisin Kexin type 9 (pcsk9)
JOP20200043A1 (en) 2011-05-10 2017-06-16 Amgen Inc Ways to treat or prevent cholesterol disorders
WO2012177741A1 (en) * 2011-06-20 2012-12-27 Genentech, Inc. Pcsk9-binding polypeptides and methods of use
AR087715A1 (en) 2011-09-16 2014-04-09 Lilly Co Eli ANTI PCSK9 ANTIBODIES AND USES OF THE SAME
EA039663B1 (en) 2012-05-03 2022-02-24 Амген Инк. Use of an anti-pcsk9 antibody for lowering serum cholesterol ldl and treating cholesterol related disorders
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US10287317B2 (en) * 2013-02-15 2019-05-14 Srx Cardio, Llc Proprotein convertase subtilisin kexin type 9 (PCSK9) allosteric binding ligands to modulate serum low density lipoprotein (LDL) levels
US8980864B2 (en) 2013-03-15 2015-03-17 Moderna Therapeutics, Inc. Compositions and methods of altering cholesterol levels
EP3052521A1 (en) 2013-10-03 2016-08-10 Moderna Therapeutics, Inc. Polynucleotides encoding low density lipoprotein receptor
US8883157B1 (en) 2013-12-17 2014-11-11 Kymab Limited Targeting rare human PCSK9 variants for cholesterol treatment
US9051378B1 (en) 2014-07-15 2015-06-09 Kymab Limited Targeting rare human PCSK9 variants for cholesterol treatment
US8986694B1 (en) 2014-07-15 2015-03-24 Kymab Limited Targeting human nav1.7 variants for treatment of pain
US9017678B1 (en) 2014-07-15 2015-04-28 Kymab Limited Method of treating rheumatoid arthritis using antibody to IL6R
US9034332B1 (en) 2014-07-15 2015-05-19 Kymab Limited Precision medicine by targeting rare human PCSK9 variants for cholesterol treatment
US9045545B1 (en) 2014-07-15 2015-06-02 Kymab Limited Precision medicine by targeting PD-L1 variants for treatment of cancer
US8992927B1 (en) 2014-07-15 2015-03-31 Kymab Limited Targeting human NAV1.7 variants for treatment of pain
US8986691B1 (en) 2014-07-15 2015-03-24 Kymab Limited Method of treating atopic dermatitis or asthma using antibody to IL4RA
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US8980273B1 (en) 2014-07-15 2015-03-17 Kymab Limited Method of treating atopic dermatitis or asthma using antibody to IL4RA
US9023359B1 (en) 2014-07-15 2015-05-05 Kymab Limited Targeting rare human PCSK9 variants for cholesterol treatment
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Publication number Priority date Publication date Assignee Title
USRE50880E1 (en) 2022-08-01 2026-05-05 Kymab Limited Anti-human OX40L antibodies and methods of treatment

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JP2011519277A (en) 2011-07-07
CA2720681A1 (en) 2009-10-29
AU2009238550A1 (en) 2009-10-29
US9994923B2 (en) 2018-06-12
CA2720681C (en) 2016-08-02
US20110117011A1 (en) 2011-05-19
EP2296694B1 (en) 2015-08-05
JP5806110B2 (en) 2015-11-10
MX2010011499A (en) 2010-11-12
EP2296694A2 (en) 2011-03-23
WO2009131740A2 (en) 2009-10-29
AU2009238550B2 (en) 2014-11-27

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