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DE19207796T1 - Antigen zur bindung von proteinen an proprotein-konvertase-subtilisin/kexin vom typ 9 (pcsk9) - Google Patents

Antigen zur bindung von proteinen an proprotein-konvertase-subtilisin/kexin vom typ 9 (pcsk9) Download PDF

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Publication number
DE19207796T1
DE19207796T1 DE19207796.4T DE19207796T DE19207796T1 DE 19207796 T1 DE19207796 T1 DE 19207796T1 DE 19207796 T DE19207796 T DE 19207796T DE 19207796 T1 DE19207796 T1 DE 19207796T1
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Prior art keywords
pcsk9
binding protein
binds
antigen
antibody
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DE19207796.4T
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DE19207796T9 (de
Inventor
Simon Mark Jackson
Nigel Pelham Clinton Walker
Derek Evan Piper
Bei Shan
Wenyan Shen
Joyce Chi Yee Chan
Chadwick Terence King
Randal Robert Ketchem
Christopher Mehlin
Teresa Arazas Carabeo
Quiong CAO
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Amgen Inc
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Amgen Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • 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
    • 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
    • A61K31/335—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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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    • 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
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    • 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
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    • C—CHEMISTRY; METALLURGY
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    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
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    • C07K2317/00—Immunoglobulins specific features
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    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

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Abstract

Neutralisierendes Antigen-bindendes Protein, das(a) an ein PCSK9-Protein bindet, das die Aminosäuresequenz von SEQ ID NO: 1 umfasst, wobei das Antigen-bindende Protein ein den LDLR kompetitiv neutralisierendes Antigen-bindendes Protein ist;(b) ein Antikörper ist, der an PCSK9 an einer Stelle bindet, die sich mit einer Stelle überschneidet, an der LDLR an PCSK9 bindet; oder(c) ein neutralisierender Antikörper ist, der an PCSK9 bindet, wobei der Antikörper an PCSK9 an einer Stelle innerhalb der Reste 31-447 von SEQ ID NO: 3 bindet.

Claims (5)

  1. Neutralisierendes Antigen-bindendes Protein, das (a) an ein PCSK9-Protein bindet, das die Aminosäuresequenz von SEQ ID NO: 1 umfasst, wobei das Antigen-bindende Protein ein den LDLR kompetitiv neutralisierendes Antigen-bindendes Protein ist; (b) ein Antikörper ist, der an PCSK9 an einer Stelle bindet, die sich mit einer Stelle überschneidet, an der LDLR an PCSK9 bindet; oder (c) ein neutralisierender Antikörper ist, der an PCSK9 bindet, wobei der Antikörper an PCSK9 an einer Stelle innerhalb der Reste 31-447 von SEQ ID NO: 3 bindet.
  2. Der Antikörper nach Anspruch 1 (c), wobei der Antikörper an ein Epitop innerhalb der Reste 31-447 von SEQ ID NO: 3 bindet.
  3. Pharmazeutische Zusammensetzung, umfassend mindestens ein Antigen-bindendes Protein nach einem der Ansprüche 1 bis 2 und einen pharmazeutisch akzeptablen Hilfsstoff.
  4. Nukleinsäuremolekül, das für das Antigen-bindende Protein nach einem der Ansprüche 1 bis 2 kodiert.
  5. Antigen-bindendes Protein nach einem der Ansprüche 1 bis 2 zur Verwendung bei der Behandlung oder Vorbeugung eines Zustands, der mit erhöhten Serumcholesterinspiegeln in einem Subjekt verbunden ist.
DE19207796.4T 2007-08-23 2008-08-22 Antigen zur bindung von proteinen an proprotein-konvertase-subtilisin/kexin vom typ 9 (pcsk9) Active DE19207796T9 (de)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US95766807P 2007-08-23 2007-08-23
US957668P 2007-08-23
US896507P 2007-12-21 2007-12-21
US8965P 2007-12-21
US1063008P 2008-01-09 2008-01-09
US10630P 2008-01-09
US8613308P 2008-08-04 2008-08-04
US86133P 2008-08-04
EP19207796.4A EP3666797B1 (de) 2007-08-23 2008-08-22 Antigen zur bindung von proteinen an proprotein-konvertase-subtilisin/kexin vom typ 9 (pcsk9)

Publications (2)

Publication Number Publication Date
DE19207796T1 true DE19207796T1 (de) 2022-03-10
DE19207796T9 DE19207796T9 (de) 2023-02-23

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ID=39951467

Family Applications (2)

Application Number Title Priority Date Filing Date
DE202008018562.9U Expired - Lifetime DE202008018562U1 (de) 2007-08-23 2008-08-22 Antigenbindende Proteine gegen Proprotein Convertase Subtilisin Kexin Typ 9 (PCSK9)
DE19207796.4T Active DE19207796T9 (de) 2007-08-23 2008-08-22 Antigen zur bindung von proteinen an proprotein-konvertase-subtilisin/kexin vom typ 9 (pcsk9)

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DE202008018562.9U Expired - Lifetime DE202008018562U1 (de) 2007-08-23 2008-08-22 Antigenbindende Proteine gegen Proprotein Convertase Subtilisin Kexin Typ 9 (PCSK9)

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Country Link
US (27) US8030457B2 (de)
EP (3) EP3202791A1 (de)
JP (7) JP5441905B2 (de)
KR (9) KR20240113594A (de)
CN (8) CN101932607B (de)
AR (1) AR068011A1 (de)
AU (1) AU2008288791B2 (de)
BR (2) BR122018012430B8 (de)
CA (1) CA2696252C (de)
CL (1) CL2008002495A1 (de)
CO (1) CO6230997A2 (de)
CR (1) CR11328A (de)
CY (3) CY1117940T1 (de)
DE (2) DE202008018562U1 (de)
DK (2) DK3666797T5 (de)
EA (1) EA032106B1 (de)
ES (3) ES2917423T3 (de)
FI (2) FI3666797T3 (de)
FR (1) FR16C0025I2 (de)
HR (2) HRP20230503T3 (de)
HU (4) HUE028162T2 (de)
IL (5) IL304868A (de)
JO (1) JOP20080381B1 (de)
LT (3) LT3666797T (de)
LU (2) LU93096I2 (de)
MA (1) MA31978B1 (de)
MX (3) MX2010001921A (de)
MY (3) MY180102A (de)
NL (1) NL300818I2 (de)
NO (3) NO2016010I1 (de)
NZ (1) NZ584101A (de)
PE (8) PE20131400A1 (de)
PH (2) PH12013502285B1 (de)
PL (2) PL2215124T5 (de)
PT (1) PT3666797T (de)
RS (2) RS54756B2 (de)
SG (2) SG10201710183TA (de)
SI (2) SI2215124T2 (de)
TN (1) TN2010000063A1 (de)
TW (6) TWI675848B (de)
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WO (1) WO2009026558A1 (de)

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JP5570806B2 (ja) 2006-05-11 2014-08-13 アルナイラム ファーマシューティカルズ， インコーポレイテッド Ｐｃｓｋ９遺伝子の発現を阻害するための組成物および方法
EP2083864A4 (de) 2006-11-07 2010-12-08 Merck Sharp & Dohme Antagonisten von pcsk9
JOP20080381B1 (ar) 2007-08-23 2023-03-28 Amgen Inc بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9)
EP4248976A3 (de) 2007-08-23 2024-04-10 Amgen Inc. Antigen zur bindung von proteinen an proprotein-konvertase-subtilisin/kexin vom typ 9 (pcsk9)
CL2008002775A1 (es) 2007-09-17 2008-11-07 Amgen Inc Uso de un agente de unión a esclerostina para inhibir la resorción ósea.
CA2713379A1 (en) * 2008-01-31 2009-11-05 Alnylam Pharmaceuticals, Inc. Optimized methods for delivery of dsrna targeting the pcsk9 gene
AR070315A1 (es) * 2008-02-07 2010-03-31 Merck & Co Inc Anticuerpos 1b20 antagonistas de pcsk9
AR070316A1 (es) * 2008-02-07 2010-03-31 Merck & Co Inc Antagonistas de pcsk9 (proproteina subtilisina-kexina tipo 9)
EP2641918A3 (de) 2008-08-04 2014-03-05 Amgen Inc. Antigenbindende Proteine an Proprotein-Konvertase-Subtilisin/Kexin vom Typ 9 (PCSK9)
TWI445716B (zh) 2008-09-12 2014-07-21 Rinat Neuroscience Corp Ｐｃｓｋ９拮抗劑類
US20130064834A1 (en) 2008-12-15 2013-03-14 Regeneron Pharmaceuticals, Inc. Methods for treating hypercholesterolemia using antibodies to pcsk9
JO3672B1 (ar) 2008-12-15 2020-08-27 Regeneron Pharma أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9).
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