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EA201590370A1 - Антитела к pcsk9 c ph-зависимыми характеристиками связывания - Google Patents

Антитела к pcsk9 c ph-зависимыми характеристиками связывания

Info

Publication number
EA201590370A1
EA201590370A1 EA201590370A EA201590370A EA201590370A1 EA 201590370 A1 EA201590370 A1 EA 201590370A1 EA 201590370 A EA201590370 A EA 201590370A EA 201590370 A EA201590370 A EA 201590370A EA 201590370 A1 EA201590370 A1 EA 201590370A1
Authority
EA
Eurasian Patent Office
Prior art keywords
antibodies
dependent binding
pcsk9
application
binding properties
Prior art date
Application number
EA201590370A
Other languages
English (en)
Other versions
EA028244B1 (ru
Inventor
Джордж Д. Янкопулос
Николас Дж. Пападопулос
Эндрю Дж. МЕРФИ
Нейл Шталь
Original Assignee
Ридженерон Фармасьютикалз, Инк.
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.)
Filing date
Publication date
Application filed by Ридженерон Фармасьютикалз, Инк. filed Critical Ридженерон Фармасьютикалз, Инк.
Publication of EA201590370A1 publication Critical patent/EA201590370A1/ru
Publication of EA028244B1 publication Critical patent/EA028244B1/ru

Links

Classifications

    • 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
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Obesity (AREA)
  • General Chemical & Material Sciences (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

Настоящее изобретение относится к антителам и их антигенсвязывающим фрагментам, которые специфически связывают конвертазу пробелков субтилизинового/кексинового типа 9 (PCSK9) с более высокой аффинностью при нейтральных значениях рН, чем при кислых значениях рН. Антитела, описанные в заявке, могут иметь одно или несколько изменений аминокислот по сравнению с антителами, которые не обладают свойствами рН-зависимого связывания. Например, изобретение относится к антителам к PCSK9, которые имеют одну или несколько замен на гистидин в одной или нескольких определяющих комплементарность областях. Антитела, описанные в заявке, со свойствами рН-зависимого связывания, остаются в кровотоке и проявляют активность снижения холестерина в течение более длительных периодов времени у животных по сравнению с антителами к PCSK9, которые не проявляют свойств рН-зависимого связывания. Таким образом, антитела, описанные в заявке, пригодны для лечения заболеваний и нарушений, связанных с повышенными уровнями холестерина HDL, где антитела, описанные в заявке, можно вводить пациенту в более низкой дозе и/или с меньшей частотой дозирования по сравнению с антителами, которые не проявляют свойств рН-зависимого связывания.
EA201590370A 2012-08-13 2013-08-12 АНТИТЕЛА К PCSK9 C pH-ЗАВИСИМЫМИ ХАРАКТЕРИСТИКАМИ СВЯЗЫВАНИЯ EA028244B1 (ru)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201261682349P 2012-08-13 2012-08-13
US201261703342P 2012-09-20 2012-09-20
US201261734398P 2012-12-07 2012-12-07
US201361761383P 2013-02-06 2013-02-06
US201361828258P 2013-05-29 2013-05-29
PCT/US2013/054456 WO2014028354A1 (en) 2012-08-13 2013-08-12 Anti-pcsk9 antibodies with ph-dependent binding characteristics

Publications (2)

Publication Number Publication Date
EA201590370A1 true EA201590370A1 (ru) 2015-05-29
EA028244B1 EA028244B1 (ru) 2017-10-31

Family

ID=50066319

Family Applications (1)

Application Number Title Priority Date Filing Date
EA201590370A EA028244B1 (ru) 2012-08-13 2013-08-12 АНТИТЕЛА К PCSK9 C pH-ЗАВИСИМЫМИ ХАРАКТЕРИСТИКАМИ СВЯЗЫВАНИЯ

Country Status (16)

Country Link
US (1) US9540449B2 (ru)
EP (1) EP2882778B1 (ru)
JP (1) JP6309521B2 (ru)
KR (1) KR20150041662A (ru)
CN (1) CN104540852B (ru)
AR (1) AR092098A1 (ru)
AU (1) AU2013302925B2 (ru)
CA (1) CA2881679C (ru)
EA (1) EA028244B1 (ru)
HK (1) HK1211603A1 (ru)
IL (1) IL236785B (ru)
MX (1) MX363213B (ru)
NZ (1) NZ704771A (ru)
TW (1) TWI596115B (ru)
UY (1) UY34975A (ru)
WO (1) WO2014028354A1 (ru)

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