ES2565757T3 - Vacuna de PCSK9 - Google Patents

Vacuna de PCSK9 Download PDF

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Publication number
ES2565757T3
ES2565757T3 ES11181090.9T ES11181090T ES2565757T3 ES 2565757 T3 ES2565757 T3 ES 2565757T3 ES 11181090 T ES11181090 T ES 11181090T ES 2565757 T3 ES2565757 T3 ES 2565757T3
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sec
pcsk9
control
amino acid
acid residues
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Sylvia Brunner
Gergana Galabova
Bettina Wanko
Markus Windwarder
Gabriele Winsauer
Günther STAFFLER
Claudia Juno
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Affiris AG
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Affiris AG
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    • 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
    • A61K39/0005—Vertebrate antigens
    • 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
    • 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
    • A61K39/0005—Vertebrate antigens
    • A61K39/0012—Lipids; Lipoproteins
    • 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
    • A61K39/385—Haptens or antigens, bound to carriers
    • 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
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/643—Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
    • 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
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies 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
    • 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
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • 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
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55505—Inorganic adjuvants
    • 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
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031—Proteins
    • A61K2039/6081—Albumin; Keyhole limpet haemocyanin [KLH]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
    • C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
    • C07K2319/23—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a GST-tag
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site
    • 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

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  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biophysics (AREA)
  • General Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biotechnology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

Vacuna que comprende por lo menos dos fragmentos de proproteína convertasa subtilisina/kexina de tipo 9 (PCSK9), en la que por lo menos un fragmento de dichos por lo menos dos fragmentos comprende por lo menos 8 residuos aminoácidos consecutivos de los residuos aminoácidos 150 a 170 de PCSK9 según el SEC ID nº 9 y en la que por lo menos un fragmento de dichos por lo menos dos fragmentos comprende por lo menos 8 residuos aminoácidos consecutivos 205 a 225 de PCSK9 según el SEC ID nº 9.

Description

imagen1
imagen2
imagen3
imagen4
imagen5
imagen6
las proteínas siguiendo protocolos estándares.
Se recubrieron placas Nunc-Maxisorb de 96 pocillos con anticuerpo policlonal de cabra anti-RLDL purificado por afinidad para RLDL de ratón (R&D Systems). Se bloqueó la unión no específica mediante incubación con BSA/PBS
5 al 1%. A continuación, los lisados hepáticos se incubaron durante 3 h a temperatura ambiente para capturar el RLDL murino. La detección del RLDL capturado se llevó a cabo con anticuerpo policlonal de pollo anti-RLDL (Abcam), seguido de la incubación con un anticuerpo secundario de cabra biotinilado anti-IgG de pollo (Southern Biotech) y con un conjugado de estreptavidina-HRP. Finalmente, se utilizó TMB como sustrato cromógeno de peroxidasa.
10 La cuantificación del receptor de lipoproteína de baja densidad se llevó a cabo mediante comparación con una curva de calibración de estándares y se normalizó frente a la concentración de proteínas totales de los lisados.
El grupo de control (vacunación de control con péptido irrelevante) se fijó en 100% y se compararon los niveles de los grupos tratados con vacunas anti-PCSK9 a dicho grupo de control.
15 Ejemplo 1. Medianas de valores de proteína contra PCSK9 humano (n=5 ratones en cada grupo).
ID de secuencia
Mediana de valor de proteína (DOmax/2)
sec 1 control
0
sec 4
45.000
sec 7
47.000
sec 5
14.000
sec 7
47.000
sec 5
14.000
sec 8
31.000
sec 6
13.000
sec 8
31.000
Ejemplo 2. Valores medios en mg/dl y porcentaje de reducción del colesterol total (n=5 ratones en cada grupo).
ID de secuencia
Valores medios (mg/dl) Stdv % de reducción de CT en comparación con el grupo de control
Combinación A
sec 1 control sec 4 sec 7 sec 4 + 7 98 88 78 71 9 12 4 5 10 20 28
Combinación B
sec 1 control sec 5 sec 7 sec 5 + 7 86 61 64 51 9 7 5 1 29 26 41
Combinación C
sec 1 control sec 5 sec 8 sec 5 + 8 83 60 55 47 7 8 3 7 28 34 43
Combinación D
sec 1 control sec 6 sec 8 sec 6 + 8 83 65 55 48 7 4 3 4 22 34 42
8

Claims (1)

  1. imagen1
ES11181090.9T 2011-09-13 2011-09-13 Vacuna de PCSK9 Active ES2565757T3 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP11181090.9A EP2570135B1 (en) 2011-09-13 2011-09-13 PCSK9 Vaccine

Publications (1)

Publication Number Publication Date
ES2565757T3 true ES2565757T3 (es) 2016-04-06

Family

ID=46851983

Family Applications (2)

Application Number Title Priority Date Filing Date
ES11181090.9T Active ES2565757T3 (es) 2011-09-13 2011-09-13 Vacuna de PCSK9
ES12759427.3T Active ES2618796T3 (es) 2011-09-13 2012-09-13 Vacuna de PCSK9

Family Applications After (1)

Application Number Title Priority Date Filing Date
ES12759427.3T Active ES2618796T3 (es) 2011-09-13 2012-09-13 Vacuna de PCSK9

Country Status (24)

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US (2) US9220762B2 (es)
EP (2) EP2570135B1 (es)
JP (1) JP6054400B2 (es)
KR (1) KR101983685B1 (es)
CN (1) CN103874504B (es)
AU (1) AU2012307348B8 (es)
BR (1) BR112014005756A2 (es)
CA (1) CA2848487A1 (es)
CY (2) CY1117335T1 (es)
DK (2) DK2570135T3 (es)
ES (2) ES2565757T3 (es)
HR (2) HRP20170328T1 (es)
HU (2) HUE028583T2 (es)
IL (1) IL231043A (es)
LT (1) LT2755678T (es)
MX (1) MX346883B (es)
PL (2) PL2570135T3 (es)
PT (1) PT2755678T (es)
RS (1) RS54639B1 (es)
RU (2) RU2017139094A (es)
SG (1) SG11201400086QA (es)
SI (2) SI2570135T1 (es)
SM (1) SMT201600082B (es)
WO (1) WO2013037889A2 (es)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9255154B2 (en) 2012-05-08 2016-02-09 Alderbio Holdings, Llc Anti-PCSK9 antibodies and use thereof
EP2703483A1 (en) 2012-08-29 2014-03-05 Affiris AG PCSK9 peptide vaccine
US10279019B2 (en) 2014-02-11 2019-05-07 Stc.Unm PCSK9 peptide vaccine conjugated to a Qbeta carrier and methods of using the same
ES2732741T3 (es) * 2014-02-28 2019-11-25 Affiris Ag Vacunas de PCSK9
CN105085684B (zh) * 2014-05-14 2020-04-17 上海亨臻实业有限公司 Pcsk9靶向重组疫苗设计及其应用
CN106822881A (zh) * 2016-12-09 2017-06-13 四川大学 一种针对pcsk9的抗高血脂蛋白疫苗
KR102401796B1 (ko) 2017-04-13 2022-05-25 카딜라 핼쓰캐어 리미티드 신규의 펩타이드 기재 pcsk9 백신
CN107488215A (zh) * 2017-07-19 2017-12-19 邱志华 人前蛋白转化酶枯草溶菌素9免疫原性肽段及其载体疫苗
AU2021214166A1 (en) * 2020-01-28 2022-09-22 United Biomedical, Inc. Peptide immunogens targeting PCSK9 and formulations thereof for prevention and treatment of PCSK9-mediated disorders
KR20210158693A (ko) * 2020-06-24 2021-12-31 바이오스트림테크놀러지스(주) 항 ｐｃｓｋ９ 항체 및 이의 용도
JPWO2022244845A1 (es) * 2021-05-19 2022-11-24
US20250186580A1 (en) 2022-02-28 2025-06-12 Tridem Bioscience Gmbh & Co Kg A CONJUGATE COMPRISING AT LEAST A ß-GLUCAN

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2194128B1 (en) * 2006-05-11 2012-08-01 Alnylam Pharmaceuticals Inc. Compositions and methods for inhibiting expression of the PCSK9 gene
WO2008125623A2 (en) * 2007-04-13 2008-10-23 Novartis Ag Molecules and methods for modulating proprotein convertase subtilisin/kexin type 9 (pcsk9)
AR070316A1 (es) * 2008-02-07 2010-03-31 Merck & Co Inc Antagonistas de pcsk9 (proproteina subtilisina-kexina tipo 9)
AT507604A1 (de) * 2008-11-19 2010-06-15 Affiris Forschungs & Entwicklungs Gmbh Behandlung von atherosklerose
PE20121544A1 (es) * 2009-09-03 2012-12-02 Pfizer Vaccines Llc Vacuna de pcsk9

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Publication number Publication date
US9669079B2 (en) 2017-06-06
RU2640258C2 (ru) 2017-12-27
KR20140067118A (ko) 2014-06-03
SI2755678T1 (sl) 2017-04-26
EP2755678B1 (en) 2016-12-21
PL2755678T3 (pl) 2017-08-31
IL231043A (en) 2017-05-29
EP2570135A1 (en) 2013-03-20
AU2012307348B8 (en) 2017-04-06
WO2013037889A3 (en) 2013-05-10
SI2570135T1 (sl) 2016-05-31
PL2570135T3 (pl) 2016-07-29
CY1118856T1 (el) 2018-01-10
JP2014527078A (ja) 2014-10-09
SG11201400086QA (en) 2014-03-28
EP2570135B1 (en) 2016-01-27
JP6054400B2 (ja) 2016-12-27
HUE031860T2 (en) 2017-08-28
CN103874504A (zh) 2014-06-18
KR101983685B1 (ko) 2019-05-29
MX346883B (es) 2017-04-05
LT2755678T (lt) 2017-03-27
IL231043A0 (en) 2014-03-31
RU2014114506A (ru) 2015-10-20
NZ621439A (en) 2015-06-26
PT2755678T (pt) 2017-03-24
RU2017139094A (ru) 2019-02-12
RU2017139094A3 (es) 2019-02-12
CA2848487A1 (en) 2013-03-21
HRP20160392T1 (hr) 2016-05-06
HUE028583T2 (en) 2016-12-28
AU2012307348A8 (en) 2017-04-06
EP2755678A2 (en) 2014-07-23
CN103874504B (zh) 2017-05-31
RS54639B1 (sr) 2016-08-31
AU2012307348B2 (en) 2017-03-02
SMT201600082B (it) 2016-04-29
US20160106822A1 (en) 2016-04-21
DK2570135T3 (en) 2016-02-15
US20150071951A1 (en) 2015-03-12
US9220762B2 (en) 2015-12-29
HRP20170328T1 (hr) 2017-05-19
CY1117335T1 (el) 2017-04-26
DK2755678T3 (en) 2017-03-13
MX2014002879A (es) 2014-04-10
BR112014005756A2 (pt) 2017-03-28
ES2618796T3 (es) 2017-06-22
AU2012307348A1 (en) 2014-03-20
WO2013037889A2 (en) 2013-03-21

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