DK2683360T3 - Pegyleret apelin og anvendelser deraf - Google Patents

Pegyleret apelin og anvendelser deraf Download PDF

Info

Publication number
DK2683360T3
DK2683360T3 DK12757055.4T DK12757055T DK2683360T3 DK 2683360 T3 DK2683360 T3 DK 2683360T3 DK 12757055 T DK12757055 T DK 12757055T DK 2683360 T3 DK2683360 T3 DK 2683360T3
Authority
DK
Denmark
Prior art keywords
apelin
peg
molecule
pegylated
amino acid
Prior art date
Application number
DK12757055.4T
Other languages
English (en)
Inventor
Zhiqiang Jia
Lihui Hou
Clark Q Pan
Geoffrey Y Akita
Original Assignee
Genzyme Corp
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 Genzyme Corp filed Critical Genzyme Corp
Application granted granted Critical
Publication of DK2683360T3 publication Critical patent/DK2683360T3/da

Links

Classifications

    • 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
    • A61K47/56—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • 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
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cardiology (AREA)
  • Organic Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Claims (14)

1. Pegyleret apelin 36-molekyle, der omfatter et eller flere polyethylenglycol (PEG)-molekyler, der er operabelt koblet til mindst én aminosyrerest i N-terminalen af apelin 36.
2. Molekyle ifølge krav 1, hvor det pegylerede apelin 36 er i stand til at fremvise en forlænget cirkulationstid eller en forlænget inotrop virkning i forhold til ikke-pegyleret apelin 36.
3. Molekyle ifølge krav 1, hvor det pegylerede apelin 36 er et monopegyleret eller et dipegyleret apelin 36.
4. Molekyle ifølge krav 1, hvor det ene eller de flere PEG-molekyler er kovalent bundet til den mindst ene aminosyrerest enten direkte eller via en linker.
5. Molekyle ifølge krav 1, hvor hvert PEG-molekyle har en molekylvægt i intervallet fra ca. 5.000 til ca. 50.000 dalton.
6. Molekyle ifølge krav 1, hvor det pegylerede apelin 36 omfatter monomert apelin 36.
7. Molekyle ifølge krav 1, hvor det pegylerede apelin 36 omfatter et oligomert apelin 36, hvor en eller flere monomerer er operabelt koblet til hinanden.
8. Molekyle ifølge krav 1, hvor apelin 36 omfatter aminosyresekvensen ifølge aminosyreresterne 42-77 af SEQ ID NO: 1.
9. Molekyle ifølge krav 8, hvor aminosyresekvensen kodes af en nukleinsyresekvens, som er 123-234 bp af SEQ ID NO: 2.
10. Fremgangsmåde til frembringelse af et molekyle ifølge krav 1, der omfatter trinet: reaktion af apelin 36 med en aktiveret PEG-aldehydlinker i nærvær af et reduktionsmiddel til frembringelse af det pegylerede apelin 36 under betingelser, hvorved linkeren bindes kovalent til leucinresten i N-terminalen af apelin 36.
11. Fremgangsmåde ifølge krav 10, hvor reduktionsmidlet er cyanoborhydrid, og reaktionstrinet udføres ved et pH på 5,0 til 7,5.
12. Farmaceutisk sammensætning, der omfatter en terapeutisk effektiv mængde af et pegyleret apelin 36, som omfatter et eller flere polyethylenglycol (PEG)-molekyler, der er operabelt koblet til mindst én aminosyrerest i N-terminalen af apelin 36, hvor den mindst ene aminosyrerest er leucin.
13. Terapeutisk effektiv mængde af det pegylerede apelin 36-molekyle ifølge krav 1 til anvendelse til behandling af en sygdom eller forstyrrelse, der er forbundet med apelin, hvor sygdommen eller forstyrrelsen er en kardiovaskulær sygdom, en iskæmireperfusionsskade, myokardieinfarkt, akut dekompenseret hjerteinsufficiens, kronisk hjerteinsufficiens, kardiomyopati, endokrin forstyrrelse, metabolisk forstyrrelse eller pulmonal hypertension.
14. Pegyleret apelin 36-molekyle til anvendelse ifølge krav 13, hvor den mindst ene aminosyrerest i N-terminalen af apelin 36 er leucin.
DK12757055.4T 2011-03-11 2012-03-08 Pegyleret apelin og anvendelser deraf DK2683360T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161451623P 2011-03-11 2011-03-11
PCT/US2012/028298 WO2012125408A1 (en) 2011-03-11 2012-03-08 Pegylated apelin and uses thereof

Publications (1)

Publication Number Publication Date
DK2683360T3 true DK2683360T3 (da) 2016-05-30

Family

ID=46831054

Family Applications (2)

Application Number Title Priority Date Filing Date
DK16155181.7T DK3045183T3 (da) 2011-03-11 2012-03-08 Pegyleret apelin og anvendelser deraf
DK12757055.4T DK2683360T3 (da) 2011-03-11 2012-03-08 Pegyleret apelin og anvendelser deraf

Family Applications Before (1)

Application Number Title Priority Date Filing Date
DK16155181.7T DK3045183T3 (da) 2011-03-11 2012-03-08 Pegyleret apelin og anvendelser deraf

Country Status (14)

Country Link
US (1) US20140142049A1 (da)
EP (2) EP2683360B1 (da)
AU (2) AU2012229336B2 (da)
CA (1) CA2829693C (da)
CY (1) CY1117654T1 (da)
DK (2) DK3045183T3 (da)
ES (2) ES2690147T3 (da)
HR (2) HRP20160547T1 (da)
HU (1) HUE027579T2 (da)
LT (1) LT3045183T (da)
PL (2) PL3045183T3 (da)
PT (1) PT3045183T (da)
SI (2) SI3045183T1 (da)
WO (1) WO2012125408A1 (da)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SI3045183T1 (sl) 2011-03-11 2018-11-30 Genzyme Corporation Pegiliran Apelin in njegove uporabe
US20160067347A1 (en) * 2012-12-20 2016-03-10 Amgen Inc. Apj receptor agonists and uses thereof
US9353163B2 (en) 2013-03-14 2016-05-31 Regeneron Pharmaceuticals, Inc. Apelin fusion proteins and uses thereof
HK1218252A1 (zh) 2013-07-25 2017-02-10 Novartis Ag 合成apelin多肽之生物结合物
KR20160031551A (ko) 2013-07-25 2016-03-22 노파르티스 아게 심부전의 치료를 위한 시클릭 폴리펩티드
CN105612174A (zh) * 2013-07-25 2016-05-25 诺华股份有限公司 用于治疗心力衰竭的二硫化物环状多肽
WO2015013165A1 (en) * 2013-07-25 2015-01-29 Novartis Ag Cyclic apelin derivatives for the treatment of heart failure
WO2015077491A1 (en) 2013-11-20 2015-05-28 Regeneron Pharmaceuticals, Inc. Aplnr modulators and uses thereof
DK3122764T3 (da) 2014-03-25 2019-04-15 Lanthiopep Bv Cykliske apelin-analoger
WO2015191781A2 (en) * 2014-06-10 2015-12-17 Amgen Inc. Apelin polypeptides
MA41580A (fr) 2015-01-23 2017-11-29 Novartis Ag Conjugués d'acides gras de l'apeline synthétique présentant une demi-vie améliorée
CN110072531A (zh) 2016-10-19 2019-07-30 阿维夫公司 用于治疗心血管相关疾病的爱帕琳的新型聚乙二醇化的脂质体制剂
EP4168054A1 (en) * 2020-06-18 2023-04-26 Universite d'Aix Marseille Conjugated and labelled apelin, preparation and uses thereof

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6420339B1 (en) * 1998-10-14 2002-07-16 Amgen Inc. Site-directed dual pegylation of proteins for improved bioactivity and biocompatibility
US20020102208A1 (en) 1999-03-01 2002-08-01 Paul Chinn Radiolabeling kit and binding assay
EP1613348B1 (en) * 2003-03-12 2010-06-23 The Arizona Board of Regents on Behalf of the University of Arizona Methods for modulating angiogenesis with apelin compositions
US7947280B2 (en) * 2003-05-22 2011-05-24 The Board Of Trustees Of The Leland Stanford Junior University Apelin and uses thereof
WO2007022123A2 (en) * 2005-08-11 2007-02-22 Amylin Pharmaceuticals, Inc. Hybrid polypeptides with selectable properties
WO2008051383A2 (en) * 2006-10-19 2008-05-02 Amgen Inc. Use of alcohol co-solvents to improve pegylation reaction yields
SI3045183T1 (sl) 2011-03-11 2018-11-30 Genzyme Corporation Pegiliran Apelin in njegove uporabe

Also Published As

Publication number Publication date
SI2683360T1 (sl) 2016-06-30
AU2017202919A1 (en) 2017-05-25
AU2012229336A1 (en) 2013-10-10
HRP20160547T1 (hr) 2016-06-17
WO2012125408A1 (en) 2012-09-20
CA2829693A1 (en) 2012-09-20
HRP20181589T1 (hr) 2018-12-28
PL3045183T3 (pl) 2018-12-31
DK3045183T3 (da) 2018-10-22
CA2829693C (en) 2020-04-21
EP2683360B1 (en) 2016-02-24
AU2012229336B2 (en) 2017-02-02
PT3045183T (pt) 2018-11-02
PL2683360T3 (pl) 2016-09-30
SI3045183T1 (sl) 2018-11-30
AU2017202919B2 (en) 2019-03-14
EP2683360A4 (en) 2014-09-03
EP3045183A1 (en) 2016-07-20
EP2683360A1 (en) 2014-01-15
CY1117654T1 (el) 2018-03-07
LT3045183T (lt) 2018-10-25
US20140142049A1 (en) 2014-05-22
WO2012125408A8 (en) 2018-01-25
HUE027579T2 (en) 2016-10-28
ES2690147T3 (es) 2018-11-19
EP3045183B1 (en) 2018-07-04
ES2573337T3 (es) 2016-06-07

Similar Documents

Publication Publication Date Title
DK2683360T3 (da) Pegyleret apelin og anvendelser deraf
EP2358749B1 (en) Fgf21 mutants and uses thereof
JP2020033366A (ja) 高可溶性レプチン
ME00277B (me) Polimerni konjugati mutiranog neublastina
PL211162B1 (pl) Polipeptyd wariantu neublastyny, zawierające go białko fuzyjne i sposób ich wytwarzania oraz dimer, kwas nukleinowy, wektor, komórka gospodarza, koniugat, kompozycja farmaceutyczna i zastosowanie
US10308917B2 (en) Nucleotide sequences encoding VEGF antagonist compositions of FLT-1 and uses thereof
JP2011078434A (ja) 変異ニューブラスチンのポリマー結合体
DK2618830T3 (da) Formuleringer til en kvæggranulocytkolonistimulerende faktor og varianter deraf
KR20180087864A (ko) 신규 엑세나타이드 변이체-고분자 복합체
HK1254031A1 (en) Vegf antagonist compositions and uses thereof
HK1186196B (en) Vegf antagonist compositions and uses thereof
HK1186196A (en) Vegf antagonist compositions and uses thereof
EA041758B1 (ru) Fgf21 мутанты и их применение