ES2947409T3 - Profármacos de insulina a base de amida lipídica - Google Patents

Profármacos de insulina a base de amida lipídica

Info

Publication number
ES2947409T3
ES2947409T3 ES15844864T ES15844864T ES2947409T3 ES 2947409 T3 ES2947409 T3 ES 2947409T3 ES 15844864 T ES15844864 T ES 15844864T ES 15844864 T ES15844864 T ES 15844864T ES 2947409 T3 ES2947409 T3 ES 2947409T3
Authority
ES
Spain
Prior art keywords
alkyl
insulin
group
prodrug
acid
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
ES15844864T
Other languages
English (en)
Spanish (es)
Inventor
Richard D Dimarchi
Binbin Kou
Fa Zhang
John P Mayer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Indiana University Research and Technology Corp
Original Assignee
Indiana University Research and Technology 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 Indiana University Research and Technology Corp filed Critical Indiana University Research and Technology Corp
Application granted granted Critical
Publication of ES2947409T3 publication Critical patent/ES2947409T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575Hormones
    • C07K14/62Insulins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22Hormones
    • A61K38/28Insulins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/54Medicinal 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 compound
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/54Medicinal 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 compound
    • A61K47/543Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/69Medicinal 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6905Medicinal 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
    • A61K47/6911Medicinal 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Organic Chemistry (AREA)
  • Endocrinology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Toxicology (AREA)
  • Immunology (AREA)
  • Dispersion Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Emergency Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
ES15844864T 2014-09-24 2015-09-23 Profármacos de insulina a base de amida lipídica Active ES2947409T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201462054670P 2014-09-24 2014-09-24
PCT/US2015/051705 WO2016049174A1 (en) 2014-09-24 2015-09-23 Lipidated amide-based insulin prodrugs

Publications (1)

Publication Number Publication Date
ES2947409T3 true ES2947409T3 (es) 2023-08-08

Family

ID=55581947

Family Applications (1)

Application Number Title Priority Date Filing Date
ES15844864T Active ES2947409T3 (es) 2014-09-24 2015-09-23 Profármacos de insulina a base de amida lipídica

Country Status (6)

Country Link
US (1) US10385107B2 (enExample)
EP (1) EP3197912B1 (enExample)
JP (1) JP6701208B2 (enExample)
CN (1) CN107001441A (enExample)
ES (1) ES2947409T3 (enExample)
WO (1) WO2016049174A1 (enExample)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HRP20220479T1 (hr) 2016-06-01 2022-05-27 Athira Pharma, Inc. Spojevi
CN111051338B (zh) * 2017-06-29 2024-12-03 乌雷卡有限公司 具有改进的药物学性能的前药肽
TW201917134A (zh) 2017-08-17 2019-05-01 丹麥商諾佛 儂迪克股份有限公司 新穎的醯基化胰島素類似物及其用途
AU2021312323A1 (en) 2020-07-22 2023-02-02 Novo Nordisk A/S Co-agonists at GLP-1 and GIP receptors suitable for oral delivery
US20230399373A1 (en) * 2020-10-22 2023-12-14 The Trustees Of Indiana University Molecular designs of glucose-responsive and glucose-cleavable insulin analogues
EP4240420A1 (en) 2020-11-06 2023-09-13 Novo Nordisk A/S Glp-1 prodrugs and uses hereof
WO2023012263A1 (en) 2021-08-04 2023-02-09 Novo Nordisk A/S Solid oral peptide formulations
TW202330584A (zh) 2022-01-20 2023-08-01 丹麥商諾佛 儂迪克股份有限公司 前藥及其用途
CN119173275A (zh) 2022-05-10 2024-12-20 诺和诺德股份有限公司 Glp-1多肽的前药及其用途
TW202421645A (zh) 2022-11-25 2024-06-01 丹麥商諾佛 儂迪克股份有限公司 如glp—1之肽治療劑的口服投與

Family Cites Families (74)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3740385A (en) 1970-05-07 1973-06-19 M Ondetti N-terminal derivatives of secretin
US4275152A (en) 1977-02-03 1981-06-23 Eastman Kodak Company Hydrolysis of protein-bound cholesterol esters
DK119785D0 (da) 1985-03-15 1985-03-15 Nordisk Gentofte Insulinpraeparat
PT83613B (en) 1985-10-28 1988-11-21 Lilly Co Eli Process for the selective chemical removal of a protein amino-terminal residue
US4741897A (en) 1986-07-08 1988-05-03 Baxter Travenol Thyroxine analogs and reagents for thyroid hormone assays
US4876242A (en) 1987-09-21 1989-10-24 Merck & Co., Inc. Human insulin-like growth factor analoges with reduced binding to serum carrier proteins and their production in yeast
GB8728561D0 (en) 1987-12-07 1988-01-13 Glaxo Group Ltd Chemical compounds
US5514646A (en) 1989-02-09 1996-05-07 Chance; Ronald E. Insulin analogs modified at position 29 of the B chain
US6225449B1 (en) 1991-10-04 2001-05-01 Washington University Hormone analogs with multiple CTP extensions
AU631868B2 (en) 1989-04-20 1992-12-10 Mount Sinai School Of Medicine Of The City University Of New York, The Hepatospecific insulin analogues
US5268453A (en) 1991-08-08 1993-12-07 Scios Inc. Tissue-selective insulin analogs
EP0688364A4 (en) 1993-03-09 1997-10-15 Abbott Lab ENZYMES PRODUCED BY GENETIC ENGINEERING AND CONJUGATES OF SAID ENZYMES FOR DIAGNOSTIC ANALYSIS
US5359030A (en) 1993-05-10 1994-10-25 Protein Delivery, Inc. Conjugation-stabilized polypeptide compositions, therapeutic delivery and diagnostic formulations comprising same, and method of making and using the same
US6476290B1 (en) 1995-04-19 2002-11-05 Dalhousie University Transgenic tilapia comprising a humanized insulin gene
AU5724996A (en) 1995-05-05 1996-11-21 Eli Lilly And Company Single chain insulin with high bioactivity
US6180767B1 (en) 1996-01-11 2001-01-30 Thomas Jefferson University Peptide nucleic acid conjugates
EP0932614A1 (en) 1996-09-09 1999-08-04 Zealand Pharmaceuticals A/S Peptide prodrugs containing an alpha-hydroxyacid linker
UA65549C2 (uk) 1996-11-05 2004-04-15 Елі Ліллі Енд Компані Спосіб регулювання ожиріння шляхом периферійного введення аналогів та похідних glp-1 (варіанти) та фармацевтична композиція
IL137904A0 (en) 1998-02-23 2001-10-31 Neurocrine Biosciences Inc Peptide analogues of insulin and pharmaceutical compositions containing the same
AU757658B2 (en) 1998-03-09 2003-02-27 Zealand Pharma A/S Pharmacologically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis
US20030236190A1 (en) 1998-09-02 2003-12-25 Renuka Pillutla Isulin and IGF-1 receptor agonists and antagonists
US6875741B2 (en) 1998-09-02 2005-04-05 Renuka Pillutla Insulin and IGF-1 receptor agonists and antagonists
DE19908041A1 (de) 1999-02-24 2000-08-31 Hoecker Hartwig Kovalent verbrückte Insulindimere
DE60012721T4 (de) 1999-03-29 2010-09-09 Uutech Ltd., Coleraine Analoge des magensaft inhibierenden peptides und ihre verwendung für die behandlung von diabetes
US6746853B1 (en) 1999-05-19 2004-06-08 Xencor, Inc. Proteins with insulin-like activity useful in the treatment of diabetes
AUPQ661800A0 (en) 2000-03-31 2000-05-04 Metabolic Pharmaceuticals Limited Insulin-potentiating compounds
EP1305338A2 (en) 2000-08-02 2003-05-02 Theratechnologies Inc. Modified peptides with increased potency
AU2001284697A1 (en) 2000-08-04 2002-02-18 Dmi Biosciences, Inc. Method of synthesizing diketopiperazines
ATE516820T1 (de) 2000-09-29 2011-08-15 Schering Corp Pegyliertes interleukin 10
KR100449454B1 (ko) 2000-10-02 2004-09-21 이현철 단일사슬 인슐린 유도체의 유전자를 포함하는 당뇨병치료용 벡터
KR101229995B1 (ko) 2000-12-11 2013-02-06 씨제이 주식회사 생체내 에리스로포이에틴 활성이 증진된 융합단백질
EP1243276A1 (en) 2001-03-23 2002-09-25 Franciscus Marinus Hendrikus De Groot Elongated and multiple spacers containing activatible prodrugs
IL158418A0 (en) 2001-04-19 2004-05-12 Scripps Research Inst In vivo incorporation of unnatural amino acids
CZ2004710A3 (cs) 2001-12-20 2005-02-16 Eli Lilly And Company Inzulínová sloučenina s protrahovaným účinkem
IL163666A0 (en) * 2002-02-22 2005-12-18 New River Pharmaceuticals Inc Active agent delivery systems and methods for protecting and administering active agents
FR2842209B1 (fr) 2002-07-09 2007-11-23 Nouvelle protease aspartique dite saspase et son utilisation dans le domaine cosmetique et therapeutique
US20050059605A1 (en) 2003-01-31 2005-03-17 Krishna Peri Chemically modified metabolites of regulatory peptides and methods of producing and using same
WO2004078777A2 (en) 2003-03-04 2004-09-16 Biorexis Pharmaceutical Corporation Dipeptidyl-peptidase protected proteins
AU2004231461B2 (en) 2003-03-19 2009-11-12 Eli Lilly And Company Polyethelene glycol linked GLP-1 compounds
CA2521784C (en) 2003-04-08 2012-03-27 Yeda Research And Development Co. Ltd. Reversible pegylated drugs
GB0310593D0 (en) * 2003-05-08 2003-06-11 Leuven K U Res & Dev Peptidic prodrugs
KR101241862B1 (ko) 2003-09-19 2013-03-13 노보 노르디스크 에이/에스 신규 glp-1 유도체
WO2005035003A2 (en) 2003-09-22 2005-04-21 Dihedron Corporation Compositions and methods for increasing drug efficiency
WO2005044839A2 (en) 2003-11-05 2005-05-19 Dana-Farber Cancer Institute, Inc. Stabilized alpha helical peptides and uses thereof
JP5697831B2 (ja) 2003-12-03 2015-04-08 ノヴォ ノルディスク アー/エス 単鎖インシュリン
CA2582552A1 (en) 2004-10-21 2006-05-04 Igf Oncology, Llc Toxins and radionuclides coupled to igf-1 receptor ligands for treatment of cancer
JP2008533100A (ja) 2005-03-18 2008-08-21 ノボ ノルディスク アクティーゼルスカブ Peg化された単鎖インスリン
US7521211B2 (en) 2005-04-05 2009-04-21 Regeneron Pharmaceuticals, Inc IGF-1 and IGF-2 chimeric polypeptides and therapeutic uses thereof
US20090209453A1 (en) 2005-04-13 2009-08-20 University Of Medicine And Dentistry Of New Jersey Glycoprotein Hormone Analogs
US8304386B2 (en) 2006-02-03 2012-11-06 Prolor Biotech, Inc. Long-acting growth hormone and methods of producing same
EP1991575A1 (en) 2006-02-21 2008-11-19 Novo Nordisk A/S Single-chain insulin analogues and pharmaceutical formulations thereof
US20090054305A1 (en) 2006-03-15 2009-02-26 Novo Nordisk A/S Mixtures of Amylin and Insulin
US9505823B2 (en) 2006-08-07 2016-11-29 TEV A Biopharmaceuticals USA, Inc. Albumin-insulin fusion proteins
WO2008021560A2 (en) 2006-08-17 2008-02-21 Amylin Pharmaceuticals, Inc. Dpp-iv resistant gip hybrid polypeptides with selectable properties
CL2007002502A1 (es) 2006-08-31 2008-05-30 Hoffmann La Roche Variantes del factor de crecimiento similar a insulina-1 humano (igf-1) pegilados en lisina; metodo de produccion; proteina de fusion que la comprende; y su uso para tratar la enfermedad de alzheimer.
WO2008030558A2 (en) 2006-09-08 2008-03-13 Ambrx, Inc. Modified human plasma polypeptide or fc scaffolds and their uses
US20090098130A1 (en) 2007-01-05 2009-04-16 Bradshaw Curt W Glucagon-like protein-1 receptor (glp-1r) agonist compounds
EP2036539A1 (en) 2007-09-11 2009-03-18 Novo Nordisk A/S Stable formulations of amylin and its analogues
EP2036923A1 (en) 2007-09-11 2009-03-18 Novo Nordisk A/S Improved derivates of amylin
US8261025B2 (en) 2007-11-12 2012-09-04 International Business Machines Corporation Software pipelining on a network on chip
ES2632504T3 (es) 2007-11-20 2017-09-13 Ambrx, Inc. Polipéptidos de insulina modificados y sus usos
WO2009099763A1 (en) 2008-01-30 2009-08-13 Indiana University Research And Technology Corporation Ester-based peptide prodrugs
CA2712224C (en) 2008-02-01 2016-03-08 Ascendis Pharma As Prodrug comprising a drug linker conjugate
US20110144306A1 (en) 2008-07-23 2011-06-16 President And Fellows Of Harvard College Ligation of stapled polypeptides
KR20110114568A (ko) 2008-12-19 2011-10-19 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 디펩티드 링크된 약효 물질
CN102245624B (zh) 2008-12-19 2016-08-10 印第安纳大学研究及科技有限公司 基于酰胺的胰岛素前药
RU2550696C2 (ru) 2008-12-19 2015-05-10 Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн Основанные на амидах пролекарства пептидов глюкагонового надсемейства
JP5789515B2 (ja) 2008-12-19 2015-10-07 インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションIndiana University Research And Technology Corporation インスリン類似体
EP2408470A4 (en) 2009-03-20 2012-08-29 Smartcells Inc SOLUBLE NONDEPOT INSULIN CONJUGATE AND ITS USE
EP2292306B1 (en) 2009-09-02 2013-05-01 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Method for separation of racemic compound-forming chiral substances by a cyclic crystallization process and a crystallization device
EP2582719B1 (en) 2010-06-16 2016-08-10 Indiana University Research and Technology Corporation Single chain insulin agonists exhibiting high activity at the insulin receptor
MX2012014576A (es) 2010-06-24 2013-02-21 Univ Indiana Res & Tech Corp Profarmacos de peptido de la superfamilia de glucagon basado en amida.
WO2011163460A1 (en) 2010-06-24 2011-12-29 Indiana University Research And Technology Corporation Yl-based insulin-like growth factors exhibiting high activity at the insulin receptor
CA2803164C (en) 2010-06-24 2018-08-21 Indiana University Research And Technology Corporation Amide-based insulin prodrugs

Also Published As

Publication number Publication date
WO2016049174A1 (en) 2016-03-31
EP3197912A4 (en) 2018-06-06
EP3197912A1 (en) 2017-08-02
US10385107B2 (en) 2019-08-20
CN107001441A (zh) 2017-08-01
US20170283479A1 (en) 2017-10-05
EP3197912B1 (en) 2023-01-04
JP6701208B2 (ja) 2020-05-27
JP2017534675A (ja) 2017-11-24

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