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)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Organic Chemistry (AREA)
  • Endocrinology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Toxicology (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Emergency Medicine (AREA)
  • Hematology (AREA)
  • Obesity (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 (OSRAM)
EP (1) EP3197912B1 (OSRAM)
JP (1) JP6701208B2 (OSRAM)
CN (1) CN107001441A (OSRAM)
ES (1) ES2947409T3 (OSRAM)
WO (1) WO2016049174A1 (OSRAM)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL3464336T3 (pl) 2016-06-01 2022-05-16 Athira Pharma, Inc. Związki
AU2018293467B2 (en) * 2017-06-29 2020-11-05 ImmuPharma Biotech SAS Pro-drug peptide with improved pharmaceutical properties
AU2018317810A1 (en) 2017-08-17 2020-03-19 Novo Nordisk A/S Novel acylated insulin analogues and uses thereof
PE20231841A1 (es) 2020-07-22 2023-11-21 Novo Nordisk As Coagonistas de los receptores glp-1 y gip adecuados para el suministro oral
US20230399373A1 (en) * 2020-10-22 2023-12-14 The Trustees Of Indiana University Molecular designs of glucose-responsive and glucose-cleavable insulin analogues
WO2022096636A1 (en) 2020-11-06 2022-05-12 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
AU6550294A (en) 1993-03-09 1994-09-26 Abbott Laboratories Genetically engineered enzymes and their conjugates for diagnostic assays
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
IL118127A0 (en) 1995-05-05 1996-09-12 Lilly Co Eli Single chain insulin with high bioactivity
US6180767B1 (en) 1996-01-11 2001-01-30 Thomas Jefferson University Peptide nucleic acid conjugates
AU724326B2 (en) 1996-09-09 2000-09-14 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
ID26788A (id) 1998-02-23 2001-02-08 Neurocrine Biosciences Inc Metoda pengobatan diabetes dengan menggunakan analogi peptida dari insulin
IL138214A0 (en) 1998-03-09 2001-10-31 Zealand Pharmaceuticals As Pharmacolgically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis
US6875741B2 (en) 1998-09-02 2005-04-05 Renuka Pillutla Insulin and IGF-1 receptor agonists and antagonists
US20030236190A1 (en) 1998-09-02 2003-12-25 Renuka Pillutla Isulin and IGF-1 receptor agonists and antagonists
DE19908041A1 (de) 1999-02-24 2000-08-31 Hoecker Hartwig Kovalent verbrückte Insulindimere
ATE272650T1 (de) 1999-03-29 2004-08-15 Uutech Ltd 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
WO2002010195A2 (en) 2000-08-02 2002-02-07 Theratechnologies Inc. Modified peptides with increased potency
WO2002012201A1 (en) 2000-08-04 2002-02-14 Dmi Biosciences, Inc. Method of synthesizing diketopiperazines
WO2003079972A2 (en) * 2002-02-22 2003-10-02 New River Parmaceuticals Inc. Active agent delivery systems and methods for protecting and administering active agents
ES2367891T3 (es) 2000-09-29 2011-11-10 Schering Corporation Interleucina-10 pegilada.
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
DK2322631T3 (en) 2001-04-19 2015-01-12 Scripps Research Inst Methods and compositions for the production of orthogonal tRNA-aminoacyl-tRNA syntetasepar
EP1545460A4 (en) 2001-12-20 2005-11-16 Lilly Co Eli INSULIN MOLECULE WITH TEMPORARY EFFECT
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
EP1626981A4 (en) 2003-03-04 2006-11-22 Biorexis Pharmaceutical Corp PROTEINS PROTECTED AGAINST DIPEPTIDYLPEPTIDASE
EA009366B1 (ru) 2003-03-19 2007-12-28 Эли Лилли Энд Компани Связанные с полиэтиленгликолем соединения гпп-1
JP4698579B2 (ja) 2003-04-08 2011-06-08 イエダ リサーチ アンド デベロップメント カンパニー リミテッド 可逆的peg化薬物
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
US20050187147A1 (en) 2003-09-22 2005-08-25 Newman Michael J. Compositions and methods for increasing drug efficiency
SI1680443T1 (sl) 2003-11-05 2014-01-31 Dana-Farber Cancer Institute, Inc. Stabilizirani peptidi z alfa vijačnico in uporabe le-teh
ATE517119T1 (de) 2003-12-03 2011-08-15 Novo Nordisk As Einzelketteninsulin
EP1812082B1 (en) 2004-10-21 2013-08-14 IGF Oncology, LLC Toxins and radionuclides coupled to IGF-1 receptor ligands for the treatment of cancer
WO2006097521A1 (en) 2005-03-18 2006-09-21 Novo Nordisk A/S Pegylated single-chain insulin
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
JP2009527526A (ja) 2006-02-21 2009-07-30 ノボ・ノルデイスク・エー/エス 単鎖インスリンのアナログとその製薬的製剤
EP2241327A1 (en) 2006-03-15 2010-10-20 Novo Nordisk A/S Mixtures of Amylin and Insulin
WO2008019368A2 (en) 2006-08-07 2008-02-14 Teva Biopharmaceuticals Usa, Inc. Albumin-insulin fusion proteins
JP5399244B2 (ja) 2006-08-17 2014-01-29 アミリン・ファーマシューティカルズ,リミテッド・ライアビリティ・カンパニー 選択可能な特性を持つdpp−iv耐性gipハイブリッドポリペプチド
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.
CN104193815A (zh) 2006-09-08 2014-12-10 Ambrx公司 经修饰的人类血浆多肽或Fc骨架和其用途
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
EP2930182A1 (en) 2007-11-20 2015-10-14 Ambrx, Inc. Modified insulin polypeptides and their uses
US20110065633A1 (en) 2008-01-30 2011-03-17 Indiana University Research And Technology Corporation Ester-based peptide prodrugs
MX2010008024A (es) 2008-02-01 2010-12-21 Ascendis Pharma As Profarmaco que comprende un enlazador que se puede separar por si mismo.
WO2010011313A2 (en) 2008-07-23 2010-01-28 President And Fellows Of Harvard College Ligation of stapled polypeptides
US20110237493A1 (en) 2008-12-19 2011-09-29 Indiana University Research And Technology Corporation Dipeptide linked medicinal agents
EP2376520B1 (en) 2008-12-19 2014-02-12 Indiana University Research&Technology Corporation Insulin analogs
WO2010071807A1 (en) 2008-12-19 2010-06-24 Indiana University Research And Technology Corporation Amide based glucagon superfamily peptide prodrugs
CA2744558A1 (en) * 2008-12-19 2010-07-15 Indiana University Research And Technology Corporation Amide-based insulin prodrugs
WO2010107520A1 (en) 2009-03-20 2010-09-23 Smartcells, Inc. Soluble non-depot insulin conjugates and uses thereof
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
CN103068842B (zh) 2010-06-16 2016-10-19 印第安纳大学研究及科技有限公司 对胰岛素受体具有高活性的单链胰岛素激动剂
CA2803164C (en) * 2010-06-24 2018-08-21 Indiana University Research And Technology Corporation Amide-based insulin prodrugs
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
KR20130102470A (ko) 2010-06-24 2013-09-17 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 아미드계 글루카곤 슈퍼패밀리 펩티드 프로드러그

Also Published As

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

Similar Documents

Publication Publication Date Title
ES2947409T3 (es) Profármacos de insulina a base de amida lipídica
AU2009335715B2 (en) Amide-based insulin prodrugs
AU2009335712B2 (en) Insulin analogs
ES2822994T3 (es) Conjugados de incretina-insulina
CA2802485C (en) Single chain insulin agonists exhibiting high activity at the insulin receptor
JP5912112B2 (ja) アミド系インスリンプロドラッグ
CA2747720A1 (en) Yl-based insulin-like growth factors exhibiting high activity at the insulin receptor
WO2011163460A1 (en) Yl-based insulin-like growth factors exhibiting high activity at the insulin receptor
WO2017210077A1 (en) Single chain insulin prodrugs