ATE263185T1 - Verfahren zur herstellung von acylierten proteinpuder - Google Patents

Verfahren zur herstellung von acylierten proteinpuder

Info

Publication number
ATE263185T1
ATE263185T1 AT96303974T AT96303974T ATE263185T1 AT E263185 T1 ATE263185 T1 AT E263185T1 AT 96303974 T AT96303974 T AT 96303974T AT 96303974 T AT96303974 T AT 96303974T AT E263185 T1 ATE263185 T1 AT E263185T1
Authority
AT
Austria
Prior art keywords
protein
protein powder
acylated protein
producing acylated
isoelectric
Prior art date
Application number
AT96303974T
Other languages
English (en)
Inventor
Jeffrey Clayton Baker
Brian A Moser
Warren E Schrader
Original Assignee
Lilly Co Eli
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 Lilly Co Eli filed Critical Lilly Co Eli
Application granted granted Critical
Publication of ATE263185T1 publication Critical patent/ATE263185T1/de

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14—Extraction; Separation; Purification
    • C07K1/30—Extraction; Separation; Purification by precipitation
    • 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
    • A61K38/22—Hormones
    • A61K38/28—Insulins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C07K14/62—Insulins

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Toxicology (AREA)
  • Analytical Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
AT96303974T 1995-06-07 1996-05-31 Verfahren zur herstellung von acylierten proteinpuder ATE263185T1 (de)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US08/484,220 US5700904A (en) 1995-06-07 1995-06-07 Preparation of an acylated protein powder

Publications (1)

Publication Number Publication Date
ATE263185T1 true ATE263185T1 (de) 2004-04-15

Family

ID=23923252

Family Applications (1)

Application Number Title Priority Date Filing Date
AT96303974T ATE263185T1 (de) 1995-06-07 1996-05-31 Verfahren zur herstellung von acylierten proteinpuder

Country Status (21)

Country Link
US (1) US5700904A (de)
EP (1) EP0747391B1 (de)
JP (1) JP3844504B2 (de)
KR (1) KR19990022590A (de)
CN (1) CN1192218A (de)
AT (1) ATE263185T1 (de)
AU (1) AU703032B2 (de)
BR (1) BR9608729A (de)
CA (1) CA2223389A1 (de)
CZ (1) CZ388197A3 (de)
DE (1) DE69631996T2 (de)
DK (1) DK0747391T3 (de)
EA (1) EA199800042A1 (de)
ES (1) ES2216039T3 (de)
HU (1) HUP9900877A3 (de)
IL (1) IL122460A0 (de)
NO (1) NO975583L (de)
NZ (1) NZ309371A (de)
PL (1) PL323994A1 (de)
TR (1) TR199701528T1 (de)
WO (1) WO1996040730A1 (de)

Families Citing this family (68)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9316895D0 (en) 1993-08-13 1993-09-29 Guy S And St Thomas Hospitals Hepatoselective insulin analogues
US5986050A (en) * 1996-12-26 1999-11-16 Poly-Med, Inc. Peracylated proteins and synthetic polypeptides and process for making the same
US5898067A (en) * 1997-02-07 1999-04-27 Novo Nordisk A/S Crystallization of proteins
AU5749198A (en) * 1997-02-07 1998-08-26 Novo Nordisk A/S Crystallisation of proteins
US5898028A (en) * 1997-03-20 1999-04-27 Novo Nordisk A/S Method for producing powder formulation comprising an insulin
US6310038B1 (en) * 1997-03-20 2001-10-30 Novo Nordisk A/S Pulmonary insulin crystals
JP3764174B2 (ja) * 1997-03-20 2006-04-05 ノボ ノルディスク アクティーゼルスカブ 肺用組成物において使用するための亜鉛非含有のインスリン結晶
JP2001521004A (ja) * 1997-10-24 2001-11-06 イーライ・リリー・アンド・カンパニー 脂肪酸−アシル化インスリン類似体
ZA989644B (en) * 1997-10-24 2000-04-25 Lilly Co Eli Insoluble insulen compositions.
ZA989744B (en) * 1997-10-31 2000-04-26 Lilly Co Eli Method for administering acylated insulin.
EP1396272A1 (de) * 1997-12-23 2004-03-10 Eli Lilly & Company Unlöslische Insulin Zusammensetzungen zur Regelung der Blutglukose
CO4970787A1 (es) * 1997-12-23 2000-11-07 Lilly Co Eli Composiciones insolubles de insulina y derivados de insulina que controlan la glucosa sanguinea
US6855260B1 (en) 1999-06-07 2005-02-15 Roe-Hoan Yoon Methods of enhancing fine particle dewatering
US6526675B1 (en) * 1999-06-07 2003-03-04 Roe-Hoan Yoon Methods of using natural products as dewatering aids for fine particles
US7169889B1 (en) 1999-06-19 2007-01-30 Biocon Limited Insulin prodrugs hydrolyzable in vivo to yield peglylated insulin
US6799682B1 (en) 2000-05-16 2004-10-05 Roe-Hoan Yoon Method of increasing flotation rate
US6663602B2 (en) 2000-06-16 2003-12-16 Novo Nordisk A/S Injection device
US6867183B2 (en) 2001-02-15 2005-03-15 Nobex Corporation Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith
US7060675B2 (en) 2001-02-15 2006-06-13 Nobex Corporation Methods of treating diabetes mellitus
US6835802B2 (en) * 2001-06-04 2004-12-28 Nobex Corporation Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties
US6828297B2 (en) 2001-06-04 2004-12-07 Nobex Corporation Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same
US7713932B2 (en) 2001-06-04 2010-05-11 Biocon Limited Calcitonin drug-oligomer conjugates, and uses thereof
US6713452B2 (en) * 2001-06-04 2004-03-30 Nobex Corporation Mixtures of calcitonin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same
US6858580B2 (en) * 2001-06-04 2005-02-22 Nobex Corporation Mixtures of drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same
US6828305B2 (en) 2001-06-04 2004-12-07 Nobex Corporation Mixtures of growth hormone drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same
US6913903B2 (en) 2001-09-07 2005-07-05 Nobex Corporation Methods of synthesizing insulin polypeptide-oligomer conjugates, and proinsulin polypeptide-oligomer conjugates and methods of synthesizing same
US7166571B2 (en) 2001-09-07 2007-01-23 Biocon Limited Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same
US6770625B2 (en) 2001-09-07 2004-08-03 Nobex Corporation Pharmaceutical compositions of calcitonin drug-oligomer conjugates and methods of treating diseases therewith
US7312192B2 (en) 2001-09-07 2007-12-25 Biocon Limited Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same
US7196059B2 (en) 2001-09-07 2007-03-27 Biocon Limited Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith
US7030082B2 (en) * 2001-09-07 2006-04-18 Nobex Corporation Pharmaceutical compositions of drug-oligomer conjugates and methods of treating disease therewith
TWI329105B (en) 2002-02-01 2010-08-21 Rigel Pharmaceuticals Inc 2,4-pyrimidinediamine compounds and their uses
US7378438B2 (en) * 2002-04-19 2008-05-27 Yissum Research Development Company Of The Hebrew University Of Jerusalem Beta-agonist compounds comprising nitric oxide donor groups and reactive oxygen species scavenger groups and their use in the treatment of respiratory disorders
AU2003236521A1 (en) 2002-06-13 2003-12-31 Nobex Corporation Methods of reducing hypoglycemic episodes in the treatment of diabetes mellitus
AU2003278565A1 (en) * 2002-10-25 2004-05-13 Yissum Research Development Company Of The Hebrew University Of Jerusalem Steroid compounds comprising superoxide dismutase mimic groups and nitric oxide donor groups, and their use in the preparation of medicaments
AU2004232858B2 (en) 2003-04-23 2009-07-09 Mannkind Corporation Hydraulically actuated pump for long duration medicament administration
CN102358738A (zh) 2003-07-30 2012-02-22 里格尔药品股份有限公司 2,4-嘧啶二胺化合物及其预防和治疗自体免疫疾病的用途
WO2006014425A1 (en) 2004-07-02 2006-02-09 Biovalve Technologies, Inc. Methods and devices for delivering glp-1 and uses thereof
CN103223160B (zh) 2004-07-19 2015-02-18 比奥孔有限公司 胰岛素-低聚物共轭物,制剂及其用途
ZA200703707B (en) 2004-10-21 2009-02-25 Novo Nordisk As Dial-Down Mechanism for Wind-up Pen
JP4022595B2 (ja) * 2004-10-26 2007-12-19 コニカミノルタオプト株式会社 撮影装置
CA2597176C (en) 2005-02-04 2013-10-22 Mineral And Coal Technologies, Inc. Improving the separation of diamond from gangue minerals
EP1877121B1 (de) 2005-04-24 2015-09-23 Novo Nordisk A/S Injektionsvorrichtung
EP1904457B1 (de) 2005-06-08 2017-09-06 Rigel Pharmaceuticals, Inc. Zusammensetzungen und verfahren zur inhibierung des jak-pfades
US20070203161A1 (en) * 2006-02-24 2007-08-30 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
US7741281B2 (en) * 2005-11-03 2010-06-22 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
JP2009528295A (ja) * 2006-02-24 2009-08-06 ライジェル ファーマシューティカルズ， インコーポレイテッド Ｊａｋ経路の阻害のための組成物および方法
WO2007104636A1 (en) 2006-03-10 2007-09-20 Novo Nordisk A/S An injection device and a method of changing a cartridge in the device
US8361036B2 (en) 2006-03-10 2013-01-29 Novo Nordisk A/S Injection device having a gearing arrangement
AU2007233231B2 (en) 2006-03-30 2011-02-24 Mannkind Corporation Multi-cartridge fluid delivery device
EP2004671B1 (de) 2006-03-30 2015-12-09 Novo Nordisk A/S Zwei-phasen fällung von proteinen
US7714025B2 (en) * 2006-05-10 2010-05-11 Arizona Biomedical Research Commission Modified chalcone compounds as antimitotic agents
WO2007132019A1 (en) 2006-05-16 2007-11-22 Novo Nordisk A/S A gearing mechanism for an injection device
PL2023982T3 (pl) 2006-05-18 2012-11-30 Novo Nordisk As Urządzenie wstrzykujące ze środkami blokującymi
RU2468829C2 (ru) 2007-03-23 2012-12-10 Ново Нордиск А/С Инъекционное устройство, содержащее стопорную гайку
US9241908B2 (en) 2007-10-16 2016-01-26 Biocon Limited Orally administrable solid pharmaceutical composition and a process thereof
PL2389372T3 (pl) 2009-01-23 2016-02-29 Rigel Pharmaceuticals Inc Kompozycje i sposoby hamowania szlaku JAK
WO2011064316A2 (en) 2009-11-25 2011-06-03 Paolo Botti Mucosal delivery of peptides
KR101937495B1 (ko) 2010-07-28 2019-01-10 리겔 파마슈티칼스, 인크. Ｊａｋ 경로의 억제를 위한 조성물 및 방법
RU2014128518A (ru) 2011-12-29 2016-02-20 Ново Нордиск А/С Механизм увеличения/уменьшения дозы для взводимого шприца-ручки
NZ629898A (en) 2012-03-23 2016-04-29 Oxigene Inc Compositions and methods for inhibition of cathepsins
US11206846B2 (en) * 2017-05-02 2021-12-28 Leprino Foods Company High purity alpha lactalbumin and methods of making
NZ762877A (en) 2017-09-26 2023-06-30 Biocon Biologics India Ltd Integrated automated filtration for separation, washing and drying of peptide crystals
WO2020092845A1 (en) 2018-11-01 2020-05-07 Rigel Pharmaceuticals, Inc. Method and composition embodiments for treating acute myeloid leukemia
US20200377518A1 (en) 2019-05-29 2020-12-03 Rigel Pharmaceuticals, Inc. Method of preventing and treating thrombosis
BR112022001418A2 (pt) 2019-08-08 2022-06-07 Rigel Pharmaceuticals Inc Compostos e método para tratar a síndrome de liberação de citocinas
WO2021030526A1 (en) 2019-08-14 2021-02-18 Rigel Pharmaceuticals, Inc. Method of blocking or ameliorating cytokine release syndrome
US12384775B2 (en) 2022-03-23 2025-08-12 Rigel Pharmaceuticals, Inc. Pyrimid-2-yl-pyrazole compounds as IRAK inhibitors

Family Cites Families (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1468831A (fr) * 1965-10-05 1967-02-10 Roussel Uclaf Procédé de préparation de nouveaux composés polypeptidiques et produits en résultant
DE1902865A1 (de) * 1968-02-01 1969-09-11 American Home Prod Substituierte Insulin-Derivate,Verfahren zu ihrer Herstellung und ihre Verwendung in pharmazeutischen Zubereitungen
US3591574A (en) * 1968-05-29 1971-07-06 American Home Prod Tri-n-phenylglycyl derivatives of insulin
US3528960A (en) * 1968-10-07 1970-09-15 Lilly Co Eli N-carboxyaroyl insulins
US3823125A (en) * 1969-10-14 1974-07-09 American Home Prod N-aminoacyl-substituted insulins
US3752798A (en) * 1969-12-02 1973-08-14 G Amird Tris-na1,nb1,nepsilonb29 - (3-x-3-oxo - 1-y-prop-1-en-1-yl)(ndelta-(4-z-6-r-pyrimidin - 2 - yl) ornithine b22)-insulins and their preparation
US3869437A (en) * 1970-05-08 1975-03-04 Nat Res Dev Mono-, di, and N{HD A1{B , N{HU B1{B , N{HU B29{B -tri-acylated insulin
US3950517A (en) * 1970-05-08 1976-04-13 National Research Development Corporation Insulin derivatives
GB1381274A (en) * 1971-01-28 1975-01-22 Nat Res Dev Insulin derivatives
GB1381273A (en) * 1971-01-28 1975-01-22 Nat Res Dev Insulin derivatives
US3864325A (en) * 1971-11-18 1975-02-04 Nat Res Dev (N{HU Al{b , N{HU Bl{b , N{HU B29{B , carbamoyl)-(O{HU A14{B , O{HU B16{B , O{HU B26{B aryl) insulin derivatives
BE791949A (fr) * 1971-11-27 1973-05-28 Schering Ag Derives d'insuline, leur preparation et leur utilisation
US3843815A (en) * 1972-02-10 1974-10-22 Gen Foods Corp Inhibiting gel formation in meat-in-gravy products
US3755569A (en) * 1972-07-25 1973-08-28 American Home Prod Acyl substituted insulins
DE2252157C3 (de) * 1972-10-25 1976-03-18 Hoechst Ag Zwischenprodukte zur herstellung von insulin, insulin-analogen und -derivaten und verfahren zur herstellung von insulin, insulin analogen und derivaten
DE2253327A1 (de) * 1972-10-31 1974-05-09 Hoechst Ag Verfahren zur herstellung von insulin, insulin-analogen und -derivaten
NL7314766A (de) * 1972-10-31 1974-05-02
DE2428412A1 (de) * 1974-06-12 1976-01-15 Hoechst Ag Verfahren zur herstellung von insulin, insulin-analogen und -derivaten
DE2439296A1 (de) * 1974-08-16 1976-02-26 Hoechst Ag Verfahren zur herstellung von insulin, insulin-analogen und -derivaten
GB1492997A (en) * 1976-07-21 1977-11-23 Nat Res Dev Insulin derivatives
EP0014815A3 (de) * 1978-12-20 1980-10-29 Ciba-Geigy Ag Peptidderivate, Verfahren zu deren Herstellung und Zwischenprodukte sowie pharmazeutische Präparate mit einer dieser Verbindungen
US4486458A (en) * 1982-09-07 1984-12-04 A. E. Staley Manufacturing Company Non-gelling corn steep liquor
PH25772A (en) * 1985-08-30 1991-10-18 Novo Industri As Insulin analogues, process for their preparation
JPS6255096A (ja) * 1986-06-12 1987-03-10 Nippon Shinyaku Co Ltd 新規な脂肪酸アシル化合物
JPH01254699A (ja) * 1988-04-05 1989-10-11 Kodama Kk インスリン誘導体及びその用途
PT93057B (pt) * 1989-02-09 1995-12-29 Lilly Co Eli Processo para a preparacao de analogos da insulina
WO1992001476A1 (en) * 1990-07-26 1992-02-06 University Of Iowa Research Foundation Novel drug delivery systems for proteins and peptides using albumin as a carrier molecule
US5304473A (en) * 1991-06-11 1994-04-19 Eli Lilly And Company A-C-B proinsulin, method of manufacturing and using same, and intermediates in insulin production
AU5574094A (en) * 1992-11-30 1994-06-22 Biosignal Kutato-Fejleszto Kft. Polyunsaturated fatty acyl-peptide composition

Also Published As

Publication number Publication date
MX9709657A (es) 1998-07-31
CZ388197A3 (cs) 1998-05-13
AU703032B2 (en) 1999-03-11
ES2216039T3 (es) 2004-10-16
EP0747391A2 (de) 1996-12-11
EP0747391A3 (de) 1997-05-21
US5700904A (en) 1997-12-23
HUP9900877A2 (hu) 1999-07-28
HUP9900877A3 (en) 1999-11-29
TR199701528T1 (xx) 1998-03-21
WO1996040730A1 (en) 1996-12-19
KR19990022590A (ko) 1999-03-25
CN1192218A (zh) 1998-09-02
IL122460A0 (en) 1998-06-15
NO975583D0 (no) 1997-12-03
EA199800042A1 (ru) 1998-08-27
CA2223389A1 (en) 1996-12-19
NO975583L (no) 1997-12-03
JP3844504B2 (ja) 2006-11-15
BR9608729A (pt) 1999-06-29
EP0747391B1 (de) 2004-03-31
DK0747391T3 (da) 2004-07-19
NZ309371A (en) 1999-09-29
DE69631996T2 (de) 2005-01-27
JPH11506738A (ja) 1999-06-15
AU5951396A (en) 1996-12-30
DE69631996D1 (de) 2004-05-06
PL323994A1 (en) 1998-04-27

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