DOP2011000244A - Sistemas basados en conjugados para entrega farmacologica controlada - Google Patents

Sistemas basados en conjugados para entrega farmacologica controlada

Info

Publication number
DOP2011000244A
DOP2011000244A DO2011000244A DO2011000244A DOP2011000244A DO P2011000244 A DOP2011000244 A DO P2011000244A DO 2011000244 A DO2011000244 A DO 2011000244A DO 2011000244 A DO2011000244 A DO 2011000244A DO P2011000244 A DOP2011000244 A DO P2011000244A
Authority
DO
Dominican Republic
Prior art keywords
certain embodiments
saccharide
glucose
ligands
conjugates
Prior art date
Application number
DO2011000244A
Other languages
English (en)
Inventor
Todd C Zion
Thomas M Lancaster
Original Assignee
Smartcells Inc
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 Smartcells Inc filed Critical Smartcells Inc
Publication of DOP2011000244A publication Critical patent/DOP2011000244A/es

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Classifications

    • 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
    • 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
    • A61K47/61—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 the organic macromolecular compound being a polysaccharide or a derivative thereof
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • 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
    • 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
    • A61K47/54—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 compound
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
    • C07K17/02—Peptides being immobilised on, or in, an organic carrier
    • C07K17/10—Peptides being immobilised on, or in, an organic carrier the carrier being a carbohydrate

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Diabetes (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Endocrinology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Biophysics (AREA)
  • Obesity (AREA)
  • Genetics & Genomics (AREA)
  • Emergency Medicine (AREA)
  • Toxicology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

En un aspecto, la divulgación proporciona procedimientos para la preparación de medicamentos útiles para controlar los perfiles farmacocinéticos (PK) y/o farmacodinán-iicos (PD) de insulina en una forma que es sensible a las concentraciones sistémicas de un sacárido tal como Ia glucosa. Como se discutió en los Ejemplos, se descubrió que cuando Ia insulina fuera conjugada con ligandos sacáridos de alta afinidad, pudo hacerse exhibir perfiles PKJPD que respondieran a cambios de concentración sacárida aún en ausencia de una molécula multivalente y exógena fijadora de sacáridos tal como Con A. Este hallazgo fue inesperado y proporciona una oportunidad sin precedentes para generar sistemas simples de insulina sensibles a sacáridos libres de lectina. En otro aspecto, Ia divulgacíón proporciona conjugados y procedimientos de ejemplo para la fabricación de los mismos. En general, estos conjugados incluyen un fármaco y uno o más Iigandos separados en donde cada uno incluye un sacárido. En ciertas realizaciones, los ligandos son capaces de competir con un sacárido (por ejemplo, glucosa o manosa) para unirse a una molécula fijadora de sacáridos endógenos. En ciertas realizaciones, los ligandos son capaces de competir con la glucosa o manosa por Ia unión a Con A. Como se explica en detalle más adelante, en ciertas realizaciones, los ligandos y el fármaco pueden estar covalente o no covalentemente unidos a una estructura de conjugado. En ciertas realizaciones, la estructura es no polimérica. En ciertas realizaciones, un conjugado puede tener un índice de polidíspersidad de uno y un peso molecular de menos de 20.000 Da aproxìmadamente. En ciertas realizaciones, el conjugado es de larga duración (es decir, presenta un perfil farmacocinético que es más sostenido que la insulina humana recombinante soluble o RHI). Como está discutido en detalle más adelante, se debe entender que los métodos, conjugados y formulaciones que se describen en este documento no están limitados de ninguna manera a solamente la entrega de insulina y se debe entender que pueden ser utilizados para liberar cualquier medicamento. También se debe entender que Ios métodos se pueden utilizar para Iiberar fármacos en respuesta a sacárídos diferentes de la glucosa. En partícular, como se indica en los ejemplos, se ha demostrado que los conjugados de ejemplo responden a sacáridos exógenos como el alfa- metil manosa y L- fucosa. En ciertas realizaciones, esto puede utilizarse para preparar conjugados que pueden ser controlados por la administración de uno de estos sacáridos exógenos (es decir, en lugar de o además de ser controlados por las fluctuaciones en la glucosa endógena).
DO2011000244A 2009-01-28 2011-07-28 Sistemas basados en conjugados para entrega farmacologica controlada DOP2011000244A (es)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US14787809P 2009-01-28 2009-01-28
US15964309P 2009-03-12 2009-03-12
US16210709P 2009-03-20 2009-03-20
US16308409P 2009-03-25 2009-03-25
US21989709P 2009-06-24 2009-06-24
US22357209P 2009-07-07 2009-07-07
US25285709P 2009-10-19 2009-10-19

Publications (1)

Publication Number Publication Date
DOP2011000244A true DOP2011000244A (es) 2011-10-15

Family

ID=42395986

Family Applications (1)

Application Number Title Priority Date Filing Date
DO2011000244A DOP2011000244A (es) 2009-01-28 2011-07-28 Sistemas basados en conjugados para entrega farmacologica controlada

Country Status (24)

Country Link
US (5) US9050370B2 (es)
EP (1) EP2391218B1 (es)
JP (3) JP5508438B2 (es)
KR (2) KR101635689B1 (es)
CN (2) CN105753965A (es)
AU (2) AU2015202872B2 (es)
BR (1) BRPI1007457A2 (es)
CA (2) CA2932926C (es)
CO (1) CO6400173A2 (es)
CR (1) CR20110408A (es)
DO (1) DOP2011000244A (es)
EA (1) EA027757B1 (es)
EC (1) ECSP11011240A (es)
ES (1) ES2791683T3 (es)
GT (1) GT201100208A (es)
IL (1) IL214099A0 (es)
MA (1) MA33064B1 (es)
MX (1) MX2011007929A (es)
NI (1) NI201100150A (es)
NZ (1) NZ594248A (es)
PE (1) PE20120583A1 (es)
SG (3) SG173112A1 (es)
TN (1) TN2011000354A1 (es)
WO (1) WO2010088294A1 (es)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BRPI1007457A2 (pt) * 2009-01-28 2015-08-25 Smartcells Inc Conjungado, formulação de liberação prolongada, e, sistema de distribuição de bomba.
WO2010088286A1 (en) 2009-01-28 2010-08-05 Smartcells, Inc. Synthetic conjugates and uses thereof
CA2750223A1 (en) 2009-01-28 2010-08-05 Smartcells, Inc. Exogenously triggered controlled release materials and uses thereof
CA2754950A1 (en) 2009-03-20 2010-09-23 Smartcells, Inc. Terminally-functionalized conjugates and uses thereof
US9095623B2 (en) 2009-03-20 2015-08-04 Smartcells, Inc. Terminally-functionalized conjugates and uses thereof
EP2598170A4 (en) * 2010-07-28 2016-07-06 Smartcells Inc MEDICINAL LIGANDEN CONJUGATES, THEIR SYNTHESIS AND INTERMEDIATE PRODUCTS THEREOF
US9074015B2 (en) 2010-07-28 2015-07-07 Smartcells, Inc. Recombinantly expressed insulin polypeptides and uses thereof
EP2598171A2 (en) * 2010-07-28 2013-06-05 Smartcells, Inc. Drug-ligand conjugates, synthesis thereof, and intermediates thereto
US9068013B2 (en) 2010-07-28 2015-06-30 Smart Cells, Inc. Recombinant lectins, binding-site modified lectins and uses thereof
US20130302825A1 (en) * 2010-10-14 2013-11-14 Merck Uses of macrophage mannose receptor to screen compounds and uses of these compounds
AR087433A1 (es) * 2011-08-08 2014-03-26 Merck Sharp & Dohme Analogos de insulina n-glicosilados
TWI439288B (zh) * 2012-10-05 2014-06-01 Univ China Medical 藥用載體及其製備方法與用途
JP6445453B2 (ja) * 2012-11-28 2018-12-26 ビクトリア リンク リミテッド 樹状コア化合物
US9707276B2 (en) 2012-12-03 2017-07-18 Merck Sharp & Dohme Corp. O-glycosylated carboxy terminal portion (CTP) peptide-based insulin and insulin analogues
US9725493B2 (en) * 2013-01-22 2017-08-08 Case Western Reserve University N-terminal truncated insulin analogues
AU2014329567B2 (en) * 2013-10-04 2019-07-25 Merck Sharp & Dohme Corp. Glucose-responsive insulin conjugates
US20180110863A1 (en) * 2015-04-08 2018-04-26 Merck Sharp & Dohme Corp. Glucose-responsive insulin conjugates
RU2018147235A (ru) * 2016-06-02 2020-07-10 Санофи Конъюгаты фармацевтического средства и фрагмента, способного связываться с глюкозочувствительным белком
WO2018136505A1 (en) 2017-01-17 2018-07-26 Wayne State University Zwitterionic polymer-insulin compositions and related methods
CN110612305B (zh) 2017-03-23 2023-11-28 维多利亚林克有限公司 硫酸乙酰肝素糖模拟化合物及其医药与化妆品用途
EP3600381A4 (en) * 2017-03-23 2021-06-16 Merck Sharp & Dohme Corp. GLUCOSE-ACTIVE INSULIN WITH A THREE-VALUE SUGAR CLUSTER FOR THE TREATMENT OF DIABETES
CN111433193A (zh) 2017-12-01 2020-07-17 赛诺菲 药剂和能够结合至葡萄糖传感蛋白的部分的新型缀合物
EP3727424A4 (en) * 2017-12-18 2021-10-27 Merck Sharp & Dohme Corp. CONJUGATE-BASED SYSTEMS FOR CONTROLLED INSULIN RELEASE
CN108610494B (zh) * 2018-03-20 2020-11-06 南京理工大学 聚醚砜/功能性含糖聚合物杂化膜的制备方法
CN110146605A (zh) * 2019-04-19 2019-08-20 南通联亚药业有限公司 一种测定格列吡嗪原料药及其缓释片中特定基因毒性杂质的分析方法
WO2020247297A1 (en) 2019-06-06 2020-12-10 Merck Sharp & Dohme Corp. Glucose-responsive insulin conjugates
CN113773400B (zh) * 2020-06-09 2023-08-18 宁波鲲鹏生物科技有限公司 一种门冬胰岛素衍生物及其应用
CN113773398B (zh) * 2020-06-10 2023-05-23 宁波鲲鹏生物科技有限公司 一种德谷胰岛素衍生物及其应用
CN112480184A (zh) * 2020-12-09 2021-03-12 上海应用技术大学 一种利用梯度点击化学合成含多种糖的树枝化糖胺的方法
CN117321695A (zh) 2021-05-05 2023-12-29 诺和诺德股份有限公司 葡萄糖敏感性胰岛素的活性胰岛素
CN120019041A (zh) * 2022-11-01 2025-05-16 三养控股公司 具有酰胺官能团和酯官能团的脂质及其制备方法
EP4620460A1 (en) * 2022-11-16 2025-09-24 Samyang Holdings Corporation Nanoparticle composition for drug delivery

Family Cites Families (131)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US39055A (en) 1863-06-30 Improvement in churns
US3591574A (en) 1968-05-29 1971-07-06 American Home Prod Tri-n-phenylglycyl derivatives of insulin
DE1793517C3 (de) 1968-09-28 1974-12-05 Farbwerke Hoechst Ag, Vormals Meister Lucius & Bruening, 6000 Frankfurt N(Al),N(B29>Bis-(tert.-butyloxycarbonyl)-insulin und Verfahren zu seiner Herstellung
US3697502A (en) * 1969-11-03 1972-10-10 Christensen Henry M Method of making iron dextran-preparations
US3847890A (en) 1971-11-01 1974-11-12 A Green Acidic monosaccharide-substituted proteins
US4086257A (en) 1976-10-12 1978-04-25 Sears Barry D Phosphatidyl quaternary ammonium compounds
EP0009842B1 (en) 1978-10-02 1982-11-10 THE PROCTER & GAMBLE COMPANY Liposomes for drug delivery and composition containing a liposome drug system
US4377567A (en) 1978-10-02 1983-03-22 The Procter & Gamble Company Lipid membrane drug delivery
US4348387A (en) 1979-07-31 1982-09-07 The Rockefeller University Method and system for the controlled release of biologically active substances to a body fluid
US4421685A (en) 1980-03-27 1983-12-20 Eli Lilly And Company Process for producing an insulin
JPS608000B2 (ja) 1980-04-11 1985-02-28 呉羽化学工業株式会社 アミノフエニル誘導体及び該誘導体を含有する生理活性剤
US4435173A (en) 1982-03-05 1984-03-06 Delta Medical Industries Variable rate syringe pump for insulin delivery
US4498843A (en) 1982-08-02 1985-02-12 Schneider Philip H Insulin infusion pump
US4444683A (en) 1982-11-17 1984-04-24 University Of Utah Glycosylated insulin derivatives
US4603044A (en) 1983-01-06 1986-07-29 Technology Unlimited, Inc. Hepatocyte Directed Vesicle delivery system
EP0119650A3 (en) 1983-03-21 1987-09-30 THE PROCTER & GAMBLE COMPANY Galactosyl-insulin conjugates useful in treating diabetics
US4863896A (en) 1984-05-03 1989-09-05 Technology Unlimited, Inc. Diabetic control by combined insulin forms
DK160633C (da) 1985-05-15 1991-09-02 Henning Munk Ejlersen Slangepumpe, isaer til avendelse som insulinpumpe
US5239062A (en) * 1986-03-20 1993-08-24 Dana-Farber Cancer Institute, Inc. Blocked lectins, methods and affinity support for making same using affinity ligands, and method of killing selected cell populations having reduced nonselective cytotoxicity
US5395924A (en) 1986-03-20 1995-03-07 Dana-Farber Cancer Institute, Inc. Blocked lectins; methods and affinity support for making the same using affinity ligands; and method of killing selected cell populations having reduced non-selective cytotoxicity
US5527524A (en) 1986-08-18 1996-06-18 The Dow Chemical Company Dense star polymer conjugates
US4853218A (en) * 1987-02-24 1989-08-01 Schering Corporation Zinc-protamine-alpha interferon complex
US5062841A (en) 1988-08-12 1991-11-05 The Regents Of The University Of California Implantable, self-regulating mechanochemical insulin pump
DK111489D0 (da) 1989-03-08 1989-03-08 Novo Nordisk As Peptider
KR930001305B1 (ko) 1989-10-19 1993-02-25 니뽕 유우시 가부시끼가이샤 당 응답형 고분자 복합체(Polymer Complexes of Sugar Response Type)
IL99699A (en) * 1990-10-10 2002-04-21 Autoimmune Inc Drug with the option of oral, intra-intestinal, or inhaled dosing for suppression of autoimmune response associated with type I diabetes
RU2003351C1 (ru) * 1991-06-26 1993-11-30 Липов Борис Петрович; Сафронов Игорь Николаевич Инъектор
GB9200638D0 (en) 1992-01-10 1992-03-11 Leicester Polytechnic Drug system
JP3455217B2 (ja) 1992-02-13 2003-10-14 バイオ−メトリック システムズ インコーポレイテッド 架橋マトリックス中の化学種の固定
GB9316895D0 (en) 1993-08-13 1993-09-29 Guy S And St Thomas Hospitals Hepatoselective insulin analogues
GB9313484D0 (en) 1993-06-30 1993-08-11 Univ Montfort Drug system ii
US6342225B1 (en) 1993-08-13 2002-01-29 Deutshces Wollforschungsinstitut Pharmaceutical active conjugates
US6869930B1 (en) 1993-09-17 2005-03-22 Novo Nordisk A/S Acylated insulin
SI0792290T1 (en) * 1993-09-17 2001-12-31 Novo Nordisk As Acylated insulin
US6011007A (en) 1993-09-17 2000-01-04 Novo Nordisk A/S Acylated insulin
US5461031A (en) 1994-06-16 1995-10-24 Eli Lilly And Company Monomeric insulin analog formulations
US5474978A (en) 1994-06-16 1995-12-12 Eli Lilly And Company Insulin analog formulations
US5504188A (en) 1994-06-16 1996-04-02 Eli Lilly And Company Preparation of stable zinc insulin analog crystals
US6500645B1 (en) 1994-06-17 2002-12-31 Novo Nordisk A/S N-terminally extended proteins expressed in yeast
US5547929A (en) 1994-09-12 1996-08-20 Eli Lilly And Company Insulin analog formulations
US5693609A (en) 1994-11-17 1997-12-02 Eli Lilly And Company Acylated insulin analogs
AR002976A1 (es) 1995-03-31 1998-05-27 Lilly Co Eli Formulaciones farmaceuticas parenterales de efecto prolongado de insulina; cristales de dichos analogos aplicables en dichas formulaciones yprocedimiento de las formulaciones mencionadas
US5902603A (en) 1995-09-14 1999-05-11 Cygnus, Inc. Polyurethane hydrogel drug reservoirs for use in transdermal drug delivery systems, and associated methods of manufacture and use
JP2000501414A (ja) 1995-11-22 2000-02-08 ザ・ジョンズ・ホプキンス・ユニバーシティー 生体分子の細胞取り込みを高めるリガンド
US5723589A (en) 1995-12-21 1998-03-03 Icn Pharmaceuticals Carbohydrate conjugated bio-active compounds
US5948751A (en) 1996-06-20 1999-09-07 Novo Nordisk A/S X14-mannitol
US5866538A (en) 1996-06-20 1999-02-02 Novo Nordisk A/S Insulin preparations containing NaCl
US5905140A (en) 1996-07-11 1999-05-18 Novo Nordisk A/S, Novo Alle Selective acylation method
JP2001527387A (ja) 1997-01-24 2001-12-25 ノボ ノルディスク アクティーゼルスカブ 合成リーダーペプチド配列
ZA984697B (en) 1997-06-13 1999-12-01 Lilly Co Eli Stable insulin formulations.
US6444641B1 (en) 1997-10-24 2002-09-03 Eli Lilly Company Fatty acid-acylated insulin analogs
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
ZA989744B (en) 1997-10-31 2000-04-26 Lilly Co Eli Method for administering acylated insulin.
DE69924232D1 (de) 1998-01-09 2005-04-21 Novo Nordisk As Stabilisierte insulin-zubereitungen
DE69926226T2 (de) 1998-04-15 2006-05-24 Novo Nordisk A/S Neues verfahren zur trennung von proteinen unter verwendung eines ca++ enthaltenden elutionsmittels
US6300319B1 (en) * 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6844166B1 (en) 1998-09-11 2005-01-18 Sensor Technologies Inc. Recombinant reduced valency carbohydrate binding ligands
US6323311B1 (en) 1999-09-22 2001-11-27 University Of Utah Research Foundation Synthesis of insulin derivatives
US6521738B2 (en) 1999-12-29 2003-02-18 Novo Nordisk A/S Method for making insulin precursors and insulin precursor analogs
US6777207B2 (en) 1999-12-29 2004-08-17 Novo Nordisk A/S Method for making insulin precursors and insulin precursor analogues having improved fermentation yield in yeast
US7316999B2 (en) 2000-06-02 2008-01-08 Novo Nordisk A/S Glucose dependent release of insulin from glucose sensing insulin derivatives
AU2001263775A1 (en) * 2000-06-02 2001-12-11 Novo-Nordisk A/S Glucose dependent release of insulin from glucose sensing insulin derivatives
US6650951B1 (en) 2000-06-19 2003-11-18 International Business Machines Corporation Method and insulin pump for providing a forgotten bolus warning
AU2001280552A1 (en) 2000-07-13 2002-01-30 The Ohio State University Research Foundation Multimeric biopolymers as structural elements, sensors and actuators in microsystems
US7060675B2 (en) 2001-02-15 2006-06-13 Nobex Corporation Methods of treating diabetes mellitus
WO2003047462A1 (en) 2001-03-12 2003-06-12 Clemson University Polysaccharide-based polmerizable hydrogels
US7105314B2 (en) 2001-04-02 2006-09-12 Novo Nordisk A/S Method for making human insulin precursors
EP2042196B1 (en) * 2001-10-10 2016-07-13 ratiopharm GmbH Remodelling and glycoconjugation of Granulocyte Colony Stimulating Factor (G-CSF)
WO2003035011A2 (en) 2001-10-26 2003-05-01 The Uab Research Foundation Multidrug multiligand conjugates for targeted drug delivery
US6736796B2 (en) 2001-11-26 2004-05-18 Nili-Med Ltd. Fluid drug delivery device
US7473680B2 (en) * 2001-11-28 2009-01-06 Neose Technologies, Inc. Remodeling and glycoconjugation of peptides
JP2005526009A (ja) * 2001-12-02 2005-09-02 ノボ　ノルディスク　アクティーゼルスカブ 新規グルコース依存性インスリン
US7317000B2 (en) 2001-12-02 2008-01-08 Novo Nordisk A/S Glucose-dependent insulins
WO2003048915A1 (en) 2001-12-07 2003-06-12 Ntt Docomo, Inc. Mobile communication terminal, method for controlling execution state of application program, application program, and recording medium wherein application program has been recorded
US6852104B2 (en) 2002-02-28 2005-02-08 Smiths Medical Md, Inc. Programmable insulin pump
US6744350B2 (en) 2002-02-28 2004-06-01 Smiths Medical Md, Inc. Insulin pump having missed meal bolus alarm
DE10209821A1 (de) 2002-03-06 2003-09-25 Biotechnologie Ges Mittelhesse Kopplung von Proteinen an ein modifiziertes Polysaccharid
WO2003094956A1 (en) 2002-05-07 2003-11-20 Novo Nordisk A/S Soluble formulations comprising monomeric insulin and acylated insulin
US7862807B2 (en) 2002-07-19 2011-01-04 University Of California, San Diego Dendrimers as molecular translocators
US7993108B2 (en) 2002-10-09 2011-08-09 Abbott Diabetes Care Inc. Variable volume, shape memory actuated insulin dispensing pump
AU2002368314A1 (en) * 2002-10-29 2004-05-25 Ranbaxy Laboratories Limited Iminosugar derivatives as glucosidase inhibitors
AU2003301064A1 (en) * 2002-12-17 2004-07-14 Massachusetts Institute Of Technology Stimuli-responsive systems for controlled drug delivery
WO2004057002A2 (en) 2002-12-20 2004-07-08 Greenovation Biotech Gmbh Production of heterologous glycosylated proteins in bryophyte cells
JPWO2004101619A1 (ja) * 2003-05-15 2006-10-26 塩野義製薬株式会社 機能的糖ペプチドの合理的設計および合成
EP1687428A1 (en) 2003-11-14 2006-08-09 Novo Nordisk A/S Processes for making acylated insulin
US20080102114A1 (en) 2004-04-23 2008-05-01 Panduranga Rao Koritala Microparticles and Nanoparticles for the Transmucosal Delivery of Therapeutic and Diagnostic Agents
WO2006008238A1 (en) 2004-07-16 2006-01-26 Novo Nordisk A/S Method for selective acylation
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
WO2006062685A2 (en) * 2004-11-11 2006-06-15 Affymax, Inc. Novel peptides that bind to the erythropoietin receptor
TWI376234B (en) 2005-02-01 2012-11-11 Msd Oss Bv Conjugates of a polypeptide and an oligosaccharide
US20070207498A1 (en) 2005-02-24 2007-09-06 Lifescan, Inc. Design and construction of dimeric concanavalin a mutants
US20060247154A1 (en) 2005-02-24 2006-11-02 Lifescan, Inc. Concanavalin a, methods of expressing, purifying and characterizing concanavalina, and sensors including the same
WO2006102762A1 (en) 2005-04-01 2006-10-05 Mcmaster University Glucose responsive microgels
WO2007041358A2 (en) 2005-09-30 2007-04-12 Miikana Therapeutics, Inc. Substituted pyrazole compounds
CA2624867A1 (en) 2005-10-10 2007-04-19 N.V. Organon Antithrombotic compound
US7517856B2 (en) 2005-10-11 2009-04-14 Ben-Gurion University Of The Negev Research And Development Authority Bioconjugates comprising sulfated polysaccharides and their uses
WO2007047922A2 (en) 2005-10-19 2007-04-26 Smartcells, Inc. Polymer-drug conjugates
JP5202338B2 (ja) 2006-02-27 2013-06-05 ノボ・ノルデイスク・エー／エス 新規インシュリン誘導体
US20100189643A1 (en) 2006-07-24 2010-07-29 Duke University Drug delivery with stimulus responsive biopolymers
EP2043692B1 (en) 2006-07-25 2016-05-18 Lipoxen Technologies Limited Polysaccharide derivatives of erythropoietin
FR2904315B1 (fr) 2006-07-26 2012-12-14 Centre Nat Rech Scient Composes pyridaziniques et pyrroliques, procedes d'obtention et applications
US7515060B2 (en) 2006-10-17 2009-04-07 Smiths Medical Md, Inc. Insulin pump for the visually impaired
US20080172028A1 (en) 2006-10-17 2008-07-17 Blomquist Michael L Insulin pump having selectable insulin absorption models
CN101273961A (zh) 2007-03-30 2008-10-01 中国人民解放军总医院 葡萄糖敏感水凝胶
US20090053167A1 (en) 2007-05-14 2009-02-26 Neose Technologies, Inc. C-, S- and N-glycosylation of peptides
US20090005726A1 (en) 2007-06-27 2009-01-01 Steven Paul Jones Insulin Pump Having Expected Bolus Interval and an Early Bolus Interval
WO2009033588A2 (en) 2007-09-11 2009-03-19 F. Hoffmann-La-Roche Ag Self-controlled insulin delivery system
WO2009059450A1 (en) 2007-11-05 2009-05-14 Shanghai Jiaotong University Peptide ligand directed drug delivery
GB2446247B (en) 2007-11-27 2008-12-17 Robert Joseph Wagener Homeostatic insulin pump
JP5647899B2 (ja) 2008-01-08 2015-01-07 ラツィオファルム ゲーエムベーハーｒａｔｉｏｐｈａｒｍ ＧｍｂＨ オリゴサッカリルトランスフェラーゼを使用するポリペプチドの複合糖質化
US20090177154A1 (en) 2008-01-08 2009-07-09 Michael Blomquist Insulin pump with convenience features
US20090177142A1 (en) 2008-01-09 2009-07-09 Smiths Medical Md, Inc Insulin pump with add-on modules
RU2381238C2 (ru) 2008-01-31 2010-02-10 Ордена Трудового Красного Знамени Институт нефтехимического синтеза им. А.В. Топчиева Российской академии наук (статус государственного учреждения) Способ получения глюкозочувствительных полимерных гидрогелей
US8802816B2 (en) 2008-02-19 2014-08-12 Biocon Limited Method of obtaining a purified, biologically active heterologous protein
EP2141620B1 (de) 2008-07-01 2018-10-31 Roche Diabetes Care GmbH Insulinpumpe und Verfahren zur Steuerung einer Benutzerschnittstelle einer Insulinpumpe
AU2010208295A1 (en) * 2009-01-28 2011-08-04 Smartcells, Inc. Polynucleotide aptamer-based cross -linked materials and uses thereof
JP2012516342A (ja) * 2009-01-28 2012-07-19 スマートセルズ・インコーポレイテツド 結晶性インスリン複合体
BRPI1007457A2 (pt) * 2009-01-28 2015-08-25 Smartcells Inc Conjungado, formulação de liberação prolongada, e, sistema de distribuição de bomba.
EP2391215A4 (en) * 2009-01-28 2013-10-30 Smartcells Inc BINDING CENTER MODIFIED LECTINS AND THEIR USE
WO2010088286A1 (en) * 2009-01-28 2010-08-05 Smartcells, Inc. Synthetic conjugates and uses thereof
CA2750223A1 (en) * 2009-01-28 2010-08-05 Smartcells, Inc. Exogenously triggered controlled release materials and uses thereof
CA2754950A1 (en) * 2009-03-20 2010-09-23 Smartcells, Inc. Terminally-functionalized conjugates and uses thereof
EP2408470A4 (en) * 2009-03-20 2012-08-29 Smartcells Inc SOLUBLE NONDEPOT INSULIN CONJUGATE AND ITS USE
US9095623B2 (en) * 2009-03-20 2015-08-04 Smartcells, Inc. Terminally-functionalized conjugates and uses thereof
EP2448962B1 (en) 2009-06-30 2016-10-19 Novo Nordisk A/S Insulin derivatives
US9068013B2 (en) * 2010-07-28 2015-06-30 Smart Cells, Inc. Recombinant lectins, binding-site modified lectins and uses thereof
US9074015B2 (en) * 2010-07-28 2015-07-07 Smartcells, Inc. Recombinantly expressed insulin polypeptides and uses thereof
EP2598171A2 (en) * 2010-07-28 2013-06-05 Smartcells, Inc. Drug-ligand conjugates, synthesis thereof, and intermediates thereto
AU2014329567B2 (en) * 2013-10-04 2019-07-25 Merck Sharp & Dohme Corp. Glucose-responsive insulin conjugates
US20180110863A1 (en) * 2015-04-08 2018-04-26 Merck Sharp & Dohme Corp. Glucose-responsive insulin conjugates
US9899205B2 (en) * 2016-05-25 2018-02-20 Kla-Tencor Corporation System and method for inhibiting VUV radiative emission of a laser-sustained plasma source

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