NZ527392A - Methods of treating diabetes mellitus - Google Patents
Methods of treating diabetes mellitusInfo
- Publication number
- NZ527392A NZ527392A NZ527392A NZ52739202A NZ527392A NZ 527392 A NZ527392 A NZ 527392A NZ 527392 A NZ527392 A NZ 527392A NZ 52739202 A NZ52739202 A NZ 52739202A NZ 527392 A NZ527392 A NZ 527392A
- Authority
- NZ
- New Zealand
- Prior art keywords
- insulin
- moiety
- human
- polypeptide
- mixture
- Prior art date
Links
- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 81
- 238000000034 method Methods 0.000 title claims description 89
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims abstract description 643
- 102000004877 Insulin Human genes 0.000 claims abstract description 386
- 108090001061 Insulin Proteins 0.000 claims abstract description 386
- 229940125396 insulin Drugs 0.000 claims abstract description 314
- 239000003814 drug Substances 0.000 claims abstract description 72
- 239000000203 mixture Substances 0.000 claims abstract description 69
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 87
- 239000008103 glucose Substances 0.000 claims description 84
- 125000000217 alkyl group Chemical group 0.000 claims description 68
- 125000003827 glycol group Chemical group 0.000 claims description 49
- 241000282414 Homo sapiens Species 0.000 claims description 47
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- 235000012054 meals Nutrition 0.000 claims description 26
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 25
- 125000005313 fatty acid group Chemical group 0.000 claims description 25
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- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical group C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 24
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 23
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- 101000976075 Homo sapiens Insulin Proteins 0.000 claims description 18
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- 238000011282 treatment Methods 0.000 claims description 18
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 claims description 15
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- 235000012000 cholesterol Nutrition 0.000 claims description 12
- 125000001033 ether group Chemical group 0.000 claims description 12
- 229920001184 polypeptide Polymers 0.000 claims description 11
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 11
- 239000004026 insulin derivative Substances 0.000 claims description 10
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- 230000002194 synthesizing effect Effects 0.000 claims description 8
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- 238000010168 coupling process Methods 0.000 claims description 3
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- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 83
- -1 but not limited to Chemical compound 0.000 description 76
- 229940079593 drug Drugs 0.000 description 61
- 229920001515 polyalkylene glycol Polymers 0.000 description 55
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- 125000004432 carbon atom Chemical group C* 0.000 description 33
- 210000004185 liver Anatomy 0.000 description 33
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 27
- 230000000694 effects Effects 0.000 description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 21
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- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Health & Medical Sciences (AREA)
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- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Toxicology (AREA)
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- Pulmonology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
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- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26919801P | 2001-02-15 | 2001-02-15 | |
| US34771302P | 2002-01-11 | 2002-01-11 | |
| PCT/US2002/004440 WO2002065985A2 (en) | 2001-02-15 | 2002-02-14 | Methods of treating diabetes mellitus |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ527392A true NZ527392A (en) | 2008-01-31 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ527392A NZ527392A (en) | 2001-02-15 | 2002-02-14 | Methods of treating diabetes mellitus |
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| JP (1) | JP4113778B2 (enExample) |
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| AU (1) | AU2002244020B2 (enExample) |
| BR (1) | BRPI0207700B8 (enExample) |
| CA (1) | CA2437940C (enExample) |
| CY (1) | CY1112034T1 (enExample) |
| DE (1) | DE60239612D1 (enExample) |
| DK (1) | DK1409006T3 (enExample) |
| MX (1) | MXPA03007374A (enExample) |
| NO (1) | NO327586B1 (enExample) |
| NZ (1) | NZ527392A (enExample) |
| PT (1) | PT1409006E (enExample) |
| WO (1) | WO2002065985A2 (enExample) |
| ZA (1) | ZA200306332B (enExample) |
Families Citing this family (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6191105B1 (en) * | 1993-05-10 | 2001-02-20 | Protein Delivery, Inc. | Hydrophilic and lipophilic balanced microemulsion formulations of free-form and/or conjugation-stabilized therapeutic agents such as insulin |
| 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 |
| 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 |
| US7713932B2 (en) * | 2001-06-04 | 2010-05-11 | Biocon Limited | Calcitonin drug-oligomer conjugates, and uses thereof |
| 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 |
| US6835802B2 (en) | 2001-06-04 | 2004-12-28 | Nobex Corporation | Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties |
| 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 |
| 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 |
| NZ519403A (en) * | 2001-06-21 | 2005-03-24 | Pfizer Prod Inc | Use of insulin in a medicament to reduce weight gain in a diabetic patient who is using exogenous insulin to control blood sugar levels |
| US7312192B2 (en) * | 2001-09-07 | 2007-12-25 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| US7030082B2 (en) * | 2001-09-07 | 2006-04-18 | Nobex Corporation | Pharmaceutical compositions of drug-oligomer conjugates and methods of treating disease therewith |
| US6770625B2 (en) * | 2001-09-07 | 2004-08-03 | Nobex Corporation | Pharmaceutical compositions of calcitonin drug-oligomer conjugates and methods of treating diseases therewith |
| US7196059B2 (en) * | 2001-09-07 | 2007-03-27 | Biocon Limited | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
| US20030198666A1 (en) * | 2002-01-07 | 2003-10-23 | Richat Abbas | Oral insulin therapy |
| WO2003105768A2 (en) * | 2002-06-13 | 2003-12-24 | Nobex Corporation | Methods of reducing hypoglycemic episodes in the treatment of diabetes mellitus |
| US20040091544A1 (en) * | 2002-11-08 | 2004-05-13 | Ruff Michael D. | Coated dibasic calcium phosphate |
| CN100558398C (zh) * | 2002-11-26 | 2009-11-11 | 拜奥康有限公司 | 修饰的钠尿化合物、缀合物及其应用 |
| CA2511530C (en) * | 2003-01-06 | 2013-07-09 | Emisphere Technologies, Inc. | Night-time oral insulin therapy |
| CA2518216C (en) * | 2003-03-06 | 2017-05-09 | Emisphere Technologies, Inc. | Oral insulin therapies and protocol |
| JP2006519881A (ja) * | 2003-03-06 | 2006-08-31 | エミスフィアー テクノロジーズ インコーポレイテッド | 経口インスリン治療及びプロトコール |
| DE602004021603D1 (de) * | 2003-07-25 | 2009-07-30 | Conjuchem Biotechnologies Inc | Insulinderivative mit langanhaltender wirkung und verfahren zu deren herstellung |
| ES2445947T3 (es) * | 2003-08-13 | 2014-03-06 | Biocon Limited | Formulaciones para dosificación de sólidos de sales de ácidos grasos en forma de micropartículas para agentes terapéuticos |
| US20050203001A1 (en) * | 2004-03-05 | 2005-09-15 | Emisphere Technologies, Inc. | Oral insulin therapies and protocol |
| GB0412181D0 (en) * | 2004-06-01 | 2004-06-30 | Celltech R&D Ltd | Biological products |
| KR101309770B1 (ko) | 2004-07-19 | 2013-09-30 | 바이오콘 리미티드 | 인슐린―올리고머 접합체，제형 및 이들의 용도 |
| JP2007063225A (ja) | 2005-09-01 | 2007-03-15 | Takeda Chem Ind Ltd | イミダゾピリジン化合物 |
| WO2007104034A2 (en) | 2006-03-08 | 2007-09-13 | Takeda San Diego, Inc. | Glucokinase activators |
| EP2049518B1 (en) | 2006-05-31 | 2011-08-31 | Takeda San Diego, Inc. | Indazole and isoindole derivatives as glucokinase activating agents. |
| KR101466933B1 (ko) | 2006-07-11 | 2014-12-01 | 큐피에스 엘엘씨 | 펩타이드의 지속 방출 전달을 위한 의약 조성물 |
| WO2008049711A1 (en) | 2006-10-27 | 2008-05-02 | Novo Nordisk A/S | Peptide extended insulins |
| WO2008079787A2 (en) | 2006-12-20 | 2008-07-03 | Takeda San Diego, Inc. | Glucokinase activators |
| WO2008116107A2 (en) | 2007-03-21 | 2008-09-25 | Takeda San Diego, Inc. | Piperazine derivatives as glucokinase activators |
| EP2514406A1 (en) * | 2007-06-01 | 2012-10-24 | Novo Nordisk A/S | Spontaneously dispersible preconcentrates including a peptide drug in a solid or semisolid carrier |
| KR20100017667A (ko) * | 2007-06-01 | 2010-02-16 | 노보 노르디스크 에이/에스 | 안정한 비-수성의 약학 조성물 |
| AU2008265973A1 (en) * | 2007-06-13 | 2008-12-24 | Wake Forest University Health Sciences | Methods of restoration of erectile function |
| PT2203181T (pt) * | 2007-10-16 | 2018-05-10 | Biocon Ltd | Uma composição farmacêutica sólida para administração por via oral e o seu processo de fabrico |
| FR2925333B1 (fr) * | 2007-12-19 | 2012-04-13 | Farid Bennis | Compositions pharmaceutiques renfermant au moins un principe actif proteinique protege des enzymes digestives |
| MY152979A (en) | 2008-01-09 | 2014-12-15 | Sanofi Aventis Deutschland | Novel insulin derivatives having an extremely delayed time-action profile |
| EP2229406B1 (de) | 2008-01-09 | 2015-04-22 | Sanofi-Aventis Deutschland GmbH | Neue insulinderivate mit extrem verzögertem zeit- / wirkungsprofil |
| DK2910570T3 (en) | 2008-03-18 | 2017-01-30 | Novo Nordisk As | Protease-stabilized acylated insulin analogues. |
| TWI451876B (zh) * | 2008-06-13 | 2014-09-11 | Lilly Co Eli | 聚乙二醇化之離脯胰島素化合物 |
| JP5480257B2 (ja) * | 2008-07-14 | 2014-04-23 | バイオコン リミテッド | 実質的に単分散のオリゴマー混合物の合成方法 |
| US20110171312A1 (en) * | 2008-09-19 | 2011-07-14 | Nektar Therapeutics | Modified therapeutic peptides, methods of their preparation and use |
| WO2010033240A2 (en) | 2008-09-19 | 2010-03-25 | Nektar Therapeutics | Carbohydrate-based drug delivery polymers and conjugates thereof |
| PL3228320T3 (pl) | 2008-10-17 | 2020-06-01 | Sanofi-Aventis Deutschland Gmbh | Kombinacja insuliny i agonisty GLP-1 |
| US20110293714A1 (en) * | 2008-11-28 | 2011-12-01 | Novo Nordisk A/S | Pharmaceutical compositions suitable for oral administration of derivatized insulin peptides |
| JP2012516339A (ja) | 2009-01-28 | 2012-07-19 | スマートセルズ・インコーポレイテツド | 外因的刺激型制御放出物質体およびその使用 |
| SG193837A1 (en) | 2009-01-28 | 2013-10-30 | Smartcells Inc | Conjugate based systems for controlled drug delivery |
| BRPI1007466A2 (pt) | 2009-01-28 | 2018-06-12 | Smartcells Inc | conjugado de insulina cristalina, 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 |
| JP2012520879A (ja) | 2009-03-20 | 2012-09-10 | スマートセルズ・インコーポレイテツド | 末端官能基化コンジュゲートおよびその用途 |
| US8569231B2 (en) | 2009-03-20 | 2013-10-29 | Smartcells, Inc. | Soluble non-depot insulin conjugates and uses thereof |
| US20110058558A1 (en) * | 2009-09-08 | 2011-03-10 | Electronics And Telecommunications Research Institute | Network control device and network control method |
| CA3011480C (en) | 2009-11-13 | 2021-11-09 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical composition comprising a glp-1 agonist, an insulin and methionine |
| SI2498801T1 (en) | 2009-11-13 | 2018-06-29 | Sanofi-Aventis Deutschland Gmbh | A pharmaceutical composition containing desPro36Exendin-4 (1-39) -Lys6-NH2 and methionine |
| CA2782056C (en) | 2009-11-25 | 2021-03-09 | Arisgen Sa | Mucosal delivery of peptides |
| EP2598170A4 (en) | 2010-07-28 | 2016-07-06 | Smartcells Inc | MEDICINAL LIGANDEN CONJUGATES, THEIR SYNTHESIS AND INTERMEDIATE PRODUCTS THEREOF |
| WO2012015692A2 (en) | 2010-07-28 | 2012-02-02 | Smartcells, Inc. | Recombinantly expressed insulin polypeptides and uses thereof |
| US9068013B2 (en) | 2010-07-28 | 2015-06-30 | Smart Cells, Inc. | Recombinant lectins, binding-site modified lectins and uses thereof |
| EP2611458B1 (en) | 2010-08-30 | 2016-09-21 | Sanofi-Aventis Deutschland GmbH | Use of ave0010 for the manufacture of a medicament for the treatment of diabetes mellitus type 2 |
| US9821032B2 (en) | 2011-05-13 | 2017-11-21 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin |
| EP2750699B1 (en) | 2011-08-29 | 2015-07-22 | Sanofi-Aventis Deutschland GmbH | Pharmaceutical combination for use in glycemic control in diabetes type 2 patients |
| TWI559929B (en) | 2011-09-01 | 2016-12-01 | Sanofi Aventis Deutschland | Pharmaceutical composition for use in the treatment of a neurodegenerative disease |
| CA2858253A1 (en) * | 2011-12-15 | 2013-06-20 | Shanghai Hengrui Pharmaceutical Co., Ltd. | Human insulin analogue and acylated derivative thereof |
| US9481721B2 (en) | 2012-04-11 | 2016-11-01 | Novo Nordisk A/S | Insulin formulations |
| US9884125B2 (en) | 2013-10-04 | 2018-02-06 | Merck Sharp & Dohme Corp. | Glucose-responsive insulin conjugates |
| PE20171622A1 (es) | 2014-12-12 | 2017-11-02 | Sanofi Aventis Deutschland | Formulacion de relacion fija de insulina glargina/lixisenatida |
| TWI748945B (zh) | 2015-03-13 | 2021-12-11 | 德商賽諾菲阿凡提斯德意志有限公司 | 第２型糖尿病病患治療 |
| TW201705975A (zh) | 2015-03-18 | 2017-02-16 | 賽諾菲阿凡提斯德意志有限公司 | 第２型糖尿病病患之治療 |
| TWI700091B (zh) | 2016-12-16 | 2020-08-01 | 丹麥商諾佛 儂迪克股份有限公司 | 含胰島素醫藥組成物 |
Family Cites Families (191)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US556742A (en) * | 1896-03-24 | Trace-fastener | ||
| US3256153A (en) * | 1963-02-08 | 1966-06-14 | Smith Kline French Lab | Method of stabilizing wax-fat coating materials and product thereof |
| US4003792A (en) * | 1967-07-01 | 1977-01-18 | Miles Laboratories, Inc. | Conjugates of acid polysaccharides and complex organic substances |
| 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 |
| US3919411A (en) | 1972-01-31 | 1975-11-11 | Bayvet Corp | Injectable adjuvant and compositions including such adjuvant |
| US4044196A (en) * | 1972-03-30 | 1977-08-23 | Bayer Aktiengesellschaft | Crosslinked copolymers of α,β-olefinically unsaturated dicarboxylic anhydrides |
| US3852353A (en) | 1972-12-12 | 1974-12-03 | C Heaphy | Oral hypoglycemic aminophenylsulfonyl-hydrocarbylbiguanides |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| FR2408387A2 (fr) | 1975-06-30 | 1979-06-08 | Oreal | Compositions a base de dispersions aqueuses de spherules lipidiques |
| US4093574A (en) * | 1977-02-02 | 1978-06-06 | Eli Lilly And Company | Somatostatin analogs and intermediates thereto |
| US4087390A (en) * | 1977-02-02 | 1978-05-02 | Eli Lilly And Company | Somatostatin analogs and intermediates thereto |
| GB1492997A (en) | 1976-07-21 | 1977-11-23 | Nat Res Dev | Insulin derivatives |
| JPS53116315A (en) | 1977-03-17 | 1978-10-11 | Ueno Seiyaku Oyo Kenkyujo Kk | Powder or granular containing improved sorbinic acid |
| US4100117A (en) * | 1977-04-21 | 1978-07-11 | Eli Lilly And Company | Somatostatin analogs and intermediates thereto |
| US4253998A (en) * | 1979-03-09 | 1981-03-03 | American Home Products Corporation | Peptides related to somatostatin |
| JPS54148722A (en) | 1978-05-12 | 1979-11-21 | Takeda Chem Ind Ltd | Nonapeptide and its preparation |
| US4277394A (en) * | 1979-04-23 | 1981-07-07 | Takeda Chemical Industries, Ltd | Tetrapeptidehydrazide derivatives |
| GB2051574B (en) * | 1979-05-10 | 1984-01-18 | Kyoto Pharma Ind | Adjuvant for promoting absorption of pharmacologically active substances through the rectum |
| 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 |
| US4469681A (en) | 1979-07-31 | 1984-09-04 | The Rockefeller University | Method and system for the controlled release of biologically active substances to a body fluid |
| FR2465486A1 (fr) | 1979-09-21 | 1981-03-27 | Roussel Uclaf | Nouvelle application utilisant la lh-rh ou des agonistes |
| JPS5692846A (en) | 1979-12-27 | 1981-07-27 | Takeda Chem Ind Ltd | Tetrapeptide derivative and its preparation |
| US4554101A (en) | 1981-01-09 | 1985-11-19 | New York Blood Center, Inc. | Identification and preparation of epitopes on antigens and allergens on the basis of hydrophilicity |
| IT1144743B (it) * | 1981-07-09 | 1986-10-29 | Mario Cane | Apparecchio infusore di insulina perfezionato |
| US4582820A (en) | 1982-12-23 | 1986-04-15 | Research Corporation | Orally administered biologically active peptides and proteins |
| DE3378250D1 (en) | 1982-04-22 | 1988-11-24 | Ici Plc | Continuous release formulations |
| US4698264A (en) | 1982-08-02 | 1987-10-06 | Durkee Industrial Foods, Corp. | Particulate composition and process for making same |
| IL68769A (en) * | 1983-05-23 | 1986-02-28 | Hadassah Med Org | Pharmaceutical compositions containing insulin for oral administration |
| US4602043A (en) * | 1983-07-18 | 1986-07-22 | Technology Unlimited Inc. | Treatment for hypoglycemia |
| US4585754A (en) * | 1984-01-09 | 1986-04-29 | Valcor Scientific, Ltd. | Stabilization of proteins and peptides by chemical binding with chondroitin |
| US4684524A (en) * | 1984-03-19 | 1987-08-04 | Alza Corporation | Rate controlled dispenser for administering beneficial agent |
| US4717566A (en) * | 1984-03-19 | 1988-01-05 | Alza Corporation | Dosage system and method of using same |
| US4704394A (en) | 1984-04-25 | 1987-11-03 | Technology Unlimited, Inc. | Treatment for hyperactivity |
| US4963367A (en) | 1984-04-27 | 1990-10-16 | Medaphore, Inc. | Drug delivery compositions and methods |
| US4849405A (en) * | 1984-05-09 | 1989-07-18 | Synthetic Blood Corporation | Oral insulin and a method of making the same |
| US4863896A (en) | 1984-05-03 | 1989-09-05 | Technology Unlimited, Inc. | Diabetic control by combined insulin forms |
| US4761287A (en) * | 1984-05-03 | 1988-08-02 | Technology Unlimited, Inc. | Diabetes control by serotonin |
| US4963526A (en) | 1984-05-09 | 1990-10-16 | Synthetic Blood Corporation | Oral insulin and a method of making the same |
| US4839341A (en) * | 1984-05-29 | 1989-06-13 | Eli Lilly And Company | Stabilized insulin formulations |
| US4622392A (en) | 1984-06-21 | 1986-11-11 | Health Research Inc. (Roswell Park Division) | Thiophospholipid conjugates of antitumor agents |
| US4629621A (en) * | 1984-07-23 | 1986-12-16 | Zetachron, Inc. | Erodible matrix for sustained release bioactive composition |
| US4797288A (en) * | 1984-10-05 | 1989-01-10 | Warner-Lambert Company | Novel drug delivery system |
| US4946828A (en) * | 1985-03-12 | 1990-08-07 | Novo Nordisk A/S | Novel insulin peptides |
| US5008241A (en) * | 1985-03-12 | 1991-04-16 | Novo Nordisk A/S | Novel insulin peptides |
| US5157021A (en) | 1985-03-15 | 1992-10-20 | Novo Nordisk A/S | Insulin derivatives and pharmaceutical preparations containing these derivatives |
| US4917888A (en) * | 1985-06-26 | 1990-04-17 | Cetus Corporation | Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation |
| US4898733A (en) * | 1985-11-04 | 1990-02-06 | International Minerals & Chemical Corp. | Layered, compression molded device for the sustained release of a beneficial agent |
| SE457326B (sv) * | 1986-02-14 | 1988-12-19 | Lejus Medical Ab | Foerfarande foer framstaellning av en snabbt soenderfallande kaerna innehaallande bl a mikrokristallin cellulosa |
| US4849227A (en) | 1986-03-21 | 1989-07-18 | Eurasiam Laboratories, Inc. | Pharmaceutical compositions |
| ZA877505B (en) | 1986-10-14 | 1989-05-30 | Lilly Co Eli | Process for transforming a human insulin precursor to human insulin |
| GB8706313D0 (en) | 1987-03-17 | 1987-04-23 | Health Lab Service Board | Treatment & prevention of viral infections |
| US5093198A (en) * | 1987-06-19 | 1992-03-03 | Temple University | Adjuvant-enhanced sustained release composition and method for making |
| US4822337A (en) * | 1987-06-22 | 1989-04-18 | Stanley Newhouse | Insulin delivery method and apparatus |
| DE3721721C1 (de) * | 1987-07-01 | 1988-06-09 | Hoechst Ag | Verfahren zur Umhuellung von Granulaten |
| US5080891A (en) | 1987-08-03 | 1992-01-14 | Ddi Pharmaceuticals, Inc. | Conjugates of superoxide dismutase coupled to high molecular weight polyalkylene glycols |
| US4840341A (en) * | 1988-05-09 | 1989-06-20 | Hasegawa Gary K | Clip and holder |
| DK257988D0 (da) * | 1988-05-11 | 1988-05-11 | Novo Industri As | Nye peptider |
| JPH01308231A (ja) | 1988-06-03 | 1989-12-12 | Takeda Chem Ind Ltd | 安定化された医薬組成物および製造法 |
| US5055300A (en) | 1988-06-17 | 1991-10-08 | Basic Bio Systems, Inc. | Time release protein |
| DK336188D0 (da) | 1988-06-20 | 1988-06-20 | Nordisk Gentofte | Propeptider |
| JPH0720857B2 (ja) | 1988-08-11 | 1995-03-08 | テルモ株式会社 | リポソームおよびその製法 |
| US5306500A (en) * | 1988-11-21 | 1994-04-26 | Collagen Corporation | Method of augmenting tissue with collagen-polymer conjugates |
| US5162430A (en) | 1988-11-21 | 1992-11-10 | Collagen Corporation | Collagen-polymer conjugates |
| HUT56857A (en) | 1988-12-23 | 1991-10-28 | Novo Nordisk As | Human insulin analogues |
| US5716927A (en) * | 1988-12-23 | 1998-02-10 | Novo Nordisk A/S | Insulin analogs having a modified B-chain |
| US4994439A (en) * | 1989-01-19 | 1991-02-19 | California Biotechnology Inc. | Transmembrane formulations for drug administration |
| US5089261A (en) * | 1989-01-23 | 1992-02-18 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
| IT1229514B (it) | 1989-01-30 | 1991-09-03 | Farmhispania S A A Montme | Glicoconiugati anfifilici sintetici per impiego neurologico. |
| US5514646A (en) * | 1989-02-09 | 1996-05-07 | Chance; Ronald E. | Insulin analogs modified at position 29 of the B chain |
| US5182258A (en) * | 1989-03-20 | 1993-01-26 | Orbon Corporation | Systemic delivery of polypeptides through the eye |
| US5324844A (en) * | 1989-04-19 | 1994-06-28 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| US5108568A (en) | 1989-07-07 | 1992-04-28 | The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration | Controlled method of reducing electrophoretic mobility of macromolecules, particles or cells |
| US5286637A (en) * | 1989-08-07 | 1994-02-15 | Debiopharm, S.A. | Biologically active drug polymer derivatives and method for preparing same |
| US5013556A (en) * | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5650388A (en) * | 1989-11-22 | 1997-07-22 | Enzon, Inc. | Fractionated polyalkylene oxide-conjugated hemoglobin solutions |
| US5312808A (en) * | 1989-11-22 | 1994-05-17 | Enzon, Inc. | Fractionation of polyalkylene oxide-conjugated hemoglobin solutions |
| CA2030174C (en) * | 1990-01-10 | 1996-12-24 | Anthony H. Cincotta | Process for the long term reduction of body fat stores, insulin resistance, hyperinsulinemia and hypoglycemia in vertebrates |
| US5545618A (en) | 1990-01-24 | 1996-08-13 | Buckley; Douglas I. | GLP-1 analogs useful for diabetes treatment |
| US5126324A (en) * | 1990-06-07 | 1992-06-30 | Genentech, Inc. | Method of enhancing growth in patients using combination therapy |
| DD297249A5 (de) | 1990-08-07 | 1992-01-02 | Veb Mineralwollewerk Flechtingen Bereich F/E Mineralwolle,De | Verfahren zur automatischen ueberwachung des aushaertegrades an materialbahnen |
| 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 |
| US5468727A (en) | 1990-12-13 | 1995-11-21 | Board Of Regents, The University Of Texas System | Methods of normalizing metabolic parameters in diabetics |
| US5595732A (en) | 1991-03-25 | 1997-01-21 | Hoffmann-La Roche Inc. | Polyethylene-protein conjugates |
| US5321009A (en) * | 1991-04-03 | 1994-06-14 | American Home Products Corporation | Method of treating diabetes |
| ATE183099T1 (de) | 1991-04-19 | 1999-08-15 | Lds Technologies Inc | Konvertierbare mikroemulsionsverbindungen |
| FR2675807B1 (fr) | 1991-04-23 | 1994-07-01 | Medgenix Group Sa | Conjugue de calcitonine et de polyethylene glycol. |
| 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 |
| US5205415A (en) * | 1991-07-10 | 1993-04-27 | The Standard Commercial Tobacco Co., Inc. | Modular classifier |
| CH683149A5 (fr) | 1991-07-22 | 1994-01-31 | Debio Rech Pharma Sa | Procédé pour la préparation de microsphères en matériau polymère biodégradable. |
| CA2114141A1 (en) | 1991-07-26 | 1993-02-18 | Panayiotis Pericleous Constantinides | W/o microemulsions |
| US5206219A (en) * | 1991-11-25 | 1993-04-27 | Applied Analytical Industries, Inc. | Oral compositions of proteinaceous medicaments |
| US5693769A (en) | 1991-12-13 | 1997-12-02 | Transcell Technologies, Inc. | Glycosylated steroid derivatives for transport across biological membranes and process for making and using same |
| US5320094A (en) * | 1992-01-10 | 1994-06-14 | The Johns Hopkins University | Method of administering insulin |
| DE59303759C5 (de) | 1992-01-17 | 2009-04-09 | Alfatec-Pharma Gmbh | Wirkstoff-enthaltende festkörper mit einem gerüst aus hydrophilen makromolekülen und verfahren zu ihrer herstellung |
| GB9212511D0 (en) | 1992-06-12 | 1992-07-22 | Cortecs Ltd | Pharmaceutical compositions |
| US5262172A (en) * | 1992-06-19 | 1993-11-16 | Digestive Care Inc. | Compositions of gastric acid-resistant microspheres containing buffered bile acids |
| US5415872A (en) * | 1992-06-22 | 1995-05-16 | Digestive Care Inc. | Compositions of gastric acid-resistant microspheres containing salts of bile acids |
| US5420108A (en) * | 1992-09-14 | 1995-05-30 | Shohet; Isaac H. | Method of controlling diabetes mellitus |
| US6093391A (en) * | 1992-10-08 | 2000-07-25 | Supratek Pharma, Inc. | Peptide copolymer compositions |
| GB9316895D0 (en) * | 1993-08-13 | 1993-09-29 | Guy S And St Thomas Hospitals | Hepatoselective insulin analogues |
| US5298643A (en) * | 1992-12-22 | 1994-03-29 | Enzon, Inc. | Aryl imidate activated polyalkylene oxides |
| US5349001A (en) * | 1993-01-19 | 1994-09-20 | Enzon, Inc. | Cyclic imide thione activated polyalkylene oxides |
| US5364838A (en) | 1993-01-29 | 1994-11-15 | Miris Medical Corporation | Method of administration of insulin |
| US5321095A (en) | 1993-02-02 | 1994-06-14 | Enzon, Inc. | Azlactone activated polyalkylene oxides |
| US5298410A (en) * | 1993-02-25 | 1994-03-29 | Sterling Winthrop Inc. | Lyophilized formulation of polyethylene oxide modified proteins with increased shelf-life |
| US6191105B1 (en) * | 1993-05-10 | 2001-02-20 | Protein Delivery, Inc. | Hydrophilic and lipophilic balanced microemulsion formulations of free-form and/or conjugation-stabilized therapeutic agents such as insulin |
| 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 |
| US5681811A (en) | 1993-05-10 | 1997-10-28 | Protein Delivery, Inc. | Conjugation-stabilized therapeutic agent compositions, delivery and diagnostic formulations comprising same, and method of making and using the same |
| US5621039A (en) | 1993-06-08 | 1997-04-15 | Hallahan; Terrence W. | Factor IX- polymeric conjugates |
| TW402506B (en) * | 1993-06-24 | 2000-08-21 | Astra Ab | Therapeutic preparation for inhalation |
| US5506203C1 (en) * | 1993-06-24 | 2001-02-06 | Astra Ab | Systemic administration of a therapeutic preparation |
| IS1796B (is) | 1993-06-24 | 2001-12-31 | Ab Astra | Fjölpeptíð lyfjablanda til innöndunar sem einnig inniheldur eykjaefnasamband |
| US5747445A (en) * | 1993-06-24 | 1998-05-05 | Astra Aktiebolag | Therapeutic preparation for inhalation |
| US5830853A (en) | 1994-06-23 | 1998-11-03 | Astra Aktiebolag | Systemic administration of a therapeutic preparation |
| US6342225B1 (en) * | 1993-08-13 | 2002-01-29 | Deutshces Wollforschungsinstitut | Pharmaceutical active conjugates |
| PT792290E (pt) * | 1993-09-17 | 2002-01-30 | Novo Nordisk As | Insulina acilada |
| US5700947A (en) | 1993-10-06 | 1997-12-23 | Nicox S.A. | Nitric esters having anti-inflammatory and/or analgesic activity and process for their preparation |
| US5919455A (en) | 1993-10-27 | 1999-07-06 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| US5605976A (en) | 1995-05-15 | 1997-02-25 | Enzon, Inc. | Method of preparing polyalkylene oxide carboxylic acids |
| US5951974A (en) * | 1993-11-10 | 1999-09-14 | Enzon, Inc. | Interferon polymer conjugates |
| WO1995014037A1 (en) * | 1993-11-17 | 1995-05-26 | Ibah, Inc. | Transparent liquid for encapsulated drug delivery |
| CZ295827B6 (cs) | 1994-03-07 | 2005-11-16 | Nektar Therapeutics | Způsob aerosolizace dávky inzulinu, inzulinový přípravek a jeho použití |
| GB9406094D0 (en) | 1994-03-28 | 1994-05-18 | Univ Nottingham And University | Polymer microspheres and a method of production thereof |
| DE69512232T2 (de) | 1994-05-10 | 2000-02-24 | Nicox S.A., Paris | Nitroverbindingen und ihre zubereitungen mit entzündungsremmenden, schmertzlindernden und antithrombotischen wirkungen |
| EP0761683B1 (en) * | 1994-05-20 | 2005-02-02 | Hisamitsu Pharmaceutical Co., Inc. | Protein or polypeptide, process for producing the same, and intermediate compound tehrefor |
| US5461031A (en) | 1994-06-16 | 1995-10-24 | Eli Lilly And Company | Monomeric insulin analog formulations |
| US5504188A (en) * | 1994-06-16 | 1996-04-02 | Eli Lilly And Company | Preparation of stable zinc insulin analog crystals |
| US6165976A (en) | 1994-06-23 | 2000-12-26 | Astra Aktiebolag | Therapeutic preparation for inhalation |
| US5730990A (en) * | 1994-06-24 | 1998-03-24 | Enzon, Inc. | Non-antigenic amine derived polymers and polymer conjugates |
| GB9417524D0 (en) | 1994-08-31 | 1994-10-19 | Cortecs Ltd | Pharmaceutical compositions |
| AU3461095A (en) | 1994-09-01 | 1996-03-22 | Allied Medical Research Associates | Compositions and methods for delivery of polypeptides |
| US5738846A (en) * | 1994-11-10 | 1998-04-14 | Enzon, Inc. | Interferon polymer conjugates and process for preparing the same |
| US5646242A (en) * | 1994-11-17 | 1997-07-08 | Eli Lilly And Company | Selective acylation of epsilon-amino groups |
| US5693609A (en) | 1994-11-17 | 1997-12-02 | Eli Lilly And Company | Acylated insulin analogs |
| MX9704137A (es) * | 1994-12-07 | 1997-09-30 | Novo Nordisk As | Polipeptidos de alergenicidad reducida. |
| GB9424902D0 (en) | 1994-12-09 | 1995-02-08 | Cortecs Ltd | Solubilisation Aids |
| SE9404468D0 (sv) | 1994-12-22 | 1994-12-22 | Astra Ab | Powder formulations |
| US5843866A (en) | 1994-12-30 | 1998-12-01 | Hampshire Chemical Corp. | Pesticidal compositions comprising solutions of polyurea and/or polyurethane |
| US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
| US5907030A (en) * | 1995-01-25 | 1999-05-25 | University Of Southern California | Method and compositions for lipidization of hydrophilic molecules |
| KR0150565B1 (ko) | 1995-02-15 | 1998-08-17 | 김정재 | 유전자 조환에 의한 사람 인슐린 전구체의 제조 및 이를 이용한 인슐린의 제조방법 |
| US6251856B1 (en) * | 1995-03-17 | 2001-06-26 | Novo Nordisk A/S | Insulin derivatives |
| 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 |
| US5606038A (en) * | 1995-04-10 | 1997-02-25 | Competitive Technologies, Inc. | Amphiphilic polyene macrolide antibiotic compounds |
| EP0741187A2 (en) * | 1995-05-05 | 1996-11-06 | F. Hoffmann-La Roche Ag | Recombinant obese (Ob) proteins |
| US5653987A (en) * | 1995-05-16 | 1997-08-05 | Modi; Pankaj | Liquid formulations for proteinic pharmaceuticals |
| US5824638A (en) | 1995-05-22 | 1998-10-20 | Shire Laboratories, Inc. | Oral insulin delivery |
| US5704910A (en) * | 1995-06-05 | 1998-01-06 | Nephros Therapeutics, Inc. | Implantable device and use therefor |
| US5700904A (en) | 1995-06-07 | 1997-12-23 | Eli Lilly And Company | Preparation of an acylated protein powder |
| US5714519A (en) | 1995-06-07 | 1998-02-03 | Ergo Science Incorporated | Method for regulating glucose metabolism |
| US5631347A (en) * | 1995-06-07 | 1997-05-20 | Eli Lilly And Company | Reducing gelation of a fatty acid-acylated protein |
| GB9516268D0 (en) * | 1995-08-08 | 1995-10-11 | Danbiosyst Uk | Compositiion for enhanced uptake of polar drugs from the colon |
| JP3628333B2 (ja) * | 1995-09-21 | 2005-03-09 | ジェネンテック インコーポレーテッド | ヒト成長ホルモン変異体 |
| US5766620A (en) * | 1995-10-23 | 1998-06-16 | Theratech, Inc. | Buccal delivery of glucagon-like insulinotropic peptides |
| US5866538A (en) * | 1996-06-20 | 1999-02-02 | Novo Nordisk A/S | Insulin preparations containing NaCl |
| US5948751A (en) | 1996-06-20 | 1999-09-07 | Novo Nordisk A/S | X14-mannitol |
| GB9613858D0 (en) * | 1996-07-02 | 1996-09-04 | Cortecs Ltd | Hydrophobic preparations |
| US5905140A (en) * | 1996-07-11 | 1999-05-18 | Novo Nordisk A/S, Novo Alle | Selective acylation method |
| US6180604B1 (en) | 1996-08-21 | 2001-01-30 | Micrologix Biotech Inc. | Compositions and methods for treating infections using analogues of indolicidin |
| US5874111A (en) * | 1997-01-07 | 1999-02-23 | Maitra; Amarnath | Process for the preparation of highly monodispersed polymeric hydrophilic nanoparticles |
| US5830918A (en) | 1997-01-15 | 1998-11-03 | Terrapin Technologies, Inc. | Nonpeptide insulin receptor agonists |
| ES2239799T3 (es) | 1997-02-05 | 2005-10-01 | F. Hoffmann-La Roche Ag | Uso de tetrahidrolipstatina en el tratamiento de la diabetes tipo ii. |
| US6043214A (en) * | 1997-03-20 | 2000-03-28 | Novo Nordisk A/S | Method for producing powder formulation comprising an insulin |
| 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 |
| CO4750643A1 (es) * | 1997-06-13 | 1999-03-31 | Lilly Co Eli | Formulacion estable de la insulina que contiene l-arginina y protamina |
| CA2306905A1 (en) * | 1997-10-24 | 1999-05-06 | Eli Lilly And Company | Fatty acid-acylated insulin analogs |
| ZA989744B (en) * | 1997-10-31 | 2000-04-26 | Lilly Co Eli | Method for administering acylated insulin. |
| US5981709A (en) | 1997-12-19 | 1999-11-09 | Enzon, Inc. | α-interferon-polymer-conjugates having enhanced biological activity and methods of preparing the same |
| US5985263A (en) | 1997-12-19 | 1999-11-16 | Enzon, Inc. | Substantially pure histidine-linked protein polymer conjugates |
| CA2334859A1 (en) | 1998-06-12 | 1999-12-23 | Kings College London | Insulin analogue |
| US6211144B1 (en) * | 1998-10-16 | 2001-04-03 | Novo Nordisk A/S | Stable concentrated insulin preparations for pulmonary delivery |
| WO2000043034A2 (en) | 1999-01-26 | 2000-07-27 | Eli Lilly And Company | Monodisperse hexameric acylated insulin analog formulations |
| DE19908041A1 (de) | 1999-02-24 | 2000-08-31 | Hoecker Hartwig | Kovalent verbrückte Insulindimere |
| US6248363B1 (en) * | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| US6309633B1 (en) | 1999-06-19 | 2001-10-30 | Nobex Corporation | Amphiphilic drug-oligomer conjugates with hydroyzable lipophile components and methods for making and using the same |
| KR100345214B1 (ko) * | 1999-08-17 | 2002-07-25 | 이강춘 | 생체적합성 고분자가 수식된 펩타이드의 비점막 전달 |
| US6323311B1 (en) | 1999-09-22 | 2001-11-27 | University Of Utah Research Foundation | Synthesis of insulin derivatives |
| US7060675B2 (en) | 2001-02-15 | 2006-06-13 | Nobex Corporation | Methods of treating diabetes mellitus |
| US6867183B2 (en) | 2001-02-15 | 2005-03-15 | Nobex Corporation | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
| 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 |
| 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 |
| 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 |
| US6835802B2 (en) | 2001-06-04 | 2004-12-28 | Nobex Corporation | Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties |
| WO2002098448A1 (en) | 2001-06-04 | 2002-12-12 | Human Genome Sciences, Inc. | Methods and compositions for modulating ace-2 activity |
| 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 |
| 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 |
| US6770625B2 (en) | 2001-09-07 | 2004-08-03 | Nobex Corporation | Pharmaceutical compositions of calcitonin drug-oligomer conjugates and methods of treating diseases therewith |
| WO2003022996A2 (en) | 2001-09-07 | 2003-03-20 | Nobex Corporation | Methods of synthesizing insulin polypeptide-oligomer conjugates, and proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| KR101309770B1 (ko) * | 2004-07-19 | 2013-09-30 | 바이오콘 리미티드 | 인슐린―올리고머 접합체，제형 및 이들의 용도 |
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|---|---|
| BR0207700A (pt) | 2005-07-19 |
| US7060675B2 (en) | 2006-06-13 |
| US20060100137A1 (en) | 2006-05-11 |
| WO2002065985A3 (en) | 2004-02-19 |
| EP1409006A4 (en) | 2005-01-19 |
| CY1112034T1 (el) | 2015-11-04 |
| US20060293219A1 (en) | 2006-12-28 |
| NO20033617D0 (no) | 2003-08-14 |
| NO20033617L (no) | 2003-10-15 |
| JP2004527487A (ja) | 2004-09-09 |
| KR20040043113A (ko) | 2004-05-22 |
| CA2437940C (en) | 2012-07-10 |
| EP1409006B1 (en) | 2011-03-30 |
| DE60239612D1 (de) | 2011-05-12 |
| WO2002065985A2 (en) | 2002-08-29 |
| BRPI0207700B8 (pt) | 2021-05-25 |
| ZA200306332B (en) | 2005-07-27 |
| JP4113778B2 (ja) | 2008-07-09 |
| CA2437940A1 (en) | 2002-08-29 |
| KR100896945B1 (ko) | 2009-05-14 |
| NO327586B1 (no) | 2009-08-24 |
| US7423014B2 (en) | 2008-09-09 |
| PT1409006E (pt) | 2011-07-01 |
| US7381702B2 (en) | 2008-06-03 |
| ATE503490T1 (de) | 2011-04-15 |
| AU2002244020B2 (en) | 2007-08-16 |
| EP1409006A2 (en) | 2004-04-21 |
| DK1409006T3 (da) | 2011-06-14 |
| US20030050228A1 (en) | 2003-03-13 |
| MXPA03007374A (es) | 2003-12-04 |
| BRPI0207700B1 (pt) | 2016-06-07 |
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