ZA200608475B - Method for the purification of albumin conjugates - Google Patents
Method for the purification of albumin conjugates Download PDFInfo
- Publication number
- ZA200608475B ZA200608475B ZA200608475A ZA200608475A ZA200608475B ZA 200608475 B ZA200608475 B ZA 200608475B ZA 200608475 A ZA200608475 A ZA 200608475A ZA 200608475 A ZA200608475 A ZA 200608475A ZA 200608475 B ZA200608475 B ZA 200608475B
- Authority
- ZA
- South Africa
- Prior art keywords
- conjugate
- albumin
- analogue
- purification
- hsa
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 115
- 102000009027 Albumins Human genes 0.000 title claims abstract description 81
- 108010088751 Albumins Proteins 0.000 title claims abstract description 81
- 238000000746 purification Methods 0.000 title description 235
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 22
- 230000003247 decreasing effect Effects 0.000 claims abstract description 6
- 239000012062 aqueous buffer Substances 0.000 claims abstract description 5
- 108091006905 Human Serum Albumin Proteins 0.000 claims description 218
- 102000008100 Human Serum Albumin Human genes 0.000 claims description 218
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims description 100
- 239000012619 Butyl Sepharose® Substances 0.000 claims description 82
- 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 description 45
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- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 claims description 12
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- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 9
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- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 claims description 8
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- 235000018417 cysteine Nutrition 0.000 claims description 7
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims description 6
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- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 5
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- GUPXYSSGJWIURR-UHFFFAOYSA-N 3-octoxypropane-1,2-diol Chemical compound CCCCCCCCOCC(O)CO GUPXYSSGJWIURR-UHFFFAOYSA-N 0.000 claims description 3
- 238000011068 loading method Methods 0.000 claims description 3
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- 101800001890 Atrial natriuretic peptide Proteins 0.000 claims description 2
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- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 2
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Classifications
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- 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
- C07K1/303—Extraction; Separation; Purification by precipitation by salting out
-
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/643—Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
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- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/32—Bonded phase chromatography
- B01D15/325—Reversed phase
- B01D15/327—Reversed phase with hydrophobic interaction
-
- 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
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/20—Partition-, reverse-phase or hydrophobic interaction chromatography
-
- 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
- C07K14/76—Albumins
-
- 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
- C07K14/76—Albumins
- C07K14/765—Serum albumin, e.g. HSA
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
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- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/16—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the fluid carrier
- B01D15/166—Fluid composition conditioning, e.g. gradient
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/42—Selective adsorption, e.g. chromatography characterised by the development mode, e.g. by displacement or by elution
- B01D15/424—Elution mode
- B01D15/426—Specific type of solvent
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
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- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6924264B1 (en) * | 1999-04-30 | 2005-08-02 | Amylin Pharmaceuticals, Inc. | Modified exendins and exendin agonists |
| ES2209885T3 (es) * | 1999-05-17 | 2004-07-01 | Conjuchem, Inc. | Peptidos insulinotropicos de larga duracion. |
| US7582301B1 (en) * | 1999-05-17 | 2009-09-01 | Conjuchem Biotechnologies, Inc. | Long-lasting antiviral fusion inhibitor peptide conjugates comprising albumin and human immunodeficiency virus (HIV) peptides |
| US6514500B1 (en) * | 1999-10-15 | 2003-02-04 | Conjuchem, Inc. | Long lasting synthetic glucagon like peptide {GLP-!} |
| US7601691B2 (en) | 1999-05-17 | 2009-10-13 | Conjuchem Biotechnologies Inc. | Anti-obesity agents |
| US20040266673A1 (en) * | 2002-07-31 | 2004-12-30 | Peter Bakis | Long lasting natriuretic peptide derivatives |
| US20090175821A1 (en) * | 1999-05-17 | 2009-07-09 | Bridon Dominique P | Modified therapeutic peptides with extended half-lives in vivo |
| CA2436399A1 (en) * | 2001-02-16 | 2002-08-29 | Conjuchem Inc. | Long lasting glucagon-like peptide 2 (glp-2) for the treatment of gastrointestinal diseases and disorders |
| DE60229677D1 (de) | 2001-05-31 | 2008-12-11 | Conjuchem Biotechnologies Inc | Langwirkende Fusionspeptidinhibitoren gegen HIV-Infektion |
| WO2005108418A1 (en) * | 2004-05-06 | 2005-11-17 | Conjuchem Biotechnologies Inc. | Compounds for specific viral target |
| WO2007053946A1 (en) | 2005-11-09 | 2007-05-18 | Conjuchem Biotechnologies Inc. | Method of treating diabetes and/or obesity with reduced nausea side effects using an insulinotropic peptide conjugated to albumin |
| MX2008008076A (es) * | 2005-12-22 | 2008-11-28 | Conjuchem Biotechnologies Inc | Procesos para la produccion de conjugados preformados de albumina y un agente terapeutico. |
| WO2008047241A2 (en) * | 2006-10-16 | 2008-04-24 | Conjuchem Biotechnologies Inc. | Modified corticotropin releasing factor peptides and uses thereof |
| US20090099074A1 (en) * | 2007-01-10 | 2009-04-16 | Conjuchem Biotechnologies Inc. | Modulating food intake |
| US20090088378A1 (en) * | 2007-01-12 | 2009-04-02 | Omar Quraishi | Long lasting inhibitors of viral infection |
| US20090088377A1 (en) * | 2007-05-16 | 2009-04-02 | Conjuchem Biotechnologies, Inc. | Cysteic acid derivatives of anti-viral peptides |
| WO2008157824A2 (en) * | 2007-06-21 | 2008-12-24 | Conjuchem Biotechnologies Inc. | Thrombopoietin peptide conjugates |
| WO2009075859A2 (en) * | 2007-12-11 | 2009-06-18 | Conjuchem Biotechnologies Inc. | Formulation of insulinotropic peptide conjugates |
| US8871899B2 (en) * | 2007-12-31 | 2014-10-28 | New York University | Control of viral-host membrane fusion with hydrogen bond surrogate-based artificial helices |
| EP2262539B1 (en) | 2008-04-01 | 2015-07-15 | Novo Nordisk A/S | Insulin albumin conjugates |
| CN101987868B (zh) * | 2009-07-30 | 2013-09-04 | 江苏豪森医药集团有限公司 | Glp-1类似物的衍生物或其可药用盐和用途 |
| BR112012012945A2 (pt) | 2009-11-25 | 2020-12-29 | Arisgen Sa | Composição de liberação mucosal, seu método de produção, complexo de peptídeo pré-formado, kit e uso de um agente ativo de peptídeo |
| US9744155B2 (en) | 2012-03-28 | 2017-08-29 | Ixcela, Inc. | IPA as a therapeutic agent, as a protective agent, and as a biomarker of disease risk |
| PT3092010T (pt) * | 2014-01-10 | 2018-09-28 | Synthon Biopharmaceuticals Bv | Método para purificação de conjugados anticorpo-fármaco ligados por cys |
| EP3099809A4 (en) * | 2014-01-31 | 2017-10-25 | Ixcela, Inc. | Covalently bound metabolites as biomarkers |
| US9616109B2 (en) * | 2014-10-22 | 2017-04-11 | Extend Biosciences, Inc. | Insulin vitamin D conjugates |
| CN105111306A (zh) * | 2015-08-28 | 2015-12-02 | 北京工业大学 | 美洲短吻鳄白蛋白的分离方法 |
| AU2017238246B2 (en) | 2016-03-24 | 2021-04-01 | The Administrators Of The Tulane Educational Fund | Conjugates of tacrolimus, their compositions, and their uses |
| TWI794897B (zh) | 2017-09-28 | 2023-03-01 | 南韓商韓美藥品股份有限公司 | Ｇｌｐ-２衍生物之長效接合物 |
| CN108840922A (zh) * | 2018-06-04 | 2018-11-20 | 河北常山生化药业股份有限公司 | 分离白蛋白非结合物、白蛋白结合物和小分子化合物的方法 |
| CN108977423A (zh) * | 2018-08-17 | 2018-12-11 | 集美大学 | 一种从猪肺中分离提纯血管紧张素转化酶的方法 |
| US11041847B1 (en) | 2019-01-25 | 2021-06-22 | Ixcela, Inc. | Detection and modification of gut microbial population |
| CN109721653B (zh) * | 2019-03-05 | 2023-02-03 | 嘉兴学院 | 一种胰高血糖素样肽-1片段类似物及其应用 |
| WO2021175275A1 (zh) * | 2020-03-06 | 2021-09-10 | 昆山新蕴达生物科技有限公司 | 疏水性修饰的白蛋白及其制备方法和用途 |
| WO2021222759A1 (en) * | 2020-04-30 | 2021-11-04 | Board Of Regents, The University Of Texas System | Albumin drug conjugates and use thereof for the treatment of cancer |
| US11739166B2 (en) | 2020-07-02 | 2023-08-29 | Davol Inc. | Reactive polysaccharide-based hemostatic agent |
Family Cites Families (90)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4206199A (en) | 1977-07-22 | 1980-06-03 | Takeda Chemical Industries, Ltd. | Novel glucagon fragment and its derivatives |
| US4251631A (en) | 1978-02-23 | 1981-02-17 | Research Products Rehovot Ltd. | Cross-linked enzyme membrane |
| US4423034A (en) | 1980-10-16 | 1983-12-27 | Toyo Jozo Kabushiki Kaisha | Process for the preparation of antibodies |
| US4678671A (en) * | 1981-12-15 | 1987-07-07 | Cordis Europa N.V. | Conjugates of anticoagulant and protein |
| US4462941A (en) | 1982-06-10 | 1984-07-31 | The Regents Of The University Of California | Dynorphin amide analogs |
| US4745100A (en) | 1985-05-14 | 1988-05-17 | Eye Research Institute Of Retina Foundation | Stimulation of tear secretion |
| US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| US5614492A (en) | 1986-05-05 | 1997-03-25 | The General Hospital Corporation | Insulinotropic hormone GLP-1 (7-36) and uses thereof |
| US5120712A (en) | 1986-05-05 | 1992-06-09 | The General Hospital Corporation | Insulinotropic hormone |
| US5118666A (en) | 1986-05-05 | 1992-06-02 | The General Hospital Corporation | Insulinotropic hormone |
| US4902505A (en) | 1986-07-30 | 1990-02-20 | Alkermes | Chimeric peptides for neuropeptide delivery through the blood-brain barrier |
| US4859604A (en) | 1987-08-27 | 1989-08-22 | Ampor, Inc. | Composition for stabilization of diagnostic reagents |
| US5545618A (en) | 1990-01-24 | 1996-08-13 | Buckley; Douglas I. | GLP-1 analogs useful for diabetes treatment |
| US5843440A (en) * | 1990-10-03 | 1998-12-01 | Redcell Canada, Inc. | Cellular and serum protein anchors for modulating pharmacokinetics |
| US5612034A (en) * | 1990-10-03 | 1997-03-18 | Redcell, Inc. | Super-globuling for in vivo extended lifetimes |
| US5725804A (en) | 1991-01-15 | 1998-03-10 | Hemosphere, Inc. | Non-crosslinked protein particles for therapeutic and diagnostic use |
| WO1992017492A1 (en) | 1991-04-05 | 1992-10-15 | Genentech, Inc. | PLATELET AGGREGATION INHIBITORS HAVING HIGH SPECIFICITY FOR GP IIbIII¿a? |
| US5103233A (en) | 1991-04-16 | 1992-04-07 | General Electric Co. | Radar system with elevation-responsive PRF control, beam multiplex control, and pulse integration control responsive to azimuth angle |
| CA2452130A1 (en) | 1992-03-05 | 1993-09-16 | Francis J. Burrows | Methods and compositions for targeting the vasculature of solid tumors |
| JPH07102148B2 (ja) * | 1992-05-20 | 1995-11-08 | 株式会社ミドリ十字 | 遺伝子操作により得られるヒト血清アルブミンの製造方法、およびそれにより得られるヒト血清アルブミン含有組成物 |
| US5807827A (en) | 1992-06-12 | 1998-09-15 | Des-Tyr Dynorphin Partnership | Des-Tyr dynorphin analogues |
| US5424286A (en) | 1993-05-24 | 1995-06-13 | Eng; John | Exendin-3 and exendin-4 polypeptides, and pharmaceutical compositions comprising same |
| US5614487A (en) | 1993-05-28 | 1997-03-25 | Genentech, Inc. | Sustained release pharmaceutical composition |
| US20020018751A1 (en) * | 1993-10-15 | 2002-02-14 | BRIDON Dominique P. | Cellular and serum protein anchors for diagnostic imaging |
| US5705483A (en) | 1993-12-09 | 1998-01-06 | Eli Lilly And Company | Glucagon-like insulinotropic peptides, compositions and methods |
| DK145493D0 (da) | 1993-12-23 | 1993-12-23 | Dako As | Antistof |
| US5580853A (en) | 1994-03-22 | 1996-12-03 | New England Deaconess Hospital | Modified polypeptides with increased biological activity |
| EP0759768A4 (en) | 1994-04-07 | 2000-08-09 | Proteinix Company | VASOACTIVE COLON PEPTIDE |
| US5574008A (en) | 1994-08-30 | 1996-11-12 | Eli Lilly And Company | Biologically active fragments of glucagon-like insulinotropic peptide |
| DE69532492T2 (de) * | 1994-08-31 | 2004-12-02 | Mitsubishi Pharma Corp. | Verfahren zur Reinigung von rekombinantem menschlichem Serumalbumin |
| US5939390A (en) | 1995-03-09 | 1999-08-17 | Novo Nordisk A/S | Pharmaceutical composition |
| US5869602A (en) | 1995-03-17 | 1999-02-09 | Novo Nordisk A/S | Peptide derivatives |
| US5654276A (en) | 1995-06-07 | 1997-08-05 | Affymax Technologies N.V. | Peptides and compounds that bind to the IL-5 receptor |
| US6277583B1 (en) * | 1996-02-07 | 2001-08-21 | Conjuchem, Inc. | Affinity labeling libraries and applications thereof |
| ES2256888T3 (es) | 1996-06-05 | 2006-07-16 | Roche Diagnostics Gmbh | Analogos de exendina, proceso para su preparacion y medicamentos que los contienen. |
| US5840733A (en) * | 1996-07-01 | 1998-11-24 | Redcell, Canada, Inc. | Methods and compositions for producing novel conjugates of thrombin inhibitors and endogenous carriers resulting in anti-thrombins with extended lifetimes |
| US5763401A (en) | 1996-07-12 | 1998-06-09 | Bayer Corporation | Stabilized albumin-free recombinant factor VIII preparation having a low sugar content |
| PT966297E (pt) | 1996-08-08 | 2009-03-18 | Amylin Pharmaceuticals Inc | Regulação da motilidade gastrintestinal |
| US6006753A (en) | 1996-08-30 | 1999-12-28 | Eli Lilly And Company | Use of GLP-1 or analogs to abolish catabolic changes after surgery |
| US6277819B1 (en) | 1996-08-30 | 2001-08-21 | Eli Lilly And Company | Use of GLP-1 or analogs in treatment of myocardial infarction |
| US6268343B1 (en) | 1996-08-30 | 2001-07-31 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
| AU4351897A (en) * | 1996-09-16 | 1998-04-02 | Conjuchem, Inc. | Affinity labeling libraries with tagged leaving groups |
| UA65549C2 (uk) | 1996-11-05 | 2004-04-15 | Елі Ліллі Енд Компані | Спосіб регулювання ожиріння шляхом периферійного введення аналогів та похідних glp-1 (варіанти) та фармацевтична композиція |
| ATE289517T1 (de) | 1996-11-12 | 2005-03-15 | Novo Nordisk As | Verwendung von glp-1 peptiden |
| HU222666B1 (hu) * | 1996-11-15 | 2003-09-29 | Genentech, Inc. | Eljárás neuorotrofinok tisztítására |
| DK1629849T4 (en) | 1997-01-07 | 2017-12-04 | Amylin Pharmaceuticals Llc | Pharmaceutical compositions comprising exedins and agonists thereof |
| US6723530B1 (en) | 1997-02-05 | 2004-04-20 | Amylin Pharmaceuticals, Inc. | Polynucleotides encoding proexendin, and methods and uses thereof |
| CA2283834A1 (en) | 1997-03-31 | 1998-10-08 | James Arthur Hoffmann | Glucagon-like peptide-1 analogs |
| DE69806066T2 (de) * | 1997-11-07 | 2003-02-06 | Conjuchem, Inc. | Affinitätsmarkierer für menschliches serum albumin |
| US6437092B1 (en) * | 1998-11-06 | 2002-08-20 | Conjuchem, Inc. | Conjugates of opioids and endogenous carriers |
| EP1007561B1 (en) * | 1997-11-07 | 2002-04-17 | Conjuchem, Inc. | Novel conjugates of opioids and endogenous carriers |
| US6703359B1 (en) | 1998-02-13 | 2004-03-09 | Amylin Pharmaceuticals, Inc. | Inotropic and diuretic effects of exendin and GLP-1 |
| JP2003522099A (ja) | 1998-02-27 | 2003-07-22 | ノボ ノルディスク アクティーゼルスカブ | 遅延作用プロファイルを有するｇｌｐ−１のｇｌｐ−１誘導体及びエキセンジン |
| US6107489A (en) * | 1998-03-17 | 2000-08-22 | Conjuchem, Inc. | Extended lifetimes in vivo renin inhibitors |
| US6998387B1 (en) | 1998-03-19 | 2006-02-14 | Amylin Pharmaceuticals, Inc. | Human appetite control by glucagon-like peptide receptor binding compounds |
| US20030170250A1 (en) * | 1998-03-23 | 2003-09-11 | Ezrin Alan M. | Local delivery of long lasting therapeutic agents |
| US6284725B1 (en) | 1998-10-08 | 2001-09-04 | Bionebraska, Inc. | Metabolic intervention with GLP-1 to improve the function of ischemic and reperfused tissue |
| US6440417B1 (en) * | 1998-11-06 | 2002-08-27 | Conjuchem, Inc. | Antibodies to argatroban derivatives and their use in therapeutic and diagnostic treatments |
| US7399489B2 (en) * | 1999-01-14 | 2008-07-15 | Amylin Pharmaceuticals, Inc. | Exendin analog formulations |
| ES2343072T3 (es) | 1999-01-14 | 2010-07-22 | Amylin Pharmaceuticals, Inc. | Exendina para la supresion del glucagon. |
| DE60021166T3 (de) | 1999-01-14 | 2019-08-22 | Amylin Pharmaceuticals, Llc | Neue exendin agonist formulierungen und deren verabreichung |
| US6924264B1 (en) | 1999-04-30 | 2005-08-02 | Amylin Pharmaceuticals, Inc. | Modified exendins and exendin agonists |
| ES2209885T3 (es) * | 1999-05-17 | 2004-07-01 | Conjuchem, Inc. | Peptidos insulinotropicos de larga duracion. |
| US7144854B1 (en) | 1999-09-10 | 2006-12-05 | Conjuchem, Inc. | Long lasting anti-angiogenic peptides |
| US6514500B1 (en) * | 1999-10-15 | 2003-02-04 | Conjuchem, Inc. | Long lasting synthetic glucagon like peptide {GLP-!} |
| US20040266673A1 (en) * | 2002-07-31 | 2004-12-30 | Peter Bakis | Long lasting natriuretic peptide derivatives |
| US7582301B1 (en) * | 1999-05-17 | 2009-09-01 | Conjuchem Biotechnologies, Inc. | Long-lasting antiviral fusion inhibitor peptide conjugates comprising albumin and human immunodeficiency virus (HIV) peptides |
| US6887470B1 (en) * | 1999-09-10 | 2005-05-03 | Conjuchem, Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
| US7601691B2 (en) * | 1999-05-17 | 2009-10-13 | Conjuchem Biotechnologies Inc. | Anti-obesity agents |
| US6849714B1 (en) * | 1999-05-17 | 2005-02-01 | Conjuchem, Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
| US6506724B1 (en) | 1999-06-01 | 2003-01-14 | Amylin Pharmaceuticals, Inc. | Use of exendins and agonists thereof for the treatment of gestational diabetes mellitus |
| DE19926154A1 (de) * | 1999-06-09 | 2000-12-14 | Ktb Tumorforschungs Gmbh | Verfahren zur Herstellung einer injizierbaren Arzneimittelzubereitung |
| AU5325200A (en) | 1999-06-21 | 2001-01-09 | Eli Lilly And Company | Synergistic use of thiazolidinediones with glucagon-like peptide-1 and agonists thereof to treat metabolic instability associated with non-insulin dependent diabetes |
| US6528486B1 (en) | 1999-07-12 | 2003-03-04 | Zealand Pharma A/S | Peptide agonists of GLP-1 activity |
| DE19932782A1 (de) * | 1999-07-14 | 2001-01-18 | Biotest Pharma Gmbh | Verfahren zur chromatographischen Fraktionierung von Plasma oder Serum, so erhaltene Präparate und deren Verwendung |
| DE19936780A1 (de) | 1999-08-09 | 2001-02-15 | Basf Ag | Neue Antagonisten von Integrinrezeptoren |
| US6706892B1 (en) * | 1999-09-07 | 2004-03-16 | Conjuchem, Inc. | Pulmonary delivery for bioconjugation |
| US7090851B1 (en) | 1999-09-10 | 2006-08-15 | Conjuchem Inc. | Long lasting fusion peptide inhibitors of viral infection |
| US20020003999A1 (en) * | 2000-03-09 | 2002-01-10 | Claus Bonde | Discharge and stacker device |
| US6926898B2 (en) * | 2000-04-12 | 2005-08-09 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| AU2001263230B2 (en) | 2000-05-19 | 2005-03-10 | Amylin Pharmaceuticals, Llc | Treatment of acute coronary syndrome with glp-1 |
| MXPA02006118A (es) | 2000-10-20 | 2004-08-23 | Amylin Pharmaceuticals Inc | Tratamiento de la invernacion del miocardio y cardiopatia diabetica con un peptido glp-1. |
| WO2002047716A2 (en) | 2000-12-13 | 2002-06-20 | Eli Lilly And Company | Chronic treatment regimen using glucagon-like insulinotropic peptides |
| EP1355941A2 (en) * | 2001-02-02 | 2003-10-29 | ConjuChem, Inc. | Long lasting growth hormone releasing factor derivatives |
| CA2436399A1 (en) * | 2001-02-16 | 2002-08-29 | Conjuchem Inc. | Long lasting glucagon-like peptide 2 (glp-2) for the treatment of gastrointestinal diseases and disorders |
| DE60229677D1 (de) * | 2001-05-31 | 2008-12-11 | Conjuchem Biotechnologies Inc | Langwirkende Fusionspeptidinhibitoren gegen HIV-Infektion |
| SE526227C2 (sv) * | 2002-05-15 | 2005-08-02 | North China Pharmaceutical Group | Metod för rening av rekombinant humant serumalbumin |
| US6861236B2 (en) | 2002-05-24 | 2005-03-01 | Applied Nanosystems B.V. | Export and modification of (poly)peptides in the lantibiotic way |
| US6989369B2 (en) * | 2003-02-07 | 2006-01-24 | Dyax Corp. | Kunitz domain peptides |
| KR20060109940A (ko) * | 2003-12-18 | 2006-10-23 | 노보 노르디스크 에이/에스 | 알부민-유사제에 연결된 신규 ｇｌｐ-1 유사체 |
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2005
- 2005-04-22 DE DE602005014969T patent/DE602005014969D1/de active Active
- 2005-04-22 RS RSP-2006/0578A patent/RS20060578A/sr unknown
- 2005-04-22 EP EP10164991A patent/EP2230257A1/en not_active Withdrawn
- 2005-04-22 CA CA002564031A patent/CA2564031A1/en not_active Abandoned
- 2005-04-22 ES ES09162758T patent/ES2347902T3/es active Active
- 2005-04-22 US US11/112,277 patent/US7307148B2/en not_active Expired - Fee Related
- 2005-04-22 BR BRPI0510117-4A patent/BRPI0510117A/pt not_active IP Right Cessation
- 2005-04-22 PT PT09162758T patent/PT2100904E/pt unknown
- 2005-04-22 DK DK05735795T patent/DK1745078T3/da active
- 2005-04-22 EP EP09162758A patent/EP2100904B1/en not_active Not-in-force
- 2005-04-22 JP JP2007508697A patent/JP2007535507A/ja active Pending
- 2005-04-22 SI SI200530766T patent/SI1745078T1/sl unknown
- 2005-04-22 PL PL09162758T patent/PL2100904T3/pl unknown
- 2005-04-22 PL PL05735795T patent/PL1745078T3/pl unknown
- 2005-04-22 AT AT09162758T patent/ATE473244T1/de active
- 2005-04-22 PT PT05735795T patent/PT1745078E/pt unknown
- 2005-04-22 ES ES05735795T patent/ES2328591T3/es active Active
- 2005-04-22 DE DE602005022239T patent/DE602005022239D1/de active Active
- 2005-04-22 DK DK09162758.8T patent/DK2100904T3/da active
- 2005-04-22 MX MXPA06012260A patent/MXPA06012260A/es active IP Right Grant
- 2005-04-22 AT AT05735795T patent/ATE433999T1/de active
- 2005-04-22 EP EP05735795A patent/EP1745078B1/en not_active Revoked
- 2005-04-22 SI SI200531088T patent/SI2100904T1/sl unknown
- 2005-04-22 EA EA200601959A patent/EA011168B1/ru not_active IP Right Cessation
- 2005-04-22 WO PCT/CA2005/000614 patent/WO2005103087A1/en active Application Filing
- 2005-04-22 CN CN2005800127938A patent/CN1956998B/zh active Active
- 2005-04-22 AU AU2005235634A patent/AU2005235634B2/en not_active Ceased
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2006
- 2006-09-28 IL IL178369A patent/IL178369A0/en unknown
- 2006-10-11 ZA ZA200608475A patent/ZA200608475B/en unknown
- 2006-10-20 TN TNP2006000340A patent/TNSN06340A1/en unknown
- 2006-10-23 HR HR20060362A patent/HRP20060362A2/xx not_active Application Discontinuation
- 2006-11-02 NO NO20065037A patent/NO20065037L/no not_active Application Discontinuation
- 2006-11-20 MA MA29463A patent/MA28587B1/fr unknown
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2007
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- 2007-10-30 US US11/981,474 patent/US20080146783A1/en not_active Abandoned
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2010
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- 2010-09-17 US US12/885,036 patent/US20120022234A1/en not_active Abandoned
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