JP2019528306A5 - - Google Patents
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- JP2019528306A5 JP2019528306A5 JP2019511610A JP2019511610A JP2019528306A5 JP 2019528306 A5 JP2019528306 A5 JP 2019528306A5 JP 2019511610 A JP2019511610 A JP 2019511610A JP 2019511610 A JP2019511610 A JP 2019511610A JP 2019528306 A5 JP2019528306 A5 JP 2019528306A5
- Authority
- JP
- Japan
- Prior art keywords
- composition
- insulin
- group
- antigen
- binding fragment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 239000000203 mixture Substances 0.000 claims description 81
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Substances 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 54
- 108010063919 Glucagon Receptors Proteins 0.000 claims description 53
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- 150000001413 amino acids Chemical group 0.000 claims description 51
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- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)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(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims description 35
- 229960004666 glucagon Drugs 0.000 claims description 35
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- 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 19
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- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims description 12
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- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 claims description 6
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 6
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- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 claims description 6
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- 229940123208 Biguanide Drugs 0.000 claims description 6
- 102100032378 Carboxypeptidase E Human genes 0.000 claims description 6
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- 102100032230 Caveolae-associated protein 1 Human genes 0.000 claims description 6
- 102100032137 Cell death activator CIDE-3 Human genes 0.000 claims description 6
- 102100024395 DCC-interacting protein 13-alpha Human genes 0.000 claims description 6
- 102100024829 DNA polymerase delta catalytic subunit Human genes 0.000 claims description 6
- 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 claims description 6
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- 102100032882 Glucagon-like peptide 1 receptor Human genes 0.000 claims description 6
- 101150090959 Grb10 gene Proteins 0.000 claims description 6
- 101000605571 Homo sapiens 1-acyl-sn-glycerol-3-phosphate acyltransferase beta Proteins 0.000 claims description 6
- 101001135306 Homo sapiens 26S proteasome non-ATPase regulatory subunit 6 Proteins 0.000 claims description 6
- 101000756842 Homo sapiens Alpha-2A adrenergic receptor Proteins 0.000 claims description 6
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- 101001069891 Homo sapiens RAS guanyl-releasing protein 1 Proteins 0.000 claims description 6
- 101000606537 Homo sapiens Receptor-type tyrosine-protein phosphatase delta Proteins 0.000 claims description 6
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- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 6
- 229930064664 L-arginine Natural products 0.000 claims description 6
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- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical compound IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 claims description 6
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Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022122568A JP7633213B2 (ja) | 2016-08-30 | 2022-08-01 | グルカゴン受容体シグナル伝達の干渉による重度のインスリン抵抗性の処置方法 |
| JP2024159035A JP2024178249A (ja) | 2016-08-30 | 2024-09-13 | グルカゴン受容体シグナル伝達の干渉による重度のインスリン抵抗性の処置方法 |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662381263P | 2016-08-30 | 2016-08-30 | |
| US62/381,263 | 2016-08-30 | ||
| US201662411032P | 2016-10-21 | 2016-10-21 | |
| US62/411,032 | 2016-10-21 | ||
| PCT/US2017/049137 WO2018044903A1 (en) | 2016-08-30 | 2017-08-29 | Methods of treating severe insulin resistance by interfering with glucagon receptor signaling |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022122568A Division JP7633213B2 (ja) | 2016-08-30 | 2022-08-01 | グルカゴン受容体シグナル伝達の干渉による重度のインスリン抵抗性の処置方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019528306A JP2019528306A (ja) | 2019-10-10 |
| JP2019528306A5 true JP2019528306A5 (cg-RX-API-DMAC7.html) | 2020-10-08 |
| JP7173962B2 JP7173962B2 (ja) | 2022-11-16 |
Family
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Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019511610A Active JP7173962B2 (ja) | 2016-08-30 | 2017-08-29 | グルカゴン受容体シグナル伝達の干渉による重度のインスリン抵抗性の処置方法 |
| JP2022122568A Active JP7633213B2 (ja) | 2016-08-30 | 2022-08-01 | グルカゴン受容体シグナル伝達の干渉による重度のインスリン抵抗性の処置方法 |
| JP2024159035A Pending JP2024178249A (ja) | 2016-08-30 | 2024-09-13 | グルカゴン受容体シグナル伝達の干渉による重度のインスリン抵抗性の処置方法 |
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| JP2024159035A Pending JP2024178249A (ja) | 2016-08-30 | 2024-09-13 | グルカゴン受容体シグナル伝達の干渉による重度のインスリン抵抗性の処置方法 |
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| KR20190044079A (ko) | 2016-08-30 | 2019-04-29 | 리제너론 파마슈티칼스 인코포레이티드 | 글루카곤 수용체 신호전달을 간섭함에 의한 중증 인슐린 저항성의 치료 방법 |
| CN110357959B (zh) * | 2018-04-10 | 2023-02-28 | 鸿运华宁（杭州）生物医药有限公司 | Gcgr抗体及其与glp-1的融合蛋白质，以及其药物组合物和应用 |
| JP2022523301A (ja) * | 2019-01-23 | 2022-04-22 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | アンジオポエチン様７（ａｎｇｐｔｌ７）阻害剤による眼疾患の治療 |
| US20220288169A1 (en) * | 2019-05-24 | 2022-09-15 | The Board of Supervisors of Louisiana State University and Agriculyural and Mechanical College | Compositions and methods for the treatment and prevention of hypoglycemic complications |
| US12398202B2 (en) | 2019-09-04 | 2025-08-26 | Apharma | Use of ITIH1 as biomarker for detection of insulin resistance in diseases accompanied by impaired glucose tolerance |
| CN113481290B (zh) * | 2021-06-30 | 2022-08-23 | 华南农业大学 | 一种klf4基因在制备检测和/或减少母鼠不良妊娠结局的产品中的应用 |
| CN114342875A (zh) * | 2022-01-12 | 2022-04-15 | 吉林大学 | 一种新型妊娠糖尿病动物模型的建立方法 |
| WO2025042188A1 (ko) | 2023-08-21 | 2025-02-27 | 주식회사 엘지에너지솔루션 | 셀 어셈블리 및 이를 포함하는 전지 모듈, 그리고 셀 어셈블리 제조방법 |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5836308B2 (ja) | 1977-02-10 | 1983-08-08 | 大塚製薬株式会社 | 抗体の製造方法 |
| US4206199A (en) | 1977-07-22 | 1980-06-03 | Takeda Chemical Industries, Ltd. | Novel glucagon fragment and its derivatives |
| JPS56163456A (en) | 1980-05-21 | 1981-12-16 | Otsuka Pharmaceut Co Ltd | Preparation of antigen |
| US4423034A (en) | 1980-10-16 | 1983-12-27 | Toyo Jozo Kabushiki Kaisha | Process for the preparation of antibodies |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| RU2184779C2 (ru) | 1992-08-28 | 2002-07-10 | Ново Нордиск А/С | Изолированная молекула днк, кодирующая рецептор глюкагона, днк-конструкция, линия клеток, способ получения рецептора глюкагона, изолированный пептид рецептора глюкагона, изолированное антитело, зонд, способ обнаружения присутствия антагонистов глюкагона |
| JP2729159B2 (ja) | 1994-10-31 | 1998-03-18 | 日清製粉株式会社 | ヒトグリセンチンのモノクローナル抗体、この抗体を産生するハイブリドーマおよびそれを用いるヒトグリセンチンの定量法 |
| US20040101920A1 (en) | 2002-11-01 | 2004-05-27 | Czeslaw Radziejewski | Modification assisted profiling (MAP) methodology |
| JP2007514794A (ja) | 2003-12-19 | 2007-06-07 | メルク エンド カムパニー インコーポレーテッド | 環式グアニジン、そのような化合物を含む組成、及び使用方法 |
| EP1740946B1 (en) | 2004-04-20 | 2013-11-06 | Genmab A/S | Human monoclonal antibodies against cd20 |
| HRP20080311T3 (hr) | 2004-06-04 | 2008-07-31 | Merck & Co. Inc. | Derivati pirazola, pripravci koji sadrže takve spojeve i postupci za njihovu primjenu |
| DE102004028862A1 (de) | 2004-06-15 | 2005-12-29 | Merck Patent Gmbh | 3-Aminoindazole |
| WO2006017055A2 (en) | 2004-07-07 | 2006-02-16 | Merck & Co., Inc. | Pyrazole amide derivatives, compositions containing such compounds and methods of use |
| US7625938B2 (en) | 2004-07-22 | 2009-12-01 | Merck & Co., Inc. | Substituted pyrazoles, compositions containing such compounds and methods of use |
| DE602006009773D1 (de) | 2005-02-11 | 2009-11-26 | Lilly Co Eli | Substituierte thiophenderivate als glucagonrezeptorantagonisten, herstellung und therapeutische anwendungen |
| JP2008533200A (ja) | 2005-03-21 | 2008-08-21 | メルク エンド カムパニー インコーポレーテッド | 置換アリールおよびヘテロアリール誘導体、かかる化合物を含有する組成物および使用法 |
| AU2006229904A1 (en) | 2005-03-30 | 2006-10-05 | Merck Sharp & Dohme Corp. | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
| AR056574A1 (es) | 2005-10-19 | 2007-10-10 | Merck & Co Inc | Derivados de pirazol, composiciones que contienen dichos compuestos y procedimientos de uso |
| WO2007124463A1 (en) | 2006-04-20 | 2007-11-01 | Amgen Inc. | Glp-1 compound/glucagon antibody compositions |
| CL2007002668A1 (es) | 2006-09-20 | 2008-05-09 | Amgen Inc | Proteina de union a antigeno que se une al receptor de glucagon humano; acido nucleico que la codifica; metodo de produccion; composicion farmaceutica que la comprende; y su uso para tratar o prevenir la diabetes tipo 2. |
| TW200821284A (en) | 2006-10-03 | 2008-05-16 | Merck & Co Inc | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
| KR101538810B1 (ko) | 2007-02-09 | 2015-07-22 | 메타베이시스 테라퓨틱스, 인크. | 글루카곤 수용체의 길항제 |
| AR070844A1 (es) | 2008-03-27 | 2010-05-05 | Lilly Co Eli | Fragmento fab o anticuerpo monoclonal humanizado que comprende el fragmento fab, y su uso para la manufactura de un medicamento antagonista del polipeptido del receptor de glucagon para el tratamiento o prevencion de diabetes de tipo 1 o 2 |
| WO2009140342A1 (en) | 2008-05-16 | 2009-11-19 | Schering Corporation | Glucagon receptor antagonists, compositions, and methods for their use |
| WO2010030722A1 (en) | 2008-09-15 | 2010-03-18 | Merck Sharp & Dohme Corp. | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
| US8445538B2 (en) | 2008-12-19 | 2013-05-21 | Merck Sharp & Dohme Corp. | Glucagon receptor antagonist compounds |
| WO2010088061A1 (en) | 2009-01-28 | 2010-08-05 | Merck Sharp & Dohme Corp. | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
| US8324384B2 (en) | 2009-02-12 | 2012-12-04 | Merck Sharp & Dohme Corp. | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
| WO2010098948A1 (en) | 2009-02-13 | 2010-09-02 | Merck Sharp & Dohme Corp. | Glucagon receptor antagonist compounds, compositions containin such compounds and methods of use |
| WO2010098994A1 (en) | 2009-02-25 | 2010-09-02 | Merck Sharp & Dohme Corp. | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
| JP2012188352A (ja) | 2009-07-13 | 2012-10-04 | Dainippon Sumitomo Pharma Co Ltd | ３−（４−置換アルキル−フェニル）−２−フランカルボン酸誘導体およびその薬学的に許容される塩 |
| JO3756B1 (ar) | 2010-11-23 | 2021-01-31 | Regeneron Pharma | اجسام مضادة بشرية لمستقبلات الجلوكاجون |
| CA2849273C (en) | 2011-09-20 | 2020-07-21 | Isis Pharmaceuticals, Inc. | Antisense modulation of gcgr expression |
| US9453073B2 (en) | 2011-12-02 | 2016-09-27 | Eli Lilly And Company | Anti-glucagon antibodies and uses thereof |
| RU2015147721A (ru) | 2013-05-07 | 2017-06-15 | Ринат Нейросаенз Корпорэйшн | Антитела против рецептора глюкагона и способы их использования |
| US9657099B2 (en) * | 2014-09-16 | 2017-05-23 | Regeneron Pharmaceuticals, Inc. | Anti-glucagon antibodies |
| KR20190044079A (ko) | 2016-08-30 | 2019-04-29 | 리제너론 파마슈티칼스 인코포레이티드 | 글루카곤 수용체 신호전달을 간섭함에 의한 중증 인슐린 저항성의 치료 방법 |
-
2017
- 2017-08-29 KR KR1020197008021A patent/KR20190044079A/ko not_active Ceased
- 2017-08-29 CN CN201780065987.7A patent/CN109922831A/zh active Pending
- 2017-08-29 JP JP2019511610A patent/JP7173962B2/ja active Active
- 2017-08-29 US US16/328,935 patent/US10995146B2/en active Active
- 2017-08-29 SG SG10201913074WA patent/SG10201913074WA/en unknown
- 2017-08-29 KR KR1020237014250A patent/KR102708864B1/ko active Active
- 2017-08-29 SG SG11201901355SA patent/SG11201901355SA/en unknown
- 2017-08-29 CA CA3034777A patent/CA3034777A1/en active Pending
- 2017-08-29 WO PCT/US2017/049137 patent/WO2018044903A1/en not_active Ceased
- 2017-08-29 IL IL322691A patent/IL322691A/en unknown
- 2017-08-29 AU AU2017321423A patent/AU2017321423C1/en active Active
- 2017-08-29 KR KR1020247021936A patent/KR20240110661A/ko not_active Ceased
- 2017-08-29 MX MX2019002437A patent/MX385598B/es unknown
- 2017-08-29 MA MA046089A patent/MA46089A/fr unknown
- 2017-08-29 CN CN202410379157.3A patent/CN118236497A/zh active Pending
- 2017-08-29 EP EP17762315.4A patent/EP3506940A1/en active Pending
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2019
- 2019-02-28 MX MX2021006457A patent/MX2021006457A/es unknown
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2021
- 2021-04-05 US US17/222,236 patent/US11708416B2/en active Active
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- 2022-08-01 JP JP2022122568A patent/JP7633213B2/ja active Active
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- 2023-06-05 US US18/329,358 patent/US20230416384A1/en active Pending
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- 2024-09-13 JP JP2024159035A patent/JP2024178249A/ja active Pending
- 2024-12-19 AU AU2024278594A patent/AU2024278594A1/en active Pending
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