JP2015532283A5 - - Google Patents
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- JP2015532283A5 JP2015532283A5 JP2015534623A JP2015534623A JP2015532283A5 JP 2015532283 A5 JP2015532283 A5 JP 2015532283A5 JP 2015534623 A JP2015534623 A JP 2015534623A JP 2015534623 A JP2015534623 A JP 2015534623A JP 2015532283 A5 JP2015532283 A5 JP 2015532283A5
- Authority
- JP
- Japan
- Prior art keywords
- seq
- chain
- insulin
- insulin polypeptide
- sequence
- 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
Links
- 102000004877 Insulin Human genes 0.000 claims description 239
- 108090001061 Insulin Proteins 0.000 claims description 239
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class 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 144
- 125000005647 linker group Chemical group 0.000 claims description 94
- 150000001413 amino acids Chemical group 0.000 claims description 79
- 239000000539 dimer Substances 0.000 claims description 69
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- 239000004026 insulin derivative Substances 0.000 claims description 65
- 125000000217 alkyl group Chemical group 0.000 claims description 50
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 38
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- 229940125396 insulin Drugs 0.000 claims description 34
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 26
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 18
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims description 17
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 17
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- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 17
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 17
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims description 17
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 17
- 229960000310 isoleucine Drugs 0.000 claims description 17
- 229960003104 ornithine Drugs 0.000 claims description 17
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 16
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 15
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 15
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 15
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 15
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- 235000003704 aspartic acid Nutrition 0.000 claims description 15
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 15
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- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 15
- 235000013922 glutamic acid Nutrition 0.000 claims description 15
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- 235000014304 histidine Nutrition 0.000 claims description 14
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 14
- 239000004474 valine Substances 0.000 claims description 14
- 239000004471 Glycine Substances 0.000 claims description 13
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 13
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 13
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 13
- 239000004472 Lysine Substances 0.000 claims description 13
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 13
- 239000004473 Threonine Substances 0.000 claims description 13
- 210000004899 c-terminal region Anatomy 0.000 claims description 13
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 12
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 12
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- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 10
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 9
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- GFQJOAYQSOWWOE-UHFFFAOYSA-N 1-amino-3-(hydrazinecarbonyl)urea Chemical compound NNC(=O)NC(=O)NN GFQJOAYQSOWWOE-UHFFFAOYSA-N 0.000 claims description 8
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- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 230000001588 bifunctional effect Effects 0.000 claims description 6
- XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 claims description 6
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- 229920001223 polyethylene glycol Polymers 0.000 claims description 6
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 5
- LXMDIEJPPQSFFB-UHFFFAOYSA-N 6,7-dimethyl-10-(2,3,4,5-tetrahydroxypentyl)benzo[g]pteridine-2,4-dione Chemical compound O=C1NC(=O)C2=NC3=C(C)C(C)=CC=C3N(CC(O)C(O)C(O)CO)C2=N1 LXMDIEJPPQSFFB-UHFFFAOYSA-N 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 4
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- CMUHFUGDYMFHEI-QMMMGPOBSA-N 4-amino-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N)C=C1 CMUHFUGDYMFHEI-QMMMGPOBSA-N 0.000 claims description 3
- PVRDHKBVCDWVPD-UHFFFAOYSA-N 6,7-Dimethyl-9-(2-acetoxyethyl)isoalloxazine Chemical compound CC(=O)OCCN1C2=CC(C)=C(C)C=C2N=C2C1=NC(=O)NC2=O PVRDHKBVCDWVPD-UHFFFAOYSA-N 0.000 claims description 3
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- 101000604197 Homo sapiens Neuronatin Proteins 0.000 claims description 3
- 101000999322 Homo sapiens Putative insulin-like growth factor 2 antisense gene protein Proteins 0.000 claims description 3
- VBOQYPQEPHKASR-VKHMYHEASA-N L-homocysteic acid Chemical compound OC(=O)[C@@H](N)CCS(O)(=O)=O VBOQYPQEPHKASR-VKHMYHEASA-N 0.000 claims description 3
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- GEYBMYRBIABFTA-UHFFFAOYSA-N O-methyltyrosine Chemical compound COC1=CC=C(CC(N)C(O)=O)C=C1 GEYBMYRBIABFTA-UHFFFAOYSA-N 0.000 claims description 3
- 102100036485 Putative insulin-like growth factor 2 antisense gene protein Human genes 0.000 claims description 3
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261705834P | 2012-09-26 | 2012-09-26 | |
| US61/705,834 | 2012-09-26 | ||
| PCT/US2013/061676 WO2014052451A2 (en) | 2012-09-26 | 2013-09-25 | Insulin analog dimers |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015532283A JP2015532283A (ja) | 2015-11-09 |
| JP2015532283A5 true JP2015532283A5 (https=) | 2016-11-10 |
| JP6387008B2 JP6387008B2 (ja) | 2018-09-05 |
Family
ID=50389126
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015534623A Expired - Fee Related JP6387008B2 (ja) | 2012-09-26 | 2013-09-25 | インスリンアナローグダイマー |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US9593156B2 (https=) |
| EP (2) | EP3395358B1 (https=) |
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| CN (2) | CN108383902A (https=) |
| AU (1) | AU2013323669B2 (https=) |
| CA (1) | CA2886228A1 (https=) |
| WO (1) | WO2014052451A2 (https=) |
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| BR112012029611A2 (pt) | 2010-05-21 | 2017-07-25 | Merrimack Pharmaceuticals Inc | proteína de fusão biespecífica, composição farmacêutica, método de tratamento de dano ao tecido em um indivíduo, método de promoção da regeração ou sobrevivência do tecido em um indivíduo e molécula de ácido nucleico |
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| EA036714B1 (ru) * | 2014-11-21 | 2020-12-10 | Мерк Шарп И Доум Корп. | Частичные агонисты инсулинового рецептора |
| KR101669140B1 (ko) * | 2015-04-28 | 2016-10-26 | (주)케어젠 | 항비만 및 항당뇨 효능을 갖는 펩타이드 및 이의 용도 |
| AR105616A1 (es) | 2015-05-07 | 2017-10-25 | Lilly Co Eli | Proteínas de fusión |
| CN115960249A (zh) | 2015-10-02 | 2023-04-14 | 银溪制药股份有限公司 | 用于组织修复的双特异性治疗性蛋白质 |
| EP3448417B1 (en) | 2016-04-26 | 2025-11-12 | Merck Sharp & Dohme LLC | Insulin dimer-incretin conjugates |
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| CN114144426A (zh) * | 2019-04-19 | 2022-03-04 | 印地安纳大学理事会 | 餐时或基础胰岛素类似物通过内部二硒桥的稳定化 |
| US12435116B2 (en) | 2019-10-16 | 2025-10-07 | Clarence Hurt | Compounds, compositions, methods, and uses for treating insulin resistance, type 2 diabetes and metabolic syndrome |
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2013
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- 2013-09-25 EP EP18174352.7A patent/EP3395358B1/en active Active
- 2013-09-25 CA CA2886228A patent/CA2886228A1/en not_active Abandoned
- 2013-09-25 US US14/431,040 patent/US9593156B2/en not_active Expired - Fee Related
- 2013-09-25 JP JP2015534623A patent/JP6387008B2/ja not_active Expired - Fee Related
- 2013-09-25 CN CN201810145984.0A patent/CN108383902A/zh active Pending
- 2013-09-25 WO PCT/US2013/061676 patent/WO2014052451A2/en not_active Ceased
- 2013-09-25 EP EP13841334.9A patent/EP2900255B1/en not_active Not-in-force
- 2013-09-25 CN CN201380061231.7A patent/CN104981251B/zh not_active Expired - Fee Related
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