JP5866120B2 - 塩素化アミノ酸を有するインスリン類似体 - Google Patents
塩素化アミノ酸を有するインスリン類似体 Download PDFInfo
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- JP5866120B2 JP5866120B2 JP2012543329A JP2012543329A JP5866120B2 JP 5866120 B2 JP5866120 B2 JP 5866120B2 JP 2012543329 A JP2012543329 A JP 2012543329A JP 2012543329 A JP2012543329 A JP 2012543329A JP 5866120 B2 JP5866120 B2 JP 5866120B2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
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Description
本出願は、2009年12月11日付で出願した係属中の米国仮出願第61/285、955号の利益を主張する。
本発明は、助成金番号DK40949およびDK074176下に国立衛生研究所により授与された協力協定の基に政府の支援でなされた。米国政府は、本発明に一定の権利を有し得る。
この出願の発明に関連する先行技術文献情報としては、以下のものがある(国際出願日以降国際段階で引用された文献及び他国に国内移行した際に引用された文献を含む)。
(先行技術文献)
(特許文献)
【特許文献1】 米国特許第5149716号明細書
【特許文献2】 米国特許第5149777号明細書
【特許文献3】 米国特許第5491216号明細書
【特許文献4】 米国特許第5506202号明細書
【特許文献5】 米国特許第5618913号明細書
【特許文献6】 米国特許第5698669号明細書
【特許文献7】 米国特許第5700662号明細書
【特許文献8】 米国特許第5716927号明細書
【特許文献9】 米国特許第5977297号明細書
【特許文献10】 米国特許第6011007号明細書
【特許文献11】 米国特許第6221633号明細書
【特許文献12】 米国特許第6268335号明細書
【特許文献13】 米国特許第6465426号明細書
【特許文献14】 米国特許第6531148号明細書
【特許文献15】 米国特許第6630348号明細書
【特許文献16】 米国特許第7129211号明細書
【特許文献17】 米国特許第7316999号明細書
【特許文献18】 米国特許第7547821号明細書
【特許文献19】 米国特許出願公開第2001/0036916号明細書
【特許文献20】 米国特許出願公開第2002/0082199号明細書
【特許文献21】 米国特許出願公開第2003/0104981号明細書
【特許文献22】 米国特許出願公開第2003/0144181号明細書
【特許文献23】 米国特許出願公開第2004/0014660号明細書
【特許文献24】 米国特許出願公開第2004/0053816号明細書
【特許文献25】 米国特許出願公開第2004/0214988号明細書
【特許文献26】 米国特許出願公開第2005/0014679号明細書
【特許文献27】 米国特許出願公開第2005/0039235号明細書
【特許文献28】 米国特許出願公開第2005/0176621号明細書
【特許文献29】 米国特許出願公開第2006/0217290号明細書
【特許文献30】 米国特許出願公開第2007/0129284号明細書
【特許文献31】 米国特許出願公開第2008/0146492号明細書
【特許文献32】 米国特許出願公開第2009/0304814号明細書
【特許文献33】 米国特許出願公開第2010/0099601号明細書
【特許文献34】 米国特許出願公開第2011/0059887号明細書
【特許文献35】 米国特許出願公開第2011/0077196号明細書
【特許文献36】 米国特許出願公開第2011/0077197号明細書
【特許文献37】 米国特許出願公開第2011/0166064号明細書
【特許文献38】 米国特許出願公開第2011/0195896号明細書
【特許文献39】 欧州特許出願公開第1090640号明細書
【特許文献40】 国際公開第2003/053339号
【特許文献41】 国際公開第2005/054291号
【特許文献42】 国際公開第2007/081824号
【特許文献43】 国際公開第2007/081824号
【特許文献44】 国際公開第2007/096332号
【特許文献45】 国際公開第2008/043033号
【特許文献46】 国際公開第2008/043033号
【特許文献47】 国際公開第2009/087081号
【特許文献48】 国際公開第2009/129250号
【特許文献49】 国際公開第2009/132129号
【特許文献50】 国際公開第2010/014946号
【特許文献51】 国際公開第2011/028813号
【特許文献52】 国際公開第2011/072288号
【特許文献53】 国際公開第2011/0103575号
(非特許文献)
【非特許文献1】 EP 07 84 3856 Supplementary European Search Report dated 12/11/2009.
【非特許文献2】 EP 09 80 3678 Supplementary European Search Report dated 01/30/2012.
【非特許文献3】 PCT/US2010/047546 International Search Report and Written Opinion dated 05/23/2011.
【非特許文献4】 PCT/US2010/060085 International Search Report and Written Opinion dated 09/16/2011.
【非特許文献5】 PCT/US11/25730 International Search Report and Written Opinion dated 07/22/2011.
【非特許文献6】 BLANQUART et al.;Characterization of IRA/IR hybrid insulin receptors using bioluminescence resonance energy transfer;Biochemical Pharmacology 76(2008);07/27/2008,pages 873−883.
【非特許文献7】 CHEN et al.;Sequences of B−Chain/Domain 1−10/1−9 of Insulin and Insulin−like Growth Factor 1 Determine Their Different Folding Behavior;Biochemistry;pages 9225−9233;2004.
【非特許文献8】 CURRIE et al.;The influence of glucose−lowering therapies on cancer risk in type 2 diabetes;Diabetologia;52(9);pages 1766−1777;09/2009.
【非特許文献9】 DOIG et al.;N− and C−capping preferences for all 20 amino acids in {alpha}−helical peptides;Protein Science;Vol.4;pages 1325−1335;1995.
【非特許文献10】 DU et al.;Insulin analogs with B24 or B25 phenylalanine replaced by biphenylalanine;Acta Biochem Biophys Sin;Vol 40,No.2;Pages 133−139;02/2008.
【非特許文献11】 DUCKWORTH et al.;Degradation products of insulin generated by hepatocytes and by insulin protease;Journal of Biological Chemistry,Vol.263,No.4,04/06/1988;pages 1826−1833.
【非特許文献12】 GARRIQUES et al.;The effect of mutations on the structure of insulin fibrils studied by Fourier transform infrared(FTIR) spectroscopy and electron microscopy;PubMed;Vol.12;1 page(abstract only);2002.
【非特許文献13】 HAIJUAN DU et al.;Insulin analogs with B24 or B25 phenylalanine replaced by bipheylalanine;ACTA Biochimica et Biophysica Sinica,Vol.40,No.2,2006,pages 133−139.
【非特許文献14】 HEMKENS et al.;Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study;Diabetologia 52(9);pages 1732−1744;09/2009.
【非特許文献15】 HUA et al.;Design of an Active Ultrastable Single−chain Insulin Analog;The Journal of Biological Chemistry;Vol.283,No.21;pages 14703−14716;05/23/2008.
【非特許文献16】 HUA et al.;Mechanism of insulin fibrillation − The structure of insulin under amyloidogenic conditions resembles a protein−folding intermediate,Journal of Biological Chemistry;Vol.279,No.20;pages 21449−21460,XP002557730,ISSN 0021−9258;05/14/2004.
【非特許文献17】 HUANG et al.;Structure−Specific Effects of Protein Topology on Cross−s Assembly: Studies of Insulin Fibrillation;Biochemistry 2006,45,pages 10278−10293,08/24/2006.
【非特許文献18】 KAARSHOLM et al.;Engineering Stability of the Insulin Monomer Fold with Application Structure−Activity Relationships;Biochemistry;32(40);pages 10773−10778,10/1993.
【非特許文献19】 KOHN et al.;pI−shifted insulin analogs with extended in vivo time action and favorable receptor selectivity;Peptides;28(4);01/25/2007;pages 935−948.
【非特許文献20】 KOHN et al.;pI−shifted insulin analogs with extended in vivo time action and favorable receptor selectivity;PubMed;28(4);1 page(abstract only);01/25/2007.
【非特許文献21】 KRISTENSEN et al.;Alanine Scanning Mutagenesis of Insulin;The Journal of Biological Chemistry;Vol.272,No.20;pages 12978−12983,05/16/1997.
【非特許文献22】 LIEFVENDAHL et al.;Mitogenic effect of the insulin analogue glargine in malignant cells in comparison with insulin and IGF−I;PubMed;1 page(abstract only);04/07/2008.
【非特許文献23】 LIU et al.;Utilization of combined chemical modification to enhance the blood−brain barrier permeability and pharmacological activity of endomorphin−a,JPET 106,106484,06/27/2006,pages 1−43.
【非特許文献24】 MAYER et al.;Proliferative effects of insulin analogues on mammary epithelial cells;Archives of Physiology and Biochemistry;114(1);pages 38−44;02/2008.
【非特許文献25】 MILAZZO et al.;ASPB10 insulin induction of increased mitogenic responses and phenotypic changes in human breast epithelial cells;evidence for enhanced interations with the insulin−like growth factor−I receptor;PubMed;18(1);1 page(abstract only);01/1997.
【非特許文献26】 MIRMIRA et al.;Disposition of the phenylalanine B25 side chain during insulin−receptor and insulin−insulin interactions,Biochemistry;Vol.30,No.33;05/01/1991,pages 8222−8229.
【非特許文献27】 MIRMIRA et al.;Importance of the character and configuration of residues B24 B25 and B26 in insulin−receptor interactions,Journal of Biological Chemistry,Vol.266,No.3;01/25/1991;pages 1428−1436.
【非特許文献28】 MIRMIRA et al.;Role of the Phenylalanine B24 Side Chain in Directing Insulin Interaction with Its Receptor;The Journal of Biological Chemistry;Vol.264,No.11;Pages 6349−6354;04/15/1989.
【非特許文献29】 NAKAGAWA,et al.;Chiral Mutagenesis of Insulin;The Journal of Biological Chemistry;Vol.281,No.31;pages 22386−22396;08/04/2006.
【非特許文献30】 NIELSEN et al.;Probing the Mechanism of Insulin Fibril Formation with Insulin Mutants;American Chemical Society;Biochemistry;Vol.40;pages 8397−8409;06/19/2001.
【非特許文献31】 OLSEN et al.;The Relationship Between Insulin Bioactivity and Structure in the NH2−terminal A−chain Helix;Journal of Molecular Biology;Vol 284,Issue 2,pages 477−488,11/27/1998.
【非特許文献32】 RAJPAL et al.;Single−Chain Insulins as Receptor Agonists;The Endrocrine Society;27 pages;02/19/2009.
【非特許文献33】 SHUKLA et al.;Analysis of signaling pathways related to cell proliferation stimulated by insulin analogs in human mammary epithelial cell lines;Endrocine−Related Cancer;16(2);pages 429−441;06/2009.
【非特許文献34】 SLEIKER et al.;Modifications in the B10 and B26−30 regions of the B chain of human insulin alter affinity for the human IGF−I receptor more than for the insulin receptor;Diabetologia;40 Suppl.2;07/1997;pages S54−S61.
【非特許文献35】 SREEKANTH et al.;Structural interpretation of reduced insulin activity as seen in the crystal structure of human Arginsulin;Biochimie;90(3);09/22/2007;pages 467−473.
【非特許文献36】 STEMASZYNSKA et al.;N−(2−Oxoacyl)amino Acids and Nitriles as Final Products of Dipeptide Chlorination Mediated by the Myeloperoxidase/H202/CI−System,European Journal of Biochemistry,Vol.92,No.1,09/25/1978,pages 301−308.
【非特許文献37】 SUMM et al.;Binding of insulin analogs to partially purified insulin receptor from rat liver membrane(author's trans.);Hoppe Seylers Z.Physiol.Chem.;357(5);05/1976;pages 683−693(Abstract only−1 page).
【非特許文献38】 TUFFS;German agency suspects that insulin analogue glargine increases risk of cancer;PubMed;BMJ;339:b2774;1 page(no abstract available);07/08/2009.
【非特許文献39】 WAN et al.;Enhancing the Activity of Insulin at the Receptor Interface: Crystal Structure and Photo−Cross−Linking of A8 Analogues;Biochemistry 2004,43;11/25/2004;pages 16119−16133.
【非特許文献40】 WEINSTEIN,et al.;Insulin analogues display IGF−I−like mitogenic and anti−apoptotic activities in cultured cancer cells;Diabetes/Metabolism Research and Reviews;25(1);pages 41−49;01/2009.
【非特許文献41】 WEISS et al.;Non−standard Insulin Design: Structure−Activity Relationships at the Periphery of the Insulin Receptor;The Journal of Molecular Biology;Vol.315;pages 103−111,2002.
【非特許文献42】 WEISS,et al.;Activities of Monomeric Insulin Analogs at Position A8 Are Uncorrelated with Their Thermodynamic Stabilities;The Journal of Biological Chemistry;Vol.276,No.43;pages 40018−40024;10/26/2001.
【非特許文献43】 YANG et al.;An Achilles' heel in an amyloidogenic protein and its repair: insulin fibrillation and therapeuric design;J Biol Chem.2010 Apr 1:285(14):10806−21,04/02/2010.
【非特許文献44】 ZAKOVA et al.;Shortened Insulin Analyogues: Marked Changes in Biological Activity Resulting from Replacement of TyrB26 and N−Methylation of Piptide Bonds in the C−Terminus of the B−Chain;Biochemistry;Vol.43;Pages 2323−2331;2004.
【非特許文献45】 ZELOBOWSKA et al.;Mitogenic potency of insulin glargine;Polish Journal of Endocrinology;Vol.60,No.1;pages 34−39;2009.
【非特許文献46】 ZHAO et al.;Design of an insulin analog with enhanced receptor binding selectivity: rationale,structure,and therapeutic implications;J.Biol.Chem.284(46);09/22/2009;pages 32178−32187.
【非特許文献47】 BEILI QUAN,DAVID L.SMILEY,VASILY M.GELFANOV and RICHARD D.DiMARCHI,Site Specific Introduction of Unnatural Amino Acids at Sites Critical to Insulin Receptor Recognition and Biological Activity,Understanding Bilogy Using Peptides,American Peptide Society,2005,pp.311−312.
【非特許文献48】 Lui Hong−Mei et al.,2006,The Journal of Pharmacology and Experimental Therapeutics,pages 314−316
【非特許文献49】 Bingham,Emma M et al.,2002,Diabetes,pages 3384−3390
配列ID番号1(プロインスリン)
Phe-Val-Asn-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Tyr-Leu-Val-Cys-Gly-Glu-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Thr-Arg-Arg-Glu-Ala-Glu-Asp-Leu-Gln-Val-Gly-Gln-Val-Glu-Leu-Gly-Gly-Gly-Pro-Gly-Ala-Gly-Ser-Leu-Gln-Pro-Leu-Ala-Leu-Glu-Gly-Ser-Leu-Gln-Lys-Arg-Gly-Ile-Val-Glu-Gln-Cys-Cys-Thr-Ser-Ile-Cys-Ser-Leu-Tyr-Gln-Leu-Glu-Asn-Tyr-Cys-Asn
配列ID番号2 (A鎖)
Gly-Ile-Val-Glu-Gln-Cys-Cys-Thr-Ser-Ile-Cys-Ser-Leu-Tyr-Gln-Leu-Glu-Asn-Tyr-Cys-Asn
配列ID番号3 (B鎖)
Phe-Val-Asn-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Tyr-Leu-Val-Cys-Gly-Glu-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Thr
配列ID番号4
Phe-Val-Asn-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Tyr-Leu-Val-Cys-Gly-Glu-Arg-Gly-Phe-Phe-Tyr-Thr-Lys-Pro-Thr
配列ID番号5
Phe-Val-Asn-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Tyr-Leu-Val-Cys-Gly-Glu-Arg-Gly-Phe-Phe-Tyr-Thr-Asp-Lys-Thr
配列ID番号6
R1-Val-Asn-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Tyr-Leu-Val-Cys-Gly-Glu-Arg-Gly-Phe-Phe-R2-Thr-R3-R4-Thr-Xaa0-35-Gly-Ile-Val-R5-Gln-Cys-Cys-R6-Ser-Ile-Cys-Ser-Leu-Tyr-Gln-Leu-Glu-Asn-Tyr-Cys-Asn;
さらに、以下のアミノ酸置換の群から選択される、少なくとも1つの置換が存在する:
R1はHisである;
R6はHisである;
R5とR6とは共にHisである。
配列ID番号7
Gly-Ile-Val-Glu-Gln-Cys-Cys-Xaa-Ser-Ile-Cys-Ser-Leu-Tyr-Gln-Leu-Glu-Asn-Tyr-Cys-Asn
[Xaa = His, Arg,或いはLys]
配列ID番号8(DKP B鎖配列)
Phe-Val-Asn-Gln-His-Leu-Cys-Gly-Ser-Asp-Leu-Val-Glu-Ala-Leu-Tyr-Leu-Val-Cys-Gly-Glu-Arg-Gly-Phe-Phe-Tyr-Thr-Lys-Pro-Thr
4−Cl−PheB24−KP−インスリン(図6では、4−Cl−リスプロインスリンと短縮)は、KP−インスリン或いは野生型インスリンよりも大幅に低下した、延長後期の"尾部"を示すことが見出された。インスリンの作用遮断が改善した事は、遅発型食後低血糖症に関して潜在的な臨床的有益性を示唆する。
(a)ヒトコドン優先性を持つ:TTTGTGAACCAACACCTGTGCGGCTCACACCTGGTGGAAGCTCTCTACCTAGT
GTGCGGGGAACGAGGCTAGTTCTACACACCCAAGACC (配列ID番号11)
(b)ピチアコドン優先性を持つ
TTTGTTAACCAACATTTGTGTGGTTCTCATTTGGTTGAAGCTTTGTACTTGGTT
TGTGGTGAAAGAGGTTAGTTTTACACTCCAAAGACT (配列ID番号12)
TTTGTGAACC AACACCTGTG CGGCTCACAC CTGGTGGAAG CTCTCTACCT AGTGTGCGGG GAACGAGGCT AGTTCTACAC ACCCAAGACC CGCCGGGAGG CAGAGGACCT GCAGGTGGGG CAGGTGGAGC TGGGCGGCGG CCCTGGTGCA GGCAGCCTGC AGCCCTTGGC CCTGGAGGGG TCCCTGCAGA AGCGTGGCAT TGTGGAACAA TGCTGTACCA GCATCTGCTC CCTCTACCAG CTGGAGAACT ACTGCAACTA G (配列ID番号13)
TTTGTTAACC AACATTTGTG TGGTTCTCAT TTGGTTGAAG CTTTGTACTT GGTTTGTGGT GAAAGAGGTT AGTTTTACAC TCCAAAGACT AGAAGAGAAG CTGAAGATTT GCAAGTTGGT CAAGTTGAAT TGGGTGGTGG TCCAGGTGCT GGTTCTTTGC AACCATTGGC TTTGGAAGGT TCTTTGCAAA AGAGAGGTAT TGTTGAACAA TGTTGTACTT CTATTTGTTC TTTGTACCAA TTGGAAAACT ACTGTAACTA A (配列ID番号14)
Matthews D.R., Hosker J.P. 1989. Unbiased and flexible iterative computer program to achieve glucose clamping. Diabetes Care. 12: 156-9.
Merrifield, R.B., Vizioli, L.D., and Boman, H.G. 1982. Synthesis of the antibacterial peptide cecropin A (1-33). Biochemistry 21: 5020-5031.
Mirmira, R.G., and Tager, H.S. 1989. Role of the phenylalanine B24 side chain in directing insulin interaction with its receptor: Importance of main chain conformation. J. Biol. Chem. 264: 6349-6354. Sosnick, T.R., Fang, X., and Shelton, V.M. 2000. Application of circular dichroism to study RNA folding transitions. Methods Enzymol. 317: 393-409.
Wang, Z.X. 1995. An exact mathematical expression for describing competitive biding of two different ligands to a protein molecule FEBS Lett. 360: 111-114.
Weiss, M.A., Hua, Q.X., Jia, W., Chu, Y.C., Wang, R.Y., and Katsoyannis, P.G. 2000.
Hierarchiacal protein "un-design": insulin's intrachain disulfide bridge tethers a recognition α-helix. Biochemistry 39: 15429-15440.
Whittaker, J., and Whittaker, L. 2005. Characterization of the functional insulin binding epitopes of the full length insulin receptor. J. Biol. Chem. 280: 20932-20936.
Xie, J. and Schultz, P.G. 2005. An expanding genetic code. Methods. 36: 227-238.
Claims (11)
- 塩素化フェニルアラニンを導入するB鎖ポリペプチドを有するインスリン類似体であって、前記塩素化フェニルアラニンは、パラ−モノクロロ−フェニルアラニンであり、B24位に位置するものである、類似体。
- 請求項1に記載のインスリン類似体において、前記類似体は、哺乳動物のインスリン類似体である、類似体。
- 請求項2に記載のインスリン類似体において、前記類似体は、ヒトインスリンの類似体である、類似体。
- 請求項2に記載のインスリン類似体において、前記類似体は、配列ID番号4〜8からなる群から選択されるアミノ酸配列と、3個或いはそれ以下の追加のアミノ酸置換を有するポリペプチドとを有するものである、類似体。
- 請求項2に記載のインスリン類似体をコードする核酸。
- 請求項5に記載の核酸において、前記塩化フェニルアラニンは、終止コドンによりコードされているものである、核酸。
- 請求項6に記載の核酸において、前記終止コドンは、核酸配列TAGである、核酸。
- 請求項5、6或いは7に記載の前記核酸配列を有する発現ベクター。
- 請求項8記載の前記発現ベクターで形質転換された宿主細胞。
- 患者を治療する薬剤を製造するための生理学的有効量のインスリン類似体或いはその生理学的に許容される塩の使用であって、前記インスリン類似体或いはその生理学的に許容される塩は、塩化フェニルアラニンを導入するB鎖ポリペプチドを含有するものであり、前記塩素化フェニルアラニンは、パラ−モノクロロ−フェニルアラニンであり、B24位に位置するものである、使用。
- 請求項10に記載の使用において、前記類似体は、配列番号4〜8からなる群から選択されるアミノ酸配列と、その3個或いはそれ以下の追加のアミノ酸置換を有するポリペプチドとを有するものである、使用。
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US61/285,955 | 2009-12-11 | ||
PCT/US2010/060085 WO2011072288A2 (en) | 2009-12-11 | 2010-12-13 | Insulin analogues with chlorinated amino acids |
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MY189079A (en) | 2022-01-25 |
CN102762589A (zh) | 2012-10-31 |
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SG181527A1 (en) | 2012-07-30 |
IL220284A0 (en) | 2012-07-31 |
US20150361153A1 (en) | 2015-12-17 |
EP2509995A4 (en) | 2013-08-21 |
US9079975B2 (en) | 2015-07-14 |
WO2011072288A2 (en) | 2011-06-16 |
US9758563B2 (en) | 2017-09-12 |
MX2012006568A (es) | 2012-12-17 |
CA2783763A1 (en) | 2011-06-16 |
WO2011072288A3 (en) | 2011-11-10 |
RU2012123642A (ru) | 2014-01-20 |
BR112012014025A2 (pt) | 2017-01-31 |
ZA201204308B (en) | 2013-08-28 |
AU2010327949A1 (en) | 2012-06-28 |
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