JP2000511881A - グルカゴン様ペプチド―2アナログ - Google Patents
グルカゴン様ペプチド―2アナログInfo
- Publication number
- JP2000511881A JP2000511881A JP09536608A JP53660897A JP2000511881A JP 2000511881 A JP2000511881 A JP 2000511881A JP 09536608 A JP09536608 A JP 09536608A JP 53660897 A JP53660897 A JP 53660897A JP 2000511881 A JP2000511881 A JP 2000511881A
- Authority
- JP
- Japan
- Prior art keywords
- hglp
- glp
- ala
- gly
- analog
- 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
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Classifications
-
- 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
- C07K14/575—Hormones
- C07K14/605—Glucagons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 下記式1を有する、腸栄養活性を示すことを特徴とするGLP-2アナログ。 R1-(Y1)m-X1-X2-X3-X4-Ser5-Phe6-Ser7-Asp8-(P1)-Leu14-Asp15-Asn16- Leu17-Ala18-X19-X20-Asp21-Phe22-(P2)-Trp25-Leu26−Ile27-Gln28- Thr29-Lys30−(P3)-(Y2)n-R2, (式中、X1はHis又はTyrであり; X2はAla又は前記アナログにDPP−IV酵素に対する耐性を与えるAla置換アミ ノ酸であり; X3はPro、HPro、Asp又はGluであり; X4はGly又はAlaであり; P1はGlu-X10-Asn-Thr-Ile又はTyr-Ser-Lys-Tyrであり; X10はMet又は酸化に安定なMet置換アミノ酸であり; X19はAla又はThrであり; X20はArg、Lys、His又はAlaであり; P2はIle-Asn、Ile-Ala又はVal-Glnであり; P3は共有結合、又はIle、Ile-Thr又はIle-Thr-Asnであり; R1はH又はN末端保護基であり; R2はOH又はC末端保護基であり; Y1はArg、Lys及びHisからなる群より選ばれた1又は2個の塩基性アミノ酸で あり; Y2はArg、Lys及びHisからなる群より選ばれた1又は2個の塩基性アミノ酸で あり; m及びnは独立して0又は1であり; X1、X2、X3、X4、P1、X10、X19、X20、P2及びP3の少なくとも1つは野生型哺 乳動物GLP-2残基以外である。) 2. 前記アナログが下記の置換より選ばれた少なくとも1種のアミノ酸置換が組 込まれている、請求項1記載のGLP-2アナログ。 a)前記腸栄養性GLP-2アナログをヒトDPP−IV酵素による切断に対して耐 性にするアミノ酸がX2に組込まれている置換; b)酸化に安定なMet置換アミノ酸がX10に組込まれている置換;及び c)His又はLysより選ばれた塩基性アミノ酸がX20に組込まれている置換。 3. X2が、DPP−IV酵素による消化に対する耐性を前記アナログに与えるアミノ 酸で置換される、請求項2記載のGLP-2アナログ。 4. X2がD-hPr、D-Pro、D-Ala、Gly、Val、Glu、Lys、Arg、Leu及び Ileからなる群より選ばれる、請求項3記載のGLP-2アナログ。 5. 次の位置X1、X3、X4、X10、X19、X20及びP2に少なくとも1種のアミノ酸 置換が組込まれている、請求項3記載のGLP-2アナログ。 6. X10がVal、Ile、Asn、Glx、Tyr、Phe、Leu、Nle、Ala、Ser及び Glyからなる群より選ばれたアミノ酸で置換される、請求項2記載のGLP-2 アナログ。 7. [Tyr1]rGLP-2;[Ala4]rGLP-2;[Val23Gln24]hGLP-2及び[Asn33]hGLP-2(1-33) からなる群より選ばれた、請求項1記載のGLP-2アナログ。 8. 下記の置換からなる群より選ばれた少なくとも1種のアミノ酸置換を含む、 ヒトGLP-2ペプチドアナログ。 a)該aアナログをDPP-IV酵素による切断に対して耐性にする置換アミノ酸が 位置X2及び/又はX3に組込まれている置換; b)酸化に安定な置換アミノ酸が位置X10に組込まれている置換;及び c)Arg以外の置換アミノ酸が位置X20に組込まれている置換。 9. D-hPr、D-Pro、D-Ala、Gly、Val、Glu、Lys、Arg、Leu及びIleか らなる群より選ばれるアミノ酸置換が位置X2に組込まれている、請求項8記載 のGLP-2アナログ。 10.下記のペプチドからなる群より選ばれる、請求項9記載のGLP-2アナログ 。 [Gly2]hGLP-2; [D-Ala2Thr19]hGLP-2; [G1y2Thr19]hGLP-2; [Ala1Gly2]hGLP-2; [Gly2Ala3]hGLP-2; [Gly2Ala4]hGLP-2; [Gly2Ala5]hGLP-2; [Gly2Ala6]hGLP-2; [Gly2Ala7]hGLP-2; [Gly2Ala8]hGLP-2; [Gly2Ala9]hGLP-2; [Gly2Ala10]hGLP-2; [Gly2Ala11]hGLP-2; [Gly2Ala12]hGLP-2; [Gly2Ala13]hGLP-2; [Gly2Ala16]hGLP-2; [Gly2Ala17]hGLP-2; [Val2Thr19]hGLP-2; [Gly2Ala20]hGLP-2; [Gly2Ala21]hGLP-2; [Gly2Ala24]hGLP-2; [Gly2Ala27]hGLP-2; [Gly2Ala28]hGLP-2;及び [Gly2Ala31]hGLP-2。 11.Val、Ile、Asn、Glx、Tyr、Phe、Leu、Nle、Ala、Ser及びGlyか らなる群より選ばれるアミノ酸置換が位置X10に組込まれている、請求項8記 載のGLP-2アナログ。 12.[Ser10]hGLP-2(1-33);[Nle10]hGLP-2(1-33);[Ala10]hGLP-2(1-33); [Leu10]rGLP-2(1-33);[Nle10]ラットGLP-2(1-33);[Gly2Ala10]hGLP-2(1-33); [Met(O)10]ラットGLP-2(1-33)及び[Tyr9Ser10Lys11Tyr12(desIle13)]hGLP-2 (1-33)からなる群より選ばれる、請求項11記載のGLP-2アナログ。 13.[Pro3]hGLP-2;[HPr3]hGLP-2;[Glu3Thr19]hGLP-2;及び[Thr19Lys20]hGLP-2 からなる群より選ばれる、請求項8記載のGLP-2アナログ。 14.下記のペプチドからなる群より選ばれる、請求項8記載のGLP-2アナログ 。 [Ser2,Gln3]hGLP-2(1-33); [Gly2,Ala25]hGLP-2(1-33); [Gly2,Ala26]hGLP-2(1-33); [Gly2,Ala14]hGLP-2(1-33); [Gly2,Ala23]hGLP-2(1-33); [Gly2,Ala30]hGLP-2(1-33); [Tyr1,G1y2]hGLP-2(1-33); [Gly2,Arg34]hGLP-2(1-34); [Gly2,Tyr34]hGLP-2(1-34); [tBuGly2]hGLp-2; [Asp2]hGLP-2(1-33); [Glu2]hGLP-2(1-33); [Phe2]hGLP-2(1-33); [His2]hGLP-2(1-33); [Ile2]hGLP-2(1-33); [Lys2]hGLP-2(1-33); [Met2]hGLP-2(1-33); [Asn2]hGLP-2(1-33); [Pro2]hGLP-2(1-33); [Gln2]hGLP-2(1-33); [Ser2]hGLP-2(1-33); [Thr2]hGLP-2(1-33); [Val2]hGLP-2(1-33); [Tyr2]hGLP-2(1-33); [D-Ala2]hGLP-2(1-33); [Pen2]hGLP-2(1-33); [bAla2]hGLP-2(1-33); [aAbu2]hGLP-2(1-33); [Nval2]hGLP-2(1-33); [PhGly2]hGLP-2(1-33);及び [Aib2]hGLP-2(1-33)。 15.下記のペプチドからなる群より選ばれた腸栄養性GLP-2アナログ。 ラットGLP-2(4-33); Ac-ラットGLP-2(1-33); ラットGLP-2(1-30); ラットGLP-2(1-25); ラットGLP-2(1-33)アミド; [Arg-2,Arg-1]ラットGLP-2(2-33); [Pro1]hGLP-2(1-33); [Gln20]hGLP-2(1-33); [Asp1]hGLP-2(1-33); [Tyr34]hGLP-2(1-34); [desNH2Tyr1]hGLP-2(1-33); [Thr5]hGLP-2(1-33); [Ser16,Arg17,Arg18]hGLP-2(1-33); [Agm34]hGLP-2(1-34); [Arg30]hGLP-2(1-33); [Ala5,Ala7]hGLP-2(1-33); [Glu33]hGLP-2(1-33); [Phe25]hGLP-2(1-33);及び [Tyr25]hGLP-2(1-33)。 16.ペプチド[Gly2]hGLP-2。 17.請求項1〜16のいずれか1項に記載のGLP-2アナログの治療的に有効な量 及び薬学的に許容しうる担体を含む医薬組成物。 18.患者又は動物において小腸組織の増殖を促進させる薬剤を製造するための請 求項1〜16のいずれか1項に記載のGLP-2アナログの使用。 19.患者又は動物において胃腸病を治療する薬剤を製造するための請求項1〜16 のいずれか1項に記載のGLP-2アナログの使用。 20.該胃腸病が潰瘍、消化障害、吸収不良症候群、ショートガット症候群、ダグ ラス窩症候群、炎症性腸疾患、セリアックスプルー;熱帯性スプルー;低ガン マグロブリン血症性スプルー、腸炎、限局性腸炎(クローン病)、毒性物質又 は他の化学療法剤による小腸損傷、及びショートバウエル症候群からなる群よ り選ばれる、請求項19記載の使用。 21.下記の段階を含む、腸栄養性GLP-2アナログを同定する方法。 a)請求項1記載のGLP-2アナログを得る段階; b)ラットGLP-2を使用した場合に腸栄養作用を誘起することができる用法 を用いて前記アナログで哺乳動物を処理する段階;及び c)擬似処理対照哺乳動物に相対する小腸重量に対する前記アナログの影響を 求め、よって前記腸栄養性GLP-2アナログが前記重量の増加を誘起するアナロ グとして同定される段階。
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US63127396A | 1996-04-12 | 1996-04-12 | |
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PCT/CA1997/000252 WO1997039031A1 (en) | 1996-04-12 | 1997-04-11 | Glucagon-like peptide-2 analogs |
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JP2008027918A Division JP5019466B2 (ja) | 1996-04-12 | 2008-02-07 | グルカゴン様ペプチド−2アナログ |
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JP2008027918A Expired - Lifetime JP5019466B2 (ja) | 1996-04-12 | 2008-02-07 | グルカゴン様ペプチド−2アナログ |
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EP (5) | EP1231219B1 (ja) |
JP (3) | JP4148994B2 (ja) |
CN (1) | CN1268640C (ja) |
AT (2) | ATE227309T1 (ja) |
AU (1) | AU733857B2 (ja) |
BR (1) | BRPI9708566B8 (ja) |
CA (1) | CA2251576C (ja) |
DE (2) | DE69716905T2 (ja) |
DK (2) | DK1231219T3 (ja) |
ES (2) | ES2188929T3 (ja) |
FR (1) | FR13C0013I2 (ja) |
HK (3) | HK1033324A1 (ja) |
LU (1) | LU92153I2 (ja) |
NZ (1) | NZ332281A (ja) |
PT (2) | PT906338E (ja) |
WO (1) | WO1997039031A1 (ja) |
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JP2007526235A (ja) * | 2003-08-21 | 2007-09-13 | ノボ ノルディスク アクティーゼルスカブ | グルカゴン様ペプチドの精製 |
JP2008539713A (ja) * | 2005-05-04 | 2008-11-20 | ジーランド ファーマ アクティーゼルスカブ | グルカゴン様ペプチド−2(glp−2)アナログ |
JP2010509197A (ja) * | 2006-11-08 | 2010-03-25 | ジーランド ファーマ アクティーゼルスカブ | 選択的グルカゴン様ペプチド−2(glp−2)類似体 |
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US5990077A (en) * | 1995-04-14 | 1999-11-23 | 1149336 Ontario Inc. | Glucagon-like peptide-2 and its therapeutic use |
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JP2014210783A (ja) * | 2003-08-21 | 2014-11-13 | ノヴォ ノルディスク アー/エス | グルカゴン様ペプチドの精製 |
JP2008539713A (ja) * | 2005-05-04 | 2008-11-20 | ジーランド ファーマ アクティーゼルスカブ | グルカゴン様ペプチド−2(glp−2)アナログ |
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