JP2014520798A5 - - Google Patents

Info

Publication number

JP2014520798A5

JP2014520798A5 JP2014518803A JP2014518803A JP2014520798A5 JP 2014520798 A5 JP2014520798 A5 JP 2014520798A5 JP 2014518803 A JP2014518803 A JP 2014518803A JP 2014518803 A JP2014518803 A JP 2014518803A JP 2014520798 A5 JP2014520798 A5 JP 2014520798A5

Authority

JP

Japan

Prior art keywords

polyethylene glycol

exendin

composition

derivative

analog

Prior art date

2012-06-28

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

• Espacenet
• Global Dossier
• Discuss

• 239000002202 Polyethylene glycol Substances 0.000 claims description 53
• 229920001223 polyethylene glycol Polymers 0.000 claims description 53
• JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=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](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)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)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 claims description 28
• 239000000203 mixture Substances 0.000 claims description 19
• 238000000034 method Methods 0.000 claims description 15
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
• PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims description 11
• 235000018417 cysteine Nutrition 0.000 claims description 11
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 11
• 150000002334 glycols Chemical class 0.000 claims description 9
• 239000013638 trimer Substances 0.000 claims description 9
• 108010011459 Exenatide Proteins 0.000 claims description 5
• 239000000539 dimer Substances 0.000 claims description 5
• 229960001519 exenatide Drugs 0.000 claims description 5
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 239000002953 phosphate buffered saline Substances 0.000 claims description 4
• AASBXERNXVFUEJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) propanoate Chemical compound CCC(=O)ON1C(=O)CCC1=O AASBXERNXVFUEJ-UHFFFAOYSA-N 0.000 claims description 3
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 3
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
• 210000004899 c-terminal region Anatomy 0.000 claims description 3
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
• 239000004480 active ingredient Substances 0.000 claims description 2
• 239000000243 solution Substances 0.000 claims description 2
• 125000006850 spacer group Chemical group 0.000 claims 7
• 235000001014 amino acid Nutrition 0.000 claims 3
• 150000001413 amino acids Chemical class 0.000 claims 3
• NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 claims 2
• 206010012601 diabetes mellitus Diseases 0.000 claims 2
• ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 claims 1
• 239000000839 emulsion Substances 0.000 claims 1
• 239000008187 granular material Substances 0.000 claims 1
• 239000007902 hard capsule Substances 0.000 claims 1
• 238000002347 injection Methods 0.000 claims 1
• 239000007924 injection Substances 0.000 claims 1
• 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 claims 1
• 239000008188 pellet Substances 0.000 claims 1
• 239000000843 powder Substances 0.000 claims 1
• 239000007901 soft capsule Substances 0.000 claims 1
• 239000000725 suspension Substances 0.000 claims 1
• 239000006188 syrup Substances 0.000 claims 1
• 235000020357 syrup Nutrition 0.000 claims 1
• 239000003826 tablet Substances 0.000 claims 1
• 230000003442 weekly effect Effects 0.000 claims 1
• 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 description 6
• 102000004877 Insulin Human genes 0.000 description 3
• 108090001061 Insulin Proteins 0.000 description 3
• 201000010099 disease Diseases 0.000 description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
• 229940125396 insulin Drugs 0.000 description 3
• 208000002249 Diabetes Complications Diseases 0.000 description 1
• 206010012655 Diabetic complications Diseases 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 239000003814 drug Substances 0.000 description 1
• 230000000694 effects Effects 0.000 description 1
• 230000006320 pegylation Effects 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1