JP2018532693A5 - - Google Patents

Info

Publication number

JP2018532693A5

JP2018532693A5 JP2018506110A JP2018506110A JP2018532693A5 JP 2018532693 A5 JP2018532693 A5 JP 2018532693A5 JP 2018506110 A JP2018506110 A JP 2018506110A JP 2018506110 A JP2018506110 A JP 2018506110A JP 2018532693 A5 JP2018532693 A5 JP 2018532693A5

Authority

JP

Japan

Prior art keywords

antibody

seq

fragment

insulin

hypoglycemia

Prior art date

2016-08-05

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.)

Pending

Links

• Espacenet
• Global Dossier
• Discuss

• 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 claims description 42
• 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 40
• 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 40
• 208000013016 Hypoglycemia Diseases 0.000 claims description 21
• 102000004877 Insulin Human genes 0.000 claims description 21
• 108090001061 Insulin Proteins 0.000 claims description 21
• 230000002218 hypoglycaemic effect Effects 0.000 claims description 21
• 229940125396 insulin Drugs 0.000 claims description 21
• 102000003746 Insulin Receptor Human genes 0.000 claims description 20
• 108010001127 Insulin Receptor Proteins 0.000 claims description 20
• 239000000203 mixture Substances 0.000 claims description 12
• 239000012634 fragment Substances 0.000 claims description 11
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 4
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 4
• 239000003795 chemical substances by application Substances 0.000 claims description 4
• 230000000422 nocturnal effect Effects 0.000 claims description 4
• 102000051325 Glucagon Human genes 0.000 claims description 3
• 108060003199 Glucagon Proteins 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical group 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 3
• 229960004666 glucagon Drugs 0.000 claims description 3
• 206010022489 Insulin Resistance Diseases 0.000 claims description 2
• 229940100389 Sulfonylurea Drugs 0.000 claims description 2
• 238000007681 bariatric surgery Methods 0.000 claims description 2
• 235000020805 dietary restrictions Nutrition 0.000 claims description 2
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
• 230000002503 metabolic effect Effects 0.000 claims description 2
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 2
• 150000001413 amino acids Chemical group 0.000 claims 4
• 238000000034 method Methods 0.000 description 30
• 125000003275 alpha amino acid group Chemical group 0.000 description 18
• 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 description 4
• 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 description 3
• 239000008280 blood Substances 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008103 glucose Substances 0.000 description 3
• 238000003556 assay Methods 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 238000010494 dissociation reaction Methods 0.000 description 2
• 230000005593 dissociations Effects 0.000 description 2
• 230000002209 hydrophobic effect Effects 0.000 description 2
• 210000004153 islets of langerhan Anatomy 0.000 description 2
• 239000008194 pharmaceutical composition Substances 0.000 description 2
• 229920001184 polypeptide Polymers 0.000 description 2
• 102000004196 processed proteins & peptides Human genes 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 230000007781 signaling event Effects 0.000 description 2
• 206010060378 Hyperinsulinaemia Diseases 0.000 description 1
• 208000001871 Tachycardia Diseases 0.000 description 1
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 230000009766 cell sprouting Effects 0.000 description 1
• 230000006999 cognitive decline Effects 0.000 description 1
• 208000010877 cognitive disease Diseases 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 238000011010 flushing procedure Methods 0.000 description 1
• 230000003451 hyperinsulinaemic effect Effects 0.000 description 1
• 208000033066 hyperinsulinemic hypoglycemia Diseases 0.000 description 1
• 201000008980 hyperinsulinism Diseases 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 230000035900 sweating Effects 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 230000006794 tachycardia Effects 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1