JP2018509394A5 - - Google Patents

Info

Publication number

JP2018509394A5

JP2018509394A5 JP2017541594A JP2017541594A JP2018509394A5 JP 2018509394 A5 JP2018509394 A5 JP 2018509394A5 JP 2017541594 A JP2017541594 A JP 2017541594A JP 2017541594 A JP2017541594 A JP 2017541594A JP 2018509394 A5 JP2018509394 A5 JP 2018509394A5

Authority

JP

Japan

Prior art keywords

polypeptide

dimer

group

terminus

terminal extension

Prior art date

2016-02-05

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.)

Granted

Links

• Espacenet
• Global Dossier
• Discuss

• 229920001184 polypeptide Polymers 0.000 claims 25
• 102000004196 processed proteins & peptides Human genes 0.000 claims 25
• 108090000765 processed proteins & peptides Proteins 0.000 claims 25
• 239000000539 dimer Substances 0.000 claims 17
• 125000005647 linker group Chemical group 0.000 claims 16
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 14
• 239000003795 chemical substances by application Substances 0.000 claims 13
• 239000003814 drug Substances 0.000 claims 13
• 210000004899 c-terminal region Anatomy 0.000 claims 12
• 229940079593 drug Drugs 0.000 claims 12
• 238000002372 labelling Methods 0.000 claims 8
• 238000000034 method Methods 0.000 claims 8
• 230000001225 therapeutic effect Effects 0.000 claims 8
• 239000003053 toxin Substances 0.000 claims 6
• 231100000765 toxin Toxicity 0.000 claims 6
• 108700012359 toxins Proteins 0.000 claims 6
• 239000011230 binding agent Substances 0.000 claims 5
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
• 108060003951 Immunoglobulin Proteins 0.000 claims 4
• 125000004450 alkenylene group Chemical group 0.000 claims 4
• 125000002947 alkylene group Chemical group 0.000 claims 4
• 230000001413 cellular effect Effects 0.000 claims 4
• 229940127089 cytotoxic agent Drugs 0.000 claims 4
• 125000006575 electron-withdrawing group Chemical group 0.000 claims 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
• 102000018358 immunoglobulin Human genes 0.000 claims 4
• LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 claims 3
• 229960003067 cystine Drugs 0.000 claims 3
• 125000000524 functional group Chemical group 0.000 claims 3
• 229920000642 polymer Polymers 0.000 claims 3
• 241000894006 Bacteria Species 0.000 claims 2
• 102000004225 Cathepsin B Human genes 0.000 claims 2
• 108090000712 Cathepsin B Proteins 0.000 claims 2
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims 2
• 241000196324 Embryophyta Species 0.000 claims 2
• 108090000790 Enzymes Proteins 0.000 claims 2
• 102000004190 Enzymes Human genes 0.000 claims 2
• 108090000371 Esterases Proteins 0.000 claims 2
• 241000233866 Fungi Species 0.000 claims 2
• 241001465754 Metazoa Species 0.000 claims 2
• 206010028980 Neoplasm Diseases 0.000 claims 2
• 108091005804 Peptidases Proteins 0.000 claims 2
• 102000035195 Peptidases Human genes 0.000 claims 2
• 239000004365 Protease Substances 0.000 claims 2
• IEDXPSOJFSVCKU-HOKPPMCLSA-N [4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrolidin-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate Chemical compound CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCc1ccc(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN2C(=O)CCC2=O)C(C)C)cc1)C(C)C IEDXPSOJFSVCKU-HOKPPMCLSA-N 0.000 claims 2
• 125000000539 amino acid group Chemical group 0.000 claims 2
• 239000002246 antineoplastic agent Substances 0.000 claims 2
• 125000004429 atom Chemical group 0.000 claims 2
• 201000011510 cancer Diseases 0.000 claims 2
• 210000004027 cell Anatomy 0.000 claims 2
• 238000003776 cleavage reaction Methods 0.000 claims 2
• 230000001268 conjugating effect Effects 0.000 claims 2
• 239000002254 cytotoxic agent Substances 0.000 claims 2
• 231100000599 cytotoxic agent Toxicity 0.000 claims 2
• 239000012634 fragment Substances 0.000 claims 2
• 239000003966 growth inhibitor Substances 0.000 claims 2
• 239000003112 inhibitor Substances 0.000 claims 2
• 238000004519 manufacturing process Methods 0.000 claims 2
• 230000000394 mitotic effect Effects 0.000 claims 2
• 230000001590 oxidative effect Effects 0.000 claims 2
• 230000007017 scission Effects 0.000 claims 2
• 150000003573 thiols Chemical group 0.000 claims 2
• JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
• PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims 1
• 238000004587 chromatography analysis Methods 0.000 claims 1
• 150000001875 compounds Chemical class 0.000 claims 1
• 239000010949 copper Substances 0.000 claims 1
• 229910001431 copper ion Inorganic materials 0.000 claims 1
• 125000004093 cyano group Chemical group *C#N 0.000 claims 1
• 238000006471 dimerization reaction Methods 0.000 claims 1
• 229910052739 hydrogen Inorganic materials 0.000 claims 1
• 239000001257 hydrogen Substances 0.000 claims 1
• 238000004949 mass spectrometry Methods 0.000 claims 1
• 239000002808 molecular sieve Substances 0.000 claims 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims 1