JP2019524759A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2019524759A5 JP2019524759A5 JP2019503986A JP2019503986A JP2019524759A5 JP 2019524759 A5 JP2019524759 A5 JP 2019524759A5 JP 2019503986 A JP2019503986 A JP 2019503986A JP 2019503986 A JP2019503986 A JP 2019503986A JP 2019524759 A5 JP2019524759 A5 JP 2019524759A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- subscript
- drug
- ligand
- needed
- 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
- 229940079593 drug Drugs 0.000 claims description 699
- 239000003814 drug Substances 0.000 claims description 699
- 150000001875 compounds Chemical class 0.000 claims description 468
- 229910052739 hydrogen Inorganic materials 0.000 claims description 355
- 239000000562 conjugate Substances 0.000 claims description 296
- 125000000217 alkyl group Chemical group 0.000 claims description 285
- -1 substituted Chemical class 0.000 claims description 271
- 150000003839 salts Chemical class 0.000 claims description 237
- 239000001257 hydrogen Substances 0.000 claims description 225
- 229910052799 carbon Inorganic materials 0.000 claims description 197
- 229910052757 nitrogen Inorganic materials 0.000 claims description 151
- 125000003118 aryl group Chemical group 0.000 claims description 145
- 239000003446 ligand Substances 0.000 claims description 142
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 108
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 105
- 101000629400 Homo sapiens Mesoderm-specific transcript homolog protein Proteins 0.000 claims description 96
- 102100026821 Mesoderm-specific transcript homolog protein Human genes 0.000 claims description 96
- 150000002431 hydrogen Chemical class 0.000 claims description 75
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 73
- 125000000623 heterocyclic group Chemical group 0.000 claims description 66
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 59
- 125000002947 alkylene group Chemical group 0.000 claims description 57
- 125000005842 heteroatom Chemical group 0.000 claims description 56
- 108010044540 auristatin Proteins 0.000 claims description 55
- 125000001072 heteroaryl group Chemical group 0.000 claims description 50
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 48
- 150000001412 amines Chemical class 0.000 claims description 47
- 235000008206 alpha-amino acids Nutrition 0.000 claims description 46
- 150000008134 glucuronides Chemical group 0.000 claims description 46
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 claims description 45
- 150000001576 beta-amino acids Chemical class 0.000 claims description 45
- 229910052717 sulfur Inorganic materials 0.000 claims description 44
- 229910052760 oxygen Inorganic materials 0.000 claims description 43
- 239000002253 acid Substances 0.000 claims description 42
- 125000004432 carbon atom Chemical group C* 0.000 claims description 42
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 42
- 150000001721 carbon Chemical group 0.000 claims description 41
- 238000007363 ring formation reaction Methods 0.000 claims description 41
- 102000005744 Glycoside Hydrolases Human genes 0.000 claims description 32
- 108010031186 Glycoside Hydrolases Proteins 0.000 claims description 32
- 125000006239 protecting group Chemical group 0.000 claims description 32
- 150000003335 secondary amines Chemical class 0.000 claims description 32
- 125000006850 spacer group Chemical group 0.000 claims description 32
- 108010016626 Dipeptides Proteins 0.000 claims description 29
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 27
- 238000003776 cleavage reaction Methods 0.000 claims description 27
- 230000007017 scission Effects 0.000 claims description 27
- 150000003512 tertiary amines Chemical group 0.000 claims description 24
- 108091005804 Peptidases Proteins 0.000 claims description 23
- 239000004365 Protease Substances 0.000 claims description 23
- 125000000524 functional group Chemical group 0.000 claims description 23
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 23
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 23
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 125000003342 alkenyl group Chemical group 0.000 claims description 20
- 125000004429 atom Chemical group 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 19
- 210000004027 cell Anatomy 0.000 claims description 17
- 230000004913 activation Effects 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
- 238000006467 substitution reaction Methods 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 13
- 239000002131 composite material Substances 0.000 claims description 13
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 150000001413 amino acids Chemical class 0.000 claims description 11
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 11
- 125000004434 sulfur atom Chemical group 0.000 claims description 11
- 230000002159 abnormal effect Effects 0.000 claims description 10
- 239000000611 antibody drug conjugate Substances 0.000 claims description 10
- 229940049595 antibody-drug conjugate Drugs 0.000 claims description 10
- 125000000837 carbohydrate group Chemical group 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 125000004122 cyclic group Chemical group 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- MFRNYXJJRJQHNW-DEMKXPNLSA-N (2s)-2-[[(2r,3r)-3-methoxy-3-[(2s)-1-[(3r,4s,5s)-3-methoxy-5-methyl-4-[methyl-[(2s)-3-methyl-2-[[(2s)-3-methyl-2-(methylamino)butanoyl]amino]butanoyl]amino]heptanoyl]pyrrolidin-2-yl]-2-methylpropanoyl]amino]-3-phenylpropanoic acid Chemical compound CN[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MFRNYXJJRJQHNW-DEMKXPNLSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 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 description 8
- 125000005647 linker group Chemical group 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 108010093470 monomethyl auristatin E Proteins 0.000 claims description 8
- 108010059074 monomethylauristatin F Proteins 0.000 claims description 8
- 239000000427 antigen Substances 0.000 claims description 7
- 102000036639 antigens Human genes 0.000 claims description 7
- 108091007433 antigens Proteins 0.000 claims description 7
- 229930182480 glucuronide Natural products 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 125000006539 C12 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 230000002209 hydrophobic effect Effects 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 230000008685 targeting Effects 0.000 claims description 6
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 6
- 229920002554 vinyl polymer Polymers 0.000 claims description 6
- 235000001014 amino acid Nutrition 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims description 5
- 150000003573 thiols Chemical group 0.000 claims description 5
- WOWDZACBATWTAU-FEFUEGSOSA-N (2s)-2-[[(2s)-2-(dimethylamino)-3-methylbutanoyl]amino]-n-[(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]-n,3-dimethylbutanamide Chemical compound CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)C1=CC=CC=C1 WOWDZACBATWTAU-FEFUEGSOSA-N 0.000 claims description 4
- 101710160107 Outer membrane protein A Proteins 0.000 claims description 4
- 108010008739 auristatin PHE Proteins 0.000 claims description 4
- 108010009065 auristatin PYE Proteins 0.000 claims description 4
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 4
- 210000004899 c-terminal region Anatomy 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 210000002919 epithelial cell Anatomy 0.000 claims description 4
- 125000005549 heteroarylene group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 230000003834 intracellular effect Effects 0.000 claims description 4
- 108010047846 soblidotin Proteins 0.000 claims description 4
- DZMVCVHATYROOS-ZBFGKEHZSA-N soblidotin Chemical compound CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)NCCC1=CC=CC=C1 DZMVCVHATYROOS-ZBFGKEHZSA-N 0.000 claims description 4
- 230000005945 translocation Effects 0.000 claims description 4
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims description 3
- 239000012634 fragment Substances 0.000 claims description 3
- 210000003712 lysosome Anatomy 0.000 claims description 3
- 230000001868 lysosomic effect Effects 0.000 claims description 3
- 230000001105 regulatory effect Effects 0.000 claims description 3
- JDVPQXZIJDEHAN-UHFFFAOYSA-N succinamic acid Chemical compound NC(=O)CCC(O)=O JDVPQXZIJDEHAN-UHFFFAOYSA-N 0.000 claims description 3
- 238000006845 Michael addition reaction Methods 0.000 claims description 2
- 102000035195 Peptidases Human genes 0.000 claims description 2
- 125000006244 carboxylic acid protecting group Chemical group 0.000 claims description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 230000002792 vascular Effects 0.000 claims description 2
- 125000003003 spiro group Chemical group 0.000 claims 8
- 125000006575 electron-withdrawing group Chemical group 0.000 claims 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 4
- 125000000732 arylene group Chemical group 0.000 claims 4
- 125000006832 (C1-C10) alkylene group Chemical group 0.000 claims 2
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims 2
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims 2
- 150000001720 carbohydrates Chemical class 0.000 claims 2
- 150000007513 acids Chemical class 0.000 claims 1
- 150000001371 alpha-amino acids Chemical class 0.000 claims 1
- 238000010504 bond cleavage reaction Methods 0.000 claims 1
- SNCZNSNPXMPCGN-UHFFFAOYSA-N butanediamide Chemical compound NC(=O)CCC(N)=O SNCZNSNPXMPCGN-UHFFFAOYSA-N 0.000 claims 1
- 230000002255 enzymatic effect Effects 0.000 claims 1
- 108010056119 protease So Proteins 0.000 claims 1
- 150000001768 cations Chemical class 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- OMRPLUKQNWNZAV-CONSDPRKSA-N (6as)-3-[3-[[(6as)-2-methoxy-8-(4-methoxyphenyl)-11-oxo-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-8-(4-aminophenyl)-2-methoxy-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-11-one Chemical compound C1=CC(OC)=CC=C1C1=CN2C(=O)C3=CC(OC)=C(OCCCOC=4C(=CC=5C(=O)N6C=C(C[C@H]6C=NC=5C=4)C=4C=CC(N)=CC=4)OC)C=C3N=C[C@@H]2C1 OMRPLUKQNWNZAV-CONSDPRKSA-N 0.000 description 5
- 125000002015 acyclic group Chemical group 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 0 CCCC(CCC*)C(*)(C(*Nc(cc(C*)cc1*)c1O*)=O)NCCCC(O)=O Chemical compound CCCC(CCC*)C(*)(C(*Nc(cc(C*)cc1*)c1O*)=O)NCCCC(O)=O 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000003463 hyperproliferative effect Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2023060933A JP7573679B2 (ja) | 2016-08-09 | 2023-04-04 | 改善された生理化学的特性を有する自己安定性リンカーを用いる薬物コンジュゲート |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662372455P | 2016-08-09 | 2016-08-09 | |
| US62/372,455 | 2016-08-09 | ||
| PCT/US2017/046157 WO2018031690A1 (en) | 2016-08-09 | 2017-08-09 | Drug conjugates with self-stabilizing linkers having improved physiochemical properties |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023060933A Division JP7573679B2 (ja) | 2016-08-09 | 2023-04-04 | 改善された生理化学的特性を有する自己安定性リンカーを用いる薬物コンジュゲート |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019524759A JP2019524759A (ja) | 2019-09-05 |
| JP2019524759A5 true JP2019524759A5 (https=) | 2020-09-24 |
| JP7257951B2 JP7257951B2 (ja) | 2023-04-14 |
Family
ID=61162990
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019503986A Active JP7257951B2 (ja) | 2016-08-09 | 2017-08-09 | 改善された生理化学的特性を有する自己安定性リンカーを用いる薬物コンジュゲート |
| JP2023060933A Active JP7573679B2 (ja) | 2016-08-09 | 2023-04-04 | 改善された生理化学的特性を有する自己安定性リンカーを用いる薬物コンジュゲート |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023060933A Active JP7573679B2 (ja) | 2016-08-09 | 2023-04-04 | 改善された生理化学的特性を有する自己安定性リンカーを用いる薬物コンジュゲート |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US11944689B2 (https=) |
| EP (1) | EP3496747A4 (https=) |
| JP (2) | JP7257951B2 (https=) |
| KR (2) | KR20190038579A (https=) |
| CN (1) | CN109562152B (https=) |
| AU (2) | AU2017310436B2 (https=) |
| BR (1) | BR112019001945A2 (https=) |
| EA (1) | EA201990470A1 (https=) |
| IL (1) | IL264453A (https=) |
| MA (1) | MA45945A (https=) |
| MX (2) | MX2019001302A (https=) |
| SG (1) | SG11201900699QA (https=) |
| TW (2) | TWI851531B (https=) |
| WO (1) | WO2018031690A1 (https=) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20180134351A (ko) | 2016-03-25 | 2018-12-18 | 시애틀 지네틱스, 인크. | 페길화된 약물-링커 및 그의 중간체의 제조를 위한 공정 |
| MX2019001302A (es) | 2016-08-09 | 2019-06-12 | Seattle Genetics Inc | Conjugados de farmaco con enlazadores autoestabilizantes que tienen propiedades fisioquimicas mejoradas. |
| AU2018237683A1 (en) | 2017-03-24 | 2019-10-31 | Seagen Inc. | Process for the preparation of glucuronide drug-linkers and intermediates thereof |
| TWI851577B (zh) | 2018-06-07 | 2024-08-11 | 美商思進公司 | 喜樹鹼結合物 |
| GB201820864D0 (en) * | 2018-12-20 | 2019-02-06 | J A Kemp | Antibody-drug conjugates |
| MA53765B2 (fr) | 2018-12-21 | 2025-04-30 | Regeneron Pharmaceuticals, Inc. | Tubulysines et conjugués tubulysines-protéines |
| JP2022530482A (ja) * | 2019-05-02 | 2022-06-29 | レゴケム バイオサイエンシズ， インク． | トリス構造を有するリンカーを含むリガンド―薬物複合体 |
| CN113727734A (zh) * | 2019-05-02 | 2021-11-30 | 乐高化学生物科学股份有限公司 | 包含具有tris结构的连接子的配体-药物偶联物 |
| AU2020296295B2 (en) * | 2019-06-21 | 2025-05-29 | Ascendis Pharma A/S | Conjugates of an electron-donating nitrogen or tertiary amine comprising compounds |
| AU2020482800B2 (en) * | 2020-12-23 | 2025-08-21 | Genequantum Healthcare (Suzhou) Co., Ltd. | Novel isomeric compounds comprising a ring-opened thiosuccinimide group, an oligopeptide fragment and a chiral moiety |
| JP7717832B2 (ja) | 2021-04-10 | 2025-08-04 | ジェンマブ エー／エス | Ｆｏｌｒ１結合剤、そのコンジュゲートおよびこれを使用する方法 |
| WO2022226317A1 (en) | 2021-04-23 | 2022-10-27 | Profoundbio Us Co. | Anti-cd70 antibodies, conjugates thereof and methods of using the same |
| TW202320857A (zh) | 2021-07-06 | 2023-06-01 | 美商普方生物製藥美國公司 | 連接子、藥物連接子及其結合物及其使用方法 |
| MX2024002571A (es) | 2021-09-03 | 2024-03-20 | Toray Industries | Composicion farmaceutica para tratamiento y/o prevencion de cancer. |
| WO2023092099A1 (en) | 2021-11-19 | 2023-05-25 | Ardeagen Corporation | Gpc3 binding agents, conjugates thereof and methods of using the same |
| KR20250031149A (ko) | 2022-06-30 | 2025-03-06 | 도레이 카부시키가이샤 | 암의 치료 및/또는 예방용 의약 조성물 |
| CN118684724A (zh) | 2023-03-22 | 2024-09-24 | 映恩生物制药（苏州）有限公司 | 连接子及其在配体药物偶联物中的应用 |
| AR132368A1 (es) | 2023-04-18 | 2025-06-18 | Astrazeneca Ab | Conjugados que comprenden enlazadores escindibles |
| KR20250074353A (ko) | 2023-11-20 | 2025-05-27 | 주식회사 에이비켐바이오 | 높은 dar를 갖는 신규한 항체-약물 중합체, 이의 제조방법 및 이의 용도 |
| KR20240159448A (ko) | 2023-04-28 | 2024-11-05 | 주식회사 에이비켐바이오 | 균일한 dar를 갖는 신규한 항체-약물 중합체의 제조방법 |
| KR20240159447A (ko) | 2023-04-28 | 2024-11-05 | 주식회사 에이비켐바이오 | 말레이미드 함유 링커-페이로드 접합체 |
| CN121568721A (zh) * | 2023-06-29 | 2026-02-24 | 广州百济神州生物制药有限公司 | 生物活性缀合物、其制备方法和其用途 |
| TW202525851A (zh) * | 2023-08-15 | 2025-07-01 | 瑞典商阿斯特捷利康公司 | 包含可切割連接子的軛合物 |
| AU2024339683A1 (en) | 2023-09-13 | 2026-03-26 | Toray Industries, Inc. | Pharmaceutical composition for treating, preventing and/or diagnosing cancer |
| AU2024353316A1 (en) | 2023-09-26 | 2026-03-26 | Genmab A/S | Ptk7 binding agents, conjugates thereof and methods of using the same |
| WO2025149661A1 (en) | 2024-01-10 | 2025-07-17 | Genmab A/S | Slitrk6 binding agents, conjugates thereof and methods of using the same |
| WO2025181219A1 (en) | 2024-02-29 | 2025-09-04 | Genmab A/S | Egfr and c-met bispecific binding agents, conjugates thereof and methods of using the same |
| WO2026039642A1 (en) | 2024-08-16 | 2026-02-19 | Ardeagen Corporation | Anti-mesothelin antibody conjugates and methods of use thereof |
Family Cites Families (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2036891B (en) | 1978-12-05 | 1983-05-05 | Windsor Smith C | Change speed gear |
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| JPS6147500A (ja) | 1984-08-15 | 1986-03-07 | Res Dev Corp Of Japan | キメラモノクロ−ナル抗体及びその製造法 |
| EP0173494A3 (en) | 1984-08-27 | 1987-11-25 | The Board Of Trustees Of The Leland Stanford Junior University | Chimeric receptors by dna splicing and expression |
| GB8422238D0 (en) | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
| JPS61134325A (ja) | 1984-12-04 | 1986-06-21 | Teijin Ltd | ハイブリツド抗体遺伝子の発現方法 |
| JPS63501765A (ja) | 1985-11-01 | 1988-07-21 | インタ−ナショナル、ジェネティック、エンジニアリング インコ−ポレ−テッド | 抗体遺伝子のモジュ−ル組立体、それにより産生された抗体及び用途 |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US4880935A (en) | 1986-07-11 | 1989-11-14 | Icrf (Patents) Limited | Heterobifunctional linking agents derived from N-succinimido-dithio-alpha methyl-methylene-benzoates |
| JPS6423340U (https=) | 1987-08-03 | 1989-02-07 | ||
| IL106992A (en) | 1988-02-11 | 1994-06-24 | Bristol Myers Squibb Co | Acylhydrazone derivatives of anthracycline and methods for their preparation |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5091542A (en) | 1990-03-09 | 1992-02-25 | Hybritech Incorporated | Tris-maleimido compounds as intermediates in trifunctional antibody synthesis |
| US5622929A (en) | 1992-01-23 | 1997-04-22 | Bristol-Myers Squibb Company | Thioether conjugates |
| WO1994001485A1 (en) | 1992-07-01 | 1994-01-20 | Akzo Nobel N.V. | Process for the modification of polyphenylene ether resin compositions |
| US6214345B1 (en) | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
| ATE234635T1 (de) | 1995-12-22 | 2003-04-15 | Bristol Myers Squibb Co | Verzweigte hydrazongruppen enthaltende kuppler |
| JP4046354B2 (ja) | 1996-03-18 | 2008-02-13 | ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム | 増大した半減期を有する免疫グロブリン様ドメイン |
| US6130237A (en) | 1996-09-12 | 2000-10-10 | Cancer Research Campaign Technology Limited | Condensed N-aclyindoles as antitumor agents |
| US5973166A (en) | 1998-03-02 | 1999-10-26 | The Dexter Corporation | Method for the preparation of maleimides |
| US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
| US7256257B2 (en) | 2001-04-30 | 2007-08-14 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
| US20030083263A1 (en) | 2001-04-30 | 2003-05-01 | Svetlana Doronina | Pentapeptide compounds and uses related thereto |
| US7091186B2 (en) | 2001-09-24 | 2006-08-15 | Seattle Genetics, Inc. | p-Amidobenzylethers in drug delivery agents |
| US7125844B2 (en) | 2002-01-03 | 2006-10-24 | Migenix Inc. | Dab9 derivatives of lipopeptide antibiotics and methods of making and using the same |
| US8877901B2 (en) | 2002-12-13 | 2014-11-04 | Immunomedics, Inc. | Camptothecin-binding moiety conjugates |
| SI1545613T1 (sl) | 2002-07-31 | 2011-11-30 | Seattle Genetics Inc | Avristatinski konjugati in njihova uporaba za zdravljenje raka avtoimunske bolezni ali infekcijskebolezni |
| US7432331B2 (en) | 2002-12-31 | 2008-10-07 | Nektar Therapeutics Al, Corporation | Hydrolytically stable maleimide-terminated polymers |
| EP1578841B2 (en) * | 2002-12-31 | 2016-10-12 | Nektar Therapeutics AL, Corporation | Maleamic acid polymer derivatives and their bioconjugates |
| US8088387B2 (en) | 2003-10-10 | 2012-01-03 | Immunogen Inc. | Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates |
| RU2448117C2 (ru) | 2003-11-06 | 2012-04-20 | Сиэтл Дженетикс, Инк. | Монометилвалиновые соединения, способные образовывать конъюгаты с лигандами |
| US7498298B2 (en) | 2003-11-06 | 2009-03-03 | Seattle Genetics, Inc. | Monomethylvaline compounds capable of conjugation to ligands |
| EP1718667B1 (en) | 2004-02-23 | 2013-01-09 | Genentech, Inc. | Heterocyclic self-immolative linkers and conjugates |
| CN1997402B (zh) * | 2004-05-19 | 2014-04-02 | 梅达雷克斯有限责任公司 | 化学连接基团及其缀合物 |
| JP4806680B2 (ja) | 2004-05-19 | 2011-11-02 | メダレックス インコーポレイテッド | 自己犠牲リンカー及び薬剤複合体 |
| KR20120064120A (ko) | 2004-06-01 | 2012-06-18 | 제넨테크, 인크. | 항체 약물 접합체 및 방법 |
| US20060292616A1 (en) * | 2005-06-23 | 2006-12-28 | U.S. Genomics, Inc. | Single molecule miRNA-based disease diagnostic methods |
| US8871720B2 (en) | 2005-07-07 | 2014-10-28 | Seattle Genetics, Inc. | Monomethylvaline compounds having phenylalanine carboxy modifications at the C-terminus |
| JP5171621B2 (ja) | 2005-07-07 | 2013-03-27 | シアトル ジェネティックス， インコーポレイテッド | フェニルアラニン側鎖修飾をｃ末端に有するモノメチルバリン化合物 |
| HUE035853T2 (en) | 2005-07-18 | 2018-05-28 | Seattle Genetics Inc | Beta-glucuronide-linker-drug conjugates |
| BRPI0617546A2 (pt) | 2005-09-26 | 2011-07-26 | Medarex Inc | conjugado de fÁrmaco-anticorpo, formulaÇço farmacÊutica, mÉtodo para matar uma cÉlula de tumor, mÉtodo para retardar ou interromper o crescimento de um tumor em um sujeito mamÍfero e composto |
| SI1813614T1 (sl) | 2006-01-25 | 2012-01-31 | Sanofi 174 | Citotoksična sredstva, ki obsegajo nove tomajmicinske derivate |
| US8257706B2 (en) | 2006-08-25 | 2012-09-04 | Seattle Genetics, Inc. | CD30 binding agents and uses thereof |
| BRPI0812970A2 (pt) | 2007-06-25 | 2019-09-24 | Endocyte Inc | conjugados contendo espaçadores hidrofílicos |
| RU2476441C2 (ru) | 2007-10-19 | 2013-02-27 | Сиэтл Дженетикс, Инк. | Cd19-связывающие средства и их применение |
| EP2265283B1 (en) | 2008-03-18 | 2014-09-03 | Seattle Genetics, Inc. | Auristatin drug linker conjugates |
| KR20200058590A (ko) | 2008-04-30 | 2020-05-27 | 이뮤노젠 아이엔씨 | 가교제 및 그 용도 |
| BRPI0923283A2 (pt) | 2008-12-05 | 2017-06-06 | Angiochem Inc | conjugados terapêuticos de peptídeo e usos dos mesmos |
| CN102365021B (zh) | 2009-02-05 | 2015-07-15 | 伊缪诺金公司 | 新型苯并二氮杂*衍生物 |
| EP3912643B8 (en) | 2009-02-13 | 2023-08-23 | Immunomedics, Inc. | Immunoconjugates with an intracellularly-cleavable linkage |
| FR2949469A1 (fr) | 2009-08-25 | 2011-03-04 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application en therapeutique |
| DK2528625T3 (da) | 2010-04-15 | 2013-10-14 | Spirogen Sarl | Pyrrolobenzodiazepiner og konjugater deraf |
| AU2011316917B2 (en) | 2010-10-22 | 2016-02-25 | Seagen Inc. | Synergistic effects between auristatin-based antibody drug conjugates and inhibitors of the PI3K-AKT mTOR pathway |
| JP6105481B2 (ja) | 2010-12-06 | 2017-03-29 | シアトル ジェネティクス，インコーポレーテッド | Ｌｉｖ−１に対するヒト化抗体および癌治療のためのその使用 |
| JP6049642B2 (ja) | 2011-02-15 | 2016-12-21 | イミュノジェン・インコーポレーテッド | 複合体の調製方法 |
| CH706603B1 (de) | 2011-08-03 | 2016-08-31 | Ophthametrics Ag Hrm Man & Treuhand Ag | Aufnahmevorrichtung zur Aufnahme einer Netzhaut eines Auges sowie Aufnahmeverfahren. |
| CN104244718A (zh) | 2011-12-05 | 2014-12-24 | 伊格尼卡生物治疗公司 | 抗体-药物缀合物以及相关化合物、组合物和方法 |
| CN104220094A (zh) | 2012-02-17 | 2014-12-17 | 西雅图基因公司 | 针对整联蛋白αvβ6的抗体和使用该抗体治疗癌症 |
| CA2864872C (en) * | 2012-02-24 | 2022-07-05 | Alteogen Inc. | Modified antibody in which motif comprising cysteine residue is bound |
| KR102557309B1 (ko) | 2012-05-15 | 2023-07-20 | 씨젠 인크. | 자가-안정화 링커 접합체 |
| US9504756B2 (en) * | 2012-05-15 | 2016-11-29 | Seattle Genetics, Inc. | Self-stabilizing linker conjugates |
| US20130309223A1 (en) | 2012-05-18 | 2013-11-21 | Seattle Genetics, Inc. | CD33 Antibodies And Use Of Same To Treat Cancer |
| EP2968591A1 (en) | 2013-03-15 | 2016-01-20 | Novartis AG | Cell proliferation inhibitors and conjugates thereof |
| ES2826398T3 (es) | 2013-10-15 | 2021-05-18 | Seagen Inc | Enlazadores-fármacos pegilados para una mejor farmacocinética de los conjugados ligando-fármaco |
| JP6701077B2 (ja) | 2013-12-19 | 2020-05-27 | シアトル ジェネティックス， インコーポレイテッド | 標的化薬物結合体と使用するためのメチレンカルバメートリンカー |
| SG10202001468UA (en) | 2014-02-17 | 2020-04-29 | Seattle Genetics Inc | Hydrophilic antibody-drug conjugates |
| SI3900742T1 (sl) | 2014-09-11 | 2024-10-30 | Seagen Inc. | Ciljana dostava zdravilnih snovi, ki vsebujejo terciarne amine |
| MX2019001302A (es) | 2016-08-09 | 2019-06-12 | Seattle Genetics Inc | Conjugados de farmaco con enlazadores autoestabilizantes que tienen propiedades fisioquimicas mejoradas. |
| JP7337698B2 (ja) | 2017-02-28 | 2023-09-04 | シージェン インコーポレイテッド | コンジュゲート化のためのシステイン突然変異抗体 |
| WO2018201087A1 (en) | 2017-04-27 | 2018-11-01 | Seattle Genetics, Inc. | Quaternized nicotinamide adenine dinucleotide salvage pathway inhibitor conjugates |
| AR114112A1 (es) | 2018-02-15 | 2020-07-22 | Seattle Genetics Inc | Anticuerpos de glipicano 3 y conjugados de los mismos |
-
2017
- 2017-08-09 MX MX2019001302A patent/MX2019001302A/es unknown
- 2017-08-09 EA EA201990470A patent/EA201990470A1/ru unknown
- 2017-08-09 JP JP2019503986A patent/JP7257951B2/ja active Active
- 2017-08-09 KR KR1020197005530A patent/KR20190038579A/ko not_active Ceased
- 2017-08-09 WO PCT/US2017/046157 patent/WO2018031690A1/en not_active Ceased
- 2017-08-09 BR BR112019001945-6A patent/BR112019001945A2/pt unknown
- 2017-08-09 TW TW106126961A patent/TWI851531B/zh active
- 2017-08-09 MA MA045945A patent/MA45945A/fr unknown
- 2017-08-09 KR KR1020247000631A patent/KR20240010534A/ko not_active Withdrawn
- 2017-08-09 US US16/324,198 patent/US11944689B2/en active Active
- 2017-08-09 TW TW113107936A patent/TW202500191A/zh unknown
- 2017-08-09 SG SG11201900699QA patent/SG11201900699QA/en unknown
- 2017-08-09 CN CN201780047894.1A patent/CN109562152B/zh active Active
- 2017-08-09 EP EP17840229.3A patent/EP3496747A4/en active Pending
- 2017-08-09 AU AU2017310436A patent/AU2017310436B2/en not_active Ceased
-
2019
- 2019-01-24 IL IL264453A patent/IL264453A/en unknown
-
2022
- 2022-11-24 AU AU2022275478A patent/AU2022275478B2/en not_active Expired - Fee Related
-
2023
- 2023-04-04 JP JP2023060933A patent/JP7573679B2/ja active Active
- 2023-12-13 MX MX2023013592A patent/MX2023013592A/es unknown
-
2024
- 2024-01-11 US US18/410,296 patent/US20240226320A1/en not_active Abandoned
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2019524759A5 (https=) | ||
| JP2023082171A5 (https=) | ||
| ES2941768T3 (es) | Compuestos de 2H-pirazolo[4,3-d]pirimidina como agonistas del receptor 7 tipo toll (TLR7) y métodos y usos para los mismos | |
| AU2008258548B2 (en) | Long-acting transient polymer conjugates of exendin | |
| JP6329673B2 (ja) | Ｐｅｇ化された組換えヒト成長ホルモン化合物 | |
| ES2536450T3 (es) | Conjugados que tienen una unión degradable y reactivos poliméricos útiles en la preparación de tales conjugados | |
| Fontaine et al. | Long-term stabilization of maleimide–thiol conjugates | |
| ES2512499T3 (es) | Fármacos pegilados reversibles | |
| ES2725805T3 (es) | Un conjugado de GLP-2 de sitio específico que usa un fragmento de inmunoglobulia | |
| JP2020517599A5 (https=) | ||
| JP2022105640A5 (https=) | ||
| JP7681054B2 (ja) | Ｍｅｔａｐ２阻害剤及び肥満症の治療方法 | |
| US20180360973A1 (en) | Protein conjugate using a fatty acid derivative and method for preparation thereof | |
| RU2015119561A (ru) | Новые конъюгаты лекарственное вещество-белок | |
| EP2768856A1 (en) | Peg conjugates of exenatide | |
| RU2015119557A (ru) | Конъюгаты лекарственное вещество-белок | |
| CN111918665A (zh) | Il-2缀合物 | |
| RU2018102358A (ru) | Нацеленные конъюгаты ksp ингибиторов | |
| AU2017336249A1 (en) | Dosage regimen for a controlled-release PTH compound | |
| JP2023129495A5 (https=) | ||
| RU2009103198A (ru) | Новые белковые конъюгаты и способы их получения | |
| WO2021053589A1 (en) | Compounds for the induction of antigen-specific immune tolerance | |
| KR20220128390A (ko) | 부갑상선기능저하증 치료 | |
| CN118359699A (zh) | 白细胞介素-22的治疗性衍生物 | |
| JP2021513990A5 (https=) |