HRP20201186T1 - Konjugati protutijela protiv cmet s lijekom i postupci njihove upotrebe - Google Patents
Konjugati protutijela protiv cmet s lijekom i postupci njihove upotrebe Download PDFInfo
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- HRP20201186T1 HRP20201186T1 HRP20201186TT HRP20201186T HRP20201186T1 HR P20201186 T1 HRP20201186 T1 HR P20201186T1 HR P20201186T T HRP20201186T T HR P20201186TT HR P20201186 T HRP20201186 T HR P20201186T HR P20201186 T1 HRP20201186 T1 HR P20201186T1
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- adc
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- drug conjugate
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- 239000000611 antibody drug conjugate Substances 0.000 title claims 34
- 229940049595 antibody-drug conjugate Drugs 0.000 title claims 34
- 238000000034 method Methods 0.000 title claims 5
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 9
- 206010028980 Neoplasm Diseases 0.000 claims 5
- 102000001301 EGF receptor Human genes 0.000 claims 4
- 108060006698 EGF receptor Proteins 0.000 claims 4
- 239000002246 antineoplastic agent Substances 0.000 claims 3
- 238000001574 biopsy Methods 0.000 claims 3
- 206010023774 Large cell lung cancer Diseases 0.000 claims 2
- 208000009956 adenocarcinoma Diseases 0.000 claims 2
- 230000009286 beneficial effect Effects 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 201000009546 lung large cell carcinoma Diseases 0.000 claims 2
- 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 class 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 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims 1
- 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 1
- 239000000562 conjugate Substances 0.000 claims 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 1
- 238000012217 deletion Methods 0.000 claims 1
- 230000037430 deletion Effects 0.000 claims 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims 1
- 229960001433 erlotinib Drugs 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- 238000012360 testing method Methods 0.000 claims 1
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 1
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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Claims (16)
1. Konjugat protutijela protiv cMet s lijekom (ADC) namijenjen upotrebi u postupku liječenja raka velikih stanica pluća (NSCLC) koji hipereksprimira cMet, gdje se postupak sastoji u primjeni na subjektu koji ima navedeni NSCLC ADC u količini i kroz dovoljno dug vremenski period za osiguravanje terapijski povoljnog učinka; naznačen time što
konjugirani lijek je monometilirani auristatin E ("MMAE"); i
ADC ima sljedeću strukturu:
[image]
,
gdje
n ima vrijednost u rasponu od 2 do 8; i
Ab je protutijelo protiv cMet koje sadrži VH lanac koji sadrži tri CDR, i to VH CDR br. 1 (SEQ ID NO: 112), VH CDR br. 2 (SEQ ID NO:1 13) i VH CDR br. 3 (SEQ ID NO: 114); VL lanac koji sadrži tri CDR, i to VL CDR br. 1 (SEQ ID NO: 115), VL CDR br. 2 (SEQ ID NO: 116) i VL CDR br. 3 (SEQ ID NO: 117); i modificirano područje zgloba sa SEQ ID NO: 170.
2. Konjugat protutijela protiv cMet s lijekom (ADC) namijenjen upotrebi u skladu s patentnim zahtjevom 1, naznačen time što vezanje na Ab je izvedeno tioeterskom vezom, ostvarenom sa sulfhidrilnom skupinom cisteinskog ostatka.
3. Konjugat protutijela protiv cMet s lijekom (ADC) namijenjen upotrebi u skladu s patentnim zahtjevom 1 ili 2, naznačen time što protutijelo protiv cMet sadrži VH lanac sa SEQ ID NO: 78 i VL lanac sa SEQ ID NO: 79.
4. Konjugat protutijela protiv cMet s lijekom (ADC) namijenjen upotrebi u skladu s patentnim zahtjevom 3, naznačen time što protutijelo protiv cMet sadrži teški lanac sa SEQ ID NO: 86 i laki lanac sa SEQ ID NO: 87.
5. Pripravak koji sadrži ADC u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time što je namijenjen upotrebi u postupku liječenja raka velikih stanica pluća (NSCLC) koji hipereksprimira cMet, gdje se postupak sastoji u primjeni na subjektu koji ima navedeni NSCLC ADC u količini i kroz dovoljno dug vremenski period za osiguravanje terapijski povoljnog učinka.
6. Pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 5, naznačen time što ADC protiv cMet u skladu s patentnim zahtjevima 2 i 4 ima prosječni omjer između lijeka i protutijela (DAR) od otprilike 3.
7. Pripravak namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 5 ili 6, naznačen time što ADC protiv cMet ima približan omjer od 1:1 za E2 i E4 ADC.
8. Konjugat protutijela protiv cMet s lijekom (ADC) ili pripravak namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačeni time što biopsija NSCLC tumorskog tkiva subjekta ima IHC bodove od 2+ ili 3+.
9. Konjugat protutijela protiv cMet s lijekom (ADC) ili pripravak namijenjen upotrebi u skladu s bilo kojim od patentnim zahtjevom 1 do 8, naznačeni time što je NSCLC pločasti NSCLC.
10. Konjugat protutijela protiv cMet s lijekom (ADC) ili pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 9, naznačeni time što biopsija pločastog NSCLC tumorskog tkiva daje IHC bodove od 2+ i/ili H-bodove od 150 do 224.
11. Konjugat protutijela protiv cMet s lijekom (ADC) ili pripravak namijenjen upotrebi u skladu s bilo kojim od patentnim zahtjevom 1 do 10, naznačeni time što je NSCLC rak koji hipereksprimira cMet adenokarcinom.
12. Konjugat protutijela protiv cMet s lijekom (ADC) ili pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 11, naznačeni time što biopsija tumorskog tkiva adenokarcinoma daje IHC bodove od 3+ i/ili H-bodove veće od 225.
13. Konjugat protutijela protiv cMet s lijekom (ADC) ili pripravak namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 1 do 12, naznačeni time što se ADC protiv cMet primijenjuje uz dodatno protutumorsko sredstvo.
14. Konjugat protutijela protiv cMet s lijekom (ADC) ili pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 13, naznačeni time što je dodatno protutumorsko sredstvo inhibitor receptora čimbenika rasta epiderme ("EGFR").
15. Konjugat protutijela protiv cMet s lijekom (ADC) ili pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 14, naznačeni time što je dodatno protutumorsko sredstvo erlotinib.
16. Konjugat protutijela protiv cMet s lijekom (ADC) ili pripravak namijenjen upotrebi u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačeni time što rak koji hipereksprimira cMet ima delecije u eksonu 19 ili supstitucije u eksonu 21 (L858R) u receptoru čimbenika rasta epiderme (EGFR), što je detektirano testom kojeg je odobrila FDA.
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PCT/US2017/033176 WO2017201204A1 (en) | 2016-05-17 | 2017-05-17 | ANTI-cMet ANTIBODY DRUG CONJUGATES AND METHODS FOR THEIR USE |
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