HRP20211058T1 - Kombinirane terapije koje sadrže molekule antitijela protiv lag-3 - Google Patents

Kombinirane terapije koje sadrže molekule antitijela protiv lag-3 Download PDF

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HRP20211058T1
HRP20211058T1 HRP20211058TT HRP20211058T HRP20211058T1 HR P20211058 T1 HRP20211058 T1 HR P20211058T1 HR P20211058T T HRP20211058T T HR P20211058TT HR P20211058 T HRP20211058 T HR P20211058T HR P20211058 T1 HRP20211058 T1 HR P20211058T1
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amino acid
acid sequence
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Glenn Dranoff
Frédéric Triebel
Chrystelle BRIGNONE
Walter A. Blattler
Jennifer Marie Mataraza
Catherine Anne SABATOS-PEYTON
Hwai Wen Chang
Johann GERHARD
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Novartis Ag
Immutep S.A.S.
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
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    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
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Claims (15)

1. Pripravak koji sadrži molekulu antitijela anti-LAG-3 i molekulu antitijela anti-PD-1, naznačen time što molekula antitijela anti-LAG-3 sadrži: (a) varijabilnu regiju teškog lanca (VH) koja sadrži VHCDR1 aminokiselinsku sekvencu SEQ ID NO: 4, VHCDR2 aminokiselinsku sekvencu SEQ ID NO: 5, i VHCDR3 aminokiselinsku sekvencu SEQ ID NO: 3; i varijabilnu regiju lakog lanca (VL) koja sadrži VLCDR1 aminokiselinsku sekvencu SEQ ID NO: 13, VLCDR2 aminokiselinsku sekvencu SEQ ID NO: 14, i VLCDR3 aminokiselinsku sekvencu SEQ ID NO: 15; (b) VH koja sadrži VHCDR1 aminokiselinsku sekvencu SEQ ID NO: 1; VHCDR2 aminokiselinsku sekvencu SEQ ID NO: 2; i VHCDR3 aminokiselinsku sekvencu SEQ ID NO: 3; i VL koja sadrži VLCDR1 aminokiselinsku sekvencu SEQ ID NO: 10, VLCDR2 aminokiselinsku sekvencu SEQ ID NO: 11, i VLCDR3 aminokiselinsku sekvencu SEQ ID NO: 12; (c) VH koja sadrži VHCDR1 aminokiselinsku sekvencu SEQ ID NO: 286, VHCDR2 aminokiselinsku sekvencu SEQ ID NO: 5, i VHCDR3 aminokiselinsku sekvencu SEQ ID NO: 3; i VL koja sadrži VLCDR1 aminokiselinsku sekvencu SEQ ID NO: 13, VLCDR2 aminokiselinsku sekvencu SEQ ID NO: 14, i VLCDR3 aminokiselinsku sekvencu SEQ ID NO: 15; ili (d) VH koja sadrži VHCDR1 aminokiselinsku sekvencu SEQ ID NO: 286; VHCDR2 aminokiselinsku sekvencu SEQ ID NO: 2; i VHCDR3 aminokiselinsku sekvencu SEQ ID NO: 3; i VL koja sadrži VLCDR1 aminokiselinsku sekvencu SEQ ID NO: 10, VLCDR2 aminokiselinsku sekvencu SEQ ID NO: 11, i VLCDR3 aminokiselinsku sekvencu SEQ ID NO: 12, i pri čemu molekula antitijela anti-PD-1 sadrži: (a) VH koja sadrži VHCDR1 aminokiselinsku sekvencu GYTFTTY (SEQ ID NO: 4 iz US 2015/0210769), VHCDR2 aminokiselinsku sekvencu YPGTGG (SEQ ID NO: 5 iz US 2015/0210769), i VHCDR3 aminokiselinsku sekvencu WTTGTGAY (SEQ ID NO: 3 iz US 2015/0210769); i varijabilnu regiju lakog lanca (VL) koja sadrži VLCDR1 aminokiselinsku sekvencu SQSLLDSGNQKNF (SEQ ID NO: 13 iz US 2015/0210769), VLCDR2 aminokiselinsku sekvencu WAS (SEQ ID NO: 14 iz US 2015/0210769), i VLCDR3 aminokiselinsku sekvencu DYSYPY ( SEQ ID NO: 33 iz US 2015/0210769); ili (b) VH koja sadrži aminokiselinsku sekvencu VHCDR1 odabranu od TYWMH (SEQ ID NO: 1 iz US 2015/0210769); VHCDR2 aminokiselinsku sekvencu NIYPGTGGSNFDEKFKN (SEQ ID NO: 2 iz US 2015/0210769); i VHCDR3 aminokiselinsku sekvencu WTTGTGAY (SEQ ID NO: 3 iz US 2015/0210769); i VL koja sadrži VLCDR1 aminokiselinsku sekvencu KSSQSLLDSGNQKNFLT (SEQ ID NO: 10 iz US 2015/0210769), VLCDR2 aminokiselinsku sekvencu WASTRES (SEQ ID NO: 11 iz US 2015/0210769), i VLCDR3 aminokiselinsku sekvencu od QNDYSYPYT (SEQ ID NO: 32 iz US 2015/0210769).
2. Pripravak prema zahtjevu 1, koji sadrži jedan ili više pripravaka ili oblika doziranja.
3. Kombinacija koja sadrži molekulu antitijela anti-LAG-3 i molekulu antitijela anti-PD-1, za uporabu u postupku liječenja raka kod subjekta, naznačena time što su molekula antitijela anti-LAG-3 i molekula antitijela anti-PD-1 definirane u zahtjevu 1.
4. Pripravak prema zahtjevu 1 ili 2, ili kombinacija za uporabu prema zahtjevu 3, naznačeni time što molekula antitijela anti-LAG-3 sadrži: varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu bilo koje od SEQ ID NO: 8, 28, 64, 68, 72, 76, 80, 100, 104 ili 108, ili aminokiselinsku sekvencu najmanje 85% identičnu bilo kojoj od SEQ ID NO: 8, 28, 64, 68, 72, 76, 80, 100, 104, ili 108; i/ili varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu bilo koje od SEQ ID NO: 32, 36, 40, 44, 48, 52, 56, 60, 84, 88, 92 ili 96, ili aminokiselinsku sekvencu najmanje 85% identičnu bilo kojoj od SEQ ID NO: 32, 36, 40, 44, 48, 52, 56, 60, 84, 88, 92, ili 96.
5. Pripravak prema bilo kojem zahtjevu 1-2 ili 4, ili kombinacija za uporabu prema zahtjevu 3 ili 4, naznačeni time što molekula antitijela anti-LAG-3 sadrži: (a) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 28 ili 100; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 32; (b) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 28 ili 100; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 36; (c) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 28 ili 100; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 40; (d) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 28 ili 100; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 44; (e) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 28 ili 100; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 48; (f) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 28 ili 100; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 52; (g) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 28 ili 100; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 56; (h) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 28 ili 100; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 60; (i) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 64 ili 104; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 36; (j) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 64 ili 104; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 40; (k) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 64 ili 104; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 56; (l) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 64 ili 104; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 60. (m) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 68 ili 108; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 36; (n) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 72 ili 8; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 40; (o) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 72 ili 8; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 60; (p) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 76; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 60; (q) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 80; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 84; (r) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 28 ili 100; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 88; (s) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 28 ili 100; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 92; ili (t) varijabilnu domenu teškog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 64 ili 104; i varijabilnu domenu lakog lanca koja sadrži aminokiselinsku sekvencu SEQ ID NO: 96.
6. Pripravak prema bilo kojem zahtjevu 1-2 ili 4-5, ili kombinacija za uporabu prema bilo kojem zahtjevu 3-5, naznačeni time što molekula antitijela anti-LAG-3 sadrži: teški lanac koji sadrži aminokiselinsku sekvencu bilo koje od SEQ ID NO: 18, 30, 66, 70, 74, 78, 82, 102, 106, 110, 113, 122, ili 134; i/ili laki lanac koji sadrži aminokiselinsku sekvencu bilo koje od SEQ ID NO: 34, 38, 42, 46, 50, 54, 58, 62, 86, 90, 94, ili 98.
7. Pripravak prema bilo kojem zahtjevu 1-2 ili 4-6, ili kombinacija za uporabu prema bilo kojem zahtjevu 3-6, naznačeni time što molekula antitijela anti-LAG-3 sadrži: (a) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 30 ili 102; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 34; (b) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 30 ili 102; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 38; (c) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 30 ili 102; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 42; (d) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 30 ili 102; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 46; (e) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 30 ili 102; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 50; (f) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 30 ili 102; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 54; (g) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 30 ili 102; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 58; (h) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 30 ili 102; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 62; (i) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 66 ili 106; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 38; (j) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 66 ili 106; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 42; (k) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 66 ili 106; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 58; (l) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 66 ili 106; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 62; (m) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 70 ili 110; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 38; (n) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 74 ili 18; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 42; (o) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 74 ili 18; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 62; (p) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 78 i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 62; (q) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 82 i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 86; (r) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 30 ili 102; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 94; (s) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 66 ili 106; i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 98; (t) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 113 i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 34; (u) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 113 i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 38; (v) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 122 i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 38; (w) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 122 i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 58; ili (x) teški lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 134 i laki lanac koji sadrži aminokiselinsku sekvencu SEQ ID NO: 38.
8. Pripravak prema bilo kojem od zahtjeva 1-2 ili 4-7, ili kombinacija za uporabu prema bilo kojem od zahtjeva 3-7, naznačeni time što molekula antitijela anti-PD-1 sadrži najmanje jednu ili dvije varijabilne domene teškog lanca koje izborno sadrže konstantnu regiju, najmanje jednu ili dvije varijabilne domene lakog lanca koje izborno sadrže konstantnu regiju, ili obje, pri čemu molekula antitijela anti-PD-1 sadrži aminokiselinsku sekvencu od: BAP049-Klon-A koji sadrži aminokiselinsku sekvencu varijabilne domene teškog lanca EVQLVQSGAEVKKPGESLRISCKGSGYTFTTYWMHWVRQATGQGLEWMGNIYPGTGG SNFDEKFKNRVTITADKSTSTAYMELSSLRSEDTAVYYCTRWTTGTGAYWGQGTTVTV SS (SEQ ID NO: 38 iz US 2015/0210769) i aminokiselinsku sekvencu varijabilne domene lakog lanca EIVLTQSPATLSLSPGERATLSCKSSQSLLDSGNQKNFLTWYQQKPGQAPRLLIYWASTR ESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQNDYSYPYTFGQGTKVEIK (SEQ ID NO. 42 iz US 2015/0210769); BAP049-Klon-B koji sadrži aminokiselinsku sekvencu varijabilne domene teškog lanca EVQLVQSGAEVKKPGESLRISCKGSGYTFTTYWMHWVRQATGQGLEWMGNIYPGTGG SNFDEKFKNRVTITADKSTSTAYMELSSLRSEDTAVYYCTRWTTGTGAYWGQGTTVTV SS (SEQ ID NO: 38 iz US 2015/0210769) i aminokiselinsku sekvencu varijabilne domene lakog lanca EIVLTQSPATLSLSPGERATLSCKSSQSLLDSGNQKNFLTWYQQKPGKAPKLLIYWASTR SGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQNDYSYPYTFGQGTKVEIK (SEQ ID NO: 54 iz US 2015/0210769); BAP049-Klon-C koji sadrži aminokiselinsku sekvencu varijabilne domene teškog lanca EVQLVQSGAEVKKPGESLRISCKGSGYTFTTYWMHWVRQATGQGLEWMGNIYPGTGG SNFDEKFKNRVTITADKSTSTAYMELSSLRSEDTAVYYCTRWTTGTGAYWGQGTTVTV SS (SEQ ID NO: 38 iz US 2015/0210769) i aminokiselinsku sekvencu varijabilne domene lakog lanca EIVLTQSPDFQSVTPKEKVTITCKSSQSLLDSGNQKNFLTWYQQKPGQAPRLLIYWASTR ESGVPSRFSGSGSGTDFTFTISSLEAEDAATYYCQNDYSYPYTFGQGTKVEIK (SEQ ID NO: 66 iz US 2015/0210769); BAP049-Klon-D koji sadrži aminokiselinsku sekvencu varijabilne domene teškog lanca EVQLVQSGAEVKKPGESLRISCKGSGYTFTTYWMHWIRQSPSRGLEWLGNIYPGTGGSN FDEKFKNRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRWTTGTGAYWGQGTTVTVSS (SEQ ID NO: 50 iz US 2015/0210769) i aminokiselinsku sekvencu varijabilne domene lakog lanca EIVLTQSPATLSLSPGERATLSCKSSQSLLDSGNQKNFLTWYQQKPGQAPRLLIYWASTR ESGVPSRFSGSGSGTDFTFTISSLEAEDAATYYCQNDYSYPYTFGQGTKVEIK (SEQ ID NO: 70 iz US 2015/0210769); ili BAP049-Klon-E koji sadrži aminokiselinsku sekvencu varijabilne domene teškog lanca EVQLVQSGAEVKKPGESLRISCKGSGYTFTTYWMHWVRQATGQGLEWMGNIYPGTGG SNFDEKFKNRVTITADKSTSTAYMELSSLRSEDTAVYYCTRWTTGTGAYWGQGTTVTV SS (SEQ ID NO: 38 iz US 2015/0210769) i aminokiselinsku sekvencu varijabilne domene lakog lanca EIVLTQSPATLSLSPGERATLSCKSSQSLLDSGNQKNFLTWYQQKPGQAPRLLIYWASTR ESGVPSRFSGSGSGTDFTFTISSLEAEDAATYYCQNDYSYPYTFGQGTKVEIK (SEQ ID NO: 70 iz US 2015/0210769); ili sekvenca koja ima najmanje 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% ili više identiteta bilo kojoj od gore navedenih sekvenci.
9. Pripravak prema bilo kojem zahtjevu 1-2 ili 4-8, ili kombinacija za uporabu prema bilo kojem zahtjevu 3-8, naznačeni time što je molekula antitijela humanizirana molekula antitijela, i/ili monospecifična molekula antitijela ili bispecifična molekula antitijela.
10. Pripravak prema bilo kojem zahtjevu 1-2 ili 4-9, ili kombinacija za uporabu prema bilo kojem zahtjevu 3-9, naznačeni time što je molekula antitijela monoklonsko antitijelo, Fab, F(ab')2, Fv , ili jednostruki Fv fragment (scFv); ili sadrži konstantnu regiju teškog lanca koja je IgG1, IgG2, IgG3, ili IgG4, i/ili konstantnu regiju lakog lanca koja je konstantna regija lakog lanca kappa ili lambda.
11. Pripravak prema zahtjevu 10, ili kombinacija za uporabu prema zahtjevu 10, naznačeni time što molekula antitijela anti-LAG-3, molekula antitijela anti-PD-1, ili oboje, sadrži: (a) konstantnu regiju humanog IgG4 teškog lanca s mutacijom na položaju 108 od SEQ ID NO: 275 ili 277 i kappa konstantnu regiju lakog lanca; (b) konstantnu regiju humanog IgG4 teškog lanca od SEQ ID NO: 275 ili 277 i kappa konstantnu regiju lakog lanca; (c) konstantnu regiju humanog IgG1 teškog lanca od SEQ ID NO: 279 i kappa konstantnu regiju lakog lanca; (d) konstantnu regiju humanog IgG1 teškog lanca od SEQ ID NO: 280 i kappa konstantnu regiju lakog lanca; ili (e) konstantnu regiju humanog IgG1 teškog lanca od SEQ ID NO: 281 i kappa konstantnu regiju lakog lanca.
12. Pripravak prema bilo kojem zahtjevu 1-2 ili 4-11, ili kombinacija za uporabu prema bilo kojem zahtjevu 3-11, naznačen time što bilo koja molekula antitijela ima prvu specifičnost vezanja za LAG-3 i drugu specifičnost vezanja za PD-1; i/ili pri čemu molekula antitijela sadrži fragment antitijela koji veže antigen, izborno pola antitijela ili fragment antitijela koji veže antigen pola antitijela.
13. Kombinacija za uporabu prema bilo kojem od zahtjeva 3-12, naznačena time što je rak rak pluća, melanom, rak bubrega, rak jetre, rak prostate, rak dojke, kolorektalni rak, rak želuca, rak gušterače, rak štitnjače, rak glave i vrata, rak endometrija, rak mozga, rak nazofarinksa, mezoteliom, solidni tumor, hematološki rak, ili metastatska lezija raka, izborno pri čemu rak je rak visoke mikrosatelitske nestabilnosti.
14. Kombinacija za uporabu prema zahtjevu 13, naznačena time što: (a) rak pluća je rak pluća nemalih stanica (NSCLC), adenokarcinom pluća, karcinom pluća skvamoznih stanica, ili rak pluća malih stanica, izborno, pri čemu NSCLC sadrži KRAS mutaciju; (b) melanom je uznapredovali melanom, neresektabilan melanom, metastatski melanom, melanom s BRAF mutacijom, melanom s NRAS mutacijom, kožni melanom, ili intraokularni melanom; (c) rak bubrega je karcinom bubrežnih stanica (RCC), metastatski karcinom bubrežnih stanica, ili karcinom bubrežnih stanica bistrih stanica (CCRCC); (d) hematološki karcinom je limfom, mijelom, ili leukemija, izborno, pri čemu je limfom ne-Hodgkinov limfom; (e) rak mozga je glioblastom; (f) rak dojke je trostruki negativni rak dojke ili ER+ rak dojke; ili (g) rak jetre je hepatocelularni karcinom.
15. Kombinacija za uporabu prema bilo kojem od zahtjeva 3-14, naznačena time što se molekula antitijela anti-LAG-3 koristi istovremeno, prije, ili nakon molekule antitijela anti-PD-1.
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