HRP20201176T1 - Antitijela protiv cd73 i njihova upotreba - Google Patents

Antitijela protiv cd73 i njihova upotreba Download PDF

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Publication number
HRP20201176T1
HRP20201176T1 HRP20201176TT HRP20201176T HRP20201176T1 HR P20201176 T1 HRP20201176 T1 HR P20201176T1 HR P20201176T T HRP20201176T T HR P20201176TT HR P20201176 T HRP20201176 T HR P20201176T HR P20201176 T1 HRP20201176 T1 HR P20201176T1
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HR
Croatia
Prior art keywords
seq
antibody
amino acid
acid sequence
set forth
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HRP20201176TT
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English (en)
Inventor
Nils Lonberg
Alan J. Korman
Bryan C. Barnhart
Aaron YAMNIUK
Mohan Srinivasan
Karla A. Henning
Ming Lei
Emanuela SEGA
Angela GOODENOUGH
Maria N. Jure-Kunkel
Guodong Chen
John SACK
Richard Huang
Martin J. Corbett
Joseph E. Myers
Liang SCHWEIZER
Sandra V. Hatcher
Haichun Huang
Pingping Zhang
Original Assignee
Bristol-Myers Squibb Company
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Application filed by Bristol-Myers Squibb Company filed Critical Bristol-Myers Squibb Company
Publication of HRP20201176T1 publication Critical patent/HRP20201176T1/hr

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    • 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
    • C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
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    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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Claims (14)

1. Izolirano antitijelo koje se vezuje za humani klaster diferencijacije 73 (CD73) i sadrži CDR1, CDR2, i CDR3 sekvence teškog lanca koje sadrže SEK ID BROJEVA (SEQ ID NOs): 5, 6, i 7, redom, i CDR1, CDR2, i CDR3 sekvence lakog lanca koje sadrže SEQ ID NOs: 13, 14, i 15, redom, gdje antitijelo sadrži konstantnu regiju teškog lanca koji sadrži IgG2 zglob i IgG2 CH1 domenu.
2. Izolirano antitijelo iz patentnog zahtjeva 1, gdje domena zgloba sadrži aminokiselinsku supstituciju C219S, u skladu sa EU indeksom Kabat sistema, u odnosu na domenu zgloba humanog IgG2 divljeg tipa (SEK ID BR - SEQ ID NO: 136).
3. Izolirano antitijelo iz patentnog zahtjeva 1 ili 2, gdje konstantna regija teškog lanca sadrži: (a) CH1 domena koji sadrži aminokiselinsku sekvencu sa SEQ ID NO: 124; i (b) zglobna domena koja sadrži aminokiselinsku sekvencu sa SEQ ID NO: 123.
4. Izolirano antitijelo iz bilo kojeg od patentnih zahtjeva 1 do 3, gdje antitijelo sadrži varijabilnu regiju teškog lanca koja sadrži aminokiselinsku sekvencu kao što je dana u SEQ ID NO: 135 i varijabilnoj regiji lakog lanca koja sadrži aminokiselinsku sekvencu kao što je dana u SEQ ID NO: 12.
5. Izolirano antitijelo iz bilo kojeg od patentnih zahtjeva 1 do 3, gdje antitijelo sadrži teški lanac koji sadrži aminokiselinsku sekvencu kao što je dana u SEQ ID NO: 133 ili 189 i laki lanac koji sadrži aminokiselinsku sekvencu kao što je dana u SEQ ID NO: 102.
6. Izolirano antitijelo iz bilo kojeg od patentnih zahtjeva 1 do 3, gdje teški i laki lanci su i teški i laki lanci pune dužine, redom.
7. Izolirano antitijelo iz patentnog zahtjeva 6, koje je IgG antitijelo.
8. Izolirano antitijelo iz bilo kojeg od patentnih zahtjeva 1 do 3, gdje antitijelo sadrži težak lanac koji sadrži aminokiselinsku sekvencu kao što je dana u SEQ ID NO: 133 i laki lanac koji sadrži aminokiselinsku sekvencu kao što je dana u SEQ ID NO: 102.
9. Izolirano antitijelo iz bilo kojeg od patentnih zahtjeva 1 do 3, gdje antitijelo sadrži težak lanac koji sadrži aminokiselinsku sekvencu kao što je dana u SEQ ID NO: 189 i laki lanac koji sadrži aminokiselinsku sekvencu kao što je dana u SEQ ID NO: 102.
10. Izolirano antitijelo iz bilo kojeg od patentnih zahtjeva 1-9 koje je humano antitijelo i pokazuje jedno ili više od sljedećih svojstava: (a) vezuje se za humani CD73 sa KD od 10 nM ili manjom kao što je određeno pomoću površinske plazmonske rezonance (Surface Plasmon Resonance - SPR); (b) inhibira CD73 enzimsku aktivnost; (c) internalizira CD73 pomoću antitijelom posredovane CD73 internalizacije u stanice, npr., stanice tumora; i (d) vezuje se za humani CD73 sa EC50 od 0.1 do 10 nM ili manjom kako je mjereno pomoću FACS.
11. Izolirano antitijelo iz patentnog zahtjeva 7, gdje konstantna regija teškog lanca dalje sadrži humani lgG1 CH2 domenu koja sadrži aminokiselinske supstitucije A330S i P331S, u skladu sa EU indeksom Kabat sistema, u odnosu na CH2 domenu humanog IgG1 divljeg tipa (SEQ ID NO: 137).
12. Kompozicija koja sadrži antitijelo iz bilo kojeg od patentnih zahtjeva 1-11, i farmaceutski prihvatljiv nosač.
13. Kompozicija iz patentnog zahtjeva 12, koja dalje sadrži jedan ili više dodatnih terapijskih agenasa.
14. Kompozicija iz patentnog zahtjeva 13, gdje dodatni terapijski agens je antitijelo antagonist na protein 1 programirane stanične smrti (PD-1), antitijelo antagonist na ligand 1 programirane smrti (PD-L1) , antitijelo antagonist na protein 4 povezan sa citotoksičnim T-limfocitima (CTLA-4), ili antitijelo antagonist na gen 3 aktivacije limfocita (LAG-3).
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