HRP20220553T1 - Polispecifična protutijela, polispecifična protutijela koja se mogu aktivirati i postupci uporabe navedenih protutijela - Google Patents
Polispecifična protutijela, polispecifična protutijela koja se mogu aktivirati i postupci uporabe navedenih protutijela Download PDFInfo
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- HRP20220553T1 HRP20220553T1 HRP20220553TT HRP20220553T HRP20220553T1 HR P20220553 T1 HRP20220553 T1 HR P20220553T1 HR P20220553T T HRP20220553T T HR P20220553TT HR P20220553 T HRP20220553 T HR P20220553T HR P20220553 T1 HRP20220553 T1 HR P20220553T1
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- antibody
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- activatable
- bispecific antibody
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- 238000000034 method Methods 0.000 title claims 6
- 230000027455 binding Effects 0.000 claims 14
- 108090000765 processed proteins & peptides Proteins 0.000 claims 12
- 210000004027 cell Anatomy 0.000 claims 8
- 229920001184 polypeptide Polymers 0.000 claims 8
- 102000004196 processed proteins & peptides Human genes 0.000 claims 8
- 239000003795 chemical substances by application Substances 0.000 claims 7
- 239000012634 fragment Substances 0.000 claims 7
- 108010075254 C-Peptide Proteins 0.000 claims 6
- 206010028980 Neoplasm Diseases 0.000 claims 5
- 210000001744 T-lymphocyte Anatomy 0.000 claims 5
- 239000000427 antigen Substances 0.000 claims 5
- 102000036639 antigens Human genes 0.000 claims 5
- 108091007433 antigens Proteins 0.000 claims 5
- 239000012642 immune effector Substances 0.000 claims 5
- 229940121354 immunomodulator Drugs 0.000 claims 5
- 230000021615 conjugation Effects 0.000 claims 4
- 238000010494 dissociation reaction Methods 0.000 claims 4
- 230000005593 dissociations Effects 0.000 claims 4
- 102000039446 nucleic acids Human genes 0.000 claims 4
- 108020004707 nucleic acids Proteins 0.000 claims 4
- 150000007523 nucleic acids Chemical class 0.000 claims 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 108091005804 Peptidases Proteins 0.000 claims 2
- 239000004365 Protease Substances 0.000 claims 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 2
- 230000000873 masking effect Effects 0.000 claims 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims 2
- 230000009870 specific binding Effects 0.000 claims 2
- 239000000758 substrate Substances 0.000 claims 2
- 208000024891 symptom Diseases 0.000 claims 2
- 229940124597 therapeutic agent Drugs 0.000 claims 2
- 102100033400 4F2 cell-surface antigen heavy chain Human genes 0.000 claims 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 claims 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 claims 1
- 229940045513 CTLA4 antagonist Drugs 0.000 claims 1
- 101000800023 Homo sapiens 4F2 cell-surface antigen heavy chain Proteins 0.000 claims 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims 1
- 206010039509 Scab Diseases 0.000 claims 1
- 229940034982 antineoplastic agent Drugs 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 239000000032 diagnostic agent Substances 0.000 claims 1
- 229940039227 diagnostic agent Drugs 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 210000000265 leukocyte Anatomy 0.000 claims 1
- 210000002540 macrophage Anatomy 0.000 claims 1
- 210000005087 mononuclear cell Anatomy 0.000 claims 1
- 210000000822 natural killer cell Anatomy 0.000 claims 1
- 239000003053 toxin Substances 0.000 claims 1
- 231100000765 toxin Toxicity 0.000 claims 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
- C07K16/2809—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 against the T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
- C07K16/2818—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 against CD28 or CD152
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
- C07K16/2896—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Engineering & Computer Science (AREA)
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Claims (21)
1. Bispecifično protutijelo kojeg se može aktivirati, pri čemu navedeno bispecifično protutijelo kojeg se može aktivirati sadrži:
(i) prvi krak koji sadrži fragment koji se veže na antigen protutijela koje se veže na imunosnu efektorsku stanicu koje uključuje prvo protutijelo ili njegov fragment koji se veže na antigen (AB1) koji se veže na prvu imunosnu efektorsku stanicu koja je meta;
(ii) drugi krak koji sadrži fragment koji se veže na antigen protutijela koje se veže na metu koje uključuje drugo protutijelo ili njegov fragment koji se veže na antigen (AB2) koji se veže na drugu metu;
pri čemu je AB1 tako vezan na prvi prikrivajući ostatak (MM1) da konjugiranje MM1 s AB1 smanjuje sposobnost vezanja AB1 na prvu metu;
pri čemu je MM1 konjugiran s AB1 preko prvog odcjepivog ostatka (CM1), čija sekvenca sadrži supstrat za proteazu;
pri čemu je AB2 tako vezan na drugi prikrivajući ostatak (MM2) da konjugiranje MM2 s AB2 smanjuje sposobnost vezanja AB2 na drugu metu;
pri čemu je MM2 konjugiran s AB2 preko drugog odcjepivog ostatka (CM2), čija sekvenca sadrži supstrat za proteazu; i
pri čemu prvi krak bispecifičnog protutijela kojeg se može aktivirati u nerascijepljenom stanju ima strukturnu građu od N-kraja do C-kraja kao što slijedi: MM1-CM1-AB1, a drugi krak bispecifičnog protutijela kojeg se može aktivirati u nerascijepljenom stanju ima strukturnu građu od N-kraja do C-kraja kao što slijedi: MM2-CM2-AB2.
2. Bispecifično protutijelo kojeg se može aktivirati u skladu s patentnim zahtjevom 1, pri čemu druga meta sadrži metu povezanu s rakom, pri čemu je meta povezana s rakom tumor kao meta, izborno čvrsti tumor.
3. Bispecifično protutijelo kojeg se može aktivirati u skladu s bilo kojim od patentnih zahtjeva 1 ili 2, pri čemu je AB1:
protutijelo koje se veže na imunosnu efektorsku stanicu;
protutijelo koje se veže na leukocit;
protutijelo koje se veže na T-stanicu;
protutijelo koje se veže na stanicu NK;
protutijelo koje se veže na makrofag; ili
protutijelo koje se veže na mononuklearnu stanicu.
4. Bispecifično protutijelo kojeg se može aktivirati u skladu s bilo kojim od prethodnih patentnih zahtjeva, pri čemu je protutijelo koje se veže na imunosnu efektorsku stanicu protutijelo koje se veže na T-stanicu, te pri čemu je prva imunosna efektorska stanica koja je meta ciljana T-stanica.
5. Bispecifično protutijelo kojeg se može aktivirati u skladu s patentnim zahtjevom 4, pri čemu je ciljana T-stanica CD3 ili CTLA-4.
6. Bispecifično protutijelo kojeg se može aktivirati u skladu s bilo kojim od prethodnih patentnih zahtjeva, pri čemu se drugu metu bira iz skupine meta u Tablici 1, pri čemu druga meta može biti Jagged ili EGFR.
7. Bispecifično protutijelo kojeg se može aktivirati u skladu s patentnim zahtjevom 4, pri čemu je ciljana T-stanica CD3, a druga meta je EGFR.
8. Bispecifično protutijelo kojeg se može aktivirati u skladu s bilo kojim od prethodnih patentnih zahtjeva, pri čemu:
prvi krak
sadrži spojni peptid između MM1 i CM1; ili
sadrži spojni peptid između CM1 i AB1; ili
sadrži prvi spojni peptid (LP1) i drugi spojni peptid (LP2), pri čemu bispecifično protutijelo kojeg se može aktivirati u nerascijepljenom stanju ima strukturnu građu od N-kraja do C-kraja kao što slijedi: MM1-LP1-CM1-LP2-AB, pri čemu dva spojna peptida ne moraju biti međusobno istovjetni; ili
CM1 u prvom kraku je tako smješten u bispecifičnom protutijelu kojeg se može aktivirati da, u nerascijepljenom stanju, MM1 ometa specifično vezanje AB1 na prvu metu.
9. Bispecifično protutijelo kojeg se može aktivirati u skladu s bilo kojim od prethodnih patentnih zahtjeva, pri čemu:
MM1 ima ravnotežnu konstantu disocijacije za vezanje na AB1 veću od ravnotežne konstante disocijacije AB1 s njegovom metom;
MM1 ne ometa niti ne konkurira s AB1 u vezanju na prvu metu kada je bispecifično protutijelo kojeg se može aktivirati u rascijepljenom stanju;
MM1 ima polipeptidnu sekvencu koja se razlikuje od polipeptidne sekvence prve mete;
MM1 ima polipeptidnu sekvencu koja je najviše 50 % istovjetan bilo kojem prirodnom vežućem partneru AB1; i/ili
MM1 je polipeptid dug najviše 40 aminokiselina.
10. Bispecifično protutijelo kojeg se može aktivirati u skladu s bilo kojim od prethodnih patentnih zahtjeva, pri čemu:
drugi krak
sadrži spojni peptid između MM2 i CM2; ili
sadrži spojni peptid između CM2 i AB2; ili
sadrži prvi spojni peptid (LP1) i drugi spojni peptid (LP2), pri čemu bispecifično protutijelo kojeg se može aktivirati u nerascijepljenom stanju ima strukturnu građu od N-kraja do C-kraja kao što slijedi: MM2-LP1-CM2-LP2-AB2, pri čemu dva spojna peptida ne moraju biti međusobno istovjetni; ili
CM2 u drugom kraku je tako smješten u bispecifičnom protutijelu kojeg se može aktivirati da, u nerascijepljenom stanju, MM2 ometa specifično vezanje AB2 na drugu metu.
11. Bispecifično protutijelo kojeg se može aktivirati u skladu s bilo kojim od prethodnih patentnih zahtjeva, pri čemu:
MM2 ima ravnotežnu konstantu disocijacije za vezanje na AB2 veću od ravnotežne konstante disocijacije AB2 s njegovom metom;
MM2 ne ometa niti ne konkurira s AB2 u vezanju na drugu metu kada je bispecifično protutijelo kojeg se može aktivirati u rascijepljenom stanju;
MM2 ima polipeptidnu sekvencu koja se razlikuje od polipeptidne sekvence druge mete;
MM2 ima polipeptidnu sekvencu koji je najviše 50 % istovjetan bilo kojem prirodnom vežućem partneru AB2; i/ili
MM2 je polipeptid dug najviše 40 aminokiselina.
12. Bispecifično protutijelo kojeg se može aktivirati u skladu s bilo kojim od prethodnih patentnih zahtjeva, pri čemu se njegov fragment koji se veže na antigen u AB1 i/ili AB2 bira iz skupine koju čine fragment Fab, fragment F(ab')2, scFv, scAb, dAb, jednodomensko teškolančano protutijelo, te jednodomensko lakolančano protutijelo.
13. Bispecifično protutijelo kojeg se može aktivirati u skladu s bilo kojim od prethodnih patentnih zahtjeva, koje sadrži sredstvo konjugirano s protutijelom, pri čemu sredstvo može biti terapijsko sredstvo, antineoplastično sredstvo, toksin ili njegov fragment, detektabilni ostatak ili dijagnostičko sredstvo, pri čemu sredstvo može biti konjugirano s protutijelom preko spojnice, pri čemu spojnica može biti odcjepljiva spojnica ili neodcjepljiva spojnica.
14. Farmaceutski pripravak koji sadrži bispecifično protutijelo kojeg se može aktivirati u skladu s bilo kojim od prethodnih patentnih zahtjeva i nosač.
15. Farmaceutski pripravak u skladu s patentnim zahtjevom 14, koji sadrži dodatno sredstvo; pri čemu dodatno sredstvo može biti terapijsko sredstvo.
16. Izolirana molekula nukleinske kiseline koja kodira bispecifično protutijelo kojeg se može aktivirati u skladu s bilo kojim od patentnih zahtjeva 1 do 12.
17. Vektor koji sadrži izoliranu molekulu nukleinske kiseline u skladu s patentnim zahtjevom 16.
18. Postupak proizvodnje bispecifičnog protutijela kojeg se može aktivirati uzgojem stanice u uvjetima koji dovode do eksprimiranja bispecifičnog protutijela kojeg se može aktivirati, pri čemu stanica sadrži molekulu nukleinske kiseline u skladu s patentnim zahtjevom 16 ili vektor u skladu s patentnim zahtjevom 17; uz izborno konjugiranje sredstva s bispecifičnim protutijelom kojeg se može aktivirati.
19. Postupak proizvodnje bispecifičnog protutijela kojeg se može aktivirati u skladu s bilo kojim od prethodnih patentnih zahtjeva, gdje se postupak sastoji u:
(a) uzgoju stanice koja sadrži nukleinskokiselinski konstrukt koji kodira bispecifično protutijelo kojeg se može aktivirati u skladu s bilo kojim od patentnih zahtjeva 1 do 12 u uvjetima koji dovode do eksprimiranja bispecifičnog protutijela kojeg se može aktivirati u skladu s bilo kojim od patentnih zahtjeva 1 do 12; i
(b) prikupljanju bispecifičnog protutijela kojeg se može aktivirati; uz izborno konjugiranje sredstva s prikupljenim protutijelom kojeg se može aktivirati.
20. Bispecifično protutijelo kojeg se može aktivirati u skladu s bilo kojim od patentnih zahtjeva 1 do 13, ili farmaceutski pripravak u skladu s bilo kojim od patentnih zahtjeva 14 ili 15, ili bispecifično protutijelo kojeg se može aktivirati dobiveno postupkom u skladu s bilo kojim od patentnih zahtjeva 18 ili 19, namijenjeni uporabi kao medikament.
21. Bispecifično protutijelo kojeg se može aktivirati u skladu s bilo kojim od patentnih zahtjeva 1 do 13, ili farmaceutski pripravak u skladu s bilo kojim od patentnih zahtjeva 14 ili 15, ili bispecifično protutijelo kojeg se može aktivirati dobiveno postupkom u skladu s bilo kojim od patentnih zahtjeva 18 ili 19, namijenjeni uporabi u ublažavanju simptoma kliničke indikacije povezane s poremećajem kod subjekta, pri čemu se bispecifično protutijelo kojeg se može aktivirati primjenjuje na subjektu kojem je to potrebno u količini dovoljnoj za ublažavanje simptoma kliničke indikacije povezane s poremećajem, pri čemu navedeni subjekt može biti čovjek, pri čemu poremećaj može biti rak.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US201361858402P | 2013-07-25 | 2013-07-25 | |
EP18163581.4A EP3406633B1 (en) | 2013-07-25 | 2014-07-25 | Multispecific antibodies, multispecific activatable antibodies and methods of using the same |
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HRP20220553T1 true HRP20220553T1 (hr) | 2022-06-10 |
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HRP20220553TT HRP20220553T1 (hr) | 2013-07-25 | 2014-07-25 | Polispecifična protutijela, polispecifična protutijela koja se mogu aktivirati i postupci uporabe navedenih protutijela |
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US (2) | US11161906B2 (hr) |
EP (3) | EP3024851B1 (hr) |
JP (4) | JP6693872B2 (hr) |
KR (1) | KR102216088B1 (hr) |
CN (2) | CN113150164A (hr) |
AU (2) | AU2014292924B2 (hr) |
BR (1) | BR112016001611B1 (hr) |
CA (1) | CA2918795A1 (hr) |
DK (2) | DK3024851T3 (hr) |
ES (2) | ES2912932T3 (hr) |
HR (1) | HRP20220553T1 (hr) |
IL (1) | IL243752B (hr) |
PL (1) | PL3406633T3 (hr) |
PT (1) | PT3406633T (hr) |
RS (1) | RS63152B1 (hr) |
RU (1) | RU2727836C2 (hr) |
WO (1) | WO2015013671A1 (hr) |
Families Citing this family (122)
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US11046784B2 (en) | 2006-03-31 | 2021-06-29 | Chugai Seiyaku Kabushiki Kaisha | Methods for controlling blood pharmacokinetics of antibodies |
MX369784B (es) | 2007-09-26 | 2019-11-21 | Chugai Pharmaceutical Co Ltd | Metodo de modificacion del punto isoelectrico de anticuerpos mediante la sustitucion de aminoacidos en region de determinacion de complementariedad (cdr). |
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