HRP20180243T1 - Dvostruko specifične vezivne molekule antigena za aktivaciju t stanica - Google Patents
Dvostruko specifične vezivne molekule antigena za aktivaciju t stanica Download PDFInfo
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- HRP20180243T1 HRP20180243T1 HRP20180243TT HRP20180243T HRP20180243T1 HR P20180243 T1 HRP20180243 T1 HR P20180243T1 HR P20180243T T HRP20180243T T HR P20180243TT HR P20180243 T HRP20180243 T HR P20180243T HR P20180243 T1 HRP20180243 T1 HR P20180243T1
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- 239000000427 antigen Substances 0.000 title claims 49
- 102000036639 antigens Human genes 0.000 title claims 49
- 108091007433 antigens Proteins 0.000 title claims 49
- 230000027455 binding Effects 0.000 title claims 49
- 230000003213 activating effect Effects 0.000 title claims 5
- 230000006044 T cell activation Effects 0.000 claims 17
- 210000004027 cell Anatomy 0.000 claims 6
- 102000009109 Fc receptors Human genes 0.000 claims 5
- 108010087819 Fc receptors Proteins 0.000 claims 5
- 125000003275 alpha amino acid group Chemical group 0.000 claims 5
- 239000012636 effector Substances 0.000 claims 5
- 238000006467 substitution reaction Methods 0.000 claims 5
- 125000000539 amino acid group Chemical group 0.000 claims 4
- 230000009870 specific binding Effects 0.000 claims 4
- 210000001744 T-lymphocyte Anatomy 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 102000040430 polynucleotide Human genes 0.000 claims 3
- 108091033319 polynucleotide Proteins 0.000 claims 3
- 239000002157 polynucleotide Substances 0.000 claims 3
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 claims 2
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 claims 2
- 102100028757 Chondroitin sulfate proteoglycan 4 Human genes 0.000 claims 2
- 102000001301 EGF receptor Human genes 0.000 claims 2
- 108060006698 EGF receptor Proteins 0.000 claims 2
- 101000916489 Homo sapiens Chondroitin sulfate proteoglycan 4 Proteins 0.000 claims 2
- 108060003951 Immunoglobulin Proteins 0.000 claims 2
- 108010037255 Member 7 Tumor Necrosis Factor Receptor Superfamily Proteins 0.000 claims 2
- 102000018358 immunoglobulin Human genes 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 2
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims 1
- 231100000023 Cell-mediated cytotoxicity Toxicity 0.000 claims 1
- 206010057250 Cell-mediated cytotoxicity Diseases 0.000 claims 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims 1
- 102000009490 IgG Receptors Human genes 0.000 claims 1
- 108010073807 IgG Receptors Proteins 0.000 claims 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 230000006037 cell lysis Effects 0.000 claims 1
- 230000005890 cell-mediated cytotoxicity Effects 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 230000003013 cytotoxicity Effects 0.000 claims 1
- 231100000135 cytotoxicity Toxicity 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000009977 dual effect Effects 0.000 claims 1
- 210000002950 fibroblast Anatomy 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 210000004881 tumor cell Anatomy 0.000 claims 1
Classifications
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- 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
-
- 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
- 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
- C07K16/2863—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
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3007—Carcino-embryonic Antigens
-
- 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
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3053—Skin, nerves, brain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- 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
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- 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
- C07K2317/626—Diabody or triabody
-
- 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
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/66—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a swap of domains, e.g. CH3-CH2, VH-CL or VL-CH1
-
- 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
-
- 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
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
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Claims (13)
1. Dvostruko specifična vezivna molekula antigena za aktivaciju T stanice, naznačena time, da obuhvaća prvu i drugu polovicu koja veže antigen, od kojih je jedna Fab molekula sposobna za specifično vezivanje na aktivirajući T-stanični antigen, a druga je Fab molekula sposobna za specifično vezivanje na antigen ciljane stanice te Fc domenu sastavljenu od prve i druge podjedinice sposobne za stabilno udruživanje;
pri čemu je prva antigen-vezivna polovica transferska Fab molekula u kojoj se recipročno izmjenjuju varijabilne ili konstantne regije Fab lakog lanca i Fab teškog lanca;
gdje su prva i druga antigen-vezivne polovice staljene jedna s drugom, po mogućnosti putem peptidne poveznice; i
dok dvostruko specifična vezivna molekula antigena za aktivaciju T stanice ne obuhvaća više od jedne antigen-vezivne polovice sposobne za specifično vezivanje na antigen koji aktivira T stanice.
2. Dvostruko specifična vezivna molekula antigena za aktivaciju T stanice prema patentnom zahtjevu 1, naznačena time, da je druga antigen-vezivna polovica staljena na C-kraju Fab teškog lanca na N-kraj Fab teškog lanca prve antigen-vezivne polovice, pri čemu prema potrebi
i) Fab laki lanac prve antigen-vezivne polovice i Fab laki lanac druge antigen-vezivne polovice su staljeni jedan s drugim, po mogućnosti putem peptidnog povezivača; i/ili
ii) prva antigen-vezivna polovica je staljena na C-kraju Fab teškog lanca na N-kraj prve ili druge podjedinice Fc domene.
3. Dvostruko specifična vezivna molekula antigena za aktivaciju T stanice prema patentnom zahtjevu 1, naznačena time, da je prva antigen-vezivna polovica staljena na C-kraju Fab teškog lanca na N-kraj Fab teškog lanca druge antigen-vezivne polovice, pri čemu prema potrebi
i) Fab laki lanac prve antigen-vezivne polovice i Fab laki lanac druge antigen-vezivne polovice su staljeni jedan s drugim, po mogućnosti putem peptidnog povezivača; i/ili
ii) pri čemu je druga antigen-vezivna polovica staljena na C-kraju Fab teškog lanca na N-kraj prve ili druge podjedinice Fc domene.
4. Dvostruko specifična vezivna molekula antigena za aktivaciju T stanice prema patentnom zahtjevu 1, naznačena time, da je druga antigen-vezivna polovica staljena na C-kraju Fab lakog lanca na N-kraj Fab lakog lanca prve antigen-vezivne polovice, i pri čemu je prema potrebi druga antigen-vezivna polovica staljena na C-kraju Fab teškog lanca na N-kraj prve ili druge podjedinice Fc domene.
5. Dvostruko specifična vezivna molekula antigena za aktivaciju T stanice prema bilo kojem od patentnih zahtjeva 1 do 4, naznačena time, da obuhvaća treću antigen-vezivnu polovicu koja je Fab molekula sposobna za specifično vezivanje za antigen ciljane stanice, pri čemu je prema potrebi treća antigen-vezivna polovica
staljena na C-kraju Fab teškog lanca na N-kraj prve ili druge podjedinice Fc domene, dok pritom prema potrebi
i) svaka od druge i treće antigen-vezivne polovice je staljena na C-kraju Fab teškog lanca na N-kraj jedne od podjedinica Fc domene,
i prva antigen-vezivna polovica je staljena na C-kraju Fab teškog lanca na N-kraj Fab teškog lanca druge antigen-vezivne polovice; ili
ii) svaka od prve i treće antigen-vezivne polovice je staljena na C-kraju Fab teškog lanca na N-kraj jedne od podjedinica Fc domene, i druga antigen-vezivna polovica je staljena na C-kraju Fab teškog lanca na N-kraj Fab teškog lanca prve antigen-vezivne polovice.
6. Dvostruko specifična vezivna molekula antigena za aktivaciju T stanice prema bilo kojem od prethodnih patentnih zahtjeva, naznačena time, da
i) dvostruko specifična vezivna molekula antigena za aktivaciju T stanice je definirana u patentom zahtjevu 5(i) te pri čemu su druga i treća antigen-vezivna polovica i Fc domena dio imunoglobulinske molekule, osobito IgG razreda imunoglobulina;
ii) Fc domena je takva Fc domena koja je IgG, specifično IgG1 ili IgG4;
iii) Fc domena je ljudska Fc domena; i/ili
iv) Fc domena obuhvaća modifikaciju koja potiče udruživanje prve i druge podjedinice Fc domene, pri čemu prema izboru u CH3 domeni prve podjedinice Fc domene aminokiselinski ostatak je zamijenjen aminokiselinskim ostatkom koji ima veći volumen bočnog lanca, čime se stvara izbočina unutar CH3 domene prve podjedinice, koja se može postaviti u šupljinu unutar CH3 domene druge podjedinice, i u CH3 domeni druge podjedinice Fc domene, aminokiselinski ostatak je zamijenjen aminokiselinskim ostatkom koji ima manji volumen bočnog lanca, čime se stvara šupljina unutar CH3 domene druge podjedinice, unutar koje se može postaviti izbočina unutar CH3 domene prve podjedinice.
7. Dvostruko specifična vezivna molekula antigena za aktivaciju T stanice prema bilo kojem od prethodnih patentnih zahtjeva, naznačena time, da
i) Fc domena pokazuje smanjeni afinitet vezivanja na Fc receptor i/ili smanjenu efektorsku funkciju, u usporedbi s izvornom IgG1 Fc domenom;
ii) Fc domena obuhvaća jednu ili više aminokiselinskih supstitucija koje smanjuju vezivanje na Fc receptor i/ili efektorsku funkciju;
iii) Fc domena obuhvaća jednu ili više aminokiselinskih supstitucija koje smanjuju vezivanje na Fc receptor i/ili efektorsku funkciju, pri čemu se navedena jedna ili više aminokiselinskih supstitucija nalazi na jednom ili više položaja odabranih iz skupine L234, L235 i P329 (EU numeriranje); i/ili
(iv) svaka podjedinica Fc domene obuhvaća tri aminokiselinske supstitucije koje smanjuju vezivanje na aktivirajući Fc receptor i/ili efektorsku funkciju, gdje se kod navedenih aminokiselinskih supstitucija radi o L234A, L235A i P329G (EU numeriranje).
8. Dvostruko specifična vezivna molekula antigena za aktivaciju T stanice prema patentnom zahtjevu 7, naznačena time, da
i) Fc receptor je Fcγ receptor; ili
ii) efektorska funkcija je citotoksičnost ovisna o protutijelu i stanično-posredovana citotoksičnost (ADCC).
9. Dvostruko specifična vezivna molekula antigena za aktivaciju T stanice prema bilo kojem od prethodnih patentnih zahtjeva, naznačena time, da
i) antigen za aktivaciju T stanice je CD3; i/ili
ii) antigen ciljane stanice je odabran iz skupine koju čine: melanom-povezani proteoglikan kondroitin sulfata (MCSP), epidermalni receptor faktora rasta (EGFR), CD19, CD20, CD33, karcinoembrijski antigen (CEA) i protein koji aktivira fibroblast (FAP).
10. Izolirani polinukleotid, naznačen time, da on kodira dvostruko specifičnu vezivnu molekulu antigena za aktivaciju T stanice prema bilo kojem od patentnih zahtjeva od 1 do 9.
11. Postupak za proizvodnju dvostruko specifične vezivne molekule antigena za aktivaciju T stanice prema bilo kojem od patentnih zahtjeva od 1 do 9, naznačen time, da obuhvaća sljedeće korake: a) kultiviranje stanice domaćina koja sadrži izolirani polinukleotid prema zahtjevu 10 ili vektor koji sadrži izolirani polinukleotid prema zahtjevu 10, pod uvjetima prikladnim za ekspresiju dvostruko specifične vezivne molekule antigena za aktivaciju T stanice i b) oporavljanje dvostruko specifične vezivne molekule antigena za aktivaciju T-stanice.
12. Farmaceutski pripravak, naznačen time, da obuhvaća dvostruko specifičnu vezivnu molekulu antigena za aktivaciju T stanice prema bilo kojem od patentnih zahtjeva od 1 do 9 te farmaceutski prihvatljiv nosač.
13. Dvostruko specifična vezivna molekula antigena za aktivaciju T stanice prema bilo kojem od patentnih zahtjeva od 1 do 9, ili farmaceutski pripravak prema patentnom zahtjevu 12, naznačen time, da
i) se upotrebljava kao lijek;
ii) se upotrebljava u liječenju bolesti kod pojedinaca kojima je to potrebno;
iii) se upotrebljava u liječenju bolesti kod pojedinaca kojima je to potrebno, gdje je bolest rak; ili
iv) se upotrebljava u postupku induciranja lize ciljane stanice kod pojedinaca, koja obuhvaća dovođenje u doticaj ciljane stanice s dvostruko specifičnom vezivnom molekulom antigena za aktivaciju T stanice u prisutnosti T stanice, pri čemu ciljana stanica je tumorska stanica.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP11178370 | 2011-08-23 | ||
EP12168192 | 2012-05-16 | ||
EP12750364.7A EP2748201B1 (en) | 2011-08-23 | 2012-08-21 | Bispecific t cell activating antigen binding molecules |
PCT/EP2012/066215 WO2013026833A1 (en) | 2011-08-23 | 2012-08-21 | Bispecific t cell activating antigen binding molecules |
Publications (1)
Publication Number | Publication Date |
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HRP20180243T1 true HRP20180243T1 (hr) | 2018-04-06 |
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HRP20180243TT HRP20180243T1 (hr) | 2011-08-23 | 2018-02-08 | Dvostruko specifične vezivne molekule antigena za aktivaciju t stanica |
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US (3) | US20130078249A1 (hr) |
EP (3) | EP2748201B1 (hr) |
JP (4) | JP6339015B2 (hr) |
KR (1) | KR101963923B1 (hr) |
CN (1) | CN103748114B (hr) |
AR (1) | AR087608A1 (hr) |
AU (1) | AU2012298537B2 (hr) |
BR (1) | BR112014003769B1 (hr) |
CA (1) | CA2837975C (hr) |
CL (1) | CL2014000126A1 (hr) |
CO (1) | CO6811817A2 (hr) |
CR (1) | CR20130669A (hr) |
DK (1) | DK2748201T3 (hr) |
EA (1) | EA030147B1 (hr) |
EC (1) | ECSP14013220A (hr) |
ES (2) | ES2659764T3 (hr) |
HR (1) | HRP20180243T1 (hr) |
HU (1) | HUE038225T2 (hr) |
IL (2) | IL229765B (hr) |
LT (1) | LT2748201T (hr) |
MA (1) | MA35448B1 (hr) |
MX (1) | MX352101B (hr) |
MY (1) | MY169358A (hr) |
NO (1) | NO2748201T3 (hr) |
PE (1) | PE20141521A1 (hr) |
PL (2) | PL2748201T3 (hr) |
PT (1) | PT2748201T (hr) |
RS (1) | RS56879B1 (hr) |
SI (1) | SI2748201T1 (hr) |
TW (1) | TWI633121B (hr) |
UA (1) | UA116192C2 (hr) |
WO (1) | WO2013026833A1 (hr) |
ZA (1) | ZA201309742B (hr) |
Families Citing this family (293)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
US9266967B2 (en) | 2007-12-21 | 2016-02-23 | Hoffmann-La Roche, Inc. | Bivalent, bispecific antibodies |
MX2011010159A (es) | 2009-04-02 | 2011-10-17 | Roche Glycart Ag | Anticuerpos multiespecificos que comprenden anticuerpos de longitud completa y fragmentos fab de cadena sencilla. |
JP5616428B2 (ja) | 2009-04-07 | 2014-10-29 | ロシュ グリクアート アクチェンゲゼルシャフト | 三価の二重特異性抗体 |
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