HRP20161211T1 - Bispecifična antitijela protiv cd3-epsilon i bcma - Google Patents
Bispecifična antitijela protiv cd3-epsilon i bcma Download PDFInfo
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- HRP20161211T1 HRP20161211T1 HRP20161211TT HRP20161211T HRP20161211T1 HR P20161211 T1 HRP20161211 T1 HR P20161211T1 HR P20161211T T HRP20161211T T HR P20161211TT HR P20161211 T HRP20161211 T HR P20161211T HR P20161211 T1 HRP20161211 T1 HR P20161211T1
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- 101100425747 Mus musculus Tnfrsf17 gene Proteins 0.000 title 1
- 235000001014 amino acid Nutrition 0.000 claims 15
- 150000001413 amino acids Chemical group 0.000 claims 15
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims 6
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims 6
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 claims 6
- 239000004475 Arginine Substances 0.000 claims 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 4
- 239000004472 Lysine Substances 0.000 claims 4
- 125000000539 amino acid group Chemical group 0.000 claims 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims 4
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 claims 3
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 claims 3
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 claims 3
- 101000801255 Homo sapiens Tumor necrosis factor receptor superfamily member 17 Proteins 0.000 claims 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims 3
- 235000003704 aspartic acid Nutrition 0.000 claims 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims 3
- 210000004027 cell Anatomy 0.000 claims 3
- 102000046935 human TNFRSF17 Human genes 0.000 claims 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 235000013922 glutamic acid Nutrition 0.000 claims 2
- 239000004220 glutamic acid Substances 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 239000013598 vector Substances 0.000 claims 2
- 101000946860 Homo sapiens T-cell surface glycoprotein CD3 epsilon chain Proteins 0.000 claims 1
- 208000034578 Multiple myelomas Diseases 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 102100035794 T-cell surface glycoprotein CD3 epsilon chain Human genes 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 230000004075 alteration Effects 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
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- C—CHEMISTRY; METALLURGY
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- 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
- C07K16/2878—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 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
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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
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- 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
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- 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
- C07K16/3061—Blood cells
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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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- 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
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- 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
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
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- 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
- C07K2317/35—Valency
-
- 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
- C07K2317/522—CH1 domain
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- 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
- C07K2317/526—CH3 domain
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- 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'
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- 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
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- 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
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- 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
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- 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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- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Animal Behavior & Ethology (AREA)
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- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (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)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Claims (14)
1. Bispecifično antitijelo koje se specifično veže za dva cilja koja su izvanstanična domena antigena maturacije humanih B-stanica (dalje označen i kao "BCMA") i humanog CD3ε (dalje označen i kao "CD3"), naznačeno time, što sadrži
a) prvi laki lanac i prvi teški lanac prvog antitijela koje se specifično veže za BCMA; i
b) drugi laki lanac i drugi teški lanac drugog antitijela koje se specifično veže za CD3, i gdje su varijabilne domene VL i VH u drugom lakom lancu i drugom teškom lancu drugog antitijela zamijenjene jedna drugom i
c) gdje je u stalnoj domeni CL prvog lakog lanca pod a) amino- kiselina na poziciji 124 supstituirana nezavisno lizinom (K), argininom (R) ili histidinom (H) (numeriranje po Kabat-u), i gdje su u stalnoj domeni CH1 prvog teškog lanca pod a) amino-kiselina na poziciji 147 i amino-kiselina na poziciji 213 supstituirane nezavisno glutaminskom kiselinom (E) ili asparaginskom kiselinom (D) (numeriranje po Kabat-u).
2. Bispecifično antitijelo koje se specifično veže za dva cilja koja su izvanstanična domena humanog BCMA i humanog CD3, naznačeno time, što sadrži
a) prvi laki lanac i prvi teški lanac prvog antitijela koje se specifično veže za BCMA; i
b) drugi laki lanac i drugi teški lanac drugog antitijela koje se specifično veže za CD3, i gdje su varijabilne domene VL i VH u drugom lakom lancu i drugom teškom lancu drugog antitijela zamijenjene jedna drugom; i
c) gdje je u stalnoj domeni CL drugog lakog lanca pod b) amino- kiselina na poziciji 124 supstituirana nezavisno lizinom (K), argininom (R) ili histidinom (H) (numeriranje po Kabat-u), i gdje su u stalnoj domeni CH1 drugog teškog lanca pod b) amino-kiselina na poziciji 147 i amino-kiselina na poziciji 213 supstituirane nezavisno glutaminskom kiselinom (E) ili asparaginskom kiselinom (D) (numeriranje po Kabat-u).
3. Bispecifično antitijelo prema zahtjevu 1, naznačeno time, što spomenuto bispecifično antitijelo sadrži dodatno Fab fragment spomenutog prvog antitijela (dalje označen i kao "BCMA-Fab") i u stalnoj domeni CL spomenutog BCMA-Fab amino-kiselina na poziciji 124 supstituirana je nezavisno lizinom (K), argininom (R) ili histidinom (H) (numeriranje po Kabat-u), i pri čemu su u stalnoj domeni CH1 spomenutog BCMA-Fab amino-kiselina na poziciji 147 i amino-kiselina na poziciji 213 supstituirane nezavisno glutaminskom kiselinom (E) ili asparaginskom kiselinom (D) (numeriranje po Kabat-u).
4. Bispecifično antitijelo prema zahtjevu 2, naznačeno time, što spomenuto bispecifično antitijelo sadrži dodatno drugi Fab fragment spomenutog prvog antitijela ("BCMA- Fab").
5. Bispecifično antitijelo prema bilo kojem od zahtjeva 1 do 4, naznačeno time, što je pored zamjene amino-kiseline na poziciji 124 u stalnoj domeni CL amino-kiselina na poziciji 123 supstituirana nezavisno lizinom (K), argininom (R) ili histidinom (H).
6. Bispecifično antitijelo prema bilo kojem od zahtjeva 1 do 5, naznačeno time, što je amino-kiselina 124 K, amino-kiselina 147 je E, amino-kiselina 213 je E i amino-kiselina 123 je R.
7. Bispecifično antitijelo koje se specifično veže za izvanstaničnu domenu humanog BCMA i za humani CD3, naznačeno time, što sadrži set teških i lakih lanaca odabran iz grupe koja se sastoji od polipeptida
i) SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45 i SEQ ID NO:46 (set 1),
ii) SEQ ID NO:45; SEQ ID NO:47, SEQ ID NO:48 i SEQ ID NO:49 (set 2), i
iii) SEQ ID NO:45, SEQ ID NO:50, SEQ ID NO:51 i SEQ ID NO:52 (set 3).
8. Antitijelo prema bilo kojem od zahtjeva 7, naznačeno time, što je u dijelu antitijela koje se specifično veže za humani CD3 varijabilna domena VH zamijenjena varijabilnom domenom VH koja sadrži teškolančane CDR SEQ ID NO: 1, 2 i 3 kao odnosne teškolančane CDR1, CDR2 i CDR3 i varijabilna domena VL je zamijenjena varijabilnom domenom VL koja sadrži lakolančane CDR SEQ ID NO: 4, 5 i 6 kao odnosne lakolančane CDR1, CDR2 i CDR3 anti-CD3ε antitijela.
9. Antitijelo prema bilo kojem od zahtjeva 1 do 6, naznačeno time, što se CH3 domene jednog teškog lanca i CH3 domene drugog teškog lanca susreću na kontaktnoj površini koja sadrži originalnu kontaktnu površinu između CH3 domene antitijela; pri čemu je spomenuta kontaktna površina promijenjena tako da se potakne formiranje bispecifičnog antitijela, pri čemu se promjena karaktezira time što je:
a) CH3 domena jednog teškog lanca izmijenjena, tako da je unutar originalne kontaktne površine CH3 domene jednog teškog lanca, koja se susreće s originalnom kontaktnom površinom CH3 domena drugog teškog lanca unutar bispecifičnog antitijela, aminokiselinska rezidua zamijenjena aminokiselinskom reziduom sa bočnim lancem većeg volumena, čime se stvara izbočina unutar kontaktne površine CH3 domene jednog teškog lanca, koja se može smjestiti u udubljenje unutar kontaktne površine CH3 domene drugog teškog lanca i
b) CH3 domena drugog teškog lanca je izmijenjena, tako da je unutar originalne kontaktne površine druge CH3 domene koja se susreće s originalnom kontaktnom površinom prve CH3 domene unutar bispecifičnog antitijela, aminokiselinska rezidua zamijenjena aminokiselinskom reziduom s bočnim lancem manjeg volumena, čime se stvara udubljenje unutar kontaktne površine druge CH3 domene u koje se može smjestiti izbočina u kontaktnoj površini prve CH3 domene.
10. Metoda pripremanja bispecifičnog antitijela prema bilo kojem od zahtjeva 1 do 9, naznačena time, što uključuje korake
a) transformiranja stanice-domaćina vektorima koji sadrže molekule nukleinskih kiselina koje kodiraju laki lanac i teški lanac antitijela prema bilo kojem od zahtjeva 1 do 9,
b) kultiviranja stanice-domaćina pod uvjetima koji dopuštaju sintezu molekule spomenutog antitijela; i
c) skupljanja molekule spomenutog antitijela iz spomenute kulture.
11. Stanica-domaćin, naznačena time, što sadrži vektore koji sadrže molekule nukleinskih kiselina koji kodiraju lake lance i teške lance antitijela prema bilo kojem od zahtjeva 1 do 9.
12. Farmaceutska smjesa, naznačena time, što sadrži antitijelo prema bilo kojem od zahtjeva 1 do 9 i farmaceutski prihvatljivi ekscipijent.
13. Antitijelo prema bilo kojem od zahtjeva 1 do 9 ili farmaceutska smjesa prema zahtjevu 12, naznačeni time, što se koriste kao lijek.
14. Antitijelo prema bilo kojem od zahtjeva 1 do 9 ili farmaceutska smjesa prema zahtjevu 12, naznačeni time, što se koriste kao lijek za liječenje poremećaja plazmocita kao što je multipli mijelom.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP14179705.0A EP2982692A1 (en) | 2014-08-04 | 2014-08-04 | Bispecific antibodies against CD3epsilon and BCMA |
EP15179545.7A EP2982694B1 (en) | 2014-08-04 | 2015-08-03 | Bispecific antibodies against cd3epsilon and bcma |
Publications (1)
Publication Number | Publication Date |
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HRP20161211T1 true HRP20161211T1 (hr) | 2016-11-18 |
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Application Number | Title | Priority Date | Filing Date |
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HRP20161211TT HRP20161211T1 (hr) | 2014-08-04 | 2016-09-21 | Bispecifična antitijela protiv cd3-epsilon i bcma |
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Country | Link |
---|---|
US (1) | US10253104B2 (hr) |
EP (2) | EP2982692A1 (hr) |
JP (2) | JP6703520B2 (hr) |
AU (2) | AU2015299101B2 (hr) |
CA (1) | CA2955685C (hr) |
CY (1) | CY1118168T1 (hr) |
DK (1) | DK2982694T3 (hr) |
ES (1) | ES2602051T3 (hr) |
HK (1) | HK1218299A1 (hr) |
HR (1) | HRP20161211T1 (hr) |
HU (1) | HUE031076T2 (hr) |
LT (1) | LT2982694T (hr) |
MA (1) | MA39266B1 (hr) |
ME (1) | ME02533B (hr) |
PL (1) | PL2982694T3 (hr) |
PT (1) | PT2982694T (hr) |
RS (1) | RS55410B1 (hr) |
SG (1) | SG11201700551TA (hr) |
SI (1) | SI2982694T1 (hr) |
SM (1) | SMT201600392B (hr) |
WO (1) | WO2016020332A1 (hr) |
Families Citing this family (90)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
PT2417156E (pt) | 2009-04-07 | 2015-04-29 | Roche Glycart Ag | Anticorpos trivalentes, biespecíficos |
US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
CN103502271B (zh) | 2011-02-28 | 2016-10-26 | 霍夫曼-拉罗奇有限公司 | 抗原结合蛋白 |
CA2824824A1 (en) | 2011-02-28 | 2012-09-07 | F. Hoffmann-La Roche Ag | Monovalent antigen binding proteins |
JP6159724B2 (ja) | 2011-08-23 | 2017-07-05 | ロシュ グリクアート アーゲー | T細胞活性化抗原に対して特異的な二重特異性抗体及び腫瘍抗原および使用方法 |
CA2879768A1 (en) | 2012-10-08 | 2014-04-17 | Roche Glycart Ag | Fc-free antibodies comprising two fab-fragments and methods of use |
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ES2602051T3 (es) | 2017-02-17 |
US20170306036A1 (en) | 2017-10-26 |
HUE031076T2 (en) | 2017-06-28 |
CA2955685A1 (en) | 2016-02-11 |
NZ728534A (en) | 2023-12-22 |
SG11201700551TA (en) | 2017-02-27 |
SI2982694T1 (sl) | 2017-01-31 |
JP2017532290A (ja) | 2017-11-02 |
AU2015299101B2 (en) | 2020-08-27 |
JP2020122013A (ja) | 2020-08-13 |
EP2982694B1 (en) | 2016-06-22 |
EP2982692A1 (en) | 2016-02-10 |
WO2016020332A1 (en) | 2016-02-11 |
AU2015299101A1 (en) | 2017-02-16 |
JP6703520B2 (ja) | 2020-06-03 |
AU2020273347A1 (en) | 2020-12-17 |
CA2955685C (en) | 2023-09-19 |
EP2982694A1 (en) | 2016-02-10 |
CY1118168T1 (el) | 2017-06-28 |
PT2982694T (pt) | 2016-09-29 |
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