CA2963696A1 - Bispecific antibodies against cd3epsilon and ror1 for use in the treatment of ovarian cancer - Google Patents
Bispecific antibodies against cd3epsilon and ror1 for use in the treatment of ovarian cancer Download PDFInfo
- Publication number
- CA2963696A1 CA2963696A1 CA2963696A CA2963696A CA2963696A1 CA 2963696 A1 CA2963696 A1 CA 2963696A1 CA 2963696 A CA2963696 A CA 2963696A CA 2963696 A CA2963696 A CA 2963696A CA 2963696 A1 CA2963696 A1 CA 2963696A1
- Authority
- CA
- Canada
- Prior art keywords
- ror1
- antibody
- fab
- seq
- domain
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 206010061535 Ovarian neoplasm Diseases 0.000 title claims abstract description 138
- 206010033128 Ovarian cancer Diseases 0.000 title claims abstract description 130
- 238000011282 treatment Methods 0.000 title claims abstract description 42
- 101001103039 Homo sapiens Inactive tyrosine-protein kinase transmembrane receptor ROR1 Proteins 0.000 claims abstract description 55
- 101001103036 Homo sapiens Nuclear receptor ROR-alpha Proteins 0.000 claims abstract 25
- 210000004027 cell Anatomy 0.000 claims description 305
- 230000027455 binding Effects 0.000 claims description 192
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 claims description 123
- 101710117290 Aldo-keto reductase family 1 member C4 Proteins 0.000 claims description 85
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 71
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 71
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 67
- 238000000034 method Methods 0.000 claims description 31
- 102000049583 human ROR1 Human genes 0.000 claims description 30
- 235000001014 amino acid Nutrition 0.000 claims description 27
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 25
- 238000011534 incubation Methods 0.000 claims description 25
- 238000000684 flow cytometry Methods 0.000 claims description 22
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 21
- 150000001413 amino acids Chemical group 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 230000002829 reductive effect Effects 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 18
- 238000006467 substitution reaction Methods 0.000 claims description 17
- 125000000539 amino acid group Chemical group 0.000 claims description 16
- 101100350216 Arabidopsis thaliana PDH2 gene Proteins 0.000 claims description 14
- 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 claims description 13
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 claims description 13
- 238000000423 cell based assay Methods 0.000 claims description 13
- 102000054751 human RUNX1T1 Human genes 0.000 claims description 13
- 230000015572 biosynthetic process Effects 0.000 claims description 12
- 239000004471 Glycine Substances 0.000 claims description 11
- 239000012537 formulation buffer Substances 0.000 claims description 8
- 239000000178 monomer Substances 0.000 claims description 8
- 235000004279 alanine Nutrition 0.000 claims description 7
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 6
- 230000008030 elimination Effects 0.000 claims description 6
- 238000003379 elimination reaction Methods 0.000 claims description 6
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 claims description 5
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 claims description 5
- 241000699670 Mus sp. Species 0.000 claims description 5
- 102100035359 Cerebellar degeneration-related protein 2-like Human genes 0.000 claims description 4
- 101000737792 Homo sapiens Cerebellar degeneration-related protein 2-like Proteins 0.000 claims description 4
- 241000282567 Macaca fascicularis Species 0.000 claims description 4
- 230000002147 killing effect Effects 0.000 claims description 4
- 230000004075 alteration Effects 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000003860 storage Methods 0.000 claims description 3
- 102100039614 Nuclear receptor ROR-alpha Human genes 0.000 claims 24
- 102100039615 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Human genes 0.000 abstract description 3
- 101000946860 Homo sapiens T-cell surface glycoprotein CD3 epsilon chain Proteins 0.000 abstract 1
- 102100035794 T-cell surface glycoprotein CD3 epsilon chain Human genes 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 description 58
- 102000004169 proteins and genes Human genes 0.000 description 45
- 239000013598 vector Substances 0.000 description 44
- 235000018102 proteins Nutrition 0.000 description 42
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 36
- 239000002609 medium Substances 0.000 description 34
- 239000012091 fetal bovine serum Substances 0.000 description 29
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 28
- 108020004414 DNA Proteins 0.000 description 28
- 239000000872 buffer Substances 0.000 description 28
- 206010028980 Neoplasm Diseases 0.000 description 26
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 25
- 108090000765 processed proteins & peptides Proteins 0.000 description 25
- 239000013604 expression vector Substances 0.000 description 24
- 239000012634 fragment Substances 0.000 description 24
- 230000014509 gene expression Effects 0.000 description 24
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 23
- 150000007523 nucleic acids Chemical class 0.000 description 22
- 238000005119 centrifugation Methods 0.000 description 21
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
- 238000004519 manufacturing process Methods 0.000 description 20
- 102000039446 nucleic acids Human genes 0.000 description 20
- 108020004707 nucleic acids Proteins 0.000 description 20
- 239000012980 RPMI-1640 medium Substances 0.000 description 19
- 238000002360 preparation method Methods 0.000 description 19
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 18
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 18
- 102000004196 processed proteins & peptides Human genes 0.000 description 18
- 239000000427 antigen Substances 0.000 description 16
- 102000036639 antigens Human genes 0.000 description 16
- 108091007433 antigens Proteins 0.000 description 16
- 229920001184 polypeptide Polymers 0.000 description 16
- 201000011510 cancer Diseases 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 125000003275 alpha amino acid group Chemical group 0.000 description 14
- 238000004113 cell culture Methods 0.000 description 14
- 210000004369 blood Anatomy 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 239000006228 supernatant Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 108091028043 Nucleic acid sequence Proteins 0.000 description 12
- 230000006870 function Effects 0.000 description 12
- 238000011160 research Methods 0.000 description 12
- 239000001488 sodium phosphate Substances 0.000 description 12
- 229910000162 sodium phosphate Inorganic materials 0.000 description 12
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 12
- 230000004913 activation Effects 0.000 description 11
- 239000012636 effector Substances 0.000 description 11
- 239000013612 plasmid Substances 0.000 description 11
- 229920000642 polymer Polymers 0.000 description 11
- 210000004881 tumor cell Anatomy 0.000 description 11
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 10
- 102000009109 Fc receptors Human genes 0.000 description 10
- 108010087819 Fc receptors Proteins 0.000 description 10
- 108060003951 Immunoglobulin Proteins 0.000 description 10
- 229930182816 L-glutamine Natural products 0.000 description 10
- 230000000875 corresponding effect Effects 0.000 description 10
- 230000001419 dependent effect Effects 0.000 description 10
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 10
- 102000018358 immunoglobulin Human genes 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 10
- 238000007920 subcutaneous administration Methods 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000007983 Tris buffer Substances 0.000 description 8
- 238000005277 cation exchange chromatography Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000012894 fetal calf serum Substances 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 239000001509 sodium citrate Substances 0.000 description 8
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 238000013459 approach Methods 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 230000007717 exclusion Effects 0.000 description 7
- 238000007912 intraperitoneal administration Methods 0.000 description 7
- 238000002955 isolation Methods 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 108020004635 Complementary DNA Proteins 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 230000000890 antigenic effect Effects 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000022534 cell killing Effects 0.000 description 6
- 230000006037 cell lysis Effects 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 210000003527 eukaryotic cell Anatomy 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- 208000013371 ovarian adenocarcinoma Diseases 0.000 description 6
- 201000006588 ovary adenocarcinoma Diseases 0.000 description 6
- 238000005498 polishing Methods 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 5
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 5
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 5
- 108091034117 Oligonucleotide Proteins 0.000 description 5
- 108010076504 Protein Sorting Signals Proteins 0.000 description 5
- 230000006044 T cell activation Effects 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 210000003719 b-lymphocyte Anatomy 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 210000004602 germ cell Anatomy 0.000 description 5
- BQVCCPGCDUSGOE-UHFFFAOYSA-N phenylarsine oxide Chemical compound O=[As]C1=CC=CC=C1 BQVCCPGCDUSGOE-UHFFFAOYSA-N 0.000 description 5
- 229940054269 sodium pyruvate Drugs 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 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 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
- 101001011741 Bos taurus Insulin Proteins 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 4
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 description 4
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 208000009956 adenocarcinoma Diseases 0.000 description 4
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 4
- 230000003833 cell viability Effects 0.000 description 4
- 230000004154 complement system Effects 0.000 description 4
- 230000009089 cytolysis Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000005734 heterodimerization reaction Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000012642 immune effector Substances 0.000 description 4
- 229940121354 immunomodulator Drugs 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 230000003211 malignant effect Effects 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 230000002611 ovarian Effects 0.000 description 4
- 201000007426 ovarian cystadenocarcinoma Diseases 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000012460 protein solution Substances 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 238000001542 size-exclusion chromatography Methods 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 208000036832 Adenocarcinoma of ovary Diseases 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- 208000032494 Clear cell adenocarcinoma of the ovary Diseases 0.000 description 3
- 238000001712 DNA sequencing Methods 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 3
- 206010061328 Ovarian epithelial cancer Diseases 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 235000009697 arginine Nutrition 0.000 description 3
- 229960000397 bevacizumab Drugs 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000012761 co-transfection Methods 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 3
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 3
- 230000002349 favourable effect Effects 0.000 description 3
- 239000012527 feed solution Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 229940072221 immunoglobulins Drugs 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 201000001649 ovarian clear cell adenocarcinoma Diseases 0.000 description 3
- 229920002959 polymer blend Polymers 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000011146 sterile filtration Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 230000001131 transforming effect Effects 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- 230000010474 transient expression Effects 0.000 description 3
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 3
- 229960000604 valproic acid Drugs 0.000 description 3
- 108020003589 5' Untranslated Regions Proteins 0.000 description 2
- 239000012114 Alexa Fluor 647 Substances 0.000 description 2
- KWTQSFXGGICVPE-WCCKRBBISA-N Arginine hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CCCN=C(N)N KWTQSFXGGICVPE-WCCKRBBISA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 101710110042 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Proteins 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 239000012518 Poros HS 50 resin Substances 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 2
- 239000012505 Superdex™ Substances 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 239000000611 antibody drug conjugate Substances 0.000 description 2
- 229940049595 antibody-drug conjugate Drugs 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229960003008 blinatumomab Drugs 0.000 description 2
- 238000013368 capillary electrophoresis sodium dodecyl sulfate analysis Methods 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 238000005341 cation exchange Methods 0.000 description 2
- 238000012832 cell culture technique Methods 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000024203 complement activation Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000022811 deglycosylation Effects 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000012149 elution buffer Substances 0.000 description 2
- 239000006167 equilibration buffer Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 230000002637 immunotoxin Effects 0.000 description 2
- 239000002596 immunotoxin Substances 0.000 description 2
- 229940051026 immunotoxin Drugs 0.000 description 2
- 231100000608 immunotoxin Toxicity 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000016507 interphase Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- AEMBWNDIEFEPTH-UHFFFAOYSA-N n-tert-butyl-n-ethylnitrous amide Chemical compound CCN(N=O)C(C)(C)C AEMBWNDIEFEPTH-UHFFFAOYSA-N 0.000 description 2
- 239000006199 nebulizer Substances 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 201000003707 ovarian clear cell carcinoma Diseases 0.000 description 2
- 201000007439 ovarian mucinous cystadenocarcinoma Diseases 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 239000012146 running buffer Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000002626 targeted therapy Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 102000027257 transmembrane receptors Human genes 0.000 description 2
- 108091008578 transmembrane receptors Proteins 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 208000010576 undifferentiated carcinoma Diseases 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101100476210 Caenorhabditis elegans rnt-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108050007261 Frizzled domains Proteins 0.000 description 1
- 102000018152 Frizzled domains Human genes 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 101000872147 Homo sapiens Biogenesis of lysosome-related organelles complex 1 subunit 6 Proteins 0.000 description 1
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 1
- 101000693011 Homo sapiens Pancreatic alpha-amylase Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- YALRCXHVQYBSJC-UHFFFAOYSA-N Mammea A/AB Chemical compound C12=C(O)C(C(=O)C(C)CC)=C(O)C(CC=C(C)C)=C2OC(=O)C=C1C1=CC=CC=C1 YALRCXHVQYBSJC-UHFFFAOYSA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 101150030083 PE38 gene Proteins 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 241000577979 Peromyscus spicilegus Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108091008680 RAR-related orphan receptors Proteins 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 201000004283 Shwachman-Diamond syndrome Diseases 0.000 description 1
- 241001591005 Siga Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000004268 Sodium erythorbin Substances 0.000 description 1
- 230000010782 T cell mediated cytotoxicity Effects 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 102000013814 Wnt Human genes 0.000 description 1
- 108050003627 Wnt Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 229960002648 alanylglutamine Drugs 0.000 description 1
- 238000012436 analytical size exclusion chromatography Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000001745 anti-biotin effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000000562 conjugate Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 238000013523 data management Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000000375 direct analysis in real time Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000012063 dual-affinity re-targeting Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 201000010255 female reproductive organ cancer Diseases 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000011354 first-line chemotherapy Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000003500 gene array Methods 0.000 description 1
- 238000012637 gene transfection Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 102000056984 human BLOC1S6 Human genes 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 238000012872 hydroxylapatite chromatography Methods 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002843 lactate dehydrogenase assay Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 238000013492 plasmid preparation Methods 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920001281 polyalkylene Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000004815 positive regulation of T cell activation Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 231100000205 reproductive and developmental toxicity Toxicity 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 208000004548 serous cystadenocarcinoma Diseases 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
Classifications
-
- 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
- C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- 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
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/10—Protein-tyrosine kinases (2.7.10)
- C12Y207/10001—Receptor protein-tyrosine kinase (2.7.10.1)
-
- 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
- C07K2317/30—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
-
- 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
- C07K2317/524—CH2 domain
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/54—F(ab')2
-
- 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
- C07K2317/50—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
-
- 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
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Reproductive Health (AREA)
- General Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Cell Biology (AREA)
- Pregnancy & Childbirth (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14188378 | 2014-10-09 | ||
| EP14188378.5 | 2014-10-09 | ||
| EP14188728 | 2014-10-14 | ||
| EP14188728.1 | 2014-10-14 | ||
| EP14188727 | 2014-10-14 | ||
| EP14188727.3 | 2014-10-14 | ||
| PCT/EP2015/073309 WO2016055593A1 (en) | 2014-10-09 | 2015-10-08 | Bispecific antibodies against cd3epsilon and ror1 for use in the treatment of ovarian cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2963696A1 true CA2963696A1 (en) | 2016-04-14 |
Family
ID=54291293
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2963696A Abandoned CA2963696A1 (en) | 2014-10-09 | 2015-10-08 | Bispecific antibodies against cd3epsilon and ror1 for use in the treatment of ovarian cancer |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20170306044A1 (cg-RX-API-DMAC7.html) |
| EP (1) | EP3204416A1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2017536341A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2015329966A1 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2963696A1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2016055593A1 (cg-RX-API-DMAC7.html) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107827984A (zh) * | 2017-09-13 | 2018-03-23 | 张慧林 | 嵌合抗ROR1抗体Fab分子及其制备方法和应用 |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6400470B2 (ja) | 2011-05-16 | 2018-10-03 | ジェネロン（シャンハイ）コーポレイション リミテッド | 多重特異性Ｆａｂ融合タンパク質および使用法 |
| MX356947B (es) | 2011-08-23 | 2018-06-20 | Roche Glycart Ag | Anticuerpos bioespecíficos específicos para antígenos que activan células t y un antígeno tumoral y métodos de uso. |
| US10087250B2 (en) | 2012-10-08 | 2018-10-02 | Roche Glycart Ag | Fc-free antibodies comprising two fab-fragments and methods of use |
| KR20180023035A (ko) | 2013-02-26 | 2018-03-06 | 로슈 글리카트 아게 | 이중특이적 t 세포 활성화 항원 결합 분자 |
| EP2789630A1 (en) * | 2013-04-09 | 2014-10-15 | EngMab AG | Bispecific antibodies against CD3e and ROR1 |
| PE20211533A1 (es) | 2014-08-04 | 2021-08-16 | Hoffmann La Roche | Moleculas biespecificas de unon a antigeno activadoras de celulas t |
| MX2017006571A (es) | 2014-11-20 | 2017-09-29 | Hoffmann La Roche | Moleculas de union a antigeno biespecificas activadoras de celulas t. |
| LT3221357T (lt) | 2014-11-20 | 2020-08-25 | F. Hoffmann-La Roche Ag | Bendros lengvosios grandinės ir naudojimo būdai |
| HRP20201928T1 (hr) | 2014-11-20 | 2021-02-05 | F. Hoffmann - La Roche Ag | Kombinirana terapija bispecifičnom antigen vezujućom molekulom koja aktivira t-stanice, za cd3 i folatni receptor 1 (folr1), i antagonistom vezivanja osi pd-1 |
| AR106188A1 (es) | 2015-10-01 | 2017-12-20 | Hoffmann La Roche | Anticuerpos anti-cd19 humano humanizados y métodos de utilización |
| BR112018000835A2 (pt) | 2015-10-02 | 2018-09-11 | Hoffmann La Roche | molécula, um ou mais polinucleotídeos, um ou mais vetores, célula, método de produção da molécula, composição, uso da molécula, método de tratamento de uma doença e método para induzir a lise de uma célula-alvo |
| AU2016345681A1 (en) | 2015-10-30 | 2018-05-10 | Nbe-Therapeutics Ag | Anti-ROR1 antibodies |
| ES2901794T3 (es) | 2015-12-09 | 2022-03-23 | Hoffmann La Roche | Anticuerpo anti-CD20 de tipo II para reducir la formación de anticuerpos antifármaco |
| KR20180097615A (ko) | 2016-01-08 | 2018-08-31 | 에프. 호프만-라 로슈 아게 | Pd-1 축 결합 길항물질 및 항-cea/항-cd3 이중특이성 항체를 사용하는 cea-양성 암의 치료 방법 |
| UA125718C2 (uk) | 2016-01-20 | 2022-05-25 | Зе Скріппс Ресеарч Інстітьют | Композиції антитіл до ror1 і пов'язані з ними способи |
| AU2017233121B2 (en) | 2016-03-15 | 2023-12-21 | Itabmed (Hk) Limited | Multispecific Fab fusion proteins and use thereof |
| RS64266B1 (sr) | 2016-03-22 | 2023-07-31 | Hoffmann La Roche | Bispecifični molekul koji aktivira t ćeliju koji se aktivira proteazom |
| JP7022123B2 (ja) * | 2016-09-30 | 2022-02-17 | エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト | Ｃｄ３に対する二重特異性抗体 |
| BR112019020940A2 (pt) | 2017-04-11 | 2020-05-05 | Inhibrx, Inc. | construções polipeptídicas multipecíficas que têm ligação a cd3 restrita e métodos de usar as mesmas |
| KR102736878B1 (ko) | 2017-06-23 | 2024-12-05 | 벨로스바이오 인코포레이티드 | Ror1 항체 면역접합체 |
| GB201710836D0 (en) | 2017-07-05 | 2017-08-16 | Ucl Business Plc | ROR1 Car T-Cells |
| GB201710835D0 (en) | 2017-07-05 | 2017-08-16 | Ucl Business Plc | ROR1 Antibodies |
| GB201710838D0 (en) | 2017-07-05 | 2017-08-16 | Ucl Business Plc | Bispecific antibodies |
| WO2019016381A1 (en) * | 2017-07-20 | 2019-01-24 | Nbe-Therapeutics Ag | MULTISPECIFIC ANTIBODY PRODUCT BINDING TO DIFFERENT ROR1 EPITOPES |
| KR102486090B1 (ko) | 2017-08-07 | 2023-01-10 | 엔비이-테라퓨틱스 아게 | 생체 내 내성이 높은 항체 약물 결합체 |
| GB201721802D0 (en) * | 2017-12-22 | 2018-02-07 | Almac Discovery Ltd | Ror1-specific antigen binding molecules |
| CN118772288A (zh) | 2018-02-08 | 2024-10-15 | 豪夫迈·罗氏有限公司 | 双特异性抗原结合分子和使用方法 |
| TWI829667B (zh) * | 2018-02-09 | 2024-01-21 | 瑞士商赫孚孟拉羅股份公司 | 結合gprc5d之抗體 |
| TW202003569A (zh) | 2018-03-30 | 2020-01-16 | 荷蘭商美勒斯公司 | 多價抗體 |
| IL323061A (en) | 2018-04-11 | 2025-10-01 | Inhibrx Biosciences Inc | Multispecific polypeptide constructs with forced CD3 binding and related methods and uses |
| US12084496B2 (en) * | 2018-04-18 | 2024-09-10 | Exelixis, Inc. | Anti-ROR antibody constructs |
| WO2020023553A1 (en) | 2018-07-24 | 2020-01-30 | Inhibrx, Inc. | Multispecific polypeptide constructs containing a constrained cd3 binding domain and a receptor binding region and methods of using the same |
| EP3847196A4 (en) | 2018-09-07 | 2023-01-04 | ITabMed (HK) Limited | BISPECIFIC ANTIGEN BINDING PROTEINS AND USES THEREOF |
| CA3114693A1 (en) * | 2018-10-11 | 2020-04-16 | Inhibrx, Inc. | 5t4 single domain antibodies and therapeutic compositions thereof |
| CN113166263A (zh) | 2018-10-11 | 2021-07-23 | 印希比股份有限公司 | Dll3单域抗体及其治疗性组合物 |
| KR20220024637A (ko) * | 2019-06-19 | 2022-03-03 | 에프. 호프만-라 로슈 아게 | 정의된 조직의 다수 발현 카세트들의 표적화 통합에 의한 3가 항체 발현 세포의 생성 방법 |
| MX2022001156A (es) * | 2019-07-31 | 2022-02-22 | Hoffmann La Roche | Anticuerpos que se fijan a gprc5d. |
| MX2022016069A (es) | 2020-06-19 | 2023-02-02 | Hoffmann La Roche | Anticuerpos que se unen a cd3 y cd19. |
| AU2021334677A1 (en) * | 2020-08-24 | 2023-03-02 | Epimab Biotherapeutics (Hk) Limited | Anti-ROR1 antibodies and related bispecific binding proteins |
| EP3988568A1 (en) * | 2020-10-21 | 2022-04-27 | Numab Therapeutics AG | Combination treatment |
| WO2022146003A1 (ko) * | 2020-12-29 | 2022-07-07 | 삼성바이오로직스 주식회사 | 이중 또는 다중 특이적 항체 |
| KR20230166075A (ko) * | 2021-02-02 | 2023-12-06 | 누맙 세러퓨틱스 아게 | Ror1 및 cd3에 대한 특이성을 가지는 다중 특이적 항체 |
| AU2021443318A1 (en) | 2021-04-30 | 2023-09-07 | F. Hoffmann-La Roche Ag | Dosing for combination treatment with anti-cd20/anti-cd3 bispecific antibody and anti-cd79b antibody drug conjugate |
| EP4669675A2 (en) * | 2023-02-23 | 2025-12-31 | Adanate, Inc. | Anti-CD3 antibodies and their methods of use |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2547600C2 (ru) * | 2008-10-01 | 2015-04-10 | Эмджен Рисерч (Мьюник) Гмбх | Pscaxcd3, cd19xcd3, c-metxcd3, эндосиалинxcd3, epcamxcd3, igf-1rxcd3 или fap-альфаxcd3 биспецифическое одноцепочечное антитело с межвидовой специфичностью |
| US20120282177A1 (en) * | 2009-11-02 | 2012-11-08 | Christian Rohlff | ROR1 as Therapeutic and Diagnostic Target |
| WO2012045085A1 (en) * | 2010-10-01 | 2012-04-05 | Oxford Biotherapeutics Ltd. | Anti-rori antibodies |
| EP2646469B1 (en) * | 2010-12-01 | 2017-11-01 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Chimeric rabbit/human ror1 antibodies |
| US20130078250A1 (en) * | 2011-08-23 | 2013-03-28 | Oliver Ast | Bispecific t cell activating antigen binding molecules |
| CN109111524B (zh) * | 2011-10-31 | 2022-10-28 | 中外制药株式会社 | 控制了重链与轻链的缔合的抗原结合分子 |
| TWI679212B (zh) * | 2011-11-15 | 2019-12-11 | 美商安進股份有限公司 | 針對ｂｃｍａ之e3以及ｃｄ３的結合分子 |
| WO2013174873A1 (en) * | 2012-05-24 | 2013-11-28 | F. Hoffmann-La Roche Ag | Multispecific antibodies |
| US10087250B2 (en) * | 2012-10-08 | 2018-10-02 | Roche Glycart Ag | Fc-free antibodies comprising two fab-fragments and methods of use |
| KR20180023035A (ko) * | 2013-02-26 | 2018-03-06 | 로슈 글리카트 아게 | 이중특이적 t 세포 활성화 항원 결합 분자 |
| PT2968552T (pt) * | 2013-03-14 | 2020-05-18 | Scripps Research Inst | Anticorpo dos agentes alvo, combinações e uso para os mesmos |
| EP3424952A1 (en) * | 2013-03-15 | 2019-01-09 | Amgen, Inc | Heterodimeric bispecific antibodies |
| EP2789630A1 (en) * | 2013-04-09 | 2014-10-15 | EngMab AG | Bispecific antibodies against CD3e and ROR1 |
-
2015
- 2015-10-08 JP JP2017518516A patent/JP2017536341A/ja active Pending
- 2015-10-08 US US15/517,329 patent/US20170306044A1/en not_active Abandoned
- 2015-10-08 CA CA2963696A patent/CA2963696A1/en not_active Abandoned
- 2015-10-08 WO PCT/EP2015/073309 patent/WO2016055593A1/en not_active Ceased
- 2015-10-08 AU AU2015329966A patent/AU2015329966A1/en not_active Abandoned
- 2015-10-08 EP EP15778295.4A patent/EP3204416A1/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107827984A (zh) * | 2017-09-13 | 2018-03-23 | 张慧林 | 嵌合抗ROR1抗体Fab分子及其制备方法和应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016055593A1 (en) | 2016-04-14 |
| US20170306044A1 (en) | 2017-10-26 |
| AU2015329966A1 (en) | 2017-04-27 |
| EP3204416A1 (en) | 2017-08-16 |
| JP2017536341A (ja) | 2017-12-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3204415B1 (en) | Bispecific antibodies against cd3epsilon and ror1 | |
| US20170306044A1 (en) | Bispecific antibodies against cd3epsilon and ror1 for use in the treatment of ovarian cancer | |
| US20200255521A1 (en) | Bispecific antibodies against cd3epsilon and ror1 | |
| CN108350073B (zh) | 针对bcma的单克隆抗体 | |
| US10253104B2 (en) | Bispecific antibodies against CD3ϵ and BCMA | |
| JP5501439B2 (ja) | 完全長抗体と単鎖Ｆａｂフラグメントとを含む多重特異的抗体 | |
| CN102574921B (zh) | 双特异性死亡受体激动型抗体 | |
| US10077315B2 (en) | Bispecific antibodies against CD3 and BCMA | |
| EP3023437A1 (en) | Bispecific antibodies against CD3epsilon and BCMA | |
| EP2762497A1 (en) | Bispecific antibodies against CD3epsilon and BCMA | |
| WO2024251154A9 (zh) | 抗gprc5d/bcma/cd3三特异性抗体的制备及其用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20201008 |