CA2965745C - Cd3/cd38 t cell retargeting hetero-dimeric immunoglobulins and methods of their production - Google Patents
Cd3/cd38 t cell retargeting hetero-dimeric immunoglobulins and methods of their production Download PDFInfo
- Publication number
- CA2965745C CA2965745C CA2965745A CA2965745A CA2965745C CA 2965745 C CA2965745 C CA 2965745C CA 2965745 A CA2965745 A CA 2965745A CA 2965745 A CA2965745 A CA 2965745A CA 2965745 C CA2965745 C CA 2965745C
- Authority
- CA
- Canada
- Prior art keywords
- seq
- antibody
- amino acid
- human
- fragment
- 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.)
- Active
Links
- 108060003951 Immunoglobulin Proteins 0.000 title claims abstract description 102
- 102000018358 immunoglobulin Human genes 0.000 title claims abstract description 102
- 229940072221 immunoglobulins Drugs 0.000 title claims abstract description 23
- 238000000034 method Methods 0.000 title abstract description 77
- 238000004519 manufacturing process Methods 0.000 title description 10
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 claims abstract description 177
- 241000282414 Homo sapiens Species 0.000 claims abstract description 158
- 102000052645 human CD38 Human genes 0.000 claims abstract description 66
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 162
- 210000004027 cell Anatomy 0.000 claims description 128
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 claims description 103
- 239000012634 fragment Substances 0.000 claims description 101
- 101000961156 Homo sapiens Immunoglobulin heavy constant gamma 1 Proteins 0.000 claims description 42
- 102100039345 Immunoglobulin heavy constant gamma 1 Human genes 0.000 claims description 42
- 241001529936 Murinae Species 0.000 claims description 15
- 239000000539 dimer Substances 0.000 claims description 13
- 101000961149 Homo sapiens Immunoglobulin heavy constant gamma 4 Proteins 0.000 claims description 11
- 102100039347 Immunoglobulin heavy constant gamma 4 Human genes 0.000 claims description 11
- 208000014951 hematologic disease Diseases 0.000 claims description 10
- 230000003211 malignant effect Effects 0.000 claims description 10
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 9
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- 208000018706 hematopoietic system disease Diseases 0.000 claims description 8
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 208000034578 Multiple myelomas Diseases 0.000 claims description 5
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 4
- 201000003444 follicular lymphoma Diseases 0.000 claims description 4
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 3
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 3
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 3
- 208000005531 Immunoglobulin Light-chain Amyloidosis Diseases 0.000 claims description 3
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims description 3
- 206010028811 Natural killer-cell leukaemia Diseases 0.000 claims description 3
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 claims description 3
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 3
- 208000022256 primary systemic amyloidosis Diseases 0.000 claims description 3
- 208000033766 Prolymphocytic Leukemia Diseases 0.000 claims description 2
- 208000025113 myeloid leukemia Diseases 0.000 claims description 2
- 208000031223 plasma cell leukemia Diseases 0.000 claims description 2
- 210000004180 plasmocyte Anatomy 0.000 claims description 2
- 229940127121 immunoconjugate Drugs 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 239000000427 antigen Substances 0.000 abstract description 73
- 108091007433 antigens Proteins 0.000 abstract description 71
- 102000036639 antigens Human genes 0.000 abstract description 71
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 10
- 230000001225 therapeutic effect Effects 0.000 abstract description 5
- 230000027455 binding Effects 0.000 description 213
- 108090000623 proteins and genes Proteins 0.000 description 184
- 102000004169 proteins and genes Human genes 0.000 description 172
- 235000018102 proteins Nutrition 0.000 description 170
- 101150057475 BEAT gene Proteins 0.000 description 121
- 108090000765 processed proteins & peptides Proteins 0.000 description 98
- 238000006467 substitution reaction Methods 0.000 description 98
- 102000004196 processed proteins & peptides Human genes 0.000 description 87
- 229920001184 polypeptide Polymers 0.000 description 85
- 235000001014 amino acid Nutrition 0.000 description 81
- 210000001744 T-lymphocyte Anatomy 0.000 description 57
- 150000001413 amino acids Chemical class 0.000 description 42
- 125000000539 amino acid group Chemical group 0.000 description 41
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 40
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 40
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 39
- 230000014509 gene expression Effects 0.000 description 37
- 230000002998 immunogenetic effect Effects 0.000 description 36
- 230000004048 modification Effects 0.000 description 25
- 238000012986 modification Methods 0.000 description 25
- 101000642536 Apis mellifera Venom serine protease 34 Proteins 0.000 description 24
- 239000012636 effector Substances 0.000 description 24
- 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 23
- 230000002147 killing effect Effects 0.000 description 22
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 22
- 241000699666 Mus <mouse, genus> Species 0.000 description 21
- 230000035772 mutation Effects 0.000 description 20
- 239000003795 chemical substances by application Substances 0.000 description 19
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 19
- 238000003556 assay Methods 0.000 description 18
- 239000000872 buffer Substances 0.000 description 18
- 101710120037 Toxin CcdB Proteins 0.000 description 17
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 17
- 239000000710 homodimer Substances 0.000 description 17
- 239000002953 phosphate buffered saline Substances 0.000 description 17
- 238000000113 differential scanning calorimetry Methods 0.000 description 15
- 238000011534 incubation Methods 0.000 description 15
- 239000002609 medium Substances 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 206010028980 Neoplasm Diseases 0.000 description 14
- 230000022534 cell killing Effects 0.000 description 14
- 238000004587 chromatography analysis Methods 0.000 description 14
- 230000004927 fusion Effects 0.000 description 14
- 108020001507 fusion proteins Proteins 0.000 description 14
- 102000037865 fusion proteins Human genes 0.000 description 14
- 239000000833 heterodimer Substances 0.000 description 14
- 238000010828 elution Methods 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- 101001055308 Homo sapiens Immunoglobulin heavy constant epsilon Proteins 0.000 description 12
- 102100026212 Immunoglobulin heavy constant epsilon Human genes 0.000 description 12
- 101100438926 Macaca fascicularis CD38 gene Proteins 0.000 description 12
- 210000004602 germ cell Anatomy 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 239000003446 ligand Substances 0.000 description 11
- 241000282567 Macaca fascicularis Species 0.000 description 10
- 238000001042 affinity chromatography Methods 0.000 description 10
- 238000013459 approach Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 102000039446 nucleic acids Human genes 0.000 description 10
- 108020004707 nucleic acids Proteins 0.000 description 10
- 150000007523 nucleic acids Chemical class 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 239000006228 supernatant Substances 0.000 description 10
- 230000008685 targeting Effects 0.000 description 10
- 102000018667 ADP-ribosyl Cyclase 1 Human genes 0.000 description 9
- 229920002873 Polyethylenimine Polymers 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 201000011510 cancer Diseases 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 8
- 102220485208 Myelin proteolipid protein_L46R_mutation Human genes 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 239000002299 complementary DNA Substances 0.000 description 8
- 239000013604 expression vector Substances 0.000 description 8
- 210000004408 hybridoma Anatomy 0.000 description 8
- 238000013507 mapping Methods 0.000 description 8
- 102220005331 rs281865555 Human genes 0.000 description 8
- 102220005402 rs33939421 Human genes 0.000 description 8
- 101001055314 Homo sapiens Immunoglobulin heavy constant alpha 2 Proteins 0.000 description 7
- 101000961145 Homo sapiens Immunoglobulin heavy constant gamma 3 Proteins 0.000 description 7
- 101000840273 Homo sapiens Immunoglobulin lambda constant 1 Proteins 0.000 description 7
- 101000840271 Homo sapiens Immunoglobulin lambda constant 2 Proteins 0.000 description 7
- 101000840272 Homo sapiens Immunoglobulin lambda constant 3 Proteins 0.000 description 7
- 101000840269 Homo sapiens Immunoglobulin lambda constant 6 Proteins 0.000 description 7
- 102100026216 Immunoglobulin heavy constant alpha 2 Human genes 0.000 description 7
- 102100039348 Immunoglobulin heavy constant gamma 3 Human genes 0.000 description 7
- 102100029610 Immunoglobulin lambda constant 1 Human genes 0.000 description 7
- 108091008874 T cell receptors Proteins 0.000 description 7
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 7
- 102220635498 Vacuolar protein sorting-associated protein 33A_I34M_mutation Human genes 0.000 description 7
- 230000009830 antibody antigen interaction Effects 0.000 description 7
- 239000011324 bead Substances 0.000 description 7
- 229940022353 herceptin Drugs 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 102220013614 rs397516692 Human genes 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 101000961146 Homo sapiens Immunoglobulin heavy constant gamma 2 Proteins 0.000 description 6
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 6
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 6
- 102100039346 Immunoglobulin heavy constant gamma 2 Human genes 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 230000037430 deletion Effects 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 210000001616 monocyte Anatomy 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 0.000 description 6
- 230000010474 transient expression Effects 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 108010027122 ADP-ribosyl Cyclase 1 Proteins 0.000 description 5
- 101001037140 Homo sapiens Immunoglobulin heavy variable 3-23 Proteins 0.000 description 5
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 230000000890 antigenic effect Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 239000000356 contaminant Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 4
- 230000005526 G1 to G0 transition Effects 0.000 description 4
- 101100126610 Homo sapiens ITIH1 gene Proteins 0.000 description 4
- 101001138089 Homo sapiens Immunoglobulin kappa variable 1-39 Proteins 0.000 description 4
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 4
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 4
- 102100040220 Immunoglobulin heavy variable 3-23 Human genes 0.000 description 4
- 102100020910 Immunoglobulin kappa variable 1-39 Human genes 0.000 description 4
- 102100023490 Inter-alpha-trypsin inhibitor heavy chain H1 Human genes 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 102220472894 Receptor-type tyrosine-protein phosphatase beta_R94K_mutation Human genes 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 239000003463 adsorbent Substances 0.000 description 4
- 229960002685 biotin Drugs 0.000 description 4
- 235000020958 biotin Nutrition 0.000 description 4
- 239000011616 biotin Substances 0.000 description 4
- 239000012539 chromatography resin Substances 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 238000002823 phage display Methods 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 4
- 102200090720 rs137852501 Human genes 0.000 description 4
- 102200145384 rs34127778 Human genes 0.000 description 4
- 102200130584 rs373562040 Human genes 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- 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 3
- 108020004635 Complementary DNA Proteins 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
- OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101001057612 Homo sapiens Dual specificity protein phosphatase 5 Proteins 0.000 description 3
- 101000840257 Homo sapiens Immunoglobulin kappa constant Proteins 0.000 description 3
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 description 3
- 101000840270 Homo sapiens Immunoglobulin lambda constant 7 Proteins 0.000 description 3
- 102100029572 Immunoglobulin kappa constant Human genes 0.000 description 3
- 102100022964 Immunoglobulin kappa variable 3-20 Human genes 0.000 description 3
- 102100029620 Immunoglobulin lambda constant 2 Human genes 0.000 description 3
- 102100029619 Immunoglobulin lambda constant 3 Human genes 0.000 description 3
- 102100029615 Immunoglobulin lambda constant 6 Human genes 0.000 description 3
- 102100029614 Immunoglobulin lambda constant 7 Human genes 0.000 description 3
- 108700026244 Open Reading Frames Proteins 0.000 description 3
- 102220632793 Ornithine aminotransferase, mitochondrial_R58Y_mutation Human genes 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- 102220580956 Voltage-dependent T-type calcium channel subunit alpha-1H_S30A_mutation Human genes 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 102000043381 human DUSP5 Human genes 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 238000004811 liquid chromatography Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000004091 panning Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000003259 recombinant expression Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 102220003317 rs137852699 Human genes 0.000 description 3
- 102220126961 rs369936288 Human genes 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- 239000013638 trimer Substances 0.000 description 3
- YXHLJMWYDTXDHS-IRFLANFNSA-N 7-aminoactinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=C(N)C=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 YXHLJMWYDTXDHS-IRFLANFNSA-N 0.000 description 2
- 108700012813 7-aminoactinomycin D Proteins 0.000 description 2
- 108010032595 Antibody Binding Sites Proteins 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 2
- 102220614803 Calmodulin-3_Y92A_mutation Human genes 0.000 description 2
- 102220505519 Class E basic helix-loop-helix protein 40_P56A_mutation Human genes 0.000 description 2
- 108010076804 DNA Restriction Enzymes Proteins 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- 102220597351 DNA-directed RNA polymerases I, II, and III subunit RPABC2_N94A_mutation Human genes 0.000 description 2
- 102220597389 G0/G1 switch protein 2_R54A_mutation Human genes 0.000 description 2
- 102220597392 G0/G1 switch protein 2_T51A_mutation Human genes 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 2
- 101000777314 Homo sapiens Choline kinase alpha Proteins 0.000 description 2
- 101000777313 Homo sapiens Choline/ethanolamine kinase Proteins 0.000 description 2
- 101001138544 Homo sapiens UMP-CMP kinase Proteins 0.000 description 2
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 2
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 2
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000012515 MabSelect SuRe Substances 0.000 description 2
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 2
- 102220627452 Paired immunoglobulin-like type 2 receptor alpha_L95A_mutation Human genes 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 102220480657 Protein LTV1 homolog_K53A_mutation Human genes 0.000 description 2
- 241000508269 Psidium Species 0.000 description 2
- 102220469433 Putative uncharacterized protein URB1-AS1_W91F_mutation Human genes 0.000 description 2
- 101800000828 RNA-directed RNA polymerase 3D-POL Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 102220469971 Tryptase delta_Y32A_mutation Human genes 0.000 description 2
- 102220475439 Vacuolar protein sorting-associated protein 33A_N31A_mutation Human genes 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 102220580702 Voltage-dependent T-type calcium channel subunit alpha-1H_N52A_mutation Human genes 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 230000003185 calcium uptake Effects 0.000 description 2
- 238000001818 capillary gel electrophoresis Methods 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 239000002254 cytotoxic agent Substances 0.000 description 2
- 231100000599 cytotoxic agent Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 231100000050 cytotoxic potential Toxicity 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000005734 heterodimerization reaction Methods 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 239000007981 phosphate-citrate buffer Substances 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 108010067988 prolactin-binding protein Proteins 0.000 description 2
- 239000012562 protein A resin Substances 0.000 description 2
- 229950010131 puromycin Drugs 0.000 description 2
- 238000009877 rendering Methods 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- 102220242557 rs142853738 Human genes 0.000 description 2
- 102220280441 rs776730435 Human genes 0.000 description 2
- 102220064391 rs786205838 Human genes 0.000 description 2
- 239000012146 running buffer Substances 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 1
- APRZHQXAAWPYHS-UHFFFAOYSA-N 4-[5-[3-(carboxymethoxy)phenyl]-3-(4,5-dimethyl-1,3-thiazol-2-yl)tetrazol-3-ium-2-yl]benzenesulfonate Chemical compound S1C(C)=C(C)N=C1[N+]1=NC(C=2C=C(OCC(O)=O)C=CC=2)=NN1C1=CC=C(S([O-])(=O)=O)C=C1 APRZHQXAAWPYHS-UHFFFAOYSA-N 0.000 description 1
- VDABVNMGKGUPEY-UHFFFAOYSA-N 6-carboxyfluorescein succinimidyl ester Chemical compound C=1C(O)=CC=C2C=1OC1=CC(O)=CC=C1C2(C1=C2)OC(=O)C1=CC=C2C(=O)ON1C(=O)CCC1=O VDABVNMGKGUPEY-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- IPWKGIFRRBGCJO-IMJSIDKUSA-N Ala-Ser Chemical compound C[C@H]([NH3+])C(=O)N[C@@H](CO)C([O-])=O IPWKGIFRRBGCJO-IMJSIDKUSA-N 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 102220549033 B-cell linker protein_Y91F_mutation Human genes 0.000 description 1
- 102220567604 BICD family-like cargo adapter 2_T29S_mutation Human genes 0.000 description 1
- 102220475086 Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6_L90A_mutation Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 241000208199 Buxus sempervirens Species 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102220604032 Clathrin heavy chain 1_Q89A_mutation Human genes 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 102220493683 HLA class II histocompatibility antigen, DRB1 beta chain_V67L_mutation Human genes 0.000 description 1
- 101100453139 Homo sapiens ITIH2 gene Proteins 0.000 description 1
- 101000840258 Homo sapiens Immunoglobulin J chain Proteins 0.000 description 1
- 101001037145 Homo sapiens Immunoglobulin heavy variable 2-5 Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102100029571 Immunoglobulin J chain Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 102100040235 Immunoglobulin heavy variable 2-5 Human genes 0.000 description 1
- 108010090227 Immunoglobulin kappa-Chains Proteins 0.000 description 1
- 102000012960 Immunoglobulin kappa-Chains Human genes 0.000 description 1
- 108010004020 Immunoglobulin lambda-Chains Proteins 0.000 description 1
- 102220465908 Importin subunit beta-1_V48L_mutation Human genes 0.000 description 1
- 102100039440 Inter-alpha-trypsin inhibitor heavy chain H2 Human genes 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 241000282838 Lama Species 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 239000012124 Opti-MEM Substances 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108091008109 Pseudogenes Proteins 0.000 description 1
- 102000057361 Pseudogenes Human genes 0.000 description 1
- 102220609663 Putative malate dehydrogenase 1B_L48I_mutation Human genes 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 102220474401 Ribitol-5-phosphate xylosyltransferase 1_F87V_mutation Human genes 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 239000012722 SDS sample buffer Substances 0.000 description 1
- 108010084592 Saporins Proteins 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 206010042971 T-cell lymphoma Diseases 0.000 description 1
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 102220506801 Vitelline membrane outer layer protein 1 homolog_N73T_mutation Human genes 0.000 description 1
- 102220580959 Voltage-dependent T-type calcium channel subunit alpha-1H_S25A_mutation Human genes 0.000 description 1
- 108010076089 accutase Proteins 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000008484 agonism Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 102220430030 c.109A>G Human genes 0.000 description 1
- 102220367300 c.201C>G Human genes 0.000 description 1
- 238000007707 calorimetry Methods 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 239000005350 fused silica glass Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 210000004524 haematopoietic cell Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000013394 immunophenotyping Methods 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000003116 impacting effect Effects 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 201000001037 lung lymphoma Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000000207 lymphocyte subset Anatomy 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- 229960003816 muromonab-cd3 Drugs 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229940029358 orthoclone okt3 Drugs 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000012510 peptide mapping method Methods 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000036515 potency Effects 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 238000000455 protein structure prediction Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 102200033974 rs1555427497 Human genes 0.000 description 1
- 102220281547 rs1555514410 Human genes 0.000 description 1
- 102200038988 rs17313469 Human genes 0.000 description 1
- 102200145330 rs72474224 Human genes 0.000 description 1
- 102220335925 rs775094277 Human genes 0.000 description 1
- 102220143207 rs779977931 Human genes 0.000 description 1
- 102200067034 rs80356913 Human genes 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 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 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 229940124598 therapeutic candidate Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 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
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—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
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- 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
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- 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
- C07K2317/55—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
- C07K2317/50—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]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/75—Agonist effect on antigen
-
- 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
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- 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)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Neurology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EPPCT/EP2014/073738 | 2014-11-04 | ||
| PCT/EP2014/073738 WO2015063339A1 (en) | 2013-11-04 | 2014-11-04 | Production of t cell retargeting hetero-dimeric immunoglobulins |
| EP15167034 | 2015-05-08 | ||
| EP15167034.6 | 2015-05-08 | ||
| PCT/EP2015/075628 WO2016071355A1 (en) | 2014-11-04 | 2015-11-03 | Cd3/cd38 t cell retargeting hetero-dimeric immunoglobulins and methods of their production |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2965745A1 CA2965745A1 (en) | 2016-05-12 |
| CA2965745C true CA2965745C (en) | 2023-12-05 |
Family
ID=53059011
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2965745A Active CA2965745C (en) | 2014-11-04 | 2015-11-03 | Cd3/cd38 t cell retargeting hetero-dimeric immunoglobulins and methods of their production |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP3215541A1 (zh) |
| JP (3) | JP2018501297A (zh) |
| KR (1) | KR20170078831A (zh) |
| CN (1) | CN107207596A (zh) |
| AU (1) | AU2015341884B2 (zh) |
| BR (1) | BR112017009263A2 (zh) |
| CA (1) | CA2965745C (zh) |
| CL (1) | CL2017001090A1 (zh) |
| CO (1) | CO2017005240A2 (zh) |
| EA (1) | EA039658B1 (zh) |
| HK (1) | HK1244014A1 (zh) |
| IL (1) | IL251848A0 (zh) |
| MA (1) | MA40894A (zh) |
| MX (1) | MX2017005814A (zh) |
| MY (1) | MY186929A (zh) |
| NZ (1) | NZ732019A (zh) |
| PE (1) | PE20171041A1 (zh) |
| PH (1) | PH12017500819A1 (zh) |
| SG (1) | SG11201703313SA (zh) |
| WO (1) | WO2016071355A1 (zh) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3620473A1 (en) | 2013-01-14 | 2020-03-11 | Xencor, Inc. | Novel heterodimeric proteins |
| US11053316B2 (en) | 2013-01-14 | 2021-07-06 | Xencor, Inc. | Optimized antibody variable regions |
| US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
| US11161906B2 (en) | 2013-07-25 | 2021-11-02 | Cytomx Therapeutics, Inc. | Multispecific antibodies, multispecific activatable antibodies and methods of using the same |
| AU2014343636A1 (en) | 2013-11-04 | 2016-06-02 | Glenmark Pharmaceuticals S.A. | Production of T cell retargeting hetero-dimeric immunoglobulins |
| US9822186B2 (en) | 2014-03-28 | 2017-11-21 | Xencor, Inc. | Bispecific antibodies that bind to CD38 and CD3 |
| CA2955947A1 (en) * | 2014-07-25 | 2016-01-28 | Cytomx Therapeutics, Inc. | Anti-cd3 antibodies, activatable anti-cd3 antibodies, multispecific anti-cd3 antibodies, multispecific activatable anti-cd3 antibodies, and methods of using the same |
| US11773166B2 (en) | 2014-11-04 | 2023-10-03 | Ichnos Sciences SA | CD3/CD38 T cell retargeting hetero-dimeric immunoglobulins and methods of their production |
| EA201791139A1 (ru) | 2014-11-26 | 2018-04-30 | Ксенкор, Инк. | Гетеродимерные антитела, которые связывают cd3 и опухолевые антигены |
| US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
| JP2017536830A (ja) | 2014-11-26 | 2017-12-14 | ゼンコー・インコーポレイテッドＸｅｎｃｏｒ、 Ｉｎｃ． | Ｃｄ３及びｃｄ３８に結合するヘテロ二量体抗体 |
| TWI829617B (zh) | 2015-07-31 | 2024-01-21 | 德商安美基研究（慕尼黑）公司 | Ｆｌｔ３及ｃｄ３抗體構築體 |
| TWI796283B (zh) | 2015-07-31 | 2023-03-21 | 德商安美基研究（慕尼黑）公司 | Ｍｓｌｎ及ｃｄ３抗體構築體 |
| EP3387013B1 (en) | 2015-12-07 | 2022-06-08 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and psma |
| EA039859B1 (ru) | 2016-02-03 | 2022-03-21 | Эмджен Рисерч (Мюник) Гмбх | Биспецифические конструкты антител, связывающие egfrviii и cd3 |
| RU2767357C2 (ru) | 2016-06-14 | 2022-03-17 | Ксенкор, Инк. | Биспецифические антитела-ингибиторы контрольных точек |
| WO2018005706A1 (en) | 2016-06-28 | 2018-01-04 | Xencor, Inc. | Heterodimeric antibodies that bind somatostatin receptor 2 |
| SG11201909498XA (en) * | 2017-04-24 | 2019-11-28 | Glenmark Pharmaceuticals Sa | T cell redirecting bispecific antibodies for the treatment of egfr positive cancers |
| CA3064163A1 (en) | 2017-06-05 | 2018-12-13 | Numab Therapeutics AG | Novel anti-cd3 antibodies |
| WO2018224441A1 (en) * | 2017-06-05 | 2018-12-13 | Numab Innovation Ag | Novel anti-cd3 antibodies |
| CN111051344B (zh) | 2017-06-08 | 2023-10-27 | 黑带医疗有限公司 | Cd38调节抗体 |
| US20210277138A1 (en) * | 2017-06-08 | 2021-09-09 | Black Belt Therapeutics Limited | Cd38 modulating antibody agents |
| EP4296680A3 (en) | 2017-08-10 | 2024-03-20 | Grifols Diagnostic Solutions Inc. | An oligomerization tag comprising an immunoglobulin fc region and a polyhis domain |
| US11236173B2 (en) | 2017-08-16 | 2022-02-01 | Black Belt Therapeutics Limited | CD38 antibody |
| WO2019035938A1 (en) | 2017-08-16 | 2019-02-21 | Elstar Therapeutics, Inc. | MULTISPECIFIC MOLECULES BINDING TO BCMA AND USES THEREOF |
| US11542338B2 (en) | 2017-08-16 | 2023-01-03 | Black Belt Therapeutics Limited | CD38 modulating antibody |
| KR20200064096A (ko) | 2017-10-14 | 2020-06-05 | 싸이톰스 테라퓨틱스, 인크. | 항체, 활성화 가능한 항체, 이중특이적 항체 및 이중특이적 활성화 가능한 항체 및 이들의 사용 방법 |
| CA3113756A1 (en) * | 2018-09-25 | 2020-04-02 | Ichnos Sciences S.A. | Antibody quantification in biological samples |
| KR102353568B1 (ko) * | 2018-11-14 | 2022-01-20 | 주식회사 헬릭스미스 | 안정성이 향상된 항 c-Met 항체 또는 그의 항원 결합 단편 |
| EP3914616A1 (en) | 2019-01-23 | 2021-12-01 | Encefa | Cd31 competitors and uses thereof |
| EP3938398A2 (en) * | 2019-03-13 | 2022-01-19 | Ichnos Sciences S.A. | Non-consensus glycosylation of bispecific antibodies |
| TW202110887A (zh) * | 2019-05-23 | 2021-03-16 | 美商維洛斯生物公司 | 抗ror1/抗cd3雙特異性結合分子 |
| EP3984554A4 (en) * | 2019-06-11 | 2023-11-08 | ONO Pharmaceutical Co., Ltd. | IMMUNOSUPPRESSION AGENT |
| CN110551222B (zh) * | 2019-08-27 | 2023-06-06 | 重庆市畜牧科学院 | 一种新型双功能抗体及其用途 |
| WO2021063330A1 (zh) * | 2019-09-30 | 2021-04-08 | 和铂医药(苏州)有限公司 | 靶向cd3的抗体、双特异性抗体及其用途 |
| CN113493519B (zh) * | 2020-03-19 | 2022-12-27 | 浙江道尔生物科技有限公司 | 一种半衰期显著延长的治疗眼部血管新生疾病的融合蛋白 |
| CN115803340A (zh) * | 2020-04-24 | 2023-03-14 | 纪念斯隆凯特琳癌症中心 | 抗cd3抗体及其用途 |
| US11919956B2 (en) | 2020-05-14 | 2024-03-05 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (PSMA) and CD3 |
| CN115916824A (zh) * | 2020-06-17 | 2023-04-04 | Y-单克隆抗体制药有限公司 | 用于人类疾病治疗的cd38抗体 |
| MX2023001962A (es) | 2020-08-19 | 2023-04-26 | Xencor Inc | Composiciones anti-cd28. |
| EP4305065A1 (en) | 2021-03-10 | 2024-01-17 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and gpc3 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2541489T3 (es) * | 2004-02-06 | 2015-07-21 | Morphosys Ag | Anticuerpos humanos anti-CD38 y usos para ellos |
| RS59399B1 (sr) * | 2005-03-23 | 2019-11-29 | Genmab As | Antitela protiv cd38 za lečenje multiplog mijeloma |
| BRPI0618399B1 (pt) * | 2005-10-12 | 2023-10-03 | Morphosys Ag | Anticorpo específico anti-cd38 humano, composição de ácido nucleico, vetor de expressão, composição farmacêutica, uso do anticorpo e uso de uma composição farmacêutica |
| EP1914242A1 (en) * | 2006-10-19 | 2008-04-23 | Sanofi-Aventis | Novel anti-CD38 antibodies for the treatment of cancer |
| KR101747103B1 (ko) * | 2009-06-26 | 2017-06-14 | 리제너론 파마슈티칼스 인코포레이티드 | 천연 면역글로불린 포맷을 가지는 용이하게 분리된 이중특이성 항체 |
| BR112012017124C1 (pt) * | 2009-12-25 | 2021-08-31 | Chugai Pharmaceutical Co Ltd | Método para produzir e para purificar um multímero polipeptídico |
| DK2580243T3 (da) * | 2010-06-09 | 2020-01-13 | Genmab As | Antibodies against human cd38 |
| JOP20210044A1 (ar) * | 2010-12-30 | 2017-06-16 | Takeda Pharmaceuticals Co | الأجسام المضادة لـ cd38 |
| CA2812739A1 (en) * | 2011-03-25 | 2012-10-04 | Glenmark Pharmaceuticals S.A. | Hetero-dimeric immunoglobulins |
| IN2015MN00139A (zh) * | 2012-09-25 | 2015-10-16 | Glenmark Pharmaceuticals Sa | |
| US9486547B2 (en) * | 2012-11-05 | 2016-11-08 | Morphosys Ag | Radiolabelled antibody and uses thereof |
| AU2014343636A1 (en) * | 2013-11-04 | 2016-06-02 | Glenmark Pharmaceuticals S.A. | Production of T cell retargeting hetero-dimeric immunoglobulins |
-
2015
- 2015-11-02 MA MA040894A patent/MA40894A/fr unknown
- 2015-11-03 MY MYPI2017701499A patent/MY186929A/en unknown
- 2015-11-03 EA EA201790961A patent/EA039658B1/ru unknown
- 2015-11-03 CA CA2965745A patent/CA2965745C/en active Active
- 2015-11-03 MX MX2017005814A patent/MX2017005814A/es unknown
- 2015-11-03 PE PE2017000802A patent/PE20171041A1/es unknown
- 2015-11-03 EP EP15790129.9A patent/EP3215541A1/en not_active Withdrawn
- 2015-11-03 WO PCT/EP2015/075628 patent/WO2016071355A1/en active Application Filing
- 2015-11-03 BR BR112017009263-8A patent/BR112017009263A2/pt not_active Application Discontinuation
- 2015-11-03 SG SG11201703313SA patent/SG11201703313SA/en unknown
- 2015-11-03 CN CN201580072196.8A patent/CN107207596A/zh active Pending
- 2015-11-03 KR KR1020177015252A patent/KR20170078831A/ko not_active Application Discontinuation
- 2015-11-03 NZ NZ732019A patent/NZ732019A/en unknown
- 2015-11-03 AU AU2015341884A patent/AU2015341884B2/en active Active
- 2015-11-03 JP JP2017542319A patent/JP2018501297A/ja active Pending
-
2017
- 2017-04-23 IL IL251848A patent/IL251848A0/en unknown
- 2017-05-02 CL CL2017001090A patent/CL2017001090A1/es unknown
- 2017-05-03 PH PH12017500819A patent/PH12017500819A1/en unknown
- 2017-05-26 CO CONC2017/0005240A patent/CO2017005240A2/es unknown
-
2018
- 2018-03-12 HK HK18103440.0A patent/HK1244014A1/zh unknown
-
2019
- 2019-07-23 JP JP2019135318A patent/JP2019214582A/ja active Pending
-
2021
- 2021-08-02 JP JP2021126392A patent/JP7403505B2/ja active Active
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016071355A1 (en) | 2016-05-12 |
| JP7403505B2 (ja) | 2023-12-22 |
| CL2017001090A1 (es) | 2018-01-05 |
| NZ732019A (en) | 2022-07-29 |
| CN107207596A (zh) | 2017-09-26 |
| SG11201703313SA (en) | 2017-05-30 |
| KR20170078831A (ko) | 2017-07-07 |
| BR112017009263A2 (pt) | 2018-01-30 |
| JP2018501297A (ja) | 2018-01-18 |
| AU2015341884A1 (en) | 2017-06-08 |
| HK1244014A1 (zh) | 2018-07-27 |
| EA039658B1 (ru) | 2022-02-22 |
| JP2019214582A (ja) | 2019-12-19 |
| JP2021184722A (ja) | 2021-12-09 |
| EP3215541A1 (en) | 2017-09-13 |
| AU2015341884B2 (en) | 2020-09-17 |
| PH12017500819A1 (en) | 2017-10-02 |
| EA201790961A1 (ru) | 2017-10-31 |
| MA40894A (fr) | 2017-09-12 |
| CO2017005240A2 (es) | 2017-10-31 |
| PE20171041A1 (es) | 2017-07-19 |
| MY186929A (en) | 2021-08-26 |
| CA2965745A1 (en) | 2016-05-12 |
| MX2017005814A (es) | 2017-08-02 |
| IL251848A0 (en) | 2017-06-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7403505B2 (ja) | Ｃｄ３／ｃｄ３８ ｔ細胞再標的化ヘテロ二量体免疫グロブリン及びその製造方法 | |
| US11891454B2 (en) | Production of T cell retargeting hetero-dimeric immunoglobulins | |
| US11845795B2 (en) | NKp46 binding proteins | |
| US12006367B2 (en) | CD3/CD38 T cell retargeting hetero-dimeric immunoglobulins and methods of their production | |
| OA17758A (en) | Production of T cell retargeting heterodimeric immunoglobulins. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20200908 |
|
| EEER | Examination request |
Effective date: 20200908 |
|
| EEER | Examination request |
Effective date: 20200908 |
|
| EEER | Examination request |
Effective date: 20200908 |
|
| EEER | Examination request |
Effective date: 20200908 |
|
| EEER | Examination request |
Effective date: 20200908 |
|
| EEER | Examination request |
Effective date: 20200908 |
|
| EEER | Examination request |
Effective date: 20200908 |