ES2829499T3 - Método para la selección de anticuerpos contra BCMA - Google Patents
Método para la selección de anticuerpos contra BCMAInfo
- Publication number
- ES2829499T3 ES2829499T3 ES14702616T ES14702616T ES2829499T3 ES 2829499 T3 ES2829499 T3 ES 2829499T3 ES 14702616 T ES14702616 T ES 14702616T ES 14702616 T ES14702616 T ES 14702616T ES 2829499 T3 ES2829499 T3 ES 2829499T3
- Authority
- ES
- Spain
- Prior art keywords
- bcma
- antibody
- cells
- antibodies
- seq
- 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
- 238000000034 method Methods 0.000 title claims description 59
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 title description 218
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 title description 218
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 title description 212
- 210000003719 b-lymphocyte Anatomy 0.000 claims abstract description 17
- 102100035359 Cerebellar degeneration-related protein 2-like Human genes 0.000 claims abstract description 13
- 101000737792 Homo sapiens Cerebellar degeneration-related protein 2-like Proteins 0.000 claims abstract description 13
- 230000011748 cell maturation Effects 0.000 claims abstract description 4
- 210000004027 cell Anatomy 0.000 claims description 387
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 112
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims description 47
- 239000013598 vector Substances 0.000 claims description 35
- 208000034578 Multiple myelomas Diseases 0.000 claims description 33
- 238000011282 treatment Methods 0.000 claims description 27
- 239000003814 drug Substances 0.000 claims description 22
- 150000007523 nucleic acids Chemical class 0.000 claims description 22
- 102000039446 nucleic acids Human genes 0.000 claims description 21
- 108020004707 nucleic acids Proteins 0.000 claims description 21
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 230000015572 biosynthetic process Effects 0.000 claims description 15
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 10
- 238000003786 synthesis reaction Methods 0.000 claims description 9
- 230000030833 cell death Effects 0.000 claims description 6
- 208000021161 Plasma cell disease Diseases 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims 1
- 230000027455 binding Effects 0.000 description 216
- 108010065323 Tumor Necrosis Factor Ligand Superfamily Member 13 Proteins 0.000 description 191
- 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 description 128
- 101710181056 Tumor necrosis factor ligand superfamily member 13B Proteins 0.000 description 122
- 210000001744 T-lymphocyte Anatomy 0.000 description 118
- 102000003945 NF-kappa B Human genes 0.000 description 84
- 108010057466 NF-kappa B Proteins 0.000 description 84
- 230000004913 activation Effects 0.000 description 82
- 101000801255 Homo sapiens Tumor necrosis factor receptor superfamily member 17 Proteins 0.000 description 79
- 239000000872 buffer Substances 0.000 description 79
- 201000000050 myeloid neoplasm Diseases 0.000 description 79
- 108090000623 proteins and genes Proteins 0.000 description 79
- 102000046935 human TNFRSF17 Human genes 0.000 description 76
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 59
- 102000004169 proteins and genes Human genes 0.000 description 58
- 235000018102 proteins Nutrition 0.000 description 56
- 230000002829 reductive effect Effects 0.000 description 53
- 239000003446 ligand Substances 0.000 description 51
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 49
- 238000010186 staining Methods 0.000 description 48
- 230000001419 dependent effect Effects 0.000 description 40
- 238000002965 ELISA Methods 0.000 description 37
- 239000012636 effector Substances 0.000 description 36
- 239000012634 fragment Substances 0.000 description 33
- 235000001014 amino acid Nutrition 0.000 description 31
- 230000014509 gene expression Effects 0.000 description 31
- 241000699670 Mus sp. Species 0.000 description 30
- 239000000427 antigen Substances 0.000 description 30
- 102000036639 antigens Human genes 0.000 description 30
- 108091007433 antigens Proteins 0.000 description 30
- 230000000903 blocking effect Effects 0.000 description 30
- 108020004414 DNA Proteins 0.000 description 29
- 241001529936 Murinae Species 0.000 description 29
- 238000011534 incubation Methods 0.000 description 27
- 239000002953 phosphate buffered saline Substances 0.000 description 27
- 238000000684 flow cytometry Methods 0.000 description 26
- 239000013604 expression vector Substances 0.000 description 25
- 230000006870 function Effects 0.000 description 25
- 230000001965 increasing effect Effects 0.000 description 25
- 229940024606 amino acid Drugs 0.000 description 24
- 239000011780 sodium chloride Substances 0.000 description 24
- 206010028980 Neoplasm Diseases 0.000 description 23
- 150000001413 amino acids Chemical class 0.000 description 23
- 210000004369 blood Anatomy 0.000 description 22
- 239000008280 blood Substances 0.000 description 22
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 21
- 238000001514 detection method Methods 0.000 description 20
- 108090000765 processed proteins & peptides Proteins 0.000 description 19
- 241000699666 Mus <mouse, genus> Species 0.000 description 18
- 239000000284 extract Substances 0.000 description 18
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 18
- 230000001404 mediated effect Effects 0.000 description 17
- 102000004196 processed proteins & peptides Human genes 0.000 description 17
- 239000006285 cell suspension Substances 0.000 description 16
- 210000004180 plasmocyte Anatomy 0.000 description 16
- 229920001184 polypeptide Polymers 0.000 description 16
- 241000588724 Escherichia coli Species 0.000 description 15
- 238000003556 assay Methods 0.000 description 15
- 210000001185 bone marrow Anatomy 0.000 description 15
- 238000005119 centrifugation Methods 0.000 description 15
- 238000010494 dissociation reaction Methods 0.000 description 15
- 230000005593 dissociations Effects 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 201000011510 cancer Diseases 0.000 description 14
- 230000003833 cell viability Effects 0.000 description 14
- 239000012228 culture supernatant Substances 0.000 description 14
- 230000004927 fusion Effects 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 14
- 239000006228 supernatant Substances 0.000 description 14
- 238000001890 transfection Methods 0.000 description 14
- 210000004881 tumor cell Anatomy 0.000 description 14
- 238000012286 ELISA Assay Methods 0.000 description 13
- 125000003275 alpha amino acid group Chemical group 0.000 description 13
- 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 13
- 239000000203 mixture Substances 0.000 description 13
- 210000002966 serum Anatomy 0.000 description 13
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 12
- 206010052779 Transplant rejections Diseases 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 230000035772 mutation Effects 0.000 description 12
- 108020004635 Complementary DNA Proteins 0.000 description 11
- 108060003951 Immunoglobulin Proteins 0.000 description 11
- 239000012980 RPMI-1640 medium Substances 0.000 description 11
- 239000007983 Tris buffer Substances 0.000 description 11
- 239000000611 antibody drug conjugate Substances 0.000 description 11
- 229940049595 antibody-drug conjugate Drugs 0.000 description 11
- 102000018358 immunoglobulin Human genes 0.000 description 11
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 11
- 108010028006 B-Cell Activating Factor Proteins 0.000 description 10
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 10
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 10
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 10
- 108091028043 Nucleic acid sequence Proteins 0.000 description 10
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 10
- 238000004113 cell culture Methods 0.000 description 10
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical group O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 10
- 230000003993 interaction Effects 0.000 description 10
- 210000003734 kidney Anatomy 0.000 description 10
- 230000004048 modification Effects 0.000 description 10
- 238000012986 modification Methods 0.000 description 10
- 239000002245 particle Substances 0.000 description 10
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 10
- 239000013612 plasmid Substances 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 9
- 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 9
- 108010087819 Fc receptors Proteins 0.000 description 9
- 102000009109 Fc receptors Human genes 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 108090000190 Thrombin Proteins 0.000 description 9
- 230000001154 acute effect Effects 0.000 description 9
- 125000000539 amino acid group Chemical group 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 239000002299 complementary DNA Substances 0.000 description 9
- 238000010790 dilution Methods 0.000 description 9
- 239000012895 dilution Substances 0.000 description 9
- 210000004408 hybridoma Anatomy 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 229960004072 thrombin Drugs 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- 241000283707 Capra Species 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 239000011324 bead Substances 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 238000002054 transplantation Methods 0.000 description 8
- 101000642536 Apis mellifera Venom serine protease 34 Proteins 0.000 description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- 108700022150 Designed Ankyrin Repeat Proteins Proteins 0.000 description 7
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 7
- 108010076504 Protein Sorting Signals Proteins 0.000 description 7
- 108010090804 Streptavidin Proteins 0.000 description 7
- 238000003149 assay kit Methods 0.000 description 7
- 239000011230 binding agent Substances 0.000 description 7
- 210000004748 cultured cell Anatomy 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000012894 fetal calf serum Substances 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000011160 research Methods 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 230000011664 signaling Effects 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 101710154606 Hemagglutinin Proteins 0.000 description 6
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 6
- 241000282567 Macaca fascicularis Species 0.000 description 6
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 6
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 6
- 101710176177 Protein A56 Proteins 0.000 description 6
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 6
- 102100040247 Tumor necrosis factor Human genes 0.000 description 6
- 150000001720 carbohydrates Chemical class 0.000 description 6
- 238000010367 cloning Methods 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 230000007717 exclusion Effects 0.000 description 6
- 239000013613 expression plasmid Substances 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 210000004602 germ cell Anatomy 0.000 description 6
- 239000000185 hemagglutinin Substances 0.000 description 6
- 230000001665 lethal effect Effects 0.000 description 6
- 238000002823 phage display Methods 0.000 description 6
- 230000010076 replication Effects 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 238000001542 size-exclusion chromatography Methods 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- 238000007920 subcutaneous administration Methods 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 230000010474 transient expression Effects 0.000 description 6
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- 108091035707 Consensus sequence Proteins 0.000 description 5
- 108010070675 Glutathione transferase Proteins 0.000 description 5
- 239000007995 HEPES buffer Substances 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 239000004365 Protease Substances 0.000 description 5
- 102000001708 Protein Isoforms Human genes 0.000 description 5
- 108010029485 Protein Isoforms Proteins 0.000 description 5
- 229920002684 Sepharose Polymers 0.000 description 5
- 229920004890 Triton X-100 Polymers 0.000 description 5
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 230000009089 cytolysis Effects 0.000 description 5
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 5
- 230000007783 downstream signaling Effects 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 210000003527 eukaryotic cell Anatomy 0.000 description 5
- 108020001507 fusion proteins Proteins 0.000 description 5
- 102000037865 fusion proteins Human genes 0.000 description 5
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 230000016784 immunoglobulin production Effects 0.000 description 5
- 230000010354 integration Effects 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 231100000518 lethal Toxicity 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- 238000010172 mouse model Methods 0.000 description 5
- 239000013642 negative control Substances 0.000 description 5
- 108010087904 neutravidin Proteins 0.000 description 5
- 230000008520 organization Effects 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- 239000001509 sodium citrate Substances 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 4
- 229920000936 Agarose Polymers 0.000 description 4
- 102000016605 B-Cell Activating Factor Human genes 0.000 description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 241000701022 Cytomegalovirus Species 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 102000005720 Glutathione transferase Human genes 0.000 description 4
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 4
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 4
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 4
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 4
- 229930182816 L-glutamine Natural products 0.000 description 4
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 4
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 4
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 4
- 239000013504 Triton X-100 Substances 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 238000001042 affinity chromatography Methods 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 210000000709 aorta Anatomy 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000001110 calcium chloride Substances 0.000 description 4
- 229910001628 calcium chloride Inorganic materials 0.000 description 4
- 235000011148 calcium chloride Nutrition 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000000432 density-gradient centrifugation Methods 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 4
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 230000013595 glycosylation Effects 0.000 description 4
- 238000006206 glycosylation reaction Methods 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 238000005734 heterodimerization reaction Methods 0.000 description 4
- 230000001900 immune effect Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000004020 luminiscence type Methods 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 229920000136 polysorbate Polymers 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 235000019419 proteases Nutrition 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 229960004641 rituximab Drugs 0.000 description 4
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 238000003146 transient transfection Methods 0.000 description 4
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 3
- 102000008102 Ankyrins Human genes 0.000 description 3
- 108010049777 Ankyrins Proteins 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 238000001712 DNA sequencing Methods 0.000 description 3
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 3
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 3
- 101000851434 Homo sapiens Tumor necrosis factor ligand superfamily member 13B Proteins 0.000 description 3
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 3
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 101100425747 Mus musculus Tnfrsf17 gene Proteins 0.000 description 3
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 3
- 229930193140 Neomycin Natural products 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 238000012408 PCR amplification Methods 0.000 description 3
- 102000003992 Peroxidases Human genes 0.000 description 3
- 239000012979 RPMI medium Substances 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000012505 Superdex™ Substances 0.000 description 3
- 230000006044 T cell activation Effects 0.000 description 3
- 230000010782 T cell mediated cytotoxicity Effects 0.000 description 3
- 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 3
- 230000003213 activating effect Effects 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 230000003872 anastomosis Effects 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 239000012148 binding buffer Substances 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000000562 conjugate Substances 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 239000002254 cytotoxic agent Substances 0.000 description 3
- 231100000599 cytotoxic agent Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 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 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 239000000833 heterodimer Substances 0.000 description 3
- 102000050326 human TNFSF13B Human genes 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000002843 lactate dehydrogenase assay Methods 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- AEMBWNDIEFEPTH-UHFFFAOYSA-N n-tert-butyl-n-ethylnitrous amide Chemical compound CCN(N=O)C(C)(C)C AEMBWNDIEFEPTH-UHFFFAOYSA-N 0.000 description 3
- 230000001338 necrotic effect Effects 0.000 description 3
- 229960004927 neomycin Drugs 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 229920001542 oligosaccharide Polymers 0.000 description 3
- 150000002482 oligosaccharides Chemical class 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 108040007629 peroxidase activity proteins Proteins 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 201000001474 proteinuria Diseases 0.000 description 3
- 230000005180 public health Effects 0.000 description 3
- 238000000163 radioactive labelling Methods 0.000 description 3
- 150000003384 small molecules Chemical group 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 210000004988 splenocyte Anatomy 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 235000011149 sulphuric acid Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000003151 transfection method Methods 0.000 description 3
- 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 3
- 210000003462 vein Anatomy 0.000 description 3
- 210000001631 vena cava inferior Anatomy 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- 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 2
- HKZAAJSTFUZYTO-LURJTMIESA-N (2s)-2-[[2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoic acid Chemical group NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O HKZAAJSTFUZYTO-LURJTMIESA-N 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- ZBQCCTCQUCOXBO-UHFFFAOYSA-N 4-(4-aminophenyl)-2,2,6,6-tetramethylcyclohex-3-en-1-amine Chemical compound CC1(C)C(N)C(C)(C)CC(C=2C=CC(N)=CC=2)=C1 ZBQCCTCQUCOXBO-UHFFFAOYSA-N 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 208000037914 B-cell disorder Diseases 0.000 description 2
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 2
- 208000008720 Bone Marrow Neoplasms Diseases 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 206010063209 Chronic allograft nephropathy Diseases 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 2
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 2
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 2
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 2
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 2
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 2
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 2
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 2
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 2
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 2
- 101000795167 Homo sapiens Tumor necrosis factor receptor superfamily member 13B Proteins 0.000 description 2
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 2
- 206010020631 Hypergammaglobulinaemia benign monoclonal Diseases 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 239000007836 KH2PO4 Substances 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
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-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
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 2
- 239000007987 MES buffer Substances 0.000 description 2
- 239000007993 MOPS buffer Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 102000016943 Muramidase Human genes 0.000 description 2
- 108010014251 Muramidase Proteins 0.000 description 2
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 239000012124 Opti-MEM Substances 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 208000035415 Reinfection Diseases 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 101710137500 T7 RNA polymerase Proteins 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 102100029675 Tumor necrosis factor receptor superfamily member 13B Human genes 0.000 description 2
- 102100033726 Tumor necrosis factor receptor superfamily member 17 Human genes 0.000 description 2
- 206010054094 Tumour necrosis Diseases 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 229960003121 arginine Drugs 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 238000007845 assembly PCR Methods 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 238000007413 biotinylation Methods 0.000 description 2
- 230000006287 biotinylation Effects 0.000 description 2
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 2
- 229960003008 blinatumomab Drugs 0.000 description 2
- 201000006491 bone marrow cancer Diseases 0.000 description 2
- 238000012832 cell culture technique Methods 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 230000004186 co-expression Effects 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 230000024203 complement activation Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000004154 complement system Effects 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 229940109239 creatinine Drugs 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000005714 functional activity Effects 0.000 description 2
- 201000006585 gastric adenocarcinoma Diseases 0.000 description 2
- 238000002523 gelfiltration Methods 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
- 230000001434 glomerular Effects 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 2
- 230000012010 growth 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
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 238000001597 immobilized metal affinity chromatography Methods 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 229940127121 immunoconjugate Drugs 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229940065638 intron a Drugs 0.000 description 2
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- 229960000274 lysozyme Drugs 0.000 description 2
- 239000004325 lysozyme Substances 0.000 description 2
- 235000010335 lysozyme Nutrition 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 201000005328 monoclonal gammopathy of uncertain significance Diseases 0.000 description 2
- 238000004264 monolayer culture Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- 230000036963 noncompetitive effect Effects 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 108091033319 polynucleotide Proteins 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
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000033300 receptor internalization Effects 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 210000002796 renal vein Anatomy 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 210000003705 ribosome Anatomy 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 229940054269 sodium pyruvate Drugs 0.000 description 2
- 230000000392 somatic effect Effects 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 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 2
- 239000000126 substance Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 239000012224 working solution Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- YDMBNDUHUNWWRP-VJBWXMMDSA-N (2s)-1-[(2r)-2-amino-3-phenylpropanoyl]-n-[(2s)-5-(diaminomethylideneamino)-1-(4-nitroanilino)-1-oxopentan-2-yl]piperidine-2-carboxamide Chemical compound C([C@@H](N)C(=O)N1[C@@H](CCCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)C1=CC=CC=C1 YDMBNDUHUNWWRP-VJBWXMMDSA-N 0.000 description 1
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- BHNQPLPANNDEGL-UHFFFAOYSA-N 2-(4-octylphenoxy)ethanol Chemical compound CCCCCCCCC1=CC=C(OCCO)C=C1 BHNQPLPANNDEGL-UHFFFAOYSA-N 0.000 description 1
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-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
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 102000051485 Bcl-2 family Human genes 0.000 description 1
- 108700038897 Bcl-2 family Proteins 0.000 description 1
- 102100026596 Bcl-2-like protein 1 Human genes 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010061728 Bone lesion Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 239000012739 FreeStyle 293 Expression medium Substances 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- 208000022461 Glomerular disease Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 208000034706 Graft dysfunction Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101001056180 Homo sapiens Induced myeloid leukemia cell differentiation protein Mcl-1 Proteins 0.000 description 1
- 101001033233 Homo sapiens Interleukin-10 Proteins 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- 101001002709 Homo sapiens Interleukin-4 Proteins 0.000 description 1
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 102100026539 Induced myeloid leukemia cell differentiation protein Mcl-1 Human genes 0.000 description 1
- 239000007760 Iscove's Modified Dulbecco's Medium Substances 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical group NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-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
- 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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-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
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 101710099301 Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 240000004658 Medicago sativa Species 0.000 description 1
- 235000010624 Medicago sativa Nutrition 0.000 description 1
- 206010060880 Monoclonal gammopathy Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 208000002774 Paraproteinemias Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 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 1
- 108010055817 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Proteins 0.000 description 1
- 102000000447 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000006994 Precancerous Conditions 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
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- 108010039286 S 2238 Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 201000004283 Shwachman-Diamond syndrome Diseases 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000004268 Sodium erythorbin Substances 0.000 description 1
- 101000677856 Stenotrophomonas maltophilia (strain K279a) Actin-binding protein Smlt3054 Proteins 0.000 description 1
- 208000018359 Systemic autoimmune disease Diseases 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 1
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 1
- 102000002933 Thioredoxin Human genes 0.000 description 1
- 108010079911 Thioredoxin-disulfide reductase Proteins 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 206010060872 Transplant failure Diseases 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
- 206010053614 Type III immune complex mediated reaction Diseases 0.000 description 1
- 108091005966 Type III transmembrane proteins Proteins 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 101100082060 Xenopus laevis pou5f1.1 gene Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 238000012436 analytical size exclusion chromatography Methods 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 229940125644 antibody drug Drugs 0.000 description 1
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000003881 arterial anastomosis Effects 0.000 description 1
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 238000013357 binding ELISA Methods 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
- 229960001467 bortezomib Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- ZEWYCNBZMPELPF-UHFFFAOYSA-J calcium;potassium;sodium;2-hydroxypropanoic acid;sodium;tetrachloride Chemical compound [Na].[Na+].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[Ca+2].CC(O)C(O)=O ZEWYCNBZMPELPF-UHFFFAOYSA-J 0.000 description 1
- 229960003669 carbenicillin Drugs 0.000 description 1
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 238000010822 cell death assay Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 238000012054 celltiter-glo Methods 0.000 description 1
- 230000005889 cellular cytotoxicity Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 230000009260 cross reactivity Effects 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
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000016396 cytokine production Effects 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
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000022811 deglycosylation Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 238000010217 densitometric analysis Methods 0.000 description 1
- 238000013461 design 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
- 239000000539 dimer Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 230000033581 fucosylation Effects 0.000 description 1
- 101150023212 fut8 gene 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
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 229960000789 guanidine hydrochloride Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 238000007489 histopathology method Methods 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 102000052620 human IL10 Human genes 0.000 description 1
- 102000055229 human IL4 Human genes 0.000 description 1
- 102000052611 human IL6 Human genes 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 238000011862 kidney biopsy Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 229940124280 l-arginine Drugs 0.000 description 1
- 210000001821 langerhans cell Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004698 lymphocyte 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
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 108010083819 mannosyl-oligosaccharide 1,3 - 1,6-alpha-mannosidase Proteins 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000000885 nephron Anatomy 0.000 description 1
- 238000007857 nested PCR Methods 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 230000003448 neutrophilic effect Effects 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000000737 periodic effect Effects 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 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
- 206010035485 plasmacytosis Diseases 0.000 description 1
- 238000013492 plasmid preparation Methods 0.000 description 1
- 229920000233 poly(alkylene oxides) Polymers 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 230000001686 pro-survival effect Effects 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 239000013643 reference control Substances 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 210000002254 renal artery Anatomy 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 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
- 210000000952 spleen Anatomy 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 108060008226 thioredoxin Proteins 0.000 description 1
- 229940094937 thioredoxin Drugs 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 208000025883 type III hypersensitivity disease Diseases 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
- 210000000626 ureter Anatomy 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 210000005253 yeast cell Anatomy 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
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- 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
-
- 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
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3061—Blood cells
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- 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
- C07K2317/56—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
- C07K2317/66—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
- C07K2317/71—Decreased effector function due to an Fc-modification
-
- 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
- C07K2317/72—Increased effector function due to an Fc-modification
-
- 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
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- 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
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/715—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons
- G01N2333/7151—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons for tumor necrosis factor [TNF]; for lymphotoxin [LT]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/04—Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cell Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- Microbiology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- General Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Food Science & Technology (AREA)
- Pathology (AREA)
- Endocrinology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13000570.5A EP2762496A1 (en) | 2013-02-05 | 2013-02-05 | Method for the selection of antibodies against BCMA |
| EP13000571.3A EP2762497A1 (en) | 2013-02-05 | 2013-02-05 | Bispecific antibodies against CD3epsilon and BCMA |
| PCT/EP2014/052189 WO2014122143A1 (en) | 2013-02-05 | 2014-02-05 | Method for the selection of antibodies against bcma |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2829499T3 true ES2829499T3 (es) | 2021-06-01 |
Family
ID=50033579
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14702616T Active ES2829499T3 (es) | 2013-02-05 | 2014-02-05 | Método para la selección de anticuerpos contra BCMA |
| ES14705304.5T Active ES2667420T3 (es) | 2013-02-05 | 2014-02-05 | Anticuerpos biespecíficos contra cd3epsilon y bcma |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14705304.5T Active ES2667420T3 (es) | 2013-02-05 | 2014-02-05 | Anticuerpos biespecíficos contra cd3epsilon y bcma |
Country Status (8)
| Country | Link |
|---|---|
| US (4) | US10077315B2 (enExample) |
| EP (3) | EP2953974B1 (enExample) |
| JP (4) | JP2016507523A (enExample) |
| CN (3) | CN111848796A (enExample) |
| DK (1) | DK2953972T3 (enExample) |
| ES (2) | ES2829499T3 (enExample) |
| PL (1) | PL2953972T3 (enExample) |
| WO (2) | WO2014122143A1 (enExample) |
Families Citing this family (190)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7608693B2 (en) | 2006-10-02 | 2009-10-27 | Regeneron Pharmaceuticals, Inc. | High affinity human antibodies to human IL-4 receptor |
| US20130058936A1 (en) | 2011-08-23 | 2013-03-07 | Peter Bruenker | Bispecific antibodies specific for t-cell activating antigens and a tumor antigen and methods of use |
| 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 |
| NZ630178A (en) | 2012-09-07 | 2017-06-30 | Regeneron Pharma | Methods for treating atopic dermatitis by administering an il-4r antagonist |
| MX2015003616A (es) | 2012-10-08 | 2015-06-05 | Roche Glycart Ag | Anticuerpos sin fc que comprenden dos fragmentos fab y metodos de uso. |
| EP2953974B1 (en) | 2013-02-05 | 2017-12-20 | EngMab Sàrl | Bispecific antibodies against cd3epsilon and bcma |
| PT2961771T (pt) | 2013-02-26 | 2020-02-28 | Roche Glycart Ag | Moléculas de ligação ao antigénio biespecíficas para ativação das células t, específicas para cd3 e cea |
| TWI755763B (zh) | 2013-06-04 | 2022-02-21 | 美商再生元醫藥公司 | 藉由投與il-4r抑制劑以治療過敏及增強過敏原-特異之免疫療法的方法 |
| TWI682781B (zh) | 2013-07-11 | 2020-01-21 | 美商再生元醫藥公司 | 藉由投與ｉｌ－４ｒ抑制劑治療嗜酸性食道炎的方法 |
| GB201317928D0 (en) * | 2013-10-10 | 2013-11-27 | Ucl Business Plc | Molecule |
| KR102480433B1 (ko) * | 2014-02-07 | 2022-12-21 | 맥마스터 유니버시티 | 3기능성 t 세포-항원 커플러 및 이의 제조 방법 및 용도 |
| KR20160120735A (ko) | 2014-02-28 | 2016-10-18 | 리제너론 파아마슈티컬스, 인크. | Ｉｌ-4ｒ 길항제의 투여에 의한 피부 감염의 치료 방법 |
| CR20170032A (es) | 2014-08-04 | 2017-04-04 | Hoffmann La Roche | Moleculas biespecíficas de unión a antígeno activadoras de células t |
| ES2850325T3 (es) | 2014-10-09 | 2021-08-27 | Engmab Sarl | Anticuerpos biespecíficos contra CD3epsilon y ROR1 |
| EP3023437A1 (en) * | 2014-11-20 | 2016-05-25 | EngMab AG | Bispecific antibodies against CD3epsilon and BCMA |
| PL3221357T3 (pl) | 2014-11-20 | 2020-11-02 | F. Hoffmann-La Roche Ag | Wspólne łańcuchy lekkie i sposoby zastosowania |
| HRP20240959T1 (hr) | 2014-11-20 | 2024-10-25 | F. Hoffmann - La Roche Ag | Kombinirana terapija bispecifičnom antigen vezujućom molekulom koja aktivira t stanice i antagonistom vezivanja osi pd-1 |
| MX2017006571A (es) | 2014-11-20 | 2017-09-29 | Hoffmann La Roche | Moleculas de union a antigeno biespecificas activadoras de celulas t. |
| EP3029068A1 (en) * | 2014-12-03 | 2016-06-08 | EngMab AG | Bispecific antibodies against CD3epsilon and BCMA for use in the treatment of diseases |
| TWI703159B (zh) | 2015-04-13 | 2020-09-01 | 美商輝瑞股份有限公司 | Bcma特異性治療性抗體及其用途 |
| SG11201707089WA (en) | 2015-04-13 | 2017-10-30 | Pfizer | Chimeric antigen receptors targeting b-cell maturation antigen |
| DK3298033T4 (da) | 2015-05-18 | 2023-10-02 | Tcr2 Therapeutics Inc | Sammensætninger og medicinske anvendelser til tcr-reprogrammering under anvendelse af fusionsproteiner |
| 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 |
| EA039859B1 (ru) | 2015-07-31 | 2022-03-21 | Эмджен Рисерч (Мюник) Гмбх | Биспецифические конструкты антител, связывающие egfrviii и cd3 |
| 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 |
| TWI744242B (zh) | 2015-07-31 | 2021-11-01 | 德商安美基研究（慕尼黑）公司 | Egfrviii及cd3抗體構築體 |
| HRP20200390T1 (hr) * | 2015-08-03 | 2020-06-12 | Engmab Sàrl | Monoklonska antitijela protiv humanog antigena starenja b stanica (bcma) |
| CN105384825B (zh) | 2015-08-11 | 2018-06-01 | 南京传奇生物科技有限公司 | 一种基于单域抗体的双特异性嵌合抗原受体及其应用 |
| UA127515C2 (uk) | 2015-08-17 | 2023-09-20 | Янссен Байотек, Інк. | Антитіло до всма, біспецифічна антигензв'язувальна молекула, що зв'язує всма і cd3, і їх використання |
| AR106188A1 (es) | 2015-10-01 | 2017-12-20 | Hoffmann La Roche | Anticuerpos anti-cd19 humano humanizados y métodos de utilización |
| MA43025A (fr) | 2015-10-02 | 2021-05-26 | Hoffmann La Roche | Molécules bispécifiques de liaison à l'antigène activant les lymphocytes t anti-ceaxcd3 |
| EP4026848A1 (en) | 2015-12-09 | 2022-07-13 | F. Hoffmann-La Roche AG | Type ii anti-cd20 antibody for reducing the cytokine release syndrome |
| AU2017205089B2 (en) | 2016-01-08 | 2023-10-05 | F. Hoffmann-La Roche Ag | Methods of treating CEA-positive cancers using PD-1 axis binding antagonists and anti-CEA/anti-CD3 bispecific antibodies |
| UA126657C2 (uk) * | 2016-02-03 | 2023-01-11 | Емджен Рісерч (Мюнік) Ґмбг | ОДНОЛАНЦЮГОВА КОНСТРУКЦІЯ АНТИТІЛА ДО BCMA І CD3<font face="Symbol">e</font> |
| HUE060504T2 (hu) | 2016-02-03 | 2023-03-28 | Amgen Res Munich Gmbh | PSMA és CD3 bispecifikus T-sejthez kötõ ellenanyag-konstrukciók |
| CN116063503A (zh) * | 2016-02-17 | 2023-05-05 | 思进股份有限公司 | Bcma抗体和其用以治疗癌症和免疫病症的用途 |
| KR20180118175A (ko) | 2016-03-04 | 2018-10-30 | 노파르티스 아게 | 다중 키메라 항원 수용체 (car) 분자를 발현하는 세포 및 그에 따른 용도 |
| MX2018011542A (es) | 2016-03-22 | 2019-02-07 | Hoffmann La Roche | Moleculas biespecificas de celulas t activadas por proteasas. |
| AR108067A1 (es) * | 2016-04-01 | 2018-07-11 | Kite Pharma Inc | Moléculas de unión y métodos de uso de los mismos |
| CN109328074A (zh) | 2016-04-01 | 2019-02-12 | 凯德药业股份有限公司 | 嵌合抗原和t细胞受体及使用的方法 |
| CA3177398A1 (en) | 2016-04-01 | 2017-10-05 | Kite Pharma, Inc. | Chimeric receptors and methods of use thereof |
| PL3443096T3 (pl) | 2016-04-15 | 2023-06-19 | Novartis Ag | Kompozycje i sposoby do selektywnej ekspresji chimerycznych receptorów antygenowych |
| WO2017223111A1 (en) | 2016-06-21 | 2017-12-28 | Teneobio, Inc. | Cd3 binding antibodies |
| JP2019527696A (ja) | 2016-08-01 | 2019-10-03 | ノバルティス アーゲー | プロｍ２マクロファージ分子の阻害剤と組み合わせてキメラ抗原受容体を用いる癌の処置 |
| JP7109789B2 (ja) | 2016-08-02 | 2022-08-01 | ティーシーアール２ セラピューティクス インク． | 融合タンパク質を使用したｔｃｒの再プログラム化のための組成物及び方法 |
| US11771743B2 (en) | 2016-09-01 | 2023-10-03 | Regeneron Pharmaceuticals, Inc. | Methods for preventing or treating allergy by administering an IL-4R antagonist |
| US20180064758A1 (en) * | 2016-09-05 | 2018-03-08 | Ucl Business Plc | Chimeric antigen receptor |
| MY200988A (en) * | 2016-09-14 | 2024-01-27 | Teneobio Inc | CD3 Binding Antibodies |
| PL3519437T3 (pl) | 2016-09-30 | 2022-01-17 | F. Hoffmann-La Roche Ag | Przeciwciała dwuswoiste przeciwko p95HER2 |
| CA3036745A1 (en) | 2016-10-07 | 2018-04-12 | TCR2 Therapeutics Inc. | Compositions and methods for t-cell receptors reprogramming using fusion proteins |
| IL266424B2 (en) * | 2016-11-02 | 2023-09-01 | Engmab Sarl | A bispecific antibody against bcma and cd3 and an immunological drug for combined treatment in multiple myeloma |
| CA3044593A1 (en) | 2016-11-22 | 2018-05-31 | TCR2 Therapeutics Inc. | Compositions and methods for tcr reprogramming using fusion proteins |
| EP3559035A1 (en) | 2016-12-21 | 2019-10-30 | TeneoBio, Inc. | Anti-bcma heavy chain-only antibodies |
| ES3039621T3 (en) * | 2016-12-22 | 2025-10-23 | Daiichi Sankyo Co Ltd | Anti-cd3 antibody, and molecule containing said antibody |
| CN108341872B (zh) * | 2017-01-23 | 2020-05-19 | 科济生物医药（上海）有限公司 | 靶向bcma的抗体及其应用 |
| WO2018144535A1 (en) | 2017-01-31 | 2018-08-09 | Novartis Ag | Treatment of cancer using chimeric t cell receptor proteins having multiple specificities |
| JP7231549B2 (ja) * | 2017-02-06 | 2023-03-01 | デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド | 抗体媒介性受容体シグナル伝達を増強するための組成物及び方法 |
| JP2020506971A (ja) | 2017-02-08 | 2020-03-05 | ドラゴンフライ セラピューティクス， インコーポレイテッド | ナチュラルキラー細胞の活性化のための多重特異性結合タンパク質およびがんを処置するためのその治療的使用 |
| MY205850A (en) * | 2017-02-10 | 2024-11-15 | Dragonfly Therapeutics Inc | Proteins binding bcma, nkg2d and cd16 |
| CN108456250B (zh) * | 2017-02-17 | 2025-11-28 | 恺兴生命科技(上海)有限公司 | 靶向il-13ra2的抗体及其应用 |
| WO2018151836A1 (en) | 2017-02-17 | 2018-08-23 | Fred Hutchinson Cancer Research Center | Combination therapies for treatment of bcma-related cancers and autoimmune disorders |
| SG11201907646YA (en) | 2017-02-20 | 2019-09-27 | Dragonfly Therapeutics Inc | Proteins binding her2, nkg2d and cd16 |
| EP3589655B1 (en) | 2017-02-28 | 2022-10-26 | Affimed GmbH | Tandem-diabody for cd16a-directed nk-cell engagement |
| EP3615055A1 (en) | 2017-04-28 | 2020-03-04 | Novartis AG | Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor |
| US20200179511A1 (en) | 2017-04-28 | 2020-06-11 | Novartis Ag | Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor |
| US11166985B2 (en) | 2017-05-12 | 2021-11-09 | Crispr Therapeutics Ag | Materials and methods for engineering cells and uses thereof in immuno-oncology |
| EP3621981A2 (en) | 2017-05-12 | 2020-03-18 | CRISPR Therapeutics AG | Materials and methods for engineering cells and uses thereof in immuno-oncology |
| EP3625253A4 (en) | 2017-05-16 | 2021-03-24 | Scalmibio, Inc. | ACTIVABLE ANTIBODIES AND THEIR METHODS OF USE |
| CN118146370A (zh) | 2017-06-20 | 2024-06-07 | 特纳奥尼股份有限公司 | 仅有重链的抗bcma抗体 |
| CA3067584A1 (en) | 2017-06-20 | 2018-12-27 | Teneobio, Inc. | Anti-bcma heavy chain-only antibodies |
| WO2019028367A1 (en) | 2017-08-04 | 2019-02-07 | Regeneron Pharmaceuticals, Inc. | METHODS OF TREATING ESOPHAGITIS WITH ACTIVE EOSINOPHILES |
| CN111542326B (zh) | 2017-08-11 | 2024-06-04 | 希望之城 | 转铁蛋白受体(TfR)的RNA适体 |
| WO2019035938A1 (en) | 2017-08-16 | 2019-02-21 | Elstar Therapeutics, Inc. | MULTISPECIFIC MOLECULES BINDING TO BCMA AND USES THEREOF |
| US20200254093A1 (en) | 2017-09-14 | 2020-08-13 | Glaxosmithkline Intellectual Property Development Limited | Combination treatment for cancer |
| BR112020005079A2 (pt) | 2017-09-14 | 2020-09-15 | Glaxosmithkline Intellectual Property Development Limited | tratamento de combinação para câncer |
| EP3692066A2 (en) | 2017-09-14 | 2020-08-12 | GlaxoSmithKline Intellectual Property Development Limited | Combination treatment for cancer |
| TWI713843B (zh) * | 2017-09-30 | 2020-12-21 | 大陸商科濟生物醫藥(上海)有限公司 | 標靶bcma的抗體及其應用 |
| WO2019071358A1 (en) | 2017-10-12 | 2019-04-18 | Mcmaster University | Y182T MUTATION T CELL ANTIGEN COUPLEUR AND METHODS AND USES THEREOF |
| IL321733A (en) | 2017-10-18 | 2025-08-01 | Novartis Ag | Compositions and methods for selective degradation of proteins |
| EP3710040A1 (en) | 2017-11-15 | 2020-09-23 | Novartis AG | Bcma-targeting chimeric antigen receptor, cd19-targeting chimeric antigen receptor, and combination therapies |
| JP2021509009A (ja) | 2017-11-30 | 2021-03-18 | ノバルティス アーゲー | Ｂｃｍａターゲティングキメラ抗原受容体及びその使用 |
| WO2019126756A1 (en) | 2017-12-22 | 2019-06-27 | Teneobio, Inc. | Heavy chain antibodies binding to cd22 |
| US20200339685A1 (en) * | 2017-12-27 | 2020-10-29 | Teneobio, Inc. | Cd3-delta/epsilon heterodimer specific antibodies |
| US20200368268A1 (en) | 2018-01-08 | 2020-11-26 | Novartis Ag | Immune-enhancing rnas for combination with chimeric antigen receptor therapy |
| WO2019139987A1 (en) | 2018-01-09 | 2019-07-18 | Elstar Therapeutics, Inc. | Calreticulin binding constructs and engineered t cells for the treatment of diseases |
| US20210038659A1 (en) | 2018-01-31 | 2021-02-11 | Novartis Ag | Combination therapy using a chimeric antigen receptor |
| PE20210375A1 (es) | 2018-02-08 | 2021-03-02 | Dragonfly Therapeutics Inc | Terapia de combinacion del cancer que incluye proteinas de union multiespecificas que activan a las celulas asesinas naturales |
| FI3749346T3 (fi) | 2018-02-08 | 2024-09-04 | Dragonfly Therapeutics Inc | Nkg2d-reseptoriin kohdistuvat vasta-aineen vaihtelevan domeenin yhdistelmät |
| AR115360A1 (es) | 2018-02-08 | 2021-01-13 | Genentech Inc | Moléculas de unión al antígeno y métodos de uso |
| EP3752203A1 (en) | 2018-02-13 | 2020-12-23 | Novartis AG | Chimeric antigen receptor therapy in combination with il-15r and il15 |
| MX2020008684A (es) | 2018-02-20 | 2020-12-07 | Dragonfly Therapeutics Inc | Proteinas de union multiespecificas que se unen a cd33, nkg2d y cd16 y metodos de uso. |
| AU2019228128A1 (en) | 2018-03-02 | 2020-09-03 | Cdr-Life Ag | Trispecific antigen binding proteins |
| US12152073B2 (en) | 2018-03-14 | 2024-11-26 | Marengo Therapeutics, Inc. | Multifunctional molecules that bind to calreticulin and uses thereof |
| JP7603578B2 (ja) | 2018-03-30 | 2024-12-20 | メルス ナムローゼ フェンノートシャップ | 多価抗体 |
| PH12020551664B1 (en) | 2018-04-13 | 2023-05-19 | Affimed Gmbh | Nk cell engaging antibody fusion constructs |
| WO2019210153A1 (en) | 2018-04-27 | 2019-10-31 | Novartis Ag | Car t cell therapies with enhanced efficacy |
| WO2019213282A1 (en) | 2018-05-01 | 2019-11-07 | Novartis Ag | Biomarkers for evaluating car-t cells to predict clinical outcome |
| CN112105420A (zh) | 2018-05-11 | 2020-12-18 | 克里斯珀医疗股份公司 | 用于治疗癌症的方法和组合物 |
| CN120227453A (zh) | 2018-05-13 | 2025-07-01 | 瑞泽恩制药公司 | 用于通过施用il-4r抑制剂治疗特应性皮炎的方法 |
| MX2020012286A (es) | 2018-05-16 | 2021-04-28 | Janssen Biotech Inc | Metodos para tratar canceres y potenciar la eficacia de agentes terapeuticos para el redireccionamiento de celulas t. |
| WO2019227003A1 (en) | 2018-05-25 | 2019-11-28 | Novartis Ag | Combination therapy with chimeric antigen receptor (car) therapies |
| EP3802611A2 (en) * | 2018-06-01 | 2021-04-14 | Novartis AG | Binding molecules against bcma and uses thereof |
| EP3802825A1 (en) | 2018-06-08 | 2021-04-14 | Intellia Therapeutics, Inc. | Compositions and methods for immunooncology |
| CN112955465A (zh) | 2018-07-03 | 2021-06-11 | 马伦戈治疗公司 | 抗tcr抗体分子及其用途 |
| AR116109A1 (es) | 2018-07-10 | 2021-03-31 | Novartis Ag | Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos |
| US11110123B2 (en) | 2018-07-17 | 2021-09-07 | Triumvira Immunologics Usa, Inc. | T cell-antigen coupler with various construct optimizations |
| US10640562B2 (en) | 2018-07-17 | 2020-05-05 | Mcmaster University | T cell-antigen coupler with various construct optimizations |
| SMT202400102T1 (it) | 2018-07-19 | 2024-05-14 | Regeneron Pharma | Recettori chimerici dell’antigene con specificità per bcma e loro usi |
| TWI838389B (zh) | 2018-07-19 | 2024-04-11 | 美商再生元醫藥公司 | 雙特異性抗-BCMAｘ抗-CD3抗體及其用途 |
| CN116769032A (zh) | 2018-07-20 | 2023-09-19 | 坦尼奥第二公司 | 与cd19结合的重链抗体 |
| JP7482363B2 (ja) | 2018-08-08 | 2024-05-14 | ドラゴンフライ セラピューティクス， インコーポレイテッド | Ｎｋｇ２ｄ、ｃｄ１６及び腫瘍関連抗原に結合するタンパク質 |
| EA202091888A1 (ru) | 2018-08-08 | 2020-10-23 | Драгонфлай Терапьютикс, Инк. | Вариабельные домены антител, нацеленные на рецептор nkg2d |
| US12384851B2 (en) | 2018-08-08 | 2025-08-12 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins that bind BCMA, NKG2D and CD16, and methods of use |
| EP3844265A2 (en) | 2018-08-31 | 2021-07-07 | Novartis AG | Methods of making chimeric antigen receptor-expressing cells |
| EP3844267B1 (en) | 2018-08-31 | 2025-06-25 | Novartis AG | Methods of making chimeric antigen receptor-expressing cells |
| CN112125974B (zh) * | 2018-09-25 | 2022-04-15 | 上海邦耀生物科技有限公司 | 靶向bcma蛋白的抗体、嵌合抗原受体和药物 |
| WO2020089794A1 (en) | 2018-10-31 | 2020-05-07 | Glaxosmithkline Intellectual Property Development Limited | Methods of treating cancer |
| US20240245670A1 (en) | 2018-12-20 | 2024-07-25 | Novartis Ag | Dosing regimen and pharmaceutical combination comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives |
| EP3897718A4 (en) * | 2018-12-20 | 2022-09-14 | Cedars-Sinai Medical Center | CLAZAKIZUMAB FOR THE TREATMENT OF CHRONIC ANTIBODY-MEDIATED REJECTION OF ORGAN TRANSPLANT |
| CN109678961A (zh) * | 2019-01-15 | 2019-04-26 | 深圳市南科生物工程有限公司 | 一种基于bmca纳米抗体序列的嵌合抗原受体的构建方法及其应用 |
| EP3924055B1 (en) | 2019-02-15 | 2024-04-03 | Novartis AG | Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
| EP3924054B1 (en) | 2019-02-15 | 2025-04-02 | Novartis AG | 3-(1-oxo-5-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
| WO2020172605A1 (en) | 2019-02-21 | 2020-08-27 | Elstar Therapeutics, Inc. | Antibody molecules that bind to nkp30 and uses thereof |
| JP7710373B2 (ja) | 2019-02-21 | 2025-07-18 | マレンゴ・セラピューティクス，インコーポレーテッド | Ｔ細胞関連のがん細胞に結合する多機能性分子およびその使用 |
| WO2020176397A1 (en) | 2019-02-25 | 2020-09-03 | Novartis Ag | Mesoporous silica particles compositions for viral delivery |
| KR20210143246A (ko) * | 2019-03-21 | 2021-11-26 | 리제너론 파아마슈티컬스, 인크. | 알레르기 치료용 il-4/il-13 경로 억제제 및 형질 세포 절제의 병용 |
| US20230074800A1 (en) | 2019-03-21 | 2023-03-09 | Novartis Ag | Car-t cell therapies with enhanced efficacy |
| EA202192736A1 (ru) | 2019-04-05 | 2022-01-27 | Тенеобио, Инк. | Антитела, содержащие только тяжелые цепи, которые связываются с псма |
| US20220168389A1 (en) | 2019-04-12 | 2022-06-02 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
| US20220251152A1 (en) | 2019-04-24 | 2022-08-11 | Novartis Ag | Compositions and methods for selective protein degradation |
| WO2020222176A1 (en) | 2019-04-30 | 2020-11-05 | Crispr Therapeutics Ag | Allogeneic cell therapy of b cell malignancies using genetically engineered t cells targeting cd19 |
| BR112021021728A2 (pt) * | 2019-05-03 | 2021-12-28 | Celgene Corp | Conjugado de anticorpo anti-bcma, composições que compreendem os mesmos e métodos para fazer e usar os mesmos |
| CU20210096A7 (es) | 2019-05-21 | 2022-06-06 | Novartis Ag | Moléculas de unión a cd19 |
| PH12021553145A1 (en) | 2019-06-14 | 2022-07-25 | Teneobio Inc | Multispecific heavy chain antibodies binding to cd22 and cd3 |
| KR20220042217A (ko) | 2019-08-05 | 2022-04-04 | 리제너론 파아마슈티컬스, 인크. | Il-4r 길항제를 투여함에 의해 알레르기를 치료하고 알레르겐-특이적 면역치료요법을 증진시키기 위한 방법 |
| EP4010373A1 (en) | 2019-08-05 | 2022-06-15 | Regeneron Pharmaceuticals, Inc. | Methods for treating atopic dermatitis by administering an il-4r antagonist |
| MX2022001626A (es) | 2019-08-06 | 2022-03-02 | Glaxosmithkline Ip Dev Ltd | Composiciones biofarmaceuticas y procedimientos conexos. |
| IL316618A (en) * | 2019-11-26 | 2024-12-01 | Shanghai Epimab Biotherapeutics Co Ltd | Antibodies to CD3 and BCMA and bispecific binding proteins produced from them |
| PH12022551291A1 (en) | 2019-11-26 | 2023-11-20 | Novartis Ag | Chimeric antigen receptors binding bcma and cd19 and uses thereof |
| KR20220119430A (ko) * | 2019-12-20 | 2022-08-29 | 메디뮨 엘엘씨 | 글리피칸 3을 표적으로 하는 키메라 항원 수용체로 암을 치료하는 조성물 및 방법 |
| KR20220116522A (ko) | 2019-12-20 | 2022-08-23 | 노파르티스 아게 | 증식성 질환의 치료를 위한 항-tgf-베타 항체 및 체크포인트 억제제의 용도 |
| CA3166629A1 (en) | 2020-01-03 | 2021-07-08 | Marengo Therapeutics, Inc. | Anti-tcr antibody molecules and uses thereof |
| CN111234020B (zh) * | 2020-01-23 | 2020-10-23 | 和铂医药(苏州)有限公司 | 一种bcma结合蛋白及其制备方法和应用 |
| WO2021168274A1 (en) | 2020-02-21 | 2021-08-26 | Silverback Therapeutics, Inc. | Nectin-4 antibody conjugates and uses thereof |
| US20230078007A1 (en) * | 2020-02-24 | 2023-03-16 | The Regents Of The University Of California | In-series synthetic receptor and-gate circuits for expression of a therapeutic payload by engineered cells |
| CN115397460A (zh) | 2020-02-27 | 2022-11-25 | 诺华股份有限公司 | 制备表达嵌合抗原受体的细胞的方法 |
| BR112022017148A2 (pt) | 2020-02-27 | 2022-11-08 | Novartis Ag | Métodos para produzir células que expressam receptor de antígeno quimérico |
| CA3214992A1 (en) | 2020-04-29 | 2021-11-04 | Teneobio, Inc. | Multispecific heavy chain antibodies with modified heavy chain constant regions |
| KR20250007022A (ko) | 2020-04-29 | 2025-01-13 | 테네오원, 인코포레이티드 | 변형된 중쇄 불변 영역을 갖는 다중특이적 중쇄 항체 |
| TW202208428A (zh) | 2020-05-06 | 2022-03-01 | 美商蜻蜓醫療公司 | 結合ｎｋｇ２ｄ、ｃｄ１６及ｃｌｅｃ１２ａ之蛋白質 |
| AU2021272291A1 (en) | 2020-05-11 | 2023-02-02 | Janssen Biotech, Inc. | Methods for treating multiple myeloma |
| KR20230013258A (ko) | 2020-05-19 | 2023-01-26 | 얀센 바이오테크 인코포레이티드 | T 세포 재유도 치료제 및 vla-4 부착 경로 억제제를 포함하는 조성물 |
| CA3185455A1 (en) | 2020-06-11 | 2021-12-16 | Novartis Ag | Zbtb32 inhibitors and uses thereof |
| TW202519548A (zh) | 2020-06-19 | 2025-05-16 | 瑞士商赫孚孟拉羅股份公司 | 與 cd3 及 cd19 結合之抗體 |
| CA3182346A1 (en) | 2020-06-23 | 2021-12-30 | Novartis Ag | Dosing regimen comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives |
| PE20230464A1 (es) | 2020-06-30 | 2023-03-14 | Teneobio Inc | Union de anticuerpos multiespecificos a bcma |
| TW202216211A (zh) | 2020-07-01 | 2022-05-01 | 美商希沃爾拜克治療公司 | 抗asgr1抗體共軛物及其用途 |
| CN116134027B (zh) | 2020-08-03 | 2025-01-24 | 诺华股份有限公司 | 杂芳基取代的3-(1-氧代异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途 |
| AU2021329404A1 (en) | 2020-08-21 | 2023-04-20 | Novartis Ag | Compositions and methods for in vivo generation of car expressing cells |
| US20230374147A1 (en) | 2020-11-02 | 2023-11-23 | Hummingbird Bioscience Pte. Ltd. | Bcma/taci antigen-binding molecules |
| WO2022135468A1 (zh) * | 2020-12-23 | 2022-06-30 | 信达生物制药(苏州)有限公司 | 抗bcma×cd3双特异性抗体及其用途 |
| US20240181073A1 (en) * | 2021-03-03 | 2024-06-06 | Sorrento Therapeutics, Inc. | Antibody-Drug Conjugates Comprising an Anti-BCMA Antibody |
| EP4301774A4 (en) | 2021-03-03 | 2025-08-13 | Dragonfly Therapeutics Inc | METHODS OF TREATING CANCER USING MULTI-SPECIFIC BINDING PROTEINS THAT BIND TO NKG2D, CD16, AND A TUMOR-ASSOCIATED ANTIGEN |
| US20240158505A1 (en) * | 2021-03-26 | 2024-05-16 | Theranotics Co., Ltd. | B7-h3 antibody or antigen-binding fragment thereof, and use thereof |
| TW202304979A (zh) | 2021-04-07 | 2023-02-01 | 瑞士商諾華公司 | 抗ＴＧＦβ抗體及其他治療劑用於治療增殖性疾病之用途 |
| US20250099579A1 (en) | 2021-04-08 | 2025-03-27 | Marengo Therapeutics, Inc. | Multispecific molecules binding to tcr and uses thereof |
| AU2022267891A1 (en) | 2021-04-27 | 2023-11-09 | Novartis Ag | Viral vector production system |
| CA3213632A1 (en) | 2021-04-30 | 2022-11-03 | F. Hoffmann-La Roche Ag | Dosing for combination treatment with anti-cd20/anti-cd3 bispecific antibody and anti-cd79b antibody drug conjugate |
| WO2022248870A1 (en) | 2021-05-28 | 2022-12-01 | Glaxosmithkline Intellectual Property Development Limited | Combination therapies for treating cancer |
| CA3173810A1 (en) | 2021-06-01 | 2022-12-01 | Andreas Bader | Claudin 18.2 t cell-antigen couplers and uses thereof |
| US11453723B1 (en) | 2021-06-25 | 2022-09-27 | Mcmaster University | BCMA T cell-antigen couplers and uses thereof |
| CA3227515A1 (en) | 2021-08-03 | 2023-02-09 | Glaxosmithkline Intellectual Property Development Limited | Biopharmaceutical compositions and stable isotope labeling peptide mapping method |
| US20250000973A1 (en) | 2021-08-20 | 2025-01-02 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
| JP2024532500A (ja) * | 2021-09-03 | 2024-09-05 | 蘇州近岸蛋白質科技股▲ふん▼有限公司 | 抗ｃｄ３ヒト化抗体 |
| EP4412713A1 (en) | 2021-10-05 | 2024-08-14 | GlaxoSmithKline Intellectual Property Development Ltd | Combination therapies for treating cancer |
| CA3237357A1 (en) | 2021-11-03 | 2023-05-11 | Janssen Biotech, Inc. | Methods of treating cancers and enhancing efficacy of bcmaxcd3 bispecific antibodies |
| CN118591560A (zh) | 2022-01-25 | 2024-09-03 | 葛兰素史密斯克莱知识产权发展有限公司 | 癌症的组合疗法 |
| WO2023215725A1 (en) | 2022-05-02 | 2023-11-09 | Fred Hutchinson Cancer Center | Compositions and methods for cellular immunotherapy |
| WO2023214325A1 (en) | 2022-05-05 | 2023-11-09 | Novartis Ag | Pyrazolopyrimidine derivatives and uses thereof as tet2 inhibitors |
| CN120092020A (zh) | 2022-07-08 | 2025-06-03 | 新加坡科技研究局 | Cnx抗原结合分子 |
| EP4581052A1 (en) | 2022-09-01 | 2025-07-09 | University of Georgia Research Foundation, Inc. | Compositions and methods for directing apolipoprotein l1 to induce mammalian cell death |
| WO2024089639A1 (en) | 2022-10-26 | 2024-05-02 | Novartis Ag | Lentiviral formulations |
| EP4630454A1 (en) | 2022-12-05 | 2025-10-15 | GlaxoSmithKline Intellectual Property Development Ltd | Methods of treatment using b-cell maturation antigen antagonists |
| US12173081B2 (en) | 2023-03-21 | 2024-12-24 | Biograph 55, Inc. | CD19/CD38 multispecific antibodies |
| AU2024276994A1 (en) | 2023-05-24 | 2025-10-23 | Kumquat Biosciences Inc. | Heterocyclic compounds and uses thereof |
| WO2025101820A1 (en) | 2023-11-08 | 2025-05-15 | Fred Hutchinson Cancer Center | Compositions and methods for cellular immunotherapy |
| US20250242018A1 (en) | 2024-01-26 | 2025-07-31 | Regeneron Pharmaceuticals, Inc. | Combination immunosuppression for inhibiting an immune response and enabling immunogen administration and re-administration |
| US20250242056A1 (en) | 2024-01-26 | 2025-07-31 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for using plasma cell depleting agents and/or b cell depleting agents to suppress host anti-aav antibody response and enable aav transduction and re-dosing |
| WO2025174963A1 (en) | 2024-02-16 | 2025-08-21 | Kite Pharma, Inc. | Systems, methods, and kits for generating and administering engineered t cells and cd38 targeting compounds as a combination therapy |
| WO2025184567A1 (en) | 2024-03-01 | 2025-09-04 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for re-dosing aav using anti-cd40 antagonistic antibody to suppress host anti-aav antibody response |
Family Cites Families (108)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US6410516B1 (en) | 1986-01-09 | 2002-06-25 | President & Fellows Of Harvard College | Nuclear factors associated with transcriptional regulation |
| EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
| ATE120761T1 (de) | 1987-05-21 | 1995-04-15 | Creative Biomolecules Inc | Multifunktionelle proteine mit vorbestimmter zielsetzung. |
| US5204244A (en) | 1987-10-27 | 1993-04-20 | Oncogen | Production of chimeric antibodies by homologous recombination |
| US5202238A (en) | 1987-10-27 | 1993-04-13 | Oncogen | Production of chimeric antibodies by homologous recombination |
| US5273743A (en) | 1990-03-09 | 1993-12-28 | Hybritech Incorporated | Trifunctional antibody-like compounds as a combined diagnostic and therapeutic agent |
| WO1994009817A1 (en) | 1992-11-04 | 1994-05-11 | City Of Hope | Novel antibody construct |
| ATE199392T1 (de) | 1992-12-04 | 2001-03-15 | Medical Res Council | Multivalente und multispezifische bindungsproteine, deren herstellung und verwendung |
| ATE204325T1 (de) | 1993-04-29 | 2001-09-15 | Unilever Nv | Herstellung von antikörpern oder funktionstüchtig gemachten teilen davon, abgeleitet von schweren ketten von immunglobulinen von camelidae |
| US5885573A (en) | 1993-06-01 | 1999-03-23 | Arch Development Corporation | Methods and materials for modulation of the immunosuppressive activity and toxicity of monoclonal antibodies |
| EP0807173B1 (en) | 1994-12-30 | 2007-08-08 | Planet Biotechnology, Inc. | Methods for producing immunoglobulins containing protection proteins in plants and their use |
| GB9501079D0 (en) | 1995-01-19 | 1995-03-08 | Bioinvent Int Ab | Activation of T-cells |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| EP0739981A1 (en) | 1995-04-25 | 1996-10-30 | Vrije Universiteit Brussel | Variable fragments of immunoglobulins - use for therapeutic or veterinary purposes |
| ATE218143T1 (de) | 1996-09-03 | 2002-06-15 | Gsf Forschungszentrum Umwelt | Verwendung bi-und trispezifischer antikörper zur induktion einer tumorimmunität |
| JP2002505574A (ja) | 1997-04-30 | 2002-02-19 | エンゾン，インコーポレイテッド | ポリアルキレンオキシド修飾された単鎖ポリペプチド |
| TR200000654T2 (tr) | 1997-09-12 | 2000-07-21 | Apotech R & D Sa | KAY-Yeni bir bağışıklık sistemi proteini. |
| US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
| PT2180007E (pt) | 1998-04-20 | 2013-11-25 | Roche Glycart Ag | Engenharia de glicosilação de anticorpos para melhorar a citotoxicidade celular dependente de anticorpos |
| GB9809951D0 (en) | 1998-05-08 | 1998-07-08 | Univ Cambridge Tech | Binding molecules |
| PL209535B1 (pl) | 1999-01-07 | 2011-09-30 | Zymogenetics Inc | Zastosowanie białka fuzyjnego |
| KR101155191B1 (ko) | 1999-01-15 | 2012-06-13 | 제넨테크, 인크. | 효과기 기능이 변화된 폴리펩티드 변이체 |
| US20020142000A1 (en) | 1999-01-15 | 2002-10-03 | Digan Mary Ellen | Anti-CD3 immunotoxins and therapeutic uses therefor |
| ES2568899T3 (es) | 1999-04-09 | 2016-05-05 | Kyowa Hakko Kirin Co., Ltd. | Procedimiento para controlar la actividad de una molécula inmunofuncional |
| UA74798C2 (uk) | 1999-10-06 | 2006-02-15 | Байоджен Айдек Ма Інк. | Спосіб лікування раку у ссавця за допомогою поліпептиду, що протидіє взаємодії april з його рецепторами |
| WO2001024812A1 (en) | 1999-10-06 | 2001-04-12 | N.V. Nutricia | USE OF TRANSFORMING GROWTH FACTOR β AND GROWTH FACTORS IN THE TREATMENT AND PREVENTION OF DISEASES OF THE INTESTINAL MUCOSA |
| AU7950400A (en) | 1999-10-19 | 2001-04-30 | Kyowa Hakko Kogyo Co. Ltd. | Process for producing polypeptide |
| US7417130B2 (en) | 2000-09-08 | 2008-08-26 | University Of Zurich | Collection of repeat proteins comprising repeat modules |
| EP1331266B1 (en) | 2000-10-06 | 2017-01-04 | Kyowa Hakko Kirin Co., Ltd. | Cells producing antibody compositions |
| US7064191B2 (en) | 2000-10-06 | 2006-06-20 | Kyowa Hakko Kogyo Co., Ltd. | Process for purifying antibody |
| EP1333032A4 (en) | 2000-10-06 | 2005-03-16 | Kyowa Hakko Kogyo Kk | PROCESS FOR PURIFYING ANTIBODY |
| GB0029407D0 (en) | 2000-12-01 | 2001-01-17 | Affitech As | Product |
| AU2002238052A1 (en) | 2001-02-20 | 2002-09-04 | Zymogenetics, Inc. | Antibodies that bind both bcma and taci |
| DK1419179T3 (da) | 2001-08-10 | 2010-06-21 | Univ Aberdeen | Antigenbindingsdomæner fra fisk |
| EP1293514B1 (en) | 2001-09-14 | 2006-11-29 | Affimed Therapeutics AG | Multimeric single chain tandem Fv-antibodies |
| DE60127143T2 (de) | 2001-11-14 | 2007-11-15 | Affimed Therapeutics Ag | Bispezifische Antikörper gegen CD19 und CD16 und deren Verwendung |
| US20080267965A1 (en) | 2002-02-21 | 2008-10-30 | Kalled Susan L | Use of Bcma as an Immunoregulatory Agent |
| US7317091B2 (en) | 2002-03-01 | 2008-01-08 | Xencor, Inc. | Optimized Fc variants |
| GB0230201D0 (en) | 2002-12-27 | 2003-02-05 | Domantis Ltd | Retargeting |
| JP5425365B2 (ja) | 2003-01-22 | 2014-02-26 | グリカート バイオテクノロジー アクチェンゲゼルシャフト | 増加したＦｃレセプター結合親和性およびエフェクター機能を有する抗体を作製するための融合構築物およびその使用 |
| PT1599504E (pt) | 2003-02-25 | 2015-03-02 | Vaccibody As | Anticorpo modificado |
| JP5010281B2 (ja) | 2003-05-31 | 2012-08-29 | マイクロメット アクツィエン ゲゼルシャフト | Ｅｐｃａｍに対する二重特異性抗体を含む薬学的組成物 |
| JP4276000B2 (ja) | 2003-06-16 | 2009-06-10 | 株式会社ブンリ | サイクロン形異物分離装置 |
| CA2533830A1 (en) | 2003-08-07 | 2005-02-24 | Epitomics, Inc. | Methods for humanizing rabbit monoclonal antibodies |
| WO2005047327A2 (en) | 2003-11-12 | 2005-05-26 | Biogen Idec Ma Inc. | NEONATAL Fc RECEPTOR (FcRn)-BINDING POLYPEPTIDE VARIANTS, DIMERIC Fc BINDING PROTEINS AND METHODS RELATED THERETO |
| US7235641B2 (en) | 2003-12-22 | 2007-06-26 | Micromet Ag | Bispecific antibodies |
| CA2554526A1 (en) | 2004-01-29 | 2005-08-18 | Genentech, Inc. | Variants of the extracellular domain of bcma and uses thereof |
| DK2330121T3 (en) | 2004-06-02 | 2014-12-15 | Adalta Pty Ltd | Binding moieties based on shark IgNar domains |
| EP2028193B1 (en) | 2005-01-05 | 2012-03-07 | f-star Biotechnologische Forschungs- und Entwicklungsges.m.b.H. | Synthetic immunoglobulin domains with binding properties engineered in regions of the molecule different from the complementarity determining regions |
| DK3050963T3 (da) | 2005-03-31 | 2019-12-09 | Chugai Pharmaceutical Co Ltd | Fremgangsmåde til fremstilling af polypeptid ved regulering af arrangement |
| WO2006113665A2 (en) | 2005-04-15 | 2006-10-26 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
| MX2007013924A (es) | 2005-05-09 | 2008-01-28 | Glycart Biotechnology Ag | Moleculas que unen antigeno que tienen regiones fc modificadas y union alterada a receptores fc. |
| EP1945668A4 (en) | 2005-08-15 | 2009-07-22 | Arana Therapeutics Ltd | SYNTHETIC ANTIBODIES WITH FRAMEWORK REGIONS OF NEUWELTPRIMATEN |
| JP5373396B2 (ja) | 2005-08-26 | 2013-12-18 | ロシュ グリクアート アクチェンゲゼルシャフト | 改変された細胞シグナル活性有する改変抗原結合分子 |
| DK1931709T3 (en) | 2005-10-03 | 2017-03-13 | Xencor Inc | FC VARIETIES WITH OPTIMIZED FC RECEPTOR BINDING PROPERTIES |
| WO2007042261A2 (en) | 2005-10-11 | 2007-04-19 | Micromet Ag | Compositions comprising cross-species-specific antibodies and uses thereof |
| CN102784392A (zh) * | 2005-10-13 | 2012-11-21 | 人体基因组科学有限公司 | 用于治疗自身抗体阳性疾病患者的方法和组合物 |
| WO2007117600A2 (en) | 2006-04-07 | 2007-10-18 | Macrogenics, Inc. | Combination therapy for treating autoimmune diseases |
| CN101466733A (zh) | 2006-04-14 | 2009-06-24 | 特鲁比昂药品公司 | 包含免疫球蛋白铰链区和Fc效应子功能改变了的Fc区的结合蛋白 |
| CA2681974C (en) | 2007-03-29 | 2019-12-31 | Genmab A/S | Bispecific antibodies and methods for production thereof |
| CN109456410B (zh) | 2007-04-03 | 2022-01-28 | 安进研发（慕尼黑）股份有限公司 | 跨物种特异性CD3-ε结合结构域 |
| US20100183615A1 (en) | 2007-04-03 | 2010-07-22 | Micromet Ag | Cross-species-specific bispecific binders |
| CN103694350B (zh) | 2007-04-03 | 2018-04-24 | 安进研发（慕尼黑）股份有限公司 | 跨物种特异性CD3-ε结合结构域 |
| US7973138B2 (en) * | 2007-09-26 | 2011-07-05 | Genentech, Inc. | Antibodies |
| US8227577B2 (en) * | 2007-12-21 | 2012-07-24 | Hoffman-La Roche Inc. | Bivalent, bispecific antibodies |
| US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
| US9266967B2 (en) | 2007-12-21 | 2016-02-23 | Hoffmann-La Roche, Inc. | Bivalent, bispecific antibodies |
| CA2710912A1 (en) | 2008-01-15 | 2009-07-23 | F. Hoffmann-La Roche Ag | Afucosylated antibodies against ccr5 and their use |
| EP2265283B1 (en) | 2008-03-18 | 2014-09-03 | Seattle Genetics, Inc. | Auristatin drug linker conjugates |
| CA2720682A1 (en) | 2008-04-25 | 2009-10-29 | Zymogenetics, Inc. | Levels of bcma protein expression on b cells and use in diagnostic methods |
| ES2582603T5 (es) | 2008-10-01 | 2022-12-02 | Amgen Res Munich Gmbh | Anticuerpos biespecíficos de cadena sencilla con especificidad por antígenos diana de alto peso molecular |
| EP4180458A1 (en) | 2008-10-01 | 2023-05-17 | Amgen Research (Munich) GmbH | Cross-species-specific psma x cd3 bispecific single chain antibody |
| US10981998B2 (en) | 2008-10-01 | 2021-04-20 | Amgen Research (Munich) Gmbh | Cross-species-specific single domain bispecific single chain antibody |
| EP3153524B1 (en) | 2008-12-03 | 2025-04-23 | Genmab A/S | Antibody variants having modifications in the constant region |
| ES2382017T3 (es) | 2008-12-12 | 2012-06-04 | Oro Clean Chemie Ag | Desinfectante virucida |
| NZ594985A (en) * | 2009-03-10 | 2013-07-26 | Biogen Idec Inc | Anti-bcma (b-cell maturation antigen, cd269, tnfrsf17) antibodies |
| US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
| WO2011013588A1 (ja) | 2009-07-29 | 2011-02-03 | アルプス電気株式会社 | 操作装置 |
| TWI409079B (zh) | 2009-08-14 | 2013-09-21 | Roche Glycart Ag | 非典型岩藻醣化ｃｄ２０抗體與苯達莫斯汀（ｂｅｎｄａｍｕｓｔｉｎｅ）之組合療法 |
| US9493578B2 (en) | 2009-09-02 | 2016-11-15 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
| PL2560993T3 (pl) | 2010-04-20 | 2024-11-04 | Genmab A/S | Heterodimeryczne białka zawierające region FC przeciwciała i sposoby ich wytwarzania |
| WO2012004811A1 (en) | 2010-07-06 | 2012-01-12 | Ind-Swift Laboratories Limited | Process for the preparation of 5-substsituted indole derivative |
| RU2584597C2 (ru) | 2010-08-13 | 2016-05-20 | Рош Гликарт Аг | Антитела против а2 тенасцина с и способы их применения |
| JP2014500879A (ja) | 2010-11-16 | 2014-01-16 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｂｃｍａ発現に相関性を有する疾患を治療する因子及び方法 |
| MX2013009151A (es) | 2011-02-10 | 2013-08-29 | Roche Glycart Ag | Inmunoterapia mejorada. |
| CA2824824A1 (en) | 2011-02-28 | 2012-09-07 | F. Hoffmann-La Roche Ag | Monovalent antigen binding proteins |
| KR20160044598A (ko) | 2011-03-29 | 2016-04-25 | 로슈 글리카트 아게 | 항체 Fc 변이체 |
| US20130101599A1 (en) | 2011-04-21 | 2013-04-25 | Boehringer Ingelheim International Gmbh | Bcma-based stratification and therapy for multiple myeloma patients |
| US9179843B2 (en) * | 2011-04-21 | 2015-11-10 | Hassan Ghaderi MOGHADDAM | Method and system for optically evaluating proximity to the inferior alveolar nerve in situ |
| EA201892619A1 (ru) | 2011-04-29 | 2019-04-30 | Роше Гликарт Аг | Иммуноконъюгаты, содержащие мутантные полипептиды интерлейкина-2 |
| EA033677B1 (ru) | 2011-05-21 | 2019-11-15 | Macrogenics Inc | Cd3-связывающие молекулы, способные к связыванию с cd3 человека и cd3, не являющимся человеческим |
| MX351069B (es) | 2011-05-27 | 2017-09-29 | Glaxo Group Ltd | Proteinas de union abcma (cd269/tnfrsf17). |
| ES2686327T3 (es) | 2011-08-23 | 2018-10-17 | Roche Glycart Ag | Moléculas de unión a antígeno biespecíficas |
| PE20141521A1 (es) | 2011-08-23 | 2014-10-25 | Roche Glycart Ag | Moleculas biespecificas de union a antigeno activadoras de celulas t |
| US20130058936A1 (en) | 2011-08-23 | 2013-03-07 | Peter Bruenker | Bispecific antibodies specific for t-cell activating antigens and a tumor antigen and methods of use |
| US20130078250A1 (en) | 2011-08-23 | 2013-03-28 | Oliver Ast | Bispecific t cell activating antigen binding molecules |
| KR101723273B1 (ko) | 2011-08-23 | 2017-04-04 | 로슈 글리카트 아게 | 2 개의 ｆａｂ 단편을 포함하는 fc-부재 항체 및 이용 방법 |
| KR102492792B1 (ko) | 2011-10-11 | 2023-01-30 | 제넨테크, 인크. | 이중특이적 항체의 개선된 어셈블리 |
| 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 |
| KR102086874B1 (ko) | 2012-04-11 | 2020-03-10 | 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 세크러테리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비씨즈 | B-세포 성숙 항원을 표적화하는 키메라 항원 수용체 |
| AR092044A1 (es) | 2012-08-07 | 2015-03-18 | Roche Glycart Ag | Inmunoterapia mejorada |
| MX2015003616A (es) | 2012-10-08 | 2015-06-05 | Roche Glycart Ag | Anticuerpos sin fc que comprenden dos fragmentos fab y metodos de uso. |
| AU2013340799B2 (en) | 2012-11-01 | 2018-08-09 | Max-Delbruck-Centrum Fur Molekulare Medizin (Mdc) | An antibody that binds CD269 (BCMA) suitable for use in the treatment of plasma cell diseases such as multiple myeloma and autoimmune diseases |
| TW201425336A (zh) | 2012-12-07 | 2014-07-01 | Amgen Inc | Ｂｃｍａ抗原結合蛋白質 |
| EP2953974B1 (en) | 2013-02-05 | 2017-12-20 | EngMab Sàrl | Bispecific antibodies against cd3epsilon and bcma |
| AR095374A1 (es) | 2013-03-15 | 2015-10-14 | Amgen Res Munich Gmbh | Moléculas de unión para bcma y cd3 |
| EP2982692A1 (en) * | 2014-08-04 | 2016-02-10 | EngMab AG | Bispecific antibodies against CD3epsilon and BCMA |
-
2014
- 2014-02-05 EP EP14705304.5A patent/EP2953974B1/en active Active
- 2014-02-05 WO PCT/EP2014/052189 patent/WO2014122143A1/en not_active Ceased
- 2014-02-05 CN CN202010603485.9A patent/CN111848796A/zh active Pending
- 2014-02-05 ES ES14702616T patent/ES2829499T3/es active Active
- 2014-02-05 EP EP14702616.5A patent/EP2953972B1/en active Active
- 2014-02-05 EP EP19189675.2A patent/EP3620468A1/en active Pending
- 2014-02-05 DK DK14702616.5T patent/DK2953972T3/da active
- 2014-02-05 US US14/764,968 patent/US10077315B2/en active Active
- 2014-02-05 CN CN201480007525.6A patent/CN104968682A/zh active Pending
- 2014-02-05 WO PCT/EP2014/052190 patent/WO2014122144A1/en not_active Ceased
- 2014-02-05 ES ES14705304.5T patent/ES2667420T3/es active Active
- 2014-02-05 US US14/764,967 patent/US9963513B2/en active Active
- 2014-02-05 PL PL14702616T patent/PL2953972T3/pl unknown
- 2014-02-05 CN CN201480007526.0A patent/CN104968683B/zh not_active Expired - Fee Related
- 2014-02-05 JP JP2015555752A patent/JP2016507523A/ja not_active Withdrawn
- 2014-02-05 JP JP2015555751A patent/JP6636803B2/ja not_active Expired - Fee Related
-
2018
- 2018-04-04 US US15/945,554 patent/US10851171B2/en not_active Expired - Fee Related
-
2019
- 2019-10-03 JP JP2019183002A patent/JP6918065B2/ja not_active Expired - Fee Related
-
2020
- 2020-07-27 JP JP2020126460A patent/JP6944573B2/ja active Active
- 2020-11-04 US US17/089,433 patent/US20210070873A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CN111848796A (zh) | 2020-10-30 |
| US20180222991A1 (en) | 2018-08-09 |
| WO2014122144A1 (en) | 2014-08-14 |
| JP6636803B2 (ja) | 2020-01-29 |
| JP2020180158A (ja) | 2020-11-05 |
| CN104968683A (zh) | 2015-10-07 |
| HK1212710A1 (zh) | 2016-06-17 |
| DK2953972T3 (da) | 2020-10-12 |
| JP2020023523A (ja) | 2020-02-13 |
| JP6944573B2 (ja) | 2021-10-06 |
| EP2953972B1 (en) | 2020-07-08 |
| US10851171B2 (en) | 2020-12-01 |
| EP2953972A1 (en) | 2015-12-16 |
| ES2667420T3 (es) | 2018-05-10 |
| US10077315B2 (en) | 2018-09-18 |
| US20210070873A1 (en) | 2021-03-11 |
| JP2016507523A (ja) | 2016-03-10 |
| US20150376287A1 (en) | 2015-12-31 |
| US20150368351A1 (en) | 2015-12-24 |
| JP6918065B2 (ja) | 2021-08-11 |
| JP2016508496A (ja) | 2016-03-22 |
| EP2953974A1 (en) | 2015-12-16 |
| CN104968682A (zh) | 2015-10-07 |
| WO2014122143A1 (en) | 2014-08-14 |
| US9963513B2 (en) | 2018-05-08 |
| HK1212709A1 (en) | 2016-06-17 |
| EP2953974B1 (en) | 2017-12-20 |
| PL2953972T3 (pl) | 2021-03-08 |
| CN104968683B (zh) | 2020-07-17 |
| EP3620468A1 (en) | 2020-03-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2829499T3 (es) | Método para la selección de anticuerpos contra BCMA | |
| ES2777602T3 (es) | Anticuerpos monoclonales contra el antígeno de maduración de células b humanas (BCMA) | |
| KR102514317B1 (ko) | 신규 b7-h3-결합 분자, 그것의 항체 약물 콘쥬게이트 및 그것의 사용 방법 | |
| ES2850325T3 (es) | Anticuerpos biespecíficos contra CD3epsilon y ROR1 | |
| EP2762497A1 (en) | Bispecific antibodies against CD3epsilon and BCMA | |
| KR20210016448A (ko) | 항-pvrig/항-tigit 이중특이적 항체 및 사용 방법 | |
| EP2762496A1 (en) | Method for the selection of antibodies against BCMA | |
| KR20170109529A (ko) | Cd3 엡실론 및 bcma에 대응하는 양특이성 항체 | |
| WO2014167022A1 (en) | BISPECIFIC ANTIBODIES AGAINST CD3EPSILON and ROR1 | |
| CN116390948A (zh) | 双功能分子 | |
| CN116234826A (zh) | Btla抗体 | |
| HK40024249A (en) | Method for the selection of antibodies against bcma | |
| CN119213034A (zh) | 双功能蛋白质及其制剂和用途 | |
| HK1212710B (en) | Method for the selection of antibodies against bcma | |
| HK1212709B (en) | Bispecific antibodies against cd3epsilon and bcma |