JP2021506325A - Cd22に結合する重鎖抗体 - Google Patents
Cd22に結合する重鎖抗体 Download PDFInfo
- Publication number
- JP2021506325A JP2021506325A JP2020534858A JP2020534858A JP2021506325A JP 2021506325 A JP2021506325 A JP 2021506325A JP 2020534858 A JP2020534858 A JP 2020534858A JP 2020534858 A JP2020534858 A JP 2020534858A JP 2021506325 A JP2021506325 A JP 2021506325A
- Authority
- JP
- Japan
- Prior art keywords
- heavy chain
- seq
- antibody
- sequence
- antibody according
- 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.)
- Granted
Links
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 title claims abstract description 106
- 102100038080 B-cell receptor CD22 Human genes 0.000 title claims abstract description 93
- 238000000034 method Methods 0.000 claims abstract description 38
- 238000011282 treatment Methods 0.000 claims abstract description 24
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
- 208000037914 B-cell disorder Diseases 0.000 claims abstract description 11
- 230000027455 binding Effects 0.000 claims description 106
- 238000009739 binding Methods 0.000 claims description 103
- 239000000427 antigen Substances 0.000 claims description 63
- 108091007433 antigens Proteins 0.000 claims description 63
- 102000036639 antigens Human genes 0.000 claims description 63
- 210000004027 cell Anatomy 0.000 claims description 62
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 claims description 55
- 102100035361 Cerebellar degeneration-related protein 2 Human genes 0.000 claims description 41
- 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 claims description 41
- 101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 claims description 41
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 claims description 40
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 28
- 241001465754 Metazoa Species 0.000 claims description 19
- 239000012636 effector Substances 0.000 claims description 18
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 14
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 13
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 13
- 208000035475 disorder Diseases 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 12
- 238000006467 substitution reaction Methods 0.000 claims description 12
- 230000003053 immunization Effects 0.000 claims description 9
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 201000006417 multiple sclerosis Diseases 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 6
- 229910052727 yttrium Inorganic materials 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 108091033319 polynucleotide Proteins 0.000 claims description 4
- 102000040430 polynucleotide Human genes 0.000 claims description 4
- 239000002157 polynucleotide Substances 0.000 claims description 4
- 239000013598 vector Substances 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 3
- 239000000203 mixture Substances 0.000 abstract description 28
- 238000010586 diagram Methods 0.000 abstract description 2
- 108090000623 proteins and genes Proteins 0.000 description 32
- 241000700159 Rattus Species 0.000 description 24
- 102000004169 proteins and genes Human genes 0.000 description 24
- 235000018102 proteins Nutrition 0.000 description 22
- 201000010099 disease Diseases 0.000 description 17
- 108060003951 Immunoglobulin Proteins 0.000 description 16
- 102000018358 immunoglobulin Human genes 0.000 description 16
- 230000006870 function Effects 0.000 description 15
- 230000009261 transgenic effect Effects 0.000 description 15
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- 102000044389 human CD22 Human genes 0.000 description 14
- 108090000765 processed proteins & peptides Proteins 0.000 description 14
- 210000002966 serum Anatomy 0.000 description 13
- 229920001184 polypeptide Polymers 0.000 description 12
- 102000004196 processed proteins & peptides Human genes 0.000 description 12
- 230000001225 therapeutic effect Effects 0.000 description 12
- 235000001014 amino acid Nutrition 0.000 description 11
- 206010025323 Lymphomas Diseases 0.000 description 10
- 125000000539 amino acid group Chemical group 0.000 description 10
- 210000003719 b-lymphocyte Anatomy 0.000 description 10
- 206010028980 Neoplasm Diseases 0.000 description 9
- 230000004071 biological effect Effects 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 101000820585 Homo sapiens SUN domain-containing ossification factor Proteins 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 102100021651 SUN domain-containing ossification factor Human genes 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 7
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 description 7
- 108010087819 Fc receptors Proteins 0.000 description 7
- 102000009109 Fc receptors Human genes 0.000 description 7
- 241000124008 Mammalia Species 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 238000002649 immunization Methods 0.000 description 7
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000002147 killing effect Effects 0.000 description 6
- 241000282567 Macaca fascicularis Species 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 239000012131 assay buffer Substances 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 230000009089 cytolysis Effects 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 238000010494 dissociation reaction Methods 0.000 description 5
- 230000005593 dissociations Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 4
- 238000012875 competitive assay Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 238000011194 good manufacturing practice Methods 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 230000001900 immune effect Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 210000003519 mature b lymphocyte Anatomy 0.000 description 4
- 210000001616 monocyte Anatomy 0.000 description 4
- 210000000822 natural killer cell Anatomy 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 230000004962 physiological condition Effects 0.000 description 4
- 230000005180 public health Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 3
- 208000003950 B-cell lymphoma Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 3
- 108010073807 IgG Receptors Proteins 0.000 description 3
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 208000007452 Plasmacytoma Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 238000012575 bio-layer interferometry Methods 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 210000004602 germ cell Anatomy 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 238000011824 transgenic rat model Methods 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 108091008875 B cell receptors Proteins 0.000 description 2
- 208000011691 Burkitt lymphomas Diseases 0.000 description 2
- 241000282836 Camelus dromedarius Species 0.000 description 2
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- -1 Framework 2 Proteins 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 2
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 2
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 2
- 101150062031 L gene Proteins 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
- 241000282838 Lama Species 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000003314 affinity selection Methods 0.000 description 2
- 239000008365 aqueous carrier Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 230000024203 complement activation Effects 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 230000006240 deamidation Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 239000000710 homodimer Substances 0.000 description 2
- 210000003297 immature b lymphocyte Anatomy 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- 231100000636 lethal dose Toxicity 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 208000024191 minimally invasive lung adenocarcinoma Diseases 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 208000037916 non-allergic rhinitis Diseases 0.000 description 2
- 230000036963 noncompetitive effect Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 231100000683 possible toxicity Toxicity 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-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
- 208000030507 AIDS Diseases 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- 108010031480 Artificial Receptors Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 description 1
- 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000012526 B-cell neoplasm Diseases 0.000 description 1
- 208000025321 B-lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 208000008720 Bone Marrow Neoplasms Diseases 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 241000282826 Camelus Species 0.000 description 1
- 241000282828 Camelus bactrianus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 235000017274 Diospyros sandwicensis Nutrition 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 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 1
- 241000283086 Equidae Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010061850 Extranodal marginal zone B-cell lymphoma (MALT type) Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101100327294 Homo sapiens CD22 gene Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class 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
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 241000282842 Lama glama Species 0.000 description 1
- 241000282852 Lama guanicoe Species 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 201000003791 MALT lymphoma Diseases 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 206010064912 Malignant transformation Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100058506 Mus musculus Bloc1s5 gene Proteins 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- JFANZQMRSJDQBK-UHFFFAOYSA-N OC1CCCCC1.OC1=CC=CC(O)=C1 Chemical compound OC1CCCCC1.OC1=CC=CC(O)=C1 JFANZQMRSJDQBK-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 241000508269 Psidium Species 0.000 description 1
- 101710138747 Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010029157 Sialic Acid Binding Ig-like Lectin 2 Proteins 0.000 description 1
- 102000007073 Sialic Acid Binding Immunoglobulin-like Lectins Human genes 0.000 description 1
- 108010047827 Sialic Acid Binding Immunoglobulin-like Lectins Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 108091005906 Type I transmembrane proteins Proteins 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 241001416177 Vicugna pacos Species 0.000 description 1
- 241000282840 Vicugna vicugna Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000240 adjuvant effect Effects 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 239000000611 antibody drug conjugate Substances 0.000 description 1
- 238000011230 antibody-based therapy Methods 0.000 description 1
- 229940049595 antibody-drug conjugate Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-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
- HUTDDBSSHVOYJR-UHFFFAOYSA-H bis[(2-oxo-1,3,2$l^{5},4$l^{2}-dioxaphosphaplumbetan-2-yl)oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O HUTDDBSSHVOYJR-UHFFFAOYSA-H 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 201000006491 bone marrow cancer Diseases 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N butyl alcohol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 238000000533 capillary isoelectric focusing Methods 0.000 description 1
- 238000005515 capillary zone electrophoresis Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 230000009827 complement-dependent cellular cytotoxicity Effects 0.000 description 1
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000000222 eosinocyte Anatomy 0.000 description 1
- 229950009760 epratuzumab Drugs 0.000 description 1
- 238000002270 exclusion chromatography Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 201000003444 follicular lymphoma Diseases 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 208000025750 heavy chain disease Diseases 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 108091008042 inhibitory receptors Proteins 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229950004101 inotuzumab ozogamicin Drugs 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 210000004692 intercellular junction Anatomy 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 201000003445 large cell neuroendocrine carcinoma Diseases 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000036212 malign transformation Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 210000003826 marginal zone b cell Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 201000000638 mature B-cell neoplasm Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Chemical class 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 208000010915 neoplasm of mature B-cells Diseases 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 208000017426 precursor B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 125000005629 sialic acid group Chemical group 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 206010062113 splenic marginal zone lymphoma Diseases 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- SFVFIFLLYFPGHH-UHFFFAOYSA-M stearalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SFVFIFLLYFPGHH-UHFFFAOYSA-M 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Images
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
- C07K16/2803—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
- C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/522—CH1 domain
-
- 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
- C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Description
本出願は、2017年12月22日に出願された米国仮特許出願第62/609,759号の出願日の優先権を主張し、この出願の開示は、本明細書に全体が参照により組み込まれる。
本発明は、CD22に結合するヒト重鎖抗体(例えば、UniAbs(商標))に関する。本発明はさらに、そのような抗体を作製する方法、そのような抗体を含む医薬組成物を含む組成物、及びCD22の発現を特徴とするB細胞障害を処置するためのそれらの使用に関する。
SIGLEC−2(UniProt P20273)としても知られるCD22は、成熟B細胞上で発現される細胞表面受容体である。CD22は、複数のIgドメインを含有し、免疫グロブリンスーパーファミリーのメンバーである。CD22の細胞外ドメインは、CD45細胞表面タンパク質に存在するものを含むシアル酸部分と相互作用する。CD22は、B細胞受容体シグナル伝達の抑制性受容体として機能すると考えられる。CD20及びCD19に加えて、CD22のB細胞発現が制限されるので、B細胞性悪性腫瘍の治療的処置のための魅力的な標的となる。CD22に特異的なモノクローナル抗体は、文献に記載されており(例えば、Jabbour,Elias,et al.“Monoclonal antibodies in acute lymphoblastic leukemia.”Blood 125.26(2015):4010−4016)、標準的なモノクローナル抗体(例えば、エプラツズマブ)及び抗体−薬物コンジュゲート(イノツズマブオゾガマイシン)として治療的に使用されている。加えて、抗CD22キメラ抗原受容体T細胞は、白血病を処置するために診療所で使用されている(Fry,Terry J.,et al.“CD22−targeted CAR T cells induce remission in B−ALL that is naive or resistant to CD19−targeted CAR immunotherapy.”Nature medicine(2017))。
従来のIgG抗体では、重鎖及び軽鎖の会合は、軽鎖定常領域及び重鎖のCH1定常ドメイン間の疎水性相互作用に一部起因している。重鎖及び軽鎖間の疎水性相互作用にも寄与する、重鎖フレームワーク2(FR2)及びフレームワーク4(FR4)領域に追加の残基がある。
GX1SIX2X3X4X5X6Y
(式中、X1は、DまたはGであり;X2は、S、T、I、またはNであり、X3は、SまたはDであり;X4は、G、S、またはNであり;X5は、D、G、またはSであり;X6は、YまたはHである)のCDR1配列、及び(b)式:
X7X8YX9GX10X11
(式中、X7は、IまたはVであり;X8は、YまたはHであり;X9は、SまたはTであり;X10は、A、V、またはSであり;X11は、TまたはAである)のCDR2配列、及び(c)式:
X12RX13DSSX14WRS
(式中、X12は、T、A、またはKであり;X13は、DまたはEであり;X14は、NまたはSである)のCDR3配列を含む重鎖可変を含む重鎖可変領域を含む。
「含むこと」は、列挙された要素が組成物/方法/キットに必要とされることを意味するが、請求項の範囲内で組成物/方法/キットなどを形成するために他の要素が含まれてもよい。
抗CD22抗体
本発明は、密接に関連するヒトCD22に結合する重鎖のみ抗体のファミリーを提供する。このファミリーの抗体は、本明細書で定義され且つ図1に示されるような一連のCDR配列を含み、図2に記載の配列番号24〜84の提供された重鎖可変領域(VH)配列で例示される。抗体のファミリーは、臨床治療薬(複数可)としての有用性に寄与する多数の利点を提供する。抗体は、ある範囲の結合親和性を有するメンバーを含み、所望の結合親和性を有する特定の配列の選択を可能にする。
CDR1
GX1SIX2X3X4X5X6Y
(式中、X1は、DまたはGであり、
X2は、S、T、I、またはNであり、
X3は、SまたはDであり、
X4は、G、S、またはNであり、
X5は、D、G、またはSであり、
X6は、YまたはHである)
CDR2
X7X8YX9GX10X11
(式中、X7は、IまたはVであり、
X8は、YまたはHであり、
X9は、SまたはTであり、
X10は、A、V、またはSであり、
X11は、TまたはAである)
CDR3
X12RX13DSSX14WRS
(式中、X12は、T、A、またはKであり、
X13は、DまたはEであり、
X14は、NまたはSである)。
本発明の重鎖抗体は、当該技術分野で既知の方法により調製することができる。好ましい実施形態では、本明細書の重鎖抗体は、内因性免疫グロブリン遺伝子がノックアウトまたは無効化されたトランスジェニックマウス及びラット、好ましくは、ラット、を含むトランスジェニック動物により産生される。好ましい実施形態では、本明細書の重鎖抗体は、UniRat(商標)で産生される。UniRat(商標)は、それらの内因性免疫グロブリン遺伝子がサイレンシングされ、完全ヒトHCAbの多様な天然に最適化されたレパートリーを発現するために、ヒト免疫グロブリン重鎖トランスローカスを使用する。ラットの内因性免疫グロブリン遺伝子座は、様々な技術を使用してノックアウトまたはサイレンシングすることができるが、UniRat(商標)では、亜鉛フィンガー(エンド)ヌクレアーゼ(ZNF)技術を使用して、内因性ラット重鎖J遺伝子座、軽鎖Cκ遺伝子座、及び軽鎖Cλ遺伝子座を不活化した。卵母細胞へのマイクロインジェクションのためのZNF構築物は、IgH及びIgLノックアウト(KO)株を生成し得る。詳細については、例えば、Geurts et al.,2009,Science 325:433を参照のこと。Ig重鎖ノックアウトの特性決定は、Menoret et al.,2010,Eur.J.Immunol.40:2932−2941により報告されている。ZNF技術の利点は、最大数kbの欠失を介して遺伝子または遺伝子座をサイレンシングする非相同末端結合が、相同的統合のための標的部位も提供し得ることである(Cui et al.,2011,Nat Biotechnol 29:64−67)。UniRat(商標)で産生されたヒト重鎖抗体は、UniAbs(商標)と呼ばれ、従来の抗体を用いて攻撃することができないエピトープと結合し得る。それらの高い特異性、親和性、及び小さいサイズにより、それらは、モノ特異的及びポリ特異的用途に最適になる。
好適な薬学的に許容される担体と混合した本発明の1つ以上の抗体を含む医薬組成物を提供することが本発明の別の態様である。本明細書で使用される薬学的に許容される担体は、限定されないが、アジュバント、固体担体、水、緩衝剤、または治療構成成分を保持するために当該技術分野で使用される他の担体、またはそれらの組み合わせを例示する。
本明細書に記載の重鎖のみ抗CD22抗体、多重特異性抗体、及び医薬組成物は、限定しないが、本明細書にさらに記載される状態及び疾患を含む、CD22の発現を特徴とする疾患及び状態の処置に使用することができる。本発明の態様はまた、CD22の発現を特徴とするB細胞障害の処置のための薬剤の調製における、本明細書に記載の抗体の使用に関する。本発明の態様はまた、CD22の発現を特徴とするB細胞障害の処置に使用される、本明細書に記載の抗体に関する。
CD22タンパク質結合
抗原抗体親和性を決定するための動態結合実験を、バイオレイヤー干渉法を使用するOctet QK−384システム(ForteBio)で実施した。抗ヒトIgG Fcキャプチャー(AHC)バイオセンサー(Forte Bio、部品番号:18−5064)をアッセイ緩衝液(1xのPBS、0.1%のBSA、0.02%のTween−20、pH7.2)で水和し、pH1.5の100mMのグリシン中で事前調整した。ベースラインを、アッセイ緩衝液で120秒間確立した。次に、AHCバイオセンサーを、5μg/mLの濃度のUniAbs(商標)で120秒間固定した。別のベースライン(120秒)を、アッセイ緩衝液で確立した。次に、それらを、250nMから開始する、アッセイ緩衝液中のヒトCD22タンパク質の7点の1:2希釈系列に浸漬した。検体列の最後のウェルは、緩衝液及びロードされたバイオセンサー間の非特異的結合を試験するために、アッセイ緩衝液のみを含有し、参照ウェルとして使用した。会合を600秒間観察し、続いて、解離を900秒間観察した。Octet Data Analysis v9.0(ForteBio)を使用して、データ分析を実施した。標準的な1:1結合モデルを使用して、結合動態を分析した。
CD22細胞結合
『ヒト−ラット』のIgH遺伝子座を、いくつかの部分で構築して、組み立てた。これは、ヒトJHの下流のラットC領域遺伝子の改変及び結合、ならびにその後のヒトVH6−Dセグメント領域の上流付加を含む。次に、ヒトVH6、全てのD、全てのJH、及び改変ラットCγ2a/1/2b(ΔCH1)を含む、組み立てられて改変された領域をコードするヒトVH遺伝子の別々のクラスターを有する2つのBAC[BAC6及びBAC3]を、Georgと呼ばれるBACと共注入した。
CD22の組み換え細胞外ドメインでの免疫化。
12匹のUniRat動物(6匹のHC27、6匹のHC28)を組み換えヒトCD22タンパク質で免疫した。Titermax/Alhydrogelアジュバントを使用して標準的なプロトコールに従って動物を免疫した。CD22の組み換え細胞外ドメインを、R&Dシステムズから購入し、滅菌生理食塩水で希釈し、アジュバントと混合した。免疫原をTitermax及びAlhydrogelアジュバントと組み合わせた。Titermax中の免疫原による初回免疫化(プライミング)を左右の脚に投与した。その後の追加免疫をAlhydrogelの存在下で行い、採取3日前に、PBS中の免疫原を用いる追加免疫を実施した。最終採血時にラットから血清を収集し、血清力価を決定した。
血清力価の要約情報は、図6に示される。図6に示されるグラフでは、各線は、個々の動物を表す。グラフの凡例は、個々の各動物のID番号を示す。huCD22+Fcタンパク質、huCD22+Hisタグ、アカゲザルCD22+Hisタグタンパク質タンパク質、及びHisタグオフターゲットタンパク質に対する血清の8点希釈系列の結合活性をELISAで試験した。この動物群の中で、ヒト及びアカゲザルの両方のCD22タンパク質に対する一連の血清反応性レベルが観察された。Hisタンパク質タグに対する血清応答も観察された。
図4は、本明細書に記載の抗CD22重鎖のみ抗体の標的結合活性をまとめたものである。列1は、抗CD22重鎖のみ抗体のクローンID番号を示す。列2は、モル濃度で測定されたタンパク質(KD)への結合親和性を示す。列3は、秒単位で測定されたタンパク質への結合の解離定数(K−off rate)を示す。列4は、バックグラウンドMFIシグナルの倍数として測定されたDaudi細胞への結合を示す。列5は、バックグラウンドMFIシグナルの倍数として測定されたcyno CD22を安定的に発現するCHO細胞への結合を示す。列6は、バックグラウンドMFIシグナルの倍数として測定されたCD22タンパク質を発現しないCHO細胞への結合を示す。
3つの異なるCD22陽性バーキットリンパ腫腫瘍細胞株(Daudi、Raji、及びRamos)を色素標識し、前活性化ヒトT細胞の存在下で、漸増量の二重特異性抗体と共にインキュベートした。二重特異性抗体は、図5Dに概略的に示されるように、抗CD22 VH結合ドメインと対になった抗CD3結合アームから構成された。陰性対照抗体は、CD22に結合しないVH結合ドメインを含んでいた。CD22陰性K562細胞は、特異的溶解を示さなかった(データを示さず)。同じ抗CD3結合ドメインと対になった3つの異なる抗CD22重鎖のみ結合ドメインを組み込んだ3つの二重特異性抗体のデータは、陰性対照と比較して図5Aに示され、活性化T細胞のリダイレクトを介してCD22陽性Daudi腫瘍細胞の抗体媒介性殺傷を示す。2つの異なる抗CD3結合ドメインと対になった同じ抗CD22重鎖のみ結合ドメインを組み込む2つの二重特異性抗体のデータは、陰性対照と比較して図5Bに示され、活性化T細胞のリダイレクトを介してCD22陽性Raji腫瘍細胞の抗体媒介性殺傷を示す。2つの異なる抗CD3結合ドメインと対になった同じ抗CD22重鎖のみ結合ドメインを組み込む2つの二重特異性抗体のデータは、陰性対照と比較して図5Cに示され、活性化T細胞のリダイレクトを介してCD22陽性Ramos腫瘍細胞の抗体媒介性殺傷を示す。
Claims (35)
- (a)配列番号1〜10のアミノ酸配列のいずれかに2つ以下の置換を有するCDR1、及び/または
(b)配列番号11〜17のアミノ酸配列のいずれかに2つ以下の置換を有するCDR2、及び/または
(c)配列番号18〜23のアミノ酸配列のいずれかに2つ以下の置換を有するCDR3、
を含む重鎖可変領域を含む、CD22に結合する重鎖のみ抗体。 - 前記CDR1、CDR2、及びCDR3配列が、ヒトフレームワークに存在する、請求項1に記載の重鎖のみ抗体。
- さらに、CH1配列が存在しない重鎖定常領域配列を含む、請求項1に記載の重鎖のみ抗体。
- (a)配列番号1〜10からなる群より選択されるCDR1配列、及び/または
(b)配列番号11〜17からなる群より選択されるCDR2配列、及び/または
(c)配列番号18〜23からなる群より選択されるCDR3配列、
を含む、請求項1〜3のいずれか1項に記載の重鎖のみ抗体。 - (a)配列番号1〜10からなる群より選択されるCDR1配列、及び
(b)配列番号11〜17からなる群より選択されるCDR2配列、及び
(c)配列番号18〜23からなる群より選択されるCDR3配列、
を含む、請求項4に記載の重鎖のみ抗体。 - (a)配列番号1のCDR1配列、配列番号11のCDR2配列、及び配列番号18のCDR3配列、または
(b)配列番号1のCDR1配列、配列番号12のCDR2配列、及び配列番号19のCDR3配列、または
(c)配列番号1のCDR1配列、配列番号12のCDR2配列、及び配列番号20のCDR3配列、
を含む、請求項5に記載の重鎖のみ抗体。 - 配列番号24〜84の配列のいずれかと少なくとも95%の配列同一性を有する重鎖可変領域を含む、請求項1〜3のいずれか1項に記載の重鎖のみ抗体。
- 配列番号24〜84からなる群より選択される重鎖可変領域配列を含む、請求項7に記載の重鎖のみ抗体。
- 配列番号24の重鎖可変領域配列を含む、請求項8に記載の重鎖のみ抗体。
- (a)式:
GX1SIX2X3X4X5X6Y
(式中、X1は、DまたはGであり、
X2は、S、T、I、またはNであり、
X3は、SまたはDであり、
X4は、G、S、またはNであり、
X5は、D、G、またはSであり、
X6は、YまたはHである)のCDR1配列、及び
(b)式:
X7X8YX9GX10X11
(式中、X7は、IまたはVであり、
X8は、YまたはHであり、
X9は、SまたはTであり、
X10は、A、V、またはSであり、
X11は、TまたはAである)のCDR2配列、及び
(c)式:
X12RX13DSSX14WRS
(式中、X12は、T、A、またはKであり、
X13は、DまたはEであり、
X14は、NまたはSである)のCDR3配列
を含む重鎖可変を含む重鎖可変領域を含む、CD22に結合する重鎖のみ抗体。 - 前記CDR配列が、配列番号1〜23からなる群より選択されるCDR配列に2つ以下の置換を有する配列である、ヒトVHフレームワークにCDR1、CDR2、及びCDR3配列を含む重鎖可変領域を含む、CD22に結合する重鎖のみ抗体。
- 前記CDR配列が、配列番号1〜23からなる群より選択される、ヒトVHフレームワークにCDR1、CDR2、及びCDR3配列を含む重鎖可変領域を含む、請求項11に記載の重鎖のみ抗体。
- ヒトVHフレームワークに
(a)配列番号1のCDR1配列、配列番号11のCDR2配列、及び配列番号18のCDR3配列、または
(b)配列番号1のCDR1配列、配列番号12のCDR2配列、及び配列番号19のCDR3配列、または
(c)配列番号1のCDR1配列、配列番号12のCDR2配列、及び配列番号20のCDR3配列、
を含む重鎖可変領域を含む、CD22に結合する重鎖のみ抗体。 - 多重特異性である、請求項1〜13のいずれか1項に記載の重鎖のみ抗体。
- 二重特異性である、請求項14に記載の重鎖のみ抗体。
- 2つの異なるCD22タンパク質に対する結合親和性を有する、請求項15に記載の重鎖のみ抗体。
- 同じCD22タンパク質上の2つの異なるエピトープに対する結合親和性を有する、請求項15に記載の重鎖のみ抗体。
- エフェクター細胞に対する結合親和性を有する、請求項14に記載の重鎖のみ抗体。
- T細胞抗原に対する結合親和性を有する、請求項14に記載の重鎖のみ抗体。
- CD3に対する結合親和性を有する、請求項19に記載の重鎖のみ抗体。
- CAR−Tフォーマットである、請求項1〜20のいずれか1項に記載の重鎖のみ抗体。
- 請求項1〜21のいずれか1項に記載の重鎖のみ抗体を含む、医薬組成物。
- CD22の発現を特徴とするB細胞障害の処置のための方法であって、前記障害を有する対象に、請求項1〜21のいずれか1項に記載の抗体または請求項22に記載の医薬組成物を投与することを含む、前記方法。
- CD22の発現を特徴とするB細胞障害の処置のための薬品の調製における、請求項1〜21のいずれか1項に記載の抗体の使用。
- CD22の発現を特徴とするB細胞障害の処置に使用される、請求項1〜21のいずれか1項に記載の抗体。
- 前記障害が、びまん性大B細胞リンパ腫(DLBCL)である、請求項23〜25のいずれか1項に記載の方法。
- 前記障害が、非ホジキンリンパ腫(NHL)である、請求項23〜25のいずれか1項に記載の方法。
- 前記障害が、全身性エリテマトーデス(SLE)である、請求項23〜25のいずれか1項に記載の方法。
- 前記障害が、関節リウマチ(RA)である、請求項23〜25のいずれか1項に記載の方法。
- 前記障害が、多発性硬化症(MS)である、請求項23〜25のいずれか1項に記載の方法。
- 請求項1〜21のいずれかに記載の抗体をコードする、ポリヌクレオチド。
- 請求項31に記載のポリヌクレオチドを含む、ベクター。
- 請求項32に記載のベクターを含む、細胞。
- 前記抗体の発現を許容する条件下で、請求項31に記載の細胞を成長させること、及び前記細胞から前記抗体を単離することを含む、請求項1〜21のいずれかに記載の抗体を産生する方法。
- CD22でUniRat動物を免疫すること及びCD22結合重鎖配列を同定することを含む、請求項1〜21のいずれか1項に記載の抗体を作製する方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2024015399A JP2024062992A (ja) | 2017-12-22 | 2024-02-05 | Cd22に結合する重鎖抗体 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762609759P | 2017-12-22 | 2017-12-22 | |
US62/609,759 | 2017-12-22 | ||
PCT/US2018/067299 WO2019126756A1 (en) | 2017-12-22 | 2018-12-21 | Heavy chain antibodies binding to cd22 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2024015399A Division JP2024062992A (ja) | 2017-12-22 | 2024-02-05 | Cd22に結合する重鎖抗体 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2021506325A true JP2021506325A (ja) | 2021-02-22 |
JP7486421B2 JP7486421B2 (ja) | 2024-05-17 |
Family
ID=65041936
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020534858A Active JP7486421B2 (ja) | 2017-12-22 | 2018-12-21 | Cd22に結合する重鎖抗体 |
JP2024015399A Pending JP2024062992A (ja) | 2017-12-22 | 2024-02-05 | Cd22に結合する重鎖抗体 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2024015399A Pending JP2024062992A (ja) | 2017-12-22 | 2024-02-05 | Cd22に結合する重鎖抗体 |
Country Status (21)
Country | Link |
---|---|
US (2) | US11873336B2 (ja) |
EP (1) | EP3728319A1 (ja) |
JP (2) | JP7486421B2 (ja) |
KR (1) | KR20200104342A (ja) |
CN (1) | CN111683966B (ja) |
AU (1) | AU2018392088A1 (ja) |
BR (1) | BR112020012554A2 (ja) |
CA (1) | CA3086665A1 (ja) |
CL (2) | CL2020001703A1 (ja) |
CO (1) | CO2020008925A2 (ja) |
CR (1) | CR20200322A (ja) |
EA (1) | EA202091557A1 (ja) |
EC (1) | ECSP20042489A (ja) |
IL (1) | IL275498A (ja) |
JO (1) | JOP20200157A1 (ja) |
MX (1) | MX2020006494A (ja) |
NI (1) | NI202000050A (ja) |
PE (1) | PE20201171A1 (ja) |
PH (1) | PH12020550964A1 (ja) |
SG (1) | SG11202005880XA (ja) |
WO (1) | WO2019126756A1 (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA3029209A1 (en) | 2016-06-21 | 2017-12-28 | Teneobio, Inc. | Cd3 binding antibodies |
BR112019004873A2 (pt) | 2016-09-14 | 2019-06-11 | Teneobio Inc | anticorpos de ligação a cd3 |
JP7240335B2 (ja) | 2017-06-20 | 2023-03-15 | テネオワン, インコーポレイテッド | 抗bcma重鎖のみ抗体 |
EP3728319A1 (en) | 2017-12-22 | 2020-10-28 | TeneoBio, Inc. | Heavy chain antibodies binding to cd22 |
WO2020252366A1 (en) | 2019-06-14 | 2020-12-17 | Teneobio, Inc. | Multispecific heavy chain antibodies binding to cd22 and cd3 |
KR20210143097A (ko) * | 2020-05-19 | 2021-11-26 | (주)이노베이션바이오 | Cd22에 특이적인 항체 및 이의 용도 |
US20230250184A1 (en) * | 2020-07-16 | 2023-08-10 | Nanjing Legend Biotech Co., Ltd. | Cd22 binding molecules and uses thereof |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20170275363A1 (en) * | 2014-02-25 | 2017-09-28 | Immunomedics, Inc. | Humanized anti-cd22 antibody |
Family Cites Families (69)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
US6407213B1 (en) | 1991-06-14 | 2002-06-18 | Genentech, Inc. | Method for making humanized antibodies |
US6096871A (en) | 1995-04-14 | 2000-08-01 | Genentech, Inc. | Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life |
EP0904107B1 (en) | 1996-03-18 | 2004-10-20 | Board Of Regents, The University Of Texas System | Immunoglobin-like domains with increased half lives |
PL357939A1 (en) | 2000-04-11 | 2004-08-09 | Genentech, Inc. | Multivalent antibodies and uses therefor |
GB0115256D0 (en) | 2001-06-21 | 2001-08-15 | Babraham Inst | Mouse light chain locus |
AU2003287345A1 (en) | 2002-10-31 | 2004-06-07 | Genentech, Inc. | Methods and compositions for increasing antibody production |
AU2004205684A1 (en) | 2003-01-23 | 2004-08-05 | Genentech, Inc. | Methods for producing humanized antibodies and improving yield of antibodies or antigen binding fragments in cell culture |
RU2398882C2 (ru) | 2004-07-22 | 2010-09-10 | Эрасмус Юниверсити Медикал Сентр Роттердам | СПОСОБ ПОЛУЧЕНИЯ АНТИГЕН-СВЯЗЫВАЮЩЕГО ДОМЕНА Vh ИСПОЛЬЗОВАНИЕ |
US20160355591A1 (en) | 2011-05-02 | 2016-12-08 | Immunomedics, Inc. | Subcutaneous anti-hla-dr monoclonal antibody for treatment of hematologic malignancies |
US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
NZ580755A (en) | 2007-04-03 | 2012-05-25 | Micromet Ag | Cross-species-specific cd3-epsilon binding domain |
WO2008151081A1 (en) | 2007-06-01 | 2008-12-11 | Omt, Inc. | Compositions and methods for inhibiting endogenous immunoglobulin genes and producing transgenic human idiotype antibodies |
US20100122358A1 (en) | 2008-06-06 | 2010-05-13 | Crescendo Biologics Limited | H-Chain-only antibodies |
CA2734330A1 (en) | 2008-09-19 | 2010-03-25 | Medimmune, Llc | Antibodies against sonic hedgehog homolog and uses thereof |
SI2356153T1 (sl) | 2008-10-01 | 2016-07-29 | Amgen Research (Munich) Gmbh | Bispecifično enoverižno protitelo, specifično za križane vrste |
PT2406284T (pt) | 2009-03-10 | 2016-09-29 | Biogen Ma Inc | Anticorpos anti-bcma |
GB0905023D0 (en) | 2009-03-24 | 2009-05-06 | Univ Erasmus Medical Ct | Binding molecules |
US9345661B2 (en) | 2009-07-31 | 2016-05-24 | Genentech, Inc. | Subcutaneous anti-HER2 antibody formulations and uses thereof |
ES2547142T5 (es) | 2010-02-08 | 2021-12-09 | Regeneron Pharma | Cadena ligera común de ratón |
TWI653333B (zh) | 2010-04-01 | 2019-03-11 | 安進研究(慕尼黑)有限責任公司 | 跨物種專一性之PSMAxCD3雙專一性單鏈抗體 |
US20130273055A1 (en) | 2010-11-16 | 2013-10-17 | Eric Borges | Agents and methods for treating diseases that correlate with bcma expression |
EP2683735A1 (en) | 2011-03-10 | 2014-01-15 | HCO Antibody, Inc. | Bispecific three-chain antibody-like molecules |
WO2012122512A1 (en) | 2011-03-10 | 2012-09-13 | Hco Antibody, Inc. | Recombinant production of mixtures of single chain antibodies |
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 |
RU2673153C2 (ru) | 2012-04-20 | 2018-11-22 | АПТЕВО РИСЁРЧ ЭНД ДИВЕЛОПМЕНТ ЭлЭлСи | Полипептиды, связывающиеся с cd3 |
MX361533B (es) | 2012-04-26 | 2018-12-07 | Bioatla Llc | Anticuerpos anti-cd22. |
US20150203591A1 (en) | 2012-08-02 | 2015-07-23 | Regeneron Pharmaceuticals, Inc. | Mutivalent antigen-binding proteins |
JOP20200236A1 (ar) | 2012-09-21 | 2017-06-16 | Regeneron Pharma | الأجسام المضادة لمضاد cd3 وجزيئات ربط الأنتيجين ثنائية التحديد التي تربط cd3 وcd20 واستخداماتها |
KR102239125B1 (ko) | 2012-12-14 | 2021-04-12 | 오픈 모노클로날 테크놀로지, 인코포레이티드 | 인간 이디오타입을 갖는 설치류 항체를 인코딩하는 폴리뉴클레오티드 및 이를 포함하는 동물 |
EP2953972B1 (en) | 2013-02-05 | 2020-07-08 | EngMab Sàrl | Method for the selection of antibodies against bcma |
AR095374A1 (es) | 2013-03-15 | 2015-10-14 | Amgen Res (Munich) Gmbh | Moléculas de unión para bcma y cd3 |
WO2015095412A1 (en) | 2013-12-19 | 2015-06-25 | Zhong Wang | Bispecific antibody with two single-domain antigen-binding fragments |
WO2015121383A1 (en) | 2014-02-12 | 2015-08-20 | Michael Uhlin | Bispecific antibodies for use in stem cell transplantation |
TWI754319B (zh) | 2014-03-19 | 2022-02-01 | 美商再生元醫藥公司 | 用於腫瘤治療之方法及抗體組成物 |
MX2017001011A (es) | 2014-07-21 | 2018-05-28 | Novartis Ag | Tratamiento de cancer de usando un receptor quimerico de antigeno anti-bcma. |
EP3172235A2 (en) | 2014-07-25 | 2017-05-31 | Cytomx Therapeutics Inc. | Anti-cd3 antibodies, activatable anti-cd3 antibodies, multispecific anti-cd3 antibodies, multispecific activatable anti-cd3 antibodies, and methods of using the same |
PT3221357T (pt) | 2014-11-20 | 2020-07-28 | Hoffmann La Roche | Cadeias leves comuns e métodos de utilização |
EP3023437A1 (en) | 2014-11-20 | 2016-05-25 | EngMab AG | Bispecific antibodies against CD3epsilon and BCMA |
CN104710528B (zh) * | 2015-03-13 | 2019-02-15 | 西北农林科技大学 | 一种特异性结合PRRS病毒非结构蛋白Nsp9纳米抗体及其应用 |
MD3411402T2 (ro) | 2016-02-03 | 2022-05-31 | Amgen Res Munich Gmbh | Constructe de anticorpi bispecifici BCMA și CD3 de angajare a celulei T |
CA3029209A1 (en) | 2016-06-21 | 2017-12-28 | Teneobio, Inc. | Cd3 binding antibodies |
AU2017316604A1 (en) * | 2016-08-24 | 2019-04-11 | Teneobio, Inc. | Transgenic non-human animals producing modified heavy chain-only antibodies |
BR112019004873A2 (pt) | 2016-09-14 | 2019-06-11 | Teneobio Inc | anticorpos de ligação a cd3 |
MX2019007379A (es) | 2016-12-21 | 2019-09-18 | Teneobio Inc | Anticuerpos anti-bcma unicamente de cadena pesada. |
JP7240335B2 (ja) | 2017-06-20 | 2023-03-15 | テネオワン, インコーポレイテッド | 抗bcma重鎖のみ抗体 |
CN117866097A (zh) | 2017-06-20 | 2024-04-12 | 特尼奥生物股份有限公司 | 仅有重链的抗bcma抗体 |
ES2928296T3 (es) | 2017-06-30 | 2022-11-16 | Us Health | Receptores de antígenos quiméricos anti-antígenos de maduración de linfocitos B con dominios humanos |
JP2020533362A (ja) | 2017-09-13 | 2020-11-19 | テネオバイオ, インコーポレイテッド | エクト酵素に結合する重鎖抗体 |
EP3728319A1 (en) | 2017-12-22 | 2020-10-28 | TeneoBio, Inc. | Heavy chain antibodies binding to cd22 |
WO2019133761A1 (en) | 2017-12-27 | 2019-07-04 | Teneobio, Inc. | Cd3-delta/epsilon heterodimer specific antibodies |
JP7439046B2 (ja) | 2018-07-20 | 2024-02-27 | テネオツー・インコーポレイテッド | Cd19に結合する重鎖抗体 |
US20210355215A1 (en) | 2018-09-21 | 2021-11-18 | Teneobio, Inc. | Methods for purifying heterodimeric, multispecific antibodies |
BR112021000173A2 (pt) | 2018-10-26 | 2021-05-04 | Teneobio, Inc. | anticorpos de cadeia pesada com ligação a cd38 |
EP3947470A1 (en) | 2019-04-05 | 2022-02-09 | TeneoBio, Inc. | Heavy chain antibodies binding to psma |
WO2020252366A1 (en) | 2019-06-14 | 2020-12-17 | Teneobio, Inc. | Multispecific heavy chain antibodies binding to cd22 and cd3 |
EP4077391A1 (en) | 2019-12-18 | 2022-10-26 | Teneofour, Inc. | Heavy chain antibodies binding to cd38 |
WO2021222578A1 (en) | 2020-04-29 | 2021-11-04 | Teneobio, Inc. | Multispecific heavy chain antibodies with modified heavy chain constant regions |
US20210403587A1 (en) | 2020-04-29 | 2021-12-30 | Teneobio, Inc. | Methods of treating multiple myeloma |
EP4171750A1 (en) | 2020-06-30 | 2023-05-03 | Teneobio, Inc. | Multi-specific antibodies binding to bcma |
TW202233684A (zh) | 2020-11-18 | 2022-09-01 | 美商泰尼歐生物公司 | 結合於葉酸受體α之重鏈抗體 |
MX2023009874A (es) | 2021-02-25 | 2023-08-30 | Teneobio Inc | Anticuerpos anti-psma y estructuras car-t. |
CA3211142A1 (en) | 2021-02-26 | 2022-09-01 | Teneobio, Inc. | Anti-muc1-c antibodies and car-t structures |
TW202304994A (zh) | 2021-04-02 | 2023-02-01 | 美商泰尼歐生物公司 | 促效性抗il-2r抗體及使用方法 |
IL306043A (en) | 2021-04-06 | 2023-11-01 | Teneobio Inc | Anti-CD19 antibodies and chimeric T-antigen receptor constructs |
IL306045A (en) | 2021-04-16 | 2023-11-01 | Teneobio Inc | Anti-CD20 antibodies and chimeric T-antigen receptor constructs |
WO2022271987A1 (en) | 2021-06-23 | 2022-12-29 | TeneoFour, Inc. | Anti-cd38 antibodies and epitopes of same |
WO2023004197A1 (en) | 2021-07-23 | 2023-01-26 | Teneoten, Inc. | Heavy chain antibodies binding to hepatitis b surface antigen |
-
2018
- 2018-12-21 EP EP18836782.5A patent/EP3728319A1/en active Pending
- 2018-12-21 CA CA3086665A patent/CA3086665A1/en active Pending
- 2018-12-21 EA EA202091557A patent/EA202091557A1/ru unknown
- 2018-12-21 KR KR1020207021048A patent/KR20200104342A/ko active Search and Examination
- 2018-12-21 JP JP2020534858A patent/JP7486421B2/ja active Active
- 2018-12-21 CR CR20200322A patent/CR20200322A/es unknown
- 2018-12-21 WO PCT/US2018/067299 patent/WO2019126756A1/en active Application Filing
- 2018-12-21 MX MX2020006494A patent/MX2020006494A/es unknown
- 2018-12-21 SG SG11202005880XA patent/SG11202005880XA/en unknown
- 2018-12-21 BR BR112020012554-7A patent/BR112020012554A2/pt active Search and Examination
- 2018-12-21 AU AU2018392088A patent/AU2018392088A1/en active Pending
- 2018-12-21 US US16/956,502 patent/US11873336B2/en active Active
- 2018-12-21 JO JOP/2020/0157A patent/JOP20200157A1/ar unknown
- 2018-12-21 PE PE2020000809A patent/PE20201171A1/es unknown
- 2018-12-21 CN CN201880083056.4A patent/CN111683966B/zh active Active
-
2020
- 2020-06-18 IL IL275498A patent/IL275498A/en unknown
- 2020-06-20 CL CL2020001703A patent/CL2020001703A1/es unknown
- 2020-06-22 PH PH12020550964A patent/PH12020550964A1/en unknown
- 2020-06-22 NI NI202000050A patent/NI202000050A/es unknown
- 2020-07-21 CO CONC2020/0008925A patent/CO2020008925A2/es unknown
- 2020-07-22 EC ECSENADI202042489A patent/ECSP20042489A/es unknown
-
2022
- 2022-08-18 CL CL2022002247A patent/CL2022002247A1/es unknown
-
2023
- 2023-12-07 US US18/532,880 patent/US20240117046A1/en active Pending
-
2024
- 2024-02-05 JP JP2024015399A patent/JP2024062992A/ja active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20170275363A1 (en) * | 2014-02-25 | 2017-09-28 | Immunomedics, Inc. | Humanized anti-cd22 antibody |
Non-Patent Citations (2)
Title |
---|
NAJMEH ZAREI ET AL.: "High efficient expression of a functional humanized single-chain variable fragment (scFv) antibody a", APPL. MICROBIOL. BIOTECHNOL., vol. 98, no. 24, JPN6022050471, 21 September 2014 (2014-09-21), pages 10023 - 10039, XP009512236, ISSN: 0005086871, DOI: 10.1007/s00253-014-6071-2 * |
SOLMAZ AGHA AMIRI ET AL.: "A novel anti-CD22 scFv-apoptin fusion protein induces apoptosis in malignant B-cells.", AMB EXPRESS, vol. 7:112, JPN6022050469, 2 June 2017 (2017-06-02), ISSN: 0005086870 * |
Also Published As
Publication number | Publication date |
---|---|
EP3728319A1 (en) | 2020-10-28 |
EA202091557A1 (ru) | 2020-11-18 |
AU2018392088A2 (en) | 2020-08-27 |
ECSP20042489A (es) | 2020-11-30 |
CL2022002247A1 (es) | 2023-02-24 |
WO2019126756A1 (en) | 2019-06-27 |
CN111683966A (zh) | 2020-09-18 |
PH12020550964A1 (en) | 2021-03-22 |
AU2018392088A1 (en) | 2020-08-13 |
CR20200322A (es) | 2021-01-12 |
US11873336B2 (en) | 2024-01-16 |
WO2019126756A9 (en) | 2019-10-17 |
IL275498A (en) | 2020-08-31 |
CN111683966B (zh) | 2023-07-11 |
RU2020124188A (ru) | 2022-01-24 |
CL2020001703A1 (es) | 2020-11-06 |
JP7486421B2 (ja) | 2024-05-17 |
US20240117046A1 (en) | 2024-04-11 |
JOP20200157A1 (ar) | 2022-10-30 |
CO2020008925A2 (es) | 2020-10-30 |
NI202000050A (es) | 2020-12-04 |
BR112020012554A2 (pt) | 2020-11-24 |
MX2020006494A (es) | 2020-11-24 |
CA3086665A1 (en) | 2019-06-27 |
PE20201171A1 (es) | 2020-10-28 |
US20210095022A1 (en) | 2021-04-01 |
KR20200104342A (ko) | 2020-09-03 |
SG11202005880XA (en) | 2020-07-29 |
JP2024062992A (ja) | 2024-05-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN110431151B (zh) | 仅有重链的抗bcma抗体 | |
US20240124599A1 (en) | Anti-bcma heavy chain-only antibodies | |
JP7240335B2 (ja) | 抗bcma重鎖のみ抗体 | |
US11873336B2 (en) | Heavy chain antibodies binding to CD22 | |
US11905326B2 (en) | Multispecific heavy chain antibodies binding to CD22 and CD3 | |
US20210332133A1 (en) | Heavy chain antibodies binding to cd19 | |
JP2020533362A (ja) | エクト酵素に結合する重鎖抗体 | |
RU2797348C2 (ru) | Антитела, содержащие только тяжелые цепи, которые связываются с cd22 | |
EA045291B1 (ru) | Антитела, содержащие только тяжелые цепи, которые связываются с cd22 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211217 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20211217 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20221129 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230215 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230501 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230620 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230920 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20231003 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240205 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20240314 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20240409 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20240507 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7486421 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |