JP7155126B2 - ヒトｉｌ－１５に特異的に結合する抗体及びその使用 - Google Patents
ヒトｉｌ－１５に特異的に結合する抗体及びその使用 Download PDFInfo
- Publication number
- JP7155126B2 JP7155126B2 JP2019533652A JP2019533652A JP7155126B2 JP 7155126 B2 JP7155126 B2 JP 7155126B2 JP 2019533652 A JP2019533652 A JP 2019533652A JP 2019533652 A JP2019533652 A JP 2019533652A JP 7155126 B2 JP7155126 B2 JP 7155126B2
- Authority
- JP
- Japan
- Prior art keywords
- seq
- antibody
- amino acid
- acid sequence
- variable region
- 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
- 101001055157 Homo sapiens Interleukin-15 Proteins 0.000 title claims description 100
- 102000056003 human IL15 Human genes 0.000 title claims description 100
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 412
- 102000003812 Interleukin-15 Human genes 0.000 claims description 252
- 108090000172 Interleukin-15 Proteins 0.000 claims description 252
- 210000004027 cell Anatomy 0.000 claims description 112
- 230000027455 binding Effects 0.000 claims description 87
- 108010068370 Glutens Proteins 0.000 claims description 59
- 235000021312 gluten Nutrition 0.000 claims description 59
- 238000011282 treatment Methods 0.000 claims description 43
- 108010017535 Interleukin-15 Receptors Proteins 0.000 claims description 41
- 102000004556 Interleukin-15 Receptors Human genes 0.000 claims description 41
- 238000004519 manufacturing process Methods 0.000 claims description 39
- 108091033319 polynucleotide Proteins 0.000 claims description 38
- 239000002157 polynucleotide Substances 0.000 claims description 38
- 102000040430 polynucleotide Human genes 0.000 claims description 38
- 208000015943 Coeliac disease Diseases 0.000 claims description 37
- 239000003814 drug Substances 0.000 claims description 37
- 239000000203 mixture Substances 0.000 claims description 32
- 210000001519 tissue Anatomy 0.000 claims description 32
- 150000007523 nucleic acids Chemical group 0.000 claims description 31
- 210000000822 natural killer cell Anatomy 0.000 claims description 29
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 25
- 238000001516 cell proliferation assay Methods 0.000 claims description 24
- 238000010494 dissociation reaction Methods 0.000 claims description 18
- 230000005593 dissociations Effects 0.000 claims description 18
- 230000000968 intestinal effect Effects 0.000 claims description 18
- 208000024891 symptom Diseases 0.000 claims description 18
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 17
- 108090000623 proteins and genes Proteins 0.000 claims description 17
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 claims description 17
- 208000027866 inflammatory disease Diseases 0.000 claims description 16
- 201000004681 Psoriasis Diseases 0.000 claims description 15
- 239000003937 drug carrier Substances 0.000 claims description 15
- 230000035945 sensitivity Effects 0.000 claims description 15
- 102000004169 proteins and genes Human genes 0.000 claims description 14
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 14
- 235000018102 proteins Nutrition 0.000 claims description 13
- 239000013598 vector Substances 0.000 claims description 13
- 208000023275 Autoimmune disease Diseases 0.000 claims description 12
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 12
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 12
- 208000004631 alopecia areata Diseases 0.000 claims description 12
- 230000004663 cell proliferation Effects 0.000 claims description 12
- 235000005911 diet Nutrition 0.000 claims description 12
- 208000006404 Large Granular Lymphocytic Leukemia Diseases 0.000 claims description 11
- 206010023791 Large granular lymphocytosis Diseases 0.000 claims description 11
- 201000008717 T-cell large granular lymphocyte leukemia Diseases 0.000 claims description 11
- 230000037213 diet Effects 0.000 claims description 11
- 102000039446 nucleic acids Human genes 0.000 claims description 11
- 108020004707 nucleic acids Proteins 0.000 claims description 11
- 208000021329 Refractory celiac disease Diseases 0.000 claims description 10
- 206010020751 Hypersensitivity Diseases 0.000 claims description 9
- 208000026935 allergic disease Diseases 0.000 claims description 9
- 230000006378 damage Effects 0.000 claims description 8
- 201000007235 gluten allergy Diseases 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 206010012735 Diarrhoea Diseases 0.000 claims description 6
- 208000027418 Wounds and injury Diseases 0.000 claims description 6
- 230000007815 allergy Effects 0.000 claims description 6
- 208000014674 injury Diseases 0.000 claims description 6
- 210000000813 small intestine Anatomy 0.000 claims description 6
- 208000019901 Anxiety disease Diseases 0.000 claims description 5
- 208000006820 Arthralgia Diseases 0.000 claims description 5
- 206010010774 Constipation Diseases 0.000 claims description 5
- 208000010201 Exanthema Diseases 0.000 claims description 5
- 206010019233 Headaches Diseases 0.000 claims description 5
- 208000019695 Migraine disease Diseases 0.000 claims description 5
- 208000007101 Muscle Cramp Diseases 0.000 claims description 5
- 208000000112 Myalgia Diseases 0.000 claims description 5
- 206010028813 Nausea Diseases 0.000 claims description 5
- 230000036506 anxiety Effects 0.000 claims description 5
- 210000004556 brain Anatomy 0.000 claims description 5
- 201000005884 exanthem Diseases 0.000 claims description 5
- 206010016256 fatigue Diseases 0.000 claims description 5
- 206010016766 flatulence Diseases 0.000 claims description 5
- 231100000869 headache Toxicity 0.000 claims description 5
- 230000008693 nausea Effects 0.000 claims description 5
- 206010037844 rash Diseases 0.000 claims description 5
- 231100000046 skin rash Toxicity 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 claims description 4
- 206010027599 migraine Diseases 0.000 claims description 4
- 208000013465 muscle pain Diseases 0.000 claims description 4
- 230000036407 pain Effects 0.000 claims description 4
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 3
- 210000004962 mammalian cell Anatomy 0.000 claims description 3
- 206010022998 Irritability Diseases 0.000 claims description 2
- 210000004877 mucosa Anatomy 0.000 claims description 2
- 230000003472 neutralizing effect Effects 0.000 claims description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 238000000034 method Methods 0.000 description 64
- 230000004075 alteration Effects 0.000 description 32
- 235000001014 amino acid Nutrition 0.000 description 31
- 238000005259 measurement Methods 0.000 description 31
- 230000003993 interaction Effects 0.000 description 25
- 229940024606 amino acid Drugs 0.000 description 23
- 210000004408 hybridoma Anatomy 0.000 description 23
- 230000035755 proliferation Effects 0.000 description 23
- 239000000427 antigen Substances 0.000 description 22
- 239000000523 sample Substances 0.000 description 20
- 238000006467 substitution reaction Methods 0.000 description 20
- 150000001413 amino acids Chemical group 0.000 description 19
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 18
- 241000282560 Macaca mulatta Species 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 18
- 108091007433 antigens Proteins 0.000 description 18
- 102000036639 antigens Human genes 0.000 description 18
- 241001465754 Metazoa Species 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 230000004048 modification Effects 0.000 description 16
- 238000012986 modification Methods 0.000 description 16
- 230000001404 mediated effect Effects 0.000 description 15
- 230000014509 gene expression Effects 0.000 description 14
- 239000001257 hydrogen Substances 0.000 description 14
- 229910052739 hydrogen Inorganic materials 0.000 description 14
- 230000005764 inhibitory process Effects 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 13
- 238000003556 assay Methods 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 210000002966 serum Anatomy 0.000 description 12
- 108020004414 DNA Proteins 0.000 description 11
- 241000700159 Rattus Species 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 238000006722 reduction reaction Methods 0.000 description 11
- 239000006228 supernatant Substances 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 238000002965 ELISA Methods 0.000 description 9
- 108010002350 Interleukin-2 Proteins 0.000 description 9
- 102000000588 Interleukin-2 Human genes 0.000 description 9
- 235000004279 alanine Nutrition 0.000 description 9
- 210000001616 monocyte Anatomy 0.000 description 9
- 238000001890 transfection Methods 0.000 description 9
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical group COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 8
- 238000010790 dilution Methods 0.000 description 8
- 239000012895 dilution Substances 0.000 description 8
- 231100000673 dose–response relationship Toxicity 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 108091035707 Consensus sequence Proteins 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 238000004020 luminiscence type Methods 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 108700039882 Protein Glutamine gamma Glutamyltransferase 2 Proteins 0.000 description 6
- 102100038095 Protein-glutamine gamma-glutamyltransferase 2 Human genes 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000013604 expression vector Substances 0.000 description 6
- -1 thiol compounds Chemical class 0.000 description 6
- 230000009261 transgenic effect Effects 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 238000012867 alanine scanning Methods 0.000 description 5
- 238000001574 biopsy Methods 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 238000011069 regeneration method Methods 0.000 description 5
- 239000012146 running buffer Substances 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 101001003140 Homo sapiens Interleukin-15 receptor subunit alpha Proteins 0.000 description 4
- 241000282567 Macaca fascicularis Species 0.000 description 4
- 206010028116 Mucosal inflammation Diseases 0.000 description 4
- 102100022682 NKG2-A/NKG2-B type II integral membrane protein Human genes 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000000423 cell based assay Methods 0.000 description 4
- 238000013480 data collection Methods 0.000 description 4
- 239000003623 enhancer Substances 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 210000004602 germ cell Anatomy 0.000 description 4
- 235000006171 gluten free diet Nutrition 0.000 description 4
- 235000020884 gluten-free diet Nutrition 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 208000028774 intestinal disease Diseases 0.000 description 4
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 230000008929 regeneration Effects 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 3
- 238000003734 CellTiter-Glo Luminescent Cell Viability Assay Methods 0.000 description 3
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 3
- 108010053727 Interleukin-15 Receptor alpha Subunit Proteins 0.000 description 3
- 102100020789 Interleukin-15 receptor subunit alpha Human genes 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 208000037902 enteropathy Diseases 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 230000009610 hypersensitivity Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 3
- 238000013507 mapping Methods 0.000 description 3
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000002424 x-ray crystallography Methods 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
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical compound CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 2
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 2
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 2
- 101001109508 Homo sapiens NKG2-A/NKG2-B type II integral membrane protein Proteins 0.000 description 2
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 108010002586 Interleukin-7 Proteins 0.000 description 2
- 108010002335 Interleukin-9 Proteins 0.000 description 2
- 101150069255 KLRC1 gene Proteins 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 2
- 101100404845 Macaca mulatta NKG2A gene Proteins 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 206010042971 T-cell lymphoma Diseases 0.000 description 2
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000009830 antibody antigen interaction Effects 0.000 description 2
- 230000009833 antibody interaction Effects 0.000 description 2
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000010804 cDNA synthesis Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000021235 carbamoylation Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 208000019902 chronic diarrheal disease Diseases 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000002447 crystallographic data Methods 0.000 description 2
- 150000001913 cyanates Chemical class 0.000 description 2
- XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 108010074108 interleukin-21 Proteins 0.000 description 2
- 210000004347 intestinal mucosa Anatomy 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 230000003562 morphometric effect Effects 0.000 description 2
- 238000013425 morphometry Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- OJUGVDODNPJEEC-UHFFFAOYSA-N phenylglyoxal Chemical compound O=CC(=O)C1=CC=CC=C1 OJUGVDODNPJEEC-UHFFFAOYSA-N 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 102220004300 rs121917779 Human genes 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- YEENEYXBHNNNGV-XEHWZWQGSA-M sodium;3-acetamido-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoate;(2r,3r,4s,5s,6r)-2-[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound [Na+].CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I.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 YEENEYXBHNNNGV-XEHWZWQGSA-M 0.000 description 2
- 238000007614 solvation Methods 0.000 description 2
- 210000004988 splenocyte Anatomy 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 235000020790 strict gluten-free diet Nutrition 0.000 description 2
- 238000011285 therapeutic regimen Methods 0.000 description 2
- AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- 208000016261 weight loss Diseases 0.000 description 2
- KMOUUZVZFBCRAM-OLQVQODUSA-N (3as,7ar)-3a,4,7,7a-tetrahydro-2-benzofuran-1,3-dione Chemical compound C1C=CC[C@@H]2C(=O)OC(=O)[C@@H]21 KMOUUZVZFBCRAM-OLQVQODUSA-N 0.000 description 1
- 150000003923 2,5-pyrrolediones Chemical class 0.000 description 1
- KFDPCYZHENQOBV-UHFFFAOYSA-N 2-(bromomethyl)-4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1CBr KFDPCYZHENQOBV-UHFFFAOYSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-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
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical compound NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
- FBTSQILOGYXGMD-LURJTMIESA-N 3-nitro-L-tyrosine Chemical class OC(=O)[C@@H](N)CC1=CC=C(O)C([N+]([O-])=O)=C1 FBTSQILOGYXGMD-LURJTMIESA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 108010032595 Antibody Binding Sites 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
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 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
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 101710205889 Cytochrome b562 Proteins 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108010066719 Interleukin Receptor Common gamma Subunit Proteins 0.000 description 1
- 102000018682 Interleukin Receptor Common gamma Subunit Human genes 0.000 description 1
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
- 239000007836 KH2PO4 Substances 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
- 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
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108010047357 Luminescent Proteins Proteins 0.000 description 1
- 102000006830 Luminescent Proteins Human genes 0.000 description 1
- 239000012515 MabSelect SuRe Substances 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 150000007930 O-acyl isoureas Chemical class 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- NYTOUQBROMCLBJ-UHFFFAOYSA-N Tetranitromethane Chemical compound [O-][N+](=O)C([N+]([O-])=O)([N+]([O-])=O)[N+]([O-])=O NYTOUQBROMCLBJ-UHFFFAOYSA-N 0.000 description 1
- 108060008539 Transglutaminase Proteins 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
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 101150117115 V gene Proteins 0.000 description 1
- 238000012452 Xenomouse strains Methods 0.000 description 1
- 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 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001295 alanines Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 230000009831 antigen interaction Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- HCHJSNHHBFGNGS-UHFFFAOYSA-L benzoyloxy(chloro)mercury Chemical compound Cl[Hg]OC(=O)C1=CC=CC=C1 HCHJSNHHBFGNGS-UHFFFAOYSA-L 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 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
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 208000027499 body ache Diseases 0.000 description 1
- 238000009933 burial Methods 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- AWGTVRDHKJQFAX-UHFFFAOYSA-M chloro(phenyl)mercury Chemical compound Cl[Hg]C1=CC=CC=C1 AWGTVRDHKJQFAX-UHFFFAOYSA-M 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- FFYPMLJYZAEMQB-UHFFFAOYSA-N diethyl pyrocarbonate Chemical compound CCOC(=O)OC(=O)OCC FFYPMLJYZAEMQB-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 230000005782 double-strand break Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
- 229940015043 glyoxal Drugs 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- 244000005709 gut microbiome Species 0.000 description 1
- 101150062840 hcr1 gene Proteins 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000002998 immunogenetic effect Effects 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000003116 impacting effect Effects 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 108040006849 interleukin-2 receptor activity proteins Proteins 0.000 description 1
- 210000004424 intermediate monocyte Anatomy 0.000 description 1
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 1
- 238000010212 intracellular staining Methods 0.000 description 1
- 210000005024 intraepithelial lymphocyte Anatomy 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 201000001091 isolated ectopia lentis Diseases 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000001165 lymph node 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
- 210000002540 macrophage Anatomy 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 150000002730 mercury Chemical class 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- SJFKGZZCMREBQH-UHFFFAOYSA-N methyl ethanimidate Chemical compound COC(C)=N SJFKGZZCMREBQH-UHFFFAOYSA-N 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 108010068617 neonatal Fc receptor Proteins 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 235000015816 nutrient absorption Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent 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
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000012562 protein A resin Substances 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 102220044643 rs587781450 Human genes 0.000 description 1
- 238000007480 sanger sequencing Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 238000012819 small-bowel biopsy Methods 0.000 description 1
- IRHWMYKYLWNHTL-UHFFFAOYSA-M sodium 2-(N-morpholino)ethanesulfonate Chemical compound [Na+].[O-]S(=O)(=O)CCN1CCOCC1 IRHWMYKYLWNHTL-UHFFFAOYSA-M 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- IHQKEDIOMGYHEB-UHFFFAOYSA-M sodium dimethylarsinate Chemical compound [Na+].C[As](C)([O-])=O IHQKEDIOMGYHEB-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 210000005222 synovial tissue Anatomy 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000011824 transgenic rat model Methods 0.000 description 1
- 102000003601 transglutaminase Human genes 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 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
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000022814 xenobiotic metabolic process Effects 0.000 description 1
- 238000012447 xenograft mouse model Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
-
- 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
- A61P37/04—Immunostimulants
-
- 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
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
-
- 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
- G01N33/6869—Interleukin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—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
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- 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
- C07K2317/567—Framework region [FR]
-
- 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
-
- 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
- G01N2333/52—Assays involving cytokines
- G01N2333/54—Interleukins [IL]
- G01N2333/5443—IL-15
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Cell Biology (AREA)
- Rheumatology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Obesity (AREA)
- Food Science & Technology (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022161059A JP2022176324A (ja) | 2016-12-21 | 2022-10-05 | ヒトｉｌ－１５に特異的に結合する抗体及びその使用 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662437143P | 2016-12-21 | 2016-12-21 | |
| US62/437,143 | 2016-12-21 | ||
| PCT/US2017/067917 WO2018119246A1 (en) | 2016-12-21 | 2017-12-21 | Antibodies that specifically bind to human il-15 and uses thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022161059A Division JP2022176324A (ja) | 2016-12-21 | 2022-10-05 | ヒトｉｌ－１５に特異的に結合する抗体及びその使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020501583A JP2020501583A (ja) | 2020-01-23 |
| JP2020501583A5 JP2020501583A5 (cg-RX-API-DMAC7.html) | 2021-02-04 |
| JP7155126B2 true JP7155126B2 (ja) | 2022-10-18 |
Family
ID=62627610
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019533652A Active JP7155126B2 (ja) | 2016-12-21 | 2017-12-21 | ヒトｉｌ－１５に特異的に結合する抗体及びその使用 |
| JP2022161059A Pending JP2022176324A (ja) | 2016-12-21 | 2022-10-05 | ヒトｉｌ－１５に特異的に結合する抗体及びその使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022161059A Pending JP2022176324A (ja) | 2016-12-21 | 2022-10-05 | ヒトｉｌ－１５に特異的に結合する抗体及びその使用 |
Country Status (30)
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2815099T3 (es) | 2013-08-05 | 2021-03-29 | Twist Bioscience Corp | Genotecas sintetizadas de novo |
| CA2975852A1 (en) | 2015-02-04 | 2016-08-11 | Twist Bioscience Corporation | Methods and devices for de novo oligonucleic acid assembly |
| WO2016172377A1 (en) | 2015-04-21 | 2016-10-27 | Twist Bioscience Corporation | Devices and methods for oligonucleic acid library synthesis |
| EP3350314A4 (en) | 2015-09-18 | 2019-02-06 | Twist Bioscience Corporation | OLIGONUCLEIC ACID VARIANT LIBRARIES VARIANT AND SYNTHESIS THEREOF |
| KR102794025B1 (ko) | 2015-09-22 | 2025-04-09 | 트위스트 바이오사이언스 코포레이션 | 핵산 합성을 위한 가요성 기판 |
| JP6871364B2 (ja) | 2016-09-21 | 2021-05-12 | ツイスト バイオサイエンス コーポレーション | 核酸に基づくデータ保存 |
| PT3558369T (pt) | 2016-12-21 | 2025-05-06 | Cephalon Llc | Anticorpos que se ligam especificamente à il-15 humana e suas utilizações |
| CN110892485B (zh) | 2017-02-22 | 2024-03-22 | 特韦斯特生物科学公司 | 基于核酸的数据存储 |
| AU2018284227B2 (en) | 2017-06-12 | 2024-05-02 | Twist Bioscience Corporation | Methods for seamless nucleic acid assembly |
| WO2018231864A1 (en) | 2017-06-12 | 2018-12-20 | Twist Bioscience Corporation | Methods for seamless nucleic acid assembly |
| JP2020536504A (ja) | 2017-09-11 | 2020-12-17 | ツイスト バイオサイエンス コーポレーション | Ｇｐｃｒ結合タンパク質およびその合成 |
| CN111565834B (zh) | 2017-10-20 | 2022-08-26 | 特韦斯特生物科学公司 | 用于多核苷酸合成的加热的纳米孔 |
| KR102804057B1 (ko) | 2018-01-04 | 2025-05-07 | 트위스트 바이오사이언스 코포레이션 | Dna 기반 디지털 정보 저장 |
| EP3814497A4 (en) | 2018-05-18 | 2022-03-02 | Twist Bioscience Corporation | POLYNUCLEOTIDES, REAGENTS AND METHODS FOR NUCLEIC ACID HYBRIDIZATION |
| US12459980B2 (en) | 2018-07-25 | 2025-11-04 | AskGene Pharma, Inc. | IL-21 prodrugs and methods of use thereof |
| US11828385B2 (en) | 2018-12-25 | 2023-11-28 | Ntn Corporation | Flow control valve seal and flow control valve device |
| CA3124980A1 (en) | 2018-12-26 | 2020-07-02 | Twist Bioscience Corporation | Highly accurate de novo polynucleotide synthesis |
| CA3131689A1 (en) | 2019-02-26 | 2020-09-03 | Twist Bioscience Corporation | Variant nucleic acid libraries for glp1 receptor |
| AU2020227802A1 (en) | 2019-02-26 | 2021-10-14 | Twist Bioscience Corporation | Variant nucleic acid libraries for antibody optimization |
| CA3141626A1 (en) | 2019-06-12 | 2020-12-17 | AskGene Pharma, Inc. | Novel il-15 prodrugs and methods of use thereof |
| WO2020257612A1 (en) | 2019-06-21 | 2020-12-24 | Twist Bioscience Corporation | Barcode-based nucleic acid sequence assembly |
| EP4034564A4 (en) | 2019-09-23 | 2023-12-13 | Twist Bioscience Corporation | VARIANT NUCLEIC ACID LIBRARIES FOR SINGLE-DOMAIN ANTIBODIES |
| EP4034566A4 (en) | 2019-09-23 | 2024-01-24 | Twist Bioscience Corporation | VARIANT NUCLEIC ACID BANKS FOR CRTH2 |
| WO2021119193A2 (en) * | 2019-12-09 | 2021-06-17 | Twist Bioscience Corporation | Variant nucleic acid libraries for adenosine receptors |
| JP2023545821A (ja) * | 2020-10-16 | 2023-10-31 | ジェネンテック， インコーポレイテッド | 抗ｉＣａｓｐａｓｅ切断基質抗体および使用方法 |
| CA3206018A1 (en) | 2021-01-21 | 2022-07-28 | Twist Bioscience Corporation | Methods and compositions relating to adenosine receptors |
| CN113185600A (zh) * | 2021-05-28 | 2021-07-30 | 苏州复融生物技术有限公司 | 一种新型白介素15突变体多肽的开发及其应用 |
| WO2024028448A1 (en) | 2022-08-04 | 2024-02-08 | Calypso Biotech Sa | Il-15 inhibitors useful for the treatment of atopic dermatitis |
| CN118894934A (zh) * | 2023-05-05 | 2024-11-05 | 北京智仁美博生物科技有限公司 | 抗人il-15的抗体及其用途 |
| CN117209605B (zh) * | 2023-11-09 | 2024-01-30 | 北京百普赛斯生物科技股份有限公司 | 特异性结合il-15的抗体及其应用 |
| WO2025227052A1 (en) * | 2024-04-26 | 2025-10-30 | Cephalon Llc | Doses and formulations of anti-il-15 antibody for the treatment of immune diseases |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008133276A (ja) | 1995-02-22 | 2008-06-12 | Immunex Corp | インターロイキン−１５のアンタゴニスト |
| WO2016001275A1 (en) | 2014-07-02 | 2016-01-07 | Calypso Biotech Sa | Antibodies to il-15 |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL209786B1 (pl) | 1999-01-15 | 2011-10-31 | Genentech Inc | Przeciwciało zawierające wariant regionu Fc ludzkiej IgG1, przeciwciało wiążące czynnik wzrostu śródbłonka naczyń oraz immunoadhezyna |
| EP1355919B1 (en) | 2000-12-12 | 2010-11-24 | MedImmune, LLC | Molecules with extended half-lives, compositions and uses thereof |
| US7132510B2 (en) * | 2000-12-29 | 2006-11-07 | Bio-Technology General (Israel) Ltd. | Specific human antibodies for selective cancer therapy |
| US7247304B2 (en) * | 2001-08-23 | 2007-07-24 | Genmab A/S | Methods of treating using anti-IL-15 antibodies |
| US7329405B2 (en) * | 2001-08-23 | 2008-02-12 | Genmab A/S | Human antibodies specific for interleukin 15 (IL-15) |
| DK1425389T3 (da) * | 2001-08-23 | 2012-01-30 | Genmab As | Interleukin-15-(IL-15)-specifikke humane antistoffer |
| US7317091B2 (en) | 2002-03-01 | 2008-01-08 | Xencor, Inc. | Optimized Fc variants |
| US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
| US7217797B2 (en) | 2002-10-15 | 2007-05-15 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
| US7285269B2 (en) * | 2002-12-02 | 2007-10-23 | Amgen Fremont, Inc. | Antibodies directed to tumor necrosis factor |
| EA015897B1 (ru) * | 2003-02-26 | 2011-12-30 | Генмаб А/С | Применение человеческого моноклонального антитела к ил-15 в составе композиции и лекарственного препарата (варианты), композиция и лекарственный препарат, его включающие |
| TW200613552A (en) * | 2004-08-11 | 2006-05-01 | Hoffmann La Roche | Mutant interleukin-15 polypeptides |
| AU2006216291B2 (en) * | 2005-02-27 | 2011-01-27 | Institute For Antibodies Co., Ltd. | Anti-IgSF4 antibody and utilization of the same |
| EP1896582A4 (en) * | 2005-05-09 | 2009-04-08 | Ono Pharmaceutical Co | HUMAN MONOCLONAL ANTIBODIES AGAINST PROGRAMMED CELL DEATH 1 (PD-1) AND METHOD FOR CREATING TREATMENT WITH ANTI-PD-1 ANTIBODIES ALONE OR IN COMBINATION WITH OTHER IMMUNOTHERAPEUTICS |
| PT2336329E (pt) | 2007-06-01 | 2012-12-24 | Omt Inc | Composições e métodos para inibição de genes de imunoglobulina endógena e produção de anticorpos transgénicos humanos idiotípicos |
| TWI489993B (zh) | 2007-10-12 | 2015-07-01 | Novartis Ag | 骨硬化素（ｓｃｌｅｒｏｓｔｉｎ）抗體組合物及使用方法 |
| NO2792236T3 (cg-RX-API-DMAC7.html) | 2009-07-08 | 2018-04-14 | ||
| EP2488201A4 (en) * | 2009-10-15 | 2013-12-25 | Abbvie Inc | IL-1 BINDING PROTEINS |
| EP2550529B1 (en) | 2010-03-23 | 2021-11-17 | Iogenetics, LLC. | Bioinformatic processes for determination of peptide binding |
| JP5972871B2 (ja) * | 2010-07-20 | 2016-08-17 | テバ・ファーマシューティカルズ・オーストラリア・ピーティワイ・リミテッド | 抗ｉｌ−２３ヘテロ二量体特異的抗体 |
| JP5820688B2 (ja) | 2011-03-23 | 2015-11-24 | 株式会社Kri | 多糖類の溶解に用いられる溶媒ならびに該溶媒を用いた成形体および多糖類誘導体の製造方法 |
| JP2014534806A (ja) * | 2011-08-23 | 2014-12-25 | ロシュ グリクアート アーゲー | 抗ｍｃｓｐ抗体 |
| ES3033729T3 (en) * | 2011-10-28 | 2025-08-07 | Teva Pharmaceuticals Australia Pty Ltd | Polypeptide constructs and uses thereof |
| WO2014131694A1 (en) * | 2013-02-26 | 2014-09-04 | Roche Glycart Ag | Bispecific t cell activating antigen binding molecules |
| UA118028C2 (uk) | 2013-04-03 | 2018-11-12 | Рош Глікарт Аг | Біспецифічне антитіло, специфічне щодо fap і dr5, антитіло, специфічне щодо dr5, і спосіб їх застосування |
| NZ736026A (en) | 2015-03-31 | 2023-02-24 | Medimmune Ltd | A novel il33 form, mutated forms of il33, antibodies, assays and methods of using the same |
| MX2024001374A (es) * | 2016-06-15 | 2024-02-27 | Amgen Inc | Anticuerpo anti-il-15 o fragmento de union a antigeno del mismo, para usarse en el tratamiento de la enfermedad celiaca, de la sensibilidad al gluten no celiaca y de la enfermedad celiaca refractaria. |
| MA46534A (fr) | 2016-10-14 | 2019-08-21 | Xencor Inc | Protéines de fusion fc hétérodimères il15/il15r |
| PT3558369T (pt) | 2016-12-21 | 2025-05-06 | Cephalon Llc | Anticorpos que se ligam especificamente à il-15 humana e suas utilizações |
-
2017
- 2017-12-21 PT PT178838009T patent/PT3558369T/pt unknown
- 2017-12-21 AU AU2017382850A patent/AU2017382850B2/en active Active
- 2017-12-21 UA UAA201908753A patent/UA126284C2/uk unknown
- 2017-12-21 EP EP17883800.9A patent/EP3558369B1/en active Active
- 2017-12-21 HR HRP20250482TT patent/HRP20250482T1/hr unknown
- 2017-12-21 KR KR1020197019269A patent/KR20190097094A/ko not_active Abandoned
- 2017-12-21 PL PL17883800.9T patent/PL3558369T3/pl unknown
- 2017-12-21 MA MA47130A patent/MA47130B1/fr unknown
- 2017-12-21 DK DK17883800.9T patent/DK3558369T3/da active
- 2017-12-21 MD MDE20191253T patent/MD3558369T2/ro unknown
- 2017-12-21 JP JP2019533652A patent/JP7155126B2/ja active Active
- 2017-12-21 US US16/471,616 patent/US11267883B2/en active Active
- 2017-12-21 FI FIEP17883800.9T patent/FI3558369T3/fi active
- 2017-12-21 BR BR112019012570A patent/BR112019012570A8/pt unknown
- 2017-12-21 KR KR1020237031493A patent/KR102706743B1/ko active Active
- 2017-12-21 HU HUE17883800A patent/HUE071878T2/hu unknown
- 2017-12-21 RS RS20250577A patent/RS66900B1/sr unknown
- 2017-12-21 SI SI201731602T patent/SI3558369T1/sl unknown
- 2017-12-21 PE PE2019001283A patent/PE20191497A1/es unknown
- 2017-12-21 CN CN201780079926.6A patent/CN110234349B/zh active Active
- 2017-12-21 LT LTEPPCT/US2017/067917T patent/LT3558369T/lt unknown
- 2017-12-21 IL IL267113A patent/IL267113B2/en unknown
- 2017-12-21 MX MX2019007357A patent/MX2019007357A/es unknown
- 2017-12-21 AR ARP170103614A patent/AR110414A1/es unknown
- 2017-12-21 ES ES17883800T patent/ES3026508T3/es active Active
- 2017-12-21 EA EA201991514A patent/EA201991514A1/ru unknown
- 2017-12-21 EP EP25165676.5A patent/EP4585261A3/en active Pending
- 2017-12-21 CA CA3046387A patent/CA3046387A1/en active Pending
- 2017-12-21 WO PCT/US2017/067917 patent/WO2018119246A1/en not_active Ceased
-
2019
- 2019-06-13 ZA ZA2019/03848A patent/ZA201903848B/en unknown
- 2019-06-19 MX MX2023014081A patent/MX2023014081A/es unknown
- 2019-06-20 CL CL2019001729A patent/CL2019001729A1/es unknown
- 2019-06-21 PH PH12019501453A patent/PH12019501453A1/en unknown
-
2022
- 2022-01-05 US US17/647,082 patent/US12410247B2/en active Active
- 2022-10-05 JP JP2022161059A patent/JP2022176324A/ja active Pending
-
2025
- 2025-02-20 AU AU2025201185A patent/AU2025201185A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008133276A (ja) | 1995-02-22 | 2008-06-12 | Immunex Corp | インターロイキン−１５のアンタゴニスト |
| WO2016001275A1 (en) | 2014-07-02 | 2016-01-07 | Calypso Biotech Sa | Antibodies to il-15 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7155126B2 (ja) | ヒトｉｌ－１５に特異的に結合する抗体及びその使用 | |
| JP6938383B2 (ja) | イヌインターロイキン４受容体アルファに対する抗体 | |
| RU2595379C2 (ru) | АНТИТЕЛА ПРОТИВ TNF-α И ИХ ПРИМЕНЕНИЯ | |
| CN102782149B (zh) | 经工程改造的抗-tslp抗体 | |
| JP2020512344A (ja) | 抗ｉｌ−３６ｒ抗体併用治療 | |
| JP2018521691A (ja) | 増殖性および炎症性疾患の処置における抗ＴｆＲ抗体およびその使用 | |
| TW201722990A (zh) | 特異性結合tl1a之抗體 | |
| JP2016515524A (ja) | 抗ｃｄ２５抗体およびそれらの使用 | |
| JP2016514690A (ja) | 抗ｃｄ２５抗体およびそれらの使用 | |
| WO2019242619A1 (zh) | 全人源的抗lag-3抗体及其应用 | |
| CA3065553A1 (en) | Il17a antibodies and antagonists for veterinary use | |
| TW202334220A (zh) | 人類腫瘤壞死因子α抗體 | |
| JP2025172766A (ja) | 抗ｉｌ２２抗体、抗体断片およびそれらの免疫コンジュゲートならびにそれらの使用 | |
| WO2022166846A1 (zh) | 抗tnfr2抗体及其用途 | |
| TWI814094B (zh) | 貓抗體變異體 | |
| BR122024020794A2 (pt) | Anticorpos que se ligam especificamente à il-15 humana e seus usos, composição, método in vitro para detecção de il-15 ou um complexo de il-15 e receptor de il-15-alfa, polinucleotídeo, vetor e método de produção do dito anticorpo | |
| HK40013673B (en) | Antibodies that specifically bind to human il-15 and uses thereof | |
| HK40013673A (en) | Antibodies that specifically bind to human il-15 and uses thereof | |
| EA040821B1 (ru) | Антитела, которые специфически связываются с ил-15, и их применение |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201218 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20201218 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20211129 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220217 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220307 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220601 |
|
| 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: 20220905 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20221005 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 7155126 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |