CA2878843A1 - Bispecific asymmetric heterodimers comprising anti-cd3 constructs - Google Patents
Bispecific asymmetric heterodimers comprising anti-cd3 constructs Download PDFInfo
- Publication number
- CA2878843A1 CA2878843A1 CA2878843A CA2878843A CA2878843A1 CA 2878843 A1 CA2878843 A1 CA 2878843A1 CA 2878843 A CA2878843 A CA 2878843A CA 2878843 A CA2878843 A CA 2878843A CA 2878843 A1 CA2878843 A1 CA 2878843A1
- Authority
- CA
- Canada
- Prior art keywords
- cell
- polypeptide
- heteromultimer
- construct
- multispecific heteromultimer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 526
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 489
- 229920001184 polypeptide Polymers 0.000 claims abstract description 484
- 230000027455 binding Effects 0.000 claims abstract description 309
- 210000004027 cell Anatomy 0.000 claims abstract description 245
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims abstract description 220
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 claims abstract description 220
- 239000000427 antigen Substances 0.000 claims abstract description 173
- 108091007433 antigens Proteins 0.000 claims abstract description 172
- 102000036639 antigens Human genes 0.000 claims abstract description 172
- 210000003719 b-lymphocyte Anatomy 0.000 claims abstract description 136
- 238000000034 method Methods 0.000 claims abstract description 102
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 52
- 201000011510 cancer Diseases 0.000 claims abstract description 37
- 235000001014 amino acid Nutrition 0.000 claims description 150
- 150000001413 amino acids Chemical class 0.000 claims description 135
- 108090000623 proteins and genes Proteins 0.000 claims description 131
- 102000004169 proteins and genes Human genes 0.000 claims description 113
- 235000018102 proteins Nutrition 0.000 claims description 107
- 230000035772 mutation Effects 0.000 claims description 90
- 230000014509 gene expression Effects 0.000 claims description 84
- 239000000833 heterodimer Substances 0.000 claims description 83
- 230000004048 modification Effects 0.000 claims description 82
- 238000012986 modification Methods 0.000 claims description 82
- 241000282414 Homo sapiens Species 0.000 claims description 81
- 108010078791 Carrier Proteins Proteins 0.000 claims description 77
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 70
- 102000009027 Albumins Human genes 0.000 claims description 69
- 108010088751 Albumins Proteins 0.000 claims description 69
- 239000000203 mixture Substances 0.000 claims description 67
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 51
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 51
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 49
- 108060003951 Immunoglobulin Proteins 0.000 claims description 42
- 102000018358 immunoglobulin Human genes 0.000 claims description 42
- 239000008194 pharmaceutical composition Substances 0.000 claims description 42
- 201000010099 disease Diseases 0.000 claims description 41
- 210000004962 mammalian cell Anatomy 0.000 claims description 40
- 102000005962 receptors Human genes 0.000 claims description 36
- 108020003175 receptors Proteins 0.000 claims description 36
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 33
- 230000015572 biosynthetic process Effects 0.000 claims description 29
- 238000011282 treatment Methods 0.000 claims description 29
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 28
- 241000124008 Mammalia Species 0.000 claims description 28
- 230000000694 effects Effects 0.000 claims description 28
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 27
- 239000000178 monomer Substances 0.000 claims description 27
- 230000001939 inductive effect Effects 0.000 claims description 19
- 230000002147 killing effect Effects 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 17
- 241000894007 species Species 0.000 claims description 17
- 108091006905 Human Serum Albumin Proteins 0.000 claims description 16
- 102000008100 Human Serum Albumin Human genes 0.000 claims description 16
- 229960003008 blinatumomab Drugs 0.000 claims description 15
- 239000013604 expression vector Substances 0.000 claims description 15
- 108010002350 Interleukin-2 Proteins 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 14
- 230000001363 autoimmune Effects 0.000 claims description 11
- 229940124597 therapeutic agent Drugs 0.000 claims description 11
- 102100028757 Chondroitin sulfate proteoglycan 4 Human genes 0.000 claims description 10
- 201000009030 Carcinoma Diseases 0.000 claims description 9
- 101000916489 Homo sapiens Chondroitin sulfate proteoglycan 4 Proteins 0.000 claims description 9
- 102100036735 Prostate stem cell antigen Human genes 0.000 claims description 9
- 101710120463 Prostate stem cell antigen Proteins 0.000 claims description 9
- 206010039491 Sarcoma Diseases 0.000 claims description 9
- 238000012258 culturing Methods 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 108700022150 Designed Ankyrin Repeat Proteins Proteins 0.000 claims description 8
- 102100038083 Endosialin Human genes 0.000 claims description 8
- 101710144543 Endosialin Proteins 0.000 claims description 8
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 claims description 8
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 claims description 8
- 108010067306 Fibronectins Proteins 0.000 claims description 8
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims description 8
- 230000004913 activation Effects 0.000 claims description 8
- 230000022534 cell killing Effects 0.000 claims description 8
- 239000003550 marker Substances 0.000 claims description 8
- 230000011218 segmentation Effects 0.000 claims description 8
- 102100033808 Glycoprotein hormone alpha-2 Human genes 0.000 claims description 7
- 101001069261 Homo sapiens Glycoprotein hormone alpha-2 Proteins 0.000 claims description 7
- 206010025323 Lymphomas Diseases 0.000 claims description 7
- 208000015181 infectious disease Diseases 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 6
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 239000012528 membrane Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 210000004698 lymphocyte Anatomy 0.000 claims description 5
- 230000002101 lytic effect Effects 0.000 claims description 5
- 230000003612 virological effect Effects 0.000 claims description 5
- 208000003950 B-cell lymphoma Diseases 0.000 claims description 4
- 208000035473 Communicable disease Diseases 0.000 claims description 4
- 241000699802 Cricetulus griseus Species 0.000 claims description 4
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims description 4
- 102100040247 Tumor necrosis factor Human genes 0.000 claims description 4
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims description 4
- 210000002950 fibroblast Anatomy 0.000 claims description 4
- 210000005260 human cell Anatomy 0.000 claims description 4
- 230000005847 immunogenicity Effects 0.000 claims description 4
- 206010025135 lupus erythematosus Diseases 0.000 claims description 4
- 210000001672 ovary Anatomy 0.000 claims description 4
- 230000002062 proliferating effect Effects 0.000 claims description 4
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 3
- 208000004736 B-Cell Leukemia Diseases 0.000 claims description 3
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 claims description 3
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 claims description 3
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims description 3
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims description 3
- 102100036305 C-C chemokine receptor type 8 Human genes 0.000 claims description 3
- 108700012439 CA9 Proteins 0.000 claims description 3
- 102100032976 CCR4-NOT transcription complex subunit 6 Human genes 0.000 claims description 3
- 108010058905 CD44v6 antigen Proteins 0.000 claims description 3
- 102100025222 CD63 antigen Human genes 0.000 claims description 3
- 102000000905 Cadherin Human genes 0.000 claims description 3
- 108050007957 Cadherin Proteins 0.000 claims description 3
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 claims description 3
- 108010009685 Cholinergic Receptors Proteins 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 102100034573 Desmoglein-4 Human genes 0.000 claims description 3
- 101710183213 Desmoglein-4 Proteins 0.000 claims description 3
- 101150078651 Epha4 gene Proteins 0.000 claims description 3
- 102100021616 Ephrin type-A receptor 4 Human genes 0.000 claims description 3
- 208000032612 Glial tumor Diseases 0.000 claims description 3
- 206010018338 Glioma Diseases 0.000 claims description 3
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims description 3
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 3
- 102000003693 Hedgehog Proteins Human genes 0.000 claims description 3
- 108090000031 Hedgehog Proteins Proteins 0.000 claims description 3
- 101000716063 Homo sapiens C-C chemokine receptor type 8 Proteins 0.000 claims description 3
- 101000934368 Homo sapiens CD63 antigen Proteins 0.000 claims description 3
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims description 3
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 claims description 3
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 claims description 3
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 claims description 3
- 101000628547 Homo sapiens Metalloreductase STEAP1 Proteins 0.000 claims description 3
- 101000623901 Homo sapiens Mucin-16 Proteins 0.000 claims description 3
- 101001133081 Homo sapiens Mucin-2 Proteins 0.000 claims description 3
- 101000972284 Homo sapiens Mucin-3A Proteins 0.000 claims description 3
- 101000972286 Homo sapiens Mucin-4 Proteins 0.000 claims description 3
- 101000972282 Homo sapiens Mucin-5AC Proteins 0.000 claims description 3
- 101000972276 Homo sapiens Mucin-5B Proteins 0.000 claims description 3
- 101000972273 Homo sapiens Mucin-7 Proteins 0.000 claims description 3
- 206010020751 Hypersensitivity Diseases 0.000 claims description 3
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims description 3
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims description 3
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 claims description 3
- 102000003735 Mesothelin Human genes 0.000 claims description 3
- 108090000015 Mesothelin Proteins 0.000 claims description 3
- 102100026712 Metalloreductase STEAP1 Human genes 0.000 claims description 3
- 108010008707 Mucin-1 Proteins 0.000 claims description 3
- 102100034256 Mucin-1 Human genes 0.000 claims description 3
- 102100023123 Mucin-16 Human genes 0.000 claims description 3
- 102100034263 Mucin-2 Human genes 0.000 claims description 3
- 102100022497 Mucin-3A Human genes 0.000 claims description 3
- 102100022693 Mucin-4 Human genes 0.000 claims description 3
- 102100022494 Mucin-5B Human genes 0.000 claims description 3
- 102100022492 Mucin-7 Human genes 0.000 claims description 3
- 108010063954 Mucins Proteins 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 3
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 3
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
- 206010046851 Uveitis Diseases 0.000 claims description 3
- 206010047115 Vasculitis Diseases 0.000 claims description 3
- 102000034337 acetylcholine receptors Human genes 0.000 claims description 3
- 208000009956 adenocarcinoma Diseases 0.000 claims description 3
- 230000021615 conjugation Effects 0.000 claims description 3
- 230000001605 fetal effect Effects 0.000 claims description 3
- 150000002270 gangliosides Chemical class 0.000 claims description 3
- 230000002489 hematologic effect Effects 0.000 claims description 3
- 208000026278 immune system disease Diseases 0.000 claims description 3
- 229940127130 immunocytokine Drugs 0.000 claims description 3
- 230000004968 inflammatory condition Effects 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 230000036210 malignancy Effects 0.000 claims description 3
- 238000002844 melting Methods 0.000 claims description 3
- 230000008018 melting Effects 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 210000000066 myeloid cell Anatomy 0.000 claims description 3
- 201000008968 osteosarcoma Diseases 0.000 claims description 3
- 230000003071 parasitic effect Effects 0.000 claims description 3
- 210000004180 plasmocyte Anatomy 0.000 claims description 3
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- 230000001373 regressive effect Effects 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 3
- 101150047061 tag-72 gene Proteins 0.000 claims description 3
- 230000007704 transition Effects 0.000 claims description 3
- 102000000989 Complement System Proteins Human genes 0.000 claims description 2
- 108010069112 Complement System Proteins Proteins 0.000 claims description 2
- 102100037362 Fibronectin Human genes 0.000 claims 3
- 101000914324 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 5 Proteins 0.000 claims 1
- 101000914321 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 7 Proteins 0.000 claims 1
- 101000617725 Homo sapiens Pregnancy-specific beta-1-glycoprotein 2 Proteins 0.000 claims 1
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 claims 1
- KUIFHYPNNRVEKZ-VIJRYAKMSA-N O-(N-acetyl-alpha-D-galactosaminyl)-L-threonine Chemical compound OC(=O)[C@@H](N)[C@@H](C)O[C@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1NC(C)=O KUIFHYPNNRVEKZ-VIJRYAKMSA-N 0.000 claims 1
- 102100022019 Pregnancy-specific beta-1-glycoprotein 2 Human genes 0.000 claims 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims 1
- 229940024606 amino acid Drugs 0.000 description 126
- 150000007523 nucleic acids Chemical class 0.000 description 46
- 102000039446 nucleic acids Human genes 0.000 description 40
- 108020004707 nucleic acids Proteins 0.000 description 40
- 102000040430 polynucleotide Human genes 0.000 description 39
- 108091033319 polynucleotide Proteins 0.000 description 39
- 239000002157 polynucleotide Substances 0.000 description 39
- 239000000047 product Substances 0.000 description 38
- 108010087819 Fc receptors Proteins 0.000 description 37
- 102000009109 Fc receptors Human genes 0.000 description 37
- 230000002829 reductive effect Effects 0.000 description 36
- 239000013598 vector Substances 0.000 description 31
- 230000003213 activating effect Effects 0.000 description 29
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 29
- 108020004414 DNA Proteins 0.000 description 28
- 125000003275 alpha amino acid group Chemical group 0.000 description 27
- 239000012636 effector Substances 0.000 description 27
- 230000001225 therapeutic effect Effects 0.000 description 27
- 125000003729 nucleotide group Chemical group 0.000 description 25
- 239000012634 fragment Substances 0.000 description 24
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 24
- 239000002773 nucleotide Substances 0.000 description 24
- 238000003556 assay Methods 0.000 description 22
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 21
- 230000037396 body weight Effects 0.000 description 21
- 238000005755 formation reaction Methods 0.000 description 21
- 230000006870 function Effects 0.000 description 21
- -1 CEA Proteins 0.000 description 20
- 125000005647 linker group Chemical group 0.000 description 19
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 17
- 210000004881 tumor cell Anatomy 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 15
- 108010076504 Protein Sorting Signals Proteins 0.000 description 14
- 238000004113 cell culture Methods 0.000 description 14
- 102000000588 Interleukin-2 Human genes 0.000 description 13
- 230000001404 mediated effect Effects 0.000 description 13
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 13
- 150000001875 compounds Chemical class 0.000 description 12
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 11
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 11
- 230000003993 interaction Effects 0.000 description 11
- 102000004127 Cytokines Human genes 0.000 description 10
- 108090000695 Cytokines Proteins 0.000 description 10
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 241000235648 Pichia Species 0.000 description 10
- 125000000539 amino acid group Chemical group 0.000 description 10
- 231100000135 cytotoxicity Toxicity 0.000 description 10
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 10
- 235000004554 glutamine Nutrition 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 230000028327 secretion Effects 0.000 description 10
- 238000006467 substitution reaction Methods 0.000 description 10
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 9
- 108020004705 Codon Proteins 0.000 description 9
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 9
- 241000282577 Pan troglodytes Species 0.000 description 9
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 9
- 230000003013 cytotoxicity Effects 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 230000000284 resting effect Effects 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 241000282412 Homo Species 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 238000009396 hybridization Methods 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 241000588724 Escherichia coli Species 0.000 description 7
- 230000006044 T cell activation Effects 0.000 description 7
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 description 7
- 230000000295 complement effect Effects 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 241000894006 Bacteria Species 0.000 description 6
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 230000001472 cytotoxic effect Effects 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 230000000069 prophylactic effect Effects 0.000 description 6
- 241000282693 Cercopithecidae Species 0.000 description 5
- 150000008574 D-amino acids Chemical class 0.000 description 5
- 102000001301 EGF receptor Human genes 0.000 description 5
- 108060006698 EGF receptor Proteins 0.000 description 5
- 241000196324 Embryophyta Species 0.000 description 5
- 102000016359 Fibronectins Human genes 0.000 description 5
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 5
- 241000235649 Kluyveromyces Species 0.000 description 5
- 241001138401 Kluyveromyces lactis Species 0.000 description 5
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 241000320412 Ogataea angusta Species 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 230000000890 antigenic effect Effects 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000013270 controlled release Methods 0.000 description 5
- 230000009089 cytolysis Effects 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 210000003527 eukaryotic cell Anatomy 0.000 description 5
- 108020001507 fusion proteins Proteins 0.000 description 5
- 102000037865 fusion proteins Human genes 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 210000004379 membrane Anatomy 0.000 description 5
- 229930182817 methionine Natural products 0.000 description 5
- 238000000302 molecular modelling Methods 0.000 description 5
- 230000001177 retroviral effect Effects 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- 230000014616 translation Effects 0.000 description 5
- 230000035899 viability Effects 0.000 description 5
- 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 4
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 4
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 241000235058 Komagataella pastoris Species 0.000 description 4
- 241000282553 Macaca Species 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- 229920002873 Polyethylenimine Polymers 0.000 description 4
- 241000288906 Primates Species 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 241000235070 Saccharomyces Species 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 description 4
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000005714 functional activity Effects 0.000 description 4
- 238000001415 gene therapy Methods 0.000 description 4
- 238000000099 in vitro assay Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 201000000050 myeloid neoplasm Diseases 0.000 description 4
- 230000004481 post-translational protein modification Effects 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 210000005253 yeast cell Anatomy 0.000 description 4
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 3
- 241000228245 Aspergillus niger Species 0.000 description 3
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 102000000844 Cell Surface Receptors Human genes 0.000 description 3
- 108010001857 Cell Surface Receptors Proteins 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 244000286779 Hansenula anomala Species 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 3
- 244000285963 Kluyveromyces fragilis Species 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 3
- 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 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
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 3
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 3
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 3
- 244000206963 Saccharomyces cerevisiae var. diastaticus Species 0.000 description 3
- 229910052775 Thulium Inorganic materials 0.000 description 3
- 241000235006 Torulaspora Species 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 230000021736 acetylation Effects 0.000 description 3
- 238000006640 acetylation reaction Methods 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 108010053847 alloalbumins Proteins 0.000 description 3
- QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 210000004102 animal cell Anatomy 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000007914 intraventricular administration Methods 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 230000001323 posttranslational effect Effects 0.000 description 3
- 210000001236 prokaryotic cell Anatomy 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 230000005030 transcription termination Effects 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 108020005065 3' Flanking Region Proteins 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 241000228212 Aspergillus Species 0.000 description 2
- 241000351920 Aspergillus nidulans Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 101150029707 ERBB2 gene Proteins 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 108010070600 Glucose-6-phosphate isomerase Proteins 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 102000003839 Human Proteins Human genes 0.000 description 2
- 108090000144 Human Proteins Proteins 0.000 description 2
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 2
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 2
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 101710096444 Killer toxin Proteins 0.000 description 2
- 150000008575 L-amino acids Chemical class 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 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
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-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
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 241000282567 Macaca fascicularis Species 0.000 description 2
- 101710141347 Major envelope glycoprotein Proteins 0.000 description 2
- 108010038049 Mating Factor Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 208000007660 Residual Neoplasm Diseases 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 241000235346 Schizosaccharomyces Species 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 108091008874 T cell receptors Proteins 0.000 description 2
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 241000235013 Yarrowia Species 0.000 description 2
- 241000235015 Yarrowia lipolytica Species 0.000 description 2
- 241000235033 Zygosaccharomyces rouxii Species 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 238000007818 agglutination assay Methods 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000009435 amidation Effects 0.000 description 2
- 238000007112 amidation reaction Methods 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 238000005571 anion exchange chromatography Methods 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 235000009697 arginine Nutrition 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000008228 bacteriostatic water for injection Substances 0.000 description 2
- 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 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 150000001720 carbohydrates Chemical group 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000005277 cation exchange chromatography Methods 0.000 description 2
- 230000006037 cell lysis Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 230000022244 formylation Effects 0.000 description 2
- 238000006170 formylation reaction Methods 0.000 description 2
- 230000037433 frameshift Effects 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 239000001963 growth medium Substances 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
- 230000006801 homologous recombination Effects 0.000 description 2
- 238000002744 homologous recombination Methods 0.000 description 2
- 238000001794 hormone therapy Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 108010068617 neonatal Fc receptor Proteins 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 210000001322 periplasm Anatomy 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 239000003016 pheromone Substances 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- 150000003839 salts Chemical group 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 238000010798 ubiquitination Methods 0.000 description 2
- 230000034512 ubiquitination Effects 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- SBKVPJHMSUXZTA-MEJXFZFPSA-N (2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-5-amino-2-[[2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-5-oxopentanoyl]pyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid Chemical compound C([C@@H](C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CNC=N1 SBKVPJHMSUXZTA-MEJXFZFPSA-N 0.000 description 1
- FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 description 1
- BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 description 1
- MRTPISKDZDHEQI-YFKPBYRVSA-N (2s)-2-(tert-butylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC(C)(C)C MRTPISKDZDHEQI-YFKPBYRVSA-N 0.000 description 1
- NPDBDJFLKKQMCM-SCSAIBSYSA-N (2s)-2-amino-3,3-dimethylbutanoic acid Chemical compound CC(C)(C)[C@H](N)C(O)=O NPDBDJFLKKQMCM-SCSAIBSYSA-N 0.000 description 1
- MSECZMWQBBVGEN-LURJTMIESA-N (2s)-2-azaniumyl-4-(1h-imidazol-5-yl)butanoate Chemical compound OC(=O)[C@@H](N)CCC1=CN=CN1 MSECZMWQBBVGEN-LURJTMIESA-N 0.000 description 1
- UYEGXSNFZXWSDV-BYPYZUCNSA-N (2s)-3-(2-amino-1h-imidazol-5-yl)-2-azaniumylpropanoate Chemical compound OC(=O)[C@@H](N)CC1=CNC(N)=N1 UYEGXSNFZXWSDV-BYPYZUCNSA-N 0.000 description 1
- FQVLRGLGWNWPSS-BXBUPLCLSA-N (4r,7s,10s,13s,16r)-16-acetamido-13-(1h-imidazol-5-ylmethyl)-10-methyl-6,9,12,15-tetraoxo-7-propan-2-yl-1,2-dithia-5,8,11,14-tetrazacycloheptadecane-4-carboxamide Chemical compound N1C(=O)[C@@H](NC(C)=O)CSSC[C@@H](C(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@@H]1CC1=CN=CN1 FQVLRGLGWNWPSS-BXBUPLCLSA-N 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- 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 1
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
- OGNSCSPNOLGXSM-UHFFFAOYSA-N 2,4-diaminobutyric acid Chemical compound NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-UHFFFAOYSA-N 0.000 description 1
- 101710163881 5,6-dihydroxyindole-2-carboxylic acid oxidase Proteins 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
- 230000005730 ADP ribosylation Effects 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 102000013563 Acid Phosphatase Human genes 0.000 description 1
- 108010051457 Acid Phosphatase Proteins 0.000 description 1
- 101100295756 Acinetobacter baumannii (strain ATCC 19606 / DSM 30007 / JCM 6841 / CCUG 19606 / CIP 70.34 / NBRC 109757 / NCIMB 12457 / NCTC 12156 / 81) omp38 gene Proteins 0.000 description 1
- 108010000239 Aequorin Proteins 0.000 description 1
- 102100034035 Alcohol dehydrogenase 1A Human genes 0.000 description 1
- 102100034044 All-trans-retinol dehydrogenase [NAD(+)] ADH1B Human genes 0.000 description 1
- 101710193111 All-trans-retinol dehydrogenase [NAD(+)] ADH4 Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 240000006108 Allium ampeloprasum Species 0.000 description 1
- 235000005254 Allium ampeloprasum Nutrition 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 101000642536 Apis mellifera Venom serine protease 34 Proteins 0.000 description 1
- 101100179978 Arabidopsis thaliana IRX10 gene Proteins 0.000 description 1
- 101100233722 Arabidopsis thaliana IRX10L gene Proteins 0.000 description 1
- 101100136076 Aspergillus oryzae (strain ATCC 42149 / RIB 40) pel1 gene Proteins 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 108091008875 B cell receptors Proteins 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 101150046766 BGL2 gene Proteins 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- 102100036850 C-C motif chemokine 23 Human genes 0.000 description 1
- 101100408676 Caenorhabditis elegans pmt-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 241001619326 Cephalosporium Species 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 241001508787 Citeromyces Species 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-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
- FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 description 1
- 229920002271 DEAE-Sepharose Polymers 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 239000012625 DNA intercalator Substances 0.000 description 1
- 108050009160 DNA polymerase 1 Proteins 0.000 description 1
- 239000003155 DNA primer Substances 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
- XPDXVDYUQZHFPV-UHFFFAOYSA-N Dansyl Chloride Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(Cl)(=O)=O XPDXVDYUQZHFPV-UHFFFAOYSA-N 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 101150039808 Egfr gene Proteins 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 101710146739 Enterotoxin Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 241000701533 Escherichia virus T4 Species 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101150094690 GAL1 gene Proteins 0.000 description 1
- 101150038242 GAL10 gene Proteins 0.000 description 1
- 102100028501 Galanin peptides Human genes 0.000 description 1
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 101000892220 Geobacillus thermodenitrificans (strain NG80-2) Long-chain-alcohol dehydrogenase 1 Proteins 0.000 description 1
- 102000030595 Glucokinase Human genes 0.000 description 1
- 108010021582 Glucokinase Proteins 0.000 description 1
- 102000005731 Glucose-6-phosphate isomerase Human genes 0.000 description 1
- 102100031132 Glucose-6-phosphate isomerase Human genes 0.000 description 1
- 108010051815 Glutamyl endopeptidase Proteins 0.000 description 1
- 235000014683 Hansenula anomala Nutrition 0.000 description 1
- 102000005548 Hexokinase Human genes 0.000 description 1
- 108700040460 Hexokinases Proteins 0.000 description 1
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 1
- 102100024594 Histone-lysine N-methyltransferase PRDM16 Human genes 0.000 description 1
- 101000780443 Homo sapiens Alcohol dehydrogenase 1A Proteins 0.000 description 1
- 101000713081 Homo sapiens C-C motif chemokine 23 Proteins 0.000 description 1
- 101100383038 Homo sapiens CD19 gene Proteins 0.000 description 1
- 101100121078 Homo sapiens GAL gene Proteins 0.000 description 1
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
- 101000686942 Homo sapiens Histone-lysine N-methyltransferase PRDM16 Proteins 0.000 description 1
- 101000955035 Homo sapiens Homeobox protein MOX-1 Proteins 0.000 description 1
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 1
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 1
- 101100495232 Homo sapiens MS4A1 gene Proteins 0.000 description 1
- 101001108219 Homo sapiens NADPH oxidase 1 Proteins 0.000 description 1
- 101001098352 Homo sapiens OX-2 membrane glycoprotein Proteins 0.000 description 1
- 101001136592 Homo sapiens Prostate stem cell antigen Proteins 0.000 description 1
- 101000946860 Homo sapiens T-cell surface glycoprotein CD3 epsilon chain Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 241000223198 Humicola Species 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 241001304302 Kuraishia capsulata Species 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- XIGSAGMEBXLVJJ-YFKPBYRVSA-N L-homocitrulline Chemical compound NC(=O)NCCCC[C@H]([NH3+])C([O-])=O XIGSAGMEBXLVJJ-YFKPBYRVSA-N 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- ZFOMKMMPBOQKMC-KXUCPTDWSA-N L-pyrrolysine Chemical compound C[C@@H]1CC=N[C@H]1C(=O)NCCCC[C@H]([NH3+])C([O-])=O ZFOMKMMPBOQKMC-KXUCPTDWSA-N 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 241000221479 Leucosporidium Species 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 102100029205 Low affinity immunoglobulin gamma Fc region receptor II-b Human genes 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 239000012515 MabSelect SuRe Substances 0.000 description 1
- 241000407429 Maja Species 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 101710089743 Mating factor alpha Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- 241000235395 Mucor Species 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 102100021873 NADPH oxidase 1 Human genes 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 241000221960 Neurospora Species 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 241000235652 Pachysolen Species 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 102000001105 Phosphofructokinases Human genes 0.000 description 1
- 108010069341 Phosphofructokinases Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100023832 Prolyl endopeptidase FAP Human genes 0.000 description 1
- 101100084022 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) lapA gene Proteins 0.000 description 1
- 108010011939 Pyruvate Decarboxylase Proteins 0.000 description 1
- 239000012614 Q-Sepharose Substances 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
- 241000223252 Rhodotorula Species 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 235000001006 Saccharomyces cerevisiae var diastaticus Nutrition 0.000 description 1
- 241000235003 Saccharomycopsis Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 108010029180 Sialic Acid Binding Ig-like Lectin 3 Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000256248 Spodoptera Species 0.000 description 1
- 241000228389 Sporidiobolus Species 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 241000187747 Streptomyces Species 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
- 241000282887 Suidae Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 230000037453 T cell priming Effects 0.000 description 1
- 102100035794 T-cell surface glycoprotein CD3 epsilon chain Human genes 0.000 description 1
- 102000003627 TRPC1 Human genes 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 108020005038 Terminator Codon Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 244000288561 Torulaspora delbrueckii Species 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 241000223259 Trichoderma Species 0.000 description 1
- 102000005924 Triose-Phosphate Isomerase Human genes 0.000 description 1
- 108700015934 Triose-phosphate isomerases Proteins 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- YJQCOFNZVFGCAF-UHFFFAOYSA-N Tunicamycin II Natural products O1C(CC(O)C2C(C(O)C(O2)N2C(NC(=O)C=C2)=O)O)C(O)C(O)C(NC(=O)C=CCCCCCCCCC(C)C)C1OC1OC(CO)C(O)C(O)C1NC(C)=O YJQCOFNZVFGCAF-UHFFFAOYSA-N 0.000 description 1
- 229940127174 UCHT1 Drugs 0.000 description 1
- 241000235017 Zygosaccharomyces Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000007801 affinity label Substances 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940124691 antibody therapeutics Drugs 0.000 description 1
- 238000011230 antibody-based therapy Methods 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 101150042295 arfA gene Proteins 0.000 description 1
- 230000010516 arginylation Effects 0.000 description 1
- 108010051210 beta-Fructofuranosidase Proteins 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000025049 binding, bridging Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 229940126587 biotherapeutics Drugs 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000002230 centromere Anatomy 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 108010039524 chondroitin sulfate proteoglycan 4 Proteins 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000001609 comparable effect Effects 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 230000004041 dendritic cell maturation Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 108020001096 dihydrofolate reductase Proteins 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229960004887 ferric hydroxide Drugs 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 108010072257 fibroblast activation protein alpha Proteins 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229910052733 gallium Inorganic materials 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 230000006251 gamma-carboxylation Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 238000012817 gel-diffusion technique Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 101150059349 gut2 gene Proteins 0.000 description 1
- 150000003278 haem Chemical group 0.000 description 1
- 230000035931 haemagglutination Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 238000005734 heterodimerization reaction Methods 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 102000050405 human PSCA Human genes 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000012872 hydroxylapatite chromatography Methods 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 239000012642 immune effector Substances 0.000 description 1
- 230000008076 immune mechanism Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000000951 immunodiffusion Effects 0.000 description 1
- 238000000760 immunoelectrophoresis Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000003017 in situ immunoassay Methods 0.000 description 1
- 238000012606 in vitro cell culture Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 239000001573 invertase Substances 0.000 description 1
- 235000011073 invertase Nutrition 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- IEECXTSVVFWGSE-UHFFFAOYSA-M iron(3+);oxygen(2-);hydroxide Chemical compound [OH-].[O-2].[Fe+3] IEECXTSVVFWGSE-UHFFFAOYSA-M 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
- 230000000998 lymphohematopoietic effect Effects 0.000 description 1
- 239000008176 lyophilized powder Substances 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
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- SKEFKEOTNIPLCQ-LWIQTABASA-N mating hormone Chemical compound C([C@@H](C(=O)NC(CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCS(C)=O)C(=O)NC(CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CN=CN1 SKEFKEOTNIPLCQ-LWIQTABASA-N 0.000 description 1
- 210000003519 mature b lymphocyte Anatomy 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- SXTAYKAGBXMACB-UHFFFAOYSA-N methionine S-imide-S-oxide Natural products CS(=N)(=O)CCC(N)C(O)=O SXTAYKAGBXMACB-UHFFFAOYSA-N 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-O methylsulfide anion Chemical compound [SH2+]C LSDPWZHWYPCBBB-UHFFFAOYSA-O 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 102000008529 molecular adaptor activity proteins Human genes 0.000 description 1
- 108040002403 molecular adaptor activity proteins Proteins 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- ZTLGJPIZUOVDMT-UHFFFAOYSA-N n,n-dichlorotriazin-4-amine Chemical compound ClN(Cl)C1=CC=NN=N1 ZTLGJPIZUOVDMT-UHFFFAOYSA-N 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000036963 noncompetitive effect 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
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000007826 nucleic acid assay Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 101150087557 omcB gene Proteins 0.000 description 1
- 101150115693 ompA gene Proteins 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 108010087558 pectate lyase Proteins 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 101150040383 pel2 gene Proteins 0.000 description 1
- 101150050446 pelB gene Proteins 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 101150009573 phoA gene Proteins 0.000 description 1
- 229940080469 phosphocellulose Drugs 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 210000002706 plastid Anatomy 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000013641 positive control Substances 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
- 239000000843 powder Substances 0.000 description 1
- 230000013823 prenylation Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000013615 primer Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 238000013197 protein A assay Methods 0.000 description 1
- 108020001775 protein parts Proteins 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 229940043131 pyroglutamate Drugs 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000012857 radioactive material Substances 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 102220024669 rs59270054 Human genes 0.000 description 1
- 102220026812 rs63750850 Human genes 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 235000016491 selenocysteine Nutrition 0.000 description 1
- ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 1
- 229940055619 selenocysteine Drugs 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 239000000725 suspension Substances 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
- 210000000225 synapse Anatomy 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229910052713 technetium Inorganic materials 0.000 description 1
- GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical compound [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 description 1
- 108010052178 teleocalcin Proteins 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229910052716 thallium Inorganic materials 0.000 description 1
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
- ZHSGGJXRNHWHRS-VIDYELAYSA-N tunicamycin Chemical compound O([C@H]1[C@@H]([C@H]([C@@H](O)[C@@H](CC(O)[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C(NC(=O)C=C2)=O)O)O1)O)NC(=O)/C=C/CC(C)C)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O ZHSGGJXRNHWHRS-VIDYELAYSA-N 0.000 description 1
- MEYZYGMYMLNUHJ-UHFFFAOYSA-N tunicamycin Natural products CC(C)CCCCCCCCCC=CC(=O)NC1C(O)C(O)C(CC(O)C2OC(C(O)C2O)N3C=CC(=O)NC3=O)OC1OC4OC(CO)C(O)C(O)C4NC(=O)C MEYZYGMYMLNUHJ-UHFFFAOYSA-N 0.000 description 1
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
- HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/14—Ectoparasiticides, e.g. scabicides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- A61P37/08—Antiallergic 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
-
- 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
- C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
-
- 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
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/35—Valency
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/524—CH2 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/526—CH3 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/528—CH4 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/71—Decreased effector function due to an Fc-modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/72—Increased effector function due to an Fc-modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- 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
- C07K2317/74—Inducing cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Virology (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261671640P | 2012-07-13 | 2012-07-13 | |
| US61/671,640 | 2012-07-13 | ||
| US201361845948P | 2013-07-12 | 2013-07-12 | |
| US61/845,948 | 2013-07-12 | ||
| PCT/US2013/050411 WO2014012085A2 (en) | 2012-07-13 | 2013-07-13 | Bispecific asymmetric heterodimers comprising anti-cd3 constructs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2878843A1 true CA2878843A1 (en) | 2014-01-16 |
Family
ID=49916711
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2878843A Abandoned CA2878843A1 (en) | 2012-07-13 | 2013-07-13 | Bispecific asymmetric heterodimers comprising anti-cd3 constructs |
Country Status (11)
| Country | Link |
|---|---|
| US (4) | US20140154253A1 (enExample) |
| EP (1) | EP2872170A4 (enExample) |
| JP (1) | JP2015528003A (enExample) |
| KR (1) | KR20150036606A (enExample) |
| CN (1) | CN104640562A (enExample) |
| AU (1) | AU2013289883B2 (enExample) |
| BR (1) | BR112015000798A2 (enExample) |
| CA (1) | CA2878843A1 (enExample) |
| HK (1) | HK1207575A1 (enExample) |
| RU (1) | RU2650868C2 (enExample) |
| WO (1) | WO2014012085A2 (enExample) |
Families Citing this family (164)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010115589A1 (en) | 2009-04-07 | 2010-10-14 | Roche Glycart Ag | Trivalent, bispecific antibodies |
| US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
| WO2011028952A1 (en) | 2009-09-02 | 2011-03-10 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
| US20120302737A1 (en) | 2009-09-16 | 2012-11-29 | Genentech, Inc. | Coiled coil and/or tether containing protein complexes and uses thereof |
| TW201138821A (en) | 2010-03-26 | 2011-11-16 | Roche Glycart Ag | Bispecific antibodies |
| JP5953303B2 (ja) | 2010-07-29 | 2016-07-20 | ゼンコア インコーポレイテッド | 改変された等電点を有する抗体 |
| BR112013001847A2 (pt) | 2010-08-24 | 2016-05-31 | Hoffmann La Roche | anticorpo biespecífico, método de preparação do anticorpo biespecífico, do anticorpo biespecífico trivalente, métodos e composição farmacêutica |
| CA2815266C (en) | 2010-11-05 | 2023-09-05 | Zymeworks Inc. | Stable heterodimeric antibody design with mutations in the fc domain |
| JP5764677B2 (ja) | 2011-02-28 | 2015-08-19 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 抗原結合タンパク質 |
| CA2824824A1 (en) | 2011-02-28 | 2012-09-07 | F. Hoffmann-La Roche Ag | Monovalent antigen binding proteins |
| DK2681245T3 (en) | 2011-03-03 | 2018-08-13 | Zymeworks Inc | MULTIVALENT HEAT-MULTIMED SCAFFOLD DESIGN AND CONSTRUCTIONS |
| MY171343A (en) | 2011-04-22 | 2019-10-09 | Aptevo Res & Development Llc | Prostate-specific membrane antigen binding proteins and related composition and methods |
| CN107903325B (zh) | 2011-05-16 | 2021-10-29 | 埃泰美德(香港)有限公司 | 多特异性fab融合蛋白及其使用方法 |
| US10851178B2 (en) | 2011-10-10 | 2020-12-01 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
| US12466897B2 (en) | 2011-10-10 | 2025-11-11 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
| HRP20211773T1 (hr) | 2011-11-04 | 2022-03-04 | Zymeworks Inc. | Stabilna heterodimerni dizajn antitijela s mutacijama u fc domeni |
| WO2014067011A1 (en) * | 2012-11-02 | 2014-05-08 | Zymeworks Inc. | Crystal structures of heterodimeric fc domains |
| 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 |
| WO2014004586A1 (en) | 2012-06-25 | 2014-01-03 | Zymeworks Inc. | Process and methods for efficient manufacturing of highly pure asymmetric antibodies in mammalian cells |
| JP6498601B2 (ja) | 2012-07-13 | 2019-04-10 | ザイムワークス，インコーポレイテッド | 多価ヘテロ多量体足場設計および構築物 |
| JOP20200236A1 (ar) | 2012-09-21 | 2017-06-16 | Regeneron Pharma | الأجسام المضادة لمضاد cd3 وجزيئات ربط الأنتيجين ثنائية التحديد التي تربط cd3 وcd20 واستخداماتها |
| CA2892059C (en) * | 2012-11-21 | 2023-02-14 | Wuhan Yzy Biopharma Co., Ltd. | Bispecific antibody |
| US9914785B2 (en) | 2012-11-28 | 2018-03-13 | Zymeworks Inc. | Engineered immunoglobulin heavy chain-light chain pairs and uses thereof |
| US9701759B2 (en) | 2013-01-14 | 2017-07-11 | Xencor, Inc. | Heterodimeric proteins |
| US11053316B2 (en) | 2013-01-14 | 2021-07-06 | Xencor, Inc. | Optimized antibody variable regions |
| US10131710B2 (en) | 2013-01-14 | 2018-11-20 | Xencor, Inc. | Optimized antibody variable regions |
| US10968276B2 (en) | 2013-03-12 | 2021-04-06 | Xencor, Inc. | Optimized anti-CD3 variable regions |
| CN110981964B (zh) | 2013-01-14 | 2023-09-15 | Xencor股份有限公司 | 新型异二聚体蛋白 |
| US10487155B2 (en) | 2013-01-14 | 2019-11-26 | Xencor, Inc. | Heterodimeric proteins |
| US9605084B2 (en) | 2013-03-15 | 2017-03-28 | Xencor, Inc. | Heterodimeric proteins |
| AU2014207549B2 (en) | 2013-01-15 | 2018-12-06 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
| TWI682941B (zh) | 2013-02-01 | 2020-01-21 | 美商再生元醫藥公司 | 含嵌合恆定區之抗體 |
| DK2970486T3 (en) | 2013-03-15 | 2018-08-06 | Xencor Inc | MODULATION OF T-CELLS WITH BISPECIFIC ANTIBODIES AND FC-FUSIONS |
| US10106624B2 (en) | 2013-03-15 | 2018-10-23 | Xencor, Inc. | Heterodimeric proteins |
| US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
| US10519242B2 (en) | 2013-03-15 | 2019-12-31 | Xencor, Inc. | Targeting regulatory T cells with heterodimeric proteins |
| MX2016000272A (es) * | 2013-07-12 | 2016-08-03 | Zymeworks Inc | Construcciones de unión a los antígenos cd19 y cd3 biespecificos. |
| EP3024851B1 (en) | 2013-07-25 | 2018-05-09 | CytomX Therapeutics, Inc. | Multispecific antibodies, multispecific activatable antibodies and methods of using the same |
| RU2016115866A (ru) | 2013-10-11 | 2017-11-16 | Ф. Хоффманн-Ля Рош Аг | Мультиспецифические антитела с обменянными доменами и одинаковыми вариабельными доменами легкой цепи |
| MX2016006301A (es) * | 2013-11-13 | 2016-12-16 | Zymeworks Inc | Construcciones de unión a antígeno monovalente que se dirigen a egfr y/o her2, y sus usos. |
| CA2936785A1 (en) * | 2014-01-15 | 2015-07-23 | Zymeworks Inc. | Bi-specific cd3 and cd19 antigen-binding constructs |
| TWI701042B (zh) * | 2014-03-19 | 2020-08-11 | 美商再生元醫藥公司 | 用於腫瘤治療之方法及抗體組成物 |
| AU2015237184B2 (en) | 2014-03-28 | 2020-11-26 | Xencor, Inc. | Bispecific antibodies that bind to CD38 and CD3 |
| EP3126384B1 (en) | 2014-04-01 | 2020-12-02 | Adimab, LLC | Multispecific antibody analogs comprising a common light chain, and methods of their preparation and use |
| KR102493430B1 (ko) | 2014-05-28 | 2023-01-31 | 자임워크스 비씨 인코포레이티드 | 변형된 항원 결합 폴리펩티드 작제물 및 이의 용도 |
| US9212225B1 (en) | 2014-07-01 | 2015-12-15 | Amphivena Therapeutics, Inc. | Bispecific CD33 and CD3 binding proteins |
| US9611325B2 (en) | 2014-07-21 | 2017-04-04 | Wuhan Yzy Biopharma Co., Ltd. | Construction and application of bispecific antibody HER2xCD3 |
| US10669337B2 (en) | 2014-07-25 | 2020-06-02 | Cytomx Therapeutics, Inc. | Bispecific anti-CD3 antibodies, bispecific activatable anti-CD3 antibodies, and methods of using the same |
| US10633443B2 (en) * | 2014-09-26 | 2020-04-28 | Macrogenics, Inc. | Bi-specific monovalent diabodies that are capable of binding CD19 and CD3, and uses thereof |
| RS60739B1 (sr) | 2014-11-17 | 2020-09-30 | Regeneron Pharma | Postupci za lečenje tumora upotrebom cd3xcd20 bispecifičnog antitela |
| MX384025B (es) | 2014-11-26 | 2025-03-14 | Xencor Inc | Anticuerpos heterodimericos que se unen a cd3 y a antigenos tumorales. |
| PE20171103A1 (es) | 2014-11-26 | 2017-08-07 | Xencor Inc | Anticuerpos heterodimericos que se unen a cd3 y cd38 |
| US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
| JP6721590B2 (ja) | 2014-12-03 | 2020-07-15 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 多重特異性抗体 |
| EP3237449A2 (en) | 2014-12-22 | 2017-11-01 | Xencor, Inc. | Trispecific antibodies |
| WO2016141387A1 (en) | 2015-03-05 | 2016-09-09 | Xencor, Inc. | Modulation of t cells with bispecific antibodies and fc fusions |
| WO2016161010A2 (en) | 2015-03-30 | 2016-10-06 | Regeneron Pharmaceuticals, Inc. | Heavy chain constant regions with reduced binding to fc gamma receptors |
| AU2016257721B2 (en) * | 2015-05-01 | 2019-11-14 | The Regents Of The University Of California | Glycan-dependent immunotherapeutic molecules |
| EP3294319B1 (en) * | 2015-05-13 | 2024-04-24 | Ablynx NV | T cell recruiting polypeptides based on cd3 reactivity |
| PL3294768T3 (pl) | 2015-05-13 | 2020-03-31 | Ablynx N.V. | Polipeptydy rekrutujące komórki T oparte na reaktywności TCR alfa/beta |
| CA2986575A1 (en) | 2015-05-21 | 2016-11-24 | Harpoon Therapeutics, Inc. | Trispecific binding proteins and methods of use |
| EP4190814A1 (en) | 2015-05-29 | 2023-06-07 | Amphivena Therapeutics, Inc. | Methods of using bispecific cd33 and cd3 binding proteins |
| CN107849145B (zh) * | 2015-06-16 | 2021-10-26 | 基因泰克公司 | 抗cd3抗体及其使用方法 |
| CN104892765B (zh) * | 2015-06-29 | 2018-04-10 | 深圳市国创纳米抗体技术有限公司 | 一种抗CD3抗原和Her‑2抗原的双特异性抗体 |
| JP2018524373A (ja) | 2015-07-15 | 2018-08-30 | ザイムワークス，インコーポレイテッド | 薬物がコンジュゲートされた二重特異性抗原結合コンストラクト |
| TWI829617B (zh) | 2015-07-31 | 2024-01-21 | 德商安美基研究（慕尼黑）公司 | Ｆｌｔ３及ｃｄ３抗體構築體 |
| TWI744242B (zh) | 2015-07-31 | 2021-11-01 | 德商安美基研究（慕尼黑）公司 | Egfrviii及cd3抗體構築體 |
| EA039859B1 (ru) | 2015-07-31 | 2022-03-21 | Эмджен Рисерч (Мюник) Гмбх | Биспецифические конструкты антител, связывающие egfrviii и cd3 |
| TWI796283B (zh) * | 2015-07-31 | 2023-03-21 | 德商安美基研究（慕尼黑）公司 | Ｍｓｌｎ及ｃｄ３抗體構築體 |
| WO2017035430A2 (en) * | 2015-08-27 | 2017-03-02 | Kolltan Pharmaceuticals, Inc. | Anti-alk antibodies and methods for use thereof |
| JP7002446B2 (ja) | 2015-09-21 | 2022-03-04 | アプティーボ リサーチ アンド デベロップメント エルエルシー | Ｃｄ３結合ポリペプチド |
| AR106188A1 (es) | 2015-10-01 | 2017-12-20 | Hoffmann La Roche | Anticuerpos anti-cd19 humano humanizados y métodos de utilización |
| JP6937746B2 (ja) * | 2015-10-02 | 2021-09-22 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 二重特異性抗ｃｄ１９×ｃｄ３ｔ細胞活性化抗原結合分子 |
| CA3007030A1 (en) | 2015-12-07 | 2017-06-15 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and psma |
| CN106883297B (zh) | 2015-12-16 | 2019-12-13 | 苏州康宁杰瑞生物科技有限公司 | 基于ch3结构域的异二聚体分子、其制备方法及用途 |
| WO2017134158A1 (en) | 2016-02-03 | 2017-08-10 | Amgen Research (Munich) Gmbh | Psma and cd3 bispecific t cell engaging antibody constructs |
| PL3411402T3 (pl) | 2016-02-03 | 2022-02-28 | Amgen Research (Munich) Gmbh | Konstrukty bispecyficznych przeciwciał angażujących komórki T BCMA i CD3 |
| CN108701172A (zh) * | 2016-02-12 | 2018-10-23 | 南托米克斯有限责任公司 | 高通量识别患者特异性新表位作为癌症免疫疗法的治疗靶点 |
| AU2017233121B2 (en) | 2016-03-15 | 2023-12-21 | Itabmed (Hk) Limited | Multispecific Fab fusion proteins and use thereof |
| AU2017251116A1 (en) * | 2016-04-15 | 2018-12-06 | Zymeworks Inc. | Multi-specific antigen-binding constructs targeting immunotherapeutics |
| WO2017201493A1 (en) * | 2016-05-20 | 2017-11-23 | Harpoon Therapeutics, Inc. | Single chain variable fragment cd3 binding proteins |
| DK3468586T3 (da) | 2016-06-14 | 2024-10-21 | Xencor Inc | Bispecifikke checkpoint-hæmmer-antistoffer |
| CN106117358A (zh) * | 2016-06-16 | 2016-11-16 | 中山大学 | 抗cd3单域抗体 |
| EP3475304B1 (en) | 2016-06-28 | 2022-03-23 | Xencor, Inc. | Heterodimeric antibodies that bind somatostatin receptor 2 |
| CN109790526A (zh) * | 2016-07-01 | 2019-05-21 | 分解治疗有限责任公司 | 优化的二核酸酶融合体和方法 |
| US10793632B2 (en) | 2016-08-30 | 2020-10-06 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
| WO2018048318A2 (en) * | 2016-09-07 | 2018-03-15 | Anti-Doping Lab Qatar | Camel derived polypeptides binding human cd3, identified using a novel one-step method |
| UA128669C2 (uk) | 2016-10-14 | 2024-09-25 | Ксенкор, Інк. | ГЕТЕРОДИМЕРНИЙ Fc-ЗЛИТИЙ БІЛОК IL15/IL15Ra |
| WO2018112069A1 (en) * | 2016-12-13 | 2018-06-21 | Delinia, Inc. | Multivalent regulatory t cell modulators |
| CN108395482B (zh) | 2017-02-08 | 2021-02-05 | 西比曼生物科技（香港）有限公司 | 一种靶向cd20抗原嵌合抗原受体的构建及其工程化t细胞的活性鉴定 |
| KR20190118172A (ko) | 2017-02-08 | 2019-10-17 | 드래곤플라이 쎄라퓨틱스, 인크. | 천연 킬러 세포의 활성화를 위한 다중-특이적 결합 단백질 및 암 치료에서의 그의 치료적 용도 |
| CA3054086A1 (en) * | 2017-02-20 | 2018-08-23 | Dragonfly Therapeutics, Inc. | Proteins binding cd123, nkg2d and cd16 |
| EP4273258A3 (en) | 2017-02-20 | 2024-01-17 | Dragonfly Therapeutics, Inc. | Proteins binding her2, nkg2d and cd16 |
| KR102732040B1 (ko) | 2017-04-11 | 2024-11-21 | 인히브릭스 바이오사이언스, 인크. | 제한된 ｃｄ3 결합을 갖는 다중특이적 폴리펩티드 컨스트럭트 및 이를 이용한 방법 |
| JOP20190222A1 (ar) | 2017-04-11 | 2019-09-24 | Zymeworks Inc | الأجسام المضادة ثنائية النوعية المضادة لـ pd-l1 والمضادة لـ tim-3 |
| WO2018199593A1 (ko) * | 2017-04-24 | 2018-11-01 | 재단법인 목암생명과학연구소 | Her3 및 cd3에 결합하는 이중특이적 항체 |
| AU2018271930B2 (en) * | 2017-05-23 | 2025-05-08 | Dragonfly Therapeutics, Inc. | A protein binding NKG2D, CD16 and a tumor-associated antigen |
| WO2018228442A1 (en) * | 2017-06-14 | 2018-12-20 | Dingfu Biotarget Co., Ltd. | Proteinaceous heterodimer and use thereof |
| CN111201242A (zh) * | 2017-06-22 | 2020-05-26 | 财团法人生物技术开发中心 | 不对称异二聚fc-scfv融合抗globo h及抗cd3双特异性抗体及其在癌症治疗上的用途 |
| JP2020529832A (ja) | 2017-06-30 | 2020-10-15 | ゼンコア インコーポレイテッド | ＩＬ−１５／ＩＬ−１５Ｒαおよび抗原結合ドメインを含む標的化ヘテロダイマーＦｃ融合タンパク質 |
| AR112603A1 (es) | 2017-07-10 | 2019-11-20 | Lilly Co Eli | Anticuerpos biespecíficos inhibidores de punto de control |
| ES3023158T3 (en) * | 2017-08-01 | 2025-05-30 | Ab Therapeutics Inc | Bispecific antibodies and uses thereof |
| KR102777015B1 (ko) | 2017-08-22 | 2025-03-10 | 사나바이오, 엘엘씨 | 가용성 인터페론 수용체 및 그의 용도 |
| CN111630070B (zh) | 2017-10-13 | 2024-07-30 | 哈普恩治疗公司 | 三特异性蛋白质及使用方法 |
| IL315737A (en) | 2017-10-13 | 2024-11-01 | Harpoon Therapeutics Inc | B-cell maturation antigen-binding proteins |
| BR112020007309A2 (pt) | 2017-10-14 | 2020-09-29 | Cytomx Therapeutics, Inc. | anticorpos, anticorpos ativáveis, anticorpos biespecíficos e anticorpos ativáveis biespecíficos e métodos de uso dos mesmos |
| EP3706793A1 (en) | 2017-11-08 | 2020-09-16 | Xencor, Inc. | Bispecific and monospecific antibodies using novel anti-pd-1 sequences |
| US10981992B2 (en) | 2017-11-08 | 2021-04-20 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
| CN107903324B (zh) * | 2017-11-15 | 2021-01-29 | 北京绿竹生物技术股份有限公司 | 一种结合人cd19和cd3的双特异性抗体 |
| AU2018390418B2 (en) | 2017-12-19 | 2023-12-21 | Xencor, Inc. | Engineered IL-2 Fc fusion proteins |
| CN108129566B (zh) * | 2017-12-31 | 2021-05-11 | 中国科学院武汉病毒研究所 | 靶向间皮素的c-型单域抗体及其制备方法与应用 |
| MX2020008333A (es) | 2018-02-08 | 2020-09-21 | Dragonfly Therapeutics Inc | Terapia de combinacion del cancer que incluye proteinas de union multiespecificas que activan a las celulas asesinas naturales. |
| WO2019157366A1 (en) | 2018-02-08 | 2019-08-15 | Dragonfly Therapeutics, Inc. | Antibody variable domains targeting the nkg2d receptor |
| CR20200391A (es) | 2018-02-08 | 2020-10-19 | Genentech Inc | Moléculas biespecíficas de unión al antígeno y métodos de uso |
| MX2020008684A (es) | 2018-02-20 | 2020-12-07 | Dragonfly Therapeutics Inc | Proteinas de union multiespecificas que se unen a cd33, nkg2d y cd16 y metodos de uso. |
| WO2019162521A1 (en) * | 2018-02-26 | 2019-08-29 | Ablynx Nv | Improved nucleotide sequences encoding peptide linkers |
| JP7464525B2 (ja) | 2018-02-28 | 2024-04-09 | エーピー バイオサイエンスィズ インコーポレイテッド | 標的療法のためのチェックポイント遮断を組み合わせる二官能性タンパク質 |
| CN110218255B (zh) * | 2018-03-02 | 2020-12-04 | 广西医科大学 | 抗CD3的纳米抗体CD3/Nb47及其制备方法与应用 |
| US10982006B2 (en) | 2018-04-04 | 2021-04-20 | Xencor, Inc. | Heterodimeric antibodies that bind fibroblast activation protein |
| WO2019200022A1 (en) | 2018-04-11 | 2019-10-17 | Inhibrx, Inc. | Multispecific polypeptide constructs having constrained cd3 binding and related methods and uses |
| EP3781599A1 (en) | 2018-04-18 | 2021-02-24 | Xencor, Inc. | Pd-1 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and pd-1 antigen binding domains and uses thereof |
| CN112437777A (zh) | 2018-04-18 | 2021-03-02 | Xencor股份有限公司 | 包含IL-15/IL-15RA Fc融合蛋白和TIM-3抗原结合结构域的靶向TIM-3的异源二聚体融合蛋白 |
| CN119192397A (zh) | 2018-05-14 | 2024-12-27 | 哈普恩治疗公司 | 用于条件性激活免疫球蛋白分子的结合部分 |
| JP7383704B2 (ja) * | 2018-06-07 | 2023-11-20 | カリナン オンコロジー インコーポレイテッド | 多重特異性結合タンパク質およびその使用方法 |
| TW202016144A (zh) * | 2018-06-21 | 2020-05-01 | 日商第一三共股份有限公司 | 包括cd3抗原結合片段之組成物及其用途 |
| US12195533B2 (en) | 2018-07-24 | 2025-01-14 | Inhibrx Biosciences, Inc. | Multispecific polypeptide constructs containing a constrained CD3 binding domain and a receptor binding region and methods of using the same |
| EA202091888A1 (ru) | 2018-08-08 | 2020-10-23 | Драгонфлай Терапьютикс, Инк. | Вариабельные домены антител, нацеленные на рецептор nkg2d |
| MX2021001527A (es) | 2018-08-08 | 2021-06-15 | Dragonfly Therapeutics Inc | Proteínas de unión a nkg2d, cd16 y a un antígeno asociado a tumor. |
| CA3108427A1 (en) | 2018-08-08 | 2020-02-13 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins that bind bcma, nkg2d and cd16, and methods of use |
| AU2019331024A1 (en) | 2018-08-31 | 2021-03-18 | Regeneron Pharmaceuticals, Inc. | Dosing strategy that mitigates cytokine release syndrome for CD3/C20 bispecific antibodies |
| JP7548587B2 (ja) | 2018-09-07 | 2024-09-10 | アイタブメッド （エイチケイ） リミテッド | 二重特異性抗原結合タンパク質及びその使用 |
| WO2020061482A1 (en) | 2018-09-21 | 2020-03-26 | Harpoon Therapeutics, Inc. | Egfr binding proteins and methods of use |
| EP3856771A4 (en) | 2018-09-25 | 2022-06-29 | Harpoon Therapeutics, Inc. | Dll3 binding proteins and methods of use |
| US11358999B2 (en) | 2018-10-03 | 2022-06-14 | Xencor, Inc. | IL-12 heterodimeric Fc-fusion proteins |
| WO2020076977A2 (en) | 2018-10-11 | 2020-04-16 | Inhibrx, Inc. | Dll3 single domain antibodies and therapeutic compositions thereof |
| BR112021007555A2 (pt) * | 2018-10-23 | 2021-08-03 | Magenta Therapeutics, Inc. | conjugados anticorpo-fármaco (adcs) silenciados em fc e usos dos mesmos |
| CN112969476B (zh) * | 2018-12-07 | 2024-06-14 | 江苏恒瑞医药股份有限公司 | 多特异性蛋白分子 |
| WO2020132810A1 (en) * | 2018-12-24 | 2020-07-02 | Generon (Shanghai) Corporation Ltd. | Multispecific antigen binding proteins capable of binding cd19 and cd3, and use thereof |
| WO2020156405A1 (en) * | 2019-01-28 | 2020-08-06 | Wuxi Biologics (Shanghai) Co. Ltd. | Novel bispecific cd3/cd20 polypeptide complexes |
| CN114173875B (zh) | 2019-03-01 | 2025-04-15 | Xencor股份有限公司 | 结合enpp3和cd3的异二聚抗体 |
| EP3972998A1 (en) | 2019-05-21 | 2022-03-30 | Novartis AG | Cd19 binding molecules and uses thereof |
| PH12022550195A1 (en) | 2019-07-26 | 2022-11-21 | Janssen Biotech Inc | Proteins comprising kallikrein related peptidase 2 antigen binding domains and their uses |
| CN112390882A (zh) * | 2019-08-19 | 2021-02-23 | 杨洋 | 靶向cd3和cd20的双特异性抗体及其应用 |
| CN110551222B (zh) * | 2019-08-27 | 2023-06-06 | 重庆市畜牧科学院 | 一种新型双功能抗体及其用途 |
| IL293725A (en) | 2019-12-11 | 2022-08-01 | Cullinan Oncology Inc | Anti-cd19 antibodies and multispecific binding proteins |
| US11845799B2 (en) | 2019-12-13 | 2023-12-19 | Genentech, Inc. | Anti-Ly6G6D antibodies and methods of use |
| US20230075633A1 (en) * | 2019-12-20 | 2023-03-09 | Shandong Boan Biotechnology Co., Ltd. | Optimized anti-cd3 arm in the generation of t-cell bispecific antibodies for immunotherapy |
| TWI869528B (zh) | 2020-01-13 | 2025-01-11 | 美商威特拉公司 | C5ar1抗體分子及其用途 |
| CN113402612A (zh) | 2020-03-17 | 2021-09-17 | 西比曼生物科技（香港）有限公司 | 靶向cd19和cd20的联合嵌合抗原受体及其应用 |
| WO2021224913A1 (en) * | 2020-05-04 | 2021-11-11 | Immunorizon Ltd. | Precursor tri-specific antibody constructs and methods of use thereof |
| EP4146271A4 (en) | 2020-05-06 | 2024-09-04 | Dragonfly Therapeutics, Inc. | PROTEINS THAT BIND NKG2D, CD16 AND CLEC12A |
| US11919956B2 (en) | 2020-05-14 | 2024-03-05 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (PSMA) and CD3 |
| CN115916825A (zh) | 2020-06-19 | 2023-04-04 | 豪夫迈·罗氏有限公司 | 与cd3和cd19结合的抗体 |
| CA3192204A1 (en) | 2020-08-19 | 2022-02-24 | Xencor, Inc. | Anti-cd28 and/or anti-b7h3 compositions |
| US11555078B2 (en) * | 2020-12-09 | 2023-01-17 | Janux Therapeutics, Inc. | Compositions and methods related to tumor activated antibodies targeting PSMA and effector cell antigens |
| EP4277931A1 (en) | 2021-01-13 | 2023-11-22 | Visterra, Inc. | Humanized complement 5a receptor 1 antibodies and methods of use thereof |
| EP4032910A1 (en) * | 2021-01-22 | 2022-07-27 | ETH Zurich | Bispecific binding agent that binds to cd3 and a fluorophore |
| EP4301774A4 (en) | 2021-03-03 | 2025-08-13 | Dragonfly Therapeutics Inc | METHODS OF TREATING CANCER USING MULTI-SPECIFIC BINDING PROTEINS THAT BIND TO NKG2D, CD16, AND A TUMOR-ASSOCIATED ANTIGEN |
| JP2024511319A (ja) | 2021-03-09 | 2024-03-13 | ゼンコア インコーポレイテッド | Ｃｄ３及びｃｌｄｎ６に結合するヘテロ二量体抗体 |
| KR20230154311A (ko) | 2021-03-10 | 2023-11-07 | 젠코어 인코포레이티드 | Cd3 및 gpc3에 결합하는 이종이량체 항체 |
| WO2022241235A1 (en) | 2021-05-14 | 2022-11-17 | Genentech, Inc. | Methods for treatment of cd20-positive proliferative disorder with mosunetuzumab and polatuzumab vedotin |
| EP4651894A2 (en) * | 2023-01-18 | 2025-11-26 | Harpoon Therapeutics, Inc. | Her2 targeting trispecific protein for treatment of cancer |
| KR20250131823A (ko) | 2023-03-31 | 2025-09-03 | 아벨제타 인크. | Cd20 및 bcma를 표적화하는 이중특이적 키메라 항원 수용체 |
| WO2025113643A1 (en) | 2023-12-01 | 2025-06-05 | Gilead Sciences Inc. | Anti-fap-light fusion protein and use thereof |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6129914A (en) * | 1992-03-27 | 2000-10-10 | Protein Design Labs, Inc. | Bispecific antibody effective to treat B-cell lymphoma and cell line |
| US20020062010A1 (en) * | 1997-05-02 | 2002-05-23 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
| US6737056B1 (en) * | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
| US7183387B1 (en) * | 1999-01-15 | 2007-02-27 | Genentech, Inc. | Polypeptide variants with altered effector function |
| US20040132101A1 (en) * | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
| TWI353991B (en) * | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
| US8101720B2 (en) * | 2004-10-21 | 2012-01-24 | Xencor, Inc. | Immunoglobulin insertions, deletions and substitutions |
| EP1820513A1 (en) * | 2006-02-15 | 2007-08-22 | Trion Pharma Gmbh | Destruction of tumor cells expressing low to medium levels of tumor associated target antigens by trifunctional bispecific antibodies |
| SI2235064T1 (sl) * | 2008-01-07 | 2016-04-29 | Amgen Inc. | Metoda za izdelavo heterodimernih molekul - protitelesa fc z uporabo elektrostatičnih usmerjevalnih učinkov |
| EP2247618B1 (en) * | 2008-01-25 | 2014-06-11 | Amgen, Inc | Ferroportin antibodies and methods of use |
| WO2010037838A2 (en) * | 2008-10-01 | 2010-04-08 | Micromet Ag | Cross-species-specific single domain bispecific single chain antibody |
| WO2010085682A2 (en) * | 2009-01-23 | 2010-07-29 | Biogen Idec Ma Inc. | Stabilized fc polypeptides with reduced effector function and methods of use |
| CN103124743A (zh) * | 2009-12-29 | 2013-05-29 | 新兴产品开发西雅图有限公司 | Ron结合构建物及其使用方法 |
| DK2560683T4 (da) * | 2010-04-23 | 2022-08-29 | Hoffmann La Roche | Fremstilling af heteromultimeriske proteiner |
| UY33707A (es) * | 2010-11-04 | 2012-05-31 | Abbott Lab | Inmunoglobulinas con dominio variable dual y usos de las mismas |
| CA2815266C (en) * | 2010-11-05 | 2023-09-05 | Zymeworks Inc. | Stable heterodimeric antibody design with mutations in the fc domain |
| HRP20211773T1 (hr) * | 2011-11-04 | 2022-03-04 | Zymeworks Inc. | Stabilna heterodimerni dizajn antitijela s mutacijama u fc domeni |
| US20140302037A1 (en) * | 2013-03-15 | 2014-10-09 | Amgen Inc. | BISPECIFIC-Fc MOLECULES |
| ES2736326T3 (es) * | 2013-05-31 | 2019-12-27 | Zymeworks Inc | Heteromultímeros con función efectora reducida o silenciada |
-
2013
- 2013-07-13 BR BR112015000798A patent/BR112015000798A2/pt not_active Application Discontinuation
- 2013-07-13 CA CA2878843A patent/CA2878843A1/en not_active Abandoned
- 2013-07-13 JP JP2015521877A patent/JP2015528003A/ja active Pending
- 2013-07-13 EP EP13816697.0A patent/EP2872170A4/en not_active Withdrawn
- 2013-07-13 US US13/941,449 patent/US20140154253A1/en not_active Abandoned
- 2013-07-13 WO PCT/US2013/050411 patent/WO2014012085A2/en not_active Ceased
- 2013-07-13 CN CN201380037369.3A patent/CN104640562A/zh active Pending
- 2013-07-13 HK HK15108247.7A patent/HK1207575A1/xx unknown
- 2013-07-13 AU AU2013289883A patent/AU2013289883B2/en not_active Ceased
- 2013-07-13 KR KR20157003872A patent/KR20150036606A/ko not_active Withdrawn
- 2013-07-13 RU RU2015102193A patent/RU2650868C2/ru active
-
2019
- 2019-01-24 US US16/256,824 patent/US20190248897A1/en not_active Abandoned
-
2021
- 2021-03-19 US US17/207,526 patent/US20210317212A1/en not_active Abandoned
-
2024
- 2024-03-21 US US18/612,960 patent/US20240343802A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20240343802A1 (en) | 2024-10-17 |
| WO2014012085A3 (en) | 2014-03-27 |
| US20140154253A1 (en) | 2014-06-05 |
| HK1207575A1 (en) | 2016-02-05 |
| AU2013289883A1 (en) | 2015-02-19 |
| CN104640562A (zh) | 2015-05-20 |
| AU2013289883B2 (en) | 2018-11-01 |
| RU2650868C2 (ru) | 2018-04-17 |
| US20210317212A1 (en) | 2021-10-14 |
| EP2872170A4 (en) | 2016-06-22 |
| BR112015000798A2 (pt) | 2017-06-27 |
| US20190248897A1 (en) | 2019-08-15 |
| WO2014012085A2 (en) | 2014-01-16 |
| EP2872170A2 (en) | 2015-05-20 |
| RU2015102193A (ru) | 2016-08-27 |
| KR20150036606A (ko) | 2015-04-07 |
| WO2014012085A9 (en) | 2015-03-19 |
| JP2015528003A (ja) | 2015-09-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20240343802A1 (en) | Bispecific Asymmetric Heterodimers Comprising Anti-CD3 Constructs | |
| JP7591917B2 (ja) | Ｓｉｒｐ－アルファドメインまたはそのバリアントを有する構築物 | |
| US20160355588A1 (en) | Bispecific CD3 and CD19 Antigen Binding Constructs | |
| US20140072581A1 (en) | Immunoglobulin Constructs Comprising Selective Pairing of the Light and Heavy Chains | |
| EP2906237B1 (en) | Multivalent heteromultimer scaffold design and constructs | |
| EP2874652A2 (en) | Immunoglobulin constructs comprising selective pairing of the light and heavy chains |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20180712 |
|
| FZDE | Discontinued |
Effective date: 20201203 |