CA2980838A1 - Anti-cancer fusion polypeptide - Google Patents
Anti-cancer fusion polypeptide Download PDFInfo
- Publication number
- CA2980838A1 CA2980838A1 CA2980838A CA2980838A CA2980838A1 CA 2980838 A1 CA2980838 A1 CA 2980838A1 CA 2980838 A CA2980838 A CA 2980838A CA 2980838 A CA2980838 A CA 2980838A CA 2980838 A1 CA2980838 A1 CA 2980838A1
- Authority
- CA
- Canada
- Prior art keywords
- fwdarw
- ser
- arg
- lys
- tyr
- 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.)
- Pending
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 460
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 455
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 454
- 230000004927 fusion Effects 0.000 title claims abstract description 362
- 230000001093 anti-cancer Effects 0.000 title description 2
- 102100032530 Glypican-3 Human genes 0.000 claims abstract description 216
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims abstract description 191
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims abstract description 180
- 101001014668 Homo sapiens Glypican-3 Proteins 0.000 claims abstract description 51
- 238000000034 method Methods 0.000 claims abstract description 43
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 42
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 39
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 39
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 26
- 230000004913 activation Effects 0.000 claims abstract description 20
- 239000000203 mixture Substances 0.000 claims abstract description 20
- 102000019298 Lipocalin Human genes 0.000 claims description 183
- 108050006654 Lipocalin Proteins 0.000 claims description 183
- 230000027455 binding Effects 0.000 claims description 156
- 238000009739 binding Methods 0.000 claims description 156
- 238000006467 substitution reaction Methods 0.000 claims description 90
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 72
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 68
- 210000004027 cell Anatomy 0.000 claims description 61
- 150000001413 amino acids Chemical class 0.000 claims description 56
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 claims description 40
- 238000003556 assay Methods 0.000 claims description 38
- 230000006044 T cell activation Effects 0.000 claims description 29
- 125000000539 amino acid group Chemical group 0.000 claims description 28
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 26
- 108060003951 Immunoglobulin Proteins 0.000 claims description 26
- 102000018358 immunoglobulin Human genes 0.000 claims description 26
- 230000035772 mutation Effects 0.000 claims description 26
- 238000012286 ELISA Assay Methods 0.000 claims description 19
- 125000003729 nucleotide group Chemical group 0.000 claims description 19
- 101000946124 Homo sapiens Lipocalin-1 Proteins 0.000 claims description 18
- 230000001419 dependent effect Effects 0.000 claims description 18
- 239000012634 fragment Substances 0.000 claims description 18
- 230000014509 gene expression Effects 0.000 claims description 17
- 238000004458 analytical method Methods 0.000 claims description 14
- 230000004073 interleukin-2 production Effects 0.000 claims description 14
- 239000002773 nucleotide Substances 0.000 claims description 14
- 230000003213 activating effect Effects 0.000 claims description 10
- 230000035755 proliferation Effects 0.000 claims description 10
- 230000001105 regulatory effect Effects 0.000 claims description 10
- 230000005867 T cell response Effects 0.000 claims description 9
- 239000000427 antigen Substances 0.000 claims description 9
- 102000036639 antigens Human genes 0.000 claims description 9
- 108091007433 antigens Proteins 0.000 claims description 9
- 230000000638 stimulation Effects 0.000 claims description 9
- 230000007783 downstream signaling Effects 0.000 claims description 7
- 239000013598 vector Substances 0.000 claims description 7
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 claims description 5
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 claims description 5
- 230000004988 N-glycosylation Effects 0.000 claims description 4
- 230000001580 bacterial effect Effects 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims description 4
- 238000010353 genetic engineering Methods 0.000 claims description 3
- 229950005972 urelumab Drugs 0.000 claims description 2
- 241000282414 Homo sapiens Species 0.000 abstract description 38
- 206010028980 Neoplasm Diseases 0.000 abstract description 18
- 230000001225 therapeutic effect Effects 0.000 abstract description 6
- 201000010099 disease Diseases 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 230000002265 prevention Effects 0.000 abstract description 3
- 239000002246 antineoplastic agent Substances 0.000 abstract description 2
- 108050001154 Glypican Proteins 0.000 description 185
- 108050007237 Glypican-3 Proteins 0.000 description 184
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 157
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 127
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 127
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 115
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 105
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 91
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 86
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 86
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 81
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 80
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 68
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 63
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 60
- 235000001014 amino acid Nutrition 0.000 description 58
- 238000002474 experimental method Methods 0.000 description 58
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 50
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 46
- 229940024606 amino acid Drugs 0.000 description 45
- 108090000623 proteins and genes Proteins 0.000 description 44
- 102000004169 proteins and genes Human genes 0.000 description 41
- 235000018102 proteins Nutrition 0.000 description 39
- 108010002350 Interleukin-2 Proteins 0.000 description 36
- 102000000588 Interleukin-2 Human genes 0.000 description 36
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 35
- 238000002965 ELISA Methods 0.000 description 23
- 108020001507 fusion proteins Proteins 0.000 description 23
- 102000037865 fusion proteins Human genes 0.000 description 23
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 23
- 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 22
- 102000048373 human GPC3 Human genes 0.000 description 17
- 229960000575 trastuzumab Drugs 0.000 description 17
- 230000000694 effects Effects 0.000 description 16
- 239000003446 ligand Substances 0.000 description 16
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 16
- 239000006228 supernatant Substances 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 102000050327 human TNFRSF9 Human genes 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 239000013642 negative control Substances 0.000 description 12
- 101001023833 Homo sapiens Neutrophil gelatinase-associated lipocalin Proteins 0.000 description 11
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 229960002685 biotin Drugs 0.000 description 11
- 235000020958 biotin Nutrition 0.000 description 11
- 239000011616 biotin Substances 0.000 description 11
- 239000001963 growth medium Substances 0.000 description 11
- 102000047202 human LCN2 Human genes 0.000 description 11
- 238000000338 in vitro Methods 0.000 description 11
- 201000001441 melanoma Diseases 0.000 description 11
- 239000000523 sample Substances 0.000 description 11
- 238000005406 washing Methods 0.000 description 11
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 10
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 10
- 208000002030 Merkel cell carcinoma Diseases 0.000 description 10
- 206010029266 Neuroendocrine carcinoma of the skin Diseases 0.000 description 10
- 208000008383 Wilms tumor Diseases 0.000 description 10
- 208000017763 cutaneous neuroendocrine carcinoma Diseases 0.000 description 10
- 238000012217 deletion Methods 0.000 description 10
- 230000037430 deletion Effects 0.000 description 10
- 208000006359 hepatoblastoma Diseases 0.000 description 10
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 10
- 238000005259 measurement Methods 0.000 description 10
- 230000008929 regeneration Effects 0.000 description 10
- 238000011069 regeneration method Methods 0.000 description 10
- 239000012146 running buffer Substances 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 9
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000010494 dissociation reaction Methods 0.000 description 9
- 230000005593 dissociations Effects 0.000 description 9
- 238000005516 engineering process Methods 0.000 description 9
- 230000004048 modification Effects 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- 238000002703 mutagenesis Methods 0.000 description 9
- 231100000350 mutagenesis Toxicity 0.000 description 9
- 239000004033 plastic Substances 0.000 description 9
- 102000002627 4-1BB Ligand Human genes 0.000 description 8
- 108010082808 4-1BB Ligand Proteins 0.000 description 8
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 8
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 8
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 8
- 239000012298 atmosphere Substances 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 238000001514 detection method Methods 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 238000003780 insertion Methods 0.000 description 8
- 230000037431 insertion Effects 0.000 description 8
- 108010073807 IgG Receptors Proteins 0.000 description 7
- 102000009490 IgG Receptors Human genes 0.000 description 7
- 102000013519 Lipocalin-2 Human genes 0.000 description 7
- 108010051335 Lipocalin-2 Proteins 0.000 description 7
- 241000282567 Macaca fascicularis Species 0.000 description 7
- 238000013459 approach Methods 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 230000009977 dual effect Effects 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 230000006698 induction Effects 0.000 description 7
- 230000036470 plasma concentration Effects 0.000 description 7
- 238000004448 titration Methods 0.000 description 7
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 6
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 6
- 108010090804 Streptavidin Proteins 0.000 description 6
- 239000005018 casein Substances 0.000 description 6
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 6
- 235000021240 caseins Nutrition 0.000 description 6
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 5
- BKAYIFDRRZZKNF-VIFPVBQESA-N N-acetylcarnosine Chemical compound CC(=O)NCCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BKAYIFDRRZZKNF-VIFPVBQESA-N 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- 210000000822 natural killer cell Anatomy 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 238000003118 sandwich ELISA Methods 0.000 description 5
- 230000011664 signaling Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- 108020004705 Codon Proteins 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- 239000007995 HEPES buffer Substances 0.000 description 4
- 125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 description 4
- 108010057281 Lipocalin 1 Proteins 0.000 description 4
- 102000003752 Lipocalin 1 Human genes 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 229920001213 Polysorbate 20 Polymers 0.000 description 4
- 208000003874 Simpson-Golabi-Behmel syndrome Diseases 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 238000013357 binding ELISA Methods 0.000 description 4
- 239000006285 cell suspension Substances 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 230000003750 conditioning effect Effects 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 230000005847 immunogenicity Effects 0.000 description 4
- 238000000111 isothermal titration calorimetry Methods 0.000 description 4
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 4
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 4
- 125000001500 prolyl group Chemical compound [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 238000001542 size-exclusion chromatography Methods 0.000 description 4
- 230000006641 stabilisation Effects 0.000 description 4
- 238000011105 stabilization Methods 0.000 description 4
- 229960005322 streptomycin Drugs 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 241000283707 Capra Species 0.000 description 3
- 102000014914 Carrier Proteins Human genes 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 3
- 241000237988 Patellidae Species 0.000 description 3
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 3
- 108010076089 accutase Proteins 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 108091008324 binding proteins Proteins 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 230000009918 complex formation Effects 0.000 description 3
- 230000004940 costimulation Effects 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- -1 for example Chemical class 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229960004857 mitomycin Drugs 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 239000005022 packaging material Substances 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- DTLVBHCSSNJCMJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-[2-[2-[2-[2-[5-(2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl)pentanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoate Chemical compound S1CC2NC(=O)NC2C1CCCCC(=O)NCCOCCOCCOCCOCCC(=O)ON1C(=O)CCC1=O DTLVBHCSSNJCMJ-UHFFFAOYSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-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
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 108010087819 Fc receptors Proteins 0.000 description 2
- 102000009109 Fc receptors Human genes 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 2
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 0.000 description 2
- 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 2
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 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
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- 108091005461 Nucleic proteins Proteins 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 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
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
- 101710165434 Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 description 2
- CGWAPUBOXJWXMS-HOTGVXAUSA-N Tyr-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 CGWAPUBOXJWXMS-HOTGVXAUSA-N 0.000 description 2
- 230000006786 activation induced cell death Effects 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 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
- 210000003719 b-lymphocyte Anatomy 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
- 230000008827 biological function Effects 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000004590 computer program Methods 0.000 description 2
- 210000000172 cytosol Anatomy 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000011033 desalting Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 108010068617 neonatal Fc receptor Proteins 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
- 238000002708 random mutagenesis Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
- 210000003171 tumor-infiltrating lymphocyte Anatomy 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
- 239000004474 valine Substances 0.000 description 2
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 1
- FVFVNNKYKYZTJU-UHFFFAOYSA-N 6-chloro-1,3,5-triazine-2,4-diamine Chemical group NC1=NC(N)=NC(Cl)=N1 FVFVNNKYKYZTJU-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 108010011170 Ala-Trp-Arg-His-Pro-Gln-Phe-Gly-Gly Proteins 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 101100026251 Caenorhabditis elegans atf-2 gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 231100000023 Cell-mediated cytotoxicity Toxicity 0.000 description 1
- 206010057250 Cell-mediated cytotoxicity Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 101100077740 Cyprinus carpio map2k2 gene Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102100034789 Epididymal-specific lipocalin-6 Human genes 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 108091006020 Fc-tagged proteins Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 102100028592 Gamma-tubulin complex component 3 Human genes 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 102000010956 Glypican Human genes 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 101000945886 Homo sapiens Epididymal-specific lipocalin-6 Proteins 0.000 description 1
- 101000605055 Homo sapiens Epididymal-specific lipocalin-8 Proteins 0.000 description 1
- 101001058968 Homo sapiens Gamma-tubulin complex component 3 Proteins 0.000 description 1
- 101001052490 Homo sapiens Mitogen-activated protein kinase 3 Proteins 0.000 description 1
- 101001052477 Homo sapiens Mitogen-activated protein kinase 4 Proteins 0.000 description 1
- 101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 description 1
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 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
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 108091029795 Intergenic region Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 1
- 102000019145 JUN kinase activity proteins Human genes 0.000 description 1
- 241000235058 Komagataella pastoris 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
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-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
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-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
- YEIYAQQKADPIBJ-GARJFASQSA-N Lys-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)N)C(=O)O YEIYAQQKADPIBJ-GARJFASQSA-N 0.000 description 1
- 102100024192 Mitogen-activated protein kinase 3 Human genes 0.000 description 1
- 102100024189 Mitogen-activated protein kinase 4 Human genes 0.000 description 1
- 102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 description 1
- 102100033127 Mitogen-activated protein kinase kinase kinase 5 Human genes 0.000 description 1
- 101710164337 Mitogen-activated protein kinase kinase kinase 5 Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100337463 Mus musculus Gpc3 gene Proteins 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 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
- 108700020796 Oncogene Proteins 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 241000508269 Psidium Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 230000010799 Receptor Interactions Effects 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- VBKBDLMWICBSCY-IMJSIDKUSA-N Ser-Asp Chemical compound OC[C@H](N)C(=O)N[C@H](C(O)=O)CC(O)=O VBKBDLMWICBSCY-IMJSIDKUSA-N 0.000 description 1
- 201000002946 Simpson-Golabi-Behmel syndrome type 1 Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 206010042566 Superinfection Diseases 0.000 description 1
- 108700026226 TATA Box Proteins 0.000 description 1
- 102000004398 TNF receptor-associated factor 1 Human genes 0.000 description 1
- 108090000920 TNF receptor-associated factor 1 Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical group N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- 239000012911 assay medium Substances 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 238000002869 basic local alignment search tool Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 230000005773 cancer-related death Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000005890 cell-mediated cytotoxicity Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 238000003745 diagnosis 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
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 101150039713 gpc3 gene Proteins 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 102000027596 immune receptors Human genes 0.000 description 1
- 108091008915 immune receptors Proteins 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000009851 immunogenic response Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000005937 nuclear translocation Effects 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 1
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- RLZZZVKAURTHCP-UHFFFAOYSA-N phenanthrene-3,4-diol Chemical compound C1=CC=C2C3=C(O)C(O)=CC=C3C=CC2=C1 RLZZZVKAURTHCP-UHFFFAOYSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000012121 regulation of immune response Effects 0.000 description 1
- 238000004153 renaturation Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- 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
- C07K2317/90—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
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15167927 | 2015-05-18 | ||
| EP15167927.1 | 2015-05-18 | ||
| EP16150508.6 | 2016-01-08 | ||
| EP16150508 | 2016-01-08 | ||
| PCT/EP2016/061071 WO2016184882A1 (en) | 2015-05-18 | 2016-05-18 | Anti-cancer fusion polypeptide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2980838A1 true CA2980838A1 (en) | 2016-11-24 |
Family
ID=56134305
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2980838A Pending CA2980838A1 (en) | 2015-05-18 | 2016-05-18 | Anti-cancer fusion polypeptide |
Country Status (22)
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2015205530B8 (en) * | 2014-01-13 | 2019-09-19 | Pieris Pharmaceuticals Gmbh | Multi-specific polypeptide useful for localized tumor immunomodulation |
| DK3292137T3 (da) * | 2015-05-04 | 2022-10-17 | Pieris Pharmaceuticals Gmbh | Proteiner specifikke for cd137 |
| JP7108535B2 (ja) | 2015-07-15 | 2022-07-28 | ピエリス ファーマシューティカルズ ゲーエムベーハー | Ｌａｇ－３に特異的な新規タンパク質 |
| AR106188A1 (es) | 2015-10-01 | 2017-12-20 | Hoffmann La Roche | Anticuerpos anti-cd19 humano humanizados y métodos de utilización |
| MX2019007795A (es) * | 2017-01-03 | 2019-08-16 | Hoffmann La Roche | Moleculas de union a antigeno biespecificas que comprenden el clon 20h4.9 anti-4-1bb. |
| US11591398B2 (en) | 2017-01-06 | 2023-02-28 | Crescendo Biologics Limited | Single domain antibodies to programmed cell death protein 1 (PD-1) |
| KR20190104409A (ko) * | 2017-01-18 | 2019-09-09 | 피어이스 파마슈티컬즈 게엠베하 | Lag-3에 대하여 결합 친화성을 갖는 리포칼린 뮤테인 |
| WO2018134279A1 (en) * | 2017-01-18 | 2018-07-26 | Pieris Pharmaceuticals Gmbh | Novel fusion polypeptides specific for lag-3 and pd-1 |
| KR20200083574A (ko) * | 2017-11-13 | 2020-07-08 | 크레센도 바이오로직스 리미티드 | Cd137 및 psma에 결합하는 분자 |
| GB201802573D0 (en) | 2018-02-16 | 2018-04-04 | Crescendo Biologics Ltd | Therapeutic molecules that bind to LAG3 |
| US12285410B2 (en) | 2018-03-26 | 2025-04-29 | 4Sc Ag | Combination comprising HDAC inhibitor and CD137 agonist for cancer therapy |
| KR20210040103A (ko) * | 2018-07-31 | 2021-04-12 | 피어이스 파마슈티컬즈 게엠베하 | Cd137 및 pd-l1에 특이적인 신규한 융합 단백질 |
| CA3124441A1 (en) * | 2019-02-26 | 2020-09-03 | Pieris Pharmaceuticals Gmbh | Novel fusion proteins specific for cd137 and gpc3 |
| CA3127973A1 (en) * | 2019-03-29 | 2020-10-08 | Pieris Pharmaceuticals Gmbh | Inhaled administration of lipocalin muteins |
| EP3952996A1 (en) * | 2019-04-12 | 2022-02-16 | F. Hoffmann-La Roche AG | Bispecific antigen binding molecules comprising lipocalin muteins |
| KR20200124176A (ko) * | 2019-04-23 | 2020-11-02 | 주식회사 엘지화학 | 면역글로불린의 Fc 영역 및 GDF15를 포함하는 융합 폴리펩타이드 |
| UA129329C2 (uk) | 2019-06-25 | 2025-03-19 | Гіліад Сайєнсіз, Інк. | ЗЛИТІ БІЛКИ FLT3L-Fc |
| TWI862640B (zh) * | 2019-07-30 | 2024-11-21 | 英商拜西可泰克斯有限公司 | 異質雙環肽複合物 |
| CN115960242B (zh) * | 2021-09-09 | 2023-10-17 | 广东东阳光药业股份有限公司 | 抗癌结合分子及其应用 |
| KR20250071257A (ko) * | 2022-09-21 | 2025-05-21 | 씨젠 인크. | Cd137 및 cd228에 특이적인 신규한 융합 단백질 |
Family Cites Families (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3779221D1 (de) | 1986-08-19 | 1992-06-25 | Genentech Inc | Einrichtung und dispersion zum intrapulmonalen eingeben von polypeptidwuchsstoffen und -zytokinen. |
| JPH01215289A (ja) | 1988-02-22 | 1989-08-29 | Toa Nenryo Kogyo Kk | 遺伝子組換えによる正常ヒト血清アルブミンａの製造方法 |
| FR2649991B2 (fr) | 1988-08-05 | 1994-03-04 | Rhone Poulenc Sante | Utilisation de derives stables du plasmide pkd1 pour l'expression et la secretion de proteines heterologues dans les levures du genre kluyveromyces |
| US5728553A (en) | 1992-09-23 | 1998-03-17 | Delta Biotechnology Limited | High purity albumin and method of producing |
| ES2245780T3 (es) | 1994-05-18 | 2006-01-16 | Nektar Therapeutics | Metodos y composiciones para la formulacion de interferones como un polvo seco. |
| DE4417598A1 (de) | 1994-05-19 | 1995-12-14 | Max Planck Gesellschaft | Verwendung des Tetracyclinpromotors zur stringent regulierten Produktion von rekombinanten Proteinen in prokaryontischen Zellen |
| AU5132096A (en) | 1995-01-30 | 1996-08-21 | Terrapin Technologies, Inc. | Glubodies - multiplicities of proteins capable of binding a variety of small molecules |
| US5908621A (en) | 1995-11-02 | 1999-06-01 | Schering Corporation | Polyethylene glycol modified interferon therapy |
| US6620413B1 (en) | 1995-12-27 | 2003-09-16 | Genentech, Inc. | OB protein-polymer chimeras |
| DE19641876B4 (de) | 1996-10-10 | 2011-09-29 | Iba Gmbh | Streptavidinmuteine |
| WO1998016873A1 (en) | 1996-10-14 | 1998-04-23 | Firm Forsat Ltd. | Method for preparing dispersions of chromogenic components |
| DE19742706B4 (de) | 1997-09-26 | 2013-07-25 | Pieris Proteolab Ag | Lipocalinmuteine |
| GB9722131D0 (en) | 1997-10-20 | 1997-12-17 | Medical Res Council | Method |
| CA2233725A1 (en) | 1998-03-31 | 1999-09-30 | Hemosol Inc. | Hemoglobin-hydroxyethyl starch complexes |
| KR20010052622A (ko) | 1998-06-08 | 2001-06-25 | 프리돌린 클라우스너, 롤란드 비. 보레르 | 만성 씨형 간염을 치료하기 위한 폴리에틸렌글리콜-인터페론-알파 및 리바비린의 용도 |
| US6403564B1 (en) | 1998-10-16 | 2002-06-11 | Schering Corporation | Ribavirin-interferon alfa combination therapy for eradicating detectable HCV-RNA in patients having chronic hepatitis C infection |
| DE19926068C1 (de) | 1999-06-08 | 2001-01-11 | Arne Skerra | Muteine des Bilin-Bindungsproteins |
| WO2002024866A2 (en) | 2000-09-21 | 2002-03-28 | University Of Massachusetts | Method of inducing apoptosis in lymphoid cells |
| US7211395B2 (en) | 2001-03-09 | 2007-05-01 | Dyax Corp. | Serum albumin binding moieties |
| AU2001298053A1 (en) | 2001-09-27 | 2003-04-14 | Pieris Proteolab Ag | Muteins of apolipoprotein D |
| WO2003029462A1 (en) | 2001-09-27 | 2003-04-10 | Pieris Proteolab Ag | Muteins of human neutrophil gelatinase-associated lipocalin and related proteins |
| AU2003275958A1 (en) | 2003-08-25 | 2005-03-10 | Pieris Proteolab Ag | Muteins of tear lipocalin |
| US7691970B2 (en) | 2003-08-25 | 2010-04-06 | Pieris Ag | Muteins of a bilin-binding protein with affinity for a given target |
| US7288638B2 (en) | 2003-10-10 | 2007-10-30 | Bristol-Myers Squibb Company | Fully human antibodies against human 4-1BB |
| JP2007284351A (ja) | 2004-07-27 | 2007-11-01 | Osaka Bioscience Institute | アミロイド蛋白質の凝集を抑制する物質とその作用 |
| US7892827B2 (en) | 2004-11-26 | 2011-02-22 | Pieris Ag | Compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4) |
| WO2007038619A2 (en) | 2005-09-27 | 2007-04-05 | Amunix, Inc. | Proteinaceous pharmaceuticals and uses thereof |
| US20070087005A1 (en) | 2005-10-14 | 2007-04-19 | Lazar Gregory A | Anti-glypican-3 antibody |
| WO2007137170A2 (en) | 2006-05-20 | 2007-11-29 | Seattle Genetics, Inc. | Anti-glypican-3 antibody drug conjugates |
| CN101516907B (zh) | 2006-08-01 | 2015-08-26 | 皮里斯股份公司 | 泪液脂质运载蛋白的突变蛋白及其获得方法 |
| JP5608368B2 (ja) | 2006-08-01 | 2014-10-15 | ピエリス アーゲー | 涙リポカリンの突然変異タンパク質およびそれを得るための方法 |
| WO2009012394A1 (en) | 2007-07-17 | 2009-01-22 | Medarex, Inc. | Monoclonal antibodies against glypican-3 |
| CA2702611A1 (en) | 2007-10-19 | 2009-04-23 | Abbott Laboratories | Immunoassays and kits for the detection of ngal |
| US8420051B2 (en) | 2008-06-24 | 2013-04-16 | Technische Universitaet Meunchen | Muteins of hNGAL and related proteins with affinity for a given target |
| RU2564125C2 (ru) | 2009-12-07 | 2015-09-27 | Пирис Аг | Мутеины липокалина 2 человека (lcn2, hngal) с аффинностью для определенной мишени |
| SG187695A1 (en) | 2010-08-16 | 2013-03-28 | Pieris Ag | Binding proteins for hepcidin |
| DK2614082T3 (en) | 2010-09-09 | 2018-11-26 | Pfizer | 4-1BB BINDING MOLECULES |
| US9260492B2 (en) | 2010-11-15 | 2016-02-16 | Pieris Ag | Muteins of human lipocalin 2 with affinity for glypican-3 (GPC-3) |
| WO2013174783A1 (en) | 2012-05-23 | 2013-11-28 | Pieris Ag | Lipocalin muteins with binding-affinity for glypican-3 (gpc-3) and use of lipocalin muteins for target-specific delivery to cells expressing gpc-3 |
| RU2015126651A (ru) * | 2012-12-10 | 2017-01-16 | Фред Хатчинсон Кэнсер Рисёрч Сентер | Способы скрининга |
| WO2014116846A2 (en) * | 2013-01-23 | 2014-07-31 | Abbvie, Inc. | Methods and compositions for modulating an immune response |
| CN107460201A (zh) * | 2013-05-08 | 2017-12-12 | 科济生物医药（上海）有限公司 | 编码gpc‑3嵌合抗原受体蛋白的核酸及表达gpc‑3嵌合抗原受体蛋白的t淋巴细胞 |
| AU2015205530B8 (en) | 2014-01-13 | 2019-09-19 | Pieris Pharmaceuticals Gmbh | Multi-specific polypeptide useful for localized tumor immunomodulation |
| KR102568808B1 (ko) * | 2014-04-07 | 2023-08-18 | 추가이 세이야쿠 가부시키가이샤 | 면역활성화 항원 결합 분자 |
| CA2973640A1 (en) | 2015-01-28 | 2016-08-04 | Rachida Siham Bel Aiba | Novel proteins specific for angiogenesis |
| CA2976687A1 (en) | 2015-02-18 | 2016-08-25 | Sanofi | Novel proteins specific for pyoverdine and pyochelin |
| BR112017020434A2 (pt) * | 2015-05-04 | 2018-06-26 | Pieris Pharmaceuticals Gmbh | polipeptídeos de fusão, molécula de ácido nucleico, célula hospedeira, método para produzir um polipeptídeo de fusão, usos do polipeptídeo de fusão, métodos para ativar as vias de sinalização, para coestimular células, para induzir a proliferação de linfócitos t, para direcionar o agrupamento de cd137, para induzir uma resposta local de células t, para induzir uma resposta local de células nk e para induzir a produção de il-2 |
| DK3292137T3 (da) | 2015-05-04 | 2022-10-17 | Pieris Pharmaceuticals Gmbh | Proteiner specifikke for cd137 |
| KR20180008649A (ko) * | 2015-05-18 | 2018-01-24 | 피어이스 파마슈티컬즈 게엠베하 | 글리피칸-3(gpc3)에 대해 친화도를 갖는 인간 리포칼린 2의 뮤테인 |
| TW201725212A (zh) | 2015-12-10 | 2017-07-16 | 第一三共股份有限公司 | 特異性於降鈣素基因相關胜肽的新穎蛋白 |
-
2016
- 2016-05-18 MX MX2017014716A patent/MX390894B/es unknown
- 2016-05-18 EP EP22216061.6A patent/EP4219535A1/en active Pending
- 2016-05-18 CA CA2980838A patent/CA2980838A1/en active Pending
- 2016-05-18 SG SG11201707426SA patent/SG11201707426SA/en unknown
- 2016-05-18 FI FIEP16729794.4T patent/FI3298030T3/fi active
- 2016-05-18 EP EP16729794.4A patent/EP3298030B1/en active Active
- 2016-05-18 HU HUE16729794A patent/HUE061108T2/hu unknown
- 2016-05-18 PL PL16729794.4T patent/PL3298030T3/pl unknown
- 2016-05-18 RS RS20230084A patent/RS64002B1/sr unknown
- 2016-05-18 RU RU2017135539A patent/RU2754466C2/ru active
- 2016-05-18 DK DK16729794.4T patent/DK3298030T5/da active
- 2016-05-18 SI SI201631659T patent/SI3298030T1/sl unknown
- 2016-05-18 SM SM20230026T patent/SMT202300026T1/it unknown
- 2016-05-18 RU RU2021119777A patent/RU2021119777A/ru unknown
- 2016-05-18 WO PCT/EP2016/061071 patent/WO2016184882A1/en not_active Ceased
- 2016-05-18 KR KR1020177035641A patent/KR102685748B1/ko active Active
- 2016-05-18 AU AU2016262845A patent/AU2016262845B2/en active Active
- 2016-05-18 JP JP2017560331A patent/JP6947642B2/ja active Active
- 2016-05-18 US US15/575,309 patent/US10913778B2/en active Active
- 2016-05-18 ES ES16729794T patent/ES2938525T3/es active Active
- 2016-05-18 LT LTEPPCT/EP2016/061071T patent/LT3298030T/lt unknown
- 2016-05-18 HR HRP20230145TT patent/HRP20230145T1/hr unknown
- 2016-05-18 CN CN201680028941.3A patent/CN108112253B/zh active Active
-
2017
- 2017-09-06 ZA ZA2017/06061A patent/ZA201706061B/en unknown
-
2021
- 2021-02-05 US US17/169,209 patent/US11919931B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11919931B2 (en) | Anti-cancer fusion polypeptide capable of binding both CD137 and glypican-3 (GPC3) | |
| US20210198380A1 (en) | Anti-cancer fusion polypeptide | |
| RU2628699C2 (ru) | Trail r2-специфические мультимерные скаффолды | |
| JP7482488B2 (ja) | Ｃｄ１３７とｐｄ－ｌ１に特異的な新規融合タンパク質 | |
| JP7476219B2 (ja) | Ｃｄ１３７およびｇｐｃ３に特異的な新規融合タンパク質 | |
| JP7225116B2 (ja) | Ｌａｇ－３に対する結合親和性を有するリポカリンムテイン | |
| HK1249526B (en) | Anti-cancer fusion polypeptide | |
| BR112017020445B1 (pt) | Proteína de fusão, molécula de ácido nucleico, célula hospedeira, método de produção de uma proteína de fusão, uso de uma ou mais proteínas de fusão e composição farmacêutica |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20210507 |
|
| EEER | Examination request |
Effective date: 20210507 |
|
| EEER | Examination request |
Effective date: 20210507 |
|
| EEER | Examination request |
Effective date: 20210507 |
|
| EEER | Examination request |
Effective date: 20210507 |
|
| EEER | Examination request |
Effective date: 20210507 |
|
| EEER | Examination request |
Effective date: 20210507 |
|
| EEER | Examination request |
Effective date: 20210507 |