JP2021531337A - 自己集合ペプチド骨格 - Google Patents
自己集合ペプチド骨格 Download PDFInfo
- Publication number
- JP2021531337A JP2021531337A JP2021523579A JP2021523579A JP2021531337A JP 2021531337 A JP2021531337 A JP 2021531337A JP 2021523579 A JP2021523579 A JP 2021523579A JP 2021523579 A JP2021523579 A JP 2021523579A JP 2021531337 A JP2021531337 A JP 2021531337A
- Authority
- JP
- Japan
- Prior art keywords
- peptide
- seq
- oligomer
- hapten
- subject
- 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 130
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 57
- 239000000203 mixture Substances 0.000 claims abstract description 32
- 229960005486 vaccine Drugs 0.000 claims abstract description 28
- 238000000034 method Methods 0.000 claims description 59
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 19
- 238000010168 coupling process Methods 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 230000008878 coupling Effects 0.000 claims description 17
- 238000005859 coupling reaction Methods 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 15
- 239000000863 peptide conjugate Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 230000001268 conjugating effect Effects 0.000 claims description 13
- 150000001413 amino acids Chemical class 0.000 claims description 12
- 230000028993 immune response Effects 0.000 claims description 12
- 230000005847 immunogenicity Effects 0.000 claims description 11
- 125000001931 aliphatic group Chemical group 0.000 claims description 9
- 238000001727 in vivo Methods 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 239000000556 agonist Substances 0.000 claims description 8
- 102000039446 nucleic acids Human genes 0.000 claims description 8
- 108020004707 nucleic acids Proteins 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 6
- 150000007523 nucleic acids Chemical class 0.000 claims description 6
- 230000002209 hydrophobic effect Effects 0.000 claims description 5
- 150000002632 lipids Chemical class 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 150000001720 carbohydrates Chemical class 0.000 claims description 4
- 210000003463 organelle Anatomy 0.000 claims description 4
- 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 3
- 108010028921 Lipopeptides Proteins 0.000 claims description 2
- 230000003834 intracellular effect Effects 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 1
- 230000002708 enhancing effect Effects 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 58
- 230000002163 immunogen Effects 0.000 abstract description 11
- 239000000562 conjugate Substances 0.000 description 29
- 125000005647 linker group Chemical group 0.000 description 23
- 239000002671 adjuvant Substances 0.000 description 20
- 235000018102 proteins Nutrition 0.000 description 17
- 102000004169 proteins and genes Human genes 0.000 description 17
- 108090000623 proteins and genes Proteins 0.000 description 17
- 230000021615 conjugation Effects 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- 230000003053 immunization Effects 0.000 description 10
- 238000002649 immunization Methods 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 8
- 239000004472 Lysine Substances 0.000 description 8
- 230000000890 antigenic effect Effects 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 150000003384 small molecules Chemical class 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 description 5
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- 235000014633 carbohydrates Nutrition 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 230000003915 cell function Effects 0.000 description 5
- 239000003431 cross linking reagent Substances 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- -1 9-fluorenylmethoxycarbonyl Chemical group 0.000 description 4
- 102000014914 Carrier Proteins Human genes 0.000 description 4
- 108010078791 Carrier Proteins Proteins 0.000 description 4
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000000470 constituent Substances 0.000 description 4
- 230000036571 hydration Effects 0.000 description 4
- 238000006703 hydration reaction Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000004971 Cross linker Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 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 3
- 108091006116 chimeric peptides Proteins 0.000 description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 239000012678 infectious agent Substances 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000001338 self-assembly Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 229940031626 subunit vaccine Drugs 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 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
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 206010010356 Congenital anomaly Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 2
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 2
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 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
- 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
- 102000004882 Lipase Human genes 0.000 description 2
- 108090001060 Lipase Proteins 0.000 description 2
- 239000004367 Lipase Substances 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 2
- 108020000411 Toll-like receptor Proteins 0.000 description 2
- 102000002689 Toll-like receptor Human genes 0.000 description 2
- 102100039360 Toll-like receptor 4 Human genes 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
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000003044 adaptive effect Effects 0.000 description 2
- 230000033289 adaptive immune response Effects 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 238000004590 computer program Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 150000002016 disaccharides Chemical class 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000001641 gel filtration chromatography Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 238000000126 in silico method Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 235000019421 lipase Nutrition 0.000 description 2
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical class O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 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 2
- 229920002521 macromolecule Polymers 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
- 230000001404 mediated effect Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 238000001426 native polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 238000006384 oligomerization reaction Methods 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 229940031439 squalene Drugs 0.000 description 2
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000012916 structural analysis Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 229940126577 synthetic vaccine Drugs 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 239000013638 trimer Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000938605 Crocodylia Species 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
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010022095 Injection Site reaction Diseases 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 206010024264 Lethargy Diseases 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 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
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 101710116435 Outer membrane protein Proteins 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 108010088535 Pep-1 peptide Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 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
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 230000008350 antigen-specific antibody response Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 238000000055 blue native polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 238000002983 circular dichroism Methods 0.000 description 1
- 238000001142 circular dichroism spectrum Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000004041 dendritic cell maturation Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000011013 endotoxin removal Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
- 238000002825 functional assay 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
- 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
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 229960004198 guanidine Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000009463 immunological memory response Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000012405 in silico analysis Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 238000000670 ligand binding assay Methods 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000002809 long lived plasma cell 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
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 210000001806 memory b lymphocyte Anatomy 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
- 229960001252 methamphetamine Drugs 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 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
- 108091005601 modified peptides Proteins 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 108010043655 penetratin Proteins 0.000 description 1
- MCYTYTUNNNZWOK-LCLOTLQISA-N penetratin Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=CC=C1 MCYTYTUNNNZWOK-LCLOTLQISA-N 0.000 description 1
- 229940023041 peptide vaccine Drugs 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000011321 prophylaxis Methods 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
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000009566 rice Nutrition 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
- 238000012216 screening Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 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
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- HHSGWIABCIVPJT-UHFFFAOYSA-M sodium;1-[4-[(2-iodoacetyl)amino]benzoyl]oxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)C1=CC=C(NC(=O)CI)C=C1 HHSGWIABCIVPJT-UHFFFAOYSA-M 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 231100000057 systemic toxicity Toxicity 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
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 150000004043 trisaccharides Chemical class 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000007502 viral entry Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/385—Haptens or antigens, bound to carriers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/646—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/64—Medicinal preparations containing antigens or antibodies characterised by the architecture of the carrier-antigen complex, e.g. repetition of carrier-antigen units
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/735—Fusion polypeptide containing domain for protein-protein interaction containing a domain for self-assembly, e.g. a viral coat protein (includes phage display)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
本出願は、その全体が参照により本明細書に組み込まれる、2018年7月12日出願の米国特許仮出願第62/697,132号の利益を主張する。
2019年7月10日前後に作成された「A070-0003PCT_ST25.txt」と題された、約7kbのファイルサイズのコンピュータ可読テキストファイルは本出願のための配列表を含み、その全体が参照により本明細書に組み込まれる。
hは、疎水性又は無極性の残基であり;
wは、正に荷電しているか、負に荷電しているか、極性非荷電であるか、又は無極性脂肪族残基であり;
xは、負に荷電しているか、正に荷電しているか、無極性脂肪族であるか、極性非荷電の残基であるか、又はハプテン若しくは任意の他の分子へのエピトープカップリングのための任意の天然若しくは非天然の残基であり;
yは、ハプテン又は任意の他の分子へのエピトープカップリングのための任意の天然又は非天然の残基であり;
zは、負に荷電しているか、正に荷電しているか、極性非荷電、無極性脂肪族の残基であるか、又はハプテン若しくは任意の他の分子へのエピトープカップリングのための任意の天然若しくは非天然の残基である。
hは、I、L、V、F、W、Y、M、W、G又はAであり;
wは、G、R、A、N、Q、H、S、D、E、K又はTであり;
xは、R、S、N、Q、A、G、T、D、E、K、H又はCであり;
yは、K、H、C、D、E、R、W、Y、Q、N、又は共有結合に適合する反応基を含有する非天然アミノ酸若しくは分子であり;
Zは、A、D、H、S、E、R、N、Q、K又はGであり;
nは、1を超える整数である。
LRSIGKD(配列番号1);
LRSIGRD(配列番号2);
IREISRA(配列番号3);
IREVAQS(配列番号4);
IRDIAKA(配列番号5);
IRDIGRA(配列番号6);
IRDVGQS(配列番号7);
IRDLAKG(配列番号8);
VKDVARG(配列番号9);
IRDIGNS(配列番号10);
IKDLARG(配列番号11);又は
IKKLKKK(配列番号12)。
LRSIGKDLRSIGKDLRSIGKDLRSIGKD(配列番号13);
LRSIGKDLRSIGKDLRSIGKDLRSIGKDS(配列番号14);
LRSIGKDLRSIGRDLRSIGKDLRSIGRD(配列番号15);
IREISRAIREVAQSIRDIAKAIREIGKS(配列番号16);
IRDIGRAIRDVGQSIRDLAKGIRDISKG(配列番号17);又は
VKDVARGIRDIGNSIKDLARGIRDIGRG(配列番号18)。
HhCコア領域は長さが少なくとも28〜30残基であり、一般的なパターンhwxhxyz(配列番号19)を有する2〜10個の7残基反復を含有し、ここで、hは、疎水性又は無極性の残基であり(例えば、I、L、V、F、W、Y、G、A又はM); wは、正に荷電しているか、負に荷電しているか、極性非荷電であるか、又は無極性脂肪族残基であり(例えば、G、R、A、N、Q、H、S、D、K、T又はE); xは、負に荷電しているか、正に荷電しているか、無極性脂肪族又は極性非荷電残基であり(例えば、R、S、N、Q、A、G、T、D、E、K、H又はC); yは、エピトープカップリングが起こる残基であり(例えば、K、H、C、D、E、R、W、Y、Q又はN); zは、負に荷電しているか、正に荷電しているか、極性非荷電であるか、又は無極性脂肪族残基である(例えば、A、D、H、S、E、R、N、Q、K又はG)。w及びz位置の塩基性及び酸性の残基は、複合体の安定性を増加させるために塩橋又は水素結合相互作用が隣接したヘリックスの間で起こるように設計される。
ハプテンコンジュゲーションのために、各六量体担体の上に最高24のカップリング部位がある(図1)が、立体的障害のために、コンジュゲーションが全ての部位に起こる可能性は低い。担体をハプテンで飽和させることが最も頑強な免疫応答を必ずしも生成しないこと、並びに、カップリング密度、正しいB細胞エピトープ提示のためのエピトープの空間的/立体的利用可能性、及び抗体価の間にトレードオフがあることが以前に示されている。したがって、選択される各エピトープのために、異なるエピトープローディングレベルを有するコンジュゲートを得るために、3つの別々の六量体コンジュゲーション反応を実行する。例えば、3つ又は4つのペプチドだけがコンジュゲートされるように1つの反応は3〜5モル当量で実行され、別の反応は、6〜10ペプチドのコンジュゲートを形成するために8〜10モル当量を含有し、第3の反応はできるだけ多くのエピトープをカップリングするために(飽和条件)、25〜50モル当量を使用して実行される。
アジュバント:適応性B細胞及びT細胞応答を増強し、防御免疫の程度を調節し、抗原特異的抗体応答を最大にするために、全ての免疫化のためにアジュバントが使用される。最良のアジュバントは樹状細胞の成熟を直接的に刺激し、これをガイドする最も有効な方法はTLR媒介活性化を通したものである。合成TLR4をベースとしたアジュバントは最も有効なものの一部であるので、これらのうちの少なくとも2つを試験する。一リン酸化リピドA(MPL)は、我々の一次アジュバントとして機能する強力なTLR4アゴニストである(PERSINGら2002; EVANSら2003; SINGH及びSRIVASTAVA 2003; PFAARら2012; DEL GIUDICEら2018)。MPLは、スクアレン(Sq)で乳化されて(CIABATTINIら2018; SEYDOUXら2018) MPL-Sqを形成する。乳剤は、記憶及び長寿命抗体応答を誘導するのに重要であるCD4 T細胞を効率的に初回刺激する。我々は、アジュバントE6020及びGLAも試験するが、その両方はヒトでの使用が承認されている。全てのアジュバントはCD4+によって誘導された樹状細胞への抗原取り込みを支援し、エピトープ特異的Th1 CD4+ T細胞を誘導する。アジュバント機能を調査するために、CD4+ T細胞及びIgGアイソタイプのクラススイッチングを、免疫化されたマウス血清で定量化する。アジュバントの別の重要な有益性は、抗原用量節約の高い可能性であり、それも試験されるものである。用量節約は免疫化ごとの抗原の量を減少させ、合成ペプチドバッチから得られる用量の数を増加させ、合成ワクチンの製造コストを低減することで鍵となる決定因子である。
Claims (28)
- 以下のアミノ酸配列: hwxhxyz(配列番号19)を有する1つ又は複数の7残基を含むペプチドであって、
以下のアミノ酸配列パターンを含み:
(hwxhxyz)n(配列番号20)、
ここで、
hは、疎水性又は無極性の残基であり;
wは、正に荷電しているか、負に荷電しているか、極性非荷電であるか、又は無極性脂肪族残基であり;
xは、負に荷電しているか、正に荷電しているか、無極性脂肪族又は極性非荷電残基であり;
yは、エピトープカップリングのための残基であり;
zは、負に荷電しているか、正に荷電しているか、極性非荷電であるか、又は無極性脂肪族残基であり;
nは、1を超える整数である、ペプチド。 - hは、I、L、V、F、W、Y、M、W、G又はAであり;
wは、G、R、A、N、Q、H、S、D、E、K又はTであり;
xは、R、S、N、Q、A、G、T、D、E、K、H又はCであり;
yは、K、H、C、D、E、R、W、Y、Q、N、又は共有結合に適合する反応基を含有する非天然アミノ酸若しくは分子であり;
zは、A、D、H、S、E、R、N、Q、K又はGであり;
nは、2〜10である、請求項1に記載のペプチド。 - 7残基が配列番号1、配列番号2、配列番号3、配列番号4、配列番号5、配列番号6、配列番号7、配列番号8、配列番号9、配列番号10、配列番号11又は配列番号12である、請求項1又は2に記載のペプチド。
- 配列番号13、配列番号14、配列番号15、配列番号16、配列番号17又は配列番号18を含む、請求項1から3のいずれか一項に記載のペプチド。
- N末端に残基M及びDを更に含む、請求項4に記載のペプチド。
- 二量体、三量体、四量体、五量体、六量体、七量体、八量体、九量体又は十量体である、請求項1から5のいずれか一項に記載のペプチドを含むオリゴマー。
- 六量体である、請求項6に記載のオリゴマー。
- 請求項6又は7に記載のオリゴマー及び1つ又は複数のハプテン又は1つ又は複数の作用剤を含むペプチドコンジュゲート。
- ハプテンがy残基を通してオリゴマーにコンジュゲートしている、請求項8に記載のペプチドコンジュゲート。
- ハプテンがペプチド、脂質、リポペプチド、核酸又は炭水化物を含む、請求項8又は9に記載のペプチドコンジュゲート。
- ペプチドがT細胞エピトープ又はB細胞エピトープである、請求項10に記載のペプチドコンジュゲート。
- オリゴマーがオリゴマーのヘリックスの1つ又は複数のN末端又はC末端に1つ又は複数のT細胞エピトープを更に含む、請求項8から11のいずれか一項に記載のペプチドコンジュゲート。
- オリゴマーがオリゴマーヘリックスのN末端及びC末端の各々にT細胞エピトープを含む、請求項12に記載のペプチドコンジュゲート。
- ハプテンがB細胞エピトープである、請求項8から13のいずれか一項に記載のペプチドコンジュゲート。
- 作用剤がin vivoで送達される分子である、請求項8又は9に記載のペプチドコンジュゲート。
- 作用剤が核酸、ペプチド、治療剤又はT細胞エピトープである、請求項15に記載のペプチドコンジュゲート。
- 請求項1から5のいずれか一項に記載のペプチド又は請求項6若しくは7に記載のオリゴマー又は請求項8から16のいずれか一項に記載のペプチドコンジュゲート及び賦形剤を含む組成物。
- 組成物が医薬組成物であり、賦形剤が薬学的に許容される賦形剤である、請求項17に記載の組成物。
- 対象を疾患から保護する方法であって、それを必要とする対象に請求項8から14のいずれか一項に記載のペプチドコンジュゲート又は請求項18に記載の組成物の有効量を投与する工程を含み、ハプテンが免疫応答を誘導して対象を疾患から保護する、方法。
- 疾患を有する対象を処置する方法であって、それを必要とする対象に請求項8から14のいずれか一項に記載のペプチドコンジュゲート又は請求項18に記載の組成物の有効量を投与する工程を含み、ハプテンが免疫応答を誘導して対象を処置する、方法。
- 対象を疾患から保護する又は疾患を有する対象を処置する方法であって、それを必要とする対象に請求項15又は16に記載のペプチドコンジュゲート又は請求項18に記載の組成物の有効量を投与する工程を含む方法。
- 対象が哺乳動物である、請求項19から21のいずれか一項に記載の方法。
- ワクチンを調製する方法であって、請求項1から5のいずれか一項に記載のペプチドを得る工程、ペプチドをオリゴマーに自己集合させる工程、及びハプテンをオリゴマーにコンジュゲートさせる工程;又は、請求項6若しくは7に記載のオリゴマーを得る工程及びハプテンをオリゴマーにコンジュゲートさせる工程を含む方法。
- ハプテンの免疫原性を増強する方法であって、請求項1から5のいずれか一項に記載のペプチドを得る工程、ペプチドをオリゴマーに自己集合させる工程、及びハプテンをオリゴマーにコンジュゲートさせる工程;又は、請求項6若しくは7に記載のオリゴマーを得る工程及びハプテンをオリゴマーにコンジュゲートさせる工程を含む方法。
- 標的部位に作用剤を送達するための送達ビヒクルを調製する方法であって、請求項1から5のいずれか一項に記載のペプチドを得る工程、ペプチドをオリゴマーに自己集合させる工程、及び作用剤をオリゴマーにコンジュゲートさせる工程;又は、請求項6若しくは7に記載のオリゴマーを得る工程及び作用剤をオリゴマーにコンジュゲートさせる工程を含む方法。
- 送達ビヒクルが、特定の部位を送達ビヒクルの標的にさせる1つ又は複数の作用剤を更に含む、請求項25に記載の方法。
- 特定の部位が細胞内又は細胞外の部位である、請求項26に記載の方法。
- 1つ又は複数の作用剤が、オルガネラを送達ビヒクルの標的にさせるペプチドを含む、請求項25に記載の方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2024014081A JP2024036461A (ja) | 2018-07-12 | 2024-02-01 | 自己集合ペプチド骨格 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201862697132P | 2018-07-12 | 2018-07-12 | |
US62/697,132 | 2018-07-12 | ||
PCT/US2019/041601 WO2020014609A2 (en) | 2018-07-12 | 2019-07-12 | Self-assembling peptide scaffold |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2024014081A Division JP2024036461A (ja) | 2018-07-12 | 2024-02-01 | 自己集合ペプチド骨格 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2021531337A true JP2021531337A (ja) | 2021-11-18 |
JPWO2020014609A5 JPWO2020014609A5 (ja) | 2022-06-21 |
Family
ID=69142622
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021523579A Pending JP2021531337A (ja) | 2018-07-12 | 2019-07-12 | 自己集合ペプチド骨格 |
JP2024014081A Pending JP2024036461A (ja) | 2018-07-12 | 2024-02-01 | 自己集合ペプチド骨格 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2024014081A Pending JP2024036461A (ja) | 2018-07-12 | 2024-02-01 | 自己集合ペプチド骨格 |
Country Status (11)
Country | Link |
---|---|
US (1) | US20210268105A1 (ja) |
EP (2) | EP4218928A3 (ja) |
JP (2) | JP2021531337A (ja) |
KR (1) | KR20210065086A (ja) |
AU (2) | AU2019300038C1 (ja) |
BR (1) | BR112021000455A2 (ja) |
CA (1) | CA3105706A1 (ja) |
MA (1) | MA52591A (ja) |
MX (1) | MX2021000444A (ja) |
WO (1) | WO2020014609A2 (ja) |
ZA (1) | ZA202100952B (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20220339238A1 (en) * | 2019-09-12 | 2022-10-27 | Hexamer Therapeutics, Inc. | An immunotherapeutic for prostate cancer treatment |
CA3173307A1 (en) * | 2020-05-04 | 2021-11-11 | Hexamer Therapeutics, Inc. | Vaccines against viral pathogens |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015164798A1 (en) * | 2014-04-25 | 2015-10-29 | Tria Bioscience Corp. | Synthetic hapten carrier compositions and methods |
WO2018027252A1 (en) * | 2016-08-11 | 2018-02-15 | The Council Of The Queensland Institute Of Medical Research | Immune-modulating compounds |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5576610B2 (ja) * | 2006-02-20 | 2014-08-20 | フィロジカ リミテッド | ペプチド構造のライブラリーの構築およびスクリーニング方法 |
EP2188303B1 (en) * | 2007-09-07 | 2011-12-21 | Complix N.V. | Non-natural proteinaceous scaffold made of three non-covalently associated peptides |
EP2271760A2 (en) * | 2008-04-29 | 2011-01-12 | Monsanto Technology LLC | Genes and uses for plant enhancement |
WO2013040142A2 (en) * | 2011-09-16 | 2013-03-21 | Iogenetics, Llc | Bioinformatic processes for determination of peptide binding |
WO2013009971A1 (en) * | 2011-07-12 | 2013-01-17 | E. I. Du Pont De Nemours And Company | Detection and screening method and materials useful in performance thereof |
WO2014126828A1 (en) * | 2013-02-15 | 2014-08-21 | Merck Sharp & Dohme Corp. | Novel ph-switchable peptides for membrane insertion and pore formation |
EP3046870B1 (en) * | 2013-09-16 | 2021-08-11 | The University of Queensland | Silica micro- and nano-capsules and methods for making them |
-
2019
- 2019-07-12 US US17/258,297 patent/US20210268105A1/en active Pending
- 2019-07-12 AU AU2019300038A patent/AU2019300038C1/en active Active
- 2019-07-12 WO PCT/US2019/041601 patent/WO2020014609A2/en unknown
- 2019-07-12 CA CA3105706A patent/CA3105706A1/en active Pending
- 2019-07-12 MA MA052591A patent/MA52591A/fr unknown
- 2019-07-12 MX MX2021000444A patent/MX2021000444A/es unknown
- 2019-07-12 EP EP23159271.8A patent/EP4218928A3/en active Pending
- 2019-07-12 BR BR112021000455-6A patent/BR112021000455A2/pt unknown
- 2019-07-12 EP EP19834786.6A patent/EP3826661A4/en not_active Withdrawn
- 2019-07-12 JP JP2021523579A patent/JP2021531337A/ja active Pending
- 2019-07-12 KR KR1020217003917A patent/KR20210065086A/ko unknown
-
2021
- 2021-02-11 ZA ZA2021/00952A patent/ZA202100952B/en unknown
-
2023
- 2023-04-11 AU AU2023202175A patent/AU2023202175A1/en active Pending
-
2024
- 2024-02-01 JP JP2024014081A patent/JP2024036461A/ja active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015164798A1 (en) * | 2014-04-25 | 2015-10-29 | Tria Bioscience Corp. | Synthetic hapten carrier compositions and methods |
WO2018027252A1 (en) * | 2016-08-11 | 2018-02-15 | The Council Of The Queensland Institute Of Medical Research | Immune-modulating compounds |
Also Published As
Publication number | Publication date |
---|---|
JP2024036461A (ja) | 2024-03-15 |
CA3105706A1 (en) | 2020-01-16 |
EP4218928A2 (en) | 2023-08-02 |
ZA202100952B (en) | 2023-10-25 |
BR112021000455A2 (pt) | 2021-04-06 |
KR20210065086A (ko) | 2021-06-03 |
EP4218928A3 (en) | 2023-12-13 |
MA52591A (fr) | 2021-06-02 |
AU2019300038C1 (en) | 2024-01-04 |
AU2023202175A1 (en) | 2023-05-04 |
WO2020014609A4 (en) | 2020-04-16 |
WO2020014609A3 (en) | 2020-02-20 |
CN112512552A (zh) | 2021-03-16 |
EP3826661A4 (en) | 2022-08-31 |
MX2021000444A (es) | 2021-05-27 |
EP3826661A2 (en) | 2021-06-02 |
US20210268105A1 (en) | 2021-09-02 |
AU2019300038A1 (en) | 2021-02-04 |
WO2020014609A2 (en) | 2020-01-16 |
AU2019300038B2 (en) | 2023-01-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6088123B2 (ja) | ワクチンとして有用な自己会合ペプチドナノ粒子 | |
AU2015205567B2 (en) | Flagellin-containing protein nanoparticles as a vaccine platform | |
JP2024036461A (ja) | 自己集合ペプチド骨格 | |
JP2017538672A (ja) | Cmv由来改変ウイルス様粒子 | |
KR20210018205A (ko) | 항원성 OspA 폴리펩타이드 | |
AU2018383708B2 (en) | Peptide immunogens of IL-31 and formulations thereof for the treatment and/or prevention of atopic dermatitis | |
CN113329762A (zh) | 用于合成肽免疫原作为免疫刺激剂的人工混杂t辅助细胞表位 | |
KR20110030554A (ko) | 항아밀로이드 면역원성 조성물, 방법 및 용도 | |
WO2019086694A1 (en) | Il31 antigen and vaccine | |
US20220119457A1 (en) | Antigenic Multimeric Respiratory Syncytial Virus Polypeptides | |
CN113574073A (zh) | 针对降钙素基因相关肽(cgrp)的肽免疫原及其用于预防和治疗偏头痛的制剂 | |
KR20220062080A (ko) | 전립선암 치료를 위한 면역요법 | |
JP2022514411A (ja) | リポペプチドビルディングブロックおよび合成ウイルス様粒子 | |
JP2023525004A (ja) | ウイルス性病原体に対するワクチン | |
CN112512552B (zh) | 自组装肽支架 | |
EP2672982B1 (en) | Ghrelin mimetic polypeptide hapten immunoconjugates having improved solubility and immunogenicity and methods of use thereof | |
RU2816208C2 (ru) | АНТИГЕННЫЕ ПОЛИПЕПТИДЫ НА ОСНОВЕ ПОСЛЕДОВАТЕЛЬНОСТИ OspA | |
JP7505788B2 (ja) | C9orf72に由来するジペプチドリピートタンパク質に対して指向化されたペプチド免疫原コンストラクト | |
RU2807992C2 (ru) | Антигенные полипептиды на основе последовательности респираторно-синцитиального вируса | |
US20240141009A1 (en) | Peptide used for immunotherapeutics | |
TW202140526A (zh) | 針對垂體腺苷酸環化酶激活胜肽的胜肽免疫原及其預防和治療偏頭痛的製劑 | |
TW202144387A (zh) | 針對胰島澱粉樣多肽(iapp)的胜肽免疫原及其預防和治療與聚集iapp相關疾病的製劑 | |
WO2021250625A2 (en) | Gbs ferritin nanoparticles |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220613 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220613 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20230419 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230424 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230721 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230920 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20231010 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240201 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240205 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20240214 |
|
A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20240222 |