CN118019527A

CN118019527A - 用于制备脂质纳米颗粒组合物的方法

用于制备脂质纳米颗粒组合物的方法 Download PDF

Info

Publication number: CN118019527A
Authority: CN; China
Prior art keywords: composition; lipid nanoparticle; lipid; nanoparticle composition; buffer
Prior art date: 2021-07-26
Legal status : Pending

Application number

CN202280065049.8A

Other languages

English (en)

Chinese (zh)

Inventor

M·H·史密斯

N·苏德

C·田

D·W·多尔蒂

Current Assignee

ModernaTx Inc

Original Assignee

ModernaTx Inc

Priority date

2021-07-26

Filing date

2022-07-25

Publication date

2024-05-10

2022-07-25 Application filed by ModernaTx Inc filed Critical ModernaTx Inc

2024-05-10 Publication of CN118019527A publication Critical patent/CN118019527A/zh

Status Pending legal-status Critical Current

Links

150000002632 lipids Chemical class 0.000 title claims abstract description 618
239000000203 mixture Substances 0.000 title claims abstract description 497
239000002105 nanoparticle Substances 0.000 title claims abstract description 393
238000000034 method Methods 0.000 title claims abstract description 153
108020004999 messenger RNA Proteins 0.000 claims abstract description 122
150000007523 nucleic acids Chemical class 0.000 claims abstract description 65
102000039446 nucleic acids Human genes 0.000 claims abstract description 63
108020004707 nucleic acids Proteins 0.000 claims abstract description 63
239000003795 chemical substances by application Substances 0.000 claims abstract description 47
230000000069 prophylactic effect Effects 0.000 claims abstract description 25
230000001225 therapeutic effect Effects 0.000 claims abstract description 21
239000000872 buffer Substances 0.000 claims description 180
239000000243 solution Substances 0.000 claims description 163
125000000217 alkyl group Chemical group 0.000 claims description 128
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150000003839 salts Chemical class 0.000 claims description 88
150000003904 phospholipids Chemical class 0.000 claims description 69
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 62
239000002577 cryoprotective agent Substances 0.000 claims description 58
108090000765 processed proteins & peptides Proteins 0.000 claims description 56
239000008351 acetate buffer Substances 0.000 claims description 55
-1 lipid amine Chemical class 0.000 claims description 54
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 48
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201000010099 disease Diseases 0.000 claims description 34
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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 claims description 29
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LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 24
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FVXDQWZBHIXIEJ-LNDKUQBDSA-N 1,2-di-[(9Z,12Z)-octadecadienoyl]-sn-glycero-3-phosphocholine Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC FVXDQWZBHIXIEJ-LNDKUQBDSA-N 0.000 claims description 4
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UKDDQGWMHWQMBI-UHFFFAOYSA-O 1,2-diphytanoyl-sn-glycero-3-phosphocholine Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)CC(=O)OCC(COP(O)(=O)OCC[N+](C)(C)C)OC(=O)CC(C)CCCC(C)CCCC(C)CCCC(C)C UKDDQGWMHWQMBI-UHFFFAOYSA-O 0.000 claims description 3
XLPHMKQBBCKEFO-DHYROEPTSA-N 2-azaniumylethyl [(2r)-2,3-bis(3,7,11,15-tetramethylhexadecanoyloxy)propyl] phosphate Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)CC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CC(C)CCCC(C)CCCC(C)CCCC(C)C XLPHMKQBBCKEFO-DHYROEPTSA-N 0.000 claims description 3
JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims description 3
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JTERLNYVBOZRHI-PPBJBQABSA-N (2-aminoethoxy)[(2r)-2,3-bis[(5z,8z,11z,14z)-icosa-5,8,11,14-tetraenoyloxy]propoxy]phosphinic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC JTERLNYVBOZRHI-PPBJBQABSA-N 0.000 claims description 2
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LVNGJLRDBYCPGB-LDLOPFEMSA-N (R)-1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-LDLOPFEMSA-N 0.000 claims description 2
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NJFCSWSRXWCWHV-USYZEHPZSA-N [(2R)-2,3-bis(octadec-1-enoxy)propyl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCCC=COC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC=CCCCCCCCCCCCCCCCC NJFCSWSRXWCWHV-USYZEHPZSA-N 0.000 claims description 2
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