Lipid compounds and lipid nanoparticle compositions

Abstract

The present application discloses compounds of formula (I) and salts and stereoisomers thereof, wherein the variables are as defined in the description. Further disclosed in the present application are nanoparticle compositions comprising the compounds, salts thereof, or stereoisomers thereof, and a use of the nanoparticle compositions for delivering an active agent.

Description

Lipid compounds and lipid nanoparticle compositions TECHNICAL FIELD

[001] This application relates to the field of biotechnology and, in particular, to lipid compounds and lipid nanoparticle compositions. In particular, this application relates to methods of applying active agents, such as nucleic acids, and to lipid compounds and lipid nanoparticle compositions for the application thereof. BACKGROUND

[002] The efficient targeted application of biologically active substances, such as drugs, proteins, and small molecule nucleic acids, is an ongoing medical challenge. The key to the success of gene therapy is determining the possibility of safely and effectively delivering the therapeutic agent via a vector to the target cell in vivo. Due to the relative instability of nucleic acids and the low cellular permeability of such substances, the application of nucleic acids to cells is difficult. Consequently, there is a need to develop methods and compositions to facilitate the application of therapeutic and / or prophylactic agents, such as nucleic acids, to cells. Gene therapy vectors are classified into viral vectors and non-viral vectors.Although viral vectors are used as a highly efficient delivery system to achieve the purpose of transfection and treatment of the target gene, due to problems such as containing immunogenic viral proteins, limited loading of target genes, high cost, and similar issues, lipid nanoparticles (LNPs) as non-viral vectors are widely considered due to advantages such as good in vitro stability, in vivo degradability, safety, and reliability, and are widely applied to gene therapy research for congenital genetic defects. Petition 870250052396, dated 06 / 23 / 2025, page 9 / 203 2 / 150 acquired.

[003] Lipid-containing nanoparticles or lipid nanoparticles, liposomes, and lipid complexes have proven to be effective transport vectors for delivering biologically active substances, such as drugs, proteins, and small-molecule nucleic acids, into and / or within cells. LNPs refer to vesicles formed from one or more lipid components that are effective in compressing and delivering a variety of nucleic acid molecules, from DNA and RNA to chromosomes and even cells; LNPs are beneficial for large-scale production due to characteristics of a particular construction scheme, modifications to be easily targeted to a ligand, and similar features.

[004] LNPs typically include one or more cationic and / or aminolipids (ionizable), phospholipids, structural lipids (such as cholesterol) and / or polyethylene glycol-containing lipids (PEG lipids). Cationic and / or ionizable lipids, including, for example, amine-containing lipids, can be readily protonated.

[005] Lipid nanoparticle (LNP) formulations represent a revolution in the field of nucleic acid application. Onpattro™ is an early example of a lipid nanoparticle product approved for clinical use. Onpattro™ is a pharmaceutical formulation of short interfering RNA (siRNA) based on lipid nanoparticles for the treatment of polyneuropathy caused by hereditary transthyretin amyloidosis. The success of said LNP delivery system paves the way for the clinical development of the leading LNP-based mRNA vaccine against COVID-19.

[006] The LNP Onpattro™ formulation consists of four main lipid components, namely ionizable aminolipid MC3, distearoyl phosphatidylcholine (DSPC), cholesterol and polyethylene glycol conjugated lipid (PEG-lipid), in molar amounts of 50 / 10 / 38.5 / 1.5, Petition 870250052396, dated 06 / 23 / 2025, page 10 / 203 3 / 150 respectively. Onpattro™ is still considered the gold standard for comparison in LNP studies.

[007] Although research related to LNP-mediated nucleic acid delivery has advanced sufficiently, it is known that the Onpattro™ formulation accumulates primarily in liver tissue. The ability of LNPs to accumulate in organs and tissues other than the liver would greatly expand the clinical utility of these delivery systems. DESCRIPTION OF THE INVENTION

[008] Based on the arguments above, the present application describes a lipid compound and a composition of lipid nanoparticles comprising such compound, and the lipid nanoparticle has advantages of high encapsulation efficiency, low toxicity, high expression, suitability for vaccine or mRNA application, extra-hepatic application, etc.

[009] Specifically, the present application includes the following modalities (Part I): 1. A compound of formula (I), or a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, where: r1í Ri is, where R1 and R1b are independently selected from H or C1-C6 alkyl groups, and R2 and R3 are independently selected. Petition 870250052396, dated 06 / 23 / 2025, page 11 / 203 4 / 150 selected from H or C1-C6 alkyl, or R1 and R2, together with the carbon atom to which they are attached, form a 5- to 7-membered substituted or unsubstituted nitrogen-containing heterocyclic ring, and R3 is selected from H or C1-C6 alkyl, or R1 and R3, together with the carbon atoms to which they are attached, form ring A, which is a substituted or unsubstituted 5- to 7-membered carbocyclic or heterocyclic ring, and R2 is selected from H or C1-C6 alkyl; R4, R5 and R6 are independently selected from C1-C14 alkyl groups; X and Y are independently selected from either O or S; X1 and X2 are independently selected from C=O or O, and Y1 and Y2 are independently selected from C=O or O, with the condition that X1 and Y1 are not both C=O or O, and X2 and Y2 are not both C=O or O; men are independently selected from 0, 1, or 2, provided that men are not both 0; OEPs are independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; q is selected from 0, 1, 2, 3, 4, 5, or 6.

[0010] 2. The compound, according to item 1, or a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, in which the compound of formula (I) is of formula (IA), Petition 870250052396, dated 06 / 23 / 2025, page 12 / 203 5 / 150 where q is selected from 1, 2, 3, or 4.

[0011] 3. The compound, according to any of the preceding items, or a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, in which R4 is C9, C10, C11 or C12 linear alkyl; and Rs and Re are each independently selected from C6, C7, C8 or C9 linear alkyl.

[0012] 4. The compound, according to any of the preceding items, is either a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, in which 0 is 5 or 6.

[0013] 5. The compound, according to any of the preceding items, is either a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, in which p is 7 or 8.

[0014] 6. The compound, according to any of the preceding items, is either a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, in which X and Y are both O.

[0015] 7. The compound, according to any of the preceding items, or a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, in which n is 1, m is 0; or n is 1, m is 1; or n is 0, m is 1; For example, n is 1, m is 0; for example, n is 1, m is 1.

[0016] 8. The compound, according to any of the preceding items, is either a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, the compound of formula (I) being selected from the following structure: Petition 870250052396, dated 06 / 23 / 2025, page 13 / 203 6 / 150

[0017] 9. The compound, according to any of the preceding items, is either a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, the compound of formula (I) being selected from the following structure: (IIA-A) (IIA-B) (IIA-D) Petition 870250052396, dated 06 / 23 / 2025, p. 14 / 203 7 / 150

[0018] 10. The compound, according to any of the preceding items, is either a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, the compound of formula (I) being selected from the following structure: (IIA-F)

[0019] 11.0 compound, according to any of the preceding items, or a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, in which C1-C6 alkyl is inde Petition 870250052396, dated 06 / 23 / 2025, page 15 / 203 8 / 150 pendingly selected from -CH3, -CH2CH3 or -CH(CH3)2; For example, C1-C6 alkyl is independently selected from CH3.

[0020] 12. The compound, according to any of the preceding items, or a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, in which: R1ae and R1b are independently selected from -CH3; R2 and R3 are independently selected from H; R4 is a linear C10, C11, or C12 alkyl; R5 and Re are identical and are selected from C6, C7 and C8 linear alkyl; X and Y are independently selected from O; X1 and X2 are independently selected from C=O or O, Y1 and Y2 are independently selected from C=O or O, with the condition that X1 and Y1 are not both C=O or O, and X2 and Y2 are not both C=O or O; m is 0 and en is 1; Is it 5 or 6? p is 7 or 8, for example, p is 7; q is 2, 3 or 4, for example q is 2 or 3, for example q is 2; For example, p is 7 and eq is 2 or 3; For example, p is 7 and eq is 2.

[0021] 13. The compound, according to any of items 1 to 12, or a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, in which X1 and X2 are both C=O, and Y1 and Y2 are both O.

[0022] 14. The compound, according to any of items 1 to 12, or a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, in which X1 is O, Y1 is C=O, and X2 is C=O, Y2 is O. Petition 870250052396, dated 06 / 23 / 2025, p. 16 / 203 9 / 150

[0023] 15. The compound, according to any of items 1 to 12, or a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, in which Xi is C=O, Yi is O, and X2 is O, Y2 is C=O; or X1 and X2 are both O, and Y1 and Y2 are both C=O.

[0024] 16. The compound, according to any of the preceding items, is either a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, in which R4 is a linear C10-C11 alkyl.

[0025] 17. The compound, according to any of the preceding items, is either a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, in which R5 and Re are both linear C8 alkyl.

[0026] 18. The compound, according to any of the preceding items, is either a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, in which: If o is 5, R4 is C11 linear alkyl, p is 7, and R5 and R6 are both C8 linear alkyl, or if o is 6, R4 is C10 linear alkyl, p is 7, and R5 and R6 are both C8 linear alkyl.

[0027] 19. The compound, according to item 1, is either a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, the compound being selected from: Compound 1 THE Compound 3 Compound 2 Petition 870250052396, dated 06 / 23 / 2025, page 17 / 203 10 / 150 Compound 4 Compound 5 THE Compound 6 Compound 7 Compound 11 Compound 14 Petition 870250052396, dated 06 / 23 / 2025, page 18 / 203 11 / 150 O Compound 15 Compound 16 Compound 19 Compound 20 Compound 21 Compound 22 Compound 17 Compound 23 Petition 870250052396, dated 06 / 23 / 2025, page 19 / 203 12 / 150 Compound 26 Compound 27 o N Compound 28 / Compound 29N' Compound 30 Compound 31 or Compound 32

[0028] 20. The compound, according to item 1, is either a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, the compound being selected from: Compound 2C 2D Composite Petition 870250052396, dated 06 / 23 / 2025, page 20 / 203 13 / 150 Compound 5C the Compound 5E Compound 13A Compound 13B Petition 870250052396, dated 06 / 23 / 2025, page 21 / 203 14 / 150 \ ,N Compound 13C \ ,N 13D Composite Compound 13E \ ,N Compound 13F

[0029] 21. A method for preparing a compound, according to Petition 870250052396, dated 06 / 23 / 2025, page 22 / 203 15 / 150 any of items 1 to 20, wherein Compound (IA) is obtained from Compound J as a starting material, (IA) wherein Zi is selected from OH, Z2 and Z3 are independently selected from OH or SH, respectively, and Z4 is selected from OMs (Ms is methylsulfonyl); and X, Y, X1, X2, Y1, Y2, R1a, R1b, R2, R3, R4, Rs, R6, m, n, o, peq are as defined in any of items 1 to 20; Whereas compound J is reacted with compound K in a benzene-based solution of pyridinium 4-methylbenzenesulfonate to give compound L, a benzene-based solvent used in said benzene solution is preferably toluene; said compound L is reacted in a haloalkane solution of (CH3SO2)2O to give a compound M, and said haloalkane is preferably DCM, dichloroethane or chloroform; said compound M is reacted in a polar aprotic solvent to form a compound IA, and said polar aprotic solvent is preferably THF.

[0030] 22. The preparation method, according to item 21, wherein Compound J is obtained from Compound H and Compound C as starting materials, Petition 870250052396, dated 06 / 23 / 2025, p. 23 / 203 16 / 150 η c , j where X is selected from among halogens; and Xi, X2, R4, R5, R6, and oep are as defined in any of items 1 through 20; wherein said compound H is reacted with Compound C in the presence of a carbonate salt, NBu4l, and a polar aprotic solvent to give Compound I, said carbonate salt is preferably Cs2CO3 or K2CO3; said polar aprotic solvent is preferably DMF or DMA; Compound I is reacted at pH 1 to 5 to give Compound J, preferably the pH is adjusted by a hydrochloric acid solution and the reaction is haloalkane and preferably DCM, dichloroethane or chloroform.

[0031] 23. The preparation method, according to item 22, whereby Compound F is reacted with Compound G to give Compound H, fgh where X is selected from among halogens; X1, Y1, R4 and o are as defined in any of items 1 to 20; Whereas said Compound F is reacted with Compound G in the presence of a carbonate salt, NBu4I, and a polar aprotic solvent to give Compound H, said carbonate salt is preferably Cs2CO3 or K2CO3; and said polar aprotic solvent is preferably DMF or DMA. Petition 870250052396, dated 06 / 23 / 2025, page 24 / 203 17 / 150

[0032] 24. A nanoparticle composition comprising a lipid component comprising a compound or a salt (especially a pharmaceutically acceptable salt) or a stereoisomer thereof, according to any one of items 1 to 20; preferably, said nanoparticle composition is of lipid nanoparticles (LNP).

[0033] 25. The composition of nanoparticles, according to item 24, wherein said lipid component further comprises a phospholipid, a structural lipid and / or a PEG lipid; whereby said phospholipid is preferably selected from one or more of the following compounds: dilauroyl lecithin (DLPC), dimyristoyl phosphatidylcholine (DMPC), dioleoyl lecithin (DOPC), dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), dioleoyl phosphatidylcholine (DUPC), palmitoyl oleoyl phosphatidylcholine (POPC), 1,2-di-O-octadecyl-sn-glycero-3-phosphocholine (18:0 diether PC), 1-oleoyl-2-cholesteryldimethylsuccinoyl-sn-glycero-3-phosphocholine (OChemsPC), l-hexadecyl-sn-glycero-3-phosphocholine (C16 Lyso PC), 1,2-divinyl-sn-glycero-3-phosphocholine, 1,2-diarylacyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphorylethanolamine (DOPE), 1,2-di-phytanoyl-sn-glycero-3-phosphoethanolamine (ME 16.0 PE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-diethenol-sn-glycero-3-phosphoethanolamine, 1,2-divinyl-sn-glycero-3-phosphoethanolamine, 1,2-diaryl-sn-glycero-3-phosphoethanolamine, Petition 870250052396, dated 06 / 23 / 2025, page 25 / 203 18 / 150 1,2-dithiohexaenoate-sn-glycero-3-phosphoethanolamine, sodium salt of 1,2-dioleoyl-sn-glycero-3-phosphate-(1-glycerol) (DOPG) or sphingomyelin, for example, said phospholipid is DOPE or DSPC; The structural lipid is preferably selected from one, two or more of cholesterol, coprosterol, sitosterol, ergosterol and stigmasterol; for example, the structural lipid is cholesterol; and / or the PEG lipid is preferably selected from one, two or more of PEG-modified phosphatidylethanolamine, PEG-modified phosphatidic acid, PEG-modified ceramide, PEG-modified dialkylamine, PEG-modified diacylglycerol or PEG-modified dialkylglycerol.

[0034] 26. The nanoparticle composition, according to any of items 24 to 25, wherein said lipid component additionally comprises cationic and / or ionizable lipid.

[0035] 27. The nanoparticle composition, according to any of items 24 to 26, further comprises a therapeutic agent and / or a prophylactic agent, said therapeutic and / or prophylactic agent being selected from vaccines or compounds capable of provoking an immune response and / or nucleic acids, the nucleic acid being preferably RNA, and said RNA being selected from one, two or more of siRNA, aiRNA, miRNA, dsRNA, shRNA or mRNA, for example, said therapeutic and / or prophylactic agent being mRNA.

[0036] 28. The nanoparticle composition, in accordance with any of items 24 to 27, wherein the encapsulation efficiency of said therapeutic and / or prophylactic agent is > 50%; or > 80%; or > 90%; and / or said nanoparticle composition has an average particle size of 50 nm to 110 nm; and / or Petition 870250052396, dated 06 / 23 / 2025, page 26 / 203 19 / 150 the said nanoparticle composition has a polydispersity index of 0.04 to 0.20.

[0037] 29. Use of the compound, according to any one of items 1 to 20, or a salt thereof (especially a pharmaceutically acceptable salt) or stereoisomer thereof in the preparation of a lipid nanoparticle composition.

[0038] 30. A pharmaceutical composition comprising the nanoparticle composition, according to any one of items 24 to 28, as well as a pharmaceutically acceptable excipient.

[0039] 31. A method of applying a therapeutic and / or prophylactic agent to a mammalian cell comprising administering the nanoparticle composition, according to any of items 24 to 28, or the pharmaceutical composition, according to item 30, to an individual, said administration comprising placing the cell in contact with said nanoparticle composition or said pharmaceutical composition to apply the therapeutic and / or prophylactic agent to the cell; for example, the mammalian cell is in a mammal; for example, said mammal is a human being; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation.

[0040] 32. A method of producing the polypeptide of interest in a mammalian cell comprising bringing the cell into contact with the nanoparticle composition, according to any one of items 24 to 28, or the pharmaceutical composition, according to item 30, to apply a therapeutic and / or prophylactic agent to the cell, wherein said therapeutic and / or prophylactic agent is an mRNA encoding the polypeptide of interest, such that the mRNA is capable of being translated in the cell to produce the polypeptide of interest; for example, the mammalian cell is in a mammal; for example Petition 870250052396, dated 06 / 23 / 2025, page 27 / 203 20 / 150 plo, the said mammal is a human being; for example, the said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation.

[0041] 33. A method of treating or preventing a disease or condition in a mammal, such as a human, comprising administering a therapeutically or prophylactically effective amount of a nanoparticle composition, according to any of items 24 to 28, or a pharmaceutical composition, according to item 30, to the mammal; for example, said disease or condition is characterized by dysfunctional or abnormal protein or polypeptide activity; for example, said disease or condition is selected from among infectious diseases, cancer and proliferative diseases, genetic diseases, autoimmune diseases, diabetes, neurodegenerative diseases, cardiovascular diseases, renal vascular diseases or metabolic diseases; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation.

[0042] 34. A method for specifically applying a therapeutic and / or prophylactic agent to a mammalian organ comprising administering to the mammal the nanoparticle composition, according to any of items 24 to 28, or the pharmaceutical composition, according to item 30, said administration comprising placing the mammalian organ in contact with said nanoparticle composition or pharmaceutical composition, thereby applying the therapeutic and / or prophylactic agent to the organ; for example, said mammal is a human being; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation; for example, said mammal is pre-treated 24 hours before the contact or inhalation step. Petition 870250052396, dated 06 / 23 / 2025, page 28 / 203 21 / 150 administration, or fewer hours; for example, about an hour before the contact or administration stage.

[0043] 35. A method of administering a therapeutic and / or prophylactic agent to a patient comprising administering to a patient in need thereof the nanoparticle composition, in accordance with any of items 24 to 28, or the pharmaceutical composition, in accordance with item 30.

[0044] 36. A method of introducing a nucleic acid into a cell comprising bringing said cell into contact with a composition of nanoparticles, according to any one of items 24 to 28, or a pharmaceutical composition, according to item 30.

[0045] 37. The nanoparticle composition, according to any of items 24 to 28, or the pharmaceutical composition, according to item 30, for use as a medicament.

[0046] 38. A nanoparticle composition, according to any of items 24 to 28, or a pharmaceutical composition, according to item 30, for use in the application of a therapeutic and / or prophylactic agent to a mammalian cell; for example, the mammalian cell is in a mammal; for example, said mammal is a human being; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation.

[0047] 39. A nanoparticle composition, according to any one of items 24 to 28, or a pharmaceutical composition, according to item 30, which is used to produce a polypeptide of interest in a mammalian cell, said composition comprising a therapeutic and / or prophylactic agent, which is an mRNA encoding the polypeptide of interest, such that the mRNA is capable of being translated in the cell to produce the polypeptide of interest; for example, the mammalian cell is in a mammal; for example, the Petition 870250052396, dated 06 / 23 / 2025, page 29 / 203 22 / 150 said mammal is a human being; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally, or by inhalation.

[0048] 40. A nanoparticle composition, according to any of items 24 to 28, or a pharmaceutical composition, according to item 30, for use in the treatment or prevention of a disease or condition in a mammal, such as a human being.

[0049] 41. A nanoparticle composition, according to any of items 24 to 28, or a pharmaceutical composition, according to item 30, for use in the treatment or prevention of a disease or condition in a mammal, such as a human being, said disease or condition being characterized by dysfunctional or abnormal protein or polypeptide activity; for example, said disease or condition being selected from infectious diseases, cancer and proliferative diseases, genetic diseases, autoimmune diseases, diabetes, neurodegenerative diseases, cardiovascular diseases, renal vascular diseases or metabolic diseases; for example, said nanoparticle composition or pharmaceutical composition being administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation.

[0050] 42. A nanoparticle composition, according to any of items 24 to 28, or a pharmaceutical composition, according to item 30, for use in the specific application of a therapeutic and / or prophylactic agent to a mammalian organ; for example, said mammal is a human being; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation.

[0051] 43. The composition of nanoparticles, according to which Petition 870250052396, dated 06 / 23 / 2025, page 30 / 203 23 / 150 requires one of items 24 to 28, or the pharmaceutical composition, according to item 30, for use in the specific application of a therapeutic and / or prophylactic agent to a mammalian organ; for example, said mammal is a human being; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation, wherein said mammal is pre-treated 24 hours before the contact or administration step or fewer hours; for example, about one hour before the contact or administration step.

[0052] 44. The nanoparticle composition, according to any of items 24 to 28, or the pharmaceutical composition, according to item 30, for applying a therapeutic and / or prophylactic agent to a patient.

[0053] 45. The nanoparticle composition, according to any of items 24 to 28, or the pharmaceutical composition, according to item 30, for introducing a nucleic acid into a cell.

[0054] 46. Use of the nanoparticle composition, according to any of items 24 to 28, or of the pharmaceutical composition, according to item 30, in the manufacture of a medicament to apply a therapeutic and / or prophylactic agent to a mammalian cell; for example, the mammalian cell is in a mammal; for example, said mammal is a human being; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation.

[0055] 47. Use of the nanoparticle composition, according to any of items 24 to 28, or of the pharmaceutical composition, according to item 30, in the manufacture of a medicament to produce a polypeptide of interest in a mammalian cell, said medicament comprising a therapeutic and / or prophylactic agent. Petition 870250052396, dated 06 / 23 / 2025, page 31 / 203 24 / 150 lactic, which is mRNA that encodes the polypeptide of interest, so that the mRNA is capable of being translated in the cell to produce the polypeptide of interest; for example, the mammalian cell is in a mammal; for example, said mammal is a human being; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally, or by inhalation.

[0056] 48. Use of the nanoparticle composition, according to any of items 24 to 28, or of the pharmaceutical composition, according to item 30, in the manufacture of a medicament for the treatment or prevention of a disease or condition in a mammal, for example, a human being.

[0057] 49. Use of the nanoparticle composition, according to any of items 24 to 28, or of the pharmaceutical composition, according to item 30, in the manufacture of a medicament for the treatment or prevention of a disease or condition in a mammal, for example, a human being, and said disease or condition is characterized by dysfunctional or abnormal protein or polypeptide activity; for example, said disease or condition is selected from among infectious diseases, cancer and proliferative diseases, genetic diseases, autoimmune diseases, diabetes, neurodegenerative diseases, cardiovascular diseases, renal vascular diseases or metabolic diseases; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation.

[0058] 50. Use of the nanoparticle composition, according to any of items 24 to 28, or of the pharmaceutical composition, according to item 30, in the manufacture of a medicament for the specific application of a therapeutic and / or prophylactic agent to a mammalian organ; for example, said mammal is a human being; by Petition 870250052396, dated 06 / 23 / 2025, page 32 / 203 25 / 150 For example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally, or by inhalation.

[0059] 51. Use of the nanoparticle composition, according to any of items 24 to 28, or of the pharmaceutical composition, according to item 30, in the manufacture of a medicament for the specific application of a therapeutic and / or prophylactic agent to a mammalian organ; for example, said mammal is a human being; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation, said mammal being pre-treated 24 hours before the contact or administration step or fewer hours; for example, about one hour before the contact or administration step.

[0060] 52. Use of the nanoparticle composition, according to any of items 24 to 28, or of the pharmaceutical composition, according to item 30, in the manufacture of a medicament to apply a therapeutic and / or prophylactic agent to a patient.

[0061] 53. Use of the nanoparticle composition, according to any of items 24 to 28, or of the pharmaceutical composition, according to item 30, in the preparation of a product for the introduction of nucleic acids into a cell.

[0062] 54. Use of the nanoparticle composition, according to any of items 24 to 28, or of the pharmaceutical composition, according to item 30, for use in the treatment or prevention of a disease or condition in a mammal, such as a human being; for example, said disease or condition is characterized by dysfunctional or abnormal protein or polypeptide activity; for example, said disease or condition is selected from among infectious diseases, cancer and proliferative diseases, genetic diseases, autistic diseases Petition 870250052396, dated 06 / 23 / 2025, page 33 / 203 26 / 150 immune, diabetes, neurodegenerative diseases, cardiovascular diseases, renal vascular diseases or metabolic diseases; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation.

[0063] This application also includes the following options (Part II): 1. A compound of formula (I), or a salt or an isomer of R1a, R1b are independently selected from H, C1-C6 alkyl, R2, R3 are independently selected from H or C1-C6 alkyl, or R1 and R2, together with the carbon atom to which they are attached, form a 5- to 7-membered substituted or unsubstituted nitrogen-containing heterocyclic ring, and R3 is selected from H or C1-C6 alkyl, or R1 and R3, together with the carbon atoms to which they are attached, form ring A, which is a 5- to 7-membered substituted or unsubstituted carbocyclic or heterocyclic ring, and R2 is selected from H or C1-C6 alkyl; R4, Rs, and Re are independently selected from C1-C14 alkyl groups; Petition 870250052396, dated 06 / 23 / 2025, page 34 / 203 27 / 150 X and Y are independently selected from either O or S; Xi and X2 are independently selected from C=O or O, and Y1 and Y2 are independently selected from C=O or O, with the condition that Xi and Yi are not both C=O or O, and X2 and Y2 are not both C=O or O; men are independently selected from 0, 1, or 2, provided that men are not both 0; OEPs are independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; q is selected from 0, 1, 2, 3, 4, 5, or 6.

[0064] 2. The compound, according to item 1, where the compound of formula (I) is of formula (IA), (IA) where q is selected from 0, 1, 2, 3 or 4.

[0065] 3. The compound, according to item 1, where the com- where R7 is selected from H or C1-C6 alkyl groups; r is selected from 0, 1, 2, or 3.

[0066] 4. The compound, according to item 1, where the com Petition 870250052396, dated 06 / 23 / 2025, page 35 / 203 28 / 150 position of formula (I) is of formula (IC) or (ID), (ID) wherein, ring A is replaced by one or more R8, wherein the said R8a, Rv ''fbrí . . R8 is ' * , wherein R8ae R8bsao are independently selected from H or C1-C6 alkyl, es is selected from 0, 1, 2, 3, 4, 5 or 6.

[0067] 5. The compound, according to item 4, wherein said ring A is selected from \ / , , \---' or '----. .

[0068] 6. The compound, according to any of items 1 to 5, wherein R4 is C10-C11 alkyl.

[0069] 7. The compound, according to item 6, where R4 is C10-C11 linear alkyl. Petition 870250052396, dated 06 / 23 / 2025, page 36 / 203 29 / 150

[0070] 8. The compound, according to any of items 1 to 7, wherein R5 and R6 are C8 alkyl.

[0071] 9. The compound, according to item 8, where R5 and R6 are linear C8 alkyl.

[0072] 10. The compound, according to any of items 1 to 9, where the said "o" is 5 or 6.

[0073] 11. The compound, according to any of items 1 to 10, where p is either 7 or 8.

[0074] 12. The compound, according to any of items 1 to 11, where o is 5, R4 is C11 linear alkyl, p is 7, and R5 and R6 are C8 linear alkyl, or o is 6, R4 is C10 linear alkyl, p is 7, and R5 and R6 are C8 linear alkyl.

[0075] 13. The compound, according to any of items 1a 12, wherein said X1, X2 are C=O, and said Y1 and Y2 are O.

[0076] 14. The compound, according to any of items 1a 12, wherein said X1 is O, Y1 is C=O, and said X2 is C=O, Y2 is O.

[0077] 15. The compound, according to any of items 1 to 12, wherein said X1 is C=O, Y1 is O, and said X2 is O, Y2 is C=O.

[0078] 16. The compound, according to any of items 1 to 12, wherein said X1 and X2 are O, and said Y1 and Y2 are C=O.

[0079] 17. The compound, according to any of items 1 to 16, where X and Y are both O.

[0080] 18. The compound, according to any of items 1a 16, wherein said n is 0, m is 1, or n is 1, m is 0, or n is 1, m is 1.

[0081] 19. The compound, according to any of items 1a 18, wherein said C1-C6 alkyl is selected from -CH3,CH2CH3 or -CH(CH3)2.

[0082] 20. Compound, according to item 1, wherein the compound of formula (I) is selected from: Petition 870250052396, dated 06 / 23 / 2025, page 37 / 203 30 / 150 Compound 1 Compound 4 THE Compound 5 Compound 6 Compound 9 Compound 12 Petition 870250052396, dated 06 / 23 / 2025, page 38 / 203 31 / 150 Compound 13 Compound 17 Compound 19 Compound 20 Compound 21 Compound 22 Petition 870250052396, dated 06 / 23 / 2025, page 39 / 203 32 / 150 Compound 24 Compound 25 Compound 26 Compound 27 Compound 28 Compound 29 Compound 30 Compound 31 Compound 23 or Petition 870250052396, dated 06 / 23 / 2025, page 40 / 203 33 / 150 Compound 32

[0083] 21. A method for preparing the compound, according to any one of items 1 to 20, wherein Compound (IA) is obtained from Compound J as a starting material, M (IA) where Z1 is selected from OH, Z2 and Z3 are independently selected from OH or SH, respectively, and Z4 is selected from OMs; X and Y are independently selected from either O or S; X1 and X2 are independently selected from C=O or O, Y1 and Y2 are independently selected from C=O or O, with the condition that X1 and Y1 are not both C=O or O, and X2 and Y2 are not both C=O or O; R1ae R1bsão independently selected from H or C1-C6 alkyl; R2 and R3 are independently selected from either H or C1-C6 alkyl groups; R4, R5 and R6 are independently selected from C1-C14 alkyl groups; Men are independently selected from 0, 1, 2, with the con Petition 870250052396, dated 06 / 23 / 2025, page 41 / 203 34 / 150 condition that men are not both 0; OEPs are independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; q is selected from 0, 1, 2, 3, 4, 5, or 6; Compound J is reacted with Compound K in a Tso-Py benzene-based solution to give Compound L, the benzene-based solvent used is preferably toluene; Compound L is reacted in a haloalkane solution of (CH3SO2)2O to give Compound M, and said haloalkane is preferably DCM, dichloroethane or chloroform; Compound M is reacted in a polar aprotic solvent to produce Compound IA, said polar aprotic solvent preferably being THF.

[0084] 22. The preparation method, according to item 21, wherein Compound J is obtained from Compound H and Compound C as starting materials, hc , j wherein X1 and X2 are independently selected from C=O or O, Y1 and Y2 are independently selected from C=O or O, on the condition that X1 and Y1 are not both C=O or O, and X2 and Y2 are not both C=O or O; X is selected from among halogens; R4, R5 and R6 are independently selected from C1-C14 alkyl groups; OEPs are independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; Compound H is reacted with Compound C in the presence of a carbonate salt, NBu4I, and a polar aprotic solvent. Petition 870250052396, dated 06 / 23 / 2025, page 42 / 203 35 / 150 to provide Compound I, said carbonate salt is preferably CS2CO3 and K2CO3; and said polar aprotic solvent is preferably DMF or DMA; Compound I is reacted at pH 1 to 5 to give Compound J, preferably the pH is adjusted by a hydrochloric acid solution and the reaction solvent is a haloalkane, preferably DCM, dichloroethane or chloroform.

[0085] 23. The preparation method, according to item 22, whereby Compound F is reacted with Compound G to give Compound H, fgh where X1 and Y1 are independently selected from C=O or O; X is selected from among halogens; R4 is selected from C1-C14 alkyl groups; The number is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10; Compound F is reacted with Compound G in the presence of a carbonate salt, NBU4I, and a polar aprotic solvent to give Compound H; said carbonate salt is preferably Cs2CO3 or K2CO3; and said polar aprotic solvent is preferably DMF or DMA.

[0086] 24. A nanoparticle composition comprising a lipid component comprising a compound, according to any one of items 1 to 20.

[0087] 25. The composition of nanoparticles, according to item 24, wherein said lipid component additionally comprises a phospholipid.

[0088] 26. The composition of nanoparticles, according to item Petition 870250052396, dated 06 / 23 / 2025, page 43 / 203 36 / 150 25, wherein said phospholipid is selected from one, two or more of the following compounds: dilauroyl lecithin (DLPC), dimyristoyl phosphatidylcholine (DMPC), dioleoyl lecithin (DOPC), dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), dioleoyl phosphatidylcholine (DUPC), palmitoyl oleoyl phosphatidylcholine (POPC), 1,2-di-O-octadecyl-sn-glycero-3-phosphocholine (18:0 diether PC), 1-oleoyl-2-cholesteryldimethylsuccinoyl-sn-glycero-3-phosphocholine (OChemsPC), l-hexadecyl-sn-glycero-3-phosphocholine (C16 Lyso PC), 1,2-divinyl-sn-glycero-3-phosphocholine, 1,2-diarylacyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphorylethanolamine (DOPE), 1,2-di-phytanoyl-sn-glycero-3-phosphoethanolamine (ME 16.0 PE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-diethenol-sn-glycero-3-phosphoethanolamine, 1,2-divinyl-sn-glycero-3-phosphoethanolamine, 1,2-diaryl-sn-glycero-3-phosphoethanolamine, 1,2-dithio-hexa-enoate-sn-glycero-3-phosphoethanolamine, sodium salt of 1,2-dioleoyl-sn-glycero-3-phosphate-(1-glycerol) (DOPG) or sphingomyelin.

[0089] 27. The composition of nanoparticles, according to item 25, where said phospholipid is DOPE.

[0090] 28. The composition of nanoparticles, according to item 25, where said phospholipid is DSPC.

[0091] 29. The nanoparticle composition, according to any of items 24 to 28, wherein the said lipid component with Petition 870250052396, dated 06 / 23 / 2025, page 44 / 203 37 / 150 additionally contains a structural lipid.

[0092] 30. The composition of nanoparticles, according to item 29, wherein said structural lipid is selected from one, two or more of cholesterol, coprosterol, sitosterol, ergosterol, stigmasterol.

[0093] 31. The composition of nanoparticles, according to item 29, where the structural lipid in question is cholesterol.

[0094] 32. The nanoparticle composition, according to any one of items 24 to 31, wherein said lipid component additionally comprises a PEG lipid.

[0095] 33. The composition of nanoparticles, according to item 32, wherein said PEG lipid is selected from one, two or more of the following: PEG-modified phosphatidylethanolamine, PEG-modified phosphatidic acid, PEG-modified ceramide, PEG-modified dialkylamine, PEG-modified diacylglycerol or PEG-modified dialkylglycerol.

[0096] 34. The nanoparticle composition, according to any of items 24 to 33, wherein said lipid component additionally comprises cationic and / or ionizable lipid.

[0097] 35. The nanoparticle composition, according to any one of items 24 to 34, which further comprises a therapeutic and / or prophylactic agent which is selected from vaccines or compounds capable of provoking an immune response, nucleic acids, preferably said nucleic acid is RNA and said RNA is selected from one, two or more of siRNA, aiRNA, miRNA, dsRNA, shRNA or mRNA.

[0098] 36. The composition of nanoparticles, according to any of items 24 to 35, wherein the encapsulation efficiency of said therapeutic and / or prophylactic agent is > 50%; or > 80%; or > Petition 870250052396, dated 06 / 23 / 2025, page 45 / 203 38 / 150 90%.

[0099] 37. The nanoparticle composition, according to any of items 24 to 36, wherein said nanoparticle composition has an average particle size of 50 nm to 110 nm.

[00100] 38. The nanoparticle composition, according to any of items 24 to 36, wherein said nanoparticle composition has a polydispersity index of 0.04 to 0.20.

[00101] 39. Use of the compound, according to any of items 1 to 20, in the preparation of a lipid nanoparticle composition.

[00102] 40. A pharmaceutical composition comprising the nanoparticle composition, according to any one of items 24 to 38, and a pharmaceutically acceptable carrier.

[00103] 41. A method of applying a therapeutic and / or prophylactic agent to a mammalian cell comprising administering the nanoparticle composition, according to any of items 24 to 38, or the pharmaceutical composition, according to item 40, to an individual, said administration comprising placing the cell in contact with said nanoparticle composition or said pharmaceutical composition in order to apply the therapeutic and / or prophylactic agent to the cell.

[00104] 42. The method, according to item 41, where the mammalian cell is in a mammal.

[00105] 43. The method, according to item 41 or 42, where the mammal is a human being.

[00106] 44. The method, according to any of items 41 to 43, whereby said nanoparticle composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally, or by inhalation.

[00107] 45. A method for producing the polypeptide of interest Petition 870250052396, dated 06 / 23 / 2025, page 46 / 203 39 / 150 in a mammalian cell comprising placing the cell in contact with the nanoparticle composition, according to any of items 24 to 38, or the pharmaceutical composition, according to item 40, to apply a therapeutic and / or prophylactic agent to the cell, wherein said therapeutic and / or prophylactic agent is mRNA encoding the polypeptide of interest, such that the mRNA is capable of being translated in the cell to produce the polypeptide of interest.

[00108] 46. The method, according to item 45, where the mammalian cell is in a mammal.

[00109] 47. The method, according to any of items 45 or 46, where the mammal is a human being.

[00110] 48. The method, according to any of items 45 to 47, whereby the nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally, or by inhalation.

[00111] 49. A method of treating a disease or condition in a mammal comprising administering a therapeutically effective amount of the nanoparticle composition, according to any one of items 24 to 38, or of the pharmaceutical composition, according to item 40, to the mammal.

[00112] 50. The method, according to item 49, wherein the said disease or condition is characterized by dysfunction or abnormality of protein or polypeptide activity.

[00113] 51. The method, according to item 49 or 50, wherein the said disease or condition is selected from among infectious diseases, cancer and proliferative diseases, genetic diseases, autoimmune diseases, diabetes, neurodegenerative diseases, cardiovascular diseases, renal vascular diseases or metabolic diseases.

[00114] 52. The method, according to any of items 49 to 51, where the mammal is a human being. Petition 870250052396, dated 06 / 23 / 2025, page 47 / 203 40 / 150

[00115] 53. The method, according to any of items 49 to 52, whereby the nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally, or by inhalation.

[00116] 54. A method for specifically applying a therapeutic and / or prophylactic agent to a mammalian organ comprising administering the nanoparticle composition, according to any of items 24 to 38, or the pharmaceutical composition, according to item 40, to the mammal, said administration comprising placing the mammalian organ in contact with said nanoparticle composition or pharmaceutical composition, thereby applying the therapeutic and / or prophylactic agent to the organ.

[00117] 55. The method, according to item 54, where the mammal is a human being.

[00118] 56. The method, according to item 54 or 55, whereby the nanoparticle composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation.

[00119] 57. The method, according to any of items 54 to 56, wherein the said mammal is pre-treated 24 hours prior to the contact or administration stage, or fewer hours.

[00120] 58. The method, according to any of items 54 to 57, whereby the said mammal is pre-treated approximately one hour before the contact or administration stage. Effects of the invention

[00121] The compound of the present application can be used for the preparation of lipid nanoparticles, and the nanoparticle composition containing the compound of the present application can achieve encapsulation and application of the therapeutic / prophylactic agent, apply the therapeutic / prophylactic agent to a target site safely, achieve high expression and exert the effects of the therapeutic agent. Petition 870250052396, dated 06 / 23 / 2025, page 48 / 203 41 / 150 co / prophylactic.

[00122] The lipid nanoparticles prepared in the present application have the advantages of small average particle size, high encapsulation efficiency and low toxicity, which has broad application prospects in the field of pharmaceutical application.

[00123] This application reports a synthetic method for a cationic lipid with asymmetric tail chains and containing an acetal structure for the first time. First, two different bromo-substituted tail chain compounds were synthesized; subsequently, nucleophilic substitution reactions with tosyl isocyanide were carried out sequentially under different alkaline conditions to obtain tosyl isocyanide-substituted long double-chain compounds; and finally, carbon double-tailed chain compounds as the main intermediates were obtained by acid hydrolysis. Specific modalities

[00124] In the following description of exemplary embodiments of this application, various details of the embodiments of this application are included to aid comprehension, which should be interpreted as merely illustrative. Consequently, those skilled in the art will recognize that various alterations and modifications of the embodiments described herein may be made without departing from the scope and spirit of this application. Furthermore, descriptions of well-known positions and structures are omitted from the following description for the sake of clarity and conciseness. Terms and definitions

[00125] As used herein, the term alkyl refers to a group containing one or more carbon atoms (e.g., one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty or more atoms). Petition 870250052396, dated 06 / 23 / 2025, p. 49 / 203 42 / 150 carbon atoms), which is optionally substituted. The term C1-C14 alkyl refers to an optionally substituted linear or branched saturated hydrocarbon containing from 1 to 14 carbon atoms. Unless otherwise indicated, the alkyl groups described herein refer to both unsubstituted and substituted alkyl groups.

[00126] As used herein, the term carbocyclic ring or carbocyclyl refers to an optionally substituted monocyclic or polycyclic system comprising one or more carbon rings. The ring may be a three-, four-, five-, six-, seven-, eight-, nine-, ten-, eleven-, twelve-, thirteen-, fourteen-, fifteen-, sixteen-, seventeen-, eighteen-, nineteen-, or twenty-membered ring. The term 5- to 7-membered ring refers to fused monocyclic spiro-carbocyclic rings with 5 to 7 carbon atoms. Carbocyclic rings may include one or more carbon-carbon double bonds or triple bonds and may be non-aromatic or aromatic (e.g., cycloalkyl or aryl). Examples of carbocyclic rings include cyclopentyl, cyclohexyl, phenyl, naphthyl, and 1,2-dihydronaphthyl.

[00127] As used herein, cycloalkyl refers to a non-aromatic carbocyclic ring and may or may not include any double or triple bonds. Unless otherwise indicated, the carbocyclic ring described herein refers to unsubstituted and substituted carbocyclic groups, i.e., an optionally substituted carbocyclic ring.

[00128] As used herein, the term heterocyclic ring or heterocyclyl refers to a monocyclic or optionally substituted polycyclic system comprising one or more rings, wherein at least one of the rings comprises at least one heteroatom, such as one, two, three, four, or five heteroatoms, which may be, for example, nitrogen, oxygen, or sulfur atoms. The ring may be a three-, four-, five-, six-, seven-, eight-, nine-, ten-, eleven-, twelve-, thirteen-, or fourteen-membered ring. The heterocyclic ring may include one or more alloys Petition 870250052396, dated 06 / 23 / 2025, page 50 / 203 43 / 150 double or triple ions and can be non-aromatic or aromatic (e.g., heterocycloalkyl or heteroaryl). Examples of heterocyclic rings include imidazolyl, imidazolinyl, oxazolyl, oxazolidinyl, thiazolyl, thiazolidinyl, pyrazolidinyl, pyrazolyl, isoxazolidinyl, isoxazolyl, isothiazolidinyl, isothiazolyl, morpholinyl, pyrrolyl, pyrrolyl, pyrrolyl group, pyrrolyl, pyrrolyl, furanyl, tienyl, pyrrolyl, pyrrolyl, pyrrolyl, furyl, tienyl, phenyl.

[00129] As used herein, the term heterocycloalkyl refers to a non-aromatic heterocyclic ring and may or may not include any double or triple bond. Unless otherwise indicated, heterocyclic ring, as used herein, refers to unsubstituted and substituted heterocyclic groups, i.e., optionally substituted heterocyclic rings.

[00130] As used herein, aryl is an optionally substituted carbocyclic group comprising one or more aromatic rings. Examples of aryl groups include phenyl and naphthyl.

[00131] As used herein, heteroaryl refers to an optionally substituted heterocyclic group comprising one or more aromatic rings. Examples of heteroaryl include pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, and thiazolyl. Both aryl and heteroaryl may be optionally substituted. Unless otherwise indicated, aryl or heteroaryl, as used herein, refers to unsubstituted and substituted groups, i.e., optionally substituted aryl or heteroaryl.

[00132] Unless otherwise indicated, the alkyl group may be optionally substituted. Optional substituents may be selected from, but not limited to, halogen atom (e.g., chlorine, bromine, fluorine or iodine group), carboxylic acid (e.g., -C(O)OH), alcohol (e.g., hydroxyl, -OH), ester (e.g., -C(O)OR or -OC(O)R), aldehyde (e.g., -C(O)H), carbonyl group (e.g., -C(O)R, or denoted by C=O), acyl halide Petition 870250052396, dated 06 / 23 / 2025, page 51 / 203 44 / 150 (e.g., -C(O)X, where X is a halide selected from bromide, fluoride, chloride, and iodide), carbonate (e.g., OC(O)OR), alkoxy (e.g., -OR), acetal, phosphate, thiol (e.g., -SH), sulfoxide (e.g., -S(O)R), sulfurous acid group (e.g., -S(O)OH), sulfonic acid group (e.g., -S(O)2OH), thiol (e.g., -C(S)H), sulfate, sulfonyl (e.g., -S(O)2-), amide (e.g., -C(O)NR2 or -N(R)C(O)R), azide (e.g., N3), nitro (e.g., -NO2), cyano (e.g., -CN), isocyano (e.g., -NC), acyloxy (e.g., -OC(O)R), amino (e.g., NR2, -NRH, or -NH2), carbamoyl (e.g., -OC(O)NR2, OC(O)NRH, or -OC(O)NH2), sulfonamide, alkyl, alkenyl, and cyclic groups (e.g., carbocyclyl or heterocyclyl). In any of the preceding cases, R is alkyl or alkenyl, as defined herein.In some embodiments, the substituent itself may be further substituted, for example, by one, two, three, four, five, or six substituents, as defined herein. For example, C1-6 alkyl may be further substituted by 1, 2, 3, 4, 5, or 6 substituents described herein.

[00133] As used herein, the term compound is intended to include all isomers and isotopes of the structures described. Isotope refers to atoms having the same atomic number but differing in mass number due to the difference in the number of neutrons in the nucleus. For example, isotopes of hydrogen include tritium and deuterium. Furthermore, the compounds, salts, or complexes of the present application may be used to form solvates and hydrates by preparation through conventional methods in combination with solvent molecules or water.

[00134] As used herein, the term "to put in contact" refers to the establishment of a physical connection between two or more entities. For example, the contact of a mammalian cell with a Petition 870250052396, dated 06 / 23 / 2025, page 52 / 203 45 / 150 nanoparticle composition means that the mammalian cell and the nanoparticle share a physical connection. The methods for bringing the cell into contact with external entities, both in vivo and ex vivo, are well known in the biological field. For example, the nanoparticle composition can come into contact with a mammalian cell in a mammal via a variety of administration routes (e.g., intravenous, intramuscular, intradermal, and subcutaneous), and varying amounts of the nanoparticle composition may be involved. Furthermore, the nanoparticle composition can come into contact with more than one mammalian cell.

[00135] As used herein, the term application refers to the delivery of an entity to a target site. For example, the application of a therapeutic and / or prophylactic agent to an individual may include the administration of a nanoparticle composition containing a therapeutic and / or prophylactic agent to an individual (e.g., intravenously, intramuscularly, intradermally, or subcutaneously). The administration of a nanoparticle composition to a mammalian or mammalian cell may involve the contact of one or more cells with the nanoparticle composition.

[00136] As used herein, the term intensify application refers to the application of more (e.g., at least 1.5 times, at least 2 times, at least 3 times, at least 4 times, at least 5 times, at least 6 times, at least 7 times, at least 8 times, at least 9 times, at least 10 times) therapeutic and / or prophylactic agent by the nanoparticle to a target tissue of interest (e.g., mammalian liver), compared to the level of therapeutic and / or prophylactic agent applied by a control nanoparticle to the target tissue (e.g., MC3, KC2, or DLinDMA). The comparison can be made by comparing the amount of protein produced in the tissue with the weight of said tissue, comparing the amount of agent Petition 870250052396, dated 06 / 23 / 2025, page 53 / 203 46 / 150 therapeutic and / or prophylactic effect in the tissue with the weight of the tissue, comparing the amount of protein produced in the tissue with the amount of total protein in the tissue, or comparing the amount of therapeutic and / or prophylactic agent in the tissue with the total amount of therapeutic and / or prophylactic agent in said tissue. It should be understood that it is not necessary that the enhanced application of nanoparticles to a target tissue be determined in the individual being treated, but can be determined in an alternative, such as an animal model (e.g., rat model). In certain embodiments, nanoparticle compositions comprising a compound of formula (I), (IA), (IB), (IC), (ID) have substantially the same level of enhanced application, regardless of the route of administration.

[00137] As used herein, the term specific application or apply specifically refers to the application of more (e.g., at least 1.5 times, at least 2 times, at least 3 times, at least 4 times, at least 5 times, at least 6 times, at least 7 times, at least 8 times, at least 9 times, at least 10 times) therapeutic and / or prophylactic agent to a target tissue (e.g., liver, spleen, stomach, mammalian intestinal tract) by a nanoparticle compared to a non-target tissue.The level of application of nanoparticles to a specific tissue can be measured by comparing the weight of the protein produced in the tissue with the weight of said tissue, by comparing the amount of therapeutic and / or prophylactic agent in the tissue with the weight of the tissue, by comparing the weight of the protein produced in the tissue with the weight of the total protein in said tissue, or by comparing the amount of therapeutic and / or prophylactic agent in the tissue with the total amount of therapeutic and / or prophylactic agent in said tissue.

[00138] As used herein, encapsulation efficiency refers Petition 870250052396, dated 06 / 23 / 2025, page 54 / 203 47 / 150 refers to the amount of therapeutic and / or prophylactic agent that becomes part of a nanoparticle composition, relative to the total amount of therapeutic or prophylactic agent used in the preparation of the nanoparticle composition. For example, if 97 mg of the therapeutic and / or prophylactic agent are encapsulated in a nanoparticle composition from a total of 100 mg of therapeutic and / or prophylactic agent initially supplied for the composition, the encapsulation efficiency may be 97%. As used herein, encapsulation may refer to complete, substantial, or partial encapsulation, closure, wrapping, or enclosing.

[00139] As used herein, expression of a nucleic acid sequence refers to the translation of mRNA into a polypeptide or protein and / or post-translational modification of a polypeptide or protein.

[00140] As used herein, the term in vitro refers to events that occur in an artificial environment, such as in a test tube or reaction vessel, in a cell culture, in a culture plate, etc., rather than events that occur within an organism (e.g., animal, plant, or microorganism).

[00141] As used herein, the term in vivo refers to events that occur within an organism (for example, an animal, plant or microorganism or a cell or tissue thereof).

[00142] As used herein, the term ex vivo refers to events that occur outside of an organism (e.g., an animal, plant, or microorganism, or a cell or tissue thereof). An ex vivo event may occur in an environment that is minimally altered from the natural environment (e.g., in vivo).

[00143] As used herein, the term isomer refers to any geometric isomer, tautomer, zwitterion, stereoisomer, enantiomer, or diastereomer of a compound. Compounds may contain Petition 870250052396, dated 06 / 23 / 2025, page 55 / 203 48 / 150 one or more chiral centers and / or double bonds and, in this way, can exist as stereoisomers, as double-bond isomers (i.e., geometric E / Z isomers) or diastereomers (e.g., enantiomers (i.e., (+) or (-)) or cis-trans isomers). The present application covers any and all isomers of the compounds described herein. Enantiomeric and stereoisomeric mixtures of compounds and methods of resolving them into their component enantiomers or stereoisomers are well known.

[00144] As used herein, a lipid component is a component of a nanoparticle composition that includes one or more lipids. For example, the lipid component may include one or more cationic / ionizable lipids, pegylated lipids, structural lipids, or other lipids such as phospholipids.

[00145] As used herein, a linker is a portion that connects two portions, for example, a linkage between two nucleosides of a cap. The linker may include one or more groups including, but not limited to, phosphate groups (e.g., phosphate, borophosphate, thiophosphate, selenophosphate, and phosphonate), alkyl, amide, or glycerol. For example, the two nucleosides of a cap analog may be linked at their 5' positions by a triphosphate group or by a chain comprising two phosphate portions and one borophosphate portion.

[00146] As used herein, method of administration may include intravenous, intramuscular, intradermal, subcutaneous or other methods of applying a composition to an individual. Any of the methods of administration may be selected for targeted application (e.g., specific application) to a specific region or system of a body.

[00147] As used herein, modified refers to non-natural. For example, RNA can be modified RNA. That is, the RNA can include one or more nucleobases, nucleosides, nucleotides, or ligands. Petition 870250052396, dated 06 / 23 / 2025, page 56 / 203 49 / 150 non-naturally occurring substitutions. A modified material may also be referred to in the present invention as a genetically modified material. The substance may be chemically, structurally, or functionally modified or altered. For example, the modified nucleobase species may comprise one or more non-naturally occurring substitutions.

[00148] As used herein, a nanoparticle composition is a composition comprising one or more lipids. The particle size of the nanoparticle composition is typically on the order of microns or less and may include a lipid bilayer. A nanoparticle composition includes a lipid nanoparticle (LNP), liposome (e.g., lipid vesicle), and lipid complex. For example, a nanoparticle composition might be a liposome with a lipid bilayer of 500 nm or less in diameter.

[00149] As used here, natural occurrence means existing naturally without artificial assistance.

[00150] As used herein, patient refers to an individual who may seek or need treatment, require treatment, is undergoing treatment, is about to undergo treatment, or is being treated for a specific illness by a trained professional.

[00151] As used herein, PEG lipid or pegylated lipid refers to a lipid comprising a polyethylene glycol component.

[00152] The term pharmaceutically acceptable is used in the present invention to refer to those compounds, materials, compositions and / or dosage forms that are, within the scope of rational medical judgment, suitable for use in contact with the tissues of humans and animals without excessive toxicity, irritation, allergic response or other problem or complication, proportionate to a ra Petition 870250052396, dated 06 / 23 / 2025, page 57 / 203 50 / 150 reasonable benefit / risk ratio

[00153] As used herein, the term pharmaceutically acceptable excipient refers to any ingredient other than the compounds described herein (for example, a vehicle capable of suspending, complexing or dissolving the active compound) that is substantially non-toxic and non-inflammatory to the patient. Excipients may include, for example: anti-adherents, antioxidants, binders, coatings, compression aids, disintegrants, colorants, humectants, emulsifiers, fillers, film formers or coatings, flavors, fragrances, glidants (flow enhancers), lubricants, preservatives, printing inks, adsorbents, suspending or dispersing agents, sweeteners and water for hydration.Exemplary excipients include, but are not limited to: butylated hydroxytoluene (BHT), calcium carbonate, calcium phosphate (dibasic acid), calcium stearate, croscarmellose, cross-linked polyvinylpyrrolidone, citric acid, crospovidone, cysteine, ethylcellulose, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose, lactose, magnesium stearate, maltitol, mannitol, methionine, methylcellulose, methylparaben, microcrystalline cellulose, polyethylene glycol, polyvinylpyrrolidone, povidone, pregelatinized starch, propylparaben, retinyl palmitate, shellac, silicon dioxide, sodium carboxymethylcellulose, sodium citrate, sodium starch glycolate, sorbitol, starch (corn), stearic acid, sucrose, talc, titanium dioxide, vitamin A, vitamin E. (alpha-tocopherol), vitamin C, xylitol and others described herein.

[00154] In the present application, the structural formula of the compound shows certain isomers for convenience, but the present application includes all isomers, such as geometric isomers, optical isomers based on asymmetric carbon, stereoisomers, tautomers and the like, and it should be understood that not all isomers may have the same level of activity. Furthermore, crystalline polymorphism may Petition 870250052396, dated 06 / 23 / 2025, page 58 / 203 51 / 150 being present in the compounds represented by the structural formulas of the compounds described in this application. It should be noted that any crystalline form, mixture of crystalline forms, or anhydride or hydrate thereof is included within the scope of this application.

[00155] The terms crystalline polymorph, polymorph, or crystalline form refer to a crystalline structure in which a compound (or a salt or solvate thereof) can crystallize in different crystal packing arrangements, all of which have the same elemental composition. Different crystalline forms typically have different X-ray diffraction patterns, infrared spectra, melting points, density hardnesses, crystal shapes, optical and electrical properties, stabilities, and solubilities. The recrystallization solvent, the crystallization rate, the storage temperature, and other factors can cause one form to predominate. Crystalline polymorphs of a compound can be prepared by crystallization under different conditions.

[00156] The nanoparticle compositions of the present application may further comprise one or more salts of a compound. The salt may be a pharmaceutically acceptable salt. As used herein, pharmaceutically acceptable salts refer to derivatives of the compounds described, wherein the parent compound is altered by converting an existing acid or base moiety into its salt form (e.g., by reacting the free base with a suitable organic acid). Examples of pharmaceutically acceptable salts include, but are not limited to, inorganic or organic acid salts of basic residues, such as amines; base or organic salts of acidic residues, such as carboxylic acids and the like. Representative acid addition salts include acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanopropionate, digluconate, dodecylsulfate, Petition 870250052396, dated 06 / 23 / 2025, page 59 / 203 52 / 150 ethanesulfonate, fumarate, glucoheptonate, hydrobromide, hydrochloride, hydroiodide, 2-hydroxyethanesulfonate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, hexadecanoate, pectate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, tosylate, undecanoate, valerate salts and similar substances.

[00157] Representative alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium and the like, as well as non-toxic ammonium, quaternary ammonium and amine cations including, but not limited to, ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine and the like. Pharmaceutically acceptable salts of the present application include, for example, conventional non-toxic salts of the parent compound formed from non-toxic inorganic or organic acids. Pharmaceutically acceptable salts of the present application may be synthesized by conventional chemical methods from parent compounds containing basic or acidic moieties. Typically, these salts may be prepared by reacting the free acidic or basic forms of these compounds with chemically calculated amounts of suitable bases or acids in water or organic solvents or mixtures thereof.Typically, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred.

[00158] As used herein, a phospholipid is a lipid that includes a phosphate moiety and one or more carbon chains, for example, chains of unsaturated fatty acids. The phospholipid may comprise one or more multiple bonds (e.g., double or triple bond) (e.g., one or more unsaturated bonds). Certain phospholipids can promote fusion with the membrane. For example, a phospholipid... Petition 870250052396, dated 06 / 23 / 2025, p. 60 / 203 53 / 150 A cationic dioxide can interact with one or more negatively charged phospholipids of a membrane (e.g., a cell membrane or an intracellular membrane). Fusion of the phospholipid to the membrane can allow one or more elements of the lipid-containing composition to pass through the membrane, thus allowing, for example, the application of one or more elements to the cell.

[00159] As used herein, polydispersity index is a ratio that describes the uniformity of the particle size distribution of a system. Relatively small values, for example, less than 0.3, indicate a narrow particle size distribution.

[00160] As used herein, the term polypeptide or polypeptide of interest refers to a polymer of amino acid residues, typically linked by peptide bonds, which may be produced naturally (e.g., isolated or purified) or synthetically.

[00161] As used herein, RNA refers to ribonucleic acids that may or may not occur naturally. For example, RNA may include modified and / or unnaturally occurring components such as one or more nucleobases, nucleosides, nucleotides, or linkers. RNA may include a cap structure, a chain-terminating nucleoside, a stem-loop, a polyA sequence, and / or a polyadenylation signal.RNA can have a nucleotide sequence that codes for a polypeptide of interest. For example, the RNA can be messenger RNA (mRNA). Translation of mRNA encoding a specific polypeptide, for example, in vivo translation of mRNA within a mammalian cell, can result in the encoded polypeptide. The RNA can be selected from the non-limiting group consisting of small interfering RNA (siRNA), asymmetric interfering RNA (airRNA), micro RNA (miRNA), double-stranded RNA (dsRNA), small hairpin RNA (shRNA), mRNA, and mixtures thereof.

[00162] As used herein, a single unit dose is a dose of Petition 870250052396, dated 06 / 23 / 2025, p. 61 / 203 54 / 150 any therapeutic agent that is administered in a single dose / once / single route / single point of contact, that is, a single administration.

[00163] As used herein, split doses refers to a single unit dose or total daily dose divided into two or more doses.

[00164] As used herein, total daily dose is the amount administered or prescribed over a 24-hour period. It may be administered as a single unit dose.

[00165] As used herein, particle size or average particle size in the context of a nanoparticle composition refers to the average diameter of the nanoparticle composition.

[00166] As used herein, the term individual or patient refers to any organism to which a composition in accordance with the present application may be administered, for example, for experimental, diagnostic, prophylactic and / or therapeutic purposes. Typical individuals include animals (e.g., mammals such as mice, rats, rabbits, non-human primates and humans) and / or plants.

[00167] As used herein, target cell refers to any one or more cells of interest. The cells may be found in vitro, in vivo, in situ, or in a tissue or organ of an organism. The organism may be an animal, preferably a mammal, most preferably a human being, with the highest preference a patient.

[00168] As used herein, target tissue refers to any one or more tissue types of interest where therapeutic and / or prophylactic application will result in a desired biological and / or pharmacological effect. Examples of target tissues include specific tissues, organs, and systems or groups thereof. For specific uses, the target tissue may be kidney (e.g., intracoronary or intrafemoral) or blood vessels (e.g., by intratumoral injection) of kidney, lung, spleen, vascular endothelium. Non-target tissue means any type of Petition 870250052396, dated 06 / 23 / 2025, p. 62 / 203 55 / 150 tissue or tissue types in which the expression of the encoded protein does not result in the desired biological and / or pharmacological effect. For specific uses, non-target tissue may include liver and spleen.

[00169] The term therapeutic agent or prophylactic agent refers to any agent that, when administered to an individual, has a therapeutic, diagnostic and / or prophylactic effect and / or produces a desired biological and / or pharmacological effect. Therapeutic agents are also called active agents or active components. Such substances include, but are not limited to, cytotoxins, radioactive ions, chemotherapeutic agents, small molecule drugs, proteins and nucleic acids.

[00170] As used herein, the term therapeutically effective amount refers to a sufficient quantity of an agent to be applied (e.g., nucleic acid, drug, composition, therapeutic agent, diagnostic agent, prophylactic agent, etc.) for the following circumstance: administering to an individual suffering from or susceptible to an infection, disease, disorder and / or condition for the purpose of treating, improving the symptoms thereof, diagnosing, preventing and / or delaying the onset of the infection, disease, disorder and / or condition.

[00171] As used herein, transfection refers to the introduction of a species (e.g., RNA) into a cell. Transfection can be performed, for example, in vitro, ex vivo, or in vivo.

[00172] As used herein, the term treatment refers to the partial or complete response, relief, improvement, remission of specific infections, diseases, disorders and / or conditions, delaying their onset, inhibiting their progression, reducing their severity and / or reducing the incidence of one or more symptoms or signs thereof. For example, treating cancer may refer to inhibiting the survival, growth and / or spread of a tumor. To reduce risk, an individual who does not exhibit a disease, disorder and / or condition, pathological condition Petition 870250052396, dated 06 / 23 / 2025, page 63 / 203 56 / 150 a pathologically progressive condition associated with a disease, disorder and / or condition and / or an individual exhibiting only early signs of a disease, disorder and / or condition, a pathologically progressive condition associated with a disease, disorder and / or condition can be treated.

[00173] The present application describes a compound described in formula (I), or a salt or an isomer thereof, where X and Y are independently selected from either O or S; Xi and X2 are independently selected from C=O or O, Y1 and Y2 are independently selected from C=O or O, with the condition that X1 and Y1 are not both C=O or O, and X2 and Y2 are not both C=O or O; Ria n R1b R1 is , wherein R1 and R1b are independently selected from H or C1-C6 alkyl, R2, R3 are independently selected from H or C1-C6 alkyl, or R1 and R2, together with the carbon atom to which they are attached, form a 5- to 7-membered substituted or unsubstituted nitrogen-containing heterocyclic ring, and R3 is selected from H or C1-C6 alkyl, or R1 and R3, together with the carbon atoms to which they are attached, form ring A, which is a substituted or unsubstituted carbocyclic or heterocyclic ring, and R2 is selected from H or C1-C6 alkyl; Petition 870250052396, dated 06 / 23 / 2025, page 64 / 203 57 / 150 R4, Rs, and Re are independently selected from C1-C14 alkyl groups; men are independently selected from 0, 1, 2, with the condition that men are not both 0; OEPs are independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; q is selected from 0, 1, 2, 3, 4, 5, or 6.

[00174] In a preferred embodiment, the said Ri is R1a , and in a specific embodiment, the compound of formula (I) is as shown in formula (IA), (IA), where q is preferably selected from 0, 1, 2, 3 or 4.

[00175] More preferably, q is selected from 2 or 3.

[00176] More preferably, q is selected from 2.

[00177] In a preferred embodiment, wherein the compound of formula (I) is of formula (IA), Petition 870250052396, dated 06 / 23 / 2025, page 65 / 203 58 / 150 where q is selected from 2 or 3, and R1 and R1b are selected from -CH3, -CH2CH3 or -CH(CH3)2, R2 is H, and R3 is H, n is 1, m is 0, X, Y are both O, o is 5 or 6, p is 7, X1 and X2 are both C=O, Y1 and Y2 is O, or X1 is O, Y1 is C=O, X2 is C=O, and Y2 is O. R4 is either a linear C10 alkyl or a linear C11 alkyl. R5 and R6 are linear C8 alkyl groups.

[00178] More preferably, R1ae R1bsão both selected from -CH3.

[00179] In a preferred embodiment, said R1 and R2, together with the carbon atom to which they are attached, form a 5- to 7-membered substituted or unsubstituted nitrogen-containing heterocyclic ring, R3 is selected from H or C1-C6 alkyl, in a specific embodiment, the compound of formula (I) is as shown in formula (IB), (IB) wherein R7 is selected from H or C1-C6 alkyl; er is selected from 0, 1, 2 or 3.

[00180] In a preferred embodiment, said R1 and R3, together with the carbon atoms to which they are attached, form ring A, which is a substituted or unsubstituted 5- to 7-membered carbocyclic or heterocyclic ring; R2 is selected from H or Petition 870250052396, dated 06 / 23 / 2025, page 66 / 203 59 / 150 C1-C6 alkyl; in a specific embodiment, the compound of formula (I) is as shown in formula (IC), (IC) wherein ring A is replaced by one or more R8, said R8 being , where R8ae R8bsão independently selected from H or C1-C6 alkyl groups, es é se se selecionado de entre de 0, 1,2, 3, 4, 5 ou 6.

[00181] In a specific embodiment, the compound of formula (I) as shown in the formula (ID),(ID), wherein ring A is replaced by one or more R8, wherein said R8 , where R8ae R8bsão are independently selected from H or C1-C6 alkyl groups, es is selected from 0, 1, 2, 3, 4, 5 or 6.

[00182] In a particular embodiment, said ring A is ; said compound of formula (IC) is as shown in (IC-1), Petition 870250052396, dated 06 / 23 / 2025, page 67 / 203 60 / 150

[00183] The compound of formula (ID) is as shown in (ID-

[00184] In a particular embodiment, said ring A is ; said compound of formula (IC) is as shown in (IC-2),

[00185] The compound of formula (ID) is as shown in (ID-

[00186] In a specific embodiment, said ring A is \J; the Petition 870250052396, dated 06 / 23 / 2025, page 68 / 203 61 / 150 of the said compound of formula (IC) is as shown in (IC-3),

[00187] The compound of formula (ID) is as shown in (ID-

[00188] In one specific embodiment, said ring A is said compound of formula (IC) is as shown in (IC-3), the said compound of formula (IC) is con.Xl .^4 íTY1 'O form shown in (IC-4), or said compound of formula (IC) is as shown in (IC-5) Petition 870250052396, dated 06 / 23 / 2025, page 69 / 203 62 / 150

[00189] The compound of formula (ID) is as shown in (ID- , the compound of formula (ID) is as shown in , or the compound of the formula (ID) is as shown in (ID-

[00190] In a preferred embodiment, in the above formula (I), (IA), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IB), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (ID), (ID-1), (ID-2), (ID-3), (ID-4), (ID-5), said R4 is selected from C1-C14 alkyl, for example, R4 is selected from C2-C14 alkyl, R4 is selected from C3-C14 alkyl, R4 is selected from C4-C14 alkyl, R4 is Petition 870250052396, dated 06 / 23 / 2025, p. 70 / 203 63 / 150 selected from C5-C14 alkyl, R4 is selected from C6-C14 alkyl, R4 is selected from C7-C14 alkyl, R4 is selected from C8-C14 alkyl, R4 is selected from C9-C14 alkyl, R4 is selected from C10-C14 alkyl, C10-C13 alkyl, C10-C12 alkyl or C10-C11 alkyl, for example, R4 is C1 alkyl, R4 is C2 alkyl, R4 is C3 alkyl, R4 is C4 alkyl, R4 is C5 alkyl, R4 is C6 alkyl, R4 is C7 alkyl, R4 is C8 alkyl, R4 is C9 alkyl, R4 is C10 alkyl, R4 is C11 alkyl, R4 is C12 alkyl, R4 is C13 alkyl or R4 is C14 alkyl. In additionally preferred embodiments, R4 is C10 alkyl; in additionally preferred embodiments, R4 is C11 alkyl.

[00191] In a preferred embodiment, said R4 is selected from linear C1-C14 alkyl, for example, R4 is selected from linear C2-C14 alkyl, R4 is selected from linear C3-C14 alkyl, R4 is selected from linear C4-C14 alkyl, R4 is selected from linear C5-C14 alkyl, R4 is selected from linear C6-C14 alkyl, R4 is selected from linear C7-C14 alkyl, R4 is selected from linear C8-C14 alkyl, R4 is selected from linear C9-C14 alkyl, R4 is selected from linear C10-C14 alkyl, linear C10-C13 alkyl, linear C10-C12 alkyl or linear C10-C11 alkyl, for example, R4 is C1 alkyl, R4 is C2 alkyl, R4 is C3 linear alkyl, R4 is C4 linear alkyl, R4 is C5 linear alkyl, R4 is C6 linear alkyl, R4 is C7 linear alkyl, R4 is C8 linear alkyl, R4 is C9 linear alkyl, R4 is C10 linear alkyl, R4 is C11 linear alkyl, R4 is C12 linear alkyl, R4 is C13 linear alkyl, or R4 is C14 linear alkyl.In other preferred embodiments, R4 is a linear C10 alkyl; in other preferred embodiments, R4 is a linear C11 alkyl.

[00192] In a specific embodiment, the compound of formula (I) is as shown in formula (IA-1), Petition 870250052396, dated 06 / 23 / 2025, page 71 / 203 64 / 150 (IA-1)

[00193] In a specific embodiment, the compound of formula (I) is as shown in formula (IA-2), (IA-2)

[00194] In a specific embodiment, the compound of formula (I) is as shown in formula (IB-1),

[00195] In a specific embodiment, the compound of formula (I) is as shown in formula (IB-2), (IB-2)

[00196] In a specific embodiment, the compound of formula (I) is as shown in formula (IC-6), Petition 870250052396, dated 06 / 23 / 2025, page 72 / 203 65 / 150

[00197] In a specific embodiment, the compound of formula (I) is as shown in formula (IC-7),

[00198] In a specific embodiment, the compound of formula (I) is as shown in formula (ID-6), (ID-6)

[00199] In a specific embodiment, the compound of formula (I) is as shown in formula (ID-7), (ID-7) Petition 870250052396, dated 06 / 23 / 2025, page 73 / 203 66 / 150

[00200] In a preferred embodiment, in the above formula (I), (IA), (IA-1), (IA-2), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIAG), (IIA-H), (IB), (IB-1), (IB-2), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (ID), (ID-1), (ID-2), (ID-3), (ID-4), (ID-5), (ID-6), (ID-7), said R5 is selected from C1-C14 alkyl, for example, R5 is selected from C2-C14 alkyl, R5 is selected from C3-C14 alkyl, R5 is selected from C4-C14 alkyl, R5 is selected from C5C14 alkyl, R5 is selected from C6-C14 alkyl, R5 is selected from C7-C14 alkyl, R5 is selected from C8-C14 alkyl, R5 is selected from C8-C13 alkyl, R5 is selected from C8-C12 alkyl, R5 is selected from C8-C11 alkyl, R5 is selected from C8-C10 alkyl or R5 is selected from C8-C9 alkyl, for example, R5 is C1 alkyl, R5 is C2 alkyl, R5 is C3 alkyl, R5 is C4 alkyl, R5 is C5 alkyl, R5 is C6 alkyl, R5 is C7 alkyl, R5 is C8 alkyl,R5 is C9 alkyl, R5 is C10 alkyl, R5 is C11 alkyl, R5 is C12 alkyl, R5 is C13 alkyl, or R5 is C14 alkyl. In a preferred embodiment, said R5 is C8 alkyl.

[00201] In a preferred embodiment, said R5 is selected from linear C1-C14 alkyl, for example, R5 is selected from linear C2-C14 alkyl, R5 is selected from linear C3-C14 alkyl, R5 is selected from linear C4-C14 alkyl, R5 is selected from linear C5-C14 alkyl, R5 is selected from linear C6-C14 alkyl, R5 is selected from linear C7-C14 alkyl, R5 is selected from linear C8-C14 alkyl, R5 is selected from linear C8-C13 alkyl, R5 is selected from linear C8-C12 alkyl, R5 is selected from linear C8-C11 alkyl, R5 is selected from linear C8-C10 alkyl, or R5 is selected from linear C8-C9 alkyl, for example, R5 is C1 alkyl, R5 is C2 alkyl, R5 is C3 linear alkyl, R5 is C4 linear alkyl, R5 is C5 linear alkyl, R5 is C6 linear alkyl, R5 is C7 linear alkyl, R5 is C8 linear alkyl, R5 is C9 linear alkyl, R5 is C10 linear alkyl, R5 is C11 Petition 870250052396, dated 06 / 23 / 2025, page 74 / 203 67 / 150 linear alkyl, R5 is C12 linear alkyl, R5 is C13 linear alkyl or R5 is C14 linear alkyl. In a preferred embodiment, said R5 is C8 linear alkyl.

[00202] In a preferred embodiment, in the above formula (I), (IA), (IA-1), (IA-2), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIAG), (IIA-H), (IB), (IB-1), (IB-2), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (ID), (ID-1), (ID-2), (ID-3), (ID-4), (ID-5), (ID-6), (ID-7), said R6 is selected from C1-C14 alkyl, for example, R6 is selected from C2-C14 alkyl, R6 is selected from C3-C14 alkyl, R6 is selected from C4-C14 alkyl, R6 is selected from C5C14 alkyl, R6 is selected from C6-C14 alkyl, R6 is selected from C7-C14 alkyl, R6 is selected from C8-C14 alkyl, R6 is selected from C8-C13 alkyl, R6 is selected from C8-C12 alkyl, R6 is selected from C8-C11 alkyl, R6 is selected from C8-C10 alkyl or R6 is selected from C8-C9 alkyl, for example, R6 is C1 alkyl, R6 is C2 alkyl, R6 is C3 alkyl, R6 is C4 alkyl, R6 is C5 alkyl, R6 is C6 alkyl, R6 is C7 alkyl, R6 is C8 alkyl,R6 is C9 alkyl, R6 is C16 alkyl, R6 is C11 alkyl, R6 is C12 alkyl, R6 is C13 alkyl, or R6 is C14 alkyl. In a preferred embodiment, said R6 is C8 alkyl.

[00203] In a preferred embodiment, said R6 is selected from linear C1-C14 alkyl, for example, R6 is selected from linear C2-C14 alkyl, R6 is selected from linear C3-C14 alkyl, R6 is selected from linear C4-C14 alkyl, R6 is selected from linear C5-C14 alkyl, R6 is selected from linear C6-C14 alkyl, R6 is selected from linear C7-C14 alkyl, R6 is selected from linear C8-C14 alkyl, R6 is selected from linear C8-C13 alkyl, R6 is selected from linear C8-C12 alkyl, R6 is selected from linear C8-C11 alkyl, R6 is selected from linear C8-C10 alkyl or R6 is selected from linear C8-C9 alkyl, for example, R6 is C1 alkyl Petition 870250052396, dated 06 / 23 / 2025, page 75 / 203 68 / 150 la, R6 is C2 alkyl, R6 is C3 linear alkyl, R6 is C4 linear alkyl, R6 is C5 linear alkyl, R6 is C6 linear alkyl, R6 is C7 linear alkyl, R6 is C8 linear alkyl, R6 is C9 linear alkyl, R6 is C10 linear alkyl, R6 is C11 linear alkyl, R6 is C12 linear alkyl, R6 is C13 linear alkyl or R6 is C14 linear alkyl. In a preferred embodiment, said R6 is C8 linear alkyl.

[00204] In a preferred embodiment, said R5 is C8 alkyl, said R6 is C8 alkyl.

[00205] In a preferred embodiment, said R5 is linear C8 alkyl, said R6 is linear C8 alkyl.

[00206] In a specific embodiment, the compound of formula (I) is as shown in formula (IA-3), (IA-3)

[00207] In a specific embodiment, the compound of formula (I)

[00208] In a specific embodiment, the compound of formula (I) is as shown in formula (IC-8), Petition 870250052396, dated 06 / 23 / 2025, page 76 / 203 69 / 150 (IC-8)

[00209] In a specific embodiment, the compound of formula (I) is as shown in formula (ID-8), (ID-8)

[00210] In a preferred embodiment, the said o is 5:

[00211] in a specific embodiment, the compound of formula (I) is as shown in formula (IA-4), (IA-4)

[00212] In a specific embodiment, the compound of formula (I)

[00213] In a specific embodiment, the compound of formula (I) Petition 870250052396, dated 06 / 23 / 2025, page 77 / 203 70 / 150

[00214] In a specific embodiment, the compound of formula (I)

[00215] In a preferred embodiment, the said o is 6: in a specific embodiment, the compound of formula (I) is as shown in formula (IA-5), (IA-5)

[00216] In a specific embodiment, the compound of formula (I)

[00217] In a specific embodiment, the compound of formula (I) Petition 870250052396, dated 06 / 23 / 2025, page 78 / 203 71 / 150 is as shown in the formula (IC-10), (IC-10)

[00218] In a specific embodiment, the compound of formula (I) is as shown in formula (ID-10),

[00219] In a preferred embodiment, said p is 7:

[00220] in a specific embodiment, the compound of formula (I) is as shown in formula (IA-6), (IA-6)

[00221] In a specific embodiment, the compound of formula (I)

[00222] In a specific embodiment, the compound of formula (I) is as shown in formula (IC-11), Petition 870250052396, dated 06 / 23 / 2025, page 79 / 203 72 / 150

[00223] In a specific embodiment, the compound of formula (I) is as shown in formula (ID-11),

[00224] In a preferred embodiment, in the above formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IB), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-1), (ID-2), (ID-3), (ID-4) (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), said Xi and X2 are C=O, and said Y1 and Y2 are O.

[00225] In a preferred embodiment, in the above formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IB), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-1), (ID-2), (ID-3), (ID-4) (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), said X1 is O, Y1 is C=O, said X2 is C=O, and Y2 is O.

[00226] In a preferred embodiment, in the above formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IB), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), Petition 870250052396, dated 06 / 23 / 2025, pp. 80 / 203 73 / 150 (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-1), (ID-2), (ID-3), (ID-4), (ID-5), (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), o dito X1 é C=O, Y1 é O, o dito X2 é O, e Y2 é C=O.

[00227] Em uma modalidade preferencial, na fórmula acima (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IB), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-1), (ID-2), (ID-3), (ID-4), (ID-5), (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), os ditos X1, X2 são O, os ditos Y1 e Y2 são C=O.

[00228] In a preferred embodiment, in the above formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IB), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-1), (ID-2), (ID-3), (ID-4) (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11) and the aforementioned X and Y are both O.

[00229] In a preferred embodiment, in the above formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IB), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-1), (ID-2), (ID-3), (ID-4) (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), the said n is 0 in is 1.

[00230] In a preferred embodiment, in the above formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IB), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-1), (ID-2), (ID-3), (ID-4) (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), the said n is 1 in is 0.

[00231] In a preferred embodiment, in the formula above (I), (IA), Petition 870250052396, dated 06 / 23 / 2025, p. 81 / 203 74 / 150 (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IB), (IB-1), (IB-1), (IB-4), (IB-4), (IB-4), (IB-4), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-1), (ID-2), (ID-3), (ID-4), (ID-5), (ID-6), (ID-8), (ID-8), (ID-8), (ID-10), (ID-11), the dito n é 1 em é 1.

[00232] In a preferential mode, in the above formula, (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IIA-H), (IIA-H), (IB-1), (IB-2), (IB3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID-1), (ID-1), (ID-4), (ID-4), (ID-5), (ID-4), (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), dito o é 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.

[00233] In a preferential mode, in the above formula, (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IIA-H), (IIA-H), (IB-1), (IB-2), (IB3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID-1), (ID-1), (ID-4), (ID-4), (ID-5), (ID-4), (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.

[00234] In a preferential mode, in the above formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-H), (IIA-H), (IIA-H), (IIA-H), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-2), (ID-3), (ID-4), (ID-4), (ID-4), (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), or say q is 0, 1, 2, 3, 4, 5 or 6.

[00235] In a preferred embodiment, in the above formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IB), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), Petition 870250052396, dated 06 / 23 / 2025, p. 82 / 203 75 / 150 (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-1), (ID-2), (ID-3), (ID-4), (ID-5), (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), said is 5 or 6.

[00236] In a preferential mode, in the above formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-H), (IIA-H), (IIA-H), (IIA-H), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-2), (ID-3), (ID-4), (ID-4), (ID-4), (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), or finger 7 or 8.

[00237] In a preferential mode, in the above formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-H), (IIA-H), (IIA-H), (IIA-H), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-2), (ID-3), (ID-4), (ID-4), (ID-4), (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), or say q is 2 or 3.

[00238] In a preferential mode, in the above formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-H), (IIA-H), (IIA-H), (IIA-H), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-2), (ID-3), (ID-4), (ID-4), (ID-4), (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), or R2é H finger.

[00239] In a preferential mode, in the above formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-H), (IIA-H), (IIA-H), (IIA-H), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-2), (ID-3), (ID-4), (ID-4), (ID-4), (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), or R3é H finger.

[00240] In a preferred embodiment, in the above formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IB), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), Petition 870250052396, dated 06 / 23 / 2025, p. 83 / 203 76 / 150 (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-1), (ID-2), (ID-3), (ID-4), (ID-5), (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), said R1a and R1b are CH3.

[00241] In a preferred embodiment, wherein the compound of formula (I) is Compound 1

[00242] In a preferred embodiment, wherein the compound of formula (I) is Compound 2 THE

[00243] In a preferred embodiment, wherein the compound of formula (I) is Compound 3 THE

[00244] In a preferred embodiment, wherein the compound of formula (I) is Compound 4

[00245] In a preferred embodiment, wherein the compound of formula (I) is Compound 5

[00246] In a preferred embodiment, wherein the compound of formula (I) is Compound 6

[00247] In a preferred embodiment, wherein the compound of formula (I) is Compound 7

[00248] In a preferred embodiment, wherein the compound of formula (I) is Compound 8 THE J Petition 870250052396, dated 06 / 23 / 2025, page 84 / 203 77 / 150

[00249] In a preferred embodiment, wherein the compound of formula (I) is Compound 9

[00250] In a preferred embodiment, wherein the compound of formula (I) is Compound 10

[00251] In a preferred embodiment, wherein the compound of formula (I) is Compound 11

[00252] In a preferred embodiment, wherein the compound of formula (I) is Compound 12

[00253] In a preferred embodiment, wherein the compound of formula (I) is Compound 13

[00254] This request also refers to optical isomers Petition 870250052396, dated 06 / 23 / 2025, p. 85 / 203 78 / 150

[00255] This application additionally provides a method for Petition 870250052396, dated 06 / 23 / 2025, p. 86 / 203 79 / 150 the compound (IA) comprising, M (IA) , where Zi is selected from OH, Z2 and Z3 are independently selected from OH or SH, respectively, and Z4 is selected from OMs; X and Y are independently selected from either O or S; X1 and X2 are independently selected from C=O or O, Y1 and Y2 are independently selected from C=O or O, with the condition that X1 and Y1 are not both C=O or O, and X2 and Y2 are not both C=O or O; R1a, R1b are independently selected from H or C1-C6 alkyl groups; R2 and R3 are independently selected from either H or C1-C6 alkyl groups; R4, R5 and R6 are independently selected from C1-C14 alkyl groups; men are independently selected from 0, 1, or 2, provided that men are not both 0; OEPs are independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; q is selected from 0, 1, 2, 3, 4, 5, or 6; whereby said Compound J is reacted with Compound K to form Petition 870250052396, dated 06 / 23 / 2025, page 87 / 203 80 / 150 mar Compound L in a benzene-based solution of pyridinium 4-methylbenzenesulfonate (Tso-Py), a benzene-based solvent used in said benzene-based solution may be toluene, xylene, trimethylbenzene and tetramethylbenzene, etc., and, in a preferred embodiment of the present application, said benzene-based solvent is toluene; Compound L is reacted in a solution of halogenated alkane (CH3SO2)2O to provide Compound M, wherein halogenated alkane, abbreviated as haloalkane or alkyl halide, refers to an organic compound in which one or more hydrogen atoms in the alkane molecule are replaced by a halogen atom (fluorine, chlorine, bromine, iodine) and said haloalkane of the present application is not limited and, in a preferred embodiment, the chlorinated alkane is preferably DCM, dichloroethane or chloroform; Compound M is reacted in a polar aprotic solvent to form Compound IA; the polar aprotic solvent may be dimethyl sulfoxide (DMSO), acetone, acetonitrile, dimethylformamide, dimethylacetamide, hexamethylphosphoramide, tetrahydrofuran (THF), N,N-dimethylformamide (DMF), dimethylacetamide (DMA), preferably tetrahydrofuran (THF).

[00256] In the synthesis method above, the source of Compound J is not limited and may be commercially available or may be synthesized internally and, in a specific embodiment, Compound J is synthesized by the following synthesis method, hcjj where X1 and X2 are independently selected from C=O or O, Y1 and Y2 are independently selected from C=O or O, with the condition that X1 and Y1 are not both C=O or O, and X2 and Y2 Petition 870250052396, dated 06 / 23 / 2025, p. 88 / 203 81 / 150 are not both C=O or O; X is selected from among halogens; R4, R5 and R6 are independently selected from C1-C14 alkyl groups; OEPs are independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; Compound H is reacted with Compound C in the presence of a carbonate salt, NBu4l, and a polar aprotic solvent to produce Compound I (Ts stands for p-toluenesulfonyl); in a preferred embodiment, the carbonate salt is an alkali metal carbonate, preferably Cs2CO3 or K2CO3; The said polar aprotic solvent may be dimethyl sulfoxide (DMSO), acetone, acetonitrile, dimethylformamide, dimethylacetamide, hexamethylphosphoramide, tetrahydrofuran (THF), N,N-dimethylformamide (DMF), dimethylacetamide (DMA), and preferably DMF or DMA; Compound I is reacted at pH 1 to 5 to give Compound J, preferably the pH value is adjusted by hydrochloric acid solution, the concentration of hydrochloric acid is preferably 12 M, the reaction solvent is a haloalkane and preferably DCM, dichloroethane or chloroform.

[00257] In the synthesis method above, the source of Compound H is not limited and may be commercially available or may be synthesized internally and, in a specific embodiment, Compound H is synthesized by the following synthesis method, fgh where X1 and Y1 are independently selected from C=O or O; Petition 870250052396, dated 06 / 23 / 2025, pp. 89 / 203 82 / 150 X is selected from among halogens; R4 is selected from C1-C14 alkyl groups; The number is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; wherein said Compound F is reacted with Compound G in the presence of a carbonate salt, NBu4I, and a polar aprotic solvent to give Compound H; in a preferred embodiment, the carbonate salt is an alkali metal carbonate, and preferably Cs2CO3 or K2CO3; The said polar aprotic solvent may be dimethyl sulfoxide (DMSO), acetone, acetonitrile, dimethylformamide, dimethylacetamide, hexamethylphosphoramide, tetrahydrofuran (THF), N,N-dimethylformamide (DMF), dimethylacetamide (DMA), and preferably DMF or DMA. This application further provides a nanoparticle composition comprising a lipid component, comprising the compound of formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IB), (IB-1), (IB-2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID1), (ID-2), (ID-3), (ID-4), (ID-5), (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), as provided by this request.

[00258] In some embodiments, said nanoparticle composition has an average particle size of 50 nm to 110 nm, such as 51 nm, 52 nm, 53 nm, 54 nm, 55 nm, 56 nm, 57 nm, 58 nm, 59 nm, 60 nm, 61 nm, 62 nm, 63 nm, 64 nm, 65 nm, 66 nm, 67 nm, 68 nm, 69 nm, 70 nm, 71 nm, 72 nm, 73 nm, 74 nm, 75 nm, 76 nm, 77 nm, 78 nm, 79 nm, 80 nm, 81 nm, 82 nm, 83 nm, 84 nm, 85 nm, 86 nm, 87 nm, 88 nm, 89 nm, 90 nm, 91 nm, 92 nm, 93 nm, 94 nm, 95 nm,96 nm, 97 nm, 98 nm, 99 nm, 100 nm, 101 nm, 102 nm, 103 nm, 104 nm, 105 nm, 106 nm, 107 nm, 108 nm or 109 nm.

[00259] The so-called nanoparticle composition may include, for Petition 870250052396, dated 06 / 23 / 2025, pp. 90 / 203 83 / 150 For example, lipid nanoparticles (LNPs), liposomes, lipid vesicles, and lipid complexes. In some embodiments, the nanoparticle composition is a vesicle comprising one or more lipid bilayers. In some embodiments, the nanoparticle composition comprises two or more concentric bilayers separated by two or more aqueous compartments. The lipid bilayers may be functionalized and / or cross-linked. The lipid bilayer may include one or more ligands, proteins, or channels.

[00260] The nanoparticle composition of this application comprises a lipid component comprising at least one compound according to formula (I), (IA), (IIA), (IB), (IC) or (ID). For example, the lipid component of the nanoparticle composition may include one or more of compounds 1 to 32. The nanoparticle composition may also include a variety of other components. For example, in addition to one compound according to formula (I), (IA), (IIA), (IB), (IC) or (ID), the lipid component of the nanoparticle composition may also include one or more other lipids.

[00261] The lipid component of the nanoparticle composition may include one or more PEG lipids or PEG-modified lipids. Such materials may alternatively be referred to as pegylated lipids. PEG lipids are lipids modified with polyethylene glycol. The PEG lipid may be selected from a non-limiting group consisting of PEG-modified phosphatidylethanolamine, PEG-modified phosphatidic acid, PEG-modified ceramide, PEG-modified dialkylamine, PEG-modified diacylglycerol, PEG-modified dialkylglycerol, and mixtures thereof. For example, the PEG lipid may be PEG-c-DOMG, PEG-DMG, PEG-DLPE, PEG-DMPE, PEG-DPPC, or PEG-DSPE lipid.

[00262] The lipid component of said nanoparticle composition may comprise one or more structural lipids. The structural lipid Petition 870250052396, dated 06 / 23 / 2025, pp. 91 / 203 84 / 150 The structural lipid may be selected from, but not limited to, cholesterol, coprosterol, sitosterol, ergosterol, stigmasterol, and mixtures thereof. In some embodiments, the structural lipid is cholesterol. In some embodiments, the structural lipid comprises cholesterol and a corticosteroid (e.g., prednisolone, dexamethasone, prednisone, and hydrocortisone), or a combination thereof.

[00263] The lipid component of said nanoparticle compositions may comprise one or more phospholipids, and the phospholipids used in said nanoparticle compositions and methods may be selected from: dilauroyl lecithin (DLPC), dimyristoyl phosphatidylcholine (DMPC), dioleoyl lecithin (DOPC), dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), dioleoyl phosphatidylcholine (DUPC), palmitoyl oleoyl phosphatidylcholine (POPC), 1,2-di-O-octadecyl-sn-glycero-3-phosphocholine (18:0 diether PC), 1-oleoyl-2-cholesteryldimethylsuccinoyl-sn-glycero-3-phosphocholine (OChemsPC), l-hexadecyl-sn-glycero-3-phosphocholine (C16 Lyso PC), 1,2-divinyl-sn-glycero-3-phosphocholine, 1,2-diarylacyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphorylethanolamine (DOPE), 1,2-di-phytanoyl-sn-glycero-3-phosphoethanolamine (ME 16.0 PE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-diethenol-sn-glycero-3-phosphoethanolamine, 1,2-divinyl-sn-glycero-3-phosphoethanolamine, 1,2-diaryl-sn-glycero-3-phosphoethanolamine, 1,2-dithiohexaenoate-sn-glycero-3-phosphoethanolamine, Petition 870250052396, dated 06 / 23 / 2025, pp. 92 / 203 85 / 150 sodium salt of 1,2-dioleoyl-sn-glycero-3-phosphate-(1-glycerol) (DOPG) or sphingomyelin.

[00264] In some embodiments, the nanoparticle composition comprises DSPC. In some embodiments, the nanoparticle composition comprises DOPE. In some embodiments, the nanoparticle composition comprises both DSPC and DOPE.

[00265] In some embodiments, a nanoparticle composition comprising one or more lipids described herein may further comprise one or more adjuvants, for example, glucopyranosyl (GLA) lipid adjuvant, CpG oligodeoxynucleotides (e.g., class A or class B), poly(I:C), aluminum hydroxide and Pam3CSK 4.

[00266] Nanoparticle compositions may comprise one or more therapeutic and / or prophylactic agents.

[00267] The present application provides methods for applying a therapeutic and / or prophylactic agent to a mammalian cell or organ, producing a polypeptide of interest in the mammalian cell and treating a disease or disorder in a mammal that is in need thereof, comprising administering to the mammal and / or placing the mammalian cell in contact with the composition comprising therapeutic and / or prophylactic nanoparticles.

[00268] The therapeutic and / or prophylactic agent includes a biologically active substance and may alternatively be called an active agent. The therapeutic and / or prophylactic agent may be a substance that, once applied to a cell or organ, produces a desired change in the cell, organ, or other body tissue or system. Such a substance may be used to treat one or more diseases, disorders, or conditions. In some embodiments, the therapeutic and / or prophylactic agent is a small molecule drug that can be used to treat a specific disease, disorder, or condition. Petition 870250052396, dated 06 / 23 / 2025, pp. 93 / 203 86 / 150 Examples of a drug that can be used in the composition of nanoparticles include, but are not limited to, antineoplastic agents (e.g., vincristine, adriamycin, mitoxantrone, camptothecin, cisplatin, bleomycin, cyclophosphamide, methotrexate, and streptozotocin), antineoplastic agents (e.g., actinomycin D, vincristine), vinblastine, cystine arabinoside, anthracyclines, alkylating agents, platinum compounds, antimetabolites and nucleoside analogs (e.g., methotrexate, purine, and pyrimidine analogs), anti-infective agents, local anesthetics (e.g., dibucaine and chlorpromazine), beta-adrenergic blockers (e.g., propranolol, timolol, and labetalol), antihypertensive agents (e.g., clonidine and hydralazine), antidepressants (e.g., imipramine, amitriptyline, and doxepin), anticonversion agents (e.g., phenytoin), antihistamines (e.g., diphenhydramine, chlorpheniramine, and promethazine),Antibiotics / antibacterials (e.g., gentamicin, ciprofloxacin, and cefoxitin), antifungals (e.g., miconazole, terconazole, econazole, isoconazole, butoconazole, clotrimazole, itraconazole, nystatin, and naftifine), antiparasitics, hormones, hormone antagonists, immunomodulators, neurotransmitter antagonists, antiglaucoma agents, vitamins, anesthetics, and imaging agents.

[00269] In some embodiments, the therapeutic and / or prophylactic agent is a cytotoxin, a radioactive ion, a chemotherapeutic agent, a vaccine, a compound that elicits an immune response, and / or another therapeutic and / or prophylactic agent. The cytotoxin or cytotoxic agent includes any agent that may be harmful to a cell. Examples include, but are not limited to, paclitaxel, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, teniposide, vincristine, vinblastine, colchicine, adriamycin, daunorubicin, dihydroxyanthraquinone, simmetasone, 1-nortestosterone, aspergillus oryzae, glucocorticoids, procaine, tetracaine, lidocaine, propra Petition 870250052396, dated 06 / 23 / 2025, pp. 94 / 203 87 / 150 nolol, puromycin, maytansinoids, for example, maytansinol, rachelomycin (CC-1065) and analogues or homologues thereof. Radioactive ions include, but are not limited to, iodine (e.g., iodine-125 or iodine-131), strontium-89, phosphorus, palladium, cesium, iridium, phosphate, cobalt, yttrium-90 and sa-153. Vaccines include compounds and formulations capable of providing immunity to one or more conditions associated with infectious diseases (e.g., influenza, measles, human papillomavirus (HPV), rabies, meningitis, pertussis, tetanus, plague, hepatitis and tuberculosis), including mRNA encoding antigens and / or epitopes derived from infectious diseases. Vaccines also include compounds and preparations that direct an immune response against cancer cells and may include mRNA encoding antigens, epitopes, and / or neoepitopes derived from tumor cells. Compounds that elicit an immune response may include vaccines, corticosteroids (e.g., dexamethasone), and other species.

[00270] Other therapeutic and / or prophylactic agents include, but are not limited to, antimetabolites (e.g., methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarboxylase), alkylating agents (e.g., methyclothiazide, thiotepacloramphenicol, raquelmycin (CC-1065), melphalan, carmustine (BSNU), lomustine (CCNU), cyclophosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C and cis-dichlorodiamineplatinum(II) (DDP), anthracyclines (e.g., daunorubicin (formerly daunomycin) and doxorubicin), antibiotics (e.g., dactinomycin (formerly actinomycin), bleomycin, mithramycin and anthramycin (AMC)) and agents antimitotics (e.g., vincristine, vinblastine, paclitaxel, and zeatin glycosides)

[00271] In some embodiments, the vaccine and / or compound capable of provoking an immune response is administered intramuscularly in a composition comprising a compound of formula (I), Petition 870250052396, dated 06 / 23 / 2025, pp. 95 / 203 88 / 150 (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IB-1), (IB-2), (IB-3), (IB-4), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-1), (ID-2), (ID-3), (ID-4), (ID-5), (ID-8), (ID-8), (ID-8), (ID-8), (ID-10), (ID-11), for example, one or more of compounds 1 to 32.Other therapeutic and / or prophylactic measures include, but are not limited to, antimetabolites (e.g., methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil, decarbazine), alkylating agents (e.g., methoxyethylamine, metsulfovax, chlorobutyric acid, raquelmycin (CC-1065), melphalan, carmustine (BSNU), lomustine (CCNU), cyclophosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C and cisdichlorodiamine platinum(II) (DDP), anthracyclines (e.g., daunorubicin (formerly daunomycin) and adriamycin), antibiotics (e.g., actinomycin, mithramycin, adriamycin, actinomycin), anthramycin (AMC)) and antimitotics (e.g., vincristine, vinblastine, paclitaxel, and maytansinoids).

[00272] In other embodiments, the therapeutic and / or prophylactic agent is a protein. Therapeutic proteins that may be used in the nanoparticle compositions described in this application include, but are not limited to, gentamicin, amikacin, insulin, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), VIR factor, luteinizing hormone-releasing hormone (LHRH) analogs, interferon, eparin, hepatitis B surface antigen, typhoid vaccine, and cholera vaccine.

[00273] In some modalities, the therapeutic agent is a polynucleotide or nucleic acid (e.g., ribonucleic acid or deoxyribonucleic acid). The term polynucleotide in its broadest sense includes any compound and / or substance that is linked or Petition 870250052396, dated 06 / 23 / 2025, pages 96 / 203 89 / 150 may be linked to an oligonucleotide chain. Exemplary polynucleotides for use according to the present invention include, but are not limited to, one or more of the following: deoxyribonucleic acid (DNA), ribonucleic acid (RNA) including messenger mRNA (mRNA), hybrids thereof, RNAi-inducing agents, RNAi-inducing agents, siRNA, shRNA, miRNA, antisense RNA, ribozymes, catalytic DNA, triple helix-inducing RNA, aptamers, vectors, and the like. In some embodiments, the therapeutic and / or prophylactic agent is RNA. The RNA that can be used in the compositions and methods described herein may be selected from, but not limited to, shortmers, antigametaphytes, antisense, ribozymes, small interfering RNA (siRNA), asymmetric interfering RNA (aiRNA), microRNA (miRNA), double-stranded RNA (dsRNA), small hairpin RNA (shRNA), transfer RNA (tRNA), messenger RNA (mRNA), and mixtures thereof. In certain embodiments, the RNA is mRNA.

[00274] In certain embodiments, the therapeutic and / or prophylactic agent is mRNA. The mRNA may encode any polypeptide of interest, including any naturally occurring or unnaturally occurring polypeptide or otherwise modified polypeptide. The polypeptide encoded by the mRNA may be of any size and may have any structure or secondary activity. In some embodiments, the polypeptide encoded by the mRNA may have a therapeutic effect when expressed in a cell.

[00275] In other modalities, the therapeutic and / or prophylactic agent is siRNA. The siRNA may be able to selectively knock down or negatively regulate the expression of the gene of interest. For example, an siRNA may be selected to silence a gene associated with a specific disease, disorder, or condition when a composition of nanoparticles including the siRNA is administered to a Petition 870250052396, dated 06 / 23 / 2025, pp. 97 / 203 90 / 150 individuals who need it. The siRNA may comprise a sequence complementary to an mRNA sequence that encodes a gene or protein of interest. In some modalities, the siRNA may be an immunomodulatory siRNA.

[00276] In some embodiments, the therapeutic and / or prophylactic agent is an shRNA or a vector or plasmid encoding shRNA. After application of the appropriate construct to the nucleus, shRNA can be produced within the target cell. Constructs and mechanisms associated with shRNA are well known in the relevant art.

[00277] The nanoparticle compositions of the present application may comprise one or more components in addition to those described above. For example, said nanoparticle compositions may comprise one or more small hydrophobic molecules, such as vitamins (e.g., vitamin A or vitamin E) or sterols.

[00278] The nanoparticle compositions may also comprise one or more permeability-enhancing molecules, carbohydrates, polymers, surface modifiers, or other components. Said permeability-enhancing molecule may be a molecule described in US patent application No. 2005 / 0222064. Said carbohydrates may include monosaccharides (e.g., glucose) and polysaccharides (e.g., glycogen and its derivatives and analogues).

[00279] Said nanoparticle composition may further comprise one or more polymers, which may be biodegradable and / or biocompatible. Said polymers may be selected from, but not limited to, polyamines, polyethers, polyamides, polyesters, polyurethanes, polyurea, polycarbonates, polystyrene, polyimides, polysulfones, polyurethanes, polyacetylene, polyethylene, polyethyleneimine, polyisocyanates, polyacrylates, polymethacrylates, polyacrylonitrile and polyaryl esters. For example, the polymer may include polycaprolactone (PCL), Petition 870250052396, dated 06 / 23 / 2025, pages 98 / 203 91 / 150 ethylene vinyl acetate polymer (EVA), polylactic acid (PLA), poly L-lactic acid (PLLA), polyglycolic acid (PGA), poly(lactic-coglycolic acid) (PLGA), poly(L-lactic-co-glycolic acid) (PLLGA), poly(D,Llactide) (PDLA), poly(L-lactide (PLLA), poly(D,L-lactidecocaprolactone), poly(D,L-lactide-caprolactone-glycolide), poly(D,Llactide-PEO-co-D,L-lactide), poly(D,L-lactide-co-PPO-co-D,Llactide), polyalkylcyanoacrylate, polyurethane, poly-L-lysine (PLL), hydroxypropyl methacrylate (HPMA), polyethylene glycol, poly-Lglutamic acid, polyhydroxy acids, polyanhydrides, polyorthoesters, poly(ester amides), polyamides, poly(ester ethers), polycarbonates, polyalkylenes, such as polyethylene and polypropylene; polyalkylene glycols, such as poly(ethylene glycol) (PEG); polyalkylene oxide (PEO); polyalkylene terephthalates, such as polyethylene glycol terephthalate; polyvinyl alcohol (PVA); polyvinyl ethers, polyvinyl esters, such as poly(vinyl acetate),Polyvinyl halides, such as polyvinyl chloride (PVC), polyvinylpyrrolidone (PVP), polysiloxanes, polystyrene (PS), polyurethanes, derivatized celluloses, such as alkylcelluloses, hydroxyalkylcelluloses, cellulose ethers, cellulose esters, nitrocellulose, hydroxypropylcellulose, carboxymethylcellulose, acrylic polymers, such as poly(methyl methacrylate) (PMMA), poly(ethyl methacrylate), poly(butyl methacrylate), poly(isobutyl methacrylate), poly(hexyl methacrylate), poly(isodecyl methacrylate), poly(lauryl methacrylate), poly(phenyl methacrylate), poly(methyl acrylate), poly(isopropyl acrylate), poly(isobutyl acrylate), poly(octadecyl acrylate) and copolymers and mixtures thereof, polydioxanone and Polymers of the same, polyhydroxyalkanoates, polypropylene fumarate, polyoxymethylene, poloxamers, polyethylenediamine, poly(orthoesters), poly(butyric acid), poly(valeric acid), poly(lactide-caprolactone), trimethylene carbonate,poly(N-acryloylmorpholine) (PAcM), poly(2-methyl-2-oxazoline) (PMOX), poly(2ethyl-2-oxazoline) (PEOZ) and polyglycerol., Petition 870250052396, dated 06 / 23 / 2025, pp. 99 / 203 92 / 150

[00280] The nanoparticle composition may further comprise one or more surface-modifying agents, which may include, but are not limited to, anionic proteins (e.g., bovine serum albumin), surfactants (e.g., cationic surfactants, such as dimethyl octacosylammonium bromide), sugars or sugar derivatives (e.g., cyclodextrins), nucleic acids, polymers (e.g., heparin, polyethylene glycol, and poloxamers), mucolytics (e.g., acetylcysteine, artemisinin, bromelain, papain, grasses, caprolactone bromide, carbocysteine, eprinodone, mesna, ambroxol, sobrerol, domiodol, letosteine, steronin, tiopronin, gelsolin, nucleosin β4, dornase alfa, neltenexin, and erdosteine) and DNase (e.g., rhDNase).Surface modifiers can be applied within nanoparticles and / or on the surface of the nanoparticle composition (e.g., by coating, adsorption, covalent bonding, or other methods).

[00281] The nanoparticle composition may additionally comprise one or more functionalized lipids. For example, a lipid may be functionalized with an alkynyl group that can undergo a cycloaddition reaction when exposed to an azide under suitable reaction conditions. In particular, the lipid bilayer may be functionalized in this way with one or more groups to facilitate membrane penetration, cell recognition, or imaging. The surface of the nanoparticle composition may also be conjugated with one or more useful antibodies. Functional groups and conjugates useful for targeted cell application, imaging, and membrane penetration are well known in the art.

[00282] In addition to the components described above, the nanoparticle composition may include any substance useful in pharmaceutical compositions. For example, the nanoparticle composition may comprise one or more pharmaceutically acceptable excipients or Petition 870250052396, dated 06 / 23 / 2025, pages 100 / 203 93 / 150 auxiliary ingredients, such as, but not limited to, one or more solvents, dispersing media, diluents, dispersing aids, suspending agents, granulating aids, disintegrants, fillers, glidants, liquid carriers, binders, surfactants, isotonic agents, thickening or emulsifying agents, buffers, lubricants, oils, preservatives and other materials. Excipients, such as waxes, butters, colorants, coatings, flavors and flavor enhancers, may also be included. Pharmaceutically acceptable excipients are well known in the art.

[00283] Examples of diluents may include, but are not limited to, calcium carbonate, sodium carbonate, calcium phosphate, dicalcium phosphate, calcium sulfate, calcium hydrogen phosphate, sodium phosphate, lactose, sucrose, cellulose, microcrystalline cellulose, kaolin, mannitol, sorbitol, inositol, sodium chloride, dry starch, corn starch, powdered sugar and / or combinations thereof.Granulating and dispersing agents may be selected from potato starch, corn starch, tapioca starch, sodium starch glycolate, clays, alginic acid, guar gum, citrus pulp, agar, bentonite, cellulose and wood products, cation exchange resins, calcium carbonate, silicates, sodium carbonate, crosslinked poly(vinylpyrrolidone), sodium carboxymethyl starch (sodium starch glycolate), carboxymethylcellulose, crosslinked sodium carboxymethylcellulose (croscarmellose), methylcellulose, pregelatinized starch (starch 1500), microcrystalline starch, water-insoluble starch, calcium carboxymethylcellulose, aluminum and magnesium silicate, sodium lauryl sulfate, quaternary ammonium compounds and / or combinations thereof.

[00284] Surfactants and / or emulsifiers may include, but are not limited to, natural emulsifiers (e.g., acacia, agar, alginic acid, sodium alginate, chondroitin, cholesterol, xanthan gum, pectin, gelatin, egg yolk, casein, lanolin, cholesterol, waxes and lecithin). Petition 870250052396, dated 06 / 23 / 2025, pages 101 / 203 94 / 150 na), colloidal clays (e.g., bentonite [aluminum silicate] and VEEGUM® [aluminum magnesium silicate]), long-chain amino acid derivatives, high molecular weight alcohols (e.g., stearyl alcohol, cetyl alcohol, oleyl alcohol), triacetin monostearate, ethylene glycol distearate, glycerol monostearate and propylene glycol monostearate, polyvinyl alcohol), carbomers (e.g., carboxypolymethylene, polyacrylic acid, acrylic acid polymers and carboxyvinyl polymers), carrageenan, cellulose derivatives (e.g., sodium carboxymethylcellulose, powdered cellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose), a sorbitan fatty acid ester (e.g., polyoxyethylene sorbitan monolaurate [TW EEN®20], polyoxyethylene sorbitan [TWEEN®60], polyoxyethylene sorbitan monooleate [TWEEN®80], sorbitan monopalmitate [SPAN®40], sorbitan monostearate [SPAN®60],sorbitan tristearate [SPAN®65], glycerol monooleate, sorbitan monooleate [SPAN®80], polyoxyethylene esters (e.g., polyoxyethylene monostearate [MYRJ®45], polyoxyethylene hydrogenated castor oil, polyethoxylated castor oil, polyoxymethylene stearate and SOLUTOL®], sucrose fatty acid esters, polyethylene glycol fatty acid esters (e.g., CREMOPHOR®), polyoxyethylene ethers (e.g., polyoxyethylene lauryl ether [BRIJ®30]), poly(vinylpyrrolidone), diethylene glycol monolaurate, triethanolamine oleate, sodium oleate, potassium oleate, ethyl oleate, oleic acid, ethyl laurate, sodium dodecyl sulfate, PLURONIC®F68, POLOXAMER®188, cetrimonium bromide, cetylpyridinium chloride, benzalkonium chloride, sodium docusate and / or combinations thereof.

[00285] Binders may be starches (e.g., corn starch and starch paste), gelatin, sugars (e.g., sucrose, glucose, dextrose, dextrin, molasses, lactose, lactitol, mannitol), gums Petition 870250052396, dated 06 / 23 / 2025, pages 102 / 203 95 / 150 natural and synthetic (e.g., acacia, sodium alginate, Irish moss extract, panwar gum, ghatti gum, Isabel bark mucilage, carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, cellulose acetate, poly(vinylpyrrolidone), aluminum magnesium silicate (VEEGUM®) and larch arabinogalactan), alginates, polyethylene oxide, polyethylene glycol, inorganic calcium salts; silicic acid, polymethacrylate, wax, water, alcohols, combinations thereof or any other suitable binder.

[00286] Examples of preservatives may include, but are not limited to, antioxidants, chelating agents, antimicrobial preservatives, antifungal preservatives, alcoholic preservatives, acidic preservatives and / or other preservatives. Examples of antioxidants include, but are not limited to, alpha-tocopherol, ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, sodium metabisulfite and / or sodium sulfite. Examples of chelating agents include ethylenediaminetetraacetic acid (EDTA), citric acid monohydrate, disodium edetate, dipotassium edetate, edetic acid, fumaric acid, malic acid, phosphoric acid, sodium edetate, tartaric acid, and / or trisodium edetate.Examples of antimicrobial preservatives include, but are not limited to, benzalkonium chloride, benzethonium chloride, benzyl alcohol, bromophenol, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, ethanol, glycerol, hexyloxybutanol, imidurea, phenethyl alcohol, phenylmercuric nitrate, propylene glycol, and / or thimerosal. Examples of antifungal preservatives include, but are not limited to, butylparaben, methylparaben, ethylparaben, propylparaben, benzoic acid, hydroxybenzoic acid, potassium benzoate, potassium sorbate, sodium benzoate, sodium propionate, and / or sorbic acid. Petition 870250052396, dated 06 / 23 / 2025, pages 103 / 203 96 / 150 Examples of alcoholic preservatives include, but are not limited to, ethanol, polyethylene glycol, benzyl alcohol, phenol, phenolic compounds, bisphenol, chlorobutanol, hydroxybenzoate, and / or phenylethyl alcohol. Examples of acidic preservatives include, but are not limited to, vitamin A, vitamin C, vitamin E, beta-carotene, citric acid, acetic acid, dehydroascorbic acid, ascorbic acid, sorbic acid, and / or phytic acid. Other preservatives include, but are not limited to, tocopherol, tocopherol acetate, deoxyoxime mesylate, cetrimide, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ethylenediamine, sodium lauryl sulfate (SLS), sodium bisulfite, sodium metabisulfite, potassium sulfite, potassium metabisulfite, GLYDANTPLUS®, PHENONIP®, methyl p-hydroxybenzoate, GERMALL®115, GERMABEN®II, NEOLONE™, KATHON™ and / or EUXYL®.

[00287] Examples of buffering agents include, but are not limited to, citrate buffer solution, acetate buffer solution, phosphate buffer solution, ammonium chloride, calcium carbonate, calcium chloride, calcium citrate, calcium gluconate, calcium gluceptate, calcium gluconate, d-gluconic acid, calcium glycerophosphate, calcium lactate, calcium lactobionate, propionic acid, calcium levulinate, pentanoic acid, dibasic calcium phosphate, phosphoric acid, tricalcium phosphate, calcium hydrogen phosphate, potassium acetate, potassium chloride, potassium gluconate, potassium mixtures, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, potassium phosphate mixtures, sodium acetate, sodium bicarbonate, sodium chloride, sodium citrate, sodium lactate, disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium phosphate mixtures, tromethamine, sulfamate buffers, magnesium hydroxide, aluminum hydroxide, alginic acid,Pyrogen-free water, isotonic saline solution, Ringer's solution, ethanol, and / or combinations thereof. The lubricant is selected from magnesium stearate, calcium stearate, acid, Petition 870250052396, dated 06 / 23 / 2025, pp. 104 / 203 97 / 150 stearic acid, silicon dioxide, talc, malt, hydrogenated vegetable oil, polyethylene glycol, sodium benzoate, sodium acetate, sodium chloride, leucine and magnesium laurate, sulfates, sodium lauryl sulfate and combinations thereof.

[00288] Examples of oils include, but are not limited to, almond, apricot kernel, avocado, babassu, bergamot, blackcurrant kernel, borage, chamomile, canola, caraway, carnauba, castor, cinnamon, cocoa butter, coconut, cod liver, coffee, corn, cottonseed, eucalyptus, evening primrose, fish, flaxseed, geraniol, gourd, grapeseed, hazelnut, hyssop, isopropyl myristate, jojoba oil, lavender, lavandin, lemon, macadamia nut, mallow, mango kernel, mink skin, nutmeg, olive, orange, palm, palm kernel, peach kernel, peanut, poppy seed, pumpkin seed, rapeseed, rice bran, rosemary, safflower, sandalwood, essence, sea buckthorn, sesame, shea butter, silicone, soy, sunflower, tea tree, thistle, Ailanthus altissima, vetiver, walnut oil and wheat germ and butyl stearate, caprylic triglyceride, capric triglyceride, cyclomethicone, diethyl sebacate, dimethicone, isopropyl myristate,Mineral oil, octyldodecanol, oleyl alcohol, silicone oil and / or combinations thereof.

[00289] The nanoparticle composition, as described in this application, may comprise a lipid component and one or more other components, such as a therapeutic and / or prophylactic agent. The nanoparticle composition may be designed for one or more specific uses or targets. The elements of the nanoparticle compositions may be selected based on a specific use or target and / or based on the efficacy, toxicity, cost, ease of use, availability, or other characteristics of one or more elements. Similarly, the specific formulation of the nanoparticle composition may be selected for a specific use or target with Petition 870250052396, dated 06 / 23 / 2025, pages 105 / 203 98 / 150 based, for example, on the efficacy and toxicity of a specific combination of elements.

[00290] The lipid component of said nanoparticle composition may comprise, for example, the compound according to formula (I), (IA), (IA-1), (IA-2), (IA-3), (IA-4), (IA-5), (IA-6), (IIA), (IIA-A), (IIA-B), (IIA-C), (IIA-D), (IIA-E), (IIA-F), (IIA-G), (IIA-H), (IB), (IB-1), (IB2), (IB-3), (IB-4), (IB-5), (IB-6), (IC), (IC-1), (IC-2), (IC-3), (IC-4), (IC-5), (IC-6), (IC-7), (IC-8), (IC-9), (IC-10), (IC-11), (ID), (ID-1), (ID-2), (ID-3), (ID-4), (ID-5), (ID-6), (ID-7), (ID-8), (ID-9), (ID-10), (ID-11), a phospholipid (e.g., unsaturated lipids such as DOPE or DSPC), a PEG lipid, and a structural lipid.

[00291] Nanoparticle compositions can be designed for one or more specific uses or targets. For example, nanoparticle compositions can be designed to apply a therapeutic and / or prophylactic agent, such as RNA, to a specific cell, tissue, organ, or system or group thereof within a mammalian body. The physicochemical properties of the nanoparticle composition can be altered to increase selectivity for specific body targets. For example, particle size can be adjusted based on the size window of different organs. The therapeutic and / or prophylactic agents included in the nanoparticle compositions can also be selected based on one or more desired application targets.For example, a therapeutic and / or prophylactic agent may be selected for a particular indication, condition, disease or disorder and / or application (e.g., local or specific application) to a specific cell, tissue, organ or system or group thereof. In certain embodiments, the nanoparticle composition may include mRNA encoding a polypeptide of interest that can be translated in a cell to produce the polypeptide of interest. Such compositions may be designed to... Petition 870250052396, dated 06 / 23 / 2025, pages 106 / 203 99 / 150 specific application to a specific organ. In some embodiments, the composition may be designed for specific application to the liver of a mammal.

[00292] The amount of therapeutic and / or prophylactic agent in the nanoparticle composition may depend on: the size, composition of the nanoparticle composition, the desired target and / or application or other properties, and the nature of the therapeutic and / or prophylactic agent; for example, the amount of RNA that can be used in the nanoparticle composition may depend on the size, sequence and other characteristics of the RNA. The relative amounts of therapeutic and / or prophylactic agent and other elements (e.g., lipids) in the nanoparticle compositions may also vary.

[00293] The properties of nanoparticle compositions can depend on their components. For example, a nanoparticle composition comprising cholesterol as a structural lipid may have different properties from a nanoparticle composition comprising a different structural lipid. Similarly, the properties of nanoparticle compositions can depend on the absolute or relative amounts of their components. For example, a nanoparticle composition comprising a phospholipid with a relatively high molar proportion may have different properties from a nanoparticle composition comprising a phospholipid with a relatively low molar proportion. Properties may also vary depending on the method and conditions of preparation of the nanoparticle composition.

[00294] Nanoparticle compositions can be characterized by a variety of methods. For example, a microscope (e.g., transmission electron microscope or scanning electron microscope) can be used to examine the morphology and Petition 870250052396, dated 06 / 23 / 2025, pages 107 / 203 100 / 150 particle size distribution of nanoparticle composition. Dynamic light scattering or potentiometry (e.g., potentiometric titration) can be used to measure the zeta potential. Dynamic light scattering can also be used to determine particle size.

[00295] The nanoparticle composition has an average particle size of 50 nm to 110 nm.

[00296] The composition of nanoparticles can be relatively homogeneous. The polydispersity index can be used to indicate the homogeneity of the nanoparticle composition, for example, the particle size distribution of the nanoparticle composition. A small polydispersity index (e.g., less than 0.3) generally indicates a narrow particle size distribution. The nanoparticle composition has a polydispersity index of 0.04 to 0.20. For example, it can be 0.05, 0.06, 0.07, 0.08, 0.09, 0.10, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, or 0.19.

[00297] The encapsulation efficiency of a therapeutic and / or prophylactic agent describes the amount of the therapeutic and / or prophylactic agent that is encapsulated or otherwise associated with the nanoparticle composition after preparation, relative to the initial amount supplied. Encapsulation efficiency is expected to be as high as possible (e.g., close to 100%). Encapsulation efficiency can be measured, for example, by comparing the amount of the therapeutic and / or prophylactic agent in a solution containing the nanoparticle composition before and after the nanoparticle composition is decomposed with one or more organic solvents or detergents. Fluorescence can be used to measure the amount of free therapeutic and / or prophylactic agent (e.g., RNA) in a solution. For the nanoparticle compositions described herein, the encapsulation efficiency of a therapeutic and / or prophylactic agent Petition 870250052396, dated 06 / 23 / 2025, pages 108 / 203 101 / 150 can be at least 50%, for example, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%. In some embodiments, the encapsulation efficiency can be at least 80%. In certain embodiments, the encapsulation efficiency can be at least 90%.

[00298] The nanoparticle composition may optionally comprise one or more coatings. For example, the nanoparticle composition may be formulated into capsules, films, or tablets with a coating. Capsules, films, or tablets containing the compositions described herein may be of any size, tensile strength, hardness, or useful density.

[00299] The nanoparticle compositions of the present application may be formulated in whole or in part as pharmaceutical compositions. The pharmaceutical composition may comprise one or more nanoparticle components. For example, the pharmaceutical composition may include one or more nanoparticle compositions comprising one or more different therapeutic and / or prophylactic agents. The pharmaceutical composition may further comprise one or more pharmaceutically acceptable excipients or auxiliary ingredients, such as those described herein, unless any conventional excipient or auxiliary ingredient may be incompatible with one or more components of the nanoparticle composition. If the excipient or auxiliary ingredient is incompatible with a component of the nanoparticle composition, its combination with that component may result in any undesirable biological effects or other adverse effects.

[00300] In some embodiments, one or more excipients or auxiliary ingredients may constitute more than 50% of the total mass or volume of the pharmaceutical composition comprising the nanoparticle composition. For example, one or more excipients or auxiliary ingredients Petition 870250052396, dated 06 / 23 / 2025, pp. 109 / 203 102 / 150 auxiliary excipients may constitute 50%, 60%, 70%, 80%, 90% or more of the pharmaceutically acceptable excipient. In some embodiments, the pharmaceutically acceptable excipient is at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% pure. In some embodiments, the excipient is approved for human and veterinary use.

[00301] The relative amounts of one or more nanoparticle compositions, one or more pharmaceutically acceptable excipients and / or any other ingredients in the pharmaceutical compositions, according to this application, will vary depending on the identity, size and / or disease condition of the individual to be treated and further depending on the route of administration of the composition. By way of example, the pharmaceutical composition may comprise one or more nanoparticle compositions in the range of 0.1% to 100% (weight / weight).

[00302] Nanoparticle compositions and / or pharmaceutical compositions comprising one or more of said nanoparticle compositions may be administered to any patient or individual, including those who may benefit from a therapeutic effect provided by the application of the therapeutic and / or prophylactic agent to one or more cells, tissues, organs or systems or specific groups thereof (e.g., the renal system). Although the descriptions of nanoparticle compositions and pharmaceutical compositions comprising nanoparticle compositions provided herein are primarily directed to compositions suitable for administration to a human being, it will be understood by those skilled in the art that such compositions are generally suitable for administration to any other mammal. Modifications to the compositions suitable for administration to humans are well known in order to make the compositions suitable for administration to various Petition 870250052396, dated 06 / 23 / 2025, pages 110 / 203 103 / 150 animal rivers, and such modifications can often be designed and / or carried out by experienced veterinary pharmacologists through ordinary experimentation (if any) only, including, but not limited to, humans, other primates and other artificial animals, including commercially relevant mammals such as cows, pigs, horses, sheep, cats, dogs, rats and / or mice.

[00303] A pharmaceutical composition comprising one or more nanoparticle compositions may be prepared by any method known or subsequently developed in the field of pharmacology. Generally, such preparation methods involve combining the active ingredient with excipients and / or one or more other auxiliary ingredients and then, if desired or necessary, dividing, shaping and / or packaging the product into the desired single or multiple dosage units.

[00304] Pharmaceutical compositions, according to the present application, may be manufactured, packaged and / or sold in bulk in a single unit dose and / or in a plurality of single unit doses. As used herein, a unit dose is the precise quantity of a pharmaceutical composition containing a predetermined amount of active ingredient (e.g., a nanoparticle composition). The amount of active ingredient is generally equal to the dose of active ingredient to be administered to the individual and / or a convenient fraction of that dose, for example, half or one-third of that dose.

[00305] Pharmaceutical compositions can be prepared in a variety of forms suitable for a variety of routes and methods of administration. For example, pharmaceutical compositions can be prepared in liquid dosage forms (e.g., emulsions, microemulsions, nanoemulsions, solutions, suspensions, syrups, and medicaments), injectable forms, dosage forms Petition 870250052396, dated 06 / 23 / 2025, page 111 / 203 104 / 150 Solid dosage forms (e.g., capsules, tablets, tablets, etc.), liquids, powders and granules), formulations for topical and / or transdermal administration (e.g., ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants and plasters), suspensions, powders and other forms. Liquid dosage forms for oral and parenteral administration include, but are not limited to, emulsions, microemulsions, nanoemulsions, solutions, suspensions, syrups and / or pharmaceutically acceptable drugs.

[00306] In addition to the active ingredients, liquid dosage forms may include inert diluents commonly used in the technique, such as water or other solvents, solubilizing and emulsifying agents such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil and sesame oil), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and sorbitol fatty acid esters and mixtures thereof. In addition to inert diluents, oral compositions may also include other therapeutic and / or prophylactic agents, other agents such as humectants, emulsifying and suspending agents, sweeteners, flavors and / or fragrances.In certain parenteral administration formulations, the composition is mixed with a solubilizing agent (e.g., an alcohol, oil, modified oil, glycol, polysorbate, cyclodextrin, polymer, and / or combinations thereof).

[00307] Injectable preparations, for example, sterile aqueous or oily injectable suspensions, may be formulated according to known techniques using suitable dispersing, wetting and / or suspending agents. The sterile injectable preparation may be a sterile injectable solution, suspension and / or emulsion in a diluent. Petition 870250052396, dated 06 / 23 / 2025, pp. 112 / 203 105 / 150 and / or a non-toxic parenterally acceptable solvent, for example, a solution in 1,3-butanediol. Acceptable vehicles and solvents, including water, may be used. Sterile, non-volatile oils are conventionally employed as a solvent or suspension medium. For this purpose, any mild non-volatile oils, including synthetic mono- or diglycerides, may be used. Fatty acids, such as oleic acid, may be used in the preparation of injectables.

[00308] Injectable formulations can be sterilized, for example, by filtration through a bacteria-retention filter and / or by incorporating sterilizing agents in the form of sterile solid compositions that can be dissolved or dispersed in sterile water or other sterile injectable medium before use.

[00309] In order to prolong the effect of the active ingredient, it is often desirable to delay the absorption of the active ingredient from subcutaneous or intramuscular injection. This can be achieved by using a liquid suspension of crystalline or amorphous material that is unsatisfactorily soluble in water. The rate of drug absorption then depends on its rate of dissolution, which in turn depends on the crystal size and crystal shape. Alternatively, delayed absorption of a parenterally administered drug form is achieved by dissolving or suspending the drug in an oil carrier. Injectable depot forms are made by forming microencapsulated matrices of the drug in biodegradable polymers (such as polylactic acid-polyethylene glycol). The drug release rate can be controlled depending on the drug-to-polymer ratio and the nature of the specific polymer used.Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Stock injection formulations are prepared by incorporating the drug into liposomes or microemulsions that are compatible with the test tubes. Petition 870250052396, dated 06 / 23 / 2025, pp. 113 / 203 106 / 150 body acids.

[00310] Compositions for rectal or vaginal administration are typically suppositories that can be prepared by mixing the composition with suitable non-irritating excipients, such as cocoa butter, polyethylene glycol or a suppository wax. Said excipients are solid at room temperature, but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active ingredient.

[00311] Solid dosage forms for oral administration include capsules, tablets, pills, films, powders, and granules.In such solid dosage forms, the active ingredient is mixed with at least one pharmaceutically acceptable inert excipient, such as sodium citrate or dicalcium phosphate and / or fillers or extenders (e.g., starches, lactose, sucrose, glucose, mannitol, and silicic acid), binders (e.g., carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and acacia), humectants (e.g., glycerol), disintegrating agents (e.g., agar, calcium carbonate, potato starch or tapioca starch, alginic acid, certain silicates, and sodium carbonate), retarding agents (e.g., paraffin), absorption enhancers (e.g., quaternary ammonium compounds), wetting agents (e.g., cetyl alcohol and glyceryl monostearate), absorbents (e.g., kaolin and bentonite, silicates), and lubricants (e.g., talc), stearate of calcium, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate) and mixtures thereof.In the case of capsules, tablets and pills, dosage forms may include buffering agents.

[00312] Solid compositions of a similar type can be used as fillers in soft and hard gelatin capsules, which use excipients such as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like. The forms of Petition 870250052396, dated 06 / 23 / 2025, pp. 114 / 203 Solid compositions, such as tablets, dragees, capsules, pills, and granules, can be prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical formulation art. They may optionally contain opacifying agents and may have a composition in which they release the active ingredient only, or preferably, in a certain part of the intestinal tract, optionally in a delayed manner. Examples of incorporation compositions that can be used include polymeric substances and waxes. Solid compositions of a similar type can be employed as excipients, such as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like, as fillers in soft and hard filled gelatin capsules.

[00313] Dosage forms for topical and / or transdermal administration of the compositions may include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants and / or patches. Typically, the active ingredient is mixed under sterile conditions with pharmaceutically acceptable excipients and / or any preservatives and / or buffers that may be necessary. In addition, the present application contemplates the use of transdermal patches, which generally have the added advantage of providing controlled application of the compound to the body. Such dosage forms may be prepared, for example, by dissolving and / or dispensing the compound in a suitable medium. Alternatively or additionally, the rate may be controlled by providing a rate-control membrane and / or dispensing the compound in a polymeric matrix and / or gel.

[00314] Suitable formulations for topical administration include, but are not limited to, liquid and / or semi-liquid formulations, such as liniments, lotions, oil-in-water and / or water-in-oil emulsions, such as creams, ointments and / or pastes and / or solutions and / or suspensions. Petition 870250052396, dated 06 / 23 / 2025, pages 115 / 203 108 / 150 doses, although the concentration of the active ingredient may be as high as the solubility limit of the active ingredient in the solvent. Topical formulations may additionally include one or more of the other ingredients described herein.

[00315] Pharmaceutical compositions may be prepared, packaged and / or sold in a formulation suitable for pulmonary administration via the oral cavity. Such formulations may comprise dry particles of the active ingredient. Such compositions are conveniently in the form of a dry powder for administration using a device comprising a dry powder reservoir to which a stream of propellant may be directed to disperse the powder and / or using a self-propelling solvent / powder dispensing container, such as a device comprising the active ingredient dissolved and / or suspended in a low-boiling-point propellant in a sealed container. Powder compositions may comprise a fine solid powder diluent, such as a sugar, and are conveniently supplied in unit dose form.

[00316] Low-boiling-point propellants typically include liquid propellants having a boiling point below 65°F at atmospheric pressure. Typically, the propellant may constitute 50% to 99.9% (w / w) of the composition, while the active ingredient may constitute 0.1% to 20% (w / w) of the composition. The propellant may additionally comprise other ingredients, such as liquid and / or solid anionic nonionic surfactants and / or solid diluents (whose particle size may be of the same order as the particles comprising the active ingredient).

[00317] Pharmaceutical compositions formulated for pulmonary application may deliver the active ingredient in the form of solution droplets and / or suspension. Such formulations may be prepared, packaged and / or sold as alcoholic solutions and / or suspensions. Petition 870250052396, dated 06 / 23 / 2025, pages 116 / 203 109 / 150 aqueous and / or diluted, optionally sterile, doses containing the active ingredient can be conveniently administered using any atomizing and / or nebulizing device. Such formulations may additionally comprise one or more other ingredients including, but not limited to, flavorings such as sodium saccharin, volatile oils, buffering agents, surfactants and / or preservatives such as methyl hydroxybenzoate. The average droplet diameter delivered by this route of administration may be in the range of 1 nm to 200 nm.

[00318] The formulations useful for pulmonary application described herein can be used for intranasal application of pharmaceutical compositions. Another suitable formulation for intranasal administration is a coarse powder comprising the active ingredient and having an average particle size of 0.2 to 500 μm. Such formulations are administered by rapid inhalation aspiration through the nasal passage from a powder container held close to the nose.

[00319] Formulations suitable for nasal administration may, for example, contain from 0.1% (w / w) to 100% (w / w) of the active ingredient and may contain one or more of the other active ingredients described herein. Pharmaceutical compositions may be prepared, packaged and / or sold in formulations suitable for oral administration. Such formulations may, for example, be in the form of tablets and / or lozenges prepared using conventional methods and may, for example, have 0.1% to 20% (w / w) of the active ingredient, the remainder comprising an orally dissolvable and / or degradable composition and, optionally, one or more other ingredients described herein. Alternatively, formulations suitable for oral administration may comprise powders and / or solutions and / or aerosolized and / or atomized suspensions containing the active ingredient. Such powder and / or aerosolized formulations, when dispersed, Petition 870250052396, dated 06 / 23 / 2025, pp. 117 / 203 110 / 150 may have an average particle and / or droplet size in the range of 0.1 nm to 200 nm and may additionally comprise one or more other ingredients described herein.

[00320] Pharmaceutical compositions may be prepared, packaged and / or sold in a formulation suitable for ophthalmic administration. Such formulations may be in the form of, for example, drops comprising, for example, a solution and / or suspension of 0.1 / 1.0% (w / w) of the active ingredient in an aqueous or oily liquid excipient. Such drops may further comprise a buffer, a salt and / or one or more of any other additive ingredients described herein. Other formulations useful for ophthalmic administration include those comprising the active ingredient in microcrystalline and / or liposomal form. Ear drops and / or eye drops are contemplated as being within the scope of this description.

[00321] Method for producing a polypeptide in a cell

[00322] The present application further provides methods for producing a polypeptide of interest in a mammalian cell. The methods for producing a polypeptide include placing a cell in contact with a nanoparticle composition comprising an mRNA encoding a polypeptide of interest. After placing the cell in contact with the nanoparticle composition, the mRNA can be absorbed and translated in the cell to produce the polypeptide of interest.

[00323] Generally, the step of placing the mammalian cell in contact with the nanoparticle composition comprising mRNA encoding the polypeptide of interest can be performed in vivo, ex vivo, in culture, or in vitro. The amount of nanoparticle composition placed in contact with the cell and / or the amount of mRNA in the same may depend on the type of cell or tissue in contact, the mode of administration, and the physicochemical properties. Petition 870250052396, dated 06 / 23 / 2025, pages 118 / 203 111 / 150 of the nanoparticle and mRNA composition (e.g., size, charge, and chemical composition) and other factors. Generally, an effective amount of nanoparticle composition will allow for efficient polypeptide production in the cell. Efficiency measures may include polypeptide translation (as indicated by polypeptide expression), mRNA degradation levels, and indicators of immune response.

[00324] The step of bringing the nanoparticle composition comprising mRNA into contact with the cell may involve or cause transfection. The phospholipid included in the lipid component of the nanoparticle composition may facilitate transfection and / or increase transfection efficiency, for example, by interaction and / or fusion with cells or intracellular membranes. Transfection may allow mRNA translation in the cell.

[00325] In some embodiments, the nanoparticle compositions described herein may be used in therapy. For example, the mRNA contained in the nanoparticle composition may encode a therapeutic polypeptide (e.g., in a translatable region) and produce the therapeutic polypeptide upon contact with and / or entry (e.g., transfection) into a cell. In other embodiments, the mRNA contained in the nanoparticle composition may encode a polypeptide that may enhance or augment immunity in an individual. For example, the mRNA may encode granulocyte colony-stimulating factor or trastuzumab.

[00326] In certain embodiments, the mRNA included in the nanoparticle composition may encode a recombinant polypeptide that can replace one or more polypeptides that may not be substantially present in the cell in contact with the nanoparticle composition. One or more substantially absent polypeptides may be absent due to genetic mutations in the encoding gene. Petition 870250052396, dated 06 / 23 / 2025, pp. 119 / 203 112 / 150 pain or regulatory pathways thereof. Alternatively, a recombinant polypeptide produced by translation of an mRNA can antagonize the activity of an endogenous protein present in, on the surface of, or secreted from the cell. Antagonistic recombinant polypeptides may be desirable to combat adverse effects caused by the activity of the endogenous protein, such as localization caused by altered activity or mutations. Alternatively, a recombinant polypeptide produced by translation of an mRNA can indirectly or directly antagonize the activity of a biological fraction present in, on the surface of, or secreted from the cell. Antagonistic biological fractions may include, but are not limited to, lipids (e.g., cholesterol), lipoproteins (e.g., low-density lipoproteins), nucleic acids, carbohydrates, and small molecule toxins.Recombinant polypeptides produced by mRNA translation can be genetically modified to be localized within a cell, for example, within a specific compartment such as the nucleus, or they can be genetically modified to be secreted from the cell or transported to the cell's plasma membrane.

[00327] In some embodiments, contact of a cell with a nanoparticle composition comprising mRNA can reduce the cell's innate immune response to exogenous nucleic acid. The cell can be brought into contact with a first nanoparticle composition comprising a first amount of an exogenous mRNA including a translatable region, and a level of the cell's innate immune response to the first exogenous mRNA can be determined. Subsequently, the cell can be brought into contact with a second composition comprising a second amount of the first exogenous mRNA, the second amount being a smaller amount of the first exogenous mRNA compared to the first composition. Petition 870250052396, dated 06 / 23 / 2025, pages 120 / 203 113 / 150 with the first quantity. Alternatively, the second composition may comprise a first quantity of a second exogenous mRNA that is different from the first exogenous mRNA. The step of exposing the cell to the first and second compositions may be repeated one or more times. Furthermore, the efficiency of polypeptide production (e.g., translation) in the cell may optionally be determined, and the cell may be repeatedly exposed to the first and / or second composition until the target protein production efficiency is achieved.

[00328] This application further provides a method for treating a disease or disorder in a mammal, comprising administering to the mammal a therapeutically effective amount of the nanoparticle composition of any of the foregoing items, in particular, the nanoparticle composition is useful for treating a disease, disorder or condition characterized by a loss or abnormality in the activity of proteins or polypeptides. For example, a nanoparticle composition comprising mRNA encoding a deleted or aberrant polypeptide can be administered or delivered to a cell. Subsequent translation of the mRNA can produce the polypeptide, thus reducing or eliminating the problems caused by the lack or aberrant activity of the polypeptide. Because translation can occur rapidly, such methods and compositions can be useful for treating acute diseases, disorders or conditions such as sepsis, stroke and myocardial infarction.The therapeutic and / or prophylactic agents included in nanoparticle compositions may also be able to alter the transcription rate of a given species, thus affecting gene expression.

[00329] Diseases, disorders and / or conditions characterized by dysfunctional or abnormal protein or polypeptide activity include, Petition 870250052396, dated 06 / 23 / 2025, pages 121 / 203 114 / 150 but are not limited to, rare diseases, infectious diseases (e.g., vaccines and therapies), cancer and proliferative diseases, genetic diseases (e.g., cystic fibrosis), autoimmune diseases, diabetes, neurodegenerative diseases, cardiovascular and renal vascular diseases, and metabolic diseases.

[00330] The present application provides methods involving the administration of nanoparticle compositions comprising one or more therapeutic and / or prophylactic agents and pharmaceutical compositions comprising the nanoparticle compositions. The terms therapeutic and prophylactic are used interchangeably in the present invention with respect to the features and embodiments of the present application. The therapeutic or imaging, diagnostic or prophylactic composition thereof may be administered to an individual using any reasonable amount and any effective route of administration to prevent, treat, diagnose or image a disease, disorder and / or condition and / or any other purpose. The specific amount administered to a specific individual may vary depending on the species, age and general condition of the individual; purposes of administration; specific ingredients; mode of administration; and so forth.The compositions, according to the present application, may be formulated in unit dosage form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily amount of the composition of the present application will be determined by the attending physician within the scope of rational medical judgment. The specific therapeutically effective, prophylactically effective, or other appropriate dosage level (e.g., for imaging) for any specific patient will depend on a variety of factors, including the severity and identification (if any) of the disease being treated; one or more therapeutic and / or prophylactic agents used; the specific ingredients. Petition 870250052396, dated 06 / 23 / 2025, pages 122 / 203 115 / 150 pharmaceutical ingredients used; the patient's age, body weight, general health, sex, and diet; the time of administration, the route of administration, and the excretion rate of the specific pharmaceutical ingredient used; the duration of treatment; drugs used in combination or concomitantly with the specific pharmaceutical ingredients, as used; and factors well known in the medical field.

[00331] This application further provides a method for specifically applying a therapeutic and / or prophylactic agent to a mammalian organ comprising administering the nanoparticle composition, according to any of the foregoing items, to the mammal, wherein said administration comprises placing the mammalian organ in contact with the nanoparticle composition, thereby applying the therapeutic and / or prophylactic agent to the organ. The therapeutic and / or prophylactic agent, such as proteins, cytotoxic agents, radioactive ions, chemotherapeutic agents or nucleic acids (e.g. RNA, e.g. mRNA) may be delivered to the cell or organ. In the case where the therapeutic and / or prophylactic agent is mRNA, the translatable mRNA may be translated in the cell to produce the polypeptide of interest when the cell is placed in contact with the nanoparticle composition. However, substantially untranslatable mRNAs may also be delivered to the cell.Substantially untranslatable mRNA can be used as a vaccine and / or can hijack translational components of the cell to reduce the expression of other species in the cell.

[00332] In some embodiments, the nanoparticle composition may target a specific cell type or class (e.g., a cell of a specific organ or system). For example, a nanoparticle composition comprising a therapeutic and / or prophylactic agent of interest may be specifically applied to the liver, kidney, spleen, femur, gastrointestinal tract, or Petition 870250052396, dated 06 / 23 / 2025, pages 123 / 203 116 / 150 lung of a mammal. The specific application to a particular class of cells, organs or systems or groups thereof means that a higher proportion of the nanoparticle composition including a therapeutic and / or prophylactic agent is applied to the target destination (e.g., a tissue) compared to other destinations, for example, when the nanoparticle composition is administered to a mammal. In some embodiments, the target tissue is selected from liver, kidney, lung, spleen, femur, eye, gastrointestinal tract tissue (e.g., by intraocular, subretinal or intravitreal injection), vascular endothelium in blood vessels (e.g., intracoronary or intrafemoral) or kidney and tumor tissue (e.g., by intratumoral injection).

[00333] As another example of targeted or specific delivery, an mRNA encoding a protein-binding partner (e.g., an antibody or functional fragment thereof, a protein scaffold or peptide) or receptor on the surface of a cell can be included in the nanoparticle composition. The mRNA can alternatively be enhanced or alternatively targeted to target the extracellular synthesis and localization of lipids, carbohydrates, or other biological fractions. Alternatively, other therapeutic and / or prophylactic agents or elements (e.g., lipids or ligands) of the nanoparticle composition can be selected based on their affinity for a specific receptor (e.g., low-density lipoprotein receptor), so that the nanoparticle composition can interact more readily with a target cell population that includes the receptor.

[00334] In some embodiments, the ligand may be a surface-bound antibody, which may allow modulation of cell-targeting specificity. This is particularly useful because highly specific antibodies can be created against the interPetição epitope. 870250052396, 23 / 06 / 2025, p. 124 / 203 117 / 150 resse at the desired target site. In one embodiment, multiple antibodies are expressed on the cell surface and each antibody may have a different specificity for a desired target. Such an approach can improve the affinity and specificity of the targeted interaction.

[00335] Target cells may include, but are not limited to, hepatocytes, epithelial cells, hematopoietic cells, epithelial cells, endothelial cells, lung cells, bone cells, stem cells, mesenchymal cells, neural cells, cardiac cells, adipocytes, vascular smooth muscle cells, cardiac muscle cells, skeletal muscle cells, beta cells, pituitary cells, synovial lining cells, ovarian cells, testicular cells, fibroblasts, B cells, T cells, reticulocytes, leukocytes, granulocytes, and tumor cells.

[00336] In some embodiments, the nanoparticle composition may target hepatocytes.

[00337] In some embodiments, the nanoparticle composition may target extra-hepatic cells.

[00338] In some preferred embodiments, the nanoparticle composition can target the spleen, stomach, or intestinal tract.

[00339] The nanoparticle composition of the present application can be administered by any route. In some embodiments, a composition comprising a prophylactic, diagnostic or imaging composition comprising one or more nanoparticle compositions of the present application is administered by one or more of a variety of routes, including oral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal or intradermal, rectal, intravaginal, intraperitoneal, intraocular, subretinal, intravitreal, topical (e.g., by powders, ointments, creams, gels, lotions and / or drops), mucosal, nasal, buccal, Petition 870250052396, dated 06 / 23 / 2025, p. 125 / 203 118 / 150 enteral, vitreous, intratumoral, sublingual, intranasal, by intratracheal instillation, bronchial instillation and / or inhalation; as an oral spray and / or dust, nasal spray and / or aerosol and / or via a portal vein catheter. In some embodiments, the composition may be administered intravenously, intramuscularly, intradermally, intra-arterially, intratumorally, subcutaneously, intraocularly, subretinally, intravitreally or by inhalation. However, in view of possible advances in the science of drug application, the present application contemplates the application or description of the compositions described herein by any suitable route.In general, the most appropriate route of administration depends on a variety of factors, including the nature of the nanoparticle composition, including one or more therapeutic and / or prophylactic measures (e.g., its stability in various body environments (e.g., blood and gastrointestinal tract)), the patient's condition (e.g., whether the patient is able to tolerate a specific route), and so on.

[00340] In certain embodiments, in which a therapeutic and / or prophylactic agent is administered to the mammal at a dose of 0.0001 mg / kg to 10 mg / kg. For example, it can be 0.0001 mg / kg to 10 mg / kg, 0.001 mg / kg to 10 mg / kg, 0.005 mg / kg to 10 mg / kg, 0.01 mg / kg to 10 mg / kg, 0.05 mg / kg to 10 mg / kg, 0.1 mg / kg to 10 mg / kg 1 mg / kg to 10 mg / kg, 2 mg / kg to 10 mg / kg, 5 mg / kg to 10 mg / kg, 0.0001 mg / kg to 5 mg / kg, 0.001 mg / kg to 5 mg / kg, 0.005 mg / kg to 5 mg / kg, 0.01 mg / kg to 5 mg / kg, 0.05 mg / kg to 5 mg / kg, 0.1 mg / kg to 5 mg / kg, 1 mg / kg at 5 mg / kg, 2 mg / kg to 5 mg / kg, 0.0001 mg / kg to 2.5 mg / kg, 0.001 mg / kg to 2.5 mg / kg, 0.005 mg / kg to 2.5 mg / kg, 0.01 mg / kg to 2.5 mg / kg 0.05 mg / kg to 2.5 mg / kg, 0.1 mg / kg to 2.5 mg / kg, 1 mg / kg to 2.5 mg / kg, 2 mg / kg to 2.5 mg / kg, 0.0001 mg / kg to 1 mg / kg, 0.001 mg / kg to 1 mg / kg, 0.005 mg / kg to 1 mg / kg, 0.01 mg / kg to 1 mg / kg, 0.05 mg / kg to 1 mg / kg, 0.1 mg / kg at 1 mg / kg, 0.0001 mg / kg to 0.25 mg / kg, 0.001 mg / kg to 0.25 mg / kg, 0.005 Petition 870250052396, dated 06 / 23 / 2025, pages 126 / 203 119 / 150 mg / kg to 0.25 mg / kg, 0.01 mg / kg to 0.25 mg / kg, 0.05 mg / kg to 0.25 mg / kg, or 0.1 mg / kg to 0.25 mg / kg. In some embodiments, a therapeutic and / or prophylactic dose (e.g., mRNA) of the nanoparticle composition can be administered in a range of about 0.001 mg / kg to about 10 mg / kg. In other embodiments, a therapeutic and / or prophylactic dose of about 0.005 mg / kg to about 2.5 mg / kg can be administered. In certain embodiments, a dose of about 0.1 mg / kg to about 1 mg / kg can be administered. In other embodiments, a dose of about 0.05 mg / kg to about 0.25 mg / kg can be administered. The dose may be administered once or more times a day in the same amounts or in different amounts to obtain the desired level of mRNA expression and / or therapeutic, diagnostic, prophylactic or imaging effect.The desired dose can be administered, for example, three times a day, twice a day, once a day, on alternate days, every three days, weekly, every two weeks, every three weeks, or every four weeks. In certain modalities, multiple administrations (e.g., two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, or more administrations) may be used to administer the desired dose. In some modalities, for example, before or after surgery, or in the case of an acute illness, disorder, or condition, a single dose may be administered.

[00341] Nanoparticle compositions comprising one or more therapeutic and / or prophylactic agents may be used in combination with one or more other therapeutic, prophylactic, diagnostic, or imaging agents. "In combination with" does not mean that the agents need to be administered simultaneously and / or formulated for combined application, although such methods of application are within the scope of this application. For example, one or more nanoparticle compositions comprising one or more Petition 870250052396, dated 06 / 23 / 2025, p. 127 / 203 120 / 150 different therapeutic and / or prophylactic agents may be administered in combination. The composition may be administered simultaneously, before or after one or more other desired therapeutic or medical procedures. Typically, each agent will be administered at a dose and / or on a schedule determined for that agent. In some embodiments, the present application includes the application of the composition or an imaging, diagnostic or prophylactic composition thereof in combination with an agent that increases its bioavailability, reduces and / or alters its metabolism, inhibits its excretion and / or modulates contractions in vivo.

[00342] It is understood that the active therapeutic, prophylactic, diagnostic or imaging agents used in combination may be administered together in a single composition or separately in different compositions. In general, it is desirable that the agents used in combination be used at levels that do not exceed the levels at which they are used individually. In some modalities, the combined use level may be lower than the level used individually.

[00343] The specific combination of treatments (treatments or procedures) used in a combination regimen will take into account the compatibility of the desired treatments and / or procedures, as well as the desired therapeutic effect to be achieved. It will also be recognized that the treatments employed may achieve the desired effect in the same condition (e.g., the composition used to treat cancer may be administered simultaneously with the chemotherapeutic agent), or they may achieve different effects (e.g., control of any side effects, such as infusion-related reactions).

[00344] In some modalities, a method of treating an individual who needs the same or application of a drug tera Petition 870250052396, dated 06 / 23 / 2025, pp. 128 / 203 121 / 150 therapeutic and / or prophylactic administration to an individual (e.g., a mammal) may comprise pretreatment of the individual with one or more agents prior to administration of the nanoparticle composition. For example, the individual may be pretreated with an effective amount (e.g., 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, or any other effective amount) of dexamethasone, methotrexate, acetaminophen, H1 receptor blockers, or H2 receptor blockers. Pretreatment can occur 24 hours or less (e.g., 24 hours, 20 hours, 16 hours, 12 hours, 8 hours, 4 hours, 2 hours, 1 hour, 50 minutes, 40 minutes, 30 minutes, 20 minutes, or 10 minutes) before administration of the nanoparticle composition and can occur, for example, once, twice, or more times with increasing doses.

[00345] The various embodiments described herein (including the Examples below) and the features in the various embodiments should be understood as being capable of being arbitrarily combined with one another, and the various embodiments resulting from such combinations are included in the scope of this application as if the embodiments resulting from such combinations were specifically and individually presented herein, unless the context clearly indicates otherwise. DESCRIPTION OF THE DRAWINGS

[00346] Figure 1 shows the results of luciferase expression of LNPs prepared based on the compounds of the present invention 24 h after intramuscular injection.

[00347] Figures 2A to 2D show the distribution of tissue organs by luciferase from LNPs prepared based on the compounds of the present invention 24 h after intravenous injection.

[00348] Figures 3A to 3B show the hepatic ALT / AST level of LNPs prepared based on the compounds of the present invention 24 h after intravenous injection. Petition 870250052396, dated 06 / 23 / 2025, p. 129 / 203 122 / 150 Examples

[00349] The following examples are illustrative of this application and are not intended to limit this application in any way. Unless otherwise indicated, all temperatures are in degrees Celsius and pressure is atmospheric or near atmospheric. All reagents and starting materials used in this application are commercially available, except as synthetic intermediates or where otherwise indicated. Example 1 Synthesis of Compound 1 Compound 1 THE

[00350] The synthetic pathway is shown as follows: NH(CH3fe THF M1 THE Compound 1

[00351] Specifically, to a solution of Compound A1 (2.0 g, 8.96 mmol) in dichloromethane (30 ml) were added Compound B1 (1.9 g, 7.47 mmol), DCC (1.8 g, 8.96 mmol) and DMAP (437 mg, 3.58 mmol), and the reaction mixture was stirred for 7 hours at room temperature (ta) and monitored by TLC. After the reaction was complete, the reaction mixture was diluted by adding an equal volume of saturated sodium bicarbonate solution and separated. The organic layer was dried with anhydrous magnesium sulfate and filtered. The filtrate was con Petition 870250052396, dated 06 / 23 / 2025, pages 130 / 203 123 / 150 centered and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30:1) to obtain Compound C1 (2.9 g, 85.00%).

[00352] To a solution of Compound E1 (5.0 g, 25.63 mmol) in dichloromethane (60 ml) were added Compound D1 (3.7 g, 21.36 mmol), DCC (5.29 g, 25.63 mmol) and DMAP (1.2 g, 10.25 mmol), and the reaction mixture was stirred for 7 hours at room temperature and monitored by TLC. After completion of the reaction, the reaction mixture was diluted by adding an equal volume of saturated sodium bicarbonate solution and separated. The organic layer was dried with anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30:1) to obtain Compound F1 (6.5 g, 88.00%).

[00353] To a solution of Compound F1 (500 mg, 1.44 mmol) in DMF (15 ml) were added Compound G (562 mg, 2.88 mmol), NBu4I (795 mg, 2.15 mmol) and K2CO3 (597 mg, 4.32 mmol), and the reaction mixture was stirred for 12 hours at room temperature and monitored by TLC. After completion of the reaction, the reaction mixture was diluted by the addition of an equal volume of water, extracted with ethyl acetate (10 ml χ 3), concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain Compound H1 (580 mg, 87% yield).

[00354] To a solution of Compound H1 (500 mg, 1.08 mmol) in DMF (15 ml) were added Compound C1 (745 mg, 1.62 mmol), NBu4l (598 mg, 1.62 mmol) and Cs2CO3 (1.4 g, 4.32 mmol), and the reaction mixture was stirred for 15 hours at room temperature and monitored by TLC. After completion of the reaction, the reaction mixture was diluted by the addition of an equal volume of water, extracted with ethyl acetate (10 ml χ 3), concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain Petition 870250052396, dated 06 / 23 / 2025, pp. 131 / 203 124 / 150 Compound I1 (811 mg, 89% yield).

[00355] Concentrated hydrochloric acid (60 ml) was added to a solution of Compound I1 (10 g, 11.85 mmol) in dichloromethane (100 ml), and the reaction mixture was stirred for 3 hours at room temperature and monitored by TLC. After the reaction was complete, the layers were separated. The organic layer was washed with a saturated sodium bicarbonate solution, dried with anhydrous magnesium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30:1) to obtain Compound J1 (6.5 g, 81.00%).

[00356] To a solution of Compound J1 (1 g, 1.48 mmol) in toluene (25 ml) were added Compound K1 (470 mg, 4.44 mmol) and pyridinium 4-methylbenzenesulfonate (744 mg, 2.96 mmol), heated under reflux for 20 h using a Dean-Stark apparatus, and the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature, diluted by the addition of an equal volume of water, extracted with ethyl acetate (10 ml χ 3), concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain Compound L1 (648 mg, 57% yield).

[00357] To a solution of Compound L1 (750 mg, 0.98 mmol) in ultra-dry dichloromethane (10 ml) were added methanesulfonic anhydride (340 mg, 1.96 mmol) and anhydrous triethylamine (0.45 ml) at 0 °C, stirred for 12 hours, and the reaction was monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, diluted by the addition of an equal volume of water, and separated. The organic layer was dried with anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain Compound M1 (800 mg, 97% yield). Petition 870250052396, dated 06 / 23 / 2025, pp. 132 / 203 125 / 150

[00358] A solution of dimethylamine (2 M in THF) (30 ml) was added to Compound M1 (750 mg, 0.89 mmol), the mixture was sealed and stirred at room temperature for 6 days, and the reaction was monitored by TLC. After completion of the reaction, it was concentrated and purified by silica gel column chromatography (dichloromethane: methanol = 30:1) to obtain Compound 1 (212 mg, 30% yield) as an oil. 1H NMR (600 MHz, CDCb) δ 4.87 - 4.82 (m, 1H), 4.05 - 4.02 (m, 2H), 3.90 - 3.85 (m, 2H), 3.59 - 3.56 (m, 2H), 2.31 - 2.23 (m, 4H), 2.21 - 2.19 (m, 8H), 1.94 - 1.87 (brs, 1H), 1.68 - 1.56 (m, 10H), 1.52 1.42 (m, 4H), 1.36 - 1.21 (m, 52H), 0.87 - 0.84 (m, 9H); 13C NMR (151 MHz, CDCl3) δ 173.98, 173.77, 100.76, 74.22, 64.55, 62.87, 62.81, 59.34, 59.31, 45.97, 35.37, 35.28, 34.86, 34.49, 34.46, 34.28 32.47, 32.39, 32.03, 31.99, 29.99, 29.72, 29.65, 29.46, 29.36, 28.80 26.06, 25.44, 25.29, 25.16, 23.49, 23.26, 23.16, 22.92, 22.79, 14.22; MS-ESI (m / z): 794.6 (M+H)+. Example 2 Synthesis of Compound 2 Compound 20 0

[00359] The preparation method is the same as for Compound 1, and 1,2,4-butanetriol was used to replace Compound K1 as a feedstock to produce Compound 2 as an oil. 1H NMR (600 MHz, CDCl3) δ 4.82 - 4.78 (m, 1H), 4.04 - 3.96 (m, 4H), 3.42 - 3.39 (m, 1H), 2.39 - 2.34 (brs, 1H), 2.29 - 2.25 (brs, 1H), 2.23 - 2.18 (m, 10H), 1.77 - 1.71 (brs, 1H), 1.66 - 1.65 (brs, 1H), 1.58 - 1.39 (m, 13H), 1.33 - 1.16 (m, 53H), 0.82 - 0.80 (m, 9H); 13C NMR (151 MHz, CDCl3) δ 173.62, 173.41, 111.82, 74.63, 74.61, 73.88, 69.89, 64.25, 56.18, 45.28, 37.73, 37.48, 37.40, 37.20, 34.59, 34.19, 34.18 34.09, 31.83, 31.78, 31.60, 29.70, 29.68, 29.52, 29.50, 29.45, 29.34 29,32, 29,25, 29,20, 29,15, 29,09, 29,07, 28,59, 25,86, 25,23, 25,07, 24.89, 23.88, 23.58, 23.56, 23.24, 22.60, 22.58, 14.01; MS-ESI (m / z): Petition 870250052396, dated 06 / 23 / 2025, p. 133 / 203 126 / 150 794.6 (M+H)+. Example 2A Synthesis of Compound 2A

[00360] The preparation method is the same as for Compound 1 and (S)1,2,4-butanetriol was used to replace Compound K1 as a raw material to produce Compound 2A as an oil. 1H NMR (400 MHz, CDCl3) δ 4.97 - 4.83 (m, 1H), 4.17 - 4.05 (m, 4H), 3.52 (t, J = 8.0 Hz, 1H), 2.58 - 2.37 (m, 2H), 2.35 - 2.23 (m, 10H), 1.91 - 1.70 (m, 2H), 1.69 - 1.50 (m, 14H), 1.48 - 1.24 (m, 52H), 0.92 (t, J = 8.0 Hz, 9H); 13C NMR (100 MHz, CDCb) δ 174.04, 173.69, 112.10, 74.59, 74.12, 69.94, 64.34, 56.22, 45.21, 37.79, 37.70, 37.44, 37.38, 34.74 34.42, 34.16, 31.91, 31.88, 31.43, 31.41, 29.80, 29.57, 29.55, 29.52 29.49, 29.32, 29.28, 29.25, 29.19, 28.63, 28.61, 25.95, 25.33, 25.17 25.00, 23.89, 23.71,23.59, 22.68, 14.12; MS-ESI (m / z): 795.0 (M+H)+. Example 3 Synthesis of Compound 3 o Compound 3 zN-- /

[00361] The preparation method is the same as for Compound 1, and 3-dimethylamino-1,2-propanediol and ptoluenesulfonic acid monohydrate were used to replace Compound K1 and pyridinium 4-methylbenzenesulfonate as raw materials to produce Compound 3 as an oil. 1H NMR (600 MHz, CDCb) δ 4.85 - 4.81 (m, 1H), 4.20 - 4.16 (m, 1H), 4.06 - 4.01 (m, 3H), 3.49 - 3.46 (m, 1H), 2.48 - 2.44 (m, 1H), 2.35 - 2.32 (m, 1H), 2.27 - 2.22 (m, 10H), 1.60 - 1.54 (m, 8H), 1.48 - 1.47 (m, 4H), 1.31 - 1.20 (m, 54H), 0.86 - 0.83 (m, 9H); 13C NMR (151 MHz, CDCb) δ 173.90, 173.69, 112.58, 74.40, 74.36, 74.13, 69.06, 64.48, 62.62, 62.59, 46.22, 37.80, 37.55, 37.51, 37.30, 34.79, 34.40, 34.38, 34.24, 31.99, 31.94, 29.88, Petition 870250052396, dated 06 / 23 / 2025, pp. 134 / 203 127 / 150 29.83, 29.68, 29.66, 29.61, 29.58, 29.52, 29.47, 29.41, 29.38, 29.33, 29.31, 29.27, 29.25, 28.74, 26.01, 25.39, 25.24, 25.06, 25.06, 24.03, 23.70, 23.35, 22.74, 14.17; MS-ESI (m / z): 780.6 (M+H)+. Example 4 Synthesis of Compound 4 Compound 4

[00362] The preparation method is the same as for Compound 1, and undecanoic acid and 6-bromo-1-hexanol were used to replace Compound D1 and Compound E1 as raw materials to produce Compound 4 as an oil. 1H NMR (600 MHz, CDCI3) δ 4.86 4.81 (m, 1H), 4.04 - 4.01 (m, 2H), 3.90 - 3.84 (m, 2H), 3.59 - 3.55 (m, 2H), 2.27 - 2.22 (m, 4H), 2.20 - 2.17 (m, 8H), 1.94 - 1.85 (brs, 1H), 1.67 - 1.55 (m, 10H), 1.48 - 1.45 (m, 4H), 1.36 - 1.22 (m, 52H), 0.86 0.83 (m, 9H); 13C NMR (151 MHz, CDCb) δ 174.01, 173.70, 100.73, 74.14, 64.40, 64.36, 62.83, 62.75, 59.31, 59.28, 45.98, 35.50, 35.25, 34.79, 34.47, 34.24, 32.45, 32.43, 32.22, 31.98, 31.95, 29.94, 29.70 29.64, 29.61, 29.59, 29.55, 29.42, 29.39, 29.35, 29.32, 29.29, 29.25 28.73, 26.05, 25.40, 25.24, 25.10, 23.45, 23.32, 23.21, 23.08, 22.75 14.18; MS-ESI (m / z): 794.6 (M+H)+. Example 5 Synthesis of Compound 5 O Compound 50 0

[00363] The preparation method is the same as for Compound 1, and undecanoic acid, 6-bromo-1-hexanol, and 1,2,4-butanetriol were used to replace Compound D1, Compound E1, and Compound K1 as raw materials to produce Compound 5 as an oil. 1H NMR (600 MHz, CDCl3) δ 4.81 (p, J = 6.2 Hz, 1H), 4.03 (t, J = 6.6 Hz, 1H), 3.99 (t, J = 6.6 Hz, 3H), 3.42 (t, J = 7.6 Hz, 1H), 2.41 - 2.36 (brs, 1H), 2.31 - 2.26 (brs, 1H), 2.23 - 2.20 (m, 10H), 1.78 - 1.73 (brs, 1H), 1.66 - 1.60 (brs, 1H), 1.58 - 1.43 (m, 12H), 1.31 - 1.20 (m, 54H), 0.82 Petition 870250052396, dated 06 / 23 / 2025, p. 135 / 203 128 / 150 (t, J = 7,0 Hz, 9H); RMN de13C (151 MHz, CDCI3) δ 173,92, 173,60, 112,00, 74,75, 74,73, 74,05, 70,00, 64,31, 56,29, 45,41, 37,83, 37,73, 37,50, 37,42, 34,73, 34,40, 34,20, 31,93, 31,90, 31,73, 31,71, 29,82, 29,80, 29,58, 29,56, 29,53, 29,50, 29,33, 29,30, 29,26, 29,20, 28,67, 28,65, 25,96, 25,35, 25,19, 25,05, 23,90, 23,71, 23,59, 22,69, 14,13; MS-ESI (m / z): 794,6 (M+H)+. Exemplo 5A Síntese do Composto 5A

[00364] The preparation method is the same as for Compound 1, and undecanoic acid, 6-bromo-1-hexanol and (S)-1,2,4-butanetriol were used to replace Compound D1, Compound E1 and Compound K1 as raw materials to produce Compound 5A as an oil. 1H NMR (400 MHz, CDCb) δ 4.97 - 4.83 (m, 1H), 4.17 - 4.06 (m, 4H), 3.51 (t, J = 4.0 Hz, 1H), 2.51 - 2.45 (m, 1H), 2.44 - 2.32 (m, 1H), 2.31 - 2.23 (m, 10H), 1.87 - 1.80 (m, 1H), 1.74 - 1.67 (m, 1H), 1.66 - 1.50 (m, 14H), 1.48 - 1.24 (m, 52H), 0.92 (t, J = 8.0 Hz, 9H); 13C NMR (100 Hz, CDCl3) δ 173.96, 173.62, 111.98, 74.71, 74.08, 69.96, 64.30, 56.24, 45.36, 37.60, 37.53, 37.50, 37.43, 34.71, 34.39, 34.13, 31.87 31.84, 31.67, 31.61, 29.78, 29.70, 29.51, 29.48, 29.30, 29.28, 29.24 29.18, 28.64, 28.61, 25.94, 25.32, 25.17, 25.03, 23.89, 23.70, 23.59 22.67, 14.11; MS-ESI (m / z): 795.0 (M+H)+. Example 5B Synthesis of Compound 5B

[00365] The preparation method is the same as for Compound 1, and undecanoic acid, 6-bromo-1-hexanol, and (R)-1,2,4-butanetriol were used to replace Compound D1, Compound E1, and Compound K1 as feedstocks to produce Compound 5B as an oil. NMR Petition 870250052396, dated 06 / 23 / 2025, p. 136 / 203 129 / 150 de1H (400 MHz, CDCI3) δ 4.97 - 4.83 (m, 1H), 4.17 - 4.05 (m, 4H), 3.51 (t, J = 4.0 Hz, 1H), 2.51 - 2.45 (m, 1H), 2.44 - 2.32 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 173.97, 173.62, 111.98, 74.71, 74.08, 69.96, 64.30, 56.24, 45.36, 37.60, 37.43, 37.50, 37.44, 34.71, 34.39, 34.13, 31.87, 31.84, 31.67, 31.61, 29.79, 29.70, 29.51, 29.48, 29.30, 29.28 29.24, 29.18, 28.64, 28.61, 25.94, 25.32, 25.18, 25.03, 23.89, 23.70 23.59, 22.67, 14.11; MS-ESI (m / z): 795.0 (M+H)+. Example 6 Synthesis of Compound 6 Compound 6

[00366] The preparation method is the same as for Compound 1, and undecanoic acid, 6-bromo-1-hexanol, and 3-dimethylamino-1,2-propanediol were used to replace Compound D1, Compound E1, and Compound K1 as raw materials to produce Compound 6 as an oil. 1H NMR (500 MHz, CDCb) δ 4.84 (p, J = 6.2 Hz, 1H), 4.19 (p, J = 6.5 Hz, 1H), 4.06 - 4.01 (m, 3H), 3.49 (t, J = 7.8 Hz, 1H), 2.48 (dd, J = 12.6, 6.8 Hz, 1H), 2.35 (dd, J = 12.6, 5.0 Hz, 1H), 2.27 - 2.23 (m, 10H), 1.62 - 1.53 (m, 10H), 1.49 - 1.46 (m, 4H), 1.33 - 1.24 (m, 52H), 0.85 (t, J = 6.8 Hz, 9H); 13C NMR (126 MHz, CDCb) δ 174.05, 173.72, 112.66, 74.44, 74.18, 69.08, 64.40, 62.65, 46.25, 37.82, 37.71, 37.49, 37.44, 34.83, 34.50, 34.26, 32.00, 31.97, 29.91, 29.86, 29.63, 29.61, 29.40, 29.37, 29.33, 29.27, 28.73, 26.04, 25.42, 25.26, 25.12, 24.06, 23.95, 23.73, 23.61, 22.77, 14.19; MS-ESI (m / z): 780.6 (M+H)+. Example 7 Synthesis of Compound 7 Compound 7 Petition 870250052396, dated 06 / 23 / 2025, p. 137 / 203 130 / 150

[00367] The preparation method is the same as for Compound 1, and 8-bromo-1-octanol, 2-octyl-decanoic acid, and 3-dimethylamino-1,2-propanediol were used to replace Compound A1, Compound B1, and Compound K1 as raw materials to produce Compound 7 as an oil. 1H NMR (500 MHz, CDCb) δ 4.22 - 4.17 (m, 1H), 4.06 - 4.01 (m, 5H), 3.48 (t, J = 7.8 Hz, 1H), 2.50 - 2.46 (m, 1H), 2.39 - 2.36 (m, 1H), 2.28 - 2.24 (m, 9H), 1.60 - 1.53 (m, 13H), 1.42 - 1.37 (m, 2H), 1.30 - 1.22 (m, 53H), 0.85 (t, J = 6.8 Hz, 9H); 13C NMR (126 MHz, CDCl3) δ 176.64, 173.92, 112.62, 74.26, 74.21, 68.96, 64.29, 64.10, 62.48, 46.07, 45.85, 37.75, 37.60, 37.42, 37.32, 34.40 32.56, 31.90, 31.87, 29.91, 29.86, 29.57, 29.46, 29.31, 29.25, 29.18 28.75, 28.64, 27.47, 25.99, 25.94, 25.03, 23.98, 23.85, 23.64, 23.51 22.67, 14.10; MS-ESI (m / z): 794.6 (M+H)+. Example 8 Preparation of Compound 8 Compound 8 THE

[00368] The preparation method is the same as for Compound 1, and 8-bromo-1-octanol, 2-octyl-decanoic acid, and 1,2,4-butanetriol were used to replace Compound A1, Compound B1, and Compound K1 as raw materials to produce Compound 8 as an oil. 1H NMR (500 MHz, CDCb) δ 4.07 - 4.00 (m, 6H), 3.44 (t, J = 7.5 Hz, 1H), 2.42 - 2.36 (brs 1H), 2.32 - 2.21 (m, 10H), 1.81 - 1.74 (brs, 1H), 1.68 - 1.51 (m, 14H), 1.42 - 1.34 (brs, 2H), 1.26 - 1.22 (m, 53H), 0.84 (t, J = 6.9 Hz, 9H); 13C NMR (126 MHz, CDCb) δ 176.69, 173.97, 112.05, 74.81, 70.06, 64.36, 64.16, 56.36, 45.92, 45.50, 37.93, 37.78, 37.59, 37.48, 34.46, 32.63, 31.97, 31.94, 31.82, 29.63, 29.53, 29.37, 29.32, 29.24, 28.81, 28.71, 27.54, 26.06, 26.02, 25.09, 24.07, 23.94, 23.77, 23.64, 22.73, 14.16; MS-ESI (m / z): 808.6 (M+H)+. Example 9 Preparation of Compound 9 Petition 870250052396, dated 06 / 23 / 2025, p. 138 / 203 131 / 150 Compound 9

[00369] The preparation method is the same as for Compound 1, and 8 bromo-1-octanol, 2-octyl-decanoic acid, undecanoic acid, and 6 bromo-1-hexanol were used to replace Compound A1, the Compound B1, Compound D1, and Compound E1 as raw materials to produce Compound 9 as an oil. 1H NMR (500 MHz, CDCl3) δ 4,04 - 4,01 (m, 4H), 3,89 - 3,85 (m, 2H), 3,59 - 3,56 (m, 2H), 2,31 - 2,18 (m, 11H), 1,93 - 1,86 (brs, 1H), 1,67 - 1,52 (m, 12H), 1,43 - 1,23 (m, 56H), 0,85 (t, J = 6,9 Hz, 9H); RMN de13C (126 MHz, CDCl3) δ 176,71, 174,00, 100,75, 64,40, 64,36, 64,18, 62,83, 62,76, 59,34, 59,31F, 45,98, 45,94, 35,46, 35,25, 34,48, 32,64, 32,54, 32,46, 32,34, 31,98, 31,96, 30,06, 29,71, 29,65, 29,55, 29,39, 29,34, 29,26, 28,83, 28,74, 27,56, 26,08, 25,11, 23,46, 23,32, 23,23, 23,09, 22,75, 14,18; MS-ESI (m / z): 808,5 (M+H)+. Exemplo 10 Preparação do Composto 10 Composto 10 o

[00370] The preparation method is the same as for Compound 1, and 1,2,4-butanetriol and NN-ethylmethylamine were used to replace Compound K1 and dimethylamine as raw materials to produce Compound 10 as an oil. 1H NMR (600 MHz, CDCI3) δ 4.83 - 4.75 (m, 1H), 4.05 - 3.93 (m, 4H), 3.42 - 3.35 (m, 1H), 2.46 - 2.30 (m, 4H), 2.23 - 2.15 (m, 7H), 1.79 - 1.70 (m, 1H), 1.67 - 1.59 (m, 1H), 1.56 1.51 (m, 6H), 1.43 (d, J = 7.2 Hz, 4H), 1.29 - 1.14 (m, 56H), 0.99 (t, J = 7.1 Hz, 3H), 0.80 (t, J = 7.0Hz, 9H); 13C NMR (151 MHz, CDCb) δ 173.72, 173.51, 111.83, 74.85, 74.81, 73.96, 69.99, 64.33, 53.70, 51.43, 41.49, 37.80, 37.56, 37.48, 37.28, 34.66, 34.26, 34.25, 34.15 31.90, 31.85, 31.30, 29.77, 29.59, 29.57, 29.51, 29.49, 29.41, 29.38 Petition 870250052396, dated 06 / 23 / 2025, p. 139 / 203 132 / 150 29.32, 29.29, 29.24, 29.22, 29.16, 29.13, 28.65, 25.92, 25.30, 25.13, 24.97, 23.96, 23.66, 23.31, 22.65, 14.08, 12.09; MS-ESI (m / z): 808.7 (M+H)+. Example 11 Preparation of Compound 11 Compound 11o o

[00371] The preparation method is the same as for Compound 1, and 1,2,4-butanetriol and diethylamine were used to replace Compound K1 and dimethylamine as raw materials to produce Compound 11 as an oil. 1H NMR (600MHz, CDCl3) 4H), 1.85 - 1.75 (m, 2H), 1.63 - 1.56 (m, 6H), 1.50 - 1.44 (m, 4H), 1.37 - 1.19 (m, 56H), 1.12 (t, J = 7.2 Hz, 6H), 0.85 (td, J = 7.1, 2.4 Hz, 9H); 13C NMR (151 MHz, CDCle) δ 173.95, 173.73, 112.22, 74.59, 74.55, 74.17, 69.94, 64.52, 49.36, 46.95, 37.84, 37.59, 37.42, 37.21, 34.80, 34.39, 34.24, 31.99, 31.95, 30.30, 29.87, 29.69, 29.67 29.62, 29.59, 29.50, 29.47, 29.42, 29.35, 29.32, 29.29, 29.26, 28.74 26.02, 25.40, 25.24, 25.07, 24.09, 23.82, 23.76, 23.47, 22.75, 14.20 10.74; MS-ESI (m / z): 822.9(M+H)+. Example 12 Preparation of Compound 12 Compound 120 0

[00372] The preparation of Compound 12 is called the preparation of Compound 2. Example 13 Preparation of Compound 13 Compound 13

[00373] The preparation method is the same as for Compound 1, and 1,2,5-pentanetriol was used to replace Compound K1 as raw material. Petition 870250052396, dated 06 / 23 / 2025, page 140 / 203 133 / 150 prime to produce Compound 13 as an oil. 1H NMR (600 MHz, CDCl3) δ 4.81 - 4.74 (m, 1H), 4.00 - 3.92 (m, 4H), 3.38 - 3.33 (m, 1H), 2.25 - 2.17 (m, 6H), 2.15 (s, 6H), 1.59 - 1.46 (m, 15H), 1.46 - 1.37 (m, 5H), 1.29 - 1.12 (m, 50H), 0.79 (td, J = 7,1,2,3 Hz, 9H); 13C NMR (151 MHz, CDCb) δ 173.69, 173.47, 111.86, 76.08, 76.05, 73.92, 69.93, 69.91, 64.29, 59.48, 53.38, 45.24, 37.80, 37.56, 37.47 37.25, 34.64, 34.24, 34.22, 34.13, 31.88, 31.83, 31.20, 29.76, 29.57 29.55, 29.49, 29.47, 29.39, 29.37, 29.30, 29.27, 29.22, 29.20, 29.14, 29.11, 28.63, 25.90, 25.28, 25.12, 24.95, 23.95, 23.89, 23.64, 23.62 23.29, 22.64, 22.62, 14.05; MS-ESI (m / z): 808.8(M+H)+. Example 14 Preparation of Compound 14

[00374] The preparation method is the same as for Compound 1, and 1,2,6hexanetriol was used to replace Compound K1 as a feedstock to produce Compound 14 as an oil. 1H NMR (600 MHz, CDCl3) δ 4.91 - 4.79 (m, 1H), 4.02 (m, 4H), 3.45 - 3.34 (m, 1H), 2.33 (t, J = 6.5 Hz, 2H), 2.27 (m, 10H), 1.60 (m, 9H), 1.53 - 1.41 (m, 8H), 1.25 (m, 55H), 0.87 (t, J = 7.0 Hz, 9H); 13C NMR (151 MHz, Chloroform-d) δ 111.89, 76.18, 74.09, 70.03, 64.42, 59.48, 45.20, 37.94 - 37.16 (m), 34.73, 34.33, 34.15, 33.31, 31.88, 29.81, 29.59, 29.51, 29.44, 29.32, 29.24, 28.66, 27.37, 25.92, 25.31, 25.16, 24.99, 23.68, 22.66, 14.09; MS-ESI (m / z): 822.9(M+H)+. Example 15 Preparation of Compound 15

[00375] The preparation method is the same as for Compound 1, and 1,2,4-butanetriol and N-methyl-n-propylamine were used to replace Compound K1 and dimethylamine as raw materials to produce the Petition 870250052396, dated 06 / 23 / 2025, p. 141 / 203 134 / 150 Compound 15 like an oil. 1H NMR (600 MHz, CDCI3) δ 4.84 4.78 (m, 1H), 4.07 - 3.97 (m, 4H), 3.42 (t, J = 7.7 Hz, 1H), 2.53 - 2.39 (m, 2H), 2.33 (t, J = 7.6 Hz, 2H), 2.26 - 2.20 (m, 7H), 1.81 - 1.74 (m, 1H), 1.74 - 1.66 (m, 1H), 1.61 - 1.54 (m, 6H), 1.51 - 1.41 (m, 5H), 1.35 - 1.14 (m, 55H), 0.84 (dt, J = 15.0, 7.3 Hz, 12H).; 13C NMR (151 MHz, CDCl3) δ 173.86, 173.64, 111.97, 74.82, 74.78, 74.09, 70.02, 64.45, 59.66, 54.18, 41.99, 37.87, 37.62, 37.52, 37.32, 34.76 34.35, 34.22, 31.97, 31.92, 31.06, 29.85, 29.83, 29.64, 29.58, 29.56 29.49, 29.46, 29.39, 29.31, 29.29, 29.25, 29.22, 28.72, 25.99, 25.37 25.21, 25.04, 24.05, 23.75, 23.72, 23.41, 22.73, 22.71, 20.09, 14.15, 11.84; MS-ESI (m / z): 822.8(M+H)+. Example 16 Preparation of Compound 16

[00376] The preparation method is the same as for Compound 1, and 1,2,4-butanetriol and NN-ethylisopropylamine were used to replace Compound K1 and dimethylamine as raw materials to produce Compound 16 as an oil. 1H NMR (600 MHz, CDCb) δ 4.84 (p, J = 6.3 Hz, 1H), 4.11 - 4.01 (m, 4H), 3.47 (t, J = 7.6 Hz, 1H), 3.34 - 2.50 (m, 5H), 2.29 - 2.22 (m, 4H), 1.64 - 1.44 (m, 14H), 1.40 - 1.03 (m, 63H), 0.86 (t, 9H); 13C NMR (151 MHz, CDCb) δ 173.95, 173.73, 112.18, 74.58, 74.19, 69.97, 64.54, 46.37, 44.49, 37.86, 37.61, 37.44, 37.23, 34.82, 34.41, 34.25, 32.01, 31.97, 29.90, 29.87, 29.80 29.70, 29.68, 29.63, 29.60, 29.50, 29.43, 29.36, 29.33, 29.28, 28.76 26.03, 25.42, 25.25, 25.10, 25.08, 24.12, 23.85, 23.79, 23.50, 22.78 22.76, 18.33, 17.19, 14.20; MS-ESI (m / z): 836.8(M+H)+ Example 17 Preparation of Compound 17 Petition 870250052396, dated 06 / 23 / 2025, pp. 142 / 203 135 / 150 M2 Compound 17

[00377] Specifically, to a solution of Compound A1 (5.24 g, 23.49 mmol) in dichloromethane (30 mL) were added Compound B2 (5.0 g, 19.57 mmol), EDCI (4.9 g, 25.44 mmol) and DMAP (0.96, 7.83 mmol), and the reaction mixture was stirred for 7 hours at room temperature and monitored by TLC. After completion of the reaction, the reaction mixture was diluted by adding an equal volume of saturated sodium bicarbonate solution and separated. The organic layer was dried with anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30:1) to obtain Compound C2 (7.19 g, 80.00%).

[00378] To a solution of Compound D2 (7.0 g, 40.8 mmol) in dichloromethane (60 ml) were added Compound E1 (9.6 g, 49.0 mmol), EDCI (10.2 g, 53.1 mmol) and DMAP (2.0 g, 16.4 mmol), and the reaction mixture was stirred for 7 hours at room temperature and monitored by TLC. After the reaction was complete, the reaction mixture was diluted by adding an equal volume of saturated sodium bicarbonate solution and separated. The organic layer was dried with sulfa Petition 870250052396, dated 06 / 23 / 2025, pages 143 / 203 136 / 150 anhydrous magnesium and filtered. The filtrate was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30:1) to obtain Compound F2 (12.20 g, 86.15%).

[00379] To a solution of Compound F2 (12.2, 35.14 mmol) in DMF (50 ml) were added Compound G1 (13.72 g, 70.28 mmol), NBu4I (13.0 g, 35.14 mmol) and K2CO3 (14.57 g, 105.43 mmol), and the reaction mixture was stirred for 12 hours at room temperature and monitored by TLC. After completion of the reaction, the reaction mixture was diluted by the addition of an equal volume of water, extracted with ethyl acetate (50 ml χ 3), concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 3:1) to obtain Compound H2 (9.9 g, 61.11% yield).

[00380] To a solution of Compound H2 (9.9 g, 21.42 mmol) in DMF (100 ml) were added Compound C2 (11.19 g, 33.12 mmol), NBu4I (8.0 g, 21.24 mmol) and Cs2CO3 (14 g, 42.84 mmol), and the reaction mixture was stirred for 15 hours at room temperature and monitored by TLC. After completion of the reaction, the reaction mixture was diluted by the addition of an equal volume of water, extracted with ethyl acetate (100 ml χ 3), concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 3:1) to obtain Compound I2 (12 g, 66.67% yield).

[00381] Concentrated hydrochloric acid (60 ml) was added to a solution of Compound I2 (12 g, 14.26 mmol) in dichloromethane (100 ml), and the reaction mixture was stirred for 3 hours at room temperature and monitored by TLC. After the reaction was complete, the layers were separated. The organic layer was washed with a saturated sodium bicarbonate solution, dried with anhydrous magnesium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain Compound G2 (7.72 g, 80.00%). Petition 870250052396, dated 06 / 23 / 2025, pp. 144 / 203 137 / 150

[00382] To a solution of Compound G2 (3 g, 4.44 mmol) in toluene (25 ml) were added Compound K2 (1.42 g, 13.32 mmol) and pyridinium 4-methylbenzenesulfonate (1.34 g, 6.65 mmol) and the reaction mixture was heated under reflux for 20 h using a DeanStark apparatus and monitored by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature, diluted by the addition of an equal volume of water, extracted with ethyl acetate (50 ml χ 3), concentrated and purified by silica gel column chromatography (dichloromethane:methanol = 40:1) to obtain Compound L2 (1.3 g, 43.33% yield).

[00383] To a solution of Compound L2 (1.3 g, 1.7 mmol) in ultra-dry dichloromethane (10 ml) were added methanesulfonic anhydride (0.59 g, 3.4 mmol) and anhydrous triethylamine (0.7 ml) at 0 °C, and the reaction mixture was stirred for 12 hours and monitored by TLC. After completion of the reaction, the reaction solution was cooled to room temperature, diluted by the addition of an equal volume of water, and separated. The organic layer was dried with anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography (dichloromethane:methanol = 40:1) to obtain Compound M2 (1.32 g, 92.30% yield).

[00384] To Compound M2 (1.32 g, 1.57 mmol) a solution of 30 ml of dimethylamine (2 M in THF) was added and the reaction mixture was sealed, stirred at room temperature for 6 days and monitored by TLC. After completion of the reaction, it was concentrated and purified by silica gel column chromatography (dichloromethane: methanol = 30:1 + ammonia water) to obtain Compound 17 as an oil (300 mg, 24% yield). 1H NMR (500 MHz, Chloroform-d) δ 5.84 - 5.69 (m, 1H), 5.34 (t, J = 9.1 Hz, 1H), 4.05 - 3.96 (m, 2H), 3.88 - 3.79 (m, 1H), 3.41 (t, J = 7.4 Hz, 1H), 3.16 (q, J = 6.7 Hz, 2H), 2.44 - 2.33 (m, 1H), 2.29 - 2.22 (m, 1H), 2.19 (d, J = 3.3 Hz, 6H), 2.09 (t, J = 7.6 Hz, Petition 870250052396, dated 06 / 23 / 2025, pages 145 / 203 138 / 150 4H), 1.79 - 1.69 (m, 1Η), 1.66 - 1.47 (m, 8H), 1.45 - 1.37 (m, 3H), 1.30 - 1.17 (m, 56H), 0.82 (t, J = 6.9, 2.4 Hz, 9H); 13C NMR (126 MHz, CDCh) δ 172.97, 172.62, 111.98, 111.94, 74.72, 74.68, 69.97, 56.31, 49.09, 45.48, 45.45, 39.53, 37.71, 37.49, 37.38, 37.25, 37.11, 36.74, 36.72, 35.33, 31.93, 31.90, 31.75, 29.73, 29.63, 29.59, 29.48, 29.36, 29.30, 29.24, 26.99, 25.99, 25.94, 25.80, 25.76, 23.92, 23.77, 23.60, 23.40, 22.69, 14.14; MS-ESI (m / z): 792.9 (M+H) + Example 18 Compound 18

[00386] Specifically, to a solution of Compound A1 (10.40 g, 46.82 mmol) in dichloromethane (100 ml) were added Compound B1 (10 g, 39.02 mmol), EDCI (14.96 g, 78.04 mmol) and DMAP (1.90 g, 15.61 mmol), and the reaction mixture was stirred for 7 hours at room temperature and monitored by TLC. After completion of the reaction, the reaction mixture was diluted by the addition of an equal volume of saturated sodium bicarbonate solution and separated. The organic layer was dried with anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30:1) to obtain Compound C1 (15 g, 83.52%).

[00387] To a solution of Compound C1 (15 g, 32.60 mmol) in DMF (100 ml) were added 0 Compound G1 (2.12 g, 10.86 Petition 870250052396, dated 06 / 23 / 2025, pages 146 / 203 139 / 150 mmol), NBu4I (4 g, 10.86 mmol) and Cs2CO3 (10.62 g, 32.6 mmol), and the reaction mixture was stirred for 12 hours at room temperature and monitored by TLC. After completion of the reaction, the reaction mixture was diluted by the addition of an equal volume of water, extracted with ethyl acetate (100 ml χ 3), concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 40:1) to obtain Compound I3 (7.95 g, 76.60% yield).

[00388] Concentrated hydrochloric acid (60 ml) was added to a solution of Compound I3 (7.95 g, 8.31 mmol) in dichloromethane (100 ml), and the reaction mixture was stirred for 3 hours at room temperature and monitored by TLC. After the reaction was complete, the layers were separated. The organic layer was washed with a saturated sodium bicarbonate solution, dried with anhydrous magnesium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 50:1) to obtain Compound J3 (5.89 g, 89.65%).

[00389] To a solution of Compound J3 (5.89 g, 7.45 mmol) in toluene (25 ml) were added Compound K2 (2.4 g, 22.35 mmol) and pyridinium 4-methylbenzenesulfonate (2.95 g, 11.73 mmol), and the reaction mixture was heated under reflux for 20 h using a DeanStark apparatus and monitored by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature, diluted by the addition of an equal volume of water, extracted with ethyl acetate (50 ml χ 3), concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain Compound L3 (2.94 g, 44.95% yield).

[00390] To a solution of Compound L3 (2.94 g, 3.34 mmol) in ultra-dry dichloromethane (10 ml) were added methanesulfonic anhydride (1.2 g, 6.68 mmol) and anhydrous triethylamine (0.8 ml) at 0 °C, and the reaction mixture was stirred for 12 hours and monitored by TLC. Petition 870250052396, dated 06 / 23 / 2025, pages 147 / 203 140 / 150 After the reaction was complete, the reaction solution was cooled to room temperature, diluted by adding an equal volume of water, and separated. The organic layer was dried with anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain Compound M3 (3.1 g, 97% yield).

[00391] To Compound M3 (3.1 g, 3.24 mmol) a solution of 30 ml of dimethylamine (2 M in THF) was added and the reaction mixture was sealed, stirred at room temperature for 6 days and monitored by TLC. After completion of the reaction, it was concentrated and purified by silica gel column chromatography (dichloromethane: methanol = 40:1) to obtain Compound 18 as an oil (439 mg, 14.98% yield). 1H NMR (500 MHz, CDCI3) δ 4.87 - 4.79 (m, 2H), 4.08 3.98 (m, 2H), 3.44 (t, J = 7.4 Hz, 1H), 2.46 - 2.37 (m, 1H), 2.36 - 2.27 (m, 1H), 2.22 (t, J = 6.7 Hz, 10H), 1.83 - 1.74 (m, 1H), 1.72 - 1.62 (m, 1H), 1.58 - 1.51 (m, 3H), 1.46 (d, J = 6.1 Hz, 8H), 1.36 - 1.14 (m, 69h), 0.84 (t, J = 6.9 Hz, 12H); 13C NMR (126 MHz, CDCls) δ 173.69, 112.11, 74.73, 74.10, 70.02, 56.33, 45.42, 37.85, 37.53, 34.78, 34.23, 31.94, 31.70, 29.87, 29.60, 29.31, 29.27, 29.24, 25.39, 25.23, 24.05, 23.75, 22.74, 14.18; MS-ESI (m / z): 906.9(M+H)+. Example 19 Compound 19 THE

[00392] The preparation method is the same as for Compound 18, and 6-bromohexanoic acid and undecanol were used to replace Compound A1 and Compound B1 as raw materials to produce Compound 19 as an oil. 1H NMR (500 MHz, CDCl3) δ 4.08 3.98 (m, 6H), 3.44 (t, J = 7.4 Hz, 1H), 2.46 - 2.38 (m, 1H), 2.37 - 2.29 (m, 1H), 2.29 - 2.20 (m, 10H), 1.83 - 1.74 (m, 1H), 1.72 - 1.65 (m, 1H), 1.61 - 1.52 (m, 11H), 1.29 - 1.22 (m, 41H), 0.85 (t, J = 6.9 Hz, Petition 870250052396, dated 06 / 23 / 2025, pp. 148 / 203 141 / 150 6H); 13C NMR (126 MHz, CDCb) δ 173.94, 111.93, 74.78, 70.07, 64.50, 56.33, 45.44, 37.67, 37.39, 34.39, 31.99, 31.67, 29.68, 29.61, 29.50, 29.42, 29.34, 28.74, 26.01, 25.06, 23.75, 23.42, 22.77, 14.21; MS-ESI (m / z): 628.6 (M+H)+ Example 20A Compound 20A —N

[00393] The synthetic route is shown below: NH(CHj12 THF Compound 20A

[00394] Specifically, to a solution of Compound A1 (0.28 g, 1.25 mmol) in dichloromethane (30 mL) were added Compound B4 (0.25 g, 1.25 mmol), DCC (0.28 g, 1.38 mmol) and DMAP (0.01 g, 0.06 mmol), and the reaction mixture was stirred for 2 hours at room temperature and monitored by TLC. After completion of the reaction, the reaction mixture was diluted by adding an equal volume of saturated sodium bicarbonate solution and separated. The organic layer was dried by adding anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30:1) to obtain Compound C4 (0.50 g, 88.90%). Petition 870250052396, dated 06 / 23 / 2025, pp. 149 / 203 142 / 150

[00395] To a solution of Compound C4 (0.50 g, 1.23 mmol) in DMF (5 ml) were added Compound G1 (0.12 g, 0.62 mmol), NBu4I (0.05 g, 0.12 mmol) and Cs2CO3 (1.21 g, 3.71 mmol), and the reaction mixture was stirred for 12 hours at room temperature and monitored by TLC. After completion of the reaction, the reaction mixture was diluted by adding an equal volume of concentrated ethyl acetate extracted water (10 ml χ 3) to obtain crude Compound I4, which was used directly in the next feeding step.

[00396] Concentrated hydrochloric acid (5 ml) was added to a solution of Compound I4 (crude, 1.23 mmol) in dichloromethane (10 ml), and the reaction mixture was stirred for 3 hours at room temperature and monitored by TLC. After the reaction was complete, the layers were separated. The organic layer was washed with saturated sodium bicarbonate solution, dried with anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30:1) to obtain Compound J4 (0.27 g, 32.27% yield over two steps).

[00397] To a solution of Compound J4 (0.27 g, 0.40 mmol) in toluene (25 ml) were added Compound K2 (0.17 g, 1.59 mmol) and pyridinium 4-methylbenzenesulfonate (0.10 g, 0.02 mmol) and the reaction was heated under reflux for 20 h using a Dean-Stark apparatus and monitored by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature, diluted by the addition of an equal volume of water, extracted with ethyl acetate (10 ml χ 3), concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain Compound L4 (0.28 g, 91.79% yield).

[00398] To a solution of Compound L4 (0.28 g, 0.36 mmol) in dichloromethane (10 ml) were added methanesulfonic anhydride (0.10 g, 0.55 mmol) and anhydrous triethylamine (0.20 ml), and the reaction was stirred. Petition 870250052396, dated 06 / 23 / 2025, pages 150 / 203 143 / 150 for 2 hours at room temperature and monitored by TLC. After the reaction was complete, the reaction solution was cooled to room temperature, diluted by adding an equal volume of water, and separated. The organic layer was dried by adding anhydrous sodium sulfate and filtered. The filtrate was concentrated to obtain crude compound M4, which was used directly for the next feeding step.

[00399] To Compound M4 (crude, 0.36 mmol) a solution of 20 ml of dimethylamine (2 M in THF) was added under nitrogen protection, and the reaction mixture was stirred at room temperature for 3 days and monitored by TLC. After the reaction was complete, it was concentrated and purified by silica gel column chromatography (dichloromethane:methanol = 30:1) to obtain Compound 20A as an oil (0.21 g, 66.50% yield over two steps).1H NMR (400 MHz, CDCI3) δ 4.20 - 4.09 (m, 6H), 3.55 (t, J = 8.0 Hz, 1H), 2.87 - 2.69 (m, 2H), 2.55 (s, 6H), 2.32 (t, J = 8.0 Hz, 4H), 1.94 - 1.87 (m, 2H), 1.68 - 1.56 (m, 12H), 1.36 - 1.21 (m, 50H), 0.92 (t, J = 8.0 Hz, 9H); 13C NMR (400 MHz, CDCI3) δ 173.96, 112.52, 73.98, 69.66, 62.94, 55.97, 44.30, 37.66, 37.17, 34.63, 34.42, 33.57, 32.49, 32.23, 29.73 29.71, 29.27, 29.14, 26.21, 24.98, 23.97, 23.71, 22.66, 14.09; MS-ESI (m / z): 795.0 (M+H)+. Example 21 Compound 21

[00400] The preparation method is the same as for Compound 18, and 6-bromohexanol and 2-hexyldecanoic acid were used to replace Compound A1 and Compound B1 as raw materials to produce Compound 21 as an oil. 1H NMR (600 MHz, Chloroform-d) δ 4.11 - 4.02 (m, 6H), 3.47 (t, J = 7.6 Hz, 1H), 2.47 - 2.41 (brs, 1H), 2.37 - 2.33 (brs, 1H), 2.32 - 2.24 (m, 8H), 1.84 - 1.78 (brs, 1H), 1.72 - 1.65 Petition 870250052396, dated 06 / 23 / 2025, pp. 151 / 203 144 / 150 (brs, 1H), 1.63 - 1.54 (m, 12H), 1.45 - 1.40 (m, 4H), 1.37 - 1.31 (m, 10H), 1.30 - 1.21 (m, 42H), 0.87 (td, J = 7.0, 1.3 Hz, 12H);13C NMR (600 MHz, Chloroform-d) δ 176.70, 111.95, 74.72, 69.98, 64.08, 56.24, 45.84, 45.34, 37.75, 37.43, 32.52, 31.85, 31.69, 31.62, 29.56, 29.44, 29.24, 29.22, 28.69, 27.46, 27.41, 25.99, 23.90, 23.60, 22.66, 22.58, 14.07; MS-ESI (m / z): 823.0 (M+H)+. Test examples Experimental example 1: encapsulation of lipid nanoparticles (LNPs)

[00401] The mRNA stock solution was dispersed in 20 mM acetic acid solution (pH 5.0) to yield a final concentration of 200 pg / ml (aqueous phase). The mixture was prepared by dissolving a mixture according to the molar ratio of Compound:cholesterol:DSPC:DMG-PEG2000 = 50:38.5:10:1.5 as shown in Table 1 with anhydrous ethanol to form a mixed lipid (oil phase). The mRNA was mixed with the lipid mixture by T-mixing and flow rate control of the aqueous and oil phases (3:1) with a total flow rate of 12-50 ml / min, to obtain mRNA encapsulated in LNP. The encapsulated LNP was diluted with buffer (pH 5.0 ~ 5.5) and then concentrated by ultrafiltration with diluent replacement. Finally, the LNP was concentrated to 200 pg / ml ~ 600 pg / ml of mRNA, while the pH of the LNP was adjusted to approximately 7 to 8. Finally, the Quant-iTTMRiboGreen™ RNA assay kit (Invirtogen by Thermo Fisher Scientific, cat.(n° R11490) and 10% Triton X-100 solution or 10% OTG solution as an emulsion breaker were used to detect the total and free mRNA content in the LNP, and the LNP encapsulation efficiency was calculated. The final LNP product was diluted with a diluent, then 1 ml was added to a particle size cell and placed in the Malvern ZetaSizer instrument to detect the LNP particle size, and the results are shown in Table 1. Petition 870250052396, dated 06 / 23 / 2025, pages 152 / 203 145 / 150 Table 1: LNP characterization data for the compounds in the Examples Serial Number Particle Size (nm) PDI Encapsulation Efficiency Example 1 66.97 0.1125 97.22% Example 2 70.27 0.03414 92.32% Example 2A 86.26 0.02967 96.44% Example 3 95.04 0.1264 95.04% Example 4 69.03 0.1387 96.23% Example 5 89.54 0.04107 94.92% Example 5A 73.41 0.1311 96.0% Example 5B 67.95 0.04848 98.4% Example 6 69.85 0.1676 95.50% Example 7 Example 8: 92.38 0.1537 96.52% Example 9: 99.68 0.09334 90.99% Example 10: 71.61 0.1368 95.07% Example 11: 78.44 0.07 96.5% Example 12: 80.34 0.06 97.5% Example 13: 98.15 0.16 89.3% Example 14: 118.1 0.16 90.97% Example 15: 61.73 0.10 97.2% Example 16: 71.68 0.03 97.6% Example 17: 125.0 0.05 98.2% Example 18: 69.23 0.10 96.5% % Example 19 110.3 0.34 93.3 % Example 20A 85.64 0.073 92.5 % Example 21 92.89 0.3138 96.8 % MC3 72.70 0.15 96.7 % SM-102 74.80 0.07 97.5 % Experimental example 2: Toxicity assay

[00402] Samples of nanoparticles containing different lipids were administered to rats (SD rats, Zhejiang Vital River Laboratory Animal Technology Co., Ltd, 3 males and 3 females per group, weight Petition 870250052396, dated 06 / 23 / 2025, pages 153 / 203 146 / 150 body weight: 220 to 300 g for females, 260 to 340 g for males) by intravenous injection at a dose of 3 mg / kg. The expression of several clinical markers was evaluated 24 hours after administration and compared with the expression induced by the SM102 LNP formulation (i.e., LNP formulation produced from the known SM102 lipid, which was prepared according to the method of Test Example 1 at the same ratio), as well as by phosphate-buffered saline (PBS). Table 2 Test Sample Alanine transaminase (U / L) Aspartate transaminase (U / L) PBS 43.72 139.42 SM102 286.51 486.42 Compound 2 116.27 342.17 Compound 5 65.72 251.10

[00403] The results as shown in Table 2 showed that the values ​​of aspartate aminotransferase and alanine aminotransferase in the group of compounds of the present invention were apparently decreased compared with the SM102 group, which indicated that the toxicity of the compounds of the present invention was further reduced, suggesting that the compounds of the present invention have higher biosafety. Experimental Example 3: Application and Expression Effects of the Lipid Nanoparticle Compositions of the Present Invention

[00404] Five balb / c mice (Zhejiang Vital River Laboratory Animal Technology Co., Ltd, females, 6 to 8 weeks old, 18 to 20 g) were taken as one group, identified with a black marker pen on the tail with the numbers 1 to 5; five mice in each group were injected sequentially intramuscularly (IM) Petition 870250052396, dated 06 / 23 / 2025, pages 154 / 203 147 / 150 with 5 μg of the lipid nanoparticle composition. The lipid nanoparticle compositions of the present invention were prepared according to Test Example 1, in which luciferase mRNA was encapsulated. A group of MC3 LNPs was established in parallel as a reference (i.e., LNP formulation produced from the known MC3 lipid, which was obtained by preparation according to the method and ratio of Test Example 1).

[00405] The fluorescence assay was performed for each group of mice 24 hours after intramuscular administration of the samples (YEASEN fluorescein sodium salt, lot: D5330150, IP, 150 mg / kg was administered 10 minutes prior to each group). The mice were anesthetized and then placed in a live small animal optical imaging system - IVIS®Lumina LT Series III according to the tail mark orders #1 and #5. Whole-body fluorescence was detected to assess the application and expression of the formulated Luciferase mRNA.

[00406] The application and expression effects of the LNPs of the compounds of the present invention are shown in Figure 1, with MC3 expression as a reference. The data show that the compounds of the present invention have excellent application and expression effects. Application and expression effects comparable to or even superior to MC3 were achieved by the compounds of the present invention. In particular, the application and expression effects of Compound 2, Compound 2A, Compound 5, Compound 5A, Compound 5B, Compound 8, Compound 13, Compound 14, and Compound 20A were 3 to 4 times superior to MC3. From the results of Compound 2, 2A, Compound 5, Compound 5A, and Compound 5B, the difference in configuration apparently does not affect the application activity of the ionizable lipids of the present invention. Experimental example 4: Trial of the effect of extrahepatic application Petition 870250052396, dated 06 / 23 / 2025, pages 155 / 203 148 / 150 of lipid compounds of the present invention

[00407] Five balb / c mice (Zhejiang Vital River Laboratory Animal Technology Co., Ltd, females, 6 to 8 weeks old, 18 to 20 g) were taken as one group, identified with a black marker pen on the tail with the numbers 1 to 5; five mice in each group were sequentially injected intravenously with 20 μg of the lipid nanoparticle composition. The lipid nanoparticle compositions of the present invention were prepared according to Test Example 1, in which luciferase mRNA was encapsulated. A phosphate-buffered saline (PBS) group was established in parallel as a blank control and an MC3 group was established as a reference (obtained by preparation according to the method and ratio of Test Example 1).

[00408] The fluorescence assay was performed for each group of mice 24 hours after intravenous administration of the samples (YEASEN fluorescein sodium salt, lot: D5330150, IP, 150 mg / kg was administered 10 minutes prior to each group). The mice were anesthetized and then placed in a live small animal optical imaging system - IVIS®Lumina LT Series III according to the tail mark orders #1 and #5. Whole-body fluorescence was detected to assess the application and expression of the prepared Luciferase mRNA.

[00409] At the end of the test, the mice were sacrificed by cervical dislocation, and the liver, spleen, stomach, and intestinal tract were harvested, and the organs were discharged according to the corresponding positions from No. 1 to No. 5 for fluorescence detection of the organs.

[00410] As shown in Figures 2A to 2D, the group of Compound 2A, Compound 5A and Compound 13 of the present invention achieved significant extrahepatic application effects, and the application effects Petition 870250052396, dated 06 / 23 / 2025, pages 156 / 203 149 / 150 extrahepatic results were significantly better than those of the MC3 and Compound 20A groups, demonstrating that the compounds of the present invention had reduced hepatic accumulation toxicity and improved extrahepatic application properties. Experimental example 5: Toxicity assay

[00411] The animals were grouped according to body weight (five animals per group) one day before administration (Zhejiang Vital River Laboratory Animal Technology Co. Ltd, males, body weight: 170 to 220 g). The animals were weighed before administration and the lipid nanoparticle compositions based on Compound 2A, Compound 5A, Compound 13 or Compound 20A (prepared according to Test Example 1) of the present invention were administered intravenously in a single dose according to body weight. Luciferase mRNA was encapsulated in said lipid nanoparticle compositions. LNP SM102, LNP MC3 (each prepared according to the method and ratio of Test Example 1) and phosphate-buffered saline (PBS) were established in parallel as a control group, respectively.

[00412] The administration volume is 10 ml / kg and the administration dosage is 3 mg / kg.

[00413] Frequency of detection: non-anticoagulated blood was collected before administration and 24 hours after administration, the blood sampling method being as follows:

[00414] Non-anticoagulated blood was collected (the night before sampling, mice were fasted overnight but had ad libitum access to water, and were fed after sampling was completed), and non-anticoagulated whole blood was left to stand at room temperature for 30 min, centrifuged at 5000 rpm for 5 min, serum (200 μL) was aspirated, and serum ALT (alanine aminotransferase) and AST (aspartate aminotransferase) were measured. Petition 870250052396, dated 06 / 23 / 2025, pages 157 / 203 150 / 150 days with an automated biochemical detector (Hitachi 7060 Automated Biochemical Detector).

[00415] During the test, four rats in the MC3 group died and all five rats in the Compound 20A group died.

[00416] The results, as shown in Figures 3A to 3B, showed that the aspartate aminotransferase and alanine aminotransferase values ​​of Compound 2A, Compound 5A, and Compound 13 groups of the present invention were lower than those of the MC3 and SM102 ionizable lipid groups used for LNPs in commercially available products, respectively, indicating that the compounds of the present invention have lower hepatotoxicity and higher biological safety.

[00417] Although the foregoing has been described in connection with embodiments of the present application, the present application should not be limited by the specific embodiments and fields of application previously mentioned. The aforementioned specific embodiments are intended to illustrate, but not limit, the scope of the present description. Multiple forms, without departing from the claimed scope of the present application, may be made by one skilled in the art under the inspiration of the descriptive report of the present application, which are within the claimed scope of the present application.

Claims

CLAIMS 1.Compound of formula (I), or a salt or stereoisomer thereof (i) characterized in that: R1a Ri being, wherein R1a and R1b are independently selected from H or C1-C6 alkyl, and R2 and R3 are independently selected from H or C1-C6 alkyl, or Ri and R2, together with the carbon atom to which they are attached, form a 5- to 7-membered substituted or unsubstituted nitrogen-containing heterocyclic ring, and R3 is selected from H or C1-C6 alkyl, or Ri and R3, together with the carbon atoms to which they are attached, form ring A, which is a 5- to 7-membered substituted or unsubstituted carbocyclic or heterocyclic ring, R2 being selected from H or C1-C6 alkyl; R4, Rs and Re being independently selected from C1-C14 alkyl; X and Y being independently selected from O or S; Xi and X2 are independently selected from C=O or O, and Yi and Y2 are independently selected from Petition 870250052396, dated 06 / 23 / 2025, page.159 / 203 2 / 18 C=O or O, provided that Xi and Yi are not both C=O or O, and X2 and Y2 are not both C=O or O; men can be independently selected from 0, 1 or 2, provided that men are not both 0; oep can be independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; q can be selected from 0, 1, 2, 3, 4, 5 or 6.

2. Compound according to claim 1, or a salt or a stereoisomer thereof, the compound of formula (I) being characterized by being of formula (IA), (IA) wherein q is selected from 1, 2, 3 or 4.

3. A compound according to any of the preceding claims, or a salt or a stereoisomer thereof, characterized in that R4 is C9, C10, C11 or C12 linear alkyl; and R5 and R6 are each independently selected from C6, C7, C8 or C9 linear alkyl.

4. A compound, according to any of the preceding claims, or a salt or a stereoisomer thereof, characterized in that it is 5 or 6.

5. A compound, according to any of the preceding claims, or a salt or a stereoisomer thereof, characterized in that p is 7 or 8.

6. Compound, according to any of the preceding claims, or a salt or a stereoisomer thereof, characterized by X and Y both being O.

7. A compound, according to any of the preceding claims, or a salt or a stereoisomer thereof, characterized in that n is 1, m is 0; or n is 1, m is 1; or n is 0, m is 1; 8. Compound according to any of the preceding claims, or a salt or a stereoisomer thereof, the compound of formula (I) being characterized by being selected from the following structure:

9. Compound, according to any of the preceding claims, or a salt or a stereoisomer thereof, the compound of formula (I) being characterized by being selected from the following structure: (IIA-B) Petition 870250052396, dated 06 / 23 / 2025, page 161 / 203 4 / 18 10. Compound, according to any of the preceding claims, or a salt or a stereoisomer thereof, the compound of formula (I) being characterized by being selected from the following structure: JU 71 z''z----70 / “ / “ u \ o π---q ' \ l / w \ O Xt ,R4 ( |< ^Y1 Ò Y2 r6 (ΠΑ-Ε) / Xl\ > / R4 r Yl ihl R5 I Y2 R6 (IIA-F) Petition 870250052396, dated 23 / 06 / 2025, page.

11. A compound, according to any of the preceding claims, or a salt or a stereoisomer thereof, characterized in that the C1-C6 alkyl group is independently selected from -CH3, -CH2CH3 or -CH(CH3)2.

12. Compound, according to any of the preceding claims, or a salt or stereoisomer thereof, characterized in that: R1a and R1b are independently selected from CH3; R2 and R3 are independently selected from H; R4 is C10, C11 or C12 linear alkyl; Rs and Re are identical and are selected from C6, C7 and C8 linear alkyl; X and Y are independently selected from O; Xi and X2 are independently selected from C=O or O; Yi and Y2 are independently selected from C=O or O, provided that X1 and Y1 are not both C=O or O, and X2 and Y2 are not both C=O or O; m is 0, n is 1; o is 5 or 6; p can be 7 or 8, for example, p can be 7; q can be 2, 3 or 4, for example, q can be 2 or 3, for example, q can be 2.

13. A compound according to any of the preceding claims, or a salt or a stereoisomer thereof, characterized in that X1 and X2 are both C=O, and Y1 and Y2 are both O.

14. Compound, according to any one of claims 1 to 12, or a salt or a stereoisomer thereof, characterized in that X1 is O, Y1 is C=O, and X2 is C=O, Y2 is O.

15. A compound according to any one of claims 1 to 12, or a salt or a stereoisomer thereof, characterized in that X1 is C=O, Y1 is O, and X2 is O, Y2 is C=O; or X1 and X2 are both O, and Y1 and Y2 are both C=O.

16. Compound, according to any of the preceding claims, or a salt or a stereoisomer thereof, characterized in that R4 is a linear C10-C11 alkyl.

17. Compound, according to any of the preceding claims, or a salt or a stereoisomer thereof, characterized in that R5 and R6 are both C8 linear alkyl.

18. A compound according to any of the preceding claims, or a salt or a stereoisomer thereof, characterized in that: o being 5, R4 is C11 linear alkyl, p being 7, and R5 and R6 are both C8 linear alkyl, or o being 6, R4 is C10 linear alkyl, p being 7, and R5 and R6 are both C8 linear alkyl.

19. Compound, according to claim 1, or a salt or a stereoisomer thereof, the compound being characterized by being selected from: Compound 1 Compound 3 Compound 2 Compound 4 Compound 5 Compound 6 Compound 9 Compound 10 Compound 11 165 / 203 8 / 18 Compound 12 ο Compound 13 Compound 16 Ο Ο Compound 17 Compound 19 ο Compound 20 Compound 21 ο Compound 22 ο Petition 870250052396, of 06 / 23 / 2025, p. 166 / 203 9 / 18 Compound 23 Compound 26 Compound 27 o ~ N^' Compound 28 ' —N Compound 29 x Compound 30 Compound 31 or Compound 32 20. Compound, according to claim 1, or a salt or a stereoisomer thereof, the compound being characterized by being selected from: Compound 5C Compound 5E Compound 5H Compound 13B Compound 13D Compound 13F Compound 13H Compound 20B Compound 20C Compound 20D Compound 20E Compound 20F 169 / 203 12 / 18 Compound 20G Compound 20H 21. Method for preparing a compound, as defined in any one of claims 1 to 20, characterized in that Compound (IA) is obtained from Compound J as a starting material, M (IA) wherein Zi is selected from OH, Z2 and Z3 are independently selected from OH or SH, respectively, and Z4 is selected from OMs; and X, Y, X1, X2, Y1, Y2, R1a, R1b, R2, R3, R4, R5, R6, m, n, o, peq are as defined in any one of claims 1 to 20; wherein compound J is reacted with compound K in a benzene-based solution of pyridinium 4-methylbenzenesulfonate to give compound L, a benzene-based solvent used in said benzene solution is preferably toluene; The said compound L is reacted in a haloalkane solution of (CH3SO2)2O to give a compound M, and the said haloalkane is preferably DCM, dichloroethane or chloroform; Petition 870250052396, dated 06 / 23 / 2025, p.170 / 203 13 / 18 said compound M is reacted in a polar aprotic solvent to form a compound IA and said polar aprotic solvent is preferably THF.

22. Method of preparation, according to claim 21, characterized in that Compound J is obtained from Compound H and Compound C as starting materials, hc, j, wherein X is selected from halogen; and Xi, X2, R4, R5, R6, oep are as defined in any of claims 1 to 20; wherein said Compound H is reacted with Compound C in the presence of a carbonate salt, NBu4I, and a polar aprotic solvent to give Compound I, said carbonate salt is preferably Cs2CO3 or K2CO3; said polar aprotic solvent is preferably DMF or DMA; said Compound I is reacted at pH 1 to 5 to give Compound J, preferably said pH is adjusted by a hydrochloric acid solution and said reaction solvent is haloalkane and preferably DCM, dichloroethane or chloroform.

23. Preparation method according to claim 22, characterized in that Compound F is reacted with Compound G to provide Compound H, fgh, wherein X is selected from halogen; X1, Yi, R4 and o are as defined in any of claims 1 to 20; wherein said Compound F is reacted with Compound G in the presence of a carbonate salt, NBU4I, and a polar aprotic solvent to provide Compound H, said carbonate salt is preferably Cs2CO3 or K2CO3; and said polar aprotic solvent is preferably DMF or DMA.

24. Nanoparticle composition characterized by comprising a lipid component comprising a compound as defined in any of claims 1 to 20, or a salt or stereoisomer thereof; preferably, said nanoparticle composition is of lipid nanoparticles (LNPs).

25. Nanoparticle composition according to claim 24, characterized in that said lipid component further comprises a phospholipid, a structural lipid and / or a PEG lipid; wherein said phospholipid is preferably selected from one, two or more of the following compounds: dilauroyl lecithin (DLPC), dimyristoyl phosphatidylcholine (DMPC), dioleoyl lecithin (DOPC), dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), dioleoyl phosphatidylcholine (DUPC), palmitoyl oleoyl phosphatidylcholine (POPC), 1,2-di-O-octadecyl-sn-glycero-3-phosphocholine (18:O diether PC), 1-oleoyl-2-cholesteryldimethylsuccinoyl-sn-glycero-3-phosphocholine (OChemsPC), l-hexadecyl-sn-glycero-3-phosphocholine (C16 Lyso PC), 1,2-divinyl-sn-glycero-3-phosphocholine, 1,2-diarylacyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphorylethanolamine (DOPE), Petition 870250052396, dated 06 / 23 / 2025, p.172 / 203 15 / 18 1,2-di-phytanoyl-sn-glycero-3-phosphoethanolamine (ME 16.0 PE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-diethenol-sn-glycero-3-phosphoethanolamine, 1,2-divinyl-sn-glycero-3-phosphoethanolamine, 1,2-diaryl-sn-glycero-3-phosphoethanolamine, 1,2-dithio-hexaenoate-sn-glycero-3-phosphoethanolamine, sodium salt of 1,2-dioleoyl-sn-glycero-3-phosphate-(1-glycerol) (DOPG) or sphingomyelin, for example, said phospholipid is DOPE or DSPC; The structural lipid is preferably selected from one, two or more of cholesterol, coprosterol, sitosterol, ergosterol and stigmasterol; for example, the structural lipid is cholesterol; and / or the PEG lipid is preferably selected from one, two or more of PEG-modified phosphatidylethanolamine, PEG-modified phosphatidic acid, PEG-modified ceramide, PEG-modified dialkylamine, PEG-modified diacylglycerol or PEG-modified dialkylglycerol.

26. Nanoparticle composition, according to any one of claims 24 to 25, characterized in that said lipid component additionally comprises cationic and / or ionizable lipid.

27. Nanoparticle composition, according to any one of claims 24 to 26, characterized by further comprising a therapeutic agent and / or a prophylactic agent, said therapeutic and / or prophylactic agent being selected from vaccines or compounds capable of eliciting an immune response and / or nucleic acids, the nucleic acid preferably being RNA, and said RNA being selected from one, two or more of siRNA, aiRNA, miRNA, dsRNA, shRNA or mRNA.

28. Nanoparticle composition, according to any Petition 870250052396, dated 06 / 23 / 2025, p. 173 / 203 16 / 18 one of claims 24 to 27, characterized in that: the encapsulation efficiency of said therapeutic and / or prophylactic agent is > 50%; or > 80%; or > 90%; and / or said nanoparticle composition has an average particle size of 50 nm to 110 nm; and / or said nanoparticle composition has a polydispersity index of 0.04 to 0.

20.

29. Use of the compound as defined in any one of claims 1 to 20, or a salt thereof or a stereoisomer thereof, characterized in that it is intended for the preparation of lipid nanoparticle compositions.

30. Pharmaceutical composition characterized by comprising the nanoparticle composition as defined in any one of claims 24 to 28, as well as a pharmaceutically acceptable excipient.

31. A method for applying a therapeutic and / or prophylactic agent to a mammalian cell, characterized by comprising administering the nanoparticle composition as defined in any one of claims 24 to 28, or the pharmaceutical composition as defined in claim 30, to an individual, wherein said administration comprises bringing the cell into contact with said nanoparticle composition or said pharmaceutical composition to apply the therapeutic and / or prophylactic agent to the cell; for example, the mammalian cell is in a mammal; for example, said mammal is a human being; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally, or by inhalation.

32. Method for producing a polypeptide of interest in a mammalian cell characterized by comprising bringing the cell into contact with the nanoparticle composition as defined in any of claims 24 to 28, or the pharmaceutical composition as defined in claim 30, to apply a therapeutic and / or prophylactic agent to the cell, wherein said therapeutic and / or prophylactic agent is an mRNA encoding the polypeptide of interest, such that the mRNA is capable of being translated in the cell to produce the polypeptide of interest; for example, the mammalian cell is in a mammal; for example, said mammal is a human being; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation.

33. A method for treating or preventing a disease or condition in a mammal, such as a human, characterized by comprising administering a therapeutically or prophylactically effective amount of a nanoparticle composition as defined in any of claims 24 to 28, or a pharmaceutical composition as defined in claim 30, to the mammal; for example, said disease or condition is characterized by dysfunctional or abnormal protein or polypeptide activity; for example, said disease or condition is selected from among infectious diseases, cancer and proliferative diseases, genetic diseases, autoimmune diseases, diabetes, neurodegenerative diseases, cardiovascular diseases, renal vascular diseases or metabolic diseases; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation.

34. Method for specifically applying a therapeutic and / or prophylactic agent to a mammalian organ characterized by comprising administering to the mammal the nanoparticle composition as defined in any of claims 24 to 28, or the pharmaceutical composition as defined in claim 30, said administration comprising placing the mammalian organ in contact with said nanoparticle composition or pharmaceutical composition, thereby applying the therapeutic and / or prophylactic agent to the organ; for example, said mammal is a human being; for example, said nanoparticle composition or pharmaceutical composition is administered intravenously, intramuscularly, intradermally, subcutaneously, intranasally or by inhalation; for example, said mammal is pretreated 24 hours or fewer hours before the contact or administration step; For example, about an hour before the contact or administration stage.

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