# US 12,667,618 B2 · Polymer nanoparticle composition for inducing immunity and preparation method therefor

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- Number: US 12,667,618 B2
- Document ID: US12667618B2
- Status: Granted
- Kind: B2
- Application number: 17/774,887
- Filed: 2020-11-05
- Published: 2022-12-29
- Granted: 2026-06-30
- Earliest claimed: 2019-11-07
- Assignees: Samyang Holdings Corporation
- Applicants: Samyang Holdings Corporation
- Inventors: So Jin Lee; Joon Young Park; Hye Yeong Nam; He Len Cho; Goo Young Kim
- Web page: https://patentgrep.com/patent/US12667618B2

## CPC

- A61K 47/50: the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 39/001156: {Tyrosinase and tyrosinase related proteinases [TRP-1 or TRP-2]}
- A61K 39/00119: {Melanoma antigens}
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 47/543: {Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine}
- A61K 47/6935: {the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol}
- A61P 35/00: Antineoplastic agents
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers}
- A61K 2039/55561: {CpG containing adjuvants; Oligonucleotide containing adjuvants}
- A61K 2039/572: {cytotoxic response}
- A61K 2039/6093: {Synthetic polymers, e.g. polyethyleneglycol [PEG], Polymers or copolymers of (D) glutamate and (D) lysine}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed are a composition for inducing immunity against an active ingredient and a method for preparing same, the composition comprising: a nucleic acid, a polypeptide, or a combination thereof as the active ingredient; a cationic compound; an amphiphilic block copolymer; and a polylactate, wherein the active ingredient is encapsulated in a nanoparticle structure formed by the amphiphilic block copolymer and the polylactate.

## Claims

### Claim 1

A method for inducing immunity to an active ingredient, comprising administering to a subject a composition which comprises:
a nucleic acid as the active ingredient;
a cationic compound represented by the following Formula 1; an A-B type block copolymer including a hydrophilic A block of alkylene glycol and a hydrophobic B block of polyester as an amphiphilic block copolymer; and
a salt of polylactic acid,
wherein a content of the cationic compound is 2 to 15 parts by weight, a content of the amphiphilic block copolymer is 15 to 50 parts by weight, and a content of the salt of polylactic acid is 5 to 30 parts by weight, based on 1 part by weight of the active ingredient;
wherein the active ingredient is entrapped in a nanoparticle structure of the amphiphilic block copolymer and the salt of polylactic acid,
wherein the composition is suitable for delivering the active ingredient to the spleen efficiently; and
wherein the composition is suitable for treating cancer by inducing immunity to the active ingredient:
in Formula 1,
each of n and m is independently 1 to 9, and 2≤n+m≤10,
each of a and b is 2 to 4,
each of R1 and R2 is independently selected from the group consisting of lauryl, myristyl, palmityl, stearyl, arachidyl, behenyl, lignoceryl, cerotyl, myristoleyl, palmitoleyl, sapienyl, oleyl, linoleyl, arachidonyl, eicosapentaenyl, erucyl, docosahexaenyl and cerotyl.

### Claim 2 (depends on 1)

The method for inducing immunity according to claim 1, wherein the nucleic acid expresses a tumor antigen.

### Claim 3 (depends on 2)

The method for inducing immunity according to claim 2, which is for treating a disease related to the tumor antigen.

### Claim 4 (depends on 2)

The method for inducing immunity according to claim 2, which is for use as a vaccine against a disease related to the tumor antigen.

### Claim 5 (depends on 1)

The method for inducing immunity according to claim 1, wherein a surface charge of the nanoparticles is −40 to 40 mV.

### Claim 6 (depends on 1)

The method for inducing immunity according to claim 1, wherein the hydrophobic block B is modified by chemically bonding tocopherol, cholesterol or a fatty acid having 10 to 24 carbon atoms to a hydroxyl group at a terminal thereof.

### Claim 7 (depends on 1)

The method for inducing immunity according to claim 1, wherein the hydrophilic A block has a number average molecular weight of 200 to 50,000 Dalton, and the hydrophobic B block has a number average molecular weight of 50 to 50,000 Dalton.

### Claim 8 (depends on 1)

The method according to claim 1, wherein:
said cationic compound is at least one member selected from the group consisting of 1,6-triethylenetetramide (N,N′-((ethane-1,2-diylbis(azanediyl))bis(ethane-2,1-dioleoyl diyl))dioleamide), 1,8-dilinoleoyl tetraethylenepentamide ((9Z,9′Z,12Z,12′Z)—N,N′-(((azanediylbis(ethane-2,1-diyl))bis(azanediyl))bis(ethane-2,1-diyl))bis(octadeca-9,12-dienamide)), 1,4-dimyristoleoyl diethylenetriamide((9Z,9′Z)—N,N′-(azanediylbis(ethane-2,1-diyl))bis(tetradec-9-enamide)), 1,10-distearoyl pentaethylenehexamide (N,N′-(3,6,9,12-tetraazatetradecane-1,14-diyl)distearamide) and 1,10-dioleoyl pentaethylenehexamide (N,N′-(3,6,9,12-tetraazatetradecanc-1,14-diyl)dioleamide);
said hydrophilic A block is at least one member selected from the group consisting of polyalkyleneglycol, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylamide and derivatives thereof; and
said hydrophobic B block is at least one member selected from the group consisting of polylactide, polyglycolide, polycaprolactone, polydioxane-2-one, a copolymer of polylactide and glycolide, a copolymer of polylactide and polydioxane-2-one, a copolymer of polylactide and polycaprolactone, and a copolymer of polyglycolide and polycaprolactone.

### Claim 9 (depends on 1)

The method according to claim 1, wherein:
said cationic compound is N,N′-((ethane-1,2-diylbis(azanediyl))bis(ethane-2,1-diyl))dioleamide;
said A-B type block copolymer is monomethoxy polyethylene glycol-polylactide block copolymer; and
said salt of polylactic acid is sodium polylactate.

### Claim 10

A method for preparing a composition for inducing immunity to an active ingredient, comprising
(a) mixing a nucleic acid as the active ingredient, a cationic compound represented by the following Formula 1, an A-B type block copolymer including a hydrophilic A block of alkylene glycol and a hydrophobic B block of polyester as an amphiphilic block copolymer and a salt of polylactic acid with a solvent which is an aqueous solution, a water-miscible organic solvent or a combination thereof; and
(b) adding an aqueous solvent to the mixture of step (a) and mixing them,
wherein a mixing amount of the cationic compound is 2 to 15 parts by weight, a mixing amount of the amphiphilic block copolymer is 15 to 50 parts by weight, and a mixing amount of the salt of polylactic acid is 5 to 30 parts by weight, based on 1 part by weight of the active ingredient;
wherein the active ingredient is entrapped in a nanoparticle structure of the amphiphilic block copolymer and the salt of polylactic acid;
wherein the composition is suitable for delivering the active ingredient to the spleen efficiently; and
wherein the composition is suitable for treating cancer by inducing immunity to the active ingredient:
in Formula 1,
each of n and m is independently 1 to 9, and 2≤n+m≤10,
each of a and b is 2 to 4,
each of R1 and R2 is independently selected from the group consisting of lauryl, myristyl, palmityl, stearyl, arachidyl, behenyl, lignoceryl, cerotyl, myristoleyl, palmitoleyl, sapienyl, oleyl, linoleyl, arachidonyl, eicosapentaenyl, erucyl, docosahexaenyl and cerotyl.

### Claim 11

A method for treating cancer by efficiently delivering a nucleic acid to the spleen and inducing immunity to a tumor antigen, comprising administering to a subject a composition which comprises:
a nucleic acid that expresses a tumor antigen;
a cationic compound represented by the following Formula 1;
an A-B type block copolymer including a hydrophilic A block of alkylene glycol and a hydrophobic B block of polyester as an amphiphilic block copolymer; and
a salt of polylactic acid,
wherein a content of the cationic compound is 2 to 15 parts by weight, a content of the amphiphilic block copolymer is 15 to 50 parts by weight, and a content of the salt of polylactic acid is 5 to 30 parts by weight, based on 1 part by weight of the nucleic acid;
wherein the nucleic acid is entrapped in a nanoparticle structure of the amphiphilic block copolymer and the salt of polylactic acid:
in Formula 1,
each of n and m is independently 1 to 9, and 2≤n+m≤10,
each of a and b is 2 to 4,
each of R1 and R2 is independently selected from the group consisting of lauryl, myristyl, palmityl, stearyl, arachidyl, behenyl, lignoceryl, cerotyl, myristoleyl, palmitoleyl, sapienyl, oleyl, linoleyl, arachidonyl, eicosapentaenyl, erucyl, docosahexaenyl and cerotyl.

### Claim 12 (depends on 11)

The method according to claim 11, wherein said tumor antigen is a member selected from the group consisting of Trp2 (tyrosinase-related protein 2), gp100 (Glycoprotein 100), tyrosinase, PSA (Prostate-specific antigen), WT1 (Wilms' tumor 1), MAGE-1 (Melanoma-associated antigen 1), NY-ESO-1 (cancer-testis antigen), and MUC-1 (Mucin 1).

### Claim 13 (depends on 11)

The method according to claim 11, wherein:
said cationic compound is at least one member selected from the group consisting of 1,6-dioleoyl triethylenetetramide (N,N′-((ethane-1,2-diylbis(azanediyl))bis(ethane-2,1-diyl))dioleamide), 1,8-dilinoleoyl tetraethylenepentamide ((9Z,9′Z,12Z,12′Z)—N,N′-(((azanediylbis(ethane-2,1-diyl))bis(azanediyl))bis(ethane-2,1-diyl))bis(octadeca-9,12-dienamide)), 1,4-dimyristoleoyl diethylenetriamide((9Z,9′Z)—N,N′-(azanediylbis(ethane-2,1-diyl))bis(tetradec-9-enamide)), 1,10-distearoyl pentaethylenehexamide (N,N′-(3,6,9,12-tetraazatetradecane-1,14-diyl)distearamide) and 1,10-dioleoyl pentaethylenehexamide (N,N′-(3,6,9,12-tetraazatetradecane-1,14-diyl)dioleamide);
said hydrophilic A block is at least one member selected from the group consisting of polyalkyleneglycol, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylamide and derivatives thereof; and
said hydrophobic B block is at least one member selected from the group consisting of polylactide, polyglycolide, polycaprolactone, polydioxane-2-one, a copolymer of polylactide and glycolide, a copolymer of polylactide and polydioxane-2-one, a copolymer of polylactide and polycaprolactone, and a copolymer of polyglycolide and polycaprolactone.

### Claim 14 (depends on 11)

The method according to claim 11, wherein:
said cationic compound is N,N′-((ethane-1,2-diylbis(azanediyl))bis(ethane-2,1-diyl))diolcamide;
said A-B type block copolymer is monomethoxy polyethylene glycol-polylactide block copolymer; and
said salt of polylactic acid is sodium polylactate.

### Claim 15 (depends on 14)

The method according to claim 14, wherein a surface charge of the nanoparticles is −40 to 40 m V.

### Claim 16 (depends on 11)

The method for inducing immunity according to claim 11, wherein a surface charge of the nanoparticles is-40 to 40 mV.