# US 2021/0330600 A1 · Nanoparticle compositions for efficient nucleic acid delivery and methods of making and using the same

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- Number: US 2021/0330600 A1
- Document ID: US20210330600A1
- Status: Published application
- Kind: A1
- Application number: 17/414,193
- Filed: 2019-12-19
- Published: 2021-10-28
- Earliest claimed: 2018-12-21
- Assignees: TIBA Biotech LLC
- Applicants: Tiba Biotech LLC
- Inventors: Poulami TALUKDER; Jasdave CHAHAL; Justine McPARTLAN; Omar KHAN; Karl RUPING
- Web page: https://patentgrep.com/patent/US20210330600A1

## CPC

- A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides}
- A61K 47/595: {Polyamides, e.g. nylon (polyamino acids A61K47/62)}
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 31/711: Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 38/1709: {from mammals}
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 47/6925: {the form being a microcapsule, nanocapsule, microbubble or nanobubble}
- A61K 49/124: {dendrimers, dendrons, hyperbranched compounds}
- A61K 49/1818: {particles, e.g. uncoated or non-functionalised microparticles or nanoparticles}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/55516: {Proteins; Peptides}
- A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers}
- A61K 2039/55561: {CpG containing adjuvants; Oligonucleotide containing adjuvants}
- 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)

## Abstract

Nanoparticle compositions for delivery of nucleic acids to subjects including modified dendrimers comprising cores, one or more of homogeneous or heterogeneous intermediate and terminal layers, and therapeutic or immunogenic nucleic acid agents enclosed within nanop article compositions are described. Methods for treating or preventing diseases or conditions in a subject by administering the nanoparticle compositions that provide immune responses and synergistic therapeutic or preventive effects are provided.

## Claims

### Claim 1

A nanoparticle composition comprising a modified dendrimer, a therapeutic or immunogenic nucleic acid agent enclosed within the nanoparticle composition, wherein the modified dendrimer comprises a plurality of terminal amine groups substituted with fatty acids or derivatives thereof.

### Claim 2 (depends on 1)

The nanoparticle composition of claim 1, wherein the modified dendrimer comprise a dendrimer selected from the group consisting of: a polyamidoamine (PAMAM) dendrimer, poly(propylene imine) (PPI) dendrimer and poly ethylene imine (PEI) dendrimer.

### Claim 3 (depends on 2)

The nanoparticle composition of claim 2, wherein the modified dendrimer is a generation 0, generation 1, or generation 2 dendrimer.

### Claim 4 (depends on 1)

The nanoparticle composition of claim 1, wherein the modified dendrimer comprises 100% of the terminal amine groups substituted with fatty acids or derivative thereof.

### Claim 5 (depends on 1)

The nanoparticle composition of claim 1, wherein the fatty acids or the derivatives thereof are selected from the group consisting of: arachidonic acid, oleic acid, eicosapentanoic acid, lauric acid, caprylic acid, capric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, and linolenic acid or esters thereof.

### Claim 6 (depends on 1)

The nanoparticle composition of claim 1, wherein the modified dendrimer comprises a core selected from the group consisting of: ethylenediamine, diaminobutane, N1-(2-aminoethyl) ethane, N1-(2-aminoethyl)propane, N3-dimethylpropan-, N1,N1′-(ethane-1,2-diyl)bis(ethane), N1-(2-(4-(2 aminoethyl)piperazin-1-yl)ethyl)ethane-1,2-diaminecyclohexan, N1-(2-(4-(2-aminoethyl)piperazin-1-yl)ethyl)ethane-1,2-diaminecyclohexan-, -poly(ethylene)-, -, N1,N1-bis(2-aminoethyl)ethane-1,2- diamine, trimesic acid/trimesoyl chloride, pentaerythritol, inositol, thiourea, hydrazinecarbothioamide, hydrazinecarbothiohydrazide, urea, 3-ureidopropanoic acid, ethane-1,2-diamine; ethane-1,2-diamine-15N2; ethane-1,2-diamine-1,2-13C2; butane-1,4-diamine; butane-1,2-diamine-15N2; butane-1,4-diamine-1,2,3,4-13C2; N1-(2-aminoethyl)propane-1,3-diamine; N1-(2-aminoethyl)-N1-methylethane-1,2-diamine; N1-methylpropane-1,3-diamine; N1, N3-dimethylpropane-1,3-diamine; N1-(2-aminoethyl)ethane-1,2-diamine; and N1, N3-(ethane-1,2-dyl)bis(ethane-1,2- diamine)thiourea, hydrazinecarbothioamide, hydrazinecarbothiohydrazide, urea, 3-ureidopropanoic acid, 2,2′-(ethane-1,2-diylbis(oxy)bis(ethan-1-amine), 2, 2′-(ethane-1,2-diylbis(azanediyl)bis(ethan-1-ol), 2-((2-aminoethyl)amino)ethan-1-ol; N1, N1-bis(2-aminoethyl)ethane-1,2-diamine; N1-(2-(4-(2-aminoethyl)piperazin-1-yl)ethyl)ethane-1,2-diamine; cyclohexane-1,2-diamine; poly(ethylene)1,n diamine; polyethylenimine, linear and polyethylenimine, branched.

### Claim 7 (depends on 1)

The nanoparticle composition of claim 1, wherein the modified dendrimer comprises a tracking moiety.

### Claim 8 (depends on 7)

The nanop article composition of claim 7, wherein the tracking moiety is a stable isotope.

### Claim 9 (depends on 8)

The nanoparticle composition of claim 8, wherein the stable isotope is a stable isotope of carbon or nitrogen.

### Claim 10 (depends on 9)

The nanoparticle composition of claim 9, wherein the stable isotope of carbon is 13C, and the stable isotope of nitrogen is 15N.

### Claim at position 11

11-16. (canceled)

### Claim 17 (depends on 1)

The nanop article composition of claim 1, wherein the therapeutic or immunogenic nucleic acid agent is selected from the group consisting of: a polynucleotide, oligonucleotide, DNA, cDNA, RNA, repRNA, siRNA, miRNA, sgRNA, and mRNA.

### Claim 18 (depends on 17)

The nanoparticle composition of claim 17, wherein the therapeutic or immunogenic nucleic acid agent encodes one or more antigens selected from the group consisting of infectious disease, pathogen, cancer, autoimmunity disease and allergenic disease.

### Claim 19 (depends on 17)

The nanoparticle composition of claim 17, wherein the therapeutic or immunogenic nucleic acid agent comprises an RNA or DNA capable of silencing, inhibiting or modifying the activity of a gene.

### Claim 20 (depends on 17)

The nanoparticle composition of claim 17, wherein the nucleic acid agent comprises at least one polynucleotide encoding a STING protein.

### Claim 21 (depends on 20)

The nanoparticle composition of claim 20, wherein the STING protein comprises an amino acid sequence with at least 90% identity to a sequence selected from the group consisting of SEQ ID NOS: 1, 3, 5 and 7.

### Claim 22 (depends on 20)

The nanop article composition of claim 20, wherein the at least one polynucleotide comprises a sequence with at least 90% identity to a sequence selected from the group consisting of SEQ ID NOS: 2, 4, 6 and 8.

### Claim 23 (depends on 20)

The nanoparticle composition of claim 20, wherein the at least one polynucleotide comprises a sequence with at least 90% identity to a sequence selected from the group consisting of SEQ ID NOS: 9-12.

### Claim 24 (depends on 1)

The nanoparticle composition of claim 1 further comprising an amphiphilic polymer.

### Claim 25 (depends on 24)

The nanoparticle composition of claim 24, wherein the amphiphilic polymer comprises a hydrophilic component selected from the group consisting of: polyalkylene oxides, block copolymers, and polyethylene glycol molecules.

### Claim 26 (depends on 24)

The nanoparticle composition of claim 24, wherein the amphiphilic polymer comprises a hydrophobic component selected from the group consisting of: lipid and a phospholipid.

### Claim 27 (depends on 24)

The nanoparticle composition of claim 24, wherein the amphiphilic polymer comprises 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (poly-ethylene glycol)-2000].

### Claim 28 (depends on 1)

The nanoparticle composition of claim 1, wherein the nanoparticle composition comprises the amphiphilic polymer in a range from 1% (w/w) to 40% (w/w) of the amphiphilic polymer per nanop article composition.

### Claim at position 24

29-52. (canceled)

### Claim 53 (depends on 1)

A method for treating or preventing a disease or condition in a subject comprising:
providing a nanop article composition of claim 1; and
administering a therapeutically effective amount of the nanoparticle composition to a subject.

### Claim 54 (depends on 53)

The method of claim 53, wherein the therapeutically effective amount of the nanoparticle composition comprises the therapeutic or immunogenic nucleic acid agent in a range from 0.01 mg nucleic acid to 10 mg nucleic acid per kg body weight of the subject.

### Claim 55 (depends on 54)

The method of claim 54, wherein the subject is a mammal selected from the group consisting of: a chicken, a rodent, a canine, a primate, an equine, a high value agricultural animal, and a human.

### Claim 56

(canceled)