# US 10,369,233 B2 · Nucleic acid products and methods of administration thereof

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- Number: US 10,369,233 B2
- Document ID: US10369233B2
- Status: Granted
- Kind: B2
- Application number: 16/030,675
- Filed: 2018-07-09
- Published: 2019-01-03
- Granted: 2019-08-06
- Earliest claimed: 2016-08-17
- Assignees: Factor Bioscience Inc.
- Applicants: Factor Bioscience Inc.
- Inventors: Matthew Angel; Christopher Rohde
- Web page: https://patentgrep.com/patent/US10369233B2

## CPC

- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/7115: Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine
- A61K 48/0058: {Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct}
- A61K 48/0066: {Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid}
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- C07K 14/001: {by chemical synthesis}
- C12N 9/22: Ribonucleases {[RNase]; Deoxyribonucleases [DNase]}
- C12N 9/222: {Clustered regularly interspaced short palindromic repeats [CRISPR]-associated [CAS] enzymes}
- C07K 14/003: {Peptide-nucleic acids (PNAs)}
- C12N 2310/20: involving clustered regularly interspaced short palindromic repeats [CRISPR]
- C12Y 301/21: Endodeoxyribonucleases producing 5'-phosphomonoesters (3.1.21)
- 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
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES

## Abstract

The present invention relates in part to nucleic acids, including nucleic acids encoding proteins, therapeutics and cosmetics comprising nucleic acids, methods for delivering nucleic acids to cells, tissues, organs, and patients, methods for inducing cells to express proteins using nucleic acids, methods, kits and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, therapeutics, and cosmetics produced using these methods, kits, and devices.

## Claims

### Claim 1

A composition comprising a synthetic RNA encoding a gene-editing protein that targets an immune checkpoint molecule gene, wherein the gene-editing protein comprises:
(a) a DNA-binding domain comprising a plurality of repeat sequences and at least one of the repeat sequences comprises the amino acid sequence: LTPvQVVAIAwxyzGHGG (SEQ ID NO: 629) and is between 36 and 39 amino acids long, wherein:
“v” is Q, D or E,
“w” is S or N,
“x” is H, N, or I,
“y” is D, A, I, N, G, H, K, S, or null, and
“z” is GGKQALETVQRLLPVLCQD (SEQ ID NO: 630) or GGKQALETVQRLLPVLCQA (SEQ ID NO: 631); and
(b) a nuclease domain comprising a catalytic domain of a nuclease.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the nuclease domain is capable of forming a dimer with another nuclease domain.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the immune checkpoint molecule is selected from PD-1, PD-L1, PD-L2, CTLA-4, ICOS, LAG3, OX40, OX40L, and TIM3.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the synthetic RNA comprises one or more non-canonical nucleotides, the one or more non-canonical nucleotides comprise one or more of 5-hydroxycytidine, 5-methylcytidine, 5-hydroxymethylcytidine, 5-carboxycytidine, 5-formylcytidine, 5-methoxycytidine, pseudouridine, 5-hydroxyuridine, 5-methyluridine, 5-hydroxymethyluridine, 5-carboxyuridine, 5-formyluridine, 5-methoxyuridine, 5-hydroxypseudouridine, 5-methylpseudouridine, 5-hydroxymethylpseudouridine, 5-carboxypseudouridine, 5-formylpseudouridine, and 5-methoxypseudouridine.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the synthetic RNA comprises a 5′ cap structure.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the synthetic RNA comprises a 5′-UTR comprising a Kozak consensus sequence.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the synthetic RNA comprises a 5′-UTR comprising a sequence that increases RNA stability in vivo.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the synthetic RNA comprises a 3′-UTR comprising a sequence that increases RNA stability in vivo.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the synthetic RNA comprises a 3′ poly(A) tail.

### Claim 10 (depends on 4)

The composition of claim 4, wherein the one or more non-canonical nucleotides comprises 5-methoxyuridine.