# US 10,246,711 B2 · RNAi inhibitors of glucose-6-phosphate dehydrogenase for treating cardiovascular and pulmonary conditions

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- Number: US 10,246,711 B2
- Document ID: US10246711B2
- Status: Granted
- Kind: B2
- Application number: 15/813,469
- Filed: 2017-11-15
- Published: 2018-05-17
- Granted: 2019-04-02
- Earliest claimed: 2016-11-16
- Assignees: Rakhee Gupte
- Applicants: Rakhee Gupte
- Inventors: Rakhee Gupte
- Web page: https://patentgrep.com/patent/US10246711B2

## CPC

- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- C12Q 1/32: involving dehydrogenase
- C12N 2310/14: interfering nucleic acids [NA]
- C12Y 101/01049: Glucose-6-phosphate dehydrogenase (1.1.1.49)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Y: ENZYMES

## Abstract

The present disclosure provides for methods of treating or preventing a cardiovascular disorder and/or a related pulmonary disorder in a subject. In certain embodiments, a therapeutically effective amount of a polynucleotide inhibitor of Glucose-6-phosphate dehydrogenase (G6PD) or a nucleic acid encoding G6PD is administered.

## Claims

### Claim 1

A method for treating a cardiovascular disorder and/or a pulmonary disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a polynucleotide inhibitor of Glucose-6-phosphate dehydrogenase (G6PD) or a nucleic acid encoding G6PD, wherein the polynucleotide inhibitor comprises the nucleotide sequence set forth in SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, or combinations thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the polynucleotide inhibitor comprises an RNA interference (RNAi) inhibitor.

### Claim 3 (depends on 1)

The method of claim 1, wherein the polynucleotide inhibitor comprises a small interfering RNA (siRNA), a short hairpin RNA (shRNA), or a combination thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein the polynucleotide inhibitor comprises an antisense oligonucleotide targeting a nucleic acid encoding G6PD.

### Claim 5 (depends on 1)

The method of claim 1, wherein the cardiovascular disorder comprises pulmonary hypertension, pulmonary hypertension-associated heart failure, cardiomyopathy, hypertension, stroke, ischemic cardiomyopathy, medial hypertrophy, acute neointimal formation following iatrogenic interventions, atherosclerosis, congestive heart failure, or combinations thereof.

### Claim 6 (depends on 1)

The method of claim 1, wherein the cardiovascular disorder and/or a pulmonary disorder comprises angiosarcoma, hemangioscarcoma, Timothy Syndrome, hypertrophic cardiomyopathy, atrial fibrillation, or combinations thereof.

### Claim 7 (depends on 1)

The method of claim 1, wherein the cardiovascular disorder and/or pulmonary disorder comprises any of the groups of pulmonary hypertension 1-5, or combinations thereof.

### Claim 8 (depends on 7)

The method of claim 7, wherein the disorder comprises scleroderma, categorized as pulmonary hypertension group I.

### Claim 9 (depends on 1)

The method of claim 1, further comprising treating the subject with a diuretic, a vasodilator, an inotropic agent, an angiotensin converting enzyme (ACE) inhibitor, a beta blocker, a neurohumoral blocker, an aldosterone antagonist, a histone deacetylase inhibitor, erythropoietin, or combinations thereof.

### Claim 10 (depends on 1)

The method of claim 1, further comprising treating the subject with a medical device and/or surgery.

### Claim 11 (depends on 10)

The method of claim 10, wherein the medical device comprises a bi-ventricular pacemaker, an implantable cardioverter-defibrillator (ICD), a ventricular assist device (VAD), a left ventricular assist device (LVAD), a cardiac resynchronization therapy (CRT), or combinations thereof.

### Claim 12

A method of treating a cardiovascular disorder and/or a pulmonary disorder in a subject in need thereof, comprising administering a composition comprising a polynucleotide inhibitor of Glucose-6-phosphate dehydrogenase (G6PD) or a nucleic acid encoding G6PD, wherein the polynucleotide inhibitor comprises the nucleotide sequence set forth in SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, or combinations thereof to the subject.