# US 2023/0414724 A1 · Treatment of hyperbilirubinemia

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- Number: US 2023/0414724 A1
- Document ID: US20230414724A1
- Status: Published application
- Kind: A1
- Application number: 18/339,842
- Filed: 2023-06-22
- Published: 2023-12-28
- Earliest claimed: 2014-04-25
- Assignees: Genethon; International Centre for Genetic Engineering and Biotechnology
- Applicants: Genethon; International Centre for Genetic Engineering and Biotechnology
- Inventors: FEDERICO MINGOZZI; GIUSEPPE RONZITTI; FANNY COLLAUD; ANDRÉS MURO; GIULIA BORTOLUSSI
- Web page: https://patentgrep.com/patent/US20230414724A1

## CPC

- A61K 38/45: Transferases (2)
- 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
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 9/1051: {Hexosyltransferases (2.4.1)}
- C12N 15/86: Viral vectors
- C12Y 204/01017: Glucuronosyltransferase (2.4.1.17)
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- C12N 2830/008: cell type or tissue specific enhancer/promoter combination
- C12N 2830/42: being an intron or intervening sequence for splicing and/or stability of RNA
- 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
- 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 invention relates to a nucleic acid sequence useful in the treatment of hyperbilirubinemia, in particular in the treatment of Crigler-Najjar syndrome. More particularly, the nucleic acid sequence of the present invention is a codon-optimized UGT1A1 coding sequence.

## Claims

### Claim 1

An intron which is a modified intron with decreased open reading frames.

### Claim 2 (depends on 1)

The intron according to claim 1, which is a modified HBB2 intron, a modified FIX intron, or a modified chicken beta-globin intron.

### Claim 3 (depends on 1)

A nucleic acid construct comprising the intron according to claim 1.

### Claim 4 (depends on 3)

The nucleic acid construct according to claim 3, further comprising a gene of interest and one or more additional expression control sequences.

### Claim 5 (depends on 4)

The nucleic acid construct according to claim 4, wherein the said additional expression control sequence is an ubiquitous or tissue-specific promoter.

### Claim 6 (depends on 1)

A vector comprising the intron according to claim 1.

### Claim 7 (depends on 6)

The vector according to claim 6, which is a viral vector.

### Claim 8 (depends on 7)

The vector according to claim 7, wherein said viral vector is a single-stranded or double-stranded self-complementary AAV vector.

### Claim 9 (depends on 8)

The vector according to claim 8, wherein the AAV vector has an AAV-derived capsid.

### Claim 10 (depends on 9)

The vector according to claim 9, wherein the AAV vector has an AAV8 capsid.

### Claim 11 (depends on 9)

The vector according to claim 9, wherein the AAV vector is a pseudotyped AAV vector.

### Claim 12 (depends on 3)

A cell transformed with the nucleic acid construct according to claim 3.

### Claim 13 (depends on 4)

A method of gene or cell therapy in a subject comprising expressing a nucleic acid construct according to claim 4 in a subject in need of gene or cell therapy.