# US 2014/0193880 A1 · Modified factor viii and factor ix genes and vectors for gene therapy

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- Number: US 2014/0193880 A1
- Document ID: US20140193880A1
- Status: Published application
- Kind: A1
- Application number: 14/157,657
- Filed: 2014-01-17
- Published: 2014-07-10
- Earliest claimed: 2006-06-19
- Assignees: Asklepios Biopharmaceutical, Inc.
- Applicants: Asklepios Biopharmaceutical, Inc.
- Inventors: RICHARD J. SAMULSKI
- Web page: https://patentgrep.com/patent/US20140193880A1

## CPC

- C12N 9/644: {Coagulation factor IXa (3.4.21.22)}
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- C07K 14/755: Factors VIII {, e.g. factor VIII C (AHF), factor VIII Ag (VWF)}
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- C12N 2799/025: where the vector is derived from a parvovirus
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- 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

The present invention relates to a modified and optimized Factor VIII or Factor IX nucleic acid for inclusion in a chimeric virus vector. Use of such vector can be used for treatment of hemophilia.

## Claims

### Claim 1

A composition comprising an isolated optimized gene modified to increase CG sequences and reduce cis motifs relative to a wild type gene, wherein the optimized gene is selected from the group consisting of FVIII and FIX, wherein when the optimized gene is FVIII, the gene has the nucleotide sequence of SEQ ID NO: 12 or 15 or a nucleotide sequence having 95% identity thereto, and wherein when the optimized gene is FIX the gene has the nucleotide sequence of SEQ ID NO 7 or a nucleotide sequence having 95% identity thereof.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the optimized FVIII or FIX gene is included in a virus vector.

### Claim 3 (depends on 2)

The composition of claim 2, wherein the virus vector is a chimeric virus vector comprising capsid components selected from AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7 AAV8, AAV9, AAV10, AAV11 and AAV12 capsids.

### Claim 4

A composition comprising an optimized FVIII or FIX peptide, wherein the optimized FVIII or FIX peptide is produced by the process comprising:
a) transfecting a host cell with an optimized FVIII or FIX gene, wherein when the optimized gene is FVIII, the gene has the nucleotide sequence of SEQ ID NO: 12 or 15 or a nucleotide sequence having 95% identity thereto, and wherein when the optimized gene is FIX the gene has the nucleotide sequence of SEQ ID NO 7 or a nucleotide sequence having 95% identity thereof; and
b) maintaining the transformed host cell under biological conditions sufficient for expression of the peptide.

### Claim 5

An optimized FVIII or FIX peptide, wherein the optimized FVIII or FIX peptide is encoded by an optimized FVIII or FIX gene, wherein when the optimized gene is FVIII, the gene has the nucleotide sequence of SEQ ID NO: 12 or 15 or a nucleotide sequence having 95% identity thereto, and wherein when the optimized gene is FIX the gene has the nucleotide sequence of SEQ ID NO 7 or a nucleotide sequence having 95% identity thereof.

### Claim 6 (depends on 5)

A composition comprising the optimized FVIII or FIX peptide of claim 5.