# US 2018/0021458 A1 · Optimized RPE65 Promoter and Coding Sequences > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2018/0021458 A1 - Document ID: US20180021458A1 - Status: Published application - Kind: A1 - Application number: 15/549,549 - Filed: 2016-02-08 - Published: 2018-01-25 - Earliest claimed: 2015-02-09 - Assignees: UCL Business PLC - Applicants: Ucl Business PLC - Inventors: Alexander Smith; Robin Ali - Web page: https://patentgrep.com/patent/US20180021458A1 ## CPC - A61K 48/0058: {Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct} - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 17/00: Drugs for dermatological disorders - A61P 27/02: Ophthalmic agents - C12N 9/18: Carboxylic ester hydrolases {(3.1.1)} - C12N 15/85: for animal cells - C12N 15/8509: {for producing genetically modified animals, e.g. transgenic} - C12Y 301/01064: Retinoid isomerohydrolase (3.1.1.64) - C12N 15/861: Adenoviral vectors - C12N 2015/8518: {expressing industrially exogenous proteins, e.g. for pharmaceutical use, human insulin, blood factors, immunoglobulins, pseudoparticles} - C12N 2750/14143: viral genome or elements thereof as genetic vector - C12N 2830/008: cell type or tissue specific enhancer/promoter combination - 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 present invention relates to the prevention and/or treatment of retinal dystrophyin a patient, including Leber congenital amaurosis (LCA). ## Claims ### Claim 1 A retinal pigment epithelium (RPE)-specific promoter which comprises: (a) a sequence of contiguous nucleotides from SEQ ID NO:1 that confers RPE-specific expression on an operably linked polynucleotide sequence, or (b) a sequence having at least 90% sequence identity to said sequence of (a) and that retains RPE-specific promoter activity. ### Claim 2 (depends on 1) The promoter of claim 1, wherein said sequence (a) comprises no more than 1300 contiguous nucleotides from SEQ ID NO:1, or said sequence (b) has at least 90% sequence identity to said sequence of no more than 1300 contiguous nucleotides from SEQ ID NO:1 and retains RPE-specific promoter activity. ### Claim 3 (depends on 2) The promoter of claim 2, wherein said sequence (a) comprises no more than 800 contiguous nucleotides from SEQ ID NO:1, or said sequence (b) has at least 90% sequence identity to said sequence of no more than 800 contiguous nucleotides from SEQ ID NO:1 and retains RPE-specific promoter activity. ### Claim 4 (depends on 3) The promoter of claim 3, wherein said sequence (a) comprises the sequence of SEQ ID NO: 2 or the sequence of nucleotides 12-761 of SEQ ID NO:2, or said sequence (b) has at least 90% sequence identity to said sequence of SEQ ID NO: 2, or to nucleotides 12-761 of SEQ ID NO:2, and retains RPE-specific promoter activity. ### Claim 5 The promoter of any one of the preceding claims, wherein said sequence of (a) or (b) is at least 500 nucleotides in length. ### Claim 6 An expression construct comprising the promoter of any one of the preceding claims, operably linked to a sequence to be expressed in an RPE-specific manner. ### Claim 7 (depends on 6) The expression construct according to claim 6, wherein the operably linked sequence is an RPE65, MERTK, LRAT, TYR, GRP143 or MYO7A coding sequence, or a sequence encoding a neurotrophic factor, an anti-angiogenic polypeptide or a polypeptide with anti-apoptotic effects in the RPE. ### Claim 8 (depends on 7) The expression construct according to claim 7 wherein the operably linked sequence comprises a sequence selected from SEQ ID NOs: 3 to 8, or that has at least 80% sequence identity to any one of SEQ ID NOs: 3 to 8 and has the ability to rescue RPE function. ### Claim 9 (depends on 7, 8) The expression construct according to claim 7 or 8 wherein the operably linked sequence comprises SEQ ID NO: 4. ### Claim 10 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9) A vector comprising a promoter according to any one of claims 1 to 5 or an expression cassette according to any one of claims 6 to 9. ### Claim 11 (depends on 10) The vector according to claim 10 which is a viral vector. ### Claim 12 The vector according 11, which is an adeno-associated virus (AAV) vector or comprises an AAV genome or a derivative thereof. ### Claim 13 (depends on 12) The vector according to claim 12 wherein said derivative is a chimeric, shuffled or capsid modified derivative. ### Claim 14 (depends on 12, 13) The vector according to claim 12 or 13 wherein said AAV genome is from a naturally derived serotype or isolate or clade of AAV. ### Claim 15 (depends on 14) The vector according to claim 14, wherein said AAV genome is from AAV serotype 2 (AAV2), AAV serotype 4 (AAV4), AAV serotype 5 (AAV5) or AAV serotype 8 (AAV8) and/or wherein the capsid is derived from AAV5 or AAV8. ### Claim 16 (depends on 15) The vector according to claim 15, wherein the genome is derived from AAV2 and the capsid is derived from AAV5 or AAV8. ### Claim 17 (depends on 10, 11, 12, 13, 14, 15, 16) A host cell that contains a vector of claim 10 or produces a viral vector of any one of claims 11 to 16. ### Claim 18 (depends on 17) The cell according to claim 17 that is a HEK293 or HEK293T cell. ### Claim 19 (depends on 10, 11, 12, 13, 14, 15, 16) A pharmaceutical composition comprising a vector of any one of claims 10 to 16 and a pharmaceutically acceptable carrier. ### Claim 20 (depends on 10, 11, 12, 13, 14, 15, 16) The vector according to any one of claims 10 to 16 for use in a method of preventing or treating retinal dystrophy. ### Claim 21 (depends on 10, 11, 12, 13, 14, 15, 16) Use of a vector according to any one of claims 10 to 16 in the manufacture of a medicament for the treatment or prevention of retinal dystrophy. ### Claim 22 (depends on 10, 11, 12, 13, 14, 15, 16) A method of treating or preventing retinal dystrophy in a patient in need thereof, comprising administering a therapeutically effective amount of a vector according to any one of claims 10 to 16 to said patient. ### Claim 23 (depends on 20, 21, 22) A vector for use according to claim 20, or a use of claim 21 or a method of claim 22, wherein the retinal dystrophy is Leber congenital amaurosis (LCA), age-related macular degeneration (AMD), oculo-cutaneous type 1 or Nettleship-Falls type ocular albinism or MERTK deficiency. ### Claim 24 (depends on 10, 11, 12, 13, 14, 15, 16, 20, 21, 22, 23) A vector for use according to claim 20 or 23, or a use or method of claim 21, 22 or 23, wherein the treatment or prevention is by administration of the vector according to any one of claims 10 to 16 to a patient by direct retinal, subretinal or intravitreal injection. ### Claim 25 (depends on 24) A vector for use, use or method according to claim 24, wherein said vector is administered directly into the retinal, subretinal space or intravitreal space.