Transgenic rpe cells overexpressing otx2 for the treatment of retinal degeneration

Patent metadata

Field	Value
Publication number	US-2017348434-A1
Application number	US-201515536725-A
Country	US
Kind code	A1
Filing date	Dec 17, 2015
Priority date	Dec 18, 2014
Publication date	Dec 7, 2017
Grant date	—

Abstract

The present invention relates to methods and composition for use in the treatment of retinal degeneration, in particular retinal degeneration due to retinal pigment epithelium dysfunction.

First claim

1 - 15 . (canceled)

16 . A method of treating retinal degeneration comprising administration of retinal pigment epithelial (RPE) cells engineered to increase intracellular levels of orthodenticle homeobox 2 protein (OTX2 protein) to a subject.

17 . The method according to claim 16 , wherein said RPE cells are genetically engineered to over-express OTX2 protein.

18 . The method according to claim 16 , wherein said OTX2 protein is a native mammalian OTX2 protein, or a variant or functional fragment thereof.

19 . The method according to claim 16 , wherein said OTX2 protein comprises SEQ ID NO: 15 or SEQ ID NO: 16, or a variant or functional fragment thereof.

20 . The method according to claim 19 , wherein said OTX2 protein comprises SEQ ID NO: 15 or SEQ ID NO: 16.

21 . The method according to claim 16 , wherein said RPE cells are obtained by differentiation of stem cells or induced pluripotent stern cells into RPE cells.

22 . The method according to claim 17 , wherein said RPE cells comprise a recombinant nucleic acid sequence encoding an OTX2 protein operably linked to one or more control sequences.

23 . The method according to claim 17 , wherein said RPE cells comprise a recombinant viral vector comprising a nucleic acid sequence encoding Otx2 protein operably linked to one or more control sequences.

24 . The method according to claim 16 , wherein said intracellular levels of OTX2 protein in said RPE cells are, after normalization, at least 1.5-fold higher levels of OTX2 as compared to the OTX2 protein in non-engineered RPE cells.

25 . The method according to claim 16 , wherein said RPE cells administered to the subject by intraocular injection.

26 . The method according to claim 25 , wherein said RPE cells are injected into the subretinal space of the eye.

27 . The method according to claim 16 , wherein said retinal degeneration is related to RPE dysfunction.

28 . The method according to claim 16 , wherein said retinal degeneration is caused by a disease selected from the group consisting of retinitis pigmentosa, age-related macular degeneration, retinal detachment, Leber congenital amaurosis, diabetic retinopathy, Best's disease, Stargardt's disease and choroideremia.

29 . The method according to claim 27 , wherein said retinal degeneration is caused by retinitis pigmentosa.

30 . A pharmaceutical composition comprising RPE cells engineered to increase intracellular levels of OTX2 protein and a pharmaceutically acceptable carrier.

31 . The pharmaceutical composition according to claim 30 , wherein said RPE cells are genetically engineered to over-express OTX2 protein.

32 . The pharmaceutical composition according to claim 30 , wherein said composition is formulated for intraocular injection.

Assignees

• Univ Pierre Et Marie Curie Paris 6
• Centre Nat Rech Scient
• Inserm (Institut National De La Sante Et De La Rech Medicale)

Inventors

• Leveillard Thierry
• Kole Christo
• Sahel Jose-Alain

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• C12N5/0621

  Eye cells, e.g. cornea, iris pigmented cells (photoreceptors C12N5/062) · CPC title

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title

• A61K35/30

  Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue · CPC title

• A61P27/02

  Ophthalmic agents · CPC title