US 11,685,767 B2 · Use of AAV-expressed M013 protein as an anti-inflammatory therapeutic

Abstract

Disclosed are methods and compositions for preventing, treating, and/or ameliorating one or more symptoms of inflammation in a mammal. In particular, viral vectors and medicaments containing them are disclosed, which are useful in the prophylaxis, therapy, or amelioration of symptoms of one or more inflammatory-mediated mammalian diseases, such as age-related macular degeneration (AMD), arthritis, Bechet's disease, Best macular dystrophy, corneal inflammation, diabetic retinopathy, drusen formation, dry AMD, dry eye, geographic atrophy, glaucomaocular neovascularization, Lupus erythematosus, macular degeneration, Mallatia Leventinese and Doyne honeycomb retinal dystrophy, nephritis, ocular hypertension, ocular inflammation, recurrent uveitis, Sorsby fundus dystrophy, vasculitis, vitreoretinopathy, wet AMD, or related disorders. In exemplary methods, administration of a pharmaceutical composition comprising a recombinant viral vector that delivers a secretable and cell-penetrating M013 protein or peptide to a subject in need thereof facilitated treatment of particular human disorders such as AMD, ocular neovascularization, uveitis, and related inflammatory ocular disease.

Claims27

Dependent claims

A method of reducing or inhibiting secretion of proinflammatory cytokines from retinal microglia during conditions of inflammation, comprising contacting a population of retinal cells in one or both eyes of a mammalian subject with a composition that comprises an effective amount of a viral particle comprising an AAV vector comprising a polynucleotide that comprises

(a) a first nucleic acid segment that encodes a virally-derived M013 polypeptide;
and
(b) a second nucleic acid segment encoding a polypeptide comprising a cell penetrating peptide comprising the sequence set forth in SEQ ID NO:
23 and a secretion signal peptide;
wherein the first and second nucleic acid segments are operably linked to a promoter sequence that expresses the encoded polypeptides in one or more retinal cells transduced with the viral particle;
wherein the viral particle has a serotype that is AAV2 or AA2-based, and the viral particle comprises an AAV2(quadY-F+T−V) capsid protein;
wherein the composition is contacted to the one or both eyes by intravitreal injection;
wherein the population comprises one or more retinal microglia;
and wherein the contacting provides a reduction or inhibition in secretion of proinflammatory cytokines from the retinal microglia.

6 more elements

A method for treating or ameliorating one or more symptoms of inflammation in a mammal, the method comprising administering to the mammal a composition that comprises a viral particle comprising an AAV vector comprising a polynucleotide that comprises

(a) a first nucleic acid segment that encodes a virally-derived M013 polypeptide;
and
(b) a second nucleic acid segment encoding a polypeptide comprising a cell penetrating peptide comprising the sequence set forth in SEQ ID NO:
23 and a secretion signal peptide;
wherein the first and second nucleic acid segments are operably linked to a promoter sequence that expresses the encoded polypeptides in one or more retinal cells transduced with the viral particle;
in an amount and for a time sufficient to treat or ameliorate the one or more symptoms of inflammation in the mammal, wherein the AAV vector is administered to one or both eyes of the mammal by intravitreal injection;
wherein the viral particle has a serotype that is AAV2 or AA2-based, and the viral particle comprises an AAV2(quadY-F+T−V) capsid protein;
wherein the one or both eyes comprises one or more retinal microglia;
and wherein the administering provides a reduction or inhibition in secretion of proinflammatory cytokines from the retinal microglia.

6 more elements

Dependencies are inferred from the claim text.

Use of AAV-expressed M013 protein as an anti-inflammatory therapeutic

Life of this patent

Use of AAV-expressed M013 protein as an anti-inflammatory therapeutic

Life of this patent

Abstract

Claims27