Pharmaceutical compositions and salts of a 1,2,4-oxadiazole benzoic acid
Provided herein are pharmaceutical compositions, which comprise a 1,2,4-oxadiazole benzoic acid or a pharmaceutically acceptable salt thereof. Further provided herein are certain pharmaceutically acceptable salts of a 1,2,4-oxadiazole benzoic acid and methods for making the same. Further provided herein are methods of treating or preventing a disease associated with a nonsense mutation or a premature stop codon, comprising administering such pharmaceutical compositions or pharmaceutically acceptable salts to a patient having a disease associated with a nonsense mutation or a premature stop codon.
1. A crystalline salt form comprising 3-[5-(2-fluoro-phenyl)-[1,2,4]oxadiazol-3-yl]benzoic acid and magnesium, wherein said crystalline salt form has an X-ray powder diffraction substantially shown in FIG. 2 .
2. A method for treating, preventing or managing an ocular disease associated with a nonsense mutation or a premature stop codon in a patient having an ocular disease associated with a nonsense mutation or premature stop codon, comprising administering a pharmaceutical composition comprising an effective amount of the crystalline salt form of claim 1 to said patient.
3. The method of claim 2 , wherein the ocular disease is selected from the group consisting of aniridia, choroideremia, renal-coloboma syndrome, Leber congenital amaurosis, retinitis pigmentosa, Bardet-Biedl syndrome, glaucoma, foveal hypoplasia, cataracts, Usher syndrome, central auditory processing difficulties, chorioretinal degeneration, congenital lens opacities, elevated intraocular pressure, exudative vascular retinopathy, glaucoma, iris hypoplasia, keratopathy (corneal degeneration), optic nerve hypoplasia, retinal detachment, secondary strabismus and tunica vasculosa lentis.
4. A crystalline salt form comprising 3-[5-(2-fluoro-phenyl)-[1,2,4]oxadiazol-3-yl]benzoic acid and potassium, wherein said crystalline salt form has an X-ray powder diffraction pattern substantially as shown in FIG. 4 .
5. A method for treating, preventing or managing an ocular disease associated with a nonsense mutation or a premature stop codon in a patient having an ocular disease associated with a nonsense mutation or a premature stop codon, comprising administering a pharmaceutical composition comprising an effective amount of the crystalline salt form of claim 4 to said patient.
6. The method of claim 5 , wherein the ocular disease is selected from the group consisting of aniridia, choroideremia, renal-coloboma syndrome, Leber congenital amaurosis, retinitis pigmentosa, Bardet-Biedl syndrome, glaucoma, foveal hypoplasia, cataracts, Usher syndrome, central auditory processing difficulties, chorioretinal degeneration, congenital lens opacities, elevated intraocular pressure, exudative vascular retinopathy, glaucoma, iris hypoplasia, keratopathy (corneal degeneration), optic nerve hypoplasia, retinal detachment, secondary strabismus and tunica vasculosa lentis.
7. A crystalline salt form comprising 3-[5-(2-fluoro-phenyl)-[1,2,4]oxadiazol-3-yl]benzoic acid and sodium, wherein said crystalline salt form has an X-ray powder diffraction pattern substantially as shown in FIG. 6 .
8. A method for treating, preventing or managing an ocular disease associated with a nonsense mutation or a premature stop codon in a patient having an ocular disease associated with a nonsense mutation or a premature stop codon, comprising administering a pharmaceutical composition comprising an effective amount of the crystalline salt form of claim 7 to said patient.
9. The method of claim 8 , wherein the ocular disease is selected from the group consisting of aniridia, choroideremia, renal-coloboma syndrome, Leber congenital amaurosis, retinitis pigmentosa, Bardet-Biedl syndrome, glaucoma, foveal hypoplasia, cataracts, Usher syndrome, central auditory processing difficulties, chorioretinal degeneration, congenital lens opacities, elevated intraocular pressure, exudative vascular retinopathy, glaucoma, iris hypoplasia, keratopathy (corneal degeneration), optic nerve hypoplasia, retinal detachment, secondary strabismus and tunica vasculosa lentis.
10. A crystalline salt form comprising 3-[5-(2-fluoro-phenyl)-[1,2,4]oxadiazol-3-yl]benzoic acid and tromethamine, wherein said crystalline salt form has an X-ray powder diffraction pattern substantially as shown in FIG. 8 .
11. A method for treating, preventing or managing an ocular disease associated with a nonsense mutation or a premature stop codon in a patient having an ocular disease associated with a nonsense mutation or a premature stop codon, comprising administering a pharmaceutical composition comprising an effective amount of the crystalline salt form of claim 10 to said patient.
12. The method of claim 11 , wherein the ocular disease is selected from the group consisting of aniridia, choroideremia, renal-coloboma syndrome, Leber congenital amaurosis, retinitis pigmentosa, Bardet-Biedl syndrome, glaucoma, foveal hypoplasia, cataracts, Usher syndrome, central auditory processing difficulties, chorioretinal degeneration, congenital lens opacities, elevated intraocular pressure, exudative vascular retinopathy, glaucoma, iris hypoplasia, keratopathy (corneal degeneration), optic nerve hypoplasia, retinal detachment, secondary strabismus and tunica vasculosa lentis.
13. A crystalline salt form comprising 3-[5-(2-fluoro-phenyl)-[1,2,4]oxadiazol-3-yl]benzoic acid and L-lysine, wherein said crystalline salt form has an X-ray powder diffraction pattern substantially as shown in FIG. 12 .
14. A method for treating, preventing or managing an ocular disease associated with a nonsense mutation or a premature stop codon in a patient having an ocular disease associated with a nonsense mutation or a premature stop codon, comprising administering a pharmaceutical composition comprising an effective amount of the crystalline salt form of claim 13 to said patient.
15. The method of claim 14 , wherein the ocular disease is selected from the group consisting of aniridia, choroideremia, renal-coloboma syndrome, Leber congenital amaurosis, retinitis pigmentosa, Bardet-Biedl syndrome, glaucoma, foveal hypoplasia, cataracts, Usher syndrome, central auditory processing difficulties, chorioretinal degeneration, congenital lens opacities, elevated intraocular pressure, exudative vascular retinopathy, glaucoma, iris hypoplasia, keratopathy (corneal degeneration), optic nerve hypoplasia, retinal detachment, secondary strabismus and tunica vasculosa lentis.
16. A crystalline salt form comprising 3-[5-(2-fluoro-phenyl)-[1,2,4]oxadiazol-3-yl]benzoic acid and L-arginine, wherein said crystalline salt form has an X-ray powder diffraction pattern substantially as shown in FIG. 14 .
17. A method for treating, preventing or managing an ocular disease associated with a nonsense mutation or a premature stop codon in a patient having an ocular disease associated with a nonsense mutation or a premature stop codon, comprising administering a pharmaceutical composition comprising an effective amount of the crystalline salt form of claim 16 to said patient.
18. The method of claim 17 , wherein the ocular disease is selected from the group consisting of aniridia, choroideremia, renal-coloboma syndrome, Leber congenital amaurosis, retinitis pigmentosa, Bardet-Biedl syndrome, glaucoma, foveal hypoplasia, cataracts, Usher syndrome, central auditory processing difficulties, chorioretinal degeneration, congenital lens opacities, elevated intraocular pressure, exudative vascular retinopathy, glaucoma, iris hypoplasia, keratopathy (corneal degeneration), optic nerve hypoplasia, retinal detachment, secondary strabismus and tunica vasculosa lentis.
19. A crystalline salt form comprising 3-[5-(2-fluoro-phenyl)-[1,2,4]oxadiazol-3-yl]benzoic acid and L-histidine, wherein said crystalline salt form has an X-ray powder diffraction pattern substantially as shown in FIG. 16 .
20. A method for treating, preventing or managing an ocular disease associated with a nonsense mutation or a premature stop codon in a patient having an ocular disease associated with a nonsense mutation or a premature stop codon, comprising administering a pharmaceutical composition comprising an effective amount of the crystalline salt form of claim 19 to said patient.
21. The method of claim 20 , wherein the ocular disease is selected from the group consisting of aniridia, choroideremia, renal-coloboma syndrome, Leber congenital amaurosis, retinitis pigmentosa, Bardet-Biedl syndrome, glaucoma, foveal hypoplasia, cataracts, Usher syndrome, central auditory processing difficulties, chorioretinal degeneration, congenital lens opacities, elevated intraocular pressure, exudative vascular retinopathy, glaucoma, iris hypoplasia, keratopathy (corneal degeneration), optic nerve hypoplasia, retinal detachment, secondary strabismus and tunica vasculosa lentis.