PHARMACEUTICAL COMPOSITIONS FOR DELIVERY TO THE EYE

1 . A composition comprising the non-pegylated aptamer 5′ NH 2 -fCmGfCfCGfCmGmGfUfCfUfCmAmGmGfCGfCfUmGmAmGfUfCfUmGmAmGfUfUfUAfCf CfUmGf CmG-3T-3′ (SEQ ID NO: 1), wherein the composition comprises:

(a) more than 85% of the aptamer in the composition is full length aptamer;

(b) less than 1.8% G cleavage product; and

(c) 1% or less of deprotection failure products.

2 . The composition of claim 1 , wherein the composition additionally has:

(d) less than 0.1% A cleavage product;

(e) less than 1.1% total of n-4, n-3 and n-2 deletion products; and

(f) less than 3% total of fluoro degradants and n-1 deletion products.

3 . A PEGylated aptamer comprising the composition of claim 1 that has the structure:

or a salt thereof.

4 . The PEGylated aptamer of claim 3 , wherein the PEGylated aptamer comprises a 2-arm branched ranging from approximately 39 kDa to approximately 47 kDa PEG.

5 . The PEGylated aptamer of claim 3 , wherein the PEGylated aptamer comprises a 2-arm branched approximately 40 kDa PEG.

6 . The PEGylated aptamer of claim 3 , wherein the PEGylated aptamer comprises a 2-arm branched approximately 43 kDa PEG.

7 . The PEGylated aptamer of claim 3 , wherein the salt is a sodium salt.

8 . A drug substance comprising avacincaptad pegol wherein the drug substance comprises:

(a) more than 92% of the aptamer in the drug substance is full length aptamer;

(b) less than 1.5% of the drug substance is relative retention time (RRT) 1 (≥0.93-<full length product (FLP)); and

(c) less than 5% of the drug substance is RRT2 (>FLP-≤1.2).

9 . The drug substance of claim 8 , wherein the drug substance comprises a sodium salt of avacincaptad pegol.

10 . The drug substance of claim 8 , wherein the potency of the drug substance, as measured by ELISA, is greater than 95%.

11 . A pharmaceutical composition comprising the drug substance of claim 8 and one or more pharmaceutically acceptable excipients.

12 . The pharmaceutical composition of claim 11 , wherein the composition is formulated at a concentration of 20 mg/mL (oligonucleotide mass) in phosphate-buffered saline at pH 6.8-7.8 as a sterile aqueous solution.

13 . The pharmaceutical composition of claim 12 , wherein the composition has an osmolality between 350-500 mOsM/kg.

14 . A method for treating an ophthalmological disease, disorder, and/or condition, the method comprising intravitreally administering the pharmaceutical composition of claim 6 at a dose of between 3-5 mg/eye to a subject in need thereof.

15 . The method of claim 14 , wherein the dose administered is about 2 mg/eye.

16 . The method of claim 15 , wherein 100 μL is injected per eye.

17 . The method of claim 14 , wherein the ophthalmological disease, disorder, and/or condition is selected from the group consisting of geographic atrophy secondary to age-related macular degeneration, dry age-related macular degeneration (dry AMD), wet age-related macular degeneration (wet AMD), neovascular age-related macular degeneration (nAMD), retinal vein occlusion (RVO), diabetic macular edema (DME), diabetic retinopathy (DR), Usher syndrome type 1, Usher syndrome type 2, Usher syndrome type 3, Stargardt disease, uveitis, red-green color blindness, blue cone monochromacy, Leber congenital amaurosis (LCA), Leber hereditary optic neuropathy (LHON), neuromyelitis optica (NMO), choroideremia, X-linked retinoschisis (XLRS), Bardet-Biedl syndrome, cone dystrophy, optic atrophy, retinitis pigmentosa, age-related retinal ganglion cell (RGC) degeneration, Best disease, glaucoma, Graves' ophthalmopathy, multiple sclerosis (MS)-associated vision loss, myopia, X-linked recessive ocular albinism, oculocutaneous albinism type 1, optic neuritis, polypoidal choroidal vasculopathy, X-linked retinitis pigmentosa (XLRP), achromatopsia (ACHM), biallelic RPE65 mutation-associated retinal dystrophy, idiopathic polypoidal choroidal vasculopathy, high-risk drusen, and a condition selected from the group consisting of risk factors for the progression to iRORA (incomplete RPE and outer retinal atrophy), iRORA, nascent geographic atrophy (nGA), and cRORA (complete RPE and outer retinal atrophy).

18 . The method of claim 14 , wherein the dose is administered once monthly.

19 . The method of claim 14 , wherein the dose is administered once monthly for up to 12 months.

20 . The drug substance of claim 8 for use as a medicament.

21 . The drug substance of claim 8 for use in the treatment of an ophthalmological disease, disorder, and/or condition.

22 . The drug substance or the pharmaceutical composition for use of claim 21 , wherein the ophthalmological disease, disorder, and/or condition is selected from the group consisting of geographic atrophy secondary to age-related macular degeneration, dry age-related macular degeneration (dry AMD), wet age-related macular degeneration (wet AMD), neovascular age-related macular degeneration (nAMD), retinal vein occlusion (RVO), diabetic macular edema (DME), diabetic retinopathy (DR), Usher syndrome type 1, Usher syndrome type 2, Usher syndrome type 3, Stargardt disease, uveitis, red-green color blindness, blue cone monochromacy, Leber congenital amaurosis (LCA), Leber hereditary optic neuropathy (LHON), neuromyelitis optica (NMO), choroideremia, X-linked retinoschisis (XLRS), Bardet-Biedl syndrome, cone dystrophy, optic atrophy, retinitis pigmentosa, age-related retinal ganglion cell (RGC) degeneration, Best disease, glaucoma, Graves' ophthalmopathy, multiple sclerosis (MS)-associated vision loss, myopia, X-linked recessive ocular albinism, oculocutaneous albinism type 1, optic neuritis, polypoidal choroidal vasculopathy, X-linked retinitis pigmentosa (XLRP), achromatopsia (ACHM), biallelic RPE65 mutation-associated retinal dystrophy, idiopathic polypoidal choroidal vasculopathy, high-risk drusen and a condition selected from the group consisting of risk factors for the progression to iRORA, iRORA, nGA, and cRORA.