Methods for Treating or Preventing Ophthalmological Conditions

Abstract

The present invention relates to methods for treating and preventing ophthalmological disease and disorders, comprising administering Antagonist A or another pharmaceutically acceptable salt thereof, optionally in combination with another treatment, to a subject in need thereof. The present invention also relates to methods for treating and preventing ophthalmological disease and disorders, comprising administering an anti-C5 agent (e.g., ARC1905), optionally in combination with another treatment, to a subject in need thereof.

1 . A method for treating or preventing wet age-related macular degeneration (wet AMD), comprising administering to a subject in need thereof (a) Antagonist A or another pharmaceutically acceptable salt thereof and (b) an VEGF antagonist, wherein (a) and (b) are administered in an amount that is effective for treating or preventing wet AMD, and wherein the administering occurs once every month, ±about seven days, for a first administration period of at least 3 consecutive months, followed by administering (a) and (b) for a second administration period at a frequency of at least every other month ±about seven days beginning at two months ±about seven days after the day of the last month of the first administration period on which (a) and (b) are administered. 
     
     
         2 . The method of  claim 1 , wherein (a) and (b) are administered within about 60 minutes of each other. 
     
     
         3 . The method of  claim 1 , wherein the VEGF antagonist is ranibizumab, bevacizumab, pegaptanib sodium, ESBA 1008 or aflibercept. 
     
     
         4 . The method of  claim 1 , wherein the VEGF antagonist is ranibizumab or bevacizumab, wherein (a) and (b) are administered at a frequency of once every month ±about seven days during the second administration period and wherein the second administration period is at least about nine months. 
     
     
         5 . The method of  claim 4 , further comprising measuring the subject's visual acuity. 
     
     
         6 . The method of  claim 5 , further comprising administering to the subject (a) and (b) in an amount that is effective for treating or preventing wet AMD, until the subject's visual acuity on the last two of any three consecutive months is ≦a five-ETDRS-letter difference from the subject's visual acuity on the first of the three consecutive months. 
     
     
         7 . The method of  claim 5 , further comprising administering to the subject (a) and (b) every other month in an amount that is effective for treating or preventing wet AMD, wherein the subject's visual acuity on the last two of any three consecutive months is ≦a five-ETDRS-letter difference from the subject's visual acuity on the first of the three consecutive months. 
     
     
         8 . The method of  claim 7 , further comprising administering to the subject (a) and (b) every month in an amount that is effective for treating or preventing wet AMD, until the subject's visual acuity on the last two of any three consecutive months is ≦a five-ETDRS-letter difference from the subject's visual acuity on the first of the three consecutive months. 
     
     
         9 . The method of  claim 1 , wherein the VEGF antagonist is aflibercept. 
     
     
         10 . The method of  claim 1 , wherein the total number of months does not exceed 24. 
     
     
         11 . The method of  claim 4 , wherein the subject has intraretinal or sub-retinal hemorrhage or a ≧50 μm increase in foveal intraretinal fluid at one month, ±about seven days, immediately following the second administration period. 
     
     
         12 . The method of  claim 11 , further comprising: administering to the subject on each month ±about seven days, beginning on the month that immediately follows the second administration period (a) and (b) in an amount that is effective for treating or preventing wet AMD, until the subject's visual acuity on the last two of any three consecutive months that follow the 12 consecutive months is ≦a five-ETDRS-letter difference from the subject's visual acuity on the first of the three consecutive months. 
     
     
         13 . The method of  claim 12 , wherein the total number of months does not exceed 24. 
     
     
         14 . The method of  claim 1 , wherein Antagonist A or another pharmaceutically acceptable salt thereof is administered intravitreally in an amount of about 1.5 mg/eye. 
     
     
         15 . The method of  claim 4 , wherein the VEGF antagonist is bevacizumab and is administered intravitreally in an amount of about 1.25 mg/eye. 
     
     
         16 . The method of  claim 9 , wherein the VEGF antagonist is administered intravitreally in an amount of about 2 mg/eye. 
     
     
         17 . The method of  claim 4 , wherein the VEGF antagonist is ranibizumab and is administered intravitreally in an amount of about 0.5 mg/eye. 
     
     
         18 . The method of  claim 1 , further comprising administering an anti-C5 agent. 
     
     
         19 . The method of  claim 1 , further comprising administering (a) and (b) on a month in which the subject has intraretinal or sub-retinal hemorrhage or a ≧50 μm increase in foveal intraretinal fluid. 
     
     
         20 . A method for treating or preventing sub-retinal fibrosis, comprising administering to a subject in need thereof (a) Antagonist A or another pharmaceutically acceptable salt thereof in an amount that is effective for treating or preventing sub-retinal fibrosis. 
     
     
         21 . The method of  claim 20 , further comprising administering to the subject (b) a VEGF antagonist, wherein (a) and (b) are administered in an amount that is effective for treating or preventing sub-retinal fibrosis. 
     
     
         22 . The method of  claim 20 , wherein the subject has wet age-related macular degeneration (wet AMD). 
     
     
         23 . The method of  claim 22 , wherein the sub-retinal fibrosis is associated with the wet AMD. 
     
     
         24 . The method of  claim 20 , wherein administering Antagonist A or another pharmaceutically acceptable salt thereof results in a decrease in the size of sub-retinal hyper-reflective material (SHRM) as evidenced by spectral domain optical coherence tomography (SD-OCT) or results in stabilization of the subject's vision. 
     
     
         25 . The method of  claim 20 , wherein Antagonist A or another pharmaceutically acceptable salt thereof is administered intravitreally in an amount of about 1.5 mg/eye. 
     
     
         26 . The method of  claim 21 , wherein the VEGF antagonist is bevacizumab, ranibizumab, aflibercept, pegaptanib sodium or ESBA1008. 
     
     
         27 . The method of  claim 26 , wherein the VEGF antagonist is bevacizumab and is administered intravitreally in an amount of about 1.25 mg/eye. 
     
     
         28 . The method of  claim 26 , wherein the VEGF antagonist is aflibercept and is administered intravitreally in an amount of about 2 mg/eye. 
     
     
         29 . The method of  claim 26 , wherein the VEGF antagonist is ranibizumab and is administered intravitreally in an amount of about 0.5 mg/eye. 
     
     
         30 . The method of  claim 21 , further comprising administering an anti-C5 agent. 
     
     
         31 . A method for treating or preventing von Hippel-Lindau (VHL) disease, comprising administering to a subject in need thereof Antagonist A or another pharmaceutically acceptable salt thereof in an amount that is effective for treating or preventing VHL disease. 
     
     
         32 . The method of  claim 31 , further comprising administering a VEGF antagonist. 
     
     
         33 . The method of  claim 31 , wherein Antagonist A or another pharmaceutically acceptable salt thereof is administered intravitreally in an amount of about 1.5 mg/eye. 
     
     
         34 . The method of  claim 32 , wherein the VEGF antagonist is bevacizumab and is administered intravitreally in an amount of about 1.25 mg/eye. 
     
     
         35 . The method of  claim 32 , wherein the VEGF antagonist is aflibercept and is administered intravitreally in an amount of about 2 mg/eye. 
     
     
         36 . The method of  claim 32 , wherein the VEGF antagonist is ranibizumab and is administered intravitreally in an amount of about 0.5 mg/eye. 
     
     
         37 . The method of  claim 32 , further comprising administering an anti-C5 agent. 
     
     
         38 . A composition comprising:
 a) Antagonist A or another pharmaceutically acceptable salt thereof; and   b) a pharmaceutically acceptable excipient, buffering agent, aqueous carrier, or combination thereof, wherein   the composition has a pH of from about 5.0 to about 8.0;   the average number of particles detected in the composition after being stored at a temperature of about 2.0° C. to about 8.0° C. for at least about twelve weeks does not exceed about 50 particles/mL, where the particles have a diameter >about 10 μm as measured by the microscopic method particle count test described in (788) Particulate Matter in Injections, Revised Bulletin, Official Oct. 1, 2011, The United States Pharmacopeial Convention; and   
       the composition is suitable for intravitreal injection. 
     
     
         39 . The composition of  claim 38 , wherein the composition comprises an aqueous carrier, sodium chloride, monobasic sodium phosphate monohydrate, dibasic sodium phosphate heptahydrate, or a combination thereof. 
     
     
         40 . The composition of  claim 38 , wherein the pH is about 7.5. 
     
     
         41 . The composition of  claim 38 , wherein the composition is buffered with hydrochloric acid. 
     
     
         42 . The composition of  claim 38 , wherein the composition is buffered with sodium hydroxide. 
     
     
         43 . The composition of  claim 38 , wherein the average number of particles detected in the composition after being stored at a temperature of about 2.0° C. to about 8.0° C. for at least about twelve weeks does not exceed 5 particles/mL, where the particles have a diameter >25 μm as measured by the microscopic method particle count test described in (788) Particulate Matter in Injections, Revised Bulletin, Official Oct. 1, 2011, The United States Pharmacopeial Convention. 
     
     
         44 . The composition of  claim 38 , wherein the average number of particles detected in the composition after being stored at a temperature of about 2.0° C. to about 8.0° C. for at least about twelve weeks does not exceed 2 particles/mL, where the particles have a diameter >50 μm as measured by the microscopic method particle count test described in (788) Particulate Matter in Injections, Revised Bulletin, Official Oct. 1, 2011, The United States Pharmacopeial Convention. 
     
     
         45 . The composition of  claim 39 , wherein the composition comprises:
 a) about 3% w/v of Antagonist A or another pharmaceutically acceptable salt thereof;   b) about 95.9% w/v of an aqueous carrier;   c) about 0.9% w/v sodium chloride;   d) about 0.03% w/v monobasic sodium phosphate monohydrate; and   e) about 0.2% w/v dibasic sodium phosphate heptahydrate.   
     
     
         46 . The composition of  claim 38 , wherein the composition comprises about 0.003-5.0 mg of Antagonist A or another pharmaceutically acceptable salt thereof. 
     
     
         47 . The composition of  claim 46 , wherein the composition is suitable for a single intravitreal administration. 
     
     
         48 . The composition of  claim 45 , wherein the composition comprises about 0.03-3.0 mg of Antagonist A or another pharmaceutically acceptable salt thereof. 
     
     
         49 . The composition of  claim 48 , wherein the composition is suitable for a single intravitreal administration. 
     
     
         50 . The composition of  claim 47  or  49 , wherein the intravitreal administration is via a 27-30 gauge needle. 
     
     
         51 . A composition comprising:
 a) Antagonist A or another pharmaceutically acceptable salt thereof; and   b) a pharmaceutically acceptable excipient, buffering agent, aqueous carrier, or combination thereof, wherein   the composition has a pH of from about 5.0 to about 8.0;   at least about 50% of the Antagonist A or another pharmaceutically acceptable salt thereof shows no sign of decomposition or modification resulting in the formation of a new chemical entity when stored at a temperature of from about 2.0° C. to about 8.0° C. for at least about 12 weeks; and   the composition is suitable for intravitreal injection.   
     
     
         52 . The composition of  claim 51 , wherein the composition comprises an aqueous carrier, sodium chloride, monobasic sodium phosphate monohydrate, dibasic sodium phosphate heptahydrate, or a combination thereof. 
     
     
         53 . The composition of  claim 51 , wherein the pH is about 7.5. 
     
     
         54 . The composition of  claim 51 , wherein the composition is buffered with hydrochloric acid. 
     
     
         55 . The composition of  claim 51 , wherein the composition is buffered with sodium hydroxide. 
     
     
         56 . The composition of  claim 51 , wherein at least about 70% of the Antagonist A or another pharmaceutically acceptable salt shows no sign of decomposition or modification resulting in the formation of a new chemical entity when stored at a temperature of from about 2.0° C. to about 8.0° C. for at least about 12 weeks. 
     
     
         57 . The composition of  claim 51 , wherein at least about 90% of the Antagonist A or another pharmaceutically acceptable salt shows no sign of decomposition or modification resulting in the formation of a new chemical entity when stored at a temperature of from about 2.0° C. to about 8.0° C. for at least about 12 weeks. 
     
     
         58 . The composition of  claim 52 , wherein the composition comprises:
 a) about 3% w/v of Antagonist A or a pharmaceutically acceptable salt thereof;   b) about 95.9% w/v of an aqueous carrier;   c) about 0.9% w/v sodium chloride;   d) about 0.03% w/v monobasic sodium phosphate monohydrate; and   e) about 0.2% w/v dibasic sodium phosphate heptahydrate.   
     
     
         59 . The composition of  claim 51 , wherein the composition comprises about 0.003-5.0 mg of Antagonist A or another pharmaceutically acceptable salt thereof. 
     
     
         60 . The composition of  claim 59 , wherein the composition is suitable for a single intravitreal administration. 
     
     
         61 . The composition of  claim 59 , wherein the composition comprises about 0.03-3.0 mg of Antagonist A or another pharmaceutically acceptable salt thereof. 
     
     
         62 . The composition of  claim 61 , wherein the composition is suitable for a single intravitreal administration. 
     
     
         63 . The composition of  claim 60  or  62 , wherein the intravitreal administration is via a 27-30 gauge needle. 
     
     
         64 . A composition comprising:
 a) about 3% w/v of Antagonist A or another pharmaceutically acceptable salt thereof;   b) about 0.9% w/v sodium chloride;   c) about 0.03% w/v monobasic sodium phosphate monohydrate;   d) about 0.2% w/v dibasic sodium phosphate heptahydrate; and   e) an aqueous carrier.   
     
     
         65 . The composition of  claim 64 , wherein the composition has a pH of from about 5.0 to about 8.0. 
     
     
         66 . The composition of  claim 64 , wherein the composition has a pH of about 7.5. 
     
     
         67 . The composition of  claim 64 , wherein the composition comprises about 95.9% w/v of the pharmaceutically acceptable aqueous carrier. 
     
     
         68 . The composition of  claim 64 , wherein the composition comprises about 0.003-5.0 mg of Antagonist A or another pharmaceutically acceptable salt thereof. 
     
     
         69 . The composition of  claim 64 , wherein the composition comprises about 0.03-3.0 mg of Antagonist A or another pharmaceutically acceptable salt thereof. 
     
     
         70 . The composition of  claim 64 , wherein the composition is suitable for intravitreal administration. 
     
     
         71 . The composition of  claim 70 , wherein the composition is suitable for a single intravitreal administration. 
     
     
         72 . The composition of  claim 70  or  71 , wherein the intravitreal administration is via a 27-30 gauge needle. 
     
     
         73 . The composition of any one of  claims 38 ,  51  and  64 , wherein the concentration of Antagonist A or the other pharmaceutically acceptable salt in the composition is from about 5 mg/mL to about 50 mg/mL. 
     
     
         74 . The composition of  claim 73 , wherein the concentration of Antagonist A or the other pharmaceutically acceptable salt thereof is about 30 mg/mL. 
     
     
         75 . The composition of any one of  claims 38 ,  51  and  64 , wherein the dosage of Antagonist A in the composition is about 1.5 mg in a volume of 0.03 mL to 0.15 mL. 
     
     
         76 . The composition of any one of  claims 38 ,  51  and  64 , wherein the composition is contained in a single undivided container. 
     
     
         77 . The composition of any one of  claims 38 ,  51  and  64 , wherein the composition is in a unit dosage form. 
     
     
         78 . A composition comprising:
 a) Antagonist A or another pharmaceutically acceptable salt thereof; and   b) a pharmaceutically acceptable excipient, buffering agent, aqueous carrier, or combination thereof, wherein   the composition has a pH of from about 5.0 to about 8.0;   the average number of particles detected in the composition after being stored at a temperature of about 2.0° C. to about 8.0° C. for at least about twelve weeks does not exceed about 50 particles/mL, where the particles have a diameter >about 10 μm as measured by the light obscuration particle count test described in (788) Particulate Matter in Injections, Revised Bulletin, Official Oct. 1, 2011, The United States Pharmacopeial Convention; and   
       the composition is suitable for intravitreal injection. 
     
     
         79 . The composition of  claim 78 , wherein the composition comprises an aqueous carrier, sodium chloride, monobasic sodium phosphate monohydrate, dibasic sodium phosphate heptahydrate, or a combination thereof. 
     
     
         80 . The composition of  claim 78 , wherein the pH is about 7.5. 
     
     
         81 . The composition of  claim 78 , wherein the composition is buffered with hydrochloric acid. 
     
     
         82 . The composition of  claim 78 , wherein the composition is buffered with sodium hydroxide. 
     
     
         83 . The composition of  claim 78 , wherein the average number of particles detected in the composition after being stored at a temperature of about 2.0° C. to about 8.0° C. for at least about twelve weeks does not exceed 5 particles/mL, where the particles have a diameter >25 μm as measured by the light obscuration particle count test described in (788) Particulate Matter in Injections, Revised Bulletin, Official Oct. 1, 2011, The United States Pharmacopeial Convention. 
     
     
         84 . The composition of  claim 78 , wherein the average number of particles detected in the composition after being stored at a temperature of about 2.0° C. to about 8.0° C. for at least about twelve weeks does not exceed 2 particles/mL, where the particles have a diameter >50 μm as measured by the light obscuration particle count test described in (788) Particulate Matter in Injections, Revised Bulletin, Official Oct. 1, 2011, The United States Pharmacopeial Convention. 
     
     
         85 . The composition of  claim 79 , wherein the composition comprises:
 a) about 3% w/v of Antagonist A or another pharmaceutically acceptable salt thereof;   b) about 95.9% w/v of an aqueous carrier;   c) about 0.9% w/v sodium chloride;   d) about 0.03% w/v monobasic sodium phosphate monohydrate; and   e) about 0.2% w/v dibasic sodium phosphate heptahydrate.   
     
     
         86 . The composition of  claim 78 , wherein the composition comprises about 0.003-5.0 mg of Antagonist A or another pharmaceutically acceptable salt thereof. 
     
     
         87 . The composition of  claim 86 , wherein the composition is suitable for a single intravitreal administration. 
     
     
         88 . The composition of  claim 85 , wherein the composition comprises about 0.03-3.0 mg of Antagonist A or another pharmaceutically acceptable salt thereof. 
     
     
         89 . The composition of  claim 88 , wherein the composition is suitable for a single intravitreal administration. 
     
     
         90 . The composition of  claim 87  or  89 , wherein the intravitreal administration is via a 27-30 gauge needle. 
     
     
         91 . The composition of  claim 78 , wherein the concentration of Antagonist A or the other pharmaceutically acceptable salt in the composition is from about 5 mg/mL to about 50 mg/mL. 
     
     
         92 . The composition of  claim 91 , wherein the concentration of Antagonist A or the other pharmaceutically acceptable salt thereof is about 30 mg/mL. 
     
     
         93 . The composition of  claim 78 , wherein the dosage of Antagonist A in the composition is about 1.5 mg in a volume of 0.03 mL to 0.15 mL. 
     
     
         94 . The composition of  claim 78 , wherein the composition is contained in a single undivided container. 
     
     
         95 . The composition of  claim 78 , wherein the composition is in a unit dosage form. 
     
     
         96 . The method of  claim 1 , wherein the antagonist A or another pharmaceutically acceptable salt thereof is administered as a component of a composition comprising:
 a) Antagonist A or another pharmaceutically acceptable salt thereof; and   b) a pharmaceutically acceptable excipient, buffering agent, aqueous carrier, or combination thereof, wherein   the composition has a pH of from about 5.0 to about 8.0;   
       the average number of particles detected in the composition after being stored at a temperature of about 2.0° C. to about 8.0° C. for at least about twelve weeks does not exceed about 50 particles/mL, where the particles have a diameter >about 10 μm as measured by the microscopic method particle count test described in (788) Particulate Matter in Injections, Revised Bulletin, Official Oct. 1, 2011, The United States Pharmacopeial Convention; and 
       the composition is suitable for intravitreal injection. 
     
     
         97 . The method of  claim 1 , wherein the antagonist A or another pharmaceutically acceptable salt thereof is administered as a component of a composition comprising:
 a) Antagonist A or another pharmaceutically acceptable salt thereof; and   b) a pharmaceutically acceptable excipient, buffering agent, aqueous carrier, or combination thereof, wherein   the composition has a pH of from about 5.0 to about 8.0;   at least about 50% of the Antagonist A or another pharmaceutically acceptable salt thereof shows no sign of decomposition or modification resulting in the formation of a new chemical entity when stored at a temperature of from about 2.0° C. to about 8.0° C. for at least about 12 weeks; and   the composition is suitable for intravitreal injection.   
     
     
         98 . The method of  claim 1 , wherein the antagonist A or another pharmaceutically acceptable salt thereof is administered as a component of a composition comprising:
 a) about 3% w/v of Antagonist A or another pharmaceutically acceptable salt thereof;   b) about 0.9% w/v sodium chloride;   c) about 0.03% w/v monobasic sodium phosphate monohydrate;   d) about 0.2% w/v dibasic sodium phosphate heptahydrate; and   e) an aqueous carrier.   
     
     
         99 . The method of  claim 1 , wherein the antagonist A or another pharmaceutically acceptable salt thereof is administered as a component of a composition comprising:
 a) Antagonist A or another pharmaceutically acceptable salt thereof; and   b) a pharmaceutically acceptable excipient, buffering agent, aqueous carrier, or combination thereof, wherein   the composition has a pH of from about 5.0 to about 8.0;   the average number of particles detected in the composition after being stored at a temperature of about 2.0° C. to about 8.0° C. for at least about twelve weeks does not exceed about 50 particles/mL, where the particles have a diameter >about 10 μm as measured by the light obscuration particle count test described in (788) Particulate Matter in Injections, Revised Bulletin, Official Oct. 1, 2011, The United States Pharmacopeial Convention; and   
       the composition is suitable for intravitreal injection. 
     
     
         100 . The method of  claim 20 , wherein the antagonist A or another pharmaceutically acceptable salt thereof is administered as a component of a composition comprising:
 a) Antagonist A or another pharmaceutically acceptable salt thereof; and   b) a pharmaceutically acceptable excipient, buffering agent, aqueous carrier, or combination thereof, wherein   the composition has a pH of from about 5.0 to about 8.0;   
       the average number of particles detected in the composition after being stored at a temperature of about 2.0° C. to about 8.0° C. for at least about twelve weeks does not exceed about 50 particles/mL, where the particles have a diameter >about 10 μm as measured by the microscopic method particle count test described in (788) Particulate Matter in Injections, Revised Bulletin, Official Oct. 1, 2011, The United States Pharmacopeial Convention; and 
       the composition is suitable for intravitreal injection. 
     
     
         101 . The method of  claim 20 , wherein the antagonist A or another pharmaceutically acceptable salt thereof is administered as a component of a composition comprising:
 a) Antagonist A or another pharmaceutically acceptable salt thereof; and   b) a pharmaceutically acceptable excipient, buffering agent, aqueous carrier, or combination thereof, wherein   the composition has a pH of from about 5.0 to about 8.0;   at least about 50% of the Antagonist A or another pharmaceutically acceptable salt thereof shows no sign of decomposition or modification resulting in the formation of a new chemical entity when stored at a temperature of from about 2.0° C. to about 8.0° C. for at least about 12 weeks; and   the composition is suitable for intravitreal injection.   
     
     
         102 . The method of  claim 20 , wherein the antagonist A or another pharmaceutically acceptable salt thereof is administered as a component of a composition comprising:
 a) about 3% w/v of Antagonist A or another pharmaceutically acceptable salt thereof;   b) about 0.9% w/v sodium chloride;   c) about 0.03% w/v monobasic sodium phosphate monohydrate;   d) about 0.2% w/v dibasic sodium phosphate heptahydrate; and   e) an aqueous carrier.   
     
     
         103 . The method of  claim 20 , wherein the antagonist A or another pharmaceutically acceptable salt thereof is administered as a component of a composition comprising:
 a) Antagonist A or another pharmaceutically acceptable salt thereof; and   b) a pharmaceutically acceptable excipient, buffering agent, aqueous carrier, or combination thereof, wherein   the composition has a pH of from about 5.0 to about 8.0;   the average number of particles detected in the composition after being stored at a temperature of about 2.0° C. to about 8.0° C. for at least about twelve weeks does not exceed about 50 particles/mL, where the particles have a diameter >about 10 μm as measured by the light obscuration particle count test described in (788) Particulate Matter in Injections, Revised Bulletin, Official Oct. 1, 2011, The United States Pharmacopeial Convention; and   
       the composition is suitable for intravitreal injection. 
     
     
         104 . The method of  claim 31 , wherein the antagonist A or another pharmaceutically acceptable salt thereof is administered as a component of a composition comprising:
 a) Antagonist A or another pharmaceutically acceptable salt thereof; and   b) a pharmaceutically acceptable excipient, buffering agent, aqueous carrier, or combination thereof, wherein   the composition has a pH of from about 5.0 to about 8.0;   
       the average number of particles detected in the composition after being stored at a temperature of about 2.0° C. to about 8.0° C. for at least about twelve weeks does not exceed about 50 particles/mL, where the particles have a diameter >about 10 μm as measured by the microscopic method particle count test described in (788) Particulate Matter in Injections, Revised Bulletin, Official Oct. 1, 2011, The United States Pharmacopeial Convention; and 
       the composition is suitable for intravitreal injection. 
     
     
         105 . The method of  claim 31 , wherein the antagonist A or another pharmaceutically acceptable salt thereof is administered as a component of a composition comprising:
 a) Antagonist A or another pharmaceutically acceptable salt thereof; and   b) a pharmaceutically acceptable excipient, buffering agent, aqueous carrier, or combination thereof, wherein   the composition has a pH of from about 5.0 to about 8.0;   at least about 50% of the Antagonist A or another pharmaceutically acceptable salt thereof shows no sign of decomposition or modification resulting in the formation of a new chemical entity when stored at a temperature of from about 2.0° C. to about 8.0° C. for at least about 12 weeks; and   the composition is suitable for intravitreal injection.   
     
     
         106 . The method of  claim 31 , wherein the antagonist A or another pharmaceutically acceptable salt thereof is administered as a component of a composition comprising:
 a) about 3% w/v of Antagonist A or another pharmaceutically acceptable salt thereof;   b) about 0.9% w/v sodium chloride;   c) about 0.03% w/v monobasic sodium phosphate monohydrate;   d) about 0.2% w/v dibasic sodium phosphate heptahydrate; and   e) an aqueous carrier.   
     
     
         107 . The method of  claim 31 , wherein the antagonist A or another pharmaceutically acceptable salt thereof is administered as a component of a composition comprising:
 a) Antagonist A or another pharmaceutically acceptable salt thereof; and   b) a pharmaceutically acceptable excipient, buffering agent, aqueous carrier, or combination thereof, wherein   the composition has a pH of from about 5.0 to about 8.0;   the average number of particles detected in the composition after being stored at a temperature of about 2.0° C. to about 8.0° C. for at least about twelve weeks does not exceed about 50 particles/mL, where the particles have a diameter >about 10 μm as measured by the light obscuration particle count test described in (788) Particulate Matter in Injections, Revised Bulletin, Official Oct. 1, 2011, The United States Pharmacopeial Convention; and   
       the composition is suitable for intravitreal injection.