Dosage regimens for and compositions including anti-rsv antibodies

Abstract

In one aspect, this disclosure describes methods of treating or preventing RSV infection in a patient in need thereof. The methods including dosing regimens for administering a composition including a fixed dose of an anti-RSV monoclonal antibody or an antigen binding fragment thereof. In another aspect, this disclosure describes pharmaceutical compositions for the treatment or prevention of RSV infection. In yet another aspect, this disclosure describes a pharmaceutical unit dose including nirsevimab.

What is claimed is: 
     
         1 . A method of treating or preventing RSV infection in a patient in need thereof, the method comprising:
 determining the age of the patient;   in response to the patient being in the second year of life, administering a composition comprising a fixed dose of 200 milligrams (mg) of an anti-RSV monoclonal antibody or an antigen binding fragment thereof;   in response to the patient being in the first year of life, determining the patient's weight; and   in response to the patient having a weight of at least 5 kilograms (kg), administering a composition comprising a fixed dose of 100 mg of an anti-RSV monoclonal antibody or an antigen binding fragment thereof,   wherein the anti-RSV monoclonal antibody or an antigen binding fragment thereof has an IC50 of 5.0 ng/ml or less in a neutralization assay of RSV A, or has an IC50 of 3.0 ng/ml or less in a neutralization assay of RSV B9320, or both.   
     
     
         2 . A method of treating or preventing RSV infection in a patient in need thereof, the method comprising administering to a patient having a weight of at least 5 kilograms (kg) a fixed dose of 200 milligrams (mg) of an anti-RSV monoclonal antibody or an antigen binding fragment thereof, wherein the anti-RSV monoclonal antibody or an antigen binding fragment thereof has an IC50 of 5.0 ng/ml or less in a neutralization assay of RSV A, or has an IC50 of 3.0 ng/ml or less in a neutralization assay of RSV B9320, or both. 
     
     
         3 . A method of treating or preventing RSV infection in a patient in need thereof, the method comprising:
 determining the weight of a patient   administering to a patient having a weight of at least 5 kilograms (kg) a fixed dose of 200 milligrams (mg) of an anti-RSV monoclonal antibody or an antigen binding fragment thereof, wherein the anti-RSV monoclonal antibody or an antigen binding fragment thereof has an IC50 of 5.0 ng/ml or less in a neutralization assay of RSV A, or has an IC50 of 3.0 ng/ml or less in a neutralization assay of RSV B9320, or both;   administering to a patient having a weight of up to 5 kg a fixed dose of 100 mg of an anti-RSV monoclonal antibody or an antigen binding fragment thereof, wherein the anti-RSV monoclonal antibody or an antigen binding fragment thereof has an IC50 of 5.0 ng/ml or less in a neutralization assay of RSV A, or has an IC50 of 3.0 ng/ml or less in a neutralization assay of RSV B9320, or both.   
     
     
         4 . A method of treating or preventing RSV infection in a patient in need thereof, the method comprising
 determining the age of the patient; and   administering a fixed dose of 200 milligrams (mg) of an anti-RSV monoclonal antibody or an antigen binding fragment thereof to a patient aged 3 months or older, wherein the anti-RSV monoclonal antibody or an antigen binding fragment thereof has an IC50 of 5.0 ng/ml or less in a neutralization assay of RSV A, or has an IC50 of 3.0 ng/ml or less in a neutralization assay of RSV B9320 or both.   
     
     
         5 . A method of treating or preventing RSV infection in a patient in need thereof, the method comprising:
 determining the age of a patient;   administering a fixed dose of 200 milligrams (mg) of an anti-RSV monoclonal antibody or an antigen binding fragment thereof to a patient aged 3 months or older;   administering a fixed dose of 100 mg of an anti-RSV monoclonal antibody or an antigen binding fragment thereof to a patient aged up to 3 months,   wherein the anti-RSV monoclonal antibody or an antigen binding fragment thereof has an IC50 of 5.0 ng/ml or less in a neutralization assay of RSV A, or has an IC50 of 3.0 ng/ml or less in a neutralization assay of RSV B9320, or both.   
     
     
         6 . A method of treating or preventing RSV infection in a patient in need thereof, the method comprising:
 determining the age of a patient;   administering a fixed dose of 200 milligrams (mg) of an anti-RSV monoclonal antibody or an antigen binding fragment thereof to a patient aged 6 months or older;   administering a fixed dose of 100 mg of an anti-RSV monoclonal antibody or an antigen binding fragment thereof to a patient aged up to 6 months,   wherein the anti-RSV monoclonal antibody or an antigen binding fragment thereof has an IC50 of 5.0 ng/ml or less in a neutralization assay of RSV A, or has an IC50 of 3.0 ng/ml or less in a neutralization assay of RSV B9320, or both.   
     
     
         7 . A method of treating or preventing RSV infection in a patient in need thereof, the method comprising:
 determining whether the patient is experiencing their first or second RSV season;   in response to the patient experiencing their second RSV season, administering a composition comprising a fixed dose of 200 milligrams (mg) of an anti-RSV monoclonal antibody or an antigen binding fragment thereof;   in response to the patient experiencing their first RSV season, determining the patient's weight; and   in response to the patient having a weight of at least 5 kilograms (kg), administering a composition comprising a fixed dose of 100 mg of an anti-RSV monoclonal antibody or an antigen binding fragment thereof,   wherein the anti-RSV monoclonal antibody or an antigen binding fragment thereof has an IC50 of 5.0 ng/ml or less in a neutralization assay of RSV A, or has an IC50 of 3.0 ng/ml or less in a neutralization assay of RSV B9320, or both.   
     
     
         8 . A method of treating or preventing RSV infection in a patient in need thereof, the method comprising
 determining whether the patient is experiencing their first or second RSV season; and   administering a fixed dose of 200 milligrams (mg) of an anti-RSV monoclonal antibody or an antigen binding fragment thereof to a patient experiencing their second RSV season, wherein the anti-RSV monoclonal antibody or an antigen binding fragment thereof has an IC50 of 5.0 ng/ml or less in a neutralization assay of RSV A, or has an IC50 of 3.0 ng/ml or less in a neutralization assay of RSV B9320 or both.   
     
     
         9 . A method of treating or preventing RSV infection in a patient in need thereof, the method comprising:
 determining whether the patient is experiencing their first or second RSV season;   administering a fixed dose of 200 milligrams (mg) of an anti-RSV monoclonal antibody or an antigen binding fragment thereof to a patient, wherein the patient is experiencing their second RSV season;   administering a fixed dose of 100 mg of an anti-RSV monoclonal antibody or an antigen binding fragment thereof to a patient, wherein the patient is experiencing their first RSV season;   wherein the anti-RSV monoclonal antibody or an antigen binding fragment thereof has an IC50 of 5.0 ng/ml or less in a neutralization assay of RSV A, or has an IC50 of 3.0 ng/ml or less in a neutralization assay of RSV B9320, or both.   
     
     
         10 . The method of any one of  claims 1  to  9 , wherein the anti-RSV monoclonal antibody comprises nirsevimab or wherein the antigen binding fragment of the anti-RSV monoclonal antibody comprises an antigen binding fragment of nirsevimab. 
     
     
         11 . The method of any one of  claims 1  to  10 , the method comprising administering the anti-RSV monoclonal antibody or an antigen binding fragment thereof in a composition, the composition comprising an ionic excipient, a buffer, a sugar, and a surfactant,
 wherein the ionic excipient comprises L-arginine hydrochloride at a concentration of 80 mM, 
 wherein the buffer comprises 30 mM L-histidine/L-histidine hydrochloride, 
 wherein the sugar comprises 120 mM sucrose, 
 wherein the surfactant comprises polysorbate-80 in a range of 0.01% (w/v) to 0.05% (w/v), and 
 wherein the composition has a pH in a range of from 5.5 to 6.5. 
 
     
     
         12 . A pharmaceutical composition for the treatment or prevention of RSV infection, the composition comprising 100 mg of nirsevimab, wherein the composition is administered to a patient in the first year of life or a patient experiencing their first RSV season, the patient having a weight of at least 5 kg. 
     
     
         13 . A pharmaceutical composition for the treatment or prevention of RSV infection, the composition comprising 200 mg of nirsevimab, wherein the composition is administered to a patient in the second year of life or a patient experiencing their second RSV season. 
     
     
         14 . The pharmaceutical composition of  claim 12  or  13 , wherein the patient exhibits AUC 0-∞  of greater than 13.4 day·mg/mL. 
     
     
         15 . The pharmaceutical composition of any one of  claims 12  to  14 , the pharmaceutical composition further comprising an ionic excipient, a buffer, a sugar, and a surfactant,
 wherein the ionic excipient comprises L-arginine hydrochloride at a concentration of 80 mM, 
 wherein the buffer comprises 30 mM L-histidine/L-histidine hydrochloride, 
 wherein the sugar comprises 120 mM sucrose, 
 wherein the surfactant comprises polysorbate-80 in a range of 0.01% (w/v) to 0.05% (w/v), and 
 wherein the composition has a pH in a range of from 5.5 to 6.5. 
 
     
     
         16 . A pharmaceutical unit dose comprising 100 mg of nirsevimab, wherein said unit dose is suitable for intramuscular administration. 
     
     
         17 . A pharmaceutical unit dose comprising 200 mg of nirsevimab, wherein said unit dose is suitable for intramuscular administration. 
     
     
         18 . The pharmaceutical unit dose of  claim 16  or  17 , wherein the pharmaceutical unit dose comprising the nirsevimab is present in a composition, the composition further comprising an ionic excipient, a buffer, a sugar, and a surfactant,
 wherein the ionic excipient comprises L-arginine hydrochloride at a concentration of 80 mM, 
 wherein the buffer comprises 30 mM L-histidine/L-histidine hydrochloride, 
 wherein the sugar comprises 120 mM sucrose, 
 wherein the surfactant comprises polysorbate-80 in a range of 0.01% (w/v) to 0.05% (w/v), and 
 wherein the composition has a pH in a range of from 5.5 to 6.5. 
 
     
     
         19 . The pharmaceutical unit dose of any one of  claims 16  to  18 , wherein the nirsevimab in the composition is stable at 2° C. to 8° C. for at least 3 months as determined by high performance size exclusion chromatography (HPSEC). 
     
     
         20 . The pharmaceutical unit dose of any one of  claims 16  to  19 , wherein the nirsevimab is present at a concentration of 100 mg/mL.