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US 2026/0308595 A1Published application
Antisense oligomer formulations
AssigneeStoke Therapeutics, Inc.
InventorsPaul Hatala, Surya Lamichhane, Tong Yun
Life of this patent
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Abstract
Provided herein is a pharmaceutical formulation comprising an antisense oligomer (ASO), a kit, and a method for use thereof for treating a disease or condition by modulating the expression of Nav1.1 protein in the cells of a subject in need thereof, wherein the ASO modulates splicing of a nonsense-mediated mRNA decay-inducing exon from a pre-mRNA in the cells of the subject, thereby modulating the expression of Nav1.1 protein in the subject.
Claims213
A pharmaceutical formulation, wherein the pharmaceutical formulation is a liquid composition comprising:
- (i) an antisense oligomer (ASO), and
- (ii) a pharmaceutically acceptable diluent;
- wherein the liquid composition is not buffered by a buffering agent;
- and
- wherein:
- (a) the liquid composition comprises calcium ion, magnesium ion, and/or potassium ion,
- (b) the pharmaceutical formulation is formulated or suitable for administration into an intrathecal space, cerebrospinal fluid, or a brain of a human subject, and/or
- (c) each nucleobase of the ASO comprises a modified sugar moiety.
5 more elements
A pharmaceutical formulation, wherein the pharmaceutical formulation is a liquid composition comprising:
- (i) an antisense oligomer (ASO), and
- (ii) a pharmaceutically acceptable diluent;
- wherein the liquid composition lacks Na2HPO4 and/or NaH2PO4;
- and
- wherein:
- (a) the liquid composition comprises calcium ion, magnesium ion, and/or potassium ion,
- (b) the pharmaceutical formulation is formulated or suitable for administration into an intrathecal space, cerebrospinal fluid, or a brain of a human subject, and/or
- (c) each nucleobase of the ASO comprises a modified sugar moiety.
5 more elements
A pharmaceutical formulation, wherein the pharmaceutical formulation is a liquid composition comprising:
- (i) an antisense oligomer (ASO), and
- (ii) a pharmaceutically acceptable diluent consisting of:
- (a) NaCl,
- (b) KCl,
- (c) MgCl2 or MgCl2 6H2O, and
- (d) CaCl2 or CaCl22H2O.
3 more elements
A pharmaceutical formulation, wherein the pharmaceutical formulation is a liquid composition comprising:
- (i) an antisense oligomer (ASO), and
- (ii) a pharmaceutically acceptable diluent;
- wherein the liquid composition lacks calcium ions and/or magnesium ions;
- and
- wherein:
- (a) the liquid composition comprises potassium ion,
- (b) the pharmaceutical formulation is formulated or suitable for administration into an intrathecal space, cerebrospinal fluid, or a brain of a human subject, and/or
- (c) each nucleobase of the ASO comprises a modified sugar moiety.
5 more elements
A pharmaceutical formulation, wherein the pharmaceutical formulation is a liquid composition comprising:
- (i) an antisense oligomer (ASO), and
- (ii) a pharmaceutically acceptable diluent,
- wherein:
- (a) the ASO is stable in the pharmaceutical formulation after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period;
- (b) the pharmaceutical formulation has a shelf life of a time period when stored at −20° C. or a temperature and relative humidity;
- (c) the percent impurities in the pharmaceutical formulation according to an HPLC relative retention time of 0.92 is not more than 2.5% after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period;
- (d) the percent impurities in the pharmaceutical formulation according to an HPLC relative retention time of 0.98 is not more than 3.5% after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period;
- (e) the percent of any unspecified impurities in the pharmaceutical formulation according to HPLC is not more than 1.8% after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period;
- (f) the percent of total impurities in the pharmaceutical formulation according to HPLC is not more than 10% after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period;
- (g) the pH of the pharmaceutical composition is from 6.6 to 7.6 after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period;
- (h) the osmolality of the pharmaceutical composition is from 310 to 360 mOsm/kg after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period;
- and/or
- (i) no observable particulate formation or no formation of particulate that has a dimension larger than 50 μm is observed after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period.
10 more elements
A kit comprising:
- (i) a concentrate comprising an antisense oligomer (ASO);
- and
- (ii) a pharmaceutically acceptable diluent, wherein the concentrate is miscible with the pharmaceutically acceptable diluent;
- and
- wherein mixing the ASO with the pharmaceutically acceptable diluent results in a liquid composition comprising the ASO, and
- wherein the liquid composition is not buffered by a buffering agent;
- and
- wherein:
- (a) the liquid composition comprises calcium ion, magnesium ion, and/or potassium ion,
- (b) the pharmaceutical formulation is formulated or suitable for administration into an intrathecal space, cerebrospinal fluid, or a brain of a human subject, and/or
- (c) each nucleobase of the ASO comprises a modified sugar moiety.
8 more elements
A kit comprising:
- (i) a concentrate comprising an antisense oligomer (ASO);
- and
- (ii) a pharmaceutically acceptable diluent, wherein the concentrate is miscible with the pharmaceutically acceptable diluent;
- and
- wherein mixing the ASO with the pharmaceutically acceptable diluent results in a liquid composition comprising the ASO,
- wherein the liquid composition lacks Na2HPO4 and/or NaH2PO4;
- and
- wherein:
- (a) the liquid composition comprises calcium ion, magnesium ion, and/or potassium ion,
- (b) the pharmaceutical formulation is formulated or suitable for administration into an intrathecal space, cerebrospinal fluid, or a brain of a human subject, and/or
- (c) each nucleobase of the ASO comprises a modified sugar moiety.
8 more elements
A kit comprising:
- (i) a concentrate comprising an antisense oligomer (ASO);
- and
- (ii) a pharmaceutically acceptable diluent consisting of:
- (a) NaCl,
- (b) KCl,
- (c) MgCl2 or MgCl2 6H2O, and
- (d) CaCl2 or CaCl22H2O,
- wherein the concentrate is miscible with the pharmaceutically acceptable diluent;
- and
- wherein mixing the ASO with the pharmaceutically acceptable diluent results in a liquid composition comprising the ASO.
7 more elements
A kit comprising:
- (i) a concentrate comprising an antisense oligomer (ASO);
- and
- (ii) a pharmaceutically acceptable diluent, wherein the concentrate is miscible with the pharmaceutically acceptable diluent;
- wherein mixing the ASO with the pharmaceutically acceptable diluent results in a liquid composition comprising the ASO,
- wherein the liquid composition lacks calcium ions and/or magnesium ions;
- and
- wherein:
- (a) the liquid composition comprises potassium ion,
- (b) the pharmaceutical formulation is formulated or suitable for administration into an intrathecal space, cerebrospinal fluid, or a brain of a human subject, and/or
- (c) each nucleobase of the ASO comprises a modified sugar moiety.
7 more elements
A kit comprising:
- (i) a concentrate comprising an antisense oligomer (ASO);
- and
- (ii) a pharmaceutically acceptable diluent, wherein the concentrate is miscible with the pharmaceutically acceptable diluent;
- wherein mixing the ASO with the pharmaceutically acceptable diluent results in a liquid composition comprising the ASO, and
- wherein:
- (a) the ASO is stable in the pharmaceutical formulation after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period;
- (b) the pharmaceutical formulation has a shelf life of a time period when stored at −20° C. or a temperature and relative humidity;
- (c) the percent impurities in the pharmaceutical formulation according to an HPLC relative retention time of 0.92 is not more than 2.5% after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period;
- (d) the percent impurities in the pharmaceutical formulation according to an HPLC relative retention time of 0.98 is not more than 3.5% after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period;
- (e) the percent of any unspecified impurities in the pharmaceutical formulation according to HPLC is not more than 1.8% after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period;
- (f) the percent of total impurities in the pharmaceutical formulation according to HPLC is not more than 10% after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period;
- (g) the pH of the pharmaceutical composition is from 6.6 to 7.6 after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period;
- (h) the osmolality of the pharmaceutical composition is from 310 to 360 mOsm/kg after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period;
- and/or
- (i) no observable particulate formation is observed after storage of the pharmaceutical formulation at −20° C. or a temperature and relative humidity for a time period.
12 more elements
A liquid pharmaceutical formulation consisting essentially of:
- (a) an antisense oligomer (ASO) at a concentration of about 0.1 mg/mL to about 500 mg/mL, wherein the ASO is a compound according to the following chemical structure (SEQ ID NO:
- 1100):
- or a salt thereof;
- (b) calcium chloride dihydrate (CaCl2 2H2O) at a concentration of about 0.1 mM to about 50 mM;
- (c) magnesium chloride hexahydrate (MgCl2 6H2O) at a concentration of about 0.1 mM to about 50 mM;
- (d) potassium chloride (KCl) at a concentration of about 0.1 mM to about 20 mM;
- (e) sodium chloride (NaCl) at a concentration of about 25 mM to about 250 mM;
- and
- (f) water.
6 more elements
A liquid pharmaceutical formulation consisting essentially of:
- (a) an antisense oligomer (ASO) at a concentration of about 0.1 mg/mL to about 500 mg/mL, wherein the ASO is a compound according to the following chemical structure (SEQ ID NO:
- 1100):
- or a salt thereof;
- (b) calcium chloride dihydrate (CaCl2 2H2O) at a concentration of about 0.1 mM to about 50 mM;
- (c) magnesium chloride hexahydrate (MgCl2 6H2O) at a concentration of about 0.1 mM to about 50 mM;
- (d) potassium chloride (KCl) at a concentration of about 0.1 mM to about 20 mM;
- (e) sodium chloride (NaCl) at a concentration of about 25 mM to about 250 mM;
- (f) sodium hydroxide (NaOH) at a concentration of about 0.1 mM to about 20 mM, and/or hydrochloric acid (HCl) at a concentration of about 0.1 mM to about 20 mM;
- and
- (g) water.
7 more elements
A liquid pharmaceutical formulation consisting essentially of:
- (a) an antisense oligomer (ASO) at a concentration of about 0.1 mg/mL to about 500 mg/mL, wherein the ASO is a compound according to the following chemical structure (SEQ ID NO:
- 1100):
- or a salt thereof;
- (b) calcium ion (Ca2+) at a concentration of about 0.1 mM to about 50 mM;
- (c) magnesium ion (Mg2+) at a concentration of about 0.1 mM to about 50 mM;
- (d) potassium ion (K+) at a concentration of about 0.1 mM to about 20 mM;
- (e) sodium ion (Na+) at a concentration of about 25 mM to about 250 mM;
- (f) chloride ion (Cl−) at a concentration of about 25 mM to about 250 mM;
- and
- (g) water.
7 more elements
A liquid pharmaceutical formulation consisting essentially of:
- (a) an antisense oligomer (ASO) at a concentration of about 0.1 mg/mL to about 500 mg/mL, wherein the ASO is a compound according to the following chemical structure (SEQ ID NO:
- 1100):
- or a salt thereof;
- (b) calcium ion (Ca2+) at a concentration of about 1.4 mM;
- (c) magnesium ion (Mg2+) at a concentration of about 0.79 mM;
- (d) potassium ion (K+) at a concentration of about 3 mM;
- (e) sodium ion (Na+) at a concentration of about 160 mM;
- (f) chloride ion (Cl−) at a concentration of about 160 mM;
- and
- (g) water.
7 more elements
Dependencies are inferred from the claim text.