Formulations of polyalkylene oxide-asparaginase and methods of making and using the same
AssigneeServier IP UK Limited
InventorsGianFranco Fornasini, Nadejda Soukhareva, Christopher Phillips
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Abstract
Aspects of the invention include polyalkylene oxide-asparaginase compositions. In some instances, the composition is a lyophilized storage stable composition. In some instances, the lyophilized compositions include one or more of a buffer, a salt, and a sugar. Aspects of the invention further include methods of making the compositions. The compositions find use in a variety of applications, e.g., in the treatment of a neoplastic condition in a subject.
Claims152
A lyophilized storage stable composition, the composition comprising:
- a polyalkylene oxide-asparaginase comprising a polyalkylene oxide group covalently linked by a linker to an asparaginase;
- a buffer;
- a salt;
- and
- a sugar.
The lyophilized storage stable composition according to any of the preceding claims, wherein the linker is a urethane linker.
The lyophilized storage stable composition according to any of the preceding claims, wherein the linker is a succinate linker.
The lyophilized storage stable composition according to any of the preceding claims, wherein the polyalkylene oxide-asparaginase is present in an amount ranging from 500 to 1,000 IU/g.
The lyophilized storage stable composition according to any of the preceding claims, wherein the buffer comprises a phosphate buffer.
The lyophilized storage stable composition according to any of the preceding claims, wherein the salt is sodium chloride.
The lyophilized storage stable composition according to any of the preceding claims, wherein the sugar comprises a disaccharide.
The lyophilized storage stable composition according to any of the preceding claims, wherein the composition is present in a unit dosage container.
A lyophilized storage stable composition, the composition comprising:
- a polyethylene glycol-asparaginase comprising a polyethylene glycol group covalently linked by a urethane linker to an E. coli asparaginase;
- a phosphate buffer;
- a salt;
- and
- a disaccharide.
A lyophilized storage stable composition, the composition comprising:
- a polyethylene glycol-asparaginase comprising a polyethylene glycol group covalently linked by a succinate linker to an E. coli asparaginase;
- a phosphate buffer;
- a salt;
- and
- a disaccharide.
A lyophilized storage stable composition, the composition comprising:
- i) a polyethylene glycol-asparaginase comprising a polyethylene glycol group covalently linked by a urethane linker to an E. coli asparaginase, wherein the polyalkylene oxide-asparaginase is present in an amount of 750 IU/g and the polyethylene glycol group has with a molecular weight of 5,000 daltons;
- ii) a buffer comprising a phosphate buffer comprising dibasic sodium phosphate in an amount of 0.279 wt. % and monobasic sodium phosphate in an amount of 0.06 wt. %;
- iii) sodium chloride in an amount of 0.425 wt. %;
- and
- iv) sucrose in an amount of 4.5 wt. %.
A lyophilized storage stable composition, the composition comprising:
- i) a polyethylene glycol-asparaginase comprising a polyethylene glycol group covalently linked by a succinate linker to an E. coli asparaginase, wherein the polyalkylene oxide-asparaginase is present in an amount of 750 IU/g and the polyethylene glycol group has with a molecular weight of 5,000 daltons;
- ii) a buffer comprising a phosphate buffer comprising dibasic sodium phosphate in an amount of 0.279 wt. % and monobasic sodium phosphate in an amount of 0.06 wt. %;
- iii) sodium chloride in an amount of 0.425 wt. %;
- and
- iv) sucrose in an amount of 4.5 wt. %.
A liquid composition, the composition comprising:
- i) a polyethylene glycol-asparaginase comprising a polyethylene glycol group covalently linked by a urethane linker to an E. coli asparaginase, wherein the polyalkylene oxide-asparaginase is present in an amount of 750 IU/g and the polyethylene glycol group has with a molecular weight of 5,000 daltons;
- ii) a buffer comprising a phosphate buffer comprising dibasic sodium phosphate in an amount of 0.558 wt. % and monobasic sodium phosphate in an amount of 0.129 wt. %;
- and
- iii) sodium chloride in an amount of 0.85 wt. %.
A method of making a lyophilized polyalkylene oxide-asparaginase composition, the method comprising:
- lyophilizing an aqueous concentrate composition comprising:
- (i) a polyalkylene oxide-asparaginase comprising a polyalkylene oxide group covalently linked by a linker to an asparaginase;
- (ii) a buffer;
- (iii) a salt;
- and
- (iii) a sugar;
- in a manner sufficient to produce a lyophilized storage stable polyalkylene oxide-asparaginase composition.
A method of treating a subject for acute myeloid leukemia (AML), the method comprising:
- administering to the subject a dosage of a polyalkylene oxide-asparaginase effective to treat the subject for AML, wherein the polyalkylene oxide-asparaginase comprises a polyalkylene oxide group covalently linked by a linker to an asparaginase.
A kit comprising one more unit dosage containers each containing a composition comprising:
- a polyalkylene oxide-asparaginase comprising a polyalkylene oxide group covalently linked by a linker to an asparaginase;
- a buffer;
- and
- a salt.
A kit comprising one more unit dosage containers each containing a lyophilized storage stable composition comprising:
- a polyalkylene oxide-asparaginase comprising a polyalkylene oxide group covalently linked by a linker to an asparaginase;
- a buffer;
- a salt;
- and
- a sugar.
Dependencies are inferred from the claim text.