POLYALKYLENE-ASPARAGINASE OXIDE FORMULATIONS AND METHODS OF PREPARATION AND USE THEREOF

Abstract

The present invention relates to a liquid composition comprising: a polyalkylene oxide-asparaginase at a concentration of 750 IU per mL of the composition; dibasic sodium phosphate at a concentration of 0.5 to 0.6% by weight; monobasic sodium phosphate at a concentration of 0.1 to 0.2% by weight; and sodium chloride at a concentration of 0.8 to 1.0% by weight, wherein the polyalkylene oxide-asparaginase comprises an asparaginase covalently linked to a polyalkylene oxide group that is a polyethylene glycol, wherein the polyalkylene oxide group is covalently linked by a carbamate linker to the asparaginase, wherein the carbamate moiety originates from a succinimidyl carbonate (SC) linker

Description

POLYALKYLENE OXIDE ASPARAGINASE FORMULATIONS AND METHODS OF PREPARATION AND USE THEREOF DESCRIPTIVE MEMORY CROSS REFERENCE TO RELATED APPLICATIONS AND INCORPORATION BY REFERENCE. This application claims the benefit of US Provisional Patent Application No. 62 / 344,249, filed June 1, 2016; US Provisional Patent Application No. 62 / 344,252, filed June 1, 2016, and US Provisional Patent Application No. 62 / 344,256, filed June 1, 2016, each one of which is incorporated by reference in its entirety. INTRODUCTION L-asparaginase is an enzyme that hydrolyzes the amino acid L-asparagine through a deamination reaction to produce L-aspartate and ammonia. E. coli contains two asparaginase isoenzymes: L-asparaginase I and L-asparaginase II. L-asparaginase I is found in the cytosol and has a low affinity for asparagine. However, L-asparaginase II is found in the periplasm and has a high affinity for L-asparagine. E. coli L-asparaginase II is a tetramer of identical subunits. E. coli L-asparaginase II is also known as L-asparagine amidohydrolase, type EC-2, EC 3.5.1.1. L-asparaginase is known to have therapeutic value in the treatment of leukemia. Lasparaginase is an amidohydrolase that catalyzes L-asparagine into L-aspartic acid and ammonia. It plays an important role in the metabolism of L-asparagine in plants, animals and microorganisms. It is now well established that the therapeutic activity of the enzyme is caused by the depletion / elimination of circulating L-asparagine, an essential nutrient for the proliferation and survival of tumor (leukemic) cells that are compromised in the ability to synthesize L-asparagine. , but not for normal cells. Administration of L-asparaginase to leukemic patients induces selective death of tumor cells by hydrolyzing L-asparagine, resulting in the treatment of malignant tumors. In some cases, L-asparaginase, by itself, has the typical drawbacks of protein therapeutics, such as the high rate of clearance of a protein foreign to the patient, and the possibility of inducing an immune response in a patient. treated with this enzyme. To address these drawbacks, a polyethylene glycol-conjugated derivative of Lasparaginase (PEG-asparaginase) can be used. PEG-asparaginase can be produced using L-asparaginase II extracted from E. coli and can be substantially non-antigenic and can have a reduced rate of clearance from a patient's circulation. A liquid injection formulation of PEG-asparaginase (Oncaspar®) has been previously approved for marketing by the US Food and Drug Administration. Oncaspar® was approved as first-line treatment for patients with acute lymphoblastic leukemia (ALL) as a component of a multi-agent chemotherapy regimen. In addition, Oncaspar® is approved for the treatment of patients with ALL and hypersensitivity to asparaginase (eg, native forms of L-asparaginase). BRIEF DESCRIPTION OF THE INVENTION Aspects of the invention include polyalkylene oxide asparaginase compositions. In some cases, the compositions include one or more of a buffer and a salt. In other aspects, the composition is a storage-stable lyophilized composition. In some cases, lyophilized compositions include one or more of a buffer, a salt, and a sugar. Aspects of the invention further include methods of preparing the compositions. The compositions find use in a variety of applications, for example, in the treatment of a neoplastic condition in a subject. BRIEF DESCRIPTION OF THE FIGURES FIG 1 shows a process flow chart for a method of preparing a storage-stable lyophilized composition according to embodiments of the present disclosure. FIG 2 shows a graph of purity (%) versus time (weeks) at 40°C for a storage-stable lyophilized composition according to embodiments of the present disclosure. FIG 3 shows a plot of potency (IU / mL) versus time (weeks) at 40°C for a storage-stable lyophilized composition according to embodiments of the present disclosure. FIG 4 shows a graph of purity (%) versus time (weeks) at 25°C for a storage-stable lyophilized composition according to embodiments of the present disclosure. FIG 5 shows a plot of potency (IU / mL) versus time (weeks) at 25°C for a storage-stable lyophilized composition according to embodiments of the present disclosure. FIG 6 shows a process flow diagram of a method for preparing a storage-stable lyophilized composition, according to embodiments of the present disclosure. The final stages of formulation and filtration are shown. FIG 7 shows a process flow diagram of a method for preparing a storage-stable lyophilized composition, according to embodiments of the present disclosure. The steps of aseptic filling and lyophilization are shown. IVIA / a / ¿U¿ I 0344 FIG 8 shows a graph of GF-HPLC purity (%) versus time (months) for a lyophilized composition stored at 2-8°C (eg, 5°C), according to embodiments of the present disclosure. FIG 9 shows a plot of potency (activity) (IU / mL) versus time (months) for a lyophilized composition stored at 2-8°C (eg, 5°C), according to embodiments herein. divulgation. FIG 10 shows a graph of total aggregates by GF-HPLC as a function of time (months) for a lyophilized composition stored at 2-8°C (eg, 5°C), in accordance with embodiments of the present disclosure. FIG 11 shows a graph of GF-HPLC purity (%) versus time (months) for a lyophilized composition stored under accelerated conditions (25 ± 3°C; 60% ± 5% RH), according to embodiments of the present disclosure. FIG 12 shows a plot of potency (activity) (IU / mL) versus time (months) for a lyophilized composition stored under accelerated conditions (25 ± 3°C; 60% ± 5% RH), according to embodiments of this disclosure. FIG 13 shows a graph of total aggregates by GF-HPLC as a function of time (months) for a lyophilized composition stored under accelerated conditions (25 ± 3°C; 60% ± 5% RH), according to embodiments of the present disclosure. . FIG 14 shows a graph of GF-HPLC purity (%) versus time (months) for a lyophilized composition stored under heat stress conditions (40 ± 2°C; 75% ± 5% RH), according to with embodiments of the present disclosure. FIG 15 shows a plot of potency (activity) (IU / mL) versus time (months) for a lyophilized composition stored under heat stress conditions (40 ± 2°C; 75% ± 5% RH), of accordance with embodiments of this disclosure. FIG 16 shows a graph of total aggregates by GF-HPLC as a function of time (months) for a lyophilized composition stored under heat stress conditions (40 ± 2°C; 75% ± 5% RH), according to embodiments of the present disclosure. DEFINITIONS In describing embodiments of the present disclosure, the following terms may be used, and are intended to be defined as follows. By substantially purified is meant the isolation of a substance such that the substance includes the majority of the sample in which it resides. For example, a sample that is substantially purified contains 50% or more of the substance of interest, such as 60% or more of the substance of interest, such as 75% or more of the substance of interest, such as 90% or more of the substance of interest, such as 95% or more of the substance of interest, including 99% or more of the substance of interest. Any convenient protocol may be employed to purify the substance of interest and includes, but is not limited to, filtration (eg, diafiltration, ultrafiltration, etc.), selective precipitation, crystallization, ion exchange chromatography, affinity chromatography, and sedimentation as per the density. By isolated is meant to describe a compound of interest that is found in an environment other than that in which the compound naturally occurs. "Isolated" is intended to include compounds that are within samples that are substantially enriched for the compound of interest and / or in which the compound of interest is partially or substantially purified. The terms patient and subject are used interchangeably and are used in their conventional sense to refer to a living organism suffering from or prone to a condition that can be prevented or treated by administration of a composition of the present disclosure, and includes both humans as non-human animals. Examples of subjects include, but are not limited to, humans, chimpanzees, and other monkey and ape species; farm animals such as cows, sheep, pigs, goats and horses; domestic mammals such as dogs and cats; laboratory animals including rodents such as mice, rats, and guinea pigs; birds, including domestic, wild, and game birds, such as chickens, turkeys, and other gallinaceous birds, ducks, geese, and the like. The term does not denote a particular age. Therefore, adult, juvenile, and newborn individuals are of interest. "Pharmaceutically effective amount" and "therapeutically effective amount" refer to an amount of a compound or composition sufficient to treat a specific disease or disorder or one or more of its symptoms and / or to prevent the onset of the disease or disorder. In reference to neoplastic conditions, a pharmaceutically or therapeutically effective amount includes an amount sufficient to, among other things, cause the amount and / or occurrence of cancer in a subject to decrease, and / or decrease the rate of cancer growth. The term "treat" or "treatment" as used herein means to treat or the treatment of a disease or medical condition in a patient, such as a mammal (eg, a human) including: (a) preventing the disease from occurring or medical condition, such as, prophylactic treatment of a subject; (b) ameliorate the disease or medical condition, such as, eliminate or cause the regression of the disease or medical condition in a patient; (c) suppress the disease or medical condition, for example, by slowing or stopping the development of the disease or medical condition in a patient; or (d) alleviate a symptom of a disease or medical condition in a patient. The term physiological conditions is intended to encompass those conditions compatible with living cells, eg, predominantly aqueous conditions of one temperature, pH, salinity, etc. that are compatible with living cells. Before the embodiments of the present disclosure are described in further detail, it should be understood that the embodiments are not limited to the particular embodiments described herein; as such, embodiments may vary. It is also to be understood that the terminology used in this document is for the purpose of describing particular embodiments only, and the terminology is not intended to be limiting. The scope of the embodiments of the present disclosure will be limited only by the appended claims. Unless otherwise defined, all technical and scientific terms used in this document have the same meaning as is commonly understood by one skilled in the art to which this invention pertains. When a range of values ​​is given, it is understood that each intermediate value is given to one tenth of the unit of the lower limit, unless the context clearly indicates otherwise, between the upper and lower limit of that range and any other declared or intermediate value in that established range is included within the embodiments of the present disclosure. The upper and lower limits of these smaller ranges may be independently included in the smaller ranges and are also included within the embodiments of the present disclosure, subject to any limits specifically excluded in the stated range. When the stated range includes one or both of the limits, ranges that exclude either or both of the included limits are also included in the invention. Certain ranges are presented in this document with numerical values ​​that are preceded by the term approximately. The term approximately is used in this document to provide literal support for the exact number that precedes it, as well as a number that is close to or approximately the number that the term precedes. In determining whether a number is close to or approximately a specifically recited number, the near or approximate non-recited number may be a number that, in the context in which it is presented, provides the substantial equivalent of the specifically recited number. All publications, patents, and patent applications cited in this specification are incorporated by reference herein to the same extent as if each individual publication, patent, or patent application were specifically and individually indicated to be incorporated by reference. In addition, each cited publication, patent, or patent application is incorporated herein by reference to disclose and describe the subject matter in connection with which the publications are cited. Citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the invention described herein is not entitled to predate such publication by virtue of prior invention. In addition, the publication dates provided may be different from the actual publication dates, which may need to be confirmed independently. It is noted that the claims may be drafted to exclude any optional elements. As such, this statement is intended to serve as the antecedent basis for the use of such proprietary terminology as solely, only, and the like in connection with the recitation of claim elements, or the use of a negative limitation. As will become apparent to those skilled in the art upon reading this description, each of the individual embodiments described and illustrated herein has discrete components and features that can be readily separated from or combined with features of any of the various other embodiments without deviating from each other. of the scope or spirit of the embodiments of the present disclosure. Any recited method can be carried out in the order of the recited events or in any other order that is logically possible. Although any methods and materials similar or equivalent to those described herein may also be used in practicing or testing embodiments of the present disclosure, representative illustrative methods and materials are now described. DETAILED DESCRIPTION Aspects of the invention include polyalkylene oxide asparaginase compositions. In some cases, the compositions include one or more of a buffer and a salt. Aspects of the invention further include methods of preparing the compositions. The compositions find use in a variety of applications, for example, in the treatment of a neoplastic condition in a subject. Aspects of the invention include storage-stable lyophilized polyalkylene asparaginase oxide compositions. In some cases, lyophilized compositions include one or more of a buffer, a salt, and a sugar. Aspects of the invention further include methods of preparing the compositions. The compositions find use in a variety of applications, eg, in the treatment of a neoplastic condition (eg, acute myeloid leukemia (AML) in a subject). Aspects of the invention include a method of treating AML in a subject. The methods include administering to the subject a dose of a polyalkylene oxide asparaginase effective to treat AML in the subject. Aspects of the invention further include compositions containing polyalkylene oxide asparaginase and kits that can be used in the subject methods. In a further description of embodiments of the present disclosure, the compositions (eg, liquid and lyophilized) are first described in greater detail. Also described below are the methods of preparation, methods of use and the kits that include the composition in question. COMPOSITIONS Aspects of the present disclosure include a polyalkylene asparaginase oxide composition that includes a polyalkylene oxide group covalently attached through a linker to an asparaginase. The composition can also include one or more of a buffer and a salt. In certain embodiments, the composition is a storage-stable lyophilized composition. The storage-stable lyophilized composition can also include one or more of a buffer, a salt, and a sugar. As described herein, the compositions of the present disclosure may include a polyalkylene oxide asparaginase. a polyalkylene oxide asparaginase includes an asparaginase covalently linked by a linker to one or more polyalkylene oxide groups. Asparaginase is an enzyme that can be composed of four identical subunits with one active site per tetramer. For example, the enzyme asparaginase may be L-asparaginase (eg, Lasparaginase II), which hydrolyzes the amino acid L-asparagine (also known as (S)-2,4-diamino-4-oxobutanoic acid, or asparaginine, or abbreviated Asn or N) to produce L-aspartate (also known as (S)-2-aminosuccinic acid) and ammonia according to the following reaction: L-asparaginase H2O + NH3 In some cases, asparaginase can hydrolyze the amino acid L-glutamine (also known as (S)-2,5-diamino-5-oxopentanoic acid, or abbreviated as Gln or Q) to produce L-glutamate (also known as (S)-2-aminopentanedioic acid) and ammonia according to the following reaction: or or 11 L-asparaginase h2n O H --------------NH2H2O The above reactions that are mediated by L-asparaginase may also be referred to as the deamination reaction. In some cases, the L-asparaginase in the composition is derived from a prokaryotic source, such as a bacterium, including but not limited to Escherichia coli (E. coli) bacteria. As such, the asparaginase in the subject composition may be an E. coli asparaginase. In some cases, asparaginase is expressed by E. coli. The asparaginase can be recovered and purified from a culture medium containing the E. coli expressing the asparaginase. In addition to wild-type asparaginases, the asparaginase may also be a non-natural and / or synthetically produced asparaginase and / or an active fragment of a natural and / or synthetic asparaginase. Examples of asparaginases that can be used in embodiments of the invention include, but are not limited to, those described in: 9,322,008; 9,127,266; 9,051,561; 8,617,868; 7,807,436; 6,991,788; 6,537,547; 6,436,396; 6,368,845; 6,274,367; 6,251,388; 6,165,735; 6,140,101; 6,087,151; 6,042,825; 5,854,051; 5,310,670; 4,729,957 and 4,617,271; the descriptions of which are incorporated herein by reference. As described above, the asparaginase in the polyalkylene oxide asparaginase composition is an asparaginase covalently attached to one or more polyalkylene oxide groups. For example, the asparaginase can include one or more polyalkylene oxide groups covalently attached to the asparaginase through a process of post-translational modification. The polyalkylene oxide asparaginase can include one or more polyalkylene oxide groups covalently attached to the asparaginase at one or more positions on the asparaginase. For example, a polyalkylene oxide group can be covalently attached to an amino acid residue of asparaginase. In some cases, the polyalkylene oxide group is covalently attached to an amino group of an amino acid residue of asparaginase. In some embodiments, the polyalkylene oxide group is covalently attached to an amino acid side chain of an N-terminal amino acid in asparaginase. In some embodiments, the polyalkylene oxide group is covalently attached to a lysine (K) epsilon-amino group on asparaginase. In some embodiments, the polyalkylene oxide group is covalently attached to an amino acid side chain of the N-terminal amino acid and a lysine (K) epsilon-amino group in asparaginase. In some cases, polyalkylene oxide asparaginase is substantially non-antigenic. By non-antigenic or substantially non-antigenic is meant a composition that does not elicit a significant immune response in a subject when the composition is administered to the subject. In some cases, polyalkylene oxide asparaginase has a reduced rate of clearance from a subject's circulation compared to an unmodified asparaginase. For example, the elimination half-life of a polyalkylene oxide asparaginase may be 1 day or more, such as 2 days or more, or 3 days or more, or 4 days or more, or 5 days or more, or 6 days. days or more, or 7 days or more, or 8 days or more, or 9 days or more, or 10 days or more, or 11 days or more, or 12 days or more, or 13 days or more, or 14 days or more, or 15 or more days, or 16 or more days, or 17 or more days, or 18 or more days, or 19 or more days, or 20 or more days. In some embodiments, the elimination half-life of a polyalkylene oxide asparaginase is 3 days or longer. In some embodiments, the elimination half-life of a polyalkylene asparaginase oxide is 5 days or longer. The polyalkylene oxide group that is attached to the asparaginase can be any physiologically compatible polyalkylene oxide group. Polyalkylene oxides (PAOs), which are also known as polyoxyalkylenes (POAs), are produced by polymerization of alkylene oxides (eg ethylene oxide, propylene oxide, butylene oxide). A homopolymer is formed from only one type of alkylene oxide, while a copolymer is formed from two or more different alkylene oxides, known as alkylene oxide copolymers (AOCs). Examples of the former are polyethylene oxide (PEO), which is a polymer of ethylene oxide (EO), and polypropylene oxide (PPO), which is a polymer of propylene oxide (PO). Polyethylene oxide is also commonly known as polyethylene glycol (PEG) or polyoxyethylene (POE). The molecular weight of such polymers is generally characterized as the average of a distribution of lengths (or repeat units). In addition to the standard linear forms, branched or star-shaped forms of polyalkylene oxides are produced by initiating the polymerization reaction with a polyfunctional initiator with multiple hydroxyl-, amino-, or thiol- groups, each of which can serve as starting point for polymer chain growth. For example, the use of glycerol (three hydroxyl groups) as an initiator results in a three-armed branched polymer, while pentaerythritol results in a four-armed polymer. Conventionally, polymers of this type with 3 to 10 arms are called branched, while those with more than 10 arms are called star polymers. Comb copolymers are similar to the branched and star forms, but the initiator for comb copolymers is a polyfunctional polymer with multiple hydroxyl-, amino-, or thiol groups spaced along the backbone of the initiator, each of which can serve as a starting point for polymer chain growth. Graft copolymers are made MA / S / ZUZl / Ul 0344 by addition of pendant polymer chains along a polymer backbone possessing unsaturated C = C bonds or pendant functional groups (eg, hydroxyl) from which pendant chains can be added using a reactive monofunctional polymer chain. All polyalkylene oxides contain, in addition to multiple repeating units derived from alkylene oxide, a single residue corresponding to the molecule used to initiate the synthesis of the polymer. For linear polymers, this may be an alkylene glycol corresponding to the alkylene oxide used for the synthesis (for example, ethylene glycol and ethylene oxide, respectively), and therefore the residue derived from the initiator will be indistinguishable from the other repeat units in the polymer chain. But small molecules other than alkylene glycols are often used as initiators, examples include methanol or N-butanol (for linear polymers) and trimethylolpropane, glycerol, and pentaerythritol (for branched polymers) or ethylenediamine. The mass of the initiator relative to the mass of the final polymer chain is generally very small and can generally be neglected. Therefore, the term polyalkylene oxide is used herein in its usual sense, and includes both polyalkylene oxides initiated with one alkylene glycol molecule and polyalkylene oxides initiated with another small molecule. In certain embodiments, a physiologically compatible polyalkylene oxide group is substantially stable under conditions compatible with living cells, eg, predominantly aqueous conditions of a temperature, pH, salinity, etc. that are compatible with living cells. In certain embodiments, a polyalkylene oxide group is soluble in water. The term "water-soluble polymer" refers to a polyalkylene oxide group that is substantially soluble in water, such as in aqueous conditions found in the body of a subject. Polyalkylene oxide groups of interest include, but are not limited to, straight chain polyalkylene glycols. Straight chain polyalkylene glycols employed in certain embodiments of the invention have the following structural formula: wherein R is selected from the group consisting of hydrogen, lower alkyl, and mixtures thereof, Ri is selected from the group consisting of hydrogen and lower alkyl, and n is a positive integer. By lower alkyl is meant an alkyl group having one to four carbon atoms, ie, methyl, ethyl, propyl, butyl, and isomers thereof. R may be selected from the group consisting of hydrogen, methyl, and mixtures thereof, Ri may be selected from the group consisting of hydrogen and methyl, and n may be a positive integer selected to provide the desired polymer size. In some cases, the poly(alkylene glycols) employed in embodiments of the invention are poly(ethylene glycol), poly(propylene glycol), mixtures thereof, and copolymers of poly(ethylene glycol) and poly(propylene glycol) , wherein one of the terminal hydroxyl groups of the polymer may be substituted with a lower alkyl group. In some embodiments, the polyalkylene oxide is a polyethylene glycol (PEG). In certain embodiments, the polyethylene glycol (PEG) has a molecular weight of 1,000 to 20,000 daltons. In certain embodiments, the PEG has a molecular weight of 1,000 to 20,000 daltons, or 1,000 to 19,000 daltons, or 1,000 to 18,000 daltons, or 1,000 to 17,000 daltons, or 1,000 to 16,000 daltons, or 1,000 to 1 5,000 daltons, or 1,000 to 14,000 daltons, or 1,000 to 13,000 daltons, or 1,000 to 12,000 daltons, or 1,000 to 11,000, or 1,000 to 10,000, or 1,500 to 10,000 daltons, or 2,000 to 10,000 daltons, or 2.0 00 to 9,000 daltons, or 2,000 to 8,000 daltons, or 2,000 to 7,000 daltons, or 2,000 to 6,000 daltons, or 3,000 to 6,000 daltons, or 4,000 to 6,000 daltons, or 4,500 to 5,500 daltons. In certain embodiments, the PEG has a molecular weight of 2,000 to 10,000 daltons. In certain embodiments, the PEG has a molecular weight of 4,000 to 6,000 daltons. In certain embodiments, the PEG has a molecular weight of 5,000 daltons. In some cases, the polyethylene glycol is a methoxy polyethylene glycol (eg, monomethoxy polyethylene glycol or mPEG). As described above, the polyalkylene oxide group can be covalently attached to asparaginase. In some cases, the polyalkylene oxide group is covalently attached via a linker to the asparaginase. As such, the polyalkylene oxide group can be covalently attached to asparaginase via the linker. The linker can be any convenient functional group that allows attachment of the polyalkylene oxide group to the asparaginase. For example, the linker can include a reactive functional group that provides a covalent bond between the polyethylene oxide group and the asparaginase. In some cases, the linker includes a reactive functional group that provides a covalent bond between the polyethylene oxide group and an amino acid residue of asparaginase. For example, the linker can include a reactive functional group that provides a covalent bond between the polyalkylene oxide group and an amino group of an amino acid residue of asparaginase. Examples of such reactive functional groups include, but are not limited to, p-nitrophenoxy, thiazolidinyl thione, N-hydroxysuccinimidyl, or other suitable reactive functional groups such as, but not limited to, N-hydroxybenzotriazolyl, halogen, N-hydroxyphthalimidyl, imidazolyl, O-acylureas, pentafluorophenol or 2,4,6-trichlorophenol, and the like. In some cases, the reactive functional group of the linker is N-hydroxysuccinimidyl. Accordingly, after covalent attachment of the polyalkylene oxide group to the asparaginase, the linker can include functional groups, such as, but not limited to, a urethane linker (also known as a carbamate linker), a succinate, and the like. In certain embodiments, the linker includes a urethane linker (also known as a carbamate linker). For example, a reaction for the attachment of methoxy polyethylene glycol (mPEG) to an amino group of an amino acid of a polypeptide (eg, asparaginase) via a urethane (carbamate) linker is shown below. + H2N-polypeptide O mPEGxpolypeptide H In the reaction shown above, methoxy polyethylene glycol succinimidyl carbonate (also called SC-PEG) is reacted with an amino group of an amino acid of a polypeptide (eg, asparaginase) to produce a polyethylene glycol asparaginase with a urethane (carbamate) linker. . SC-PEG-asparaginase is also described in Angiolillo, AL, et al, Pharmacokinetics (PK) and pharmacodynamic (PD) properties of E. coli SC-PEG 1-asparaginase (EZN-2285) in the treatment of patients with Leukemia Lymphoblastic Cancer (ALL): Results of the Children's Oncology Group (COG) Study AALL07P4, American Society of Clinical Oncology (ASCO) Annual Meeting 2012, Poster 9543; and Angiolillo, A.L., et al., Pharmacokinetic and Pharmacodynamic Properties of Escherichia coli L-Asparaginase Calaspargase Pegol in the Treatment of Patients with Acute Lymphoblastic Leukemia: Results of the AALL07P4 Pediatric Oncology Group Study, J. Clin. Oncology, 32(34), 2014, 3874-3882. In certain embodiments, the linker includes a succinate linker (also called a succinyl linker). For example, a reaction for the attachment of methoxy polyethylene glycol (mPEG) to an amino group of an amino acid of a polypeptide (eg, asparaginase) via a succinate linker is shown below. + H2N-polypeptide polypeptide In the reaction shown above, methoxy polyethylene glycol succinimidyl succinate (also called SS-PEG) is reacted with an amino group of an amino acid of a polypeptide (eg, asparaginase) to produce a polyethylene glycol asparaginase with a succinate linker. SS-PEG-asparaginase is also described in US Patent Nos. 5,122,614; 5,324,844; and 5,612,460, the disclosures of each of which are incorporated herein by reference. In certain embodiments, the composition containing the polyalkylene oxide asparaginase is a dehydrated composition. As used herein, a dehydrated composition is a composition that includes water in a low amount, such as 25% or less, or 20% or less, or 15% or less, or 10% or less, or 9% or less. less, or 8% or less, or 7% or less, or 6% or less, or 5% or less, or 4% or less, or 3% or less, or 2% or less, or 1% or less of water as measured by Karl Fischer (KF) titration. In some cases, a dehydrated composition has 3% or less water as measured by Karl Fischer titration. In some cases, a dehydrated composition has 1% or less water, as measured by Karl Fischer titration. In some cases, a dehydrated composition has 0.5% or less water as measured by Karl Fischer titration. Any convenient protocol can be used to produce a dehydrated composition, such as increasing the temperature of the composition (eg, heating), reducing pressure, lyophilization (also known as freeze-drying), and the like, and combinations thereof. In certain embodiments, lyophilization is used to produce a dehydrated composition, and therefore the composition (eg, the composition containing the polyalkylene oxide asparaginase) is a lyophilized composition. In some cases, a lyophilized composition is a composition in which water has been removed from the composition by sublimation, where the water in the composition undergoes a phase transition from a solid to a gas. For example, a lyophilized composition can be a composition in which water has been removed from the composition by freezing the composition (eg, freezing the water in the composition) and then reducing the pressure surrounding the composition so that the water in the composition undergoes sublimation. As described above, a lyophilized composition may include water in a low amount, such as 25% or less, or 20% or less, or 15% or less, or 10% or less, or 9% or less, or 8%. or less, or 7% or less, or 6% or less, or 5% or less, or 4% or less, or 3% or less, or 2% or less, or 1% or less, or 0.5% or less, or 0.25% or less, or 0.1% or less water as measured by Karl Fischer (KF) titration. In certain embodiments, the lyophilized composition can include water in a low amount, such as between about 0.1% to about 25%, or about 0.25% to about 20%, or about 0.5% to about 15%, or about 1% to about 10%, or about 2% to about 9%, or about 3% to about 8%, or about 4% to about 7%, or about 5% to about 6%, as measured by the Karl Fischer (KF) titration. In certain embodiments, the lyophilized composition can include water in a low amount, such as between about 0.1% to about 5%, or about 0.25% to about 4%, or about 0.5% to about 3%, or about 1% to about 2%, as measured by Karl Fischer (KF) titration. In some cases, a lyophilized composition has 3% or less water, as measured by Karl Fischer titration. In some cases, a lyophilized composition has 1% or less water, as measured by Karl Fischer titration. In some cases, a lyophilized composition has 0.5% or less water as measured by Karl Fischer titration. Due to the low water content of a lyophilized composition as described above, the lyophilized composition can be in the form of a solid. In some cases, the solid lyophilized composition is a powder. In some cases, a lyophilized composition may facilitate storage of the composition for an extended period of time (eg, compared to a liquid formulation of the same composition). For example, a freeze-dried composition can be a storage-stable composition (eg, a storage-stable freeze-dried composition), where the composition is substantially stable over an extended period of time. By stable or storage stable or substantially stable is meant a composition that does not significantly degrade and / or lose activity over an extended period of time. For example, a storage-stable composition may not have significant impurities due to degradation of the composition over an extended period of time, such as 10% or less impurities, or 9% or less, or 8% or less, or 7 % or less, or 6% or less, or 5% or less, or 4% or less, or 3% or less, or 2% or less, or 1% or less of degradation products over an extended period of time. In certain embodiments, a storage stable composition may have between about 1% to about 10%, or about 2% to about 9%, or about 3% to about 8%, or about 4% to about 7%, or about 6 % to approximately 5% less degradation products over an extended period of time. In certain cases, a storage stable composition has 5% or less impurities over an extended period of time. In some cases, a storage-stable composition substantially retains its activity over an extended period of time, retaining such as 100% of its activity, or 99% or more, or 98% or more, or 97% or more, or 96 % or more, or 95% or more, or 94% or more, or 93% or more, or 92% or more, or 91% or more, or 90% or more, or 85% or more, or 80% or more, or 75% or more of their activity over an extended period of time. In some embodiments, a storage-stable composition substantially retains its activity for an extended period of time, such as from about 75% to about 100%, or about 80% to about 99%, or about 85% to about 98%, or about 90% to about 97%, or about 91% to about 96%, or about 92% to about 95%, or about 93% to about 94% more of your activity for an extended period of time . For example, a storage stable composition may retain 90% or more of its activity over an extended period of time. In some cases, a storage stable composition retains 95% or more of its activity over an extended period of time. An extended period of time is a period of time such as 1 week or more, or 2 weeks or more, or 3 weeks or more, or 1 month or more, or 2 months or more, or 3 months or more, or 4 months. or more, or 6 months or more, or 9 months or more, or 1 year or more, or 1.5 years (for example, 18 months) or more, or 2 years or more, or 2.5 years (for example, , 30 months) or more, or 3 years or more, or 3.5 years (for example, 42 months) or more, or 4 years or more, or 4.5 years (for example, 54 months) or more, or 5 years or more. For example, an extended time period may be 6 months or more. In some cases, an extended time period is 9 months or more. In some cases, an extended time period is 1 year (for example, 12 months) or more. In some cases, an extended time period is 1.5 years (for example, 18 months) or more. In some cases, an extended time period is 2 years (for example, 24 months) or more. In some embodiments, an extended period of time may be from about 1 week to about 3 weeks, or from about 1 month to about 6 months, or from about 6 months to about 9 months, or from about 1 year to about 1.5 years, or from about 1 year to about 2 years, or from about 1 year to about 3 years, or from about 1 year to about 4 years, or from about 1 year to about 5 years.In some embodiments, a storage-stable composition is substantially stable for an extended period of time at room temperature, such as 20 to 408C, or 25 to 35SC, or 25 to 30sC. In some cases, a storage-stable composition is substantially stable for an extended period of time at a temperature below room temperature, such as a temperature of 0 to 20°C, or 0 to 15°C, or 0 to 10°C, or 2 to 8°C. In some cases, the composition includes a therapeutically effective amount of the polyalkylene oxide asparaginase. The enzymatic activity of polyalkylene oxide-asparaginase can be measured in International Units (Iu), which corresponds to the amount of enzyme required to generate 1 pmol of ammonia per minute at a pH of 7.3 and a temperature of 37°C. In some cases, polyalkylene oxide asparaginase may be present in the composition in an amount (for example, polyalkylene oxide asparaginase may have a potency (activity)) ranging from 100 to 5,000 IU / g, such as 500 to 4,500 IU / g, or from 500 to 4,000 IU / g, or from 500 to 3,500 IU / g, or from 500 to 3,000 IU / g, or from 500 to 2,500 IU / g, or from 500 to 2,000 IU / g , or from 500 to 1,500 IU / g, or from 500 to 1,000 IU / g, or from 600 to 900 IU / g, or from 700 to 800 IU / g. In certain cases, the polyalkylene oxide asparaginase may be present in the composition in an amount ranging from 500 to 1,000 IU / g. For example, polyalkylene asparaginase oxide can have a potency (activity) ranging from 500 to 1,000 IU / g. In certain cases, polyalkylene oxide asparaginase is present in the composition in an amount ranging from 700 to 800 IU / g. For example, polyalkylene oxide asparaginase may have a potency (activity) ranging from 700 to 800 IU / g. In certain cases, polyalkylene oxide asparaginase is present in the composition in an amount of 750 IU / g. For example, polyalkylene oxide asparaginase may have a potency (activity) of 750 IU / g. In some cases, the polyalkylene oxide asparaginase in the composition is present in a therapeutically effective amount, where the polyalkylene oxide asparaginase has a specific activity of 50 IU / mg protein or more, such as 55 IU / mg protein. or more, or 60 IU / mg protein or more, or 65 IU / mg protein or more, or 70 IU / mg protein or more, or 75 IU / mg protein or more, or 80 IU / mg protein or more, or 85 IU / mg protein or more, or 90 IU / mg protein or more, or 95 IU / mg protein or more, or 100 IU / mg protein or more, or 105 IU / mg protein or more, or 110 IU / mg protein or more, or 115 IU / mg protein or more, or 120 IU / mg protein or more, or 125 IU / mg protein or more, or 130 IU / mg protein or more, or 135 IU / mg protein or more, or 140 IU / mg protein or more, or 145 IU / mg protein or more, or 150 IU / mg protein or more. For example, the polyalkylene asparaginase oxide in the composition may have a specific activity of 85 IU / mg protein or more. In some embodiments, the polyalkylene oxide asparaginase in the composition has a specific activity ranging from 50 to 150 IU / mg protein, or 55 to 145 IU / mg protein, or 60 to 140 IU / mg protein, or 65 to 135 IU / mg protein, or 70 to 130 IU / mg protein, or 75 to 125 IU / mg protein, or 80 to 120 IU / mg protein, or 85 to 115 IU / mg protein, or 90 to 110 IU / mg of protein, or 95 to 105 IU / mg of protein. In some cases, the polyalkylene asparaginase oxide in the composition has a specific activity ranging from 50 to 150 IU / mg protein, such as 65 to 140 IU / mg protein, or 70 to 135 IU / mg protein, or 75 to 130 IU / mg protein, or 75 to 125 IU / mg protein. For example, the polyalkylene oxide asparaginase in the composition may have a specific activity ranging from 75 to 125 IU / mg protein. In certain embodiments, the polyalkylene oxide asparaginase in the composition is present in a therapeutically effective amount, wherein the polyalkylene oxide asparaginase in the composition is present in an amount ranging from 1 mg / mL to 15 mg / mL, such as 1.5 mg / mL to 14.5 mg / mL, or 2 mg / mL to 14 mg / mL, or 2.5 mg / mL to 13.5 mg / mL, or 3 mg / mL to 13 mg / mL, or 3.5 mg / mL to 12.5 mg / mL, or 4 mg / mL to 12 mg / mL, or 4.5 mg / mL to 11.5 mg / mL, or 4.5 mg / mL to 11 mg / mL, or 4.5 mg / mL to 10.5 mg / mL, or 4.5 mg / ML, or 1 mg / mL to 10 mg / mL, or 4.5 mg / mL to 9, 5 mg / mL, or 4.5 mg / mL to 9 mg / mL, or 4.5 mg / mL to 8.5 mg / mL, or 5 mg / mL to 8 mg / mL. In some cases, the polyalkylene oxide asparaginase in the composition is present in an amount ranging from 4.5 mg / mL to 8.5 mg / mL. When administered to a subject, the composition may include an amount of polyalkylene oxide asparaginase sufficient to deliver 100 to 5,000 Iu / m2 of polyalkylene asparaginase oxide to the subject, such as 500 to 5,000 Iu / m2, or 500 to 4,500 Iu / m2, or 500 to 4,000 IU / m2, or 500 to 3,500 IU / m2, or 500 to 3,000 IU / m2, or 1,000 to 3,000 IU / m2, or 1,500 to 3,000 IU / m2, or 1,750 to 3,000 IU / m2 , or 2,000 to 3,000 IU / m2, or 2,000 to 2,750 IU / m2, or 2,250 to 2,750 IU / m2 of polyalkylene oxide asparaginase to the subject. For example, the composition can include an amount of polyalkylene oxide asparaginase sufficient to deliver 1,500 to 3,000 IU / m 2 of polyalkylene oxide asparaginase to the subject. In certain instances, the composition includes an amount of polyalkylene oxide asparaginase sufficient to deliver from 2,000 to 2,750 IU / m 2 of polyalkylene oxide asparaginase to the subject. In certain instances, the composition includes an amount of polyalkylene oxide asparaginase sufficient to deliver 2,250 to 2,750 IU / m 2 of polyalkylene oxide asparaginase to the subject. For example, the composition can include an amount of polyalkylene oxide asparaginase sufficient to deliver 2,500 IU / m 2 of polyalkylene oxide asparaginase to the subject. In certain embodiments, the dose administered to the subject is a liquid dose, eg, an aqueous dose. In some embodiments, in addition to polyalkylene oxide asparaginase, the dosage includes a buffer and a salt. The compositions of the present disclosure, in addition to polyalkylene oxide asparaginase, may include additional components. For example, the composition can include a buffer. Suitable buffers for use in the compositions of the present disclosure include buffers that are compatible with polyalkylene oxide asparaginase and suitable for administration to a subject, eg, by injection or intravenous administration. Examples of suitable buffers include, but are not limited to, phosphate buffers (for example, phosphate buffered saline (PBS)), Dulbecco's phosphate buffered saline (DPBS), Hank's balanced salt solution (HBSS), Earle's balanced salt solution (EBSS), Tris buffer, lactated Ringer's buffer, and the like, and combinations thereof. The buffer included in the composition can be a buffer that maintains the pH of the composition at a physiologically compatible pH, such as a pH ranging between 6 and 8, or a pH of about 7, for example 7.2, 7.3. or 7.4. In some cases, the buffer is a phosphate buffer. The phosphate buffer may include dibasic sodium phosphate (also known as MA / a / ZUZI / U1 0344 sodium phosphate or sodium hydrogen phosphate; Na2HPO4) and / or monobasic sodium phosphate (also known as monosodium phosphate; Na2HPO4). In some cases, the amount of dibasic sodium phosphate in the composition ranges from 0.05 to 5% by weight, such as 0.1 to 4.5% by weight, or 0.1 to 4% by weight, or 0. 1 to 3.5% by weight, or 0.1 to 3% by weight, or 0.1 to 2.5% by weight, or 0.1 to 2% by weight, or 0.1 to 1% by weight , or 0.1 to 0.9% by weight, or 0.1 to 0.8% by weight, or 0.1 to 0.7% by weight, or 0.1 to 0.6% by weight, or 0.2 to 0.6% by weight, or 0.3 to 0.6% by weight, or 0.4 to 0.6% by weight, or 0.5 to 0.6% by weight. For example, dibasic sodium phosphate may be present in the composition in an amount ranging from 0.1 to 1.0% by weight. In certain cases, dibasic sodium phosphate may be present in the composition in an amount ranging from 0.2 to 0.8% by weight. In certain cases, dibasic sodium phosphate may be present in the composition in an amount ranging from 0.3 to 0.6% by weight. In certain cases, dibasic sodium phosphate may be present in the composition in an amount ranging from 0.5 to 0.6% by weight. For example, dibasic sodium phosphate may be present in the composition in an amount of about 0.6% by weight, such as 0.56% by weight (or 0.558% by weight). In certain embodiments, the amount of monobasic sodium phosphate in the composition ranges from 0.005 to 2% by weight, such as 0.01 to 1.8% by weight, or 0.01 to 1.6% by weight, or 0. 01 to 1.4% by weight, or 0.01 to 1.2% by weight, or 0.01 to 1.0% by weight, or 0.01 to 0.8% by weight, or 0.01 to 0.6% by weight, or 0.01 to 0.4% by weight, or 0.01 to 0.2% by weight, or 0.02 to 0.18% by weight, or 0.03 to 0, 16% by weight, or 0.04 to 0.16% by weight, or 0.045 to 0.15% by weight, or 0.04 to 0.14% by weight, or 0.05 to 0.14% by weight , or 0.1 to 0.2% by weight, or 0.1 to 0.15% by weight. For example, monobasic sodium phosphate may be present in the composition in an amount ranging from 0.05 to 0.2% by weight. In certain cases, monobasic sodium phosphate may be present in the composition in an amount ranging from 0.01 to 0.2% by weight. In certain cases, monobasic sodium phosphate may be present in the composition in an amount ranging from 0.09 to 0.15% by weight. In certain cases, monobasic sodium phosphate may be present in the composition in an amount ranging from 0.1 to 0.2% by weight. In certain cases, monobasic sodium phosphate may be present in the composition in an amount ranging from 0.1 to 0.15% by weight. For example, monobasic sodium phosphate may be present in the composition in an amount of 0.12% by weight (or 0.129% by weight). Another additional component that can be included in the compositions of the present disclosure is a salt. Salts suitable for use in the compositions of the present disclosure include salts that are compatible with polyalkylene oxide asparaginase and suitable for administration to a subject, for example, by injection or intravenous administration. Examples of suitable salts include, but are not limited to, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, and the like, and combinations thereof. In certain cases, the salt is sodium chloride. In some cases, the amount of salt (for example, Sodium Chloride) in the composition ranges from 0.05 to 5% by weight, such as 0.05 to 4% by weight, or 0.05 to 3% by weight. , or 0.05 to 2% by weight, or 0.1 to 5% by weight, or 0.1 to 4% by weight, or 0.1 to 3% by weight, or 0.1 to 2% by weight , or 0.1 to 1.5% by weight, or 0.1 to 1% by weight, or 0.2 to 1% by weight, or 0.3 to 1% by weight, or 0.4 to 1% by weight, or 0.5 to 1% by weight, or 0.6 to 1% by ΙνΙΛ / α / ΖυΖΊ / U1 0344 weight, or 0.7 to 1% by weight, or 0.8 to 1% by weight, or 0.8 to 0.9% by weight. For example, salt (eg sodium chloride) may be present in the composition in an amount ranging from 0.5 to 1% by weight. For example, salt (eg sodium chloride) may be present in the composition in an amount ranging from 0.2 to 2% by weight. In certain cases, the salt (for example, sodium chloride) may be present in the composition in an amount ranging from 0.7 to 1% by weight. In certain cases, the salt (for example, sodium chloride) may be present in the composition in an amount ranging from 0.8 to 0.9% by weight. For example, salt (eg sodium chloride) may be present in the composition in an amount of 0.85% by weight. In certain embodiments, the polyalkylene oxide-asparaginase-containing composition is a lyophilized composition. The lyophilized compositions of the present disclosure, in addition to polyalkylene oxide asparaginase, may also include a buffer, a salt, and a sugar. For example, aspects of the present disclosure include a storage-stable lyophilized composition of a polyalkylene oxide asparaginase that includes a polyalkylene oxide group covalently linked through a linker to an asparaginase, a buffer, a salt, and a sugar. Buffers suitable for use in the lyophilized compositions of the present disclosure include buffers that are compatible with polyalkylene oxide asparaginase and suitable for administration to a subject, eg, by injection or intravenous administration. Examples of suitable buffers include those described above. In some cases, the buffer is a phosphate buffer. In certain embodiments, the phosphate buffer can include dibasic sodium phosphate and monobasic sodium phosphate. In some cases, the amount of dibasic sodium phosphate in the composition ranges from 0.05 to 1% by weight, such as 0.1 to 0.9% by weight, or 0.1 to 0.8% by weight, or 0.1 to 0.7% by weight, or 0.1 to 0.6% by weight, or 0.1 to 0.5% by weight, or 0.1 to 0.4% by weight, or 0, 2 to 0.4% by weight, or 0.2 to 0.3% by weight, or 0.25 to 0.3% by weight. For example, dibasic sodium phosphate may be present in the composition in an amount ranging from 0.1 to 0.5% by weight. In certain cases, dibasic sodium phosphate may be present in the composition in an amount ranging from 0.2 to 0.4% by weight. In certain cases, dibasic sodium phosphate may be present in the composition in an amount ranging from 0.25 to 0.3% by weight. For example, dibasic sodium phosphate may be present in the composition in an amount of about 0.3% by weight, such as 0.28% by weight (or 0.279% by weight). In certain embodiments, the amount of monobasic sodium phosphate in the composition ranges from 0.005 to 1% by weight, such as 0.01 to 0.9% by weight, or 0.01 to 0.8% by weight, or 0. 01 to 0.7% by weight, or 0.01 to 0.6% by weight, or 0.01 to 0.5% by weight, or 0.01 to 0.4% by weight, or 0.01 to 0.3% by weight, or 0.01 to 0.2% by weight, or 0.01 to 0.1% by weight, or 0.02 to 0.09% by weight, or 0.03 to 0, 08% by weight, or 0.04 to 0.08% by weight, or 0.045 to 0.075% by weight, or 0.04 to 0.07% by weight, or 0.05 to 0.07% by weight. For example, monobasic sodium phosphate may be present in the composition in an amount ranging from 0.01 to 0.1% by weight. In certain cases, monobasic sodium phosphate may be present in the composition in an amount ranging from 0.05 to 0.07% by weight. In certain cases, monobasic sodium phosphate may be present in the composition in an amount ranging from 0.045 to 0.075% by weight. For example, monobasic sodium phosphate may be present in the composition in an amount of 0.06% by weight. In certain aspects, the lyophilized compositions of the present disclosure include a salt. Salts suitable for use in the compositions of the present disclosure include salts that are compatible with polyalkylene oxide asparaginase and suitable for administration to a subject, for example, by injection or intravenous administration. Examples of suitable salts include those described above. In certain cases, the salt is sodium chloride. In some cases, the amount of salt (for example, sodium chloride) in the composition ranges from 0.05 to 1% by weight, such as 0.1 to 0.9% by weight, or 0.1 to 0, 8% by weight, or 0.1 to 0.7% by weight, or 0.1 to 0.6% by weight, or 0.1 to 0.5% by weight, or 0.2 to 0.5% by weight, or 0.3 to 0.5% by weight, or 0.4 to 0.5% by weight, or 0.4 to 0.45% by weight. For example, salt (eg sodium chloride) may be present in the composition in an amount ranging from 0.1 to 1% by weight. In certain cases, the salt (for example, sodium chloride) may be present in the composition in an amount ranging from 0.3 to 0.5% by weight. In certain cases, the salt (eg Sodium Chloride) may be present in the composition in an amount ranging from 0.4 to 0.45% by weight. For example, salt (eg sodium chloride) may be present in the composition in an amount of about 0.4% by weight, such as 0.425% by weight. Another component that can be included in the compositions of the present disclosure is a sugar. Sugars suitable for use in the compositions of the present disclosure include sugars that are compatible with polyalkylene oxide asparaginase and suitable for administration to a subject, for example, by injection or intravenous administration. Examples of suitable sugars include, but are not limited to, sucrose, mannitol, maltose, trehalose, 2-hydroxypropylbeta-cyclodextrin (β-HPCD), lactose, glucose, fructose, galactose, glucosamine, and the like, and combinations thereof. In certain cases, sugar is a disaccharide. For example, the disaccharide can be sucrose. In some cases, the amount of sugar (for example, Sucrose) in the composition ranges from 0.1 to 25% by weight, such as 0.5 to 20% by weight, or 1 to 15% by weight, or 1 to 10% by weight, or 1 to 9% by weight, or 1 to 8% by weight, or 2 to 7% by weight, or 2 to 6% by weight, or 3 to 5% by weight, or 4 to 5% in weigh. For example, sugar (eg Sucrose) may be present in the composition in an amount ranging from 1 to 10% by weight. In certain cases, sugar (eg sucrose) may be present in the composition in an amount ranging from 3 to 5% by weight. In certain cases, sugar (eg sucrose) may be present in the composition in an amount ranging from 4 to 5% by weight. For example, sugar (eg sucrose) may be present in the composition in an amount of 4.5% by weight. In some embodiments, the composition comprises, consists essentially of, or consists of a polyalkylene oxide asparaginase having a potency (activity) ranging from 500 to 1,000 IU / g, dibasic sodium phosphate in an amount ranging from 0.1 to 1.0% by weight of monobasic sodium phosphate in an amount ranging from 0.01 to 0.2% by weight, a salt (for example, sodium chloride) in an amount ranging from 0.2 to 2% by weight, and water. In some embodiments, the composition comprises, consists essentially of, or consists of a polyalkylene oxide asparaginase having a potency (activity) ranging from 700 to 800 IU / g, dibasic sodium phosphate in an amount ranging from 0.2 at 0.8% by weight, monobasic sodium phosphate in an amount ranging from 0.1 to 0.14% by weight, a salt (for example, sodium chloride) in an amount ranging from 0.6 to 1, 0% by weight, and water. In some embodiments, the composition comprises, consists essentially of, or consists of a polyalkylene oxide asparaginase having a potency (activity) ranging from 700 to 800 IU / g, dibasic sodium phosphate in an amount ranging from 0.5 at 0.6% by weight, monobasic sodium phosphate in an amount ranging from 0.09 to 0.15% by weight, a salt (for example, sodium chloride) in an amount ranging from 0.8 to 0, 9% by weight, and water. In some embodiments, the composition comprises, consists essentially of, or consists of a polyalkylene oxide asparaginase having a potency (activity) of 750 IU / g, dibasic sodium phosphate in an amount of about 0.6% by weight, phosphate monobasic sodium in an amount of about 0.1% by weight, a salt (for example, sodium chloride) in an amount of about 0.9% by weight, and water. In some embodiments, the composition comprises, consists essentially of, or consists of a polyalkylene oxide asparaginase having a potency (activity) of 750 IU / g, dibasic sodium phosphate in an amount of 0.56% by weight (or 0.558 %)), monobasic sodium phosphate in an amount of 0.13% by weight (or 0.129% by weight), a salt (for example, sodium chloride) in an amount of 0.85% by weight, and water. In some embodiments, the composition comprises, consists essentially of, or consists of a polyalkylene oxide asparaginase, dibasic sodium phosphate, monobasic sodium phosphate, salt (eg, sodium chloride), and water. In other embodiments, the composition comprises, consists essentially of, or consists of a polyalkylene oxide asparaginase, dibasic sodium phosphate, monobasic sodium phosphate, salt (eg, sodium chloride), sugar (eg, sucrose), and water. In some embodiments, the composition comprises, consists essentially of, or consists of a polyalkylene oxide asparaginase having a potency (activity) ranging from 500 to 1,000 IU / g, dibasic sodium phosphate in an amount ranging from 0.1 at 0.5% by weight, monobasic sodium phosphate in an amount ranging from 0.01 to 0.1% by weight, a salt (for example, sodium chloride) in an amount ranging from 0.1 to 1% by weight, a sugar (for example, sucrose) in an amount ranging from 1 to 10% by weight, and water. In some embodiments, the composition comprises, consists essentially of, or consists of a polyalkylene oxide asparaginase having a potency (activity) ranging from 700 to 800 IU / g, dibasic sodium phosphate in an amount ranging from 0.2 to 0.4% by weight, monobasic sodium phosphate in an amount ranging from 0.05 to 0.07% by weight, a salt (for example, sodium chloride) in an amount MA / a / ZUZI 0344 ranging from 0.3 to 0.5% by weight, a sugar (for example, sucrose) in an amount ranging from 3 to 5% by weight, and water. In some embodiments, the composition comprises, consists essentially of, or consists of a polyalkylene oxide asparaginase having a potency (activity) ranging from 700 to 800 IU / g, dibasic sodium phosphate in an amount ranging from 0.25 to 0.3% by weight, monobasic sodium phosphate in an amount ranging from 0.045 to 0.075% by weight, a salt (for example, sodium chloride) in an amount ranging from 0.4 to 0.45% by weight , a sugar (for example, sucrose) in an amount ranging from 4 to 5% by weight, and water. In some embodiments, the composition comprises, consists essentially of, or consists of a polyalkylene oxide asparaginase having a potency (activity) of 750 IU / g, dibasic sodium phosphate in an amount of about 0.3% by weight, phosphate monobasic sodium in an amount of about 0.06% by weight, a salt (for example, sodium chloride) in an amount of about 0.4% by weight, a sugar (for example, sucrose) in an amount of about 4 0.5% by weight, and water. In some embodiments, the composition comprises, consists essentially of, or consists of a polyalkylene oxide asparaginase having a potency (activity) of 750 IU / g, dibasic sodium phosphate in an amount of 0.28% by weight (or 0.279 % by weight), monobasic sodium phosphate in an amount of 0.06% by weight, a salt (for example, sodium chloride) in an amount of 0.43% by weight (or 0.425% by weight), a sugar ( for example, sucrose) in an amount of 4.5% by weight, and water. In certain cases, the composition (eg, liquid or lyophilized composition) is a sterile composition. By sterile is meant that there are substantially no immunogenic components in the composition, such as for example substantially no microbes (eg, fungi, bacteria, viruses, spore forms, etc.). In some cases, the composition is present in a container. Providing the composition in a container can facilitate maintenance of the composition as a sterile composition. For example, the container can be configured to keep the composition enclosed in the container in a sterile environment. As such, the container may be a sealed container, for example, the container may include a seal, such as a watertight seal and / or an airtight seal. The seal may be removable from the container to allow a user to access the contents of the container. In some cases, the seal may be a frangible seal, or in other cases, the seal may be configured to allow insertion of a needle, cannula, or syringe into the interior of the container without removing the seal from the container. In some cases, a seal configured to allow access to the interior of the container without removing the seal from the container may facilitate keeping the contents of the container (eg, the composition in the container) in a sterile environment prior to administration of the composition. to a subject. Suitable seal materials include, for example, rubber or polymer seals, such as, but not limited to, silicone rubber, natural rubber, styrene-butadiene rubber, ethylene-propylene copolymers, polychloroprene, polyacrylate, polybutadiene, polyurethane , styrene butadiene, and the like, and combinations thereof. For example, in certain embodiments, the seal is a septum pierceable by a needle, syringe, or cannula. The seal can also provide convenient access to a sample in the container, as well as a protective barrier that covers the opening of the container. In some cases, the seal is a removable seal, such as a screw or snap cap or other suitable sealing element that can be applied to the opening of the container. For example, a screw cap can be screwed onto the opening before or after a sample is added to the container, such as a screw or snap cap or other suitable sealing element that can be applied to the container opening. For example, a screw cap can be screwed onto the opening before or after a sample is added to the container. Such as a screw or snap-on cap or other suitable sealing element that can be applied to the container opening. For example, a screw cap can be screwed onto the opening before or after a sample is added to the container. In some cases, the container is a unit dosage container. A unit dosage container refers to a container that contains one or more unit dosages for administration to a subject. In some embodiments, a unit dosage container includes a predetermined amount of a subject composition calculated in an amount sufficient to produce a desired effect in a subject. Certain embodiments of the compositions may be provided in a unit dosage container suitable for individual administration of precise dosages. The amount of active composition administered to a subject may depend on the subject being treated, the severity of the affliction, and the manner of administration. For example, the unit dosage container may contain an amount of the composition to be administered as described herein in an amount effective to achieve the desired effect in the subject being treated. In certain instances, a unit dosage container includes a composition having a polyalkylene oxide asparagine in a therapeutically effective amount. Therapeutically effective amounts of polyalkylene oxide-asparagine are described above. In certain embodiments, the unit dosage container is a vial. In some cases, the vial is a sealed vial (eg, as described above with respect to a sealed container). The container can be made of any convenient material that is compatible with the polyalkylene oxide asparaginase and other components of the composition. For example, the container may be a solid-compatible container configured to hold a solid (eg, a lyophilized composition). In some cases, the container is a liquid compatible container configured to hold a liquid. Containers can also support solids and liquids, where the container is configured to hold both solids and liquids. In some cases, a liquid in the container may be an aqueous liquid, and in these cases, the container may be compatible with aqueous compositions. By compatible is meant that the container is substantially inert (eg, does not significantly react with) the liquid and / or compositions or other components in contact with the container. Examples of suitable container materials include, but are not limited to, glass and plastic. For example, the container may be comprised of glass, such as, but not limited to, silicate glass, borosilicate glass, borosilicate glass, MA / S / ZUZl / Ul 0344 sodium (eg, PYREX™), fused quartz glass, fused silica glass, and the like. Other examples of suitable container materials for the container include plastics, such as, but not limited to, polypropylene, polymethylpentene, polytetrafluoroethylene (PTFE), perfluoroethers (PFE), fluorinated ethylene propylene (FEP), perfluoroalkoxy alloys (PFA), polyethylene terephthalate (PET), polyethylene (PE), polyetheretherketone (PEEK), polystyrene, and the like. In certain cases, as described above, the container is a vial, and as such may be a glass vial. As described above, the container may be a sealed container, and as such may be a sealed glass vial. As described in more detail below, the liquid or reconstituted compositions of the present disclosure can be administered to a subject, for example by injection or intravenously. In certain embodiments, prior to administration of the reconstituted composition to a subject, a solid composition, for example as described above, may be combined with a liquid to provide a liquid composition suitable for administration, for example by injection or intravenously. In some cases, prior to administration of the composition to a subject, a solid composition may be combined with water (eg, Water for Injection, WFI) to provide an aqueous composition suitable for administration, eg, by injection or via intravenous. For example, a lyophilized composition can be reconstituted with water (eg, Water for Injection, WFI) to produce a reconstituted dosage unit suitable for administration to a subject, eg, by injection or intravenously. As set forth herein, aspects of the present disclosure include a composition that includes: a polyalkylene oxide asparaginase that includes a polyalkylene oxide group covalently linked through a linker to an asparaginase; a buffer and a salt. In certain embodiments, as described above, the polyalkylene oxide is a polyethylene glycol. In certain embodiments, as described above, the linker is a urethane (carbamate) linker. In certain embodiments, as described above, the asparaginase is an E. cali asparaginase. In certain embodiments, as described above, the buffer is a phosphate buffer. In certain embodiments, as described above, the salt is sodium chloride. Accordingly, certain embodiments of the composition include a polyethylene glycol paraginase that includes a polyethylene glycol group covalently linked by a urethane linker to an E. coti asparaginase, a phosphate buffer, and a salt. Each of the components of these compositions (eg, molecular weight of polyethylene glycol, amount of polyethylene glycol paraginase, amount and type of phosphate buffer, amount and type of salt) is as described in detail above. As set forth herein, aspects of the present disclosure include a storage-stable lyophilized composition that includes: a polyalkylene oxide asparaginase that includes a polyalkylene oxide group covalently linked through a linker to an asparaginase; a buffer, a salt and a sugar. In certain embodiments, as described above, the polyalkylene oxide is a polyethylene glycol. In certain embodiments, as described above, the linker is a urethane (carbamate) linker. In certain embodiments, as described above, the asparaginase is an E. coli asparaginase. In certain embodiments, as described above, the buffer is a phosphate buffer. In certain embodiments, as described above, the salt is sodium chloride. In certain embodiments, as described above, the sugar is a disaccharide (eg, sucrose). Accordingly, certain embodiments of the storage-stable lyophilized composition include a polyethylene glycol paraginase that includes a polyethylene glycol group covalently linked by a urethane linker to an E. coli asparaginase; a phosphate buffer, a salt and a disaccharide. Each of the components of these compositions (for example, the molecular weight of polyethylene glycol, the amount of polyethylene glycol asparaginase, the amount and type of phosphate buffer, the amount and type of salt, the amount and type of disaccharide , etc.) is as described in detail above. The compositions of the present disclosure may also include other components, such as additional pharmaceutically acceptable excipients or a dose delivery vehicle as part of the composition. Excipients may include, but are not limited to, carbohydrates, inorganic salts, organic salts, antimicrobial agents, antioxidants, surfactants, water (for example, Water for Injection (WFI)), alcohols, polyols, glycerin, vegetable oils, phospholipids, buffers, acids, bases, and any combination thereof. A carbohydrate such as a sugar, a derivatized sugar such as an alditol, aldonic acid, an esterified sugar, and / or a sugar polymer may also be employed. Some carbohydrate excipients of interest include, for example, monosaccharides, such as fructose, maltose, galactose, glucose, D-mannose, sorbose, and the like; disaccharides, such as lactose, sucrose, trehalose, cellobiose, and the like; polysaccharides, such as raffinose, melezitose, maltodextrins, dextrans, starches, and the like; and alditols, such as mannitol, xylitol, maltitol, lactitol, xylitol, sorbitol (glucitol), pyranosyl sorbitol, myo-inositol, and the like. The inorganic and organic salts may include, but are not limited to, citric acid, sodium chloride, potassium chloride, sodium sulfate, potassium nitrate, monobasic sodium phosphate, dibasic sodium phosphate, and any combination thereof. In certain embodiments, the compositions of the present disclosure may also include an antimicrobial agent to prevent or inhibit microbial growth, such as for example benzalkonium chloride, benzethonium chloride, benzyl alcohol, cetylpyridinium chloride, chlorobutanol, phenol, phenylethyl alcohol, phenylmercuric nitrate, timersol, and any combination thereof. One or more antioxidants may also be included in the composition. Antioxidants, which can reduce or prevent oxidation and therefore deterioration of the composition, can include, for example, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, hypophosphorous acid, monothioglycerol, propyl gallate, sodium bisulfite. , sodium formaldehyde sulfoxylate, sodium metabisulfite, and any combination thereof. MA / a / ZUZI 0344 One or more surfactants may also be included in the compositions of the present disclosure. For example, suitable surfactants can include, but are not limited to, polysorbates, such as Tween 20 and Tween 80, and pluronics such as F68 and F88 (BASF, Mount Olive, New Jersey); sorbitan esters; lipids, such as phospholipids such as lecithin and other phosphatidylcholines, phosphatidylethanolamines, fatty acids and fatty esters; steroids, such as cholesterol; chelating agents, such as EDTA; and zinc and other cations. Acids or bases may also be present in compositions of the present disclosure. For example, acids may include, but are not limited to, hydrochloric acid, acetic acid, phosphoric acid, citric acid, malic acid, lactic acid, formic acid, trichloroacetic acid, nitric acid, perchloric acid, phosphoric acid, sulfuric acid, fumaric acid, and any combination thereof. Examples of bases include, but are not limited to, sodium hydroxide, sodium acetate, ammonium hydroxide, potassium hydroxide, ammonium acetate, potassium acetate, sodium phosphate, potassium phosphate, sodium citrate, sodium formate, sodium sulfate, potassium sulfate, potassium sulfate, and any combination thereof. The amount of any individual excipient in the composition may vary depending on the nature and function of the excipient, the vehicle of administration of the dose, and the particular needs of the composition. In some cases, the optimal amount of any individual excipient is determined through routine experimentation, that is, by preparing compositions containing varying amounts of the excipient (ranging from low to high), examining stability and other parameters, and then determining the amount of the excipient. range at which optimal performance is achieved without significant adverse effects. In general, however, the excipient(s) will be present in the composition in an amount of from 1% to 99% by weight, such as from 5% to 98% by weight, such as from 15% to 95% by weight of excipient. , including 30% or less by weight, or 20% or less by weight, or 10% or less by weight. Pharmaceutical excipients along with other excipients that may be employed in the compositions are described in Remington: The Science & Practice of Pharmacy, 22nd., Williams & Williams, (2012), Medical Desktop Reference, 70th., PDR Network, Montvale, NJ (2015), and Rowe, RC, Handbook of Pharmaceutical Excipients, 7th ed., Pharmaceutical Press, New York, NY, (2012), the disclosures of which are incorporated herein by reference. METHODS OF USE Aspects of the present disclosure also include methods of using the compositions (eg, liquid and lyophilized) described herein. In certain embodiments, the method of use is a method of deaminating asparagine in a subject. As described above, the enzyme asparaginase can mediate a deamination reaction where the amino acid asparagine is hydrolyzed to produce aspartate and ammonia, for example, according to the following reaction: EITHER L-asparaginase HO JL ------------► úl ΊΓ^οη+ NH3 H2° O NH2 In some cases, asparaginase activity reduces the concentration of asparagine in a subject, such as reduces the plasma concentration of asparagine in the subject. A depletion of asparagine in a subject can adversely affect cells in the subject that are dependent on the presence of asparagine for protein synthesis. For example, protein synthesis in cells that lack the ability to synthesize their own asparagine (for example, cells that lack the enzyme asparagine synthetase) can be negatively affected by a lack of exogenous asparagine, which in turn can lead to to cell apoptosis. In some cases, cells in a subject that are dependent on the presence of asparagine for protein synthesis may be associated with a neoplastic condition, such as cancer. Accordingly, the methods of the present disclosure include methods of treating a neoplastic condition in a subject, such as methods of treating a cancer in a subject. Accordingly, the compositions of the present disclosure that include a polyalkylene oxide asparaginase may be therapeutically effective for the treatment of neoplastic conditions, such as cancer. In certain embodiments, non-neoplastic cells in the subject are not significantly affected by the polyalkylene asparaginase oxide compositions of the present disclosure. For example, non-neoplastic cells in the subject may have the enzyme asparagine synthetase and therefore retain the ability to synthesize asparagine. In certain embodiments, the neoplastic condition in the subject to be treated includes neoplastic conditions that are amenable to treatment by administration of a polyalkyleneasparaginase oxide to the subject, eg, exogenous asparagine-dependent neoplastic conditions. For example, neoplastic conditions that can be treated by administering a polyalkylene asparaginase oxide to a subject include cancers, such as solid tumors or liquid tumors. In certain cases, the neoplastic condition is characterized by the presence of a solid tumor. Accordingly, in some embodiments, a method of the present disclosure is a method of treating a solid tumor in a subject using a polyalkylene oxide asparaginase composition (for example, a reconstituted liquid or lyophilized polyalkylene oxide asparaginase composition). the present description). Methods for treating a neoplastic condition in a subject are useful for treating a wide variety of solid tumors, including carcinomas and sarcomas. Solid tumor types may include, but are not limited to, pancreatic cancer, melanoma, squamous cell cancer, non-squamous cell lung cancer (NSCLC), colon cancer, breast cancer, ovarian cancer, cervix, prostate cancer, and the like. For example, carcinomas that can be treated using a subject method include, but are not limited to, esophageal carcinoma, hepatocellular carcinoma, basal cell carcinoma (a form of skin cancer), squamous cell carcinoma (various tissues), Bladder carcinoma, including transitional cell carcinoma (a malignancy of the bladder), bronchogenic carcinoma, colon carcinoma, colorectal carcinoma, gastric carcinoma, lung carcinoma, including small cell carcinoma and non-small cell carcinoma of the lung , adrenocortical carcinoma, thyroid carcinoma, pancreatic carcinoma, breast carcinoma, ovarian carcinoma, prostate carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, cell carcinoma renal cells, ductal carcinoma in situ or bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilm's tumor, cervical carcinoma, uterine carcinoma, testicular carcinoma, osteogenic carcinoma, epithelial carcinoma, and nasopharyngeal carcinoma, etc. Sarcomas that can be treated with a method in question include, but are not limited to, fibrosarcoma, mixosarcoma, liposarchom omiosarcoma , rhabdomyosarcoma, and other soft tissue sarcomas. Other solid tumors that can be treated with a subject method include, but are not limited to, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, melanoma, neuroblastoma, and retinoblastoma. In certain cases, the neoplastic condition is characterized by the presence of a fluid tumor. For example, a fluid tumor can include metastatic cancer cells (eg, circulating tumor cells (CTCs)), blood cancers, and the like, and combinations thereof. Examples of blood cancers include, but are not limited to, leukemia, lymphoma, and myeloma. In some cases, the cancer is leukemia. Accordingly, in some embodiments, the method is a method of treating leukemia in a subject using a polyalkylene oxide asparaginase composition (eg, a reconstituted liquid or lyophilized polyalkylene oxide asparaginase composition of the present disclosure). Various types of leukemia may be amenable to treatment using the methods in question. For example, the leukemia can be an acute leukemia. An acute leukemia can be characterized by a rapid increase in the number of immature blood cells. A rapid increase in immature blood cells can result in crowding, which in turn can cause the bone marrow to produce significantly less healthy blood cells. Thus, the methods of the present disclosure include methods of treating acute leukemia in a subject, for example, by administering to the subject a dose of a polyalkylene oxide asparaginase composition (for example, a reconstituted liquid or lyophilized oxide composition). of polyalkylene asparaginase of the present disclosure) effective for treating acute leukemia in the subject. In other cases, the leukemia is chronic leukemia. In some cases, chronic leukemia can be characterized by an increase in the number of relatively mature, but abnormal, white blood cells. Chronic leukemia can take an extended time to develop (for example, months or years), where the abnormal white blood cells are produced at a significantly higher rate than normal. MA / a / ZUZI / U1 0344 normal. Thus, the methods of the present disclosure include methods of treating a subject for chronic leukemia, for example, by administering to the subject a dose of a polyalkylene oxide asparaginase composition (for example, a reconstituted liquid or lyophilized oxide composition). of polyalkylene asparaginase of the present disclosure) effective for treating chronic leukemia in the subject. In certain embodiments, the leukemia is lymphoblastic leukemia (also called lymphocytic leukemia). A lymphoblastic leukemia can be characterized by the type of blood cell affected by the leukemia. In lymphoblastic leukemia, the abnormal change in blood cells occurs in bone marrow cells that normally become lymphocytes. For example, the lymphoblastic leukemia can be B-cell leukemia. Thus, the methods of the present disclosure include methods of treating a subject for lymphoblastic leukemia (lymphocytic leukemia), for example, by administering to the subject a dose of a composition of polyalkylene oxide asparaginase (eg, a liquid or reconstituted lyophilized polyalkylene oxide asparaginase composition of the present disclosure) effective for treating the subject for lymphoblastic leukemia (lymphocytic leukemia). For example, a specific type of lymphoblastic leukemia that can be treated with the methods in question includes acute lymphoblastic leukemia (ALL). In these embodiments, the methods of the present disclosure include methods of treating acute lymphoblastic leukemia (ALL) in a subject, for example, by administering to the subject a dose of a polyalkylene oxide asparaginase (for example, a lyophilized liquid or reconstituted composition of polyalkylene oxide asparaginase of the present disclosure) effective in treating ALL in the subject. Other types of lymphoblastic leukemia that can be treated using the subject methods include, but are not limited to, chronic lymphocytic leukemia (CLL). In these embodiments, the methods of the present disclosure include methods of treating chronic lymphocytic leukemia (CLL) in a subject, for example, by administering to the subject a dosage of a polyalkylene oxide asparaginase (for example, a lyophilized liquid or reconstituted composition of polyalkylene oxide asparaginase of the present disclosure) effective in treating CLL in the subject. In other embodiments, the leukemia is a myeloid leukemia (also called myelogenous leukemia). A myeloid leukemia can be characterized by the type of blood cell affected by the leukemia. In myeloid leukemia, the abnormal change in blood cells occurs in bone marrow cells that normally develop into red blood cells and / or platelets. Thus, the methods of the present disclosure include methods of treating myeloid leukemia (myelogenous leukemia) in a subject, for example, by administering to the subject a dose of a polyalkylene oxide asparaginase composition (for example, a liquid composition or lyophilized reconstituted with polyalkylene oxide asparaginase of the present disclosure) effective in treating the subject of myeloid leukemia (myelogenous leukemia). For example, a specific type of myeloid leukemia that can be treated using the subject methods includes acute myeloid leukemia (AML). In these embodiments, the methods of the present disclosure include methods of treating acute myeloid leukemia (AML) in a subject, for example, by administering to the subject a dose of a polyalkylene oxide asparaginase (for example, a lyophilized liquid or reconstituted composition of polyalkylene oxide asparaginase of the present disclosure) effective in treating AML in the subject. Examples of AML include, but are not limited to, AML with recurrent cytogenetic translocations, AML with multilineage dysplasia, and other AMLs. For example, AMLs with recurrent cytogenetic translocations include, but are not limited to, AML with t(8;21)(q22;q22), AML1(CBF-alpha) / ETO, acute promyelocytic leukemia (AML with t(15; 17)(q22;q11 -12) and variants, PML / RAR-alpha), AML with abnormal bone marrow eosinophils (inv(16)(p13q22) or t(16;16)(p13;q11), CBFb / MYH11X ), and AML with abnormalities of 11 q23 (MLL). Examples of AML with multilineage dysplasia may include those that are associated with or without prior myelodysplastic syndrome. Other types of acute myeloid leukemia include, for example, minimally differentiated AML, AML without maturation, AML with maturation, acute myelomonocytic leukemia, acute monocytic leukemia, acute erythroid leukemia, acute megakaryocyte leukemia, acute basophilic leukemia, and acute panmellosis with myelofibrosis. Other types of myeloid leukemia that can be treated using the subject methods include, but are not limited to, chronic myelogenous leukemia (CML). In these embodiments, the methods of the present disclosure include methods of treating chronic myelogenous leukemia (CML) in a subject, for example, by administering to the subject a dose of a polyalkylene oxide asparaginase (for example, a lyophilized liquid or reconstituted composition of polyalkylene oxide asparaginase of the present disclosure) effective in treating CML in the subject. In certain cases, asparaginase can mediate the deamination of glutamine, where the amino acid glutamine is hydrolyzed to produce glutamate and ammonia, for example, according to the following reaction: O 0 0 O ^Y^OH nh2 L-asparaginase He·'- ^Y^OH nh2 + NHo H2O ' INI 13 In some instances, asparaginase activity reduces the glutamine concentration in a subject, such as reduces the subject's plasma glutamine concentration. Similar to the discussion above, glutamine depletion in a subject can adversely affect cells in the subject that are dependent on the presence of glutamine for protein synthesis. For example, protein synthesis in cells that lack the ability to synthesize their own glutamine (for example, cells that lack the enzyme glutamine synthetase) can be negatively affected by a lack of exogenous glutamine, which in turn can lead to cell apoptosis. In some cases, cells in a subject that are dependent on the presence of glutamine for protein synthesis may be associated with a neoplastic condition, such as cancer. Accordingly, the methods of the present disclosure include methods of treating a neoplastic condition in a subject, such as methods of treating a cancer in a subject, where the neoplastic condition may be dependent on exogenous glutamine. For example, embodiments of the subject methods include methods of glutamine deamination in a subject. In certain embodiments, non-neoplastic cells in the subject are not significantly affected by polyalkylene oxide asparaginase administered to the subject. For example, non-neoplastic cells in the subject may have the enzyme glutamine synthetase and therefore retain the ability to synthesize glutamine. As described above, the compositions of the present disclosure include storage-stable lyophilized compositions. Prior to administration of the composition to a subject, a lyophilized composition can be combined with a liquid to provide a liquid composition suitable for administration, for example, by injection or intravenously. In some cases, prior to administration of the composition to a subject, a lyophilized composition is combined with water (eg, Water for Injection, WFI) to provide an aqueous composition suitable for administration, eg, by injection or intravenously. For example, the methods of the present disclosure may include reconstitution of a lyophilized composition (eg, a storage-stable lyophilized composition) of the present disclosure. Reconstitution of a lyophilized composition can produce a reconstituted dosage unit. In some cases, the reconstituted dosage unit is suitable for administration to the subject, eg, by injection or intravenously. In certain embodiments, reconstitution of the lyophilized composition includes combining the lyophilized composition (eg, storage-stable lyophilized composition) with water (eg, water for injection, WFI). The liquid or reconstituted dosage unit may include a predetermined amount of the composition of the present disclosure calculated in an amount sufficient to produce a desired therapeutic effect in a subject. The amount of the composition in a dosage unit (eg, liquid or reconstituted) that is administered to a subject may depend on the subject being treated, the severity of the affliction, and the mode of administration. For example, the dosage unit can include an amount of the composition to be administered as described herein in a therapeutically effective amount. Certain embodiments of the dosage unit may include an amount of polyalkylene oxide asparaginase ranging from 100 to 5,000 IU / mL, such as 500 to 4,500 IU / mL, or 500 to 4,000 IU / mL, or 500 to 3,500 IU / mL. mL. or 500 to 3,000 IU / mL, or 500 to 2,500 IU / mL, or 500 to 2,000 IU / mL, or 500 to 1,500 IU / mL, or 500 to 1,000 IU / mL, or 600 to 900 IU / mL, or or 700 at 800 IU / mL. In certain cases, the dosage unit includes an amount of polyalkylene oxide asparaginase ranging from 500 to 1,000 IU / mL. In certain cases, the dosage unit includes an amount of polyalkylene asparaginase oxide ranging from 700 to 800 IU / mL. For example, the dosage unit may include 750 IU / mL of polyalkylene oxide asparaginase. In certain embodiments, the dosage unit includes a therapeutically effective amount (eg, specific activity) of the polyalkylene oxide asparaginase, such as 50 IU / mg protein or more, such as 55 IU / mg protein or more, or 60 IU / mg protein or more, or 65 IU / mg protein or more, or 70 IU / mg protein or more, or 75 IU / mg protein or more, or 80 IU / mg protein or more, or 85 IU / mg protein or more, or 90 IU / mg protein or more, or 95 IU / mg protein or more, or 100 IU / mg protein or more, or 105 IU / mg protein or more, or 110 IU / mg protein or more, or 115 IU / mg protein or more, or 120 IU / mg protein or more, or 125 IU / mg protein or more, or 130 IU / mg protein or more, or 135 IU / mg protein or more, or 140 IU / mg protein or more, or 145 IU / mg protein or more, or 150 IU / mg protein or more. For example, the dosage unit may have a specific activity of 85 IU / mg protein or more. In some embodiments, the dosage unit has a specific activity ranging from 50 to 150 IU / mg protein, or 55 to 145 IU / mg protein, or 60 to 140 IU / mg protein, or 65 to 135 IU / mg protein, or 70 to 130 IU / mg protein, or 75 to 125 IU / mg protein, or 80 to 120 IU / mg protein, or 85 to 115 IU / mg protein, or from 90 to 110 IU / mg of protein, or from 95 to 105 IU / mg of protein. In some cases, the dosage unit has a specific activity ranging from 50 to 150 IU / mg protein, such as 65 to 140 IU / mg protein, or 70 to 135 IU / mg protein, or 75 to 130 IU / mg protein, or 75 to 125 IU / mg protein. For example, the dosage unit may have a specific activity of 75 to 125 IU / mg protein. In certain embodiments, the dosage unit includes a therapeutically effective amount (eg, protein concentration) of polyalkylene oxide asparaginase in an amount ranging from 1 mg / mL to 15 mg / mL, such as 1.5 mg / mL to 14.5 mg / mL, or 2 mg / mL to 14 mg / mL, or 2.5 mg / mL to 13.5 mg / mL, or 3 mg / mL to 13 mg / mL, or 3.5 mg / mL to 12.5 mg / mL, or 4 mg / mL to 12 mg / mL, or 4.5 mg / mL to 11.5 mg / mL, or 4.5 mg / mL to 11 mg / mL, or 4.5 mg / mL to 10.5 mg / mL, or 4.5 mg / mL to 10 mg / mL, or 4.5 mg / mL to 9.5 mg / mL, or 4.5 mg / mL to 9 mg / mL, or 4.5 mg / mL to 8.5 mg / mL, or 5 mg / mL to 8 mg / mL. In some cases, the dosage unit includes the polyalkylene oxide asparaginase in an amount ranging from 4.5 mg / mL to 8.5 mg / mL. When administered to a subject, the dosage unit may include a therapeutically effective amount of the polyalkylene oxide asparaginase such that the dosage unit delivers from 100 to 5,000 IU / m2 of the polyalkylene oxide asparaginase to the subject, for example, 500 to 5,000 IU / m2, or 500 to 4,500 IU / m2, or 500 to 4,000 IU / m2, or 500 to 3,500 IU / m2, or 500 to 3,000 IU / m2, or 1,000 to 3,000 IU / m2, or 1,500 to 3,000 Iu / m2, or 1,750 to 3,000 Iu / m2, or 2,000 to 3,000 Iu / m2, or 2,000 to 2,750 Iu / m2, or 2,250 to 2,750 Iu / m2 of polyalkylene oxide asparaginase to the subject. For example, the dosage unit can deliver 1,500 to 3,000 IU / m 2 of polyalkylene oxide asparaginase to the subject. In certain instances, the dosage unit delivers from 2,000 to 2,750 IU / m 2 of polyalkylene asparaginase oxide to the subject. In certain cases, the dosage unit delivers 2,250 to 2,750 IU / m 2 of polyalkylene oxide asparaginase to the subject. For example, the dosage unit may administer 2,500 IU / m 2 of polyalkylene oxide asparaginase to the subject. In certain embodiments, the dosage unit includes a buffer, such as a buffer described in detail above. For example, the dosage unit may include a phosphate buffer, and as such may include dibasic sodium phosphate and monobasic sodium phosphate. MA / a / ZUZI 0344 In some cases, the dosage unit includes a phosphate buffer, and as such may include dibasic sodium phosphate and monobasic sodium phosphate. In certain cases, the dosage unit includes dibasic sodium phosphate in an amount ranging from 0.5 to 10 mg / g, such as 1 to 9 mg / g, or 1 to 8 mg / g, or 1 to 7 mg / g, or 2 to 7 mg / g, or 3 to 6 mg / g, or 4 to 6 mg / g, or 5 to 6 mg / g. For example, the dosage unit may include dibasic sodium phosphate in an amount ranging from 4 to 6 mg / g. In certain cases, the dosage unit includes dibasic sodium phosphate in an amount ranging from 5 to 6 mg / g. For example, the dosage unit may include dibasic sodium phosphate in an amount of about 5.5 mg / g, such as 5.6 mg / g (or 5.58 mg / g). In certain embodiments, the dosage unit includes monobasic sodium phosphate in an amount ranging from 0.05 to 5 mg / g, such as 0.1 to 4.5 mg / g, or 0.1 to 4 mg / g, o 0.1 to 3.5 mg / g, o 0.1 to 3 mg / g, o 0.1 to 2.5 mg / g, o 0.1 to 2 mg / g, o 0.5 to 2 mg / g, or 1 to 2 mg / g, or 1 to 1.5 mg / g. For example, the dosage unit may include monobasic sodium phosphate in an amount ranging from 1 to 2 mg / g. In certain cases, the dosage unit includes monobasic sodium phosphate in an amount ranging from 1 to 1.5 mg / g. For example, the dosage unit may include monobasic sodium phosphate in an amount of 1.2 mg / g (or 1.29 mg / g). In certain embodiments, the dosage unit includes a salt. Salts suitable for use in the dosage unit include salts that are compatible with polyalkylene asparaginase oxide and suitable for administration to a subject, for example, by injection or intravenous administration. Examples of suitable salts include, but are not limited to, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, and the like, and combinations thereof. In certain cases, the dosage unit includes a salt, such as sodium chloride. In some cases, the dosage unit includes a salt (for example, sodium chloride) in an amount ranging from 1 to 20 mg / g, such as 1 to 19 mg / g, or 1 to 18 mg / g, or 1 to 17 mg / g, or 1 to 16 mg / g, or 1 to 15 mg / g, or 2 to 15 mg / g, or 3 to 15 mg / g, or 4 to 15 mg / g, or 5 to 14 mg / g, or 5 to 13 mg / g, or 5 to 12 mg / g, or 5 to 11 mg / g, or 5 to 10 mg / g, or 5 to 9 mg / g, or 6 to 9 mg / g, or 7 to 9 mg / g, or 8 to 9 mg / g. For example, the dosage unit may include a salt (eg, sodium chloride) in an amount ranging from 1 to 10 mg / g. In certain cases, the dosage unit includes a salt (eg, sodium chloride) in an amount ranging from 5 to 10 mg / g. In certain cases, the dosage unit includes a salt (eg, sodium chloride) in an amount ranging from 6 to 9 mg / g. In certain cases, the dosage unit includes a salt (eg, sodium chloride) in an amount ranging from 8 to 9 mg / g. For example, the dosage unit may include a salt (eg, sodium chloride) in an amount of 8.5 mg / g. In some instances, the formulation being administered to a subject is the liquid injection formulation of PEG-asparaginase known commercially as Oncaspar®, which is approved for commercialization by the US Food and Drug Administration. Oncaspar® (pegaspargase) is L-asparaginase (L-asparagine amidohydrolase) that is covalently conjugated with monomethoxy polyethylene glycol (mPEG), which is present as a clear, colorless, preservative-free solution in sterile, isotonic phosphate-buffered saline, pH 7.3. Each milliliter contains 750 ± 150 International Units of pegaspargase, dibasic sodium phosphate, USP (5.58 mg), monobasic sodium phosphate, USP (1.20 mg), and sodium chloride, USP (9.5 mg) in water for injections , USP. In certain embodiments, the dosage unit administered to the subject is a dosage unit prepared from a lyophilized composition, eg, a storage-stable lyophilized composition as described herein. The dosage unit prepared from the lyophilized composition can be a liquid dosage. In addition to polyalkylene oxide asparaginase, unit dosage embodiments (eg, a reconstituted dosage from a lyophilized composition) can include a buffer, salt, and sugar. In certain embodiments, the reconstituted dosage unit includes a buffer, such as a buffer described in detail above. In some cases, the reconstituted dosage unit includes dibasic sodium phosphate in an amount ranging from 0.5 to 10 mg / g, such as 1 to 9 mg / g, or 1 to 8 mg / g, or 1 to 7 mg. / g, or 1 to 6 mg / g, or 1 to 5 mg / g, or 1 to 4 mg / g, or 2 to 4 mg / g, or 2 to 3 mg / g, or 2.5 to 3 mg / g. For example, the reconstituted dosage unit may include dibasic sodium phosphate in an amount ranging from 1 to 5 mg / g. In certain cases, the reconstituted dosage unit may include dibasic sodium phosphate in an amount ranging from 2 to 4 mg / g. In certain cases, the reconstituted dosage unit may include dibasic sodium phosphate in an amount ranging from 2.5 to 3 mg / g. For example, the reconstituted dosage unit can include dibasic sodium phosphate in an amount of about 3 mg / g, such as 2.8 mg / g (or 2.79 mg / g). In certain embodiments, the reconstituted dosage unit includes monobasic sodium phosphate in an amount ranging from 0.05 to 1 mg / g, such as 0.1 to 0.9 mg / g, or 0.1 to 0.8 mg / g, or 0.2 to 0.8 mg / g, or 0.3 to 0.8 mg / g, or 0.4 to 0.8 mg / g, or 0.45 to 0.75 mg / g , or 0.5 to 0.7 mg / g. For example, the reconstituted dosage unit may include monobasic sodium phosphate in an amount ranging from 0.45 to 0.75 mg / g. In certain cases, the reconstituted dosage unit includes monobasic sodium phosphate in an amount ranging from 0.5 to 0.7 mg / g. For example, the reconstituted dosage unit may include monobasic sodium phosphate in an amount of 0.6 mg / g. In certain embodiments, the reconstituted dosage unit includes a salt, such as a salt described in detail above. In certain cases, the reconstituted dosage unit includes a salt, such as sodium chloride. In some cases, the reconstituted dosage unit includes a salt (for example, Sodium Chloride) in an amount ranging from 0.5 to 10 mg / g, such as 1 to 9 mg / g, or 1 to 8 mg / g, or 1 to 7 mg / g, or 1 to 6 mg / g, or 1 to 5 mg / g, or 2 to 5 mg / g, or 3 to 5 mg / g, or 4 to 5 mg / g, or 4 to 4.5 mg / g. For example, the reconstituted dosage unit may include a salt (eg, sodium chloride) in an amount ranging from 1 to 10 mg / g. In certain cases, the reconstituted dosage unit includes a salt (eg, sodium chloride) in an amount ranging from 3 to 5 mg / g. In certain cases, the reconstituted dosage unit includes a salt (eg, sodium chloride) in an amount ranging from 4 to 4.55 mg / g. For example, the reconstituted dosage unit can include a salt (eg, sodium chloride) in an amount of about 4 mg / g, such as 4.25 mg / g. In certain embodiments, the reconstituted dosage unit includes a sugar, such as a sugar described in detail above. In certain cases, the reconstituted dosage unit includes a sugar, such as a disaccharide. In some cases, the reconstituted dosage unit includes a sugar, such as sucrose. In some cases, the reconstituted dosage unit includes an amount of sugar (for example, Sucrose) ranging from 1 to 250 mg / g, such as 5 to 200 mg / g, or 10 to 150 mg / g, or 10 to 100 mg / g, or 10 to 90 mg / g, or 10 to 80 mg / g, or 20 to 70 mg / g, or 20 to 60 mg / g, or 30 to 50 mg / g, or 40 to 50 mg / g. For example, the reconstituted dosage unit may include a sugar (eg, sucrose) in an amount ranging from 10 to 100 mg / g. In certain cases, the reconstituted dosage unit may include a sugar (eg, sucrose) in an amount ranging from 30 to 50 mg / g. In certain cases, the reconstituted dosage unit may include a sugar (eg, sucrose) in an amount ranging from 40 to 50 mg / g. For example, the reconstituted dosage unit may include a sugar (eg, sucrose) in an amount of 45 mg / g. In certain embodiments, the dosage unit (eg, liquid or reconstituted) has a pH compatible with physiological conditions. In some cases, unit dosage pH ranges from 6 to 8. In some cases, unit dosage pH ranges from 7 to 8. For example, unit dosage pH can range from 7 to 7 ,5. In some cases, the pH of the dosage unit is 7.2. In some cases, the pH of the dosage unit is 7.3. In some cases, the pH of the dosage unit is 7.4. In certain embodiments, the method may include administering the dosage unit to the subject to deaminate asparagine in the subject. The route of administration can be selected according to a variety of factors including, but not limited to, the condition to be treated, the type of composition and / or device used, the patient to be treated, and the like. Routes of administration useful in the described methods include, but are not limited to, oral and parenteral routes, such as intravenous (iv), intraperitoneal (ip), intramuscular (im), rectal, topical, ophthalmic, nasal, and transdermal. For example, compositions suitable for injection can be administered by intravenous, intramuscular, intradermal, subcutaneous, sublingual, intraosseous, or other route of administration. In some cases, administration of the dosage unit to the subject includes intravenous administration of the dosage unit to the subject. In some cases, administration of the dosage unit to the subject includes intramuscular administration of the dosage unit to the subject. In some cases, administration of the reconstituted dosage unit to the subject includes intravenous administration of the reconstituted dosage unit to the subject. In some cases, administration of the reconstituted dosage unit to the subject includes intramuscular administration of the reconstituted dosage unit to the subject. In certain embodiments, the method includes administering the dosage unit to the subject in accordance with a treatment regimen. For example, in some cases, a subject to be treated may have been prescribed a treatment regimen by a health care provider. In some cases, a treatment regimen includes, but is not necessarily limited to, administration five times a day, four times a day, three times a day, twice a day, once a day, three times a week, two times a week, once a week, once every two weeks, once every three weeks, once a month, once every 5 weeks, once every 6 weeks, once every 7 weeks, once every two months, and any combination thereof. In some embodiments, the treatment regimen includes administering one or more doses over an extended period of time. In certain instances, a single dose (eg, a single dose unit) is administered to the subject, and the initial dose may be followed by one or more doses administered to the subject at a later time. In some cases, more than one dose (eg, more than one dosage unit) is administered to the subject, and the initial doses may be followed by one or more doses administered to the subject at a later time. For example, a single dose (eg, a single dosage unit) may be administered to the subject, and the single dose may be followed by a single dose administered to the subject at a later time. Additional single doses may be administered at later points in time. In other cases, a single dose (eg, a single dosage unit may be administered to the subject, and the single dose may be followed by two doses administered to the subject at a later time. Additional single or multiple doses may be administered at points later in time. In certain cases, the treatment regimen includes multiple phases. The treatment regimen can include multiple phases in which the dosing schedule is different in each phase of the treatment regimen. In some cases, a subject is prescribed a treatment regimen with two phases; an induction phase and a consolidation phase. In certain instances, a subject is prescribed a treatment regimen with two phases in which the dosing schedule in the first phase is different from the dosing schedule in the second phase. For example, a subject may be prescribed a treatment regimen with two phases including an induction phase and a consolidation phase, where the induction phase dosing schedule is different from the consolidation phase dosing schedule. . In other embodiments, a subject may be prescribed a treatment regimen with three phases; an induction phase, a consolidation phase, and a maintenance phase. In some cases, a subject is prescribed a treatment regimen with three phases including an induction phase, a consolidation phase, and a maintenance phase, where the dosing schedule of each phase is different from the other phases. For example, a subject may be prescribed a treatment regimen with three phases including an induction phase, a consolidation phase, and a maintenance phase, where the dosing schedules of the induction phase, the consolidation phase , and the maintenance phase are different from each other. In certain embodiments, the length of treatment time during each phase of the treatment regimen is the same, or in other cases may be different. For example, the period of time during the induction phase can be 1 week or more, such as 2 weeks or more, or 3 weeks or more, or 4 weeks or more, or 5 weeks or more, or 6 weeks or more. , or 7 weeks or more, or 8 weeks or more. In MA / S / ZUZl / Ul 0344 In some cases, the time during the induction phase is 4 weeks. In some cases, the time during the induction phase is 5 weeks. In certain embodiments, the time during the consolidation phase is 1 week or more, such as 2 weeks or more, or 3 weeks or more, or 4 weeks or more, or 5 weeks or more, or 6 weeks or more, or 7 weeks or more, or 8 weeks or more, or 9 weeks or more, or 10 weeks or more, or 11 weeks or more, or 12 weeks or more, or 13 weeks or more, or 14 weeks or more, or 15 weeks or more, or 16 weeks or more, or 17 weeks or more, or 18 weeks or more, or 19 weeks or more, or 20 weeks or more, or 21 weeks or more, or 22 weeks or more, or 23 weeks or more , or 24 weeks or more, or 25 weeks or more, or 26 weeks or more, or 27 weeks or more, or 28 weeks or more, or 29 weeks or more, or 30 weeks or more, or 31 weeks or more, or 32 weeks or more. In some cases, the time during the consolidation phase is 8 weeks. In some cases, the time during the consolidation phase is 27 weeks. In some cases, the time during the consolidation phase is 30 weeks. In certain embodiments, the duration of time during the maintenance phase is 1 week or more, such as 2 weeks or more, or 3 weeks or more, or 4 weeks or more, or 5 weeks or more, or 6 weeks or more. , or 7 weeks or more, or 8 weeks or more, or 9 weeks or more, or 10 weeks or more, or 12 weeks or more, or 16 weeks or more, or 20 weeks or more, or 24 weeks or more, or 28 weeks or more, or 32 weeks or more, or 36 weeks or more, or 40 weeks or more, or 44 weeks or more, or 48 weeks or more, or 52 weeks or more, or 56 weeks or more, or 60 weeks or more, or 64 or more weeks, or 68 or more weeks, or 72 or more weeks, or 76 or more weeks, or 80 or more weeks, or 84 or more weeks, or 88 or more weeks, or 92 or more weeks , or 96 or more weeks, or 100 or more weeks, or 104 or more weeks, or 108 or more weeks, or 112 or more weeks, or 116 or more weeks, or 120 or more weeks, or 124 or more weeks, or 128 weeks or more, or 132 weeks or more, or 136 weeks or more, or 140 weeks or more, or 144 weeks or more, or 148 weeks or more, or 152 weeks or more, or 156 weeks or more, or 160 weeks or more, or 164 or more weeks, or 168 or more weeks, or 172 or more weeks, or 176 or more weeks, or 180 or more weeks. In some cases, the time during the maintenance phase is 8 weeks. In some cases, the time during the maintenance phase is 88 weeks. In some cases, the time during the maintenance phase is 104 weeks. In some cases, the time during the consolidation phase is 140 weeks. In some cases, the time during the maintenance phase is 156 weeks. In some cases, the length of time during the maintenance phase ranges from 88 to 104 weeks. In some cases, the length of time during the maintenance phase varies from 88 to 140 weeks. In some cases, the length of time during the maintenance phase ranges from 88 to 156 weeks. Examples of treatment regimens that can be administered to a subject include, but are not limited to, those described herein. In certain embodiments, the treatment regimen includes administering a single dosage unit to a subject in an induction phase and multiple dosage units during a maintenance phase. In certain embodiments, the treatment regimen includes administering a single dosage unit to a subject in an induction phase and multiple dosage units during a consolidation phase. For example, multiple dosage units can be administered to the subject by administering one dosage unit to the subject every 3 weeks (eg, during the consolidation phase). In some cases, a single dose unit is administered to the subject once every 3 weeks. As described above, the consolidation phase may be 30 weeks, and therefore a total of 10 dosage units may be administered to the subject (for example, a single dosage unit may be administered to the subject once every 3 weeks for 30 weeks). Additional (or fewer) dosage units may be administered to the subject between the induction phase and the consolidation phase, or after the consolidation phase, as desired or prescribed by a healthcare provider. In other examples, the treatment regimen may include administering a single dosage unit to a subject in an induction phase and multiple dosage units during a consolidation phase, where the multiple dosage units may be administered to the subject by administering one unit of dosage. Dosing to subject every 2 weeks. In some cases, a single dose unit is administered to the subject once every 2 weeks. As described above, the consolidation phase may be 30 weeks and therefore a total of 15 dosage units may be administered to the subject (for example, a single dosage unit may be administered to the subject once every 2 weeks for 30 weeks). Additional (or fewer) dosage units may be administered to the subject between the induction phase and the consolidation phase, or after the consolidation phase, as desired or prescribed by a healthcare provider. In other embodiments, the treatment regimen includes administering a single dosage unit to a subject in an induction phase, multiple dosage units during a consolidation phase, and multiple dosage units during a maintenance phase. For example, multiple dosage units during the consolidation phase may be administered to the subject on certain days after the initiation of the consolidation phase. In some cases, multiple dosage units during the consolidation phase can be administered to the subject by administering more than one dosage unit to the subject at the same time. For example, multiple dosage units during the consolidation phase can be administered to the subject by administering more than one dosage unit to the subject on a particular day after the initiation of the consolidation phase and more than one dosage unit to the subject on a day. later during the consolidation phase. An example of this type of treatment regimen may include administering 2 dosage units to the subject on day 15 after the start of the consolidation phase and 2 dosage units on day 43 after the start of the consolidation phase. Additional (or fewer) dosage units may be administered to the subject between the induction phase and the consolidation phase, or after the consolidation phase but before the maintenance phase, as desired or prescribed by a healthcare provider. . In certain embodiments, multiple dosage units during the maintenance phase may be administered to the subject on certain days after the start of the maintenance phase. In In some cases, multiple dosage units during the maintenance phase can be administered to the subject by administering more than one dosage unit to the subject at the same time. For example, multiple units during the maintenance phase can be administered to the subject by administering more than one dosage unit to the subject on a particular day after the start of the maintenance phase and more than one dosage unit to the subject on a subsequent day during the maintenance phase. the maintenance phase. An example of this type of treatment regimen may include administering 2 dosage units to the subject on day 2 after the start of the maintenance phase and 2 dosage units on day 22 after the start of the maintenance phase. Another example of a treatment regimen during the maintenance phase may include administering 2 dosage units to the subject on day 4 after the start of the maintenance phase and 2 dosage units on day 43 after the start of the maintenance phase. In some cases, a treatment regimen may include multiple maintenance phases. In certain cases, the dosing schedule during each maintenance phase may be the same, or in other cases the dosing schedule during each maintenance phase may be different. Additional (or fewer) dosage units may be administered to the subject between the consolidation phase and the maintenance phase, or after the maintenance phase, or between different maintenance phases, as desired or prescribed by a drug provider. medical attention. In certain embodiments, the dosage units of the present disclosure may be administered before, concurrently with, or after other active agents to treat related or unrelated conditions, eg, in combination therapy. Examples of such additional therapies include radiation therapies, surgical therapies, and chemotherapy therapies. If provided at the same time as other active agents, the dosage units of the present disclosure may be provided in the same formulation or in a different formulation. For example, concurrent therapy can be achieved by administering a dosage unit and a pharmaceutical composition having at least one other active agent, such as a chemotherapeutic agent, which in combination provides a therapeutically effective dose, in accordance with a particular treatment regimen. The administration of separate pharmaceutical compositions can be carried out simultaneously or at different times (for example, sequentially, in any order, on the same day or on different days), as long as a therapeutically effective effect of the combination of these substances occurs in the subject undergoing therapy. Accordingly, aspects of the present disclosure further include combination therapies. In certain embodiments, the subject method includes administering a therapeutically effective amount of one or more additional active agents. By combination therapy is meant that a polyalkylene oxide asparaginase (eg, as described herein) can be used in combination with another therapeutic agent to treat a single disease or condition. In certain embodiments, a compound of the present disclosure is administered simultaneously with the administration of another therapeutic agent, which may be administered as a component of a composition that includes the compound of the present disclosure or as a component of a different composition. In certain embodiments, a composition that includes a compound of the present disclosure is administered before or after the administration of another therapeutic agent. The subject compounds can be used in conjunction with any agent useful in the treatment of a neoplastic condition, such as anticancer agents and antitumor agents. One class of anticancer agents of interest includes chemotherapeutic agents. Chemotherapy means the administration of one or more chemotherapeutic drugs and / or other agents to a cancer patient by various methods, including intravenous, oral, intramuscular, intraperitoneal, intravesical, subcutaneous, transdermal, buccal, or by inhalation. Agents of interest that may be used in conjunction with the subject compounds include, but are not limited to, cancer chemotherapeutic agents, agents that act to reduce cell proliferation, antimetabolite agents, agents that affect microtubules, hormone modulators, and steroids, natural products, and biological response modifiers, for example, as described in more detail below. Cancer chemotherapeutic agents include non-peptide (ie, non-protein) compounds that reduce the proliferation of cancer cells, and include cytotoxic agents and cytostatic agents. Non-limiting examples of chemotherapeutic agents include alkylating agents, nitrosoureas, antimetabolites, antitumor antibiotics, plant (vinca) alkaloids, and steroid hormones. Peptide compounds can also be used. Suitable cancer chemotherapeutic agents include dolastatin and active analogs and derivatives thereof; and auristatin and active analogs and derivatives thereof (eg, monomethyl auristatin D (MMAD), monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), and the like). See, for example, WO 96 / 33212, WO 96 / 14856 and US 6,323,315. For example, dolastatin 10 or auristatin PE can be included in an antibody-drug conjugate of the present disclosure. Suitable cancer chemotherapeutic agents also include maytansinoids and active analogs and derivatives thereof (see, for example, EP 1391213; and Liu et al (1996) Proc. Nati. Acad. Sci. USA 93: 8618-8623); duocarmycins and active analogs and derivatives thereof (eg, including the synthetic analogs, KW-2189 and CB 1-TM1); and benzodiazepines and active analogs and derivatives thereof (for example, pyrrolobenzodiazepine (PBD). Agents that act to reduce cell proliferation are known in the art and are widely used. Such agents include alkylating agents, such as nitrogen mustards, nitrosoureas, ethyleneimine derivatives, alkyl sulfonates, and triazenes, including, but not limited to, mechlorethamine, cyclophosphamide (Cytoxan™), melphalan (L-sarcolysin), carmustine ( BCNU), lomustine (CCNU), semustine (methyl-CCNU), streptozocin, chlorozotocin, uracil mustard, chlormethine, ifosfamide, chlorambucil, pipobromane, triethylenemelamine, triethylenethiophosphoramine, busulfan, dacarbazine, and temozolomide. IVIA / a / ¿U¿ I 0344 Antimetabolite agents include folic acid analogues, pyrimidine analogues, purine analogues, and adenosine deaminase inhibitors, including, but not limited to, cytarabine (CYTOSAR-U), cytosine arabinoside, fluorouracil (5-FU) , floxuridine (FudR), 6-thioguanine, 6-mercaptopurine (6-MP), pentostatin, 5-fluorouracil (5-FU), methotrexate, 10-propargyl-5,8-dideazafolate (PDDF, CB3717), 5,8-acid dideazatetrahydrofolic acid (DDATHF), leucovorin, fludarabine phosphate, pentostatin, and gemcitabine. Suitable natural products and their derivatives (for example, vinca alkaloids, antitumor antibiotics, enzymes, lymphokines, and epipodophyllotoxins), include, but are not limited to, Ara-C, paclitaxel (Taxol®), docetaxel (Taxotere®) , deoxycoformycin, mitomycin-C, azathioprine; break up; alkaloids, for example, vincristine, vinblastine, vinorelbine, vindesine, etc.; podophyllotoxins, eg etoposide, teniposide, etc.; antibiotics, for example, anthracycline, daunorubicin hydrochloride (daunomycin, rubidomycin, cerubidin), idarubicin, doxorubicin, epirubicin and morpholino derivatives, etc.; phenoxyzone biscyclopeptides, eg, dactinomycin; basic glycopeptides, eg bleomycin; anthraquinone glycosides, eg, plicamycin (mitramycin); anthracenediones, eg mitoxantrone; azirinopyrrole indoledions, eg mitomycin; macrocyclic immunosuppressants, eg, cyclosporine, FK-506 (tacrolimus, prograf), rapamycin, etc.; and the like. Other anti-proliferative cytotoxic agents include navelbene, CPT-11, anastrazole, letrazole, capecitabine, reloxafine, cyclophosphamide, ifosamide, and droloxafine. Agents that affect microtubules that have antiproliferative activity are also suitable for use and include, but are not limited to, allocolchicine (NSC 406042), Halichondrin B (NSC 609395), colchicine (NSC 757), colchicine derivatives ( eg, NSC 33410), dolstatin. 10 (NSC 376128), maytansine (NSC 153858), rhizoxin (NSC 332598), paclitaxel (Taxol®), Taxol® derivatives, docetaxel (Taxotere®), thiocolchicine (NSC 361792), trityl cisterna, vinblastine sulfate, vincristine sulfate, natural and synthetic epothilones including, but not limited to, eoptilone A, epothilone B, discodermolide; estramustine, nocodazole, and the like. Hormone modulators and steroids (including synthetic analogues) that are suitable for use include, but are not limited to, adrenocorticosteroids, eg, prednisone, dexamethasone, etc.; estrogens and pregestins, eg hydroxyprogesterone caproate, medroxyprogesterone acetate, megestrol acetate, estradiol, clomiphene, tamoxifen; etc.; and adrenocortical suppressants, eg, aminoglutethimide; 17a-ethinylestradiol; diethylstilbestrol, testosterone, fluoxymesterone, dromostanolone propionate, testolactone, methylprednisolone, methyl-testosterone, prednisolone, triamcinolone, chlorotrianisene, hydroxyprogesterone, aminoglutethimide, estramustine, medroxyprogesterone acetate, leuprolide, Flutamide (Drogenil), Toremifene (Fareston), and Zoladex®. Estrogens stimulate proliferation and differentiation; therefore, compounds that bind to the estrogen receptor are used to block this activity. Corticosteroids can inhibit T cell proliferation. ινΐΛ / a / zuz i / un 0344 Other suitable chemotherapeutic agents include metal complexes, eg, cisplatin (cis-DDP), carboplatin, etc.; ureas, eg hydroxyurea; and hydrazines, for example, N-methylhydrazine; epidophyllotoxin; a topoisomerase inhibitor; procarbazine; mitoxantrone; leucovorin; tegafur; etc Other anti-proliferative agents of interest include immunosuppressants, eg mycophenolic acid, thalidomide, deoxyspergualin, azasporin, leflunomide, mizoribine, azaspiran (SKF 105685); Iressa® (ZD 1839, 4-(3-chloro-4-fluorophenylamino)-7-methoxy-6-(3-(4-morphol¡n¡l)propoxy¡)quinazoline); etc Taxanes are suitable for use. Taxanes include paclitaxel, as well as any active taxane derivative or prodrug. Paclitaxel (which is to be understood herein to include analogues, formulations, and derivatives such as, for example, docetaxel, TAXOL™, TAXOTERE™ (a formulation of docetaxel), 10-deacetyl analogues of paclitaxel, and 3'N- debenzoyl-3'N-t-butoxycarbonyl paclitaxel analogues) can be readily prepared using techniques known to those skilled in the art (see also WO 94 / 07882, WO 94 / 07881, WO 94 / 07880, WO 94 / 07876, WO 93 / 23555 , WO 93 / 10076; US Patent Nos. 5,294,637; 5,283,253; 5,279,949; 5,274,137; 5,202,448; 5,200,534; 5,229,529; and EP 590,267), or obtained from a variety of commercial sources, including, for example, Sigma Chemical Co., St Louis, Mo. (T7402 from Taxus brevifolia; or T-1912 from Taxus yannanensis). It should be understood that paclitaxel refers not only to the commonly available chemical form of paclitaxel, but to analogs and derivatives (for example, Taxotere™ docetaxel, as noted above) and conjugates of paclitaxel (for example, Paclitaxel-PEG, paclitaxel -dextran, or paclitaxel-xylose). Also included within the term taxane are a variety of known derivatives, including both hydrophilic derivatives and hydrophobic derivatives. Taxane derivatives include, but are not limited to, galactose and mannose derivatives described in International Patent Application No. WO 99 / 18113; piperazino and other derivatives described in WO 99 / 14209; taxane derivatives described in WO 99 / 09021, WO 98 / 22451, and US Patent No. 5,869,680; 6-thio derivatives described in WO 98 / 28288; sulfenamide derivatives described in US Patent No. 5,821,263; and taxol derivative described in US Patent No. 5,415,869. It further includes paclitaxel prodrugs including, but not limited to, those described in WO 98 / 58927; WO 98 / 13059; and US Patent No. 5,824,701. Biological response modifiers suitable for use include, but are not limited to, (1) inhibitors of tyrosine kinase (RTK) activity; (2) inhibitors of serine / threonine kinase activity; (3) tumor-associated antigen antagonists, such as antibodies that specifically bind to a tumor antigen; (4) apoptosis receptor agonists; (5) interleukin-2; (6) IFN-a; (7) IFN-γ; (8) colony stimulating factors; and (9) angiogenesis inhibitors. Subjects that can be treated using the methods and compositions of the present disclosure include subjects of any age. In some cases, the subject may be an adult. For example, an adult human subject may be 18 years of age or older. Subjects that can be treated using the methods and compositions of the present disclosure also include minor subjects. For example, a human minor subject may be less than 18 years of age. In some cases, subjects range in age from 1 month to 18 years, such as 1 year to 18 years, including 2 years to 18 years, eg, 5 years to 16 years. In some cases, the methods include the diagnosis of a subject with AML. A subject can be diagnosed with AML using any convenient protocol. In some cases, the French, American, and British (FAB) classification system is used to diagnose and classify acute myeloid leukemia. The diagnosis of acute myeloid leukemia requires myeloblasts to constitute 30% (or 20% according to a recent World Health Organization (WHO) classification system) or more of bone marrow cells or circulating white blood cells. The hematological properties of the disease define the various subtypes that are described below. The FAB nomenclature (M1 to M7) classifies the subtypes of acute myeloid leukemia according to the elements of normal marrow that the blasts most closely resemble. In certain instances, the methods include determining the suitability of a subject diagnosed as having AML for treatment using a polyalkylene oxide asparaginase composition, for example, as described herein. In some cases, the methods include monitoring the effectiveness of the treatment. The effectiveness of the treatment can be monitored using any convenient protocol. PREPARATION METHODS Aspects of the present disclosure include methods for preparing the polyalkylene oxide asparaginase compositions described herein. In certain instances, the method is a method of preparing a liquid polyalkylene oxide asparaginase composition as described herein. The method may include the production of an aqueous composition including a polyalkylene oxide asparaginase having a polyalkylene oxide group covalently attached via a linker to an asparaginase, a buffer and a salt. Embodiments of the methods for preparing the polyalkylene asparaginase oxide composition may include the production of an aqueous concentrate composition. For example, the method for producing the aqueous concentrate composition may include one or more of the steps of: preparing an asparaginase (eg, L-asparaginase) solution; attaching a polyalkylene oxide (eg, polyethylene glycol) to the asparaginase; clarify the polyalkylene oxide asparaginase; filter and concentrate the polyalkylene oxide asparaginase solution; dilute polyalkylene oxide asparaginase solution; filter the polyalkylene oxide asparaginase solution and fill the polyalkylene oxide asparaginase solution into a sterile container; and storing the polyalkylene oxide asparaginase solution. In the method for producing the aqueous concentrate composition, an asparaginase solution (for example, L-asparaginase) can be prepared. The asparaginase can be mixed with a solution, such as an aqueous solution (eg, a buffered aqueous solution). Examples of suitable buffers include, but are not limited to, a phosphate buffer, phosphate buffered saline (PBS), Dulbecco's phosphate buffered saline (DPBS), Hank's balanced salt solution (HBSS), balanced salt solution Earle's buffer (EBSS), Tris buffer, Lactated Ringer's buffer, borate buffer, and the like, and combinations thereof. In some cases, the asparaginase is mixed with a phosphate buffer. The phosphate buffer can include dibasic sodium phosphate and monobasic sodium phosphate. In some cases, the amount of dibasic sodium phosphate in the aqueous concentrate composition ranges from 0.05 to 5% by weight, such as 0.1 to 4.5% by weight, or 0.1 to 4% by weight, or 0.1 to 3.5% by weight, or 0.1 to 3% by weight, or 0.1 to 2.5% by weight, or 0.1 to 2% by weight, or 0.1 to 1 % by weight, or 0.1 to 0.9% by weight, or 0.1 to 0.8% by weight, or 0.1 to 0.7% by weight, or 0.1 to 0.6% by weight weight, or 0.2 to 0.6% by weight, or 0.3 to 0.6% by weight, or 0.4 to 0.6% by weight, or 0.5 to 0.6% by weight. For example, dibasic sodium phosphate may be present in the aqueous concentrate composition in an amount ranging from 0.1 to 1% by weight. In certain cases, dibasic sodium phosphate may be present in the composition in an amount ranging from 0.2 to 0.8% by weight. In certain cases, dibasic sodium phosphate may be present in the composition in an amount ranging from 0.3 to 0.6% by weight. In certain cases, dibasic sodium phosphate may be present in the composition in an amount ranging from 0.5 to 0.6% by weight. For example, dibasic sodium phosphate may be present in the composition in an amount of about 0.6% by weight, such as 0.56% by weight (or 0.558% by weight). In certain embodiments, the amount of monobasic sodium phosphate in the aqueous concentrate composition ranges from 0.005 to 2% by weight, such as 0.01 to 1.8% by weight, or 0.01 to 1.6% by weight, or 0.01 to 1.4% by weight, or 0.01 to 1.2% by weight, or 0.01 to 1.0% by weight, or 0.01 to 0.8% by weight, or 0 0.01 to 0.6% by weight, or 0.01 to 0.4% by weight, or 0.01 to 0.2% by weight, or 0.02 to 0.18% by weight, or 0.03 to 0.16% by weight, or 0.04 to 0.16% by weight, or 0.045 to 0.15% by weight, or 0.04 to 0.14% by weight, or 0.05 to 0.14 % by weight, or 0.1 to 0.2% by weight, or 0.1 to 0.15% by weight. For example, monobasic sodium phosphate may be present in the aqueous concentrate composition in an amount ranging from 0.05 to 0.2% by weight. In certain cases, monobasic sodium phosphate may be present in the composition in an amount ranging from 0.01 to 0.2% by weight. In certain cases, monobasic sodium phosphate may be present in the composition in an amount ranging from 0.09 to 0.15% by weight. In certain cases, monobasic sodium phosphate may be present in the composition in an amount ranging from 0.1 to 0.2% by weight. In certain cases, monobasic sodium phosphate may be present in the composition in an amount ranging from 0.1 to 0.15% by weight. For example, monobasic sodium phosphate may be present in the composition in an amount of 0.12% by weight (or 0.129% by weight). Additional components that can be included in the aqueous concentrate composition include a salt. Examples of suitable salts include, but are not limited to, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, and the like, and combinations thereof. In certain cases, the salt is sodium chloride. In some cases, the amount of salt (for example, sodium chloride) in the aqueous concentrate composition ranges from 0.05 to 5% by weight, such as 0.05 to 4% by weight, or 0.05 to 3 % by weight, or 0.05 to 2% by weight, or 0.1 to 5% by weight, or 0.1 to 4% by weight, or 0.1 to 3% by weight, or 0.1 to 2 % by weight, or 0.1 to 1.5% by weight, or 0.1 to 1% by weight, or 0.2 to 1% by weight, or 0.3 to 1% by weight, or 0.4 to 1% by weight , or 0.5 to 1% by weight, or 0.6 to 1% by weight, or 0.7 to 1% by weight, or 0.8 to 1% by weight, or 0.8 to 0.9% in weigh. For example, salt (eg Sodium Chloride) may be present in the composition in an amount ranging from 0.5 to 1% by weight. For example, salt (eg sodium chloride) may be present in the composition in an amount ranging from 0.2 to 2% by weight. In certain cases, the salt (for example, sodium chloride) may be present in the composition in an amount ranging from 0.7 to 1% by weight. In certain cases, the salt (for example, sodium chloride) may be present in the composition in an amount ranging from 0.8 to 0.9% by weight. For example, salt (eg sodium chloride) may be present in the composition in an amount of 0.85% by weight. Other aspects of the present disclosure include methods for making the storage-stable lyophilized compositions described herein. In certain instances, the method is a method of preparing a lyophilized polyalkylene oxide asparaginase composition as described herein. The method may include lyophilization of an aqueous composition including a polyalkylene oxide asparaginase having a polyalkylene oxide group covalently linked by a linker to an asparaginase, a buffer, a salt, and a sugar in a manner sufficient to produce a Storage-stable lyophilized composition of polyalkylene asparaginase oxide. In certain embodiments, lyophilization is used to dehydrate the aqueous concentrate composition. In some cases, lyophilization includes removing water from the aqueous concentrate composition. The water can be removed by sublimating the water into the composition. For example, the water in the composition can undergo a phase transition from solid to gas. In certain instances, lyophilization includes freezing the composition (eg, freezing the water in the composition) and then reducing the pressure surrounding the composition such that the water in the composition sublimates. During freeze-drying, the temperature of the composition can be reduced, for example, to a temperature below the freezing point of the water in the composition. For example, the temperature of the composition can be reduced to 0°C or less, or -5°C or less, or -10°C or less, or -15°C or less, or 20°C or less, or -25°C or less, or -30°C or less, or -35°C or less, or -40°C or less, or -45°C or less, or -50°C or less, or -55 °C or less, or -60°C or less, or -65°C or less, or -75°C or less. In some cases, the temperature of the composition is reduced to -45°C. In some cases, the temperature of the composition is reduced to -30°C. In certain embodiments, the pressure surrounding the composition is reduced to below standard atmospheric pressure. For example, the pressure surrounding the composition can be reduced to 500 T or less, such as 250 T or less, or 100 T or less, or 50 T or less, or 10 T or less, or 1 T or less, or 500 mT or less, or 400 mT or less, or 300 mT or less, or 200 mT or less, or 100 mT or less, or 90 mT or less, or 80 mT or less, or 70 mT or less, or 60 mT or less, or 50 mT or less, or 40 mT or less, or 30 mT or less, or 20 mT or less, or 10 mT or less. In some cases, the pressure surrounding the composition is reduced to 60 mT or less, such as 50 mT. In some embodiments, lyophilization can also include increasing the temperature of the composition while reducing the pressure surrounding the composition. For example, the temperature of the composition can be increased from a minimum temperature as described above to a temperature greater than the minimum temperature. In some cases, the temperature is increased to facilitate sublimation of the water in the composition at the reduced surrounding pressure. Embodiments of the method for preparing the lyophilized polyalkylene asparaginase oxide composition may also include the production of the aqueous concentrate composition, which is subsequently lyophilized. A process flow diagram of a method for producing the aqueous concentrate composition is shown in FIG 1. As shown in FIG 1, the method for producing the aqueous concentrate composition may include one or more of the steps of: preparing an asparaginase solution (eg, L-asparaginase) (10); attaching a polyalkylene oxide (eg, polyethylene glycol) to asparaginase (20); clarify polyalkylene oxide asparaginase (30); filter and concentrate the polyalkylene oxide asparaginase solution (40); dilute polyalkylene oxide-asparaginase solution (50); filtering the polyalkylene oxide asparaginase solution and filling the polyalkylene oxide asparaginase solution into a sterile container (60); and storing the polyalkylene oxide asparaginase solution (70). In the method for producing the aqueous concentrate composition, an asparaginase solution (for example, L-asparaginase) can be prepared. The asparaginase can be mixed with a solution, such as an aqueous solution (eg, a buffered aqueous solution). Examples of suitable buffers include, but are not limited to, a phosphate buffer, phosphate buffered saline (PBS), Dulbecco's phosphate buffered saline (DPBS), Hank's balanced salt solution (HBSS), balanced salt solution Earle's buffer (EBSS), Tris buffer, Lactated Ringer's buffer, borate buffer, and the like, and combinations thereof. In some cases, the asparaginase is mixed with a phosphate buffer. In some embodiments, the phosphate buffer can include dibasic sodium phosphate and monobasic sodium phosphate. In some cases, the amount of dibasic sodium phosphate in the aqueous concentrate composition ranges from 0.05 to 1% by weight, such as 0.1 to 0.9% by weight, or 0.1 to 0.8% in weight, or 0.1 to 0.7% by weight, or 0.1 to 0.6% by weight, or 0.1 to 0.5% by weight, or 0.1 to 0.4% by weight, or 0.2 to 0.4% by weight, or 0.2 to 0.3% by weight, or 0.25 to 0.3% by weight. For example, dibasic sodium phosphate may be present in the aqueous concentrate composition in an amount ranging from 0.1 to 0.5% by weight. In certain embodiments, the amount of monobasic sodium phosphate in the aqueous concentrate composition ranges from 0.005 to 1% by weight, such as 0.01 to 0.9% by weight, or 0.01 to 0.8% by weight, or 0.01 to 0.7% by weight, or 0.01 to 0.6% by weight, or 0.01 to 0.5% by weight, or 0.01 to 0.4% by weight, or 0 0.01 to 0.3% by weight, or 0.01 to 0.2% by weight, or 0.01 to 0.1% by weight, or 0.02 to 0.09% by weight, or 0.03 to 0.08% by weight, or 0.04 to 0.08% by weight, or 0.045 to 0.075% by weight, or 0.04 to 0.07% by weight, or 0.05 to 0.07% by weight weight. For example, monobasic sodium phosphate may be present in the aqueous concentrate composition in an amount ranging from 0.01 to 0.1% by weight. MA / a / ZUZI 0344 Additional components that can be included in the aqueous concentrate composition include a salt. Examples of suitable salts include, but are not limited to, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, and the like, and combinations thereof. In certain cases, the salt is sodium chloride. In some cases, the amount of salt (for example, sodium chloride) in the aqueous concentrate composition ranges from 0.05 to 1% by weight, such as 0.1 to 0.9% by weight, or 0.1 to 0.8% by weight, or 0.1 to 0.7% by weight, or 0.1 to 0.6% by weight, or 0.1 to 0.5% by weight, or 0.2 to 0 0.5% by weight, or 0.3 to 0.5% by weight, or 0.4 to 0.5% by weight, or 0.4 to 0.45% by weight. For example, salt (eg sodium chloride) may be present in the aqueous concentrate composition in an amount ranging from 0.1 to 1% by weight. Another component that can be included in the aqueous concentrate composition is a sugar. Examples of suitable sugars include, but are not limited to, sucrose, mannitol, maltose, trehalose, 2-hydroxypropyl-beta-cyclodextrin (β-HPCD), lactose, glucose, fructose, galactose, glucosamine, and the like, and combinations thereof. In certain cases, sugar is a disaccharide. For example, the disaccharide can be sucrose. In some cases, the amount of sugar (for example, Sucrose) in the aqueous concentrate composition ranges from 0.1 to 25% by weight, such as 0.5 to 20% by weight, or 1 to 15% by weight, or 1 to 10% by weight, or 1 to 9% by weight, or 1 to 8% by weight, or 2 to 7% by weight, or 2 to 6% by weight, or 3 to 5% by weight, or 4 to 5% by weight. For example, sugar (eg sucrose) may be present in the aqueous concentrate composition in an amount ranging from 1 to 10% by weight. After preparation of the asparaginase solution, the asparaginase can be attached to a polyalkylene oxide (eg, polyethylene glycol), whereby the polyalkylene oxide is covalently attached to the asparaginase to produce a polyalkylene oxide-asparaginase conjugate. . After preparation of the polyalkylene oxide asparaginase, the solution can be clarified. In some cases, clarification includes filtering the solution through a filter to remove particles from the solution. The filtering step can produce a substantially purified polyalkylene oxide asparaginase. In some cases, the filtered polyalkylene oxide asparaginase solution is then subjected to a diafiltration and concentration step. The polyalkylene oxide asparaginase solution can be diafiltered using an ultrafiltration membrane and a resulting polyalkylene oxide asparaginase concentrate can be obtained. The concentrate from the diafiltration step can be diluted such that the solution contains a desired concentration of polyalkylene oxide asparaginase. Suitable buffers useful for the dilution step include those described above. In some cases, a phosphate buffer is used to dilute the polyalkylene oxide asparaginase solution, thus producing the desired aqueous concentrate composition. For example, the concentrate from the diafiltration step can be diluted so that the resulting aqueous concentrate composition includes an amount of polyalkylene oxide asparaginase having a potency (activity) ranging from 100 to 5,000 IU / mL, such such as 500 to 4,500 IU / mL, or 500 to 4,000 IU / mL, or 500 to 3,500 IU / mL, or 500 to 3,000 IU / mL, or 1,000 to 3,000 IU / mL, or 1,500 to 3,000 IU / mL. In certain cases, the aqueous concentrate composition includes the polyalkylene oxide asparaginase in an amount ranging from 1,500 to 3,000 IU / mL. In some cases, the amount of polyalkylene oxide asparaginase in the aqueous concentrate composition is greater than the amount of polyalkylene oxide asparaginase in the reconstituted lyophilized composition described herein. In some cases, diafiltration produces a substantially purified polyalkylene oxide asparaginase. the aqueous concentrate composition can then be filtered and filled into a sterile container. Examples of suitable container materials for the container include polymers, such as, but not limited to, polypropylene, polymethylpentene, polytetrafluoroethylene (PTFE), perfluoroethers (PFE), fluorinated ethylene propylene (FEP), perfluoroalkoxy alloys (PFA), polyethylene terephthalate (PET ), polyethylene (PE), polyetheretherketone (PEEK), polystyrene, and the like. For example, the container can be a sterile polymer bag. The aqueous concentrate composition can be stored in the container for a period of time, and can be processed into the storage-stable lyophilized composition of the present disclosure. Embodiments of the method may further include shipping the aqueous concentrate composition to a remote location. A remote location is a location other than the location where the aqueous concentrate composition is produced. For example, a remote location could be another location (eg, office, lab, etc.) in the same city, another location in a different city, another location in a different state, another location in a different country, etc. As such, when one item is indicated as being remote from another, what is meant is that the two items may be in the same room but separate, or at least in different rooms or different buildings, and may be at least a mile away. , ten miles, or a hundred miles, or more away. In certain embodiments, as described above, the method includes lyophilizing the composition from aqueous concentrate in a manner sufficient to produce a storage-stable lyophilized composition of polyalkylene oxide asparaginase. In some cases, freeze drying can be performed in a unit dosage container. Lyophilization of the aqueous concentrate composition to produce the lyophilized polyalkylene oxide asparaginase composition in the unit dosage container can facilitate production of the lyophilized composition in the unit dosage container, for example, by eliminating the need to lyophilize the composition from the aqueous concentrate into a separate container and then transferring the lyophilized composition from the separate container to the unit dosage container. As such, in some embodiments, the method includes introducing the aqueous concentrate composition into a unit dosage container and lyophilizing the aqueous concentrate composition in the unit dosage container. As described above, the unit dosage container can be a vial, such as a glass vial. MA / a / ZUZI 0344 After lyophilization, the method may further include sealing the lyophilized composition in the unit dosage container. For example, a seal or cap may be applied to the opening of the unit dosage container, thus sealing the unit dosage container. Sealed containers can be stored for an extended period of time, such as 1 week or more, or 2 weeks or more, or 3 weeks or more, or 1 month or more, or 2 months or more, or 3 months or more, or 4 months or more, or 6 months or more, or 9 months or more, or 1 year or more, or 1.5 years (for example, 18 months) or more, or 2 years or more, or 2.5 years ( (for example, 30 months) or more, or 3 years or more, or 3.5 years (for example, 42 months) or more, or 4 years or more, or 4.5 years (for example, 54 months) or more , or 5 years or more. For example, an extended time period may be 6 months or more. In some cases, sealed containers can be stored for 9 months or more. In some cases, sealed containers can be stored for 1 year (for example, 12 months) or longer. In some cases, sealed containers can be stored for 1.5 years (for example, 18 months) or more. In some cases, sealed containers can be stored for 2 years (for example, 24 months) or longer. KITS Kits for use in practicing the subject methods are also provided, where the kits may include one or more of the above liquid and / or lyophilized compositions. For example, the kit can include a unit dosage container containing a liquid composition as described herein. Or, for example, the kit can include a unit dosage container containing a lyophilized composition as described herein. In some cases, the kit includes two or more unit dosage containers, each containing a liquid composition as described herein. In some cases, the kit includes two or more unit dosage containers, each containing a lyophilized composition as described herein. In some cases, the kit includes two or more unit dosage containers, where one or more of the unit dosage containers contains a liquid composition as described herein and one or more of the unit dosage containers contains a lyophilized composition. as described in this document. In certain embodiments, the kit includes packaging configured to contain the unit dosage container(s). The packaging may be a sealed package, such as a sterile sealed package. A sterile container can be configured to be sealed from the outside environment so that there are substantially no microbes (such as fungi, bacteria, viruses, spore forms, etc.) within the package. In some cases, the package is sealed, such as a steam resistant package, optionally under a hermetic and / or vacuum seal. In certain embodiments, the kit includes a buffer. For example, the kit may include a dilution fluid, eg, a dilution buffer, which may be suitable for administration to a subject, and the like. The kit may further include other components, eg, delivery devices, fluid sources, etc., that may be useful in practicing the subject methods. The various components in the kits can be packaged as desired, eg together or separately. The subject kit components may be present in separate containers, or multiple components may be present in a single container, where the kit containers and / or packaging (or a portion thereof) may be sterile, as desired. In addition to the components mentioned above, the subject kits may further include instructions for using the kit components to practice the subject methods. Instructions for practicing the methods in question are usually recorded on a suitable recording medium. For example, the instructions can be printed, such as on paper or plastic, etc. As such, instructions may be present in kits as a package insert, on the labeling of the kit container or its components (i.e., associated with the package or subpackage), etc. In other embodiments, the instructions are present as an electronic storage data file present on a suitable computer-readable storage medium, eg, portable flash drive, CD-ROM, DVD-ROM, Blu-ray, etc. In still other embodiments, the instructions are not present in the kit, but instructions are provided to obtain the instructions from a remote source, eg, over the Internet. An example of this embodiment is a kit that includes a web address where the instructions can be viewed and / or from where the instructions can be downloaded. As with the instructions, this embodiment to obtain the instructions is recorded on a suitable substrate. UTILITY The subject compositions (eg, storage-stable liquid or lyophilized compositions) and methods find use in applications where there is a desire to treat a disease or condition amenable to treatment by administration of a polyalkylene oxide asparaginase in a subject. For example, the subject compositions (eg, storage-stable liquid or lyophilized compositions) and methods find use in the treatment of a neoplastic condition in a subject. In some instances, the subject compositions (eg, storage-stable liquid or lyophilized compositions) and methods find use in the treatment of a cancer in the subject. Examples of cancer types amenable to treatment using the subject compositions (eg, storage-stable liquid or lyophilized compositions) and methods include, but are not limited to, leukemia, such as acute lymphoblastic leukemia (ALL), myeloid leukemia acute (AML), and the like. Accordingly, the subject lyophilized storage-stable compositions and methods find use in providing therapeutically effective treatment for neoplastic conditions, such as cancer, including, but not limited to, leukemia, such as acute lymphoblastic leukemia (ALL). , acute myeloid leukemia (AML), and the like. The lyophilized storage-stable compositions and methods of the present disclosure find use in the treatment of subjects of any age. In some cases, the subject compositions (eg, storage-stable liquid or lyophilized compositions) and methods find use in the treatment of an adult. For example, an adult human subject may be 18 years of age or older. In other instances, the compositions (eg, storage-stable liquid or lyophilized compositions) and methods find use in the treatment of a minor. For example, a human minor subject may be less than 18 years of age. The compositions and methods of the present disclosure find use in applications where a storage stable composition is desired. For example, the compositions and methods of the present disclosure find use in providing a storage-stable composition that is stable (eg, does not degrade significantly and / or retains substantially all of its activity) for an extended period of time. . For example, the compositions and methods of the present disclosure find use in providing a storage-stable composition that is stable for an extended period of time, such as 1 week or more, or 2 weeks or more, or 3 weeks or more, or 1 month or more, or 2 months or more, or 3 months or more, or 4 months or more, or 6 months or more, or 9 months or more, or 1 year or more, or 1.5 years (for example, 18 months) or more, or 2 years or more, or 2.5 years (for example, 30 months) or more, or 3 years or more, or 3.5 years (for example, 42 months) or more, or 4 years or more, or 4.5 years (for example, 54 months) or more, or 5 years or more. In some cases, the compositions and methods of the present disclosure find use in providing a storage-stable composition that is stable for 9 months or longer. In some cases, the compositions and methods of the present disclosure find use in providing a storage-stable composition that is stable for 1 year (eg, 12 months) or longer. In some cases, the compositions and methods of the present disclosure find use in providing a storage-stable composition that is stable for 1.5 years (eg, 18 months) or longer. In some cases, the compositions and methods of the present disclosure find use in providing a storage-stable composition that is stable for 2 years (eg, 24 months) or longer. In certain embodiments, the compositions and methods of the present disclosure find use in providing a storage-stable composition that increases the shelf life of the composition up to 1 week, 2 weeks, 3 weeks, 1 month, 2 months, or 3 months, or 4 months, or 6 months, or 9 months, or 1 year, or 1.5 years (for example, 18 months), or 2 years, or 2.5 years (for example, 30 months), or 3 years, or 3.5 years (for example, 42 months), or 4 years or more, or 4.5 years (for example, 54 months), or 5 years. In certain embodiments, the compositions and methods of the present disclosure find use in providing a storage stable composition that increases the shelf life of the composition from 1 month to 5 years, or from 6 months to 4 years, or from 9 months to 3 years. years, or 1 year to 2 years. In certain embodiments, the doses of the present disclosure may be administered before, in conjunction with, or after one or more other neoplastic condition therapies to treat related or unrelated conditions. If given at the same time as other therapies for neoplastic conditions, the doses of the present disclosure may be given in the same formulation or in a different formulation. For example, concurrent therapy can be achieved by administering a dose and a pharmaceutical composition having at least one other active agent, such as a chemotherapeutic agent, which in combination provides a therapeutically effective dose, in accordance with a particular treatment regimen. Administration of separate pharmaceutical compositions or treatments can be performed ΜΛ / a / ZUZl / Ul 0344 simultaneously or at different times (for example, sequentially, in any order, on the same day or on different days), provided that a therapeutically effective effect of the combination of these substances occurs in the subject undergoing therapy. Accordingly, the methods and compositions of the present disclosure find use in the treatment of a subject using combination therapy that includes administration of a polyalkylene oxide asparaginase of the present disclosure in combination with one or more additional active agents and / or therapies (eg radiation, chemotherapy, immunotherapy, etc.). As can be appreciated from the disclosure provided above, embodiments of the present disclosure have a wide variety of applications. Accordingly, the examples presented herein are offered for illustrative purposes and are not intended to be construed as limiting the embodiments of the present disclosure in any way. Those skilled in the art will readily recognize a variety of non-critical parameters that could be changed or modified to produce essentially similar results. Therefore, the following examples are presented to provide those skilled in the art with a complete description and description of how to make and use the embodiments of the present disclosure, and are not intended to limit the scope of what the inventors consider to be their invention nor are they intended to represent that the experiments below are all or the only experiments performed. Efforts have been made to ensure accuracy with respect to the numbers used (eg amounts, temperature, etc.) but some experimental errors and deviations should be accounted for. Unless otherwise indicated, parts are parts by weight, molecular weight is weight average molecular weight, temperature is in degrees Celsius, and pressure is at or near atmospheric. The following examples are offered for illustrative purposes only, and are not intended to limit the scope of embodiments of this disclosure in any way. Efforts have been made to ensure accuracy with respect to the numbers used (eg, amounts, temperatures, etc.), but some experimental error and deviation should of course be allowed for. EXAMPLES Example 1 According to the following protocol, a bulk concentrate composition was produced that included a polyethylene glycol asparaginase having an SS-PEG linker. Following production of the bulk concentrate composition, a lyophilized composition was produced from the bulk concentrate composition according to the protocol described below. FIG 1 shows a process flow chart for a method of preparing a storage-stable lyophilized composition according to embodiments of the present disclosure. Preparation of the L-asparaginase solution The amount of L-asparaginase required for processing was calculated and weighed into a 6 L stainless steel beaker, and mixed for 5 to 10 minutes. The (EEA) was calculated and weighed, measured after 15 minutes and 30 minutes to ensure that the product was retained by the diafiltration membrane. Free PEG and N-hydroxysuccinimide (NHS) were components of the process-related impurity profile measured in the final product. The formal controls in process for the operation of the diafiltration unit are presented in Table 1 below. The NHS and free PEG data generated from three drug substance compositions (eg, concentrated bulk drug substance compositions) destined for lyophilization are shown in Table 2 below. The data generated demonstrated that small changes in the diafiltration / concentration process did not affect the quality of the product. IVIA / a / ¿U¿ I 0344 Table 1: Specifications for Bulk Drug Substance Compositions Intended for Lyophilization Test Acceptance Criteria for Drug Substance Compositions for Lyophilization N-Hydroxysuccinimide (NHS) <6.0 ppm Modified by 2,4,6-Trinitrobenzenesulfonic Acid (TNBS) 69 -82 mol PEG / mol protein Endotoxin <35 EU / mL Bioburden <2 CFU / 20 mL Sterility (developed after sterile filtration) Complies Table 2: Analysis of Concentrated Bulk Drug Substance Composition Lots Test Acceptance Criteria Lot 1 Lot 2 Lot 3 Protein concentration 19.0 to 21.0 mg / mL 20.94 19.65' 18.37 Potency ( activity) > 1850 IU / mL 2305 2360' 2091 Appearance Colorless solution Passes Passes Passes Clarity Clear, no visible particles Passes Passes Passes PH 7.2 to 7.4 7.2 7.2 7.2 Specific activity > 85 lU / mG of protein 110 110 110 Purity by GF-HPLC > 95% active components; < 8% Aggregates 98.30, 5.07 98.26. 5.23 97.80, 0.70 Total free PEG by RP-HPLC < 6.0 mg / mL < 0.07 < 0.07 0.74 Free 10K PEG by RP-HPLC < 6.0 mg / mL < 0, 07 < 0.07 < 0.07 N-Hydroxysuccinimide (NHS) < 6.0 ppm Not tested 1.87 0.65 Modification by 2,4,6-trinitrobenzenesulfonic acid (TNBS) 69-82 mol PEG / mol protein Not tested 76 73 Endotoxin < 35 EU / mL < 5 < 5 < 5 Bioburden < 2 CFU / 20 mL 0 0 0 Sterility (performed after sterile filtration) Meets USP Not tested Not tested Not tested values ​​taken from post-diafiltration / sample tests pre-dilution Dilution In-process material was mixed in the 7-gallon stainless steel pressure container prior to extracting samples for activity and protein testing. The volume of in-process material was then diluted with PBS to bring the protein concentration to a target value of >18.0 mg / mL (20.0 mg / mL target), (>1850 IU / mL activity) for the drug substance intended for the lyophilized composition. The in-process diluted material was mixed before samples were withdrawn for quality assurance testing (see Table 1). sterile filtration The concentrated solution for lyophilization was filtered at 0.2 pm into a 20 L disposable sterile bag for storage until lyophilization was performed. A sample was collected and tested for sterility. Bulk drug substance composition including polletllengcol-asparaginase for lyophilization can be kept in the 20 L bag at 2-8°C for up to 2 months prior to lyophilization. Container Closure The bulk drug substance composition including polyethylene glycol asparaginase for lyophilization was processed into a lyophilized composition after the 0.2 pm filtration step and dispensed into a pre-sterilized 20 L bioprocess disposable bag. The bag construction material includes layers of low density polyethylene (LDPE), linear low density polyethylene (LLDPE), nylon, and ethylene vinyl alcohol (EVOH). The direct contact surface of the product (inner layer) was LDPE. Each bag had two openings with attached tubing which were attached to the bag and clamped closed until ready to receive the drug substance composition including polyethylene glycol asparaginase for lyophilization. The bags were irradiated and released based on 25-40 kGy exposure, and subjected to a Lysate Amebocyte Limulus (LAL) endotoxin test, 100% visual seal and air leak test, as well as a visual inspection of 100% after assembly. Qualification test results showed that the inner layer of the pouch passed tests for biological reactivity, including USP <88> Class IV Plastics tests, USP <87> Cytotoxicity tests, and USP <661> tests of the physicochemical attributes. In addition, the bags met USP <788> for injection particulate matter and all extractable tests met the manufacturer's requirements. Stability of the pharmaceutical substance in Withdrawal Times Bulk concentrated drug substance material was monitored at 0, 2, 4, 6, 8, and 12 weeks at 2-8°C. Stability samples were maintained in 250 mL sample bags with a polyethylene product contact surface. The test plan data is presented in Table 3 for Lot 1, Table 4 for Lot 2, and Table 5 for Lot 3. The stability data for the concentrated drug substance intended for the lyophilized compositions met the acceptance criteria throughout the 12-week test plan and indicated that a 2-month lead time between production of the concentrated drug substance was acceptable. in bulk and the production of the lyophilized composition. IVIA / a / ¿U¿ I 0344 Table 3: Stability Data for Lot 1 Stored at 2-8°C Test Acceptance Criteria Time (Weeks) Initial 2 4 6 8 12 Protein Concentration > 18.0 mg / mL 20.94 21.31 21.31 21 .18 21.15 21.34 Potency (activity) > 1850 IU / mL 2305 2413 2448 2432 2498 2538 Appearance Colorless solution Pass Pass Pass Pass Pass Pass Clarity Clear, no visible particles Pass Pass Pass Pass Pass Pass PH 7.2 to 7.4 7.2 7.2 7.2 7.2 7.2 7.3 Specific activity > 85 LII / mG of protein 110 113 115 115 118 119 Purity by GF-HPLC >95% active components; < 8% Aggregates 98.30, 5.07 97.83, 4.48 98.99, 4.38 99.24, 4.39 98.14, 4.43 97.34, 3.36 Total free PEG per PR- HPLC < 6.0 mg / mL < 0.07 < 0.07 < 0.07 0.24 0.24 0.33 Free PEG 10K by RP-HPLC < 6.0 mg / mL 0.07 3.03 2.41 3.07 3 .11 4.19 N-Hydroxysuccinimide (NHS) < 6.0 ppm Not tested 2.23 2.31 2.31 2.32 2.34 TNBS modification 69-82 mol PEG / mol protein Not tested 76 75 76 74 73 ΜΛ / α / ΖυΖΊ / U I 0044 Table 4: Stability data for batch 2 stored at 2-8°C Test Acceptance criteria Time (weeks) Initial 2 4 6 8 12 Protein concentration >18.0 mg / mL 19.65' 20.28 20.11 19.82 20.25 20.09 Potency (activity) > 1850 lU / mL 2279 2248 2263 2344 2360 2426 Appearance Colorless solution Pass Pass Pass Pass Pass Pass Clarity Clear, no visible particles Pass Pass Pass Pass Pass Pass pH 7.2 a 7.4 7.2 7.2 7.2 7.3 7.2 7.2 Specific activity > 85 lU / mG protein 116 111 113 118 117 128 Purity by GF-HPLC > 95% active components; < 8% Aggregates 98.26. 5.23 98.17, 5.19 98.16, 4.71 98.27, 4.79 98.16, 4.71 98.24, 4.30 Total free PEG by RPHPLC < 6.0 mg / mL <0.07 0.27 0.33 0.37 0.44 0.47 Free PEG 10K by RPHPLC < 6.0 mg / mL <0.07 1.25 2.05 2.75 4.15 4.5 N-Hydroxysuccinimide ( NHS) <6.0 ppm 1.87 2.55 2.76 2.79 2.82 2.83 Modification by TNBS 69-82 mol PEG / mol protein 76 74 78 75 75 76 •values ​​taken from post sample testing -diafiltration / pre-dilution Table 5: Stability Data for Lot 3 Stored at 2-8°C Test Acceptance Criteria Time (weeks) Initial 2 4 6 8 12 Protein Concentration > 18.0 mg / mL 18.39 17.79 18.22 18 .20 18.56 18.49 Potency (activity) > 1850 lU / mL 2091 2212 2256 2202 2199 2290 Appearance Colorless solution Pass Pass Pass Pass Pass Pass Clarity Clear, no visible particles Pass Pass Pass Pass Pass Pass PH 7.2 to 7 ,4 7.2 7.3 7.2 7.3 7.3 7.3 Specific activity > 85 lU / mG of protein 114 124 124 121 118 124 Purity by GF-HPLC > 95% active components; < 8% Aggregates 97.80. 0.7 98.00, 0.65 97.61. 0 97.76. 0 97.24. 0.55 97.94, 0 Total free PEG by RP-HPLC < 6.0 mg / mL < 0.07 < 0.07 < 0.07 < 0.07 0.07 < 0.07 10K free PEG by RP -HPLC < 6.0 mg / mL < 0.07 2.23 2.00 3.00 3.98 5.00 N-Hydroxysuccinimide (NHS) < 6.0 mg / mL 0.65 0.70 0.70 0.70 0.68 0.64 Modification by TNBS 69-82 mol PEG / mol protein 73 Not tested 70 70 74 76 The lyophilized powder composition for injection was produced in a single-use vial containing 3,750 IU of active PEGylated L-asparaginase (750 IU / mL after reconstitution with 5.2 mL of WFI). The components of the lyophilized composition included 4.5% sucrose, dibasic sodium phosphate, monobasic sodium phosphate, and sodium chloride after reconstitution. The composition of the lyophilized composition is given in Table 6. In addition, the lyophilized composition was provided in a treated glass vial container (Nipro Type 1) having a 20 mm aluminum crimp seal. MA / a / ZUZI / Ul 0344 Table 6: Components of the composition Polyethylene glycol-Asparaginase Component Grade Amount per g* Polyethylene Glycol Asparaginase n / a 750 IU Sodium Phosphate Dibasic USP 2.79 mg Sodium Phosphate Monobasic USP 0.60 mg Sodium Chloride USP 4.25 mg Sucrose National Formulary (NF) 45 mg Water for Injections ( WFI) USP QS at 1.0g * value post reconstitution with WFI Development of the Lyophilized Formulation of polyethylene glycol-asparaginase The goal of developing a lyophilized formulation of polyethylene glycol asparaginase was to achieve a stable lyophilized composition that would be suitable for storage at 2-8°C or 25°C for at least 18 months. Initial experiments were performed to evaluate the feasibility of a lyophilized polyethylene glycol asparaginase composition. Five variations of lyophilized compositions were investigated. Each formulation contained ~5 mg / mL polyethylene glycol asparaginase in 50 mM phosphate buffer, pH 6.5, and 5% w / v of one of five different cryoprotectants (mannitol, maltose, sucrose, trehalose, and / or β-HPCD). ). In addition, polyethylene glycol asparaginase without cryoprotectant was also subjected to lyophilization. These six lyophilized compositions were compared to a large amount of polyethylene glycol asparaginase liquid formulation (Oncaspar®) that was used for the preparation of these different formulations. The SEC-Purity (GF-HPLC) method was used to assess the quality of the polyethylene glycol paraginase compositions. The results of the study are presented in Table 7. As seen in Table 7, sucrose was found to be the most effective in preserving the purity of polyethylene glycol asparaginase during lyophilization. The purity (83.0%) of the 5% sucrose freeze-dried composition was comparable to the purity (83.8%) of the liquid polyethylene glycol asparaginase formulation that was used for the preparation of the six formulations for subsequent freeze-drying. . Table 7: Feasibility Study Results for Lyophilizing Polyethylene Glycol-Asparaginase Composition 1 % Purity (SEC-HPLC; RT-minutes) 10.0 10.2 10.5 11.2 2 12.0 Oncaspar (Control, liquid composition) - 3.0 83.8 13.2 5% mannitol 0.9 1.4 74.7 23.1 5% maltose - 0.9 2.3 78.8 17.9 5% sucrose - - 3.1 83, 0 14.0 5% trehalose - - 3.2 79.5 17.3 5% r.-HPCD - 2.9 78.9 18.3 Lyophilized, without preservative 0.4 0.8 9.4 65.7 23.7 All formulations also contain -5 mL Oncaspar in 5mM phosphate buffer, pH 6.5 2 Expected retention time of Oncaspar Several different excipients (eg, Sucrose, trehalose, mannitol, polysorbate 80) were evaluated as possible stabilizing agents to include in the lyophilized composition. Four experiments were carried out, each one including four different compositions. Small scale lyophilized batches of polyethylene glycol asparaginase were prepared with the different excipients and their stability was evaluated. A list of formulations that were tested is shown in Table 8. Table 8: Polyethylene Glycol-Asparginase Compositions Tested Lot Composition 1A 5% Sucrose, 12.5 mg / mL PEG-asparginase, Phosphate Buffer IB 2.5% Sucrose, 2.5% Mannitol, 12.5 mg / mL PEG-asparginase , Phosphate Buffer 1C 2.5% Sucrose, 2.5% Mannitol, 0.01% Polysorbate-80, 12.5 mg / mL PEG-asparginase, ID Phosphate Buffer 5% Sucrose, 0.01% Polysorbate-80, 12 .5 mg / mL PEG-asparginase, Phosphate Buffer 2A 5% Trehalose, 12.5 mg / mL PEG-asparginase, Phosphate Buffer 2B 2.5% Trehalose, 2.5% Mannitol, 12.5 mg / mL PEG-asparginase , Phosphate Buffer 2C 2.5% Trehalose, 2.5% Mannitol, 0.01% Polysorbate-80, 12.5 mg / mL PEG-asparginase, Phosphate Buffer 2D 5% Trehalose, 0.01% Polysorbate-80, 12 0.5 mg / mL PEG-asparginase, 3A Phosphate Buffer 5% Sucrose. 6.5 mg / mL PEG-asparginase, Phosphate Buffer 3B 2.5% Sucrose, 2.5% Mannitol, 6.5 mg / mL L-asparginase, Phosphate Buffer 3C 2.5% Sucrose, 2.5% Mannitol, 0.01% Polysorbate 80, 6.5 mg / mL L-asparginase, Phosphate Buffer 3D 5% Sucrose, 0.01% Polysorbate-80, 6.5 mg / mL L-asparginase, Phosphate Buffer 4A 5% Trehalose, 6 0.5 mg / mL L-asparginase, Phosphate Buffer 4B 2.5% Trehalose, 2.5% Mannitol, 6.5 mg / mL L-asparginase, Phosphate Buffer 4C 2.5% Trehalose, 2.5% Mannitol, 0 0.01% Polysorbate-80, 6.5 mg / mL L-asparginase, Phosphate Buffer 4D 5% Trehalose, 0.01% Polysorbate-80, 6.5 mg / mL L-asparginase, Phosphate Buffer All batches described in Table 8 were evaluated in stability tests at 5°C, 25°C and 40°C, and evaluated with a panel of tests (Activity, Specific Activity, Protein, pH, Purity (GFUPLC), Aggregates (GF-HPLC) and Particles), which evaluated the primary quality attributes of polyethylene glycol-asparaginase at time of release and stability. Based on these analyzes of the stability data collected from the 16 different formulations described in Table 8, sucrose was identified as a suitable cryoprotectant (eg, stabilizing agent). Various concentrations of sucrose were tested to assess the appropriate concentration for a more robust (ie, less shocking lyophilization protocol) and more stable product. Additional pilot scale batches containing different concentrations of sucrose were prepared as summarized in Table 9. The concentrations of sucrose and PEG-asparaginase shown in Table 9 show the amounts present in the bulk concentrated drug substance. During the freeze-drying process, the vials were filled to 2.5 mL before starting freeze-drying. These lyophilized vials were reconstituted with 5.0 mL, resulting in final sucrose and PEG-asparaginase concentrations that were approximately half of those shown in the table. This study demonstrated that the increase in sugar content allowed for higher freeze-drying temperatures, which were less stressful to the freeze-dried product, and also reduced overall freeze-drying cycle time and resulted in a drier (more stable) freeze-dried product. ). Table 9: Sucrose Compositions Tested Lot Phosphate buffer (M) NaCI (%) Sucrose (mg / mL)1 PEG-Asparginase (mg / mL)1 5A 0.1 0.85 10 (1%) 12.5 5B 0.1 0.85 25 ( 2.5%) 12.5 5C 0.1 0.85 50 (5%) 12.5 5D 0.1 0.85 75 (7.5%) 12.5 5E 0.1 0.85 100 (10 %) 12.5 1 Concentration during lyophilization in 2.5 mL / vial. The concentration decreases by half after reconstitution of the final product with 5mL / vial of WFI MA / a / ZUZI / U1 0344 The five lots described in Table 9 were also evaluated in stability tests at 5°C, 25°C and 40°C. Quality attributes such as Activity, Specific Activity, Protein, pH, Purity (GF-HPLC), Aggregates (GF-HPLC), and Particles were evaluated during this stability study. The Purity and Potency results from the accelerated (25°C) and stressed (40°C) stability studies for these lots are shown in FIGS 2-5. These stability data indicated that the formulation containing 10% sucrose (5% sucrose after reconstitution of the final product with 5 mLWFI) provided a product with the best stability in terms of purity and potency. Other quality attributes were less affected by different formulations, and were also stable in the 10% sucrose batch. FIG 2 shows a graph of purity (%) versus time (weeks) at 40°C for lyophilized PEG-asparaginase compositions from Lots 5A, 5B, 5C, 5D, 5E, and 1A. FIG 3 shows a plot of potency (IU / mL) versus time (weeks) at 40°C for lyophilized PEG-asparaginase compositions from lots 5C, 5D, 5E and 1A. FIG 4 shows a plot of purity (%) as a function of time (weeks) at 25°C for lyophilized PEGasparaginase compositions of Lots 5A, 5B, 5C, 5D, 5E and 1A. FIG 5 shows a plot of potency (IU / mL) versus time (weeks) at 25°C for lyophilized PEG-asparaginase compositions from Lots 5C, 5D, 5E and 1A. lyophilization A buffer was prepared including water for injection (WFI), dibasic sodium phosphate, monobasic sodium phosphate, sodium chloride, and sucrose. The buffer was used for dilution of the bulk concentrated drug substance. WFI was added to a beaker at 90% of the required target weight to produce the buffer solution. Sodium phosphate monobasic, sodium phosphate dibasic, and sodium chloride were individually weighed and added to the WFI and mixed until dissolved. The required amount of sucrose was weighed out and added to the mixing buffer solution and mixed until dissolved. The pH of the solution was then measured and adjusted to 7.3 ± 0.1 with a slow addition of NaOH. WFI was added to the buffer solution as necessary, and the density of the bulk stock solution was used to weigh out the required volume of bulk stock solution needed for the batch size. A sample of the buffer was collected for a sucrose assay. The bulk concentrated solution was added to the buffer solution and the final solution was mixed for not less than (NLT) 10 minutes. Upon completion of mixing, confirmatory pH measurements (7.3 ± 0.1) were obtained from the top, middle, and bottom of the container, and samples were collected for protein, density, sucrose, and bioburden tests. prefiltration in the process. After final formulation, the solution was subjected to sterile filtration. The pre-sterilized filtration tube assembly was placed in the formulated bulk container and then the volume was filtered through two 0.22 µm filters located in the filtration tube assembly into a pre-sterilized 10 L bioprocess bag. sterilized in preparation for filling. Once all of the product was transferred to the 10 L bioprocess bag, the filtration tube set was disconnected from the bioprocess bag and the filters were tested for integrity. A 20 mL pre-lyophilization sample was collected upstream of the filter (unfiltered) and analyzed according to the specifications of the finished drug product. A flowchart illustrating the final formulation and sterile filtration process step is shown in FIG 6. Aseptic Filling and Freeze Drying After the sterile filtration was complete, the 10 L bag containing the bulk API solution was connected to the fill tube assembly and the product vials were then filled to a target fill weight of 2.5 g / vial and partially plugged with Flexicon FMB210 filler. Fill weights were monitored by performing a minimum of one weight check (1 vial) for each filled tray (action limit: 2.43-2.57 g, alert limit: 2.38-2.62 g) for the filling operation. When the filling operation was complete, 20 pre-lyophilized vials were tested and all remaining filled vials were transferred to stainless steel freeze-drying trays and subsequently loaded into a pre-chilled (5°C) 270 ft2 shell freeze-drying system. ) for lyophilization. The lyophilization process included the phases shown in Table 10. Table 10: Lyophilization Cycle - Process Parameters Heat treatment phase Step Temp. (°C) Ramp time (minutes) Immersion time (minutes) 1 5 0 30 2 -45 100 120 Condensation Phase by Freezing and Evacuation Condensation S.P. -45 °C Evacuation S.P. 60 mT Primary Drying Phase Step Temp. (°C) Ramp time (minutes) Immersion time (minutes) Vac. Cont. S.P. (mT) 1 -45 0 30 50 2 -28 60 3860 50 Secondary Drying Phase Step Temp. (°C) Ramp time (minutes) Immersion time (minutes) Vac. Cont. S.P. (mT) 1 35 630 1920 50 After the lyophilization cycle was complete, the evacuated chamber was filled with nitrogen gas and the vials were tightly capped. A flowchart illustrating the aseptic filling and lyophilization process step is shown in FIG 7. The fully capped vials were packed into boxes (90 vials / box) and then stored and / or shipped. Specifications of the Lyophilized Composition Product specifications for the lyophilized composition are shown in Table 11. Table 11: Specifications for the Lyophilized Composition Test Acceptance Criteria Method Composition Lyophilized1 Appearance ACM-1504 Cake white to almost white (prereconstitution); Colorless solution after reconstitution Clarity Clear, no visible particles after reconstitution Fill Volume To deliver 5.0 mL (USP) pH 7.2-7.4 Potency (activity) RDM-10004 600-900 IU / mL Specific Activity ACM-1510 2 85 IU / mg protein Purity by GF-HPLC ACM-1517 RDM-10006 at 95% active components <8% aggregated PEG Total Free by RP-HPLC ACM-1509 RDM-10007 < 2.0 mg / mL PEG Free 10K by RP-HPLC < 0.2 mg / mL N-hydroxysuccinimide (NHS) ACM-1505 2.0 ppm Modification by TNBS ACM-15007 RDM-10015 69-82 mol PEG / mol protein Protein Concentration ACM-1506 RDM -10005 4.5-8.5 mg / mL USP Sterility <71> Passes USP Sterility Test USP General Safety <88> 21 CFR 610.11 Passes USP Test in Guinea Pig Passes USP Test in Mice LAL Endotoxin ACM-1511 < 35 EU / mL Particulate Material ACM-0070 > 2 um NMT 27,000 Particles / Container1 2 10 um NMT 6000 Particles / Container > 25um NMT 600 Particles / Container Test of Identity ACM-1805 Deaminate Asparagine Content Uniformity RDM-10004 USP Compliant Reconstitution Time LSNE SOP CQC032 : NMT 3 minutes Water (KF) LSNE SOPCQC0320 NMT 3.0% :With the exception of the pre-reconstitution appearance test, all tests were performed post-reconstitution with WFI Batch Analysis Batch analyzes for product batches of lyophilized compositions are provided in Table 12 below. Results for all three batches were within release specifications. Table 12: Batch Analysis of Lyophilized Compositions Test Acceptance Criteria Lot 1 Lot 2 Lot 3 Appearance White to almost white cake Pass Pass Pass Appearance after reconstitution Colorless solution Pass Pass Pass Clarity after reconstitution Clear, no visible particles after reconstitution Pass Pass Pass Volume of fill To deliver 5, 0 mL (USP) 5.5 5.4 5.2 pH 7.2-7.4 7.4 7.4 7.4 Potency (activity) 600-900 IU / mL 805 718 741 Specific activity > 85 IU / mg protein 114 111 113 Purity by GF-HPLC > 95% active components <8% added 97, 5 97, 4 97, 1 PEG Total Free by RP-HPLC < 2.0 mg / mL 0.9 1.3 0, 5 PEG Free 10K by RP-HPLC < 0.2 mg / mL 0.1 0.2 0.1 N-Hydroxysuccinimide (NHS) < 2.0 ppm 0.1 0.9 0.2 Modification by TNBS 69-82 moles PEG / mol protein 77 77 75 Protein Concentration 4.5-8.5 mg / mL 7.1 6.5 6.6 Sterility Passes USP sterility test n / a Passes Passes General Safety Passes USP test on Guinea Pig Passes USP test in mice Pass Pass Pass Endotoxin per LAL <35 EU / mL < 4 < 4 < 4 Particulate Material 2 2 um NMT 27000 Particles / Container 1835 530 5834 2 10 um NMT 6000 Particles / Container 116 12 96 > 25 um NMT 600 Particles / Container 1 1 2 Proof of Identity Deaminates Asparagine n / a n / a n / a Content Uniformity USP Compliant Complies Complies Complies Reconstitution Time NMT 3 minutes < 1 < 1 < 1 Water (KF) NMT 3.0% 0.1 0.2 0.1 Stability studies Lots 1, 2, and 3 of lyophilized drug product were placed in long-term (2-8°C) and accelerated (25 ± 3°C; 60 ± 5% RH) stability tests. These batches were also placed in the Heat Stress Stability Test (40 ± 2°C; 75% ± 5% RH) to assess the heat-induced degradation profile in the product. Long Term Stability (2-8 °C) Stability data generated for batches of lyophilized pharmaceuticals stored under long-term conditions (2-8°C) are provided in Tables 13-16. Long-term stability data indicated that the lyophilized drug product stored at 5 ± 3°C remained within the acceptance criteria for all stability time points. The water content (KF) data ranged from 0.96% -1.35% (specification = NMT 3.0%) in the storage condition of 2-8°C up to 12 weeks. Unlike the commercial liquid pharmaceutical, which demonstrated an increase in activity and a decrease in purity over time, this trend was not observed for lyophilized compositions. Stability graphs for purity (FIG 8) and potency (FIG 9), as well as aggregates (FIG 10), at 2-8°C are shown in the attached figures. MA / a / ZUZ 1 0344 Table 13: Long-Term Stability Analysis of Lot 1 Test Initial Acceptance Criteria 3 6 9 Appearance Cake white to almost white; Colorless solution after reconstitution Pass Pass Pass - Clarity Clear, no visible particles after reconstitution Pass Pass Pass - pH 7.2-7.4 7.4 7.4 7.4 - Potency (activity) 600-900 lU / mL 805 750 801 Specific activity at 85 IU / mg protein 114 107 111 - Purity by GF-HPLC > 85% active components s 8% added 97.07, 4.73 96.53, 3.82 97.68, 5.05 - PEG Total Free by RP-HPLC s 6.0 mg / mL 0.86 0.86 1.13 - PEG Total Free 10K by RP-HPLC < 0.6 mg / mL 0.13 0.13 0.14 - Concentration of Protein 4.5-8.5 mg / mL 7.06 7.01 7.2 - Particulate Material > 2 um NMT 27000 Particles / Container 1835 - - 204- > 10 um NMT 6000 Particles / Container 116 21 126 - > 25 um NMT 600 Particles / Container 1 0 2 - Reconstitution Time NMT 3 minutes 0.99 0.99 0.99 - Water (KF) NMT 3.0% - - - - 1Test conducted at 9 months using MilliQ water for drug product reconstitution Table 14: Long-Term Stability Analysis of Lot 2 Test Initial Acceptance Criteria 3 6 9 Appearance Cake white to almost white; Colorless solution after reconstitution Pass Pass Pass - Clarity Clear, no visible particles after reconstitution Pass Pass Pass - pH 7.2-7.4 7.4 7.4 7.4 - Potency (activity) 600-900 lU / mL 718 738 741 - Specific activity > 85 IU / mg protein 111 115 115 - Purity by GF-HPLC > 85% active components < 8% added 97.16, 4.35 96.94, 3.85 96.99, 0, 79 - Total Free PEG by RP-HPLC £ 6.0 mg / mL 1.31 1.11 0.88 - Total Free PEG 10K by RP-HPLC £ 0.6 mg / mL 0.15 0.13 69 - Concentration of Protein 4.5-8.5 mg / mL 6.48 6.44 6.44 - Particulate Matter > 2 um NMT 27000 Particles / Container 530 - - 207- > 10 um NMT 6000 Particles / Container 12 55 69 - 25 um NMT 600 Particles / Container 1 0 0 - Reconstitution Time NMT 3 minutes 0.99 0.99 0.99 - Water (KF) NMT 3.0% 0.2% - - - ' Test carried out at 9 months using MIIIIQ water for reconstitution of the pharmaceutical product Table 15: Long-Term Stability Analysis of Lot 3 (on the right) Test Initial Acceptance Criteria 3 6 9 Appearance Cake white to almost white; Colorless solution after reconstitution Pass Pass - - Clarity Clear, no visible particles after reconstitution Pass Pass - - pH 7.2-7.4 7.4 7.4 - - Potency (activity) 600-900 IU / mL 741 733 - - Specific activity > 85 IU / mg protein 113 117 - - Purity by GF-HPLC 85% active components £ 8% added 97.05, 0.55 98.87, 0.65 - - PEG Total Free by RP-HPLC s 6.0 mg / mL 0.45 1.2 - - Total Free PEG 10K by RP-HPLC < 0.6 mg / mL 0.11 69 - - Protein Concentration 4.5-8.5 mg / mL 6 .55 6.25 - - Particulate Material > 2 um NMT 27000 Particles / Container 5834 - 165- - > 10 um NMT 6000 Particles / Container 96 90 - - > 25 um NMT 600 Particles / Container 2 0 - - Recovery Time NMT 3 minutes 0.99 0.99 - - Water (KF) NMT 3.0% 0.1% - - - 1Test conducted at 9 months using MIIHQ water for drug product reconstitution Table 16: Long-Term Stability Analysis of Lot 3 (inverted) Test Initial Acceptance Criteria 3 6 9 Appearance Cake white to almost white; Colorless solution after reconstitution Pass Pass - - Clarity Clear, no visible particles after reconstitution Pass Pass - - pH 7.2-7.4 7.4 7.4 - - Potency (activity) 600-900 IU / mL 741 745 - - Specific activity at 85 Iul / mg protein 113 118 - - Purity by GF-HPLC > 85 Iul / mg protein 97.05, 0.55 98.90, 0.63 - - PEG Total Free by RP-HPLC > 85 % active components < 8% added 0.45 1.18 - - Total Free PEG 10K by RP-HPLC £ 6.0 mg / mL 0.11 < 0.07 - - Protein Concentration £ 0.6 mg / mL 6 .55 6.29 - - Particulate Material 4.5-8.5 mg / mL 5834 - - - > 2 um NMT 27,000 Particles / Container 96 50 - - > 10 um NMT 6000 Particles / Container 2 0 - - Reconstitution Time > 25um NMT 600 Particles / Container 0.99 0.99 - - Water (KF) NMT 3.0% 0.1% - - - Accelerated stability (25 + 3°C; 60% ± 5% RH) Stability data for batches of lyophilized pharmaceuticals stored under accelerated conditions (25 ± 3°C; 60% ± 5% RH) are provided in Tables 17-20. The stability data indicates that the lyophilized drug product stored in the accelerated condition remained within the acceptance criteria for all stability time points. The water content (KF) ranged from 1.12%-1.23% (specification = NMT 3.0%) in the storage condition of 25°C up to 4 weeks. Stability plots for quality attributes, purity (FIG 11) and potency (FIG 12), as well as aggregates (FIG 13), at 25 + 3°C are provided in the attached figures. IVIA / a / ¿U¿ I 0344 Table 17: Accelerated Stability Analysis of Lot 1 Test Acceptance Criteria Time (months) Initial 1 2 3 6 Appearance Cake white to almost white; Colorless solution after reconstitution Pass Pass Pass Pass Pass Clarity Clear, no visible particles after reconstitution Pass Pass Pass Pass Pass PH 7.2-7.4 7.4 7.4 7.4 7.4 7.4 Potency (activity ) 600-900 IU / mL 805 782 809 778 805 Specific activity > 85 IU / mq protein 114 111 112 111 Purity by GF-HPLC > 85% active components < 8% added 97.07 4.73 96.43 96.58 4.6 96.29 4.11 96.88 5.9 PEG Total Free by RP-HPLC s 6.0 mg / mL 0.86 0.99 1.12 0.74 0.88 PEG Total Free 10K by RP-HPLC < 0 .6 mg / mL 0.13 0.14 0.17 0.12 0.13 Protein Concentration 4.5-8.5 mg / mL 7.06 7.03 7.2 7.02 7.13 Particulate Matter > 2 um NMT 27000 Particles / Container 1835 - 11753 12096 > 10 um NMT 6000 Particles / Container 116 • • 70 116 > 25 um NMT600 Particles / Container 1 - - 1 1 Recovery Time NMT 3 minutes < 1 < 1 < 1 < 1 < 1 Aqua (KF) NMT 3.0% - Table 18: Accelerated Stability Analysis of Lot 2 Test Acceptance Criteria Time (months) Initial 1 2 3 6 Appearance Cake white to almost white; Colorless solution after reconstitution Pass Pass Pass Pass - Clarity Clear, no visible particles after reconstitution Pass Pass Pass Pass - pH 7.2-7.4 7.4 7.4 7.4 7.4 - Potency (activity) 600 -900 IU / mL 718 748 733 720 - Specific activity > 85 IU / mg protein 111 115 113 116 - Purity by GF-HPLC 85% active components < 8% added 97.16, 4.35 96.69, 4.01 96.52, 3.76 96.79, 4.31 - PEG Total Free by RP-HPLC s 6.0 mg / mL 1.31 1.48 1.12 1.16 - PEG Total Free 10K by RP-HPLC < 0.6 mg / mL 0.15 0.18 0.16 0.14 - Protein Concentration 4.5-8.5 mg / mL 6.48 6.51 6.46 6.21 - Particulate Matter > 2 um NMT 27000 Particles / Container 530 - - 10051 - >10 um NMT6000 Particles / Container 12 - 121 • > 25 um NMT600 Particles / Container 1 - - 6 - Reconstitution Time NMT 3 minutes < 1 < 1 < 1 < 1 - Water (KF) NMT 3.0% 0.2% - - - - Table 19: Accelerated Stability Analysis of Lot 3 (on the right) MA / a / ZUZ 1 0344 Test Acceptance Criteria Time (months) Initial 1 2 3 6 Appearance Cake white to almost white; Colorless solution after reconstitution Pass Pass Pass Pass Clarity Clear, no visible particles after reconstitution Pass Pass Pass Pass pH 7.2-7.4 7.4 7.4 7.4 7.4 Potency (activity) 600-900 IU / mL 741 700 750 718 Specific activity at 85 IU / mg protein 113 111 113 Purity by GF-HPLC > 85% active components < 8% added 97.05 0.55 96.88 0.62 97.25 0.75 96.98 0.89 PEG Total Free by RP-HPLC s 6.0 mg / mL 0.45 0.95 1.06 0.87 PEG Total Free 10K by RP-HPLC < 0.6 mg / mL 0.11 < 0.07 < 0, 07 < 0.07 Protein Concentration 4.5-8.5 mg / mL 6.55 6.28 6.63 6.34 Particulate Matter > 2 um NMT 27000 Particles / Container 5834 8000 > 10 um NMT 6000 Particles / Container 96 83 > 25 um NMT 600 Particles / Container 2 2 Reconstitution Time NMT 3 minutes < 1 < 1 < 1 < 1 Water (KF) NMT 3.0% 0.1% Table 20: Accelerated Stability Analysis of Lot 3 (inverted) Test Acceptance Criteria Time (months) Initial 1 2 3 6 Appearance Queque white to almost white; Colorless solution after reconstitution Pass Pass Pass Pass Clarity Clear, no visible particles after reconstitution Pass Pass Pass Pass PH 7.2-7.4 7.4 7.4 7.4 7.4 - Potency (activity) 600-900 IU / mL 741 719 733 721 - Specific activity > 85 IU / mg protein 113 113 113 113 - Purity by GF-HPLC » 85% active components < 8% added 97.05 0.55 96.76 0.63 97.31 0.72 97.02 0.74 PEG Total Free by RP-HPLC « 6.0 mg / mL 0.45 0.92 1.04 1.22 - PEG Total Free 10K by RP-HPLC < 0.6 mg / mL 0.11 < 0.07 < 0.07 0.14 Protein Concentration 4.5-8.5 mg / mL 6.55 6.37 6.49 6.38 Particulate Matter > 2 um NMT 27000 Particles / Container 5834 10277 > 10 um NMT 6000 Particles / Container 96 113 > 25 um NMT 600 Particles / Container 2 1 Reconstitution Time NMT 3 minutes < 1 < 1 < 1 < 1 Water (KF) NMT 3.0% 0.1% Heat Stress Stability (40 ± 2°C; 75% ± 5% RH) Stability data for batches of lyophilized pharmaceuticals stored under stress (40 ± 2°C; 75% ± 5% RH) are provided in Tables 21-24. The stability data indicated that the lyophilized drug product stored under stress conditions remained within the acceptance criteria for the duration of the study. The water content (KF) varied between 1.16% and 1.45% (specification = NMT 3.0%) in the storage condition of 40°C up to 4 weeks. Stability plots for potency (FIG 14) and purity (FIG 15), as well as aggregates (FIG 16), at 40 ±2°C are provided in the accompanying figures. Table 21: Heat Stress Stability Data Lot 1 Test Acceptance Criteria Time (months) Initial 1 2 3 6 Appearance Cake white to almost white; Colorless solution after reconstitution Pass Pass Pass Pass Pass Clarity Clear, no visible particles after reconstitution Pass Pass Pass Pass pH 7.2-7.4 7.4 7.4 7.4 7.4 7.4 Potency (activity ) 600-900 IU / mL 805 757 747 759 746 Specific activity > 85 IU / mg protein 114 109 107 107 - Purity by GF-HPLC > 8 5% active components < 8% added 97.07 4.73 95.02 94 .52 4.74 93.64 4.31 92.64 6.01 Total Free PEG by RP-HPLC < 6.0 mg / mL 0.86 1.07 1.15 0.86 1.07 Total Free PEG 10K by RP-HPLC 0.6 mg / mL 0.13 0.15 0.16 0.13 0.14 Protein Concentration 4.5-8.5 mg / mL 7.06 6.94 7.01 7.09 7.08 Particulate Material > 2 um NMT 27000 Particles / Container 1835 12025 >10 um NMT 6000 Particles / Container 116 - - - 53 > 25 um NMT 600 Particles / Container 1 - - - 1 Reconstitution Time NMT 3 minutes < 1 < 1 < 1 < 1 - Water (KF) NMT 3.0% - - - - Table 22: Lot 2 Heat Stress Stability Data Test Acceptance Criteria Time (months) Initial 1 2 3 6 Appearance Cake white to almost white; Colorless solution after reconstitution Pass Pass Pass Pass - Clarity Clear, no visible particles after reconstitution Pass Pass Pass Pass - PH 7.2-7.4 7.4 7.4 7.4 7.4 - Potency (activity) 600 -900 IU / mL 718 738 690 694 - Specific activity > 85 IU / mg protein 114 109 107 107 - Purity by GF-HPLC > 85% active components < 8% added 97.16 4.35 93.91 3.99 114 109 107 Total Free PEG by RP-HPLC < 6.0 mg / mL 1.31 1.45 97.16 4.35 93.91 3.99 93.92 3.71 Total Free PEG 10K by RP-HPLC < 0 .6 mg / mL 0.15 0.17 0.16 0.14 - Protein Concentration 4.5-8.5 mg / mL 6.48 6.42 6.4 6.3 - Particulate Material > 2 um NMT 27000 Particles / Container 530 - - - - >10 um NMT 6000 Particles / Container 12 - - - - > 25 um NMT 600 Particles / Container 1 - - - - Recovery Time NMT 3 minutes < 1 < 1 < 1 < 1 - Water (KF) NMT 3.0% 0.2% - - - - Table 23: Heat Stress Stability Data Lot 3 (right) Test Acceptance Criteria Time (months) Initial 1 2 3 6 Appearance Cake white to almost white; Colorless solution after reconstitution Pass Pass Pass Pass - Clarity Clear, no visible particles after reconstitution Pass Pass Pass Pass - pH 7.2-7.4 7.4 7.4 7.4 7.4 - Potency (activity) 600 -900 IU / mL 741 722 691 681 - Specific activity > 85 IU / mg protein 113 112 111 109 - Purity by GF-HPLC 75 > 85% active components < 8% added 97.05 0.55 96.11 0.98 95.4 2.58 93.1 2.88 - PEG Total Free by RP-HPLC s 6.0 mg / mL 0.45 1.1 1.25 0.64 - PEG Total Free 10K by RP-HPLC < 0 .6 mg / mL 0.11 < 0.07 < 0.07 < 0.07 - Protein Concentration 4.5-8.5 mg / mL 6.55 6.43 6.23 6.25 - Particulate Material > 2 um NMT 27000 Particles / Container 5834 - - 8989 - >10 um NMT 6000 Particles / Container 96 - - 116 - > 25 um NMT 600 Particles / Container 2 - - 2 - Reconstitution Time NMT 3 minutes < 1 < 1 < 1 < 1 - Aqua (KF) NMT 3.0% 0.1% - - - Table 24: Heat Stress Stability Data Lot 3 (inverted) Test Acceptance Criteria Time (months) Initial 1 2 3 6 Appearance Cake white to almost white; Colorless solution after reconstitution Pass Pass Pass Pass - Clarity Clear, no visible particles after reconstitution Pass Pass Pass Pass - pH 7.2-7.4 7.4 7.4 7.4 7.4 - Potency (activity) 600-900 IU / mL 741 719 668 663 - Specific activity > 85 IU / mg protein 113 113 107 106 - Purity by GF-HPLC > 85% active components < 8% added 97.05 0.55 96.12 1.02 95.31 1.01 96.45 2.74 - PEG Total Free by RP-HPLC < 6.0 mg / mL 0.45 1.08 1.25 0.62 - PEG Total Free 10K by RP-HPLC 0.6 mg / mL 0.11 < 0.07 < 0.07 < 0.07 - Protein Concentration 4.5-8.5 mg / mL 6.55 6.38 6.23 6.25 - Particulate Material > 2 um NMT 27000 Particles / Container 5834 - - 9963 - >10 um NMT 6000 Particles / Container 96 - - 157 - > 25 um NMT 600 Particles / Container 2 - - 3 - Reset Time NMT 3 minutes < 1 < 1 < 1 < 1 - Aqua (KF) NMT 3.0% 0.1% - - - - MA / a / ZUZ 1 / Ul 0344 Example 2 A composition was produced that included a polyethylene glycol asparaginase having a SC-PEG linker (ie, a succinimidyl carbonate linker) - calasparga pegol (succinimidyl carbonate polyethylene glycol [SC-PEG] L-asparaginase from E. coli) . The composition of the composition is given in Table 25. Table 25: Components of Composition Calaspargase Pegol Component Grade Amount per g* Calaspargase Pegol n / a 750 Ul Sodium Phosphate Dibasic USP 5.58 mg Sodium Phosphate Monobasic USP 1.29 mg Sodium Chloride USP 8.50 mg Aqua for Injection (WFI) USP QS at 1.0 q Example 3 After production of the concentrated bulk composition, a lyophilized pegol de calasparga composition can be produced from the concentrated bulk composition. FIG 1 shows an example of a process flow chart that can be used to make a storage-stable lyophilized composition in accordance with embodiments of the present disclosure. The lyophilized powder for injection composition can be produced in a single-use vial containing 3,750 IU of active pegol de calasparga (750 IU / mL after reconstitution with 5.2 mL of WFI). The components of the lyophilized composition may include 4.5% sucrose, dibasic sodium phosphate, monobasic sodium phosphate, and sodium chloride after reconstitution. The composition of the lyophilized composition is given in Table 26. Table 26: Composition Components Calaspargase Pegol Component Grade Amount per g* Calaspargase Pegol n / a 750 Ul Sodium Phosphate Dibasic USP 2.79 mg Sodium Phosphate Monobasic USP 0.60 mg Sodium Chloride USP 4.25 mg Sucrose National Formulary (NF) 45 mg Water for Injection (WFI) USP QS to 1.0g * Values ​​are post-reconstituted with WFI Example 4 The purpose of this study was to provide comparative pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity information for liquid pegaspargase (PEG-L-asparaginase; Oncaspar®) and lyophilized pegaspargase, when administered intravenously, by slow bolus injection. , to beagle dogs once (Day 1) or once a week for 4 weeks (Days 1, 15, 22, 29 and 36). Because reconstituted lyophilized pegaspargase will be administered intravenously to humans, the same route of administration was used in this study. A single dose and repeat dose PK / PD study was necessary to determine and compare the pharmacokinetics and pharmacodynamics of liquid lyophilized versions and reconstituted at an equivalent dose. Beagle dogs (nominally 5 / sex / group) were administered 500 IU / kg of liquid pegaspargase or reconstituted lyophilized pegaspargase by intravenous injection at a dose volume of 0.667 mL / kg (see Table 27). The beagles were approximately 6 months old, with males from 7.2 kg to 10.7 kg and females from 5.6 kg to 8.2 kg. Liquid pegaspargase (5 mL of 50 mM phosphate PBS buffer and 0.85% saline pH 7.2-7.4) was used as supplied and no preparation was required. Lyophilized pegaspargase (see Example 1) was prepared for administration (using a 21 gauge syringe) by reconstituting the contents of one vial with 5.2 mL of Water for Injection (WFI) using aseptic technique to achieve a concentration of 750 IU / mL. The contents of the vial were gently shaken until completely dissolved. The mixture was visually inspected for particulate matter, cloudiness, or discolorations prior to administration. Fresh formulations were prepared for each day of dosing, kept at room temperature, and used within 2 hours of preparation. Table 27: Protocol and Dose Regimen Treatment Group Dose (Ul / Kg) Concentration (IU / mL) Volume Dose (mL / Kg) Dogs (males) Bitches (females) 1 Pegaspargase liquid-One Dose 500 750 0.667 5 6 2 Liquid Pegaspargase-Double Dose 500 750 0.667 5 5 3 Freeze-dried Pegaspargase-Single Dose 500 750 0.667 5 5 4 Freeze-dried Pegaspargase-Double Dose 500 750 0.667 6 5 Animals in Groups 1 and 3 received a single dose of pegaspargase liquid or lyophilized pegaspargase, respectively on Day 1. Animals in Groups 2 and 4 received repeated doses of pegaspargase liquid or lyophilized pegaspargase, respectively. A slow bolus intravenous injection (over approximately 2 minutes) was administered within 2 hours of preparation of the test article. An indwelling catheter (non-butterfly catheter) was used, followed by saline to clear the catheter cap of any remaining dose volume. A straight needle was inserted into the catheter cap to ensure that needle placement would remain consistent throughout the 2 minute duration. Blood samples were obtained from all animals on Days 1 and 36 for pharmacokinetic and pharmacodynamic analysis. Approximately 1.0 mL of whole blood was obtained at each time point. Animals were not anesthetized or fasted prior to blood collection. Blood was collected in tubes containing sodium heparin anticoagulant and placed on wet ice in an upright position. Centrifugation for 5 minutes (at approximately 3000 rpm, at approximately 4°C) of the blood sample to obtain plasma began 5 minutes after the collection of the blood sample. PS: A 125 pL aliquot of plasma was pipetted into a cryotube pre-filled with 125 pL of SeraPrep for asparagine determination. The tube was inverted 3 times to mix the SeraPrep and immediately snap-frozen with liquid nitrogen or methanol / dry ice within 15 minutes of blood sample collection. All aliquots containing SeraPrep were analyzed for asparagine by High Performance Liquid Chromatography (HPLC) with mass spectrometric detection (LC-MS / MS). PK: The remainder of the plasma was divided into two cryotubes for asparaginase activity determination and deep-frozen within 30 minutes of blood sample collection. All aliquots that did not contain SeraPrep were tested for asparaginase activity using a mixed colorimetric enzymatic reaction. Results Analyzes performed during the treatment period for lyophilized pegaspargase confirmed that appropriate concentration dose formulations were administered (expected protein concentration of 6.6 mg / mL and activity of 741 IU / mL, per Batch Analysis) (Table 28). . MA / a / ZUZI 0344 Table 28: Analytical Chemistry Range Protein (mg / mL) Activity (IU / mL) Male Female Male Female Injection Day 1 6.36 6.30 738 722 Injection Day 22 6.55 6.54 794 785 Injection Day 36 6.3 6.44 722 741 Pooled mean plasma asparaginase concentrations (Cmax) and pooled mean areas under plasma asparaginase concentration, estimated time curves up to 552 hours post-dose (AUC0-552) on Day 1 and after repeat dosing on Day 36 are summarized for each group (sexes combined) in Table 29. Table 29: Bioequivalence: Pooled Group Mean Data (sexes combined) Formulation (500 Ul / kg) Group Mean Cmai (mIU / mL) Group Mean AUC0 522 (mIU,h / mL) Day 1 Day 36 Day 1 Day 36 Liquid Geo mean 9947 19440 2929202 4514287 Average 10018 19580 2953000 456100 0 SD 1300 2404 405245 648322 cv% 13.0 12.3 13.7 14.2 Freeze-dried Average geo 9393 17416 2603255 4258048 Average 9416 17480 2611000 4350000 SD 688 1555 214758 797663 cv% 7.3 8.9 8.2 18.3 The study was designed as a parallel group design and the data was statistically analyzed using analysis of variance techniques. Data for Cmax and AUC0-552 from both days were analyzed using an ANOVA model with formulation, time, gender, and their interactions as factors. The two pegaspargase formulations were analyzed for Cmax and AUC0552 and the corresponding two-sided 90% CIs for the ratio of geometric means are summarized in Table 30. Table 30: Pharmacokinetic data Parameter Table of Formulation Averages (recalculated - mIU / mL) Confidence Interval 90% of average ratio (Lyophilized / Liquid) Lyophilized Liquids Lower Upper Ratio 12790 13943 0.867 0.917 0.970 auq,552 3329382 3636380 0, 841 0.916 0.996 For Cmax there was evidence of bioequivalence since the confidence interval (0.867 to 0.970) was contained in the critical region. For AUC0-552 there was evidence of bioequivalence as the confidence interval (0.841 to 0.996) was contained in the critical region. The mean maximum plasma concentrations (Cmax) of pegaspargase and the mean areas under the plasma pegaspargase concentration-time curves estimated up to 552 hours post-dose (AUC0-552) on Day 1 and after repeated dosing on on Day 36 are summarized below (by gender) with Standard Deviations in parentheses in Table 31. Table 31: Concentration profiles in plasma vs. Time Formulation (500 Ul / kg) C^mUI / mL) AUC0 552(mUl.h / mL) Day 1 Day 36 Day 1 Day 36 Male Female Male Female Male Female Male Female Liquid 10700 9450 20200 19000 3250000 2660000 4660000 4470000 (1600) (610) (2700) (2200) (370000) (140000) (690000) (670000) Freeze-dried 9580 9250 17800 17200 2700000 2520000 4170000 4530000 (540) (840) (1400 ) (1800) (190000) (220000) (1120000 ) (320000) The relationships between the mean maximum plasma concentrations (Cmax) of asparaginase, the mean areas under the plasma asparaginase concentration-time curves (AUC0-552), and the dose level for the lyophilized formulation are expressed as a quotient compared to the liquid formulation and are presented in Table 32. Table 32: Relationship Between Mean Cmax, Mean AUC, and Dose Level Formulation (500 Ul / kg) Dose level quotient AUCO 552quotient Day 1 Day 36 Day 1 Day 36 Males Females Males Females Males Females Males Females Liquid 1 1 1 1 1 1 1 1 1 Lyophilized 1 0.9 0.98 0 .88 0.91 0.83 0.95 0.89 1.0 Cmax and AUC0-552 values ​​for systemic asparaginase exposure in dogs were similar after administration of reconstituted lyophilized pegaspargase, compared to the liquid formulation, on Day 1 and after repeated administrations on Day 36. There was no evidence of a significant difference between formulations for AUC0-552, but there was some evidence of a difference between the Cmax values ​​of the different formulations where Cmax after administration of the lyophilized product was slightly lower (8%) than when it was dosed as the liquid formulation. The Cmax and AUC0-552 values ​​for systemic exposure to asparaginase in bitches were generally similar to the exposure indices in males and there was no evidence of statistically significant sex-related differences in systemic exposure for Cmax or AUCo552. Other parameters evaluated during the study were: viability, clinical observations, body weight, food consumption, respiration rates, body temperature, hematology, coagulation, and blood chemistry; no adverse effects related to the test article were observed for these. After repeated intravenous doses (Day 36), the Cmax values ​​and range (AUC0-552) of the systemic exposure of dogs to asparaginase were greater than those values ​​after a single dose (Day 1) and these differences were statistically significant (p <0.001). The mean accumulation ratios, calculated based on AUCo 552 values ​​(note that different animals provided data for each day), were greater than one, indicating that asparaginase accumulation occurred after repeated intravenous administration of liquid pegaspargase. In general, the two pegaspargase formulations were shown to be equivalent with respect to Cmax and AUC0-552, as the corresponding two-sided 90% CI for the ratio of geometric means lie well within conventional bioequivalence ranges ranging from 0.8 to 1.25. There were no significant differences between the two formulations for AUC0-552. Systemic exposure to asparaginase was similar between the two products and some accumulation occurred in both sexes with repeated dosing. Asparagine was completely eliminated up to 336 hours in all animals and up to 552 hours in most of them. In summary, there were no notable differences between the 500 IU / kg doses with liquid pegaspargase or reconstituted lyophilized pegaspargase and had comparable pharmacokinetic, pharmacodynamic, and immunogenic profiles. ACHIEVEMENTS In one embodiment, the present disclosure provides a storage-stable lyophilized composition that includes a polyalkylene oxide asparaginase having a polyalkylene oxide group covalently attached through a linker to an asparaginase. The storage-stable lyophilized composition also includes a buffer, a salt, and a sugar. In some embodiments, the polyalkylene oxide group includes a polyethylene glycol group. In some embodiments, the polyethylene glycol group has a molecular weight ranging from 2,000 to 10,000 daltons. In some embodiments, the polyethylene glycol group has a molecular weight of 5,000 daltons. In some embodiments, the asparaginase is E. cali asparaginase. In some embodiments, the binder is a urethane binder. In some embodiments, the linker is a succinate linker. In some embodiments, the polyalkylene oxide asparaginase is present in an amount ranging from 500 to 1,000 IU / g. In some embodiments, the buffer includes a phosphate buffer. In some embodiments, the phosphate buffer includes dibasic sodium phosphate and monobasic sodium phosphate. In some embodiments, dibasic sodium phosphate is present in an amount ranging from 0.1 to 0.5% by weight. In some embodiments, monobasic sodium phosphate is present in an amount ranging from 0.01 to 0.1% by weight. In some embodiments, the salt is sodium chloride. In some embodiments, sodium chloride is present in an amount ranging from 0.1 to 1% by weight. In some embodiments, the sugar includes a disaccharide. In some embodiments, the disaccharide includes sucrose. In some embodiments, the sugar includes sucrose in an amount ranging from 1 to 10% by weight. In some embodiments, the composition is present in a unit dosage container. In some embodiments, the unit dosage container is a vial. In some embodiments, the vial is a sealed glass vial. In some embodiments, the polyalkylene oxide asparaginase is present in an amount of 750 IU / g, the polyalkylene oxide group includes a polyethylene glycol group with a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a urethane linker, buffer is a phosphate buffer including dibasic sodium phosphate in an amount ranging from 0.25 to 0.3% by weight and monobasic sodium phosphate in an amount ranging from 0.05 to 0 0.07% by weight, the salt is sodium chloride in an amount ranging from 0.4 to 0.45% by weight, and the sugar is sucrose in an amount ranging from 4 to 5% by weight. In some embodiments, the polyalkylene oxide asparaginase is present in an amount of 750 IU / g, the polyalkylene oxide group includes a polyethylene glycol group with a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the The linker is a urethane linker, the buffer is a phosphate buffer including dibasic sodium phosphate in an amount of 0.279% by weight and monobasic sodium phosphate in an amount of 0.06% by weight, the salt is sodium chloride in a amount of 0.425% by weight, and the sugar is sucrose in an amount of 4.5% by weight. In some embodiments, the polyalkylene oxide asparaginase is present in an amount of 750 IU / g, the polyalkylene oxide group includes a polyethylene glycol group with a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a succinate, buffer is a phosphate buffer including dibasic sodium phosphate in an amount ranging from 0.25 to 0.3% by weight and monobasic sodium phosphate in an amount ranging from 0.05 to 0.07 % by weight, the salt is sodium chloride in an amount ranging from 0.4 to 0.45% by weight, and the sugar is sucrose in an amount ranging from 4 to 5% by weight. In some embodiments, the polyalkylene oxide asparaginase is present in an amount of 750 IU / g, the polyalkylene oxide group includes a polyethylene glycol group with a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the The linker is a succinate linker, the buffer is a phosphate buffer including dibasic sodium phosphate in an amount of 0.279% by weight and monobasic sodium phosphate in an amount of 0.06% by weight, the salt is sodium chloride in a amount of 0.425% by weight, and the sugar is sucrose in an amount of 4.5% by weight. In some embodiments, the polyalkylene oxide asparaginase is present in an amount of 750 IU / g, the polyalkylene oxide group includes a polyethylene glycol group with a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the The linker is a urethane linker, the buffer is a phosphate buffer including dibasic sodium phosphate in an amount of 0.558% by weight and monobasic sodium phosphate in an amount of 0.129% by weight, and the salt is sodium chloride in an amount of 0.85% by weight. In another embodiment, the present disclosure provides a storage-stable lyophilized composition that includes a polyethylene glycol asparaginase having a polyethylene glycol group covalently attached via a succinate linker to an E. coli asparaginase. In another embodiment, the present disclosure provides a storage-stable lyophilized composition that includes a polyethylene glycol asparaginase having a polyethylene glycol group covalently attached via a urethane linker to an E. coli asparaginase. The storage-stable lyophilized composition also includes a phosphate buffer, a salt, and optionally, a disaccharide as described in the above embodiments. In another embodiment, the present disclosure provides a method of deaminating asparagine in a subject by administration of a composition as described herein. In some embodiments, the method includes reconstituting a storage-stable lyophilized composition in accordance with the present disclosure to produce a reconstituted dosage unit, and administering the reconstituted dosage unit to the subject to deaminate the asparagine in the subject. In some embodiments, reconstitution includes combining the storage-stable lyophilized composition with water for injection (WFI). ΜΛ / a / ZUZ 1 / U1 0344 In some embodiments, the dosage unit includes 700 to 800 IU / mL of polyalkylene oxide asparaginase. In some embodiments, the dosage unit includes 2.5 to 6 mg / g of dibasic sodium phosphate. In some embodiments, the dosage unit includes 2.5 to 3 mg / g of dibasic sodium phosphate. In some embodiments, the dosage unit includes 5 to 6 mg / g of dibasic sodium phosphate. In some embodiments, the dosage unit includes 5.25 to 5.75 mg / g of dibasic sodium phosphate. In some embodiments, the dosage unit includes 0.45 to 1.5 mg / g of monobasic sodium phosphate. In some embodiments, the dosage unit includes 0.45 to 0.75 mg / g of monobasic sodium phosphate. In some embodiments, the dosage unit includes 1 to 2 mg / g of monobasic sodium phosphate. In some embodiments, the dosage unit includes 1 to 1.5 mg / g of monobasic sodium phosphate. In some embodiments, the dosage unit includes 4 to 9 mg / g of sodium chloride. In some embodiments, the dosage unit includes 4 to 4.5 mg / g of sodium chloride. In some embodiments, the dosage unit includes 8 to 9 mg / g of sodium chloride. In some embodiments, the dosage unit includes sucrose. In some embodiments, sucrose is present in an amount ranging from 40 to 50 mg / g. In some embodiments, the reconstituted dosage unit delivers from 1,500 to 3,000 IU / m 2 of polyalkylene oxide asparaginase to the subject. In some embodiments, the reconstituted dosage unit delivers from 2,000 to 2,750 IU / m 2 of polyalkylene oxide asparaginase to the subject. In some embodiments, the method is a method of treating the subject for a neoplastic condition. In some embodiments, the neoplastic condition is cancer. In some embodiments, the cancer is a leukemia. In some embodiments, the leukemia is acute lymphoblastic leukemia (ALL). In some embodiments, the leukemia is acute myeloid leukemia (AML). In some embodiments, the subject has been prescribed a treatment regimen that includes an induction phase, a consolidation phase, and a maintenance phase. In some embodiments, the method includes administering a single reconstituted dosage unit to the subject in the induction phase and multiple reconstituted dosage units during the maintenance phase. In some embodiments, multiple reconstituted dosage units are administered to the subject by administering one reconstituted dosage unit to the subject every 3 weeks. In some embodiments, multiple reconstituted dosage units are administered to the subject by administering one reconstituted dosage unit to the subject every 2 weeks. In some embodiments, the subject is a minor. In some embodiments, the subject is an adult. In some embodiments, the polyalkylene oxide asparaginase is present in an amount of 750 IU / mL, the polyalkylene oxide group includes a polyethylene glycol group with a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a urethane linker, buffer is a phosphate buffer including dibasic sodium phosphate in an amount ranging from 2.5 to 3 mg / g and monobasic sodium phosphate in an amount of 0.5 to 0.7 mg / g , the salt is sodium chloride in an amount of 4 to 4.5 mg / g, and the sugar is sucrose in an amount that varies from 40 to 50 mg / g. In some embodiments, the polyalkylene oxide asparaginase is present in an amount of 750 IU / rnL, the polyalkylene oxide group includes a polyethylene glycol group with a molecular weight of 5,000 daltons, the asparaginase is E. cali asparaginase, the The linker is a urethane linker, the buffer is a phosphate buffer including dibasic sodium phosphate in an amount of 2.79 mg / g and monobasic sodium phosphate in an amount of 0.6 mg / g, the salt is sodium chloride in an amount of 4.25 mg / g, and the sugar is sucrose in an amount of 45 mg / g. In some embodiments, the polyalkylene oxide asparaginase is present in an amount of 750 IU / mL, the polyalkylene oxide group includes a polyethylene glycol group with a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a succinate linker, buffer is a phosphate buffer including dibasic sodium phosphate in an amount ranging from 2.5 to 3 mg / g and monobasic sodium phosphate in an amount ranging from 0.5 to 0.7 mg / g, the salt is sodium chloride in an amount ranging from 4 to 4.5 mg / g, and the sugar is sucrose in an amount ranging from 40 to 50 mg / g. In some embodiments, the polyalkylene oxide asparaginase is present in an amount of 750 IU / mL, the polyalkylene oxide group includes a polyethylene glycol group with a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a succinate linker, the buffer is a phosphate buffer including dibasic sodium phosphate in an amount of 2.79 mg / g and monobasic sodium phosphate in an amount of 0.6 mg / g, the salt is sodium chloride in an amount of 4.25 mg / g, and the sugar is sucrose in an amount of 45 mg / g. In another embodiment, the present disclosure provides a method of manufacturing a lyophilized polyalkylene oxide asparaginase composition by lyophilizing an aqueous concentrate composition in a manner sufficient to produce a storage-stable lyophilized polyalkylene oxide asparaginase composition. The aqueous concentrate composition includes a polyalkylene oxide asparaginase having a polyalkylene oxide group covalently attached via a linker to an asparaginase, a buffer, a salt, and a sugar. In some embodiments, the aqueous concentrate composition includes 1,500 to 3,000 IU / mL of polyalkylene oxide asparaginase. In some embodiments, the aqueous concentrate composition includes 0.1 to 0.5% by weight of dibasic sodium phosphate. In some embodiments, the aqueous concentrate composition includes 0.01 to 0.1% by weight of monobasic sodium phosphate. In some embodiments, the aqueous concentrate composition includes 0.1 to 1% by weight of sodium chloride. In some embodiments, the aqueous concentrate composition includes sucrose. In some embodiments, sucrose is present in an amount ranging from 1 to 10% by weight. In some embodiments, the method also includes the production of the aqueous concentrate composition. In some embodiments, the method also includes introducing the aqueous concentrate composition into a unit dosage container and lyophilizing the aqueous concentrate composition in the MA / a / ZUZI / U1 0344 unit dosage container. In some embodiments, the unit dosage container is a vial. In some embodiments, the vial is a glass vial. In some embodiments, the method also includes sealing the lyophilized composition in the unit dosage container. In some embodiments, the polyalkylene oxide group includes a polyethylene glycol group. In some embodiments, the polyethylene glycol group has a molecular weight ranging from 2,000 to 10,000 daltons. In some embodiments, the polyethylene glycol group has a molecular weight of 5,000 daltons. In some embodiments, the asparaginase is E. cali asparaginase. In some embodiments, the binder is a urethane binder. In some embodiments, the linker is a succinate linker. In some embodiments, the polyalkylene oxide asparaginase is present in an amount of 750 IU / g, the polyalkylene oxide group includes a polyethylene glycol group with a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a urethane linker, buffer is a phosphate buffer including dibasic sodium phosphate in an amount ranging from 0.25 to 0.3% by weight and monobasic sodium phosphate in an amount ranging from 0.05 to 0 0.07% by weight, the salt is sodium chloride in an amount ranging from 0.4 to 0.45% by weight, and the sugar is sucrose in an amount ranging from 4 to 5% by weight. In some embodiments, the polyalkylene oxide asparaginase is present in an amount of 750 IU / g, the polyalkylene oxide group includes a polyethylene glycol group with a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a succinate linker, buffer is a phosphate buffer including dibasic sodium phosphate in an amount ranging from 0.25 to 0.3% by weight and monobasic sodium phosphate in an amount ranging from 0.05 to 0 0.07% by weight, the salt is sodium chloride in an amount ranging from 0.4 to 0.45% by weight, and the sugar is sucrose in an amount ranging from 4 to 5% by weight. In other embodiments, the present disclosure provides a kit that includes two more unit dosage containers, each containing a storage-stable lyophilized composition. The storage-stable lyophilized composition includes a polyalkylene asparaginase oxide having a polyalkylene oxide group covalently attached via a linker to an asparaginase, a buffer, a salt, and a sugar. In some embodiments, the polyalkylene oxide group includes a polyethylene glycol group. In some embodiments, the polyethylene glycol group has a molecular weight ranging from 2,000 to 10,000 daltons. In some embodiments, the polyethylene glycol group has a molecular weight of 5,000 daltons. In some embodiments, the asparaginase is E. coli asparaginase. In some embodiments, the binder is a urethane binder. In some embodiments, the linker is a succinate linker. In some embodiments, the polyalkylene oxide asparaginase is present in an amount ranging from 500 to 1,000 IU / g. In some embodiments, the buffer includes a phosphate buffer. In some embodiments, the phosphate buffer includes dibasic sodium phosphate and monobasic sodium phosphate. In some embodiments, dibasic sodium phosphate is present in an amount ranging from 0.1 to 0.5% by weight. In some embodiments, monobasic sodium phosphate is present in an amount ranging from 0.01 to 0.1% by weight. In some embodiments, the salt is sodium chloride. In some embodiments, sodium chloride is present in an amount ranging from 0.1 to 1% by weight. In some embodiments, the sugar includes a disaccharide. In some embodiments, the disaccharide includes sucrose. In some embodiments, the sugar includes sucrose in an amount ranging from 1 to 10% by weight. In some embodiments, the unit dosage containers are vials. In some embodiments, the vials are glass vials. In some embodiments, the unit dosage containers are sealed. In some embodiments, the polyalkylene oxide asparaginase is present in an amount of 750 IU / g, the polyalkylene oxide group includes a polyethylene glycol group with a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a urethane linker, buffer is a phosphate buffer including dibasic sodium phosphate in an amount ranging from 0.25 to 0.3% by weight and monobasic sodium phosphate in an amount ranging from 0.05 to 0 0.07% by weight, the salt is sodium chloride in an amount ranging from 0.4 to 0.45% by weight, and the sugar is sucrose in an amount ranging from 4 to 5% by weight. In some embodiments, the polyalkylene oxide asparaginase is present in an amount of 750 IU / g, the polyalkylene oxide group includes a polyethylene glycol group with a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a succinate linker, buffer is a phosphate buffer including dibasic sodium phosphate in an amount ranging from 0.25 to 0.3% by weight and monobasic sodium phosphate in an amount ranging from 0.05 to 0 0.07% by weight, the salt is sodium chloride in an amount ranging from 0.4 to 0.45% by weight, and the sugar is sucrose in an amount ranging from 4 to 5% by weight. In another embodiment, the present disclosure provides a method of treating acute myeloid leukemia (AML) in a subject. The method includes administering to the subject a dose of a polyalkylene oxide asparaginase effective to treat AML in the subject, wherein the polyalkylene oxide asparaginase has a polyalkylene oxide group covalently attached through a linker to an asparaginase. In some embodiments, the polyalkylene oxide group includes a polyethylene glycol group. In some embodiments, the polyethylene glycol group has a molecular weight ranging from 2,000 to 10,000 daltons. In some embodiments, the polyethylene glycol group has a molecular weight of 5,000 daltons. In some embodiments, the asparaginase is E. coli asparaginase. In some embodiments, the binder is a urethane binder. In some embodiments, the linker is a succinate linker. In some embodiments, the dose includes 700 to 800 IU / mL of the polyalkylene asparaginase oxide. In some embodiments, the dosage includes a buffer and a salt. In some embodiments, the buffer includes a phosphate buffer. In some embodiments, the phosphate buffer includes dibasic sodium phosphate and monobasic sodium phosphate. In some embodiments, the dose includes 5.25 to 5.75 mg / g dibasic sodium phosphate. In some embodiments, the dose includes 1.0 to 1.5 mg / g of monobasic sodium phosphate. In some embodiments, the salt is sodium chloride. In some embodiments, the dose includes 8 to 9 mg / g of sodium chloride. In some embodiments, the dose includes 750 IU / mL polyalkylene oxide asparaginase, the polyethylene glycol group has a molecular weight of 5,000 daltons, the asparaginase is E. cali asparaginase, the linker is a urethane linker, the buffer is a phosphate buffer including 5.25 to 5.75 mg / g dibasic sodium phosphate and 1 to 1.5 mg / g monobasic sodium phosphate, and the salt includes 8 to 9 mg / g sodium chloride. In some embodiments, the dose includes 750 IU / mL polyalkylene oxide asparaginase, the polyethylene glycol group has a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a urethane linker, the buffer is a phosphate buffer including 5.58 mg / g dibasic sodium phosphate and 1.29 mg / g monobasic sodium phosphate, and the salt includes 8.5 mg / g sodium chloride. In some embodiments, the dose includes 750 IU / mL polyalkylene oxide asparaginase, the polyethylene glycol group has a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a succinate linker, the buffer is a phosphate buffer including 5.25 to 5.75 mg / g dibasic sodium phosphate and 1 to 1.5 mg / g monobasic sodium phosphate, and the salt includes 8 to 9 mg / g sodium chloride. In some embodiments, the dose includes 750 IU / mL polyalkylene oxide asparaginase, the polyethylene glycol group has a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a succinate linker, the buffer is a phosphate buffer including 5.58 mg / g dibasic sodium phosphate and 1.29 mg / g monobasic sodium phosphate, and the salt includes 8.5 mg / g sodium chloride. In some embodiments, the dosage includes a buffer, a salt, and a sugar. In some embodiments, the buffer includes a phosphate buffer. In some embodiments, the phosphate buffer includes dibasic sodium phosphate and monobasic sodium phosphate. In some embodiments, the dose includes 2.5 to 3 mg / g dibasic sodium phosphate. In some embodiments, the dose includes 0.45 to 0.75 mg / g of monobasic sodium phosphate. In some embodiments, the salt is sodium chloride. In some embodiments, the dose includes 4 to 4.5 mg / g of sodium chloride. In some embodiments, the sugar includes a disaccharide. In some embodiments, the disaccharide includes sucrose. In some embodiments, sucrose is present in an amount ranging from 40 to 50 mg / g. In some embodiments, the dose includes 750 IU / mL polyalkylene oxide asparaginase, the polyethylene glycol group has a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a urethane linker, the buffer is a phosphate buffer including 2.5 to 3 mg / g dibasic sodium phosphate and 0.5 to 0.7 mg / g monobasic sodium phosphate, the salt includes 4 to 4.5 mg / g chloride of sodium, and sugar includes 40 to 50 mg / g of sucrose. In some embodiments, the dose includes 750 IU / mL polyalkylene oxide asparaginase, the polyethylene glycol group has a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a urethane linker, the buffer is a phosphate buffer including 2.79 mg / g dibasic sodium phosphate and 0.6 mg / g monobasic sodium phosphate, salt including 4.25 mg / g sodium chloride, and sugar including 45 mg / g of sucrose. In some embodiments, the dose includes 750 IU / mL polyalkylene oxide asparaginase, the polyethylene glycol group has a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a succinate linker, the buffer is a phosphate buffer including 2.5 to 3 mg / g dibasic sodium phosphate and 0.5 to 0.7 mg / g monobasic sodium phosphate, the salt includes 4 to 4.5 mg / g chloride of sodium, and sugar includes 40 to 50 mg / g of sucrose. In some embodiments, the dose includes 750 IU / mL polyalkylene oxide asparaginase, the polyethylene glycol group has a molecular weight of 5,000 daltons, the asparaginase is E. coli asparaginase, the linker is a succinate linker, the buffer is a phosphate buffer including 2.79 mg / g dibasic sodium phosphate and 0.6 mg / g monobasic sodium phosphate, salt including 4.25 mg / g sodium chloride, and sugar including 45 mg / g of sucrose. In some embodiments, the method also includes producing the dosage by reconstituting a storage-stable lyophilized composition. In some embodiments, the dose delivers from 1,500 to 3,000 IU / m 2 of polyalkylene asparaginase oxide to the subject. In some embodiments, the dose delivers from 2,000 to 2,750 IU / m 2 of polyalkylene oxide asparaginase to the subject. In some embodiments, the subject has been prescribed a treatment regimen that includes an induction phase, a consolidation phase, and a maintenance phase. In some embodiments, the method includes administering a single dose to the subject in the induction phase and multiple doses during the maintenance phase. In some embodiments, multiple doses are administered to the subject by administering one dose to the subject every 3 weeks. In some embodiments, multiple doses are administered to the subject by administering one dose to the subject every 2 weeks. In some embodiments, the subject is a minor. In some embodiments, the subject is an adult. Although the above embodiments have been described in some detail by way of illustration and example for purposes of clarity of understanding, it is apparent to those skilled in the art in light of the teachings of this description that certain changes and modifications may be made to the same without departing from the spirit or scope of the appended claims. Accordingly, the foregoing merely illustrates the principles of the embodiments of the present disclosure. It will be appreciated that those skilled in the art will be able to devise various arrangements which, while not explicitly described or shown herein, incorporate the principles of the embodiments of the present disclosure and are included within its spirit and scope. In addition, all examples and conditional language cited in this document are primarily intended to assist the reader in understanding the principles of the embodiments of the present disclosure and concepts contributed by the inventors in furtherance of the art, and should be construed as such. without any limitation. Examples and conditions are specifically recited. Furthermore, all statements herein set forth principles, aspects, and embodiments of the present disclosure, as well as 5 specific examples thereof, these are intended to encompass both structural and functional equivalents thereof. Furthermore, such equivalents are intended to include both currently known equivalents and future developed equivalents, ie, any developed element that performs the same function, regardless of structure. The scope of the embodiments of the present disclosure, therefore, is not intended to be limited to the embodiments shown and described in this document. Rather, the scope and spirit of the embodiments of the present disclosure are embodied in the appended claims.

Claims

CLAIMS 1. A liquid composition derived from a reconstituted lyophilized sample, the composition comprising: a polyalkylene-asparaginase oxide at a concentration of 750 IU per mL of said composition; dibasic sodium phosphate at a concentration of 0.279% by weight; monobasic sodium phosphate at a concentration of 0.06% by weight; sodium chloride at a concentration of 0.425%; and sucrose at a concentration of 4.5% by weight, wherein the polyalkylene-asparaginase oxide comprises an asparaginase covalently linked to a polyalkylene oxide group which is a polyethylene glycol. 2 - The composition according to claim 1, wherein the asparaginase is Lasparaginase.

3. The composition according to claim 1, wherein the polyethylene glycol is methoxypolyethylene glycol.

4. The composition according to claim 1, wherein the polyalkylene oxide group is covalently linked by a succinate linker to the asparaginase.

5. The composition according to claim 1, wherein the polyethylene glycol has a molecular weight ranging from 2,000 to 10,000 daltons. 6 - The composition according to claim 1, wherein the polyethylene glycol has a molecular weight of 5,000 daltons.

7. The composition according to claim 1, further comprising sodium hydroxide, hydrochloric acid, or a combination thereof.

8. A storage-stable lyophilized composition comprising: a polyalkylene-asparaginase oxide; a buffer; a salt; and a sugar, wherein the storage-stable lyophilized composition is capable of forming the liquid composition according to any of claims 1 to 7 by reconstituting the storage-stable lyophilized composition with water for injection (WFI).

9. A method for preparing a freeze-dried polyalkylene oxide-asparaginase composition, wherein the method comprises freeze-drying 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 (iv) a sugar; in a manner sufficient to produce a storage-stable freeze-dried polyalkylene oxide-asparaginase composition according to claim 8, optionally wherein the method further comprises introducing an aqueous concentrate composition into a unit-dose container and freeze-drying the aqueous concentrate composition in the unit-dose container, optionally wherein the unit-dose container is a vial, such as a sealed glass vial. 10 - A composition according to any one of claims 1 to 8, for use as a medicament useful in the treatment of a neoplastic condition.

11. The composition for use according to claim 10, wherein the neoplastic condition is a cancer, optionally wherein the cancer is leukemia, optionally wherein the leukemia is: (i) acute lymphoblastic leukemia (ALL), or (ii) acute myeloid leukemia (AML).

12. The composition for use according to claim 10 or 11, wherein the treatment involves a regimen that includes an induction phase, a consolidation phase, and a maintenance phase, optionally wherein the use comprises administering a single unit dose to a subject in the induction phase and multiple unit doses during the maintenance phase, further optionally wherein the multiple unit doses are administered to a subject by administering a unit dose to the subject every 3 weeks or every 2 weeks. 13.- A kit comprising one or more unit dosage containers each containing a storage-stable lyophilized composition according to claim 8.