Alkaline phosphatase formulations
AssigneeTheriva Biologics, Inc.
InventorsVincent WACHER, J. Blair WEST, Michael KALEKO, Christian FURLAN FREGUIA
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Abstract
The present invention provides, in part, formulations comprising an alkaline phosphatase (AP)-based agent. Particularly, modified-release powder formulations comprising an AP-based agent are provided which release a substantial amount of the AP-based agent in the intestines. Therapeutic uses of the formulations are also provided.
Claims64
A modified-release formulation comprising an alkaline phosphatase (AP)-based agent, and being in the form of a powder, comprising:
- about 1-10% by weight AP-based agent,
- about 80-95% by weight polymer,
- about 1-10% by weight buffer,
- about 0.01-0.1% by weight zinc,
- about 0.1-1% by weight magnesium stearate,
- about 1-10% by weight protein stabilizer
- and optionally having the capacity to transition into a gel in a pH-dependent manner,
- wherein the formulation is suitable for compressing and releases a substantial amount of the AP-based agent in the intestines.
The modified-release formulation of any one of the above claims, wherein the AP-based agent comprises an amino acid sequence having at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, or at least about 90%, or at least about 95%, or at least about 96%, or at least about 97%, or at least about 98%, or at least about 99%, or at least about 100% identity with any of SEQ ID Nos:
- 1-17 disclosed herein.
The modified-release formulation of any one of the above claims, wherein the powder transforms into a gel in the presence of stomach acid.
The modified-release formulation of any one of the above claims, wherein the powder is substantially stable for compression into a tablet.
The modified-release formulation of any one of the above claims, wherein the powder is in a sachet and is optionally suitable for addition to food or drink.
The modified-release formulation of any one of the above claims, wherein the powder is included in a tablet.
The modified-release formulation of any one of the above claims, wherein the tablet further comprises an enteric agent, optionally an Eudragit polymer.
The modified-release formulation of any one of the above claims, wherein the formulation further comprises an additional therapeutic agent.
The modified release formulation of any one of the above claims, wherein the polymer is HPMCAS.
The modified release formulation of any one of the above claims, wherein the AP-based agent comprises an amino acid sequence having at least 95%, or 97%, or 99% sequence identity with any one of SEQ ID NOs:
- 1-17.
The modified release formulation of any one of the above claims, wherein the AP-based agent comprises an amino acid sequence having at least 95%, or 97%, or 99% sequence identity with SEQ ID NO:
- 2.
A method of treating or preventing a microbiome-related disorder in a subject in need thereof comprising, administering to the subject a modified-release formulation of any one of the above claims.
A method of treating an antibiotic-induced adverse effect in the GI tract and/or preventing or treating C. difficile infection (CDI) and/or a C. difficile-associated disease (CDAD) in a subject in need thereof comprising, administering to the subject a modified-release formulation of any one of the above claims.
A method of treating a metabolic disorder in a subject in need thereof comprising, administering to the subject a modified-release formulation of any one of the above claims.
A method of treating a neurological disease in a subject in need thereof comprising, administering to a subject in need thereof a modified-release formulation of any one of the above claims.
A method of treating sepsis in a subject in need thereof comprising, administering to the subject a modified-release formulation of any one of the above claims.
A method of treating HIV-mediated gut dysbiosis and/or GI barrier dysfunction in a subject in need thereof comprising, administering to the subject a modified-release formulation of any one of the above claims.
A method of treating celiac disease in a subject in need thereof comprising, administering to the subject a modified-release formulation of any one of the above claims.
A method of treating cystic fibrosis in a subject in need thereof comprising, administering to the subject a modified-release formulation of any one of the above claims.
A method for generating a modified-release powder formulation comprising an AP-based agent, comprising the steps of:
- a) dissolving the AP-based agent and a polymer in a solvent to form a spray-drying solution;
- b) spray-dry the spray-drying solution;
- and
- c) collecting the spray-dried powder.
A modified-release formulation comprising an alkaline phosphatase (AP)-based agent and being in the form of a powder, comprising:
- about 5% by weight AP-based agent, wherein the AP-based agent has an amino acid sequence of SEQ ID NO:
- 2;
- about 87% by weight polymer, wherein the polymer is HPMCAS;
- about 2% by weight buffer;
- about 0.06% by weight zinc;
- about 0.5% by weight magnesium stearate;
- and
- about 5% by weight protein stabilizer.
Dependencies are inferred from the claim text.