# US 2014/0193390 A1 · High Concentration Alpha-Glucosidase Compositions for the Treatment of Pompe Disease

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- Number: US 2014/0193390 A1
- Document ID: US20140193390A1
- Status: Published application
- Kind: A1
- Application number: 14/106,670
- Filed: 2013-12-13
- Published: 2014-07-10
- Earliest claimed: 2012-03-07
- Assignees: Amicus Therapeutics, Inc.
- Applicants: Amicus Therapeutics, Inc.
- Inventors: Kenneth Valenzano; John Crowley; Richie Khanna; John Flanagan
- Web page: https://patentgrep.com/patent/US20140193390A1

## CPC

- A61K 38/47: acting on glycosyl compounds (3.2), e.g. cellulases, lactases
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K 31/7008: Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
- A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 9/2408: {acting on alpha -1,4-glucosidic bonds}
- C12N 9/96: Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
- C12Y 302/0102: Alpha-glucosidase (3.2.1.20)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES

## Abstract

The present application provides for compositions comprising high concentrations of acid α-glucosidase in combination with an active site-specific chaperone for the acid α-glucosidase, and methods for treating Pompe disease in a subject in need thereof, that includes a method of administering to the subject such compositions. The present application also provides methods for increasing the in vitro and in vivo stability of an acid α-glucosidase enzyme formulation.

## Claims

### Claim 1

A composition comprising acid α-glucosidase and an active site-specific chaperone selected from the group consisting of 1-deoxynojirimycin and n-butyldeoxynojirimycin, wherein the acid α-glucosidase is present in an amount greater than about 5 mg/mL.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the acid α-glucosidase enzyme is a recombinant human wild-type acid α-glucosidase.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the active site-specific chaperone is 1-deoxynojirimycin or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 3)

The composition of claim 3, wherein the active site-specific chaperone is a hydrochloride salt of 1-deoxynojirimycin.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the active site-specific chaperone is n-butyl-deoxynojirimycin or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the acid α-glucosidase is present in an amount between about 5 mg/mL and about 250 mg/mL.

### Claim 7 (depends on 6)

The composition of claim 6, wherein the acid α-glucosidase is present in an amount selected from the group consisting of about 25 mg/mL, about 80 mg/mL, about 115 mg/mL, about 160 mg/mL, about 200 mg/mL and about 240 mg/mL.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the active site-specific chaperone is 1-deoxynojirimycin present in an amount between about 0.5 mM and about 20 mM.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the active site-specific chaperone is 1-deoxynojirimycin present in an amount between about 20 mg/mL and about 200 mg/mL.

### Claim 10 (depends on 1)

The composition of claim 1, wherein the composition is formulated for subcutaneous administration to a subject.

### Claim 11 (depends on 1)

The composition of claim 1, wherein the composition is formulated for intravenous administration to a subject.

### Claim 12 (depends on 1)

The composition of claim 1, further comprising a buffer selected from the group consisting of citrate buffer, acetate buffer, bicarbonate buffer, phosphate buffer and combinations thereof.

### Claim 13 (depends on 1)

The composition of claim 1, further comprising an excipient selected from the group consisting of polyethylene glycol 400, arginine, glutamic acid, proline, gamma-cyclodextrin and combinations thereof.

### Claim 14

A method of treating Pompe disease in a subject comprising administering to the subject a composition comprising acid α-glucosidase and an active site-specific chaperone selected from the group consisting of 1-deoxynojirimycin and n-butyldeoxynojirimycin, wherein the acid α-glucosidase is present in an amount greater than about 5 mg/mL.

### Claim 15 (depends on 14)

The method of claim 14, wherein the active site-specific chaperone is 1-deoxynojirimycin or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 14)

The method of claim 14, wherein the acid α-glucosidase is present in an amount between about 5 mg/mL and about 250 mg/mL.

### Claim 17 (depends on 14)

The method of claim 14, wherein the active site-specific chaperone is 1-deoxynojirimycin present in an amount between about 0.5 mM and about 20 mM.

### Claim 18 (depends on 14)

The method of claim 14, wherein the active site-specific chaperone is 1-deoxynojirimycin present in an amount between about 20 mg/mL and about 200 mg/mL.

### Claim 19 (depends on 14)

The method of claim 14, wherein the active site-specific chaperone is n-butyldeoxynojirimycin or a pharmaceutically acceptable salt thereof.

### Claim 20 (depends on 14)

The method of claim 14, wherein the composition is administered subcutaneously.

### Claim 21 (depends on 14)

The method of claim 14, wherein the composition is administered in a sufficient dose to result in a peak concentration of acid α-glucosidase in muscle tissue of the subject within about 10 hours to about 50 hours after the administration of the dose.

### Claim 22 (depends on 14)

The method of claim 14, wherein the composition is administered in a sufficient dose to result in a peak concentration of acid α-glucosidase in muscle tissue of the subject within about 24 hours after the administration of the dose.

### Claim 23 (depends on 14)

The method of claim 14, wherein the composition is a single dose formulation.

### Claim 24 (depends on 14)

The method of claim 14, wherein the composition is a multi-dose formulation.

### Claim 25 (depends on 14)

The method of claim 14, wherein the composition is administered once per day, once every two days, once every three days, once every four days, once every five days, once every six days, or once every seven days.

### Claim 26 (depends on 14)

The method of claim 14, wherein the composition is administered two times per week.

### Claim 27

A method for increasing the stability of acid α-glucosidase in a formulation for subcutaneous administration to a subject, comprising combining the acid α-glucosidase with an active site-specific chaperone selected from the group consisting of 1-deoxynojirimycin and n-butyl-deoxynojirimycin, wherein the acid α-glucosidase is present in an amount greater than about 5 mg/mL.

### Claim 28 (depends on 27)

The method of claim 27, wherein the active site-specific chaperone is 1-deoxynojirimycin or a pharmaceutically acceptable salt thereof.

### Claim 29 (depends on 27)

The method of claim 27, wherein the acid α-glucosidase is present in an amount between about 5 mg/mL and about 250 mg/mL.

### Claim 30 (depends on 27)

The method of claim 27, wherein the active site-specific chaperone is 1-deoxynojirimycin present in an amount between about 0.5 and about 20 mM.

### Claim 31 (depends on 27)

The method of claim 27, wherein the active site-specific chaperone is 1-deoxynojirimycin present in an amount between about 20 mg/mL and about 200 mg/mL.

### Claim 32 (depends on 27)

The method of claim 27, wherein the active site-specific chaperone is n-butyl-deoxynojirimycin or a pharmaceutically acceptable salt thereof.

### Claim 33 (depends on 27)

The method of claim 27, wherein the acid α-glucosidase is combined with the active site-specific chaperone in an amount effective to reduce aggregation of the acid α-glucosidase in the formulation.

### Claim 34 (depends on 27, 28, 29, 30, 31, 32, 33)

The method of any one of claims 27 to 33, wherein the acid α-glucosidase is stabilized in vitro.

### Claim 35 (depends on 27, 28, 29, 30, 31, 32, 33)

The method of any one of claims 27 to 33, wherein the acid α-glucosidase is stabilized in vivo.

### Claim 36 (depends on 25, 26)

The method of claim 25 or 26, wherein the composition is administered via multiple injection sites.

### Claim 37 (depends on 25, 26)

The method of claim 25 or 26, wherein the composition is administered via multiple injection sites simultaneously.

### Claim 38 (depends on 25, 26)

The method of claim 25 or 26, wherein the administration alternates between multiple injection sites.

### Claim 39 (depends on 25, 26)

The method of claim 25 or 26, wherein the administration alternates between a leg and a shoulder blade.

### Claim 40 (depends on 1)

The composition of claim 1, wherein the composition is suitable for self-administration by a patient.

### Claim 41

A method of treating a tissue or an organ affected by Pompe disease in a subject comprising subcutaneous administration to the subject a composition comprising acid α-glucosidase and an active site-specific chaperone selected from the group consisting of 1-deoxynojirimycin and n-butyldeoxynojirimycin, wherein the acid α-glucosidase is present in an amount greater than about 5 mg/mL, and wherein the composition is administered in close proximity to the affected tissue or the organ.

### Claim 42 (depends on 41)

The method of claim 41 wherein the subcutaneous administration of the composition is administered in the patient's leg.

### Claim 43 (depends on 41)

The method of claim 41 wherein the subcutaneous administration of the composition is administered in the patient's torso.

### Claim 44 (depends on 41)

The method of claim 41 wherein the subcutaneous administration of the composition is administered in the patient's back.

### Claim 45 (depends on 41)

The method of claim 41 wherein the subcutaneous administration of the composition is administered in different sites in the patient's body.

### Claim 46 (depends on 41)

The method of claim 41 wherein the subcutaneous administration of the composition is administered in alternative sites in the patient's body.

### Claim 47 (depends on 41)

The method of claim 41 wherein the subcutaneous administration of the composition is administered continuously in the patient's body.

### Claim 48 (depends on 41)

The method of claim 41 wherein the subcutaneous administration of the composition is self-administered by the patient.

### Claim 49 (depends on 41)

The method of claim 41 wherein the subcutaneous administration of the composition is administered in different concentrations.

### Claim 50 (depends on 41)

The method of claim 41 wherein the subcutaneous administration of the composition comprises different doses.

### Claim 51 (depends on 41)

The method of claim 41, wherein the acid α-glucosidase is present in an amount between about 5 mg/mL and about 250 mg/mL.

### Claim 52 (depends on 41)

The method of claim 41, wherein the active site-specific chaperone is 1-deoxynojirimycin present in an amount between about 0.5 mM and about 20 mM.

### Claim 53 (depends on 41)

The method of claim 41, wherein the active site-specific chaperone is 1-deoxynojirimycin present in an amount between about 20 mg/mL and about 200 mg/mL.

### Claim 54 (depends on 41)

The method of claim 41, wherein the composition is administered in a sufficient dose to result in a peak concentration of acid α-glucosidase in the affected tissue or the organ of the subject within about 10 hours to about 50 hours after the administration of the dose.

### Claim 55 (depends on 41)

The method of claim 41, wherein the composition is administered in a sufficient dose to result in a peak concentration of acid α-glucosidase in the affected tissue or the organ of the subject within about 24 hours after the administration of the dose.

### Claim 56 (depends on 41)

The method of claim 41, wherein the composition is a single dose formulation.

### Claim 57 (depends on 41)

The method of claim 41, wherein the composition is a multi-dose formulation.

### Claim 58 (depends on 41)

The method of claim 41, wherein the composition is administered once per day, once every two days, once every three days, once every four days, once every five days, once every six days, or once every seven days.

### Claim 59 (depends on 41)

The method of claim 41, wherein the composition is administered two times per week.

### Claim 60 (depends on 59)

The method of claim 59 wherein once a week the composition is administered in the patient's back and once a week the composition is administered in the patient's leg.