IP Library › Granted Patent US 12,734,160
Granted Patent B2
US 12,734,160 · App. 17/428,504 · Granted Sep 15, 2026

Methods for treating symptoms and disorders associated with lysosomal storage diseases

Inventors: Nigel Patrick Somerville Crawford (Califon, NJ); Tanya Zaremba Fischer (Newton, MA)
Assignee: Genzyme Corporation
A61K31/439A61K38/47A61P3/00A61P17/00A61P25/02C12Y302/01045
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Quick Facts
Patent No.
US 12,734,160
App. No.
17/428,504
Granted
Sep 15, 2026
Kind
B2
Abstract

This disclosure to methods for treating or preventing particular symptoms and disorders which are associated with lysosomal storage diseases using quinuclidine compounds of formula (I), optionally in combination with enzyme replacement therapy. This includes pain, such as abdominal pain, and dermatological disorders, such as angiokeratoma, in a patient having a disease such as Fabry disease. Also disclosed is a pharmaceutical composition comprising a quinuclidine compound for use in said methods.

Claims (25)

1 . A method for treating pain associated with Fabry disease, comprising: administering to a human subject in need thereof an effective amount of a compound of formula (I),

or a pharmaceutically acceptable salt or prodrug thereof, wherein:

R 1 is selected from hydrogen, halogen, cyano, nitro, hydroxy, thio, amino, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 1-6 -alkyloxy, C 2-6 -alkenyloxy, and C 2-6 -alkynyloxy;

R 2 and R 3 are independently selected from C 1-3 -alkyl, or R 2 and R 3 together form a cyclopropyl or cyclobutyl group;

R 4 , R 5 and R 6 are each independently selected from hydrogen, halogen, nitro, hydroxy, thio, amino, C 1-6 -alkyl, and C 1-6 -alkyloxy; and

A is a 5- or 6-membered aryl or heteroaryl group.

2 . The method of claim 1 , wherein R 2 and R 3 are each independently selected from C 1-2 -alkyl.

3 . The method of claim 1 , wherein R 4 is selected from a halogen, C 1-3 -alkyl, and C 1-3 -alkyloxy.

4 . The method of claim 1 , wherein R 4 is fluorine or 2-methoxyethoxy, and R 5 and R 6 are hydrogen.

5 . The method of claim 1 , wherein A is chosen from phenyl and a 5-membered heteroaryl group comprising 1 or 2 heteroatoms selected from N and S.

6 . The method of claim 1 , wherein said compound is a compound of formula (II), (III), (IV), (V), (VI), (VII), (VIII), (IX) or (XI),

or a pharmaceutically acceptable salt or prodrug thereof.

7 . The method of claim 1 , wherein said compound is selected from: quinuclidin-3-yl (2-(4′-fluoro-[1,1′-biphenyl]-3-yl) propan-2-yl) carbamate; (S)-quinuclidin-3-yl (2-(2-(4-fluorophenyl) thiazol-4-yl) propan-2-yl) carbamate; (S)-quinuclidin-3-yl (2-(4′-(2-methoxyethoxy)-[1,1′-biphenyl]-4-yl) propan-2-yl) carbamate; and the pharmaceutically acceptable salts and prodrugs thereof; and (S)-quinuclidin-3-yl (2-(2-(4-fluorophenyl) thiazol-4-yl) propan-2-yl) carbamate in malate salt form.

8 . The method of claim 1 , wherein the pain is selected from the group consisting of neuropathic pain, gastrointestinal pain, and peripheral neuropathy.

9 . The method of claim 1 , wherein the method comprises administering the compound of formula (I) by systemic administration.

10 . The method of claim 1 , wherein the method comprises administering the compound of formula (I) in a single daily dose of 5 mg, 10 mg, 15 mg, or 20 mg.

11 . The method of claim 1 , wherein the pain is abdominal pain.

12 . The method of claim 1 , wherein the method comprises administering the compound of formula (I) in a daily dose of about 1 mg to about 150 mg of the compound.

13 . The method of claim 1 , wherein the method comprises administering the compound of formula (I) by systemic administration in a daily dose of about 1 mg to about 150 mg of the compound.

14 . The method of claim 1 , wherein the compound of formula (I) is (S)-quinuclidin-3-yl (2-(2-(4-fluorophenyl) thiazol-4-yl) propan-2-yl) carbamate or a pharmaceutically acceptable salt thereof.

15 . The method of claim 14 , wherein the method comprises administering (S)-quinuclidin-3-yl (2-(2-(4-fluorophenyl) thiazol-4-yl) propan-2-yl) carbamate in a single daily dose of 15 mg, or an equivalent amount of a pharmaceutically acceptable salt thereof.

16 . The method of claim 8 , wherein the compound of formula (I) is(S)-quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl) propan-2-yl)carbamate or a pharmaceutically acceptable salt thereof.

17 . The method of claim 9 , wherein the compound of formula (I) is(S)-quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl) propan-2-yl)carbamate or a pharmaceutically acceptable salt thereof.

18 . The method of claim 10 , wherein the compound of formula (I) is(S)-quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl) propan-2-yl)carbamate or a pharmaceutically acceptable salt thereof.

19 . The method of claim 11 , wherein the compound of formula (I) is(S)-quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl) propan-2-yl)carbamate or a pharmaceutically acceptable salt thereof.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 12, 2025
From: CRAWFORD, NIGEL PATRICK SOMERVILLE; FISCHER, TANYA ZAREMBA
To: GENZYME CORPORATION
Reel/Frame 071993/0669 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 17, 2025
From: CRAWFORD, NIGEL PATRICK SOMERVILLE; FISCHER, TANYA ZAREMBA
To: GENZYME CORPORATION
Reel/Frame 071749/0119 →
Continuity (6)
Provisional Application 62962647 · Jan 17, 2020
Provisional Application 62937618 · Nov 19, 2019
Provisional Application 62894167 · Aug 30, 2019
Provisional Application 62851433 · May 22, 2019
Provisional Application 62800996 · Feb 4, 2019
Related Publication 20220023273A1 · Jan 27, 2022
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