IP Library › Granted Patent US 12,194,079
Granted Patent B2
US 12,194,079 · App. 16/476,084 · Granted Jan 14, 2025

Therapeutic regimen for the treatment of Fabry using stabilized alpha-galactosidase

Inventors: Einat Almon (Timrat, IL); Raul Chertkoff (Adi, IL); Sari Alon (Kibbutz Moran, IL); Yoseph Shaaltiel (Timrat, IL)
Assignee: Protalix Ltd.
A61K38/47C12N15/85C12Y302/01022
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Quick Facts
Patent No.
US 12,194,079
App. No.
16/476,084
Granted
Jan 14, 2025
Kind
B2
Abstract

Methods of treating Fabry disease via administration of stabilized plant recombinant human alpha galactosidase protein comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety, and unit dosages of protein are disclosed herein. The disclosed protocols are safe, have greater than 2 week intervals between administrations and exhibit important improvement in patient's disease parameters, in terms of reduced Gb3 accumulation, pain and GI parameters, kidney and cardiac stabilization in the clinical setting.

Claims (10)

1. A method of treating Fabry disease in a human subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of recombinant human α-galactosidase A, wherein said therapeutically effective amount of said recombinant human α-galactosidase A is 2.0 mg/Kg body weight, thereby treating Fabry disease in the subject, wherein said administering is effected in intervals of 4 weeks and wherein said recombinant human a-galactosidase A is plant recombinant human α-galactosidase A cross-linked with bis-NHS-PEG 45 , and wherein said subject is a subject maintaining a similar rate of deterioration in at least one Fabry disease parameter following administration of said recombinant human α-galactosidase A at the indicated dosage of 2.0 mg/kg body weight at intervals of 4 weeks.

2. The method of claim 1 , wherein administration of said therapeutically effective amount of recombinant human α-galactosidase results in at least one of the following in said subject:

(i) attenuation of deterioration of cardiac parameters Left Ventricle Mass (LVM) or Left Ventricle Mass Index (LVMI);

(ii) attenuation of Fabry disease-related deterioration of kidney function;

(iii) attenuation of deterioration of at least one gastrointestinal parameter; or

(iv) attenuation of deterioration of a Mainz Severity Score Index (MSSI) score.

3. The method of claim 1 , wherein said recombinant human α-galactosidase A has a circulating half-life (T 1/2 ) of at least 50 hours following administration.

4. The method of claim 1 , wherein said recombinant human α-galactosidase A has a C max of at least 8000 ng/ml following administration of 2 mg/Kg body weight.

5. The method of claim 1 , wherein said recombinant human α-galactosidase A has a bioavailability (AUC 0-∞ ) of at least 400,000 ng*hr/ml following administration of 2.0 mg/Kg body weight of said recombinant human α-galactosidase A.

6. The method of claim 1 , wherein administration of said therapeutically effective amount of recombinant human α-galactosidase A in intervals of 4 weeks does not result in de novo serum anti-recombinant human α-galactosidase A antibodies after 12 months of treatment.

Assignments (3)
RELEASE OF SECURITY INTEREST Recorded Sep 6, 2024
From: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS COLLATERAL AGENT
To: PROTALIX LTD.
Reel/Frame 068856/0589 →
SECURITY INTEREST Recorded Sep 3, 2021
From: PROTALIX LTD.
To: WILMINGTON SAVINGS FUND SOCIETY, FSB
Reel/Frame 057383/0155 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 11, 2019
From: ALMON, EINAT; CHERTKOFF, RAUL; ALON, SARI; SHAALTIEL, YOSEPH
To: PROTALIX LTD.
Reel/Frame 049723/0148 →
Continuity (2)
Provisional Application 62442537 · Jan 5, 2017
Related Publication 20200155654A1 · May 21, 2020
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