Granted Patent
B2
US 12,673,093 · App. 18/344,083 · Granted Jul 7, 2026
Method and composition for treating arginase 1 deficiency
Inventors:
Scott W. Rowlinson (Austin, TX); Anthony G. Quinn (Gloucester, MA); Ann Lowe (Austin, TX); David Lowe (Austin, TX)
Assignee:
Immedica Pharma AB
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Abstract
A method and composition to treat a subject with arginase 1 (ARG1) deficiency (ARG1-D) and to rapidly reduce the levels of at least one of arginine and/or a guanidino compound in the subject.
Claims (22)
1 . A method for reducing a plasma level of at least one compound selected from the group consisting of: arginine, N-α-acetylarginine (NAArg), argininic acid (ArgA), α-keto-δ-guanidinovaleric acid (GVA), guanidinoacetic acid (GAA), to a normal level in a subject with Arginase 1 (ARG1) deficiency (ARG1-D) comprising administering to the subject a composition comprising a therapeutically effective amount of a pegylated arginase, wherein the pegylated arginase is administered intravenously initially at a dosage of about 0.1 mg/kg, and weekly thereafter either subcutaneously or intravenously at a dosage of about 0.01 mg/kg to about 1.00 mg/kg.
2 . The method of claim 1 , wherein the pegylated arginase is administered intravenously initially at a dosage of about 0.1 mg/kg, and weekly thereafter either subcutaneously or intravenously at a dosage of about 0.01 mg/kg to about 0.50 mg/kg.
3 . The method of claim 2 , wherein the pegylated arginase is administered intravenously initially at a dosage of about 0.1 mg/kg, and weekly thereafter either subcutaneously or intravenously at a dosage of about 0.01 mg/kg to about 0.25 mg/kg.
4 . The method of any one of claims 1-3 , wherein the pegylated arginase is pegzilarginase.
5 . The method of claim 1 , wherein a plasma level of at least one compound selected from the group consisting of: ArgA, NAArg, GVA, GAA, and arginine, is reduced to a normal level in the subject in less than 3 days after initial administration of the pegylated arginase.
6 . The method of claim 1 , wherein a plasma level of at least one compound selected from the group consisting of: ArgA, NAArg, GVA, GAA, and arginine, is reduced to a normal level in the subject in less than 2 days after initial administration of the pegylated arginase.
7 . The method of claim 1 , wherein a plasma level of at least one compound selected from the group consisting of: ArgA, NAArg, GVA, GAA, and arginine, is reduced to a normal level in the subject in less than 1 day after initial administration of the pegylated arginase.
8 . The method of claim 1 , wherein the dosage of the pegylated arginase administered to the subject is sufficient to reduce by at least 2 fold a plasma level of at least one compound selected from the group consisting of: ArgA, NAArg, GVA, GAA, and arginine, wherein the plasma level is assayed about 24 to 48 hours after administration of the pegylated arginase.
9 . A method for reducing a plasma level of at least one compound selected from the group consisting of: arginine, N-α-acetylarginine (NAArg), argininic acid (ArgA), α-keto-δ-guanidinovaleric acid (GVA), guanidinoacetic acid (GAA), to a normal level in a subject with Arginase 1 (ARG1) deficiency (ARG1-D) comprising administering to the subject a composition comprising a therapeutically effective amount of a pegylated arginase, wherein the pegylated arginase is administered subcutaneously initially at a dosage of about 0.1 mg/kg, and weekly thereafter either subcutaneously or intravenously at a dosage of about 0.01 mg/kg to about 1.00 mg/kg.
10 . The method of claim 9 , wherein the pegylated arginase is administered subcutaneously initially at a dosage of about 0.1 mg/kg, and weekly thereafter either subcutaneously or intravenously at a dosage of about 0.01 mg/kg to about 0.50 mg/kg.
11 . The method of claim 10 , wherein the pegylated arginase is administered subcutaneously initially at a dosage of about 0.1 mg/kg, and weekly thereafter either subcutaneously or intravenously at a dosage of about 0.01 mg/kg to about 0.25 mg/kg.
12 . The method of any one of claims 9-11 , wherein the pegylated arginase is pegzilarginase.
13 . The method of claim 9 , wherein a plasma level of at least one compound selected from the group consisting of: ArgA, NAArg, GVA, GAA, and arginine, is reduced to a normal level in the subject in less than 3 days after initial administration of the pegylated arginase.
14 . The method of claim 9 , wherein a plasma level of at least one compound selected from the group consisting of: ArgA, NAArg, GVA, GAA, and arginine, is reduced to a normal level in the subject in less than 2 days after initial administration of the pegylated arginase.
15 . The method of claim 9 , wherein a plasma level of at least one compound selected from the group consisting of: ArgA, NAArg, GVA, GAA, and arginine, is reduced to a normal level in the subject in less than 1 day after initial administration of the pegylated arginase.
16 . The method of claim 9 , wherein the dosage of the pegylated arginase administered to the subject is sufficient to reduce by at least 2 fold a plasma level of at least one compound selected from the group consisting of: ArgA, NAArg, GVA, GAA, and arginine, wherein the plasma level is assayed about 24 to 48 hours after administration of the pegylated arginase.
17 . The method of claim 1 , wherein the subject has a minimal clinically important difference (MCID) of greater than 1 after 9 days of treatment.
18 . The method of claim 17 , wherein the plasma level of arginine is correlated with the MCID.
19 . The method of claim 1 , wherein the pegylated arginase has the sequence of SEQ ID NO: 13.
20 . The method of claim 19 , wherein the pegylated arginase lacks the N-terminal methionine.
21 . The method of claim 9 , wherein the pegylated arginase has the sequence of SEQ ID NO: 13.
22 . The method of claim 21 , wherein the pegylated arginase lacks the N-terminal methionine.
Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Nov 21, 2023
From: LOWE, DAVID; LOWE, ANN
To: AERASE, INC.
Reel/Frame 065637/0650 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Nov 21, 2023
From: ROWLINSON, SCOTT W.; QUINN, ANTHONY G.
To: AERASE, INC.
Reel/Frame 065637/0840 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 2, 2023
From: AEGLEA BIOTHERAPEUTICS, INC.; AERASE, INC.
To: IMMEDICA PHARMA AB
Reel/Frame 065100/0963 →
Continuity (5)
Provisional Application
62745000
· Oct 12, 2018
Provisional Application
62725612
· Aug 31, 2018
Provisional Application
62594747
· Dec 5, 2017
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