Granted Patent
B2
US 12,721,847 · App. 18/226,633 · Granted Sep 1, 2026
Methods of treating erythropoietic protoporphyria, x-linked protoporphyria, or congenital erythropoietic porphyria with glycine transport inhibitors
Inventors:
Brian Richard MacDonald (Watertown, MA); Maria Gabriela Beconi (Watertown, MA); Vu Hong (Watertown, MA)
Assignee:
Disc Medicine, Inc.
A61K31/496A61K31/69A61K31/785A61K33/26A61K33/44A61K35/14A61K35/28A61K35/407A61K38/10A61K45/06A61P1/16
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The present embodiments are directed to methods of using glycine transporter inhibitors, such as GlyT1 inhibitors, or pharmaceutically acceptable salts, solvates or prodrugs thereof, or pharmaceutical compositions thereof, for preventing or treating erythropoietic protoporphyria (EPP), X-linked protoporphyria (XLPP), and/or congenital erythropoietic porphyria (CEP), and related syndromes thereof.
Claims (3)
1 . A method of treating erythropoietic protoporphyria (EPP), X-linked protoporphyria (XLPP), or congenital erythropoietic porphyria (CEP) in a subject, the method comprising administering to the subject a pharmaceutical composition comprising one or more glycine transporter 1 (GlyT1) inhibitor, or a pharmaceutically acceptable salt thereof, or a prodrug of the one or more GlyT1 inhibitor or its salt.
2 . The method of claim 1 , comprising further administering to the subject an additional active agent and/or supportive therapy.
3 . The method of claim 2 , wherein the additional active agent and/or supportive therapy is selected from the group consisting of: avoiding sunlight, topical sunscreens, skin protection, UVB phototherapy, Afamelanotide, bortezomib, proteasome inhibitors, chemical chaperones, cholestyramine, activated charcoal, iron supplementation, liver transplantation, bone marrow transplantation, splenectomy, and blood transfusion.
Assignments (2)
CORRECTIVE ASSIGNMENT TO CORRECT THE FIRST ASSIGNOR LAST NAME PREVIOUSLY RECORDED ON REEL 66244 FRAME 508. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT.
Recorded May 21, 2026
From: MACDONALD, BRIAN RICHARD; BECONI, MARIA GABRIELA; HONG, VU
To: DISC MEDICINE, INC.
Reel/Frame 075618/0658 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 25, 2024
From: RICHARD, BRIAN RICHARD; BECONI, MARIA GABRIELA; HONG, VU
To: DISC MEDICINE, INC.
Reel/Frame 066244/0508 →
Continuity (4)
Provisional Application
63085942
· Sep 30, 2020
Provisional Application
62958892
· Jan 9, 2020
References Cited (63)
US 7196234B2
· Doswald et al.
· 2007
[cited by applicant]
US 7319099B2
· Jolidon et al.
· 2008
[cited by applicant]
US 7504544B2
· Puentener et al.
· 2009
[cited by applicant]
US 7605163B2
· Jolidon et al.
· 2009
[cited by applicant]
US 7812161B2
· Pfleger et al.
· 2010
[cited by applicant]
US 8039473B2
· Bubendorf et al.
· 2011
[cited by applicant]
US 8124639B2
· McHardy et al.
· 2012
[cited by applicant]
US 8188139B2
· Jolidon et al.
· 2012
[cited by applicant]
US 9012489B2
· Giovannini et al.
· 2015
[cited by applicant]
US 9233953B2
· Hoenke et al.
· 2016
[cited by applicant]
US 9877963B2
· Alberati et al.
· 2018
[cited by applicant]
US 20160271126A1
· Buurman et al.
· 2016
[cited by applicant]
US 20240269132A1
· Quisel et al.
· 2024
[cited by applicant]
US 20240325382A1
· MacDonald et al.
· 2024
[cited by applicant]
US 20240366574A1
· MacDonald et al.
· 2024
[cited by applicant]
US 20240390362A1
· MacDonald et al.
· 2024
[cited by applicant]
US 20250228827A1
· MacDonald et al.
· 2025
[cited by applicant]
US 20250248995A1
· Quisel et al.
· 2025
[cited by applicant]
US 20250262204A1
· MacDonald et al.
· 2025
[cited by applicant]
US 20250302823A1
· Beconi et al.
· 2025
[cited by applicant]
US 20260027107A1
· Quisel et al.
· 2026
[cited by applicant]
WO WO2005094514
· 2005
[cited by applicant]
WO WO2006082001
· 2006
[cited by applicant]
WO WO2008080821
· 2008
[cited by applicant]
WO WO2009068463
· 2009
[cited by applicant]
WO WO2012019970
· 2012
[cited by applicant]
WO WO2015165842
· 2015
[cited by applicant]
WO WO2018192973
· 2018
[cited by applicant]
WO WO2020223419
· 2020
[cited by applicant]
WO WO2021142329
· 2021
[cited by applicant]
WO WO2022192730
· 2022
[cited by applicant]
WO WO2022192731
· 2022
[cited by applicant]
WO WO2022241274
· 2022
[cited by applicant]
WO WO2022251458
· 2022
[cited by applicant]
WO WO2023235326
· 2023
[cited by applicant]
WO WO2025059425
· 2025
[cited by applicant]
Winter, M. et al. “Effects of GlyT1 inhibition on erythropoiesis and iron homeostasis in rats” Experimental Hematology 2016;44:964- 974 (Year: 2016).
[cited by examiner]
PorphyriaFoundation (https://porphyriafoundation.org/for-patients/types-of-porphyria/epp-xlp/) pp. 1-9, accessed 2023 (Year: 2023).
[cited by examiner]
U.S. Appl. No. 18/647,495, filed Apr. 26, 2024, Disc Medicine, Inc.
[cited by applicant]
Balwani M., et al., “Clinical, Biochemical, and Genetic Characterization of North American Patients With Erythropoietic Protoporphyria and X-linked Protoporphyria”, JAMA DermatolOGY, 2017; 153(8):789-796.(Aug. 9, 2017).
[cited by applicant]
Cioffi, “Glycine transporter-1 inhibitors: a patent review (2011-2016)”; Expert Opinion on Therapeutic Patents, 2018, pp. 1-14. https://doi.org/10.1080/13543776.2018.1429408.
[cited by applicant]
Citrome, “A Review of the Pharmacology, Efficacy and Tolerability of Recently Approved and Upcoming Oral Antipsychotics: An Evidence-Based Medicine Approach”, CNS Drugs (2013) 27, pp. 879-911.
[cited by applicant]
Dawe, “An overview of the cutaneous porphyrias”, F1000Research (2017), 6(F1000 Faculty Rev):1906, pp. 1-11.
[cited by applicant]
Freed, et al., “When ribosomes go bad: diseases of ribosome biogenesis”, Mol Biosyst. Mar. 2010 ; 6(3); pp. 481-493.
[cited by applicant]
Halloy, et al., “Repurposing of glycine transport inhibitors for the treatment of erythropoietic protoporphyria”, Cell Chemical Biology (2021) vol. 28, pp. 1-14; 1221-1234, e1-e6; (Epub Mar. 22, 2021). https://doi.org/1…
[cited by applicant]
History of Changes for Study NCT05308472, “Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and PPIX Concentrations in Particpants With EPP,” Mar. 24, 2022, Retrieved from www.clinicaltrials.gov on Ma…
[cited by applicant]
Heerfordt, et al., “Protoporphyrin IX in the skin measured noninvasively predicts photosensitivity in patients with erythropoietic protoporphyria”, British Journal of Dermatology (2016) 175, pp. 1284-1289.
[cited by applicant]
Linenberger, et al., “Updates on the diagnosis and management of the most common hereditary porphyrias: AIP and EPP”, Hematology 2020, pp. 400-410. DOI 10.1182/hematology.2020000124.
[cited by applicant]
Matte, et al., “Bitopertin, a selective oral GLYT1 inhibitor, improves anemia in a mouse model of β-thalassemia”, JCI Insight (2019); 4(22); pp. 1-16: e130111.; https://doi.org/10.1172/jci.insight.130111.
[cited by applicant]
Pinard, et al., “Discovery of benzoylisoindolines as a novel class of potent, selective and orally active GlyT1 inhibitors”, Bioorganic & Medicinal Chemistry Letters 20 (2010), pp. 6960-6965.
[cited by applicant]
Pinard, et al., “Glycine Transporter Type I (GlyT1) Inhibitor, Bitopertin: A Journey from Lab to Patient”, SCS Laureates and Awards & Fall Meeting 2018, Chimia 72 (2018), pp. 477-484.
[cited by applicant]
Winter, et al., “Effects of GlyT1 inhibition on erythropoiesis and iron homeostasis in rats”, Experimental Hematology (2016) vol. 44, pp. 964-974, 974.e1-974.e4.
[cited by applicant]
Wulf HC, et al., “Inactivation of protoporphyrin IX in erythrocytes in patients with erythropoietic protoporphyria: A new treatment modality”, Photodiagnosis Photodyn Ther. 2020;29:101582.(Dec. 3, 2019).
[cited by applicant]
Yang, et al., “Delayed globin synthesis leads to excess heme and the macrocytic anemia of Diamond Blackfan anemia and del(5q) myelodysplastic syndrome”, Science Translational Medicine, May 11, 2016; vol. 8 Issue 338 338…
[cited by applicant]
PCT International Search Report for PCT/US2021/012786, dated Apr. 12, 2021 (7 pages).
[cited by applicant]
PCT International Search Report for PCT/US2023/023886, dated Jul. 25, 2023 (17 pages).
[cited by applicant]
PCT International Search Report for PCT/US2022/029283, dated Aug. 2, 2022 (6 pages).
[cited by applicant]
PCT International Search Report for PCT/US2022/031081, dated Aug. 2, 2022 (6 pages).
[cited by applicant]
Puy, et al., “Heme-Related Blood Disorders”, Blood, 2013, vol. 122, No. 21, http://doi.org/10.1182/blood.V122.21.SCI-18.SCI-18.
[cited by applicant]