IP Library › Granted Patent US 12,496,287
Granted Patent B2
US 12,496,287 · App. 17/771,172 · Granted Dec 16, 2025

Compositions and methods for treating macrophage activation syndrome

Inventors: Edward M. Behrens (West Chester, PA); Chhanda Biswas (Wynnewood, PA)
Assignee: THE CHILDREN'S HOSPITAL OF PHILADELPHIA
A61K31/225A61K45/06A61P37/00
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,496,287
App. No.
17/771,172
Granted
Dec 16, 2025
Kind
B2
Abstract

Compositions and methods for treating macrophage activation syndrome are provided.

Claims (8)

1 . A method for inhibiting, treating, and/or preventing macrophage activation syndrome, hemophagocytic lymphohistiocytosis (HLH), or adult-onset Still's disease (ASD) in a subject, said method comprising administering to said subject monomethyl fumarate or a pharmaceutically acceptable salt or prodrug thereof and/or dimethyl fumarate or a pharmaceutically acceptable salt or prodrug thereof.

2 . The method of claim 1 for inhibiting, treating, and/or preventing macrophage activation syndrome.

3 . The method of claim 1 , comprising administering to said subject monomethyl fumarate or a pharmaceutically acceptable salt or prodrug thereof.

4 . The method of claim 1 , comprising administering to said subject dimethyl fumarate or a pharmaceutically acceptable salt or prodrug thereof.

5 . The method of claim 2 , further comprising diagnosing macrophage activation syndrome in the subject prior to administration of the therapy.

6 . The method of claim 2 , further comprising monitoring macrophage activation syndrome in the subject prior to, during, and/or after administration of the therapy.

7 . The method of claim 1 , further comprising administering at least one other therapeutic for the treatment of macrophage activation syndrome.

8 . The method of claim 7 , wherein said other therapeutic is selected from the group consisting of corticosteroids, glucocorticoids, cyclosporine A, and interferon gamma (IFN-γ) inhibitors.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 29, 2022
From: BEHRENS, EDWARD; BISWAS, CHHANDA
To: THE CHILDREN'S HOSPITAL OF PHILADELPHIA
Reel/Frame 060925/0966 →
Continuity (2)
Provisional Application 62932551 · Nov 8, 2019
Related Publication 20220362196A1 · Nov 17, 2022
References Cited (25)
US 8669281B1 · Zeidan et al. · 2014 [cited by applicant]
US 10040859B2 · Behrens et al. · 2018 [cited by applicant]
US 20120165404A1 · Lukashev · 2012 [cited by applicant]
US 20130216615A1 · Goldman · 2013 [cited by applicant]
US 20140093449A1 · Williams et al. · 2014 [cited by applicant]
US 20160214948A1 · Albrecht et al. · 2016 [cited by applicant]
US 20180117171A1 · Mooney et al. · 2018 [cited by applicant]
US 20190167638A1 · Rajasekhar · 2019 [cited by applicant]
US 20190256481A1 · Virsik et al. · 2019 [cited by applicant]
WO 2019173676A1 · 2019 [cited by applicant]
Biswas et al., “MonomethylFumarate as a Novel Therapy for Macrophage Activation Syndrome: Mechanism o fAction in an Animal Model”, Oct. 3, 2019 (Oct. 3, 2019) ArthritisRheumatol. 2019;71(suppl10), retrieved on Mar. 17, … [cited by examiner]
Biswas, et al., “Amelioration of Murine Macrophage Activation Syndrome by Monomethyl Fumarate in Both a Heme Oxygenase 1-Dependent and Heme Oxygenase 1-Independent Manner” Arthritis Rheumatol. (2021) 73(5):885-895. [cited by applicant]
Biswas, et al., “Monomethyl Fumarate as a Novel Therapy for Macrophage Activation Syndrome: Mechanism of Action in an Animal Model” Arthritis Rheumatol. (2019) 71 (suppl 10):Abstract 811; available at https://acrabstrac… [cited by applicant]
Gold, et al., “Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: Interim analysis of Endorse, a randomized extension study” Mult. Scler. (2017) 23(2):253-265. [cited by applicant]
Singh, et al., “Neuro-protective effect of monomethyl fumarate on ischemia reperfusion injury in rats: Role of Nrf2/HO1 pathway in peri-infarct region” Neurochem. Int. (2019) 126:96-108. [cited by applicant]
Behrens, et al., “Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice” J. Clin. Invest. (2011) 121(6):2264-77. [cited by applicant]
Weaver, et al., “TLR9-mediated inflammation drives a Ccr2-independent peripheral monocytosis through enhanced extramedullary monocytopoiesis” Proc. Natl. Acad. Sci. (2016) 113(39):10944-9. [cited by applicant]
Yu, et al., “Sulforaphane Suppresses Hepatitis C Virus Replication by Up-Regulating Heme Oxygenase-1 Expression through PI3K/Nrf2 Pathway” PLoS One (2016) 11(3):e0152236. [cited by applicant]
Uddin, et al., “Carbon Monoxide Inhibits Tenascin-C Mediated Inflammation via IL-10 Expression in a Septic Mouse Model” Mediators Inflamm. (2015) 2015:613249. [cited by applicant]
Lee, et al., “Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice” Nat. Med. (2002) 8(3):240-6. [cited by applicant]
Drechsler, et al., “Heme oxygenase-1 mediates the anti-inflammatory effects of acute alcohol on IL-10 induction involving p38 MAPK activation in monocytes” J. Immunol. (2006) 177(4):2592-600. [cited by applicant]
Weaver, et al., “Hyperinflammation, rather than hemophagocytosis, is the common link between macrophage activation syndrome and hemophagocytic lymphohistiocytosis” Curr. Opin. Rheumatol. (2014) 26(5):562-9. [cited by applicant]
Weaver, et al., “Brief Report: Interferon-γ-Mediated Immunopathology Potentiated by Toll-Like Receptor 9 Activation in a Murine Model of Macrophage Activation Syndrome” Arthritis Rheumatol. (2019) 71(1):161-168. [cited by applicant]
Rood, et al., “IL-10 distinguishes a unique population of activated, effector-like CD8 + T cells in murine acute liver inflammation” J. Leukoc. Biol. (2017) 101(4):1037-1044. [cited by applicant]
Weaver, et al., “Weathering the storm: Improving therapeutic interventions for cytokine storm syndromes by targeting disease pathogenesis” Curr. Treatm. Opt. Rheumatol. (2017) 3(1):33-48. [cited by applicant]