IP Library Granted Patent US 12,509,729
Granted Patent B2
US 12,509,729 · App. 17/815,647 · Granted Dec 30, 2025

Compositions and methods for the diagnosis and treatment of lymphatic system disorders

Inventors: Hakon Hakonarson (Malvern, PA); Dong Li (Drexel Hill, PA); Lifeng Tian (Wilmington, DE); Kenny Nguyen (Aberdeen, NJ); Patrick Sleiman (Philadelphia, PA)
Assignee: THE CHILDREN'S HOSPTAL OF PHILADELPHIA
C12Q1/6883A61K31/4184A61K31/436A61K31/4427A61K31/4709A61K31/501A61K31/519A61K31/5377A61P43/00A61K45/06C12Q2600/156
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Quick Facts
Patent No.
US 12,509,729
App. No.
17/815,647
Granted
Dec 30, 2025
Kind
B2
Abstract

Compositions and methods for the diagnosis and treatment of lymphatic anomaly are disclosed.

Claims (9)

1 . A method for treating a lymphatic anomaly in a human patient, wherein the patient has a single nucleotide variation (SNV) in ARAF, the method comprising administering an effective amount of an agent selected from one or more mTOR inhibitors, one or more PIK3K inhibitors, one or more MEK/ERK inhibitors, and a combination of any of said agents, thereby treating the lymphatic anomaly, wherein

the SNV in ARAF is a mutation of a conserved phosphorylation site in ARAF.

2 . The method of claim 1 , wherein the lymphatic anomaly is characterized by abnormal formation of lymphatic vessels and/or tissue overgrowth.

3 . The method of claim 1 , wherein the lymphatic anomaly is lymphangiomatosis (LAM).

4 . The method of claim 1 , wherein the lymphatic anomaly is generalized lymphatic anomaly (GLA).

5 . The method of claim 1 , wherein the lymphatic anomaly is characterized by chylous effusions, including pericardial, pleural, or peritoneal effusions.

6 . The method of claim 1 , wherein the treatment further comprises administering systemic chemotherapy, interferon alfa, radiotherapy, and/or surgery.

7 . The method of claim 1 , wherein the SNV is associated with a disruption or aberration in PI3K/mTOR signaling pathway.

8 . The method of claim 1 , wherein said one or more agents are selected from the group consisting of rapamycin, everolimus, AZD8055, temsirolimus, KU-0063794, MHY1485, BEZ235, PI-103, torkinib, tacrolimus, selumetinib, PD0325901, trametinib, pimasertib, AZD8330, binimetinib, SL-327, refametinib, cobimetinib, ridaforolimus, INK 128, voxtalisib, torin 1, omipalisib, OSI-027, PF-04691502, apitolisib, GSK1059615, gedatolisib, WYE-354, AZD2014, torin 2, WYE-125123, PP121, WYE-687, CH5132799, WAY-600, ETP-46464, GDC-0349, XL388, zotarolimus, BGT226, palomid 529, chrysophanic acid, TAK-733, and PD184352.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 30, 2022
From: HAKONARSON, HAKON; SLEIMAN, PATRICK; NGUYEN, KENNY; TIAN, LIFENG; LI, DONG
To: THE CHILDREN'S HOSPITAL OF PHILADELPHIA
Reel/Frame 060940/0392 →
Continuity (3)
Continuation 16327060
Provisional Application 62382147 · Aug 31, 2016
Related Publication 20230048706A1 · Feb 16, 2023
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