Granted Patent
B2
US 12,522,614 · App. 18/297,698 · Granted Jan 13, 2026
Topical phosphoinositide 3-kinase inhibitors
Inventors:
Ahmed F. Abdel-Magid (Ambler, PA); Agis Kydonieus (Kendall Park, NJ); Thomas Rossi (Portsmouth, NH); Hock S. Tan (North Brunswick, NJ)
Assignee:
Venthera, Inc.
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Abstract
The present invention provides compounds and topical formulations including the compounds for the treatment of vascular malformations, wherein the compounds are according to formula (I): wherein subscript m, L 1 , R 1 , and L 1 -R 1 are as described herein.
Claims (14)
1 . A compound having formula (I):
or a hydrate, solvate, and/or a pharmaceutically acceptable salt thereof,
wherein:
subscript m is an integer from 0 to 2;
L 1 is —C(O)—, —C(O)O—, or —C(O)S—; and
R 1 is C 1-6 alkyl or C 2-6 alkenyl.
2 . The compound of claim 1 , wherein m is 0 or 1.
3 . The compound of claim 1 , having formula (II):
4 . The compound of claim 1 , having formula (IIa):
5 . The compound of claim 4 , wherein R 1 is methyl, ethyl, propyl, or isopropyl.
6 . The compound of claim 1 , selected from the group consisting of:
7 . The compound of claim 1 , selected from the group consisting of:
8 . The compound of claim 1 , selected from the group consisting of:
9 . The compound of claim 1 , represented by the formula:
Assignments (3)
RELEASE OF SECURITY INTEREST IN PATENT COLLATERAL
Recorded Mar 5, 2025
From: BLUE OWL CAPITAL CORPORATION, AS ADMINISTRATIVE AGENT
To: BRIDGEBIO PHARMA, INC.; QED THERAPEUTICS, INC.; EIDOS THERAPEUTICS, INC.; ML BIO SOLUTIONS INC.; CALCILYTIX THERAPEUTICS INC.; ADRENAS THERAPEUTICS INC.; PHOENIX TISSUE REPAIR, INC.; NAVIRE PHARMA, INC.; VENTHERA, INC.; MOLECULAR SKIN THERAPEUTICS, INC.; CANTERO THERAPEUTICS, INC.; COA THERAPEUTICS, INC.; PORTAL THERAPEUTICS, INC.; BRIDGEBIO GENE THERAPY RESEARCH, INC.; FERRO THERAPEUTICS, INC.
Reel/Frame 070551/0095 →
SECURITY INTEREST
Recorded Jan 19, 2024
From: BRIDGEBIO PHARMA, INC.; QED THERAPEUTICS, INC.; EIDOS THERAPEUTICS, INC.; THERAS, INC.; ML BIO SOLUTIONS INC.; CALCILYTIX THERAPEUTICS INC.; ADRENAS THERAPEUTICS INC.; PHOENIX TISSUE REPAIR, INC.; NAVIRE PHARMA, INC.; VENTHERA, INC.; MOLECULAR SKIN THERAPEUTICS, INC.; CANTERO THERAPEUTICS, INC.; COA THERAPEUTICS, INC.; PORTAL THERAPEUTICS, INC.; BRIDGEBIO GENE THERAPY RESEARCH, INC.; FERRO THERAPEUTICS, INC.; SUB21, INC.
To: BLUE OWL CAPITAL CORPORATION, AS ADMINISTRATIVE AGENT
Reel/Frame 066355/0126 →
SECURITY INTEREST
Recorded Jan 17, 2024
From: CALCILYTIX THERAPEUTICS INC.; ADRENAS THERAPEUTICS INC.; PHOENIX TISSUE REPAIR, INC.; NAVIRE PHARMA, INC.; VENTHERA, INC.; MOLECULAR SKIN THERAPEUTICS, INC.; CANTERO THERAPEUTICS, INC.; COA THERAPEUTICS, INC.; PORTAL THERAPEUTICS, INC.; BRIDGEBIO GENE THERAPY RESEARCH, INC.; FERRO THERAPEUTICS, INC.; SUB21, INC.
To: BLUE OWL CAPITAL CORPORATION, AS ADMINISTRATIVE AGENT
Reel/Frame 066342/0154 →
Continuity (4)
Provisional Application
62958049
· Jan 7, 2020
Provisional Application
62802093
· Feb 6, 2019
References Cited (59)
US 6838457B2
· Hayakawa et al.
· 2005
[cited by applicant]
US 8906909B2
· Cai et al.
· 2014
[cited by applicant]
US 8921361B2
· Cmiljanovic et al.
· 2014
[cited by applicant]
US 20040009978A1
· Hayakawa
· 2004
[cited by applicant]
US 20100137449A1
· Tripp et al.
· 2010
[cited by applicant]
US 20110275762A1
· Cmiljanovic et al.
· 2011
[cited by applicant]
US 20130189260A1
· Hanson et al.
· 2013
[cited by applicant]
US 20130189274A1
· Berkenblit et al.
· 2013
[cited by applicant]
US 20130203847A1
· Chappell et al.
· 2013
[cited by applicant]
US 20130345232A1
· Lane et al.
· 2013
[cited by applicant]
US 20180117055A1
· Baselga et al.
· 2018
[cited by applicant]
US 20210060031A1
· Baselga et al.
· 2021
[cited by applicant]
US 20220040193A1
· Kydonieus et al.
· 2022
[cited by applicant]
CN 102268014A
· 2011
[cited by applicant]
EP 3251657A1
· 2017
[cited by applicant]
EP 3563840A1
· 2019
[cited by applicant]
WO WO2001083456A1
· 2001
[cited by applicant]
WO WO2006046040A1
· 2006
[cited by applicant]
WO WO2007021933A2
· 2007
[cited by applicant]
WO WO2009052145A1
· 2009
[cited by applicant]
WO WO2010053489A1
· 2010
[cited by applicant]
WO WO2010080996A1
· 2010
[cited by applicant]
WO WO2012051416A1
· 2012
[cited by applicant]
WO WO2013015833A2
· 2013
[cited by applicant]
WO WO2013182668A1
· 2013
[cited by applicant]
WO WO2014046617A1
· 2014
[cited by applicant]
WO WO2016187157A1
· 2016
[cited by applicant]
WO WO2017140828A1
· 2017
[cited by applicant]
WO WO2020163525A1
· 2020
[cited by applicant]
Database CAS Registry No. 1349711-67-6, STN entry date Dec. 6, 2011.
[cited by applicant]
European Patent Office, Extended European Search Report for EP Application No. 20752673.2, mailed Feb. 3, 2023, 13 pages.
[cited by applicant]
Al-Olabi et al., Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to targeted therapy, The Journal of Clinical Investigation, Apr. 2018, vol. 128, No. 4, pp. 1496-1508.
[cited by applicant]
Asano et al., Suzuki-Miyaura cross-coupling reaction of aryl and heteroaryl pinacol boronates for the synthesis of 2-substituted pyrimidines, Tetrahedron, 2012, vol. 68, pp. 272-279.
[cited by applicant]
Castel et al., Somatic PIK3CA mutations as a driver of sporadic venous malformations, Science Translational Medicine, Mar. 30, 2016, vol. 8, No. 332, pp. 1-10, 11 pages.
[cited by applicant]
Couto et al., A Somatic MAP3K3 Mutation Is Associated with Verrucous Venous Malformation, The American Journal of Human Genetics, Mar. 5, 2015, vol. 96, pp. 480-486.
[cited by applicant]
Dannemann et al., Phosphatidylinositol 4,5-bisphosphate (PIP2)-specific AKT1 is oncogenic, Int J Cancer, Jul. 1, 2010, vol. 127, No. 1, pp. 239-244.
[cited by applicant]
Di Blasio et al., PI3K/mTOR inhibition promotes the regression of experimental vascular malformations driven by PIK3CA-activating mutations. Cell Death & Disease, 2018, vol. 9, No. 2, Article No. 25, 15 pages.
[cited by applicant]
European Patent Office, extended European Search Report for European Patent Application No. 16797120.9 mailed Dec. 14, 2018, 9 pages.
[cited by applicant]
European Patent Office, Partial supplementary European search report for EP Application No. 20752673.2, mailed Oct. 11, 2022, 12 pages.
[cited by applicant]
Fritsch et al., Characterization of the Novel and Specific PI3Kα Inhibitor NVP-BYL719 and Development of the Patient Stratification Strategy for Clinical Trials, American Association for Cancer Research Journals, Molecu…
[cited by applicant]
Hayakawa et al., Synthesis and biological evaluation of 4-morpholino-2-phenylquinazolines and related derivatives as novel PI3 kinase p110α inhibitors, Bioorganic & Medicinal Chemistry, 2006, vol. 14, pp. 6847-6858.
[cited by applicant]
Hu et al., Tie2-R849W Mutant in Venous Malformations Chronically Activates a Functional STAT1 to Modulate Gene Expression, Journal of Investigative Dermatology, 2008, vol. 128, pp. 2325-2333.
[cited by applicant]
International Search Report for International Application No. PCT/US2016/032779, mailed Sep. 15, 2016, 5 pages.
[cited by applicant]
International Search Report for PCT/US2020/016876, mailed Jun. 15, 2020, 4 pages.
[cited by applicant]
International Search report for International Application No. PCT/US2021/044381, mailed Nov. 29, 2021, 5 pages.
[cited by applicant]
Kangas et al., Development of Molecular Therapies for Venous Malformations, Basic & Clinical Pharmacology & Toxicology, 2018, vol. 123, pp. 6-19.
[cited by applicant]
Kurek et al., Somatic Mosaic Activating Mutations in PIK3CA Cause CLOVES Syndrome, The American Journal of Human Genetics, Jun. 8, 2012, vol. 90, pp. 1108-1115.
[cited by applicant]
Luks et al., Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA, J. Pediatr., Apr. 2015, vol. 166, No. 4, pp. 1048-1054.
[cited by applicant]
Rewcastle et al., “Biological characterization of SN32976, a selective inhibitor of P13K and mTOR with preferential activity to P13k, in comparison to established pan P13kα inhibitors”, Oncotarget, 2017, vol. 8, No. 29,…
[cited by applicant]
Sapp et al., A dyadic genotype-phenotype approach to diagnostic criteria for Proteus syndrome, Am J Med Genet, 2019, vol. 181, pp. 565-570.
[cited by applicant]
Shirley et al., Sturge-Weber Syndrome and Port-Wine Stains Caused by Somatic Mutation in GNAQ, N Engl J Med., May 23, 2013, vol. 368, No. 21, pp. 1971-1979.
[cited by applicant]
Tan et al., Synthesis and anticancer activities of thieno[3,2-d]pyrimidines as novel HDAC inhibitors, Bioorganic & Medicinal Chemistry, 2014, vol. 22, pp. 358-365.
[cited by applicant]
Vikkula et al., Vascular Dysmorphogenesis Caused by an Activating Mutation in the receptor tyrosine Kinase TIE2, Cell, Dec. 27, 1996, vol. 87, pp. 1181-1190.
[cited by applicant]
Written Opinion for International Application No. PCT/US2016/032779, mailed Sep. 15, 2016, 11 pages.
[cited by applicant]
Written Opinion of the International Searching Authority for PCT/US2020/016876 mailed Jun. 15, 2020, 5 pages.
[cited by applicant]
Written Opinion for International Application No. PCT/US2021/044381, mailed Nov. 29, 2021, 7 pages.
[cited by applicant]
Yang et al., Design, synthesis, and biological evaluation of thieno[3,2-d]pyrimidine derivatives as potential simplified phosphatidylinositol 3-kinase alpha inhibitors, Chem Biol Drug Des., 2019, vol. 94, pp. 2013-2022.
[cited by applicant]