IP Library › Granted Patent US 12,544,373
Granted Patent B2
US 12,544,373 · App. 18/093,599 · Granted Feb 10, 2026

Treatment of cancer, inflammatory diseases and autoimmune diseases

Inventors: Mahdi Farhan (Chicago, IL); James M. Hamby (Chicago, IL); Tracey L. Fletcher (Chicago, IL)
Assignee: Usher III Initiative, Inc.
A61K31/5025A61K45/06A61P1/00A61P1/18A61P13/08A61P15/08A61P17/00A61P19/08A61P25/00A61P35/00
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 12,544,373
App. No.
18/093,599
Granted
Feb 10, 2026
Kind
B2
Abstract

The present disclosure relates to methods for the treatment or prevention of cancer, an inflammatory disease or an autoimmune disease with compounds of the invention as disclosed herein. The present disclosure also relates to methods for reducing risk of developing cancer, an inflammatory disease or an autoimmune disease with compounds of the invention as disclosed herein.

Claims (25)

1 . A method for treating cancer, comprising administering to a subject in need thereof an effective amount of a compound having the structure

or a pharmaceutically acceptable salt thereof, wherein

the cancer is colorectal cancer, glioblastoma, lung cancer, ovarian cancer, pancreatic cancer, cervical cancer, prostate cancer, breast cancer, gastric cancer, head and neck cancer, liver cancer, melanoma, lymphopoietic cancer, hematopoietic cancer, soft tissue sarcoma, or osteosarcoma.

2 . The method of claim 1 , wherein the cancer has one or more disease-associated mutations in BRCA1 or BRCA2.

3 . The method of claim 1 , wherein the cancer has one or more disease-associated mutations in BRCA1 and one or more disease-associated mutations in BRCA2.

4 . The method of claim 1 , wherein the cancer has one or more disease-associated mutations in BRCA1 but harbors no disease-associated mutations in BRCA2.

5 . The method of claim 1 , wherein the cancer has one or more disease-associated mutations in BRCA2 but harbors no disease-associated mutations in BRCA1.

6 . The method of claim 1 , wherein the cancer has no disease-associated mutations in BRCA1 or BRCA2.

7 . The method of claim 1 , wherein the cancer is BRCA-driven cancer.

8 . The method of claim 1 , wherein the cancer is BRCA1-driven cancer.

9 . The method of claim 1 , wherein the cancer is BRCA2-driven cancer.

10 . The method of claim 1 , wherein the cancer is BRCA1- and BRCA2-driven cancer.

11 . The method of claim 1 , wherein the cancer is neither BRCA1-nor BRCA2 driven cancer.

12 . The method of any one of claims 1 and 2-11 , wherein the method further comprises administering an anti-cancer therapy to the subject.

13 . The method of claim 12 , wherein the anti-cancer therapy is neoadjuvant therapy or an adjuvant therapy.

14 . The method of claim 12 , wherein the anti-cancer therapy is chemotherapy, targeted therapy, hormone therapy, immunotherapy, T-cell therapy, or stem cell therapy.

15 . A method for treating or preventing an inflammatory disease or treating an autoimmune disease, comprising administering to a subject in need thereof an effective amount of a compound having the structure

or a pharmaceutically acceptable salt thereof.

16 . The method of claim 15 , wherein the inflammatory disease is atherosclerosis, cardiac myopathy, epidermolysis bullosa, asthma, psoriasis, or inflammatory bowel disease, and the autoimmune disease is rheumatoid arthritis, juvenile idiopathic arthritis, celiac disease, dermatitis herpetiformis, autoimmune blistering skin disease, type 1 diabetes, dermatomyositis, alopecia areata, antiphospholipid antibody syndrome, autoimmune hepatitis, multiple sclerosis, Guillain-Barre syndrome, demyelinating polyneuropathy, Graves's disease, Hashimoto's thyroiditis, myasthenia gravis, vasculitis, hemolytic anemia, idiopathic thrombocytopeniapurpura, inflammatory myopathy, primary biliary cirrhosis, scleroderma, Sjögren's syndrome, systemic lupus erythematosus, or vitiligo.

17 . The method of claim 16 , wherein the inflammatory disease is inflammatory bowel disease, and the inflammatory bowel disease is colitis or Crohn's disease.

18 . The method of claim 13 , wherein the neoadjuvant therapy or the adjuvant therapy is chemotherapy, targeted therapy, hormone therapy, immunotherapy, T-cell therapy, or stem cell therapy.

19 . The method of claim 1 , wherein the subject is a human.

20 . The method of any one of claims 15, 16, and 17 wherein the subject is a human.

21 . The method of claim 19 , comprising administering to the subject in need thereof an effective amount of a compound having the structure

22 . The method of claim 20 , comprising administering to the subject in need thereof an effective amount of a compound having the structure

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 5, 2023
From: HAMBY, JAMES M.; FLETCHER, TRACEY L.
To: USHER III INITIATIVE, INC.
Reel/Frame 063227/0152 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 5, 2023
From: FARHAN, MAHDI
To: UNITECHPHARMA LIMITED
Reel/Frame 063227/0160 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 5, 2023
From: UNITECHPHARMA LIMITED
To: USHER III INITIATIVE, INC.
Reel/Frame 063227/0266 →
Continuity (3)
Continuation PCTUS2021040810 · Jul 8, 2021
Provisional Application 63049948 · Jul 9, 2020
Related Publication 20230149399A1 · May 18, 2023
References Cited (105)
US 7390808B2 · Green et al. · 2008 [cited by applicant]
US 7666647B2 · Ter Haar et al. · 2010 [cited by applicant]
US 7812166B2 · Dai et al. · 2010 [cited by applicant]
US 7883881B2 · Ter Haar et al. · 2011 [cited by applicant]
US 8318467B2 · Ter Haar et al. · 2012 [cited by applicant]
US 8338439B2 · Singh et al. · 2012 [cited by applicant]
US 8450335B2 · Singh et al. · 2013 [cited by applicant]
US 8609679B2 · Singh et al. · 2013 [cited by applicant]
US 8765762B2 · Bürli et al. · 2014 [cited by applicant]
US 8785391B2 · Johansson · 2014 [cited by applicant]
US 9079909B2 · Bürli et al. · 2015 [cited by applicant]
US 9212181B2 · Singh et al. · 2015 [cited by applicant]
US 9227976B2 · Bürli et al. · 2016 [cited by applicant]
US 9260381B2 · Bürli et al. · 2016 [cited by applicant]
US 9371332B2 · Bürli et al. · 2016 [cited by applicant]
US 9549910B2 · Bürli et al. · 2017 [cited by applicant]
US 9783545B2 · Bürli et al. · 2017 [cited by applicant]
US 9925187B2 · Bürli et al. · 2018 [cited by applicant]
US 10307422B2 · Bürli et al. · 2019 [cited by applicant]
US 20080194562A1 · Wyatt et al. · 2008 [cited by applicant]
US 20100029610A1 · Singh et al. · 2010 [cited by applicant]
US 20130065879A1 · Singh et al. · 2013 [cited by applicant]
US 20130065899A1 · Singh et al. · 2013 [cited by applicant]
US 20130072469A1 · Singh et al. · 2013 [cited by applicant]
US 20130165462A1 · Singh et al. · 2013 [cited by applicant]
US 20130252936A1 · Bürli et al. · 2013 [cited by applicant]
US 20140121197A1 · Bürli et al. · 2014 [cited by applicant]
US 20140121205A1 · Bürli et al. · 2014 [cited by applicant]
US 20140288005A1 · Johansson · 2014 [cited by applicant]
US 20140288093A1 · Krainc et al. · 2014 [cited by applicant]
US 20150265617A1 · Bürli et al. · 2015 [cited by applicant]
US 20150266812A1 · Bürli et al. · 2015 [cited by applicant]
US 20160158172A1 · Bürli et al. · 2016 [cited by applicant]
US 20160272647A1 · Bürli et al. · 2016 [cited by applicant]
US 20170143718A1 · Bürli et al. · 2017 [cited by applicant]
US 20180099974A1 · Saperstein · 2018 [cited by applicant]
US 20180207159A1 · Bürli et al. · 2018 [cited by applicant]
US 20240279229A1 · Saperstein · 2024 [cited by applicant]
JP 2014515758A · 2014 [cited by applicant]
WO WO03080616A1 · 2003 [cited by applicant]
WO WO2006077401A1 · 2006 [cited by applicant]
WO WO2006091246A1 · 2006 [cited by applicant]
WO WO2006127396A1 · 2006 [cited by applicant]
WO WO2007075911A2 · 2007 [cited by applicant]
WO WO2007120827A2 · 2007 [cited by applicant]
WO WO2008051757A1 · 2008 [cited by applicant]
WO WO2009039420A1 · 2009 [cited by applicant]
WO WO2009062118A2 · 2009 [cited by applicant]
WO WO2010046013A1 · 2010 [cited by applicant]
WO WO2012148994A1 · 2012 [cited by applicant]
WO WO2014066835A1 · 2014 [cited by applicant]
WO WO2014066836A1 · 2014 [cited by applicant]
WO WO2014121205A1 · 2014 [cited by applicant]
WO WO2016201266A1 · 2016 [cited by applicant]
WO WO2017098367A1 · 2017 [cited by applicant]
WO WO2022011091A1 · 2022 [cited by applicant]
Vocka, M. et al., “Novel serum markers HSP60, CHI3L1, and IGFBP-2 in metastatic colorectal cancer,” Oncology Letters, 18:6284-6292 (2019). [cited by applicant]
Alagramam, K. N. et al., “A Small Molecule Mitigates Hearing Loss in a Mouse Model of Usher Syndrome III,” Nature Chemical Biology, Jun. 2016, vol. 12, No. 6, pp. 444-451. [cited by applicant]
Brana, M. F. et al., “Pyrazolo[3,4-c]pyridazines as Novel and Selective Inhibitors of Cyclin-dependent Kinases,” Journal of Medicinal Chemistry, Nov. 2005, vol. 48, No. 22, pp. 6843-6854. [cited by applicant]
Churcher, I. “Tau Therapeutic Strategies for the Treatment of Alzheimer's Disease,” Current Topics in Medicinal Chemistry, 2006, vol. 6, No. 6, pp. 579-595. [cited by applicant]
El-Amraoui, A. et al., “Usher I Syndrome: Unravelling the Mechanisms That Underlie the Cohesion of the Growing Hair Bundle in Inner Ear Sensory Cells,” Journal of Cell Science, Oct. 2005, vol. 118(Pt 20), pp. 4593-4603. [cited by applicant]
Geng, R. et al., “Noddy, a Mouse Harboring a Missense Mutation in Protocadherin-15, Reveals the Impact of Disrupting a Critical Interaction Site Between Tip-link Cadherins in Inner Ear Hair Cells,” The Journal of Neuros… [cited by applicant]
Geng, R. et al., “The Mechanosensory Structure of the Hair Cell Requires Clarin-1, a Protein Encoded by Usher Syndrome III Causative Gene,” The Journal of Neuroscience, Jul. 2012, vol. 32, No. 28, pp. 9485-9498. [cited by applicant]
Geng, R. et al., “Usher Syndrome IIIA Gene Clarin-1 is Essential for Hair Cell Function and Associated Neural Activation,” Human Molecular Genetics, Aug. 2009, vol. 18, No. 15, pp. 2748-2760. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/US2021/040810 dated Jan. 19, 2023, 8 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2012/034959, mailed Sep. 21, 2012, 10 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2013/066938, mailed Jan. 30, 2014, 6 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2013/066939, mailed Mar. 5, 2014, 8 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/036945, mailed Sep. 7, 2016, 12 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2021/040810 dated Dec. 15, 2021, 11 pages. [cited by applicant]
Office Action for U.S. Appl. No. 13/791,205, mailed Aug. 6, 2014, 7 pages. [cited by applicant]
Office Action for U.S. Appl. No. 13/791,744, mailed Jun. 27, 2014, 9 pages. [cited by applicant]
Office Action for U.S. Appl. No. 14/731,535, mailed Oct. 5, 2015, 6 pages. [cited by applicant]
Office Action for U.S. Appl. No. 15/141,949, mailed Feb. 3, 2017, 6 pages. [cited by applicant]
Office Action for U.S. Appl. No. 15/924,831, mailed Dec. 19, 2018, 5 pages. [cited by applicant]
Shelkovnikova, T. A. et al., “Proteinopathies, neurodegenerative disorders with protein aggregation-based pathology,” Molecular Biology, vol. 46, No. 3, pp. 362-374 (Jun. 2012). [cited by applicant]
Tian, G. et al., “Clarin-1, Encoded by the Usher Syndrome III Causative Gene, Forms a Membranous Microdomain: Possible Role of Clarin-1 in Organizing the Actin Cytoskeleton,” The Journal of Biological Chemistry, Jul. 20… [cited by applicant]
Tian, G. et al., “Impairment of vision in a mouse model of Usher Syndrome Type III,” Investigative Ophthalmology & Visual Science, Mar. 2016, vol. 57, 866-875. doi:10.1167/iovs.15-16946. [cited by applicant]
Tretyakov, E. V. et al., “Investigations of the Richter reaction in a series of vicinal alkynylpyrazolediazonium salts,” J. Chem. Soc., Perkin Trans., vol. 1, No. 24, pp. 3721-3726 (1999). [cited by applicant]
Tretyakov, E. V. et al., “New findings in the Richter reaction in series of vicinal alkynylpyrazolyldiazonium salts,” Heterocyclic Communications, vol. 4, No. 6, pp. 519-524 (1998). [cited by applicant]
Vasilevsky, S. F. et al., “Cinnolines and pyrazolopyridazines. Novel synthetic and mechanistic aspects of the Richter reaction,” Liebigs Ann., vol. 5, pp. 775-779 (1995). [cited by applicant]
Becq, F. et al., “The rescue of F508del-CFTR by elexacaftor/tezacaftor/ivacaftor (Trikafta) in human airway epithelial cells is underestimated due to the presence of ivacaftor,” Eur Respir J, (Feb. 2022); 59(2):2100671,… [cited by applicant]
Bertrand, C. A. et al., “SLC26A9 is a constitutively active, CFTR-regulated anion conductance in human bronchial epithelia,” J Gen Physiol. (Apr. 2009), 133(4):421-438. [cited by applicant]
Chan, C-H et al., “Transcript and in silico analysis of CLN3 in juvenile neuronal ceroid lipofuscinosis and associated mouse models,” Human Molecular Genetics, 2008, vol. 17, No. 21, pp. 3332-3339. doi:10.1093/hmg/ddn22… [cited by applicant]
Fauvet, B. et al., “Repair or Degrade: the Thermodynamic Dilemma of Cellular Protein Quality-Control,” Frontiers in Molecular Biosciences, vol. 8, Article 768888, Oct. 2021, 11 pages. [cited by applicant]
Fiedorczuk, K. et al., “Molecular structures reveal synergistic rescue of A508 Cftr by Trikafta modulators,” Science, (Oct. 2022), 378(6617):284-290. [cited by applicant]
Gomez-Giro, G. et al., “Synapse alterations precede neuronal damage and storage pathology in a human cerebral organoid model of CLN3-juvenile neuronal ceroid lipofuscinosis,” Acta Neuropathologica Communications (2019) … [cited by applicant]
Laselva, O. et al., “Rescue of multiple class II CFTR mutations by elexacaftor+tezacaftor+ivacaftor mediated in part by the dual activities of elexacaftor as both corrector and potentiator,” Eur Respir J. (Jun. 2021), 5… [cited by applicant]
Ostergaard, J. R., “Juvenile neuronal ceroid lipofuscinosis (Batten disease): current insights,” Degenerative Neurological and Neuromuscular Disease 2016:6, pp. 73-83. [cited by applicant]
Singh, M. K. et al., “Molecular Chaperonin HSP60: Current Understanding and Future Prospects,” Int. J. Mol. Sci. 2024, 25, 5483, 25 pages. [cited by applicant]
Stefl, S. et al., “Molecular mechanisms of disease-causing missense mutations,” J Mol Biol. Nov. 1, 2013; 425(21):3919-3936. doi:10.1016/j.jmb.2013.07.014. [cited by applicant]
Van Goor, F. et al., “Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770,” Proc Natl Acad Sci USA, (Nov. 2009), 106(44):18825-18830. [cited by applicant]
Carrell, R.W., et al., “Alpha1-antitrypsin Deficiency—a Model for Conformational Diseases,” The New England Journal of Medicine, Jan. 3, 2002, vol. 346(1), pp. 45-53. [cited by applicant]
Dichgans, M., et al., “Small in-frame Deletions and Missense Mutations in Cadasil: 3D Models Predict Misfolding of Notch3 EGF-like Repeat Domains,” European Journal of Human Genetics, Apr. 2000, vol. 8(4), pp. 280-285. [cited by applicant]
Dietz, H. C., et al., “Marfan Syndrome Caused by a Recurrent De Novo Missense Mutation in the Fibrillin Gene,” Nature, Jul. 25, 1991, vol. 352 (6333), pp. 337-339. [cited by applicant]
Gao, H., et al., “Mutations in a Novel CLN6-Encoded Transmembrane Protein Cause Variant Neuronal Ceroid Lipofuscinosis in Man and Mouse,” American Journal of Human Genetics, Feb. 2002, vol. 70 (2), pp. 324-335. [cited by applicant]
Menaa, F., “Stroke in Sickle Cell Anemia Patients: a Need for Multidisciplinary Approaches,” Atherosclerosis, Aug. 2013, vol. 229(2), pp. 496-503. [cited by applicant]
Meriin, A. B., and Sherman, M. Y., “Role of Molecular Chaperones in Neurodegenerative Disorders,” International Journal of Hyperthermia, Aug. 2005, vol. 21(5), pp. 403-419. [cited by applicant]
Polymeropoulos, M.H., et al., “Mutation in the Alpha-synuclein Gene Identified in Families With Parkinson's Disease,” Science, Jun. 27, 1997, vol. 276(6321), pp. 2045-2047. [cited by applicant]
Ranta, S., et al., “The Neuronal Ceroid Lipofuscinoses in Human EPMR and mnd Mutant Mice are Associated with Mutations in CLN8,” Nature Genetics, Oct. 1999, vol. 23(2), pp. 233-236. [cited by applicant]
Savukoski, M., et al., “CLN5, a Novel Gene Encoding a Putative Transmembrane Protein Mutated in Finnish Variant Late Infantile Neuronal Ceroid Lipofuscinosis,” Nature Genetics, Jul. 1998, vol. 19(3), pp. 286-288. [cited by applicant]
Sleat, D.E., et al., “Association of Mutations in a Lysosomal Protein With Classical Late-infantile Neuronal Ceroid Lipofuscinosis,” Science, Sep. 19, 1997, vol. 277 (5333), pp. 1802-1805. [cited by applicant]
Tang, G., et al., “Autophagy Induced by Alexander Disease-Mutant GFAP Accumulation is Regulated by p38/MAPK and mTOR Signaling Pathways,” Human Molecular Genetics, Jun. 1, 2008, vol. 17 (11), pp. 1540-1555. [cited by applicant]
Vesa, J., et al., “Mutations in the Palmitoyl Protein Thioesterase Gene Causing Infantile Neuronal Ceroid Lipofuscinosis,” Nature, Aug. 17, 1995, vol. 376(6451), pp. 584-587. [cited by applicant]
Windpassinger, C., et al., “Heterozygous Missense Mutations in BSCL2 Are Associated With Distal Hereditary Motor Neuropathy and Silver Syndrome,” Nature Genetics, Mar. 2004, vol. 36(3), pp. 271-276. [cited by applicant]