IP Library Granted Patent US 12,383,528
Granted Patent B2
US 12,383,528 · App. 17/312,810 · Granted Aug 12, 2025

Cromolyn esters and uses thereof

Inventors: David R. Elmaleh (Newton, MA); Timothy M. Shoup (Franklin, MA)
Assignee: The General Hospital Corporation
A61K31/352A61K51/0421
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Quick Facts
Patent No.
US 12,383,528
App. No.
17/312,810
Granted
Aug 12, 2025
Kind
B2
Abstract

Described herein are compounds and methods of treating or imaging a disease or disorder, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, ischemic stroke, and prion disease, comprising administering a therapeutically effective amount of a cromolyn ester.

Claims (11)

1. A method of treating or preventing a disease or condition in a subject in need thereof comprising administering a compound selected from

wherein the disease or condition is a head injury, a traumatic brain injury, or asthma.

2. The method of claim 1 , further comprising administering a pharmaceutically acceptable carrier.

3. The method of claim 1 , wherein the compound is administered orally.

4. The method of claim 1 , wherein the compound is in a solid dosage form.

5. The method of claim 1 , wherein the compound is

6. The method of claim 1 , wherein the compound is

7. The method of claim 1 , wherein the method is a method of treating the disease or condition.

8. The method of claim 1 , wherein the disease or condition is a head injury.

9. The method of claim 1 , wherein the disease or condition is a traumatic brain injury.

10. The method of claim 1 , wherein the disease or condition is asthma.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 14, 2022
From: ELMALEH, DAVID R.; SHOUP, TIMOTHY M.
To: THE GENERAL HOSPITAL CORPORATION
Reel/Frame 062120/0409 →
Continuity (2)
Provisional Application 62777456 · Dec 10, 2018
Related Publication 20220062222A1 · Mar 3, 2022
References Cited (400)
US 3419578A · Fitzmaurice et al. · 1968 [cited by applicant]
US 3634582A · Hartley et al. · 1972 [cited by applicant]
US 3686412A · Fitzmaurice et al. · 1972 [cited by applicant]
US 3957965A · Hartley et al. · 1976 [cited by applicant]
US 4120285A · Nugent · 1978 [cited by applicant]
US 4405598A · Brown · 1983 [cited by applicant]
US 4405735A · Wiezer et al. · 1983 [cited by applicant]
US 4429545A · Steinberg · 1984 [cited by applicant]
US 4481206A · Spiegel et al. · 1984 [cited by applicant]
US 4996296A · Pecht et al. · 1991 [cited by applicant]
US 5376386A · Ganderton et al. · 1994 [cited by applicant]
US 5567720A · Averback · 1996 [cited by applicant]
US 5594142A · Gaa et al. · 1997 [cited by applicant]
US 5655523A · Hodson et al. · 1997 [cited by applicant]
US 5830920A · Chucholowski et al. · 1998 [cited by applicant]
US 5904937A · Augello et al. · 1999 [cited by applicant]
US 6168776B1 · Klunk et al. · 2001 [cited by applicant]
US 6197963B1 · Hirschmann et al. · 2001 [cited by applicant]
US 6309623B1 · Weers et al. · 2001 [cited by applicant]
US 6696039B2 · Kung et al. · 2004 [cited by applicant]
US 6911466B2 · Koo et al. · 2005 [cited by applicant]
US 6946116B2 · Kung et al. · 2005 [cited by applicant]
US 6972127B2 · Schenk · 2005 [cited by applicant]
US 7160559B1 · McGee et al. · 2007 [cited by applicant]
US 7186401B2 · Keller et al. · 2007 [cited by applicant]
US 7858803B2 · Elmaleh et al. · 2010 [cited by applicant]
US 8381454B1 · Robinson · 2013 [cited by applicant]
US 8613920B2 · Lieberburg et al. · 2013 [cited by applicant]
US 8617517B2 · Elmaleh et al. · 2013 [cited by applicant]
US 8765742B2 · Hilfiker et al. · 2014 [cited by applicant]
US 9283230B2 · Clunas et al. · 2016 [cited by applicant]
US 9855276B2 · Elmaleh · 2018 [cited by applicant]
US 9861608B2 · Elmaleh et al. · 2018 [cited by applicant]
US 9913847B2 · Elmaleh · 2018 [cited by applicant]
US 9918992B2 · Elmaleh · 2018 [cited by applicant]
US 9925282B2 · Elmaleh et al. · 2018 [cited by applicant]
US 9968618B1 · Elmaleh · 2018 [cited by applicant]
US 10058530B2 · Elmaleh · 2018 [cited by applicant]
US 10092564B2 · Moussy et al. · 2018 [cited by applicant]
US 10188757B2 · Elmaleh · 2019 [cited by applicant]
US 10238628B2 · Gerhart et al. · 2019 [cited by applicant]
US 10245331B2 · Elmaleh · 2019 [cited by applicant]
US 10251961B2 · Elmaleh · 2019 [cited by applicant]
US 10398704B2 · Elmaleh · 2019 [cited by applicant]
US 10406164B2 · Elmaleh · 2019 [cited by applicant]
US 10413551B2 · Elmaleh · 2019 [cited by applicant]
US 10525005B2 · Elmaleh · 2020 [cited by applicant]
US 10561612B2 · Elmaleh et al. · 2020 [cited by applicant]
US 10576171B2 · Elmaleh · 2020 [cited by applicant]
US 11013686B2 · Elmaleh · 2021 [cited by applicant]
US 11110097B2 · Elmaleh · 2021 [cited by applicant]
US 11291648B2 · Elmaleh et al. · 2022 [cited by applicant]
US 11666669B2 · Elmaleh · 2023 [cited by applicant]
US 11679095B2 · Elmaleh et al. · 2023 [cited by applicant]
US 11801316B2 · Elamaleh · 2023 [cited by applicant]
US 20020009491A1 · Rothbard et al. · 2002 [cited by applicant]
US 20020016359A1 · Hellberg et al. · 2002 [cited by applicant]
US 20020091100A1 · Lezdey et al. · 2002 [cited by applicant]
US 20020107173A1 · Friedhoff et al. · 2002 [cited by applicant]
US 20040176469A1 · Thomas · 2004 [cited by applicant]
US 20040223918A1 · Pham et al. · 2004 [cited by applicant]
US 20040259952A1 · Abbas et al. · 2004 [cited by applicant]
US 20060051319A1 · Yoo · 2006 [cited by applicant]
US 20060142241A1 · Yoo · 2006 [cited by applicant]
US 20060159629A1 · Tarara et al. · 2006 [cited by applicant]
US 20060240007A1 · Sanders · 2006 [cited by applicant]
US 20060276455A1 · Lindsberg et al. · 2006 [cited by applicant]
US 20070015813A1 · Carter et al. · 2007 [cited by applicant]
US 20070053843A1 · Dawson et al. · 2007 [cited by applicant]
US 20070071690A1 · Mueller-Walz et al. · 2007 [cited by applicant]
US 20070086981A1 · Meijer et al. · 2007 [cited by applicant]
US 20070093457A1 · Arber et al. · 2007 [cited by applicant]
US 20070107173A1 · Yamada · 2007 [cited by applicant]
US 20070178166A1 · Bernstein et al. · 2007 [cited by applicant]
US 20070193577A1 · Keller · 2007 [cited by applicant]
US 20070249644A1 · Pearson et al. · 2007 [cited by applicant]
US 20070293538A1 · Hobden · 2007 [cited by applicant]
US 20080021085A1 · Koo et al. · 2008 [cited by applicant]
US 20090110679A1 · Li et al. · 2009 [cited by applicant]
US 20090155256A1 · Black et al. · 2009 [cited by applicant]
US 20100113613A1 · McLaurin et al. · 2010 [cited by applicant]
US 20100143251A1 · Tamagnan et al. · 2010 [cited by applicant]
US 20100173960A1 · Cruz et al. · 2010 [cited by applicant]
US 20100234295A1 · Chen · 2010 [cited by applicant]
US 20100236550A1 · Zeng et al. · 2010 [cited by applicant]
US 20100266531A1 · Hsieh et al. · 2010 [cited by applicant]
US 20100298389A1 · Elmaleh et al. · 2010 [cited by applicant]
US 20110060138A1 · Elmaleh et al. · 2011 [cited by applicant]
US 20110129530A1 · Venkatesh et al. · 2011 [cited by applicant]
US 20110132434A1 · Correia et al. · 2011 [cited by applicant]
US 20110262442A1 · Hamilton et al. · 2011 [cited by applicant]
US 20120058049A1 · Elmaleh et al. · 2012 [cited by applicant]
US 20120082727A1 · Cocconi et al. · 2012 [cited by applicant]
US 20120118991A1 · Keller et al. · 2012 [cited by applicant]
US 20120121656A1 · Watson et al. · 2012 [cited by applicant]
US 20120134929A1 · McGrath et al. · 2012 [cited by applicant]
US 20120165366A1 · Ibrahim et al. · 2012 [cited by applicant]
US 20120175082A1 · Kmetovicz et al. · 2012 [cited by applicant]
US 20120308613A1 · Staniforth et al. · 2012 [cited by applicant]
US 20130197105A1 · Pipkin et al. · 2013 [cited by applicant]
US 20140140927A1 · Elmaleh et al. · 2014 [cited by applicant]
US 20140228304A1 · Jones et al. · 2014 [cited by applicant]
US 20150224077A1 · Gerhart et al. · 2015 [cited by applicant]
US 20150224078A1 · Gerhart et al. · 2015 [cited by applicant]
US 20150274680A1 · Ueda et al. · 2015 [cited by applicant]
US 20150283113A1 · Elmaleh · 2015 [cited by applicant]
US 20160106704A1 · Elmaleh et al. · 2016 [cited by applicant]
US 20160158150A1 · Morton et al. · 2016 [cited by applicant]
US 20160166534A1 · Elmaleh · 2016 [cited by applicant]
US 20160310503A1 · Elmaleh · 2016 [cited by applicant]
US 20170290797A1 · Elmaleh · 2017 [cited by applicant]
US 20180066039A1 · Hyde-Deruyscher et al. · 2018 [cited by applicant]
US 20180153803A1 · Elmaleh · 2018 [cited by applicant]
US 20180169277A1 · Elmaleh · 2018 [cited by applicant]
US 20180177789A1 · Elmaleh · 2018 [cited by applicant]
US 20180177790A1 · Elmaleh · 2018 [cited by applicant]
US 20180177791A1 · Elmaleh · 2018 [cited by applicant]
US 20180193491A1 · Elmaleh · 2018 [cited by applicant]
US 20180193492A1 · Elmaleh · 2018 [cited by applicant]
US 20180344682A1 · Elmaleh · 2018 [cited by applicant]
US 20190022006A1 · Elmaleh et al. · 2019 [cited by applicant]
US 20190388568A1 · Elmaleh · 2019 [cited by applicant]
US 20200022947A1 · Elmaleh et al. · 2020 [cited by applicant]
US 20200078366A1 · Elmaleh · 2020 [cited by applicant]
US 20200338040A1 · Elmaleh · 2020 [cited by applicant]
US 20200383908A1 · Elmaleh · 2020 [cited by applicant]
US 20210023010A1 · Elmaleh et al. · 2021 [cited by applicant]
US 20210059977A1 · Elmaleh · 2021 [cited by applicant]
US 20210085601A1 · Elmaleh · 2021 [cited by applicant]
US 20220079914A1 · Elmaleh et al. · 2022 [cited by applicant]
US 20220125753A1 · Elmaleh · 2022 [cited by applicant]
US 20220193087A1 · Elmaleh · 2022 [cited by applicant]
US 20220218652A1 · Elmaleh et al. · 2022 [cited by applicant]
US 20230226017A1 · Elmaleh · 2023 [cited by applicant]
US 20230248646A1 · Elmaleh · 2023 [cited by applicant]
US 20230248650A1 · Elmaleh et al. · 2023 [cited by applicant]
US 20240058480A1 · Elmaleh · 2024 [cited by applicant]
US 20240067635A1 · Elmaleh et al. · 2024 [cited by applicant]
US 20240082207A1 · Elmaleh · 2024 [cited by applicant]
CA 2408793A1 · 2001 [cited by applicant]
CN 101754746A · 2010 [cited by applicant]
CN 101848733A · 2010 [cited by applicant]
CN 105377037A · 2016 [cited by applicant]
CN 108164409A · 2018 [cited by applicant]
CN 108403708A · 2018 [cited by applicant]
DE 1543479 · 2005 [cited by applicant]
EP 1632242A2 · 2006 [cited by applicant]
EP 2322163A1 · 2011 [cited by applicant]
EP 2377860A1 · 2011 [cited by applicant]
EP 2391618A2 · 2011 [cited by applicant]
EP 2911664B1 · 2019 [cited by applicant]
GB 1144906A · 1969 [cited by applicant]
GB 1257162A · 1971 [cited by applicant]
JP S56043448B1 · 1981 [cited by applicant]
JP 2001151673A · 2001 [cited by applicant]
JP 2005510535A · 2005 [cited by applicant]
JP 2005232171A · 2005 [cited by applicant]
JP 2005532091A · 2005 [cited by applicant]
JP 2007534693A · 2007 [cited by applicant]
JP 2009536918A · 2009 [cited by applicant]
JP 2010510254A · 2010 [cited by applicant]
JP 2012515712A · 2012 [cited by applicant]
JP 2012516356A · 2012 [cited by applicant]
WO WO1987001115A1 · 1987 [cited by applicant]
WO WO9009789A2 · 1990 [cited by applicant]
WO WO1997026934A2 · 1997 [cited by applicant]
WO WO9834596A2 · 1998 [cited by applicant]
WO WO1999016422A1 · 1999 [cited by applicant]
WO WO1999064095A2 · 1999 [cited by applicant]
WO WO0228820A1 · 2002 [cited by applicant]
WO WO03045331A2 · 2003 [cited by applicant]
WO WO2004071532A1 · 2004 [cited by applicant]
WO WO2005063732A1 · 2005 [cited by applicant]
WO WO2005104712A2 · 2005 [cited by applicant]
WO WO2006056492A1 · 2006 [cited by applicant]
WO WO2007094718A1 · 2007 [cited by applicant]
WO WO2007102059A1 · 2007 [cited by applicant]
WO WO2008013799A2 · 2008 [cited by applicant]
WO WO2008061373A1 · 2008 [cited by applicant]
WO WO2008128981A1 · 2008 [cited by applicant]
WO WO2008131298A2 · 2008 [cited by applicant]
WO WO2009010770A2 · 2009 [cited by applicant]
WO WO2009133128A1 · 2009 [cited by applicant]
WO WO2010084767A1 · 2010 [cited by applicant]
WO WO2010088455A2 · 2010 [cited by applicant]
WO WO2011136754A1 · 2011 [cited by applicant]
WO WO2013148366A1 · 2013 [cited by applicant]
WO WO2014066318A1 · 2014 [cited by applicant]
WO WO2015002703A1 · 2015 [cited by applicant]
WO WO2015061397A1 · 2015 [cited by applicant]
WO WO2016081466A1 · 2016 [cited by applicant]
WO WO2016196401A1 · 2016 [cited by applicant]
WO WO2017027387A1 · 2017 [cited by applicant]
WO WO2017027402A1 · 2017 [cited by applicant]
WO WO2017072335A1 · 2017 [cited by applicant]
WO WO2017087962A1 · 2017 [cited by applicant]
WO WO2017091644A1 · 2017 [cited by applicant]
WO WO2017162884A1 · 2017 [cited by applicant]
WO WO2018045217A1 · 2018 [cited by applicant]
WO WO2018048989A1 · 2018 [cited by applicant]
WO WO2019199776A1 · 2019 [cited by applicant]
WO WO2020010049A1 · 2020 [cited by applicant]
WO WO2020051322A1 · 2020 [cited by applicant]
WO WO2020123449A1 · 2020 [cited by applicant]
WO WO2021207060A1 · 2021 [cited by applicant]
WO WO2021248022A1 · 2021 [cited by applicant]
WO WO2022146914A1 · 2022 [cited by applicant]
Yoshimi et al., Importance of Hydrolysis of Amino Acid Moiety in Water-Soluble Prodrugs of Disodium Cromoglycate for Increased Oral Bioavailability, J. Pharmacobio-Dyn., 1992, vol. 15, p. 339-345 (Year: 1992). [cited by examiner]
Manuelidis et al, Transmissible encephalopathy agents, 2010, Virulence, vol. 1, No. 2, p. 101-104 (Year: 2010). [cited by examiner]
Tsivgoulis et al, Recent Advances in Primary and Secondary Prevention of Atherosclerotic Stroke, 2018, Journal of Stroke, vol. 20, No. 2, p. 145-166 (Year: 2018). [cited by examiner]
Andreasen et al. “Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample,” Neurology. (1999) 53: 1488-94 (19 pages). [cited by applicant]
Arnaiz et al., “Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease,” Acta Neurol Scand Suppl. (2003) 179: 34-41. [cited by applicant]
Baig et al., “Use of Peptides for the Management of Alzheimer's Disease: Diagnosis and Inhibition,” Frontiers in Aging Neuroscience, 10: 1-6 (2018). [cited by applicant]
Blennow K., “Biomarkers in Alzheimer's disease drug development,” Nat Med. (2010) 16: 1218-22. [cited by applicant]
Buchhave et al., “Cerebrospinal fluid levels of β-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia,” Arch Gen Psychiatry. (2012) 69: 98-106. [cited by applicant]
Bäckman et al., “Multiple Cognitive Deficits During the Transition to Alzheimer's Disease,” Journal of Internal Medicine, (2004) 256(3): 195-204. [cited by applicant]
Carlesimo et al., “Memory Deficits in Alzheimer's Patients: A Comprehensive Review,” Neuropsychol Rev. (1992) 3(2): 119-169. [cited by applicant]
Dickson et al., “Diffuse Lewy body disease,” Acta Neuropathol (Berl), 75: 8-15 (1987). [cited by applicant]
Gomperts et al., “Imaging amyloid deposition in Lewy body disease,” Neurology, 71(12): 903-910 (2008). [cited by applicant]
Grundman et al., “Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials,” Arch. Neurol. (2004) 61(1): 59-66. [cited by applicant]
Lanari, et al., “Cerebrospinal fluid biomarkers and prediction of conversion in patients with mild cognitive impairment: 4-year follow-up in a routine clinical setting,” Scientific World Journal. (2009) 9: 961-6. [cited by applicant]
Lewis et al., “Quantification of Alzheimer pathology in aging and dementia: age-related accumulation of amyloid-β (42) peptide in vascular dementia,” Neuropathology and Applied Neurobiology, 32(2): 103-118 (2006). [cited by applicant]
Mohammed et al., “Effect of Sampling Volume on Dry Powder Inhaler (DPI)-Emitted Aerosol Aerodynamic Particle Size Distributions (APSDs) Measured by the Next-Generation Pharmaceutical Impactor (NGI) and the Andersen Eigh… [cited by applicant]
Monge-Argiles et al. “Biomarkers of Alzheimer's disease in the cerebrospinal fluid of Spanish patients with mild cognitive impairment,” Neurochem Res. (2011) 36: 986-993. [cited by applicant]
Mrak et al., Common Inflammatory Mechanisms in Lewy Body Disease and Alzheimer Disease, J Neuropathol Exp Neurol, 66(8): 683-686 (2007). [cited by applicant]
Newman et al., “Evolution of dry powder inhaler design, formulation, and performance,” Respiratory Medicine, 96(5): 293-304 (2002). [cited by applicant]
Omer et al., “Comparison between the next generation impactor and the twin glass impinge as model pulmonary drug delivery devices,” Zanco J. Med. Sci., 23(1): 74-80 (2019). [cited by applicant]
Partial European Search Report for EP Application No. 19786110.7 dated Dec. 2, 2021. [cited by applicant]
Petersen et al., “Neuropathologic features of amnestic mild cognitive impairment,” Arch. Neurol. (2006) 63 (5): 665-672. [cited by applicant]
Petersen R.C., “The Current Status of Mild Cognitive Impairment—What do we Tell our Patients?” Nat. Clin. Pract. Neurol., (2007) 3(2): 60-61. [cited by applicant]
Petersen, et al., “Mild cognitive impairment: clinical characterization and outcome,” Arch. Neurol., (1999) 56 (3): 303-308. [cited by applicant]
Steckel et al., “In-situ-micronization of disodium cromoglycate for pulmonary delivery,” European Journal of Pharmaceutics and Biopharmaceutics, 55: 173-180 (2003). [cited by applicant]
Sunderland et al., “Decreased beta-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease,” JAMA. (2003) 289: 2094-103. [cited by applicant]
Tabert, et al., “Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment,” Arch Gen Psychiatry. (2006) 63(8): 916-924. [cited by applicant]
Thal et al., “A Randomized, Double-Blind, Study of Rofecoxib in Patients with Mild Cognitive Impairment,” Neuropsychopharmacology (2005) 30: 1204-1215. [cited by applicant]
Vidgren et al., “Effect of powder inhaler design on drug deposition in the respiratory tract,” International Journal of Pharmaceutics, 42: 211-216 (1988). [cited by applicant]
Waldemar G., “Recommendations for the Diagnosis and Management of Alzheimer's Disease and Other Disorders Associated with Dementia: EFNS Guideline,” Eur J Neurol. (2007) 14(1): e1-26. [cited by applicant]
Zheng et al., “Cerebral Atheroschlerosis is Associated with Cystic Infarcts and Microinfarcts, but not Alzheimer Pathologic Changes,” Stroke, 44(10): 2835-2841 (2013). [cited by applicant]
Chow et al., “Investigation of Electrostatic Behavior of a Lactose Carrier for Dry Powder Inhalers,” Pharmaceutical Research, 25(12): 2822-2834 (2008). [cited by applicant]
Extended European Search Report for EP Application No. 19786110.7 dated Mar. 7, 2022. [cited by applicant]
Extended European Search Report for EP Application No. 19830061.8 dated Mar. 11, 2022. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2021/065200 dated Mar. 24, 2022. [cited by applicant]
Shalash et al., “The Relationship Between the Permeability and the Performance of Carrier-Based Dry Powder Inhalation Mixtures: New Insights and Practical Guidance,” AAPS PharmSciTech, 19(2): 912-922 (2017). [cited by applicant]
Shoup et al., “Evaluation of fluorinated cromolyn derivatives as potential therapeutics for Alzheimer's Disease,” Journal of Alzheimer's Disease, 80(2): 775-786 (2021). [cited by applicant]
Shur et al., “From single excipients to dual excipient platforms in dry powder inhaler products,” International Journal of Pharmaceutics, 514: 374-383 (2016). [cited by applicant]
Wang et al., “Pharmaceutical stabilization of mast cells attenuates experimental atherogenesis in low-density lipoprotein receptor-deficient mice,” Atherosclerosis, 229: 304-309 (2013). [cited by applicant]
Young et al., “Lactose Composite Carriers for Respiratory Delivery,” Pharmaceutical Research, 26(4): 802-810 (2008). [cited by applicant]
Anonymous: “Facts about variant Creutzfeldt-Jakob disease”, European Centre for Disease Prevention and Control, Jun. 26, 2017 (Jun. 26, 2017), pp. 1-10, XP093093988, European Centre for Disease Prevention and Control we… [cited by applicant]
Brazier et al., “Pharmacokinetics of cromolyn and ibuprofen in healthy elderly volunteers”, [cited by applicant]
Extended European Search Report for EP Application No. 19895399.4 dated Oct. 27, 2022. [cited by applicant]
Garringer et al., “Modeling familial British and Danish dementia”, Brain Struct Funct 214(2-3): 235-244 (2010). [cited by applicant]
Hofman et al., “Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study,” Lancet 349: pp. 151-154 (1997). [cited by applicant]
Prins et al., “Treating Alzheimer's disease with monoclonal antibodies: current status and outlook for the future”, [cited by applicant]
Thal et al., “Frontotemporal lobar degeneration FTLD-tau: Preclinical lesions, vascular and Alzheimer-related co-pathologies”, J Neural Transm (Vienna), 122(7): 1007-1018 (2015). [cited by applicant]
CG Wikipedia, “Familial Amyloidosis, Finnish Type”, Oct. 30, 2022, Retrieved online from “https://en.wikipedia.org/w/index.php?title=Familial_Amyloidosis,_Finnish_Type&oldid=1119142865”. [cited by applicant]
CH Wikipedia, “Majority”, Sep. 1, 2022, Retrieved online from “https://en.wikipedia.org/w/index.php?title=Majority&oldid=1107851583”. [cited by applicant]
U.S. Appl. No. 14/437,316, Granted. [cited by applicant]
U.S. Appl. No. 15/046,486, Granted. [cited by applicant]
U.S. Appl. No. 15/046,489, Granted. [cited by applicant]
U.S. Appl. No. 15/046,490, Abandoned. [cited by applicant]
U.S. Appl. No. 15/046,494, Abandoned. [cited by applicant]
U.S. Appl. No. 15/046,499, Abandoned. [cited by applicant]
U.S. Appl. No. 15/047,700, Abandoned. [cited by applicant]
U.S. Appl. No. 15/047,705, Abandoned. [cited by applicant]
U.S. Appl. No. 15/047,716, Abandoned. [cited by applicant]
U.S. Appl. No. 15/047,723, Abandoned. [cited by applicant]
U.S. Appl. No. 15/047,730, Abandoned. [cited by applicant]
U.S. Appl. No. 15/360,451, Granted. [cited by applicant]
U.S. Appl. No. 15/895,312, Granted. [cited by applicant]
U.S. Appl. No. 15/902,486, Granted. [cited by applicant]
U.S. Appl. No. 15/902,491, Granted. [cited by applicant]
U.S. Appl. No. 15/902,498, Granted. [cited by applicant]
U.S. Appl. No. 16/570,377, Granted. [cited by applicant]
U.S. Appl. No. 17/466,495, Pending. [cited by applicant]
U.S. Appl. No. 13/146,842, Granted. [cited by applicant]
U.S. Appl. No. 14/059,924, Granted. [cited by applicant]
U.S. Appl. No. 15/031,098, Granted. [cited by applicant]
U.S. Appl. No. 15/899,644, Granted. [cited by applicant]
U.S. Appl. No. 15/916,715, Granted. [cited by applicant]
U.S. Appl. No. 15/916,740, Granted. [cited by applicant]
U.S. Appl. No. 16/259,542, Pending. [cited by applicant]
U.S. Appl. No. 16/377,959, Pending. [cited by applicant]
U.S. Appl. No. 16/328,956, Abandoned. [cited by applicant]
U.S. Appl. No. 17/323,514, Pending. [cited by applicant]
U.S. Appl. No. 17/046,186, Pending. [cited by applicant]
U.S. Appl. No. 17/273,646, Pending. [cited by applicant]
U.S. Appl. No. 14/893,487, Granted. [cited by applicant]
U.S. Appl. No. 15/830,980, Granted. [cited by applicant]
U.S. Appl. No. 16/733,667, Pending. [cited by applicant]
U.S. Appl. No. 17/108,895, Granted. [cited by applicant]
U.S. Appl. No. 15/777,069, Abandoned. [cited by applicant]
U.S. Appl. No. 16/804,802, Pending. [cited by applicant]
U.S. Appl. No. 15/777,062, Abandoned. [cited by applicant]
U.S. Appl. No. 17/338,172, Pending. [cited by applicant]
U.S. Appl. No. 15/838,753, Granted. [cited by applicant]
U.S. Appl. No. 16/789,775, Abandoned. [cited by applicant]
U.S. Appl. No. 17/939,396, Pending. [cited by applicant]
U.S. Appl. No. 16/585,871, Granted. [cited by applicant]
“Stages of ASL” ALS Association Texas Chapter, Retrieved online <https://www.alstexas.org/understanding-als/stages/>: 4 pages (2019). [cited by applicant]
Abraham et al., “Mast cell-orchestrated immunity to pathogens,” Nat Rev Immunol, 10: 440-452 (2010). [cited by applicant]
Aisen et al., “Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial,” JAMA, 289(21):2819-2826 (2003). [cited by applicant]
Akiyama et al., “Inflammation and Alzheimer's Disease,” Neurobiol Aging, 21(3): 383-421 (2000). [cited by applicant]
Alafuzoff et al., “Lower counts of astroglia and activated microglia in patients with Alzheimer's disease with regular use of non-steroidal anti-inflammatory drugs,” J Alzheimers Dis, 2(1):37-46 (2000). [cited by applicant]
Albert et al., “Effects of age on the clinical pharmacokinetics of ibuprofen,” Am J Med, 77(1, Part 1):47-50 (1984). [cited by applicant]
Albert et al., “Pharmacokinetics of ibuprofen,” Am J Med, 77(1A):40-46 (1984). [cited by applicant]
Aloisi F. “Immune function of microglia”. [cited by applicant]
Aswania et al., “Relative bioavailability of sodium cromoglycate to the lung following inhalation, using urinary excretion,” J Clin Pharmacol, 47:613-618 (1999). [cited by applicant]
Banati, R. B. et al., “Cytotoxicity of microglia”. [cited by applicant]
Bannwarth et al., “Stereoselective disposition of ibuprofen enantiomers in human cerebrospinal fluid.,” Br J Clin Pharmacol, 40(3):266-269 (1995). [cited by applicant]
Barone, F.C. et al., “Tumor necrosis factor-a: a mediator of focal ischemic brain injury”. [cited by applicant]
Basek et al., “Efficacy of an Isotonic Small Droplet Size Nebulized DSCG on Asthma Control in Children,” Acta Paediatrica, 99(Suppl 462):115 (2010). [cited by applicant]
Beach et al., “Cromolyn sodium toxicity studies in primates,” Toxicol Appl Pharmacol, 57(3):367-400 (1981). [cited by applicant]
Beigel JH, et al. “Remdesivir for the treatment of Covid-19—preliminary report,” The New England Journal of Medicine: 1-12 (2020). [cited by applicant]
Berge et al., “Pharmaceutical salts,” J Pharm Sci, 66(1):1-19 (1977). [cited by applicant]
Bodor et al., “Improved delivery through biological membranes VII. Dermal delivery of cromoglycic acid (cromolyn) via its prodrugs,” International Journal of Pharmaceutics, 7(1):63-75 (1980). [cited by applicant]
Bona, E. et al., “Chemokine and inflammatory cell response to hypoxia-ischemia in immature rats”. [cited by applicant]
Bot et al., “Perivascular mast cells promote atherogenesis and induce plaque destabilization in apolipoprotein E-deficient mice,” Circulation, 115(19):2516-2525 (2007). [cited by applicant]
Breitner et al., “Extended results of the Alzheimer's disease anti-inflammatory prevention trial,” Alzheimers Dement, 7(4):402-411 (2011). [cited by applicant]
Breitner, “Alzheimer disease: The changing view,” Annals Neurol, 49(3):418-419 (2001). [cited by applicant]
Broe et al., “Anti-inflammatory drugs protect against Alzheimer disease at low doses,” Arch Neurol, 57:1586-1591 (2000). [cited by applicant]
Bulic et al., “Tau protein and tau aggregation inhibitors,” Neuropharmacology, 59: 276-289 (2010). [cited by applicant]
Butovsky et al., “Identification of a unique TGF-?-dependent molecular and functional signature in microglia,” Nat Neurosci, 17(3): 131-143 (2014). [cited by applicant]
Byron et al., “Selection and Validation of Cascade Impactor Test Methods,” Respiratory Drug Delivery IX, 1: 169-178 (2004). [cited by applicant]
Cacabelos, “Donepezil in Alzheimer's disease: From conventional trials to pharmacogenetics,” Neuropsychiatric Disease and Treatment 3(3):303-333 (2007). [cited by applicant]
Cairns et al., “Synthesis and Structure-Activity Relationships of Disodium Cromoglycate and Some Related Compounds,” Journal of Medicinal Chemistry, 15(6):583-589 (1972). [cited by applicant]
Certificate of Analysis for Lactohale LH 201, Alpha-Lactose Monohydrate EP and USP, Full Release (DFE Pharma); Jan. 18, 2016. [cited by applicant]
Chen et al., “Current experimental therapy for Alzheimer's Disease,” Curr Neuropharmacol, 5(2): 127-134 (2007). [cited by applicant]
Cherry et al., “Neuroinflammation and M2 microglia: the good, the bad, and the inflamed,” J Neuroinflammation, 11(98): 1-15 (2014). [cited by applicant]
Choi et al., “A three-dimensional human neural cell culture model of Alzheimer's disease,” Nature, 515: 274-278 (2014). [cited by applicant]
ClinicalTrials.gov. Phase 1 Study of ALZT-OP1 Combination Therapy in Normal Healthy Volunteers. Sponsor: AZTherapies, Inc. Identifier: NCT02482324. Retrieved Apr. 9, 2020 from: http://clinicaltrials.gov/ct/show/NCT02482… [cited by applicant]
ClinicalTrials.gov. Safety and Efficacy of ALZT-OP1a as Adjuvant Treatment in Subjects With Post-Ischemic Stroke Cognitive Impairment (PSCI). Sponsor: AZTherapies, Inc. Identifier: NCT03202147. Retrieved Feb. 6, 2020, 2… [cited by applicant]
ClinicalTrials.gov. Safety and Efficacy Study of ALZT-OP1 in Subjects With Evidence of Early Alzheimer's Disease (COGNITE). Sponsor: AZTherapies, Inc. Identifier: NCT02547818. Retrieved Apr. 9, 2020 from: https://clinic… [cited by applicant]
ClinicalTrials.gov. Treatment of Acute Stroke With Cromolyn(Single Dose). Sponsor: Wolfson Medical Center. Identifier: NCT01175525. Retrieved Feb. 6, 2020 from: https://clinicaltrials.gov/ct2/show/NCT01175525. [cited by applicant]
Cole et al., “Mechanisms of action of non-steroidal anti-inflammatory drugs for the prevention of Alzheimer's disease,” CNS Neurol Disord Drug Targets, 9(2):140-148 (2010). [cited by applicant]
Cowell, R.M. et al., “Hypoxic-ischemic injury induces macrophage inflammatory protein-1alpha expression in immature rat brain,” [cited by applicant]
Cox et al., “Disodium Cromoglycate (FPL 670) (‘Intal’*): A Specific Inhibitor of Reaginic Antibody-Antigen Mechanisms,” Nature, 216: 1328-1329 (1967). [cited by applicant]
Cruz M.P., “Edaravone (Radicava): A novel neuroprotective agent for the treatment of amyotrophic lateral sclerosis,” P&T. (2018) 43(1):25-28. [cited by applicant]
Cummings, “Alzheimer's Disease,” N Engl J Med, 351(1):56-67 (2004). [cited by applicant]
Das et al., “Importance of particle size and shape on the tensile strength distribution and de-agglomeration of cohesive powders,” Powder Technology, 249: 297-303 (2013). [cited by applicant]
Davies, “Clinical pharmacokinetics of ibuprofen. The first 30 years,” Clin Pharmacokinet, 34(2):101-154 (1998). [cited by applicant]
Deiana et al., “Methylthioninium Chloride Versus Rivastigmine and Their Co-Administration Efficacy in Reversing Scopolamine-Induced Cognitive Deficits in a Pharmacological Mouse Model of Alzheimer's Disease,” Alzheimer'… [cited by applicant]
Dello Russo et al., “The human microglial HMC3 cell line: where do we stand? A systematic literature review,” J Neuroinflammation, 15: 259 (24 pages) (2018). [cited by applicant]
Denes, A. et al., “Proliferating resident microglia after focal cerebral ischaemia in mice,” [cited by applicant]
Desmond, D.W. et al., “Frequency and clinical determinants of dementia after ischemic stroke.” [cited by applicant]
Doody et al., “Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial,” Neurology, 72(18):1555-1581 (2009). [cited by applicant]
Du et al., “Role of Microglia in Neurological Disorders and Their Potentials as a Therapeutic Target,” Mol Neurobiol, 54: 7567-7584 (2017). [cited by applicant]
Dubbelaar et al., “The Kaleidoscope of Microglial Phenotypes,” Front Immunol, 9: 1753 (2018). [cited by applicant]
Dunbar et al., “Dispersion and Characterization of Pharmaceutical Dry Powder Aerosols,” Kona, 16:7-45 (1998). [cited by applicant]
Elmaleh, D.R. et al., “Evaluation of F-18 Radiolabeled Cromolyn as a Potential AB Polymerization Inhibitor and PET Tracer”. Poster at [cited by applicant]
EPAR (European Public Assessment Report) Seebri Breezhaler: Retrevied online at <http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002430/human_med_001580.jsp&mid=WC0b01ac058001d124>: 6 pages (… [cited by applicant]
Etminan et al., “Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies,” Brit Med J, 327:128-131 (2003). [cited by applicant]
European Search Report for EP Application No. 13848340 dated Feb. 11, 2016. [cited by applicant]
European Search Report for European Application No. 14819448.3 dated Feb. 2, 2017. [cited by applicant]
Extended European Search Report for EP Application No. 10736439.0 issued Jun. 12, 2012. [cited by applicant]
Extended European Search Report for EP Application No. 16867341.6 mailed Jun. 13, 2019. [cited by applicant]
Extended European Search Report for EP Application No. 17934303 mailed Aug. 13, 2021. [cited by applicant]
Extended European Search Report for EP Application No. EP 16869210 dated Sep. 19, 2019. [cited by applicant]
Extended European Search Report for EP Application No. EP 17847576 dated Jun. 30, 2020. [cited by applicant]
Extended European Search Report for EP Application No. EP 17918310 mailed Mar. 12, 2021. [cited by applicant]
Extended European Search Report for EP Application No. EP 19166810 dated Sep. 23, 2019. [cited by applicant]
Extended European Search Report for EP Application No. EP 19172666 dated Jan. 10, 2020. [cited by applicant]
Extended European Search Report, EP 14855211.0, dated May 29, 2017. [cited by applicant]
Fiala, M. et al., “IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients,” [cited by applicant]
Findeis et al., “Design and testing of inhibitors of fibril formation,” Methods Enzymol, 309:476-488 (1999). [cited by applicant]
Findeis et al., “Modified-peptide inhibitors of amyloid B-peptide polymerization,” Biochemistry, 38(21):6791-6800 (1999). [cited by applicant]
Francesch et al., “Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases,” J Gerontol A Biol Sci Med Sci, 69(S1): S4-9 (2014). [cited by applicant]
Franzius, D., et al., “Non-specific effects of calcium entry antagonists in mast cells,” [cited by applicant]
Gadani et al., “IL-4 in the brain: a cytokine to remember,” J Immunol, 189(9): 4213-4219 (2012). [cited by applicant]
Galimberti et al., “Disease-modifying treatments for Alzheimer's disease,” Ther Adv Neurol Disord, 4(4): 203-216 (2011). [cited by applicant]
Garmise, “Novel Dry Powder Preparations of Whole Inactivated Influenza Virus for Nasal Vaccination,” Dissertation, University of North Carolina at Chapel Hill (2007). [cited by applicant]
Gasparini et al., “Non-steroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease: old and new mechanisms of action,” J Neurochem, 91(3):521-536 (2004). [cited by applicant]
Ghasemi. M. and Brown. R.H. Jr. “Genetics of amyotrophic lateral sclerosis,” [cited by applicant]
Gilani et al., “Influence of Formulation Variables and Inhalation Device on the Deposition Profiles of Cromolyn Sodium Dry Powder Aerosols,” Daru 12(3):123-130 (2004). [cited by applicant]
Gilead Announces Approval of Veklury (remdesivir) in Japan for Patients With Severe COVID-19. The press release of Gilead Sciences. May 7, 2020. URL: < https://www.gilead.com/news-and-press/press-room/press-releases/202… [cited by applicant]
Gorelick, P.B. et al., “Vascular Contributions to Cognitive Impairment and Dementia, A Statement for Healthcare Professionals from the American Heart Association/American Stroke Association,” [cited by applicant]
Gosselin et al., “An environment-dependent transcriptional network specifies human microglia identity,” Science, 356: eaal3222 (2017). [cited by applicant]
Granucci et al., “Cromolyn sodium delays disease onset and is neuroprotective in the SOD1G93A Mouse Model of amyotrophic lateral sclerosis,” Sci Rep, 9: 17728 (17 pages) (2019). [cited by applicant]
Granucci et al., “Inducible IL-2 production by dendritic cells revealed by global gene expression analysis,” Nat Immunol, 2(9): 882-888 (2001). [cited by applicant]
Granucci. E.J. et al., “Cromolyn sodium delays disease onset and is neuroprotective in the SOD1G93A mouse model of amyotrophic lateral sclerosis.” [cited by applicant]
Greenhalgh et al., “Immune cell regulation of glia during CNS injury and disease,” Nat Rev Neurosci, 21: 139-152 (2020). [cited by applicant]
Grenier et al., “Three-dimensional modeling of human neurodegeneration: brain organoids coming of age,” Mol Psychiatry, 25: 254-274 (2020). [cited by applicant]
Griffin, “What causes Alzheimer's?” The Scientist, 25:36-40 (2011). [cited by applicant]
Guchardi et al., “Influence of fine lactose and magnesium stearate on low dose dry powder inhaler formulations,” International Journal of Pharmaceutics 348:10-17 (2008). [cited by applicant]
Gudesblatt et al., “Hexosaminidase A activity and amyotrophic lateral sclerosis,” Muscle and Nerve, II: 227-230 (1988). [cited by applicant]
Guo et al., “Comparison of Delivery Characteristics from a Combination Metered-Dose Inhaler Using the Andersen Cascade Impactor and the Next Generation Pharmaceutical Impactor,” J Pharm Sci, 97(8): 3321-3334 (2008). [cited by applicant]
Guo, J. et al., “Evaluating the levels of CSF and serum factors in ALS,” [cited by applicant]
Gwin et al., “Cromolyn sodium in the treatment of asthma associated with aspirin hypersensitivity and nasal polyps,” Chest, 72(2):148-153 (1977). [cited by applicant]
Haass et al., “Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid [beta]-peptide,” Nat Rev Mol Cell Biol, 8(2):101-112 (2007). [cited by applicant]
Hallenbeck, J.M. “The many faces of tumor necrosis factor in stroke”. [cited by applicant]
Hashimoto et al., “Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide,” J Neurosci, 32(43):15181-15192 (2012). [cited by applicant]
He et al., “Progress of Inhaled Devices for Asthma,” Journal of Applied Clinical Pediatrics, 22(4):309-311 (2007). [cited by applicant]
Hemonnot et al., “Microglia in Alzheimer Disease: Well-Known Targets and New Opportunities,” Front Aging Neurosci, 11:233(20 pages) (2019). [cited by applicant]
Heneka et al., “Acute treatment with the PPARγ agonist pioglitazone and ibuprofen reduces glial inflammation and Aβ1-42 levels in APPV7171 transgenic mice,” Brain, 128:1442-1453 (2005). [cited by applicant]
Hensley, “Neuroinflammation in Alzheimer's Disease: Mechanisms, Pathologic Consequences, and Potential for Therapeutic Manipulation,” J Alzheimers Dis, 21(1):1-14 (2010). [cited by applicant]
Hirouchi, “Current status and perspectives on the development of therapeutic agents for Alzheimer's disease,” Nihon Yakurigaku Zasshi, 123(6):421-427 (2004). [cited by applicant]
Holian et al., “Mechanistic aspects of cromolyn sodium action on the alveolar macrophage: inhibition of stimulation by soluble agonists,” Agents Actions, 33: 318-325 (1991). [cited by applicant]
Hoozemans et al., “Soothing the inflamed brain: effect of non-steroidal anti-inflammatory drugs on Alzheimer's disease pathology,” CNS Neurol Disord Drug Targets, 10(1):57-67 (2011). [cited by applicant]
Hopperton et al., “Markers of microglia in post-mortem brain samples from patients with Alzheimer's disease: a systematic review,” Mol Psychiatry, 23: 177-198 (2018). [cited by applicant]
Hori et al., “A Food and Drug Administration-approved asthma therapeutic agent impacts amyloid β in the brain in a transgenic model of Alzheimer disease,” J Biol Chem, 290(4):1966-1978 (2015). [cited by applicant]
Hori et al., “A Food and Drug Administration-approved asthma therapeutic agent impacts amyloid beta in the brain in a transgenic model of Alzheimer disease,” J Biol Chem, 290(4): 1966-1978 (2015). [cited by applicant]
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