Granted Patent
B2
US 12,642,813 · App. 19/278,380 · Granted Jun 2, 2026
Hydroxypropyl beta-cyclodextrin compositions and methods
Assignee:
Mandos LLC
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Abstract
This disclosure provides mixtures of beta-cyclodextrin molecules substituted at one or more hydroxyl positions by hydroxypropyl groups, the mixture optionally including unsubstituted beta-cyclodextrin molecules, for use as a pharmaceutically active ingredient; methods of making such mixtures; methods of qualifying such mixtures for use in a pharmaceutical composition suitable for intrathecal or intracerebroventricular administration; pharmaceutical compositions suitable for intrathecal or intracerebroventricular administration comprising such mixtures; and methods of using the pharmaceutical compositions for treatment of Niemann-Pick disease Type C.
Claims (27)
1 . A method of modulating the plasma level of one or more cholesterol metabolites in a human subject comprising administering to the subject a composition comprising a pharmaceutically effective amount of a mixture of beta-cyclodextrin molecules substituted at one or more hydroxyl positions by hydroxypropyl groups, wherein the composition comprises less than 5 International Units (IU) of endotoxins per gram.
2 . The method of claim 1 , wherein the one or more cholesterol metabolites is selected from the group consisting of 7-ketocholesterol, 7β-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol, and cholestane-3β,5α,6β-triol.
3 . The method of claim 1 , wherein the composition comprises less than 4 IU of endotoxins per gram.
4 . The method of claim 1 , wherein the composition comprises less than 3 IU of endotoxins per gram.
5 . The method of claim 1 , wherein the composition comprises less than 1 ppm propylene oxide.
6 . The method of claim 1 , wherein the composition comprises less than 0.8 ppm propylene oxide.
7 . The method of claim 1 , wherein the composition comprises less than 0.6 ppm propylene oxide.
8 . The method of claim 1 , wherein the composition comprises less than 0.5 ppm propylene oxide.
9 . The method of claim 1 , wherein the composition is suitable for intrathecal administration.
10 . The method of claim 1 , wherein the mixture of beta-cyclodextrin molecules comprises less than 1% unsubstituted beta-cyclodextrin (“DS-0”).
11 . The method of claim 1 , wherein the mixture of beta-cyclodextrin molecules comprises 10% to 30% molecules having three hydroxypropyl substitutions (“DS-3”).
12 . The method of claim 1 , wherein the mixture of beta-cyclodextrin molecules comprises at least 75% molecules having three, four, five, and six hydroxypropyl substitutions, collectively (“DS-3”, “DS-4”, “DS-5”, and “DS-6”).
13 . The method of claim 1 , wherein the mixture of beta-cyclodextrin molecules comprises less than 1% molecules having nine and ten hydroxypropyl substitutions, collectively (“DS-9” and “DS-10”).
14 . The method of claim 1 , wherein the mixture of beta-cyclodextrin molecules comprises less than 0.1% molecules having nine and ten hydroxypropyl substitutions, collectively (“DS-9” and “DS-10”).
15 . The method of claim 1 , wherein the composition comprises less than 0.9% propylene glycol.
16 . The method of claim 1 , wherein the composition comprises less than 0.8% propylene glycol.
17 . The method of claim 1 , wherein the composition comprises less than 0.7% propylene glycol.
18 . The method of claim 1 , wherein the composition comprises less than 0.6% propylene glycol.
19 . The method of claim 1 , wherein the composition further comprises sodium chloride.
20 . The method of claim 1 , wherein the composition is suitable for lumbar injection.
21 . A method of modulating the plasma level of one or more cholesterol metabolites in a human subject comprising administering to the subject a composition comprising a pharmaceutically effective amount of a mixture of beta-cyclodextrin molecules substituted at one or more hydroxyl positions by hydroxypropyl groups, wherein the composition comprises less than 10 International Units (IU) of endotoxins per gram, wherein the one or more cholesterol metabolites is selected from the group consisting of 7-ketocholesterol, 7β-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol, and cholestane-3β,5α,6β-triol.
22 . The method of claim 21 , wherein the one or more cholesterol metabolites is 7-ketocholesterol.
23 . The method of claim 21 , wherein the one or more cholesterol metabolites is 7β-hydroxycholesterol.
24 . The method of claim 21 , wherein the one or more cholesterol metabolites is 24S-hydroxycholesterol, and wherein the composition comprises less than 2 IU of endotoxins per gram.
25 . The method of claim 21 , wherein the one or more cholesterol metabolites is 25-hydroxycholesterol.
26 . The method of claim 21 , wherein the one or more cholesterol metabolites is 27-hydroxycholesterol.
27 . The method of claim 21 , wherein the one or more cholesterol metabolites is cholestane-3β,5α,6β-triol.
Assignments (3)
SECURITY INTEREST
Recorded Oct 8, 2025
From: BEREN THERAPEUTICS P.B.C.; MANDOS LLC
To: HERCULES CAPITAL, INC., AS AGENT
Reel/Frame 073056/0214 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 29, 2025
From: MACHIELSE, BERNARDUS NICOLAAS; DARLING, ALLAN
To: VTESSE, INC.
Reel/Frame 071864/0923 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 29, 2025
From: VTESSE, INC.
To: MANDOS LLC
Reel/Frame 071865/0073 →
Continuity (24)
Provisional Application
62345721
· Jun 3, 2016
Provisional Application
62331385
· May 3, 2016
Provisional Application
62314765
· Mar 29, 2016
Provisional Application
62308736
· Mar 15, 2016
Provisional Application
62276728
· Jan 8, 2016
Provisional Application
62263599
· Dec 4, 2015
Provisional Application
62249876
· Nov 2, 2015
Provisional Application
62245974
· Oct 23, 2015
Provisional Application
62189114
· Jul 6, 2015
Provisional Application
62175075
· Jun 12, 2015
Provisional Application
62173889
· Jun 10, 2015
References Cited (322)
US 4727064A
· Pitha
· 1988
[cited by applicant]
US 4877778A
· Carpenter et al.
· 1989
[cited by applicant]
US 5262404A
· Weisz et al.
· 1993
[cited by applicant]
US 5376645A
· Stella et al.
· 1994
[cited by applicant]
US 5624914A
· Patel et al.
· 1997
[cited by applicant]
US 6407079B1
· Müller et al.
· 2002
[cited by applicant]
US 6528642B1
· Duval et al.
· 2003
[cited by applicant]
US 6878695B2
· Woo et al.
· 2005
[cited by applicant]
US 9044451B2
· Zheng et al.
· 2015
[cited by applicant]
US 9675634B2
· Machielse et al.
· 2017
[cited by applicant]
US 20010056080A1
· Woo et al.
· 2001
[cited by applicant]
US 20040076591A1
· Anthony Nelson et al.
· 2004
[cited by applicant]
US 20060025380A1
· Thorsteinsson et al.
· 2006
[cited by applicant]
US 20090258001A1
· Ponath et al.
· 2009
[cited by applicant]
US 20110028432A1
· Cataldo et al.
· 2011
[cited by applicant]
US 20150065457A1
· Fornoni et al.
· 2015
[cited by applicant]
US 20150216895A1
· McKew et al.
· 2015
[cited by applicant]
US 20160361345A1
· Machielse et al.
· 2016
[cited by applicant]
US 20240067760A1
· Pfeiffer et al.
· 2024
[cited by applicant]
US 20240270877A1
· Pfeiffer et al.
· 2024
[cited by applicant]
US 20240287211A1
· Pfeiffer et al.
· 2024
[cited by applicant]
CN 1073359A
· 1993
[cited by applicant]
CN 102040675A
· 2011
[cited by applicant]
CN 109675054A
· 2019
[cited by applicant]
EP 1747785A1
· 2007
[cited by applicant]
JP 2007504166A
· 2007
[cited by applicant]
TW 491715B
· 2002
[cited by applicant]
WO 1990012035A1
· 1990
[cited by applicant]
WO 2007013123A1
· 2007
[cited by applicant]
WO 2010138802A2
· 2010
[cited by applicant]
WO 2012012473A1
· 2012
[cited by applicant]
WO 2013155485A2
· 2013
[cited by applicant]
WO 2014022841A1
· 2014
[cited by applicant]
WO 2015087016A1
· 2015
[cited by applicant]
WO 2016201137A1
· 2016
[cited by applicant]
WO 2020092107A1
· 2020
[cited by applicant]
WO 2021050890A1
· 2021
[cited by applicant]
WO 2022047241A1
· 2022
[cited by applicant]
“Hydroxypropyl Beta Cyclodextrin for Niemann-Pick Type C1 Disease,” Dec. 10, 2012, retrieved from the Internet: URL: http://clinicaltrials.gov/archive/NCTO1747135/2012_12_10, 6 pages.
[cited by applicant]
“Hydroxypropyl Betadex”., Official Monographs, The United States Pharmacopeial Convention, May 1, 2012, pp. 1819-1821.
[cited by applicant]
Innovation Hub., “Kleptose HPB parenteral Grade Hydroxypropyl Beta-Cyclodextrin-Pyrogen-Free-Low Molar Substitution,” Pharma Virtual lab by Roquette, retrieved on Mar. 13, 2025, 5 pages, Retrieved from Internet URL: htt…
[cited by applicant]
International Preliminary Report on Patentability for Application No. PCT/IB2023/051462, mailed on Aug. 29, 2024, 5 pages.
[cited by applicant]
International Preliminary Report on Patentability for Application No. PCT/US2013/053527, mailed on Feb. 3, 2015, 10 Pages.
[cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/US2016/036753, mailed Dec. 21, 2017, 09 Pages.
[cited by applicant]
International Search Report and Written Opinion for Application No. PCT/US2013/053527, mailed on Oct. 16, 2013, 14 Pages.
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/036753, mailed Aug. 30, 2016, 11 Pages.
[cited by applicant]
Irie T., et al., “Hydroxypropylcyclodextrins in Parenteral Use. II: Effects on Transport and Disposition of Lipids in Rabbit and Humans,” Journal of Pharmaceutical Sciences, Jun. 1992, vol. 81, No. 6, pp. 524-528.
[cited by applicant]
Irie T., et al., “Pharmaceutical Applications of Cyclodextrins. III. Toxicological Issues and Safety Evaluation,” Journal of Pharmaceutical Sciences, Feb. 1997, vol. 86, No. 2, pp. 147-162.
[cited by applicant]
Jiang H., et al., “Development and Validation of Sensitive LC-MS/MS Assays for Quantification of HP-CD in Human Plasma and CSF,” Journal of Lipid Research, 2014, vol. 55, No. 7, pp. 1537-1548.
[cited by applicant]
Jiang X., et al., “Development of a Bile Acid-Based Newborn Screen for Niemann-Pick C Disease,” Science Translational Medicine, May 4, 2016, vol. 8, No. 337, 26 Pages.
[cited by applicant]
Kali G., et al., “Cyclodextrins and Derivatives in Drug Delivery: New Developments, Relevant Clinical Trials, and Advanced Products,” Carbohydrate Polymers, 2024, vol. 324, pp. 1-23.
[cited by applicant]
King K., et al., “Auditory Phenotype of Niemann-Pick Disease, Type C1,” Ear and Hearing, 2014, vol. 35, No. 1, 17 pages.
[cited by applicant]
Ko D.C., et al., “Cell-Autonomous Death of Cerebellar Purkinje Neurons with Autophagy in Niemann-Pick Type C Disease,” PLoS Genetics, Jul. 2005, vol. 1, No. 1, pp. 81-95.
[cited by applicant]
Kondo Y., et al., “In Vitro Evaluation of 2-Hydroxyalkylated-Cyclodextrins as Potential Therapeutic Agents for Niemann-Pick Type C Disease,” Molecular Genetics and Metabolism, 2016, vol. 118, pp. 214-219.
[cited by applicant]
Lachmann R.H., et al., “Treatment with Miglustat Reverses the Lipid-Trafficking Defect in NiemannPick Disease Type C,” Neurobiology of Disease, 2004, vol. 16, No. 3, pp. 654-658.
[cited by applicant]
Leigh-Paffenroth E., et al., “Objective Measures of Ototoxicity,” Hearing and Hearing Disorders: Research and Diagnostics, Sep. 2005, vol. 9, No. 1,7 pages.
[cited by applicant]
Liao G., et al., “Allopregnanolone Treatment Delays Cholesterol Accumulation and Reduces Autophagic/Lysosomal Dysfunction and Inflammation in Npc1-/- Mouse Brain,” Brain Research, May 13, 2009, vol. 1270, 20 pages.
[cited by applicant]
Lieberman A.P., et al., “Autophagy in Lysosomal Storage Disorders,” Autophagy, 2012, vol. 8, No. 5, pp. 719-730.
[cited by applicant]
Liu B., et al., “Cyclodextrin Overcomes the Transport Defect in Nearly Every Organ of NPC1 Mice Leading to Excretion of Sequestered Cholesterol as Bile Acid,” Journal of Lipid Research, 2010, vol. 51, pp. 933-944.
[cited by applicant]
Liu B., et al., “Genetic Variations and Treatments that Affect the Lifespan of the NPC1 Mouse,” Journal of Lipid Research, 2008, vol. 49, pp. 663-669.
[cited by applicant]
Liu B., et al., “Reversal of Defective Lysosomal Transport in NPC Disease Ameliorates Liver Dysfunction and Neurodegeneration in the npc1-/- Mouse,” Proceedings of the National Academy of Sciences (PNAS), Feb. 17, 2009,…
[cited by applicant]
Loftsson T., et al., “Pharmaceutical Applications of Cyclodextrins: Basic Science and Product Development” Journal of Pharmacy and Pharmacology, 2010, vol. 62, pp. 1607-1621.
[cited by applicant]
Lopez A. M., et al., “Systemic Administration of 2-Hydroxypropyl-Beta-Cyclodextrin to Symptomatic Npc1-Deficient Mice Slows Cholesterol Sequestration in the Major Organs and Improves Liver Function,” Clinical and Experi…
[cited by applicant]
Maarup T.J., et al., “Intrathecal 2-Hydroxypropyl-Beta-Cyclodextrin in a Single Patient with Niemann-Pick C1,” Molecular Genetics Metabolism, 2015, vol. 116, 13 pages.
[cited by applicant]
Machine Translation for CN102040675A, 2011, 12 pages.
[cited by applicant]
Maetzel D., et al., “Genetic and Chemical Correction of Cholesterol Accumulation and Impaired Autophagy in Hepatic and Neural Cells Derived From Niemann-Pick Type C Patient-Specific iPS Cells,” Stem Cell Reports, Jun. 3…
[cited by applicant]
Malanga M., et al., ““Back to the Future”: A New Look at Hydroxypropyl Beta-Cyclodextrins,” Journal of Pharmaceutical Sciences, 2016, vol. 105, No. 9, pp. 2921-2931.
[cited by applicant]
Marcus A.D., “A Mom Brokers Treatment for Her Twins' Fatal Illness,” The Wall Street Journal, Apr. 3, 2009, 4 pages, Retrieved from the Internet: URL: https://www.wsj.com/articles/SB123871183055784317.
[cited by applicant]
Marcus A.D., “Small Biotech Gets Rights to Rare Disease Drug,” Press Release, Jan. 7, 2015, 3 pages, Retrieved from the Internet: URL: http://www.wsj.com/articles/small-biotech-vtesse-gets-rights-to-rare-disease-drug-14…
[cited by applicant]
Matsuo M., et al., “Effects of Cyclodextrin in Two Patients with Niemann-Pick Type C Disease,” Molecular Genetics and Metabolism, 2013, vol. 108, pp. 76-81.
[cited by applicant]
Matsuo M., et al., “Effects of Intracerebroventricular Administration of 2-Hydroxypropyl-B-Cyclodextrin in a Patient with Niemann-Pick Type C Disease,” Molecular Genetics and Metabolism Reports, 2014, vol. 1, pp. 391-40…
[cited by applicant]
Maue R.A., et al., “A Novel Mouse Model of Niemann-Pick Type C Disease Carrying a D1005G-Npc1 Mutation Comparable to Commonly Observed Human Mutations,” Human Molecular Genetics, 2012, vol. 21, No. 4, pp. 730-750.
[cited by applicant]
Mccook A., “Twin Disorders,” The Scientist, Nov. 1, 2008, 7 pages.
[cited by applicant]
Mendelsohn A.R., et al., “Preclinical Reversal of Atherosclerosis by FDA-Approved Compound that Transforms Cholesterol into an Anti-Inflammatory “Prodrug”,” Rejuvenation Research, Jun. 20, 2016 [Published Online], vol. …
[cited by applicant]
Mengel E., et al., “Niemann-Pick Disease Type C Symptomatology: An Expert-Based Clinical Description,” Orphanet Journal of Rare Diseases, 2013, vol. 8, No. 166,11 Pages.
[cited by applicant]
Meske V., et al., “How To Reduce The Accumulation of Autophagic Vacuoles In NPC1-Deficient Neurons: A Comparison of Two Pharmacological Strategies,” Neuropharmacology, 2015, vol. 89, pp. 282-289.
[cited by applicant]
Meske V., et al., “The Autophagic Defect in Niemann-Pick Disease Type C Neurons Differs from Somatic Cells and Reduces Neuronal Viability,” Neurobiology of Disease, 2014, vol. 64, pp. 88-97.
[cited by applicant]
Millat G., et al., “Niemann-Pick C1 Disease: The l1061T Substitution is a Frequent Mutant Allele in Patients of Western European Descent and Correlates with a Classic Juvenile Phenotype,” American Journal of Human Genet…
[cited by applicant]
Mller B.W., et al., “Solubilization of Drugs by Modified-Cyclodextrins,” International Journal of Pharmaceutics, 1985, vol. 26, pp. 77-88.
[cited by applicant]
Montecucco F., et al. “Treatment with Kleptose Crysmeb Reduces Mouse Atherogenesis by Impacting on Lipid Profile and Th1 Lymphocyte Response,” Vascular Pharmacology, 2015, vol. 72, pp. 197-208.
[cited by applicant]
Munkacsi A.B., et al., “An “Exacerbate-Reverse” Strategy in Yeast Identifies Histone Deacetylase Inhibition as a Correction for Cholesterol and Sphingolipid Transport Defects in Human Niemann-Pick Type C Disease,” The J…
[cited by applicant]
Nah J., et al., “Autophagy in Neurodegenerative Diseases: From Mechanism to Therapeutic Approach,” Molecules and Cells, 2015, vol. 38, No. 5, pp. 381-389.
[cited by applicant]
NanoSonic Products, Inc. and CTD, Inc., “Certificate of Analysis, Trappsol THPB-EC,” dated Apr. 22, 2015.
[cited by applicant]
Non Final Office action for U.S. Appl. No. 18/141,832, mailed on Sep. 14, 2023, 12 pages.
[cited by applicant]
Non Final Office action for U.S. Appl. No. 19/028,631, mailed on Mar. 19, 2025, 30 pages.
[cited by applicant]
Non-Final Office Action for U.S. Appl. No. 18/633,063, mailed on Jun. 28, 2024, 21 Pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 17/745,487, mailed on Sep. 8, 2022, 8 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 17/970,080, mailed on Dec. 7, 2023, 10 pages.
[cited by applicant]
Vtesse Inc., “Vtesse Secures Additional $17 Million in Series A Extension to Support Further Product Development and Expand the Ongoing Clinical Trial of VTS-270 for the Treatment of Niemann-Pick Type C1 Disease,” Press…
[cited by applicant]
Walenbergh S.M.A, et al., “Weekly Treatment of 2-Hydroxypropyl-cyclodextrin Improves Intracellular Cholesterol Levels in LDL Receptor Knockout Mice,” International Journal of Molecular Sciences, 2015, vol. 16, No. 9, pp…
[cited by applicant]
Walkley S., et al., “141. Cyclodextrin Treatment Not Only Delays but also Reduces Established Intraneuronal Storage in Niemann-Pick Type C Disease,” Molecular Genetics and Metabolism, 2010, vol. 99, No. 2, 1 page.
[cited by applicant]
Walkley S.U., “Cellular Pathology of Lysosomal Storage Disorders,” Brain Pathology, 1998, vol. 8, pp. 175-193.
[cited by applicant]
Walkley S.U., et al., “Consequences of NPC1 and NPC2 Loss of Function in Mammalian Neurons,” Biochimica et Biophysica Acta (BBA)—Molecular and Cell Biology of Lipids, 2004, vol. 1685, No. 1-3, pp. 48-62.
[cited by applicant]
Walkley S.U., et al., “Gangliosides as Modulators of Dendritogenesis in Normal and Storage Disease-affected Pyramidal Neurons,” Cerebral Cortex, Oct. 2000, vol. 10, No. 10, pp. 1028-1037.
[cited by applicant]
Walkley S.U., et al., “Lysosomal Compromise and Brain Dysfunction: Examining the Role of Neuroaxonal Dystrophy,” Biochemical Society Transactions, Dec. 2010, vol. 38, No. 6, 13 pages.
[cited by applicant]
Walpole S.C., et al., “The Weight of Nations: An Estimation of Adult Human Biomass,” BMC Public Health, 2012, vol. 12, No. 439, 6 pages.
[cited by applicant]
Wang M.L., et al., “Identification of Surface Residues on Niemann-Pick C2 Essential for Hydrophobic Handoff of Cholesterol to NPC1 in Lysosomes,” Cell Metabolism, Aug. 4, 2010, vol. 12, No. 2, pp. 166-173.
[cited by applicant]
Ward S., et al., “2-hydroxypropyl-beta-Cyclodextrin Raises Hearing Threshold in Normal Cats and in Cats with Niemann-pick Type C Disease,” Pediatric Research, 2010, vol. 68, No. 1, pp. 52-56.
[cited by applicant]
Wehrmann Z.T., et al., “Quantitative Comparison of the Efficacy of Various Compounds in Lowering Intracellular Cholesterol Levels in Niemann-Pick Type C Fibroblasts,” PLoS One, Oct. 2012, vol. 7, No. 10, 9 pages.
[cited by applicant]
Wistrand L.G., et al., “A Method for Removal of Endotoxin from Pharmaceutical Formulation,” BioPharm Interntional, Nov. 1, 2012, vol. 25, No. 9, 26 pages.
[cited by applicant]
Wraith J.E., et al., “Miglustat in Adult and Juvenile Patients with NiemannPick Disease Type C: Long-term Data from a Clinical Trial,” Molecular Genetics and Metabolism, 2009, 7 pages.
[cited by applicant]
Xu M., et al., “A Phenotypic Compound Screening Assay for Lysosomal Storage Diseases,” Journal of Biomolecular Screening, 2014, vol. 19, No. 1, pp. 168-175.
[cited by applicant]
Xu M., et al., “-Tocopherol Reduces Lipid Accumulation in Niemann-Pick Type C1 and Wolman Cholesterol Storage Disorders,” The Journal of Biological Chemistry, Nov. 16, 2012, vol. 287, No. 47, pp. 39349-39360.
[cited by applicant]
Yanjanin N.M., et al., “Linear Clinical Progression, Independent of Age of Onset, in NiemannPick Disease, Type C,” American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Jan. 5, 2010, vol. 153B, No. 1, …
[cited by applicant]
Yergey A.L., et al., “Characterization of Hydroxypropyl-Beta-Cyclodextrins by ESI Ion Mobility Mass Spectrometry,” Michael, Marcia, and Christa Parseghian Scientific Conference for Niemann-Pick Type C Research, 2016, 1 …
[cited by applicant]
Yergey A.L., et al., “Characterization of Hydroxypropyl-Beta-Cyclodextrins Used in the Treatment of Niemann-Pick Disease Type C1,” PLOS One, Apr. 17, 2017, vol. 12, No. 4, pp. 1-13.
[cited by applicant]
Yu D., et al., “NiemannPick Disease Type C: Induced Pluripotent Stem CellDerived Neuronal Cells for Modeling Neural Disease and Evaluating Drug Efficacy,” Journal of Biomolecular Screening, 2014, vol. 19, No. 8, pp. 116…
[cited by applicant]
Yuan C., et al., “Characterization of Hydroxypropyl-Cyclodextrins with Different Substitution Patterns via FTIR, GCMS, andTGDTA,” Carbohydrate Polymers, 2015, vol. 118, pp. 36-40.
[cited by applicant]
Zervas M., et al., “Critical Role for Glycosphingolipids in Niemann-Pick Disease Type C,” Current Biology, 2001, vol. 11, No. 16, pp. 1283-1287.
[cited by applicant]
Zimmer S., et al., “Cyclodextrin Promotes Atherosclerosis Regression via Macrophage Reprogramming,” Science Translational Medicine, Apr. 6, 2016, vol. 8, No. 333, 12 pages.
[cited by applicant]
Zimmer S., et al., “Cyclodextrin Promotes Atherosclerosis Regression via Macrophage Reprogramming,” Science Translational Medicine, 2016, vol. 8, No. 333, pp. 1-31.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/219,596, dated Jul. 29, 2025, 8 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/072,260, mailed on Jun. 30, 2023, 22 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/115,897, mailed on May 5, 2023, 10 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/115,898, mailed on Jun. 7, 2023, 49 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/115,901, mailed on Jun. 29, 2023, 55 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/130,132, mailed on Jul. 11, 2023, 09 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/141,832, mailed on Oct. 25, 2023, 13 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/175,757, dated Jul. 1, 2025, 8 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/028,631, dated May 27, 2025, 7 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/061,509, dated May 7, 2025, 8 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/061,577, dated May 19, 2025, 9 pages.
[cited by applicant]
Nunes M.J., et al., “Histone Deacetylase Inhibition Decreases Cholesterol Levels in Neuronal Cells by Modulating Key Genes in Cholesterol Synthesis, Uptake And Efflux,” PLOS One, Jan. 2013, vol. 8, No. 1,10 pages.
[cited by applicant]
Office Action for Chinese Application No. 201380052023.0, mailed on Jul. 28, 2016, 14 Pages.
[cited by applicant]
Office action for Chinese Application No. 201680041193.2, mailed on Jul. 11, 2019, 12 pages.
[cited by applicant]
Office action for Eurasian Application No. 201792487/28, mailed on Nov. 29, 2018, 2 pages.
[cited by applicant]
Office action for European Application No. 16808313.7, mailed on Feb. 8, 2019, 4 pages.
[cited by applicant]
Office action for European Application No. 16808313.7, mailed on May 29, 2018, 10 pages.
[cited by applicant]
Office action for Israell Application No. 255991, mailed on Jun. 3, 2019, 6 pages.
[cited by applicant]
Office action for Singapore Application No. 11201710032U, mailed on Dec. 13, 2018, 10 pages.
[cited by applicant]
Office Action for U.S. Appl. No. 14/419,471, mailed on Apr. 19, 2016, 18 Pages.
[cited by applicant]
Office Action for U.S. Appl. No. 14/419,471, mailed on Dec. 12, 2016, 16 Pages.
[cited by applicant]
Office action for U.S. Appl. No. 16/134,028, mailed on Nov. 16, 2018, 10 pages.
[cited by applicant]
Office action for U.S. Appl. No. 16/372,899, mailed on Nov. 21, 2019, 6 pages.
[cited by applicant]
Office action for U.S. Appl. No. 16/430,664, mailed on Feb. 18, 2020, 9 pages.
[cited by applicant]
Office Action for U.S. Appl. No. 17/985,762, mailed on Mar. 13, 2023, 14 pages.
[cited by applicant]
Office Action for U.S. Appl. No. 18/072,260, mailed on Apr. 18, 2023, 26 pages.
[cited by applicant]
Office Action for Venezuela Application No. 2016000260, mailed on Dec. 1, 2022, 4 pages.
[cited by applicant]
Ordonez M.P., et al., “Disruption and Therapeutic Rescue of Autophagy in a Human Neuronal Model of Niemann PickType C1,” Human Molecular Genetics, 2012, vol. 21, No. 12, pp. 2651-2662.
[cited by applicant]
Ottinger E.A., et al., “Collaborative Development of 2-Hydroxypropyl-Cyclodextrin for the Treatment of Niemann-Pick Type C1 Disease,” Current Topics in Medicinal Chemistry, 2014, vol. 14, No. 3, 20 pages.
[cited by applicant]
Ozkok A., “Cholesterol-Embolization Syndrome: Current Perspectives,” Vascular Health and Risk Management [Online], Jul. 2019, vol. 15, pp. 209-220, XP093169720, DOI: 10.2147/VHRM.S175150, Retrieved from the Internet: UR…
[cited by applicant]
Pacheco C.D., et al., “Autophagy in NiemannPick C Disease is Dependent Upon Beclin-1 and Responsive to Lipid Trafficking Defects,” Human Molecular Genetics, 2007, vol. 16, No. 12, pp. 1495-1503.
[cited by applicant]
Papandreou A., et al., “Diagnostic Workup and Management of C Patients with Suspected Niemann-Pick Type C Disease,” Therapeutic Advances in Neurological Disorders, 2016, vol. 9, No. 3, pp. 216-229.
[cited by applicant]
Patterson M., “Niemann-Pick Disease Type C,” GeneReviews [Online], 2000, 24 pages, Retrieved from the Internet: URL: https://www.ncbi.nlm.nih.gov/books/NBK1296/.
[cited by applicant]
Patterson M.C., et al., “Long-Term Miglustat Therapy in Children With Niemann-Pick Disease Type C,” Journal of Child Neurology, Mar. 2010, vol. 25, No. 3, pp. 300-305.
[cited by applicant]
Patterson M.C., et al., “Recommendations for the Diagnosis and Management of Niemann-Pick Disease Type C: An Update,” Molecular Genetics and Metabolism, 2012, vol. 106, No. 3,15 pages.
[cited by applicant]
Patterson M.C., “Miglustat for Treatment of Niemann-Pick C Disease: A Randomised Controlled Study,” The Lancet Neurology, 2007, vol. 6, 8 pages.
[cited by applicant]
Peake K.B., et al., “Normalization of Cholesterol Homeostasis by 2-Hydroxypropyl-cyclodextrin in Neurons and Glia from Niemann-Pick C1 (NPC1)-deficient Mice,” The Journal of Biological Chemistry, Mar. 16, 2012, vol. 287…
[cited by applicant]
Pharmacopeia Online, “Hydroxypropyl Betadex,” USP32-NF27 p. 1250, Pharmacopeial Forum: retrieved on Oct. 19, 2023, vol. 32, No. 5, 4 pages, Retrieved from the Internet URL: http://www.uspbpep.com/usp32/pub/data/v32270/u…
[cited by applicant]
Pillai B.K., et al., “Fast Diffusion of Very Long Chain Saturated Fatty Acids across a Bilayer Membrane and Their Rapid Extraction by Cyclodextrins: Implications for Adrenoleukodystrophy,” The Journal of Biological Chem…
[cited by applicant]
Pipalia N.H., et al., “Histone Deacetylase Inhibitor Treatment Dramatically Reduces Cholesterol Accumulation in Niemann-Pick Type C1 Mutant Human Fibroblasts,” Proceedings of the National Academy of Sciences (PNAS), Apr…
[cited by applicant]
Pitha J., et al., “Distribution of Substituents in Hydroxypropyl Ethers of Cyclomaltoheptaose,” Carbohydrate Research, 1990, vol. 200, pp. 429-435.
[cited by applicant]
Pitha J., et al., “Drug Solubilizers to Aid Pharmacologists: Amorphous Cylodextrin Derivatives,” Life Sciences, 1988, vol. 43, No. 6, pp. 493-502.
[cited by applicant]
Pitha J., et al., “Hydroxypropyl-Cyclodextrin: Preparation and Characterization; Effects on Solubility of Drugs,” International Journal of Pharmaceutics, 1986, vol. 29, No. 1, pp. 73-82.
[cited by applicant]
Pontikis C.C., et al., “Cyclodextrin Alleviates Neuronal Storage of Cholesterol in Niemann-Pick C Disease Without Evidence of Detectable Blood-Brain Barrier Permeability,” Journal of Inherited Metabolic Disease, May 201…
[cited by applicant]
Porter F.D., et al., “Phase 1/2 Evaluation of Intrathecal 2-Hydroxypropyl-Cyclodextrin for the Treatment of Niemann-Pick Disease Type C1,” Molecular Genetics and Metabolism, 2016, vol. 117, 1 page.
[cited by applicant]
Puskas I., et al, “Aggregation Behavior of Cyclodextrin and Cholesterol in Simulated Human Cerebrospinal Fluid,” Bioactive Carbohydrates and Dietary Fibre, 2013, vol. 2, No. 2, pp. 157-163.
[cited by applicant]
Raal F.J., et al., “Familial Hypercholesterolemia Treatments: Guidelines and New Therapies,” Atherosclerosis, Oct. 2018, vol. 277, pp. 483-492.
[cited by applicant]
Ramirez C.M., et al., “Quantitative Role of LAL, NPC2, and NPC1 in Lysosomal Cholesterol Processing Defined by Genetic and Pharmacological Manipulations,” Journal of Lipid Research, 2011, vol. 52, No. 4, pp. 688-698.
[cited by applicant]
Ramirez C.M., et al., “Weekly Cyclodextrin Administration Normalizes Cholesterol Metabolism in Nearly Every Organ of the Niemann-Pick Type C1 Mouse and Markedly Prolongs Life,” Pediatric Research, 2010, vol. 68, No. 4, …
[cited by applicant]
Rao C.T., et al., “Distribution of Substituents in O-(2-hydroxypropyl) Derivatives of Cyclomalto-oligosaccharides Cyclodextrins): Influence of Increasing Substitution, of the Base Used in the Preparation, and of Macrocy…
[cited by applicant]
Rao C.T., et al., “Substitution in Beta-Cyclodextrin Directed by Basicity: Preparation of 2-O-and 6-O-[(R)-and (S)-2-hydroxypropyl] Derivatives,” The Journal of Organic Chemistry, 1991, vol. 56, No. 1, pp. 1327-1329.
[cited by applicant]
Abi-Mosleh L., et al., “Cyclodextrin Overcomes Deficient Lysosome-To-Endoplasmic Reticulum Transport of Cholesterol in Niemann-Pick Type C Cells,” Proceedings of the National Academy of Sciences, Nov. 17, 2009, vol. 106…
[cited by applicant]
Acucena R.W., “Defining a strategy for the Validation and Qualification of Sterile Filtration Processes of Investigational Medicinal Compounds,” PDA Metro Chapter Dinner, Mar. 4, 2014, 45 pages.
[cited by applicant]
Alvarez A.R., et al., “Imatinib Therapy Blocks Cerebellar Apoptosis and Improves Neurological Symptoms in A Mouse Model of Niemann-Pick Type C Disease,” The FASEB Journal, Oct. 2008, vol. 22, pp. 3617-3627.
[cited by applicant]
Aqul A., et al., “Unesterified Cholesterol Accumulation in Late Endosomes/Lysosomes Causes Neurodegeneration and Is Prevented by Driving Cholesterol Export from This Compartment,” The Journal of Neuroscience, Jun. 22, 2…
[cited by applicant]
Beers M.H., et al., “Hydroxypropyl Beta-Cyclodextrin Compositions and Methods,” The Merck Manual of Diagnosis and Therapy, 1992, pp. 1049-1051.
[cited by applicant]
Bhandari T., “Protein Linked to Alzheimer's, Strokes Cleared from Brain Blood Vessels,” Washington University School of Medicine, Feb. 17, 2021,6 pages, Retrieved from the Internet: URL: https://medicine.wustl.edu/news/…
[cited by applicant]
Boldrini R., et al., “Wolman Disease and Cholesteryl Ester Storage Disease Diagnosed by Histological and Ultrastructural Examination of Intestinal and Liver Biopsy,” Pathology—Research and Practice, 2004, vol. 200, pp. …
[cited by applicant]
Brewster M. E., et al., “An Intravenous Toxicity Study of 2-Hydroxypropyl-Cyclodextrin, a Useful Drug Solubilizer, in Rats and Monkeys,” International Journal of Pharmaceutics, 1990, vol. 59, pp. 231-243.
[cited by applicant]
Byun K., et al., “Alteration of the Glutamate and GABA Transporters in the Hippocampus of the Niemann-Pick Disease, Type C Mouse Using Proteomic Analysis,” Proteomics, 2006, vol. 6, pp. 1230-1236.
[cited by applicant]
Camargo F., et al., “Cyclodextrins in the Treatment of a Mouse Model of Niemann-Pick C Disease,” Life Sciences, 2001, vol. 70, No. 2, pp. 131-142.
[cited by applicant]
Cantz M., et al., Disorders of Glycoprotein Degradation, Journal of Inherited Metabolic Disease, 1990, vol. 13 pp. 523-537.
[cited by applicant]
Carstea E.D., et al., “Niemann-Pick C1 Disease Gene: Homology to Mediators of Cholesterol Homeostasis,” Science, Jul. 11, 1997, vol. 277, pp. 228-231.
[cited by applicant]
Chen F.W., et al., “Cyclodextrin Induces Calcium-Dependent Lysosomal Exocytosis,” PLOS One, Nov. 2010, vol. 5, No. 11, 7 Pages.
[cited by applicant]
Chien Y.H., et al., “Long-Term Efficacy of Miglustat in Paediatric Patients with Niemann-Pick Disease Type C,” Journal of Inherited Metabolic Disease, 2013, vol. 36, pp. 129-137.
[cited by applicant]
Choi H.Y., et al., “Impaired ABCA1-Dependent Lipid Efflux and Hypoalphalipoproteinemia in Human Niemann-Pick Type C Disease,” Journal of Biological Chemistry, Aug. 29, 2003, vol. 278, No. 35, pp. 32569-32577.
[cited by applicant]
Cluzeau C.V.M., et al., “Microarray Expression Analysis and Identification of Serum Biomarkers for Niemann-Pick Disease, Type C1,” Human Molecular Genetics, 2012, vol. 21, No. 16, pp. 3632-3646.
[cited by applicant]
Coisne C., et al., “Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases,” Molecules, Dec. 20, 2016, vol. 21, No. 12, pp. 1-22, XP055548026, DOI:…
[cited by applicant]
Cologna S.M., et al., “Quantitative Proteomic Analysis of Niemann-Pick Disease, Type C1 Cerebellum Identifies Protein Biomarkers and Provides Pathological Insight,” PLoS One, Oct. 2012, vol. 7, No. 10, 13 pages.
[cited by applicant]
Crumling M.A., et al., “Hearing Loss and Hair Cell Death in Mice Given the Cholesterol-Chelating Agent Hydroxypropyl-Cyclodextrin,” PLoS One, Dec. 2012, vol. 7, No. 12, 8 pages.
[cited by applicant]
Cruz-Pardos S., et al., “Treatment with Cyclodextrin for Niemann Pick's Disease,” Farm Hospital, 2013, vol. 37, No. 3, pp. 263-272.
[cited by applicant]
CTD, Inc., “Cyclo Powder, Product Brochure,” Retrieved from the Internet on Nov. 21, 2023, 3 pages.
[cited by applicant]
Davidson, C. D., et al., “Efficacy of Different Cyclodextrins in the Treatment of Niemann-Pick type C Disease,” Jun. 2012, Abstract, Retrieved from the Internet: URL: http://niemannpick.nd.edu/assets/69394/abstracts_in_…
[cited by applicant]
Davidson C., et al., “Chronic Cyclodextrin Administration Ameliorates Clinical Symptoms and Storage Accumulation in Niemann-Pick Type C1 Mice,” Lysosomal Disease Network Annual Meeting, Feb. 18-20, 2009, 1 page.
[cited by applicant]
Davidson C., et al., “Different Cyclodextrins for the Treatment of Niemann-Pick Disease Type C,” Molecular Genetics and Metabolism, 2016, vol. 117, 1 page.
[cited by applicant]
Davidson C., et al., “Poster: Combinatorial Therapy for Niemann-Pick Type C Disease: Treatment of an NPC1 Murine Model with 2-Hydroxypropyl-Beta-Cyclodextrin and Miglustat,” World Symposium, 2015.
[cited by applicant]
Davidson C.D., et al., “Chronic Cyclodextrin Treatment of Murine Niemann-Pick C Disease Ameliorates Neuronal Cholesterol and Glycosphingolipid Storage and Disease Progression,” PLoS One, Sep. 2009, vol. 4, No. 9, 15 Pag…
[cited by applicant]
Davidson C.D., et al., “Efficacy and Ototoxicity of Different Cyclodextrins in Niemann-Pick C Disease,” Annals of Clinical and Translational Neurology, 2016, vol. 3, No. 5, pp. 366-380.
[cited by applicant]
De Windt A., et al., “Gene Set Enrichment Analyses Revealed Several Affected Pathways in Niemann-Pick Disease Type C Fibroblasts,” DNA and Cell Biology, 2007, vol. 26, No. 9, pp. 665-671.
[cited by applicant]
Decroocq C., et al., “Cyclodextrin-Based Iminosugar Click Clusters: The First Examples of Multivalent Pharmacological Chaperones for the Treatment of Lysosomal Storage Disorders,” ChemBioChem, 2012, vol. 13, No. 5, pp. …
[cited by applicant]
Dekaban A.S., et al., “Changes in Brain Weights during the Span of Human Life: Relation of Brain Weights to Body Heights and Body Weights,” Annals of Neurology, 1978, vol. 4, pp. 345-356.
[cited by applicant]
Elrick M.J., et al., “Autophagic Dysfunction in a Lysosomal Storage Disorder Due To Impaired Proteolysis,” Autophagy, Feb. 2013, vol. 9, No. 2, 2 pages.
[cited by applicant]
European Medicines Agency, “Background Review for Cyclodextrins Used as Excipients,” Committee for Human Medicinal Products (CHMP), Nov. 20, 2014, 17 pages, Retrieved from the Internet: URL: http://www.ema.europa.eu/doc…
[cited by applicant]
European Medicines Agency, “Background Review for the Excipient Propylene Glycol,” Committee for Human Medicinal Products (CHMP), Nov. 20, 2014, 96 pages.
[cited by applicant]
Favier M.L., et al., “Effect of Cyclodextrin on Plasma Lipids and Cholesterol Metabolism in the Rat,” Metabolism, Feb. 1995, vol. 44, No. 02, pp. 200-206.
[cited by applicant]
Fenyvesi F., et al., “Fluorescently Labeled Methyl-Beta-Cyclodextrin Enters Intestinal Epithelial Caco-2 Cells By Fluid-Phase Endocytosis,” PLoS One, Jan. 2014, vol. 9, No. 1,11 pages.
[cited by applicant]
First Examination Report for Australian Application No. 2013296170, mailed on May 5, 2017, 4 pages.
[cited by applicant]
Fromming K.H., et al., “Pharmacokinetics and Toxicology of Cyclodextrins,” Cyclodextrins in Pharmacy, Chapter 3, 1994, pp. 33-44.
[cited by applicant]
Garcia-Robels A.A., et al., “Use of 2 Hydroxypropyl-Beta-Cyclodextrin Therapy in Two Adult Niemann Pick Type C Patients,” Journal of the Neurological Sciences, 2016, vol. 366, pp. 65-67.
[cited by applicant]
Gelsthorpe M.E., et al., “Niemann-Pick Type C1 l1061T Mutant Encodes A Functional Protein That Is Selected For Endoplasmic Reticulum-Associated Degradation Due To Protein Misfolding,” The Journal of Biological Chemistry…
[cited by applicant]
Ginocchio V.M., et al., “Efficacy of Miglustat in NiemannPick C Disease: A Single Centre Experience,” Molecular Genetics and Metabolism, 2013, vol. 110, No. 3, pp. 329-335.
[cited by applicant]
Gould S., et al., “2-Hydroxypropyl-Cyclodextrin (HP-CD): A Toxicology Review,” Food and Chemical Toxicology, 2005, vol. 43, pp. 1451-1459.
[cited by applicant]
Grebe A., “Targeting Cholesterol Crystals in Atherosclerosis with Cholesterol Solubilizing 2-Hydroxypropyl-Cyclodextrin,” Dissertation, Mar. 2016, 157 pages.
[cited by applicant]
Hastings C. A., et al., “Clinical Experience with Intravenous and Intrathecal Infusions of Hydroxy-Propyl-Beta-Cyclodextrin in Identical Twin Patients with Niemann-Pick Type C Disease,” Jun. 2011, Abstract, Retrieved fr…
[cited by applicant]
Hempel C., “Dear British Media—Feel Free to Call or Email!,” Mar. 26, 2009, 2 pages, Retrieved from the Internet: URL http://addiandcassi.com/dear-british-media/.
[cited by applicant]
Hempel C., “Dr. Caroline Hastings Submission Letter to FDA: Investigational New Drug Application,” May 2009, 23 pages, Retrieved from the Internet: URL: http://addiandcassi.com/wordpress/wp-content/uploads/2009/09/FDA-C…
[cited by applicant]
Hempel C., “FDA Filing Requesting to put Cyclodextrin into the Brains of the Addi and Cassi,” Aug. 2010, 239 pages, Retrieved from the Internet: URL: http://addiandcassi.com/wordpress/wp-content/uploads/Hempel-Cyclodext…
[cited by applicant]
Hempel C., “FDA Investigational New Drug Application Documents for Cyclodextrin Treatment for Niemann Pick Type C Disease,” Addi & Cassi Fund [Online], Sep. 13, 2009, pp. 1-5, Retrieved from the Internet: URL: https…
[cited by applicant]
Heron B., et al., “Miglustat Therapy in the French Cohort of Paediatric Patients with Niemann-Pick Disease Type C,” Orphanet Journal of Rare Diseases, 2012, vol. 7, No. 36, 14 Pages.
[cited by applicant]
Herrmann H.C., et al., “Inhibition of Smooth Muscle Cell Proliferation and Experimental Angioplasty Restenosis by Beta-Cyclodextrin Tetradecasulfate,” Arteriosclerosis and Thrombosis, Jun. 1993, vol. 13, No. 6, pp. 924-…
[cited by applicant]
Hospira, “0.9% Sodium Chloride Injection,” USP, May 2014, 13 pages.
[cited by applicant]
Final Office Action for U.S. Appl. No. 18/958,956, dated Jun. 5, 2025, 27 pages.
[cited by applicant]
Frijlink H.W., et al., “The Effect of Parenterally Administered Cyclodextrins on Cholesterol Levels in the Rat,” Pharmaceutical Research, Jan. 1991, vol. 8, No. 1, pp. 9-16.
[cited by applicant]
Fu R., et al., “Apolipoprotein E Genotype and Neurological Disease Onset in Niemann-Pick Disease, Type C1,” American Journal of Medical Genetics Part A, Sep. 2012, pp. 2775-2780.
[cited by applicant]
Hackam D.G., et al., “Translation of Research Evidence From Animals to Humans,” Journal of the American Medical Association (JAMA), Oct. 11, 2006, vol. 296, No. 14, pp. 1731-1732.
[cited by applicant]
Helquist P., et al., “Treatment of Niemann-Pick Type C Disease by Histone Deacetylase Inhibitors,” Neurotherapeutics, Sep. 2013, vol. 10, pp. 688-697.
[cited by applicant]
International Search Report and Written Opinion in PCT/IB2023/051462 mailed on May 4, 2023, 10 pages.
[cited by applicant]
Liu B., “Therapeutic Potential of Cyclodextrins in the Treatment of NiemannPick Type C Disease,” Clinical Lipidology, Jun. 2012, vol. 7, No. 3, pp. 289-301.
[cited by applicant]
Mak I.W.Y., et al., “Lost in Translation: Animal Models and Clinical Trials in Cancer Treatment,” American Journal of Translational Research, 2014, vol. 6, No. 2, pp. 114-118.
[cited by applicant]
Matsuo M., et al., “Long-Term Efficacy of Intrathecal Cyclodextrin in Patients with Niemann-Pick Disease type C,” Brain and Development, 2024, vol. 46, pp. 207-212.
[cited by applicant]
Non-Final Office Action for U.S. Appl. No. 17/749,644, mailed on Feb. 12, 2024, 17 pages.
[cited by applicant]
Non-Final Office Action for U.S. Appl. No. 18/384,643, mailed on Mar. 14, 2024, 12 pages.
[cited by applicant]
Non-Final Office Action for U.S. Appl. No. 18/633,087 mailed on Jul. 15, 2024, 23 pages.
[cited by applicant]
Non-Final Office Action for U.S. Appl. No. 18/111,237, mailed on Sep. 28, 2023, 44 pages.
[cited by applicant]
Non-Final Office Action for U.S. Appl. No. 18/813,368, mailed on Dec. 5, 2024, 30 pages.
[cited by applicant]
Notice of Acceptance for Australian Application 2018202964 dated Aug. 8, 2019, 3 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/111,237, mailed on Nov. 24, 2023, 9 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/384,643, mailed on Aug. 14, 2024, 12 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/633,063, mailed on Sep. 26, 2024, 14 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/633,087, mailed on Nov. 20, 2024, 13 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/813,368, dated Sep. 30, 2025, 15 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/958,956, dated Aug. 26, 2025, 12 pages.
[cited by applicant]
Office Action for European Application 13762617.2, dated Mar. 27, 2019, 4 pages.
[cited by applicant]
Office Action for Australian Application No. 2018202964 dated Apr. 5, 2019, 9 pages.
[cited by applicant]
Office Action for Canadian Application No. 2880880 dated Aug. 23, 2019, 5 pages.
[cited by applicant]
Office Action for Chinese Application No. 201711057517.4 dated Jul. 1, 2020, 9 pages.
[cited by applicant]
Office Action for Japanese Application No. 2018-116666 dated Jun. 10, 2019, 5 pages.
[cited by applicant]
Office Action for Japanese Application No. 2018-116666 dated Oct. 23, 2019, 2 pages.
[cited by applicant]
Ory D.S., et al., “Intrathecal 2-hydroxypropyl-cyclodextrin Decreases Neurological Disease Progression in Niemann-Pick Disease, type C1: a Non-Randomised, Open-Label, phase 1-2 trial,” The Lancet, Oct. 2017, vol. 390, p…
[cited by applicant]
Peake K.B., et al., “Defective Cholesterol Trafficking in Niemann-Pick C-Deficient Cells,” FEBS Letters, vol. 584, No. 13, Jul. 2, 2010, pp. 2731-2739.
[cited by applicant]
Perlman R.L., “Mouse Models of Human Disease: An Evolutionary Perspective,” Evolution, Medicine, and Public Health, 2016, vol. 2016, No. 01, pp. 170-176.
[cited by applicant]
Reynolds M., et al., “A phase 1/2 Open Label Nonrandomized Clinical Trial of Intravenous 2-Hydroxypropyl-Cyclodextrin for Acute Liver Disease in Infants with Niemann-Pick C1,” Molecular Genetics and Metabolism Reports, …
[cited by applicant]
Stern W.C., et al., “Cyclodextrin-Based Drug Delivery,” Drug News and Perspectives, Oct. 1989, vol. 2, No. 7, pp. 410-415.
[cited by applicant]
Rao T.C., et al., “Pharmaceutical Usefulness of Hydroxypropylcyclodextrins: “E Pluribus Unum” Is an Essential Feature,” Pharmaceutical Research, 1990, vol. 7, No. 6, 4 pages.
[cited by applicant]
Rauniyar N., et al., “Quantitative Proteomics of Human Fibroblasts with l1061T Mutation in NiemannPick C1 (NPC1) Protein Provides Insights into the Disease Pathogenesis,” Molecular & Cellular Proteomics, 2015, vol. …
[cited by applicant]
Reagan J.W., et al., “Posttranslational Regulation of Acid Sphingomyelinase in Niemann-Pick Type C1 Fibroblasts and Free Cholesterol-enriched Chinese Hamster Ovary Cells,” The Journal of Biological Chemistry, Dec. 1, 20…
[cited by applicant]
Reddy J.V., et al., “Clues to Neuro-Degeneration in Niemann-Pick Type C Disease from Global Gene Expression Profiling,” PLoS One, Dec. 2006, vol. 1, No. 1, 7 pages.
[cited by applicant]
Rodal S.K., et al., “Extraction of Cholesterol with Methyl-Cyclodextrin Perturbs Formation of Clathrin-Coated Endocytic Vesicles,” Molecular Biology of the Cell, Apr. 1999, vol. 10, pp. 961-974.
[cited by applicant]
Roquette, Brochure: “Kleptose HP / Kleptose HPB, multifunctional excipients for molecular encapsulation,” 2005, retrieved from the Internet: URL: http://www.roquette-pharma.com/brochures/23/visio.html, on Sep. 16, 2016.
[cited by applicant]
Roquette, “Kleptose HPB Parenteral Grade product specification sheet,” dated Jul. 28, 2014.
[cited by applicant]
Roquette, “Kleptose HPB Parenteral Grade product specification sheet,” dated Mar. 2, 2015, 2 pages.
[cited by applicant]
Rosenbaum A.I., et al., “Endocytosis of Beta-Cyclodextrins is Responsible for Cholesterol Reduction in Niemann-Pick Type C Mutant Cells,” Proceedings of the National Academy of Sciences, Mar. 23, 2010, vol. 107, No. 12,…
[cited by applicant]
Rosenbaum A.I., et al., “Niemann-Pick Type C Disease: Molecular Mechanisms and Potential Therapeutic Approaches,” Journal of Neurochemistry, 2011, vol. 116, No. 5, pp. 789-795.
[cited by applicant]
Rosseels M.L.A., et al., “Hydroxypropyl-Cyclodextrin Impacts Renal and Systemic Hemodynamics in the Anesthetized Dog,” Regulatory Toxicology and Pharmacology, 2013, vol. 67, No. 3, pp. 1-9.
[cited by applicant]
Sakiyama Y., et al., “Intrathecal 2-Hydroxypropyl-Beta-Cyclodextrin (HPBCD) Therapy in Adult-Onset Niemann-Pick Disease Type C (NPC),” Journal of the Neurological Sciences, 2015, vol. 357, pp. e193-e214.
[cited by applicant]
Sarkar S., et al., “Impaired Autophagy in the Lipid-Storage Disorder Niemann-Pick Type C1 Disease,” Cell Reports, Dec. 12, 2013, vol. 5, pp. 1302-1315.
[cited by applicant]
Sarkar S., et al., “Restarting Stalled Autophagy a Potential Therapeutic Approach for the Lipid Storage Disorder, Niemann-Pick Type C1 Disease,” Autophagy, Jun. 2014, vol. 10, No. 6, pp. 1137-1140.
[cited by applicant]
Schonbeck C., et al., “Hydroxypropyl-Substituted Beta-Cydodextrins: Influence Of Degree of Substitution on the Thermodynamics of Complexation with Tauroconjugated and Glycoconjugated Bile Salts,” Langmuir, 2010, vol. 26…
[cited by applicant]
Schultz M.L., et al., “Clarifying Lysosomal Storage Diseases,” Trends in Neurosciences, Aug. 2011, vol. 34, No. 8, 20 pages.
[cited by applicant]
Soga M., et al., HPGCD Outperforms HPBCD as a Potential Treatment for Niemann-Pick Disease Type C During Disease Modeling with iPS Cells, Stem Cells, 2015, vol. 33, pp. 1075-1088.
[cited by applicant]
Song W., et al., “2-Hydroxypropyl-Cyclodextrin Promotes Transcription Factor EB-Mediated Activation of Autophagy,” The Journal of Biological Chemistry, Apr. 4, 2014, vol. 289, No. 14, pp. 10211-10222.
[cited by applicant]
Stella V., et al., “Cyclodextrins,” Toxicologic Pathology, 2008, vol. 36, pp. 30-42.
[cited by applicant]
Study NCT01747135, Clinical Trials, Comparison of Dec. 8, 2012 version and Apr. 2, 2014 version, retrieved from the internet: URL: https://clinicaltrials.gov/ct2/history/NCT01747135?A=1&B=19&C-Side-by-Side, 18 p…
[cited by applicant]
Sun D., et al., “Effect of the Platelet-Activating Factor Antagonist BN 50739 and Its Diluents on Mitochondrial Respiration and Membrane Lipids During and Following Cerebral Ischemia,” Journal of Neurochemistry, 1994, v…
[cited by applicant]
Swaroop M., et al., “Evaluation of Cholesterol Reduction Activity of Methyl-cyclodextrin Using Differentiated Human Neurons and Astrocytes,” Journal of Biomolecular Screening, 2012, vol. 17, No. 9, pp. 1243-1251.
[cited by applicant]
Szejtli J_, “Medicinal Applications of Cyclodextrins,” Medicinal Research Reviews, 1994, vol. 14, No. 3, pp. 353-386.
[cited by applicant]
Tamura A., et al., “-Cyclodextrin-Threaded Biocleavable Polyrotaxanes Ameliorate Impaired Autophagic Flux in Niemann-Pick Type C Disease,” The Journal of Biological Chemistry, Apr. 10, 2015, vol. 290, No. 15, pp. 9442-9…
[cited by applicant]
Tanaka Y., et al., “Efficacy of 2-Hydroxypropyl-p-cyclodextrin in Niemann-Pick Disease Type C Model Mice and Its Pharmacokinetic Analysis in a Patient with the Disease,” Biological and Pharmaceutical Bulletin, 2015, vol…
[cited by applicant]
Thackaberry E.A., et al., “Comprehensive Investigation of Hydroxypropyl Methylcellulose, Propylene Glycol, Polysorbate 80, and Hydroxypropyl-Beta-Cyclodextrin for use in General Toxicology Studies,” Toxicological Scienc…
[cited by applicant]
Thein P., et al., “In Vitro Assessment of Antiretroviral Drugs Demonstrates Potential for Ototoxicity,” Hearing Research, Apr. 2014, vol. 310, 19 pages.
[cited by applicant]
Tortelli B., et al., “Cholesterol Homeostatic Responses Provide Biomarkers for Monitoring Treatment for the Neurodegenerative Disease NiemannPick C1 (NPC1),” Human Molecular Genetics, 2014, vol. 23, No. 22, pp. 6022-603…
[cited by applicant]
United States Pharmacopeia Convention, “Hydroxypropyl Betadex,” NF Monographs, 2023, 1 page.
[cited by applicant]
Vance J.E., et al., “Function of the NiemannPick type C proteins and their bypass by cyclodextrin,” Current Opinion in Lipidology, 2011, vol. 22, pp. 204-209.
[cited by applicant]
Vance J.E., et al., “Niemann-Pick C Disease and Mobilization of Lysosomal Cholesterol by Cyclodextrin,” Journal of Lipid Research, 2014, vol. 55, pp. 1609-1621.
[cited by applicant]
Vanier M.T., et al., “NiemannPick disease type C,” Clinical Genetics, 2003, vol. 64, pp. 269-281.
[cited by applicant]
Vanier M.T., “Niemann-Pick Disease Type C,” Orphanet Journal of Rare Diseases, 2010, vol. 5, No. 16, 18 pages.
[cited by applicant]
Vazquez M.C., et al., “Alteration of Gene Expression Profile in Niemann-Pick Type C Mice Correlates with Tissue Damage and Oxidative Stress,” PLoS One, Dec. 2011, vol. 6, No. 12, 9 pages.
[cited by applicant]
Vieira C., “APMRF 2011 Meeting Summary for Npc Families and the NPC Community,” Jun. 2011, retrieved from the Internet: URL: http://niemannpick.nd.edu/assets/52704/apmrf_2011_summary_for_npc_families_and_the_npc_communi…
[cited by applicant]
Vieira C., et al., “Use of Cyclodextrin in Two Brazilian Girls With Niemann-Pick Type C-Intrathecal Report,” Jun. 2012, retrieved from the Internet URL: http://niemannpick.nd.edu/assets/69394/abstracts_in_speaking_order…
[cited by applicant]
Vieira C., “The Use of Cyclodextrin in Niemann-pick Type C Disease in Two Girls—Report After One Year of Treatment,” Jun. 2011, Abstract, retrieved on Jul. 20, 2016] Retrieved from the Internet URL: http://niemannpick.n…
[cited by applicant]
Vite C.H., et al., “Clinical, Electrophysiological, and Serum Biochemical Measures of Progressive Neurological and Hepatic Dysfunction in Feline Niemann-Pick Type C Disease,” Pediatric Research, 2008, vol. 64, No. 5, pp…
[cited by applicant]
Vite C.H., et al., “Intracisternal Cyclodextrin Prevents Cerebellar Dysfunction and Purkinje Cell Death in Feline Niemann-Pick Type C1 Disease,” Science Translational Medicine, Feb. 25, 2015, vol. 7, No. 276, 35 pages.
[cited by applicant]
Vite C.H., et al., “Intrathecal Cyclodextrin Therapy of Feline Niemann-pick Type C Disease,” Molecular Genetics and Metabolism, 2011, vol. 102, 4 pages.
[cited by applicant]
Vtesse Inc., “Leading Life Science Syndicate Commits $25 Million to Series A Funding to Launch Vtesse, Inc., the First Rare Disease Company Spun Out of Cydan Development, Inc.,” Press Release, Jan. 7, 2015, 5 pages.
[cited by applicant]
Vtesse Inc., “NIH Teams with Industry to Develop Treatments for Niemann-pick Type C Disease.,” Press Release, Jan. 7, 2015, 4 pages, Retrieved from the Internet: URL: https://www.nih.gov/news-events/news-releases/nih-te…
[cited by applicant]
Vtesse Inc., “Vtesse Advances Phase 2b/3 Clinical Trial of VTS-270 in Niemann-Pick Type C1 Disease with Dose Selection for Evaluation in Second and Final Portion of Trial and Expansion into Europe,” Press Release, May 2…
[cited by applicant]
Vtesse Inc., “Vtesse, Inc. Announces FDA's Granting of Breakthrough Therapy Designation for VTS-270 in Niemann-Pick Type C1 Disease,” Press Release, Jan. 6, 2016, 4 pages.
[cited by applicant]
Vtesse Inc., “Vtesse, Inc. Announces Phase 1/2 Clinical Data Showing Slowing of Disease Progression from VTS-270 Treatment for Niemann-Pick Type C1 Disease,” Press Release, Mar. 4, 2016, 3 pages.
[cited by applicant]
Vtesse Inc., “Vtesse, Inc. Announces Preliminary Data from Ongoing Phase 1 Study of VTS-270 for Treatment of Niemann-Pick Disease Type C,” Press Release, Aug. 6, 2015, 4 pages.
[cited by applicant]
Vtesse Inc., “Vtesse, Inc. Expands Scientific Advisory Board and Appoints New VP of Clinical Operations to Support Late-Stage Clinical Study of Lead Drug Candidate VTS-270,” Press Release, Oct. 22, 2015, 4 pages.
[cited by applicant]
Vtesse Inc., “Vtesse, Inc. Expands Scientific Advisory Board, Fills Key Patient Advocacy Position to Prepare for Further Clinical Development of VTS-270 in Niemann-Pick Disease Type C (NPC),” Press Release, Jun. 15, 201…
[cited by applicant]
Vtesse Inc., “Vtesse, Inc. Forms Scientific Advisory Board,” Press Release, Mar. 25, 2015, 3 pages.
[cited by applicant]
Vtesse Inc., “Vtesse, Inc. Initiates Phase 2b/3 Clinical Trial of VTS-270 for Treatment of Niemann-Pick Type C1 (NPC) Disease,” Press Release, Sep. 28, 2015, 4 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/533,373, dated Dec. 29, 2025, 9 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/350,944 dated Dec. 30, 2025, 10 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/278,356, dated Feb. 2, 2026, 9 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/278,422, dated Feb. 18, 2026, 9 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/350,939, dated Mar. 2, 2026, 9 pages.
[cited by applicant]
Kalydi E., et al., “Solving the Puzzle of 2-hydroxypropyl ß-cyclodextrin: Detailed Assignment of the Substituent Distribution by NMR Spectroscopy,” Carbohydrate Polymers, 2024, vol. 338, 122167, 11 Pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 18/533,373 mailed on Mar. 13, 2026, 2 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/278,356, mailed on Mar. 20, 2026, 2 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/278,380, dated Feb. 13, 2026, 9 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/278,422 mailed on Mar. 10, 2026, 2 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/312,906, dated Mar. 3, 2026, 9 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/332,924, mailed on Mar. 26, 2026, 13 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/350,933, dated Mar. 3, 2026, 9 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/350,944, mailed on Mar. 20, 2026, 2 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/371,517, dated Mar. 5, 2026, 9 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/371,517 mailed on Mar. 20, 2026, 6 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/371,529 mailed on Apr. 1, 2026, 2 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/371,529, mailed on Mar. 17, 2026, 12 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/371,542, mailed on Mar. 24, 2026, 13 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/371,584 dated Mar. 30, 2026, 11 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/406,162 dated Mar. 31, 2026, 11 pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/406,190 dated Apr. 7, 2026, 11 Pages.
[cited by applicant]
Notice of Allowance for U.S. Appl. No. 19/406,370, dated Apr. 21, 2026, 12 Pages.
[cited by applicant]