IP Library › Granted Patent US 12,589,097
Granted Patent B2
US 12,589,097 · App. 18/230,099 · Granted Mar 31, 2026

Apilimod compositions and methods of use

Inventor: Peter Ronald Young (Short Hills, NJ)
Assignee: OrphAl Therapeutics Inc.
A61K31/5377A61K9/0053A61K31/428A61K45/06A61P25/00A61P25/08A61P25/28
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,589,097
App. No.
18/230,099
Granted
Mar 31, 2026
Kind
B2
Abstract

Provided are compositions and methods related to the use of apilimod alone or in combination with glutamatergic agents or other agents for treating neurological diseases and disorders, and for the treatment of cancer.

Claims (18)

1 . A method of reducing neuromuscular degradation, reducing motor dysfunction, reducing deterioration of muscle strength, reducing deterioration of fine motor skills, maintaining fine motor skills, and/or improving muscle strength in a patient with a neurological disease or disorder comprising administering to the patient, an effective amount of apilimod, or a pharmaceutically acceptable salt thereof,

thereby reducing neuromuscular degradation, reducing motor dysfunction, reducing deterioration of muscle strength, reducing deterioration of fine motor skills, maintaining fine motor skills, and/or improving muscle strength in the patient.

2 . The method of claim 1 , wherein the apilimod is apilimod dimesylate.

3 . The method of claim 1 , wherein the apilimod is administered at a dose of about 75 mg to 125 mg twice daily (BID).

4 . The method of claim 3 , wherein the apilimod is administered at a dose of about 125 mg BID.

5 . The method of claim 3 , wherein the apilimod is administered at a dose of about 100 mg, two times a day (BID).

6 . The method of claim 3 , wherein the apilimod is administered at a dose of about 75 mg two times a day (BID).

7 . The method of claim 1 , wherein the apilimod, or a pharmaceutically acceptable salt thereof is in an oral dosage form or a sublingual dosage form.

8 . The method of claim 1 , wherein the neurological disease or disorder is selected from amyotrophic lateral sclerosis (ALS), Alzheimer's disease, attention deficit hyperactivity disorder, autism, cerebellar ataxia, Charcot-Marie-Tooth disease, Creutzfeldt-Jakob disease, dementia, epilepsy, Friedreich's ataxia, Huntington's disease, multiple sclerosis, obsessive compulsive disorder (OCD), Parkinson's disease, progressive supranuclear palsy, Rett syndrome, senile chorea, spinal ataxia, spinal cord injury, and traumatic brain injury.

9 . The method of claim 1 , further comprising administering an effective amount of a glutamatergic agent or an antioxidant.

10 . The method of claim 9 , wherein the glutamatergic agent is selected from a glutamate transporter modulating agent and a glutamate receptor antagonist.

11 . The method of claim 10 , wherein the glutamate transporter modulating agent is an excitatory amino acid reuptake inhibitor.

12 . The method of claim 10 , wherein the glutamate receptor antagonist is an N-methyl-D-aspartate (NMDA) receptor antagonist.

13 . The method of claim 10 , wherein the glutamate receptor antagonist is selected from AP5 (R-2-amino-5-phosphonopentanoate), AP7 (2-amino-7-phosphonoheptanoic acid), CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), CPPene (3-[(R)-2-carboxypiperazin-4-yl]-prop-2-enyl-1-phosphonic acid), NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione), and selfotel (CGS-19755).

14 . The method of claim 10 , wherein the glutamate receptor antagonist is selected from amantadine, atomoxetine, AZD6765, agmatine, gacyclidine, ketamine, memantine, eliprodil, and delucemin.

15 . The method of claim 9 , wherein the glutamatergic agent is selected from BHV-5000, lamotrigine, lanicemine, riluzole, trigriluzole, and topiramate.

16 . The method of claim 9 , wherein the antioxidant is edaravone, vitamin E, vitamin C, beta-carotene or a combination thereof.

17 . The method of claim 8 , wherein the neurological disease or disorder is ALS.

Assignments (4)
SECURITY INTEREST Recorded Feb 18, 2026
From: ORPHAI THERAPEUTICS INC.
To: ACADIA WOODS PARTNERS, LLC, AS AGENT
Reel/Frame 074910/0274 →
CORRECTIVE ASSIGNMENT TO CORRECT THE INCORRECTLY IDENTIFIED NUMBERS IN THE ORIGINAL RECORDATION. SPECIFICALLY, APPLICATION NO. 12171874, WHICH SHOULD CORRECTLY HAVE BEEN IDENTIFIED AS PATENT NO. 12171874, AND APPLICATION NO. 18239099, WHICH SHOULD CORRECTLY HAVE BEEN IDENTIFIED AS APPLICATION NO. 18230099 PREVIOUSLY RECORDED ON REEL 71697 FRAME 788. ASSIGNOR(S) HEREBY CONFIRMS THE SECURITY INTEREST. Recorded Jul 17, 2025
From: ORPHAI THERAPEUTICS INC.
To: ACADIA WOODS PARTNERS, LLC
Reel/Frame 072608/0124 →
CHANGE OF NAME Recorded Jul 17, 2024
From: AI THERAPEUTICS, INC.
To: ORPHAI THERAPEUTICS INC.
Reel/Frame 068410/0591 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 23, 2023
From: YOUNG, PETER RONALD
To: AI THERAPEUTICS, INC.
Reel/Frame 064684/0874 →
Continuity (1)
Related Publication 20240024332A1 · Jan 25, 2024
References Cited (303)
US 3536809A · Applezweig · 1970 [cited by applicant]
US 3598123A · Zaffaroni · 1971 [cited by applicant]
US 3683080A · Francis · 1972 [cited by applicant]
US 3822287A · Bolger · 1974 [cited by applicant]
US 3845770A · Theeuwes et al. · 1974 [cited by applicant]
US 3916899A · Theeuwes et al. · 1975 [cited by applicant]
US 3927197A · Monkhouse · 1975 [cited by applicant]
US 3932389A · Johnson et al. · 1976 [cited by applicant]
US 3982016A · Walsh · 1976 [cited by applicant]
US 4000309A · Walsh · 1976 [cited by applicant]
US 4008719A · Theeuwes et al. · 1977 [cited by applicant]
US 4018892A · Walsh · 1977 [cited by applicant]
US 4132847A · Kuhla et al. · 1979 [cited by applicant]
US 4133814A · Jones et al. · 1979 [cited by applicant]
US 4171331A · Biddlecom et al. · 1979 [cited by applicant]
US 4219483A · Kuhla et al. · 1980 [cited by applicant]
US 4418068A · Jones · 1983 [cited by applicant]
US 4536516A · Harper et al. · 1985 [cited by applicant]
US 4621100A · Lund et al. · 1986 [cited by applicant]
US 4623660A · Richardson · 1986 [cited by applicant]
US 4658019A · Kung et al. · 1987 [cited by applicant]
US 4839155A · Mccague · 1989 [cited by applicant]
US 4904478A · Walsdorf et al. · 1990 [cited by applicant]
US 4946778A · Ladner et al. · 1990 [cited by applicant]
US 4996225A · Toivola et al. · 1991 [cited by applicant]
US 5017691A · Lee et al. · 1991 [cited by applicant]
US 5047431A · Schickaneder et al. · 1991 [cited by applicant]
US 5059595A · Le Grazie · 1991 [cited by applicant]
US 5073543A · Marshall et al. · 1991 [cited by applicant]
US 5120548A · Mcclelland et al. · 1992 [cited by applicant]
US 5216183A · Sugiura et al. · 1993 [cited by applicant]
US 5225539A · Winter · 1993 [cited by applicant]
US 5354556A · Sparks et al. · 1994 [cited by applicant]
US 5484795A · Bryant et al. · 1996 [cited by applicant]
US 5488058A · Palkowitz · 1996 [cited by applicant]
US 5498538A · Fowlkes et al. · 1996 [cited by applicant]
US 5552412A · Cameron et al. · 1996 [cited by applicant]
US 5591767A · Mohr et al. · 1997 [cited by applicant]
US 5597898A · Ghosh · 1997 [cited by applicant]
US 5639476A · Oshlack et al. · 1997 [cited by applicant]
US 5674533A · Santus et al. · 1997 [cited by applicant]
US 5733566A · Lewis · 1998 [cited by applicant]
US 6001652A · Monia et al. · 1999 [cited by applicant]
US 6162432A · Wallner et al. · 2000 [cited by applicant]
US 6190619B1 · Kilcoin et al. · 2001 [cited by applicant]
US 6194612B1 · Boger et al. · 2001 [cited by applicant]
US 6384032B1 · Ono et al. · 2002 [cited by applicant]
US 6660733B2 · Sun et al. · 2003 [cited by applicant]
US 6680315B2 · Ono et al. · 2004 [cited by applicant]
US 6693097B2 · Ono et al. · 2004 [cited by applicant]
US 6774130B2 · Klein et al. · 2004 [cited by applicant]
US 6858606B2 · Sun et al. · 2005 [cited by applicant]
US 6958332B2 · Sun et al. · 2005 [cited by applicant]
US 7045517B2 · Ono et al. · 2006 [cited by applicant]
US 7067514B2 · Ono et al. · 2006 [cited by applicant]
US 7470681B2 · Sun et al. · 2008 [cited by applicant]
US 7745436B2 · Kostik et al. · 2010 [cited by applicant]
US 7851466B2 · Wada et al. · 2010 [cited by applicant]
US 7863270B2 · Demko et al. · 2011 [cited by applicant]
US 7919487B2 · Sun et al. · 2011 [cited by applicant]
US 7923557B2 · Zhang et al. · 2011 [cited by applicant]
US 8318730B2 · Ono et al. · 2012 [cited by applicant]
US 9910031B2 · Lu et al. · 2018 [cited by applicant]
US 10751345B2 · Lichenstein et al. · 2020 [cited by applicant]
US 11439649B2 · Lichenstein et al. · 2022 [cited by applicant]
US 20020045235A1 · Karin et al. · 2002 [cited by applicant]
US 20020082259A1 · Ono et al. · 2002 [cited by applicant]
US 20030114446A1 · Sun et al. · 2003 [cited by applicant]
US 20030139403A1 · Ono et al. · 2003 [cited by applicant]
US 20040024206A1 · Sun et al. · 2004 [cited by applicant]
US 20040048873A1 · Ono et al. · 2004 [cited by applicant]
US 20040053926A1 · Ono et al. · 2004 [cited by applicant]
US 20040053937A1 · Sun et al. · 2004 [cited by applicant]
US 20050282232A1 · Lu et al. · 2005 [cited by applicant]
US 20080058297A1 · Ono et al. · 2008 [cited by applicant]
US 20080227114A1 · Lu et al. · 2008 [cited by applicant]
US 20090118291A1 · Belvedere et al. · 2009 [cited by applicant]
US 20110081338A1 · Roberts et al. · 2011 [cited by applicant]
US 20110287018A1 · Bosch · 2011 [cited by applicant]
US 20120208203A1 · Lu et al. · 2012 [cited by applicant]
US 20130267521A1 · Castro et al. · 2013 [cited by applicant]
US 20160003804A1 · Lu et al. · 2016 [cited by applicant]
US 20170007613A1 · Lichenstein et al. · 2017 [cited by applicant]
US 20170020884A1 · Lichenstein et al. · 2017 [cited by applicant]
US 20180015098A1 · Lichenstein et al. · 2018 [cited by applicant]
US 20180036420A1 · Xu et al. · 2018 [cited by applicant]
US 20180050041A1 · Conrad et al. · 2018 [cited by applicant]
US 20180217130A1 · Lu et al. · 2018 [cited by applicant]
US 20190255061A1 · Lichenstein et al. · 2019 [cited by applicant]
US 20190365771A1 · Lichenstein et al. · 2019 [cited by applicant]
US 20200306255A1 · Conrad et al. · 2020 [cited by applicant]
US 20210077502A1 · Licehnstein et al. · 2021 [cited by applicant]
US 20210140945A1 · Lu et al. · 2021 [cited by applicant]
CN 103536594 · 2014 [cited by applicant]
EA 201270225A1 · 2012 [cited by applicant]
JP 2014510707A · 2014 [cited by applicant]
JP 2017503842 · 2017 [cited by applicant]
JP 2017533963 · 2017 [cited by applicant]
JP 2017535600 · 2017 [cited by applicant]
JP 2017535601 · 2017 [cited by applicant]
JP 2017535613 · 2017 [cited by applicant]
WO WO199013678A1 · 1990 [cited by applicant]
WO WO199308656A1 · 1993 [cited by applicant]
WO WO199320242A1 · 1993 [cited by applicant]
WO WO199401460A1 · 1994 [cited by applicant]
WO WO199413696A1 · 1994 [cited by applicant]
WO WO199418318A1 · 1994 [cited by applicant]
WO WO199419367A1 · 1994 [cited by applicant]
WO WO199510513A1 · 1995 [cited by applicant]
WO WO199513069A1 · 1995 [cited by applicant]
WO WO199514666A1 · 1995 [cited by applicant]
WO WO199534311A1 · 1995 [cited by applicant]
WO WO200078757A1 · 2000 [cited by applicant]
WO WO2002069904A2 · 2002 [cited by applicant]
WO WO2002098370A2 · 2002 [cited by applicant]
WO WO2003047516A2 · 2003 [cited by applicant]
WO WO2005046619A2 · 2004 [cited by applicant]
WO WO2005000404A2 · 2005 [cited by applicant]
WO WO2005046604A2 · 2005 [cited by applicant]
WO WO2005112938A2 · 2005 [cited by applicant]
WO WO2005046619A3 · 2006 [cited by applicant]
WO WO2006053109A1 · 2006 [cited by applicant]
WO WO2006053112A1 · 2006 [cited by applicant]
WO WO2006060194A1 · 2006 [cited by applicant]
WO WO2006128129A2 · 2006 [cited by applicant]
WO WO2006128172A2 · 2006 [cited by applicant]
WO WO2008008433A2 · 2008 [cited by applicant]
WO WO2008008433A3 · 2008 [cited by applicant]
WO WO2006128129A3 · 2008 [cited by applicant]
WO WO2012093127A2 · 2012 [cited by applicant]
WO WO2015112888A1 · 2015 [cited by applicant]
WO WO2016073871A1 · 2016 [cited by applicant]
WO WO2016073877A1 · 2016 [cited by applicant]
WO WO2016081466A1 · 2016 [cited by applicant]
WO WO2016112072A1 · 2016 [cited by applicant]
WO WO2016118709A1 · 2016 [cited by applicant]
WO WO2016126707A1 · 2016 [cited by applicant]
WO WO2016160102A1 · 2016 [cited by applicant]
WO WO2016210372A2 · 2016 [cited by applicant]
WO WO2017015262A1 · 2017 [cited by applicant]
WO WO2017040971A1 · 2017 [cited by applicant]
WO WO2017201501A1 · 2017 [cited by applicant]
WO WO2017201502A1 · 2017 [cited by applicant]
WO WO2018071548A1 · 2018 [cited by applicant]
WO WO2019164861A1 · 2019 [cited by applicant]
Adams (Dec. 12, 1985) “The c-myc Oncogene Driven by Immunoglobulin Enhancers Induces Lymphoid Malignancy in Transgenic Mice”, Nature, 318:533-538. [cited by applicant]
Alexander et al. (Apr. 1987) “Expression of the c-myc Oncogene Under Control of an Immuno-globulin En-hancer in E mu-myc Transgenic Mice”, Molecular and Cellular Biology, 7(4):1436-1444. [cited by applicant]
Alzforum (Feb. 9, 2018) “Lack of C9ORF72 Protein Renders Neurons More Vulnerable to Degeneration”, ALS Research Forum, 5 pages. [cited by applicant]
Anderson (May 1, 1995) “Analytical Techniques in Combinatorial Chemistry: MAS CH Correla-tion in Solvent-Swollen Resin”, The Journal of Organic Chemistry, 60(9):2650-2651. [cited by applicant]
Askew et al. (Feb. 1, 1989) “Molecular Recognition with Convergent Functional Groups. VI. Syn-thetic And Structural Studies with a Model Receptor for Nucleic Acid Components”, Journal of the American Chemical Society, 1… [cited by applicant]
Baird et al. (Jun. 19, 2013) “IL-23R is Epigenetically Regulated and Modulated by Chemo-therapy in Non-Small Cell Lung Cancer”, Frontiers in Oncology, 3(162):1-9. [cited by applicant]
Benoist et al. (Mar. 26, 1981) “In Vivo Sequence Requirements of the SV40 Early Promoter Region”. Nature, 290:304-310. [cited by applicant]
Berg, et al. (Nov. 25, 2012) “Inhibition of IL-12/IL-23 Signaling Reduces Alzheimer's Disease-like Patholo-gy and Cognitive”, Nature Medicine, pp. 1-10. [cited by applicant]
Bhakar et al. (Oct. 1, 2002) “Constitutive Nuclear Factor-Kappa B Activity Is Required for Central Neuron Survival”, The Journal of Neuroscience, 22(19):8466-8475. [cited by applicant]
Boyle et al. (May 15, 2003) “Osteoclast Differentiation and Activation”, Nature, 423(6937):337-342. [cited by applicant]
Brenner et al. (Jun. 15, 1992) “Encoded Combinatorial Chemistry”, Proceedings of the National Academy of Sciences, 89(12):5381-5383. [cited by applicant]
Brinster et al. (Mar. 4, 1982) “Regulation of Metallothionein-Thymidine Kinase Fusion Plasmids Injected into Mouse Eggs”, Nature, 296(5852):39-42. [cited by applicant]
Brummel, et al. (Apr. 15, 1994) “A mass spectrometric solution to the address problem of combinatorial libraries”, Science, 264(5157):399-402. [cited by applicant]
Buchwald et al. (Oct. 1980) “Long-Term, Continuous Intravenous Heparin Administration by an Implantable Infusion Pump in Ambulatory Patients with Recurrent Venous Thrombosis”, Surgery, 88(4):507-516. [cited by applicant]
Bunin et al. (May 24, 1994) “The Combinatorial Synthesis and Chemical and Biological Evaluation of a 1,4-Benzodiazepine Library”, Proceedings of the National Academy of Sciences of the United States of America, 91 (11):… [cited by applicant]
Burke (Jul. 14, 2014) “Why Alzheimer's Drugs Keep Failing”, Scientific American, 7 pages. [cited by applicant]
Busse et al. (Feb. 2001) “Anti-immunoglobulin E for the Treatment of Allergic Disease”, Current Opinion in Allergy and Clinical Immunology, 1 (1):105-108. [cited by applicant]
Butler, (1981) “The Amplified ELISA: Principles of and Applications for the Comparative Quantitation of Class and Subclass Antibodies and the Distribution of Antibodies and Antigens in Biochemical Separates”, Methods in… [cited by applicant]
Butterworth (2020) “Guidelines for the Pharmacological Management of Dementia”, Drugs and Therapeutics Committee, 33 pages. [cited by applicant]
Cai et al. (Jul. 25, 2013) “PIKfyve, a Class III PI Kinase, Is the Target of the Small Molecular IL-12/IL-23 Inhibitor Apilimod and a Player in Toll-like Receptor Signaling”, Chemistry & Biology, 20(7):912-921. [cited by applicant]
Chang et al. (Apr. 14, 2005) “Niemann-Pick Type C Disease and Intracellular Cholesterol Trafficking”, The Journal of Biological Chemistry, 280(22):20917-20920. [cited by applicant]
Chen et al. (May 2004) “Shaping the Nuclear Action of NF-kappaB”, Nature Reviews Molecular Cell Biology, 5(5):392-401. [cited by applicant]
Chen et al. (Sep. 2017) “Amyloid beta: Structure, Biology and Structure-Based Therapeutic Development”, Acta Pharmacologica Sinica, 38(9):1205-1235. [cited by applicant]
Cheng et al. (Dec. 2, 2014) “Systematic Evaluation of Connectivity Map for Disease Indications”, Genome Medicine, 8 Pages. [cited by applicant]
Chu et al. (May 1, 1995) “Free Solution Identification of Candidate Peptides from Combinatorial Libraries by Affinity Capillary Electrophoresis/Mass Spectrometry”, Journal of the American Chemical Society, 117(19):5419-… [cited by applicant]
CN Office Action in Chinese Application No. 201980014793.3, dated Feb. 10, 2023, 44 pages (with English translation). [cited by applicant]
Cole et al. (1985) “The Ebv Hybridoma Technique and its Application to Human Lung Cancer”, Monoclonal Antibodies and Cancer Therapy, 77-96. [cited by applicant]
Corren et al. (Jan. 2003) “Omalizumab, A Recombinant Humanized Anti-IgE Antibody, Reduces Asthma-related Emergency Room Visits And Hospitalizations in Patients with Allergic Asthma”, The Journal of Allergy and Clinical … [cited by applicant]
Cote et al. (Apr. 1983) “Generation of human monoclonal antibodies reactive with cellular antigens”, Proceedings of the National Academy of Sciences, 80:2026-2030. [cited by applicant]
De Boer et al., Jan. 1, 1983, “The tac promoter: a Functional Hybrid Derived from the trp and lac Promoters”, Proceedings of the National Academy of Sciences, 80(1 ):21-25. [cited by applicant]
Delague (Aug. 8, 2013) “Charcot-Marie-Tooth Neuropathy Type 4H”, Gene Reviews, 13 pages. [cited by applicant]
Dudley et al. (Aug. 17, 2011) “Computational Repositioning of the Anticonvulsant Topiramate for Inflammatory Bowel Disease”, Science Translational Medicine, 12 pages. [cited by applicant]
Durie et al. (Sep. 1994) “The Role of CD40 In The Regulation of Humoral and Cell-Mediated Immunity”, Immunology Today, 15(9):406-411. [cited by applicant]
During et al. (Apr. 1989) “Controlled Release of Dopamine from a Polymeric Brain Implant: In Vivo Characterization”, Annals of Neurology, 25(4):351-356. [cited by applicant]
Egner et al. (Mar. 1997) “Analytical Techniques for Solid-Phase Organic and Combinatorial Synthesis”, Drug Discovery Today, 2(3):102-109. [cited by applicant]
EP Office Action in European Application No. 19710520.8, dated Jul. 12, 2023, 7 pages. [cited by applicant]
Erb et al. (Nov. 22, 1994) “Recursive Deconvolution of Combinatorial Chemical Libraries”, PNAS, 91 (24):11422-11426. [cited by applicant]
Fairbrother et al. (Dec. 4, 1998) “Novel Peptides Selected to Bind Vascular Endothelial Growth Factor Tar-get the Receptor-Binding Site”, Biochemistry, 37(51):17754-17764. [cited by applicant]
Farg et al. (Jul. 1, 2014) “C9ORF72, Implicated in Amytrophic Lateral Sclerosis and Frontotemporal Dementia, Regulates Endosomal Trafficking”, Human Molecular Genetics, 23(13):3579-3595. [cited by applicant]
Finn et al. (Feb. 2003) “Omalizumab Improves Asthma-related Quality of Life In Patients with Severe Allergic Asthma”, The Journal of Allergy and Clinical Immunology, 111 (2):278284. [cited by applicant]
Fitch et al. (Dec. 1, 1994) “High-Resolution 1 H NMR in Solid-Phase Organic Synthesis”, The Journal of Organic Chemistry, 59(26):7955-7956. [cited by applicant]
Flanders et al. (May 11, 1998) “Prevention of Type 1 Diabetes from Laboratory to Public Health”, Autoimmunity, 29(3):235-246. [cited by applicant]
Gallop et al. (Apr. 29, 1994) “Applications of Combinatorial Technologies to Drug Discovery. 1. Background and Peptide Combinatorial Libraries”, Journal of Medicinal Chemistry, 37(9):1233-1251. [cited by applicant]
Gardner et al. (Jun. 25, 1981) “The Complete Nucleotide Sequence of an Infectious Clone of Cauliflower Mosaic Virus by M13mp7 Shotgun Sequencing”, Nucleic Acids Research, 9(12):2871-2888. [cited by applicant]
Gilbert et al. (Apr. 1980) “Useful Proteins from Recombinant Bacteria”, Scientific American, 242(4):74-94. [cited by applicant]
Goodson (1984) “Dental Applications”, Medical Applications of Controlled Release, 2: 115-138. [cited by applicant]
Gould et al. (Nov. 1986) “Salt selection for basic drugs”, International Journal of Pharmaceutics, 33(1-3):201-217. [cited by applicant]
Grier et al. (Jan. 1996) “The Use of Dual-Energy X-Ray Absorptiometry in Animals”, Investigative Radiology, 31 (1):50-62. [cited by applicant]
Grosschedl et al. (Oct. 1984) “Introduction of aμ Immunoglobulin Gene into the Mouse Germ Line: Specific Expression in Lymphoid Cells and Synthesis of Functional Antibody”, Cell, 38(3):647-658. [cited by applicant]
Guarente, (Dec. 1987) “Regulatory Proteins In Yeast”, Annual Review of Genetics, 21 :425-452. [cited by applicant]
Gustafsson et al. (Jan. 1991) “SPAM-8, a mouse-human heteromyeloma fusion partner in the production of human monoclonal antibodies. Establishment of a human monoclonal antibody against cytomegalovirus”, Human Antibodies… [cited by applicant]
Hamilton et al. (Nov. 1998) “Oxidized LDL Modulates Activation of Nfkappab in Mononuclear Phagocytes by Altering the Degradation if Ikappabs”, Journal of Leukocyte Biology, 64(5):667-674. [cited by applicant]
Hammer et al. (Jan. 2, 1987) “Diversity of alpha-Fetoprotein Gene Expression in Mice is Generated by a Combination of Separate Enhancer Elements”, Science, 235(4784):53-58. [cited by applicant]
Hanahan (May 9, 1985) “Heritable Formation of Pancreatic-Cell Tumours in Transgenic Mice Expressing Recombinant Insulin/Simian Virus 40 Oncogenes”, Nature, 315(6015):115-122. [cited by applicant]
Hansen et al. (1992) “A Novel Complex Between the P65 Subunit of Nk-kappab And C-rel Binds to a Dna Element Involved in the Phorbol Ester Induction of the Human Urokinase”, The EMBO Journal, 11 (1):205-213. [cited by applicant]
Hayakawa et al. (Jun. 2014) “Structure-Activity Relationship Study, Target Identification, and Pharmacological Characterization of a Small Molecular IL-12/23 Inhibitor, APY0201”, Bioorganic & Medicinal Chemistry, 22(11 … [cited by applicant]
He et al. (Mar. 1, 2003) “The Inhibition of Mast Cell Activation by Neutrophil Lactoferrin: Uptake by Mast Cells and Interaction with Tryptase, Chymase and Cathepsin G”, Biochemical Pharmacology, 65(6):1007-1015. [cited by applicant]
Heinrich et al. (Aug. 1, 2020) “Inhibition of C-kit Receptor Tyrosine Kinase Activity by STI 571, A Selective Tyrosine Kinase Inhibitor”, Blood, 96(3):925-932. [cited by applicant]
Herrera-Estrella et al. (1983) “Expression of Chimaeric Genes Transferred into Plant Cells Using a Ti-Plasmid-Derived Vector”, Nature, 303(5914):209-213. [cited by applicant]
Herrera-Estrella et al. (Jul. 12, 1984) “Light-Inducible and Chloroplast-Associated Expression of a Chimaeric Gene Introduced into Nicotiana Tabacum Using a Ti Plasmid Vector”, Nature, 310:115-120. [cited by applicant]
Hilliard et al. (Sep. 15, 2002) “Critical Roles of c-Rel in Autoimmune Inflammation and Helper T Cell Differentiation”, Journal of Clinical Investigation, 110(6): 843-850. [cited by applicant]
Houghten et al. (Nov. 7, 1991) “Generation and Use of Synthetic Peptide Combinatorial Libraries for Basic Research and Drug Discovery”, Nature, 354(6348):84-86. [cited by applicant]
Houghten et al. (Sep. 1992) “The Use of Synthetic Peptide Combinatorial Libraries for The Identification of Bioactive Peptides”, Biotechniques, 13(3):412-421. [cited by applicant]
Howard et al. (Dec. 1989) “Acute Subdural Hematomas: An Age-Dependent Clinical Entity”, Journal of Neurosurgery, 71 (6):858-863. [cited by applicant]
Huse et al. (Dec. 8, 1989) “Generation of a Large Combinatorial Library of the Immunoglobulin Repertoire in Phage Lambda”, Science, 246(4935):1275-1281. [cited by applicant]
Ito et al. (May 1999) “FK506 and Cyclosporin a Inhibit Stem Cell Factor-dependent Cell Proliferation/survival, While Inducing Upregulation of C-kit Expression In Cells of the Mast Cell Line MC/9”, Archives of Dermatolog… [cited by applicant]
Jahchan et al. (Dec. 2013) “A Drug Repositioning Approach Identifies Tricyclic Antidepressants as Inhibitors of Small Cell Lung Cancer and Other Neuroendocrine Tumors”, Cancer Discovery, 3(12):1364-1377. [cited by applicant]
Jayawickreme et al. (Mar. 1, 1994) “Creation and Functional Screening of a Multi-Use Peptide Library”, Proceedings of the National Academy of Sciences of the United States of America, 91 (5):1614-1618. [cited by applicant]
Jefferies et al. (Feb. 2008) “A Selective PIKfyve Inhibitor Blocks PtdIns(3,5)P(2) Production and Disrupts Endomembrane Transport and Retroviral Budding”, EMBO Reports, 9(2):164-170. [cited by applicant]
Jeon et al. (Jul. 1998) “Inhibition of NF-kappaB/Rel Nuclear Translocation by Dexamethasone: Mechanism for the Inhibition of iNOS Gene Expression”, Biochemistry and Molecular Biology International, 45(3):435-441. [cited by applicant]
Jeon et al. (Jul. 20, 2000) “Dexamethasone Inhibits IL-1 Beta Gene Expression in LPSstimulated Raw 264.7 Cells by Blocking NF-kappa B/rel and AP-1 Activation”, Immunopharmacology, 48(2):173-183. [cited by applicant]
Johnston (Dec. 1987) “A Model Fungal Gene Regulatory Mechanism: the GAL Genes of [cited by applicant]
JP Office Action in Japanese Application No. 2020-543481, dated Nov. 24, 2022, 13 pages (with English translation). [cited by applicant]
Kauvar et al. (Feb. 1995) “Predicting Ligand Binding to Proteins by Affinity Fingerprinting”, Chemistry & Biology, 2(2):107-118. [cited by applicant]
Kay et al. (Jun. 15, 1993) “An M13 Phage Library Displaying Random 38-amino-acid Peptides as a Source of Novel Sequences with Affinity to Selected Targets”, Gene, 128(1):59-65. [cited by applicant]
Kelsey et al. (Apr. 1987) “Species- and Tissue-Specific Expression of Human alpha 1-Antitrypsin in Transgenic Mice”, Genes and Development, 1: 161-171. [cited by applicant]
Kohler et al. (Aug. 7, 1975) “Continuous Cultures of Fused Cells Secreting Antibody of Predefined Specificity”, Nature, 256(5517):495-497. [cited by applicant]
Kollias et al. (Jul. 4, 1986) “Regulated Expression of Human Ay-, 13-, and hybrid v13-Globin Genes in Transgenic Mice: Manipulation of the Developmental Expression Patterns”, Cell, 46(1 ):89-94. [cited by applicant]
Kozbor et al. (Mar. 1983) “The Production of Monoclonal Antibodies from Human Lymphocytes”, Immunology Today, 4(3):72-79. [cited by applicant]
Krausz et al. (May 25, 2012) “A Phase IIa, Randomized, Double-Blind, Placebo-Controlled Trial of Apilimod Mesylate, an Interleukin-12/1nterleukin-23 Inhibitor, in Patients with Rheumatoid Arthritis”, Arthritis and Rheum… [cited by applicant]
Krumlauf et al. (Jul. 1985) “Developmental Regulation of a-Fetoprotein Genes in Transgenic Mice”, Molecular and Cellular Biology, 5(7):1639-1648. [cited by applicant]
Lam et al. (1997) “The “One-Bead-One-Compound” Combinatorial Library Method”, Chemical Reviews, 97:411-448. [cited by applicant]
Lam et al. (Nov. 7, 1991) “A New Type of Synthetic Peptide Library for Identifying Ligand-Binding Activity”, Nature, 354:82-84. [cited by applicant]
Lamb et al. (Sep. 29, 2006) “The Connectivity Map: Using Gene-expression Signatures to Connect Small Molecules, Genes, and Disease”, Science, 313(5795):1929-1935. [cited by applicant]
Langer et al. (1983) “Chemical and Physical Structure of Polymers as Carriers for Controlled Release of Bioactive Agents: A Review”, Journal of Macromolecular Science, o Part C, Polymer Reviews, 23(1):61-126. [cited by applicant]
Langer (Sep. 28, 1990) “New Methods of Drug Delivery”, Science, 249: 1527-1533. [cited by applicant]
Leder et al. (May 23, 1986) “Consequences of Widespread Deregulation of the c-myc Gene in Transgenic Mice: Multiple Neoplasms and Normal Development”, Cell, 45(4):485-495. [cited by applicant]
Lenk et al. (Jun. 2011) “Pathogenic mechanism of the FIG4 mutation responsible for Charcot-Marie-Tooth disease CMT4J”, PLoS Genetics, e1002104, 7(6):13 pages. [cited by applicant]
Levy et al. (1985) “Inhibition of Calcification of Bioprosthetic Heart Valves by Local Controlled-Release Diphosphonate”, Science, 228: 190-192. [cited by applicant]
Look et al. (Dec. 1, 1994) “Methods for Combinatorial Organic Synthesis: The Use of Fast 13C NMR Analysis for Gel Phase Reaction Monitoring”, The Journal of Organic Chemistry, 59(25):7588-7590. [cited by applicant]
Lopez-Berestein et al. (1989) “Treatment of Systemic Fungal Infections with Liposomal-Amphotericin B”, Liposomes in the Therapy of Infectious Diseases and Cancer, 317-327. [cited by applicant]
Macdonald (Jan.-Feb. 1987) “Expression of the Pancreatic Elastase | Gene in Transgenic Mice”, Hepatology, 7(7):425-515. [cited by applicant]
Mason et al. (Dec. 12, 1986) “The Hypogonadal Mouse: Reproductive Functions Restored by Gene Therapy”, Science, 234(4782):1372-1378. [cited by applicant]
Matter (Apr. 11, 1997) “Selecting Optimally Diverse Compounds from Structure Databases: A Validation Study of Two-Dimensional and Three-Dimensional Molecular Descriptors”, Journal of Medicinal Chemistry, 40(8):1219-1229. [cited by applicant]
Mckinlay et al. (1989) “Rational Design of Antiviral Agents”, Annual Review of Pharmacology and Toxicology, 29:111-122. [cited by applicant]
Medynski, Dan (Jul. 1, 1994) “Synthetic Peptide Combinatorial Libraries”, BioTechnology, 12:709-710. [cited by applicant]
Mendiaz et al. (Aug. 1, 1996) “Epitope Mapping and Immunoneutralization of Recombinant Human Stem-cell Factor”, European Journal of Biochemistry, 239(3):842-o 849. [cited by applicant]
Metcalfe et al. (Aug. 1995) “Mast Cell Ontogeny and Apoptosis”, Experimental Dermatology, 4(4):227-230. [cited by applicant]
Metzger et al. (Jun. 1993) “Ion-Spray Mass Spectrometry and High-Performance Liquid Chromatography-Mass Spectrometry of Synthetic Peptide Librariest+”, Angewandte Chemie International Edition, 32(6):894-896. [cited by applicant]
Miyajima et al. (May 2002) “Rat Monoclonal Anti-murine IgE Antibody Removes IgE Molecules Already Bound to Mast Cells or Basophilic Leukemia Cells, Resulting in the Inhibition of Systemic Anaphylaxis and Passive Cutaneo… [cited by applicant]
Morrison et al. (Nov. 1984) “Chimeric Human Antibody Molecules: Mouse Antigen-Binding Domains with Human Constant Region Domains”, Proceedings of the National Academy of Sciences, 81 :6851-6855. [cited by applicant]
Mullan et al. (Aug. 1, 1992) “A Pathogenic Mutation for Probable Alzheimer's Disease in the App Gene at the N-terminus of B-amyloid”, Nature Genetics, 1(5):345-347. [cited by applicant]
Murphy et al. (Jan. 2010) “Alzheimer's Disease and the 13-Amyloid Peptide”, Journal of Alzheimer's Disease, 19(1):311. [cited by applicant]
Nagahara et al. (Sep. 25, 2013) “Early BDNF Treatment Ameliorates Cell Loss in the Entorhinal Cortex of APP Transgenic Mice”, The Journal of Neuroscience, 33(39): 15596-15602. [cited by applicant]
Nagai et al. (Mar. 17, 1995) “Pharmacological Study of Stem-Cell-Factor-Induced Mast Cell Histamine Release with Kinase Inhibitors”, Biochemical and Biophysical Research Communications, 208(2):576-581. [cited by applicant]
Neerven et al. (2001) “Humanized Anti-IgE mAb Hu-901 Prevents the Activation of Allergen-Specific T Cells”, International Archives of Allergy and Immunology, 124(1-3):400402. [cited by applicant]
Nefzi et al. (Apr. 1, 1997) “The Current Status of Heterocyclic Combinatorial Libraries”, Chemical Reviews, 97(2):449-472. [cited by applicant]
Neubauer et al. (Jan. 21, 1997) “Identification of the Proteins of the Yeast UI Small Nuclear Ribonucleoprotein Complex by Mass Spectrometry”, Proceedings of the National Academy of Sciences of the United States of Amer… [cited by applicant]
Neubauer et al. (Sep. 1998) “Mass Spectrometry and EST-database Searching Allows Characterization of the Multi-protein Spliceosome Complex”, Nature Genetics, 20:46-50. [cited by applicant]
Neuberger et al. (Dec. 13, 1984) “Recombinant Antibodies Possessing Novel Effector Functions”, Nature, 312:604-608. [cited by applicant]
Norrdin et al. (Nov. 1990) “The Role of Prostaglandins in Bone in Vivo”, Prostaglandins, Leukotrienes and Essential Fatty Acids, 41 (3):139-149. [cited by applicant]
Ohlmeyer et al. (Dec. 1, 1993) “Complex Synthetic Chemical Libraries Indexed with Molecular Tags”, Proceedings of the National Academy of Sciences, USA, National Academy of Science, Washington DC, 90:10922-10926. [cited by applicant]
Ono et al. (Dec. 1996) “Promotion of the Osteogenetic Activity of Recombinant Human Bone Morphogenetic Protein by Prostaglandin El ”, Bone, 19(6):581-588. [cited by applicant]
Ostresh et al. (Nov. 8, 1994) “Libraries from Libraries”: Chemical Transformation of Combinatorial Libraries to Extend the Range and Repertoire of Chemical Diversity, Proceedings of the National Academy of Sciences, 91 … [cited by applicant]
Pinkert et al. (1987) “An Albumin Enhancer Located 10 kb Upstream Functions along with its Promoter to Direct Efficient, Liver-Specific Expression in Transgenic Mice”, Genes & Development, 1 :268-277. [cited by applicant]
Read et al. (Feb. 27, 1987) “Expression of a Myelin Basic Protein Gene in Transgenic Shiverer Mice: Correction of the Dysmyelinating Phenotype”, Cell, 48(4):703-712. [cited by applicant]
Reeve et al. (1993) “Human Parathyroid Peptide Treatment of Vertebral Osteoporosis”, Osteoporosis International, 3:199-203. [cited by applicant]
Reeve et al. (Jun. 1991) “hPTH 1-34 Treatment of Osteoporosis with Added Hormone Replacement Therapy: Biochemical, Kinetic and Histological Responses”, Osteoporosis o International, 1:162-170. [cited by applicant]
Rentzos, et al., (2006) “Interleukin-12 is Reduced in Cerebrospinal Fluid of Patients with Alzheimer's Disease and Frontotemporal Dementia”, Journal of the Neurological Sciences, 249:110-114. [cited by applicant]
Ritchie et al. (Jan. 20, 2015) “Limma Powers Differential Expression Analyses for RNA-Sequencing and Microarray Studies”, Nucleic Acids Research, 43(7): 13 pages. [cited by applicant]
Sadigh-Eteghad et al. (Jan. 2015) “Amyloid-Beta: A Crucial Factor in Alzheimer's Disease”, Medical Principles and Practice, 24(1):1-10. [cited by applicant]
Salmon et al. (Dec. 15, 1993) “Discovery of Biologically Active Peptides in Random Libraries: Solution-phase Testing After Staged Orthogonal Release from Resin Beads”, Proceedings of the National Academy of Sciences of … [cited by applicant]
Saud et al. (Aug. 31, 1989) “A Prelimiary Trial of the Programmable Implantable Medication System for Insulin Delivery”, The New England Journal of Medicine, 321(9):574579. [cited by applicant]
Schisler et al. (1987) “Alternative Promoters In Developmental Gene Expression”, Annual Review of Genetics, 21 :237-257. [cited by applicant]
Sefton (1987) “Implantable Pumps”, Critical Reviews in Biomedical Engineering, 14(3):201-240. [cited by applicant]
Shani Moshe (Mar. 21, 1985) “Tissue-specific Expression of Rat Myosin Light-chain 2 Gene in Transgenic Mice”, Nature, 314:283-286. [cited by applicant]
Shi et al. (Feb. 5, 2018) “Haploinsufficiency Leads to Neurodegeneration in C9ORF72 ALS/FTD Human Induced Motor Neurons”, Nature Medicine, 24(3):313-325. [cited by applicant]
Simon et al. (Oct. 15, 1992) “Peptoids: A Modular Approach to Drug Discovery”, Proceedings of the National Academy of Sciences of the United States of America, 89(20): 9367-9371. [cited by applicant]
Singh et al. (Nov.-Dec. 1997) “Circulating Cytokines in Alzheimer's Disease”, Journal of Psychiatric Research, 31(6):657-660. [cited by applicant]
Smith et al. (Jul. 15, 1988) “Single-Step Purification of Polypeptides Expressed in [cited by applicant]
Stevanovic et al. (Mar. 1993) “Natural and Synthetic Peptide Pools: Characterization by Sequencing and Electrospray Mass Spectrometry”, Bioorganic & Medicinal Chemistry Letters, 3(3):431-436. [cited by applicant]
Struhl (1995) “Yeast Transcriptional Regulatory Mechanisms”, Annual Review of Genetics, 29:651-674. [cited by applicant]
Suzuki et al. (May 27, 1994) “An Increased Percentage of Long Amyloid Beta Protein Secreted by Familial Amyloid Beta Protein Precursor (Beta App717) Mutants”, Science, o 264(5163):1336-1340. [cited by applicant]
Swift et al. (Oct. 1984) “Tissue-Specific Expression of the Rat Pancreatic Elastase | Gene in Transgenic Mice”, Cell, 38(3):639-646. [cited by applicant]
Takeda et al. (Apr. 1, 1985) “Construction of Chimaeric Processed Immunoglobulin Genes Containing Mouse Variable and Human Constant Region Sequences”, Nature, 314:452-454. [cited by applicant]
Tan, et al., (Sep. 2018) “Current Approaches to the Pharmacological Treatment of Alzheimer's Disease”, Australian Journal of General Practice, 47(9):586-592. [cited by applicant]
Tang et al. (Dec. 2001) “Childhood Asthma as an Allergic Disease: Rationale for the Development of Future Treatment”, European Journal of Pediatrics, 160(12):696-704. [cited by applicant]
Temkin et al. (Sep. 1, 2002) “Tryptase Activates the Mitogen-Activated Protein Kinase/Activator Protein-1 Pathway in Human Peripheral Blood Eosinophils, Causing Cytokine Production and Release”, Journal of Immunology, 1… [cited by applicant]
Treat et al. (1989) “Liposome Encapsulated Doxorubicin Preliminary Results of Phase I and Phase II Trials”, Liposomes in the Therapy of Infectious Disease and Cancer, 89:353-365. [cited by applicant]
Trinchieri (Feb. 2003) “Interleukin-12 and the Regulation of Innate Resistance and Adaptive Immunity”, Nature Reviews Immunology, 3(2):133-146. [cited by applicant]
Vaccari et al. (Oct. 2011) “Genetic Interaction between MTMR2 and FIG4 Phospholipid Phosphatases Involved in Charcot-Marie-Tooth Neuropathies”, PLoS Genetics, 7(10):15 pages. [cited by applicant]
Villa-Komaroff et al. (Aug. 1, 1978) “A Bacterial Clone Synthesizing Proinsulin”, Proceedings of the National Academy of Sciences, 75(8):3727-3731. [cited by applicant]
Voller et al. (1978) “Enzyme Immunoassays with Special Reference to ELISA Techniques”, Journal of Clinical Pathology, 31 :507-520. [cited by applicant]
Vosseller et al. (May 1997) “c-kit Receptor Signaling Through its Phosphatidylinositide-3′-kinase-binding Site and Protein Kinase C: Role in Mast Cell Enhancement of Degranulation, Adhesion, and Membrane Ruffling”, Mole… [cited by applicant]
Wada et al. (Apr. 6, 2012) “Apilimod Inhibits the Production of IL-12 And IL-23 and Reduces Dendritic Cell Infiltration in Psoriasis”, PLOS One, 7(4):e35069:1-10. [cited by applicant]
Wada et al. (Oct. 19, 2006) “Selective Abrogation of Thl Response by STA-5326, a Potent IL-12/IL-23 Inhibitor”, Blood, 109(3):1156-1164. [cited by applicant]
Wagner et al. (Mar. 1981) “Nucleotide Sequence of the Thymidine Kinase Gene of Herpes Simplex Virus Type 1”, Proceedings of the National Academy of Sciences of the United States of America, 78(3):1441-1445. [cited by applicant]
Wang et al. (Mar. 2, 2015) “Up-regulation of Lysosomal TRPML 1 Channels is Essential for Lysosomal Adaptation to Nutrient Starvation”, Proceedings of the National Academy of Sciences, 112(11): E1373-E1381. [cited by applicant]
Willson et al. (Sep. 1, 1997) “Dissection of the Molecular Mechanism of Action of GW5638, a Novel Estrogen Receptor Ligand, Provides Insights into the Role of Estrogen Receptor in Bone”, Endocrinology. 138(9):3901-3911. [cited by applicant]
Wilm et al. (1996) “Analytical Properties of the Nanoelectrospray Ion Source”, Analytical Chemistry, 68(1):1-8. [cited by applicant]
Wilm et al. (Feb. 1, 1996) “Femtomole Sequencing of Proteins from Polyacrylamide Gels by Nano-electrospray Mass Spectrometry”, Nature, 379:466-469. [cited by applicant]
Wolff et al. (1996) “Metabolic Considerations in Prodrug Design”, Burger's Medicinal Chemistry and Drug Discovery. 5th edition, 1 :949-982. [cited by applicant]
Wu et al. (1987) “Receptor-Mediated in Vitro Gene Transformation by a Soluble DNA Carrier System”, The Journal of Biological Chemistry, 262(10):4429-4432. [cited by applicant]
Yamamoto et al. (Dec. 1980) “Identification of a Functional Promoter in the Long Terminal Repeat of Rous Sarcoma Virus”, Cell, 22(3):787-797. [cited by applicant]
Yang, et al., (2021) “Plasma IL-12/IFN-y Axis Predicts Cognitive Trajectories in Cognitively Unimpaired Older Adults”, Alzheimer's & Dementia, The Journal of the Alzheimer's Association, Dement, pp. 1-9. [cited by applicant]
Yokota et al. (Aug. 1, 1986) “Isolation and Characterization of a Human Interleukin cDNA Clone, Homologous to Mouse B-cell Stimulatory Factor 1, that Expresses B-cell- and T-cell-Stimulating Activities”, Proceedings of … [cited by applicant]
Youngquist et al. (Jan. 1994) “Matrix-assisted Laser Desorption Ionization for Rapid Determination of the Sequences of Biologically Active Peptides Isolated From Support-bound Combinatorial Peptide Libraries”, Rapid Com… [cited by applicant]
Zampatti et al., “C9orf72-Related Neurodegenerative Diseases: From Clinical Diagnosis to Therapeutic Strategies”, Frontiers in Aging Neuroscience, Jun. 2022, 14:907122, 9 pages. [cited by applicant]