HRP20231172T1 - Spojevi za upotrebu u liječenju alzheimerove bolesti kod apoe4+/+ pacijenata - Google Patents

Spojevi za upotrebu u liječenju alzheimerove bolesti kod apoe4+/+ pacijenata Download PDF

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Publication number
HRP20231172T1
HRP20231172T1 HRP20231172TT HRP20231172T HRP20231172T1 HR P20231172 T1 HRP20231172 T1 HR P20231172T1 HR P20231172T T HRP20231172T T HR P20231172TT HR P20231172 T HRP20231172 T HR P20231172T HR P20231172 T1 HRP20231172 T1 HR P20231172T1
Authority
HR
Croatia
Prior art keywords
patient
apoe4
compound
formula
image
Prior art date
Application number
HRP20231172TT
Other languages
English (en)
Croatian (hr)
Inventor
Martin TOLAR
John Hey
Petr Kocis
Jeremy Yu
Original Assignee
Alzheon, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=54145492&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=HRP20231172(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Alzheon, Inc. filed Critical Alzheon, Inc.
Publication of HRP20231172T1 publication Critical patent/HRP20231172T1/hr

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05Dipeptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/542Carboxylic acids, e.g. a fatty acid or an amino acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G01N33/6896Neurological disorders, e.g. Alzheimer's disease
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/106Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/158Expression markers
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H10/00ICT specially adapted for the handling or processing of patient-related medical or healthcare data
    • G16H10/20ICT specially adapted for the handling or processing of patient-related medical or healthcare data for electronic clinical trials or questionnaires
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/10ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/70ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to mental therapies, e.g. psychological therapy or autogenous training
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H40/00ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices
    • G16H40/20ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the management or administration of healthcare resources or facilities, e.g. managing hospital staff or surgery rooms

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biomedical Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Pathology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Food Science & Technology (AREA)
  • Cell Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Biophysics (AREA)
HRP20231172TT 2014-03-21 2015-03-23 Spojevi za upotrebu u liječenju alzheimerove bolesti kod apoe4+/+ pacijenata HRP20231172T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201461968595P 2014-03-21 2014-03-21
PCT/US2015/022058 WO2015143447A2 (en) 2014-03-21 2015-03-23 Methods for treating neurological disorders
EP15764560.7A EP3119911B1 (en) 2014-03-21 2015-03-23 Compounds for use in treating alzheimer's disease in apoe4+/+ patients

Publications (1)

Publication Number Publication Date
HRP20231172T1 true HRP20231172T1 (hr) 2024-01-05

Family

ID=54145492

Family Applications (1)

Application Number Title Priority Date Filing Date
HRP20231172TT HRP20231172T1 (hr) 2014-03-21 2015-03-23 Spojevi za upotrebu u liječenju alzheimerove bolesti kod apoe4+/+ pacijenata

Country Status (19)

Country Link
US (3) US10471029B2 (https=)
EP (2) EP3119911B1 (https=)
JP (5) JP6588962B2 (https=)
KR (2) KR102645633B1 (https=)
CN (1) CN106170563A (https=)
AU (1) AU2015230972B2 (https=)
CA (1) CA2941415A1 (https=)
DK (1) DK3119911T3 (https=)
ES (1) ES2960625T3 (https=)
FI (1) FI3119911T3 (https=)
HR (1) HRP20231172T1 (https=)
HU (1) HUE063369T2 (https=)
LT (1) LT3119911T (https=)
PL (1) PL3119911T3 (https=)
PT (1) PT3119911T (https=)
RS (1) RS64744B1 (https=)
SI (1) SI3119911T1 (https=)
SM (1) SMT202300369T1 (https=)
WO (1) WO2015143447A2 (https=)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4275750B1 (en) * 2015-09-10 2026-05-06 Alzheon, Inc. Treatment of alzheimer's disease in a particular patient population
WO2018012596A1 (ja) * 2016-07-13 2018-01-18 株式会社マイトス 水素を有効成分として含む軽度認知障害又は認知症の予防又は治療用組成物
CN114805211B (zh) 2017-03-21 2024-08-23 润佳(苏州)医药科技有限公司 同位素富集3-氨基-1-丙磺酸衍生物、药物组合物及其用途
CN110003058B (zh) 2018-01-04 2022-01-25 润佳(苏州)医药科技有限公司 3-((l-缬氨酰基)氨基)-3,3-二氘-1-丙磺酸晶型、制备方法及用途
CN110668980A (zh) * 2018-07-03 2020-01-10 浙江京新药业股份有限公司 一种2-取代的高牛磺酸衍生物
SI3829568T1 (sl) * 2018-08-01 2024-02-29 Alzheon, Inc. Derivati sulfopropanojske kisline za zdravljenje nevrodegenerativnih motenj
HUE070101T2 (hu) * 2018-08-01 2025-05-28 Alzheon Inc 3-Szulfopropánsav neurodegeneratív rendellenességek kezelésére
CN111170901A (zh) * 2018-11-13 2020-05-19 润佳(苏州)医药科技有限公司 3-((l-缬氨酰基)氨基)-1-丙磺酸晶型、制备方法及其用途
UA129160C2 (uk) * 2019-06-17 2025-01-29 Алзхеон, Інк. Спосіб лікування хвороби альцгеймера
CN116059192B (zh) 2019-11-13 2024-10-29 润佳(苏州)医药科技有限公司 同位素富集的3-氨基-1-丙磺酸及其衍生物的用途
US20250345298A1 (en) * 2022-04-28 2025-11-13 Alzheon, Inc. Apoe4 correctors and methods of use
AU2023403257A1 (en) 2022-12-02 2025-06-12 Alzheon, Inc. Methods for treating neurodegenerative disorders with tramiprosate

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5698155A (en) 1991-05-31 1997-12-16 Gs Technologies, Inc. Method for the manufacture of pharmaceutical cellulose capsules
JP3265577B2 (ja) 1992-10-13 2002-03-11 デューク・ユニバーシティ アポリポ蛋白eの4型イソ型の測定法
US20050031651A1 (en) 2002-12-24 2005-02-10 Francine Gervais Therapeutic formulations for the treatment of beta-amyloid related diseases
US20070010573A1 (en) 2003-06-23 2007-01-11 Xianqi Kong Methods and compositions for treating amyloid-related diseases
US20060079578A1 (en) 2003-06-23 2006-04-13 Julie Laurin Pharmaceutical formulations of amyloid inhibiting compounds
US20050142191A1 (en) 2003-06-23 2005-06-30 Neurochem (International) Limited Pharmaceutical formulations of amyloid inhibiting compounds
SG145784A1 (en) 2003-08-11 2008-09-29 California Inst Of Techn Microfluidic large scale integration
DK2089417T3 (en) 2006-10-12 2015-03-23 Bhi Ltd Partnership Methods, Compounds, Compositions and Vehicles for Delivery of 3-Amion-1-Propanesulfonic Acid
KR101450356B1 (ko) 2006-11-24 2014-10-15 에이씨 이뮨 에스.에이. 알츠하이머와 같은 아밀로이드 또는 아밀로이드-유사 단백질과 관련된 질환의 치료를 위한 n-(메틸)-1h-피라졸-3-아민, n-(메틸)-피리딘-2-아민 및 n-(메틸)-티아졸-2-아민 유도체
US20120009125A1 (en) * 2010-07-06 2012-01-12 Lombard Jay L Apoe4 and apoj biomarker-based prevention and treatment of dementia
ES2705027T3 (es) 2010-08-19 2019-03-21 Buck Institute For Age Res Métodos de tratamiento del deterioro cognitivo leve (DCL) y trastornos relacionados
HUE044737T2 (hu) 2013-05-06 2019-11-28 Baxalta Inc Alzheimer-kór szubpopulációk kezelése egyesített immunglubulin G-vel
CA2938466C (en) * 2014-02-08 2021-11-02 Genentech, Inc. Methods of treating alzheimer's disease
EP4275750B1 (en) 2015-09-10 2026-05-06 Alzheon, Inc. Treatment of alzheimer's disease in a particular patient population
US20180250249A1 (en) 2016-02-02 2018-09-06 Alzheon, Inc. Methods of treating neurodegenerative disorders in a particular population

Also Published As

Publication number Publication date
PL3119911T3 (pl) 2024-01-22
AU2015230972A1 (en) 2016-09-15
EP3119911B1 (en) 2023-08-09
JP2019065044A (ja) 2019-04-25
KR20220136476A (ko) 2022-10-07
HUE063369T2 (hu) 2024-01-28
JP2022159555A (ja) 2022-10-17
JP2025022992A (ja) 2025-02-14
EP3119911A4 (en) 2017-12-13
US20170172952A1 (en) 2017-06-22
CA2941415A1 (en) 2015-09-24
RS64744B1 (sr) 2023-11-30
KR102645633B1 (ko) 2024-03-11
EP4289820A3 (en) 2024-03-13
EP3119911A2 (en) 2017-01-25
CN106170563A (zh) 2016-11-30
KR102448386B1 (ko) 2022-09-28
US10471029B2 (en) 2019-11-12
ES2960625T3 (es) 2024-03-05
WO2015143447A3 (en) 2016-01-14
SMT202300369T1 (it) 2023-11-13
KR20160128391A (ko) 2016-11-07
JP2020109123A (ja) 2020-07-16
EP4289820A2 (en) 2023-12-13
US20230087041A1 (en) 2023-03-23
DK3119911T3 (da) 2023-10-30
JP6588962B2 (ja) 2019-10-09
FI3119911T3 (fi) 2023-09-27
PT3119911T (pt) 2023-11-03
WO2015143447A2 (en) 2015-09-24
US20200101031A1 (en) 2020-04-02
AU2015230972B2 (en) 2021-05-27
JP2017511377A (ja) 2017-04-20
LT3119911T (lt) 2023-10-10
SI3119911T1 (sl) 2023-12-29

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