RU2016147398A - Способы оценивания и лечения острого миелоидного лейкоза - Google Patents

Способы оценивания и лечения острого миелоидного лейкоза Download PDF

Info

Publication number
RU2016147398A
RU2016147398A RU2016147398A RU2016147398A RU2016147398A RU 2016147398 A RU2016147398 A RU 2016147398A RU 2016147398 A RU2016147398 A RU 2016147398A RU 2016147398 A RU2016147398 A RU 2016147398A RU 2016147398 A RU2016147398 A RU 2016147398A
Authority
RU
Russia
Prior art keywords
subject
immunoconjugate
variable region
seq
antibody
Prior art date
Application number
RU2016147398A
Other languages
English (en)
Russian (ru)
Other versions
RU2016147398A3 (cg-RX-API-DMAC7.html
Inventor
Кэтлин Р. УАЙТМЭН
Паул НООРДХЁЙС
Елена Ковтун
Роберт Дж. ЛУЦ
Геррит Ян СХЮЮРХЁЙС
Рассел Марлин УОКЕР
Original Assignee
Иммуноджен, Инк.
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
Application filed by Иммуноджен, Инк. filed Critical Иммуноджен, Инк.
Publication of RU2016147398A publication Critical patent/RU2016147398A/ru
Publication of RU2016147398A3 publication Critical patent/RU2016147398A3/ru

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/55131,4-Benzodiazepines, e.g. diazepam or clozapine
    • A61K31/55171,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
    • 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
    • A61K47/68Medicinal 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6889Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • 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
    • A61K47/68Medicinal 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • 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
    • A61K47/68Medicinal 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835Medicinal 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851Medicinal 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6867Medicinal 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from a cell of a blood cancer
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • 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
    • C12Q1/6886Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • 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
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407Specifically defined cancers
    • G01N33/57426Specifically defined cancers leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94Stability, e.g. half-life, pH, temperature or enzyme-resistance
    • 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
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70596Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/82Translation products from oncogenes

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Cell Biology (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Biophysics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Hospice & Palliative Care (AREA)
  • Urology & Nephrology (AREA)
  • Physics & Mathematics (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Food Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • General Physics & Mathematics (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
RU2016147398A 2014-05-20 2015-05-19 Способы оценивания и лечения острого миелоидного лейкоза RU2016147398A (ru)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201462001015P 2014-05-20 2014-05-20
US62/001,015 2014-05-20
US201462011456P 2014-06-12 2014-06-12
US62/011,456 2014-06-12
US201462075715P 2014-11-05 2014-11-05
US62/075,715 2014-11-05
PCT/US2015/031580 WO2015179400A2 (en) 2014-05-20 2015-05-19 Methods for characterizing and treating acute myeloid leukemia

Publications (2)

Publication Number Publication Date
RU2016147398A true RU2016147398A (ru) 2018-06-21
RU2016147398A3 RU2016147398A3 (cg-RX-API-DMAC7.html) 2019-05-28

Family

ID=54554957

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2016147398A RU2016147398A (ru) 2014-05-20 2015-05-19 Способы оценивания и лечения острого миелоидного лейкоза

Country Status (13)

Country Link
US (1) US20170080102A1 (cg-RX-API-DMAC7.html)
EP (1) EP3145542A4 (cg-RX-API-DMAC7.html)
JP (1) JP2017517507A (cg-RX-API-DMAC7.html)
KR (1) KR20170004003A (cg-RX-API-DMAC7.html)
CN (1) CN106456762A (cg-RX-API-DMAC7.html)
AU (1) AU2015264322A1 (cg-RX-API-DMAC7.html)
BR (1) BR112016026730A2 (cg-RX-API-DMAC7.html)
CA (1) CA2947602A1 (cg-RX-API-DMAC7.html)
IL (1) IL248555A0 (cg-RX-API-DMAC7.html)
MA (1) MA39885A (cg-RX-API-DMAC7.html)
RU (1) RU2016147398A (cg-RX-API-DMAC7.html)
SG (1) SG11201609357PA (cg-RX-API-DMAC7.html)
WO (1) WO2015179400A2 (cg-RX-API-DMAC7.html)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SI1578446T1 (sl) * 2002-11-07 2015-07-31 Immunogen, Inc. Protitelesa proti-cd33 in metoda za zdravljenje akutne mieloidne levkemije z uporabo istega
SI3313884T1 (sl) * 2015-06-29 2021-04-30 Immunogen, Inc. Protitelesa proti CD123 ter njihovi konjugati in derivati
EP3469001A4 (en) * 2016-06-09 2020-05-06 Seattle Genetics, Inc. COMBINATIONS OF PBD-BASED ANTIBODY CONJUGATES WITH FLT3 INHIBITORS
MA46779A (fr) * 2016-11-02 2019-09-11 Health Research Inc Traitement combiné avec des conjugués anticorps-médicament et des inhibiteurs de parp
WO2018183494A1 (en) * 2017-03-31 2018-10-04 Immunogen, Inc. Cd19-targeting antibody-drug conjugates
MA49152A (fr) * 2017-05-17 2020-03-25 Immunogen Inc Schémas posologiques d'immunoconjugués anti-cd33
US20190160089A1 (en) * 2017-10-31 2019-05-30 Immunogen, Inc. Combination treatment with antibody-drug conjugates and cytarabine
KR20200094181A (ko) 2017-11-29 2020-08-06 마젠타 테라퓨틱스 인코포레이티드 Cd5+ 세포를 고갈시키기 위한 조성물 및 방법
TW202003048A (zh) * 2018-05-15 2020-01-16 美商伊繆諾金公司 用抗體-藥物偶聯物及flt3抑制劑之組合治療
WO2020010262A1 (en) * 2018-07-06 2020-01-09 University Of Washington High throughput drug screening of cancer stem cells
WO2020051013A2 (en) * 2018-08-24 2020-03-12 The Trustees Of Columbia University In The City Of New York Anti-cd33 and nkg2d ligand chimeras for treatment of myeloid malignancies
EP3990022A4 (en) * 2019-06-26 2023-06-28 Memorial Sloan Kettering Cancer Center Anti-cd33 antibodies for treating cancer

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6007814A (en) * 1992-06-15 1999-12-28 Sloan-Kettering Institute For Cancer Research Therapeutic uses of the hypervariable region of monoclonal antibody M195 and constructs thereof
SI1578446T1 (sl) * 2002-11-07 2015-07-31 Immunogen, Inc. Protitelesa proti-cd33 in metoda za zdravljenje akutne mieloidne levkemije z uporabo istega
WO2010126552A1 (en) * 2009-04-30 2010-11-04 Immunogen, Inc. Potent cell-binding agent drug conjugates
WO2012044696A2 (en) * 2010-09-30 2012-04-05 The Board Of Trustees Of The Leland Stanford Junior University Prediction of clinical outcome in hematological malignancies using a self-renewal expression signature
RS58620B1 (sr) * 2011-02-15 2019-05-31 Immunogen Inc Metodi pripremanja konjugata
US20120282282A1 (en) * 2011-04-04 2012-11-08 Immunogen, Inc. Methods for Decreasing Ocular Toxicity of Antibody Drug Conjugates

Also Published As

Publication number Publication date
CA2947602A1 (en) 2015-11-26
RU2016147398A3 (cg-RX-API-DMAC7.html) 2019-05-28
EP3145542A2 (en) 2017-03-29
WO2015179400A2 (en) 2015-11-26
CN106456762A (zh) 2017-02-22
SG11201609357PA (en) 2016-12-29
EP3145542A4 (en) 2018-01-17
AU2015264322A1 (en) 2016-11-10
WO2015179400A3 (en) 2016-02-04
US20170080102A1 (en) 2017-03-23
JP2017517507A (ja) 2017-06-29
BR112016026730A2 (pt) 2017-12-12
IL248555A0 (en) 2016-12-29
KR20170004003A (ko) 2017-01-10
MA39885A (fr) 2015-11-26

Similar Documents

Publication Publication Date Title
RU2016147398A (ru) Способы оценивания и лечения острого миелоидного лейкоза
AU2021203744B2 (en) Treatment regimens using anti-NKG2A antibodies
RU2756275C2 (ru) Антитела, специфические к рецептору полиовируса (pvr) человека
JP7531667B2 (ja) リンパ球における阻害経路の中和
JP2017517507A5 (cg-RX-API-DMAC7.html)
AU2015316991B2 (en) Neutralization of inhibitory pathways in lymphocytes
JP6025563B2 (ja) Notch3アンタゴニストを用いたNotch1アンタゴニスト耐性癌の治療
TWI469792B (zh) 新穎之抗cxcr4抗體及其於治療癌症之用途
ES2657458T3 (es) Procedimientos para tratar el cáncer colorrectal
TWI505836B (zh) 抗-vegf-c抗體及其使用方法
DK3004167T3 (en) ONCOSTATIN M-RECEPTOR ANTIGIN BINDING PROTEINS
BR112020007309A2 (pt) anticorpos, anticorpos ativáveis, anticorpos biespecíficos e anticorpos ativáveis biespecíficos e métodos de uso dos mesmos
JP2019048896A (ja) ヒトタンパク質チロシンホスファターゼβ(HPTPβ)に結合する抗体及びその使用
JP2018512435A (ja) Gdf8阻害剤を用いて、強度及び機能を増加させる方法
TW200817435A (en) Compositions and methods for modulating vascular development
JP2018500014A5 (cg-RX-API-DMAC7.html)
KR20230155605A (ko) 이중 특이적 항체
US20140271644A1 (en) Combination/adjuvant therapy for wt-1-positive disease
TW201106972A (en) Combination treatments
JP2012521218A5 (cg-RX-API-DMAC7.html)
JP2010534195A (ja) アルテミン及び関連するリガンドについてのポリペプチド及びポリヌクレオチド、並びにその使用方法
EP2992018B1 (en) Targeting o-acetylated gd2 ganglioside as a new therapeutic and diagnostic strategy for cancer stem cells cancer
CN109069606A (zh) 干扰素β抗体及其用途
JP2015512877A (ja) 癌を治療するためのクラステリン阻害剤とegfr阻害剤の併用
ES2575430T3 (es) Composición farmacéutica para el tratamiento y la prevención del cáncer

Legal Events

Date Code Title Description
FA92 Acknowledgement of application withdrawn (lack of supplementary materials submitted)

Effective date: 20190911