RU2678450C2 - Способы контроля восприимчивости анти-smad7 терапии - Google Patents

Способы контроля восприимчивости анти-smad7 терапии Download PDF

Info

Publication number
RU2678450C2
RU2678450C2 RU2014114838A RU2014114838A RU2678450C2 RU 2678450 C2 RU2678450 C2 RU 2678450C2 RU 2014114838 A RU2014114838 A RU 2014114838A RU 2014114838 A RU2014114838 A RU 2014114838A RU 2678450 C2 RU2678450 C2 RU 2678450C2
Authority
RU
Russia
Prior art keywords
cells
individual
ccr9
susceptible
foxp3
Prior art date
Application number
RU2014114838A
Other languages
English (en)
Russian (ru)
Other versions
RU2014114838A (ru
Inventor
Джованни Монтелеоне
Франческа Вити
Сальваторе Беллинвия
Original Assignee
Ногра Фарма Лимитед
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 Ногра Фарма Лимитед filed Critical Ногра Фарма Лимитед
Publication of RU2014114838A publication Critical patent/RU2014114838A/ru
Application granted granted Critical
Publication of RU2678450C2 publication Critical patent/RU2678450C2/ru

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047—Cells of the immune system
    • G01N33/505—Cells of the immune system involving T-cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5094—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for blood cell populations
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56966—Animal cells
    • G01N33/56972—White blood cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
    • G01N33/6866—Interferon
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
    • G01N33/6869—Interleukin
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/52—Assays involving cytokines
    • G01N2333/54—Interleukins [IL]
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/715—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons
    • G01N2333/7158—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons for chemokines
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/06—Gastro-intestinal diseases
    • G01N2800/065—Bowel diseases, e.g. Crohn, ulcerative colitis, IBS
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Virology (AREA)
  • Zoology (AREA)
  • Ecology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Toxicology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
RU2014114838A 2011-09-15 2012-09-14 Способы контроля восприимчивости анти-smad7 терапии RU2678450C2 (ru)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
EP11425234.9 2011-09-15
EP11425234 2011-09-15
US201161576556P 2011-12-16 2011-12-16
US61/576,556 2011-12-16
PCT/EP2012/068146 WO2013037970A1 (en) 2011-09-15 2012-09-14 Methods for monitoring responsiveness to anti-smad7 therapy

Publications (2)

Publication Number Publication Date
RU2014114838A RU2014114838A (ru) 2015-10-20
RU2678450C2 true RU2678450C2 (ru) 2019-01-29

Family

ID=47882658

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2014114838A RU2678450C2 (ru) 2011-09-15 2012-09-14 Способы контроля восприимчивости анти-smad7 терапии

Country Status (11)

Country Link
US (2) US9791442B2 (enExample)
EP (2) EP2748611B1 (enExample)
JP (1) JP6389122B2 (enExample)
KR (1) KR102099990B1 (enExample)
CN (1) CN104040349B (enExample)
AU (1) AU2012307336B2 (enExample)
CA (1) CA2848595A1 (enExample)
ES (1) ES2617200T3 (enExample)
MX (1) MX350087B (enExample)
RU (1) RU2678450C2 (enExample)
WO (1) WO2013037970A1 (enExample)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITRM20030149A1 (it) 2003-04-02 2004-10-03 Giuliani Spa Oligonucleotidi (odn) antisenso per smad7 e loro usi in campo medico
JP5719776B2 (ja) 2008-11-13 2015-05-20 ノグラ ファーマ リミテッド アンチセンス組成物およびその作製および使用
NZ630914A (en) 2012-04-18 2017-01-27 Nogra Pharma Ltd Methods of treating diabetes and/or promoting survival of pancreatic islets after transplantation
US10006029B2 (en) 2013-03-15 2018-06-26 Nogra Pharma Limited Methods of treating colorectal cancer
JP6502863B2 (ja) * 2013-03-15 2019-04-17 ノグラ ファーマ リミテッド 結腸直腸癌を処置する方法
US20160139123A1 (en) * 2013-07-12 2016-05-19 Institut National De La Sante Et De La Recherche Medicale (Inserm) Shear Wave Imaging Method and Installation for Collecting Information on a Soft Solid
KR20170005058A (ko) * 2014-05-09 2017-01-11 노그라 파마 리미티드 염증성 장 질환을 치료하는 방법
US10337004B2 (en) * 2014-10-17 2019-07-02 Nogra Pharma Limited Methods and compositions for treating a subject with a SMAD7 antisense oligonucleotide
US20170233736A1 (en) * 2014-10-17 2017-08-17 Nogra Pharma Limited Methods for dosing and monitoring smad7 antisense oligonucleotide treatment using biomarker levels
MA41271A (fr) * 2014-12-26 2017-10-31 Celgene Alpine Invest Company Ii Llc Méthodes d'utilisation d'oligonucléotides antisens ciblant smad7
CN108139385A (zh) * 2015-07-27 2018-06-08 豪夫迈·罗氏有限公司 用于诊断和治疗炎症性肠病的方法
EP3356530A4 (en) * 2015-09-30 2019-04-10 Celgene Alpine Investment Company II, LLC TLR-MODULATORS AND METHOD OF USE
EP3355896A2 (en) * 2015-09-30 2018-08-08 Nogra Pharma Limited Methods of using smad7 antisense oligonucleotides based on biomarker expression
JP2019505598A (ja) 2016-02-23 2019-02-28 セルジーン アルパイン インベストメント カンパニー Ｉｉ， エルエルシー Ｓｍａｄ７の阻害を用いて、腸線維症を治療する方法
WO2019051173A1 (en) 2017-09-08 2019-03-14 Ionis Pharmaceuticals, Inc. MODULATORS OF SMAD7 EXPRESSION
US11619832B2 (en) 2018-03-08 2023-04-04 Coopervision International Limited Identification of contact lens wearers predisposed to contact lens discomfort
CN110082538B (zh) * 2019-04-19 2021-12-03 中山大学附属第六医院 CCR9+IL-17+Treg细胞在制备用于检测NEC的试剂盒中的应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6159697A (en) * 2000-01-19 2000-12-12 Isis Pharmaceuticals, Inc. Antisense modulation of Smad7 expression
RU2185627C2 (ru) * 2000-09-11 2002-07-20 Новосибирская государственная медицинская академия Способ определения чувствительности (восприимчивости) к внутривенной лазеротерапии больных ишемической болезнью сердца
JP2010185878A (ja) * 2006-03-10 2010-08-26 Mount Sinai Hospital 栄養膜細胞の細胞死、分化、浸潤、および／または細胞融合および代謝回転に関連する状態の診断用組成物および治療方法

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1456380B1 (en) 2001-11-02 2012-04-18 Giuliani International Limited Smad7 inhibitors for the treatment of cns diseases
ITRM20030149A1 (it) * 2003-04-02 2004-10-03 Giuliani Spa Oligonucleotidi (odn) antisenso per smad7 e loro usi in campo medico
US20090275496A1 (en) 2004-05-07 2009-11-05 Peptimmune, Inc. Effective quantitation of complex peptide mixtures in tissue samples and improved therapeutic methods
JP5122454B2 (ja) * 2005-08-02 2013-01-16 センテナリ インスティチュート オブ キャンサー メディシン アンド セル バイオロジー 調節性ｔ細胞を同定する方法
WO2008157394A2 (en) * 2007-06-13 2008-12-24 La Jolla Institute For Allergy And Immunology Regulatory t cells and methods of making and using same
EP2264182A1 (en) 2008-02-28 2010-12-22 Sysmex Corporation Marker for detection of il-17-producing helper t-cell, and method for detection of il-17-producing helper t-cell
JP2010051307A (ja) 2008-07-28 2010-03-11 Eisai R & D Management Co Ltd Ｔｈ１７細胞およびＴｒｅｇ細胞の分化誘導を調節する物質のスクリーニング方法
JP5719776B2 (ja) 2008-11-13 2015-05-20 ノグラ ファーマ リミテッド アンチセンス組成物およびその作製および使用
CN102483405B (zh) 2009-07-10 2015-12-02 特朗斯吉有限公司 用于选择患者的生物标志物及相关方法
US8766034B2 (en) 2010-09-22 2014-07-01 Cedars-Sinai Medical Center TL1A model of inflammation fibrosis and autoimmunity
NZ630914A (en) 2012-04-18 2017-01-27 Nogra Pharma Ltd Methods of treating diabetes and/or promoting survival of pancreatic islets after transplantation
JP6502863B2 (ja) 2013-03-15 2019-04-17 ノグラ ファーマ リミテッド 結腸直腸癌を処置する方法
US10006029B2 (en) 2013-03-15 2018-06-26 Nogra Pharma Limited Methods of treating colorectal cancer
KR20170005058A (ko) 2014-05-09 2017-01-11 노그라 파마 리미티드 염증성 장 질환을 치료하는 방법
US10337004B2 (en) 2014-10-17 2019-07-02 Nogra Pharma Limited Methods and compositions for treating a subject with a SMAD7 antisense oligonucleotide
US20170233736A1 (en) 2014-10-17 2017-08-17 Nogra Pharma Limited Methods for dosing and monitoring smad7 antisense oligonucleotide treatment using biomarker levels
EP3355896A2 (en) 2015-09-30 2018-08-08 Nogra Pharma Limited Methods of using smad7 antisense oligonucleotides based on biomarker expression

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6159697A (en) * 2000-01-19 2000-12-12 Isis Pharmaceuticals, Inc. Antisense modulation of Smad7 expression
RU2185627C2 (ru) * 2000-09-11 2002-07-20 Новосибирская государственная медицинская академия Способ определения чувствительности (восприимчивости) к внутривенной лазеротерапии больных ишемической болезнью сердца
JP2010185878A (ja) * 2006-03-10 2010-08-26 Mount Sinai Hospital 栄養膜細胞の細胞死、分化、浸潤、および／または細胞融合および代謝回転に関連する状態の診断用組成物および治療方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MONTELEONE G et al. Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel disease. J Clin Invest. 2001 Aug; N108(4), c. 601-9. онлайн [найдено из Интернет][найдено 13.09.2016]http://www.ncbi.nlm.nih.gov/pubmed/11518734. *

Also Published As

Publication number Publication date
US20150148245A1 (en) 2015-05-28
CN104040349A (zh) 2014-09-10
KR102099990B1 (ko) 2020-04-13
EP3165929A3 (en) 2017-06-21
HK1199095A1 (en) 2015-06-19
JP6389122B2 (ja) 2018-09-12
AU2012307336B2 (en) 2017-08-24
MX2014003295A (es) 2014-05-28
AU2012307336A1 (en) 2014-03-27
US20180128829A1 (en) 2018-05-10
CN104040349B (zh) 2017-07-04
CA2848595A1 (en) 2013-03-21
EP3165929A2 (en) 2017-05-10
EP2748611B1 (en) 2016-11-23
MX350087B (es) 2017-08-24
RU2014114838A (ru) 2015-10-20
KR20140059859A (ko) 2014-05-16
EP2748611A1 (en) 2014-07-02
JP2014531584A (ja) 2014-11-27
NZ719884A (en) 2020-02-28
NZ622067A (en) 2016-05-27
WO2013037970A1 (en) 2013-03-21
ES2617200T3 (es) 2017-06-15
US9791442B2 (en) 2017-10-17

Similar Documents

Publication Publication Date Title
RU2678450C2 (ru) Способы контроля восприимчивости анти-smad7 терапии
Hollerbach et al. Pathogenic lipid‐binding antiphospholipid antibodies are associated with severity of COVID‐19
Goldstein et al. Defective leukocyte GM-CSF receptor (CD116) expression and function in inflammatory bowel disease
US20230051905A1 (en) Triaging method using cell free nucleosome levels
Vogelsang et al. Levels of plasmacytoid dendritic cells and type-2 myeloid dendritic cells are reduced in peripheral blood of patients with primary Sjögren's syndrome
US12360103B2 (en) Blood biomarker for eosinophilic gastrointestinal disorders
Gavriilidis et al. Neutrophil-fibroblast crosstalk drives immunofibrosis in Crohn’s disease through IFNα pathway
Fang et al. CXCL12/CXCR4 axis drives the chemotaxis and differentiation of B cells in bullous pemphigoid
WO2019195823A1 (en) Prediction and treatment of immunotherapeutic toxicity
EP3922641A1 (en) Methods for detecting and treating covid patients requiring intensive care
JP2013021932A (ja) 関節リウマチに対する抗ｉｌ−６受容体抗体療法の有効性の予測方法
HK1199095B (en) Methods for monitoring responsiveness to anti-smad7 therapy
NZ622067B2 (en) Methods for monitoring responsiveness to anti-smad7 therapy
CN113533737A (zh) Nfam1在筛选防治冠心病药物或制备试剂盒中的应用
NZ719884B2 (en) Methods for monitoring responsiveness to anti-SMAD7 therapy
WO2018200755A1 (en) Monocyte biomarkers for hypertension
Duizendstra Rejection and Tolerance after Liver Transplantation
Barker Stromal Cell Diversity Drives Pathogenic Mechanisms in Rheumatoid Arthritis and Pre-Disease Onset
Munasinghe et al. A Myeloid Lineage Signifying Anti-Tumor Necrosis Factor Resistance in Crohn’s Disease.
HK40100515A (en) Triaging method using cell free nucleosome levels
TW202300511A (zh) 包含人類白蛋白之組成物
CN120685907A (zh) Gal-9+Th细胞和/或Gal-9+Treg作为AIH检测靶点的应用
Eakin Discovery of circulating DMARD response biomarkers in rheumatoid arthritis
WO2008100217A1 (en) Polymorphisms in genes of the cryopyrin inflammasome and their uses in the treatment of inflammatory diseases

Legal Events

Date Code Title Description
MM4A The patent is invalid due to non-payment of fees

Effective date: 20200915