AU2021361844A1 - Immunomodulatory peptides - Google Patents

Immunomodulatory peptides Download PDF

Info

Publication number
AU2021361844A1
AU2021361844A1 AU2021361844A AU2021361844A AU2021361844A1 AU 2021361844 A1 AU2021361844 A1 AU 2021361844A1 AU 2021361844 A AU2021361844 A AU 2021361844A AU 2021361844 A AU2021361844 A AU 2021361844A AU 2021361844 A1 AU2021361844 A1 AU 2021361844A1
Authority
AU
Australia
Prior art keywords
peptide
cancer
seq
group
cell
Prior art date
Legal status (The legal status 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 status listed.)
Abandoned
Application number
AU2021361844A
Other languages
English (en)
Other versions
AU2021361844A9 (en
Inventor
Cecille D. BROWNE
Peter J. BUONTEMPO
Gabriel M. Gutierrez
Vinayaka Kotraiah
James PANNUCCI
Timothy W. Phares
Michael Ryan Weil
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Leidos Inc
Original Assignee
Leidos 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
Application filed by Leidos Inc filed Critical Leidos Inc
Publication of AU2021361844A1 publication Critical patent/AU2021361844A1/en
Publication of AU2021361844A9 publication Critical patent/AU2021361844A9/en
Abandoned legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/08Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14Blood; Artificial blood
    • A61K35/17Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66Microorganisms or materials therefrom
    • A61K35/76Viruses; Subviral particles; Bacteriophages
    • 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
    • A61K38/10Peptides having 12 to 20 amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/002Protozoa antigens
    • A61K39/015Hemosporidia antigens, e.g. Plasmodium antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/39Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64Proteins; Peptides; Derivatives or degradation products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00Preparations for affecting hair growth
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503Immunoglobulin superfamily
    • C07K14/7051T-cell receptor (TcR)-CD3 complex
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503Immunoglobulin superfamily
    • C07K14/70521CD28, CD152
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IG], 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
    • C07K16/2818Immunoglobulins [IG], 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 against CD28 or CD152
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/06Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86Viral vectors
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00Animals characterised by species
    • A01K2227/10Mammal
    • A01K2227/105Murine
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00Animals characterised by purpose
    • A01K2267/03Animal model, e.g. for test or diseases
    • A01K2267/0331Animal model for proliferative diseases
    • 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
    • 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
    • A61K2039/507Comprising a combination of two or more separate antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/51Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525Virus
    • A61K2039/5256Virus expressing foreign proteins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • A61K2039/55516Proteins; Peptides
    • 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
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Cell Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Virology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Mycology (AREA)
  • Toxicology (AREA)
  • Hematology (AREA)
  • General Engineering & Computer Science (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Wood Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Dermatology (AREA)
AU2021361844A 2020-10-12 2021-10-08 Immunomodulatory peptides Abandoned AU2021361844A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US202063090324P 2020-10-12 2020-10-12
US63/090,324 2020-10-12
PCT/US2021/054127 WO2022081426A1 (en) 2020-10-12 2021-10-08 Immunomodulatory peptides

Publications (2)

Publication Number Publication Date
AU2021361844A1 true AU2021361844A1 (en) 2023-06-15
AU2021361844A9 AU2021361844A9 (en) 2024-09-12

Family

ID=78463990

Family Applications (1)

Application Number Title Priority Date Filing Date
AU2021361844A Abandoned AU2021361844A1 (en) 2020-10-12 2021-10-08 Immunomodulatory peptides

Country Status (6)

Country Link
US (1) US11987646B2 (enExample)
EP (1) EP4225444A1 (enExample)
JP (1) JP2023548662A (enExample)
AU (1) AU2021361844A1 (enExample)
CA (1) CA3198203A1 (enExample)
WO (1) WO2022081426A1 (enExample)

Family Cites Families (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001523958A (ja) 1997-03-21 2001-11-27 ブライハム アンド ウィミンズ ホスピタル,インコーポレイテッド 免疫療法のctla−4結合ペプチド
JP2002513811A (ja) 1998-05-06 2002-05-14 ファルマシア・アンド・アップジョン・カンパニー 非−ヒト脊椎動物への、非−ヒト脊椎動物のペプチドホルモンまたはサイトカインをコードする裸のdnaまたは裸のrnaの導入
CA2541006C (en) 2003-10-03 2015-02-17 Brigham And Women's Hospital Tim-3 polypeptides
US10668119B2 (en) 2005-08-01 2020-06-02 Virocure, Inc. Attenuated reovirus
BR112012007875A2 (pt) 2009-07-31 2016-11-22 Medarex Inc anticorpos totalmente humanos para btla
US20130202623A1 (en) 2010-02-16 2013-08-08 Nicolas Chomont Pd-1 modulation and uses thereof for modulating hiv replication
MX2012009632A (es) 2010-02-18 2012-09-28 Athenix Corp Genes delta-endotoxinicos axmi221z, axmi222z, axmi223z, axmi224z, axmi225z y metodos para su uso.
MX374075B (es) 2010-03-26 2025-03-05 Dartmouth College Proteina mediadora de celula t regulatoria vista, agentes de enlace de vista y uso de los mismos.
US8907053B2 (en) 2010-06-25 2014-12-09 Aurigene Discovery Technologies Limited Immunosuppression modulating compounds
US9845362B2 (en) 2010-10-08 2017-12-19 The University Of North Carolina At Charlotte Compositions comprising chimeric antigen receptors, T cells comprising the same, and methods of using the same
US20130267515A1 (en) 2010-10-26 2013-10-10 Alberta Health Services Combination comprising an atp analog and an adenosine receptor antagonist or a nucleobase/nucleoside analog for the treatment of cancer
CN102085735B (zh) 2010-11-09 2013-03-27 浙江大东南包装股份有限公司 一种多功能bopp烟用包装膜及其制造方法
PH12013501201A1 (en) 2010-12-09 2013-07-29 Univ Pennsylvania Use of chimeric antigen receptor-modified t cells to treat cancer
WO2012116714A1 (en) 2011-03-02 2012-09-07 Curevac Gmbh Vaccination in elderly patients
WO2012168944A1 (en) 2011-06-08 2012-12-13 Aurigene Discovery Technologies Limited Therapeutic compounds for immunomodulation
WO2013043569A1 (en) 2011-09-20 2013-03-28 Vical Incorporated Synergistic anti-tumor efficacy using alloantigen combination immunotherapy
WO2013132317A1 (en) 2012-03-07 2013-09-12 Aurigene Discovery Technologies Limited Peptidomimetic compounds as immunomodulators
CA2868408A1 (en) 2012-03-29 2013-10-03 Aurigene Discovery Technologies Limited Immunomodulating cyclic compounds from the bc loop of human pd1
US9381244B2 (en) 2012-09-07 2016-07-05 King's College London VISTA modulators for diagnosis and treatment of cancer
US20150250837A1 (en) 2012-09-20 2015-09-10 Morningside Technology Ventures Ltd. Oncolytic virus encoding pd-1 binding agents and uses of the same
PL2904011T3 (pl) 2012-10-02 2018-01-31 Bristol Myers Squibb Co Połączenie przeciwciał anty-kir i przeciwciał anty-pd-1 w leczeniu raka
US9974845B2 (en) 2013-02-22 2018-05-22 Curevac Ag Combination of vaccination and inhibition of the PD-1 pathway
US9320706B2 (en) 2013-03-13 2016-04-26 Transdermal Biotechnology, Inc. Immune modulation using peptides and other compositions
US9295647B2 (en) 2013-03-13 2016-03-29 Transdermal Biotechnology, Inc. Systems and methods for delivery of peptides
US20160145355A1 (en) 2013-06-24 2016-05-26 Biomed Valley Discoveries, Inc. Bispecific antibodies
CN104072615B (zh) 2014-01-26 2016-08-24 中国人民解放军军事医学科学院基础医学研究所 一种能阻断Tim-3信号通路的人Tim-3融合蛋白
HUE045065T2 (hu) 2014-01-31 2019-12-30 Novartis Ag TIM-3 antitest molekulák és felhasználásaik
US10899840B2 (en) 2014-02-04 2021-01-26 Pfizer Inc. Combination of a PD-1 antagonist and a 4-1BB agonist for treating cancer
SG11201606428UA (en) 2014-02-04 2016-09-29 Incyte Corp Combination of a pd-1 antagonist and an ido1 inhibitor for treating cancer
ES2833425T3 (es) 2014-07-16 2021-06-15 Roussy Inst Gustave Combinación de virus oncolítico con moduladores de punto de control inmunitario
RU2696312C2 (ru) 2014-07-16 2019-08-01 Трансген Са Онколитический вирус для экспрессии модуляторов иммунологических контрольных точек
US10695426B2 (en) 2014-08-25 2020-06-30 Pfizer Inc. Combination of a PD-1 antagonist and an ALK inhibitor for treating cancer
US10016480B2 (en) 2014-10-14 2018-07-10 The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services Peptide-based methods for treating pancreatic cancer
BR112017007765B1 (pt) 2014-10-14 2023-10-03 Halozyme, Inc Composições de adenosina deaminase-2 (ada2), variantes do mesmo e métodos de usar o mesmo
GB201504502D0 (en) 2015-03-17 2015-04-29 Immatics Biotechnologies Gmbh Novel peptides and combination of peptides for use in immunotherapy against pancreatic cancer and other cancers
CA2994241A1 (en) 2015-07-31 2017-02-09 University Of Florida Research Foundation, Inc. Hematopoietic stem cells in combinatorial therapy with immune checkpoint inhibitors against cancer
US9957325B2 (en) 2015-10-13 2018-05-01 Formurex, Inc. Synthetic antibody mimic peptides
TWI808055B (zh) 2016-05-11 2023-07-11 美商滬亞生物國際有限公司 Hdac 抑制劑與 pd-1 抑制劑之組合治療
AU2017290828A1 (en) 2016-06-30 2019-01-24 Virogin Biotech Canada Ltd Pseudotyped oncolytic viral delivery of therapeutic polypeptides
US10098950B2 (en) 2016-09-15 2018-10-16 Leidos, Inc. PD-1 Peptide Inhibitors
US10799555B2 (en) 2016-09-15 2020-10-13 Leidos, Inc. PD-1 peptide inhibitors
WO2018218137A1 (en) * 2017-05-25 2018-11-29 Leidos, Inc. Pd-1 and ctla-4 dual inhibitor peptides
CN107383174B (zh) 2017-08-21 2019-01-18 生工生物工程(上海)股份有限公司 一种能与pd-1特异性结合的肿瘤抑制肽及其用途
DK3758732T3 (da) * 2018-02-27 2024-10-07 Leidos Inc PD-1-peptidinhibitorer
CA3185657A1 (en) * 2020-06-04 2021-12-09 Leidos, Inc. Immunomodulatory compounds

Also Published As

Publication number Publication date
US20220112243A1 (en) 2022-04-14
EP4225444A1 (en) 2023-08-16
JP2023548662A (ja) 2023-11-20
US11987646B2 (en) 2024-05-21
CA3198203A1 (en) 2022-04-21
WO2022081426A1 (en) 2022-04-21

Similar Documents

Publication Publication Date Title
US12370258B2 (en) PD-1 and CTLA-4 dual inhibitor peptides
US12269880B2 (en) LAG3 binding peptides
US20230414703A1 (en) PD-1 Peptide Inhibitors
US11338040B2 (en) Immunomodulatory compounds
US11578102B2 (en) LAG3 binding peptides
AU2018410849B2 (en) PD-1 peptide inhibitors
US11987646B2 (en) Immunomodulatory peptides

Legal Events

Date Code Title Description
SREP Specification republished
MK1 Application lapsed section 142(2)(a) - no request for examination in relevant period