AU2018224852B2 - VSIG8-based chimeric proteins - Google Patents

VSIG8-based chimeric proteins Download PDF

Info

Publication number
AU2018224852B2
AU2018224852B2 AU2018224852A AU2018224852A AU2018224852B2 AU 2018224852 B2 AU2018224852 B2 AU 2018224852B2 AU 2018224852 A AU2018224852 A AU 2018224852A AU 2018224852 A AU2018224852 A AU 2018224852A AU 2018224852 B2 AU2018224852 B2 AU 2018224852B2
Authority
AU
Australia
Prior art keywords
leu
ser
gly
val
ala
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.)
Expired - Fee Related
Application number
AU2018224852A
Other languages
English (en)
Other versions
AU2018224852A1 (en
Inventor
Suresh DE SILVA
George FROMM
Taylor Schreiber
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.)
Shattuck Labs Inc
Original Assignee
Shattuck Labs 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 Shattuck Labs Inc filed Critical Shattuck Labs Inc
Publication of AU2018224852A1 publication Critical patent/AU2018224852A1/en
Application granted granted Critical
Publication of AU2018224852B2 publication Critical patent/AU2018224852B2/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70514—CD4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/62—Medicinal 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 a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702—Regulators; Modulating activity
    • C07K14/4703—Inhibitors; Suppressors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70517—CD8
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Plant Pathology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
AU2018224852A 2017-02-27 2018-02-27 VSIG8-based chimeric proteins Expired - Fee Related AU2018224852B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201762463999P 2017-02-27 2017-02-27
US62/463,999 2017-02-27
PCT/US2018/020038 WO2018157163A1 (en) 2017-02-27 2018-02-27 Vsig8-based chimeric proteins

Publications (2)

Publication Number Publication Date
AU2018224852A1 AU2018224852A1 (en) 2019-07-11
AU2018224852B2 true AU2018224852B2 (en) 2025-03-06

Family

ID=63253418

Family Applications (1)

Application Number Title Priority Date Filing Date
AU2018224852A Expired - Fee Related AU2018224852B2 (en) 2017-02-27 2018-02-27 VSIG8-based chimeric proteins

Country Status (8)

Country Link
US (4) US11192933B2 (cg-RX-API-DMAC7.html)
EP (2) EP3585410B9 (cg-RX-API-DMAC7.html)
JP (3) JP7244428B2 (cg-RX-API-DMAC7.html)
CN (2) CN118184797A (cg-RX-API-DMAC7.html)
AU (1) AU2018224852B2 (cg-RX-API-DMAC7.html)
CA (1) CA3054130A1 (cg-RX-API-DMAC7.html)
IL (1) IL268170A (cg-RX-API-DMAC7.html)
WO (1) WO2018157163A1 (cg-RX-API-DMAC7.html)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020176718A1 (en) * 2019-02-28 2020-09-03 Shattuck Labs, Inc. Combination therapies
EP3986442A4 (en) * 2019-06-21 2023-10-25 Shattuck Labs, Inc. Chimeric protein expressing t-cells
IL310472A (en) * 2021-07-26 2024-03-01 Kite Pharma Inc Dnvsig3 and dnvsig8 receptors and methods of using the same
WO2024123812A1 (en) 2022-12-05 2024-06-13 Shattuck Labs, Inc. Fusion proteins for the treatment of cardiometabolic diseases

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017059168A1 (en) * 2015-10-01 2017-04-06 Heat Biologics, Inc. Compositions and methods for adjoining type i and type ii extracellular domains as heterologous chimeric proteins

Family Cites Families (69)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3536809A (en) 1969-02-17 1970-10-27 Alza Corp Medication method
US3598123A (en) 1969-04-01 1971-08-10 Alza Corp Bandage for administering drugs
US3845770A (en) 1972-06-05 1974-11-05 Alza Corp Osmatic dispensing device for releasing beneficial agent
US3916899A (en) 1973-04-25 1975-11-04 Alza Corp Osmotic dispensing device with maximum and minimum sizes for the passageway
US4008719A (en) 1976-02-02 1977-02-22 Alza Corporation Osmotic system having laminar arrangement for programming delivery of active agent
IE58110B1 (en) 1984-10-30 1993-07-14 Elan Corp Plc Controlled release powder and process for its preparation
US5073543A (en) 1988-07-21 1991-12-17 G. D. Searle & Co. Controlled release formulations of trophic factors in ganglioside-lipsome vehicle
IT1229203B (it) 1989-03-22 1991-07-25 Bioresearch Spa Impiego di acido 5 metiltetraidrofolico, di acido 5 formiltetraidrofolico e dei loro sali farmaceuticamente accettabili per la preparazione di composizioni farmaceutiche in forma a rilascio controllato attive nella terapia dei disturbi mentali organici e composizioni farmaceutiche relative.
US5120548A (en) 1989-11-07 1992-06-09 Merck & Co., Inc. Swelling modulated polymeric drug delivery device
US5698155A (en) 1991-05-31 1997-12-16 Gs Technologies, Inc. Method for the manufacture of pharmaceutical cellulose capsules
US5844095A (en) 1991-06-27 1998-12-01 Bristol-Myers Squibb Company CTLA4 Ig fusion proteins
US5580578A (en) 1992-01-27 1996-12-03 Euro-Celtique, S.A. Controlled release formulations coated with aqueous dispersions of acrylic polymers
DE69334150T2 (de) 1992-05-14 2008-03-13 Baylor College Of Medicine, Houston Mutierte steroidhormonrezeptoren, methoden für ihre benutzung und molekularer schalter für gentherapie
US5591767A (en) 1993-01-25 1997-01-07 Pharmetrix Corporation Liquid reservoir transdermal patch for the administration of ketorolac
US6004941A (en) 1993-06-14 1999-12-21 Basf Aktiengesellschaft Methods for regulating gene expression
IT1270594B (it) 1994-07-07 1997-05-07 Recordati Chem Pharm Composizione farmaceutica a rilascio controllato di moguisteina in sospensione liquida
US5733556A (en) 1995-10-18 1998-03-31 Akzo Nobel N.V. Newcastle disease virus combination vaccine
US6015709A (en) 1997-08-26 2000-01-18 Ariad Pharmaceuticals, Inc. Transcriptional activators, and compositions and uses related thereto
US5989910A (en) 1998-08-03 1999-11-23 University Of Lausanne Potent genetic switch allowing regulated gene expression in eukaryotic cells
US7569663B2 (en) 2000-01-03 2009-08-04 Mark L. Tykocinski Chimeric proteins and methods for using the same
US20110041190A1 (en) 2002-10-31 2011-02-17 Tykocinski Mark L Novel chimeric proteins
PT1355919E (pt) 2000-12-12 2011-03-02 Medimmune Llc Moléculas com semivida longa, composições que as contêm e suas utilizações
IL164376A0 (en) * 2002-04-03 2005-12-18 Applied Research Systems Ox4or binding agents, their preparation and pharmaceutical compositions containing them
JP2006345852A (ja) 2005-06-16 2006-12-28 Virxsys Corp 抗体複合体
MX2008015524A (es) 2006-06-12 2009-01-13 Trubion Pharmaceuticals Inc Proteinas de union multivalentes monocatenarias con funcion efectora.
US20090226435A1 (en) 2008-03-08 2009-09-10 Sanjay Khare Engineered fusion molecules immunotherapy in cancer and inflammatory diseases
CN102137869B (zh) 2008-06-30 2018-07-06 宾夕法尼亚大学 Fn14/TRAIL融合蛋白
JP2011526794A (ja) 2008-07-02 2011-10-20 エマージェント プロダクト デベロップメント シアトル， エルエルシー ＴＧＦ−βアンタゴニスト多重標的結合性分子
US8080246B2 (en) 2008-11-26 2011-12-20 Five Prime Therapeutics, Inc. Colony stimulating factor 1 receptor (CSF1R) extracellular domain fusion molecules
EP2406388B1 (en) 2009-03-13 2016-09-28 The Trustees Of The University Of Pennsylvania Ox40/trail fusion proteins
CA2769822C (en) * 2009-08-13 2019-02-19 The Johns Hopkins University Methods of modulating immune function
US8993524B2 (en) 2010-03-05 2015-03-31 The Johns Hopkins University Compositions and methods for targeted immunomodulatory antibodies and fusion proteins
US20180237525A9 (en) 2010-03-26 2018-08-23 Randolph J. Noelle VISTA Agonist and Methods of Use
MX342017B (es) 2010-03-26 2016-09-09 Dartmouth College Proteina mediadora de celula t regulatoria vista, agentes de enlace de vista y uso de los mismos.
EP2621514B1 (en) 2010-09-28 2016-09-21 KAHR Medical (2005) Ltd Compositions and methods for treatment of hematological malignancies
WO2012062218A1 (en) 2010-11-11 2012-05-18 The University Of Hong Kong Soluble pd-1 variants, fusion constructs, and uses thereof
US10179164B2 (en) 2011-05-25 2019-01-15 Cel-Sci Corporation Method for inducing an immune response for treatment of cancer and autoimmune diseases or conditions
CN114835823A (zh) 2011-07-29 2022-08-02 宾夕法尼亚大学董事会 转换共刺激受体
EP2804623B1 (en) * 2012-01-12 2019-08-07 Bioverativ Therapeutics Inc. Chimeric factor viii polypeptides and uses thereof
AU2012369202A1 (en) 2012-02-06 2014-09-25 Providence Health & Services - Oregon Cancer treatment and monitoring methods using OX40 agonists
EP3333183B1 (en) 2012-04-30 2023-02-22 Biocon Limited Targeted/immunomodulatory fusion proteins and methods for making same
EP2850106B1 (en) 2012-05-18 2022-03-23 Aptevo Research and Development LLC Bispecific scfv immunofusion (bif) binding to cd123 and cd3
WO2013184912A2 (en) 2012-06-06 2013-12-12 Oncomed Pharmaceuticals, Inc. Binding agents that modulate the hippo pathway and uses thereof
JP6285923B2 (ja) 2012-06-22 2018-02-28 トラスティーズ・オブ・ダートマス・カレッジ 新規ＶＩＳＴＡ−Ｉｇコンストラクト及び自己免疫、アレルギー性及び炎症性障害の処置のためのＶＩＳＴＡ−Ｉｇの使用
CN103566377A (zh) 2012-07-18 2014-02-12 上海博笛生物科技有限公司 癌症的靶向免疫治疗
EP3552628A1 (en) 2012-09-07 2019-10-16 The Trustees Of Dartmouth College Vista modulators for diagnosis and treatment of cancer
LT2931752T (lt) 2012-12-17 2019-12-10 Trillium Therapeutics Inc Ligos cd47+ ląstelių gydymas su sirp alfa-fc junginiais
CN105026424A (zh) 2013-01-01 2015-11-04 卡尔医疗有限公司 稳定形式的信号转化蛋白融合蛋白、及其使用和制备的方法
WO2014116846A2 (en) 2013-01-23 2014-07-31 Abbvie, Inc. Methods and compositions for modulating an immune response
WO2015116178A1 (en) 2014-01-31 2015-08-06 Thomas Jefferson University Fusion proteins for modulating regulatory and effector t cells
WO2014121093A1 (en) 2013-01-31 2014-08-07 Thomas Jefferson University Fusion proteins that facilitate cancer cell destruction
EP2951209A4 (en) 2013-01-31 2016-06-22 Univ Jefferson CD40 OX40 AGONIST FUSION PROTEIN AND USES THEREOF
EP2950814A4 (en) 2013-01-31 2016-06-08 Univ Jefferson FUSION PROTEINS BASED ON PD-L1 AND PD-L2 AND USES THEREOF
EP2951199A4 (en) 2013-01-31 2016-07-20 Univ Jefferson Fusion proteins for the modulation of regulatory and effector T cells
EP3811954A1 (en) 2013-02-26 2021-04-28 Memorial Sloan Kettering Cancer Center Compositions and methods for immunotherapy
CA3081073C (en) 2013-03-12 2023-09-12 Biocon Ltd. Fusion immunomodulatory proteins and methods for making same
US10196435B2 (en) 2013-11-18 2019-02-05 University Of Southern California OX40L fusion protein for the immunotherapy of tumors of veterinary animals
JP2017501167A (ja) 2013-12-17 2017-01-12 ジェネンテック， インコーポレイテッド Ｏｘ４０結合アゴニスト及びｐｄ−１軸結合アンタゴニストを含む併用療法
CA2936611A1 (en) 2014-01-13 2015-07-16 Pieris Pharmaceuticals Gmbh Multi-specific polypeptide useful for localized tumor immunomodulation
US20170015758A1 (en) 2014-01-21 2017-01-19 Medimmune, Llc Compositions And Methods For Modulating And Redirecting Immune Responses
EP3148573A4 (en) 2014-05-29 2017-11-15 Medimmune, LLC Ox40l fusion proteins and uses thereof
WO2015200828A1 (en) 2014-06-27 2015-12-30 H. Lee Moffit Cancer Center And Research Institute, Inc. Conjugates for immunotherapy
EP3180020B1 (en) 2014-08-11 2018-12-26 Delinia, Inc. Modified il-2 variants that selectively activate regulatory t cells for the treatment of autoimmune diseases
PT3180363T (pt) 2014-08-15 2019-11-05 Merck Patent Gmbh Proteínas de fusão de sirp-alfa e imunoglobulina
SG10201807625PA (en) 2014-11-17 2018-10-30 Genentech Inc Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists
MX2017007136A (es) * 2014-12-05 2017-12-04 Immunext Inc Identificacion de vsig8 como el receptor vista putativo y su uso para producir moduladores vista/vsig8.
MA41460A (fr) * 2015-02-03 2017-12-12 Oncomed Pharm Inc Agents de liaison à la tnfrsf et leurs utilisations
ES2845727T3 (es) * 2015-02-06 2021-07-27 Heat Biologics Inc Vector que coexpresa una vacuna y moléculas coestimuladoras
US11649285B2 (en) 2016-08-03 2023-05-16 Bio-Techne Corporation Identification of VSIG3/VISTA as a novel immune checkpoint and use thereof for immunotherapy

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017059168A1 (en) * 2015-10-01 2017-04-06 Heat Biologics, Inc. Compositions and methods for adjoining type i and type ii extracellular domains as heterologous chimeric proteins

Also Published As

Publication number Publication date
EP4249503A3 (en) 2023-12-20
JP2023071979A (ja) 2023-05-23
AU2018224852A1 (en) 2019-07-11
JP7244428B2 (ja) 2023-03-22
CN110290798A (zh) 2019-09-27
US11192933B2 (en) 2021-12-07
US11192934B2 (en) 2021-12-07
EP3585410A1 (en) 2020-01-01
US11834488B2 (en) 2023-12-05
US20190367581A1 (en) 2019-12-05
US20220119481A1 (en) 2022-04-21
US20240067698A1 (en) 2024-02-29
EP3585410B9 (en) 2023-10-04
CA3054130A1 (en) 2018-08-30
EP4249503A2 (en) 2023-09-27
WO2018157163A1 (en) 2018-08-30
EP3585410B1 (en) 2023-06-07
JP2020508066A (ja) 2020-03-19
US20200071378A1 (en) 2020-03-05
IL268170A (en) 2019-09-26
EP3585410A4 (en) 2020-12-16
JP2025065443A (ja) 2025-04-17
CN110290798B (zh) 2024-04-05
CN118184797A (zh) 2024-06-14

Similar Documents

Publication Publication Date Title
US20220227831A1 (en) Tigit- and light-based chimeric proteins
US20220144909A1 (en) Csf1r-based chimeric proteins
US11834488B2 (en) VSIG8-based chimeric proteins
US20230048633A1 (en) Tgfbr2-based chimeric proteins
HK40101388A (en) Vsig8-based chimeric proteins
RU2792239C2 (ru) Химерные белки на основе csf1r
HK40019689B (en) Vsig8-based chimeric proteins
HK40019689A (en) Vsig8-based chimeric proteins

Legal Events

Date Code Title Description
MK25 Application lapsed reg. 22.2i(2) - failure to pay acceptance fee