DOCSLIB.ORG

A Preclinical Evaluation of the Discriminative And

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Preclinical Evaluation of the Discriminative And NP5101_proof ■ 12 June 2013 ■ 1/11 Neuropharmacology xxx (2013) 1e11 Contents lists available at SciVerse ScienceDirect Neuropharmacology journal homepage: www.elsevier.com/locate/neuropharm 1 56 2 A preclinical evaluation of the discriminative and reinforcing 57 3 58 4 properties of lisdexamfetamine in comparison to D-amfetamine, 59 5 fi 60 6 methylphenidate and moda nil 61 7 62 a,* a a a b 8 Q5 David J. Heal , Niki W. Buckley , Jane Gosden , Nigel Slater , Charles P. France , 63 9 David Hackett c 64 10 65 a 11 RenaSci Ltd, BioCity Nottingham, Pennyfoot Street, Nottingham NG1 1GF, UK 66 b University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA 12 c Shire Pharmaceutical Development Ltd, Hampshire International Business Park, Chineham, Basingstoke RG24 8EP, Hampshire, UK 67 13 68 14 69 15 article info abstract 70 16 71 17 Article history: Lisdexamfetamine dimesylate, which consists of L-lysine covalently bound to D-amfetamine, is the first 72 18 Received 12 December 2012 prodrug for treating ADHD. Its metabolic conversion to yield D-amfetamine by rate-limited, enzymatic 73 19 Received in revised form hydrolysis is unusual because it is performed by peptidases associated with red blood cells. Other 74 3 April 2013 20 stimulants shown to be effective in managing ADHD include D-amfetamine, methylphenidate and 75 Accepted 13 May 2013 21 modafinil. All have the potential for misuse or recreational abuse. The discriminative and reinforcing 76 effects of these compounds were determined in rats using a 2-choice, D-amfetamine (0.5 mg/kg, i.p.)- 77 22 Keywords: cued drug-discrimination test, and by substitution for intravenous cocaine in self-administration. Lis- 23 Lisdexamfetamine 78 dexamfetamine (0.5e1.5 mg/kg [D-amfetamine base], p.o.) generalised to saline when tested 15 min 24 D-Amfetamine 79 post-dosing, but dose-dependently generalised to D-amfetamine at 60 min. At 120 min, its D-amfet- 25 Methylphenidate 80 fi amine-like effects were substantially diminished. At 15 min, methylphenidate (3.0e10 mg/kg, p.o.) and 26 Moda nil 81 Drug discrimination D-amfetamine (0.1e1.5 mg/kg, p.o.) dose-dependently generalised to the intraperitoneal D-amfetamine 27 Discriminative effects cue. Switching to the intraperitoneal route reduced the interval required for lisdexamfetamine to be 82 28 Self-administration recognised as D-amfetamine-like, but did not alter its potency. Switching to intraperitoneal injection 83 Reinforcer 29 increased the potency of methylphenidate and D-amfetamine by 3.4Â and 2.2Â, respectively. Modafinil 84 30 (50e200 mg/kg, i.p.) generalised partially, but not fully, to D-amfetamine. Methylphenidate (0.1, 0.3, 85 31 1.0 mg/kg/injection, i.v.) maintained robust self-administration at the 2 highest doses. Neither lisdex- 86 32 amfetamine (0.05, 0.15 or 0.5 mg/kg/injection [D-amfetamine base], i.v.) nor modafinil (0.166, 0.498 or 87 33 1.66 mg/kg/injection, i.v.) served as reinforcers. The results reveal important differences between the 88 fi 34 pro les of these stimulants. Lisdexamfetamine did not serve as a positive reinforcer in cocaine-trained 89 fl 35 rats, and although it generalised fully to D-amfetamine, its discriminative effects were markedly in u- 90 enced by its unusual pharmacokinetics. 36 91 Ó 2013 Published by Elsevier Ltd. 37 92 38 93 39 94 40 95 41 1. Introduction 96 42 97 43 Attention deficit hyperactivity disorder (ADHD) is a childhood- 98 44 onset, psychiatric, cognitive and behavioural disorder that is 99 45 widely treated with the catecholaminergic stimulants, D-amfet- 100 amine and methylphenidate. These drugs are effective in managing 46 Abbreviations: ADHD, attention deficit hyperactivity disorder; AMF, amfet- 101 47 amine; C-II, Schedule 2 Controlled Drug; C-IV, Schedule 4 Controlled Drug; CD, the symptoms of approximately three quarters of children and 102 48 controlled drug; Cmax, maximum plasma drug concentration; DAT, dopamine re- adults (Spencer et al., 1996; Elia et al., 1999; Heal and Pierce, 2006; 103 49 uptake transporter; FR, fixed ratio; IACUC, Institutional Animal Care and Use Heal et al., 2009, 2012a; Buitelaar and Medori, 2010). Although 104 Committee; i.p., intraperitoneal; IR, immediate release; i.v., intravenous; PET, 50 these stimulants are undoubtedly effective, they have two major 105 positron emission tomography; PFC, prefrontal cortex; p.o., per os (oral); SAL, saline; 51 shortcomings. First, D-amfetamine and methylphenidate have 106 SR, sustained release; tmax, time to reach maximum plasma drug concentration. 52 * Corresponding author. Tel.: þ44 (0) 115 9124260; fax: þ44 (0) 115 9124263. relatively short half-lives that require the drugs to be administered 107 53 E-mail addresses: [email protected], [email protected] (D.J. Heal). several times a day, which makes them particularly unsuitable for 108 54 109 e Ó 55 0028-3908/$ see front matter 2013 Published by Elsevier Ltd. 110 http://dx.doi.org/10.1016/j.neuropharm.2013.05.021 Please cite this article in press as: Heal, D.J., et al., A preclinical evaluation of the discriminative and reinforcing properties of lisdexamfetamine in comparison to D-amfetamine, methylphenidate and modafinil, Neuropharmacology (2013), http://dx.doi.org/10.1016/ j.neuropharm.2013.05.021 NP5101_proof ■ 12 June 2013 ■ 2/11 2 D.J. Heal et al. / Neuropharmacology xxx (2013) 1e11 111 use by individuals whose disorder is characterised by inattention, cages with sawdust covered floors in a temperature and humidity controlled room. 176 112 distractibility and impulsivity. Second, when these catecholamin- Animals were maintained on 12 h:12 h lightedark cycle with free access to food and 177 tap water at all times when in their home cages. Rats were accustomed to these 113 ergic drugs are taken at doses above those recommended in the 178 conditions for 1 week before the start of training. 114 prescribing instructions and often by non-clinical routes, e.g. nasal For the self-administration study, 54 male, Sprague-Dawley rats (277e352 g at 179 115 insufflation (“snorting”) or intravenous injection, they have start of study) were purchased from Charles River UK, and 58 male, Sprague-Dawley 180 116 powerful psychostimulant and euphoriant properties which makes rats (277 ge342 g at start of study) from Harlan, USA. Rats were housed individually 181 117 them liable to diversion and recreational abuse. Both shortcomings in plastic cages containing rodent bedding and environmental enrichment on a 182 12 h:12 h lightedark cycle in a temperature and humidity controlled room. Animals 118 have to some extent been addressed by the development of long- were allowed to acclimatise to these conditions for at least 4 days before the study 183 119 acting formulations and by the use of novel delivery systems, e.g. commenced, during which time they underwent daily weighing and handling. Rats 184 120 osmotically controlled release or transdermal patches, that are also were allowed free access to tap water and standard rodent diet during the accli- 185 121 tamper deterrent (see reviews by Heal and Pierce, 2006; Heal et al., matisation period. After the acclimatisation period, food was restricted to 10 g/day 186 over 5 days, after which daily food intake was restricted to w90% of normal levels 122 2009, 2012a); nonetheless, all formulations of methylphenidate 187 (calculation based on the mean daily food intake during the acclimatisation period). 123 and D-amfetamine are classified as Schedule 2 Controlled Drugs Rats were given sufficient food to maintain age-appropriate growth. Body weights 188 124 (C-II) in the UK, USA and many other countries. were monitored and the amount of food given in home cages was altered when 189 Ò 125 Lisdexamfetamine dimesylate (Vyvanse ) is a relatively recent necessary. This regime was maintained throughout the remainder of the study, 190 except during the recovery period after surgery. 126 entry to the portfolio of ADHD medications. It is a D-amfetamine 191 In both studies, animals were tested in the light part of the lightedark cycle. 127 prodrug, which comprises the naturally occurring amino acid, L- 192 128 lysine, covalently bound to D-amfetamine via an amide linking 2.2. Drug-discrimination training and testing 193 129 group. Lisdexamfetamine is the first prodrug to have been 194 130 approved in the USA and Canada for the management of ADHD in D-Amfetamine-cued drug-discrimination testing in rats was based on the 195 fl 131 children (age 6e12), adolescents (age 13e17) and adults. It is method previously described by Heal et al. (1992). Brie y, female PVG rats were 196 trained to distinguish between D-amfetamine (0.5 mg/kg, i.p.) and saline (1 ml/kg, 197 132 currently undergoing evaluation for the treatment of ADHD in a i.p.) in a 2-choice lever-pressing task in response to a sweetened milk reward made 133 number of European countries. The metabolic route of conversion available on a FR-5 reward schedule (i.e. 5 lever-presses for 1 reward). Rats were 198 134 of lisdexamfetamine is unusual because after absorption into the randomly allocated one lever for D-amfetamine (0.5 mg/kg, i.p.) and the other for 199 135 bloodstream it is metabolised by red blood cells to yield D-amfet- saline. Once a rat had achieved approximately 60% correct lever-presses on most 200 trials, it began the test regime. 136 amine and the natural amino acid, L-lysine, by rate-limited, enzy- 201 On the test regime, rats were injected with drug cue or saline and then placed in 137 matic hydrolysis (Pennick, 2010). The prodrug is pharmacologically the test chamber.
Load more

Recommended publications
  • Directory of Companies A
    65 Directory of Companies A An alphabetical list of pharmaceutical companies, as well as manufacturers and suppliers of products and services for Medicinal Chemistry in Europe 3B PHARMACEUTICALS GMBH Magnusstraße 11 12489 BERLIN DE 3M BELGIUM Canadastraat 11, Haven 1005 2070 ZWIJNDRECHT BE 3V-LSI Rubicondreef 18 3561 JC UTRECHT NL of Companies 4SC AG Am Klopferspitz 19a 82152 MARTINSRIED DE A & D INSTRUMENTS LTD Abingdon Science Park OX14 3YX ABINGDON GB ABBVIE DEUTSCHLAND GMBH & CO. KG Knollstrasse 67061 LUDWIGSHAFEN DE Directory ABCR GMBH Im Schlehert 10 76187 Karlsruhe, GERMANY Contact person: Dr. Ute Kiso Tel: +49 721 95061-0 - [email protected] www.abcr.de Gute Chemie. Welcome to abcr. With abcr, you have access to over 260,000 products from the organic, organometallic and inorganic specialty chemicals area. These can be conveniently ordered via our webshop www.abcr.de > Catalogue & Bulk business from grams to tons > Scale up & Commercial manufacturing from our own facility > Sourcing & Logistic management worldwide > Feasibility studies & Synthesis at the laboratory scale > Custom syntheses & Contract Manufacturing ABSORPTION SYSTEMS 440 Creamery Way Suite 300 PA 19341 EXTON US AC IMMUNE SA EPFL Innovation Park Building B 1015 LAUSANNE FR ACCELA CHEMBIO 9823 Pacific Heights Blvd # F 92121 SAN DIEGO US ACRAF S.P.A. Piazzale della Stazione 40 S. PALOMBA - POMEZIA IT ACROS ORGANICS Janssen Pharmaceuticalaan 3a 2440 GEEL BE ACS Journal of Medicinal Chemistry & ACS Medicinal Chemistry Letters Contact person: Janice E. Silverman, Acquisitions Editor Tel: +1 202-577-5975 [email protected] Journal of Medicinal Chemistry – pubs.acs.org/jmc ACS Medicinal Chemistry Letters – pubs.acs.org/acsmedchemlett In 2017 Journal of Medicinal Chemistry is celebrating 60 years of publishing the field’s best peer-reviewed research.
    [Show full text]
  • Contents Page
    Statement of Development Principles: Regeneration Of Boots Campus, Beeston, Nottingham June 2007 STATEMENT OF DEVELOPMENT PRINCIPLES: REGENERATION OF BOOTS CAMPUS, BEESTON, NOTTINGHAM (June 2007) Contents 1. Introduction................................................................................................2 PURPOSE.............................................................................................................................. 2 POLICY CONTEXT................................................................................................................ 3 2. Development Principles ............................................................................4 THE VISION........................................................................................................................... 4 KEY DEVELOPMENT PRINCIPLES ..................................................................................... 4 3. Key Issues ..................................................................................................7 HIGHWAYS AND ACCESS ................................................................................................... 7 BALANCE OF USES ............................................................................................................. 7 LISTED BUILDINGS .............................................................................................................. 9 ENVIRONMENT.....................................................................................................................9
    [Show full text]
  • Acacia Pharma Group
    This document comprises a prospectus (the “Prospectus”) relating to Acacia Pharma Group plc (the “Company” or “Acacia Pharma”) prepared in accordance with the prospectus regulation rules (the “Prospectus Regulation Rules”) of the UK Financial Conduct Authority (the “FCA”) made pursuant to section 73A of the Financial Services and Markets Act 2000, as amended (“FSMA”). This Prospectus has been approved by the FCA as the competent authority under Regulation (EU) 2017/1129 (the “Prospectus Regulation”) and has been filed with and made available to the public in accordance with Rule 3.2 of the Prospectus Regulation Rules. The FCA only approves this Prospectus as meeting the standards of completeness, comprehensibility and consistency imposed by the Prospectus Regulation. Such approval should not be considered as an endorsement of the Company or of the quality of the Ordinary Shares that are the subject of this Prospectus. Investors should make their own assessment as to the suitability of investing in the Ordinary Shares. In addition, this Prospectus has been drawn up as a simplified prospectus in accordance with Article 14 of the Prospectus Regulation. The Belgian Financial Services and Markets Authority (“Belgian FSMA”) was notified of the passporting of this Prospectus in accordance with Article 25 of the Prospectus Regulation. The Company and the Directors, whose names appear on page 39 of this document, accept responsibility for the information contained in this document. To the best of the knowledge of the Company and the Directors, the information contained in this document is in accordance with the facts and this document makes no omission likely to affect its import.
    [Show full text]
  • A Science and Innovation Audit Report for the Midlands Engine
    A Science and Innovation Audit Report for the Midlands Engine, sponsored by the Department for Business, Energy & Industrial Strategy Volume 1: Main Report 01 November 2016 A Science and Innovation Audit Report for the Midlands Engine, sponsored by the Department for Business, Energy & Industrial Strategy Volume 1: Main Report Contents Midlands Engine SIA – the headlines ....................................................................................1 1. Introduction to the Midlands Engine SIA...........................................................................4 2. SIA ‘hypotheses’ and ‘framework’ ...................................................................................10 3. Regional science and innovation assets and excellence..............................................19 4. Innovation strengths and our growth priorities..............................................................30 5. Market and technology drivers of change.......................................................................53 6. Innovation networks and behaviours ..............................................................................59 7. Next Steps – unlocking our productivity potential.........................................................67 A Science and Innovation Audit Report for the Midlands Engine, sponsored by the Department for Business, Energy & Industrial Strategy Volume 1: Main Report Midlands Engine SIA – the headlines 1. In Autumn 2015 the UK Government announced regional Science and Innovation Audits (SIAs) to catalyse
    [Show full text]
  • BIO-SCIENCE FACILITY, LOWER PARLIAMENT STREET, NOTTINGHAM Nottingham City Council Lease the OPPORTUNITY
    Significant Capital Allowance Investment Opportunity BIO-SCIENCE FACILITY, LOWER PARLIAMENT STREET, NOTTINGHAM Nottingham City Council Lease THE OPPORTUNITY Unique opportunity to acquire a new bio-science incubator facility let on a long lease to a major city council with significant capital allowances providing an attractive post tax return. Prominently located at Lower Parliament Street, Nottingham There are estimated £9,750,000 of available capital allowances to a adjacent to the existing Bio-City buildings within Nottingham’s purchaser which at a higher tax rate of 45% are worth £4,387,500 creative quarter. over a 5 year period. 150 years long-leasehold interest at a peppercorn rent from Nottingham City Council is to provide a loan to the purchaser of Nottingham City Council. £11,011,200 for a 5 years period at a fixed interest rate of 4.50% which equates to £495,484 interest per annum. No amortisation required during this period. Construction commenced in August 2015 on the new Biocity Science building over ground and 4 upper floors providing state of the art laboratory and office accommodation and extending to 52,475 sq ft Purchaser equity requirement of £6,748,800 which after interest NIA. Willmott Dixon is the appointed contractor. charges provides a net annual pre tax yield of 3.18%. To be let to Nottingham City Council for 30 years from completion of this transaction on a full repairing and insuring lease at an initial rent of Post tax annual yields are Year 1 - 7.54%, Year 2 - 6.86%, Year 3 - £714,000 per annum equating to £13.61 per sq ft.
    [Show full text]
  • Economic Strategy Research Bureau
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Nottingham Trent Institutional Repository (IRep) Biotechnology, life sciences and skills in D2N2: A report for Learn Direct and the D2N2 Local Enterprise Partnership Will Rossiter, David J. Smith, Nikolas Pautz, Daniel McDonald-Junor Economic Strategy Research Bureau Nottingham Business School Nottingham Trent University July 2018 2018 Contents Executive Summary............................................................................................................................ 4 1 Introduction ................................................................................................................................ 6 1.1 Approach ................................................................................................................................. 7 2 What are life sciences and the biotech industry? ....................................................................... 9 2.1 Origins of the Biotechnology industry .................................................................................. 10 2.2 Features of the emerging UK biotechnology industry .......................................................... 13 2.3 The Bioincubator boom of the 2000-2008 ............................................................................ 14 3 Restructuring, Open Innovation and Outsourcing in the Pharmaceutical Industry ................. 17 4 The Decline in Laboratory Technician training ........................................................................
    [Show full text]
  • Title: the Rise and Rise of Biotech and Life Sciences in Nottingham Will Rossiter, David Smith, & Daniel Mcdonald-Junor
    Title: The rise and rise of biotech and life sciences in Nottingham Will Rossiter, David Smith, & Daniel McDonald-Junor, Nottingham Business School Notable in this years’ Top 200 list are an increasing number of local companies involved in the applications of biotechnology and life sciences – companies like Fresenius Medical , Source Bioscience Limited, and Robinsons Healthcare. Indeed this phenomenon has come to symbolise Nottingham’s reinvention as a post-industrial economy. Recent research at Nottingham Business School has started to explain how it happened. At the start of the millennium, Nottingham looked to be a city facing serious industrial decline. Former mainstays of the local economy like Raleigh, Players, and Royal Ordnance had ceased large scale manufacturing operations in the City and employment in the sector continued to shrink as the balance of the economy shifted towards the service sector. Move forward a decade or two however, and you’ll find a different story. A new development path has been forged through the application of biotechnology and life sciences. That this should have happened in a former manufacturing city in the North Midlands is remarkable. The most obvious symbol of this is BioCity, where more than 75 bioscience-related companies have been established since 2003. Although modest in scale by the standards of bioscience concentrations in London and the South East, the emergence of bioscience in Nottingham is significant. Not least because this momentum has been sustained over a 15-year timeframe and shows no signs of slowing. Indeed BioCity is now the country’s largest life science themed business incubation facility.
    [Show full text]
  • Report Title
    The Midlands Engine Science and Innovation Audit Volume 2: Supporting Annexes 30 September 2016 Science and Innovation Audit Volume 2: Supporting Annexes Contents Annex A: Organisations responding to the e-consultation ................................................. 1 Annex B: Midlands Engine Innovation Group Vision ........................................................... 2 Annex C: Theme-level data ..................................................................................................... 3 Annex D: Thematic workshop notes .................................................................................... 13 Annex E: Further Sci-Val data .............................................................................................. 32 Annex F: Long list of assets ................................................................................................. 46 Annex G: Case examples ...................................................................................................... 68 Annex H: Detailed market priority templates ...................................................................... 78 Annex I: E-consultation responses ...................................................................................... 98 Annex J: Driving competitiveness through our Enabling Competencies ...................... 109 Annex K: Innovation networks and behaviours ............................................................... 112 Science and Innovation Audit Volume 2: Supporting Annexes Annex A: Organisations responding
    [Show full text]
  • Life Science CLUSTERS the Magazine for Pharmaceutical and Bio-Clusters Spring 2007 • Volume 1 • Number 1
    Life Science CLUSTERS The magazine for pharmaceutical and bio-clusters Spring 2007 • Volume 1 • Number 1 Cluster Proles on: San Jose, Basel, London, Scotland, Ireland Biotech law companies Super League Biotechnology Clusters – supporting the UK as Europe’s No1 in Bioscience UK Trade & Investment In 1999 the DTI report, “Biotechnology providers with biotechnology personnel London Development Agency has strongly Clusters”, defined ten critical factors in the at focused events, providing a source of committed to the sector by funding the generation of a successful biotechnology local information and mentoring and London Biotechnology Innovation Centre bio cluster in the UK: strong science base; promoting the cluster externally to encourage incubator, which provides space and support entrepreneurial culture; growing company commercial partnering. Increasingly, these for 20 early-stage bioscience enterprises and base; ability to attract key staff; availability networks are associated with bioincubators, has close ties with the London Biotechnology of finance; premises and infrastructure; such as Diagnox in Oxford, BioCity Network (LBN). At over 2,000 members, business support services and large companies Nottingham and CELS in the North East. LBN is one of the largest of its kind in Europe, in related industries; skilled workforce; providing the internationally renowned effective networks and a supportive policy The UK Mega-Cluster BioWednesday event series and the annual environment. Genesis Conference. Cambridge In this article, we will present
    [Show full text]
  • Delegate List
    DELEGATE LIST Firstname Surname Job Title Company Aisha Ajij Project Support and Industry Liason Officer East Midlands Academic Health Science Network Ayo Akinduko Fellow University of Leicester Lucy Alexander Head of Research and Enterprise Partnerships Life Science University of Leicester Danielle Allen Marketing Executive TBAT Innovation Peter Anderton TEDx Speaker & Director Internal Alignment Alex Archibald Project Manager Midlands Health Innovation Colin Baker Patent Attorney Potter Clarkson LLP Max Bardwell Strategic Partnership Manager Life Sciences Nottingham Trent University Chris Barker CEO Spirit Healthcare Neil Barnes Project Leader Innovation Medilink East Midlands Yvonne Barnett Board Member Medilink East Midlands Timothy Bates Chief Scientific Officer Drugs With A Difference Limited Pamela Bellis Director WPS (Worldwide Product Sourcing) Ltd Malcolm Bennett Professor of Zoonotic and Emerging Diseases University of Nottingham Jennifer Benson Managing Director WPS (Worldwide Product Sourcing) Ltd Simon Bernard Operations Director Ariane Medical Systems Philippa Bevan Director Accelerate Associates Ian Bolland Web Content Editor Rapid News Group Page 1 of 8 Sarah Bolton Business Manager CHEATA - Centre for Healthcare Equipment and Technology Adoption Chas Bountra Pro-Vice Chancellor for Innovation University of Oxford Katherine Bourne Director Accelerate Associates Julian Bowrey Regional Manager Innovate UK Laura Boyd Deputy Director NHS Innovation Accelerator Raymond Bratty Pain Development Director Orion Pharma Philip Breedon
    [Show full text]
  • Trade Marks Journal No: 1792, 10/04/2017 P`Kasana : Baart Sarkar Vyaapar Icanh Rijast/I Esa.Ema.Raod Emta^P Ihla Ko Pasa Paos
    Trade Marks Journal No: 1792, 10/04/2017 Reg. No. TECH/47-714/MBI/2000 Registered as News Paper p`kaSana : Baart sarkar vyaapar icanh rijasT/I esa.ema.raoD eMTa^p ihla ko pasa paosT Aa^ifsa ko pasa vaDalaa mauMba[- 400037 durBaaYa : 022 24101144 ,24101177 ,24148251 ,24112211. fO@sa : 022 24140808 Published by: The Government of India, Office of The Trade Marks Registry, Baudhik Sampada Bhavan (I.P. Bhavan) Near Antop Hill, Head Post Office, S.M. Road, Mumbai-400037. Tel:022-24140808 1 Trade Marks Journal No: 1792, 10/04/2017 Anauk/maiNaka INDEX AiQakairk saucanaaeM Official Notes vyaapar icanh rijasT/IkrNa kayaa-laya ka AiQakar xao~ Jurisdiction of Offices of the Trade Marks Registry sauiBannata ko baaro maoM rijaYT/ar kao p`arMiBak salaah AaoOr Kaoja ko ilayao inavaodna Preliminary advice by Registrar as to distinctiveness and request for search saMbaw icanh Associated Marks ivaraoQa Opposition ivaiQak p`maaNa p`~ iT.ema.46 pr AnauraoQa Legal Certificate/ Request on Form TM-46 k^apIra[T p`maaNa p`~ Copyright Certificate t%kala kaya- Operation Tatkal saava-jainak saucanaaeM Public Notices svaIkRit ko puva- iva&aipt Aavaodna Applications advertised before acceptance-class-wise: 2 Trade Marks Journal No: 1792, 10/04/2017 vaga- / Class - 1 11-121 vaga- / Class - 2 122-159 vaga- / Class - 3 160-334 vaga- / Class - 4 335-361 vaga- / Class - 5 362-980 vaga- / Class - 6 981-1037 vaga- / Class - 7 1038-1131 vaga- / Class - 8 1132-1154 vaga- / Class - 9 1155-1335 vaga- / Class - 10 1336-1378 vaga- / Class - 11 1379-1481 vaga- / Class - 12 1482-1537
    [Show full text]
  • Business Acceleration Manager- Medicity Scotland Overview
    Business Acceleration Manager- MediCity Scotland Location: BioCity Scotland campus, Newhouse, Scotland Full time, permanent. Salary: competitive, plus participation in BioCity Group employee share option scheme Overview BioCity Group is seeking a dynamic, entrepreneurial person to lead its company creation and accelerator programme activities at its new medical technology incubator near Glasgow. The successful candidate will join the wider BioCity Group team and benefit from the opportunities and rewards arising from being part of this fast growing business. Background The BioCity Group is dedicated to channelling entrepreneurship to meet the world’s healthcare needs. We believe much of the innovation needed to tackle the challenges of an expanding and ageing population along with rising costs of care will come from new entrepreneurial companies. So at each of our locations we provide the best environment for these growing and ambitious life science businesses to maximise their chances of success. BioCity was first established in Nottingham in 2003. It was one of the first incubators offering laboratories alongside business support to early stage companies in the life science sector. Since then, the BioCity Group has grown to include locations in Cheshire, Scotland and Nottingham and has launched MediCity in Nottingham and now Scotland. Whilst in the early years the facilities at BioCity led to a focus on companies in drug discovery and delivery, therapeutics and medical devices, the launch of MediCity widens the type of companies to also include, alongside med tech, the areas of digital health, well-being and beauty. The first MediCity facility, MedCity Nottingham, opened in early 2014 and already has more than 30 companies within its community.
    [Show full text]