DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 7,271,156 B2 Krieg Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 7,271,156 B2 Krieg Et Al US007 271156 B2 (12) United States Patent (10) Patent No.: US 7,271,156 B2 Krieg et al. (45) Date of Patent: Sep. 18, 2007 (54) IMMUNOSTIMULATORY NUCLEIC ACIDS 6,544,518 B1 * 4/2003 Friede et al. ............ 424,184.1 6,653.292 B1* 11/2003 Krieg et al. .................. 514,44 (75) Inventors: Arthur M. Krieg, Wellesley, MA (US); 6,727,230 B1 4/2004 Hutcherson et al. Jörg Vollmer, Düsseldorf (DE): 6.821,957 B2 11/2004 Krieg et al. 6,943,240 B2 9, 2005 Bauer et al. Christian Schetter, Hilden (DE) 6,949,520 B1 9, 2005 Hartmann et al. Assignees: University of Iowa Research 2001/0044416 A1 11/2001 McCluskie et al. (73) 2002/009 1097 A1 7/2002 Bratzler et al. Foundation, Iowa City, IA (US); Coley 2002/0156033 A1 10, 2002 Bratzler et al. Pharmaceutical GmbH, Dusseldorf 2002/0164341 A1 11/2002 Davis et al. (DE) 2002fO165178 A1 11/2002 Schetter et al. Notice: 2002fO1981.65 A1 12/2002 Bratzler et al. (*) Subject to any disclaimer, the term of this 2003/0026782 A1 2/2003 Krieg et al. patent is extended or adjusted under 35 2003/0026801 A1 2/2003 Weiner et al. U.S.C. 154(b) by 0 days. 2003/0050261 A1 3/2003 Krieg et al. 2003/0050268 A1* 3/2003 Krieg et al. .................. 514,44 (21) Appl. No.: 10/314,578 2003/0055014 A1 3/2003 Bratzler 2003/009 1599 A1 5/2003 Davis et al. (22) Filed: Dec. 9, 2002 2003/010.0527 A1 5/2003 Krieg et al. 2003. O139364 A1 7/2003 Krieg et al. (65) Prior Publication Data 2003. O14831.6 A1 8/2003 Lipford et al. US 2003/0212026 A1 Nov. 13, 2003 2003/0148976 A1* 8/2003 Krieg et al. .................. 514,44 2003. O166001 A1 9/2003 Lipford Related U.S. Application Data 2003/0181406 A1* 9, 2003 Schetter et al. ............... 514,44 2003/019 1079 A1 10/2003 Krieg et al. (63) Continuation of application No. 09/669,187, filed on 2003/0212026 A1* 11/2003 Krieg et al. .................. 514,44 Sep. 25, 2000. 2003/022401.0 A1 12/2003 Davis et al. (60) Provisional application No. 60/227,436, filed on Aug. 23, 2000, provisional application No. 60/156,135, (Continued) filed on Sep. 27, 1999, provisional application No. 60/156,113, filed on Sep. 25, 1999. FOREIGN PATENT DOCUMENTS WO WO96.O2555 A1 2, 1996 (51) Int. C. WO WO98.37919 A1 * 9, 1998 (2006.01) WO WO98,401.00 9, 1998 (2006.01) WO WO99,56755 A1 11, 1999 (2006.01) WO WO99,58118 11, 1999 (2006.01) A 6LX 9/52 (2006.01) (Continued) AOIN 25/08 (2006.01) AOIN 43/04 (2006.01) OTHER PUBLICATIONS (52) U.S. Cl. ...................... 514/44; 536/23.1536/25.3: Krieg et al. Immunopharmacology, 2000, 48:303-305.* 536/25.6; 424/408; 424/409: 424/422; 424/430; Tighe et al. J. Allergy Clin. Immunol. 2000, 106:124-134.* 424/434; 424/450; 424/457; 424/468; 424/490 McCluskie et al. Vaccine, 2001, 19:2657-2660.* (58) Field of Classification Search .................. 514/44; Jones et al. Vaccine, 1999, 17:3065-3071.* 536/23.1, 23.6, 23.4, 23.5, 23.51, 23.52, 536/24.3, 25.3, 25.6; 424/408,409, 422, (Continued) 424/430, 434, 450, 457, 468, 490 Primary Examiner Nita Minnifield See application file for complete search history. (74) Attorney, Agent, or Firm Wolf Greenfield & Sacks, (56) References Cited P.C. U.S. PATENT DOCUMENTS (57) ABSTRACT 5,663,153 9, 1997 Hutcherson et al. 5,723,335 3, 1998 Hutcherson et al. The invention relates to immunostimulatory nucleic acid 6,194,388 2, 2001 Krieg et al. compositions and methods of using the compositions. The 6,207,646 3, 2001 Krieg et al. T-rich nucleic acids contain poly T sequences and/or have 6,214,806 4, 2001 Krieg et al. .................. 514,44 greater than 25% T nucleotide residues. The TG nucleic 6,218,371 4, 2001 Krieg et al. .................. 514,44 acids have TG dinucleotides. The C-rich nucleic acids have 6,221,882 4, 2001 Macfarlane at least one poly-C region and/ore greater than 50% c 6,239,116 5, 2001 Krieg et al. .................. 514,44 nucleotides. These immunostimulatory nucleic acids func 6,339,068 1, 2002 Krieg et al. .................. 514,44 tion in a similar manner to nucleic acids containing CpG 6,399,630 6, 2002 Macfarlane 6,406,705 6, 2002 Davis et al. ............. 424,278.1 motifs. The invention also encompasses preferred CpG 6,429,199 8, 2002 Krieg et al. .................. 514,44 nucleic acids. 6.479,504 11, 2002 Macfarlane et al. 6,521,637 2, 2003 Macfarlane 33 Claims, 12 Drawing Sheets US 7,271,156 B2 Page 2 U.S. PATENT DOCUMENTS 2007/0037767 A1 2/2007 Bratzler et al. ............... 514,44 2003/0232074 12, 2003 Lipford et al. FOREIGN PATENT DOCUMENTS 2003/0232856 12, 2003 Macfarlane 2004/OOO9949 1, 2004 Krieg WO WO99, 61056 12/1999 2004.?003.0118 2, 2004 Wagner et al. WO WOOOO6588 A1 2, 2000 2004.0053880 3, 2004 Krieg ............ - - - - - - - - - - - 514,44 WO WOOO.75304 A1 12/2000 2004, OO67902 4, 2004 Bratzler et al. - - - - - - - - - - - - - - - 514,44 WO WO O1/22972 A2 * 4, 2001 2004, OO67905 4, 2004 Krieg WO WO O1/62909 A1 8, 2001 2004/OO87534 5, 2004 Krieg et al. WO WO O2/O69369 A2 * 9, 2002 2004/OO87538 5, 2004 Krieg et al. WO WO O3,O15711 A2 * 2/2003 2004/00924.72 5, 2004 Krieg .......................... 514,44 WO WO 2004/OO7743 A2 1, 2004 2004/0106568 6, 2004 Krieg et al. ... 514/44 WO WO 2004/026888 A2 4/2004 2004/O131628 T/2004 Bratzler et al. 424,184.1 WO WO 2004/094671 A2 11/2004 2004/O132685 T/2004 Krieg et al. .................. 514,44 2004/0142469 T/2004 Krieg et al. OTHER PUBLICATIONS 2004/O143112 T/2004 Krieg et al. 2004/O147468 T/2004 Krieg et al. Askenase, J. Allergy Clin. Immunol., 2000, 106:37-40.* 2004/O152649 8, 2004 Krieg .......................... 514,44 Vollmer et al. Antisense and Nucleic Acid Drug Development, 2002, 2004/O152656 8, 2004 Krieg et al. 12:165-175.* 2004/O152657 8, 2004 Krieg et al. Weiner, J. Leukocyte Biology, 200, 68:455-463.* 2004O162258 8, 2004 Krieg et al. Agrawal et al. TRENDS in Molecular Medicine, 2002. 8/3:114 2004O162262 8, 2004 Krieg et al. 121.* 2004/O167089 8, 2004 Krieg et al. Gelfand, J. Allergy Clin. Immunol., 2004, 114:S135-S138.* 2004/0171150 9, 2004 Krieg et al. Saito et al. Immunology, 2001, 104:226-234.* 2004/0171571 9, 2004 Krieg et al. - - - - - - - - - - - - - - - - - - 514,44 2004/O181045 9, 2004 Krieg et al. Taube et al. Int. Arch. Allergy Immunol., 2004, 135:173-186.* 2004/O198680 10, 2004 Krieg .......................... 514,44 Asakura et al. International Archives of Allergy and Immunology, 2004/O198688 10, 2004 Krieg et al. 1998, 116:49-52.* 2004/02298.35 11, 2004 Krieg et al. Takeda et al., J. Exp. Med., Aug. 4, 1997, 186/3:449-454.* 2004/0234512 11, 2004 Wagner et al. Kataoka, et al., “Antitumor activity of synthetic oligonucleotides 2004/O235770 11, 2004 Davis et al. .................. 514,44 with sequences from cDNA encoding proteins of Mycobacterium 2004/O235774 11, 2004 Bratzler et al. ............... 514,44 bovis BCG”, Jpn. J. Cancer Res., 83:244-247 (1992). 2004/0235777 11/2004 Wagner et al. Krieg, et al., “Editorial:Phosphorothioate oligodeoxynucleotides: 2004/O235778 11, 2004 Wagner et al. antisense or anti-protein’?”. Anitsense Res. Devlp., 5:241 (1995). 2004/0266719 12, 2004 McCluskie et al. Krieg, A.M., "Leukocyte stimulation by oligodeoxynucleotides'. 2005, 0004061 1/2005 Krieg et al. Applied Antisense Oligonucleotide Technology, 24:431-448 (1998). 2005, 0004062 1/2005 Krieg et al. Sun, et al., “Mitogenicity of DNA from different organisms for 2005/OOO9774 1/2005 Krieg et al. murine B cells”. J. Immunol. 159:3119-3125 (1997(. 2005/OO32734 2, 2005 Davis et al. Krieg, et al., “Brief Communication: Oligodeoxynucleotide modi 2005/OO32736 2, 2005 Krieg et al. fications determine the magnitude of B cell stimulation by CpG 2005/OO37403 2, 2005 Krieg et al. motifs'. Antisense Nucleic Acid. Drug Developmen, 6:133-139 2005, 0037985 2, 2005 Krieg et al. (1996). 2005.0043529 2, 2005 Davis et al. Messina, et al., “Stimulation of in vitro murine lymphocyte prolif 2005.00492.15 3, 2005 Krieg et al. eration by bacterial DNA”, J. of Immunol., 147(6): 1759-1764 2005.0049216 3, 2005 Krieg et al. (1991). 2005.00546O1 3, 2005 Wagner et al. McIntyre, et al., “A sense phosphorothioate oligonucleotide directed 2005.00546O2 3, 2005 Krieg et al. to the intiation codon of transcription factor NF-kB p65 causes 2005/0059619 3, 2005 Krieg et al. sequence-specific immune stimulation'. Antisense Res. and 2005/00596.25 3, 2005 Krieg et al. Devlop., 3:309-322 (1993). 2005/0070491 3, 2005 Krieg et al. Hartmann, et al., “Mechanism and function of a newly identified 2005.00753O2 4, 2005 Hutcherson et al. CpG DNA motif in human primary b cells'. J. of Immunol. 2005. O080034 4, 2005 Standring et al. ............. 514.46 164:944-952 (2000). 2005, 0100983 5/2005 Bauer et al. Yi, et al., “CpG DNA rescues B cells from apoptosis by activating 2005/0101554 5/2005 Krieg et al. NFKB and preventing mitochondrial membrane potential disruption 2005/0101557 5/2005 Krieg et al. via a chloroquine-sensitive pathway. International Immunol. 2005/O119273 6, 2005 Lipford et al. 11(2):2015-2024 (1999). 2005/O123523 6, 2005 Krieg et al.
Load more

Recommended publications
  • Biotechnology and the Economics of Discovery in the Pharmaceutical Industry
    BIOTECHNOLOGY AND THE ECONOMICS OF DISCOVERY IN THE PHARMACEUTICAL INDUSTRY HELEN SIMPSON Office of Health Economics 12 Whitehall London SWlA 2DY ©October 1998. Office of Health Economics. Price £7.50 ISBN 1 899040 60 9 Printed by BSC Print Ltd, London. About the Author Helen Simpson is currently a researc~ economist at the Institute for Fiscal Studies and was formerly an economist at the Department of Trade and Industry. However, the opinions expressed here are her own and do not necessarily reflect the views of the IFS or of DTI officials or ministers. Acknowledgements This paper has been developed from my MPhil Economics thesis Scientist Entrepreneurs and the Finance of Biotech Companies. I would like to thank Margaret Meyer, Paul David and Gervas Huxley for their valuable suggestions. I am particularly grateful to Hannah Kettler and Jon Sussex for their advice and editorial inputs to the paper. My thanks also go to Adrian Towse and members of the OHE Editorial Board for their comments, and to the following individuals who gave me their insights into the pharmaceutical industry: Dr Trevor Jones, Director General, ABPI; Dr Janet Dewdney, Chairman, Adprotech; Dr Clive Halliday, Head of Global External Scientific Affairs, Glaxo Wellcome; Mr Alan Galloway, Head of Research Administration, Dr Nick Scott-Ram, Director of Corporate Affairs, and Dr Philip Huxley, all of British Biotech; Christine Soden, Finance Director, Chiroscience; Ian Smith, Lehman Brothers Pharmaceutical Research; and Paul Murray, 31. The Office of Health Economics Terms of Reference The Office of Health Economics (OHE) was founded in 1962. Its terms of reference are to: • commission and undertake research on the economics of health and health care; • collect and analyse health and health care data from the UK and other countries; • disseminate the results of this work and stimulate discussion of them and their policy implications.
    [Show full text]
  • Programme 10.00 Registration 10.20 Welcome from the Host
    Leadership Seminar: Respiratory and Inflammatory Diseases 22 September 2016 Penningtons Manches, 125 Wood Street, London EC2V 7AW Sponsored by Hosted by Programme 10.00 Registration 10.20 Welcome from the Host 10.30 Introduction Adrian Dawkes, PharmaVentures 10.45 Keynote presentations and discussion on unmet clinical needs including: 10.45 Symptoms vs Disease Modification Approach Lars Larson, TranScrip 11.05 Prospects for the prevention and treatment of respiratory virus-induced exacerbations in asthma and COPD Garth Rapeport, Pulmocide 11.25 Eosinophil depletion with benralizumab (anti-IL-5R) for the management of Severe Asthma and Chronic Obstructive Pulmonary Disease (COPD) Suzanne Cohen, MedImmune 11.45 Breath Biopsy - Breath Volatile Organic Compounds (VOCs) as Markers for Respiratory Disease Billy Boyle, Owlstone Medical 12.05 Panel discussion and Q&A 12.30 Lunch and networking 14.00 Data Protection and Liability in Respiratory Connected Devices Oliver Bett, Penningtons Manches 14.20 Adaptive Design in Respiratory Clinical Trials – A Sponsor’s Business Case Alethea Wieland, Scope International 14.40 Development of Immunoassays and Point-of-Care Tests for the Measurement of Active Protease Biomarkers of Chronic Respiratory Disease David Ribeiro, ProAxsis 15.00 Aiming for the Lungs - Formulation Strategies for Delivery of Inhaled Biologics Charlotte Yates, Vectura 15.30 Tea, coffee and networking 16.00 Innovative therapeutic options 16.00 The Development of an IL-17BR therapeutic antibody for the treatment of Asthma and IPF David Matthews, MRC Technology 16.20 Mycobacterium Tuberculosis Derived Peptide as a Disease Modifying Therapy for Asthma Nicky Cooper, Peptinnovate 16.40 Closing Remarks and Drinks Reception 18.00 Event closes Speaker Profiles Oliver Bett Associate, Penningtons Manches Oliver is an associate in our IP, IT and commercial team of Penningtons Manches, based in the London office.
    [Show full text]
  • United States Securities and Exchange Commission Form 10-K Shire Pharmaceuticals Group
    UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 10-K (Mark One) ፤ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 1999 អ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Commission file number 0-29630 SHIRE PHARMACEUTICALS GROUP PLC (Exact name of registrant as specified in its charter) England and Wales (State or other jurisdiction (I.R.S. Employer of incorporation or organization) Identification No.) N.A. East Anton, Andover, Hampshire SP10 5RG England (Address of principal executive offices) (Zip Code) 44 1264 333455 (Registrant's telephone number, including area code) Securities registered pursuant to Section 12(b) of the Act: Title of each class Name of exchange on which registered American Depository Shares, each representing Nasdaq National Market 3 Ordinary Shares, 5 pence nominal value per share Securities registered pursuant to Section 12(g) of the Act: None (Title of class) Indicate by check mark whether the Registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the Registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ፤ No អ Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K is not contained herein, and will not be contained, to the best of the Registrant's knowledge, in definitive proxy or information statements incorporated by reference to Part III of this Form 10-K or any amendment to this Form 10-K.
    [Show full text]
  • Appendix One the CELLTECH CASE STUDY
    City Research Online City, University of London Institutional Repository Citation: Mc Namara, P. (2000). Managing the tension between knowledge exploration and exploitation: the case of UK biotechnology. (Unpublished Doctoral thesis, City University London) This is the accepted version of the paper. This version of the publication may differ from the final published version. Permanent repository link: https://openaccess.city.ac.uk/id/eprint/7870/ Link to published version: Copyright: City Research Online aims to make research outputs of City, University of London available to a wider audience. Copyright and Moral Rights remain with the author(s) and/or copyright holders. URLs from City Research Online may be freely distributed and linked to. Reuse: Copies of full items can be used for personal research or study, educational, or not-for-profit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. City Research Online: http://openaccess.city.ac.uk/ [email protected] Managing the Tension Between Knowledge Exploration and Exploitation: The Case of UK Biotechnology By Peter Mc Namara Presented in fulfilment of the requirements of the: Degree of Doctor of Philosophy Strategy and International Business City University Business School Department of Strategy and Marketing March 2000 TABLE OF CONTENTS ACKNOWLEDGEMENTS ..........................................................................................................................
    [Show full text]
  • SHIRE PLC (Exact Name of Registrant As Specified in Its Charter)
    UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K [X] ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2009 [ ] TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Commission file number 0-29630 SHIRE PLC (Exact name of registrant as specified in its charter) Jersey (Channel Islands) 98-0601486 (State or other jurisdiction of incorporation or (I.R.S. Employer Identification No.) organization) 5 Riverwalk, Citywest Business Campus, Dublin +353 1 429 7700 24, Republic of Ireland (Address of principal executive offices and zip code) (Registrant’s telephone number, including area code) Securities registered pursuant to Section 12(b) of the Act: Title of each class Name of exchange on which registered American Depositary Shares, each representing three NASDAQ Global Select Market Ordinary Shares 5 pence par value per share Securities registered pursuant to Section 12(g) of the Act: None (Title of class) 1 Indicate by check mark whether the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act Yes [X] No [ ] Indicate by check mark if the Registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act Yes [ ] No [X] Indicate by check mark whether the Registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the Registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.
    [Show full text]
  • Consolidation Revisited Is the Founder of Managing Resources, a Date Received *In Revised Form) 8Th October, 2001 Consultancy Focused on the Life Science Industries
    Alan Williams Consolidation revisited is the founder of Managing Resources, a Date received *in revised form) 8th October, 2001 consultancy focused on the life science industries. The Alan Williams company undertakes strategic assignments and also assists public and private sector clients with regulatory affairs, investor Abstract In 1998, the author produced two papers that argued that consolidation was relations and human a necessary activity for biotechnology companies to pay greater attention to. Three resources development. years later a further consideration of the subject seems worthwhile. Examples of Alan has also been an investment manager in successful consolidators are reviewed. a venture capital company, and held Keywords: consolidation, mergers, acquisitions marketing and licensing positions in Fisons. Introduction drink, vaccines and animal health but there is now greater focus on the highest In the early/mid-1970s, the pharmaceutical pro®tability sector, human pharmaceuticals. industry consisted of more than 100 At the time of writing, GSK is rumoured to research-based businesses of some be a possible purchaser of Bayer's signi®cant size, although none of them pharmaceutical business, the future of could convincingly claim a global presence. which has been questioned after the Typically, a leading company had a strong withdrawal of cerivastatin. position in its local market "examples Aventis, the eighth largest pharmaceutical included Merck and P®zer in the USA, company by sales in 2000,1 includes the Bayer in Germany, Beecham in the UK, operations of 1970s companies such as Roussel-Uclaf in France and Fujisawa in Rhone-Poulenc, Rorer, Fisons, Hoechst, Japan) and possibly some other Marion, Richardson Merrell, and some neighbouring countries "US companies in smaller companies.
    [Show full text]
  • Overview of Ftc Actions in Pharmaceutical Products and Distribution*
    OVERVIEW OF FTC ACTIONS IN PHARMACEUTICAL PRODUCTS AND DISTRIBUTION* Health Care Division Bureau of Competition Federal Trade Commission Washington D.C. 20580 Markus H. Meier Assistant Director Bradley S. Albert Deputy Assistant Director Kara Monahan Deputy Assistant Director September 2019 * Actions involving health care services and products are contained in a separate document, Overview of FTC Actions in Health Care Services and Products. Information about advisory opinions in the health care and pharmaceutical sectors is contained in the document Topic and Yearly Indices of Health Care Antitrust Advisory Opinions by Commission and by Staff. TABLE OF CONTENTS I. INTRODUCTION ...............................................................................................................1 II. CONDUCT INVOLVING PHARMACEUTICAL PRODUCTS .......................................3 A. Monopolization ........................................................................................................3 B. Agreements Not to Compete ..................................................................................14 III. CONDUCT INVOLVING PHARMACEUTICAL DISTRIBUTION ..............................20 A. Monopolization ......................................................................................................20 B. Agreements on Price and Price-Related Terms .....................................................20 C. Agreements to Obstruct Innovative Forms of Health Care Delivery or Financing................................................................................................................27
    [Show full text]
  • UNITED STATES SECURITIES and EXCHANGE COMMISSION Washington, D.C
    UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K/A (Amendment No. 1) [ X ] Annual Report Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 OR Transition Report Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 for the Transition Period from ________ to ________ For the fiscal year ended Commission File number 0-50626 December 31, 2005 CYCLACEL PHARMACEUTICALS, INC. (Exact name of registrant as specified in its charter) Delaware 91-1707622 (State or other jurisdiction (I.R.S. Employer of incorporation or organization) Identification No.) 150 John F. Kennedy Parkway, Suite 100 Short Hills, NJ 07078 (Address of principal executive office) Registrant’s telephone number, including area code (732) 225-8910 Securities registered pursuant to Section 12(b) of the Act: NONE Securities registered pursuant to Section 12(g) of the Act: Common Stock, par value $0.001 per share 6% Convertible Exchangeable Preferred Stock, par value $0.001 per share (Title of class) Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Exchange Act of 1934. Yes No Indicate by check mark if the registrant is not required to file reports required to be filed by Section 13 or Section 15(d) of the Act. Yes No Indicate by check mark whether the Registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the Registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.
    [Show full text]
  • Case No COMP/M.1846 - GLAXO WELLCOME / SMITHKLINE BEECHAM
    EN Case No COMP/M.1846 - GLAXO WELLCOME / SMITHKLINE BEECHAM Only the English text is available and authentic. REGULATION (EEC) No 4064/89 MERGER PROCEDURE Article 6(1)(b) NON-OPPOSITION Date: 08/05/2000 Also available in the CELEX database Document No 300M1846 Office for Official Publications of the European Communities L-2985 Luxembourg COMMISSION OF THE EUROPEAN COMMUNITIES Brussels, 08.05.2000 In the published version of this decision, some PUBLIC VERSION information has been omitted pursuant to Article 17(2) of Council Regulation (EEC) No 4064/89 concerning non-disclosure of business secrets and MERGER PROCEDURE other confidential information. The omissions are ARTICLE 6(2) DECISION shown thus […]. Where possible the information omitted has been replaced by ranges of figures or a general description. To the notifying parties Dear Sirs, Subject: Case No COMP/M.1846-GLAXO WELLCOME/SMITHKLINE BEECHAM Notification of 20.3.2000 pursuant to Article 4 of Council Regulation No 4064/89 1 1. On 20 March 2000, the Commission received a notification of a proposed concentration pursuant to Article 4 of Council Regulation (EEC) No 4064/89 (“the Merger Regulation”) by which the undertaking Glaxo Wellcome plc (“GW”) and SmithKline Beecham plc (“SB”) notified their intention to enter into a full merger within the meaning of Article 3(1)a of the Merger Regulation. The merger was announced on 17 January 2000. 2. In the course of the proceedings, the parties submitted undertakings designed to eliminate competition concerns identified by the Commission, in accordance with Article 6(2) of the Merger Regulation. In the light of these modifications, the Commission has concluded that the notified operation falls within the scope of the Merger Regulation as amended and does not raise serious doubts as to its compatibility with the common market and with the functioning of the EEA Agreement.
    [Show full text]
  • Orphan Drug Designations and Approvals List As of 12-02-2013 Governs January 1, 2014
    Orphan Drug Designations and Approvals List as of 12‐02‐2013 Governs January 1, 2014 ‐ March 31, 2014 Row Designation Generic Name Trade Name Orphan Designation Contact Company/Sponsor Num Date Treatment of Follicular Lymphoma, Small Lymphocytic Lymphoma, Lymphoplasmacytic Lymphoma, Splenic Marginal Zone Lymphoma, Extranodal Marginal Zone B‐cell Lymphoma of Mucosa‐ Associated Lymphoma Tissue (MALT), and Nodal Marginal Zone Lymphoma (Collectively Indolent B‐cell Non‐Hodgkin's 1 bendamustine hydrochloride Treanda 11/26/2013 Lymphoma) Cephalon, Inc. Treatment of subjects at risk of developing myelosuppression after a radiological or nuclear 2 Filgrastim Neupogen 11/20/2013 incident Amgen, Inc. adeno‐associated viral vector containing the human NADH Treatment of Leber Hereditary 3 Dehydrogenase 4 Gene n/a 11/20/2013 Optic Neuropathy Gen Sight Biologics Treatment of liver transplant recipients with reestablished fibrosis to delay the progression to cirrhosis and 4 emricasan n/a 11/20/2013 end stage liver disease Conatus Pharmaceuticals Inc. Page 1 of 262 Orphan Drug Designations and Approvals List as of 12‐02‐2013 Governs January 1, 2014 ‐ March 31, 2014 5‐((4‐bromo‐2‐ fluorophenyl)amino)‐4‐fluoro‐N‐(2‐ hydroxyethoxy)‐1‐methyl‐1H‐ Treatment Stage IIB‐IV Novartis Pharmaceuticals 5 benzo[d]imidazole‐6‐carboxamide n/a 11/19/2013 melanoma. Corporation Treatment of Hepatitis Delta 6 Lonafarnib n/a 11/19/2013 Virus (HDV)infection Eiger Biopharmaceuticals, Inc. Treatment in Stage IIB‐IV melanoma positive for the Novartis Pharmaceuticalues 7 MEK162
    [Show full text]
  • PROTEIN DESIGN LABS, INC. (Exact Name of Registrant As Specified in Its Charter)
    UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K [X] ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE FISCAL YEAR ENDED DECEMBER 31, 2000 OR [ ] TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE TRANSITION PERIOD FROM ___________ TO _____________ Commission file number 0-19756 PROTEIN DESIGN LABS, INC. (Exact name of Registrant as Specified in its Charter) Delaware 94-3023969 (State or Other Jurisdiction of Incorporation or Organization) (I.R.S. Employer Identification Number) 34801 Campus Drive Fremont, California, 94555 (Address of Principal Executive Offices including Zip Code) (510) 574-1400 (Registrant's Telephone Number, Including Area Code) Securities registered pursuant to Section 12(b) of the Act: None Securities registered pursuant to Section 12(g) of the Act: Common Stock, Par value $.01 (Title of Class) Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes [X] No [ ] Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K is not contained herein, and will not be contained to the best of the registrant's knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to this Form 10-K.
    [Show full text]
  • Opportunity on Your Doorstep: a Guide to Investing in the UK Biotech Sector
    Opportunity on your doorstep: A guide to investing in the UK biotech sector September 2020 Contents 3 opportunity on your doorstep Forewords Introduction 4 7 Biotech What to The biotech Ways to invest delivers consider opportunity on in biotech benefits across when investing your doorstep industrial in biotech sectors What is biotech? 11 Biotech dominates Biotech delivers Multiple opportunities the medical competitive to diversify and Biotechnology innovation returns 40 spread risk 51 is transforming pipeline 24 medicine 14 Global investors Widely accessible The global recognise the vehicles 52 The next generation drugs market is European biotech of therapies 16 growing rapidly 25 opportunity 42 Less widely accessible vehicles (venture Biotech offers various The R&D and regulatory The UK is the leading capital funds) 55 company models and processes 27 European biotech risk-profiles 17 cluster 45 Success rates vary by Industrial and technology, targeting agricultural and therapy area 29 biotech 22 Biotech financing sources 32 The medicines market is not like other markets 33 Glossary The best-trodden routes to realising 56 returns: licensing, M&A and IPO 35 References How to value biotech 38 58 4 Forewords Steve Bates OBE high. Several companies’ share prices also hit all- CEO, UK BioIndustry Association time highs; AstraZeneca became the most valuable company on the London Stock Exchange. The importance of the biotech industry has never been clearer. As the sector mobilises to find solutions Most pundits agree that the world will never be to the COVID-19 crisis, there is acute interest from the same again, even after lock-downs are lifted.
    [Show full text]