Extract from the Register of European Patents

About this file: EP1313508

EP1313508 - COMBINATION CONTAINING AN ANTIFOLATE AND METHYLMALONIC ACID LOWERING AGENT [Right-click to bookmark this link]
StatusOpposition rejected
Status updated on  12.08.2016
Database last updated on 08.12.2018
Most recent event   Tooltip12.08.2016Opposition rejectedpublished on 14.09.2016  [2016/37]
Applicant(s)For all designated states
ELI LILLY AND COMPANY
Lilly Corporate Center
Indianapolis, IN 46285 / US
[N/P]
Former [2007/16]For all designated states
ELI LILLY AND COMPANY
Lilly Corporate Center
Indianapolis IN 46285 / US
Former [2003/22]For all designated states
ELI LILLY AND COMPANY
Lilly Corporate Center
Indianapolis, Indiana 46285 / US
Inventor(s)01 / NIYIKIZA, Clet
6802 Antietam Place
Indianapolis, IN 46278 / US
02 / PAOLETTI, Paolo
8015 Hayward Drive
Indianapolis, IN 46240 / US
03 / RUSTHOVEN, James, Jacob
15 Lovers Lane
Ancaster, Ontario L9G 1G4 / CA
 [2003/22]
Representative(s)Burnside, Ivan John , et al
Eli Lilly and Company Limited
Lilly Research Centre
Erl Wood Manor
Sunninghill Road, Windlesham
Surrey GU20 6PH / GB
[N/P]
Former [2003/22]Burnside, Ivan John , et al
Eli Lilly and Company Limited, European Patent Operations, Lilly Research Centre, Erl Wood Manor, Sunnighill Road
Windlesham, Surrey GU20 6PH / GB
Application number, filing date01948214.015.06.2001
[2003/22]
WO2001US14860
Priority number, dateUS20000215310P30.06.2000         Original published format: US 215310 P
US20000235859P27.09.2000         Original published format: US 235859 P
US20010284448P18.04.2001         Original published format: US 284448 P
[2003/22]
Filing languageEN
Procedural languageEN
PublicationType: A2  Application without search report
No.:WO0202093
Date:10.01.2002
Language:EN
[2002/02]
Type: A2 Application without search report 
No.:EP1313508
Date:28.05.2003
Language:EN
The application has been published by WIPO in one of the EPO official languages on 10.01.2002
[2003/22]
Type: B1 Patent specification 
No.:EP1313508
Date:18.04.2007
Language:EN
[2007/16]
Search report(s)International search report - published on:EP06.02.2003
ClassificationInternational:A61K45/06, A61P35/00, A61K31/505, A61K31/70
[2003/22]
Designated contracting statesAT,   BE,   CH,   CY,   DE,   DK,   ES,   FI,   FR,   GB,   GR,   IE,   IT,   LI,   LU,   MC,   NL,   PT,   SE,   TR [2003/22]
Extension statesAL06.08.2003
LT06.08.2003
LV06.08.2003
MK06.08.2003
RO06.08.2003
SI06.08.2003
TitleGerman:ZUSAMMENSETZUNG, WELCHE EIN ANTIFOLATE UND EIN METHYLMALONSÄURESENKENDES MITTEL ENTHÄLT[2003/22]
English:COMBINATION CONTAINING AN ANTIFOLATE AND METHYLMALONIC ACID LOWERING AGENT[2003/22]
French:COMPOSITION COMPRENANT UN ANTIFOLATE ET UN AGENT REDUCTEUR D'ACIDE METHYLMALONIQUE[2003/22]
Entry into regional phase30.01.2003National basic fee paid 
06.08.2003Designation fee(s) paid 
06.08.2003Examination fee paid 
Examination procedure10.12.2001Request for preliminary examination filed
International Preliminary Examining Authority: EP
06.08.2003Examination requested  [2003/41]
09.03.2004Despatch of a communication from the examining division (Time limit: M06)
23.12.2004Reply to a communication from the examining division
17.05.2005Despatch of a communication from the examining division (Time limit: M06)
09.01.2006Despatch of communication that the application is deemed to be withdrawn, reason: reply to the communication from the examining division not received in time
08.03.2006Reply to a communication from the examining division
04.10.2006Communication of intention to grant the patent
14.02.2007Fee for grant paid
14.02.2007Fee for publishing/printing paid
16.11.2011Observations by third parties
15.06.2012Observations by third parties
Opposition(s)Opponent(s)01  17.01.2008  29.02.2008  ADMISSIBLE
Teva Pharmaceutical Industries Ltd.
5 Basel Street
49131 Petah Tiqva / IL
Opponent's representative
Pohlman, Sandra M., et al
df-mp Dörries Frank-Molnia & Pohlman
Patentanwälte Rechtsanwälte PartG mbB
Theatinerstrasse 16
80333 München / DE
 02  30.10.2012  30.10.2012  INTERVENTION
Actavis Deutschland GmbH & Co. KG
Willy-Brandt-Allee 2
81829 München / DE
Opponent's representative
Gillard, Richard Edward
Elkington and Fife LLP
Thavies Inn House
3-4 Holborn Circus
London EC1N 2HA / GB
 [N/P]
Former [2012/51]
Opponent(s)01  17.01.2008  29.02.2008  ADMISSIBLE
Teva Pharmaceutical Industries Ltd.
5 Basel Street
49131 Petah Tiqva / IL
Opponent's representative
Pohlman, Sandra M., et al
df-mp Fünf Höfe Theatinerstrasse 16
80333 München / DE
 02  30.10.2012  30.10.2012  INTERVENTION
Actavis Deutschland GmbH & Co. KG
Willy-Brandt-Allee 2
81829 München / DE
Opponent's representative
Gillard, Richard Edward
Elkington and Fife LLP
Thavies Inn House
3-4 Holborn Circus
GB-London EC1N 2HA / GB
Former [2008/41]
Opponent(s)01  17.01.2008  29.02.2008  ADMISSIBLE
Teva Pharmaceutical Industries Ltd.
5 Basel Street
49131 Petah Tiqva / IL
Opponent's representative
Pohlman, Sandra M., et al
df-mp Fünf Höfe Theatinerstrasse 16
80333 München / DE
Former [2008/19]
Opponent(s)01  17.01.2008  29.02.2008  ADMISSIBLE
Teva Pharmaceutical Industries Ltd.
5 Basel Street
49131 Petah Tiqva / IL
Opponent's representative
Pohlman, Sandra M., et al
df-mp Fünf Höfe Theatinerstrasse 16
80333 München / DE
Former [2008/10]
Opponent(s)01  17.01.2008   
Teva Pharmaceutical Industries Ltd.
5 Basel Street
49131 Petah Tiqva / IL
Opponent's representative
Biagini, Giuditta, et al
df-mp Fünf Höfe Theatinerstrasse 16
D-80333 München / DE
31.07.2008Invitation to proprietor to file observations on the notice of opposition
09.04.2009Reply of patent proprietor to notice(s) of opposition
08.06.2009Communication of observations of patent proprietor (Time limit: M04)
15.10.2009Reply of parties involved to observations of patent proprietor
18.11.2010Date of oral proceedings
27.12.2010Despatch of minutes of oral proceedings
27.12.2010Date of despatch of rejection of opposition
28.10.2015Legal effect of rejection of opposition [2016/37]
Appeal following opposition03.03.2011Appeal received No.  T0542/11
05.05.2011Statement of grounds filed
28.10.2015Result of appeal procedure: appeal of the opponent withdrawn
Request for further processing for:08.03.2006Request for further processing filed
08.03.2006Full payment received (date of receipt of payment)
Request granted
22.05.2006Decision despatched
23.12.2004Request for further processing filed
23.12.2004Full payment received (date of receipt of payment)
Request granted
13.01.2005Decision despatched
08.03.2006Request for further processing filed
08.03.2006Full payment received (date of receipt of payment)
Request granted
22.05.2006Decision despatched
23.12.2004Request for further processing filed
23.12.2004Full payment received (date of receipt of payment)
Request granted
13.01.2005Decision despatched
Fees paidRenewal fee
30.06.2003Renewal fee patent year 03
30.06.2004Renewal fee patent year 04
30.06.2005Renewal fee patent year 05
30.06.2006Renewal fee patent year 06
Cited inInternational search[X]EP0546870  (SNOW BRAND MILK PROD CO LTD [JP]) [X] 1-8,10-14,16-22,24-26,28 * page 7; tables 3,4 *;
 [X]US5405839  (TORAYA TETSUO [JP], et al) [X] 1-3,7,11,13,17,18,21,25,26 * example 15 *;
 [T]  - CALVERT H., "Folate status and the safety profile of antifolates.", SEMINARS IN ONCOLOGY, (2002) 29/2 SUPPL. 5 (3-7)., XP008005755 [T] 1-28 * see discussion; page 5, column 1 *

DOI:   http://dx.doi.org/10.1016/S0093-7754(02)70209-1
 [T]  - CALVERT H., "Future directions in the development of pemetrexed", SEMINARS IN ONCOLOGY, (2002) 29/2 SUPPL. 5 (54-61)., XP008005744 [T] 1-28 * see conclusions; page 57 *

DOI:   http://dx.doi.org/10.1053/sonc.2002.30748
 [Y]  - WESTERHOF, G. ROBBIN ET AL, "Carrier- and receptor-mediated transport of folate antagonists targeting folate -dependent enzymes: correlates of molecular-structure and biological activity", MOL. PHARMACOL. (1995), 48(3), 459-71, XP008005762 [Y] 4-10,12-16,19-28 * page 467, column 2 * * page 469, column 1 *
 [Y]  - WORZALLA, JOHN F. ET AL, "Role of folic acid in modulating the toxicity and efficacy of the multitargeted antifolate, LY231514", ANTICANCER RESEARCH (1998), 18(5A), 3235-3239, XP008005757 [Y] 4-10,12-16,19-28 * abstract * * page 3236, column 2 *
 [T]  - HANAUSKE A-R ET AL, "PEMETREXED DISODIUM: A NOVEL ANTIFOLATE CLINICALLY ACTIVE AGAINST MULTIPLE SOLID TUMORS", ONCOLOGIST, ALPHAMED PRESS, US, (2001), vol. 4, no. 6, ISSN 1083-7159, pages 363 - 373, XP008005751 [T] 1-28 * abstract * * page 370, column 2 - page 371, column 1 *

DOI:   http://dx.doi.org/10.1634/theoncologist.6-4-363
 [T]  - BUNN P ET AL, "VITAMIN B12 AND FOLATE REDUCE TOXICITY OF ALIMTA (PEMETREXED DISODIUM, LY231514, MTA), A NOVEL ANTIFOLATE/ANTIMETABOLITE", PROGRAM/PROCEEDINGS - AMERICAN SOCIETY OF CLINICAL ONCOLOGY, THE SOCIETY, US, (2001), vol. 76A, no. 20, ISSN 1081-0641, page 300, XP008005885 [T] 1-28 * abstract *
other   - "Methotrexate", IBIS Guide to Drug-Herb and Drug-Nutrient Interactions, Integrative Medical Arts Group, Inc.,, pages 1 - 13, XP055245765
    - RUSTHOVEN J.J. ET AL, "Multitargeted antifolate LY231514 as first-line chemotherapy for patients with advanced non-small-cell lung cancer: A phase II study", JOURNAL OF CLINICAL ONCOLOGY, (199904), vol. 17, no. 4, pages 1194 - 1199, XP003028633
    - DEN HEIJER M. ET AL, "Vitamin supplementation reduces blood homocysteine levels a controlled trial in patients with venous thrombosis and healthy volunteers", ARTERIOSCLER. THROMB. VASC. BIOL., (1998), vol. 18, pages 356 - 361, XP000910826
    - BRONSTRUP A. ET AL, "Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy, young women", AM. J. CLIN. NUTR., (1998), vol. 68, pages 1104 - 1110, XP003028634
    - OMENN G.S. ET AL, "Preventing coronary heart disease B vitamins and homocysteine", CIRCULATION, (1998), vol. 97, pages 421 - 424, XP003028635

DOI:   http://dx.doi.org/10.1161/01.CIR.97.5.421
    - MORGAN S.L. ET AL, "The effect of folic acid supplementation on the toxicity of low-dose methotrexate in patients with rheumatoid arthritis", ARTHRITIS AND RHEUMATISM, (199001), vol. 33, no. 1, pages 9 - 18, XP003028636

DOI:   http://dx.doi.org/10.1002/art.1780330102
    - NIYIKIZA C. ET AL, "LY231514 (MTA): relationship of vitamin metabolite profile to toxicity", PROCEEDINGS OF ASCO, ABSTRACT NO. 2139, (1998), vol. 17, page 558A, XP003028637
    - HAMMOND L. ET AL, "A phase I and pharmacokinetic (PK) study of the multitargeted antifol (MTA) LY231514 with folic acid", 1998 ASCO ANNUAL MEETING, ABSTRACT NO. 866, (1998), page 1, XP003028638
    - BISHOP M.L. ET AL, Clinical Chemistry: Principles, Procedures, Correlations, Third Edition, pages 618 - 627, XP003028639
    - ELI LILLY AND COMPANY LIMITED, "Label for Alimta(R)", pages 1 - 25, XP003028640
    - CALVERT H., "An overview of folate metabolism: features relevant to the action and toxicities of antifolate anticancer agents", SEMINARS IN ONCOLOGY, (199904), vol. 26, no. 2, pages 3 - 10, XP008005750
    - BUNN P. ET AL, "Vitamin B12 and folate reduce toxicity of AlimtaTM (Pemetrexed Disodium, LY231514, MTA), a novel antifolate/antimetabolite", PROCEEDINGS OF ASCO, ABSTRACT NO. 300, (2001), vol. 20, page 302, XP008005885
    - NIYIKIZA C. ET AL, "Homocysteine and methylmalonic acid: Markers to predict and avoid toxicity from pemetrexed therapy", MOLECULAR CANCER THERAPEUTICS, (200205), vol. 1, pages 545 - 552, XP002987306
    - CLARKE R. ET AL, "Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials", BMJ, (19980321), vol. 316, pages 894 - 898, XP003028641