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Extract from the Register of European Patents

EP About this file: EP2269604

EP2269604 - Treatment of solid kidney tumours with a rapamycin derivative [Right-click to bookmark this link]
Former [2011/01]Treatment of solid tumours with rapamycin derivatives
[2016/03]
StatusPatent revoked
Status updated on  18.10.2021
Database last updated on 11.04.2026
FormerThe patent has been granted
Status updated on  11.09.2019
Most recent event   Tooltip12.11.2021Change - opposition data/opponents data or that of the opponents representativepublished on 15.12.2021  [2021/50]
Applicant(s)For all designated states
Novartis Pharma AG
Lichtstrasse 35
4056 Basel / CH
[2020/51]
Former [2016/28]For all designated states
Novartis AG
Lichtstrasse 35
4056 Basel / CH
Former [2011/01]For:BE  CH  CY  DE  DK  ES  FI  FR  GB  GR  IE  IT  LI  LU  MC  NL  PT  SE  TR 
Novartis AG
Lichtstrasse 35
4056 Basel / CH
For:AT 
Novartis Pharma GmbH
Brunner Strasse 59
1230 Wien / AT
Inventor(s)01 / Lane, Heidi
Jakobsweg 22
4105 Biel-Benken / CH
02 / O'Reilly, Terence
Drahtzugstrasse 51
4057 Basel / CH
03 / Wood, Jeanette Marjorie
In den Kleematten 18
4105 Biel-Benken BL / CH
 [2016/30]
Former [2011/01]01 / Lane, Heidi
Jakobsweg 22
4105 Biel-Benken / CH
02 / O'Reilly, Terence
Drahtzugstrasse 51
4057 Basel / CH
03 / Wood, Jeanette Marjorie
In den Kleematten 18
4105 Biel-Benken BL / CH
Representative(s)Carpmaels & Ransford LLP
One Southampton Row
London WC1B 5HA / GB
[N/P]
Former [2016/30]Gruber, Markus
Novartis Pharma AG
Patent Department
4002 Basel / CH
Former [2011/01]Gruber, Markus
Novartis Pharma AG Patent Department
4002 Basel / CH
Application number, filing date10174985.118.02.2002
[2011/01]
Priority number, dateGB2001000407219.02.2001         Original published format: GB 0104072
GB2001002495717.10.2001         Original published format: GB 0124957
[2011/01]
Filing languageEN
Procedural languageEN
PublicationType: A1 Application with search report 
No.:EP2269604
Date:05.01.2011
Language:EN
[2011/01]
Type: B1 Patent specification 
No.:EP2269604
Date:27.07.2016
Language:EN
[2016/30]
Search report(s)(Supplementary) European search report - dispatched on:EP06.12.2010
ClassificationIPC:A61K45/06, A61K31/436, A61K31/337, A61K31/475, A61K31/502, A61K31/555, A61K31/5685, A61K31/704, A61K31/7068, A61P35/00
[2016/03]
CPC:
A61K31/436 (EP,CN,CZ,IL,KR,NO,RU,US); A61K31/337 (EP,IL,US); A61K31/366 (EP,IL,US);
A61K31/4196 (EP,IL,NO,US); A61K31/439 (US); A61K31/451 (EP,US);
A61K31/4545 (EP,US); A61K31/4745 (US); A61K31/475 (EP,US);
A61K31/502 (EP,US); A61K31/555 (EP,US); A61K31/5685 (EP,US);
A61K31/58 (EP,US); A61K31/704 (EP,US); A61K31/7068 (EP,US);
A61K33/243 (EP,CN,NO,RU,US); A61K39/3955 (US); A61K39/39558 (US);
A61K45/06 (EP,IL,US); A61P1/02 (EP); A61P1/04 (EP);
A61P1/16 (EP); A61P1/18 (EP); A61P11/00 (EP);
A61P11/02 (EP); A61P11/04 (EP); A61P13/00 (EP);
A61P13/02 (EP); A61P13/10 (EP); A61P13/12 (EP);
A61P15/00 (EP); A61P15/14 (EP); A61P17/00 (EP);
A61P19/00 (EP); A61P21/00 (EP); A61P25/00 (EP);
A61P25/02 (EP); A61P27/02 (EP); A61P27/16 (EP);
A61P3/00 (EP); A61P35/00 (EP,CZ,NO,RU); A61P35/02 (EP);
A61P35/04 (EP,NO); A61P43/00 (EP); A61P5/00 (EP);
A61P5/28 (EP); A61P5/32 (EP); A61P9/00 (EP);
C07D491/00 (IL); A61K33/24 (EP) (-)
C-Set:
A61K31/337, A61K2300/00 (US,EP);
A61K31/366, A61K2300/00 (US,EP);
A61K31/4196, A61K2300/00 (EP,US);
A61K31/436, A61K2300/00 (US,EP);
A61K31/436, A61K31/4196 (US);
A61K31/451, A61K2300/00 (US,EP);
A61K31/4545, A61K2300/00 (EP,US);
A61K31/475, A61K2300/00 (US,EP);
A61K31/502, A61K2300/00 (US,EP);
A61K31/555, A61K2300/00 (US,EP);
A61K31/5685, A61K2300/00 (EP,US);
A61K31/58, A61K2300/00 (US,EP);
A61K31/704, A61K2300/00 (US,EP);
A61K31/7068, A61K2300/00 (US,EP);
A61K33/243, A61K2300/00 (EP);
A61K33/24, A61K2300/00 (US)
(-)
Former IPC [2011/01]A61K31/436, A61P35/00, A61P35/04
Designated contracting statesAT,   BE,   CH,   CY,   DE,   DK,   ES,   FI,   FR,   GB,   GR,   IE,   IT,   LI,   LU,   MC,   NL,   PT,   SE,   TR [2016/30]
Former [2011/01]AT,  BE,  CH,  CY,  DE,  DK,  ES,  FI,  FR,  GB,  GR,  IE,  IT,  LI,  LU,  MC,  NL,  PT,  SE,  TR 
Extension statesLT05.07.2011
LV05.07.2011
RO05.07.2011
SI05.07.2011
TitleGerman:Behandlung von soliden Nierentumoren mit einem Rapamycin-Derivat[2016/03]
English:Treatment of solid kidney tumours with a rapamycin derivative[2016/03]
French:Traitement de tumeurs solides rénales avec un dérivé de la rapamycine[2016/03]
Former [2011/01]Behandlung von festen Tumoren mit Rapamycin Derivaten
Former [2011/01]Treatment of solid tumours with rapamycin derivatives
Former [2011/01]Traitement de tumeurs solides avec des dérivés de la rapamycine
Examination procedure05.07.2011Examination requested  [2011/32]
09.08.2011Despatch of communication that the application is deemed to be withdrawn, reason: reply to the Extended European Search Report/Written Opinion of the International Searching Authority/International Preliminary Examination Report/Supplementary international search report not received in time
06.10.2011Amendment by applicant (claims and/or description)
21.01.2014Despatch of a communication from the examining division (Time limit: M04)
09.04.2014Reply to a communication from the examining division
01.09.2014Despatch of a communication from the examining division (Time limit: M04)
19.12.2014Reply to a communication from the examining division
10.12.2015Cancellation of oral proceeding that was planned for 11.12.2015
11.12.2015Date of oral proceedings (cancelled)
25.01.2016Communication of intention to grant the patent
18.02.2016Observations by third parties
15.04.2016Fee for grant paid
15.04.2016Fee for publishing/printing paid
15.04.2016Receipt of the translation of the claim(s)
20.03.2020Observations by third parties
Parent application(s)   TooltipEP02719864.7  / EP1363627
Divisional application(s)The date of the Examining Division's first communication in respect of the earliest application for which a communication has been issued (EP20020719864) is  19.04.2007
Opposition(s)Opponent(s)01  24.04.2017  03.05.2017  ADMISSIBLE
Synthon Biopharmaceuticals B.V.
Microweg 22
6545 CM Nijmegen / NL
Opponent's representative
Prins, Hendrik Willem
Arnold & Siedsma
Bezuidenhoutseweg 57
2594 AC The Hague / NL
 02  26.04.2017  02.05.2017  ADMISSIBLE
Fresenius Kabi Deutschland GmbH
Else-Krömer-Strasse 1
61352 Bad Homburg / DE
Opponent's representative
Fresenius Kabi Deutschland GmbH, et al, et al
Patent Department - MedTech
Else-Kröner-Straße 1
61352 Bad Homburg / DE
 03  26.04.2017  02.05.2017  ADMISSIBLE
KRKA, d.d., Novo mesto
Smarjeska cesta 6
8501 Novo Mesto / SI
Opponent's representative
Hoefer & Partner Patentanwälte mbB, et al, et al
Pilgersheimer Straße 20
81543 München / DE
 04  27.04.2017  03.05.2017  ADMISSIBLE
Teva Pharmaceutical Industries Ltd
124 Dvora HaNevi'a St.
6944020 Tel Aviv / IL
Opponent's representative
Schiener, Jens
Wächtershäuser & Hartz
Patentanwaltspartnerschaft mbB
Weinstraße 8
80333 München / DE
 05  27.04.2017  03.05.2017  ADMISSIBLE
STADA Arzneimittel AG
Stadastrasse 2-18
61118 Bad Vilbel / DE
Opponent's representative
Hamm&Wittkopp Patentanwälte PartmbB, et al, et al
Jungfernstieg 38
20354 Hamburg / DE
 06  27.04.2017  03.05.2017  ADMISSIBLE
Wittkopp, Alexander
Jungfernstieg 38
20354 Hamburg / DE
Opponent's representative
Hamm&Wittkopp Patentanwälte PartmbB
Jungfernstieg 38
20354 Hamburg / DE
 07  27.04.2017  03.05.2017  ADMISSIBLE
Generics [UK] Ltd
Station Close
Potters Bar
Hertfordshire EN6 1TL / GB
Opponent's representative
Elkington and Fife LLP, et al, et al
Prospect House
8 Pembroke Road
Sevenoaks, Kent TN13 1XR / GB
 08  27.04.2017  03.05.2017  ADMISSIBLE
Intas Pharmaceuticals Ltd.
2nd Floor Chinubhai Centre
Ashram Road
Ahmedabad 380009
GUJ / IN
Opponent's representative
Plougmann Vingtoft a/s, et al, et al
Strandvejen 70
2900 Hellerup / DK
 [N/P]
Former [2021/50]
Opponent(s)01  24.04.2017  03.05.2017  ADMISSIBLE
Synthon Biopharmaceuticals B.V.
Microweg 22
6545 CM Nijmegen / NL
Opponent's representative
Prins, Hendrik Willem
Arnold & Siedsma
Bezuidenhoutseweg 57
2594 AC The Hague / NL
 02  26.04.2017  02.05.2017  ADMISSIBLE
Fresenius Kabi Deutschland GmbH
Else-Krömer-Strasse 1
61352 Bad Homburg / DE
Opponent's representative
Fresenius Kabi Deutschland GmbH, et al, et al
Patent Department
Else-Kröner-Straße 1
61352 Bad Homburg / DE
 03  26.04.2017  02.05.2017  ADMISSIBLE
KRKA, d.d., Novo mesto
Smarjeska cesta 6
8501 Novo Mesto / SI
Opponent's representative
Hoefer & Partner Patentanwälte mbB, et al, et al
Pilgersheimer Straße 20
81543 München / DE
 04  27.04.2017  03.05.2017  ADMISSIBLE
Teva Pharmaceutical Industries Ltd
124 Dvora HaNevi'a St.
6944020 Tel Aviv / IL
Opponent's representative
Schiener, Jens
Wächtershäuser & Hartz
Patentanwaltspartnerschaft mbB
Weinstraße 8
80333 München / DE
 05  27.04.2017  03.05.2017  ADMISSIBLE
STADA Arzneimittel AG
Stadastrasse 2-18
61118 Bad Vilbel / DE
Opponent's representative
Hamm&Wittkopp Patentanwälte PartmbB, et al, et al
Jungfernstieg 38
20354 Hamburg / DE
 06  27.04.2017  03.05.2017  ADMISSIBLE
Wittkopp, Alexander
Jungfernstieg 38
20354 Hamburg / DE
Opponent's representative
Hamm&Wittkopp Patentanwälte PartmbB
Jungfernstieg 38
20354 Hamburg / DE
 07  27.04.2017  03.05.2017  ADMISSIBLE
Generics [UK] Ltd
Station Close
Potters Bar
Hertfordshire EN6 1TL / GB
Opponent's representative
Elkington and Fife LLP, et al, et al
Prospect House
8 Pembroke Road
Sevenoaks, Kent TN13 1XR / GB
 08  27.04.2017  03.05.2017  ADMISSIBLE
Intas Pharmaceuticals Ltd.
2nd Floor Chinubhai Centre
Ashram Road
Ahmedabad 380009
GUJ / IN
Opponent's representative
Plougmann Vingtoft a/s, et al, et al
Strandvejen 70
2900 Hellerup / DK
Former [2019/13]
Opponent(s)01  24.04.2017  03.05.2017  ADMISSIBLE
Synthon Biopharmaceuticals B.V.
Microweg 22
6545 CM Nijmegen / NL
Opponent's representative
Prins, Hendrik Willem
Arnold & Siedsma
Bezuidenhoutseweg 57
2594 AC The Hague / NL
 02  26.04.2017  02.05.2017  ADMISSIBLE
Fresenius Kabi Deutschland GmbH
Else-Krömer-Strasse 1
61352 Bad Homburg / DE
Opponent's representative
Fresenius Kabi Deutschland GmbH, et al, et al
Patent Department
Else-Kröner-Straße 1
61352 Bad Homburg / DE
 03  26.04.2017  02.05.2017  ADMISSIBLE
KRKA, d.d., Novo mesto
Smarjeska cesta 6
8501 Novo Mesto / SI
Opponent's representative
Hoefer & Partner Patentanwälte mbB, et al, et al
Pilgersheimer Straße 20
81543 München / DE
 04  27.04.2017  03.05.2017  ADMISSIBLE
Teva Pharmaceutical Industries Ltd
5 Basel Street
49131 Petach-Tikva / IL
Opponent's representative
Schiener, Jens
Wächtershäuser & Hartz
Patentanwaltspartnerschaft mbB
Weinstraße 8
80333 München / DE
 05  27.04.2017  03.05.2017  ADMISSIBLE
STADA Arzneimittel AG
Stadastrasse 2-18
61118 Bad Vilbel / DE
Opponent's representative
Hamm&Wittkopp Patentanwälte PartmbB, et al, et al
Jungfernstieg 38
20354 Hamburg / DE
 06  27.04.2017  03.05.2017  ADMISSIBLE
Wittkopp, Alexander
Jungfernstieg 38
20354 Hamburg / DE
Opponent's representative
Hamm&Wittkopp Patentanwälte PartmbB
Jungfernstieg 38
20354 Hamburg / DE
 07  27.04.2017  03.05.2017  ADMISSIBLE
Generics [UK] Ltd
Station Close
Potters Bar
Hertfordshire EN6 1TL / GB
Opponent's representative
Elkington & Fife LLP, et al, et al
Prospect House
8 Pembroke Road
Sevenoaks, Kent TN13 1XR / GB
 08  27.04.2017  03.05.2017  ADMISSIBLE
Intas Pharmaceuticals Ltd.
2nd Floor Chinubhai Centre
Ashram Road
Ahmedabad 380009
GUJ / IN
Opponent's representative
Plougmann Vingtoft a/s, et al, et al
Strandvejen 70
2900 Hellerup / DK
Former [2018/52]
Opponent(s)01  24.04.2017  03.05.2017  ADMISSIBLE
Synthon Biopharmaceuticals B.V.
Microweg 22
6545 CM Nijmegen / NL
Opponent's representative
Prins, Hendrik Willem
Arnold & Siedsma
Bezuidenhoutseweg 57
2594 AC The Hague / NL
 02  26.04.2017  02.05.2017  ADMISSIBLE
Fresenius Kabi Deutschland GmbH
Else-Krömer-Strasse 1
61352 Bad Homburg / DE
Opponent's representative
Fresenius Kabi Deutschland GmbH, et al, et al
Patent Department
Else-Kröner-Straße 1
61352 Bad Homburg / DE
 03  26.04.2017  02.05.2017  ADMISSIBLE
KRKA, d.d., Novo mesto
Smarjeska cesta 6
8501 Novo Mesto / SI
Opponent's representative
Andrae | Westendorp Patentanwälte Partnerschaft, et al, et al
Uhlandstraße 2
80336 München / DE
 04  27.04.2017  03.05.2017  ADMISSIBLE
Teva Pharmaceutical Industries Ltd
5 Basel Street
49131 Petach-Tikva / IL
Opponent's representative
Schiener, Jens
Wächtershäuser & Hartz
Patentanwaltspartnerschaft mbB
Weinstraße 8
80333 München / DE
 05  27.04.2017  03.05.2017  ADMISSIBLE
STADA Arzneimittel AG
Stadastrasse 2-18
61118 Bad Vilbel / DE
Opponent's representative
Hamm&Wittkopp Patentanwälte PartmbB, et al, et al
Jungfernstieg 38
20354 Hamburg / DE
 06  27.04.2017  03.05.2017  ADMISSIBLE
Wittkopp, Alexander
Jungfernstieg 38
20354 Hamburg / DE
Opponent's representative
Hamm&Wittkopp Patentanwälte PartmbB
Jungfernstieg 38
20354 Hamburg / DE
 07  27.04.2017  03.05.2017  ADMISSIBLE
Generics [UK] Ltd
Station Close
Potters Bar
Hertfordshire EN6 1TL / GB
Opponent's representative
Elkington & Fife LLP, et al, et al
Prospect House
8 Pembroke Road
Sevenoaks, Kent TN13 1XR / GB
 08  27.04.2017  03.05.2017  ADMISSIBLE
Intas Pharmaceuticals Ltd.
2nd Floor Chinubhai Centre
Ashram Road
Ahmedabad 380009
GUJ / IN
Opponent's representative
Plougmann Vingtoft a/s, et al, et al
Rued Langgaards Vej 8
2300 Copenhagen S / DK
Former [2017/23]
Opponent(s)01  24.04.2017  03.05.2017  ADMISSIBLE
Synthon Biopharmaceuticals B.V.
Microweg 22
6545 CM Nijmegen / NL
Opponent's representative
Prins, Hendrik Willem
Arnold & Siedsma
Bezuidenhoutseweg 57
2594 AC The Hague / NL
 02  26.04.2017  02.05.2017  ADMISSIBLE
Fresenius Kabi Deutschland GmbH
Else-Krömer-Strasse 1
61352 Bad Homburg / DE
Opponent's representative
Fresenius Kabi Deutschland GmbH, et al, et al
Patent Department
Else-Kröner-Straße 1
61352 Bad Homburg / DE
 03  26.04.2017  02.05.2017  ADMISSIBLE
KRKA, d.d., Novo mesto
Smarjeska cesta 6
8501 Novo Mesto / SI
Opponent's representative
Andrae | Westendorp Patentanwälte Partnerschaft, et al, et al
Uhlandstraße 2
80336 München / DE
 04  27.04.2017  03.05.2017  ADMISSIBLE
Teva Pharmaceutical Industries Ltd
5 Basel Street
49131 Petach-Tikva / IL
Opponent's representative
Schiener, Jens
Wächtershäuser & Hartz
Patentanwaltspartnerschaft mbB
Weinstraße 8
80333 München / DE
 05  27.04.2017  03.05.2017  ADMISSIBLE
STADA Arzneimittel AG
Stadastrasse 2-18
61118 Bad Vilbel / DE
Opponent's representative
Hamm & Wittkopp Patentanwälte PartmbB, et al, et al
Jungfernstieg 38
20354 Hamburg / DE
 06  27.04.2017  03.05.2017  ADMISSIBLE
Wittkopp, Alexander
Jungfernstieg 38
20354 Hamburg / DE
Opponent's representative
Hamm & Wittkopp Patentanwälte PartmbB
Jungfernstieg 38
20354 Hamburg / DE
 07  27.04.2017  03.05.2017  ADMISSIBLE
Generics [UK] Ltd
Station Close
Potters Bar
Hertfordshire EN6 1TL / GB
Opponent's representative
Cooke, Richard Spencer, et al, et al
Elkington and Fife LLP
Patents Department
3-4 Holborn Circus
London EC1N 2HA / GB
 08  27.04.2017  03.05.2017  ADMISSIBLE
Intas Pharmaceuticals Ltd.
2nd Floor Chinubhai Centre
Ashram Road
Ahmedabad 380009
GUJ / IN
Opponent's representative
Plougmann Vingtoft a/s, et al, et al
Rued Langgaards Vej 8
2300 Copenhagen S / DK
Former [2017/22]
Opponent(s)01  24.04.2017    ADMISSIBLE
Synthon Biopharmaceuticals B.V.
Microweg 22
6545 CM Nijmegen / NL
Opponent's representative
Prins, Hendrik Willem
Arnold & Siedsma
Bezuidenhoutseweg 57
2594 AC The Hague / NL
deletedDeletion: Legal effect of rejection of opposition [ N /P ]
09.06.2017Invitation to proprietor to file observations on the notice of opposition
19.12.2017Reply of patent proprietor to notice(s) of opposition
11.06.2019Date of oral proceedings
12.09.2019Despatch of minutes of oral proceedings
12.09.2019Date of despatch of rejection of opposition
29.07.2021Legal effect of revocation of patent [2021/47]
05.10.2021Despatch of communication that the patent will be revoked
Appeal following opposition15.11.2019Appeal received No.  T3139/19
29.07.2021Result of appeal procedure: revocation of the patent
05.10.2021Despatch of the decision of the Board of Appeal
14.11.2019Appeal received No.  T3139/19
29.07.2021Result of appeal procedure: revocation of the patent
05.10.2021Despatch of the decision of the Board of Appeal
12.11.2019Appeal received No.  T3139/19
29.07.2021Result of appeal procedure: revocation of the patent
05.10.2021Despatch of the decision of the Board of Appeal
11.11.2019Appeal received No.  T3139/19
29.07.2021Result of appeal procedure: revocation of the patent
05.10.2021Despatch of the decision of the Board of Appeal
29.07.2021Date of oral proceedings
Request for further processing for:The application is deemed to be withdrawn due to failure to reply to the Extended European Search Report/Written Opinion of the International Searching Authority/International Preliminary Examination Report/Supplementary international search report/Supplementary European search report
06.10.2011Request for further processing filed
06.10.2011Full payment received (date of receipt of payment)
Request granted
14.10.2011Decision despatched
Fees paidRenewal fee
03.01.2011Renewal fee patent year 03
03.01.2011Renewal fee patent year 04
03.01.2011Renewal fee patent year 05
03.01.2011Renewal fee patent year 06
03.01.2011Renewal fee patent year 07
03.01.2011Renewal fee patent year 08
03.01.2011Renewal fee patent year 09
15.02.2011Renewal fee patent year 10
15.02.2012Renewal fee patent year 11
28.02.2013Renewal fee patent year 12
12.02.2014Renewal fee patent year 13
11.02.2015Renewal fee patent year 14
10.02.2016Renewal fee patent year 15
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Documents cited:Search[ID] WO9409010  (SANDOZ AG et al.)
 [ID] WO9516691  (SANDOZ LTD et al.)
 [ID] WO9641807  (SANDOZ LTD et al.)
 [I] EP1074263  (NOVARTIS AG et al.)
 [X] WO9747317  (CIBA GEIGY AG et al.)
 [E] WO0213802  (AMERICAN HOME PROD et al.)
 [X] WO9811908  (BRITISH BIOTECH PHARM et al.)
 [XP] WO0187372  (CORDIS CORP et al.)
 [X] US5066493  (SEHGAL SURENDRA N et al.)
 [X] US5206018  (SEHGAL SURENDRA N et al.)
 [X]   GUBA, M. ET AL: "Rapamycin inhibits tumor growth and metastasis by antiangiogenesis", CHIRURGISCHES FORUM FUER EXPERIMENTELLE UND KLINISCHE FORSCHUNG (2001) 37-39, 1 January 2001 (2001-01-01), XP001088707

DOI:   http://dx.doi.org/10.1007/978-3-642-56698-1_10
ExaminationWO9316189
 EP1074255
 WO0151049
 WO02098416
 WO02080975
   MAJEWSKI M ET AL: "THE IMMUNOSUPPRESSIVE MACROLIDE RAD INHIBITS GROWTH OF HUMAN EPSTEIN-BARR VIRUS-TRANSFORMED B LYMPHOCYTES IN VITRO AND IN VIVO: A POTENTIAL APPROACH TO PREVENTION AND TREATMENT OF POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, US, vol. 97, no. 8, 11 April 2000 (2000-04-11), pages 4285 - 4290, XP001093844, ISSN: 0027-8424, DOI: 10.1073/PNAS.080068597

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