EP2493453 - THERAPEUTIC USE OF BIOCOMPATIBLE COMPOSITIONS AND MATERIALS POLYMERIZED THEREFROM FOR INHIBITING ANGIOGENESIS [Right-click to bookmark this link] | |||
Former [2012/36] | USE OF BIOCOMPATIBLE COMPOSITIONS AND MATERIALS POLYMERIZED THEREFROM FOR INHIBITING ANGIOGENESIS | ||
[2022/04] | Status | No opposition filed within time limit Status updated on 19.05.2023 Database last updated on 03.04.2025 | |
Former | The patent has been granted Status updated on 10.06.2022 | ||
Former | Grant of patent is intended Status updated on 09.02.2022 | Most recent event Tooltip | 06.09.2024 | Lapse of the patent in a contracting state New state(s): MT | published on 09.10.2024 [2024/41] | Applicant(s) | For all designated states NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen Markwiesenstrasse 55 72770 Reutlingen / DE | [2012/36] | Inventor(s) | 01 /
MOLLENHAUER, Juergen Bismarckstrasse 31 72764 Reutlingen / DE | 02 /
SCHLOSSHAUER, Burkhard Friedrich-Schaal-Strasse 56 72074 Tuebingen / DE | 03 /
SCHOLZ, Beate Im Fuchsloch 14 69221 Dossenheim / DE | [2012/37] |
Former [2012/36] | 01 /
MOLLENHAUER, Juergen Bismarckstrasse 31 72764 Reutlingen / DE | ||
02 /
SCHLOSSHAUER, Burkhard Friedrich-Schaal-Strasse 56 72074 Tuebingen / DE | |||
03 /
SCHOLZ, Beate Wollreffenweg 86 74613 Oehringen / DE | Representative(s) | Witte, Weller & Partner Patentanwälte mbB Postfach 10 54 62 70047 Stuttgart / DE | [2022/28] |
Former [2012/36] | Witte, Weller & Partner Königstrasse 5 70173 Stuttgart / DE | Application number, filing date | 10768958.0 | 26.10.2010 | [2022/28] | WO2010EP66158 | Priority number, date | DE20091051575 | 26.10.2009 Original published format: DE102009051575 | [2012/36] | Filing language | DE | Procedural language | DE | Publication | Type: | A1 Application with search report | No.: | WO2011054699 | Date: | 12.05.2011 | Language: | DE | [2011/19] | Type: | A1 Application with search report | No.: | EP2493453 | Date: | 05.09.2012 | Language: | DE | The application published by WIPO in one of the EPO official languages on 12.05.2011 takes the place of the publication of the European patent application. | [2012/36] | Type: | B1 Patent specification | No.: | EP2493453 | Date: | 13.07.2022 | Language: | DE | [2022/28] | Search report(s) | International search report - published on: | EP | 12.05.2011 | Classification | IPC: | A61L27/22, A61L27/34, A61L27/52, A61K9/06, A61K47/42, A61K31/00, A61K35/30, A61K35/32, A61K38/38, A61K9/00, A61L27/54, A61K47/64, A61P3/04, A61P9/00, A61P9/12, A61P11/06, A61P17/06, A61P19/04, A61P27/02, A61P31/00, A61P37/00 | [2022/04] | CPC: |
A61K31/00 (EP,US);
A61K35/30 (EP,US);
A61K35/32 (EP,US);
A61K38/385 (EP,US);
A61K47/42 (EP,US);
A61K47/643 (EP,US);
A61K9/0024 (EP,US);
A61K9/06 (EP,US);
A61L27/227 (EP,US);
A61L27/34 (EP,US);
A61L27/52 (EP,US);
A61L27/54 (EP,US);
A61P11/06 (EP);
A61P17/06 (EP);
A61P19/02 (EP);
A61P19/04 (EP);
A61P27/02 (EP);
A61P3/04 (EP);
A61P31/00 (EP);
A61P35/00 (EP);
A61P37/00 (EP);
A61P9/00 (EP);
A61P9/10 (EP);
A61P9/12 (EP);
A61L2300/406 (EP,US);
A61L2300/41 (EP,US);
A61L2300/416 (EP,US);
A61L2400/06 (EP,US)
(-)
| C-Set: |
A61K35/30, A61K2300/00 (US,EP);
A61K35/32, A61K2300/00 (US,EP);
A61K38/385, A61K2300/00 (EP,US);
A61L27/34, C08L89/00 (US,EP) |
Former IPC [2014/32] | A61L27/22, A61L27/34, A61L27/52, A61K9/06, A61K47/42, A61K31/00, A61K35/30, A61K35/32, A61K38/38, A61K47/48, A61K9/00, A61L27/54 | ||
Former IPC [2012/36] | A61K9/16, A61K9/20, A61K35/16, A61K47/48, A61K9/00, A61P9/00 | Designated contracting states | AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR [2012/36] | Extension states | BA | Not yet paid | ME | Not yet paid | Title | German: | THERAPEUTISCHE VERWENDUNG VON BIOKOMPATIBLEN ZUSAMMENSETZUNGEN UND HIERAUS POLYMERISIERTEN MATERIALIEN ZUR INHIBIERUNG DER ANGIOGENESE | [2022/10] | English: | THERAPEUTIC USE OF BIOCOMPATIBLE COMPOSITIONS AND MATERIALS POLYMERIZED THEREFROM FOR INHIBITING ANGIOGENESIS | [2022/10] | French: | UTILISATION THERAPEUTIQUE DE COMPOSITIONS BIOCOMPATIBLES ET DE MATIÈRES POLYMÉRISÉES À PARTIR DE CES DERNIÈRES POUR INHIBER L'ANGIOGENÈSE | [2022/10] |
Former [2012/36] | VERWENDUNG VON BIOKOMPATIBLEN ZUSAMMENSETZUNGEN UND HIERAUS POLYMERISIERTEN MATERIALIEN ZUR INHIBIERUNG DER ANGIOGENESE | ||
Former [2012/36] | USE OF BIOCOMPATIBLE COMPOSITIONS AND MATERIALS POLYMERIZED THEREFROM FOR INHIBITING ANGIOGENESIS | ||
Former [2012/36] | UTILISATION DE COMPOSITIONS BIOCOMPATIBLES ET DE MATIÈRES POLYMÉRISÉES À PARTIR DE CES DERNIÈRES POUR INHIBER L'ANGIOGENÈSE | Entry into regional phase | 28.03.2012 | National basic fee paid | 28.03.2012 | Designation fee(s) paid | 28.03.2012 | Examination fee paid | Examination procedure | 18.08.2011 | Request for preliminary examination filed International Preliminary Examining Authority: EP | 28.03.2012 | Examination requested [2012/36] | 20.08.2012 | Amendment by applicant (claims and/or description) | 13.10.2014 | Despatch of a communication from the examining division (Time limit: M06) | 21.05.2015 | Despatch of communication that the application is deemed to be withdrawn, reason: reply to the communication from the examining division not received in time | 31.07.2015 | Reply to a communication from the examining division | 20.02.2018 | Date of oral proceedings | 16.03.2018 | Despatch of communication that the application is refused, reason: substantive examination {1} | 16.03.2018 | Minutes of oral proceedings despatched | 10.02.2022 | Communication of intention to grant the patent | 07.06.2022 | Fee for grant paid | 07.06.2022 | Fee for publishing/printing paid | 07.06.2022 | Receipt of the translation of the claim(s) | Appeal following examination | 18.05.2018 | Appeal received No. T2147/18 | 26.07.2018 | Statement of grounds filed | 11.09.2020 | Invitation to file observations in an appeal (Time limit: M02) [2020/37] | 19.11.2020 | Date of receipt of observations in an appeal [2020/47] | 05.10.2021 | Result of appeal procedure: remittal for grant | 11.10.2021 | Despatch of the decision of the Board of Appeal | 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 is 13.10.2014 | Opposition(s) | 14.04.2023 | No opposition filed within time limit [2023/25] | Request for further processing for: | The application is deemed to be withdrawn due to failure to reply to the examination report | 31.07.2015 | Request for further processing filed | 31.07.2015 | Full payment received (date of receipt of payment) Request granted | 14.08.2015 | Decision despatched | Fees paid | Renewal fee | 19.10.2012 | Renewal fee patent year 03 | 22.10.2013 | Renewal fee patent year 04 | 22.10.2014 | Renewal fee patent year 05 | 21.10.2015 | Renewal fee patent year 06 | 20.10.2016 | Renewal fee patent year 07 | 18.10.2017 | Renewal fee patent year 08 | 24.10.2018 | Renewal fee patent year 09 | 22.10.2019 | Renewal fee patent year 10 | 22.10.2020 | Renewal fee patent year 11 | 19.10.2021 | Renewal fee patent year 12 |
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Responsibility for the accuracy, completeness or quality of the data displayed under the link provided lies entirely with the Unified Patent Court. | Lapses during opposition Tooltip | HU | 26.10.2010 | AL | 13.07.2022 | BG | 13.07.2022 | CY | 13.07.2022 | CZ | 13.07.2022 | DK | 13.07.2022 | EE | 13.07.2022 | FI | 13.07.2022 | HR | 13.07.2022 | LT | 13.07.2022 | LV | 13.07.2022 | MC | 13.07.2022 | MK | 13.07.2022 | MT | 13.07.2022 | NL | 13.07.2022 | PL | 13.07.2022 | RO | 13.07.2022 | RS | 13.07.2022 | SE | 13.07.2022 | SI | 13.07.2022 | SK | 13.07.2022 | SM | 13.07.2022 | NO | 13.10.2022 | GR | 14.10.2022 | AT | 26.10.2022 | IE | 26.10.2022 | LU | 26.10.2022 | BE | 31.10.2022 | IS | 13.11.2022 | PT | 14.11.2022 | [2024/41] |
Former [2024/34] | HU | 26.10.2010 | |
AL | 13.07.2022 | ||
BG | 13.07.2022 | ||
CY | 13.07.2022 | ||
CZ | 13.07.2022 | ||
DK | 13.07.2022 | ||
EE | 13.07.2022 | ||
FI | 13.07.2022 | ||
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
MC | 13.07.2022 | ||
MK | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RO | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SI | 13.07.2022 | ||
SK | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
AT | 26.10.2022 | ||
IE | 26.10.2022 | ||
LU | 26.10.2022 | ||
BE | 31.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2024/27] | HU | 26.10.2010 | |
AL | 13.07.2022 | ||
CY | 13.07.2022 | ||
CZ | 13.07.2022 | ||
DK | 13.07.2022 | ||
EE | 13.07.2022 | ||
FI | 13.07.2022 | ||
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
MC | 13.07.2022 | ||
MK | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RO | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SI | 13.07.2022 | ||
SK | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
AT | 26.10.2022 | ||
IE | 26.10.2022 | ||
LU | 26.10.2022 | ||
BE | 31.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2024/21] | HU | 26.10.2010 | |
AL | 13.07.2022 | ||
CY | 13.07.2022 | ||
CZ | 13.07.2022 | ||
DK | 13.07.2022 | ||
EE | 13.07.2022 | ||
FI | 13.07.2022 | ||
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
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MC | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RO | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SI | 13.07.2022 | ||
SK | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
AT | 26.10.2022 | ||
IE | 26.10.2022 | ||
LU | 26.10.2022 | ||
BE | 31.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2024/18] | HU | 26.10.2010 | |
AL | 13.07.2022 | ||
CZ | 13.07.2022 | ||
DK | 13.07.2022 | ||
EE | 13.07.2022 | ||
FI | 13.07.2022 | ||
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
MC | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RO | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SI | 13.07.2022 | ||
SK | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
AT | 26.10.2022 | ||
IE | 26.10.2022 | ||
LU | 26.10.2022 | ||
BE | 31.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2024/09] | AL | 13.07.2022 | |
CZ | 13.07.2022 | ||
DK | 13.07.2022 | ||
EE | 13.07.2022 | ||
FI | 13.07.2022 | ||
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
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MC | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RO | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SI | 13.07.2022 | ||
SK | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
AT | 26.10.2022 | ||
IE | 26.10.2022 | ||
LU | 26.10.2022 | ||
BE | 31.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2023/48] | AL | 13.07.2022 | |
CZ | 13.07.2022 | ||
DK | 13.07.2022 | ||
EE | 13.07.2022 | ||
FI | 13.07.2022 | ||
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
MC | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RO | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SI | 13.07.2022 | ||
SK | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
IE | 26.10.2022 | ||
LU | 26.10.2022 | ||
BE | 31.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2023/42] | AL | 13.07.2022 | |
CZ | 13.07.2022 | ||
DK | 13.07.2022 | ||
EE | 13.07.2022 | ||
FI | 13.07.2022 | ||
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
MC | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RO | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SI | 13.07.2022 | ||
SK | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
LU | 26.10.2022 | ||
BE | 31.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2023/37] | AL | 13.07.2022 | |
CZ | 13.07.2022 | ||
DK | 13.07.2022 | ||
EE | 13.07.2022 | ||
FI | 13.07.2022 | ||
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
MC | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RO | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SI | 13.07.2022 | ||
SK | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
LU | 26.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2023/30] | AL | 13.07.2022 | |
CZ | 13.07.2022 | ||
DK | 13.07.2022 | ||
EE | 13.07.2022 | ||
FI | 13.07.2022 | ||
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
MC | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RO | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SK | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
LU | 26.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2023/29] | AL | 13.07.2022 | |
CZ | 13.07.2022 | ||
DK | 13.07.2022 | ||
EE | 13.07.2022 | ||
FI | 13.07.2022 | ||
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
MC | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RO | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SK | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2023/25] | CZ | 13.07.2022 | |
DK | 13.07.2022 | ||
EE | 13.07.2022 | ||
FI | 13.07.2022 | ||
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
MC | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RO | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SK | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2023/23] | CZ | 13.07.2022 | |
DK | 13.07.2022 | ||
EE | 13.07.2022 | ||
FI | 13.07.2022 | ||
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RO | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SK | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2023/22] | CZ | 13.07.2022 | |
DK | 13.07.2022 | ||
FI | 13.07.2022 | ||
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RO | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2023/21] | DK | 13.07.2022 | |
FI | 13.07.2022 | ||
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2023/20] | FI | 13.07.2022 | |
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
SM | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2023/12] | FI | 13.07.2022 | |
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
IS | 13.11.2022 | ||
PT | 14.11.2022 | ||
Former [2023/11] | FI | 13.07.2022 | |
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
NL | 13.07.2022 | ||
PL | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
PT | 14.11.2022 | ||
Former [2023/10] | FI | 13.07.2022 | |
HR | 13.07.2022 | ||
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
NL | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
NO | 13.10.2022 | ||
GR | 14.10.2022 | ||
PT | 14.11.2022 | ||
Former [2023/09] | FI | 13.07.2022 | |
LT | 13.07.2022 | ||
LV | 13.07.2022 | ||
NL | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
NO | 13.10.2022 | ||
PT | 14.11.2022 | ||
Former [2023/08] | FI | 13.07.2022 | |
LT | 13.07.2022 | ||
NL | 13.07.2022 | ||
RS | 13.07.2022 | ||
SE | 13.07.2022 | ||
NO | 13.10.2022 | ||
Former [2023/06] | NL | 13.07.2022 | Cited in | International search | [A]WO0160335 (3M INNOVATIVE PROPERTIES CO [US]) [A] 1-10* the whole document *; | [X]WO2009010232 (NMI UNIV TUEBINGEN [DE], et al) [X] 1-10 * page 3 - page 12; examples 1-5; claims 1-19 *; | [X]DE102008008071 (NMI UNIV TUEBINGEN [DE]) [X] 1-10 * page 4 - page 10; claims 1-14 * | by applicant | - POLVERINI, "Angiogenesis in health and Disease: Insights into Basic Mechanisms and Therapeutic Opportunities", JOURNAL OF DENTAL EDUCATION, (2002), vol. 66, pages 962 - 975 | - CARMELIET, "Angiogenesis in health and disease", NATURE MEDICINE, (2003), vol. 9, no. 6, doi:doi:10.1038/nm0603-653, pages 653 - 660, XP009022168 DOI: http://dx.doi.org/10.1038/nm0603-653 |