EP2439747B1 - Générateur 68 Ga - Google Patents

Générateur 68 Ga Download PDF

Info

Publication number
EP2439747B1
EP2439747B1 EP11176249.8A EP11176249A EP2439747B1 EP 2439747 B1 EP2439747 B1 EP 2439747B1 EP 11176249 A EP11176249 A EP 11176249A EP 2439747 B1 EP2439747 B1 EP 2439747B1
Authority
EP
European Patent Office
Prior art keywords
group
generator according
acrylonitrile
styrene
ppb
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP11176249.8A
Other languages
German (de)
English (en)
Other versions
EP2439747A8 (fr
EP2439747A2 (fr
EP2439747A3 (fr
Inventor
Konstantin Zhernosekov
Tuomo Nikula
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
ITM Isotopen Technologien Muenchen AG
Original Assignee
ITM Isotopen Technologien Muenchen AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by ITM Isotopen Technologien Muenchen AG filed Critical ITM Isotopen Technologien Muenchen AG
Priority to PL11176249T priority Critical patent/PL2439747T3/pl
Publication of EP2439747A2 publication Critical patent/EP2439747A2/fr
Publication of EP2439747A3 publication Critical patent/EP2439747A3/fr
Publication of EP2439747A8 publication Critical patent/EP2439747A8/fr
Application granted granted Critical
Publication of EP2439747B1 publication Critical patent/EP2439747B1/fr
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G1/00—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
    • G21G1/0005—Isotope delivery systems
    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G1/00—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
    • G21G1/001—Recovery of specific isotopes from irradiated targets
    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G1/00—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
    • G21G1/001—Recovery of specific isotopes from irradiated targets
    • G21G2001/0021—Gallium

Definitions

  • the present invention relates to a generator for a 68 Ga daughter nuclide according to the preamble of claim 1.
  • Radionuclides of the positron emitter type are used in so-called positron emission tomography.
  • Positron emission tomography PET
  • PET is an imaging method of nuclear medicine that produces sectional images of living organisms by visualizing the distribution of a weakly radioactively labeled substance (radiopharmaceutical) in the organism and thus depicting biochemical and physiological functions , and thus belongs to the diagnostic department of so-called functional imaging.
  • the distribution of a weakly radioactively labeled with a positron emitter substance is made visible in an organism by means of the radioactive decay of the positron emitter by means of usually several detectors.
  • a radiopharmaceutical is administered intravenously to the patient at the beginning of a PET examination.
  • PET uses radionuclides that emit positrons ( ⁇ + radiation).
  • positrons ⁇ + radiation
  • two high-energy photons are emitted in exactly opposite directions, ie at an angle of 180 degrees to one another. In terms of nuclear physics, this is so-called destructive radiation.
  • the PET device typically includes many detectors for the photons annularly disposed about the patient. The principle of the PET study is to record coincidences between any two opposing detectors.
  • the most commonly used nuclide in PET is the radioactive isotope 18 F. It is produced with the help of a cyclotron and, because of its relatively long half-life of about 110 minutes, can be transported from the cyclotron to a nuclear medicine unit of a hospital. For this reason, it is currently the most frequently used in PET examinations.
  • 68 Ga and 82 Rb are generator radioisotopes.
  • the radioisotope arises here by decay of an unstable mother isotope in a nuclide generator in which it accumulates. All other mentioned PET nuclides are produced by means of a cyclotron.
  • generator radioisotopes and in particular the 68 Ga are of particular interest for nuclear medicine and especially for the PET process.
  • a radionuclide is coupled to a molecule (covalently bound or else in the form of a coordinative bond), which participates in the metabolism or in another way a biological and / or pharmacological effect, such as the binding to a specific receptor , having.
  • FDG-6 phosphate is not further metabolized after phosphorylation in vivo, it is enriched ("metabolic trapping"), which is particularly beneficial for the early diagnosis of cancers, as well as finding FDG in the body tumors and metastases but also general conclusions about the glucose metabolism of tissues.
  • 68 Ga PET for example, a 68 Ga DOTATOC chelate with the following structure is used:
  • 68 Ga-DOTATOC By means of such a 68 Ga-DOTATOC it is possible, for example, to detect and localize neuroendocrine tumors and their metastases by means of imaging methods such as PET.
  • imaging methods such as PET.
  • somatostatin-expressing tumors and their metastases can be detected by positron emission tomography.
  • the 68 Ga-DOTATOC accumulates. These areas radiate much stronger than the normal tissue. The radiation is localized by means of detectors and processed by image processing into a three-dimensional representation.
  • gallium-68 is a radionuclide that is of great interest to PET and new access sources are of great importance for clinical diagnostics and research.
  • 68 Ga can be obtained with a germanium-68 / gallium-68 radionuclide generator system, such as from the European patent application EP 2 216 789 A1 known.
  • gallium-68 decays with a half-life of 67.63 minutes while emitting a positron.
  • gallium-68 is very well suited for nuclear medicine examinations because of its physical and chemical properties.
  • 68 Ga can be generated by electron capture from the parent nuclide 68 Ge, which decays with a half-life of 270.82 days.
  • the 68 Ge is bound to an insoluble matrix of an inert support, with the continuous decay of the germanium constantly producing 68 Ga, which can be extracted from the generator by elution with a solvent.
  • radiopharmaceuticals require high quality standards for the radionuclides used.
  • the radionuclides produced must have a high degree of purity and be substantially free of metallic impurities since they can negatively influence the labeling of the radiopharmaceuticals by competing reactions and can reduce the production-technically achievable yield.
  • metallic contaminants can disrupt sensitive biomedical measurement systems.
  • radionuclide generators are known wherein the parent nuclide binds to an oxygen-containing functional group attached to an organic linker attached to an inorganically linked network.
  • the parent nuclide may be 224 Ra, 225 Ra or 225 Ac.
  • the exchanger material may be formed from covalently linked inorganic oxides capable of forming oxygen-linked networks.
  • the functional groups may include sulfato groups, especially -SO 3 H, -SO 3 Na, -SO 3 K, -SO 3 Li, -SO 3 NH 4 , or may be selected from -PO (OX) 2 or -COOX, wherein X is selected from H, Na, K or NH 4 or combinations thereof.
  • the describes GB 2 056 471 A an ion exchanger for separating gallium-68 from its parent nuclide germanium-68.
  • the ion exchanger according to GB 2 056 471 A consists entirely or essentially of a condensation product obtained from a polyhydroxybenzene having not less than two adjacent ones Hydroxyl groups and formaldehyde in a molar excess of 5 to 15%, or contains such a condensation product which is incorporated therein, wherein the condensation product has a reversible water content of not less than 40 wt .-%.
  • the ion exchange material must be treated with bound 68 Ge with 2M to 5M HCl.
  • the column materials were then eluted with 0.05 M HCl with the eluate containing essentially 68 Ga and the mother nucleate breakthrough ranging from 1.0 x 10 -5 to 3 x 10 -3 %.
  • gallium-68 could be used directly and without further chemical post-processing to prepare injectable gallium-68 radiopharmaceuticals
  • the hydrophobic compound to which the polyhydroxyphenol was coupled over time and led to contamination of the desired 68 Ga nuclide, so that before use as a radiopharmaceutical after a certain period of the support materials yet another purification step was required before the 68 Ga fraction could be used for the production of a radiopharmaceutical.
  • the present invention relates to a 68 Ga daughter nuclide generator in which its 68 Ge parent nuclide is specifically immobilized on a support via a trihydroxyphenyl group or a dihydroxybenzene group and continuously decays to 68 Ga with a half-life of 270.82d by electron capture the trihydroxyphenyl group (or dihydroxyphenyl group) is covalently bound to a support material via a linker, the linker being selected from the group consisting of: C 2 to C 20 esters, C 2 to C 20 alkylene, phenyl, thiourea, C 2 C 20 amines, melamine, maleimide, trihydroxyphenylalkoxysilanes, in particular 1,2,3-trihydroxyphenyltriethoxysilane, 1,2,3-trihydroxyphenyldiethoxysilane, 1,2,3-trihydroxyphenylethoxysilane, 1,2,3-trihydroxyphenyltripropoxysilane, 1,2,3- Trihydroxyphenyl
  • a preferred embodiment of the present invention is a 68 Ga generator, wherein the carrier material is selected from the group consisting of: inorganic inert oxide materials, in particular silica gel, SiO 2 , TiO 2 , SnO 2 , Al 2 O 3 , ZnO, ZrO 2 , HfO 2 or organic inert polymers and copolymers, in particular styrene-divinylbenzene, polystyrene, styrene-acrylonitrile, styrene-acrylonitrile-methyl methacrylate, Acrylonitrile-methyl methacrylate, polyacrylonitrile, polyacrylates, acrylic or methacrylic esters, acrylonitrile-unsaturated dicarboxylic acid-styrene, vinylidene chloride-acrylonitrile.
  • inorganic inert oxide materials in particular silica gel, SiO 2 , TiO 2 , SnO 2 , Al 2 O 3 , Z
  • the trihydroxyphenyl group is 1,2,3-trihydroxybenzene (pyrogallol), with preference being given to using silica gel as carrier material and 1,2,3-trihydroxyphenyltriethoxysilane as linker.
  • the silica gel has an average grain size of 10-150 ⁇ m and an average pore size of 6-50 nm.
  • 68 Ga generator of the present invention preferably 68 Ge salts in the form of a compound having the oxidation number IV are used to load the support material.
  • an aqueous solution of a 68 Ge (IV) salt is used for the immobilization of 68 Ge to the trihydroxyphenyl group, more preferably 68 Ge are aquaions.
  • the generated Ga 68 has a purity which permits immediate radiopharmaceutical use, the content of impurities, especially metallic impurities, in the range of 10 to 100 ppb (by weight), preferably between 1 and 10 ppb (by mass), and more preferably below 1 ppb (by mass).
  • a germanium-specific resin was prepared by treating an inert silica gel having a grain size of about 40 ⁇ m and a pore size of about 6 nm with 1,2,3-trihydroxyphenyltriethoxysilane. Silanation of the native silica gel resulted in covalently bonded 1,2,3-trihydroxybenzene functional groups on the inert support. Measurements of the weight distribution factors of Ge (IV) on the resin confirmed the high affinity of the material for germanium. The resin was used in the form of small chromatographic columns.
  • Aqueous solutions containing HCl or HNO 3 or NaCl of radionuclide 68 Ge with activities ranging from 100 to 1000 MBq were pumped through the columns. Due to the specific binding of the 68 Ge this was quantitatively adsorbed or immobilized on the column materials.
  • the 68 Ga thus obtained could be used immediately, ie, without any chemical post-processing, to produce injectable 68 Ga radiopharmaceuticals.
  • the resin of the present invention can be used to remove any traces of germanium (both radioactive and stable isotopes) from aqueous solutions for analytical or pharmaceutical applications.
  • the resin By a covalent coupling to the carrier material, the resin has an increased chemical and radiolytic stability over the prior art EP 2 216 789 A1 as well as improved chemical-mechanical properties such as lower hydrodynamic resistance.

Claims (9)

  1. Générateur de nucléide fille de 68Ga dans lequel son nucléide mère de 68Ge est immobilisé spécifiquement sur un support par un groupe trihydroxyphényle ou un groupe dihydroxyphényle et est décomposé en continu en 68Ga, avec un temps de demi-vie de 270,82 j, par capture d'électrons,
    caractérisé en ce que
    le groupe trihydroxyphényle ou dihydroxyphényle est lié de façon covalente à un matériau de support par un segment de liaison, le segment de liaison étant choisi dans le groupe constitué de : esters de C2 à C20 ; alkylène de C2 à C20, phényle, thio-urée, amines de C2 à C20, mélamine, maléimide, trihydroxyphénylalcoxysilanes, en particulier, 1,2,3-trihydroxyphényltriéthoxysilane, 1,2,3-trihydroxy-phényldiéthoxysilane, 1,2,3-trihydroxyphényl-éthoxysilane, 1,2,3-trihydroxyphényltripropoxysilane, 1,2,3-trihydroxyphénylchlorosilane, épichlorohydrine, isothiocyanates, thiols.
  2. Générateur de 68Ga selon la revendication 1, caractérisé en ce que le matériau de support est choisi dans le groupe constitué de : matériaux d'oxydes inertes inorganiques, en particulier, gel de silice, SiO2, TiO2, SnO2, Al2O3, ZnO, ZrO2, HfO2, des polymères et des copolymères inertes organiques, en particulier le styrène-divinylbenzène, le polystyrène, le styrène-acrylonitrile, le styrène-acrylonitrile-méthyl-méthacrylate, l'acrylonitrile-méthylméthacrylate, le polyacrylonitrile, les polyacrylates, les esters acryliques ou méthacryliques, l'acide dicarboxylique insaturé au niveau du groupe acrylonitrile-styrène, le chlorure de vinylidène-acrylonitrile.
  3. Générateur de 68Ga selon la revendication 1 ou 2, caractérisé en ce que le groupe trihydroxyphényle est le 1,2,3-trihydroxybenzène (pyrogallol).
  4. Générateur de 68Ga selon l'une des revendications 1 à 3, caractérisé en ce que l'on utilise comme matériau de support, du gel de silice et comme segment de liaison, le 1,2,3-trihydroxyphényltriéthoxysilane.
  5. Générateur de 68Ga selon la revendication 4, caractérisé en ce que le gel de silice présente une taille moyenne de particules de 10 à 150 µm et une taille de pores moyenne de 6 à 50 nm.
  6. Générateur de 68Ga selon la revendication 4 ou 5, caractérisé en ce que le groupe trihydroxyphénol du matériau de support chargé avec le 68Ge est traité pour l'élution spécifique des ions 68Ga obtenus, formés par décomposition radioactive du nucléide mère, avec du HCl 0,05 à 0,5 M.
  7. Générateur de 68Ga selon l'une des revendications 1 à 6, caractérisé en ce que le nucléide mère 68Ge est utilisé sous la forme d'un composé présentant un indice d'oxydation IV.
  8. Générateur de 68Ga selon la revendication 7, caractérisé en ce qu'une solution aqueuse d'un sel de 68Ge (IV) est utilisée pour l'immobilisation de 68Ge sur le groupe trihydroxyphénol, en particulier, des ions 68Ge aqueux.
  9. Générateur de 68Ga selon l'une des revendications précédentes, caractérisé en ce que le 68Ga généré présente une pureté qui autorise l'utilisation radiopharmaceutique immédiate, la teneur en impuretés, en particulier en impuretés métalliques étant de l'ordre de 10 à 100 ppb (en masse), de préférence, entre 1 et 10 ppb (en masse) et de manière particulièrement préférée, étant inférieure à 1 ppb (en masse).
EP11176249.8A 2010-10-05 2011-08-02 Générateur 68 Ga Active EP2439747B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PL11176249T PL2439747T3 (pl) 2010-10-05 2011-08-02 Generator <sup>68</sup>GA

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE102010037964A DE102010037964B3 (de) 2010-10-05 2010-10-05 68Ga-Generator

Publications (4)

Publication Number Publication Date
EP2439747A2 EP2439747A2 (fr) 2012-04-11
EP2439747A3 EP2439747A3 (fr) 2012-08-29
EP2439747A8 EP2439747A8 (fr) 2013-01-02
EP2439747B1 true EP2439747B1 (fr) 2013-09-18

Family

ID=44645527

Family Applications (1)

Application Number Title Priority Date Filing Date
EP11176249.8A Active EP2439747B1 (fr) 2010-10-05 2011-08-02 Générateur 68 Ga

Country Status (11)

Country Link
US (2) US8487047B2 (fr)
EP (1) EP2439747B1 (fr)
JP (1) JP5335048B2 (fr)
CN (1) CN102446570B (fr)
AU (1) AU2011211435B2 (fr)
BR (1) BRPI1103916B1 (fr)
CA (1) CA2749505C (fr)
DE (1) DE102010037964B3 (fr)
DK (1) DK2439747T3 (fr)
ES (1) ES2439821T3 (fr)
PL (1) PL2439747T3 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3343570A1 (fr) 2016-12-27 2018-07-04 ITM Isotopen Technologien München AG Générateur 68ge/68ga
EP3401283A1 (fr) 2017-05-10 2018-11-14 ITM Isotopen Technologien München AG Procédé de fabrication de matériau 68ge hautement purifié à des fins radiopharmaceutiques

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2974415C (fr) * 2015-01-30 2023-07-04 Lorenza Fugazza Procede de purification de ga-68 d'eluat provenant de generateurs de 68ge/68ga et colonnes chromatographiques a utiliser dans ledit procede
KR102218075B1 (ko) * 2018-06-04 2021-02-19 동국대학교 경주캠퍼스 산학협력단 방사성동위원소 발생장치용 키토산 코팅 금속산화물 흡착제, 그 제조방법 및 이를 이용한 방사성동위원소 발생방법
AU2019399674A1 (en) 2018-12-11 2021-06-24 Societe de Commercialisation des Produits de la Recherche Appliquée Socpra Sciences et Génie S.E.C. Processes and systems for producing and/or purifying gallium-68

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AT334084B (de) * 1975-02-25 1976-12-27 Radiation Int Ag Verfahren zur herstellung von insbesondere fur die selektive abtrennung mehrwertiger metalle aus wasserigen losungen geeigneten harzen
US4264468A (en) * 1979-01-08 1981-04-28 Massachusetts Institute Of Technology Generator for gallium-68 and compositions obtained therefrom
FR2455334A1 (fr) * 1979-04-24 1980-11-21 Commissariat Energie Atomique Procede de preparation d'une solution de gallium 68 sous forme ionique
DE2932948C2 (de) * 1979-08-14 1982-11-18 Stiftung Deutsches Krebsforschungszentrum, 6900 Heidelberg Verfahren zur Herstellung eines Ionenaustauschers und dessen Verwendung
AT383643B (de) * 1984-10-19 1987-07-27 Blum Gmbh Julius Scharnier
US7011816B2 (en) * 2001-12-26 2006-03-14 Immunomedics, Inc. Labeling targeting agents with gallium-68 and gallium-67
US7023000B2 (en) * 2003-05-21 2006-04-04 Triumf Isotope generator
DE102004057225B4 (de) * 2004-11-26 2006-10-12 Johannes-Gutenberg-Universität Mainz Verfahren und Vorrichtung zur Isolierung eines chemisch und radiochemisch gereinigten 68Ga-Radionuklids und zum Markieren eines Markierungsvorläufers mit dem 68Ga-Radionuklid
US20070009409A1 (en) * 2005-07-11 2007-01-11 Hariprasad Gali 212Bi or 213Bi Generator from supported parent isotope
JP4509083B2 (ja) 2006-10-24 2010-07-21 パナソニック株式会社 ディスク駆動装置
WO2008108311A1 (fr) * 2007-03-02 2008-09-12 Nagasaki University ADSORBANT DE Ge
DE102009007799B4 (de) * 2009-02-06 2010-10-14 ITM Isotopen Technologien München AG Molekül zur Funktionalisierung eines Trägers, Bindung eines Radionuklids an den Träger und Radionuklidgenerator zur Herstellung des Radionuklids sowie Herstellungsverfahren

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3343570A1 (fr) 2016-12-27 2018-07-04 ITM Isotopen Technologien München AG Générateur 68ge/68ga
WO2018122250A1 (fr) 2016-12-27 2018-07-05 ITM Isotopen Technologien München AG Générateur de 68ge/68ga
EP3401283A1 (fr) 2017-05-10 2018-11-14 ITM Isotopen Technologien München AG Procédé de fabrication de matériau 68ge hautement purifié à des fins radiopharmaceutiques
WO2018206188A1 (fr) 2017-05-10 2018-11-15 ITM Isotopen Technologien München AG Méthode de fabrication d'un matériau de 68ge hautement purifié à des fins radiopharmaceutiques

Also Published As

Publication number Publication date
DE102010037964B3 (de) 2012-03-22
PL2439747T3 (pl) 2014-02-28
DK2439747T3 (da) 2013-10-07
CA2749505C (fr) 2013-12-03
BRPI1103916B1 (pt) 2020-10-20
EP2439747A8 (fr) 2013-01-02
JP2012078353A (ja) 2012-04-19
CN102446570B (zh) 2014-12-03
CA2749505A1 (fr) 2012-04-05
US20120252981A1 (en) 2012-10-04
BRPI1103916A2 (pt) 2015-03-31
EP2439747A2 (fr) 2012-04-11
US8487047B2 (en) 2013-07-16
US8937166B2 (en) 2015-01-20
US20140163211A1 (en) 2014-06-12
AU2011211435A1 (en) 2012-04-19
ES2439821T3 (es) 2014-01-24
CN102446570A (zh) 2012-05-09
JP5335048B2 (ja) 2013-11-06
AU2011211435B2 (en) 2012-11-08
EP2439747A3 (fr) 2012-08-29

Similar Documents

Publication Publication Date Title
EP2439747B1 (fr) Générateur 68 Ga
Reissig et al. Recent insights in barium-131 as a diagnostic match for radium-223: Cyclotron production, separation, radiolabeling, and imaging
EP2849807B1 (fr) Kit et procédé permettant de préparer un produit radiopharmaceutique
DE102009007799B4 (de) Molekül zur Funktionalisierung eines Trägers, Bindung eines Radionuklids an den Träger und Radionuklidgenerator zur Herstellung des Radionuklids sowie Herstellungsverfahren
DE102008050557B4 (de) Anionisches Boranpolymer sowie dessen Verwendung und Herstellung
DE102006042191A1 (de) Verfahren zur Reinigung von Radium aus verschiedenen Quellen
Da Silva et al. A high separation factor for 165Er from HO for targeted radionuclide therapy
EP2849808B1 (fr) Kit et procédé permettant de préparer un produit radiopharmaceutique
EP2849805B1 (fr) Kit et procédé de production d&#39;un composé radiopharmaceutique
DE102012208377B4 (de) Satz und Verfahren zur Herstellung eines Radiopharmakons
DE10028056A1 (de) Radionuklidgenerator und Verfahren zur Abtrennung von trägerfreiem 72As
DE2030102C3 (de) Verfahren zur Gewinnung von Technet!um-99m aus einer wässrigen Lösung eines anorganischen Salzes von Molybdän-99
DE2213137A1 (de) Verfahren zum Wiederbeladen eines Technetium-99m-Generators
DE112021003173T5 (de) Chitosan/titan-verbundstoff und herstellungsverfahren und verwendung davon
Zhernosekov et al. 68 Ga generator
DE2030102B2 (de) Verfahren zur gewinnung von technetium-99m aus einer waessrigen loesung eines anorganischen salzes von molybdaen99
DD272726A1 (de) Verfahren zur gewinnung von radionuklidisch reinem scandium-43

Legal Events

Date Code Title Description
AK Designated contracting states

Kind code of ref document: A2

Designated state(s): 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

AX Request for extension of the european patent

Extension state: BA ME

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

PUAL Search report despatched

Free format text: ORIGINAL CODE: 0009013

AK Designated contracting states

Kind code of ref document: A3

Designated state(s): 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

AX Request for extension of the european patent

Extension state: BA ME

RIC1 Information provided on ipc code assigned before grant

Ipc: G21G 1/00 20060101AFI20120720BHEP

Ipc: A61K 51/12 20060101ALI20120720BHEP

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: ITM ISOTOPEN TECHNOLOGIEN MUENCHEN AG

17P Request for examination filed

Effective date: 20130108

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

INTG Intention to grant announced

Effective date: 20130325

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

RIN1 Information on inventor provided before grant (corrected)

Inventor name: NIKULA, TUOMO

Inventor name: ZHERNOSEKOV, KONSTANTIN

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): 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

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

Free format text: NOT ENGLISH

REG Reference to a national code

Ref country code: CH

Ref legal event code: NV

Representative=s name: ISLER AND PEDRAZZINI AG, CH

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

Free format text: LANGUAGE OF EP DOCUMENT: GERMAN

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 633157

Country of ref document: AT

Kind code of ref document: T

Effective date: 20131015

REG Reference to a national code

Ref country code: NL

Ref legal event code: T3

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 502011001359

Country of ref document: DE

Effective date: 20131114

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2439821

Country of ref document: ES

Kind code of ref document: T3

Effective date: 20140124

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130821

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131218

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG4D

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131219

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

Ref country code: RS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

REG Reference to a national code

Ref country code: PL

Ref legal event code: T3

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20140118

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 502011001359

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20140120

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20140619

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 502011001359

Country of ref document: DE

Effective date: 20140619

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

Ref country code: LU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20140802

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 5

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20140802

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SM

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO

Effective date: 20110802

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 6

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 7

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 8

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20130918

REG Reference to a national code

Ref country code: DE

Ref legal event code: R081

Ref document number: 502011001359

Country of ref document: DE

Owner name: ITM ISOTOPE TECHNOLOGIES MUNICH SE, DE

Free format text: FORMER OWNER: ITM ISOTOPEN TECHNOLOGIEN MUENCHEN AG, 85748 GARCHING, DE

REG Reference to a national code

Ref country code: NL

Ref legal event code: PD

Owner name: ITM ISOTOPE TECHNOLOGIES MUNICH SE; DE

Free format text: DETAILS ASSIGNMENT: CHANGE OF OWNER(S), MERGE; FORMER OWNER NAME: ITM ISOTOPEN TECHNOLOGIEN MUENCHEN AG

Effective date: 20211130

REG Reference to a national code

Ref country code: FI

Ref legal event code: PCE

Owner name: ITM ISOTOPE TECHNOLOGIES MUNICH SE

REG Reference to a national code

Ref country code: BE

Ref legal event code: PD

Owner name: ITM ISOTOPE TECHNOLOGIES MUNICH SE; DE

Free format text: DETAILS ASSIGNMENT: CHANGE OF OWNER(S), MERGE; FORMER OWNER NAME: ITM ISOTOPEN TECHNOLOGIEN MUENCHEN AG

Effective date: 20211123

REG Reference to a national code

Ref country code: ES

Ref legal event code: PC2A

Owner name: ITM ISOTOPE TECHNOLOGIES MUNICH SE

Effective date: 20220428

REG Reference to a national code

Ref country code: AT

Ref legal event code: PC

Ref document number: 633157

Country of ref document: AT

Kind code of ref document: T

Owner name: ITM ISOTOPE TECHNOLOGIES MUNICH SE, DE

Effective date: 20220411

P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20230505

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 20230823

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: TR

Payment date: 20230728

Year of fee payment: 13

Ref country code: IT

Payment date: 20230831

Year of fee payment: 13

Ref country code: GB

Payment date: 20230824

Year of fee payment: 13

Ref country code: FI

Payment date: 20230823

Year of fee payment: 13

Ref country code: ES

Payment date: 20230918

Year of fee payment: 13

Ref country code: CH

Payment date: 20230902

Year of fee payment: 13

Ref country code: AT

Payment date: 20230818

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: PL

Payment date: 20230801

Year of fee payment: 13

Ref country code: FR

Payment date: 20230821

Year of fee payment: 13

Ref country code: DK

Payment date: 20230823

Year of fee payment: 13

Ref country code: DE

Payment date: 20230710

Year of fee payment: 13

Ref country code: BE

Payment date: 20230822

Year of fee payment: 13