The present invention relates to tissue-targeting compounds. In particular, the present invention relates to tissue-targeting compounds comprising a monoclonal antibody or an antigen-binding fragment thereof having binding affinity for the prostate-specific membrane antigen (PSMA). Further, the present invention relates to combinations, preferably pharmaceutical combinations comprising a tissue-targeting compound of formula (I) and a further pharmaceutical agent. Said combinations are useful in therapy, preferably in treating hyperproliferative diseases such as cancer.
The present invention relates to tissue-targeting compounds. In particular, the present invention relates to tissue-targeting compounds comprising a monoclonal antibody or an antigen-binding fragment thereof having binding affinity for the prostate-specific membrane antigen (PSMA). Further, the present invention relates to combinations, preferably pharmaceutical combinations comprising a tissue-targeting compound of formula (I) and a further pharmaceutical agent. Said combinations are useful in therapy, preferably in treating hyperproliferative diseases such as cancer.
C07B 59/00 - Introduction d'isotopes d'éléments dans les composés organiques
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
A61K 51/10 - Anticorps ou immunoglobulinesLeurs fragments
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
C07K 16/32 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des produits de traduction des oncogènes
C07K 16/40 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre des enzymes
The present invention relates to tissue-targeting compounds. In particular, the present invention relates to tissue-targeting compounds comprising a monoclonal antibody or an antigen-binding fragment thereof having binding affinity for HER2, GPC3, CEACAM5, TROP2, GUCY2C, cMet, FolRa, DLL3, Nectin-4 or STEAP1. Further, the present invention relates to combinations, preferably pharmaceutical combinations comprising a tissue-targeting compound of formula (I) and a further pharmaceutical agent. Said combinations are useful in therapy, preferably in treating hyperproliferative diseases such as cancer.
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
C07K 16/32 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des produits de traduction des oncogènes
C07K 16/40 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre des enzymes
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
The present disclosure relates to novel antibodies binding to GPC3 or antigen-binding fragments thereof. These anti-GPC3 antibodies or fragments thereof preferably don't comprise lysine residues within their CDRs and are therefore especially suitable for conjugation. The present disclosure further relates to targeted radionuclide conjugates such as targeted actinium-225 conjugates (TACs). Preferred are TACs of formula (I) comprising the anti-GPC3 antibodies according to the present disclosure or fragments thereof. Said antibodies or antigen binding fragments thereof, and/or said antibody conjugates and/or said TACs are useful in diagnostics and/or therapy, preferably in therapy, more preferably in treating cancer, most preferably in treating hepatocellular carcinoma (HCC). Provided are pharmaceutical compositions and kits with instructions for use comprising these antibodies, functional fragments and conjugates. The disclosure further provides methods and tools to generate these antibodies, functional fragments and conjugates.
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
The present invention covers compounds of general formula (I): [(C)n-L]-(V)m (I) where C is a chelator and n>1, L is a multi-functional linker moiety comprising multiple functional groups for the covalent attachment of chelator such as a polyamine or polyacid-containing backbone or amino acid containing polymer comprising side-chains with amino, thiol or carboxylic acid moieties such as lysine, cysteine or glutamic acid and V is a tissue targeting moiety where m=1-5 which preferentially coupled through a coupling moiety to either the multifunctional linker moiety L or directly to the chelator moiety C, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.
C07D 413/14 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle contenant au moins trois hétérocycles
The present invention relates to conjugates comprising a chelator arranged for complexation of a radionuclide and a targeting moiety binding to LRRC15. For example, the conjugates according to the current invention can be targeted alpha therapeutics such as targeted thorium conjugates (TTCs), i.e. radioconjugates comprising an alpha emitter, such as 227Th. The present invention further relates to sequence-defined antibodies binding LRRC15 and antigen-binding fragments thereof. Also provided are conjugates comprising these antibodies or functional fragments thereof. The antibodies, functional fragments and conjugates according to the current invention can be used to treat cancer and other disorders and conditions associated with the expression of LRRC15.
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
9.
RADIOPHARMACEUTICAL COMPLEXES TARGETING PROSTATE-SPECIFIC MEMBRANE ANTIGEN AND ITS COMBINATIONS
A61K 31/4155 - 1,2-Diazoles non condensés et contenant d'autres hétérocycles
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61K 51/10 - Anticorps ou immunoglobulinesLeurs fragments
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
10.
RADIOPHARMACEUTICAL COMPLEXES TARGETING PROSTATE-SPECIFIC MEMBRANE ANTIGEN AND ITS COMBINATIONS
The present invention relates to tissue-targeting compounds. In particular, the present invention relates to tissue-targeting compounds comprising a monoclonal antibody or an antigen-binding fragment thereof having binding affinity for the prostate-specific membrane antigen (PSMA). Further, the present invention relates to combinations, preferably pharmaceutical combinations comprising a tissue-targeting compound of formula (I) and a further pharmaceutical agent. Said combinations are useful in therapy, preferably in treating hyperproliferative diseases such as cancer.
C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
A61K 31/4155 - 1,2-Diazoles non condensés et contenant d'autres hétérocycles
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
11.
TARGETED RADIOPHARMACEUTICALS FOR THE DIAGNOSIS AND TREATMENT OF PROSTATE CANCER
A compound of general formula (I): wherein: n is 1, 2 or 3; R1, R2, R3 and R4, independently represent OH or Q; and 20 Q represents a tissue-targeting moeity selected from the group consisting of or a stereoisomer, a hydrate, a solvate, or a salt thereof, or a mixture of same, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said 25 compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of soft tissue diseases, as a sole agent or in combination with other active ingredients.
A compound of general formula (I): wherein: n is 1, 2 or 3; R1, R2, R3 and R4, independently represent OH or Q; and 20 Q represents a tissue-targeting moeity selected from the group consisting of or a stereoisomer, a hydrate, a solvate, or a salt thereof, or a mixture of same, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said 25 compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of soft tissue diseases, as a sole agent or in combination with other active ingredients.
The present invention covers compounds of general formula (I): [(C)n-L]-(V)m (I) where C is a chelator and n > 1, L is a multi-functional linker moiety comprising multiple functional groups for the covalent attachment of chelator such as a polyamine or polyacid-containing backbone or amino acid containing polymer comprising side-chains with amino, thiol or carboxylic acid moieties such as lysine, cysteine or glutamic acid and V is a tissue targeting moiety where m= 1-5 which preferentially coupled through a coupling moiety to either the multifunctional linker moiety L or directly to the chelator moiety C, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.
A61K 51/10 - Anticorps ou immunoglobulinesLeurs fragments
C07D 413/14 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle contenant au moins trois hétérocycles
13.
MULTIMERIC CHELATOR COMPOUNDS FOR USE IN TARGETED RADIOTHERAPY
The present invention covers compounds of general formula (I): [(C)n-L]-(V)m (I) where C is a chelator and n > 1, L is a multi-functional linker moiety comprising multiple functional groups for the covalent attachment of chelator such as a polyamine or polyacid-containing backbone or amino acid containing polymer comprising side-chains with amino, thiol or carboxylic acid moieties such as lysine, cysteine or glutamic acid and V is a tissue targeting moiety where m= 1-5 which preferentially coupled through a coupling moiety to either the multifunctional linker moiety L or directly to the chelator moiety C, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same.
A61K 51/10 - Anticorps ou immunoglobulinesLeurs fragments
C07D 413/14 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle contenant au moins trois hétérocycles
The present invention relates to conjugates comprising a chelator arranged for complexation of a radionuclide and a targeting moiety binding to LRRC15. For example, the conjugates according to the current invention can be targeted alpha therapeutics such as targeted thorium conjugates (TTCs), i.e. radioconjugates comprising an alpha emitter, such as 227Th. The present invention further relates to sequence-defined antibodies binding LRRC15 and antigen-binding fragments thereof. Also provided are conjugates comprising these antibodies or functional fragments thereof. The antibodies, functional fragments and conjugates according to the current invention can be used to treat cancer and other disorders and conditions associated with the expression of LRRC15. Provided are pharmaceutical compositions and kits with instructions for use comprising the antibodies, functional fragments and conjugates according to the current invention. The invention further provides methods and tools to generate the antibodies, functional fragments and conjugates according to the invention. For example, provided are polynucleotides encoding the foregoing antibodies or fragments, vectors containing the same, and cells for production.
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
A61K 51/10 - Anticorps ou immunoglobulinesLeurs fragments
The invention provides a method for the formation of a tissue-targeting thorium complex, said method comprising;
a) forming an octadentate chelator comprising four hydroxypyridinone (HOPO) moieties, substituted in the N-position with a methyl group, and a coupling moiety terminating in a carboxylic acid group;
b) coupling said octadentate chelator to at least one tissue-targeting moiety targeting HER2; and
c) contacting said tissue-targeting chelator with an aqueous solution comprising an ion of at least one alpha-emitting thorium isotope.
A method of treatment of a neoplastic or hyperplastic disease comprising administration of such a tissue-targeting thorium complex, as well as the complex and corresponding pharmaceutical formulations are also provided
The present invention relates to combinations of at least two components, component A and component B, component A being a PD-1/PD-L1 inhibitor, and component B being a targeted thorium conjugate. Another aspect of the present invention relates to the use of such combinations as described herein for the preparation of a medicament for the treatment or prophylaxis of a disease, particularly for the treatment of breast and prostate cancer.
A61K 51/10 - Anticorps ou immunoglobulinesLeurs fragments
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
The present invention provides a method for the generation of 223Ra of pharmaceutically tolerable purity comprising i) preparing a generator mixture comprising 227Ac, 227Th and 223Ra; ii) loading said generator mixture onto a strong base anion exchange resin; iii) eluting said 223Ra from said strong base anion exchange resin using a first mineral acid in an alcoholic aqueous solution to give a first eluted 223Ra solution; iv) loading the 223Ra of the first eluted 223Ra solution onto a strong acid cation exchange resin; and v) eluting the 223Ra from said strong acid cation exchange resin using a second mineral acid in aqueous solution to provide a second eluted solution. The invention additionally provides products of corresponding purity and/or products obtained or obtainable by such a method.
A61K 51/12 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo caractérisées par un aspect physique particulier, p. ex. émulsion, microcapsules, liposomes
G21G 1/00 - Dispositions pour la conversion des éléments chimiques par rayonnement électromagnétique, radiations corpusculaires ou bombardement par des particules, p. ex. production d'isotopes radioactifs
A61K 51/00 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo
A61K 51/02 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo caractérisées par le support
18.
TARGETED RADIOPHARMACEUTICALS FOR THE DIAGNOSIS AND TREATMENT OF PROSTATE CANCER
A compound of general formula (I): wherein: n is 1, 2 or 3; R1, R2, R3 and R4, independently represent OH or Q; and 20 Q represents a tissue-targeting moeity selected from the group consisting of or a stereoisomer, a hydrate, a solvate, or a salt thereof, or a mixture of same, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said 25 compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of soft tissue diseases, as a sole agent or in combination with other active ingredients.
B01J 41/05 - Procédés utilisant des échangeurs organiques sous forme fortement basique
B01J 39/05 - Procédés utilisant des échangeurs organiques sous forme fortement acide
B01D 15/18 - Adsorption sélective, p. ex. chromatographie caractérisée par des caractéristiques de structure ou de fonctionnement relatives aux différents types d'écoulement
B01D 15/36 - Adsorption sélective, p. ex. chromatographie caractérisée par le mécanisme de séparation impliquant une interaction ionique, p. ex. échange d'ions, paire d'ions, suppression d'ions ou exclusion d'ions
G21G 1/00 - Dispositions pour la conversion des éléments chimiques par rayonnement électromagnétique, radiations corpusculaires ou bombardement par des particules, p. ex. production d'isotopes radioactifs
B01J 49/60 - Nettoyage ou rinçage des lits d’échange d’ions
A61K 51/00 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo
20.
COMBINATION OF PI3K-INHIBITORS AND TARGETED THORIUM CONJUGATES
The present invention relates to combinations of at least two components, component A and component B, component A being an inhibitor of PI3K kinase, and component B being a targeted thorium conjugate. Another aspect of the present invention relates to the use of such combinations as described herein for the preparation of a medicament for the treatment or prophylaxis of a disease, particurlarly for the treatment of breast and prostate cancer.
The invention provides a method for the formation of a tissue-targeting thorium complex, said method comprising; a) forming an octadentate chelator comprising four hydroxypyridinone (HOPO) moieties, substituted in the N-position with a methyl group, and a coupling moiety terminating in a carboxylic acid group; b) coupling said octadentate chelator to at least one tissue-targeting moiety targeting HER2; and c) contacting said tissue-targeting chelator with an aqueous solution comprising an ion of at least one alpha-emitting thorium isotope. A method of treatment of a neoplastic or hyperplastic disease comprising admistration of such a tissue-targeting thorium complex, as well as the complex and corresponding pharmaceutical formulations are also provided.
A61K 51/10 - Anticorps ou immunoglobulinesLeurs fragments
C07K 16/32 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des produits de traduction des oncogènes
The invention provides a method for the purification of 227 Th from a mixture comprising 227 Th and 223 Ra, said method comprising: i) preparing a first solution comprising a mixture of 227 Th and 223 Ra ions dissolved in a first aqueous buffer; ii) loading said first solution onto a separation material such as a strong cation exchange resin; iii) eluting 227 Th from the separation material, whereby to generate a second solution comprising 227 Th; iv) Optionally rinsing said separation material using a first aqueous washing medium; The invention additionally provides a method for forming a radio pharmaceutical comprising complexing the purified 227 Th, the pharmaceutical product and its use in treatment of disease such as cancer and a kit for generation of such a product.
A61K 51/10 - Anticorps ou immunoglobulinesLeurs fragments
B01D 15/36 - Adsorption sélective, p. ex. chromatographie caractérisée par le mécanisme de séparation impliquant une interaction ionique, p. ex. échange d'ions, paire d'ions, suppression d'ions ou exclusion d'ions
B01J 39/05 - Procédés utilisant des échangeurs organiques sous forme fortement acide
B01J 39/17 - Substance organique contenant également des substances inorganiques, p. ex. une substance inerte enrobée d’une résine échangeuse d’ions
A61N 5/10 - RadiothérapieTraitement aux rayons gammaTraitement par irradiation de particules
B01J 39/26 - Échangeurs de cations pour procédés chromatographiques
C07K 16/32 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des produits de traduction des oncogènes
23.
COMBINATION THERAPY COMPRISING A RADIOPHARMACEUTICAL AND A DNA-REPAIR INHIBITOR
The present invention provides a method of combination therapy comprising administration of a tissue-targeting radiopharmaceutical and a DNA-repair inhibitor. The method may be used in the treatment of hyperplastic or neoplastic disease, such as a carcinoma, sarcoma, myeloma, leukemia, lymphoma or mixed type cancer.
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61K 31/4745 - QuinoléinesIsoquinoléines condensées en ortho ou en péri avec des systèmes hétérocycliques condensées avec des systèmes cycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. phénanthrolines
A61K 31/502 - PyridazinesPyridazines hydrogénées condensées en ortho ou en péri avec des systèmes carbocycliques, p. ex. cinnoline, phtalazine
A61K 31/506 - PyrimidinesPyrimidines hydrogénées, p. ex. triméthoprime non condensées et contenant d'autres hétérocycles
A61K 31/5377 - 1,4-Oxazines, p. ex. morpholine non condensées et contenant d'autres hétérocycles, p. ex. timolol
A61K 51/10 - Anticorps ou immunoglobulinesLeurs fragments
The invention provides a method for the formation of a tissue-targeting thorium complex, said method comprising; a) forming an octadentate chelator comprising four hydroxypyridinone (HOPO) moieties, substituted in the N-position with a methyl group, and a coupling moiety terminating in a carboxylic acid group; b) coupling said octadentate chelator to at least one tissue-targeting moiety targeting prolyl endopeptidase FAP; and c) contacting said tissue-targeting chelator with an aqueous solution comprising an ion of at least one alpha-emitting thorium isotope. A method of treatment of a neoplastic or hyperplastic disease comprising admistration of such a tissue-targeting thorium complex, as well as the complex and corresponding pharmaceutical formulations are also provided.
The invention provides a method for the formation of a tissue-targeting thorium complex, said method comprising; a) forming an octadentate chelator comprising four hydroxypyridinone (HOPO) moieties, substituted in the N-position with a methyl group, and a coupling moiety terminating in a carboxylic acid group; b) coupling said octadentate chelator to at least one tissue-targeting moiety targeting HER2; and c) contacting said tissue-targeting chelator with an aqueous solution comprising an ion of at least one alpha-emitting thorium isotope. A method of treatment of a neoplastic or hyperplastic disease comprising admistration of such a tissue-targeting thorium complex, as well as the complex and corresponding pharmaceutical formulations are also provided
A61K 51/10 - Anticorps ou immunoglobulinesLeurs fragments
C07K 16/32 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des produits de traduction des oncogènes
The present invention comprises a method for the generation of 227 Th of pharmaceutically tolerable purity comprising i) preparing a generator mixture comprising 227 Ac, 227 Th and 223 Ra; ii) loading said generator mixture onto a strong base anion exchange resin; iii) eluting a mixture of said 223 Ra and 227 Ac from said strong base anion exchange resin using a first mineral acid in an aqueous solution; iv) eluting 227 Th from said strong base anion exchange resin using a second mineral acid in an aqueous solution whereby to generate a first 227 Th solution containing contaminant 223 Ra and 227 Ac; v) loading the first 227 Th solution onto a strong acid cation exchange resin; vi) eluting at least a part of the contaminant 223 Ra and 227 Ac from said strong acid cation exchange resin using a third mineral acid in aqueous solution; and vii) eluting the 227 Th from said strong acid cation exchange resin using a first aqueous buffer solution to provide a second 227 Th solution. Purified thorium-227 of pharmaceutical purity and a pharmaceutical composition comprising the same are also provided.
B01D 15/18 - Adsorption sélective, p. ex. chromatographie caractérisée par des caractéristiques de structure ou de fonctionnement relatives aux différents types d'écoulement
B01D 15/36 - Adsorption sélective, p. ex. chromatographie caractérisée par le mécanisme de séparation impliquant une interaction ionique, p. ex. échange d'ions, paire d'ions, suppression d'ions ou exclusion d'ions
B01J 39/05 - Procédés utilisant des échangeurs organiques sous forme fortement acide
B01J 41/05 - Procédés utilisant des échangeurs organiques sous forme fortement basique
A61K 51/12 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo caractérisées par un aspect physique particulier, p. ex. émulsion, microcapsules, liposomes
G21G 1/00 - Dispositions pour la conversion des éléments chimiques par rayonnement électromagnétique, radiations corpusculaires ou bombardement par des particules, p. ex. production d'isotopes radioactifs
The present invention provides a method for the purification of 227Th from a mixture comprising 227Th and 223Ra, said method comprising: i) preparing a first solution comprising a mixture of 227Th and 223Ra ions dissolved in an aqueous solution of first mineral acid; ii) loading said first solution onto a strong base anion exchange resin; iii) eluting 223Ra from said strong base anion exchange resin using a second mineral acid in an aqueous solution; iv) optionally rinsing said strong base anion exchange resin using a first aqueous medium; v) eluting 227Th from said strong base anion exchange resin using a third mineral acid in an aqueous solution whereby to generate a second solution comprising 227Th. The invention further provides a purified 227Th solution, a corresponding pharmaceutical formulation and methods of treatment of neoplastic disease.
B01D 15/36 - Adsorption sélective, p. ex. chromatographie caractérisée par le mécanisme de séparation impliquant une interaction ionique, p. ex. échange d'ions, paire d'ions, suppression d'ions ou exclusion d'ions
A61K 51/12 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo caractérisées par un aspect physique particulier, p. ex. émulsion, microcapsules, liposomes
B01J 41/05 - Procédés utilisant des échangeurs organiques sous forme fortement basique
The invention provides a method for the purification of 227 Th from a mixture comprising 227 Th and 223 Ra, said method comprising: i) preparing a first solution comprising a mixture of 227 Th and 223 Ra ions dissolved in a first aqueous buffer; ii) loading said first solution onto a separation material such as a strong cation exchange resin; iii) eluting 227 Th from the separation material, whereby to generate a second solution comprising 227 Th; iv) Optionally rinsing said separation material using a first aqueous washing medium; The invention additionally provides a method for forming a radio pharmaceutical comprising complexing the purified 227 Th, the pharmaceutical product and its use in treatment of disease such as cancer and a kit for generation of such a product.
B01D 15/36 - Adsorption sélective, p. ex. chromatographie caractérisée par le mécanisme de séparation impliquant une interaction ionique, p. ex. échange d'ions, paire d'ions, suppression d'ions ou exclusion d'ions
A61K 51/12 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo caractérisées par un aspect physique particulier, p. ex. émulsion, microcapsules, liposomes
B01J 39/05 - Procédés utilisant des échangeurs organiques sous forme fortement acide
The invention provides a method for the purification of complexed 227Th from a mixture comprising complexed 227Th and 223Ra (complexed or in solution), said method comprising: i) preparing a first solution comprising a mixture of complexed 227Th ions and 223Ra ions in a first aqueous buffer; ii) loading said first solution onto a separation material; iii) eluting complexed 227Th from said separation material whereby to generate a second solution comprising complexed 227Th; iv) Optionally rinsing said separation material using a first aqueous washing medium; The invention additionally provides a purified 227Th solution, a pharmaceutical product and its use in treatment of disease such as cancer and a kit for generation of such a product.
B01D 15/36 - Adsorption sélective, p. ex. chromatographie caractérisée par le mécanisme de séparation impliquant une interaction ionique, p. ex. échange d'ions, paire d'ions, suppression d'ions ou exclusion d'ions
A61K 51/12 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo caractérisées par un aspect physique particulier, p. ex. émulsion, microcapsules, liposomes
B01J 39/05 - Procédés utilisant des échangeurs organiques sous forme fortement acide
30.
Method for the quantification of 227AC in 223RA compositions
B01D 15/08 - Adsorption sélective, p. ex. chromatographie
B01D 15/18 - Adsorption sélective, p. ex. chromatographie caractérisée par des caractéristiques de structure ou de fonctionnement relatives aux différents types d'écoulement
G01N 30/00 - Recherche ou analyse de matériaux par séparation en constituants utilisant l'adsorption, l'absorption ou des phénomènes similaires ou utilisant l'échange d'ions, p. ex. la chromatographie
G01T 1/36 - Mesure de la distribution spectrale des rayons X ou d'une radiation nucléaire
G01N 30/88 - Systèmes intégrés d'analyse, spécialement adaptés à cet effet, non couverts par un seul des groupes
G21G 1/00 - Dispositions pour la conversion des éléments chimiques par rayonnement électromagnétique, radiations corpusculaires ou bombardement par des particules, p. ex. production d'isotopes radioactifs
G01N 33/00 - Recherche ou analyse des matériaux par des méthodes spécifiques non couvertes par les groupes
The invention provides a method for the formation of a tissue-targeting thorium complex, said method comprising; a) forming an octadentate chelator comprising four hydroxypyridinone (HOPO) moieties, substituted in the N-position with a C l-C 3alkyl group, and a coupling moiety terminating in a carboxylic acid group; b) coupling said octadentate chelator to at least one tissue-targeting peptide or protein comprising at least one amine moiety by means of at least one amide-coupling reagent whereby to generate a tissue-targeting chelator; and c) contacting said tissue-targeting chelator with an aqueous solution comprising an ion of at least one alpha-emitting thorium isotope. A method of treatment of a neoplastic or hyperplastic disease comprising administration of such a tissue-targeting thorium complex, as well as the complex and corresponding pharmaceutical formulations are also provided.
A tissue-targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand comprising four HOPO moieties and the ion of an alpha-emitting thorium radionuclide, where at least one of the four HOPO moieties is substituted at the N-position with a hydroxyalkyl solubilising group.
C07K 16/32 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des produits de traduction des oncogènes
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
33.
METHOD FOR THE QUANTIFICATION OF 227AC IN 223RA COMPOSITIONS
A method for the quantification of 227Ac in a 223Ra composition comprising passing the composition through a first solid phase extraction column A, wherein said column comprises a thorium specific resin, passing the eluate of column A through a second solid phase extraction column B, wherein said column comprises an actinium specific resin and recovering the 227Ac absorbed onto the resin in column B and determining the amount thereof.
B01D 15/08 - Adsorption sélective, p. ex. chromatographie
B01D 15/18 - Adsorption sélective, p. ex. chromatographie caractérisée par des caractéristiques de structure ou de fonctionnement relatives aux différents types d'écoulement
B01D 59/26 - Séparation par extraction par sorption, c.-à-d. absorption, adsorption, persorption
A61K 51/00 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo
C22B 60/00 - Obtention des métaux ayant un nombre atomique de 87 ou plus, c.-à-d. métaux radioactifs
G21G 4/08 - Sources radioactives autres que les sources de neutrons caractérisées par des aspects de leur structure spécialement adaptées aux applications médicales
G21G 4/10 - Sources radioactives autres que les sources de neutrons à émanation de radium
The present invention provides a method for generating a purified solution of at least one alpha-emitting radionuclide complex. The method comprises contacting a solution of the alpha-emitting radionuclide complex and at least one daughter nuclide with at least one selective binder for the daughter nuclide and subsequently separating the solution from the selective binder. The invention also provides a method for the removal of at least one daughter radionuclide from a solution comprising at least one alpha-emitting radionuclide complex. The method comprises contacting the solution with at least one selective binder for the daughter nuclide.
The present invention provides a tissue-targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand and the ion of an alpha-emitting thorium radionuclide. The invention additionally provides therapeutic methods employing such complexes, methods of their production and use, and kits and pharmaceutical compositions comprising such complexes.
223Ra from said strong acid cation exchange resin using a second mineral acid in aqueous solution to provide a second eluted solution. The invention additionally provides products of corresponding purity and/or products obtained or obtainable by such a method.
A61K 51/12 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo caractérisées par un aspect physique particulier, p. ex. émulsion, microcapsules, liposomes
G21G 1/00 - Dispositions pour la conversion des éléments chimiques par rayonnement électromagnétique, radiations corpusculaires ou bombardement par des particules, p. ex. production d'isotopes radioactifs
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