Patents Assigned to BAYER AS
  • Publication number: 20240156999
    Abstract: 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.
    Type: Application
    Filed: January 31, 2022
    Publication date: May 16, 2024
    Applicants: Bayer Aktiengesellschaft, Bayer AS
    Inventors: Thomas BRUMBY, Alan CUTHBERTSON, Bård INDREVOLL, Waqas RAFIQUE, Vilde Roko KROGSTIE, Véronique CRUCIANI, Alexander KRISTIAN
  • Publication number: 20230072421
    Abstract: 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.
    Type: Application
    Filed: July 24, 2020
    Publication date: March 9, 2023
    Applicants: Bayer AS, Bayer Aktiengesellschaft
    Inventors: Niels BÖHNKE, Sabine ZITZMANN-KOLBE, Stefanie HAMMER, Sven WITTROCK, Donald BIERER, Thorsten POETHKO, Hans BRIEM, Holger Magnus STEUBER, Martina SCHÄFER, Robin Michael MEIER, Arif CELIK, Cornelia PREUSSE, Antje ROTTMANN, Nicolas WERBECK, Alexander KRISTIAN, Bård INDREVOLL, Alan CUTHBERTSON, Alex PAPPLE
  • Patent number: 11452999
    Abstract: The present invention comprises a method for the generation of 227Th 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 a mixture of said 223Ra and 227Ac from said strong base anion exchange resin using a first mineral acid in an aqueous solution; iv) eluting 227Th from said strong base anion exchange resin using a second mineral acid in an aqueous solution whereby to generate a first 227Th solution containing contaminant 223Ra and 227Ac; v) loading the first 227Th solution onto a strong acid cation exchange resin; vi) eluting at least a part of the contaminant 223Ra and 227Ac from said strong acid cation exchange resin using a third mineral acid in aqueous solution; and vii) eluting the 227Th from said strong acid cation exchange resin using a first aqueous buffer solution to provide a second 227Th solution.
    Type: Grant
    Filed: June 10, 2020
    Date of Patent: September 27, 2022
    Assignee: Bayer AS
    Inventors: Dimitrios Mantzilas, Jan Roger Karlson, Judit Tjelmeland Østby
  • Publication number: 20220143229
    Abstract: 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.
    Type: Application
    Filed: January 21, 2022
    Publication date: May 12, 2022
    Applicants: Bayer Pharma Aktiengesellschaft, Bayer AS
    Inventors: Lars LINDEN, Alan CUTHBERTSON
  • Publication number: 20220125960
    Abstract: 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.
    Type: Application
    Filed: February 17, 2020
    Publication date: April 28, 2022
    Applicants: Bayer Aktiengesellschaft, Bayer AS
    Inventors: Urs Beat HAGEMANN, Pascale LEJEUNE, Jenny KARLSSON, Alan CUTHBERTSON, Stefanie HAMMER
  • Publication number: 20220118123
    Abstract: The present invention covers combinations of at least two components, component A and component B, comprising component A being PSMA-TTC, and component B being an antiandrogen selected form AR antagonists such as from cyproterone acetate, bicalutamide, flutamide, nilutamide, enzalutamide, apalutamide, darolutamide or keto-darolutamide, or an AR degrader such as ARV-110, or an ARN-terminal domain binder such as EPI-506, or an antisense oligonucleotide that reduces AR expression such as EZN-4176 or AZD-5312, or an androgen synthesis inhibitor such as abiraterone, particularly abiraterone acetate, seviteronel, galeterone, orteronel or ketoconazole, or a dual AR antagonist and androgen synthesis inhibitor such as ODM-204. Another aspect of the present invention covers 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 a hyper-proliferative disease.
    Type: Application
    Filed: February 17, 2020
    Publication date: April 21, 2022
    Applicants: Bayer Aktiengesellschaft, BAYER AS
    Inventors: Stefanie HAMMER, Urs Beat HAGEMANN, Bernard HAENDLER, Pascale LEJEUNE, Sabine ZITZMANN-KOLBE, Christoph SCHATZ, Jenny KARLSSON
  • Patent number: 11260136
    Abstract: 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.
    Type: Grant
    Filed: March 20, 2017
    Date of Patent: March 1, 2022
    Assignees: BAYER PHARMA AKTIENGESELLSCHAFT, Bayer AS
    Inventors: Lars Linden, Alan Cuthbertson
  • Publication number: 20220023449
    Abstract: The present invention provides a method for generating purified solution of at least on 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.
    Type: Application
    Filed: May 4, 2021
    Publication date: January 27, 2022
    Applicant: Bayer AS
    Inventors: Janne Olsen FRENVIK, Olav B. RYAN, Alan CUTHBERTSON
  • Publication number: 20210387861
    Abstract: 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.
    Type: Application
    Filed: November 9, 2020
    Publication date: December 16, 2021
    Applicant: BAYER AS
    Inventors: Jan Roger KARLSON, Peer BØRRETZEN
  • Publication number: 20210322583
    Abstract: 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 C1-C3alkyl 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.
    Type: Application
    Filed: January 15, 2021
    Publication date: October 21, 2021
    Applicant: Bayer AS
    Inventor: Alan CUTHBERTSON
  • Publication number: 20210187134
    Abstract: 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, particularly for the treatment of breast and prostate cancer.
    Type: Application
    Filed: August 23, 2019
    Publication date: June 24, 2021
    Applicants: Bayer AS, Bayer Aktiengesellschaft
    Inventors: Urs HAGEMANN, Stefanie HAMMER, Alan CUTHBERTSON
  • Publication number: 20210130253
    Abstract: 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.
    Type: Application
    Filed: June 16, 2020
    Publication date: May 6, 2021
    Applicant: Bayer AS
    Inventors: Janne Olsen FRENVIK, Olav B. RYAN
  • Publication number: 20200406247
    Abstract: The present invention comprises a method for the generation of 227Th 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 a mixture of said 223Ra and 227Ac from said strong base anion exchange resin using a first mineral acid in an aqueous solution; iv) eluting 227Th from said strong base anion exchange resin using a second mineral acid in an aqueous solution whereby to generate a first 227Th solution containing contaminant 223Ra and 227Ac; v) loading the first 227Th solution onto a strong acid cation exchange resin; vi) eluting at least a part of the contaminant 223Ra and 227Ac from said strong acid cation exchange resin using a third mineral acid in aqueous solution; and vii) eluting the 227Th from said strong acid cation exchange resin using a first aqueous buffer solution to provide a second 227Th solution.
    Type: Application
    Filed: June 10, 2020
    Publication date: December 31, 2020
    Applicant: Bayer AS
    Inventors: Dimitrios MANTZILAS, Jan Roger KARLSON, Judit Tjelmeland ØSTBY
  • Patent number: 10729794
    Abstract: 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.
    Type: Grant
    Filed: December 29, 2016
    Date of Patent: August 4, 2020
    Assignee: BAYER AS
    Inventors: Janne Olsen Frenvik, Olav B. Ryan
  • Patent number: 10702613
    Abstract: 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.
    Type: Grant
    Filed: December 29, 2016
    Date of Patent: July 7, 2020
    Assignee: BAYER AS
    Inventors: Dimitrios Mantzilas, Jan Roger Karlson, Judit Tjelmeland Østby, Janne Olsen Frenvik
  • Patent number: 10682430
    Abstract: 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.
    Type: Grant
    Filed: June 21, 2017
    Date of Patent: June 16, 2020
    Assignee: BAYER AS
    Inventor: Thomas Ramdahl
  • Publication number: 20200016283
    Abstract: The present invention provides a method of combination therapy comprising administration of a tissue-targeting radio-pharmaceutical 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.
    Type: Application
    Filed: February 22, 2018
    Publication date: January 16, 2020
    Applicant: Bayer AS
    Inventor: Alan CUTHBERTSON
  • Publication number: 20190298865
    Abstract: 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 administration of such a tissue-targeting thorium complex, as well as the complex and corresponding pharmaceutical formulations are also provided.
    Type: Application
    Filed: June 6, 2017
    Publication date: October 3, 2019
    Applicants: BAYER PHARMA AKTIENGESELLSCHAFT, BAYER AS
    Inventors: Alan CUTHBERTSON, Mark TRAUTWEIN, Ernst WEBER, Jenny KARLSSON, Stefanie HAMMER
  • Publication number: 20190091354
    Abstract: 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.
    Type: Application
    Filed: March 20, 2017
    Publication date: March 28, 2019
    Applicants: BAYER PHARMA AKTIENGESELLSCHAFT, Bayer AS
    Inventors: Lars LINDEN, Alan CUTHBERTSON
  • Publication number: 20190015530
    Abstract: 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.
    Type: Application
    Filed: December 29, 2016
    Publication date: January 17, 2019
    Applicant: BAYER AS
    Inventors: Dimitrios MANTZILAS, Jan Roger KARLSON, Judit Tjemeland ØSTBY, Janne Olsen FRENVIK