Patents Assigned to Heidelberg Pharma Research GmbH
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Patent number: 11926631Abstract: The invention relates to methods for synthesizing amanitin derivatives having an amino group attached to position 6? of the central tryptophan moiety. The invention furthermore relates to an amanitin derivative having an amino group attached to position 6? of the central tryptophan moiety, conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.Type: GrantFiled: May 11, 2022Date of Patent: March 12, 2024Assignee: Heidelberg Pharma Research GmbHInventors: Werner Simon, Susanne Werner-Simon, Christian Lutz, Christoph Müller, Torsten Hechler, Michael Kulke
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Publication number: 20230355792Abstract: The present invention pertains to treatment regimens to increase the therapeutic index of antibody-drug conjugates in particular antibody-drug conjuagtes comprising amatoxins. The present invention furthermore pertains to amatoxin-based antibody-drug conjuagtes for use in said treatment regimens.Type: ApplicationFiled: April 6, 2023Publication date: November 9, 2023Applicant: Heidelberg Pharma Research GmbHInventors: Michael KULKE, Torsten HECHLER, Kristin DECKER, Andreas PAHL
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Publication number: 20230250189Abstract: The present application relates to humanized and/or deimmunized antibodies, antibody fragments or antibody derivatives that bind to Prostate Specific Membrane Antigen (PSMA) and methods for using said antibodies, antibody fragments or antibody derivatives in the treatment of prostate cancer and other neoplastic as well as neurological diseases.Type: ApplicationFiled: July 30, 2019Publication date: August 10, 2023Applicant: Heidelberg Pharma Research GmbHInventors: Torsten Hechler, Andreas Pahl
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Patent number: 11702451Abstract: The invention relates to novel methods for synthesizing amanitin derivatives having a hydroxy group attached to the central tryptophan moiety. The invention furthermore relates to novel amanitin derivatives having a hydroxy group attached to position 4?, 5? or 7? of the central tryptophan moiety, novel conjugates of such amanitin derivatives, and pharmaceutical compositions comprising such conjugates.Type: GrantFiled: January 13, 2021Date of Patent: July 18, 2023Assignee: Heidelberg Pharma Research GmbHInventors: Christian Lutz, Werner Simon, Susanne Werner-Simon, Christoph Müller, Torsten Hechler, Michael Kulke
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Publication number: 20230220001Abstract: The present invention relates to a method of formation of a sulphur bridge between tryptophan and cysteine in solid phase peptide synthesis under iodine treatment. The invention also relates to the resulting compounds of the method and their respective use.Type: ApplicationFiled: June 9, 2021Publication date: July 13, 2023Applicant: HEIDELBERG PHARMA RESEARCH GMBHInventors: Hendrik GRUSS, Christian LUTZ, Roderich SÜSSMUTH, Guiyang YAO, Caroline KNITTEL, Simone KOSOL, Andi MAINZ
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Publication number: 20230173087Abstract: The present invention relates to prodrugs comprising a linker comprising five- or six-membered cyclic acetals and an adjacent specific cleavage site, and to precursor compounds for the synthesis of said prodrugs. In one aspect the present invention relates to antibody-targeted amatoxin conjugates comprising said linkers, to methods for their synthesis, and to the use of said antibody-targeted amatoxin conjugates. In a further aspect, the invention relates to pharmaceutical compositions comprising said conjugates, and to the use of said conjugates or compositions for therapeutic purposes, in particular for tumor therapy and oncology.Type: ApplicationFiled: May 22, 2020Publication date: June 8, 2023Applicant: Heidelberg Pharma Research GmbHInventors: Christoph Mueller, Werner Simon, Susanne Werner-Simon, Francesca Gallo, Torsten Hechler, Michael Kulke, Andreas Pahl
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Publication number: 20230135930Abstract: Amatoxins, as well as antibody-drug conjugates (ADCs) comprising an amatoxin are provided, as well as compositions and methods of using the same. The compositions and methods provided herein can be used for cancer therapy. They can also be used to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure. Methods and compositions for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, as well as prevention of graft-versus-host-disease (GVHD), are provided.Type: ApplicationFiled: April 24, 2020Publication date: May 4, 2023Applicant: Heidelberg Pharma Research GmbHInventors: Charlotte Fenton McDonagh, Rajiv Panwar, Torsten Hechler, Michael Kulke, Ganapathy N. Sarma, Andreas Pahl, Christoph Mueller, Wermer Simon, Christian Lutz, Francesca Gallo
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Patent number: 11590238Abstract: The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6?-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a target-binding moiety; and (c) optionally a linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.Type: GrantFiled: March 2, 2017Date of Patent: February 28, 2023Assignee: Heidelberg Pharma Research GmbHInventors: Christian Lutz, Jan Anderl, Christoph Müller, Werner Simon, Susanne Werner-Simon, Torsten Hechler, Michael Kulke
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Patent number: 11583569Abstract: The invention relates to a PSMA-targeting conjugate comprising (a) an amatoxin; (b) a small molecule PSMA-targeting moiety; and (c) optionally a linker linking said amatoxin and said small molecule PSMA-targeting moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.Type: GrantFiled: September 24, 2018Date of Patent: February 21, 2023Assignee: Heidelberg Pharma Research GmbHInventors: Francesca Gallo, Barbara Korsak, Christoph Mueller, Torsten Hechler, Andreas Pahl, Michael Kulke, Werner Simon, Christian Lutz
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Patent number: 11584708Abstract: The invention relates to a method for the preparation of a 4,5-dihydroxyisoleucine derivative comprising the steps of asymmetric Claisen rearrangement of a Z-aminocrotyl-glycin ester and subsequent kinetic resolution of the product diastereomer mix by acylase, and subsequent Sharpless dihydroxylation of the resulting 2-amino-3-methylpent-4-enoic acid derivative.Type: GrantFiled: March 29, 2019Date of Patent: February 21, 2023Assignee: Heidelberg Pharma Research GmbHInventors: Caroline Knittel, Mary-Ann Siegert, Roderich Süssmuth, Christoph Wink, Gerhard Jas
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Publication number: 20230039142Abstract: The present invention relates to the chemical synthesis of amanin and its derivatives. The present invention also relates to intermediate products of the amanin synthesis.Type: ApplicationFiled: December 16, 2020Publication date: February 9, 2023Applicant: HEIDELBERG PHARMA RESEARCH GMBHInventors: Mary-Ann SIEGERT, Caroline KNITTEL, Roderich SÜSSMUTH
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Publication number: 20220370632Abstract: The present application relates to conjugates comprising an amatoxin, a target-binding moiety wherein the target is CD37, i.e., a CD37-binding moiety, and optionally a linker linking said amatoxin and said CD37-binding moiety. The invention further relates to the synthesis of said conjugates. In addition, the invention relates to a pharmaceutical composition comprising such conjugate for use in the treatment of immune cell-, particularly B-cell and/or lymphoma associated diseases and/or malignancies.Type: ApplicationFiled: March 17, 2022Publication date: November 24, 2022Applicant: Heidelberg Pharma Research GmbHInventors: Torsten Hechler, Michael Kulke, Andreas Pahl
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Patent number: 11446388Abstract: The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6?-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a BCMA-binding moiety comprising (i) the variable domains of humanized antibody J22.9-ISY, and (ii) a heavy chain constant region comprising a D265C mutation; and (c) a protease-cleavable linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate, particularly for use in the treatment of multiple myeloma.Type: GrantFiled: December 22, 2017Date of Patent: September 20, 2022Assignee: HEIDELBERG PHARMA RESEARCH GMBHInventors: Torsten Hechler, Michael Kulke, Christian Lutz, Andreas Pahl, Christoph Müller, Werner Simon, Anikó Pálfi
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Publication number: 20220274995Abstract: The invention relates to novel methods for synthesizing amanitin derivatives having an amino group attached to position 6? of the central tryptophan moiety. The invention furthermore relates to a novel amanitin derivative having an amino group attached to position 6? of the central tryptophan moiety, novel conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.Type: ApplicationFiled: May 11, 2022Publication date: September 1, 2022Applicant: Heidelberg Pharma Research GmbHInventors: Werner Simon, Susanne Werner-Simon, Christian Lutz, Christoph Müller, Torsten Hechler, Michael Kulke
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Patent number: 11420971Abstract: The invention relates to novel methods for synthesizing amanitin derivatives having an amino group attached to position 6? of the central tryptophan moiety. The invention furthermore relates to a novel amanitin derivative having an amino group attached to position 6? of the central tryptophan moiety, novel conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.Type: GrantFiled: August 6, 2018Date of Patent: August 23, 2022Assignee: Heidelberg Pharma Research GmbHInventors: Werner Simon, Susanne Werner-Simon, Christian Lutz, Christoph Müller, Torsten Hechler, Michael Kulke
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Publication number: 20220133902Abstract: The present application relates to a composition comprising (a) at least one immune checkpoint inhibitor and (b) at least one conjugate, wherein said conjugate is comprising (i) a target binding moiety, (ii) at least one amatoxin, and (iii) optionally at least one linker connecting said target binding moiety with said at least one amatoxin. The present application further relates to said composition for use in treating a patient having a cancer, and to a pharmaceutical formulation comprising said composition and additional excipients, as well as to methods of producing and using said composition.Type: ApplicationFiled: November 4, 2021Publication date: May 5, 2022Applicant: Heidelberg Pharma Research GmbHInventors: Michael Kulke, Torsten Hechler, Andreas Pahl, Christoph Müller, Susanne Werner-Simon
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Publication number: 20220024870Abstract: The present invention relates to novel methods and compounds for synthesizing amanitin derivatives. The invention in particular relates to methods for synthesizing (S)-6-hydroxy-tryptophan derivatives which can be used as building blocks for synthesizing amanitin derivatives or amatoxin drug conjugates. The invention further relates to intermediate compounds of said synthesis pathways for use in amanitin derivative and amatoxin drug conjugate synthesis, and to the use of particular catalysts suited for mediating said synthesis pathways.Type: ApplicationFiled: December 11, 2019Publication date: January 27, 2022Applicant: Heidelberg Pharma Research GmbHInventors: Werner Simon, Susanne Werner-Simon, Christoph Müller
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Publication number: 20210130412Abstract: The invention relates to novel methods for synthesizing amanitin derivatives having a hydroxy group attached to the central tryptophan moiety. The invention furthermore relates to novel amanitin derivatives having a hydroxy group attached to position 4?, 5? or 7? of the central tryptophan moiety, novel conjugates of such amanitin derivatives, and pharmaceutical compositions comprising such conjugates.Type: ApplicationFiled: January 13, 2021Publication date: May 6, 2021Applicant: Heidelberg Pharma Research GmbHInventors: Christian Lutz, Werner Simon, Susanne Werner-Simon, Christoph Müller, Torsten Hechler, Michael Kulke
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Patent number: 10961277Abstract: The invention relates to novel methods for synthesizing amanitin derivatives having a hydroxy group attached to the central tryptophan moiety. The invention furthermore relates to novel amanitin derivatives having a hydroxy group attached to position 4?, 5? or 7? of the central tryptophan moiety, novel conjugates of such amanitin derivatives, and pharmaceutical compositions comprising such conjugates.Type: GrantFiled: August 6, 2018Date of Patent: March 30, 2021Assignee: Heidelberg Pharma Research GmbHInventors: Christian Lutz, Werner Simon, Susanne Werner-Simon, Christoph Müller, Torsten Hechler, Michael Kulke
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Publication number: 20210077571Abstract: The present invention relates to an amatoxin-linker construct comprising an amatoxin according to formula (I) wherein: R1 and R2 are each —OH, R3 is NH2, or a linker which carries a reactive group Y for linking said amatoxin to a target-binding moiety, R4 is H or a linker which carries a reactive group Y for linking said amatoxin to a target-binding moiety, R5 is absent or ?O, wherein R3 and R4 cannot be the same, for use in the manufacture of a binding moiety-toxin conjugate for the treatment of a solid tumor, and a respective binding moiety-toxin conjugate for the treatment of a solid tumor.Type: ApplicationFiled: April 12, 2019Publication date: March 18, 2021Applicant: Heidelberg Pharma Research GmbHInventors: Christoph Müller, Werner Simon, Christian Lutz, Susanne Werner-Simon, Torsten Hechler, Michael Kulke, Andreas Pahl