Deutsches Krebsforschungszentrum

Bayer Pharma Aktiengesellschaft

Bayer Aktiengesellschaft

Leland Stanford Junior University

Carnegie Institution of Washington

Electrophoretics Limited

Ruprecht-karls-universität

Ruprecht-karls-univeristaet Heidelberg

Deutschland Krebsforschungszentrum

Deutsches Krebsforschungszentrum Stiftung Des Offentlichen Rechts

Ruprecht-karls-universitat Heidelberg

Michael Platten

Benjamin Bader

Detlef Stöckigt

Lars Röse

Ilona Gutcher

Ludwig Zorn

Ulrike Röhn

Norbert Schmees

Wolfgang Wick

Rafael Carretero

Christina Kober

Lawrence Steinman

Judith Günther

Thijs Kaper

Wolf B Frommer

Julien Lefranc

Horst Irlbacher

Christiane Opitz

Theresa Bunse

Ian Hugo Pike

Karsten Kuhn

Peter Schulz-Knappe

Na Zhao

Ulrike Roehn

Katharina Ochs

Martina Ott

Lukas Bunse

Ulrike Litzenburger

Sasa Koncarevic

Lars Roese

Theresa Schumacher

The present invention covers 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamide compounds of general formula (1): in which X, R, R, R, Rand Rare as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer or conditions with dysregulated immune responses or other disorders associated with aberrant AHR signaling, as a sole agent or in combination with other active ingredients.

2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamides for the treatment of cancer

The present invention pertains to novel immunogenic peptide sequences that can be used as vaccines in the treatment of cancer diseases such as brain cancers and specifically glioma. The cancer vaccines of the invention are designed based on the K27M mutated variant of the human Histone 3. Provided are further fusion proteins comprising the sequences of the cancer vaccines, nucleic acids encoding such vaccines, such as RNA vaccines, and vectors and host cells comprising these sequences. Furthermore the invention pertains to T cells and T cell receptors binding the cancer vaccines of the invention, preferably when presented by the human Major Histocompatibility Complex (MHC). The peptide immunogens of the invention elicit a HLA restricted immune response and therefore are of use in the treatment of cancer diseases, in particular glioma. Further aspects of the invention pertain to pharmaceutical compositions as well as diagnostic methods based on the immunogenic capacity of the disclosed peptides.

Histone anti-cancer vaccines

The present invention covers 3-oxo-6-heteroaryl-2-phenyl-2,3-dihydropyri-dazine-4-carboxamide compounds of general formula (I): in which R, R, R, R, R, X, Y and Z are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer or conditions with dysregulated immune responses or other disorders associated with aberrant AHR signaling, as a sole agent or in combination with other active ingredients. 

3-oxo-6-heteroaryl-2-phenyl-2,3-dihydropyridazine-4-carboxamides

The present invention covers 2-phenylpyrimidine-4-carboxamide compounds of general formula (I): (I) 5 in which X, Y, Z, R1, R2, R4, R5 and R6 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer or conditions with 10 dysregulated immune responses or other disorders associated with aberrant AHR signaling, as a sole agent or in combination with other active ingredients. 

2-phenylpyrimidine-4-carboxamides as AHR inhibitors

Disclosed are compounds of general formula (I): wherein R, R, A, X, Y and Z are as defined herein, methods of preparing the compounds, intermediate compounds useful for preparing the compounds, pharmaceutical compositions and combinations comprising the compounds and the use of the compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer or conditions with dysregulated immune responses or other disorders associated with aberrant AHR signaling, as a sole agent or in combination with other active ingredients.

Sulphur substituted 3-oxo-2,3-dihydropyridazine-4-carboxamides

Tryptophan degradation is a key metabolic pathway controlling immune reactions and evidence suggests that during cancer progression generation of tryptophan metabolites may be fundamental for immune escape promoting the malignant phenotype of cancer cells in an autocrine fashion. The present invention relates to methods of measuring mass tag labelled tryptophan and metabolites thereof and methods using the labelled molecules for monitoring in a subject the effectiveness of a treatment and of disease recurrence after treatment, for stratifying patients and for diagnosing suppression of an immune response in a subject.

Isotopic methods for measurement of tryptophan and metabolites thereof

The present invention covers 2-hetarylpyrimidine-4-carboxamide compounds of general formula (I): in which X, Y, Z, R, Rand Rare as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer or conditions with dysregulated immune responses or other disorders associated with aberrant AHR signaling, as a sole agent or in combination with other active ingredients. 

2-hetarylpyrimidine-4-carboxamides as aryl hydrocarbon receptor antagonists

The present invention covers 3-oxo-2,6-diphenyl-2,3-dihydropyridazine-4-carboxamide compounds of general formula (I): in which R1, R2, R3, R4, R5 and R6 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer or conditions with 10 dysregulated immune responses or other disorders associated with aberrant AHR signaling, as a sole agent or in combination with other active ingredients. 

3-oxo-2,6-diphenyl-2,3-dihydropyridazine-4-carboxamides

The present invention concerns the field of tumor therapeutics and diagnostics. Specifically, it relates to a peptide comprising at least 8 amino acids in length which are present as contiguous amino acid sequence in the human Isocitratdehydrogenase Type 1 (IDH1), wherein said peptide has at least one amino acid exchange from R to H at a position corresponding to position 132, for use in preventing and/or treating cancer. Further contemplated is a medicament comprising the said peptide. Furthermore, the invention relates to a method for diagnosing cancer characterized by having a mutation in the genome of at least some cancer cells which results in the expression of a mutant IDH1 having the R132H mutation comprising the steps of contacting a blood sample of a subject suspected to suffer from such a cancer with a peptide comprising at least 10 amino acids in length which are present as contiguous amino acid sequence in the IDH1, wherein said peptide has at least one amino acid exchange from R to H at a position corresponding to position 132 for a time and under conditions which allow for specific binding of a component of the immune system to the peptide, and determining whether, or not, binding of the said component of the immune system to the peptide occurred, wherein the cancer is diagnosed if the occurrence of binding has been determined. Provided by the invention is also a kit and a device for carrying out said method.

Means and methods for treating or diagnosing IDH1 R132H mutant-positive cancers

The present invention relates to the field of cancer therapeutics and treatment of cancer. In particular, it relates to a method for treating and/or preventing a natural AHR ligand-dependent cancer comprising administering to a subject suffering from said cancer a therapeutically effective amount of an AHR inhibitor. Moreover, contemplated is a AHR inhibitor for use in treating and/or preventing a natural AHR ligand-dependent cancer.

Means and methods for treating and/or preventing natural AHR ligand-dependent cancer

The present invention provides methods for detecting changes in tryptophan concentrations in a cell and methods for identifying agents that modulate cellular tryptophan concentrations. In particular, the present invention provides methods for detecting cellular exchange between tryptophan and kynurenine, and methods for identifying agents that modulate this exchange. The present invention also provides methods for treating a disease associated with immunosuppression in a subject in need thereof. In particular, the present invention is directed toward a method of treating a disease associated with immunosuppression comprising contacting the disease with an agent that modulates cellular Trp/kynurenine exchange. Furthermore, the present invention provides methods for identifying an agent that modulates an immunosuppression.

TRP/HIS exchange and kynurenin induced TRP transport

Trp/his exchange and kynurenine induced Trp transport

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Heidelberg, Germany

Michael Platten