Janssen Pharmaceutica Nv

Dirk Brehmer

Tongfei Wu

Lieven Meerpoel

Vineet Pande

Johannes Wilhelmus John F Thuring

Weimei Sun

Lijs Beke

Edward Charles Lawson

Gaston Stanislas Marcella Diels

Marcel Viellevoye

An Boeckx

Wim Bert Griet Schepens

Marcus Cornelis Bernardus Catharina Paradé

Ronaldus Arnodus Hendrika Joseph Gilissen

Scott E Denmark

Guido Alfons F Verniest

Jonas Verhoeven

Dana Suzanne Gaffney

Christopher H Moy

Didier Jean-Claude Berthelot

Brian Christopher Shook

Kathryn Elizabeth Packman

Hong Xie

Hillary Joy Millar Quinn

Nahor Haddish-Berhane

Geert S J Mannens

Junguo Zhou

Anthony T Greway

Yue Guo

Josh Lauring

Marcus Cornelius Bernardus Catharina Parade

The present disclosure describes methods of identifying a patient that is likely to be responsive to treatment with a protein arginine N-methyltransferase 5 (PRMT5) inhibitor. The methods include evaluating a biological sample from the patient for the presence of a spliceosome mutation or alteration, wherein the presence of the alteration indicates a higher likelihood for the patient to be responsive to treatment with the PRMT5 inhibitor than in the absence of the mutation or alteration.

Use of biomarkers in identifying cancer patients that will be responsive to treatment with a PRMT5 inhibitor

The present invention relates to novel monocyclic and bicyclic ring system substituted carbanucleoside analogues of Formula (I), wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as PRMT5 inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

Monocyclic and bicyclic ring system substituted carbanucleoside analogues for use as PRMT5 inhibitors

The present invention relates to novel spirobicyclic analogues of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as PRMT5 inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

Spirobicyclic analogues

The present disclosure provides methods for treating a human patient diagnosed with a cancer, comprising administering a therapeutically effective amount of a PRMT5 (protein arginine methyltransferase 5) inhibitor, certain methods comprising (i) administering to the patient initial doses of at least about 0.1 mg per day of the PRMT5 inhibitor that is (1S,2R,3S,5R)-3-(2-(2-amino-3-bromoquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol or a pharmaceutically acceptable addition salt or solvate thereof for an initial dosing period of about 5 to about 21 days; and (ii) administering to the patient subsequent doses of at least about 0.1 mg per day of the PRMT5 inhibitor for one or more subsequent dosing periods of about 5 to about 21 days each. In these methods, a first subsequent dosing period is separated in time from the initial dosing period by at least about 5 days and the subsequent dosing periods are separated in time from each other by at least about 5 days.

Methods of treating cancer using PRMT5 inhibitors

Embodiments of the present invention relate to 6-6 bicyclic aromatic ring substituted nucleoside analogues, including, for example, the following compound:  Embodiments of the present invention also relate to uses of the disclosed compounds for the inhibition of protein arginine methyltransferase 5 (PRMT5).

6-6 bicyclic aromatic ring substituted nucleoside analogues for use as PRMT5 inhibitors

The present invention relates to novel novel monocyclic and bicyclic ring system substituted carbanucleoside analogues of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as PRMT5 inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

The present invention relates to novel spirobicyclic analogues of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as PRMT5 inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament. 

The present invention relates novel substituted nucleoside analogues of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as PRMT5 inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

Substituted nucleoside analogues for use as PRMT5 inhibitors

Embodiments of the present invention relate to 6-6 bicyclic aromatic ring substituted nucleoside analogues, including, for example, the following compound: Embodiments of the present invention also relate to uses of the disclosed compounds for the inhibition of protein arginine methyltransferase 5 (PRMT5).

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Freiburg, Germany

Dirk Brehmer