Cyclacel Limited

Ian Fleming

Simon Richard Green

Eric Raymond

Ruth Mackay

Sheelagh Frame

Simon Green

The present invention relates to combination comprising (i) an ErbB inhibitor; and (ii) a CDK inhibitor, or a pharmaceutically acceptable salt thereof, selected from: (a) roscovitine; (b) 3-{9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]-9H-purin-2-ylamino}-2-methyl-pentan-2-ol; (c) 3-{9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]-9H-purin-2-ylamino}-pentan-2-ol; and (d) (2R,3S-3-(6-((4,6-dimethylpyridin-3-ylmethylamino)-9-isopropyl-9H-purin-2-ylamino)pentan-2-ol. Further aspects of the invention relate to pharmaceutical products and pharmaceutical compositions comprising combinations according to the invention, and methods of treatment using the same.

Combination of a purine-based CDK inhibitor with a tyrosine kinase inhibitor and use thereof in the treatment of proliferative disorders

A first aspect of the invention relates to a combination comprising a DNA methyltransferase inhibitor and 1-(2-C-cyano-2-dioxy-&#x3b2;-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof. A second aspect of the invention relates to a pharmaceutical product comprising a DNA methyltransferase inhibitor and 1-(2-C-cyano-2-dioxy-&#x3b2;-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof, as a combined preparation for simultaneous, sequential or separate use in therapy. A third aspect of the invention relates to a method of treating a proliferative disorder, said method comprising simultaneously, sequentially or separately administering a DNA methyltransferase inhibitor and 1-(2-C-cyano-2-dioxy-&#x3b2;-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof, to a subject.

Combinations of sapacitabine or CNDAC with DNA methyltransferase inhibitors such as decitabine and procaine

A first aspect of the invention relates to a combination comprising 2'-cyano-2&#x2032;-deoxy-N-palmitoyl-1-&#x3b2;-D-arabinofuranosyl-cytosine, or a metabolite thereof, or a pharmaceutically acceptable salt thereof, and a cytotoxic agent selected from: (a) a HDAC inhibitor; and (b) a topoisomerase inhibitor selected from etoposide, topotecan and SN-38, or a prodrug thereof. A second aspect relates to a pharmaceutical product comprising (i) 2&#x2032;-cyano-2&#x2032;-deoxy-N-palmitoyl-1-&#x3b2;-D-arabinofuranosyl-cytosine, or a metabolite thereof, or a pharmaceutically acceptable salt thereof, and (ii) a cytotoxic agent selected from: (a) a HDAC inhibitor; and (b) a topoisomerase inhibitor selected from etoposide, topotecan and SN-38, or a prodrug thereof, as a combined preparation for simultaneous, sequential or separate use in therapy. A third aspect relates to a method of treating a proliferative disorder, said method comprising simultaneously, separately or sequentially administering to a subject 2&#x2032;-cyano-2&#x2032;-deoxy-N-palmitoyl-1-&#x3b2;-D-arabinofuranosyl-cytosine, or a metabolite thereof, or a pharmaceutically acceptable salt thereof, and a cytotoxic agent selected from: (a) a HDAC inhibitor; and (b) a topoisomerase inhibitor selected from etoposide, topotecan and SN-38, or a prodrug thereof. A fourth aspect of the invention relates to the use of a subject 2&#x2032;-cyano-2&#x2032;-deoxy-N-palmitoyl-1-&#x3b2;-D-arabinofuranosyl-cytosine, or a metabolite thereof, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for treating cutaneous T-cell lymphoma (CTCL).

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Angus, United Kingdom

Ian Fleming