Cyclacel Limited

Janssen Pharmaceutica Nv

International Rectifier Corporation

Cancer Research Technology Limited

Simon Richard Green

Lieven Meerpoel

Janusz Jozef Kulagowski

George Hynd

Olivier Alexis Georges Querolle

Calum MacLeod

Edgar Jacoby

Samuel Edward Mann

Ian Stansfield

Gerhard Max Gross

Ian Fleming

Yannick Aime Eddy Ligny

Sheelagh Frame

Ruth Mackay

Virginie Sophie Poncelet

Roger Kingdon Craig

Edward McDonald

Peter William Sheldrake

Hugo R Burke

John Colyer

Calum Macleod

Judy H Chiao

Butrus Atrash

Susan Davis

Yannick Aimé Eddy Ligny

Daniella I Zheleva

Geoffrey I Shapiro

David Blake

Roger Neil Sleigh

Olivier Alexis Querolle

Ian Neil Fleming

The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-&#x3ba;B-inducing kinase (NIK&#x2014;also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.

Cyanoindoline derivatives as NIK inhibitors

The present invention relates to pharmaceutical agents of formula (I) useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-B-inducing kinase (NIK&#x2014;also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders. 

Substituted cyanoindoline derivatives as NIK inhibitors

Heteroaromatic derivatives as NIK inhibitors

The present invention relates to pharmaceutical agents of formula (I), useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-&#x3ba;B-inducing kinase (NIK&#x2014;also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as a cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders. 

6-membered heteroaromatic substituted cyanoindoline derivatives as NIK inhibitors

A first aspect of the invention relates to a method of treating a proliferative disorder in a subject, said method comprising administering to the subject a therapeutically effective amount of (i) sapacitabine, or a metabolite thereof; and (ii) seliciclib; in accordance with a dosing regimen comprising at least one first treatment cycle and at least one second treatment cycle, wherein said first treatment cycle comprises: (a) administering a therapeutically effective amount of sapacitabine, or a metabolite thereof, for 3 to 5 consecutive days for 2 weeks, starting on day d, where d is the first day of treatment with sapacitabine, or the metabolite thereof, in said first treatment cycle; and (b) optionally administering a therapeutically effective amount of seliciclib for 3 to 5 consecutive days for 2 weeks, starting on day (d&#x2212;1) relative to the administration of sapacitabine or the metabolite thereof, in said first treatment cycle; followed by a rest period of at least 2 weeks, or until treatment-related toxicities are resolved, whichever is longer; and wherein said second treatment cycle comprises: (a) administering a therapeutically effective amount of sapacitabine, or a metabolite thereof, for 3 to 5 consecutive days for 2 weeks, starting on day d, where d is the first day of treatment with sapacitabine, or the metabolite thereof, in said second treatment cycle; and (b) administering a therapeutically effective amount of seliciclib for 3 to 5 consecutive days for 2 weeks, starting on day (d&#x2212;1) relative to the administration of sapacitabine or the metabolite thereof, in said second treatment cycle; followed by a rest period of at least 2 weeks, or until treatment-related toxicities are resolved, whichever is longer. Further aspects of the invention relate to a kit of parts, and corresponding uses.

Dosage regimen for sapacitabine and seliciclib

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

The present invention relates to compounds of formula (I) wherein: where one of X, Y and Z is N and the remainder are CR; A further aspect of the invention relates to pharmaceutical compositions comprising compounds of formula (I), and the use of said compounds in treating proliferative disorders, viral disorders, stroke, alopecia, CNS disorders, neurodegenerative disorders, or diabetes.

Trisubstituted purine derivatives

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).

Combination comprising CNDAC (2'-cyano-2&#x2032;-deoxy-N4-palmitoyl-1-beta-D-arabinofuranosyl-cytosine) and a cytotoxic agent

A first aspect of the invention relates to a combination comprising a CDK 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 CDK 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 CDK inhibitor and 1-(2-C-cyano-2-dioxy-&#x3b2;-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof, to a subject.

Combination of a CDK inhibitor and CS-682 or a metabolite thereof

The size of BVdistribution is controlled by the active manipulation of the distribution of silicon parameters across a wafer to offset opposing effects inherent in the wafer fabrication process. Thus, the resistivity of the silicon wafer is increased toward the edge of the wafer. This offsets the drop-off of BVacross the wafer caused in wafer fabrication by deeper trenches at the edge of the wafer. This causes a flatter BVprofile across the wafer and significantly reduced BV distribution over the wafer.

Process to control semiconductor wafer yield

A power semiconductor device that includes a plurality of gate structure each having a gate insulation of a first thickness, and a termination region, the termination including a field insulation body surrounding the active region and having a recess that includes a bottom insulation thicker than the first thickness.

Power semiconductor device

A method is provided for measuring in vivo in a transgenic non-human multicellular organism the activity of a cellular enzyme, which organism is transgenic by virtue of comprising one or more nucleic acid constructs encoding a binding domain and a binding partner thereof wherein: (i) the binding domain and/or binding partner comprise a site subject to post-translational modification by the cellular enzyme; (ii) modification of the site by the enzyme affects the interaction between the binding domain and the binding partner; and (iii) the binding domain and the binding partner each comprise a detectable label such that when the binding domain and binding partner interact, a detectable physical characteristic of one or both of the labels is altered, which method comprises measuring the interaction between the binding domain and the binding partner by measuring changes in the physical characteristic in one or more cells of the transgenic organism. A transgenic non-human multicellular organism is also provided.

Assay for measuring enzyme activity in vivo

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Cardiff, United Kingdom

Simon Richard Green