Abstract: The invention relates to antibodies specific for 4-1BB and OX40, as well as to methods for using such antibodies and therapeutic uses thereof.

Abstract: The present invention relates to compounds of formula I as defined herein. The compounds of the present invention are inhibitors of heat shock factor 1 (HSF1). In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

Abstract: The invention provides a compound of formula (I): or tautomer or a solvate or a pharmaceutically acceptable salt thereof, wherein the various substituents are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds.

Abstract: The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to 5-[[4-[[morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile compounds (referred to herein as “TFM compounds”) which, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc.

Abstract: The present invention relates to methods for identifying a subject with cancer who is suitable for treatment with an immune checkpoint intervention, and to methods of treatment of such subjects. The invention further relates to a method for predicting or determining the prognosis of a subject with cancer.

Abstract: Through a combination of in vitro and in vivo approaches, the inventors show that human IgG2 (h2) delivers unique Fc?R-independent agonistic activity to anti-CD40 antibodies and to antibodies specific to other immunostimulatory receptors, including 4-1BB and CD28. Investigation of an anti-human CD40 mAb, LOB7.4, revealed that the unique activity of h2 was dependent upon the precise arrangement of hinge and CH1 disulfide bonds. Chemical ‘shuffling’ or mutagenesis to ‘lock’ LOB7.4 into either a more flexible ‘h2A’ or more compact ‘h2B’ conformation endowed antagonistic and agonistic properties, respectively. Engineering of h2 in this way allows development of reagents with either immunostimulatory or immunosuppressive characteristics, with direct implication for the design of therapeutic mAb agents and fusion proteins.

Abstract: The present invention relates to compounds of formula I wherein R1, R4, Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1—also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

Abstract: The present invention relates to compounds of formula I as defined herein, and salts and solvates thereof, that function as inhibitors of cell division cycle 7 (Cdc7) kinase enzyme activity. The present invention also relates to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which Cdc7 kinase activity is implicated.

Abstract: The invention relates to antibodies specific for 4-1BB and OX40, as well as to methods for using such antibodies and therapeutic uses thereof.

Abstract: The present invention relates to compounds of formula I that function as inhibitors of PARG (Poly ADP-ribose glycohydrolase) enzyme activity: wherein R1a, R1b, R1c, R1d, R1e, W, X1, X2, X3, X4, X5, X6, X7, c are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which PARG activity is implicated.

Abstract: The invention provides a compound of formula (I): or tautomer or a solvate or a pharmaceutically acceptable salt thereof, wherein the various substituents are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds.

Abstract: A compound of Formula (I): or a pharmaceutically acceptable salt thereof, where: Q can be 1,2,4-triazin-3-yl, pyridazin-3-yl, 6-methylpyridazin-3-yl, or 6-fluoropyridazin-3-yl; R1 can be hydrogen, methoxy, trifluoromethoxy, oxetan-3-yl, 3-fluoroazetidin-1-yl, 3-methoxyazetidin-1-yl, or 3,3-difluoroazetidin-1-yl; R2 can be hydrogen or fluoro; R3 can be hydrogen or methoxy; and R4 can be methoxy, ethoxy, or methoxymethyl; provided that when R1 is hydrogen, methoxy or trifluoromethoxy, then R3 is not hydrogen, and/or R4 is methoxymethyl. The compound of formula (I) can inhibit glutaminase, e.g., GLS1.

Abstract: The invention relates to processes for preparing isoindolin-1-one derivatives, and in particular processes for preparing (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoic acid. The invention also relates to crystalline forms of the compound (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoic acid and its salts.

Abstract: The present invention relates to compounds of Formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, bonds a, b, c and d, X1, X2, X3, X4, R2, and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.

Abstract: The present application provides a compound of formula (I) or a salt thereof, wherein R1, R2, R3, R4, R5, R6, A, G, M, Q and X are as defined herein. A compound of formula (I) and its salts have a PKC inhibitory activity, and may be used to treat proliferative disorders.

Abstract: The invention provides a method of inhibiting angiogenesis in an individual, the method comprising administering to the individual an agent that inhibits the interaction between CLEC14A and MMRN2. The inhibitor may be an antibody, a polypeptide, a peptide, a polynucleotide, a peptidomimetic, a natural product, a carbohydrate, an aptamer or a small molecule.

Abstract: Certain pyrazolo[1,5-a]pyrimidine-5,7-diamine compounds that inhibit cycline dependent kinase (CDK) (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.) are disclosed. Pharmaceutical compositions comprising these compounds, and the use of these compounds and compositions to inhibit CDK; to treat disorders associated with CDK such as those arising from an inappropriate activity, mutation, overexpression, or upstream pathway activation of CDK; or disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections; neurodegenerative disorders; ischaemia; renal diseases; and cardiovascular disorders are also disclosed. Optionally, the treatment further comprises simultaneous or sequential treatment with a further active agent, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.

Abstract: The present invention relates to compounds of formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, X1, X2, X3, X4, integer a and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.

Abstract: The present invention provides a method for inducing a cancer specific immune response against MUC1 using an immunogenic glycopeptide. Other aspects of the invention are a pharmaceutical composition comprising the immunogenic glycopeptide and a cancer vaccine comprising the immunogenic glycopeptide. Another aspect is an antibody generated using the immunogenic glycopeptide and the use of said antibody in therapy and diagnosis.

Abstract: The present invention relates to compounds of formula (I), and salts and solvates thereof, that function as inhibitors of cell division cycle 7 (Cdc7) kinase enzyme activity: wherein X, R1, R2, and n are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which Cdc7 kinase activity is implicated.