Abstract: The tricyclic heterocycles disclosed herein are useful as TEAD binders and/or inhibitors of YAP-TEAD and TAZ-TEAD protein-protein interaction or binding and for the prevention and/or treatment of several medical conditions including hyperproliferative disorders and diseases, in particular cancer.

Abstract: Tricyclic heterocycles are disclosed. These heterocyclic compounds are useful as TEAD binders and/or inhibitors of YAP-TEAD and TAZ-TEAD protein-protein interaction or binding and for the prevention and/or treatment of several medical conditions including hyperproliferative disorders and diseases, in particular cancer.

Abstract: Methods for treating hedgehog pathway-dependent cancers are provided. Aspects of the methods include the inhibition of hedgehog pathway-dependent cancer growth, proliferation, or metastasis that is promoted by hedgehog pathway signaling. In particular, methods of treating hedgehog pathway-dependent cancers with inhibitors of atypical protein kinase C iota are disclosed.

Abstract: Anti-CD19 B4 antibodies with modified variable regions are disclosed. The modified anti-CD19 variable region polypeptides have alterations to one or more framework regions or complementarity determining regions of the heavy chain variable region or light chain variable region, thereby to reduce a T-cell response.

Abstract: The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

Abstract: The present invention provides a method for targeted cell retrieval, comprising: providing a population of barcoded cells, said population comprising a plurality of different barcodes, each of the plurality of different barcodes being uniquely targetable with a target-specific CRISPR RNA; introducing a CRISPR-Cas system, or one or more vectors encoding the components of the CRISPR-Cas system, into the population of barcoded cells said CRISPR-Cas system having a target-specific CRISPR RNA that targets a first barcode of said plurality of different barcodes, thereby causing a CRISPR-Cas system-mediated change at a target site leading to a change in one or more detectable properties of at least one cell carrying said first barcode; and retrieving said at least one cell carrying said first barcode based on the change in said one or more detectable properties. Also provided are products and kits for use in the method of the invention.

Abstract: The present invention relates to dietary product comprising a plurality of amino acids, wherein the dietary product comprises all the essential amino acids and wherein the dietary product is substantially devoid of asparagine, processes of preparation of the product and methods and uses thereof in therapeutic applications such as the treatment of cancer.

Abstract: Chemokine receptor CCR4 and its ligands CCL17 and CCL22 are used as markers for the identification and/or staging of cancer. The level of CCR4, CCL17 and CCL22 are found to increase during malignant tumour progression. CCR4, CCL17 and CCL22 are used as markers for the stratification of cancer patients according to their suitability for treatment with anti-cancer agents. Information of diagnostic character is provided by measuring the level of one or more of CCR4, CCL17 and CCL22 present in a patient sample. Methods of treatment of cancer patients which agents that modulate the activity of CCR4, CCL17 and CCL22. Methods of screening for agents which modulate the biological activities of CCR4, CCL17 and CCL22 provide anti-cancer agents.

Abstract: The invention provides novel substituted indazole compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases such as cancer, inflammatory or degenerative diseases.

Abstract: Chemokine receptor CCR4 and its ligands CCL1 7 and CCL22 are used as markers for the identification and/or staging of cancer. The level of CCR4, CCL17 and CCL22 are found to increase during malignant tumor progression. CCR4, CCL17 and CCL22 are used as markers for the stratification of cancer patients according to their suitability for treatment with anti-cancer agents. Information of diagnostic character is provided by measuring the level of one or more of CCR4, CCL 17 and CCL22 present in a patient sample. Methods of treatment of cancer patients which agents that modulate the activity of CCR4, CCL17 and CCL22. Methods of screening for agents which modulate the biological activities of CCR4, CCL 17 and CCL22 provide anti-cancer agents.

Abstract: The present invention relates to pyridine and pyrimidine based compounds, pharmaceutical compositions comprising these compounds and their potential use as therapeutic agents for the treatment and/or prevention of cancer.

Abstract: Compounds of formula (1) are inhibitors of HSP90 activity in vitro or in vivo, and of use in the treatment of inter alia, cancer: wherein R2 is a group of formula —(Ar1)m-(Alk1)P-(Z)r-(Alk2)S-Q wherein Ar1 is an optionally substituted aryl or heteroaryl radical, Alk? and Alk 2 are optionally substituted divalent C1-C3 alkylene or C2-C3 alkenylene radicals, m, p, r and s are independently 0 or 1, Z is —O—, —S—, —(C?O)—, —(C?S)—, —SO2—, —C(?O)O—, —C(?O)NRA—, —C(?S)NRA—, —SO2NRA—, —NRAC(?O)—, —NRASO2— or —NRA— wherein RA is hydrogen or C1-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R3 is hydrogen, an optional substituent, or an optionally substituted (C1-C6)alkyl, aryl or heteroaryl radical; and R4 is a carboxylic ester, carboxamide or sulfonamide group.

Abstract: Isoxazoles of formula (A) or (B) wherein R1 is a group of formula (IB) The isoxazoles are inhibitors of HSP90 activity, and useful for the treatment of, for example, cancers.

Abstract: The present invention relates to nucleotide sequences of vertebrate Delta genes, and amino acid sequences of their encoded proteins, as well as derivatives (e.g., fragments) and analogs thereof. In a specific embodiment, the vertebrate Delta protein is a human protein. The invention further relates to fragments (and derivatives and analogs thereof) of Delta which comprise one or more domains of the Delta protein, including but not limited to the intracellular domain, extracellular domain, DSL domain, domain amino-terminal to the DSL domain, transmembrane region, or one or more EGF-like repeats of a Delta protein, or any combination of the foregoing. Antibodies to Delta, its derivatives and analogs, are additionally provided. Methods of production of the Delta proteins, derivatives and analogs, e.g., by recombinant means, are also provided. Therapeutic and diagnostic methods and pharmaceutical compositions are provided.

Abstract: Isoxazoles of formula (A) or (B) wherein R1 is a group of formula (IB) The isoxazoles are inhibitors of HSP90 activity, and useful for the treatment of, for example, cancers.

Abstract: The present invention provides a pharmaceutical composition which is useful as a phosphatidylinositol 3 kinase (PI3K) inhibitor and an antitumor agent, and it provides a novel bicyclic or tricyclic fused heteroaryl derivative or a salt thereof which possesses an excellent PI3K inhibiting activity and cancer cell growth inhibiting activity.

Abstract: The invention relates to the use of a polypeptide that comprises i) a first portion comprising the part of human Fc that binds to CD64, and ii) a second portion comprising one or more heterologous T cell epitopes for stimulating a cytotoxic T cell response. The polypeptide may be an antibody that may be used to stimulate a cytotoxic T cell response against pathogens and tumour cells in patients in need of such treatment.

Abstract: The present invention concerns the discovery that proteins encoded by a family of vertebrate genes, termed here hedgehog-related genes, comprise morphogenic signals produced by embryonic patterning centers, and are involved in the formation of ordered spatial arrangements of differentiated tissues in vertebrates. The present invention makes available compositions and methods that can be utilized, for example to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

Abstract: Compounds of formula (1) are inhibitors of HSP90 activity in vitro or in vivo, and of use in the treatment of inter alia, Cancer: wherein R2 is a group of formula —(Ar1)m-(Alk1)P-(Z)r-(Alk 2)S-Q wherein Ar1 is an optionally substituted aryl or heteroaryl radical, Alk? and Alk 2 are optionally substituted divalent C1-C3 alkylene or C2-C3 alkenylene radicals, m, p, r and s are independently 0 or 1, Z is —O—, —S—, —(C?O)—, —(C?S)—, —SO2—, —C(?O)O—, —C(?O)NRA—, —C(?S)NRA—, —SO2NRA—, —NRAC(?O)_, —NRASO2- or —NRA—wherein RA is hydrogen or C1-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R3 is hydrogen, an optional substituent, or an optionally substituted (C1-C6)alkyl, aryl or heteroaryl radical; and R4 is a carboxylic ester, carboxamide or sulfonamide group.

Abstract: Described are peptides and polypeptides derived from the MUC-1 polypeptide which are able to activate Cytotoxic T Lymphocyte (CTL) response, analogues of such peptides and polypeptides nucleotide sequences encoding such peptides and polypeptides and therapeutic uses thereof. Moreover, indications for selecting appropriate minimal antigenic MUC-1 polypeptides with reference to the HLA-type of the patient to be treated or tested are described.