Abstract: The present invention concerns an antibody specific for human ALK (Anaplastic Lymphoma Kinase), in particular a scFv, a nucleic acid sequence encoding it, its production and its use as a pharmaceutical or for diagnostic purposes. Said antibody is suitable for the local treatment of tumors, in particular glioblastoma.

Abstract: A method for the isolation of CDRs in a defined framework that is stable and soluble in reducing environment is described as well as thus obtainable scFv. Starting from such scFv with defined framework a scFv library can be generated wherein the framework is conserved while at least one complementary determining region (CDR) is randomized. Such library, e.g. in yeast cells, is suitable for screening for antibody/CDR-interactions or for screening for antibodies.

Abstract: A method for the isolation of CDRs in a defined framework that is stable and soluble in reducing environment is described as well as thus obtainable scFv. Starting from such scFv with defined framework a scFv library can be generated wherein the framework is conserved while at least one complementary determining region (CDR) is randomized. Such library, e.g. in yeast cells, is suitable for screening for antibody/CDR-interactions or for screening for antibodies.

Abstract: The present invention relates to angiogenesis inhibitors, in particular receptor tyrosine kinase inhibitors, and their use for the treatment of hyperproliferative diseases, angiogenesis and disorders depending on angiogenesis such as tumour forming cancers. It also relates to a method of inhibiting angiogenesis or treating a vascular anomaly in a mammal comprising administering to the mammal an amount of an Eph receptor inhibitor which is effective for inhibiting angiogenesis or for treating the vascular anomaly in the mammal. Further, the present invention relates to the use of compounds for the treatment of angiogenesis related disorders involving a protein kinase, preferably a tyrosine kinase, and to some specific forms of said compounds as a medicament. Compounds useful in the practice of the invention have the general formula I wherein R1, R2, R3, R4 and R5 are as defined in the specification.

Abstract: The present invention relates to a cellular screening method for the identification of modulators of secretases. Said method comprises contacting suitable host cells with a test substance wherein said suitable host cells comprise: a) a fusion protein secretory protein, a membrane anchor domain and a secrease cleavage sequence, b) a protein comprising a secretase activity recognising said cleavage sequence of said fusion protein and a) at least one reporter gene under control of a transcriptional activation system wherein said transcriptional activation system is regulated by the release of said secretory protein from said fusion protein by said secretase activity and its subsequent secretion then culturing said cells under suitable conditions such that said reporter gene allowing detection and/or survival of cells is only expressed or repressed in a manner that is dependent on an altered secretase activity due to said test substance.

Abstract: Compositions are provided, which can be used as frameworks for the creation of very stable and soluble single-chain Fv antibody fragments. These frameworks have been selected for intracellular performance and are thus ideally suited for the creation of scFv antibody fragments or scFv antibody libraries for applications where stability and solubility are limiting factors for the performance of antibody fragments, such as in the reducing environment of a cell. Such frameworks can also be used to identify highly conserved residues and consensus sequences which demonstrate enhanced solubility and stability.

Abstract: The properties of yeast help, a type I ER membrane protein which is involved in the unfolded protein response (UPR), have been exploited to develop â. system for the detection and study of interactions between extracellular and/or membrane proteins. In the system, proteins of interest are fused to the lumenal N-terminus of a truncated Ire1p. A specific interaction between two partners may be visualized through dimerization of the Ire1p moiety which, either, directly or indirectly, results in a detection means, for example, the expression of a selectable reporter gene. Depending on the type of reporter gene used, its expression can positively or negatively influence cell growth, thus allowing selection of both stimulation and inhibition of protein-protein interactions. The system presented here can also be used to study intracellular protein interactions.

Abstract: An in vivo method for the identification and/or validation of receptor tyrosine kinase inhibitors is described. Said method is characterised by the following steps: providing host cells comprising a nucleic acid construct encoding a peptide which comprises a tyrosine kinase domain of a receptor tyrosine kinase wherein said peptide lacks a transmembrane domain or a functional fragment thereof and said tyrosine kinase activity in the cytoplasma leads to proliferation arrest, contacting said host cells with a candidate compound and identification of inhibitors of said tyrosine kinase activity by cultivation of said host cells under suitable conditions such that the modulation of the tyrosine kinase activity by the candidate compound leads to cell growth.

Abstract: The present invention concerns a screening system for screening effector peptides that can act as agonists or antagonists, as well as means to produce such a screening system, in particular a specific DNA library encoding peptides. In order to perform the screening, host cells comprising a selection system are transformed with the DNA library and the thus obtained screening system is then cultivated under conditions selectively allowing survival of cells with desired interaction.

Abstract: A method for the isolation of CDRs in a defined framework that is stable and soluble in reducing environment is described as well as thus obtainable scFv. Starting from such scFv with defined framework a scFv library can be generated wherein the framework is conserved while at least one complementary determining region (CDR) is randomized. Such library, e.g. in yeast cells, is suitable for screening for antibody/CDR-interactions or for screening for antibodies.

Abstract: A method for the isolation of CDRs in a defined framework that is stable and soluble in reducing environment is described as well as thus obtainable scFv. Starting from such scFv with defined framework a scFv library can be generated wherein the framework is conserved while at least one complementary determining region (CDR) is randomized. Such library, e.g. in yeast cells, is suitable for screening for antibody/CDR-interactions or for screening for antibodies.