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: scFv antibodies which specifically bind selected antigens and are obtainable by a method comprising (i) selecting from a pool of soluble and stable antibody frameworks a soluble and stable framework matching best the framework of a non-human antibody against the antigen with a certain binding specificity, (ii) either providing said soluble and stable framework with CDRs that bind specifically to said antigen, or mutating the framework of said non-human antibody towards the sequence of said soluble and stable framework, to generate scFv antibodies, (iii) testing the generated antibody for solubility and stability, and testing the generated antibody for antigen binding, and (iv) selecting an scFV that is soluble, stable and binds to the antigen specifically. Also provided are pharmaceutical compositions comprising said scFv antibody, methods of treatment and diagnosis for diseases related to over expression of antigens that are specifically bound by said antibody.

Abstract: The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNF?, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNF?, and low immunogenicity. Said antibodies are designed for the diagnosis and/or treatment of TNF?-related disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of said antibodies in medicine are also disclosed.

Abstract: The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNF?, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNF?, and low immunogenicity. Said antibodies are designed for the diagnosis and/or treatment of TNF?-related disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of said antibodies in medicine are also disclosed.

Abstract: Provided in some embodiments are compositions comprising a compound having a structure according to Formula A or Formula B: or a pharmaceutically acceptable salt, tautomer or hydrate thereof, where X2 is a bond or linker, X3 is bond or —PO4—, and X1, R1, R2, R3, and n are described herein. Also provided in some embodiments are methods for making and using such compounds and compositions.

Abstract: Provided in some embodiments are compositions comprising a compound having a structure according to Formula A or Formula B: or a pharmaceutically acceptable salt, tautomer or hydrate thereof, where X2 is a bond or linker, X3 is bond or —PO4—, and X1, R1, R2, R3, and n are described herein. Also provided in some embodiments are methods for making and using such compounds and compositions.

Abstract: Provided in some embodiments are compositions comprising a compound having a structure according to Formula A or Formula B: or a pharmaceutically acceptable salt, tautomer or hydrate thereof, where X2 is a bond or linker, X3 is bond or —PO4—, and X1, R1, R2, R3, and n are described herein. Also provided in some embodiments are methods for making and using such compounds and compositions.

Abstract: The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNF?, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNF?, and low immunogenicity. Said antibodies are designed for the diagnosis and/or treatment of TNF?-related disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of said antibodies in medicine are also disclosed.

Abstract: Provided herein are methods for treating certain conditions, including fibrosis, inflammatory, and autoimmune conditions, with conjugated compounds having Toll-like receptor modulatory activity.

Abstract: The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNF?, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNF?, and low immunogenicity. Said antibodies are designed for the diagnosis and/or treatment of TNF?-related disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of said antibodies in medicine are also disclosed.

Abstract: Provided in some embodiments are compositions comprising a compound having a structure according to Formula A or Formula B: or a pharmaceutically acceptable salt, tautomer or hydrate thereof, where X2 is a bond or linker, X3 is bond or —PO4—, and X1, R1, R2, R3, and n are described herein. Also provided in some embodiments are methods for making and using such compounds and compositions.

Abstract: Provided in some embodiments are methods for inducing an antigen-specific immune response in a subject, comprising administering a compound having a structure according to Formula A or Formula B: or a pharmaceutically acceptable salt, tautomer or hydrate thereof, where X2 is a bond or linker, X3 is —PO4—, and X1, R1, R2, R3, and n are described herein. Also provided in some embodiments are methods for making and using such compounds and compositions.

Abstract: The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNF?, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNF?, and low immunogenicity. Said antibodies are designed for the diagnosis and/or treatment of TNF?-related disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of said antibodies in medicine are also disclosed.

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: 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: scFv antibodies which specifically bind selected antigens and are obtainable by a method comprising (i) selecting from a pool of soluble and stable antibody frameworks a soluble and stable framework matching best the framework of a non-human antibody against the antigen with a certain binding specificity, (ii) either providing said soluble and stable framework with CDRs that bind specifically to said antigen, or mutating the framework of said non-human antibody towards the sequence of said soluble and stable framework, to generate scFv antibodies, (iii) testing the generated antibody for solubility and stability, and testing the generated antibody for antigen binding, and (iv) selecting an scFV that is soluble, stable and binds to the antigen specifically. Also provided are pharmaceutical compositions comprising said scFv antibody, methods of treatment and diagnosis for diseases related to over expression of antigens that are specifically bound by said antibody.

Abstract: The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNF?, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNF?, and low immunogenicity. Said antibodies are designed for the diagnosis and/or treatment of TNF?-related disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of said antibodies in medicine are also disclosed.

Abstract: An in vivo method for the identification and/or validation of receptor tyrosine kinase inhibitors is described. Said method is characterized 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 tester protein for identifying and/or monitoring protease activity in a cellular assay suitable for high throughput screenings by growth selection, wherein the tester polypeptide is a non-regulatory protein carrying a protease cleavage sequence. Upon co-expression of the protease recognizing said cleavage sequence the tester protein is inactivated, which influences the growth and/or survival of the host cells under the chosen conditions. However, in the presence of protease inhibitor the growth phenotype is reversed. The system can be used to identify proteases, protease inhibitors, and protease cleavage sites.

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.