Abstract: The invention provides methods of using sequence based analysis and rational strategies to modify and improve the structural and biophysical properties of single chain antibodies (scFvs), including stability, solubility, and antigen binding affinity. These methods and strategies can be used individually or in combination. The methods of the present invention also include the use of a database comprising scFv sequences from an experimentally screened scFv library of antibodies that have been selected to have superior solubility and stability. The invention also provides methods of using the properties found for these selected antibodies in a general approach for reshaping scFv antibodies to improve stability and solubility properties of a single chain antibody fragment.

Abstract: The present invention relates to an universal antibody acceptor framework and to methods for grafting non-human antibodies, e.g., rabbit antibodies, using a universal antibody acceptor framework. Antibodies generated by the methods of the invention are useful in a variety of diagnostic and therapeutic applications.

Abstract: The present invention relates to soluble and stable anti-VEGF immunobinders comprising CDRs from rabbit monoclonal antibodies. Said antibodies are designed for the diagnosis and/or treatment of VEGF-mediated disorders. The hybridomas, 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 invention provides methods for identifying immunobinders, such as scFv antibodies, capable of specifically binding to cell surface antigens, and compositions identified according to said methods.

Abstract: The present invention relates to an universal antibody acceptor framework and to methods for grafting non-human antibodies, e.g., rabbit antibodies, using a universal antibody acceptor framework. Antibodies generated by the methods of the invention are useful in a variety of diagnostic and therapeutic applications.

Abstract: The invention provides methods of using sequence based analysis and rational strategies to modify and improve the structural and biophysical properties of single chain antibodies (scFvs), including stability, solubility, and antigen binding affinity. These methods and strategies can be used individually or in combination. The methods of the present invention also include the use of a database comprising scFv sequences from an experimentally screened scFv library of antibodies that have been selected to have superior solubility and stability. The invention also provides methods of using the properties found for these selected antibodies in a general approach for reshaping scFv antibodies to improve stability and solubility properties of a single chain antibody fragment.

Abstract: The invention provides methods for identifying immunobinders, such as scFv antibodies, capable of specifically binding to cell surface antigens, and compositions identified according to said methods.

Abstract: The invention provides antibodies that are modified to reduce aggregration propensity, and methods of producing such antibodies. The present invention also provides 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. 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: The present invention relates to soluble and stable anti-VEGF immunobinders comprising CDRs from rabbit monoclonal antibodies. Said antibodies are designed for the diagnosis and/or treatment of VEGF-mediated disorders. The hybridomas, 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: The invention provides methods of using sequence based analysis and rational strategies to improve the solubility of immunobinders, and in particular of single chain antibodies (scFvs). The invention provides methods of engineering immunobinders, and in particular scFvs, by performing one or more substitutions with hydrophilic residues identified by analysis of a database of selected, stable scFv sequences. The invention also provides immunobinders with optimized solubility prepared according to the engineering methods of the invention.

Abstract: The invention provides functionalized polypeptides, especially therapeutic polypeptides (e.g., scFv), comprising a linker sequence that can be rapidly and specifically functionalized by the addition of one or functional moieties (e.g., PEG) or binding specificities (e.g., an amino acid sequence with a particular binding specificity). Such functionalized polypeptides are advantageous in that they have improved pharmacokinetic properties (e.g., improved in vivo half-life, tissue penetration and tissue residency time) over non-functionalized polypeptides. Methods for the rapid and reproducible generation of functionalized polypeptides are also provided.

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-mediated 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: A method for decreasing the immunogenicity of antibody variable domains is disclosed.

Abstract: The invention provides compositions and methods that enhance the delivery of large macromolecules (i.e., greater than 10 kDa), such as antigen-binding polypeptides, across tight junctions. Such methods and compositions are particularly useful for delivering therapeutic antigen-binding polypeptides to the CNS, via intranasal administration, for the treatment of neurological disorders.

Abstract: The present invention relates to an universal antibody acceptor framework and to methods for grafting non-human antibodies, e.g., rabbit antibodies, using a universal antibody acceptor framework. Antibodies generated by the methods of the invention are useful in a variety of diagnostic and therapeutic applications.

Abstract: An in vivo method for the construction of randomized gene libraries and/or domain replacement in gene libraries by homologous recombination using a Kluyveromyces lactis killer toxin, in particular the ?-subunit of the K. lactis killer toxin, as negative selection marker is described. The use of the ?-subunit of K. lactis as negative selectable marker increases the percentage of randomized clones.

Abstract: An in vivo method for the construction of randomized gene libraries and/or domain replacement in gene libraries by homologous recombination using a Kluyveromyces lactis killer toxin, in particular the (?-subunit of the K. lactis killer toxin, as negative selection marker is described. The use of the (?-subunit of K. lactis as negative selectable marker increases the percentage of randomized clones.