Abstract: The present disclosure relates to the development of drug delivery systems comprising single domain antibodies (sdAbs). For this purpose, antibody-drug conjugates (ADCs) are provided with high selectivity and efficiency to be used advantageously in cancer therapy, and a drug-delivery system targeting the central nervous system (CNS) pathologies. The ADC molecules developed for therapy, namely for cancer therapy are obtained from rabbit derived sdAbs comprising a potent cytotoxic payload, a SN38 small molecule conjugated with the free exposed cysteine at position 80, 23 or 88 of the VL framework. The drug delivery systems developed targeting the BBB endothelial cell receptors of the central nervous system (CNS) comprise rabbit derived single-domain antibodies (sdAb) conjugated at the surface of liposomes encapsulated with a suitable drug enabling an efficient blood-brain barrier (BBB) translocation. The respective process of production is also herein disclosed.

Abstract: The present invention relates to antibody molecules and peptide delivery systems for use in the treatment and management of Alzheimer's disease and related disorders. In particular, the antibody molecules preferentially bind oligomeric forms of beta-amyloid peptide, in single domain format, and the peptide delivery systems facilitate specific transport of such antibody molecules, as well as other cargo molecules, across the blood-brain barrier. The invention also relates to constructs of the antibody molecules and the delivery peptides, as well as pharmaceutical compositions comprising effective amounts of the antibody molecules, delivery peptides, and/or their constructs, including humanized versions of the antibody molecules and constructs.

Abstract: The present invention relates to antibody molecules and peptide delivery systems for use in the treatment and management of Alzheimer's disease and related disorders. In particular, the antibody molecules preferentially bind oligomeric forms of beta-amyloid peptide, in single domain format, and the peptide delivery systems facilitate specific transport of such antibody molecules, as well as other cargo molecules, across the blood-brain barrier. The invention also relates to constructs of the antibody molecules and the delivery peptides, as well as pharmaceutical compositions comprising effective amounts of the antibody molecules, delivery peptides, and/or their constructs, including humanized versions of the antibody molecules and constructs.

Abstract: The present invention relates to methods for screening and producing polypeptides that immunospecifically bind to an antigen, which polypeptides comprise binding domains that are derived from rabbit immunoglobulin. Using rabbit antibody heavy-chain or light-chain scaffolds, the methods of the invention allow identification of novel CDR loops and framework regions that confer enhanced stability and/or affinity to isolated immunoglobulin variable domains, in particular, relative to those derived from rodent antibodies. The enhanced stability and/or affinity of the variable domains of the invention permit their use in the production research tools or therapeutic immunospecific polypeptides, including single domain immunospecific polypeptides, i.e., comprising one of a VH or VL domain.

Abstract: The present invention relates to methods for screening and producing polypeptides that immunospecifically bind to an antigen, which: polypeptides comprise binding domains that are derived from rabbit immunoglobulin. Using rabbit antibody heavy-chain or light-chain scaffolds, the methods of the invention allow identification of novel CDR loops and framework regions that confer enhanced stability and/or affinity to isolated immunoglobulin variable domains, in particular, relative to those derived from rodent antibodies. The enhanced stability and/or affinity of the variable domains of the invention permit their use in the production research tools or therapeutic immunospecific polypeptides, including single domain immunospecific polypeptides, i.e., comprising one of a VH or VL domain.

Abstract: The present invention relates to antibody molecules and peptide delivery systems for use in the treatment and management of Alzheimer's disease and related disorders. In particular, the antibody molecules preferentially bind oligomeric forms of beta-amyloid peptide, in single domain format, and the peptide delivery systems facilitate specific transport of such antibody molecules, as well as other cargo molecules, across the blood-brain barrier. The invention also relates to constructs of the antibody molecules and the delivery peptides, as well as pharmaceutical compositions comprising effective amounts of the antibody molecules, delivery peptides, and/or their constructs, including humanized versions of the antibody molecules and constructs.

Abstract: The present invention relates to polypeptides comprising one or more antibody single domains, or antigen-binding fragments thereof, directed against Tumor Necrosis Factor-alpha, in particular, two light chain variable domains in dimeric form, where the dimer has high solubility. It also relates to methods of using anti-Tumor Necrosis Factor-alpha polypeptides in treating inflammatory disorders, including rheumatoid arthritis. Compositions and methods for enhancing therapeutic potential of anti-Tumor Necrosis Factor-alpha polypeptides are provided, including linking the polypeptide to an albumin-binding domain and/or de-immunizing the polypeptide, to provide therapeutic agents with good solubility, enhanced serum half-life, and/or reduced immunogenicity, while substantially maintaining the specific binding properties of the anti-Tumor Necrosis Factor-alpha polypeptides.

Abstract: The invention relates to cell-based methods for diversifying, expressing and selecting binding molecules, e.g., antibodies, and target molecules to which they bind, all of which are expressed in the same cell. The target molecule can be a member of a ligand binding pair comprising a cell-surface expressed ligand binding receptor molecule and its cognate ligand, which interact within the cell. The methods provide retaining either the antibody or its target in a cell organelle as the site of binding and interaction. By performance of the methods, the binding or non-binding of the antibody to its target molecule within the cell produces a cell phenotype that is detectable at the cell surface via high throughput assays, e.g., flow cytometry. The methods are particularly useful for generating, recovering and providing antibodies that have optimal target molecule binding properties or activities for potential therapeutic use. Methods for generating diversity in such antibodies are also provided.

Abstract: The present invention relates to polypeptides comprising one or more antibody single domains, or antigen-binding fragments thereof, directed against Tumor Necrosis Factor-alpha, in particular, two light chain variable domains in dimeric form, where the dimer has high solubility. It also relates to methods of using anti-Tumor Necrosis Factor-alpha polypeptides in treating inflammatory disorders, including rheumatoid arthritis. Compositions and methods for enhancing therapeutic potential of anti-Tumor Necrosis Factor-alpha polypeptides are provided, including linking the polypeptide to an albumin-binding domain and/or de-immunizing the polypeptide, to provide therapeutic agents with good solubility, enhanced serum half-life, and/or reduced immunogenicity, while substantially maintaining the specific binding properties of the anti-Tumor Necrosis Factor-alpha polypeptides.

Abstract: The present invention relates to compositions and methods comprising a modified albumin-binding domain to improve the pharmacokinetic properties of therapeutic molecules. The modified peptides show reduced immunogenicity and/or proved solubility. In particular, compositions and methods for enhancing therapeutic potential of protein therapeutics are provided including linking a protein albumin-binding domain, which has been modified to reduce immunogenicity and/or improve solubility, to a therapeutic protein, including therapeutic antibodies, antibody fragments, antibody single domains and/or dimers of antibody single domains. These linked polypeptides can exhibit enhanced serum half life without exacerbated immunogenicity and/or without decreased solubility, and without substantially affecting the specific binding properties of the therapeutic protein.

Abstract: The present invention relates to polypeptides comprising one or more antibody single domains, or antigen-binding fragments thereof, directed against Tumor Necrosis Factor-alpha, in particular, two light chain variable domains in dimeric form, where the dimer has high solubility. It also relates to methods of using anti-Tumor Necrosis Factor-alpha polypeptides in treating inflammatory disorders, including rheumatoid arthritis. Compositions and methods for enhancing therapeutic potential of anti-Tumor Necrosis Factor-alpha polypeptides are provided, including linking the polypeptide to an albumin-binding domain and/or de-immunizing the polypeptide, to provide therapeutic agents with good solubility, enhanced serum half-life, and/or reduced immunogenicity, while substantially maintaining the specific binding properties of the anti-Tumor Necrosis Factor-alpha polypeptides.

Abstract: The invention relates to cell-based methods for diversifying, expressing and selecting binding molecules, e.g., antibodies, and target molecules to which they bind, all of which are expressed in the same cell. The target molecule can be a member of a ligand binding pair comprising a cell-surface expressed ligand binding receptor molecule and its cognate ligand, which interact within the cell. The methods provide retaining either the antibody or its target in a cell organelle as the site of binding and interaction. By performance of the methods, the binding or non-binding of the antibody to its target molecule within the cell produces a cell phenotype that is detectable at the cell surface via high throughput assays, e.g., flow cytometry. The methods are particularly useful for generating, recovering and providing antibodies that have optimal target molecule binding properties or activities for potential therapeutic use. Methods for generating diversity in such antibodies are also provided.

Abstract: The present invention relates to methods for screening and producing polypeptides that immunospecifically bind to an antigen, which: polypeptides comprise binding domains that are derived from rabbit immunoglobulin. Using rabbit antibody heavy-chain or light-chain scaffolds, the methods of the invention allow identification of novel CDR loops and framework regions that confer enhanced stability and/or affinity to isolated immunoglobulin variable domains, in particular, relative to those derived from rodent antibodies. The enhanced stability and/or affinity of the variable domains of the invention permit their use in the production research tools or therapeutic immunospecific polypeptides, including single domain immunospecific polypeptides, i.e., comprising one of a VH or VL domain.