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 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 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 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.