Compounds and molecular complexes comprising multiple binding regions directed to transcytotic ligands
First Claim
1. A multimeric molecular complex comprising at least 2 compounds, each compound comprising at least one targeting element directed to a ligand that confers transcytotic or paracellular transporting properties to a molecular complex specifically bound to said ligand.
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Abstract
Disclosed herein are multimeric molecular complexes and compounds that are multivalent, i.e., they have two or more targeting elements directed to a ligand that confers paracellular transporting properties and/or transcytotic properties to complexes and compounds to which it is bound. The complexes and compounds have properties that are different from the properties of monomers, complexes and compounds having only one targeting element directed to a paracellular and/or transcytotic ligand. The complexes and compounds of the invention undergo endocytosis, transcytosis and exocytosis; following endocytosis, the complexes or compounds may be transported into the cytosol or an organelle of a cell. In polarized cells, transcytosis can proceed in a “forward” or “reverse” direction. Reverse transcytosis is used for the non-invasive delivery of biologically active agents from the lumen of, e.g., the gastrointestinal tract or the airways of lungs, to the circulatory system. The complexes and compounds are incorporated in various compositions and medical devices suitable for medicinal or veterinary use.
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Citations
38 Claims
- 1. A multimeric molecular complex comprising at least 2 compounds, each compound comprising at least one targeting element directed to a ligand that confers transcytotic or paracellular transporting properties to a molecular complex specifically bound to said ligand.
- 3. A first multimeric molecular complex comprising n targeting elements directed to a ligand that confers transcytotic or paracellular transporting properties to a compound bound to said ligand, wherein one or more of said properties of said first multimeric molecular complex are enhanced as compared to a second multimeric molecular complex having m targeting elements, wherein n and m are both whole integers, and n>
- 11. A compound comprising at least 2 targeting element directed to a ligand that confers transcytotic or paracellular transporting properties to a compound specifically bound to said ligand.
- 13. A compound comprising n targeting elements directed to a ligand that confers transcytotic or paracellular transporting properties to a compound bound to said ligand, wherein one or more of said properties of said compound are enhanced as compared to a second compound having m targeting elements, wherein n and m are both whole integers, and n>
- 20. A protein conjugate comprising a biologically active calcitonin polypeptide having a chemical linkage to at least one targeting element directed to a ligand that confers transcytotic or paracellular transporting properties to a molecular complex specifically bound to said ligand.
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21. The protein conjugate of claim 21, wherein said protein conjugate is capable of undergoing apical to basolateral transcytosis.
Specification