Compositions and methods for the transport of biologically active agents across cellular barriers
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Abstract
Disclosed herein are complexes and compounds that pass through cellular barriers to deliver compounds into, through and out of cells, and methods of producing and using such complexes and compounds. The complexes and compounds of the invention comprise a biologically active portion and a targeting element directed to a ligand that confers transcellular, transcytotic or paracellular transporting properties to an agent specifically bound to the ligand. Also disclosed are complexes and compounds that comprise two or more targeting elements directed to a ligand that confers transcellular, transcytotic or paracellular transporting properties to an agent specifically bound to the ligand. Preferred ligands include but are not limited to the stalk of pIgR, a pIgR domain, an amino acid sequence that is conserved among pIgR'"'"'s from different animals, and one of several regions of pIgR defined herein.
64 Citations
66 Claims
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1-17. -17. (canceled)
- 18. A complex or compound comprising 2 or more targeting elements directed to one or more ligands that confer transcellular, transcytotic or paracellular transporting properties to an agent specifically bound to said ligand.
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19. (canceled)
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20. (canceled)
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25-46. -46. (canceled)
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50-53. -53. (canceled)
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54. A method for delivery of a molecule to an animal in need thereof, comprising:
administering via a pulmonary or nasopharyngeal route a composition comprising a multimeric targeting element comprising two to four single chain variable region fragments (sFv), each sFv comprising a heavy chain variable domain covalently linked, directly or through a polypeptide linker, to a light chain variable domain, wherein one or more of said sFvs is covalently or noncovalently associated with said molecule, and wherein said multimeric targeting element confers apical to basolateral transcytosis to said molecule in an in vitro transcytotic assay. - View Dependent Claims (55, 56, 57, 58, 59, 60, 61)
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62. A method for delivery of a polypeptide molecule to an animal in need thereof, comprising:
administering via a pulmonary or nasopharyngeal route a composition comprising a multimeric targeting element comprising two to four sFvs that specifically bind to an epitope on pIgR, each sFv comprising a heavy chain variable domain covalently linked, directly or through a polypeptide linker, to a light chain variable domain, wherein one or more of said sFvs is synthesized as a fusion protein with said polypeptide molecule. - View Dependent Claims (63, 64, 65, 66)
Specification