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CMCC 1663

Oral delivery of therapeutic large molecules

Inventors: Wayne Lencer, Daniel Chinnapen, Randall Mrsny

Invention Types: Therapeutics

Research Areas: Gastrointestinal/Nutrition

Keywords: Drug Delivery

For More Information Contact:  Meyer, Abbie

 

Invention Description:

Wayne Lencer, MD, chief of the Division of Gastroenterology has developed a drug delivery platform that fuses a ceramide chain containing short or “kinked” unsaturated fatty acids (C12:0 or C16:1 as examples) to therapeutic peptides, proteins, vaccine antigens, or small molecules. The permeability and half-life are often limiting factors in the development of new drugs, particularly large molecules.


The investigators have recently discovered that the fatty acid structure of a particular ceramide dictates trafficking of the lipid into either the recycling endosome (short or unsaturated FA’s) or lysosome pathways (long chain FA’s) of cultured human epithelial cells. This technology exploits a pathway that a pathogen normally uses to direct intracellular trafficking of its toxin, harnessing it to enable safe macromolecular transport of drugs across mucosal epithelial barriers while increasing that drug’s serum half-life. This invention could avoid the need for parenteral administration of large protein drugs and potentially overcome unintended side effects. In some forms, it could also allow for restricted (local) delivery of therapeutic molecules to mucosal surfaces without systemic absorption. Coupling therapeutic molecules to this delivery platform could enhance the therapeutic potential of new molecules.

Applications:

Drug Delivery Platform for therapeutic drugs:

• Peptides

• Proteins

• Vaccine Antigens

• Small molecules|

Competitive Advantages:

• Increases the half-life of a drug

• Deliver drug to the cell membrane of mucosal surfaces and through to the other side (absorption), or to intracellular organelles (recycling endosome, lysosome, ER)

• Eliminates need for parenteral administration of large protein drugs|

Business Opportunity:

• Non-exclusive license to worldwide patents|
• Collaboration with a drug delivery industry partner

Related Publications: • Chinnapen DJ, Chinnapen H, Saslowsky D, 2007 Rafting with cholera toxin: endocytosis and trafficking from plasma membrane to ER.Jan;266(2):129-37 ®. Lencer, W.I., S. Moe, P.A. Rufo, and J.L. Madara. 1995. Transcytosis of cholera toxin subunits across model human intestinal epithelia. Proc. Natl. Acad. Sci. USA. 92:10094-10098. |
• Wolf, A.A., M.G. Jobling, S. Wimer-Mackin, J.L. Madara, R.K. Holmes, and W.I. Lencer. 1998. Ganglioside structure dictates signal transduction by cholera toxin in polarized epithelia and association with caveolae-like membrane domains. J Cell Biol. 141:917-927.|
• Lencer, W.I., and B. Tsai. 2003. The intracellular voyage of cholera toxin: going retro. Trends Biochem Sci. 28:639-45.

IPStatus: Pat. Pend.