Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence
Reexamination Certificate
2007-07-16
2011-12-13
Lukton, David (Department: 1654)
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
25 or more amino acid residues in defined sequence
C514S021300
Reexamination Certificate
active
08076451
ABSTRACT:
A polypeptide with a predominantly hydrophobic sequence long enough to span a membrane lipid bilayer as a transmembrane helix (TM) and comprising one or more dissociable groups inserts across a membrane spontaneously in a pH-dependant fashion placing one terminus inside cell. The polypeptide conjugated with various functional moieties delivers and accumulates them at cell membrane with low extracellular pH. The functional moiety conjugated with polypeptide terminus placed inside cell are translocated through the cell membrane in cytosol. The peptide and its variants or non-peptide analogs can be used to deliver therapeutic, prophylactic, diagnostic, imaging, gene regulation, cell regulation, or immunologic agents to or inside of cells in vitro or in vivo in tissue at low extracellular pH. The claimed method provides a new approach for diagnostic and treatment diseases with naturally occurred (or artificially created) low pH extracellular environment such as tumors, infarction, stroke, atherosclerosis, inflammation, infection, or trauma. The method allows to translocate cell impermeable molecules (peptides, toxins, drugs, inhibitors, nucleic acids, peptide nucleic acids, imaging probes) into cells at low pH. The method allows to attach to the cell surface a variety of functional moieties and particles including peptides, polysaccharides, virus, antigens, liposomes and nanoparticles made of any materials.
REFERENCES:
patent: 5739273 (1998-04-01), Engelman et al.
patent: 03106491 (2003-12-01), None
Andreev Oleg A.
Engelman Donald M.
Lehnert Ursula
Reshetnyak Yana K.
Beattie Ingrid A.
Board of Governors for Higher Education, State of Rhode Island a
Lukton David
Mintz Levin Cohn Ferris Glovsky and Popeo P.C.
Yale University
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