# US 9,040,477 B2 · Macromolecule transduction domains and methods for identification and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,040,477 B2 - Document ID: US9040477B2 - Status: Granted - Kind: B2 - Application number: 14/091,823 - Filed: 2013-11-27 - Published: 2014-07-03 - Granted: 2015-05-26 - Earliest claimed: 2007-01-29 - Assignees: Procell Therapeutics Inc. - Applicants: Procell Therapeutics Inc. - Inventors: Dae Woong Jo; Jae Sun Ko; Jin Sook Kim; Kyung Mi Park; Jin Kyung Song; Jung Hee Lim; Thi Thuy Nga Do; Thi Lan Phuong Do; Minh Tam Duong - Web page: https://patentgrep.com/patent/US9040477B2 ## CPC - A61K 48/0041: {the non-active part being polymeric} - A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants - C07K 7/06: having 5 to 11 amino acids - C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) - C07K 14/195: from bacteria - C07K 14/47: from mammals - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract The present invention discloses novel macromolecule transduction domain (MTD) peptides which facilitate the traverse of a biologically active molecule across the cell membrane. Also disclosed are polynucleotides encoding the MTD peptides, methods of identifying the MTD peptides; methods of genetically engineering a biologically active molecule to have cell permeability by using the MTD peptides, methods of importing a biologically active molecule into a cell by using the MTD peptides, and uses thereof. ## Claims ### Claim 1 An isolated macromolecule transduction domain (MTD) peptide wherein the peptide comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 123, 124, 156, and 173 wherein said MTD peptide comprises a single hydrophobic region at the N-terminus, forms a helix structure, exhibits flexibility, mediates transports of a biologically active molecule into a cell, and is 7 to 17 amino acids in length. ### Claim 2 (depends on 1) An isolated polynucleotide encoding the macromolecule transduction domain (MTD) peptide according to claim 1, wherein the isolated polynucleotide comprises a nucleotide sequence selected from the group consisting of SEQ ID NOS: 316, 317, 349. ### Claim 3 An isolated recombinant protein having cell permeability comprising a macromolecule transduction domain (MTD) peptide wherein the MTD comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 3123, 124, 156, and 173 wherein said MTD peptide comprises a single hydrophobic region at the N-terminus, forms a helix structure, exhibits flexibility, mediates transports of a biologically active molecule into a cell, and is 7 to 17 amino acids in length; and a biologically active molecule. ### Claim 4 (depends on 3) The isolated recombinant protein according to claim 3, wherein the biologically active molecule is selected from the group consisting of a protein, a polypeptide and a peptide. ### Claim 5 (depends on 3) The isolated recombinant protein according to claim 3, wherein the biologically active molecule is selected from the group consisting of a growth factor, an enzyme, a transcription factor, a toxin, an antigenic peptide, an antibody, and an antibody fragment. ### Claim 6 (depends on 3) The isolated recombinant protein according to claim 3, wherein the biologically active molecule is selected from the group consisting of an enzyme, a hormone, a transport protein, an immunoglobulin, an antibody, a structural protein, a motor function protein, a receptor, a signaling protein, a storage protein, a membrane protein, a transmembrane protein, an internal protein, an external protein, a secreted protein, a viral protein, a native protein, a glycoprotein, a cleaved protein, a protein with a disulfide bond, a protein complex, a chemically modified protein and a prion. ### Claim 7 (depends on 3) The isolated recombinant protein according to claim 3, wherein the biologically active molecule is selected from the group consisting of a nucleic acid, a coding nucleic acid sequence, an mRNA, an antisense RNA molecule, a carbohydrate, a lipid, and a glycolipid. ### Claim 8 (depends on 3) The isolated recombinant protein according to claim 3, wherein the biologically active molecule is a therapeutic agent. ### Claim 9 (depends on 8) The isolated recombinant protein according to claim 8, wherein the therapeutic agent is selected from the group consisting of a therapeutic drug and a toxic chemical. ### Claim 10 (depends on 1) A method of making a biologically active molecule having cell permeability comprising attaching a macromolecule transduction domain (MTD) peptide of claim 1 to a biologically active molecule under conditions effective to produce a biologically active molecule having cell permeability. ### Claim 11 (depends on 10) The method according to claim 10, wherein said attaching comprises attaching a MTD peptide to the N-terminal, C-terminal, both or middle of the biologically active molecule, wherein the biologically active molecule is a peptide, polypeptide or protein. ### Claim 12 (depends on 10) The method according to claim 10, wherein said attaching comprises attaching a MTD peptide to the biologically active molecule by a peptide bond. ### Claim 13 (depends on 10) The method according to claim 10, wherein said attaching comprises attaching a MTD peptide to the biologically active molecule by a covalent bond. ### Claim 14 (depends on 1) A method of transporting a biologically active molecule into a cell in a subject comprising administering to a subject a cell permeable recombinant protein comprising a macromolecule transduction domain (MTD) peptide of claim 1 attached to a biologically active molecule. ### Claim 15 (depends on 1) A method of delivering a drug to a subject, the method comprising administering the drug in combination with a macromolecule transduction domain (MTD) peptide of claim 1.