# US 7,611,868 B2 · Recombinant modified adenovirus fiber protein > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,611,868 B2 - Document ID: US7611868B2 - Status: Granted - Kind: B2 - Application number: 10/556,877 - Filed: 2004-05-10 - Published: 2006-12-14 - Granted: 2009-11-03 - Earliest claimed: 2003-05-14 - Assignees: Instituto di Ricerche di Biologia Molecolare P. Angeletti S.p.A. - Inventors: Paolo Monaci; Laura Fontana - Web page: https://patentgrep.com/patent/US7611868B2 ## CPC - C07K 14/005: from viruses - C12N 15/86: Viral vectors - A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy - C07K 2319/00: Fusion polypeptide - C07K 2319/735: containing a domain for self-assembly, e.g. a viral coat protein (includes phage display) - C12N 2710/10322: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2710/10343: viral genome or elements thereof as genetic vector - C12N 2710/10345: Special targeting system for viral vectors - C12N 2810/40: Vectors comprising a peptide as targeting moiety, e.g. a synthetic peptide, from undefined source - C12N 2810/80: from vertebrates - C12N 2840/20: translation of more than one cistron - 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) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - 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) ## Abstract Recombinant adenoviruses comprising modified fiber proteins which expand the tropism of the adenovirus in comparison to wild-type virus are disclosed. The modified fiber proteins described herein contain a peptide ligand for a cell surface binding site other than CAR comprising a 14 amino acid core sequence containing both fixed and variable amino acid residues. The invention includes isolated nucleic acid molecules encoding the modified adenovirus fiber proteins disclosed, as well as recombinant vectors and host cells containing said nucleic acid molecules. Methods of identifying peptide ligands that bind to cell binding sites other than CAR are included comprising screening a phage-display library of peptide ligands expressed within an adenovirus fiber knob context on CAR-negative cells. Recombinant adenoviruses of the present invention will increase the ability of an adenovirus to transduce important cell and tissue targets as part of a gene therapy/gene vaccination regime that have been shown to be refractory to adenoviral infection. ## Claims ### Claim 1 A recombinant adenovirus having a modified fiber protein which comprises a peptide ligand for a cell surface binding site other than CAR, said peptide ligand comprising the amino acid sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15. ### Claim 2 (depends on 1) A recombinant adenovirus of claim 1, wherein said peptide ligand is contained within a loop domain of a fiber protein knob. ### Claim 3 (depends on 1) A recombinant adenovirus of claim 1, wherein said modified fiber protein is an Ad5 fiber protein. ### Claim 4 (depends on 1) A recombinant adenovirus of claim 1, wherein said modified fiber protein does not bind CAR. ### Claim 5 An isolated adenovirus fiber protein which comprises a peptide ligand for a cell surface binding site other than CAR, said peptide ligand comprising the amino acid sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15. ### Claim 6 (depends on 5) An isolated adenovirus fiber protein of claim 5, wherein said peptide ligand is contained within a loop domain of a fiber protein knob. ### Claim 7 (depends on 5) An isolated adenovirus fiber protein of claim 5, wherein said modified fiber protein is an Ad5 fiber protein. ### Claim 8 (depends on 5) A recombinant adenovirus of claim 5, wherein said modified fiber protein does not bind CAR. ### Claim 9 An isolated nucleic acid molecule encoding a modified adenovirus fiber protein which comprises a peptide ligand for a cell surface binding site other than CAR, said peptide ligand comprising the amino acid sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15. ### Claim 10 (depends on 9) An expression vector for expressing a modified adenovirus fiber protein in a recombinant cell wherein said expression vector comprises a nucleic acid molecule of claim 9. ### Claim 11 (depends on 10) An isolated host cell which expresses a modified adenovirus fiber protein wherein said host cell contains the expression vector of claim 10. ### Claim 12 (depends on 10) A process of expressing a modified adenovirus fiber protein in a recombinant host cell, comprising: (a) transfecting the expression vector of claim 10 into a suitable host cell; and (b) culturing the host cell of step (a) under conditions which allow expression of said modified adenovirus fiber protein from said expression vector.