P
USRE50753EActiveUtilityPatentIndex 59

Recombinant adenoviruses and use thereof

Assignee: BETH ISRAEL DEACONESS MEDICAL CT INCPriority: Nov 16, 2012Filed: Sep 22, 2022Granted: Jan 20, 2026
Est. expiryNov 16, 2032(~6.4 yrs left)· nominal 20-yr term from priority
Inventors:BAROUCH DAN HVIRGIN IV HERBERTABBINK PETER
C12N 2710/10042A61K 39/00C12N 2710/10321C12N 2740/15034C12N 2710/10343A61K 2039/5258A61K 2039/5256A61K 39/12C12N 7/00A61P 37/04A61P 35/00A61P 33/06A61P 33/02A61P 33/00A61P 31/22A61P 31/20A61P 31/18A61P 31/16A61P 31/14A61P 31/12A61P 31/10A61P 31/08A61P 31/06A61P 31/04A61P 17/04A61P 17/02A61P 17/00A61P 11/14A61P 11/02A61P 11/00A61P 1/16Y02A50/30A61P 29/00C12N 15/861
59
PatentIndex Score
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Cited by
238
References
69
Claims

Abstract

The present invention relates to recombinant adenoviruses and vectors thereof. In particular, the adenoviruses are novel simian adenoviruses having a low seroprevalence and high immunogenicity relative to other adenoviruses and vectors thereof. The invention also provides methods for production of the adenoviruses and for the treatment of diseases by administering the adenoviral vector(s) to a subject (e.g., a human).

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A recombinant adenovirus comprising a nucleotide sequence having at least 90% sequence identity over the entire sequence of any one of SEQ ID NOs: 10 and 12, or a complementary sequence to a nucleotide sequence having at least 90% sequence identity over the entire sequence of any one of SEQ ID NOs: 10 and 12;
 wherein said recombinant adenovirus comprises a deletion in or of an E1 region, an E3 region, and/or an E4 region, said deletion rendering said recombinant adenovirus a replication-defective virus.   
     
     
         2 . The recombinant adenovirus of  claim 1 , wherein said nucleotide sequence further comprises all or a portion of any one of SEQ ID NOs: 4, 6, 7, 9, 13, 15, 16, and 18, or a complementary sequence to all or a portion of any one of SEQ ID NOs: 4, 6, 7, 9, 13, 15, 16, and 18. 
     
     
         3 . The recombinant adenovirus of  claim 1 , further comprising a nucleotide sequence having at least 90% sequence identity to the sequence of any one of SEQ ID NOs: 1 and 3 or a complementary sequence to a nucleotide sequence having at least 90% sequence identity over the entire sequence of any one of SEQ ID NOs: 1 and 3. 
     
     
         4 . The recombinant adenovirus of  claim 2 , wherein said nucleotide sequence comprises the nucleotide sequence of any one of SEQ ID NOs: 34-39 and 46-51. 
     
     
         5 . The recombinant adenovirus of  claim 1 , further comprising a heterologous nucleotide sequence encoding an antigenic or therapeutic gene product of interest, or fragment thereof, wherein said antigenic gene product, or fragment thereof, comprises a bacterial, viral, parasitic, or fungal protein, or fragment thereof. 
     
     
         6 . The recombinant adenovirus of  claim 5 , wherein:
 (i) said bacterial protein, or fragment thereof, is from Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum, Mycobacterium microti, Mycobacterium leprae, Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus, Francisella tularensis, Brucella, Burkholderia mallei, Yersinia pestis, Corynebacterium diphtheria, Neisseria meningitidis, Bordetella pertussis, Clostridium tetani, or Bacillus anthracis;   (ii) said parasitic protein, or fragment thereof, is from Toxoplasma gondii, Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, Trypanosoma spp., or Legionella spp; or   (iii) said fungal protein, or fragment thereof, is from Aspergillus, Blastomyces dermatitidis, Candida, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum var. capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii, Zygomycetes spp., Absidia corymbifera, Rhizomucor pusillus, or Rhizopus arrhizus.   
     
     
         7 . The recombinant adenovirus of  claim 5 , wherein said viral protein, or fragment thereof, is from a viral family selected from the group consisting of Retroviridae, Flaviviridae, Arenaviridae, Bunyaviridae, Filoviridae, Togaviridae, Poxviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, Rhabdoviridae, Paramyxoviridae, Picornaviridae, Hepadnaviridae, Papillomaviridae, Parvoviridae, Astroviridae, Polyomaviridae, Calciviridae, and Reoviridae, or
 said viral protein, or fragment thereof, is from human immunodeficiency virus (HIV), human papillomavirus (HPV), hepatitis A virus (Hep A), hepatitis B virus (HBV), hepatitis C virus (HCV), Variola major, Variola minor, monkeypox virus, measles virus, rubella virus, mumps virus, varicella zoster virus (VZV), poliovirus, rabies virus, Japanese encephalitis virus, herpes simplex virus (HSV), cytomegalovirus (CMV), rotavirus, influenza, Ebola virus, yellow fever virus, Zika virus, or Marburg virus.   
     
     
         8 . The recombinant adenovirus of  claim 7 , wherein said viral protein, or fragment thereof, from HIV is Gag, Pol, Env, Nef, Tat, Rev, Vif, Vpr, or Vpu. 
     
     
         9 . A method of treating a subject having a disease, said method comprising administering the recombinant adenovirus of  claim 5  to said subject. 
     
     
         10 . The method of  claim 9 , wherein said recombinant adenovirus comprises an antigenic gene product, or fragment thereof, that promotes an immune response in said subject against an infective agent, wherein said infective agent is a bacterium, a virus, a parasite, or a fungus. 
     
     
         11 . The method of  claim 9 , wherein:
 (a) said subject is human;   (b) said adenovirus is administered intramuscularly; and/or   (c) said adenovirus is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier.   
     
     
         12 . The method of  claim 11 , wherein:
 (i) said subject is administered at least one dose of said pharmaceutical composition;   (ii) said subject is administered at least two doses of said pharmaceutical composition; or    (iii) said pharmaceutical composition is administered to said subject as a prime boost.   
     
     
         13 . A method of producing a recombinant adenovirus comprising transfecting a cell with: (a) an isolated polynucleotide comprising a nucleotide sequence having at least 90% sequence identity over the entire sequence of any one of SEQ ID NOs: 10 and 12, or a complementary sequence to a nucleotide sequence having at least 90% sequence identity over the entire sequence of any one of SEQ ID NOs: 10 and 12 or (b) a recombinant vector comprising said polynucleotide; culturing said cell in a suitable medium to allow replication of said polynucleotide or vector in said cell; and harvesting produced recombinant adenovirus from said medium and/or said cell. 
     
     
         14 . The method of  claim 13 , wherein said cell is a bacterial, plant, or mammalian cell, wherein optionally said mammalian cell is a PER.55K cell or a Chinese hamster ovary (CHO) cell. 
     
     
         15 . The recombinant adenovirus of  claim 5 , wherein the viral gene product is an envelope glycoprotein or fragment thereof. 
     
     
         16 . A method of inducing an immune response against a flavivirus in a subject comprising administering the recombinant adenovirus of  claim 5  to said subject, wherein the antigenic gene product, or fragment thereof, is a viral gene product from the flavivirus. 
     
     
         17 . The method of  claim 16 , wherein the viral gene product is an envelope glycoprotein or fragment thereof. 
     
     
         18 . The method of  claim 16 , wherein the subject is a human. 
     
     
         19 . The method of  claim 16 , wherein the adenovirus is administered intramuscularly. 
     
     
         20 . The method of  claim 16 , wherein the adenovirus is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier. 
     
     
         21 . The method of  claim 20 , wherein the subject is administered at least one or two doses of the pharmaceutical composition, optionally wherein the pharmaceutical composition is administered to the subject as a prime boost. 
     
     
         22 . A method of inducing an immune response against a retrovirus in a subject comprising administering the recombinant adenovirus of  claim 5  to the subject, wherein the antigenic gene product, or fragment thereof, is a viral gene product from the retrovirus. 
     
     
         23 . The method of  claim 22 , wherein the retrovirus is human immunodeficiency virus (HIV). 
     
     
         24 . The method of  claim 22 , wherein the subject is a human. 
     
     
         25 . The method of  claim 22 , wherein the viral gene product is an envelope glycoprotein or fragment thereof. 
     
     
         26 . The method of  claim 25 , wherein the viral gene product is a protein or fragment thereof from HIV. 
     
     
         27 . The method of  claim 22 , wherein the recombinant adenovirus is administered intramuscularly. 
     
     
         28 . The method of  claim 22 , wherein the recombinant adenovirus is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier. 
     
     
         29 . The method of  claim 28 , wherein the subject is administered at least one or two doses of the pharmaceutical composition, optionally wherein the pharmaceutical composition is administered to the subject as a prime boost. 
     
     
       30. A vector comprising an E1 region of sAd4287, sAd4310A or sAd4312.  
     
     
       31. The vector of  claim 30 , wherein the E1 region is the E1 region of sAd4287.  
     
     
       32. The vector of  claim 31 , wherein the E1 region comprises nucleotides 474 to 3085 of SEQ ID NO: 1.  
     
     
       33. The vector of  claim 30 , wherein the E1 region is the E1 region of sAd4310A.  
     
     
       34. The vector of  claim 33 , wherein the E1 region comprises nucleotides 474 to 3088 of SEQ ID NO: 2.  
     
     
       35. The vector of  claim 30 , wherein the E1 region is the E1 region of sAd4312.  
     
     
       36. The vector of  claim 35 , wherein the E1 reoion comprises nucleotides 487 to 3100 of SEQ ID NO: 3.  
     
     
       37. A cell comprising a vector which comprises an E1 region of sAd4287, sAd4310A or sAd43120.  
     
     
       38. The cell of  claim 37 , wherein the E1 region is the E1 region of sAd4287.  
     
     
       39. The cell of  claim 38 , wherein the E1 region comprises nucleotides 474 to 3085 of SEQ ID NO: 1.  
     
     
       40. The cell of  claim 37 , wherein the E1 region is the E1 region of sAd4310A.  
     
     
       41. The cell of  claim 40 , wherein the E1 region comprises nucleotides 474 to 3088 of SEQ ID NO: 2.  
     
     
       42. The cell of  claim 37 , wherein the E1 region is the E1 region of sAd4312.  
     
     
       43. The cell of  claim 42 , wherein the E1 region comprises nucleotides 487 to 3100 of SEQ ID NO: 3.  
     
     
       44. A cell line comprising a portion of sAd4287, sAd4310A or sAd4312 that complements an E1-deficient sAd4287, sAd4310A or sAd4312, respectively.  
     
     
       45. The cell line of  claim 44 , which is a PER.55K cell line.  
     
     
       46. The cell line of  claim 44 , which is a 293 cell line.  
     
     
       47. The cell line of  claim 44 , which complements an E1-deficient sAd4287.  
     
     
       48. The cell line of  claim 47 , which comprises an sAd4287 E1 region.  
     
     
       49. The cell line of  claim 44 , which complements an E1-deficient sAd4310A.  
     
     
       50. The cell line of  claim 49 , which comprises an sAd4310A E1 reqion.  
     
     
       51. The cell line of  claim 44 , which complements an E1-deficient sAd4312.  
     
     
       52. The cell line of  claim 51 , which comprises an sAd4312 E1 region.  
     
     
       53. The method of  claim 13 , wherein the isolated polynucleotide comprises a deletion in or of an E1 region as compared to sAd4287 or sAd4312, and wherein the cell comprises a rescue vector comprising an E1 region of sAd4287 or sAd4312.  
     
     
       54. The method of  claim 53 , wherein the rescue vector comprises an E1 region of sAd4287.  
     
     
       55. The method of  claim 54 , wherein the rescue vector comprises nucleotides 474 to 3085 of SEQ ID NO:1.  
     
     
       56. The method of  claim 53 , wherein the rescue vector comprises an E1 region of sAd4312.  
     
     
       57. The method of  claim 56 , wherein the rescue vector comprises nucleotides 487 to 3100 of SEQ ID NO:3.  
     
     
       58. A method of producinq a recombinant adenovirus comprisinq:
 (a) transfecting a cell with an isolated polynucleotide having a deletion in or of an E1 region as compared to sAd4310 and comprising a nucleotide sequence havinq at least 90% sequence identity over the entire sequence of SEQ ID NO:11, or a complementary sequence to a nucleotide sequence havinq at least 90% sequence identity over the entire sequence of SEQ ID NO:11, wherein the cell comprises a rescue vector comprising an E1 region of sAd4310;   (b) culturing said cell in a suitable medium to allow replication of said polynucleotide in said cell; and   (c) harvesting produced recombinant adenovirus from said medium and/or said cell.    
     
     
       59. The method of  claim 58 , wherein the vector comprises nucleotides 474 to 3088 of SEQ ID NO:2.  
     
     
       60. A replication-defective recombinant adenovirus whose genome comprises:
 (a) a nucleotide sequence encoding a hexon protein comprising the amino acid sequence of any one of SEQ ID NQs: 25, 26 and 27;   (b) a deletion in or of an E1 region; and   (c) an expression cassette for a transgene in the deleted E1 region.    
     
     
       61. The replication-defective recombinant adenovirus of  claim 60 , wherein the nucleotide sequence encodes a hexon protein comprising the amino acid sequence of SEQ ID NO:25.  
     
     
       62. The replication-defective recombinant adenovirus of  claim 60 , wherein the nucleotide sequence encodes a hexon protein comprising the amino acid sequence of SEQ ID NO:26.  
     
     
       63. The replication-defective recombinant adenovirus of  claim 60 , wherein the nucleotide sequence encodes a hexon protein comprising the amino acid sequence of SEQ ID NO:27.  
     
     
       64. A method of producing the replication-defective recombinant adenovirus of  claim 60 , comprising:
 (a) transfecting a cell that is enqineered to rescue the E1 deletion with a polynucleotide comprising the nucleotide sequence of the adenovirus genome;   (b) culturing said cell in a suitable medium to allow replication of said polynucleotide in said cell; and   (c) harvesting produced recombinant adenovirus from said medium and/or said cell.    
     
     
       65. The method of  claim 64 , wherein the cell is a PER.55K cell.  
     
     
       66. The method of  claim 64 , wherein the cell is a 293 cell.  
     
     
       67. The method of  claim 14 , wherein said mammalian cell is a PER.55K cell or a Chinese hamster ovary (CHO) cell.  
     
     
       68. The method of  claim 21 , wherein the pharmaceutical composition is administered to the subject as a prime boost.  
     
     
       69. The method of  claim 29 , wherein the pharmaceutical composition is administered to the subject as a prime boost.

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