Serotype of adenovirus and uses thereof

• US 7,270,811 B2
• Filed: 09/27/2004
• Issued: 09/18/2007
• Est. Priority Date: 05/18/1999
• Status: Expired due to Term

• Current Assignee: Crucell Holland B.V (Johnson & Johnson)
• Original Assignee: Crucell Holland B.V (Johnson & Johnson)
• Inventors: Havenga, Menzo, Vogels, Ronald, Bout, Abraham
• Primary Examiner(s): Whiteman; Brian
• Application Number:
  US10/951,102
• Publication Number:
  US 20050084480A1
• Time in Patent Office: 1,086 Days
• Field of Search: 435/320.1, 424/93.2
• US Class Current: 424/93.2
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/10321 Viruses as such, e.g. new isolates, mutants or their genomic sequences
• CPC Class Codes: C12N 2710/10322 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/10345 Special targeting system for viral vectors
• CPC Class Codes: C12N 2710/10352 relating to complementing cells and packaging systems for producing virus or viral particles
• CPC Class Codes: C12N 2810/6018 Adenoviridae
• CPC Class Codes: C12N 2830/00 Vector systems having a special element relevant for transcription
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

The invention provides a gene delivery vehicle and a gene of interest comprising at least one Ad35 element or a functional equivalent thereof, responsible for avoiding or diminishing neutralizing activity against adenoviral elements by the host to which the gene is to be delivered. A functional equivalent/homologue of an Ad35 (element) includes an adenovirus (element) which, like adenovirus 35, encounters pre-existing immunity in less than about 10% of the hosts to which it is administered for the first time, or which is capable in more than about 90% of the hosts to which it is administered of avoiding or diminishing the immune response.

Claims

1. A recombinant adenovirus comprising a heterologous gene of interest, wherein said adenovirus is selected from the group consisting of:

adenovirus serotype 11 and 35.

5. The recombinant adenovirus of claim 1, wherein said adenovirus is a chimera of an adenovirus selected from the group consisting of:

adenovirus serotype 11 and 35, with at least one other adenovirus serotype.

6. The recombinant adenovirus of claim 5, wherein said other adenovirus is adenovirus serotype 16.

7. A pharmaceutical formulation comprising a recombinant adenovirus of claim 1, and a suitable excipient.

17. A method of avoiding pre-existing adenoviral neutralizing antibodies in a subject in need of gene therapy, the method comprising:

administering a replication defective adenoviral vector to the subject in need of gene therapy

wherein the replication defective adenoviral vector is the recombinant adenovirus of claim 1.

2. A recombinant adenovirus comprising an adenoviral nucleic acid comprising a deletion in the E1 region, said deletion rendering the recombinant adenovirus replication-defective, and wherein said adenovirus is selected from the group consisting of:

adenovirus serotype 11 and 35.

3. The recombinant adenovirus of claim 2, further comprising a gene of interest.

4. The recombinant adenovirus of claim 3, wherein said gene of interest is inserted in the E1 region of said adenoviral nucleic acid.

8. An adenoviral nucleic acid comprising a deletion in the E1 region, said adenoviral nucleic acid further encoding a recombinant adenovirus selected from the group consisting of:

adenovirus serotype 1 and 35, and wherein said deletion renders the encoded recombinant adenovirus replication-defective.

9. The adenoviral nucleic acid of claim 8, further comprising a gene of interest.

10. The adenoviral nucleic acid of claim 9, wherein said gene of interest is inserted in the E1 region of said adenoviral nucleic acid.

11. The adenoviral nucleic acid of claim 8 further comprising a sequence encoding a tissue tropism determining part of adenovirus serotype 16.

12. A cell comprising the adenoviral nucleic acid of claim 8.

13. The cell of claim 12, which complements the functional deletion in the E1 region of said adenoviral nucleic acid.

14. An adenoviral nucleic acid comprising:

a recombinant adenoviral nucleic acid based on an adenoviral serotype selected from the group consisting of Ad11, and Ad35; and

a nucleotide sequence of interest present in the recombinant adenoviral nucleic acid;

where the recombinant adenoviral nucleic acid has a deletion in the E1 region that renders the recombinant adenoviral nucleic acid replication-defective.

15. The adenoviral nucleic acid of claim 14, wherein the nucleotide sequence of interest is inserted in the E1 region of the adenoviral nucleic acid.

16. The adenoviral nucleic acid of claim 14, comprising a sequence encoding a fiber protein of adenovirus serotype 16.