Adeno-associated virus capsid immunologic determinants

Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Virus or component thereof

Reexamination Certificate

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Details

C424S199100, C435S235100, C435S173300, C435S069300, C530S403000

Reexamination Certificate

active

06733757

ABSTRACT:

BACKGROUND OF THE INVENTION
Recombinant Adeno-associated virus (AAV) vectors are promising gene delivery vehicles because, for example, the virus is not pathogenic; the virus transduces both dividing and non-dividing cells; the virus infects a wide range of cells; and the virus integrates into the genome, which results in long term expression of the transgene.
AAV vector delivery can be obstructed by the immune response of a host to the AAV component proteins. In the case of recombinant AAV vectors, the primary target of the immune response is the capsid of the vector particle since the vectors do not encode viral proteins. For example, virus neutralizing antibodies may be generated in response to exposure to the virus.
SUMMARY OF THE INVENTION
Regions of the AAV capsid proteins were mapped to identify immunogenic sites and regions.
An object of the instant invention is to provide the amino acid sequence of such immunogenic sites and regions.
The sites can be modified, for example, to render the recombinant AAV less immunogenic or non-immunogenic; to alter the tropism of the virus; to enhance binding of the virus to a cell; and to identify analogous sites in related viruses, such as canine parvovirus.
Another object of the instant invention is to provide isolated oligopeptides that can intercede or supplant the attachment of virus and cell. Immunogenic equivalent derivatives thereof also are provided.


REFERENCES:
patent: 5863541 (1999-01-01), Samulski et al.
Candace Summerford et al., “Membrane-Associated Heparan Sulfate Proteoglycan is a Receptor for Adeno-associated Virus Type 2 Virons”, Journal of Virology, 72, 1438-1445 (Feb. 1998).
Candace Summerford et al., “&agr;v&bgr;5 Integrin: a Co-Receptor for Adeno-Associated Virus Type 2 Infection”, Nature Medicine, vol. 5, p. 78-82 (Jan. 1999).
Keyun Qing et al., “Human Fibroblast Growth Factor Receptor 1 is a Co-Receptor for Infection by Adeno-Associated Virus 2”, Nature Medicine, vol. 5, p. 71-77 (Jan. 1999).
Marina Moskalenko, et al., “Epitope Mapping of Human Anti-Adeno-Associated Virus Type 2 Neutralizing Antibodies: Implications for Gene Therapy and Virus Structure”, Journal of Virology, vol. 74, p. 1761-1766 (Feb. 2000).
Narendra Chirmule et al., “Humoral Immunity to Adeno-Associated Virus Type 2 Vectors Following Administration to Murine and Nonhuman Primate Muscle”, Journal of Virology, vol. 74, p. 2420-2425 (Mar. 2000).
Chirmule N. et al., “Immune Responses to Adenovirus and Adeno-Associated Virus in Humans”, Gene Ther., Sep. 1999 6(9):1574-83. (Abstract only).

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