Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing – Genetically modified micro-organism – cell – or virus
Reexamination Certificate
1998-08-17
2003-03-18
Guzo, David (Department: 1636)
Drug, bio-affecting and body treating compositions
Whole live micro-organism, cell, or virus containing
Genetically modified micro-organism, cell, or virus
C435S320100, C435S069100, C435S455000, C435S456000, C435S325000, C435S326000, C435S005000, C435S006120, C424S093100, C424S093600, C536S023100, C536S023500, C536S023530
Reexamination Certificate
active
06534051
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to retroviral vector particles having target cell specificity. The retroviral vector particles comprise a retroviral vector having a chimeric envelope protein consisting of an antigen binding site of an antibody or another peptide fused to the envelope protein of the retroviral vector. The antigen binding site or the other peptide replaces or disrupts the natural viral receptor binding site. The resulting chimeric envelope is referred to as the “targeting envelope”. This invention relates to retroviral vectors that contain not only the targeting envelope but also wild-type envelope protein. The presence of wild-type envelope in addition to the targeting envelope acts as a helper molecule by supplying a fully functional membrane fusion domain, which may be impaired in targeting envelopes. This helper function enables and/or enhances infection of cells that do not contain a receptor for the wild-type envelope but do contain a receptor for the binding for the targeting molecule. This invention also relates to a method for preparing the retroviral particles and for using the retroviral vectors to introduce genes into vertebrate cells.
2. Description of the Background
The disclosures referred to herein to illustrate the background of the invention and to provide additional detail with respect to its practice are incorporated herein by reference. For convenience, the disclosures are referenced in the following text and respectively grouped in the appended bibliography.
Retroviral vectors are the most efficient tools to introduce genes into vertebrate cells. Clinical experiments have been conducted to use retrovirus vectors to cure a genetic disease in humans (adenosine deaminase (ADA) deficiency). Besides correcting inborn errors of metabolism, gene therapy is also being tested in clinical trials to cure cancer and various other diseases (Science 1992, Vol. 258, pp. 744-746).
Retroviral vectors are basically retroviral particles that contain a genome in which all viral protein coding sequences have been replaced with the gene(s) of interest. As a result, such viruses cannot further replicate after one round of infection. Retroviral vector particles are produced by helper cells (FIG.
1
). Such helper cells are cell lines that contain plasmid constructs, which express all retroviral proteins necessary for replication. After transfection of the vector genome into such helper cells, the vector genome is encapsidated into virus particles (due the presence of specific encapsidation sequences). Virus particles are released from the helper cell carrying a genome containing only the gene(s) of interest (FIG.
1
). In the last decade, several retroviral vector systems derived from chicken or murine retroviruses, have been developed for the expression of various genes (for reviews see Temin, 1987; Gilboa, 1990).
Retroviral vectors have several limitations. Besides the limited genome size that can be encapsidated into viral particles, the most limiting factor for the application of retroviral vectors is the restricted host range of the vector particle. Some retroviruses can only infect cells of one species (ecotropic retroviruses) or even only one cell-type of one species (e.g., HIV). Other retroviruses have a very broad host range and can infect many different types of tissues of many different species (amphotropic retroviruses).
The initial step of retroviral infection is the binding of the viral envelope (env) glycoprotein to specific cell membrane receptors, the nature of which is unknown for most retroviruses. However, the interaction of the viral env protein with the cell surface receptor is very specific and determines cell-type specificity of a particular virus (Weiss et al., 1985). The envelope protein of all known retroviruses is made up of two associated peptides, (e.g., gp70 and p20(E) in SNV). These peptides are derived by proteolytic cleavage from the same precursor (gPR90env) encoded by the retroviral env gene. One peptide p20(E), also termed TM, anchors the protein in the membrane of the virus and, as shown with HIV, mediates the fusion of the virus and cell membranes. The second peptide gp70, also termed SU, mediates the binding of the virus to its receptor and, therefore, determines the host range (Weiss et al., 1985; Varmus and Brown, 1989).
Data obtained with several retroviruses indicate that the retroviral envelope protein forms trimers or tetramers. The formation of trimers appears to be mediated by the TM peptide (reviewed in Hunter, E. et al., 1990). Targeting envelopes retain TM in order to (i.) maintain a membrane fusion function and (ii) maintain oligomerization. However, since X-ray pictures are not available, it is unclear whether or to what degree the construction of targeting-molecules impaired the structure of the membrane fusion domain.
REFERENCES:
patent: 5869331 (1999-02-01), Dornburg
patent: 6133029 (2000-10-01), Gruber et al.
patent: WO 90 12087 (1990-10-01), None
patent: WO 92/05266 (1992-04-01), None
patent: WO 92 06180 (1992-04-01), None
patent: WO 93 00103 (1993-01-01), None
patent: WO 94 06920 (1994-03-01), None
patent: WO 94 12626 (1994-06-01), None
patent: WO 95/23846 (1995-09-01), None
Marshall, “Gene Therapy's Growing Pains,”Sciencevol. 269, Aug. 25, 1995, pp. 1050-1055.
Morgan, et al. “Human Gene Therapy,”Annual Rev. Bunhem. vol. 62 (1991) 217, pp. 191-217.
Weiss, et al. (Ed.) “RNA Tumor Viruses,” Cold Spring Harbor Laboratory (1984) pp. 46-51 and 226-260.
Te-Hua, et al., “Toward Highly Efficient Cell-Type-Specific Gene Transfer with Retroviral Vectors Displaying Single-Chain Antibodies,” Journal of Virology, vol. 71, 1997, pp. 720-725.
Te-Hua, et al., “Retroviral Vector Particles Displaying the Antigen-Binding Site of an Antibody Enable Cell-Type-Specific Gene Transfer,” Journal of Virology, vol. 69 [1], 1995, pp. 2659-2663.
Kewalramani, V.N., et al. “Spleen Necrosis Virus, an avian innunossupressive retrovirus, shares a receptor with the type D simian retroviruses”,Journal of Virology, vol. 66, No. 5, May 1992, pp. 3026-3031.
Riley, S.C., et al. “Preferential expression of variable region heavy chain gene segments by predominant 2,4-dinitrophenyl-specific BALB/c neonatal antibody clonotypes,”Proceedings of the National Academy of Sciences of USA, vol. 83, No. 8, Apr. 1986, pp. 2589-2593.
Russell, S.J. et al. “Retroviral vectors displaying functional antibody fragments,”Nucleic Acids Res.(1993), 21(5), pp. 1081-1085.
Te-Hua, T.C., et al. “Cell targeting with retroviral vector particles containing antibody-envelope fusion proteins,”Gene Therapy, vol. 1, No. 5, Sep. 1994, pp. 292-299.
Orkin et al., “Report and Recommendations of the Panel to Asses the NIH Investment in Research on Gene Therapy,” Dec. 7, 1995.
Vera et al.,Nature, vol. 389, pp. 239-242, Sep. 18, 1997.
Guzo David
Senniger Powers Leavitt & Roedel
University of Medicine and Dentistry of New Jersey
LandOfFree
Cell type specific gene transfer using retroviral vectors... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Cell type specific gene transfer using retroviral vectors..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Cell type specific gene transfer using retroviral vectors... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3044726