Chemistry: molecular biology and microbiology – Vector – per se
Reexamination Certificate
2000-06-12
2004-01-06
Crouch, Deborah (Department: 1632)
Chemistry: molecular biology and microbiology
Vector, per se
C435S005000, C435S069100, C424S199100, C424S205100, C424S231100
Reexamination Certificate
active
06673602
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to viral vectors useful for specifically targeting one or more selected cell types. More specifically, the present invention relates to herpes simplex virus (HSV) virions comprising HSV amplicon vectors or a mixture of HSV amplicon vectors and recombinant HSV vectors, which are modified to target and infect a selected cell type. The present invention also relates to methods of making such virions, as well as methods of using such virions to target a cell in order to treat a pathologic condition.
2. Related Art
Many pathologies have a genetic basis. For example, genes have been identified that, when expressed, prevent cells from becoming cancer cells. When a mutation occurs in such a tumor suppressor gene, the cell is released from its normal growth control and can give rise to a cancer in an individual. Many other diseases are also associated with genetic defects, including, for example, cystic fibrosis, hemophilia, sickle cell anemia, and Huntington's disease. More diseases having a genetic component are likely to be identified in the future.
Methods for treating such diseases often are not selective for the disease, or only moderate the symptoms associated with the disease. For example, chemotherapy often is used to treat cancer patients, particularly patients with disseminated disease. However, while chemotherapy can kill cancer cells, for example, due to their rapid growth rate, chemotherapeutic agents also kill normal cells such as intestinal cells and blood precursor cells, which, like cancer cells, have a rapid growth rate. In fact, treatments for cancer often are limited by the damage the treatment causes to the normal cells in a patient.
Gene therapy provides a means for selectively treating genetic diseases such as cancer by replacing the defective gene, for example, a mutated tumor suppressor gene, with a normal copy of the gene, or by introducing into the cancer cells a gene that, when expressed, results in a product that kills the cancer cells. The transfer of specific genes into cells through gene therapy paradigms offers almost unlimited potential for the treatment of human disease, most of which is yet unrealized. Gene-based therapies are now expanding into fields such as cardiovascular disease, autoimmune disease, and neurodegenerative disease. However, to be effective, gene therapy must be selective, i.e., the gene must be delivered to target cells that have the defect to be corrected, or the cells that are to be killed.
This is particularly true for the treatment of cancer, where the transgenes or vectors are usually intended to be toxic. Each cancer therapy currently in use (surgery, radiation, or chemotherapy) has its own mechanism and profile of selective elimination of tumor cells as opposed to normal cells, and thus provides a unique contribution to the therapeutic ratio. Therapies are often combined such that additive or synergistic toxicity to tumor cells is maximized, while toxicity to normal tissue is minimized. Cure is frequently not achieved because each modality first reaches a point at which toxicity to vital normal tissues is limiting and overlaps with other agents. This issue is also relevant to other non-cytotoxic therapeutic goals, in for which the inappropriate introduction of viral or therapeutic proteins and genes could still impair or alter the function of non-target cells.
Gene therapy requires the use of viral-based or non-viral-based vectors to carry the gene into the target cells. Often, however, the vectors are not selective for a particular cell type, but can be taken up by any cell the vector contacts. Viral vectors provide an advantage in that many viruses only infect one or a few different types of cells. However, the use of such viral vectors is limited, at best, to treating the particular cells the virus infects. Some viral vectors, however, actually infect a relatively broad spectrum of host cells.
An overview of viral vectors that have been used in gene therapy can be found in Wilson, J. M.,
Clin. Exp. Immunol
. 107(Suppl. 1):31-32 (1997), Nakanishi, M.,
Crit. Rev. Therapeu. Drug Carrier Systems
12:263-310 (1995); Robbins, P. D., et al.,
Trends Biotechnol
. 16:35-40 (1998); Zhang, J., et al.,
Cancer Metastasis Rev
. 15:385-401 (1996); and Kramm, C. M., et al.,
Brain Pathology
5:345-381 (1995). Such vectors may be derived from viruses that contain RNA (Vile, R. G., et al.,
Br. Med Bull
. 51:12-30 (1995)) or DNA (Ali M., et al.,
Gene Ther
. 1:367-384 (1994)).
Specific examples of viral vector systems that have been utilized include: retroviruses (Vile, R. G., supra; U.S. Pat. Nos. 5,741,486 and 5,763,242); adenoviruses (Heise, C. et al.,
Nat. Med
. 3:639-645 (1997)); adenoviral/retroviral chimeras (Bilbao, G., et al.,
FASEB J
. 11:624-634 (1997); adeno-associated viruses (Flotte, T. R. and Carter, B. J.,
Gene Ther
. 2:357-362 (1995); U.S. Pat. No. 5,756,283); herpes simplex virus 1 or 2 (Latchman, D. S.,
Mol. Biotechnol
. 2:179195 (1994); U.S. Pat. Nos. 5,501,979 and 5,763,217; Chase, M., et al.,
Nature Biotechnol
. 16:444-448 (1998)); parvovirus (Shaughnessy, E., et al.,
Semin Oncol
. 23:159-171 (1996)); reticuloendotheliosis virus (Donburg, R.,
Gene Therap
. 2:301-310 (1995)). Other viruses that can be used as vectors for gene delivery include poliovirus, papillomavirus, vaccinia virus, lentivirus, as well as hybrid or chimeric vectors incorporating favorable aspects of two or more viruses (Nakanishi, M., supra; Zhang, J., et al., supra; Jacoby, D. R., et al.,
Gene Therapy
4:1281-1283 (1997)).
General guidance in the construction of gene therapy vectors and the introduction thereof into affected animals for therapeutic purposes may be obtained in the above-referenced publications, as well as U.S. Pat. Nos. 5,631,236, 5,688,773, 5,691,177, 5,670,488, 5,529,774, and 5,601,818.
Most viruses, which most vectors are or resemble, use viral surface proteins that bind to specific cell surface molecules (receptors) as the primary means of initiating cellular attachment. Expression of the receptors on a single or limited range of cell types produces the tissue tropism seen with many viruses. This effect is frequently a major determinant in the disease syndrome produced. A separate domain of the binding protein, an associated protein, or a completely unrelated protein usually provides a subsequent and usually less specific membrane fusion or penetration function.
Since many of the commonly used viral vectors actually infect a relatively broad spectrum of host cells, and the non-viral vectors have almost no intrinsic selectivity, significant advantages can be obtained by targeting vector transduction to one or a few specific cell types. For example, targeting vector toxicity to tumor cells can provide a unique contribution to the therapeutic ratio of a combined modality cancer therapy regimen. Significant interest exists in increasing the specificity of vector infectivity by adding or altering receptor-binding moieties, thus increasing the transduction of tumor and tumor associated cells, while decreasing gene delivery to non-target cells.
This has been attempted by attaching or conjugating various receptor ligands and specific antibodies, as well as by recombinant modification of viral surface molecules, with binding domains from ligands or antibodies (for review, see, Spear, M. A.,
Anticancer Research
18:3223-3231 (1998)). For example, the Moloney murine leukemia virus (MMLV) gp70 envelope protein has been modified in a variety of ways and expressed in trans in packaging cell lines. Kasahara et al. inserted the receptor-binding domain of erythropoietin and achieved increased transduction of erythropoietin receptor-bearing human cells, including erythroid and erythroleukemia cell lines, and decreased transduction of cell lines not expressing erythropoietin receptors (Kasahara, N., et al.,
Science
266:1373-1375 (1991). Modifications have also been introduced into the fiber protein of adenovirus to increase infectivit
Breakefield Xandra O.
Spear Matthew A.
Crouch Deborah
Sterne Kessler Goldstein & Fox P.L.L.C.
The General Hospital Corporation
Woitach Joseph
LandOfFree
Herpes simplex virus amplicon vector targeting system and... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Herpes simplex virus amplicon vector targeting system and..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Herpes simplex virus amplicon vector targeting system and... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3220087