Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
2000-11-22
2003-11-04
Salimi, Ali (Department: 1648)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C435S006120, C435S007940
Reexamination Certificate
active
06642008
ABSTRACT:
BACKGROUND OF THE INVENTION
This is in the area of the prevention, diagnosis, and treatment of latent viral infections, such as infections with DNA viruses like Epstein-Barr virus.
This application claims priority to U.S. Ser. No. 60/167,212 filed Nov. 24, 1999, by John B. Harley, Judith Ann James, and Kenneth M. Kaufman.
Epstein-Barr virus has been known for more than three decades. Epstein-Barr has been associated with cancer and several autoimmune diseases. Since there is evidence implicating Epstein-Barr virus in infectious mononucleosis, B cell lymphoma (in immunocompromised hosts), Burkitt's lymphoma, nasopharyngeal carcinoma, and some cases of Hodgkin's lymphoma, there have been efforts to provide a vaccine against Epstein-Barr virus (Morgan, A. J., et al.
J. Med. Virol
. 29:74-78 (1989); Morgan, A. J.
Vaccine
10:563-571 (1992); Morgan, A. J.
Development of Epstein-Barr Virus Vaccines
(R. G. Landes Company, Austin, Tex. (1995 by Springer-Verlag, Heidleberg, Germany)); Krause, P. R. & Strauss, S. E.
Infect. Dis. Clin. N.A
. 13:61-81 (1999)). Recombinant vectors expressing gp340/220 in a bovine papillomavirus vector or in an adenovirus vector protected five of six cottontop tamarins from lymphomas that otherwise occur after infection with Epstein-Barr virus (Finerty, S., et al.
J. Gen. Virol
. 73:449-453 (1992)). A subunit of the gp340/200 in alum only protected three of five cotton top tamarins from lymphomas (Finerty, S., et al.
Vaccine
12:1180-1184 (1994)), suggesting that this strategy might not be especially effective. A trial of an Epstein-Barr virus vaccine of gp340/220 in a Vaccinia virus vector has been reported from China and failed to protect a third of those immunized from infection (Gu, S. et al.
Dev. Biol. Stand
. 84:171-177 (1995)), consistent with the primate data. Khanna, et al.,
J. Immunol
. 162:3063-3069 (1999) reports on the potential use of gp350/gp85 CTL epitopes in vaccine design to protect against EBV. However, as they note, evidence of neutralizing antibodies does not always correlate with protection against infection. Their research is focused on structural antigens, gp350 and gp85, from which they synthesized specific peptides to use as vaccines. They observed higher CTL reactivity to lytic antigens as compared to a latent antigen, LMP-1. Jackman, et al.,
Vaccine
17:660-668 (1999) also reported on studies using gp350. Gu, et al.,
Dev. Biol. Stand
. 84:171-177 (1995) reports on a clinical trial based on live recombinant vaccinia virus expression gp350 as an immunogen, but there were safety concerns.
Another method of vaccine development has been considered. Cytotoxic T cell epitopes have been mapped for several different EBV antigens in persons of specific HLA haplotypes. For example, trials are underway to evaluate the usefulness of immunization with an EBNA-3 peptide which is a dominant CTL epitope in HLA-B8 restricted persons (Schmidt, et al.
Proc. Natl. Acad. Sci. USA
88:9478-82 (1991)). Efficacy of these vaccines is currently unknown.
A variety of additional therapies against Epstein-Barr virus have been attempted. These include inducing the lytic cycle in cells latently infected by virus (Gutierrez, M. I., et al.
Cancer Res
. 56:969-972 (1996)). Patients with the Epstein-Barr virus related lymphomatoid granulomatosis have been treated with interferon-alpha 2b (Wilson, W. H., et al.
Blood
87:4531-4537 (1996)). Cycloheximide and acycloguanosine have been demonstrated to be useful in vitro (Ishii, H. H., et al.
Immunol. Cell Biol
. 73:463-468 (1995)); however, only limited further evaluation of this therapy has proceeded due to the limited clinical benefit of acycloguanosine in primary EBV infection.
Therapy with a T cell line has been attempted (Kimura, H. et al.
Clin. Exp. Immunol
. 103:192-298 (1996)), as has adoptive transfer of gene-modified virus-specific
T lymphocytes
(Heslop, H. E. et al.
Nature Med
. 2:551-555 (1996)). Data available do not appear to particularly support the use of acyclovir for Epstein-Barr virus infections (Wagstaff, A. J., et al.
Drugs
47:153-205 (1994)), though FK506 (a relative of cyclosporine) may have some benefit (Singh, N., et al.
Digestive Dis. Sci
. 39:15-18 (1994)). Monoclonal antibodies have been used to treat the virus-induced lymphoproliferative syndrome (Lazarovots, A. I., et al.
Clin. Invest. Med
. 17:621-625 (1994)) with modest early success.
Therapeutic strategies directed against the latent phase of the viral infection have been considered. Among these is the consideration of the use of T cell epitopes of particular HLA-restricted cytotoxic T cells (e.g. see Morgan, A. J.
Development of Epstein
-
Barr Virus Vaccines
(R. G. Landes Company, Austin, Tex. (1995 by Springer-Verlag, Heidleberg, Germany), pp109-115; or Barnes J.
Pharma Weekly
1:11 (1995)). The latent membrane proteins have not been shown to be accessible on the outside of the cell.
Epstein-Barr virus is most similar to the other members of the Herpesviridae family. Although only gamma herpesvirus which infects humans, all human herpesviruses have linear double-stranded DNA, an icosadeltahedral capsid, a tegument which surrounds the capsid and an envelope containing viral glycoprotein spikes on its surface. All human herpesviruses remain with and survive in the host after primary infection.
Cytomegalovirus, in a manner similar to Epstein-Barr virus, is able to establish latency in peripheral immune cells; however, the exact cellular location is still in dispute (Mocarski, E. S. “Cytomegaloviruses and their replication”
Fields Virology
, third edition (eds. B. N. Fields, et al., Lippincott-Raven (1996)), 2447-2480). Human CMV has been treated with a host of antiviral agents, including leukocyte interferon, interferon stimulators, transfer factor, acyclovir and nucleoside inhibitors, as well as combination therapy with interferon and ara-A (reviewed by Alford, C. A.
Antiviral agents and viral diseases of man
2
nd
ed. New York: Raven Press; 433-86 (1984); Ho, M.
Cytomegalovirus, biology and infection: current topics in infectious disease
New York: Plenum Press; 105-18 (1982)). Very little to no clinical benefit has been demonstrated with these therapies and overwhelming toxicities are present (Alford, C. A.
Antiviral agents and viral diseases of man
2
nd
ed. New York: Raven Press; 433-86 (1984)).
Gancyclovir (through its nucleic acid chain-terminating activity) and foscarnet (through inhibition of viral DNA polymerase directly) have both been used with success (Snoeck, R., Neyts, J., De Clerq, E.
Multidisciplinary approach to understanding cytomegalovirus disease
Amsterdam: Excerpta Medica: 1993, 269-78). Both of these drugs have been used with some success in the prophylaxis of invasive CMV in the post-transplant setting. However, drug toxicity and no evident decrease in overall mortality limits their standard use for all patients (Goodrich, J. M, et al.
Ann. Intern. Med
. 118:173-8 (1993); Reusser P, et al.
J. Infect. Dis
. 166:473-79 (1992)).
Passive immunoprophylaxis remains very controversial. Newer drugs targeting the CMV protease and DNA processivity activity are under development (Digard, P., Chow, C. S., Pirrit, L., Coen, D. M.
J. Virol
. 67:1159-68 (1993); Ertl, P. F., Powell, K. L.
J. Virol
. 66:4126-33 (1992)).
Vaccine development for CMV has met with only limited success. Initial studies were performed using an attenuated laboratory strain of CMV (Elek, S. D., Stern, H.
Lancet
1:1-5 (1974); Plotkin, S. A., et al.
Infect. Immun
. 12:521-27 (1975)). These British studies showed limited immunity which decreased with time (Plotkin, S. A. , et al.
J. Infect. Dis
. 159:860-65 (1989)). Safety issues concerning immunization of slightly immnunocompromized subjects and women of childbearing age have also limited excitement over these studies. Subunit vaccines for CMV prevention are also under consideration. Early studies with the major envelope glycoprotein, gB, are under way (Plotkin, S. A., et al.
Rev. Infect. Dis
. 12:827-38 (1990); Spaete, R. R.,
Transplant Proc
. 23:90-96
Harley John B.
James Judith Ann
Kaufman Kenneth M.
Holland & Knight LLP
Oklahoma Medical Research Foundation
Salimi Ali
LandOfFree
Assays and therapies for latent viral infection does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Assays and therapies for latent viral infection, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Assays and therapies for latent viral infection will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3163977