Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...
Reexamination Certificate
2002-03-13
2004-11-16
Park, Hankyel T. (Department: 1648)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Blood proteins or globulins, e.g., proteoglycans, platelet...
C530S389400, C530S866000, C536S023100
Reexamination Certificate
active
06818748
ABSTRACT:
FIELD OF INVENTION
This invention relates to the cloning, expression, sequencing, mutagenesis and functional enhancement of reactivity of recombinant monoclonal single-chain variable fragment (ScFv) antibodies against Venezuelan equine encephalitis (VEE) virus antigens.
BACKGROUND OF THE INVENTION
List of Prior Art Literatures
Reference Formatting is Not Consistent
1. Johnston, R. E, Peters, C. J., “Alphaviruses”, Fields, B. N., Knipe, D. M., Howley, P. M. et al. (Eds), FieldsVirology, third edition, Lippincott B Raven, Philadelphia, 1996, pp. 843-898.
2. Roehrig, J. T., et al. “Use of a new synthetic peptide derived monoclonal antibody to differentiate between vaccine and wild type Venezuelan equine encephalomyelitis viruses”, J. Clinical Microbiol.,29, 3, pp.630-631, 1991.
Insert Other Authors
3. Schlesinger, S. and Schlesinger, M. J., “Togaviridae: The viruses and their replication”, Fields, B. N., Knipe, D. M., Howley, P. M. et al.(Eds), Fields Virology, third edition, Lippincott B Raven, Philadelphia, 1996, pp. 825-841.
4. Anthony, R. P., Brown, D. T., “Protein-protein interaction in an alphavirus membrane”, J. Virol., 65, pp. 1187-1194, 1991.
5. France, J. K., Wyrick, B. C., and Trent, D. W., “Biochemical and antigenic comparisons of the envelope glycoproteins of Venezuelan equine encephalomyelitis virus strains”, J. Gen. Virol., 44, pp. 725-740, 1979.
6. Kohler, G., and Milstein, C., “Continuos culture of fused cells secreting antibody of predefined specificity”, Nature, 256, pp.495-497, 1975.
7. Roehrig, J. T., and Mathews, J. H., “The neutralization site on the E2 glycoprotein of Venezuelan equine encephalomyelitis (TC-83) virus is composed of multiple conformationally stable epitopes”, Virology, 142, pp. 347-356, 1985.
8. Bird, R. E., Hardman, K. D., Jacobson, J. W., Johnson, S., Kaufman, B. M., Lee, S. M., Lee, T., Pope, S. H., Riordan, G. S., and Whitlow, M., “Single chain antigen-binding proteins.”, Science, 242, pp. 423-426, 1988.
9. Bird, R. E., and Webb-Walker, B., “Single chain antibody variable regions.”, Trends Biotechnol., 9, pp. 132-137, 1991.
10. Better, M., and Horwitz, A. H., “Expression of engineered antibodies and antibody fragments in microorganisms.”, Methods Enzymol., 178, 466-496, 1989.
11. Alvi A Z, Stadnyk L L, Nagata L P, Fulton R E, and Suresh M R: Development of second generation monoclonal functional single chain variable fragment (ScFv) antibodies against Venezuelan equine encephalitis virus (VEE): Cloning, Expression, Sequencing and functional analysis of two ScFv antibodies. Defence Research Establishment Suffield Report TR1999-033, 1999.
12. Sambrook J, Fritsch E F, and Maniatis T: Molecular Cloning, A Laboratory Manual, 2nd edition. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1989.
13. Alvi A Z: Re-engineering of single chain variable fragment (ScFv) antibody. Final report for personal services contract #W7702-P059 to AFAM Alvi researchers and consultants. Submitted December 1999 to Defence Research Establishment Suffield.
14. Brewer J M, Pesce A J, and Ashworth R B (Eds): “Appendices”, Experimental Techniques in Biochemistry, Prentice-Hall iinc, New Jersey, 1974, pp 328.
15. Kabat E A, Wu T T, Perry H M, Gottesman K S, and Foeller C: “Sequences of proteins of immunological interest”, 5
th
ed. U.S. Department of Health and Human services. Public Health Service, National Institutes of Health. Bathedsa, Md., 1991.
16. Kinney R M, Tsuchiya K R, Sneider J M, and Trent D W: “Molecular evidence for the origin of the widespread Venezuelan equine encephalitis epizootic of 1969-1972”. J Gen Virol 1992; 73:3301-3305.
17. Weaver, S C, Salas R, Rico-Hesse R, Ludwig G V, Oberste M S, and Boshell J: “Re-emergence of epidemic Venezuelan equine encephalomyelitis in South America. VEE study group”. Lancet 1996; 348: 436-440.
18. Roehrig J T, Day J W, and Kinney R M: “Antigenic analysis of the surface glycoproteins of a Venezuelan equine encephalomyelitis virus (TC-83) using monoclonal antibodies”. Virology 1982; 118:269-278.
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Escherichia coli
”. Nature 1989; 341:544-546.
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The alphavirus family comprises of a large number of viruses that are closely related in their molecular structure but cause a variety of different diseases in humans and other animals [1]. Some alphaviruses, upon infection, enter the central nervous system (CNS) and lead to encephalitis. A New World Alpha virus of particular importance in this regard is Venezuelan equine encephalitis (VEE) virus. VEE virus infections mainly target the CNS and lymphoid tissues causing severe encephalitis in equines and systemic febrile infection with occasional encephalitis in humans. VEE virus is highly infectious by aerosol inhalation for humans [1].
Serologically the VEE complex of viruses can be subdivided into six subtypes (I-VI), with subtype I exhibiting five variants (I
AB
, I
C
, I
D
, I
E
, I
F
) [1]. VEE epizootics are associated with members of subtypes I
AB
or I
C
. The other subtype I variants (I
D
, I
E
and I
F
) and subtypes II-VI have been associated with enzootic VEE transmission [2].
The molecular structure of the VEE virion consists of a plus sense RNA genome encapsulated in an enveloped icosahedral nucleocapsid [3]. The envelope contains two important structural glycoproteins (gp), E
2
(56 KDa) and E
1
(50 KDa) [4]. The viral neutralization sites reside in the E
2
envelope protein [5]. Thus the E
2
protein of VEE is an important target for immunodetection/protection studies.
Hybridoma technology [6] made it possible to generate monoclonal antibodies (Mab) directed against viruses. The disadvantages of using monoclonal antibodies (Mabs) as immunodiagnostic or immunotherapeutic reagents are known. The cost of large-scale production of Mabs is excessive. The potential for genetic variations introduced during repeated cycles of cell growth make Mabs difficult to handle and potentially unreliable. In addition, antigenicity of the complete antibody molecule, when administered as therapeutic reagent, is associated with “serum sickness” in recipients. Furthermore, due to the large size of the whole antibody molecule, there is low penetrability of administered antibody into target tissues. These features make the complete antibody molecule unattractive for use as therapeutic reagent [19, 20].
However, with the development of recombinant antibody technology, where functional antibody fragments can be produced in bacteria, the appl
Alvi Azhar
Fulton R. Elaine
Nagata Leslie
Her Majesty the Queen in right of Canada as represented by the
Park Hankyel T.
Rader & Fishman & Grauer, PLLC
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