United States Patent (19) 11 Patent Number: 5,766,598 Paoletti Et Al

United States Patent (19) 11 Patent Number: 5,766,598 Paoletti Et Al

USOO5766598A United States Patent (19) 11 Patent Number: 5,766,598 Paoletti et al. 45) Date of Patent: Jun. 16, 1998 54 RECOMBINANTATTENUATED ALVAC Murphy. F., 1996. "Virus Taxonomy", in Fields Virology, CANARYPOXVIRUS EXPRESSION Third Edition, Fields et al., eds. Lippincott-Raven Publish WECTORS CONTAINING HETEROLOGOUS ers. Philadelphia, pp. 15-57. DNA SEGMENTS ENCODNG LENTWRAL Taylor et al., 1991. Vaccine 9(3):190-193. GENE PRODUCTS Berman et al., 1990, Nature 345:622-625. Girard et al., 1991 Proc. Natl. Acad. Sci., USA 88:542-546. 75 Inventors: Enzo Paoletti, Delmar; James Tartaglia. Schenectady; William Irvin Hu et al., 1986. Nature 320:537-540. Cox. Troy, all of N.Y. Ho et al., 1990, Eur, J. Immunol. 20:477-483. Virology, vol. 173, No. 1, issued Nov. 1989, S. Dallo et al. 73) Assignee: Wirogenetics Corporation, Troy, N.Y. "Humoral Immune Response Elicited by Highly Attenuated Variants of Vaccinia Virus and by an Attenuated Recombi nant Expressing HIV-1 Envelope Protein". pp. 323-328 21 Appl. No.: 303,275 (entire document). (22 Filed: Sep. 7, 1994 Virology, vol. 152, issued 1986. M.E. Perkus et al., “Inser tion and Deletion Mutants of Vaccinia Virus". pp. 285-297 Related U.S. Application Data (entire document). Nature, vol. 317, issued 31 Oct. 1985, R.M.L. Buller et al., 63 Continuation of Ser. No. 897,382, Jun. 11, 1992, abandoned, which is a continuation-in-part of Ser. No. 715,921, Jun. 14, "Decreased Virulence of Recombinant Vaccinia Virus 1991, abandoned, and Ser. No. 847,951, Mar. 6, 1992, which Expression Vectors is Associated With a Thymidine is a continuation-in-part of Ser. No. 713,967, Jun. 11, 1991, Kinase-Negative Phenotype", pp. 813-815 (entire docu which is a continuation-in-part of Ser. No. 666,056, Mar. 7, ment). 199. Journal of Virology, vol. 62. No. 12, issued Dec. 1988, H. (51) Int. Cl. ....................... A61K 39/12: A61K 39/295; Shida et al., “Effects and Virulences of Recombinant Vac A61K 39/21: A61K 39/275 cinia Viruses Derived From Attenuated Strains That Express 52 U.S. C. .................................... 424/199.1; 424/208.1: the Human T-Cell Leukemia Virus Type 1 Envelope Gene". 424/232.1; 424/2011; 435/320.1; 435/236: pp. 4474-4480 (entire document). 435/1723 Critical Reviews in Immunology, vol. 10, No. 1 issued 58) Field of Search ................................ 435/69.1, 172.3, 1990.J. Tartaglia et al., "Poxvirus-Based Vectors as Vaccine 435/235. 236, 237; 424/199.1, 202.1, 208.1. Candidates", pp. 13-30 (entire document). (Tartaglia 900). 209.1 Virology, vol. 188, No. 1, issued May 1992, J. Tartaglia et al., "NYVAC: A Highly Attenuated Strain of Vaccinia 56) References Cited Virus". pp. 217-232 (entire document). U.S. PATENT DOCUMENTS Hosmalin. A. Nara, P.L., Zweig, M., Lerche. N.W., Cease. K.B., Gard, E.A., Markham, P.D., Putney, S.D. Daniel, 5,093,258 3/1992 Cohen .................................. 435/235.1 M.D.. Desrosiers, R.C. and Berzofsky, J.A. J. Immunol. 5,174,993 12/1992 Paoletti ..................................... 424/89 146. 1667-1673 (1991). 5,180,675 1/1993 Prillien ... 435/235. 5,185,146 2/1993 Attenburger .............................. 424/89 (List continued on next page.) FOREIGN PATENT DOCUMENTS Primary Examiner-Laurie Scheiner WO 89/O3429 of 1989 WIPO Assistant Examiner-Jeffrey S. Parkin WOA Attorney, Agent, or Firm-Frommer Lawrence & Haug 89/O3429 4f1989 WIPO. LLP: William S. Frommer; Thomas J. Kowalski WOA 90/10693 9/1990 WIPO 57 ABSTRACT WOA 90/210. Of 1990 WIPO This invention is directed toward recombinant attenuated canarypox virus expression vectors containing exogenous OTHER PUBLICATIONS DNA segments encoding lentiviral gene products. A parental Turner, P.C. et al. (90) Current topics in Microbiol. Immu canarypox virus (Rentschler strain) was obtained and attenu no. 163: 125-151. ated through more than 200 serial passages on chick embryo Lerner. R.A. et al. (83) in: The Biology of Immunologic fibroblasts. A master viral seed was subjected to four suc Disease, eds. F.J. Dixon & D.W. Fisher, H.P. Publishing Co. cessive plaque purifications under agar and one plaque clone New York, NY, pp. 331-338. was amplified through five additional passages after which Wain-Hobson. S. et al. (85) Cell 40:9-17. the stock virus was used as the parental virus in in vitro Cooney. E.L. et al. (91) Lancet 337:567-572. recombination studies. This attenuated plaque purified Tartaglia, J. et al. (906) in: Immunochemistry of Viruses, canarypox isolate was designated ALVAC. A series of eds. M.H.V. van Regenwortel and A.R. Newrath, Elsevier ALVAC recombinants were generated that are capable of Science Publishers B.V. pp. 125-151. expressing different HTV and SIV gene products including Norley, S. et al. Immunobiology 184: 193-207 (1992). Gag, Pol, Env, and Nef. These recombinants provide useful Cohen, J. et al. Science 262: 980-81 (1993). reagents for the generation of viral-specific immune Moss, B., 1996, "Poxviridae: The Viruses and Their Repli responses. cation" in Fields Virology, Third Edition, Fields et al., eds. Lippincott-Raven Publishers, Philadelphia, pp. 2637-2671. 14 Claims, 9 Drawing Sheets 5,766,598 Page 2 OTHER PUBLICATIONS Tartaglia.J. and Paoletti. E. In Immunochemistry of viruses, II, eds. van Regenmortel, M.H.V and Neurath, A.R., Letvin, N.L., and King. N.W..J. AIDS3. 1023-1040 (1990). McMichael, A.J., Gotch, F.M., Noble, G.R., and Beare, (Elsevier Science Publishers B.V., Amsterdam) pp. 125 P.A.S. New Engl. J. Med. 309, 13-17 (1983). (1990). Moss, D.J. Rickinson, A.B., and Pope, J.H., Int. J. Cancer Taylor, J. et al., Vaccine 6, 466-467 (1988). 22, 662-668 (1978). Taylor, J. et al., Vaccine 9, 190-193 (1991). Schmaljohn et al., Virology 155, 633–643 (1986). 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