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Patent Searching and Data


Title:
BOTULINUM NEUROTOXIN VACCINE
Document Type and Number:
WIPO Patent Application WO/2000/002524
Kind Code:
A2
Abstract:
Using the nontoxic heavy chain fragment from botulinum neurotoxins A-G, compositions and methods of use in inducing an immune response which is protective against intoxication with botulinum in subjects is described.

Inventors:
LEE JOHN S (US)
PUSHKO PETER (US)
SMITH JONATHAN F (US)
PARKER MICHAEL (US)
DERTZBAUGH MARK T (US)
SMITH LEONARD (US)
Application Number:
PCT/US1999/015570
Publication Date:
January 20, 2000
Filing Date:
July 09, 1999
Export Citation:
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Assignee:
US MED RES INST INFECT DISEASE (US)
LEE JOHN S (US)
PUSHKO PETER (US)
SMITH JONATHAN F (US)
PARKER MICHAEL (US)
DERTZBAUGH MARK T (US)
SMITH LEONARD (US)
International Classes:
C07K14/31; C07K14/32; C07K14/33; C12N7/01; C12N15/31; (IPC1-7): A61K/
Domestic Patent References:
WO1996037616A11996-11-28
WO1998008540A11998-03-05
Other References:
ANDERSON R ET AL: "Immune response in mice following immunization with DNA encoding fragment C of tetanus toxin" INFECTION AND IMMUNITY, vol. 64, no. 8, August 1996 (1996-08), pages 3168-3173, XP002139492
PUSHKO P ET AL: "Replicon-helper systems from attenuated Venezuelan equine encephalitis virus: expression of heterologous genes in vitro and immunization against heterologous pathogens in vivo" VIROLOGY, vol. 239, no. 2, December 1997 (1997-12), pages 389-401, XP002139493
Attorney, Agent or Firm:
Harris, Charles H. (MD, US)
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Claims:
What is claimed is:
1. A recombinant DNA construct comprising: (i) a vector, and (ii) at least one nucleic acid fragment comprising a carboxy terminal heavy chain fragment from any of BoNTA, BoNTB, BoNTC, BoNTD, BoNTE, BoNTF, and BoNTG.
2. A recombinant DNA construct according to claim 1 wherein said vector is an expression vector.
3. A recombinant DNA construct according to claim 1 wherein said vector is a prokaryotic vector.
4. A recombinant DNA construct according to claim 1 wherein said vector is a eukaryotic vector.
5. The recombinant DNA construct of claim 1 wherein said vector is a VEE virus replicon vector.
6. The recombinant DNA construct according to claim 5 wherein said construct is p301440A.
7. The recombinant DNA construct according to claim 5 wherein said construct is p3014114al.
8. The recombinant DNA construct according to claim 5 wherein said construct is p3014102a2.
9. The recombinant DNA construct according to claim 5 wherein said construct is p301473B.
10. The recombinant DNA construct according to claim 5 wherein said construct is p3014110C.
11. The recombinant DNA construct according to claim 5 wherein said construct is p301475E.
12. The recombinant DNA construct according to claim 5 wherein said construct is p301477F.
13. The recombinant DNA construct according to claim 5 wherein said construct is p3014107G.
14. Self replicating RNA produced from any of the constructs chosen from the group consisting of: p3014 40a, p3014114al, p3014102a2, p301473B, p3014110C, p301475E, p301477F, and p3014107G.
15. Infectious alphavirus particles produced from packaging the self replicating RNA of claim 14.
16. A pharmaceutical composition comprising infectious alphavirus particles according to claim 15 in an effective immunogenic amount in a pharmaceutically acceptable carrier and/or adjuvant.
17. A host cell transformed with a recombinant DNA construct according to claim 5.
18. A host cell according to claim 17 wherein said host cell is prokaryotic.
19. A host cell according to claim 17 wherein said host cell is eukaryotic.
20. A method for producing BoNT Hc protein comprising culturing the cells according to claim 19 under conditions such that said DNA fragment is expressed and said protein is produced.
21. A method for producing BoNT Hc protein comprising culturing the cells according to claim 18 under conditions such that said DNA fragment is expressed and said protein is produced.
22. A vaccine for BoNTA comprising viral particles containing one or more replicon RNA encoding one or more BoNTA proteins and, optionally one or more antigens selected from the group consisting of HcBoNTB, HcBoNTC, HcBoNTD, HcBoNTE, HcBoNTF, and HcBoNTG.
23. A vaccine for BoNTB comprising viral particles containing one or more replicon RNA encoding one or more BoNTB proteins and, optionally, one or more antigens selected from the group consisting of HcBoNTA, HcBoNTC, HcBoNTD, HcBoNTE, HcBoNTF, and HcBoNTG.
24. A vaccine for BoNTC comprising viral particles containing one or more replicon RNA encoding one or more BoNTC proteins and, optionally, one or more antigens selected from the group consisting of HcBoNTA, HcBoNTB, HcBoNTD, HcBoNTE, HcBoNTF, and HcBoNTG.
25. A vaccine for BoNTD comprising viral particles containing one or more replicon RNA encoding one or more BoNTD proteins and, optionally, one or more antigens selected from the group consisting of HcBoNTA, HcBoNTB, HcBoNTC, HcBoNTE, HcBoNTF, and HcBoNTG.
26. A vaccine for BoNTE comprising viral particles containing one or more replicon RNA encoding one or more BoNTE proteins and, optionally, one or more antigens selected from the group consisting of HcBoNTA, HcBoNTB, HcBoNTC, HcBoNTD, HcBoNTF, and HcBoNTG.
27. A vaccine for BoNTF comprising viral particles containing one or more replicon RNA encoding one or more BoNTF proteins and, optionally, one or more antigens selected from the group consisting of HcBoNTA, HcBoNTB, HcBoNTC, HcBoNTD, HcBoNTE, and HcBoNTG.
28. A vaccine for BoNTG comprising viral particles containing one or more replicon RNA encoding one or more BoNTG proteins and, optionally, one or more antigens selected from the group consisting of HcBoNTA, HcBoNTB, HcBoNTC, HcBoNTD, HcBoNTE, and HcBoNTF.
29. A pharmaceutical composition comprising the self replication RNA of claim 14 in an effective immunogenic amount in a pharmaceutically acceptable carrier and/or adjuvant.
30. 24 A pharmaceutical composition comprising one or more recombinant DNA constructs chosen from the group consisting of p301440a, p3014114al, p3014 102a2, p301473B, p3014110C, p301475E, p301477F, and p3014107G in a pharmaceutically acceptable amount, in a pharmaceutically accpetable carrier/and or adjuvant.
Description:
INTERNATIONAL SEARCH REPORT 1 latlonal Application No PCT/US 99/15570 C. (Continuatlon) DOCUMENTS CONSIDERED TO BE RELEVANT Category ° Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. A PUSHKO P ET AL :"Replicon-helper systems from attenuated Venezuelan equine encephalitis virus: expression of heterologous genes in vitro and immunization against heterologous pathogens in vivo" VIROLOGY, vol. 239, no. 2, December 1997 (1997-12), pages 389-401, XP002139493 1 iternational application No. INTERNATIONAL SEARCH REPORT PCT/US 99/15570 Boxi Observations where certain claims were found unsearchable (Continuation of item 1 of first skeet) This International Search Report has not been established in respect of certain claims under Article 17 (2) (a) for the following reasons: 1. ij Claims Nos.: because they relate to subject matter not required to be searched by this Authority, namely: Although claim 20, as far as an in vivo method is concerned, is directed to a method of treatment of the human/animal body, the search has been carried out and based on the alleged effects of the compound/composition. 2. j Claims Nos.: because they relate to parts of the International Application that do not comply with the prescribed requirements to such an extent that no meaningful International Search can be carried out, specifically: 3. Claims Nos.: because they are dependent claims and are not drafted in accordance with the second and third sentences of Rule 6.4 (a). Box 11 Observations where unity of invention Is lacking (Continuation of Item 2 of first sheet) This International Searching Authority found multiple inventions in this international application, as follows: see additional sheet 1. As all required additional search fees were timely paid by the applicant, this International Search Report covers all searchable claims. 2. X As all searchable claims could be searched without effort justifying an additional fee, this Authority did not invite payment of any additional fee. 3. As only some of the required additional search fees were timely paid by the applicant, this International Search Report covers only those claims for which fees were paid, specifically claims Nos.: 4. No required additional search fees were timely paid by the applicant. Consequently, this International Search Report is restricted to the invention first mentioned in the claims; it is covered by claims Nos.: Remark on Protest The additional search fees were accompanied by the applicant's protest. j No protest accompanied the payment of additional search fees. u FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 This International Searching Authority found multiple (groups of) inventions in this international application, as follows: 1. Claims: 6 (totally) and 1-5,14-30 (all partially) A recombinant DNA construct comprising a VEE virus replicon vector and at least one nucleic acid fragment comprising a carboxy-terminal heavy chain fragment of BoNT ; said DNA construct being p3014-40a ; compositions, host cells, methods, and vaccine applications thereof. 2. Claims: 7 (totally) and 1-5,14-30 (all partially) As for subject 1, but relating to p3014-114al 3. Claims: 8 (totally) and 1-5,14-30 (all partially) As for subject 1, but relating to p3014-102a2 4. Claims: 9 (totally) and 1-5,14-30 (all partially) As for subject 1, but relating to p3014-73b 5. Claims: 10 (totally) and 1-5,14-30 (all partially) As for subject 1, but relating to p3014-110c 6. Claims: 11 (totally) and 1-5,14-30 (all partially) As for subject 1, but relating to p3014-75e 7. Claims: 12 (totally) and 1-5,14-30 (all partially) As for subject 1, but relating to p3014-77f 8. Claims: 13 (totally) and 1-5,14-30 (all partially) As for subject 1, but relating to p3014-107g INTERNATIONAL SEARCH -------------------) I natlonal Application No Information on patentfamily n-r/ ! ! f- nn/it-r-7n PU ; TUS 99/15570 Patent document Publication Patent family Publication cited in search report date member (s) date WO 9637616 A 28-11-1996 US 5792462 A 11-08-1998 AU 5925696 A 11-12-1996 CA 2220964 A 28-11-1996 JP 11505719 T 25-05-1999 WO 9808540 A 05-03-1998 AU 4245097 A 19-03-1998