Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
1998-10-15
2002-09-17
Nguyen, Dave T. (Department: 1633)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C435S091400, C435S091410, C435S320100, C435S455000
Reexamination Certificate
active
06451769
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to compositions and methods for administering Borrelia genospecies DNA encoding antigen(s) in vivo or in vitro. More particularly, this invention relates to compositions and methods for administering Borrelia genospecies DNA encoding an antigen or antigens, e.g., OspA (outer surface protein A) and/or OspB (outer surface protein B), and/or OspC (outer surface protein C), or fragments thereof such as fragments thereof containing at least one epitope of interest, for expression thereof, in vivo, ex vivo or in vitro.
BACKGROUND OF THE INVENTION
Lyme disease is a multisystem illness, transmitted by ticks of the
Ixodes ricinus
complex. The spirochaete
Borrelia burgdorferi
sensu lato is the etiologic agent of Lyme disease, which is now the most common arthropod borne disease in the United States, and is endemic in Central Europe (Barbour and Fish 1993). More particularly, there are three genospecies of Borrelia associated with Lyme disease:
Borrelia burgdorferi, Borrelia afzelii
and
Borrelia garinii. Borrelia burgdorferi
is the etiologic agent of Lyme disease in North America, and some European Lyme disease is considered to be
Borrelia burgdorferi
sensu stricto.
Borrelia afzelii
and
Borrelia garinii
are the major cause of European Lyme disease and are considered
Borrelia burgdorferi
sensu lato.
Although Lyme disease is curable by antibiotic therapy in its early stages, if Lyme disease is allowed to progress, cardiac, neurological and joint abnormalities can arise. Investigations into the development of a human vaccine for Lyme disease are under way. The outer surface lipoprotein OspA of
Borrelia burgdorferi
is the current major candidate molecule for development of such a vaccine.
Recombinant OspA lipoprotein (rOspA) is known to elicit a protective immune response in mice against challenge by infectious
B. burgdorferi
(Fikrig et al., 1990; Erdile et al., 1993; U.S. Ser. No. 08/373,455). OspA is currently undergoing human field trials as a subcutaneously administered vaccine in the United States (Keller et al., 1994). Above-cited U.S. Pat. No. 5,688,512 relates to substantially pure OspA, vaccines including substantially pure OspA, and methods for inducing a protective immunological response against
B. burgdorferi
employing such vaccines, inter alia.
Above-cited applications Ser. No. 08/373,455 and PCT/US92/08697 relate to rOspA vaccines, especially lipidated rospA, and methods for expressing DNA encoding OspA. Above-cited applications Ser. No. 08/320,416 (now U.S. Pat. No. 5,582,990) and WO 90/04411 relate to DNA encoding OspA, the amino acid sequence of OspA, synthetic OspA, compositions containing OspA or synthetic OspA, and methods of using such compositions. Above cited application Ser. No. 08/137,175, filed Oct. 26, 1993 (now U.S. Pat. No. 5,777,095) relates to DNA coding for various OspAs and OspBs, OspAs and OspBs encoded by such DNA (including amino acid sequences therefor), and immunologically interesting fragments of OspAs and OspBs and DNA coding therefor.
In approximately half of the European isolates of
B. burgdorferi
, outer surface protein C (OspC) is the major surface antigen found on these spirochetes. Immunization of gerbils and mice with purified recombinant OspC produces protective immunity to
B. burgdorferi
strains expressing the homologous OspC protein (Preac-Mursic et al., INFECTION (1992) 20:342-349; Probert et al., INFECTION AND IMMUNITY (1994) 62:1920-1926). Published international patent application WO 91/09870 (Mikrogen Molekularbiologische Entwicklungs-GmbH) describes the DNA sequence of the ospC gene of
B. burgdorferi
strain Pko and the OspC protein encoded thereby of 22 kDa molecular weight (termed “pC” therein). This sequence reveals that OspC is a lipoprotein that employs a signal sequence similar to that used for OspA. As to DNA encoding OspC or recombinant OspC, reference is also made to WO96/05313 (Max-Planck Institute); Leuba-Garcia et al., Zentralbl Bakteriol. 287(4):475-84, 1998; Rauer et al., J. Clin. Microbiol. 36(4):857-61, 1998; Masuzawa et al., Clin. Diagn. Lab. Immunol. 4(1):60-63, 1997; Fukunaga et al. J. Clin. Microbiol. 33(9):2415-2420, 1995; Jauris-Heipke et al., J. Clin. Microbiol. 33(7):1860-66, 1995; Theisen et al., J. Bacteriol. 177(11):3036-3044, 1995; Stevenson et al. FEMS Microbiol. Lett. 124(3):367-72, 1994; and Padula et al., Infect. Immun. 61(12):5097-5105, 1993.
The other above-cited applications relate to DNA encoding other Borrelia antigens or other Osps, or to DNA encoding useful fragments of OspA or of other Osps, amino acid sequences thereof, compositions containing such fragments or other Osps, and methods for using such compositions; and, such DNA that can be used in the methods of Ser. No. 08/373,455 or PCT/US92/08697 to produce OspA, other Borrelia antigens or outer surface proteins (Osps), or fragments thereof, can be used in this invention. In regard to DNA useful in this invention, reference again made to V. Preac-Mursic et al., supra, W. S. Probert et al., supra, WO 91/09870, supra, as well as to all of the documents cited herein and also to Molecular Microbiology (1989), 3(4), 479-486, and PCT publications WO 93/04175, and WO 96/06165.
Alternative vaccination strategies are desirable as such provide alternative routes to administration or alternative routes to responses.
In particular, it is believed that heretofore the art has not taught or suggested administration to a eukaryotic cell in vitro or ex vivo, or to a mammalian host—domesticated or wild or human—susceptible to Lyme disease, of Borrelia genospecies DNA e.g., DNA encoding OspA and/or OspB, and/or OspC or expression thereof in vivo, especially as herein disclosed.
OBJECTS AND SUMMARY OF THE INVENTION
It is an object of the invention to provide methods and compositions for administering to a host, such as a mammalian host susceptible to Lyme Disease, Borrelia genospecies isolated and/or purified DNA encoding an antigen or antigens or a fragment or fragments thereof such as fragment or fragments containing at least one epitope of interest, e.g., isolated and/or purified DNA encoding an antigen or antigens or a fragment or fragments thereof such as fragment or fragments containing at least one epitope of interest from
Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii
or combinations thereof, such as isolated and/or purified DNA encoding OspA, and/or OspB and/or OspC, or isolated and/or purified DNA encoding at least one epitope of OspA and/or OspB and/or OspC; for instance, DNA encoding
Borrelia burgdorferi
OspA and/or OspB and/or OspC. The compositions can include a carrier or diluent. The DNA is administered in a form to be expressed by the host, and preferably in an amount sufficient to induce a response such as a protective immune response; and, the DNA can be administered without any necessity of adding any immunogenicity-enhancing adjuvant.
Accordingly, the present invention provides Borrelia genospecies antigen or epitope DNA plasmids for expression by eukaryotic cells, compositions containing the plasmids, and methods for using the compositions and for using the products from the compositions.
The plasmid of the invention can comprise from upstream to downstream (5′ to 3′): DNA encoding a promoter for driving expression in eukaryotic cells, DNA encoding a leader peptide for enabling secretion of a prokaryotic protein sequence from a mammalian cell, Borrelia genospecies antigen or epitope DNA, and DNA encoding a terminator.
The DNA encoding a promoter for driving expression in eukaryotic cells can be a eukaryotic, e.g., mammalian, viral promoter, such as a herpes virus promoter. A human cytomegalovirus promoter is presently preferred. The human cytomegalovirus promoter can be an immediate early human cytomegalovirus promoter such as HCMV-IE. The plasmid can contain the HCMV-IE gene 5′ untranslated region (UTR) which includes Intron A. This sequence can be 3′ to the HCMV-IE promoter and 5′ to the portion of the chimeric 5′ UTR s
Barbour Alan G.
Carner Kristin R.
Huebner Robert C.
Liang Xiaowu
Luke Catherine J.
Frommer William S.
Frommer & Lawrence & Haug LLP
Kowalski Thomas J.
Nguyen Dave T.
Pasteur Merieux Serums et Vaccins
LandOfFree
Compositions and methods for administering Borrelia DNA does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compositions and methods for administering Borrelia DNA, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compositions and methods for administering Borrelia DNA will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2852263