Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Reexamination Certificate
1989-02-23
2001-09-18
Stucker, Jeffrey (Department: 1648)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
C424S085100, C424S184100, C424S204100, C424S207100, C424S208100, C435S005000, C530S350000
Reexamination Certificate
active
06290963
ABSTRACT:
The present invention is related to certain substantially pure, antigenic, native and recombinant HIV envelope polypeptides. More particularly, the present invention is related to certain peptides which elicit a cellular immune response and anti-HIV antibodies in a responsive host. The peptides are also useful as diagnostic reagents for detecting HIV infection.
Human immunodeficiency virus (HIV) is a causative factor of acquired immunodeficiency syndrome (AIDS). Effective methods and products to prevent or control HIV infection are still needed.
SUMMARY OF INVENTION
It is, therefore, an object of the present invention to provide native and recombinant HIV envelope proteins which elicit a cellular immune response and/or antibodies against HIV.
It is another object of the present invention to provide anti-HIV compositions and methods of inhibiting HIV infection.
It is a further object of the present invention to demonstrate that purified gp160, gp120, and their deglycosylated analogues interfere with viral infection and block the process of multi-nucleated giant cell formation, i.e. the fusion of uninfected cells with infected cells. It is also shown that deglycosylation of gp120 results in a reagent which nearly eliminates cell fusion or syncytia formation.
It is also shown that native gp120 and recombinant peptides gp160 and PB1 elicit neutralizing antibodies in responsive hosts to which these immunogenic peptides are administered. These immunogens are, therefore, useful as active ingredient in anti-HIV compositions.
Additionally, an increasing body of evidence suggests that the primary mode of transmission of HIV is from infected to uninfected cell. Clearly, the ability of the preparations of the present invention to block the fusion of uninfected to infected cells is of critical importance in understanding the AIDS disease and in devising treatment modalities against the disease.
The complete nucleotide sequence of the envelope gene of HIV is 2,619 nucleotides in length and encodes 873 amino acids. The exterior portion of the envelope glycoprotein constitutes a major immunologic stimulus. It has been shown that a spectrum of diversity exists among the HIV virus isolates; it is the envelope gene which varies most. Furthermore, within the envelope gene, the extracellular region varies considerably more than does the transmembrane region, containing localized regions of high variability and high conservation. This knowledge is useful in developing strategies for combating HIV infection across divergent strains of the virus.
Any of a large number of available host cells may be used to test the infectivity of HIV. The selection of a particular host is dependent upon a number of factors recognized in the art. These include, for example, compatibility with the virus, toxicity of proteins encoded by the virus, ease of recovery of the desired virus or protein product, expression characteristics, bio-safety, and costs. A balance of these factors must be struck with the understanding that not all hosts may be equally effective for expression of a particular recombinant DNA molecule.
Prior to the present invention, AIDS virus variants were propagated in an HT parental cell line, H9. This cell line, as well as other OKT4
+
mcell lines capable of immortalizing AIDS virus variants are described in Popovic et al,
Science,
224:497 (1984) and Sarngadharan et al,
Science,
224:506 (1984). Of critical concern is evidence that the T-cell tropism of the virus may be acquired behavior resulting from the continual propagation of the virus in T4
+
cells (particularly, H9 cells) both in vitro and in vivo. Quantitative titration of an HTLV-III
B
isolate on T-cells and monocyte/macrophage (M/M) cells showed a 10,000-fold greater susceptibility on OKT4
+
T-cells than M/M cells. Limited evidence suggests that cells other than T-lymphocytes can be infected by the virus. See Montagnier et al,
Science
, Vol. 225, p. 63 (1984); Dalgleish et al,
Nature
, Vol. 312, p. 763 (1984); and Levy et al,
Virology
, Vol. 147, p. 441 (1985).
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patent: 5019387 (1991-05-01), Haynes et al.
patent: 5142025 (1992-08-01), Putney et al.
Brown, “AIDS Vaccine Trials Viewed with Caution”. Wash. Post Newspaper Jun. 10, 1993.*
Cohen “Jitters Jeopardize AIDS Vaccine Trials”. Science 262:980-981, 1993.*
Fox, “No Winners Against AIDS”, Bio/Technology vol. 12:128, 1994.*
Robey, et al. : Characterization of envelope and core . . . : Science: vol. 228: pp. 593-595, May 1985.*
Crowl, et al, 1985, Cell 41: 979-986.*
Lasky, et al, 1986, Science 233:209-212.*
Chang, et al, 1985, Biotechnology 3:905-909.*
Putney et al., 1986, Science 234: 1392-1395.*
Crowl, et al., 1985, “HTLV-III Gene Products Synthesized . . . ” Cell 41:979-986.*
Lasky, et al., 1986, “Neutralization of the AIDS Retrovirus . . . ” Science 233: 209-212.*
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Putney, et al., 1986 “HTLV-III/LAN-Neutralizing Antibodies to anE. coli. . . . ” Science 234:1392-5.*
Starcich, et al., 1986 Identification and Characterization of Conserved . . . . Cell, vol. 45, 637-648.*
Siliciano, et al., 1988, Analysis of Host-Virus Interactions in AIDS . . . , Cell, vol. 54, 561-575.*
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Fox: No winners against AIDS: Biotechnology vol. 12: 128, 1994.
Bolognesi Dani P.
Fischinger Peter J.
Gallo Robert C.
Krohn Kai
Matthews Thomas J.
Stucker Jeffrey
The United States of America as represented by the Secretary of
Townsend and Townsend / and Crew LLP
Winkler Ulrike
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