Title:  Polypeptides displaying HBV antigenicity or hbv antigen specificity

United States Patent:  6,297,355

Assignee:  Biogen, Inc. (Cambridge, MA)

Filed:  June 7, 1995

Foreign Application Priority Data:  Dec 22, 1978[GB] (49907/78);  Dec 27, 1978[GB] (50039/78)

Recombinant DNA molecules and hosts transformed with them which produce polypeptides displaying HBV antigenicity and genes coding therefor and methods of making and using these molecules, hosts, genes and polypeptides. The recombinant DNA molecules of this invention are characterized by structural genes that code for at least one polypeptide displaying HBV antigenicity. In appropriate hosts these recombinant DNA molecules permit the production and identification of genes and polypeptides characteristic of HBV antigenicity and their use in compositions and methods for detecting HBV virus infections in humans and stimulating the production of antibodies against this infection.

DISCLOSURE OF THE INVENTION

The present invention solves the problems referred to by providing in accordance with the invention a recombinant DNA molecule characterized by a structural gene coding for a polypeptide displaying HBV antigenicity.

By virtue of our invention, it is possible to obtain HBV antigens and genes in substantial and uncontaminated quantities for vaccine preparations and for use in detection of the viral infection and determination of its pathology and molecular biology. Such supplies have not hitherto been available, because of the narrow host range of the virus and its inability to be grown in tissue culture.

As will be appreciated from the disclosure to follow, the recombinant DNA molecule of the invention is capable of producing, in an appropriate host, at least one viral polypeptide displaying HBV antigenicity and the structural genes that code therefor. These recombinant DNA molecules and hosts may be utilized to prepare polypeptides displaying HBV antigenicity and structural genes coding for these polypeptides. These products may also be identified and characterized and are useful either as produced in the host or after appropriate derivatization or modification in compositions and methods for improving production of these products themselves and for detecting HBV infection, tracing its pathology and stimulating the production of HBV antibodies in humans.

In accordance with the invention we also provide a process for producing a recombinant DNA molecule, characterized by linking a DNA sequence prepared from the endogenous DNA of a Dane particle to another DNA sequence prepared from a source other than the Dane particle.

Our process may be distinguished from the prior processes above mentioned in that none of the prior processes employs a natural gene or DNA for a particular protein for construction of the recombinant DNA molecule and production of that protein or gene. Instead, they employ either synthetic genes made by chemical synthesis or artificial genes made by enzymatically copying the mRNA isolated from the donor cell to produce cDNA sequences.

One reason that natural DNA has not been previously employed directly in recombinant DNA synthesis of proteins is that natural DNA's from most higher organisms and at least some animal viruses contain "introns" or additional nucleotide sequences as part of the gene. These introns do not form part of the final message of the gene. Instead, they are removed in vivo in higher organisms by special processing enzymes acting upon the primary transcription product to afford the ultimate message (mRNA) of the gene. Bacteria are presumed to be unable to process such introns so that natural DNA would not be expected to be expressed in bacterial hosts and the desired proteins would not be expected to be produced by these hosts.

Claim 1 of 1 Claim

I claim:

1. A polypeptide displaying HBV antigenicity or antigen specificity, said polypeptide being free of any human serum proteins and any primate serum proteins and produced by a unicellular host transformed with a recombinant DNA molecule, said molecule comprising an HBV DNA sequence coding on expression in a unicellular host for said polypeptide, and being operatively linked to an expression control sequence in said molecule.

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