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Home Drugs Molecularly-cloned-acquired-immunodeficiency-syndrome-polypeptides-and-methods-of-use

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 Molecularly cloned acquired immunodeficiency syndrome polypeptides and methods of use

Details
Inventors: Berman, Phillip W.; Capon, Daniel J.; Lasky, Laurence A.;
Assignee: Genentech, Inc. (San Francisco, CA)
Primary Examiner: Smith; Lynette F.
Assistant Examiner:
Attorney, Agent or Firm: Torchia; Timothy E.

Diagnostic product and vaccine for Acquired Immuno-deficiency Syndrome (AIDS) and methods for making and using same, wherein viral polypeptide sequences from an AIDS associated retrovirus are expressed directly or as a fusion polypeptide in a prokaryotic or mammalian cell expression host to produce a diagnostic product which specifically binds complementary antibody produced by individuals afflicted with AIDS or a vaccine against AIDS which confers resistance to infection by AIDS associated retrovirus. The reverse transcriptase of an AIDS associated retrovirus is used separately or in a whole cell assay to identify compounds which selectively inhibit retroviral reverse transcriptase.

DETAILED DESCRIPTION In accordance with this invention, DNA encoding AIDS-associated polypeptides is identified and employed in recombinant prokaryotic or mammalian cell culture systems to synthesize predetermined AIDS-associated polypeptides and derivatives and amino acid sequence variants thereof.
Derivatives of AIDS-associated polypeptides include unglycosylated or variantly glycosylated polypeptides, as well as formylmethionyl N-terminal species.
Variants of normal AIDS-associated virus polypeptides are provided wherein one or more amino acid residues of the normal polypeptides have been deleted or substituted by other residues, or one or more amino acid residues inserted.
These variants include predetermined fragments of normal polypeptides (deletion variants), fusion polypeptides containing an AIDS-associated virus polypeptide or fragment thereof with a second polypeptide which is not AIDS-associated virus polypeptide or fragment thereof (fusion or insertional variants), and all of the above in which an amino residue has been substituted.
Preferred deletion variants are gp41 or gp160 envelope proteins from which one or more hydrophobic regions have been deleted.
DNA encoding the polypeptides of this invention are provided, as well as vectors operably incorporating such DNA and mammalian or prokaryotic cell cultures transformed therewith.
The predetermined polypeptide sequences of an AIDS-associated retrovirus produced herein are essentially free of other naturally occurring AIDS related polypeptides.
These polypeptides contain at least one antigenic determinant which is capable of specifically binding complementary antibody.
Specific polypeptide sequences described herein are designated p-24, p-15, E', reverse transcriptase and envelope (env) polypeptides.
In preferred embodiments, fragments and/or fusions of predetermined polypeptide sequences of an AIDS associated retrovirus, containing at least one antigenic determinant capable of specifically binding complementary antibody, are provided



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