E.i. Dupont De Nemours and Company

Bristol-myers Squibb Compnay

Bruce D Korant

Charles A Kettner

Michael W Hunkapiller

Ernest Knight, Jr

David J Ganfield

David L Anton

Chia-Lin J Wang

This invention relates to a method of treating human immunodeficiency virus (HIV) infection in a mammal comprising administering to the mammal a therapeutically effective amount of a combination of: (i) at least one cytotoxic agent and (ii) at least one non-nucleoside reverse transcriptase HIV inhibitor (NNRTI). This invention also relates to a method of treating chronic viral infections comprising administering to the mammal a therapeutically effective amount of a combination of: (i) at least one cytotoxic agent and (ii) at least one antiviral agent.

Method of treating HIV infection by combined use of a cytotoxic agent and a non-nucleoside reverse transcriptase inhibitor

A method for preparing selected peptide substrates for detecting the activity of virus-specified proteases is provided. Specific tetrapeptide substrates are disclosed which are conjugates of protease-cleavable indicator groups and peptide sequences resembling picornavirus protease cleavage recognition sites.

Peptide substrates for detecting virus-specified protease activity

S-Modified Adenosyl-1,8-Diamino-3-Thiooctane derivatives which are useful as interferon potentiators and polyamine biosynthesis inhibitors are disclosed.

S-modified adenosyl-1,8-diamino-3-thiooctane derivatives

A method for extracting protein produced by procaryotic or eucaryotic cells comprising contacting said cells with a solution containing from about 50 to about 100 volume percent of an organic acid having from 1 to 5 carbon atoms and mixtures thereof is disclosed.

Method for extracting protein with organic acid

Certain peptide methyl ketone derivatives inhibit picornavirus replication by inhibition of virus-specified protease activity.

Tetrapeptide methyl ketone inhibitors of viral proteases

A general method for preparing specific inhibitors of virus-specified proteases is disclosed. The inhibitors comprise a halomethyl ketone or methyl ketone moiety covalently linked to a peptide sequence of three, four or five amino acids or amino acid residues, which peptide sequence corresponds to an amino acid sequence found adjacent to and upstream of a cleavage site recognized by a virus-specified protease.

Method for preparing specific inhibitors of virus-specified proteases

Selected tripeptide and tetrapeptide halomethyl ketones are employed in processes for treating viral infection in mammals. These compounds inhibit picornavirus protease activity.

Inhibition of viral protease activity by peptide halomethyl ketones

Antibodies to the twenty-one acid peptide: (X-Ser-Tyr-Asn-Leu-Leu-Gly-Phe-Leu-Gln-Arg-Ser-Ser-Asn-Phe-Gln-Y-Gln-Lys-L eu-Leu).sub.n, where X is Met or Ser, Y is His or Cys and n is 1 to 12; peptide/protein conjugates and antibodies thereto; process for producing the antibodies; and processes for assaying human fibroblast interferon and for purifying it.

Antibodies to immunogenic peptides and their use to purify human

The twenty-one amino acid peptides, (X-Ser-Tyr-Asn-Leu-Leu-Gly-Phe-Leu-Gln-Arg-Ser-Ser-Asn-Phe-Gln-Y-Gln-Lys-L eu-Leu).sub.n, where X is Met or Ser, Y is His or Cys and n is 1 to 12, useful for assaying human fibroblast interferon and for purifying it.

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Wilmington, DE, United States of America

Bruce D Korant