PHS/NIH is number one in terms of inventions and licenses in the virus-related and antiviral therapeutics-related areas (as discussed above concerning patents presented in the Antiviral Agents Bulletin, 1989-1993).11 This reflects the dominance of the federal government and, particularly, PHS/NIH in basic molecular biology and biotechnology and PHS/NIH leadership in basic and directed anti-HIV and antiviral therapeutics research and development.

Besides antiviral drugs and vaccines, the federal government is the source for many basic and enabling technologies, screening methods and research reagents. For example, besides the co-discovery of HIV and development of HIV immunodiagnostics, PHS/NIH was instrumental in developing the infrastructure and technologies that ultimately enabled the discovery of the anti-HIV activity of AZT and other anti-HIV drugs and vaccines. Note, PHS/NIH status as a co-assignee of patents currently held by Burroughs Wellcome Co. covering use of AZT for treatment of HIV-infection is an issue currently in federal court.

Licensed virus- and antiviral-related federal inventions under development or already on the market include:

* DDI (Videx from Bristol-Myers Squibb Co.) and DDC (HIVID from Hoffman-La Roche Inc.), both marketed for treatment of HIV-infection;

* the basic patents concerning HIV, human herpesvirus-6 (HHV-6) and other viruses and related vaccines and diagnostics;

* HIV large-scale culture methods and HIV immunodiagnostics marketed by many companies;

* the broad class of first-generation antisense phosphorothioate oligonucleotides including antiviral antisense drugs from multiple companies currently in clinical trials;

* hepatitis A virus vaccine (Havrix from SmithKline Beecham) on the market in many countries and expected to be approved imminently in the U.S.;

* marketed hepatitis B virus immune globulin therapeutics;

* widely used vaccinia virus expression vectors;

* HIV vaccines under development by various companies;

* herpes simplex virus (HSV) immunodiagnostics;

* retroviral gene therapy vectors currently in clinical trials;

* human papillomavirus vectors and cervical cancer prophylactic vaccines;

* adenovirus gene therapy vectors;

* parvovirus empty capsids useful for vaccines and as vaccine and gene carriers;

* respiratory syncytial virus (RSV) immune globulin (RespiGam) recently considered for approval for prevention of infant RSV infections;

* Peptide T currently in trials for treatment of HIV-infection and chronic fatigue syndrome;

* liposomal nystatin currently in clinical trials for treatment of HIV-infection;

* liver cell culture methods for culture of hepatitis viruses and vaccine production;

* antisense DNA triplex-forming therapeutics and reagents;

* adeno-associated virus expression and gene therapy vectors;

* broad patents covering hepatitis C, E and X virus clones, vaccines and immunodiagnostics;

* recombinant soluble CD4 and CD4-Pseudomonas exotoxin fusion proteins currently in clinical trials;

* baculovirus-expressed herpes simplex virus and rabies virus vaccines;

* attenuated rotavirus vaccines currently in clinical trials;

* transgenic rabbits as models for testing HIV-infection treatments, and primate and other animal models for HIV-infection;

* basic patents covering immunotoxins and Pseudomonas exotoxins;

* magainin peptides currently in clinical trials;

* fludarabine (F-araA) for antiviral uses;

* HIV TAR-based and other HIV-infection gene therapies;

* numerous antiviral and antiretroviral nucleoside analogs;

* interleukin-2 receptors and IL-2 receptor-targeted immunotoxins;

* recombinant reverse transcriptase;

* HTLV-I envelope proteins and related diagnostics and vaccines;

* liposome-encapsulated phosphorylated nucleosides;

* N-(phosphonoacetyl)-L-aspartic acid (PALA) salts;

* anti-HIV napthoquinones;

* dimeric dideoxynucleosides; and

* various antiviral screening assays including those for inhibitors of HIV aspartyl protease, HIV integrase inhibitors and syncytia formation.

The federal government also claims involvement in the discovery and is seeking reassignment (through conditional licenses granted to generic drug companies) of the patents concerning the use of AZT for treatment of HIV-infection.