Review of 1997

This article reviews some of the more significant and interesting news and developments concerning antiviral therapeutics and vaccines reported in 1997 issues (Volume 10) of the Antiviral Agents Bulletin. Various indexes (e.g., Organization, Agent, and Virus/Disease) of 1997 news articles are also included in this issue. Indexes of 1997 U.S. patents will be published in an upcoming issue of the Bulletin.

In 1997, the Bulletin published over 380 pages of news, U.S. and international patent abstracts, and other information concerning antiviral therapeutics and vaccines development. This included nearly 400 news articles. HIV-infection remains the predominant target for antiviral therapeutics development activities, with nearly one-half of 1997 Bulletin articles related to HIV-infection. However, important advances, including the approval of new drugs, clinical trial reports of efficacy and new agents entering trials, occurred with therapeutics for other viral diseases, notably herpes simplex virus, cytomegalovirus and hepatitis B and C virus infections.

In terms of health care, the major antiviral news from 1997 was the continued rapid adoption of HIV combination drug therapy, with combinations of multiple nucleoside analog HIV reverse transcriptase inhibitors plus an HIV protease inhibitor becoming standard therapy in the U.S. and other affluent countries. It is now commonplace for clinical trials with various combinations of HIV reverse transcriptase and protease inhibitors to report sustained drastic reductions in HIV plasma viral load, often below detectable levels, along with increases in CD4+ T-cell count and alleviation of symptoms. However, little is known about the long-term clinical efficacy and side effects of various drugs and combinations, while in the short-term many HIV-infected patients simply cannot afford, tolerate and/or comply with complex drug treatments. New drugs including HIV protease inhibitors, new combination regimens and more patients starting treatment earlier are keeping many HIV-infected patients significantly healthier, with studies now showing clinical efficacy in terms of slowing disease progression with decreases in mortality and opportunistic diseases for two or more years. However, available therapeutics have not yet been proven to affect the long-term (e.g., 5 years or longer) course of HIV-infection, and products in development have yet to show dramatic, improved efficacy over currently available therapy. Also, the efficacy observed in clinical trials may not translate into actual practice. Combination drug treatment failures, often related to the development of drug-resistant HIV and noncompliance with complex multi-drug administration regimens, will likely increase with time. Reservoirs of HIV-infected cells remain and HIV-infection still must be considered an ultimately terminal disease. There were few major advances in terms of significantly improved efficacy with non-HIV antiviral therapeutics. Several new agents and combinations became available for hepatitis C, herpes simplex virus, cytomegalovirus retinitis and rabies, but these were often variations of or similar to currently available agents.

HIV (and other) prophylactic vaccine development continues to progress at a seemingly glacial pace, even though prophylactic vaccines are recognized as the only way to effectively control the HIV epidemic worldwide. There were few substantive news stories in 1997 concerning progress with HIV vaccines, and no major news stories about HIV vaccines showing significant efficacy in clinical trials or entering large-scale trials. Incentives remain too few and uncertainty remains too high for private sector development, and the U.S. and other major governments have not made any bold moves in this area.

The need and commercial opportunities for antiviral therapeutics and vaccines remain high. New, improved and even additional Òme-tooÓ therapeutics are needed for essentially all viral diseases. Targeted drug development efforts, such as those based on structure-based drug design, have been successful in the antiviral area as illustrated by the HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors; and many new combinatorial and structure-based drug design efforts are underway. Those companies which took a considerable risk with rather costly efforts to develop HIV protease inhibitors have been rewarded with successful drugs. New antiviral therapeutics and vaccines have been shown to be quickly accepted by the medical and regulatory establishments, patients and the general public. The market for antiviral therapeutics generally expands with the entry of new products. Regulatory approvals, especially in the U.S., are no longer a major concern. Approvals, particularly for HIV/AIDS-related therapeutics, have become rather predictable and noncontroversial. HIV and other antiviral therapeutics are being approved quickly, often solely on the basis of effects on surrogate markers or a single pivotal clinical trial. Treatment activists now seem to be more often encouraging and advising companies than protesting their actions.

Encouraging Developments and Trends

Product approvals (primarily U.S.) included:

• Nelfinavir mesylate (Viracept), an HIV protease inhibitor, from Agouron Pharmaceuticals received approval for treatment of HIV-infection in adults and children.
  
• Delavirdine mesylate (Rescriptor), an HIV non-nucleoside reverse transcriptase inhibitor (NNRTI), from Pharmacia & Upjohn, Inc. received approval for treatment of HIV-infection.
  
• Interferon alfacon-1 (Infergen) from Amgen Corp. received approval for treatment of chronic hepatitis C virus infection.
  
• Imiquimod cream (Aldara), an immune modulator, from 3M Pharmaceuticals received approval for treatment of external genital and perianal warts.
  
• RabAvert, a cell cultured inactivated rabies vaccine, from Chiron Corp. received FDA approval for both pre-exposure and post-exposure prophylaxis, becoming the first new rabies vaccine to be introduced in the U.S. for nearly ten years.
  
• Fortovase, a soft gel formulation of the HIV protease inhibitor saquinavir with improved bioavailability, from Hoffmann-La Roche Inc. received approval for treatment of HIV-infection.
  
• Ritonavir (Norvir), an HIV protease inhibitor, from Abbott Labs. received supplemental approval for treatment of HIV-infection in pediatric patients.
  
• Zerit for Oral Solution, a liquid formulation of D4T, from Bristol-Myers Squibb Co. received approval for treatment of HIV-infection in pediatric patients.
  
• Famciclovir (Famvir) from SmithKline Beecham Corp. received supplemental approval for a major new indication, suppression (prophylaxis) of recurrent genital herpes.
  
• Combivir, a tablet combining AZT (Retrovir) and lamivudine (Epivir; 3TC), from Glaxo Wellcome Inc. received approval for treatment of HIV-infection.
  
• WF10 (tetrachlorodecaoxygen; Oxoferin), an anion complex oxidizing agent that acts as an immune modulator, from Dimethaid Research Inc. and Oxo Chemie AG received approval in Thailand for treatment of HIV-infection.
  
• SmithKline Beecham Corp. formally launched penciclovir cream (Denavir) in the U.S. for oral herpes.
  
• The combination of intravenous foscarnet sodium (Foscavir) from Astra USA, Inc. and intravenous ganciclovir (Cytovene) from Hoffmann-La Roche Inc. received approval for treatment of cytomegalovirus retinitis in patients having relapsed after initial treatment with either drug alone.
  
• Lamivudine (Epivir; 3TC) from Glaxo Wellcome Inc., previously having received accelerated approval, was granted full approval for treatment of HIV-infection.
  
• Valacyclovir (Valtrex) from Glaxo Wellcome Inc. received supplemental approval for a major new indication, suppression (prophylaxis) of recurrent genital herpes, becoming the first once-a-day drug treatment available for suppression of genital herpes outbreaks.
  
• Expanded use of inactivated poliovirus vaccine (IPOL) from Pasteur Merieux Connaught received approval including protocols involving just IPOL and sequential schedules involving IPOL followed by oral poliovirus vaccine (OPV).
  
• Hepatitis A Vaccine, Inactivated (Havrix) from SmithKline Beecham Corp. received approval for a new indication, prevention of hepatitis A in persons with chronic liver disease.
  
• Interferon alfa-2b (Intron A) from Schering-Plough Corp. received approval for extended (18-24 months) treatment of chronic hepatitis C virus infection.
  
• Topical 0.5% podophyllotoxin gel (Condylox Gel) from Oclassen Pharmaceuticals, Inc. received approval for patient-applied treatment of external genital and perianal warts.
  
• Retrovir (AZT) from Glaxo Wellcome Inc. received approval as 300 mg tablets, allowing increased patient convenience and compliance.
  
• PureBright (involving microsecond bursts of extremely intense light) and CoolPure (involving microsecond bursts of a pulsed electrical field) systems from PurePulse Technologies, Inc. received approval for destruction of viruses, bacteria and oocysts in food and drink.
  
• Use of a second viral inactivation process, heat treatment, received approval for use with solvent detergent inactivated Antihemophilic Factor (Human), a Factor VIII preparation, from Alpha Therapeutic Corp.
  
• With the lapsing of Glaxo WellcomeÕs patents covering acyclovir, over a dozen companies have received approval and introduced generic versions of acyclovir.
  
• The FDA recognized Superquant HCV, a quantitative polymerase chain reaction assay for hepatitis C virus (HCV), from National Genetics Institute as acceptable to determine the antiviral efficacy of treatments for chronic hepatitis C.
  
• A hepatitis A virus vaccine, Expaxal Berna, from the Swiss Serum and Vaccine Institute received approval in Sweden, its first approval in the European Union.
  
• Infanrix Hep B vaccine, a combination of currently available Infanrix (diphtheria, tetanus and acellular pertussis vaccines) plus recombinant hepatitis B vaccine (Engerix-B), from SmithKline Beecham Biologicals received approval in the European Union.
  
• D4T (Zerit) from Bristol-Myers Squibb Co. received approval in the European Union for first-line combination treatment of HIV-infection, an indication not yet approved in the U.S.
  

Encouraging clinical trial results and treatment-related trends included:

• Various combination anti-HIV drug regimens, generally involving an HIV protease inhibitor and two nucleoside analog reverse transcriptase inhibitors, continued to show efficacy for treating patients at various stages of HIV-infection. It has become common for combination regimens to maintain reductions in HIV plasma viral load below conventional limits of detection for months or even years.
  
• The Centers for Disease Control and Prevention reported that U.S. mortality due to AIDS fell 19% in the first nine months of 1996 compared to 1995, continuing an apparent year-long trend. New and improved drugs for treatment of HIV and AIDS were major factors contributing to the drop in mortality. However, there were still 30,700 deaths reported to CDC during this period.
  
• Combination anti-HIV drug regimens are being documented to have significant clinical efficacy, including improving survival and reducing opportunistic diseases, for up to two or more years and have been shown to be cost-effective in the long-term. Many HIV patients who had been sick or even facing death are now healthy and reentering society, going back to work, etc.
  
• Clinical endpoint studies demonstrated the benefits of triple anti-HIV drug combination therapy over single and double nucleoside therapy.
  
• Lamivudine (3TC) from Glaxo Wellcome PLC and BioChem Pharma Inc. showed efficacy for treatment of chronic hepatitis B in a Phase III trial, and the drug appears on track for approval in 1998.
  
• DMP 266, an HIV non-nucleoside reverse transcriptase inhibitor, from DuPont Merck Pharmaceutical Co. demonstrated efficacy after 48 weeks in combination with indinavir, and appears on track for approval in 1998.
  
• MEDI-493, a humanized respiratory syncytial virus (RSV) monoclonal antibody, from MedImmune, Inc. showed efficacy in a large Phase III and other trials for treatment of RSV disease in high-risk infants and children, and appears to be on track for approval in 1998.
  
• Lidakol cream from Lidak Pharmaceuticals Inc. demonstrated efficacy for treatment of oral herpes in a Phase III trial, and appears on track for approval in 1998. Lidakol also showed indications of antiviral efficacy for treatment of KaposiÕs sarcoma.
  
• Fortovase, a soft gel formulation of the HIV protease inhibitor saquinavir, from Hoffmann-La Roche Inc. demonstrated efficacy in combination therapy comparable to that of indinavir, the most widely used HIV protease inhibitor.
  
• A live recombinant intranasally administered influenza virus vaccine from Aviron, Inc. demonstrated significant prophylactic efficacy in a large pediatric Phase III trial.
  
• The addition of oral ribavirin from ICN Pharmaceuticals to conventional treatment with interferon alfa-2b (Intron A) from Schering-Plough Corp. was shown in large Phase III trials to improve the efficacy of Intron A treatment for chronic hepatitis C.
  
• 141W94, an HIV protease inhibitor, from Glaxo Wellcome Inc. showed promise in Phase II trials for treatment of HIV-infection.
  
• Zanamivir, an oral neuraminidase inhibitor, from Glaxo Wellcome Inc. and Biota Holdings Ltd. demonstrated efficacy for treatment of influenza A virus infections.
  
• GS 4104, an oral neuraminidase inhibitor, from Gilead Sciences and Hoffmann-La Roche Ltd. demonstrated efficacy for treatment of influenza virus infections.
  
• Pleconaril from ViroPharma Inc. demonstrated efficacy for treatment of viral meningitis.
  
• HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs), including DMP 266 from Merck, nevirapine from Boehringer Ingelheim Corp., delavirdine from Pharmacia & Upjohn, Inc. and MKC-442 from Triangle Pharmaceuticals, demonstrated safety and efficacy often comparable to HIV protease inhibitors when used in various combination regimens.
  
• Protovir, a humanized cytomegalovirus (CMV) antibody, from Protein Design Labs, Inc. demonstrated efficacy for prevention of CMV infection in bone marrow transplant recipients.
  
• ISIS 2922 (fomivirsen) from Isis Pharmaceuticals, Inc. demonstrated efficacy for treatment of cytomegalovirus retinitis in patients not responding to other drugs.
  
• A recombinant hepatitis B virus vaccine, Hepagene, from Medeva PLC demonstrated efficacy for use as a prophylactic vaccine and for immunotherapeutic use in chronic carriers.
  
• Combinations of two HIV protease inhibitors showed efficacy comparable to conventional triple combination therapy for treatment of HIV-infection.
  
• GEM 91, an HIV antisense oligonucleotide, from Hybridon, Inc. showed indications of efficacy.
  
• Self-administered subcutaneous injections of interleukin-2 (IL-2) from Chiron Corp. showed efficacy and safety for treatment of HIV-infection.
  
• AZT was reported to reduce the risk of contracting HIV-infection by about 80% if treatment is started immediately after percutaneous exposure to HIV-infected blood, e.g., from a stick with a needle or other sharp object.
  
• The combination of DDI (Videx) and D4T (Zerit), both nucleoside analog reverse transcriptase inhibitors from Bristol-Myers Squibb Co., was shown to be safe and effective; and DDI/D4T could replace AZT/3TC as the nucleoside analogs used in many HIV combination drug regimens.
  
• Studies demonstrated long-term safety and efficacy with varicella-zoster virus vaccine (Varivax) from Merck & Co., Inc., and supported universal vaccination of children for chickenpox prevention.
  
• Oral ganciclovir (Cytovene) from Hoffmann-La Roche Inc. demonstrated efficacy for prevention of cytomegalovirus disease in renal transplant recipients.
  
• Valganciclovir, an oral prodrug of ganciclovir, from Hoffmann-La Roche Inc. showed promise in early trials for treatment of cytomegalovirus retinitis and trials were expanded, despite concerns that the company might not continue development of this drug.
  
• Ganciclovir intraocular implant (Vitrasert) from Chiron Vision/Bausch & Lomb combined with oral ganciclovir from Hoffmann-La Roche Inc. was shown to reduce cytomegalovirus (CMV) disease in other organs, delay the onset of CMV retinitis in the unaffected eyes of AIDS patients and have other desirable effects.
  
• The combination of DDI (Videx) and hydroxyurea, both drugs from Bristol-Myers Squibb Co., showed significant efficacy for treatment of HIV-infection, including eliminating culturable HIV in several patients.
  
• RBC-CD4, red blood cells impregnated with CD4, from Sheffield Medical Technologies Inc. showed safety and antiviral activity in HIV-infected patients.
  
• BIRR 4, recombinant soluble ICAM-1 rhinovirus receptor, nasal spray from Boehringer Ingelheim Pharmaceuticals, Inc. showed indications of efficacy for treatment of rhinovirus infections.
  
• The combination of two HIV protease inhibitors, ritonavir from Abbott Labs. and Invirase from Hoffmann-La Roche Inc., was shown to significantly reduce HIV RNA levels in the cerebrospinal fluid.
  
• Four-drug combination regimens including nucleoside analogs and one or two HIV protease inhibitors showed promise for treatment of HIV-infection.
  
• Lobucavir and BMS-200475 from Bristol-Myers Squibb Co. showed indications of efficacy for treatment of chronic hepatitis B.
  
• TA-GW, a human papillomavirus immunotherapeutic vaccine, from Cantab Pharmaceuticals PLC in combination with cryotherapy showed efficacy for treatment of recurring genital warts after 6 months of follow-up.
  
• HRG214, a formulation of five recombinant HIV antibodies, from Cervida Corp. Ltd. in combination with immune modulators showed indications of efficacy for treatment of advanced HIV-infection.
  
• A cell culture-based influenza vaccine from BioChem Pharma Inc. demonstrated safety and boosted immunity, and progressed into Phase II/III trials.
  
• Flustat, an orally administered influenza vaccine, from Cortecs International was shown safe in a Phase I trial.
  
• Triple anti-HIV drug combinations including an HIV protease inhibitor were reported to have the potential to prevent or delay progression of cytomegalovirus retinitis in AIDS patients.
  
• Hepatitis B antigen DNA-coated gold particles directly injected into the outer layers of the skin using a needleless delivery system from PowderJect Vaccines, Inc. was shown to be safe in a Phase I trial.
  
• Famciclovir (Famvir) from SmithKline Beecham Corp. was shown effective in suppressing asymptomatic viral shedding in patients being treated for suppression of genital herpes recurrences. Famciclovir also showed efficacy for treatment of herpes simplex virus infections in HIV-infected patients.
  
• A community-based trial showed viral load benefits from offering drugs for treatment of primary HIV-infection.
  
• Foscarnet (Foscavir) cream from Astra USA, Inc. showed promise for treatment of oral herpes.
  
• Rubella Vaccine Live (Meruvax) from Merck & Co. was shown not to increase the risk of persistent joint and neurologic symptoms in women, a concern that had affected use of the vaccine.
  
• Patterns of immune response to primary (initial) HIV-infection were shown to be highly predictive of an individualÕs subsequent rate of disease progression.
  
• A mixture of two topical anesthetics was shown to substantially reduce the pain associated with surgical removal of genital warts.
  
• Ampligen, an immune modulator, from HemispheRx Biopharma Inc. showed efficacy for treatment of chronic fatigue syndrome.
  
• An HIV immunotherapeutic vaccine, Remune, from Immune Response Corp. was shown to induce production of anti-HIV chemokines.
  
• The combination of Ritonavir (Norvir), an HIV protease inhibitor, from Abbott Laboratories and D4T (Zerit) from Bristol-Myers Squibb Co. demonstrated efficacy for treatment of pediatric HIV-infection.
  
• Triple-drug combination treatment including nevirapine (Viramune), a non-nucleoside reverse transcriptase inhibitor (NNRTI), from Boehringer Ingelheim was reported as safe and effective in pediatric patients.
  
• Zintevir, an HIV integrase inhibitor drug, from Aronex Pharmaceuticals, Inc. showed safety and a good pharmacokinetic profile in Phase I studies.
  
  

• SmithKline Beecham Corp. began a trial to determine if a single ten-day treatment regimen with famciclovir (Famvir) for first episode genital herpes can stop future genital herpes outbreaks and eliminate the need for subsequent therapy.
  
• A clinical trial is testing valacyclovir (Valtrex) from Glaxo Wellcome Inc. in 1,500 discordant couples for its ability to reduce genital herpes transmission.
  
• 141W94, an HIV protease inhibitor, from Glaxo Wellcome Inc. entered a Phase III trial in combination with nucleoside analogs in HIV-infected children.
  
• GEM 92, a second-generation oral HIV antisense oligonucleotide from Hybridon, Inc. entered clinical trials for treatment of HIV-infection.
  
• Adefovir dipivoxil [GS 840 or bis(POM)PMEA] from Gilead Sciences, Inc. entered Phase III trials for treatment of HIV and CMV infections, and entered Phase II trials for treatment of chronic hepatitis B.
  
• ISIS 5320, an oligonucleotide drug, from Isis Pharmaceuticals entered trials for treatment of HIV-infection.
  
• A controlled-release formulation of acyclovir from Flamel Technologies S.A. entered Phase III trials for treatment of genital herpes. Acyclovir CD, a controlled-release formulation of acyclovir, from Shire Pharmaceuticals Group PLC entered trials in the U.S. for treatment of herpesvirus infections.
  
• A controversial clinical trial began using combination drug regimens for prevention of infection with HIV very shortly after, e.g., the morning after, uninfected persons realize they risk infection from having engaged in high-risk sexual activity.
  
• A prophylactic human papillomavirus vaccine, MEDI-501, from MedImmune, Inc. entered clinical trials.
  
• CI-1012, an HIV zinc finger inhibitor drug, from Warner-Lambert Co. entered clinical trials.
  
• An HIV ribozyme ex vivo gene therapy from Ribozyme Pharmaceuticals, Inc. entered clinical trials.
  
• GEM 132, a cytomegalovirus antisense oligonucleotide, from Hybridon, Inc. entered clinical trials.
  
• Low-dose oral interferon-alpha from Amarillo Biosciences, Inc. for six months followed by six months of conventional injectable interferon-alpha entered trials for treatment of chronic hepatitis C.
  
• A new intravenous formulation of hepatitis B virus immune globulin (H-BIG 5% I.V.) from Nabi entered trials for hepatitis B virus infection prophylaxis in liver transplant recipients.
  
• A prime-plus-boost prophylactic HIV vaccine trial began using TBC-3B, a live vaccinia virus vector HIV vaccine, from Therion Biologics Corp. and booster vaccinations with HIV gp120 vaccine from VaxGen, Inc.
  
• The largest prime-plus-boost prophylactic HIV vaccine trial to date began, testing a trivalent canarypox virus vector vaccine (vCP205) from Pasteur-Merieux Connaught Labs. and a booster vaccination with HIV-1SF gp120 from Chiron Corp.
  
• Phase III pediatric trials with an intranasal influenza vaccine from Aviron, Inc. are a year ahead of schedule.
  
• PEG-Intron A from Enzon, Inc., a modified version of interferon alfa-2b (Intron A) from Schering-Plough Corp., entered Phase III trials for treatment of chronic hepatitis C.
  
• A recombinant Epstein-Barr virus vaccine from Aviron, Inc. and SmithKline Beecham Biologicals entered clinical trials.
  
• Maxamine H2 receptor agonist from Maxim Pharmaceuticals, Inc. in combination with interferon-alpha entered trials for treatment of chronic hepatitis C.
  
• An oral prodrug of PMPA from Gilead Sciences entered clinical trials for treatment of HIV-infection.
  
• BCX-34, an oral immune modulator, from BioCryst Pharmaceuticals, Inc. entered trials for treatment of HIV-infection.
  
• Cidofovir from Gilead Sciences, Inc. entered clinical trials for treatment of KaposiÕs sarcoma (associated with KaposiÕs sarcoma-associated herpesvirus).
  
• Ampligen from HemispheRx Biopharma Inc. entered Phase II trials for HIV-infection; and an expanded access trial for chronic fatigue syndrome started that included cost-recovery.
  
• PRO 2000 intravaginal gel from Procept, Inc. entered clinical trials after demonstrating contraceptive efficacy and preventing HIV-infection in animal studies.
  
• XQ-9302, a formulation of 20 Chinese medicinal herbs, produced by Shanghai Xiong-Qi Biological Products Co. entered U.S. trials for treatment of HIV-infection.
  
• CY2301, an immunotherapeutic vaccine designed to induce HIV-specific cellular immunity, from Cytel Corp. entered clinical trials.
  
• Procaine, HCl (Anticort), a steroidogenesis inhibitor, from Steroidogenesis Inhibitors, Inc. entered Phase II trials for treatment of HIV-infection.
  
• Infusions of ex vivo HIV antigen-activated lymphocytes (HIV activated cellular therapy) from Neoprobe Corp. and independently from the Center for Blood Research, Harvard Univ., entered trials for treatment of HIV-infection.
  
• GPI-2A, a liposomal formulation of an HIV antisense oligonucleotide, from Genesys Pharma Inc./Novopharm Biotech Inc. entered clinical trials.
  
• Oral rotavirus vaccines from both the Virus Research Institute, Inc. and AMRAD Corp. entered Phase II trials.
  
• 1,1'-Azobisformamide from Hubriphar SPRL entered trials for treatment of HIV-infection.
  
• A number of companies are conducting clinical trials with thalidomide for treatment of HIV-infection related indications.
  
• Clinical trials were expanded with HIV-IT (V), an immunotherapeutic retroviral vector HIV gene therapy, from Chiron Corp. and Green Cross Corp.
  
• Topical SP-303 (Virend) from Shaman Pharmaceuticals, Inc. in combination with acyclovir entered Phase II trials for treatment of genital herpes in AIDS patients.
  
• HGP-30, an HIV immunotherapeutic peptide vaccine, from CEL-SCI Corp. with a novel adjuvant, granulocyte-macrophage colony stimulating factor (GM-CSF), from Immunex Corp. entered clinical trials.
  
• A cell culture-based inactivated influenza virus vaccine from BioChem Pharma Inc. entered Phase II/III trials in Canada.
  
• A study documented the utility of HIV plasma viral load as a surrogate marker in infants to predict disease severity and which infants might benefit most from antiretroviral therapy.
  
• Nevirapine (Viramune), an HIV non-nucleoside reverse transcriptase inhibitor (NNRTI), from Boehringer Ingelheim Pharmaceuticals entered Phase II trials for prevention of maternal transmission of HIV-infection.
  
• A trial began using abacavir (1592U89), a nucleoside reverse transcriptase inhibitor, from Glaxo Wellcome Inc. for treatment of AIDS Dementia Complex.
  
  

• Infectious hepatitis C virus was cloned for the first time.
  
• The most recently discovered hepatitis virus, hepatitis G virus (HGV), was found not to be a serious pathogen or health threat.
  
• Caprine arthritis-encephalitis virus (CAEV), a common goat virus, was shown to induce human antibodies that neutralize HIV, and CAEV may be useful for HIV vaccine development.
  
• KaposiÕs sarcoma-associated herpesvirus (KSHV; human herpesvirus-8) was shown to express a chemokine with anti-HIV activity, providing leads for development of chemokines for treatment of HIV-infection.
  
• Systemic effects with low-dose oral alpha interferon from Amarillo Biosciences Inc. were documented for the first time, including efficacy in animal models and in a clinical trial for treatment of a nonviral disease.
  
• Mixtures of HIV monoclonal antibodies and HIV immune globulin were reported by the Walter Reed Army Inst. of Research to neutralize HIV-infection of lymphocytes in vitro.
  
• Human chorionic gonadotropin (hCG), a pregnancy-related hormone, was reported to have potential for the treatment of HIV-infection.
  
• HYB 101400 from Hybridon, Inc. and Hoffmann-La Roche Inc. was selected for development for treatment of HPV-associated genital warts.
  
• HIV Rev M10 and HIV gag antisense RNA gene therapies from SyStemix, Inc. can significantly improve antiretroviral drug efficacy in vitro.
  
• QS-21 (Stimulon) adjuvant from Aquila Biopharmaceuticals, Inc. enhanced immune responses to HIV DNA plasmid vaccines in animal studies.
  
• Researchers from Schering-Plough Corp. reported resolving the three-dimensional structure of hepatitis C virus helicase, an enzyme critical to viral replication.
  
• A new porcine virus, swine hepatitis E virus (SHEV), closely related to human hepatitis E virus (HEV), was identified and may facilitate HEV vaccine development.
  
• Glaxo Wellcome Inc. began expanded access programs for abacavir (1592U89) for HIV-infection and AIDS dementia.
  
• Researchers from RiboGene, Inc. reported that the hepatitis C virus nonstructural 5A (NS5A) protein is associated with interferon-resistance.
  
• CEL-SCI Corp. is developing a new version, HGP-30W, of its HGP-30 HIV p17 vaccine for prophylactic use.
  
• Intracellular expression of chemokines (intrakines) in transduced lymphocytes may be useful to inactivate HIV coreceptors and prevent HIV-1 infection.
  
• In vitro studies indicated that sequential rather than combination treatment with anti-HIV drugs may be useful in some circumstances.
  
• Herpes simplex virus type 1 (HSV-1) heteroconjugate vaccines from CEL-SCI Corp. showed efficacy in animal studies for prevention of HSV-1 infection.
  
• RiboTargets Ltd., affiliated with the U.K. Medical Research Council, started programs to develop drugs for treatment of HIV and hepatitis C virus infections.
  
• More HIV coreceptors (e.g., CCR2, Bonzo, BOB) and their mechanisms were reported.
  
• A gene therapy approach involving constitutive low-level production of interferon-beta was proposed for treatment of HIV-infection.
  
• Vesicular stomatitis virus modified to express CD4 and the HIV coreceptor CXCR4 was shown to selectively target and kill HIV-infected cells in vitro.
  
  

• The National Institutes of Health reaffirmed the importance of treating pregnant HIV-infected women and their babies with AZT despite studies demonstrating that AZT can cause tumors in mice.
  
• A large U.S. survey showed popular support for expanding the supply of AIDS drugs and earlier treatment to indigent persons covered by the state-run, federally-funded Medicaid programs.
  
• The number of newly diagnosed HIV patients receiving triple combination drug therapy more than doubled to 21% in the second quarter of 1997 compared 10% in the first quarter.
  
• Merck & Co., Inc. pledged full-scale development of a prophylactic HIV DNA plasmid (naked DNA) vaccine.
  
• The International Association of Physicians in AIDS Care (IAPAC) is promoting the first human trials for live-attenuated HIV vaccines.
  
• The National Institute of Allergy and Infectious Diseases started a new grant program, the INNOVATION Grant Program for Approaches in HIV Vaccine Research.
  
• The Centers for Disease Control and Prevention reported that 78% of infants in the U.S. received a full course of recommended vaccinations in 1996.
  
• The incidence and mortality rates in children for hepatocellular carcinoma (linked with hepatitis B virus infection) decreased in Taiwan after the institution of universal hepatitis B virus childhood vaccination.
  
• The largest-selling anti-HIV drug, lamivudine (3TC; Epivir) from Glaxo Wellcome and BioChem Pharma achieved sales at an annual rate over $750 million. Indinavir (Crixivan) from Merck & Co., Inc. was the leading HIV protease inhibitor in terms of sales, selling at a rate equivalent to over $550 million/year. Sales of D4T (Zerit), a thymidine analog like AZT, from Bristol-Myers Squibb Co. are growing rapidly as the drug is replacing AZT in many combination regimens.

Discouraging Developments and Trends

• Matrix Pharmaceutical Inc. suspended the planned launch of AccuSite (fluorouracil) Injectable Gel for treatment of genital warts in the U.S. after receiving nonapprovable letters from FDA citing safety concerns related to local inflammation at the site of injection. However, the same product is entering the market in European countries based on the same clinical data.
  
• Allelix Biopharmaceuticals Inc. halted further development with ALX40-4C, a Tat inhibitor, for treatment of HIV and cytomegalovirus infections.
  
• Nabi halted development of HIV immune globulin (HIV-IG) in combination with AZT for prevention of maternal transmission of HIV-infection after it was found infeasible to show improved efficacy compared to AZT monotherapy in a Phase III trial. However, the trial further confirmed the efficacy of AZT for prevention of maternal transmission.
  
• Cangene Corp. halted trials with varicella-zoster virus immune globulin (VZVIG) for treatment of post-herpetic neuralgia after it failed to show significant efficacy in a Phase II trial.
  
• Pasteur Merieux Connaught withdrew its application for U.S. approval of a live oral polio vaccine citing reasons including the slight risk for polio from live vaccines and the changes in polio vaccination recommendations.
  
• Paracelsian, Inc. halted development of AndroVir-DS, a plant-derived HIV protein-tyrosine kinase inhibitor, after FDA warned the company against trying to market it as a largely unregulated nutraceutical (nutritional supplement) product rather than as a drug.
  
• The FDA issued a warning letter and halted sales of SPV-30, a plant-derived anti-HIV drug from Arkopharma Labs., that had been a popular nutraceutical for treatment of HIV-infection
  
• Hybridon, Inc. halted further development of GEM 91, an HIV antisense oligonucleotide, in favor of later generation antisense oligonucleotides after noting decreases in patientsÕ platelet counts.
  
• The National Inst. of Allergy and Infectious Diseases halted a clinical trial to determine whether low-dose oral alpha interferon is effective for alleviating symptoms of AIDS, and the efficacy of low-dose oral interferon for treatment of HIV/AIDS may never be resolved.
  
• HNK20, a respiratory syncytial virus (RSV) monoclonal antibody, from OraVax, Inc. failed to show efficacy in a Phase III trial for prevention of severe RSV infection.
  
• The FDA informed Gilead Sciences, Inc. that its single Phase I/II clinical trial with cidofovir gel (Forvade) for treatment of refractory anogenital herpes simplex virus infection in patients with AIDS was insufficient to support approval.
  
• HemaSure Inc. halted development of the SteriPath Blood Inactivation System using hydroxymethylglycinate (HMG) for viral and other pathogen inactivation of blood products after the FDA raised concerns about the genotoxicity, mutagenicity and removal of HMG.
  
• A large triple-drug combination clinical trial was halted after the two-drug arm (AZT/3TC) used for comparison was concluded to be suboptimal and unethical, signaling that triple-drug combination should be the standard therapy in HIV drug treatment clinical trials.
  
• LXR Biotechnology Inc. halted development of Lexirin, an HIV apoptosis inhibitor drug, for treatment of severe diarrhea in patients with HIV-infection/AIDS.
  
• The FDA issued a warning regarding a small risk of developing diabetes from use of HIV protease inhibitors.
  
• Merck & Co. halted a Phase III clinical endpoint trial in Brazil that included an AZT monotherapy arm after being criticized for using AZT monotherapy, now considered an outmoded therapy in advanced countries.
  
• Johnson & Johnson Co. halted marketing of its HIV home test kit, Confide, marketed by its Direct Access Diagnostics subsidiary, apparently due to low sales.
  
  

• Infectious HIV was shown to persist in reservoirs of latently infected cells in patients receiving potent anti-HIV triple-drug combination therapy and maintaining undetectable levels of plasma viral load.
  
• Even a brief halt in HIV combination drug treatment was shown to allow reseeding of the lymph nodes, further showing the importance of strict compliance with complex HIV drug combination regimens. Noncompliance with complex HIV drug combination regimens was linked to increases in viral load and development of resistant virus.
  
• A survey of HIV-infected patients showed that many simply do not fully comply with complex regimens.
  
• Treatment failures among patients treated with HIV protease inhibitors may be considerably higher than the failure rates observed in clinical trials.
  
• Several groups of investigators and companies are preparing for eventual clinical trials with live attenuated HIV vaccines, but they face a number of problems and trials do not appear likely to start for several years.
  
• A Phase III clinical trial with HNK20, a respiratory syncytial virus monoclonal antibody, from OraVax Inc. was postponed until the 1998-1999 winter season due to production problems.
  
• Inconsistent results were reported from a Phase II trial with a novel influenza virus vaccine from Virus Research Institute, Inc. and Pasteur Merieux Connaught.
  
• Glaxo Wellcome sent a letter to U.S. physicians warning of recurrent hepatitis B in AIDS patients with chronic hepatitis B discontinuing use of lamivudine (3TC; Epivir) for treatment of HIV-infection.
  
• A contraceptive nonoxynol-9 film from Apothecus Pharmaceutical Corp. showed no effect on transmission of HIV and other sexually transmitted diseases.
  
• The National Institutes of Health recommended that physicians need to closely monitor the CD4+ T-cell counts of patients being treated with D4T and AZT.
  
• Opportunistic infections in latter stage HIV-infected patients were reported to set off waves of production of HIV virions from reservoirs of HIV in macrophages.
  
• Adding or switching nucleoside analogs in advanced HIV/AIDS patients receiving AZT monotherapy was reported to potentially increase mortality.
  
• Symptomatic urinary tract disease and transient kidney dysfunction were reported to be potential side effects of indinavir from Merck & Co.
  
• Up to 25% of cases of insulin-dependent diabetes mellitus before age 15 may be prevented by immunization at birth, a common practice in Europe, rather than waiting until eight weeks of life, a common practice in the U.S.
  
  

• The cost of antiretroviral drug therapy for HIV-infection remains expensive, generally over $10,000/year.
  
• The AIDS Vaccine Advocacy Coalition documented the overall low level of industry involvement in the development of prophylactic HIV vaccines.
  
• Neither antiviral nor immune stimulant therapy was reported to be sufficient to restore CD4+ T-cell immune function in patients with advanced HIV-infection.
  
• HIV may be mutating into more pathogenic forms as the epidemic continues.
  
• Studies suggested that drugs and vaccines targeted to one HIV receptor may result in HIV mutating to use other receptors, perhaps even accelerating disease progression as a result.
  
• beta-Chemokines which block certain strains of HIV from entering lymphocytes may have the paradoxical effect of enhancing replication of other HIV strains.
  
• Unknown factors besides mutant CCR5, a cofactor for HIV-infection, were shown to contribute to some HIV-infected patients being long-term nonprogressors.
  
• HIV envelope proteins, even without HIV infecting cells, were shown to initiate a biochemical cascade that can activate cells and make them more susceptible to HIV-infection.
  
• Human herpesvirus-6 (HHV-6) appears to be a cause or involved in the pathogenesis of multiple sclerosis.
  
• Latent infection with KaposiÕs sarcoma-associated herpesvirus (KSHV; human herpesvirus-8) was demonstrated in KaposiÕs sarcoma lesions. KSHV was also reported to be a cause or involved in multiple myeloma.
  
• A new in vivo analytical method showed that conventional aluminum-based vaccine adjuvants dissolve quickly upon injection rather than forming a long-term repository for complexed antigen as had long been presumed.
  
• MedImmune, Inc. ran into supply problems with RespiGam, respiratory syncytial virus (RSV) immune globulin, during the 1996-1997 RSV season.
  
• Adenovirus 36 (Ad-36) was reported to be a possible cause of obesity.
  
• Borna disease virus was reported to be a possible cause of depression.
  
• Simian virus 40 (SV40) was linked with human mesothelioma, a rare lung cancer associated with inhalation exposure to certain types of asbestos fibers.
  
• In an alleged act of Òbiological sabotage,Ó a lethal rabbit calcivirus disease was apparently introduced in New Zealand in an attempt to kill off or reduce the number of rabbits which are considered pests by many farmers.
  
• A new U.S. strain of hepatitis E virus was isolated.
  
• The three-dimensional structure of AZT was reported to be a poor substrate for the enzyme thymidylate kinase.
  
• The 1592 Access Coalition, a group of AIDS treatment activist and other groups, launched an international boycott of several Glaxo Wellcome products, protesting the slow development of abacavir for treatment of HIV-infection.
  
• Large health care maintenance and insurance companies had problems adopting the U.S. Department of Health and Human Services guidelines for treatment of HIV-infection.
  
• A survey demonstrated that minorities in the U.S. were much less informed about HIV-infection and its treatment than whites (Caucasians).
  
• The Michigan Biologic Products Institute which produces rabies and other vaccines is up for sale.
  
• A survey reported that only about one-third of patients with symptomatic HIV-infection discuss their treatment preferences with their physician.
  
• BioChem Pharma Inc. was the target of multiple bomb attacks, but there were no serious injuries or damage.

Corporate and Federal Activities

• Hybridon, Inc. formed a five-year collaboration with the Institute of Human Virology for research and development of antisense therapeutics for HIV and human herpesvirus-6 (HHV-6) infections.
  
• ViroPharma Inc. and 3-Dimensional Pharmaceuticals, Inc. linked for RNA virus drug discovery.
  
• Merck & Co. linked with NanoSystems LLC for development of Nanocrystal liquid nanoparticle suspension oral pediatric formulations of indinavir.
  
• Advanced Viral Research Corp. concluded a Collaborative Research & Development Agreement (CRADA) with the National Cancer Institute (NCI) for study of reticulose, a peptide nucleic acid immune modulator; and MediChem Research, Inc. entered into a CRADA with NCI for development of calanolide compounds for treatment of HIV-infection.
  
• Schering-Plough K.K. committed to development of thymosin alpha 1 (Zadaxin) from SciClone Pharmaceuticals, Inc. for treatment of chronic hepatitis C in Japan.
  
• Pasteur Merieux Connaught linked with Corixa Corp. and optioned rights to license LeIF, a novel adjuvant.
  
• Wyeth-Lederle Vaccines and Pediatrics linked with BioDelivery Sciences, Inc. to develop cochleates for intracellular delivery of vaccines, drugs, etc.
  
• Glaxo Wellcome PLC linked with Affymetrix, Inc. to build a database of HIV mutation patterns.
  
• MediChem linked with Sarawak (Malaysia) for development of calanolide A for treatment of HIV-infection.
  
• Sequus Pharmaceuticals Inc. linked with Protein Sciences Corp. for manufacture of liposome-incorporated CD4 for treatment of HIV-infection.
  
• Structural Bioinformatics Inc. linked with CyberChemics Inc. for hepatitis C virus protease inhibitor design.
  
• Aviron, Inc. linked with Medeva PLC for production of recombinant intranasal influenza vaccines.
  
• ViroPharma Inc. linked with subsidiaries of Schwarz Pharma AG for production of pleconaril for picornavirus infection treatment.
  
• Agouron Pharmaceuticals, Inc. linked with Nastech Pharmaceutical Co., Inc. for development of nasally delivered rhinovirus 3C protease inhibitors.
  
• Schering-Plough Corp. linked with Corvas Intl., Inc. for development of hepatitis C virus protease inhibitors.
  
• Eli Lilly & Co. and Vertex Pharmaceuticals Inc. linked for development of hepatitis C virus protease inhibitors.
  
• ArQule, Inc. linked with the Univ. of California for KaposiÕs sarcoma-associated herpesvirus (KSHV) and HIV protease inhibitor drug discovery; linked with RiboGene, Inc. for antiviral and other drug discovery; and linked with ViroPharma Inc. for discovery of drugs for treatment of RNA virus infections.
  
• Ribozyme Pharmaceuticals, Inc. linked with Schering AG and its Berlex Laboratories, Inc. U.S. subsidiary for ribozymes research and development.
  
• BioChem Pharma Inc. linked with Structural Bioinformatics Inc. for hepatitis C virus drug discovery.
  
• Chiron Corp. linked with AMRAD Corp. for development of natural products for treatment of hepatitis C.
  
• Bristol-Myers Squibb Co. and Arris Pharmaceutical Corp. linked for development of hepatitis C virus protease inhibitors.
  
• Trimeris, Inc. linked with MiniMed Inc. for development of infusion systems for delivery of antiviral drugs, such as the anti-HIV drug pentafuside (T-20).
  
• The American Red Cross entered into agreements with two companies, Interferon Sciences, Inc. and Viragen, Inc., to supply human leukocytes for production of natural interferon.
  
• HemispheRx Biopharma, Inc. linked with Beaufour Ipsen for development and marketing of nucleic acid-based drugs for treatment of hepatitis B.
  
• Interferon Sciences, Inc. linked with Alternate Site Distributors, Inc., a subsidiary of Bergen Brunswig Corp., for U.S. marketing of natural interferon alfa-n3.
  
• MedImmune, Inc. linked with Abbott Laboratories for marketing of MEDI-493, a humanized respiratory syncytial virus monoclonal antibody. MedImmune also concluded an agreement with a subsidiary of Boehringer Ingelheim GmbH to supplement its own production capacity for MEDI-493.
  
• Nabi linked with Cangene Corp. for production of H-BIG 5% I.V., a new 5% intravenously administered hepatitis B virus immune globulin product.
  
• Biota Holdings Ltd. and the Biomolecular Research Institute linked for respiratory syncytial virus and other antiviral drug design.
  
• Dr. L. Montagnier, Institut Pasteur, linked with KS Biomedix Holdings PLC for development of sheep monoclonal antibodies for treatment of HIV-infection.
  
• Hoffmann-La Roche Ltd. ended its collaboration with Hybridon, Inc. for development of antisense therapeutics for human papillomavirus and hepatitis C virus infections.
  

• Triangle Pharmaceuticals, Inc. acquired Avid Corp., including DMP-450, a novel HIV protease inhibitor, licensed by Avid from DuPont Merck Pharmaceutical Co.
  
• VIMRx Pharmaceuticals Inc. acquired Innovir Laboratories, Inc., a company developing antiviral and other therapeutic ribozymes, and consolidated its own ribozyme subsidiary, Ribonetics GmbH, with Innovir.
  
• Bausch & Lomb acquired Chiron Vision Corp. including its Vitrasert intraocular ganciclovir implant product used for treatment of cytomegalovirus retinitis.
  
• Roche Holding Ltd. acquired privately-held Corange Ltd. which fully owns the Boehringer Mannheim Group.
  
• Vaxcel, Inc. acquired Zynaxis Inc., another company developing vaccine and drug delivery systems.
  
• Auragen, Inc. and Oxford BioSciences Ltd. merged to form Geniva, Inc. to develop gene therapy-type vaccines using needleless injection systems.
  
• Cell Genesys, Inc. acquired Somatix Therapy Corp., another gene therapy company.
  
  

• President Clinton pledged that the United States will find a vaccine for prevention of HIV-infection within a decade, giving this higher public visibility (but he did not pledge new funds for the effort).
  
• The U.S. Department of Health and Human Services issued guidelines for treatment of HIV-infection.
  
• Congress appropriated additional funds to the AIDS Drug Assistance Program (ADAP) for states to expand Medicaid coverage for treatment of HIV-infection.
  
• Unable to find a way around current regulations restricting Medicaid coverage to AIDS patients judged disabled, the Clinton administration abandoned efforts to expand Medicaid coverage to include combination drug treatment for earlier stages of HIV-infection.
  
• The U.S. Securities and Exchange Commission (SEC) filed insider trading charges against 13 individuals alleging unfair trading in stocks of Alpha 1 Biomedicals Inc. and SciClone Pharmaceuticals Inc. resulting from knowledge of the progress of clinical trials with thymosin alpha 1 for treatment of chronic hepatitis B.
  
• The Joint United Nations Programme on HIV/AIDS (UNAIDS) launched the pilot phase of the UNAIDS HIV Drug Access Initiative, a collaborative effort between the public and private sectors to increase access to HIV/AIDS drugs in developing countries.
  
• The FDA warned Agouron Pharmaceuticals, Inc. concerning a press release about a clinical trial showing efficacy with combination therapy including nelfinavir.
  
• Paclitaxel (Taxol) from Bristol-Myers Squibb Co. was approved for second-line treatment of KaposiÕs sarcoma, setting the stage for a test of FDAÕs interpretation of the Orphan Drug Act.
  
• An FDA advisory committee recommended that anyone having received a blood transfusion before 1992 should be tested for hepatitis C virus infection, and that there should be a massive campaign to inform the public about risks from pre-1992 transfusions.
  
  

Patents & Technology Transfer

• Merck & Co., Inc. licensed worldwide rights for use of ÒnakedÓ DNA plasmid vaccine technology from Vical Inc. for use with HIV and hepatitis B virus vaccines.
  
• Hoffmann-La Roche Ltd. acquired exclusive marketing rights for the HIV protease inhibitor nelfinavir (Viracept) from Agouron Pharmaceuticals, Inc. and its partner, Japan Tobacco Inc., in Europe and other territories outside North America, Japan and Asia.
  
• Glaxo Wellcome Ltd. licensed immunotherapeutic Disabled Infectious Single Cycle (DISC) herpes simplex virus type 2 (HSV-2) vaccines from Cantab Pharmaceuticals PLC.
  
• Ciba Vision Corp., a subsidiary of Novartis Pharma AG, licensed rights to ISIS 2922 (fomivirsen), a cytomegalovirus antisense drug, from Isis Pharmaceuticals, Inc.
  
• Bristol-Myers Squibb Co. licensed two HIV protease inhibitors from Novartis Pharma AG.
  
• MedImmune, Inc. licensed antibody humanization patents (for MEDI-493) from Protein Design Labs.
  
• Triangle Pharmaceuticals, Inc. licensed MKC-442, an HIV non-nucleoside reverse transcriptase inhibitor (NNRTI), from Mitsubishi Chemical Corp.
  
• Virologix Corp. licensed use of topoisomerase I inhibitors including camptothecin for treatment of HIV-infection from the National Institutes of Health.
  
• Geniva, Inc. and Hawaii Biotechnology Group, Inc. licensed flavivirus vaccine technology from the National Institutes of Health.
  
• Medicorp Inc. consolidated its rights for passive hyperimmune therapy for treatment of HIV-infection.
  
• OraVax, Inc. licensed yellow fever virus vector vaccine technology for Japanese encephalitis, dengue, hepatitis C and other viral vaccines from St. Louis University.
  
• SmithKline Beecham Biologicals licensed use of monophosphoryl lipid adjuvants in human papillomavirus vaccines from Ribi ImmunoChem Research Inc.
  
• Monarch Pharmaceuticals, Inc. acquired U.S. rights to 1% trifluridine (Viroptic Ophthalmic Solution) from Glaxo Wellcome Inc. for treatment of corneal inflammation due to herpes simplex virus infection.
  
• Chiron Corp. granted licenses to Bristol-Myers Squibb Co. and Arris Pharmaceutical Corp. for use of its hepatitis C virus patent portfolio for hepatitis C virus protease inhibitor drug discovery.
  
• Igen International Inc. licensed assays for HIV-1 p7 antibodies from the National Institutes of Health.
  
• Henderson Morley Ltd. was seeking partners for development of a subunit herpes simplex virus vaccine.
  
• Mycogen Corp. licensed human and animal edible plant-produced vaccine technology from Washington University.
  
  

• Merck & Co., Inc. brought suit against SmithKline Beecham Corp. over U.S. rights to varicella-zoster virus (chickenpox) vaccines.
  
• Biogen Inc. charged Amgen Inc. with infringement of U.S. patents used in the production of recombinant consensus interferon (Infergen).
  
  

• The National Institutes of Health abandoned its U.S. patent covering a distinct strain of HTLV-I (MEL1) found in Papua New Guinea, placing the virus and host cell line in the public domain, after being accused of biopiracy and misappropriating the genetic heritage of lesser-developed countries.
  
• Amarillo Biosciences, Inc. licensed patents related to natural alpha interferon from Hoffmann-La Roche Inc. even though the company believed that its natural oral interferon products do not infringe RocheÕs patents.
  
• The European Patent Office revoked a recombinant interferon-beta production patent from Biogen, Inc.
  
• The European Patent Office revoked a recombinant interferon-beta production patent from Dr. Rentschler Biotechnologie GmbH (licensed to Schering AG).
  
• Cell Genesys, Inc. withdrew its suit against GenPharm International, Inc. over ownership of transgenic mice for production of human monoclonal antibodies.