Dr. Dennis A. Carson, from a 2017 article
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Dr. Robert Wallace Malone (born 1959) ( Multiple shared patents, and worked together at Vical Incorporated - See Dr. Malone's 2017 resume at [HL0080][GDrive] )
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Vical Incorporated ( Main founder was Dr. Karl Yoder Hostetler (born 1939) , and co-founders included Dr. Dennis A. Carson (born 1936) , Dr. Douglas Daniel Richman (born 1943) , and Dr. Philip Louis Felgner (born 1950) )
Dennis A. Carson is an American physician and hematologist credited as co-discoverer of the CpG adjuvant that is used for hepatitis vaccination.[1] He is a member of the National Academy of Sciences and the 2002 recipient of the International Rheumatology Award from the Japan Rheumatism Association.[2] From 2003 to 2007 he was associate dean for health sciences at the University of California San Diego.[2][3]
Full newspaper page : [HN01WM][GDrive] / Text form [HN01WX][GDrive] / Mentioned : Dr. Philip Louis Felgner (born 1950) / Dr. Jon Asher Wolff (born 1956) / Dr. Robert Wallace Malone (born 1959) / Vical Incorporated /
Also mentioned : Dr. Dennis A. Carson (born 1936) / Dr. Karl Yoder Hostetler (born 1939) / Dr. Douglas Daniel Richman (born 1943)
The experiment was so elementary, and the results so surprising, that researchers working with San Diego’s Vical Inc. couldn’t really believe what they were seeing. It all seemed too simple.
They had been injecting submicroscopic fatty globules containing DNA or RNA into mice to see what would happen. The idea was that the fat globules, called liposomes, would be taken up by cells. The cells would use the genetic material inside to make proteins they couldn’t otherwise make.
The researchers found moderate success with that, but the rigors of science demanded that the experiment have a “control” portion--injecting the raw DNA or RNA into the mice to show that the liposomes themselves were making it possible for the new genes to be incorporated into the cell’s processes.
It turned out the cells like the raw material even better and began making the new proteins for as long as six months.
“This was a big surprise, and that’s really what you’re looking for in this area,” said [Dr. Philip Louis Felgner (born 1950)], director of product development at Vical. Felgner worked on the experiment with [Dr. Jon Asher Wolff (born 1956)] and others at the University of Wisconsin at Madison.
Researchers spent several months longer trying to find flaws in their methods or their conclusions. The literature of science is littered with examples of experimental results that deserved the label of too good to be true, explained [Dr. Karl Yoder Hostetler (born 1939)], vice president for research and development at Vical.
“We didn’t want any fiascoes,” he said.
Vical hopes that the results of this checking and double-checking, reported in today’s issue of the journal Science, will convert the company from a bare-bones start-up to a major player in the ranks of San Diego’s biotechnology community.
The company, which was founded in 1987, hopes to find financing to more than double its scientific staff of 22 as a result of the study. It is talking with several large drug companies to see if any would like to buy into the follow-up studies on the new gene transfer method, said Vical President Wick Goodspeed.
Some familiar names in San Diego science and business have played a role in Vical. Among them:
[Dr. Karl Yoder Hostetler (born 1939)], who is on leave from his longtime post as professor of medicine in residence at UC San Diego. His specialties include investigating ways to use lipid chemistry to improve the effectiveness of drugs.
[Dr. Douglas Daniel Richman (born 1943)], a founder and scientific adviser to the firm. Richman is a professor in residence of medicine and pathology at UCSD, specializing in virology and clinical trials of AIDS treatments.
[Dr. Dennis A. Carson (born 1936) ], also a scientific adviser to the firm. Carson recently resigned as head of the division of clinical immunology at Scripps Clinic to become head of UCSD’s new institute for research on aging.
Timothy Wollaeger, chairman of the board. Wollaeger formerly was senior vice president in charge of finance and administration for Hybritech Inc., the monoclonal antibody firm whose success was capped in 1986 with its $485-million acquisition by Eli Lilly & Co.
Howard E. (Ted) Greene, a director of Vical. He formerly was chief executive officer for Hybritech. Greene and Wollaeger were the driving forces behind Biovest Partners, a venture capital firm that financed several San Diego biotech firms.
W. Larry Respess, a Vical director. A leader in biotech patent law, he formerly was general counsel of Gen-Probe and Hybritech.
Until now, the best combination of science and business for Vical has been the multi-year research contract it received last summer from Burroughs Wellcome Co. to develop new forms of AZT for AIDS therapy. The study is investigating the idea that encasing AZT in fat globules would make it more powerful within the body.
The gene-insertion technique reported in Science this week is being suggested as a way to cause the body to generate proteins that would block persistent viral infections, ranging from AIDS to herpes. It also is seen as having potential use as a way to trigger cells to immunize the body against diseases, researchers say.
Vical is calling the new method “gene therapeutics,” to distinguish it from the traditional goal of gene therapy, which uses viruses to insert missing genes into the genetic codes of people with genetic diseases.
The so-called retroviral method has proved difficult and slow, despite several years of intense effort by research groups around the country, including a group led by Dr. Theodore Friedmann at UCSD.
Because retroviruses insert their own genetic code into the cells of their host, the method is also expected to be problematic as a gene therapy technique--since some scientists worry that this could harm the patient irreversibly in some unforeseen way.
Inserting the genes themselves into muscle cells--without any retroviral carrier--avoids this stumbling block entirely, [Dr. Philip Louis Felgner (born 1950)] said. The genes do their work of producing proteins, called expression, but they don’t seem to affect the cell’s own genetic structure, he said.
“People have worked in the gene therapy area for years assuming that a rather complex viral delivery system would be required in order to get expression. And we have found that you can do it very simply,” Felgner said.
It was the slowness of the gene therapy field that led Felgner’s collaborator, of the University of Wisconsin, to decide less than two years ago to get out of it altogether, Wolff said in a telephone interview.
Wolff was an assistant professor and a researcher in Friedmann’s UCSD lab before going to Wisconsin as an assistant professor of pediatrics and medical genetics in 1988.
“I had pretty much planned to get out of the gene therapy field because I got discouraged with the retroviral approach. Scientifically, it wasn’t very challenging,” he said. “Everybody was doing the same thing, and nothing was working that well.”
The results of the research contract with Vical, begun in January, 1989, have rekindled his enthusiasm, [Dr. Jon Asher Wolff (born 1956)] said.
He believes that, in the end, genetic therapies will involve a variety of techniques, not just the Vical method. But he and [Dr. Philip Louis Felgner (born 1950)] acknowledge that they expect some resistance to their ideas from the traditional gene therapy community.
“You’re talking about somebody who has spent his life in this field, and who would like to make the real breakthroughs that are going to allow it to be used in patients with diseases,” Felgner said. “There’s quite a bit at stake.”
Other collaborators with Wolff and Felgner on the research were [Dr. Robert Wallace Malone (born 1959)] of Vical and Phillip Williams, Wang Chong, Gyula Acsadi and Agnes Jani in Wisconsin.
Vical is planning to try to patent the technique, even though it involves no novel or complex steps unfamiliar to molecular biologists. In essence, it involves preparing DNA or RNA with standard techniques and then injecting it in the conventional way into muscle.
“The reason why we have patent position is that it was such a total surprise. Some of those things are the best patents you can get,” Felgner said. “Nobody who was ‘skilled in the art’ would have ever thought that what we have accomplished here was even possible. Nobody would have even thought to do the experiment.”
https://www.newspapers.com/image/175531231/?terms=%22dennis%20A.%20Carson%22&match=1
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December 5th, 2017
The reaction on Wall Street was a little anticlimactic after the FDA approved a new hepatitis B vaccine last month for Berkeley, CA-based Dynavax Technologies (NASDAQ: DVAX).
Many investors sold stock on the news. In the days following the company’s Nov. 9 announcement, the price of Dynavax shares slipped about 8 percent, from $20.05 a share to $18.45 on Nov. 16.
For Dennis Carson, however, the FDA announcement represented the culmination of a scientific odyssey that took 21 years. To him, vaccines represent a paradigm in preventive health—even though vaccines take longer to develop and typically don’t bring the kind of financial payoffs that blockbuster drugs yield in the life sciences industry.
Carson, a 71-year-old professor emeritus at the UC San Diego School of Medicine, co-founded Dynavax in 1996 with the idea of developing a new hepatitis B vaccine based on short bacterial DNA sequences. The intended result would provoke a stronger and longer-lasting immune response, and Carson says that has been borne out. It may have been a long slog to win FDA approval, but “It hasn’t been a long slog because the science was wrong,” he said.
The recombinant vaccine, known commercially as Heplisav-B, is the first Dynavax product to win FDA approval, and the first new hepatitis B vaccine in the United States in more than 25 years.
The underlying idea, based on research led by Carson and UC San Diego’s Eyal Raz, is that “immunostimulatory DNA,” serving as the adjuvant in recombinant biologic vaccines, would be a kind of interchangeable part in an array of new vaccines. The idea is only now coming into its own. Carson, who still operates a lab at the Sanford Consortium for Regenerative Medicine, says similar DNA sequences could some day be used in other vaccines to stimulate an immune response to tuberculosis, malaria, flu, and even cancer.
Dynavax is now conducting trials of cancer vaccines based on immunostimulatory DNA oligonucleotides. The selected agents are injected directly into the tumors (for melanoma and head and neck cancers), or given by inhalation (in lung cancer).
Getting this far in hepatitis B, though, has required the patience of Job.
As a point of comparison, it took 13 years to win FDA approval for the chemotherapy drug 2-CdA (Cladribine), which Carson helped develop with Ernest Beutler, his mentor at The Scripps Research Institute. Yet in his office, which overlooks the Torrey Pines Golf Course and the Pacific Ocean, Carson takes a serene view.
“Twenty [plus] years sounds like a long time,” he said. “But for a vaccine that is given to a lot of people, and where safety is the prime issue, it takes a long time.”
Dynavax initially submitted its application for Heplisav-B in 2012. A few of the recipients in clinical trials had developed autoimmune diseases and cardiac events, so the FDA asked Dynavax to conduct an additional clinical trial in 2013 to determine if these events were related to the vaccine or just random. The FDA sought more information and analyses again in 2016.
Only large-scale studies could provide a definitive answer, and the company says its Heplisav-B studies included 10,038 patients altogether. According to Carson, an FDA advisory committee concluded that the adverse reactions were no more than could be expected by chance. Nontheless, they asked that Dynavax conduct post-marketing vigilance studies.
Dynavax plans to introduce Heplisav-B as its first commercial product in early 2018. The company managed to sustain itself initially through the support of individual investors and research grants from the National Institutes of Health. The company went public in 2004. “It’s wonderful in the United States that investors will keep pouring money into a company to keep it going,” Carson said.
There is no cure for hepatitis B, an extremely infectious virus that causes serious liver disease. While most people recover, about 15 percent of the cases become chronic—and can lead to liver cirrhosis and even cancer. Dynavax says results from one of its clinical trials (with 6,665 participants) showed that its Heplisav-B vaccine provided a higher rate of protection—95 percent versus 81 percent for Engerix-B, the current standard vaccine marketed by GlaxoSmithKline (NYSE: GSK).
https://digital.sciencehistory.org/works/evlnhbq
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