WARF, Oatmeal and the Patenting of Life

The battle over the WARF patent on human embryonic stem cells caught the attention of the Los Angeles Times last week, which added some oatmeal and history to the tale.

Michael Hiltzik, a business columnist with the largest circulation newspaper in the Golden State, reported on the challenge by Consumer Watchdog of Santa Monica, Ca., Jeanne Loring, head of the stem cell program at Scripps, and the Public Patent Foundation of New York.

The trio on Friday asked the U.S. Supreme Court to intervene and affirm their right to sue(See here and here.).  Hiltzik said, 

“The group has challenged the patent on two grounds: first, that the work covered wasn't novel or original, and second, that the Supreme Court has ruled that a ‘product of nature’ can't be patented.   

“All this is happening, researchers say, because WARF (Wisconsin Alumni Research Foundation) made exceptionally broad claims for its patent rights and exercised them very aggressively. This is, in fact, WARF's business; the nonprofit foundation was formed in the 1920s to exploit a patent issued to a University of Wisconsin professor on fortifying food with vitamin D, which it promptly licensed to Quaker Oats. By 1930, the deal was producing $1,000 a day. WARF also owns the rights to the drug Warfarin, which is named after the foundation.”

Hiltzik continued,

“The foundation demanded steep licensing fees of $5,000 a year from academic researchers and as much as $400,000 from commercial firms, plus royalties from product sales. 

“Eventually this backfired. When San Diego researcher Jeanne Loring was confronted by a demand for $75,000 a year from her start-up company—‘that's a lot, when your entire budget is $75,000,’ she told me--she looked closely at the patents only to conclude that they should never have been issued. 

“The key to (Wisconsin researcher Jamie) Thomson's success, she contends, was that he was able to get his hands on human embryos at a time when other researchers could not; the techniques he used had been applied to embryos of other species and shown to be effective. ‘Had I or any other stem cell scientist been given human embryos and sufficient funding, we could have made the same accomplishment, because the science...was obvious at the time,’ Loring says in a court declaration.  

“WARF disagrees. Thomson's success, it says in its own legal filings, ‘was anything but routine....He identified the critical steps needed to generate and culture these cells....No prior art reference taught these insights.’"

Judicial Activism, WARF and Embryonic Stem Cell Patents

The Corporate Counsel Web site/magazine today called up some interesting history involving an appellate court judge in the California-based challenge to an important patent on human embryonic stem cells.

The case involves WARF, the Wisconsin Alumni Research Foundation, which holds the patent on the work done by Jamie Thomson of the University of Wisconsin. Challenging the patent is Consumer Watchdog of Santa Monica, Ca., and Jeanne Loring, head of the stem cell program at Scripps, and Daniel Ravicher of Public Patent Foundation of New York.

Today they filed a petition with the U.S. Supreme Court to overturn an appellate court ruling that they had no standing to sue (see here and here). That ruling was written by Randall Rader, one of three judges on the appellate panel.  

Lisa Shuchman, a reporter for Corporate Counsel, wrote,

“It was one of the last decisions written by then-Chief Judge Rader before he resigned (as head judge) amid an ethics controversy.”

She continued,

“WARF did not raise the issue of standing in its Federal Circuit briefs. But about 20 seconds into Ravicher’s oral argument before the court, Rader interrupted, asking him, ‘Do you have standing to be here?’ That question eventually led the panel to rule against the advocacy group.

“On Twitter, Ravicher on Friday called that ruling ‘judicial activism at its finest.’

“'Statutes expressly say non profit groups like @ConsumerWD can challenge patents in court. Fed Cir decision judicial activism at its finest.— Daniel B. Ravicher (@danravicher) October 31, 2014’ 

“A year before the Federal Circuit’s June decision, the Supreme Court reversed the Federal Circuit in Association for Molecular Pathology v. Myriad Genetics Inc., ruling that a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated.

“'Under Myriad, there’s no way WARF’s patent would survive,’ Ravicher said. ‘Rader was on the record saying he thought the Supreme Court got Myriad wrong, and he looked for a way to avoid hearing this case on the merits because he didn’t want to further enforce the Myriad rule.’”

'Wipe This Thing Off the Books:' More Coverage of WARF Patent Challenge

The San Diego U-T is carrying a story on today’s filing with the United States Supreme Court on the California-based challenge to the WARF patent on human embryonic stem cells.

Bradley Fikes quoted one of the parties in the matter, Jeanne Loring, head of the stem cell program at Scripps, as saying,

“We think that now embryonic stem cells really are showing their worth in clinical studies, it's very important to just wipe this thing off the books, so nobody can either shut down trials or require huge licensing fees for successful efforts.”

Here is a link to the petition to the high court, which deals with a standing to sue issue – not the heart of the dispute. Here is a link to the press release from Consumer Watchdog of Santa Monica, Ca., another party in the matter. Here is a link to the earlier story on the California Stem Cell Report.

U.S. Supreme Court Action Being Sought in Major Human Embryonic Stem Cell Patent Case

The California-based  challenge to WARF’s patent on human embryonic stem cells is headed for the United States Supreme Court.

The nation’s highest court is expected to be asked Friday to overturn an earlier appellate court decision and allow two public interest groups to seek to cancel the patent held by WARF, the Wisconsin Alumni Research Foundation.

The specific issue is whether the California parties have the right to sue. But at the heart of the matter is the question of who profits from stem cell research along with whether the Wisconsin patents stifle scientific research.

As far back as 2006, executives of biotech firms in California complained that the Wisconsin patents were onerous and posed a significant obstacle to private investment.  That year the royalties from California alone generated an estimated $200 million for WARF.

Consumer Watchdog of Santa Monica, Ca., and Jeanne Loring, head of the stem cell program at Scripps, are pushing the eight-year-old case along with the Public Patent Foundation of New York, which is doing the legal lifting.  In 2013, the patent foundation won the famous Myriad case in which the Supreme Court ruled that genes cannot be patented because they occur naturally in nature. 

In a statement about Friday’s appeal to the high court, Dan Ravicher, executive director of the

Dan Ravicher and Jeanne Loring at Post Office when
they made the first filing in the WARF case in 2006.

foundation, said,

“The Court of Appeals’ refusal to allow Consumer Watchdog to appeal the (Patent and Trademark Office’s) faulty decision to uphold a patent on human embryonic stem cells is a clear violation of the express language of statutes passed by Congress and signed by the President to empower the public to seek revocation of invalid patents.”

John M. Simpson, stem cell project director for Consumer Watchdog, said,

“The patent should clearly be rejected because it covers ineligible subject matter and was obvious in view of earlier research.”

Loring said,

“This is an important battle. Human embryonic stem cells hold great promise for advancing human health, and no one has the ethical right to own them,”

Others who have filed affidavits supporting the challenge include Douglas Melton and Chad Cowan of Harvard and Alan Trounson, who was then with Monash University. He later became president of the $3 billion California stem cell agency but left that organization earlier this year to return to Australia.

The research that led to the patents was performed by Jamie Thomson at the University of Wisconsin. Thomson has a lab at UC Santa Barbara as well, where he is also a professor.

Coincidentally the Supreme Court filing comes during the week when Jonas Salk, who developed the polio vaccine, would have turned 100. He famously commented in 1955 about patenting the vaccine.

In a televised interview, Salk was asked who owns the patent on the vaccine. Salk replied,

"Well, the people, I would say. There is no patent. Could you patent the sun?"

That statement has led to a range of interpretations about what Salk meant. Michael Hiltzik, a Pulitzer Prize-winning columnist for the Los Angeles Times, wrote earlier this weekabout the issue. 

He quoted from a 2005 book on the vaccine that reported that Salk dissuaded his backers from seeking a patent because his techniques weren’t novel. He said his work was based on years of prior work by others.

The patent attorney looking into the matter for Salk and the backers said,

"If there were any patentable novelty to be found in this phase, it would lie within an extremely narrow scope and would be of doubtful value."

That is not much different than the argument being made by Loring, Consumer Watchdog and the Public Patent Foundation.

$55 Million California Investment: First Patient Receives Viacyte Diabetes Device

Viacyte's diabetes device
San Diego U-T photo

The California stem cell agency and Viacyte, Inc., today marked a diabetic and stem cell first.

The first of about 40 patients has received the San Diego firm’s human embryonic stem cell device as part of a clinical trial testing what could be a virtual cure for type 1 diabetes.

The stem cell agency, which has invested $55 million in Viacyte, carried the news on its blog, The Stem Cellar. Kevin McCormack, a spokesman for the agency, wrote,

Viacyte graphic

“The beauty of the VC-01 is that while it lets cells secrete insulin out, it prevents the body’s own immune system from getting in and attacking the device. The device is about the length and thickness of a credit card but only half as wide which makes it easy to implant under the skin.”

The $55 million is believed to the be largest amount that the state has invested in a single company.  

Paul Laikind, president of Viacyte, said in a press release, 

“To our knowledge, this is the first time that an embryonic stem cell-derived cell replacement therapy for diabetes has been studied in human subjects, and it represents the culmination of a decade of effort by the ViaCyte team, our collaborators, and our supporters at the California Institute for Regenerative Medicine (the stem cell agency)  and at JDRF (Juvenile Diabetes Research Foundation).”  

The trial is being led by Robert Henry at the UC San Diego Health System with the support of the UC San Diego Sanford Stem Cell Clinical Center.

The initial testing involves the safety of the device. It could take years before it might reach the marketplace. 

Text of Letter by Ellen Feigal on Her Resignation

Here is a copy of the letter that Ellen Feigal sent to her co-workers at the California stem cell agency earlier this week, announcing her departure.

"To my colleagues at CIRM:

"With some regret and after careful consideration, I have submitted my resignation as Senior Vice President of Research and Development at CIRM, effective November 10, 2014, in order to pursue other opportunities.

"It’s been an amazing four years.  I am proud of what’s been accomplished under my leadership for the research and development programs, none of which would have been possible without all of the contributions you each made, and was built on the foundation of science, education, training, basic biology and early translational programs of the previous 5 years. 

"The list of our accomplishments is indeed long, but let me highlight just a few.  When I began there were no operational development programs, and to date we have awarded over 27 disease and strategic partnership teams, 18 to move into the clinic, 8 already actively enrolling or ready to enroll patients, with a total of 10 expected to reach the clinic by the end of this year.

"In addition, there are more than 60 preclinical projects in the pipeline. I’m especially proud that our efforts have led to clinical trials reaching a broad range of patients with serious medical conditions including diabetes, spinal cord injury, blinding eye diseases, heart failure, cancer, sickle cell disease, beta-thalassemia, and HIV/AIDS.  With funding just approved Thursday for the first alpha stem cell clinics, CIRM and our investigators are well-positioned to reach the next level of progress – it will be an exciting time.

"I want to particularly thank the development team for the tremendous work of the hands-on management of the development projects – disease teams and strategic partnerships; the grants management team for handling the financial and business aspects of the projects; and our business development team for forging the substantive industry partnerships that will facilitate moving these projects towards commercialization.  Special thanks to our grants review officers for their expert handling of concepts and RFA solicitations and external peer review, in close collaboration with our science officers, and administrative support.

"I am proud to have created CIRM’s first external Clinical Development Advisory Panels.  These panels of multidisciplinary advisors served as a resource to our funded disease and strategic partnership team investigators in areas of preclinical, manufacturing, disease, stem cell biology, regulatory, clinical, and commercialization, to better position the disease and strategic partnership teams for success.

"I want to particularly thank the contracting officers and the legal office for their contributions to vetting the external advisors and ensuring all was done with due regard for COI and CIRM regulations; to science officers on the development team for the extensive discussions they held with the CIRM funded investigators to prepare the questions and issues to address --  your in depth knowledge of the projects and working relationships with the investigators greatly benefited the projects’ ability to progress. I forged a strong working relationship between CIRM and the FDA.  This included twice yearly webinars and yearly roundtables involving FDA, industry and academia to tackle regulatory issues on the product development pathway, and included CIRM scientific team input and participation in elucidating the topics selected for discussion; in addition, it included organizing in 2013, the first meeting of international regulatory authorities from the US, Japan, Europe, United Kingdom and Canada, and investigators from industry and academia, to discuss the regulatory pathways for stem cell treatments. Once again, the contracting office and administrative program support was instrumental in ensuring the webinars, roundtables and workshops proceeded smoothly, and the communications team facilitated the rapid dissemination of these sessions and white papers through CIRM’s public website.

"Over this time period, our repertoire of communications has steadily strengthened due to the direct efforts of our communications team – I have enjoyed working with the group in this critical component of CIRM’s mission.

"Our basic biology and early preclinical translational teams harnessed the engine of discovery to help increase our scientific understanding of diseases, stem cell biology, and how stem cells could function as tools for elucidating disease pathogenesis, target identification and drug discovery and as cellular candidates to fill the pipeline for the development projects – I want to extend my sincere thanks to the teams in their expert management of the CIRM funded investigator projects in these endeavors.

"We have invested in the future creating the next generation of researchers with our training programs – thanks again to the hard work of the teams managing these CIRM funded programs.

"Together – and by this I mean every single one of you – administrative and HR support teams, communications team, grants review officers, basic biology team, early translation team, development team, grants management, contracting officers, legal team, business development officers, financial officers, information technology team, and the leadership team of CIRM - I think we have accomplished a great deal. While there is much yet to be done, this is a good time for me to pursue other opportunities.  I am confident you will all continue to build on what has been accomplished.  I look forward to learning about CIRM’s successes in the future.' 

A Top Exec Departs from California Stem Cell Agency

The No. 2 person at the $3 billion California stem cell agency resigned this week, becoming the fifth person to leave the research enterprise since Randy Mills became president last spring.

Ellen Feigal
CIRM photo

Ellen Feigal gave two weeks notice on Monday that she would be departing as senior vice president for research and development.  The No. 3 person at the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, left last July and has not been replaced.

The agency staff now numbers 54.

Asked today whether Michelle Williams, the former chief scientific officer of Mills’ previous firm, Osiris Therapeutics of Maryland, would replace Feigal, a spokesman for the agency, Kevin McCormack, said,

 “I can say categorically that Ellen will not be replaced, by Michelle Williams or anyone else.”

Williams was at Osiris Therapeutics in Maryland while Mills was president of the publicly traded business. Williams left Osiris in March. She is now listed on Linked In as a consultant. Williams is also on the panel of scientists who review CIRM grant applications.

Elona Baum, who was general counsel and vice president for business development, left her position in July to join Coherus BioSciences of Redwood City, Ca., as vice president and associate general counsel.  McCormack said discussions are “ongoing” about whether her position will be filled.

McCormack said that Feigal “decided that this is a good time to leave and pursue other opportunities.” McCormack reported,

“In an email to staff she wrote: ‘It’s been an amazing four years.  I am proud of what’s been accomplished under my leadership for the research and development programs, none of which would have been possible without all of the contributions you each made.’"

No public mention of Feigal’s imminent departure was made at the agency’s governing board meeting last Thursday.

In addition to Feigal and Baum, those who have left include Natalie DeWitt, former special projects officer for former CIRM President Alan Trounson. She joined Stanford University. Others are Celeste Heidler,  a financial services officer who retired, and Ian Sweedler, an attorney who joined the Moore Foundation.  

No job openings are currently listed on the CIRM Web site. 

Correction

The item Oct. 26, 2014, dealing with news coverage of the Alpha stem cell clinic plan misidentified the person directing the UCLA/UC Irvine effort. The principal investigator on the project is John Adams, a member of the UCLA Broad Stem Cell Research Center and professor in the department of orthopaedic surgery.

California's Alpha Stem Cell Clinics Garner Little News Coverage

The California stem cell agency’s $34 million Alpha clinic venture last week received minimal attention from the mainstream media.

The effort was also was subordinated by the agency itself, which issued a press release that focused heavily instead on the plan by its new president, Randy Mills, to improve operations at the agency.

News stories, however, led with the action on the Alpha clinics. Articles appeared by Bradley Fikes in the San Diego U-T, Rebecca Kheel in the Orange County Register and in The Sacramento Bee by yours truly. John Schreiber of City News Service in Los Angeles also wrote a brief article that was picked up by smaller outlets.

The occasion was approval of the first stage of the Alpha clinic plan, which was originally budgeted for $70 million by former agency president Alan Trounson and the agency board.

Last Thursday, the agency’s board handed out three awards of $8 million each, trimming the applicants’ proposals by as much as 26 percent.  Next year, the agency is expected to add a $10 million information/data center to the Alpha effort. The center was cut from $15 million earlier this year.

The winners last week were the City of Hope, Duarte, Ca.; UC San Diego and UCLA/UC Irvine. The latter two issued press releases quickly (see here and here), but the City of Hope has still not issued one.

The press releases provided a few more details about the research, including the names of the principal investigators. At UC San Diego, it is Catriona Jamieson, deputy director of the Sanford Stem Cell Clinical Center. For the UCLA/Irvine effort, it is John Adams, a member of the UCLA Broad Stem Cell Research Center and professor in the department of orthopaedic surgery. Donald Kohn and Antoni Ribas are directing the two clinical trials. Normally the stem cell agency identifies the principal investigators in a press release following board action but did not do so in this case.

(An earlier version of this incorrectly said Kohn and Aribas were the principal investigators for UCLA-Irvine.)

Today's California Stem Cell Meeting Concludes

Directors of the California stem cell agency adjourned their meeting at 1:07 p.m. PDT today.

More than $9 Million Approved for California Stem Cell Training Programs

Directors of the California stem cell agency today approved $9 million to continue its state and community college training program after supporters  hailed it as “truly transformative” and a valuable addition to the research field.

The agency extended the "Bridges" effort for one year, which has cost the state $51 million already. The college program has trained 782 young people.

The agency also approved $550,000 for a one-year extension of its high school internship program, which has involved 200 persons over the years.

The actions came despite increasing financial sensitivity on the part of directors of the $3 billion research enterprise as the program nears its 10^th anniversary. It faces increasing expenses because of its desire to become more heavily involved in the costly clinical trials that are needed to actual put stem cell treatments into the clinic. Its cash is dwindling at the same time.

Susan Fisher, director of the human embryonic stem cell program at UC San Francisco, told the board in a letter that the state college training program  “offers unprecedented value in terms of the dollars that are spent.”

She said,

“It is very hard for me to put into words the transformative experience that the Bridges Program provides to trainees. They enter UCSF very uncertain of their place in a major research enterprise. To a person, they leave with boundless enthusiasm for a career dedicated to advancing the goals of the CIRM research agenda. Moreover, this life-changing experience is being offered to students who have traditionally not had these sorts of opportunities, making the program even more valuable.”

$34 Million Stem Cell Effort: California Kicks Off Its Alpha Clinic Global Leadership Plan

Directors of the California stem cell today launched a $34 million effort to create a string of Alpha stem cell clinics intended to make the Golden State the leading spot globally for stem treatments and research.

The winners of $8 million grants each were the City of Hope in Duarte, Ca.; the University of California, San Diego, and UCLA, whose proposal included UC Irvine.  Three applications were rejected including those from Cedars-Sinai and UC Davis, which appealed an earlier negative reviewer decision. Action on a fourth application was delayed because of an unspecified allegation of a conflict-of-interest during the closed-door review process.

(Here is a link to the CIRM press release.)

Upcoming in a grant round next year will be creation of a related, $10 million Alpha data and information center that would be both a central repository for research and an education/marketing effort for patients and the public.

The concept for the one-stop centers was first offered in 2011 by former agency President Alan Trounson, who resigned earlier this year to return to Australia.  Nature Medicine reported that the Alpha clinics would be the first-ever “clinical trials network focused around a broad therapeutic platform.”

 The Alpha proposal was originally budgeted at $70 million with up to five Alpha clinics including a $15 million information center.  However, there was no requirement that all five awards be made.

Earlier this year, Randy Mills, the new president of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, successfully recommended slicing $5 million from the data center. The proposal is now being recast. 

Each of the winners is contributing considerable resources to the Alpha plan along with two clinical trials. The nature of those contributions and their size was not disclosed to the public or the directors. Seven applications were considered by reviewers with some including more than one major institution.

Afflictions targeted by the winning institutions range from cancer and heart disease to diabetes and spinal cord injury.  The effort is part of CIRM’s push to fulfill the promises of the ballot campaign of 2004 that created the agency.

The drive to produce actual treatments is also critical to generating fresh financial support for CIRM, which is expected to run out of cash in about 2020. It currently relies on money that the state is borrowing and that flows directly to the agency without going through the normal budgetary process.

Today’s action included cuts in the research budgets proposed by the winners, who sought $11 million to $11.7 million each. Instead the board put a cap of $8 million on the grants. The cuts came after concerns were raised about duplication of costs and inclusion of expenses related to the proposed data/information center.

The nature of each grant’s budget changes will be subject to negotiations with members of the agency’s team.

Here are links to selected, previous items on the Alpha clinic plan:

TUESDAY, MAY 28, 2013

Trounson Proposes $70 Million, Fast-Track Stem Cell Clinic Plan for California

Alan Trounson, president of the California stem cell agency, this summer plans to seek $70 million for creation of what he calls Alpha Clinics, high-powered organizations that will fast-track stem cell therapies to patients.

WEDNESDAY, MAY 29, 2013

$70 Million Alpha Stem Cell Clinic Proposal Draws Reader Comment

In addition to the comments filed online in connection with the $70 million proposal to create Alpha Clinics in California for stem cell treatments,  two other readers commented privately in emails. 

One came from a close observer of the stem cell agency who said, “If done right -- and I'm sure you and I agree that is a big 'if' – it could be an outstanding legacy.”

The other comment came from a physician-researcher at a major California institution and was longer and more critical.

MONDAY, JULY 22, 2013

Inside the Business in California's $70 Million Alpha Stem Cell Clinic Proposal

Want to know more about the business aspects of a $70 million proposal to create a chain of“Alpha” stem cell clinics in California?

More details can be found in a report from the California stem cell agency titled “Alpha Stem Cell Clinics: Delivering a New Kind of Medicine.”

WEDNESDAY, JULY 24, 2013

$70 Million Alpha Stem Cell Clinic Project Garners Mainstream Media Attention

California's $70 million plan for a chain of “Alpha” stem cell clinics today received its first major attention from the mainstream media. 

TUESDAY, FEBRUARY 04, 2014

California's $70 Million Alpha Stem Cell Clinic Competition Ratchets Up

A $70 million race was kicked off last month as the California stem cell agency invited eight institutions to compete to create what it calls Alpha Clinics, enterprises that would attract patients from throughout the world for stem cell therapies.

Alpha Clinic Applications Now Being Considered by California Stem Cell Agency

The Alpha clinic awards are now coming up at today's meeting of the governing board of the California stem cell agency.

Earlier today, Randy Mills, the new president of the agency, outlined in more detail his plan to speed up the grant award process beginning next January. His goal is to substantially reduce the time it takes the agency to process an application until a scientist receives funding.

A press release from the agency later said,

“Right now it can take almost two years for a promising idea to go from the application to the final funding stage. That’s just unacceptable,” says Mills. “We are going to shorten that to just 120 days. But we’re not just making it faster, we’re also making it easier for companies or institutions with a therapy that is ready to go into clinical trials to be able to get funding for their project when they need it. Under this new system they will be able to apply anytime, and not have to try and shoehorn their needs into our application process.”

He said the plan would include ongoing funding opportunities each month during which researchers could apply when ready and have their requests acted on within a matter of a couple of months.

He told the board,

"We don't want loitering."

Mills also told the board that 26 percent of the funding of the agency is going for non-cellular research, the sort of thing that is commonly done by Big Pharma and the NIH. He asked for expression of sentiment whether that should  continue.

In a brief discussion, there was little opposition to that continued expenditure.

In 2004, the ballot initiative that created the $3 billion stem cell agency was peddled to California voters on the basis that it would fund human embryonic stem cell research that the federal government would no longer finance. There was no discussion of funding conventional therapies.

(Editor's note: An earlier version of this item carried an incorrect timeline for funding CIRM grants.)

Directors of the California Stem Cell Begin Los Angeles Meeting

The governing board of the California stem cell agency opened its meeting this morning at 11:08 a.m. PDT with a report from chairman J.T. Thomas. We will carry stories as warranted.

Upcoming: Live Coverage on Alpha Stem Cell Clinics, Training at State Colleges

From California's new Alpha clinics to threatened training programs, catch it all today with updates from the meeting of the governing board of the $3 billion California stem cell agency.

The California Stem Cell Report will be monitoring the session via the Internet from its post in Banderas Bay in Mexico and will file stories as warranted. Today's meeting in Los Angeles begins at 9 a.m. PDT.

If you are interested in following the session directly, the meeting agenda has directions on how to listen in.

California's Alpha Stem Cell Clinic Plan Hits Budget Buzz Saw

The $3 billion California stem cell agency today put the squeeze on applicants in its ambitious Alpha stem cell clinic round, which is aimed at helping to make the Golden State a global leader in stem cell treatment and research.

The action came as one rejected applicant, UC Davis, publicly appealed to the agency’s governing board to overturn tomorrow a negative decision by the agency’s out-of-state reviewers.  Cedar-Sinai in Los Angeles also filed a letter aimed at beefing up consideration of its application, which wound up on the reviewers’ funding fence.

                                                                                                                                                         

A proposal by Randy Mills, the agency’s new president, however, contained the most surprising news – a plan to cut millions from the budgets of the expected winning applicants – City of Hope (application AC1-07659), UC San Diego (AC1-07764) and UCLA (AC1-07675).

The cuts were specified in a slide presentation  posted  yesterday or today for the board meeting in Los Angeles tomorrow. The presentation recommended approval of the three applications but with revised budgets to hit a funding cap of $8 million each. The reviewers had recommended approval of the three with budgets ranging from about $11 million to $11.7 million. 

The presentation and another document based on the closed-door review indicated that reviewers were concerned about duplicative clinical trial costs and expenses associated with a proposed $10 million information center, which was trimmed earlier this year from $15 million. The request for applications to create the center is being rewritten to sharpen its focus.­­­

The other document from the review represented the first time that such a commentary has been prepared and released publicly. It was requested by an unidentified agency board member who was present at the review session.  (When queried, the agency later identified the member as Os Steward, director of the Reeve-Irvine Research Center at UC Irvine.)

 The unusual document said, among other things,

“Some reviewers had questions regarding the wording of the RFA and the potential for duplication of costs. Specifically, there was confusion over the portion of the RFA that listed ‘Clinical Trial Costs’ as specifically being outside the scope of the RFA, while simultaneously permitting  a funded Alpha Clinic to ‘defray some costs, such as clinical operations.’”

As originally proposed, the Alpha plan would have hit $70 million with up to five clinics, although there was no requirement to fund that many. It is now down to something around $40 million if four applications are approved tomorrow at $8 million each, and the information center moves forward with $10 million.

The four-page letter from the Cedars-Sinai Medical Center in Los Angeles to the directors of the stem cell agency was signed by Timothy Henry, director of the division of cardiology.  Reviewers gave the $11 million application (AC1-07650) a scientific score of 68 and said,

“Given the large expansion into regenerative medicine that the institution has undertaken, many of the activities described as elements of the (Alpha clinic) have already been initiated or will soon be put in place. Some reviewers questioned whether the additional resources provided by (Alpha) funding would substantially supplement ongoing activities and if the (Alpha clinic) would add significant value." 

Henry’s letter did not appear to break new ground but emphasized the strengths of Cedars-Sinai, declaring that one of the clinical trials proposed is “the furthest advanced of any CIRM-funded trials.”

The score for the UC Davis’ $10.8 million application (AC1-07637) was not released by the agency.  Reviewers said,

 “While some reviewers felt that the large number of trials ongoing or planned would clearly benefit from additional resources, others questioned the added value of establishing a (an Alpha clinic) at this site and did not think the application clearly conveyed how CIRM funds would be used to leverage and enhance the already ongoing activities.”

The three-page Davis appeal letter was signed by Ted Wun,  chief of hematology oncology, Jan Nolta, director of the UC Davis stem cell program, and Frederick Meyers, vice dean of the UC Davis School of Medicine.

The letter said that since the review of its application, it has received a favorable FDA judgment on a proposed clinical trial for HIV that would begin in 2015.  In an attempt to deal with concerns about personnel, Davis said the Alpha clinic would pull over the most experienced researchers with their old positions being “backfilled.”

The letter also noted Davis’ location in Northern California. All of the top-ranked applications are situated in Southern California, presenting a scientific-geopolitical issue for the statewide stem cell agency.

(The stem cell agency does not release the names of winning applicants prior to board action. However, they were derived by the California Stem Cell Report from a variety of sources.  All of the reviews can be found on this document.) 

California's $40 Million Alpha Clinic Round: Appeals Filed by Two Rejected Applicants

Two of the three rejected applicants in California’s $40 million-plus Alpha Stem Cell Clinic competition are seeking to overturn the decisions, but none of the cases is expected to be made public.

The appeals are being considered behind closed doors by the staff of the $3 billion state stem cell agency, which will make decisions on whether to proceed further. Directors of the agency are not expected to see the appeals at their public meeting on Thursday in Los Angeles.

Up until last year, appeals were considered in public by the board. The process was altered in the wake of often emotional outpourings involving patient advocates and the public. However, scientists and others can appear before the board on any matter, including applications. Researchers can also choose to disclose publicly their appeals.

The governing board is scheduled to ratify three awards in the Alpha round, which is designed to make the stem cell agency a one-stop, global center for stem cell treatments. The Alpha effort also will help to fund additional clinical trials aimed at afflictions ranging from cancer to heart disease.

The expected winners are the City of Hope, UC San Diego and UCLA, based on an analysis by the California Stem Cell Report. A fourth applicant is on the fence. The agency declines to reveal the names of applicants for fear of embarrassing rejected institutions and researchers. In response to a query, Don Gibbons, a spokesman for the agency, Monday said two applicants had filed appeals.

The agency’s blue-ribbon, out-of-state scientific reviewers make the de facto decisions on funding of applications during closed-door meetings. The agency’s governing  board almost never overturns the reviewers’ positive decision for funding. Occasionally, the board will approve funding for a rejected application.

Summaries of the reviews can be found here.

California Stem Cells, College Football and Success

The $3 billion California stem cell agency this week will deal with the sort of odds that often figure in the financial fate of college football players.

The issue at hand involves education, helping young people and setting priorities. Should the Golden State’s stem cell effort train a few hundred college students at $65,000 a pop or spend $9 million to give a piece of advanced research the critical lift to turn it into a cure?

At least that is one way to look at the issues coming up on Thursday at the Los Angeles meeting of the 29-member governing board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.

Up for decisions are two training programs on which CIRM has already spent $52.4 million. Costs per student average nearly $65,000 in one effort.

Extension of the high school training program would cost only $550,000 for one year. However, training at community and state colleges would cost $9 million for one year. That is the program that has schooled 782 students at a cost of about $65,000 each.

Extending both programs for one year would mean nearly $10 million less for basic research or support of clinical trials that could lead to actual stem cell treatments. Keep in mind that board has turned its focus sharply towards aiding clinical trials – which are very expensive -- in hopes of fulfilling the promises of the 2004 ballot campaign that led to the creation of the stem cell agency.

Strong cases have been made for continuation of the programs, most recently by Susan Baxter, executive director of the California State University’s system-wide program for biotechnology, who appeared before the board and asked for a review of the college program.

She said,

“The number one workforce need in this industry is hands-on practice and participation in multi-disciplinary, team-based research projects.  Research experience is baked into the Bridges (college training) program; as a result, graduates have many career options.  Despite the Great Recession, Bridges graduates have succeeded in landing jobs and gaining admittance to graduate and medical schools at much higher rates than peer groups.”

Jeanne Loring, director the Scripps stem cell program, also supported the college training program.  She said recently,

“I think it's a tragic loss to mothball the equipment and shut down the training labs just when work in those labs is leading to the cures that are CIRM's mission. Some of our best-trained stem cell researchers are losing their jobs, just when they are most needed."

One of the arguments made by backers is that one of those relatively few college or high school students could become the next Jamie Thomson, the scientist who is widely credited with starting what may be the stem cell revolution.  It is an appealing vision with strong emotional impact.

And it is also where college football comes in. Many persons support such athletic programs, contending that they provide a way for young persons to train and become a high profile athlete who earns tens of millions of dollars annually, possibly leading a pro team to the Super Bowl year after year.

The odds of that happening for an individual college student are supremely low. Only 1.6 percent of college players ever join pro teams – 254 out of 70,174 college players, according to the latest NCAA figures. Even fewer achieve stardom.

The odds of professional success resulting from the college football and CIRM training programs are not too different, this writer suggests.

Does that mean that the agency should not continue the training efforts. Of course not. But directors should be very clear about the message they deliver about their priorities and their limited resources. Funds likely run out in 2020, according the agency’s latest estimate, and it is years away from producing all the cures promised by the 2004 campaign – something that, in fact, may never happen.

Some might ask whether these programs – if they are so valuable – should not be funded by the state or community colleges themselves. The answer is that those systems have been starved for state funding for years and that situation is not likely to change dramatically any time soon. Of course, those institutions can change their own priorities if they truly believe that stem cell training is more valuable than some of their other offerings.

CIRM’s new president, Randy Mills, has not taken a public position on the training efforts. But he has offered four criteria to evaluate funding decisions by the agency.  They are:

“1. Will it speed up the development of treatments for patients?
“2. Will it increase the likelihood of developing a successful treatment for patients?
“3. Will it meet an unmet medical need?
“4. Is it efficient?” 

Come Thursday, California’s stem cell agency will apply those criteria and maybe some others to decide the fate of the two training programs.

No Appeals Filed Yet in California's $44 Million Alpha Stem Cell Clinic Round

None of the rejected California universities seeking multimillion dollar grants to join the Golden State’s new, ambitious network of Alpha Stem Cell Clinics has yet filed an appeal of the decisions, the state stem cell agency said today.

That word comes from Don Gibbons, a spokesman for the $3 billion enterprise. In response to a query from the California Stem Cell Report, he said, however, the deadline for appeals is Friday.

If appeals are filed as expected, they will handled behind closed doors by the agency’s staff. Under state law, the applicants can also appear publicly before the agency’s governing board on Oct. 23 in Los Angeles to make their case. The board, however, has not responded favorably to most such pitches in the last year or so.

The Oct. 23 meeting will be the first public vetting of the proposals, which are outlined briefly in review summaries. The summaries were prepared by the agency's staff following closed-door meetings in which out-of-state scientific reviewers voted the applications up or down. The board almost never rejects a positive decision by its reviewers. Occasionally, it will approve an application that is rejected by reviewers.

Three applications survived the private review and total about $33.6 million. A fourth is on the fence for $11 million more. The agency refuses most of the time to disclose the names of applicants. But based on the review summaries and other information, the City of Hope, UC San Diego and UCLA appear to be the top-ranked applications. 

California to Spend Up to $44 Million for Ambitious Alpha Stem Cell Clinic Plan

California late next week is expected to plunk down as much as $44 million to help make the Golden State the global leader in stem cell research as well as a go-to location worldwide for patient stem cell therapies.

The ambitious proposal comes from the state's $3 billion stem cell agency which aims to create high-powered Alpha Stem Cell Clinics at major universities around the state. The clinics would be one-stop centers for stem cell treatment and would be designed to attract patients from throughout the world.

Afflictions under attack include cancer and heart disease along with diabetes and spinal cord injury.

Just who will get the cash will be determined on Oct. 23 when directors of the agency will meet in Los Angeles to consider seven proposals. The directors will be working from summaries of the closed-door review and subsequent decisions on the applications by the agency’s blue-ribbon panel of out-of-state reviewers. 

The reviewers approved three proposals for a total of $33.6 million. A fourth, $11 million application received partial support but fell short of a flat recommendation for funding, which agency directors almost never reject. However, the board could decide to back the proposal despite reviewers' concerns. 

All of the applications come from the cream of California universities. The agency withholds the identities of grant applicants in nearly all cases until after the board acts. However, proposals from the City of Hope and UC San Diego appear to be ranked No. 1 and No. 2. UCLA is ranked No. 3, based on the review summaries and other information.

Other likely applicants include USC,  UC San Francisco and Children’s Hospital Oakland,  UC Davis, Stanford and UC Irvine. Some of the proposals brought together two or three institutions. 

All of the institutions have representatives on the 29-member governing board of the California Institute of Regenerative Medicine(CIRM), as the agency is formally known. They will not be allowed to vote on or discuss applications involving their institutions or businesses.

Viacyte, Inc., of San Diego, also appears to be a beneficiary because of its involvement in a trial with UC San Diego, one of the three top applicants (see the review summary for application 7764.) Viacyte has already received $55 million from the agency.

All of the clinical trials proposed or underway are early stage efforts. With early trials, the general odds of a specific therapy becoming available for widespread use are slim and could take a decade or more. 

The three apparent winners are all located in Southern California, leaving Northern California unrepresented, which poses a ticklish scientific-political problem. If the 4th-ranked application is located in Northern California, that fact could well push it into approval.

However, the review summary of the application said,

"The PD and institution have ties to one of the lead clinical trials, which could result in the appearance of a conflict of interest. Reviewers commented that policies should be in place to ensure that the relationships are clearly defined and separated."

The candidates rejected outright by reviewers may well appeal the decisions. The California Stem Cell Report has queried the agency concerning appeals, but the agency has moved much of the appeals process behind closed doors to be handled by its staff. Previously appeals often came directly to the board in public. However, applicants still have the right to appear before the board on any matter.  

Also undisclosed is the full amount of matching funds and other commitments offered by the competing applicants, which appear to be substantial. One applicant (application 7650) mentioned $10 million in its review summary.  Another applicant, which appears to be UC San Diego, touted a single, large private donor. Multibillionaire Denny Sanford has funneled $100 million into stem cell research through a linkage with the San Diego university.

The Alpha Clinic plan is the brainchild of former stem cell agency president, Alan Trounson, who is not expected to attend next week’s meeting. Trounson earlier this year resigned to return to Australia. Seven days after he left the agency, he accepted an appointment to the board of StemCells, Inc., which has received $19 million from CIRM. The agency was shocked by the move and suffered a spate of bad publicity as a result.

Trounson first broached the Alpha concept in 2011.  And in 2013, he told the Los Angeles Times, 

“It will make California a go-to place for stem cell therapies. I want to make sure it's part of our medical fabric."

An article in the journal Nature Medicine said the proposal would create the first-ever “clinical trials network focused around a broad therapeutic platform.”

To dig into the applications and scores, see this document. All of the review summaries are jumbled into the document, but you can scroll through or use a search tool to find specifics.