Stem Cell Scientist Jeanne Loring on hESC Research, Proposition 14 and California Stem Cell Agency

(Editor's Note: The following commentary concerning the California Institute for Regenerative Medicine (CIRM) and Proposition 14 was submitted to the California Stem Cell Report by Jeanne Loring, professor emeritus from the Scripps Research Institute and co-founder of Aspen Neuroscience, Inc., of San Diego.)

By Jeanne Loring

"Long ago, when Bob (Klein) and Jeff (Sheehy) were both CIRM’s oversight board members, their arguments were legend. I was at the meetings for most of them.

"After listening to the broadcast (KQED’s Forum), I want to make 3 points:

"I want to once more correct the idea that George Bush banned embryonic stem cell research; he did not, and I was disappointed that KQED perpetuated that misconception.

"In 2004 when Prop. 71 was on the ballot, I was already receiving funding from the NIH for human embryonic stem cell research. Bush’s decision was NOT to ban hESC research, but was in fact the opposite. He decreed that hESC research could receive NIH funding for the first time. In effect, he REVERSED A BAN. On the 9th of August 2001, a group of us who had already made hESC lines with private funding became eligible, for the first time, to receive NIH funding. Article: Stem cell research gets federal OK, Aug. 9, 2001.

"In 2004 when voters were approving Proposition 71, there were NIH grants funded for Jamie Thomson in Wisconsin, for Bresagen in Georgia, for several groups in other countries, and for Roger Pederson (UCSF) and me in California. Here’s an announcement from UCSF on September 17, 2002: UCSF begins distributing the first of its two embryonic stem cell lines.

"I supported Prop 71 not because it was necessary, but because it would make California an embryonic stem cell research juggernaut. I believed in the potential of embryonic stem cells and CIRM gave me the opportunity to prove it.

"Bob Klein and I used to talk often, and I admire him for his persistence in getting CIRM established. But as time passed, he seemed to tire of my opinions. Last year I published an opinion piece in Nature that pointed out the unanticipated parallel growth of legitimate stem cell research and charlatan “stem cell” clinics: World View Nature. I immediately received this message from Americans for Cures (Bob Klein’s organization).

'Dear Jeanne,

'On behalf of the organization, I must let you know the following. 

'Unfortunately, Americans for Cures must remove you from its Scientific Advisory Board, effective immediately. Your views in the recent article in Nature are not consistent with the views of Americans for Cures as to CIRM and the importance of CIRM’s accomplishments.'

""I have mixed feelings about Prop. 14. I have benefited greatly from CIRM funding, and after many years of CIRM funding, I was able to attract private venture funding to launch a company developing a cell replacement therapy for Parkinson’s disease.

"'But I agree with Jeff Sheehy that the current measure does not fix the flaws in Prop 71. Having watched the process of approving grants by the oversight board (ICOC) for 13 years, I came to the conclusion that because the Board was made up largely of members representing institutions that were competing for grants, bias was unavoidable, and the large size of the Board, 29 members, was a detriment. The current proposition, Prop. 14, makes the situation worse by increasing the number of board members to 35 and not fixing the conflicts.

"There is a moment at which one’s trust in an organization is dashed. For me this it was this event: the president of CIRM was hosted by a professor at Stanford for at least 2 luxurious fishing trips in Montana and Alaska. This president then argued strongly in favor of large grants to Stanford, and also grants to a company that that same Stanford professor had founded. Finally, when the president stepped down from CIRM he waited less than a week before taking a paid position on the board of the company that he supported for CIRM funding. It was then that the full impact of the intrinsic bias became real to me."

(Editor's note: The reference to the president of CIRM is to its former president Alan Trounson. The reference to the Stanford University professor is to Irv Weissman.)

A Scripps Scientist Deflates Cancer-Stem Cell Nexus

The sky is not falling, says a Scripps Research Institute scientist, despite headlines that seem to link "mutation" and "cancer" and "stem cells."

That comes from Jeanne Loring, head of the stem cell program at Scripps, who was writing on the blog of UC Davis stem cell researcher Paul Knoepfler. Loring said,

"'Mutation' and 'cancer' are eye-catching words for a headline; add 'stem cells' and there is a good chance that a lot of people will hear about it. These words have been liberally used in the press to describe the results of a recent publication: 'Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations.'"

Loring said she has been on a soapbox on this issue since 2000.  She said, 

"Every time a scientific report suggests that human stem cells are dangerous, I feel the need to reassure both scientists and non-scientists that we should not panic.  The sky is NOT falling (contrary to Henny Penny), and pluripotent stem cells remain valuable for cell replacement therapies."

Loring went into the rather technical reasons for her position as well as identifying issues having to do with not knowing enough about the cells used in research. She also provided some tools for researchers to use to identify cells with "functionally important mutations."

Loring's bottom line to researchers:

"Don't panic! Check your cells instead."

Scripps' Loring Picked as Stem Cell Person of the Year

Jeanne Loring (center with sunglasses) and her lab team at Scripps in La Jolla

Jeanne Loring, head of the stem cell program at the Scripps Research Institute, last week was named Stem Cell Person of the Year.

The award was made by UC Davis researcher Paul Knoepfler, who funds the $2,000 prize personally. Loring, however, has declined the cash, and Knoepfler is looking for a cause to donate the money to.

Writing on his blog, The Niche, Knoepfler said that overall Loring “has had a transformative,

positive impact at least in part via taking risks and thinking outside the box.”

Knoepfler said,

“Jeanne came out as the winner for her exceptional contributions in 2015 and throughout her many years in the field. She not only has made numerous advances scientifically, but also gone the extra mile in many respects as an advocate and educator.

“Her scientific contributions include outstanding research on human stem cells and in particular in stem cell epigenetics. See her publications on GoogleScholar.  She has been a great mentor to her trainees. You can visit her lab page here.

“She has also been a creative leader in producing IPS cells from endangered species, an area with huge potential ecologically and at a societal level in terms of preventing extinctions.

“Jeanne has mobilized patient advocates and catalyzed exciting work in the clinical pipeline in a number of areas including most prominently in the last few years for Parkinson’s Disease.”

As for the destination of the $2,000 award, Knoepfler wrote,

“I’m currently considering whether to donate the funds to a charity or put them towards a novel educational outreach project in the stem cell field.”

Text of McCormack and Loring Emails on Stem Cell Board Meeting

Here is the text of the Sept. 9, 2015, email message to Sherrie Gould, executive director of Summit4stemcell, from Kevin McCormack, senior director of communications for the California stem cell agency, along with one from Jeanne Loring, head of the stem cell program at Scripps, to McCormack.  Loring sent her email to McCormack after she received a copy of his email to Gould.

The Gould-McCormack email comes first with the Loring-McCormack email following.

“Dear Sherrie
“I just wanted to let you know that there has been a change in plans for our September board meeting. As you know, it was originally scheduled to be held in San Diego, however, that has changed and it is now simply a telephonic meeting. The reason is that the agenda is going to be lighter than originally anticipated and it didn’t make sense to incur the cost of an in-person meeting for one hour’s worth of business. 

“I know you were planning to have many of the Parkinson’s group attend the meeting so I wanted to let you know so you can alert them to the change.
 “Our next in-person meeting will now be in Los Angeles on December 17th.
“Cheers,
“Kevin McCormack”

Loring’s email to McCormack:

“Hi Kevin:
 “Two in a row??  CIRM has rather pulled the rug out from under the patient advocates -these meetings are supposed to be public, so how is the public going to participate if there is no access?  Does CIRM have a plan to give access?  More importantly, is CIRM doing this to avoid having public access?
 “I'm disappointed and the Parkinson's patients are exceedingly disappointed.  The Parkinson's group is trying to find out the resolution, if any, of the timing of the grant applications.  Has anything been done in that regard yet?
 “In addition to the advocates, my students will be disappointed.  I always bring my interns and my CIRM fellows to the meetings so they can meet their benefactors.
 “Any plans for access to the public would be welcome.
 “Jeanne”

California's Consumer Watchdog Loses U.S. Supreme Court Challege to WARF Stem Cell Patents

The U.S. Supreme Court yesterday appeared to have put an end to a California’s group nine-year effort to overturn patents on human embryonic stem cells held by the Wisconsin Alumni Research Foundation (WARF).

The court refused to hear the case that was brought by Consumer Watchdog of Santa Monica, Ca., and Jeanne Loring, head of the stem cell program at Scripps. The court issued its decision with no comment.

An article by Lisa Shuchman in The Litigation Daily said,

“The high court's denial leaves in place a ruling last year by the U.S. Court of Appeals for the Federal Circuit, which found that Consumer Watchdog lacked standing to appeal the findings of the PTO's (Patent and Trademark Office) administrative patent review board.” 

While today’s ruling involved relatively technical legal matters, the heart of the challenge to WARF’s patents involves who profits from stem cell research along with whether its patents have or will stifle scientific research.

Royalties from WARF patents in California alone generated an estimated $200 million in 2006 for the foundation. Executives of biotech firms in California have complained that WARF’s restrictions have posed a significant barrier to private investment. 

Asked for comment, Loring said,

"This doesn't mean they believe that human cells can or cannot be patented, but only that they decided that we had not been sufficiently harmed by the patent for them to become involved.

"Even without a Supreme Court decision, we have succeeded.  WARF wanted their patents to include iPS cells as well as ES cells, but they had to narrow their claims as a result of our challenge, and they cannot claim ownership of iPSCs."  

Doing the legal lifting in the WARF challenge was Dan Ravicher, executive director of the Public Patent Foundation of New York. Shuchman carried a comment from Ravicher on yesterday’s ruling. She wrote, 

“Ravicher said Monday that the Supreme Court's decision could impact many would-be patent challengers. ‘This case could have severe consequences for other third parties that challenge patents with IPRs or the other proceedings created under the America Invents Act,’ Ravicher said. ‘Now they will have no right to appeal an adverse decision.’

“But he also said the decision wouldn't preclude individuals who can claim direct harm, such as stem cell research scientists, from challenging WARF's patent—much the same way doctors successfully challenged the Myriad patents.

“Under the America Invents Act, third parties, such as nonprofits, public interest groups and industry organizations, have the right to challenge patents at the PTAB (Patent Trial and Appeal Board). But under the Federal Circuit’s ruling that now stands, they don't have the right to appeal a PTAB decision.”

Shuchman also recounted briefly some unusual history on the federal appellate ruling that declared Consumer Watchdog had no standing to sue. A more detailed account of that hearing can be found here.

The California Stem Cell Report has asked Consumer Watchdog and WARF for comments. We will carry them when we receive them. Here is the full text of what Loring had to say.

"Being involved for nearly 9 years in the challenge of WARF's patent on human ES cells has given me a fascinating glimpse into our legal system. I hoped that the Supreme Court would decide on the patentability of human embryonic stem cells. But ultimately, the Court decided not to take our case.  This doesn't mean they believe that human cells can or cannot be patented, but only that they decided that we had not been sufficiently harmed by the patent for them to become involved. Even without a Supreme Court decision, we have succeeded.  WARF wanted their patents to include iPS cells as well as ES cells, but they had to narrow their claims as a result of our challenge, and they cannot claim ownership of iPSCs.  

"I've learned that the law is every bit as complex as scientific research, and have gained great admiration for people like our attorney, Dan Ravicher, who relentlessly pursue the question of patent ethics - what should and should not be patented in the public interest.  Dan brought the issue of patenting the human genome to the Court, and won (the Myriad Genetics case).  Working on this challenge with Dan and John Simpson (of Consumer Watchdog) has been a joy, and if they ever want my help in the future, I'd agree in a second."

'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.

Chasing the Sun and Stem Cells From San Diego

The San Diego U-T this morning carried a profile of stem cell researcher Jeanne Loring of Scripps, describing her as a “stem cell evangelist” and a believer in scientific collaboration as opposed to the solitary work her geologist father pursued.

Bradley Fikes, who covers biotech for the San Diego newspaper, wrote the piece about Loring, who is director of the Center for Regenerative Medicine at Scripps.

The article was unusual for the mainstream media, which generally focus its profiles on persons who are more in the public limelight – not scientists.

Fikes noted Loring's early career in biotech businesses in the San Francisco Bay Area in addition to the San Diego, both of which are biotech hot spots. He wrote,

“Unlike the 'pure' academic who regards partnerships with businesses as compromising science, Loring said ties with industry can be rewarding. Businesses can take basic research discoveries and turn them into drugs and other therapies, she said, and that 'translational' arrangement is hard to replicate in a walled-off academic setting.”

The article also touched on Loring's life away from the lab including a pursuit -- eclipses of the sun --that has taken her to Zambia, Libya and Bolivia.

“'The eclipse vacations are the perfect thing for us,' Loring said. 'You can always work, but the eclipse is going to happen at a certain time and a certain place, and you have to be there when it happens.'”  

WARF Stem Cell Challenge: Appeal Says Patent Involves Cells Not 'Markedly Different' Than Found in Human Body

The battle over whether excessive protection of stem cell IP stifles research that can lead to cures was engaged once more today with a broadside against the powerful Wisconsin Alumni Research Foundation(WARF).

The attack came from California’s Consumer Watchdog organization and New York’s Public Patent Foundation which have been tussling with WARF for seven years. The dispute over intellectual property (IP) centers on a patent on human embryonic stem cells held by WARF and which the other organizations are challenging in a federal appellate court in Washington, D.C.

More specifically, the patent involves research by Jamie Thomson of the University of Wisconsin, and now also of UC Santa Barbara, in which he isolated human embryonic stem cells.

Consumer Watchdog of Santa Monica, Ca., this morning issued a news release concerning the organizations’ appellate brief that was filed last week. It cited the U.S. Supreme Court ruling earlier this year that said genes cannot be patented because they exist in nature.  The lead attorney in that successful case, Dan Ravicher of the Public Patent Foundation, is also handling the challenge to WARF.

The news release said that Thomson deserved credit for being first to isolate and maintain human embryonic stem cells, but “his achievement was not the result of his having created a patentable invention.” The brief said that the work involved was “obvious.” One of the main reasons for Thomson’s achievement, the news release said, was that “he had access to human embryos and financial support that other researchers did not have.”

The brief said,

“The claims at issue here cover human embryonic stem (hES) cells that are not markedly different from those in our bodies. Thus, the claims are invalid under 35 U.S.C. § 101 for covering ineligible subject matter, an issue the Court may and, as a matter of judicial economy and public policy, should address.”

The challenge to the WARF patent has drawn impressive support in the scientific community, including  Jeanne Loring, now director of the Center for Regenerative Medicine at The Scripps Research Institute, who was involved from the start. In 2007, Loring wrote in Nature that she became involved in the case because “scientists have an obligation not only to perform research but to make sure that our research can benefit the society that supports it.”

The news release said,

“Later in the case Dr. Alan Trounson, then of Australia’s Monash University and now president of the California Institute for Regenerative Medicine, Dr. Douglas Melton of Harvard and Dr. Chad Cowan of Harvard filed affidavits supporting the challenge.”

Here is a link to legal documents and other material in the case.