Narrowed Stemgenex suit proceeds as court implies stem cell clinic loopholes

stemgenex

Screenshot from Stemgenex website on reported patient satisfaction rates

Can California stem cell clinics make questionable marketing claims about their experimental, non-FDA approved offerings as long as they are not demonstrably false?

Do such clinics not bear any legal requirement to provide informed consent to patients?

A new court ruling raises such striking questions.

San Diego stem cell clinic Stemgenex sells non-FDA approved experimental stem cell offerings to patients suffering from a variety of conditions and last year a lawsuit was filed against the clinic on behalf of some of their customers. The proposed class suit included a number of allegations and much of it is centered on how the clinic marketed its offerings online on its website. The screenshot above from some months back, for instance, seems to claim 100% patient satisfaction.

A judge has now issued a mixed ruling that part of the lawsuit against Stemgenex can continue, while most other parts cannot. For three different takes on the court ruling see what appears to be a Stemgenex PR here mostly claiming victory, a blog piece by Harvard Law Professor Rebecca Tushnet here, and an LA Times piece here by Michael Hiltzik.

The key take home messages from Hiltzik on the overall ruling:

“Judge Antony J. Battaglia dismissed several claims brought by three former patients at the clinic, including an allegation that Stemgenex has misled patients because it has produced no evidence that its treatments have any scientific basis. He said it’s unclear that the plaintiffs would be able to show that Stemgenex’s representations about the effectiveness of its treatments are “actually false or misleading” because they haven’t shown that the clinic’s claims have “actually been disproved.”

But he allowed the case to proceed on grounds that Stemgenex misrepresented customer satisfaction statistics on its website. The clinic claimed 100% patient satisfaction, even after the plaintiffs themselves complained that they hadn’t seen any improvement in their medical conditions.”

Therefore, as to claims of 100% patient satisfaction, the case can proceed, but most of the rest of the case at least at this point is out.

Aspects of the judge’s ruling are concerning such as this statement:

“False-advertising claims based on a lack of substantiation, rather than provable falsehood, are not recognizable under the California consumer-protection laws.”

Is it then the case based on California law that consumers here at present can be recruited by dubious advertising by stem cell clinics and the state won’t protect them unless the advertising claims can conclusively be proven false?

It may be in this particular case that the plaintiffs did not present enough evidence to make such a claim here, but more generally the court language suggests a very high hurdle for challenges to stem cell clinic marketing and even medical marketing more generally. As to stem cells, context is important. In general, how does one prove a stem cell clinic’s advertising is definitively false when concrete information is hard or impossible to come by? Most clinics never publish their data, they generally won’t share their cells with independent researchers to test, and much of what they are doing is considered confidential.

Stemgenex

Stemgenex

Was Battaglia’s court aware of FDA broad warnings about stem cell clinics and offerings across the U.S.? The FDA rightly recognizes the potential of stem cells as the basis for new treatments but is very cautionary in general about what is being marketed directly to consumers already:

“the Food and Drug Administration (FDA) is concerned that the hope that patients have for cures not yet available may leave them vulnerable to unscrupulous providers of stem cell treatments that are illegal and potentially harmful.

FDA cautions consumers to make sure that any stem cell treatment they are considering has been approved by FDA or is being studied under a clinical investigation that has been submitted to and allowed to proceed by FDA.”

That’s strong language in past years from the FDA, but since the FDA has not really subsequently backed this talk up with actual actions related to stem cell clinics marketing non-FDA approved offerings (such as the 100+ clinics here in California), how seriously do people take the language alone? I would hope a court would take it seriously, but it’s hard to say and the lack of FDA action puts more pressure on states and the civil courts in a sense to potentially oversee stem cell clinics. Are states and courts adequately prepared to do so? I also wonder if Battaglia’s court read new 2016 ISSCR guidelines that raise issues regarding stem cell clinics.

Another section of the court statement remarkably suggests that in its view of California law that patient informed consent may not be required by stem cell clinics:

“…the stem cell treatments are at least ‘reasonably related’ to maintaining or improving the health of a prospective customer and do not constitute ‘pure research’…to the extent that stem cell treatments represent a fairly newer body of research and development, the court does not find the innovative nature of the treatment to rise to the level of requiring informed consent under the Code.”

This blows my mind as a scientist, but maybe as a matter of law it is accurate? Maybe not?

What the clinics are doing is highly experimental in most cases and it seems to me that proper consent must be obtained or patients will be at much greater risk. The clinics themselves sometimes outright state that they are doing experimental research and they get their offerings listed on clinicaltrials.gov. They seem to like to think of and portray what they are doing as clinical trials. How can consent not be required in such a context? Is it because of some idiosyncrasy of California law on consent?

The court’s language suggests that California stem cell clinic patients in general may get the worst of both worlds right now as paying research subjects subject to questionable advertising for unproven experimental offerings who nonetheless mostly are without some key state protections. This ruling seems to temporarily create or at least highlight some big potential loopholes that could transcend this one fascinating case.

Washington State considers stem cell regenerative medicine funding

Washington State is considering state funding for regenerative medicine. How cool is that? You can read more about this effort in an opinion piece authored by Washington stem cell researcher, Professor Charles Murry.ISCRM Washington stem cells

There’s so much important stem cell research going on that federal funding, private and biotech investors, and philanthropy simply cannot fund it all so in many cases state funding can fulfill a crucial role as we’ve seen here in California with CIRM and in other states such as New York and Maryland.

Now Washington is working to make this a reality there too. Murry, the Director of the UW Medicine’s Institute for Stem Cell and Regenerative Medicine (ISCRM), makes a convincing case for moving forward on this new state stem cell funding effort. He uses the example of regenerative medicine research on cardiac regeneration, but mentions other important areas too.

What is the UW looking for in the way of the funding and what will it do with it?

“the UW seeks $6 million in operating funds from the Legislature, starting with the next biennium, to recruit and retain top scientists, fund promising results at early stages, and train young researchers and clinicians.”

You can see the core faculty at the ISCRM here.

I grew up in Seattle and did my postdoc at the Hutch so I know how great the UW is and have met some of the wonderful stem cell researchers there.

I hope Washington State approves this and makes stem cell state funding there a regular occurrence as it would be a big boost to the ISCRM and their cool stem cell research.

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Find $250 Easter egg in GMO Sapiens #CRISPR book: here’s a hint

egg crackingWant $250 as well as at least a sliver of science-related glory?

Within my book GMO Sapiens on CRISPR and human genetic modification, I’ve hidden a scientific Easter egg.

There’s more Easter egg info over here including the rules.

If you are the first one to find and properly explain this egg to me after buying the book, you win $250. I had originally limited it to the print edition, but e-version purchase is fine too.

So far no one has gotten the hidden egg right.

To give people a better chance, I’m giving a hint. The clue is: crack the Easter egg code.

Good luck.

This is largely a repost of last year’s Easter piece.

Why UC Berkeley deserves the main CRISPR patent

crispr nihSome months back a USPTO court issued a ruling that most interpreted as meaning the Broad Institute had won the so-called ‘CRISPR patent battle’ in the U.S. and that UC Berkeley, Jennifer Doudna, and Emmanuelle Charpentier had lost. Now this week Berkeley has appealed that ruling. It seems the odds are against Berkeley prevailing in its appeal, but frankly Berkeley deserves the main CRISPR patent and Broad doesn’t. Interestingly, the European Patent Office apparently agrees with this view and disagrees with the USPTO. Update: note that the Berkeley patent application itself also mentions eukaryotic use.

At the heart of the original decision that favored the Broad was an illogical argument by the USPTO court. They said that the research of Doudna and Charpentier did not make the work that the Broad later patented based on the work of Feng Zhang obvious. In my view Doudna and Charpentier’s work in fact did render Zhang’s later work a totally obvious next step.

Why?

A hypothetical scenario can help to illustrate this.

Let’s say a colleague tells me something along the lines of “Hey, I found this novel nuclease we are calling ‘DUH1’ that cuts DNA in a nifty new way in a prokaryote and in a test tube” and they publish that. Of course, after that many people are going to want to try DUH1 in eukaryotes. Duh, it’s a no-brainer, right? It’s therefore bizarre that the USPTO would think the step to try CRISPR in eukaryotes was not obvious after Doudna & colleagues groundbreaking work.

Flip it around too and imagine that the hypothetical colleague who discovered DUH1 only reported that it worked in vivo and then someone else was allowed to patent that DUH1 could be used in vitro on plasmid DNA in a tube. Does that make any sense? Someone else could patent the in vitro use of DUH1 over the inventor who discovered DUH1 first and reported how it worked in vivo? Even if was a bit of a challenge to get DUH1 to work in vitro, I don’t think that makes sense.

Back to the real CRISPR world, does the in vivo to in vitro or in vitro to in vivo or prokaryote to eukaryote “directionality” of the research flow matter for a patent? I’m not sure, but in theory it shouldn’t in this case as the next steps were obvious. How obvious?

If you read Doudna and Charpentier’s seminal Science paper, the abstract concludes with a statement for all the world suggesting the use of CRISPR-Cas9 for genomic editing in general and I took that to mean in eukaryotes too:

“Our study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.”

and the paper itself ends:

“We propose an alternative methodology based on RNA-programmed Cas9 that could offer considerable potential for gene-targeting and genome-editing applications.”

You’re telling me that these statements were meant to be restricted to only prokaryotes or DNA in a tube? Really? Nope.

Strangely the patent court apparently felt that Doudna’s public statements about it being a challenge to get CRISPR to work in eukaryotes was a big deal in rendering their decision, but again technical difficulty does not equate to an idea being non-obvious. For sure kudos to Zhang, who was technically speaking quite adept to get the CRISPR-Cas9 system to work well in eukaryotes quickly, but even if the Broad ironed out key technical kinks in getting CRISPR-Cas9 to work well inside eukaryotic cells that still doesn’t justify them having the main CRISPR patent. It’s just not conceptually or technically different enough from the earlier Doudna and Charpentier work. To me it’s not even a close call, but USPTO got it totally wrong.

Another exercise reinforces my argument. Can anyone imagine Zhang publishing his first CRISPR work (which by the way cites and heavily relies on the works of Doudna and Charpentier) if he didn’t have those earlier key papers of Doudna and Charpentier to build on moving forward? No way. Could Doudna and/or Charpentier and others have gotten CRISPR to work in eukaryotes without Zhang? Yes and almost certainly it was already inevitable before Zhang even published his key Science paper.

For all these reasons, Berkeley deserves the main patent based on simple common sense, but whether things will turn out that way longer term seems far less clear.

Some may say that no one should get to patent CRISPR, but these days that’s probably a naive perspective. For more on the history of patenting (or lack thereof) of nucleases and in particular restriction enzymes, this is an interesting read.