Corante

About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Is Palbociclib Promising? Or Not? | Main | Biotech Boom, Biotech Bust? »

April 8, 2014

Can You Patent A Natural Product? Prepare For a Different Answer

Email This Entry

Posted by Derek

So, can you patent naturally occurring substances, or not? That's a rather complicated question, and some recent Supreme Court decisions have recomplicated it in US patent law. Mayo v. Prometheus and Assoc. Mol. Pathology v. Myriad Genetics. The latter, especially, has sent the PTO (and the IP lawyers) back to staring out their respective windows, thinking about what to do next.

The Patent Office has now issued new guidelines for its examiners in light of these rulings, though, and things may be changing. Previous standards for patenting naturally occurring compounds have been tightened up - if I'm reading this correctly, no longer is the process of isolation and purification itself seen as enough of a modification to make a case for patentability. The four "judicial exception" categories, to be used in patentability decisions, are (1) abstract ideas, (2) laws of nature, (3) natural phenomena, and (4) natural products. And examiners are specifically asked to determine if a patent application's claims recite something "significantly different" than these.

Here's the blog of an IP firm that thinks that the USPTO has gone too far:

Now we learn that grant of these and similar patents were mistakes, that 100 years of consistent practice in the field of patents was wrong, that what was invented was no more than products of nature without significant structural difference from the naturally-occurring materials, and that the USPTO will endeavour to avoid such mistakes in future. . .

. . .Whatever workable rule of law is derivable from Prometheus, it is apparent from the opinion of Justice Breyer that it was not the Court’s intention to bring about a radical change in pharmaceutical practice. The opinion gives a warning against undue breadth:

“The Court has recognized, however, that too broad an interpretation of this exclusionary principle could eviscerate patent law. For all inventions at some level embody, use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas.”

The problem (and it's the usual problem with fresh patent law) is that we really don't know what the phrases in the decisions or guidance mean, in practice, until there's been some practice. This is going to be thrashed out application by application, lawsuit by lawsuit, until some new equilibrium is reached. Right now, though, if you're trying to patent something that could be considered an isolated natural product, your life has become much more complicated and uncertain. Here's another IP law firm:

What is the "significantly different" standard? With respect to natural products, the Guidance offers that what is claimed should be "non-naturally occurring and markedly different in structure from the naturally occurring products". Again, it is unclear at this point how different "markedly different" will be. How different it needs to be will be worked out on a case-by-case basis, beginning at the level of the patent examiner at the USPTO.

So how can you protect your IP if it involves subject matter that could be considered a "product of nature" by a US examiner? Since we don't yet really know how different "markedly different" is, one prudent strategy would be to include multiple claims having varying degrees of modifications relative to the naturally occurring thing, to the extent these makes sense commercially and scientifically. The more different your claimed product is from the naturally occurring thing, the more likely it is to be considered patent eligible by the USPTO.

Comments (20) + TrackBacks (0) | Category: Patents and IP


COMMENTS

1. earth23 on April 8, 2014 7:41 AM writes...

Thanks Derek for picking this story up. As a chemist-turned-lawyer, I was a bit surprised that the USPTO would take the Myriad precedent this far. While it's correct that only time will tell how the patent office implements this guidance, it's a disturbing opening salvo.

Permalink to Comment

2. Nile on April 8, 2014 7:44 AM writes...

Start with an easy question: is aspirin patentable?

Assuming, of course, that it had been discovered last week by screening a library of synthetic compounds...

...If it is patented, what happens a year or two from now, when botanists discover salicylates in willow bark and challenge the patent?

I don't think we'll see many fluorinated derivatives of naturally-occurring compounds turning up in this sort of challenge, but there's scope for capricious and inconsistent 'degree of similarity' decisions on just about everything else.

Permalink to Comment

3. Anonymous on April 8, 2014 9:40 AM writes...

Also looking into the future- we have a better idea of what molecules are natural products, but what if at some point we start challenging that and find ways to get nature to better produce or manipulate molecules?

Permalink to Comment

4. Anon on April 8, 2014 9:46 AM writes...

I get the feeling isolation and purification is no longer sufficient because we have better technologies to do this(which make it less non-obvious from a lawyer's perspective) which I very much disagree with.
Who is to say I don't spend a couple hundred million R&Ding a molecule only for a secondary technology to have developed in parallel over that period which makes my previous R&D very easy to do (if one were to repeat it in the current time)? Does that suddenly make what I am working towards less non-obvious when I'm challenged?

Permalink to Comment

5. Anon on April 8, 2014 9:56 AM writes...

@3
What about this thought experiment. A novel antibiotic or pyrrolizidine alkaloid that comes about via a selection process? What if this selection is done intentionally in a lab? What if this selection is instead done intentionally in an open field? What if this is done unintentionally in an open field?
Now what was done in nature? Who is to say the pressure you put on that farm land wouldn't have otherwise occurred 20 miles up the road or 20 decades in the past/future?

Permalink to Comment

6. Derek Freyberg on April 8, 2014 9:58 AM writes...

@Nile:
Aspirin is, under your scenario, patentable, as it is not a naturally occurring substance. The Guidance agrees - see the Example B, looking at the "5-methylamazonic acid" part (I'm not even sure that you'd need to recite "purified"). I think the answer to your second question depends on what salicylates are found and in what quantity.
But like the authors of the blogs, I feel that the PTO has gone WAY too far in the Guidance - the idea that gunpowder (in Example C) is somehow unpatentable because the three ingredients individually may be found in nature defies the language of the statute and I think distorts the holdings of Mayo and AMP.

Permalink to Comment

7. a. nonymaus on April 8, 2014 10:11 AM writes...

Oh, so you can't get a government-granted monopoly on a substance that already exists in nature, even if you sprinkle it on green eggs and ham.
Re: 2
A slightly harder question: Suppose cocaine was isolated for the first time next Thursday. Should it be possible to patent it, ignoring all the bulge-cheeked Bolivians? What about patenting its crystalline salts (which clearly do not exist in nature)? What about patenting its tosylate? When does it cease to be an obvious thing to do with a naturally-occurring alkaloid?

Permalink to Comment

8. Derek Freyberg on April 8, 2014 10:48 AM writes...

@a. nonymaus:
I think that the Guidance makes it clear that isolated cocaine would not be patentable; but that crystalline salts would be, as would the tosylate, as long as we are only considering the Guidance issues.
My concern as a patent attorney with the Guidance is that I see the likelihood of it being used as a mantra by PTO examiners in rejections regardless of (1) the statute itself, and (2) the actual *holdings* of Myriad and AMP. There was an unfortunate decision by the Federal Circuit in 1985, In re Durden, that held that a (chemical) process to make a novel and unobvious (chemical) product was not itself novel and unobvious. You can argue with the holding of Durden - I think it was wrong - but the real consequence of the decision for quite some time examiners in chemical cases would reject process claims with more or less the following statement "It's a process, it's unpatentable, Durden", and that was that. It took years and a number of Fed. Cir. decisions to force the PTO back into actually looking at the obviousness of processes rather than just blindly invoking Durden to reject them. Let's hope we don't see a repeat.

Permalink to Comment

9. anonandon on April 8, 2014 12:47 PM writes...

Don't get your legal advice from the PTO. But as 8 points out it takes a long time to overcome the PTO's misinformed conclusions. It took ten years for the Fed. Cir. to fix the way Durden was applied.

Permalink to Comment

10. Anonymous on April 9, 2014 1:42 AM writes...

What's the difference between combining naturally occurring ingredients in some novel order, and combining naturally occurring *atoms* in some novel molecule? Aren't atoms just a form of naturally occurring ingredient?

And aren't we humans and what we might invent just part of "nature" anyway?

Permalink to Comment

11. MIke C on April 9, 2014 1:01 PM writes...

For new drugs I think the main question is: will this ultimately affect formulation claims for natural(ish) products? So long as you can make combinatoric claims which cover your API and all of the known useful excipients you'll be safe even if you can't patent the API on its own.

A competitor would have to come up with a brand new excipient/formulation and successfully route the resulting new drug through the entire NDA process. If that new excipient doesn't improve phase III trial results over the original formulation, why would the FDA approve that new drug? If the new excipient does improve the trial results then, well, that drug should be on the market too. You still probably received several years of exclusivity for your efforts, and with only one competitor there won't be a price war.

Permalink to Comment

12. Anonymous on April 9, 2014 1:32 PM writes...

@10 Patents are designed to protect innovations of man- not discoveries of nature. Thus, patents cannot be obtained for: "(1) laws of nature; (2) natural phenomena; and (3) abstract ideas." Natural products falls under the 2nd group and thus cannot be patented. There is some fuzziness of what is a manmade/unnatural phenomena and what is a natural one, but it isn't that fuzzy yet.

Permalink to Comment

13. JAB on April 10, 2014 7:44 AM writes...

@12 How has nature "discovered" compounds? Natural products are by definition not found in all organisms, unlike DNA, usually in a rather small number of species, and are not produced constantly by that organism, sometimes in response to an external challenge. It's not like they are lying around in plain sight of anyone who cares to look. If a compound synthesis goes awry and leads to an unintended structure, is this innovation or just the laws of nature in operation?

I take some comfort in Derek Freyburg's comments about PTO guidance not being law, but it very well could take a long time to thresh out, and will take motivated sponsors to bring it about.

Permalink to Comment

14. Derek Freyberg on April 10, 2014 4:45 PM writes...

@Anonymous (12):
A "natural product" pharmaceutical is in no sense a "natural phenomenon": it is, in its simplest form, a single isolated and purified compound from all the compounds found within some particular organism, compounded with excipients designed to ensure that it is usefully bioavailable when administered, tested to ensure that in that form it is safe and effective at a particular dose, and manufactured in a way that ensures that safety and efficacy.
Take vincristine (ONCOVIN): the compound itself is present at around 0.05% by weight in periwinkle the percentage varying dramatically with, for example, the amount of nitrogen fertilizer applied to the plants), along with a number of other alkaloids (Wikipedia says around 70), at least several of which are also cytotoxic. The extraction is not simple, and sterile formulation for IV injection is required.
Periwinkle was used as a folk remedy for years, probably still is, to treat diarrhea, hypertension, memory/focus, and menorrhagia (http://www.anniesremedy.com/herb_detail492.php), but that hardly tells you that vincristine will be an effective antileukemic when administered IV in the right dose. Isolated and purified vincristine would not be patentable under the Guidance. That's a loss to the world, because who's going to spend the time and money to find that ONCOVIN is an effective antileukemic if all they know is that nibbling periwinkle helps diarrhea. And by the way, the plant and its extracts are toxic.

Permalink to Comment

15. Derek Freyberg on April 10, 2014 5:09 PM writes...

@JAB:
The PTO has explained its rationale for the Guidance as "we needed to put out something so all our examiners interpret the cases the same way now rather than going through the interminable publish and comment process for rulemaking", which is fair enough. There's been huge pushback, as Derek notes in his article, and the PTO, to its credit, is receiving public comments and may well tighten up the Guidance. If they do listen and reconsider, a revised Guidance may be more reasonable. But, let's face it, the Supreme Court "guidance" on patentability in AMP, particularly, is not exactly transparent; so I fear it will be a number of years and a number of cases before we know how it all plays out.

Permalink to Comment

16. JAB on April 11, 2014 10:16 AM writes...

@ Derek Freyberg:
So where does one comment to PTO on this?

Permalink to Comment

17. Derek Freyberg on April 11, 2014 4:46 PM writes...

@JAB:
See the USPTO web page on the Guidance at http://www.uspto.gov/patents/announce/myriad-mayo.jsp. It gives a clickable link to open an e-mail to myriad-mayo_2014@uspto.gov.

Permalink to Comment

18. Derek Freyberg on April 11, 2014 4:55 PM writes...

@JAB:
Sorry, the link I gave you in 17, despite copy/pasting it from the address in Firefox, does not work. You might try http://www.uspto.gov/patents/law/exam/memoranda.jsp, which is one step back; or, if that is munged also, just Google "pto myriad guideline" and it should take you to the page with all the guidelines, allowing you to select the Myriad page. The e-mail address is good, though - at least clicking on the link gives me an open e-mail to that address.

Permalink to Comment

19. JAB on April 14, 2014 9:07 AM writes...

Thanks, Derek F

Permalink to Comment

20. ASH TREAHN on August 13, 2014 2:16 PM writes...

Can a known natural product can be patented for its use which has not been claimed. If this product is modified by substituting different groups keeping the core structure ring structure same. And on top of that the natural product is a CNS active.

Permalink to Comment

POST A COMMENT




Remember Me?



EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
The Worst Seminar
Conference in Basel
Messed-Up Clinical Studies: A First-Hand Report
Pharma and Ebola
Lilly Steps In for AstraZeneca's Secretase Inhibitor
Update on Alnylam (And the Direction of Things to Come)
There Must Have Been Multiple Chances to Catch This
Weirdly, Tramadol Is Not a Natural Product After All