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June 16, 2009

Comments

Great to see an unbiased opinion with nothing to gain or lose from the debate... Not.

There's a real cultural divide at issue here. In Europe, nearly 90% of funding for basic science comes from government sources (whereas in the US it's only about 28%), and there's plenty of industry capitalizing on it, getting patents on downstream innovations from that science, and in my adoptive country, The Netherlands, we are weathering the financial crisis quite nicely, thank you. And do some research before you say it's socialist, it ain't. It's the most capitalist continental European country. We even have to pay for health insurance here. Heavens!

The point is, there are differing ways to do things. Basic science is thriving here, and the European Patent Office will not grant claims on gene sequences (unless engineered). They recently accepted Myriad's appeal giving a patent on the BRCA test as a whole, but not on the claims containing the gene sequences. That's my prefered alternative too, it makes good sense from a policy perspective, and theoretically too.

The strawman approach, of pitting the so-called "patent" camp against the "anti-patent" camp, is misleading, since it isn't that simple. Many of us want to see some middle ground taken, that benefits both science and industry.

Anyway, launch the invective and ad hominem, I'd be disappointed if I got away unscathed on this one.

best,
-dk

Just noticed this strawman/hyperbole:

"[B]anning patents on gene-related breakthroughs would slow biomedical innovation to a halt -- taking away the hope biotechnology offers to patients suffering from debilitating diseases such as cancer, Parkinson's and HIV/AIDS -- while doing nothing to address what is really a much more complicated set of issues."

Of course, that broadens my position beyond reason. I favor patents on any number of "gene-related breaktrhoughs," I just want to see the claims on bare sequences invalidated... that leaves lots of room for patentable innovation, as in Myriad's European patent.

Now who's fearmongering?

Kevin, one point you didn't mention yesterday or today in response to the charge that gene patenting will slow innovation: patents eventually expire. In many cases, it's the patent that provides the incentive to do the work in the first place. Even if patent holders were to sue academic researchers - which as you pointed out yesterday, is something that has not and is unlikely to come to pass - those patents disclose useful information, and others will always be able to put that information to use, if not on the day the patent issues, then within 20 years of its earliest filing date. I'd rather see the knowledge created now, with some possible limitations on its use and immediate tangible benefits for many people, than wait to see it created many years down the road - if it is eventually created at all in the absence of the commercial incentive a patent gives to invest in the necessary research.

DK, I appreciate the value of a middle ground, but you do not provide justification for disallowing patents on bare sequences. While advocates on both sides may go too far in their arguments, those in favor of gene patents have generally provided arguments and evidence that counter all of the justifications for banning patents on gene sequences. So, what justification is there?

Bob Hodges,

I have given those justifications in depth in my original, invited post here:

http://www.ipwatchdog.com/2009/06/13/the-case-against-gene-patents/

(I only ended up commenting here to defend my honor against the "lie" charge, not to reiterate my arguments in two different blogs)

Gene at IPWatchdog kindly linked to my book, which goes in even more depth than my post or the subsequent comments. I really haven't time to repeat them here, so please go check them out. If you don't want to buy the book, there's a torrent out there somewhere. Irony of ironies.

all my best,
David

Who the heck is this David Koepsell, and what is up with his shrill, Rifkinesque screeds? Take a deep breath DK and get over the hissy fit you're still throwing about the "lie" thing from the other thread. "The thin-skinned in the academic ranks" ... spot on Kevin.

"The point is, there are differing ways to do things. Basic science is thriving here, and the European Patent Office will not grant claims on gene sequences (unless engineered)."

David:

If by "gene sequences (unless engineered)," you mean an isolated nucleic acid molecule that encodes a protein that is naturally expressed in a human cell, then the above statement is simply not true. I have prosecuted EP patents containing such claims to allowance, and I would guess that a number of our readers have done likewise.

Don

wow, got me there Tired... yet another anonymous coward (see countless others above).

I am insulted by the Rifkin slur, given in all of my work I have favored genetic engineering, and patents on genetically engineered organisms (see, e.g., http://www.centerforinquiry.net/uploads/attachments/genetic-engineering-ethics_2.pdf ). Do a little background research before you throw insults so far off the mark.

And I'm only calling attention to the "lie" thing to explain to Bob why I bothered coming here in the first place, and to draw his attention to my arguments in another forum, not to get any further mileage out of it.

poor Tired, no one is forcing you to read anything. Maybe a nap will help?

regarding the EPO:

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31998L0044:EN:NOT

Inventions only may be patented, not discoveries (unlike the US Patent Enabling provision of the US Constitution, which makes the Patent Act applicable to both new discoveries and inventions).

"Directive 98/44/EC also takes this line. Among other things it says: "... the granting of a patent for inventions which concern such sequences or partial sequences should be subject to the same criteria of patentability as in all other areas of technology: novelty, inventive step, and industrial application; whereas the industrial application of a sequence or partial sequence must be disclosed in the patent application.

Whereas a DNA sequence without the indication of a function does not contain any technical information and is therefore not a patentable invention. "

from : http://www.ipr-helpdesk.org/documents/protectionBiotechnological_0000001089_00.xml.html

and in the Myriad EPO patent, the latest ruling explicitly excludes the BRCA1 gene itself from coverage:

http://www.nature.com/nbt/journal/v27/n1/full/nbt0109-8a.html

David:

As Kevin noted in yesterday's thread, and as you did at least twice in your IPWatchdog post, you are once again confusing the issue of patent eligibility with patentability. The EPO Directive to which you cite concerns the issue of industrial applicability (or what we refer to as utility in the U.S.). I did not say that I prosecuted claims to nucleic acid molecules lacking patentable utility (or industrial applicability) to allowance. Thus, this EPO Directive does not support your argument, but rather, supports mine (i.e., that such claims can be obtained provided that all conditions for patentability have been met).

Don

DK,
Do you actually work or just sit in your ivory tower of academia, get offended easily and pontificate to the rest of us how stupid we are for actually disagreeing with you?

Don,

granted (see, I admit my lapses, Kevin), but in the case of the Myriad claims, the sequences were specifically excluded, whereas in their USPTO patents, the sequences are part of the claims, under the guise of "methods"

Nonetheless, as I pointed out either here or elsewhere, in Europe there is a blanket mandatory license that allows basic researchers to do their research without fear of violating patents. That should be the case in the US, and the Myriad suit wouldn't be happening if it were.

best,
David

Dear legal pharmer:

Have I once used the term "stupid"?

I work quite a bit, thanks... And trust me, my office is in no "ivory tower."

My questions to you are, did your question give you joy? Does it please you to be insulting? Do you lack courage to make arguments?

What's your point, essentially?

Good to see you folks have kept the debate going in my absence.

Actually, David, we have a good experiment going on here. We have the situation as it exists in Europe, and the situation as it exists in the U.S. It might be informative to look at some measure of innovation to compare how the two systems are doing.

It would not be helpful to look at healthcare costs, which are subsidized so extensively in Europe compared to the US. And if you are right and 92% of investment in R&D is government-subsidized in Europe (compared to 28% in the US) that won't work, either. But maybe anyone following this thread could provide some data points for us to consider.

Finally, I know David come to visit because he felt we had besmirched his honor, and he has explained that his title was not meant to imply human ownership - it's possible it isn't even his title, I guess. But at the risk of appearing hypocritical, we try here not to emulate those blogs where "you're an idiot" seems to be the stock-in-trade. I think David is completely wrong, but he isn't an idiot, so let's try to ask him to justify his positions and not his existence as an academic.

Thanks for all the comments.

Thanks, Kevin.

Actually, I live in the most capitalistic European country: The Netherlands, where we actually have to buy our own health insurance (though buying it is mandatory), but as a result, it's also affordable as is health care. Our employment rate is the best in Europe, with only 4.6% unemployment, and a thriving business economy exists.

It is an interesting experiment, and the European model does differ, yet here in NL, DSM, and other large companies are weathering the recession pretty well. The basic science is nicely funded, there's room for downstream patents, and there's a good amount of public/private partnership... see, e.g, this article:

http://pharmtech.findpharma.com/pharmtech/In+the+Field/Report-From-The-Netherlands/ArticleStandard/Article/detail/529172

I'd like to see us work in this direction back in the US, as I fear that the US is ceding ground, and in danger of losing its pre-eminence in science and technology. Science must succeed if technology is to grow, and my basic argument has been, and remains, that by patenting too far upstream (over what are essentially parts of nature) we risk stifling innovation, new inventions and applications of that science downstream. I think there is evidence that this is occurring, and there is a good consensus on the science-side in the US that this is a real danger with real effects.

best,
David

"If you don't want to buy the book"

ROTFLMAO

"by patenting too far upstream (over what are essentially parts of nature) we risk stifling innovation, new inventions and applications of that science downstream. I think there is evidence that this is occurring, and there is a good consensus on the science-side in the US that this is a real danger with real effects"

David, as I said in the earlier thread, you have a point that the PTO does occasionally issue claims that are too broad but my impression is that, at least with respect to life sciences, the "bubble" has contracted considerably. Both the courts and the PTO appear to have done their best to reign in the worst abuses. The broadest claims in Myriad's portfolio were issued in the gravy days.

If you're worried about patenting "too far upstream" you should focus on the art units at the PTO that are **not** staffed with over-educated Ph.D.s who likely share many of your concerns regarding the social impact of excessively broad claims.

With regard to the Myriad patent in Europe, my understanding is that it was invalidated not because of patent-eligibility issues, but rather because something along the lines of the following happened:
1. Priority application was filed with errors in BRCA sequence.
2. Correct sequence was published.
3. Convention-year application was filed with correct sequence.
Thus, the claims in the eventual patent to the BRCA sequence were found to not have support in the priority application, and the intervening publication destroyed novelty. A garden-variety prior art issue, in other words, with nothing to do with patent-eligibility. Am I totally off-base here?

Curious, you are right to say that it was not a question of patent eligibility. The link provided by David K. also includes the following sections:

(20) Whereas, therefore, it should be made clear that an invention based on an element isolated from the human body or otherwise produced by means of a technical process, which is susceptible of industrial application, is not excluded from patentability, even where the structure of that element is identical to that of a natural element, given that the rights conferred by the patent do not extend to the human body and its elements in their natural environment;

(21) Whereas such an element isolated from the human body or otherwise produced is not excluded from patentability since it is, for example, the result of technical processes used to identify, purify and classify it and to reproduce it outside the human body, techniques which human beings alone are capable of putting into practice and which nature is incapable of accomplishing by itself;

(22) Whereas the discussion on the patentability of sequences or partial sequences of genes is controversial; whereas, according to this Directive, the granting of a patent for inventions which concern such sequences or partial sequences should be subject to the same criteria of patentability as in all other areas of technology: novelty, inventive step and industrial application; whereas the industrial application of a sequence or partial sequence must be disclosed in the patent application as filed;

Don's point in his comment above:
(23) Whereas a mere DNA sequence without indication of a function does not contain any technical information and is therefore not a patentable invention;

(24) Whereas, in order to comply with the industrial application criterion it is necessary in cases where a sequence or partial sequence of a gene is used to produce a protein or part of a protein, to specify which protein or part of a protein is produced or what function it performs;

(25) Whereas, for the purposes of interpreting rights conferred by a patent, when sequences overlap only in parts which are not essential to the invention, each sequence will be considered as an independent sequence in patent law terms;

(26) Whereas if an invention is based on biological material of human origin or if it uses such material, where a patent application is filed, the person from whose body the material is taken must have had an opportunity of expressing free and informed consent thereto, in accordance with national law;

-Chris


Chris

Another oasis - thank you Dr. Singer

Curious,

To my opinion you hit the nail on the head. The Myriad patents were not limited to what they are now because of fundamental differences in the way the European patent convention looks at gene patenting but because of simple novelty and inventive step arguments (molded together with priority issues).
Further, also from a European point of view (and even a Dutch point of view) I have to disagree with David here: also in Europe there is no 'ban' on the patenting of genetic sequences that already exist in nature (i.e. in situ in the human being or in animals). I have drafted and been granted several European patents on animal and plant genes and proteins.
There are, however, some exceptions to patentability in Europe in the filed of biotechnology, and they are nicely mentioned in the EPC in Rule 28: not patentable are processes for cloning human beings, processes for human germ line modification, uses of human embryos and processes for modifying the genetic identity of animals (if they suffer more than benefit for humanity). Further, Rule 29 mentions that the human body and the simple discovery of one of its elements, including the (partial) sequence of a gene, cannot constitute a patentable invention, but this is immediately followed by paragraph (2) that says: "An element isolated from the human body or otherwise produced by means of a technical process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if the structure of that element is identical to that of a natural element." However, as DK rightly has mentioned earlier: the industrial application of a sequence or a partial sequence of a gene must be disclosed in the patent application (Rule 29(3)).
Thus, overall, this does not vary very much from the US situation where patentability is governed by In re Chakrabarty with the addition of the utility requirements.

Further, but more belonging to the debate in the previous topic, it seems that there is a consensus that compounds (including DNA and proteins) would be patentable if they were made by man (and not just isolated from nature). The debate focuses whether compounds that are occurring in nature and are isolated from a human or an animal (or plant, or micro-organism?) should be patent-eligible.
Consider the following line of thought: a researcher isolates a human protein (e.g. insulin) and tries to improve it by changing some amino acids. He succeeds in getting a variant that e.g. has a longer half-life or less toxic side-effects. Anybody would agree that such a novel protein would be patentable. Now, what if the exact same protein is later found to occur naturally, e.g. in some animal or maybe even in some special group of people. Should then this compound with retroactive effect become unpatentable?

It thus seems that patentability objections are not held against the compound itself, but against the way the researcher has obtained the compound. This seems unjustified.

Thanks Chris and Dutch. Dutch, an admittedly simplistic response to the question you raise in your next-to-last paragraph is that it depends on how your insulin variant is claimed. If the claims did not, for example, recite "isolated," but rather depended on the previously unknown modfications along with the assumption that they did not occur in nature, then the claims could be invalidated on an inherent anticipation and/or product-of-nature basis. If, however, the claims did include "isolated" or "purified" or something similar, then it seems such claims would survive.

Curious:

I think you missed the point of Dutch's hypothetical. In Dr. Koepsell's opinion, naturally-occurring sequences should not be patent-eligible, and "engineered" or "modified" sequences should be. Under Dr. Koepsell's system, it does not matter whether the naturally-occurring sequence is recited as being "isolated" -- to Dr. Koepsell, the sequence remains unpatentable. Dutch's hypothetical, therefore, raises a few interesting questions that Dr. Koepsell would need to address: What do you do with engineered sequences that are discovered to be naturally-occurring after a patent on the engineered sequence issues? Would applicants have to prove that their claimed sequences are non-naturally-occurring? Could applicants really do this? Would this in effect render all sequences (even non-naturally-occurring sequences) unpatentable or would there be some minimum amount of modifications required for a modified sequence to constitute patentable subject matter? What would be the scientific basis for drawing such a line?

Alternatively, we could just stick with the system we currently have, which finds support in both the science and the law, and which contrary to Dr. Koepsell's criticism, works just fine.

Don

Wow, actual debate was had while I was busy. Good to see, and thanks to all for the input and clarifications. It's great to be challenged like this, and it's an honest area for genuine thought and disagreement.

My understanding is that the fundamental difference between the EPO and the USPTO approaches is that the EPO looks to the work as a whole, and bare sequence claims do not foreclose others from utilizing the sequences in other inventions. Whereas in the US, the sequence claims could be a basis for an infringement claim against a different invention that includes that same sequence. This is why the scope of the EPO's grant to Myriad differs from that under US law. I think this makes plenty of sense, and in respect to Dutch's comment, to the extent that one cannot get a valid claim on a sequence, but only the combination of some sequence with a specific useful invention, I'd say my analysis was accurate. In Myriad's and numerous other US gene patents, plenty of claims are just sequences. My simple solution is, let's admit those claims are not inventive, let's not invalidate actual inventions utilizing those sequences in new and inventive products or processes, but make it clear that researchers can now do their research on the sequences (which require replication by PCR for that research) without fear of infringement. Of course, as I pointed out, the mandatory licensing for research in Europe (which isn't the case in the US) makes this not an issue here.

As to the question of what we'd do if we discovered that an engineered sequence occurred first in nature, it would seem at first blush like we'd have to invalidate it as prior art. Once again I'd note that SCOTUS in Gottschalk makes this point pretty clearly. Just because we later discover something that was long inherent in nature (like the laws of gravity, relativity, etc.) doesn't make the thing "new."

Excellent points and arguments, folks, thanks for the discussion.

best,
David (please, not "Dr. Koepsell," we can dispense with formalities)

"[I]n respect to Dutch's comment, to the extent that one cannot get a valid claim on a sequence, but only the combination of some sequence with a specific useful invention, I'd say my analysis was accurate."

David:

What do you mean by "the combination of some sequence with a specific useful invention"?

Don

The European Journal of Human Genetics has a nice empirical study of the state of gene patenting in Europe at:

European Journal of Human Genetics (2006) 14, 26–33. doi:10.1038/sj.ejhg.5201503; published online 12 October 2005

Table 2 is informative.

Don,

Take, as an example the difference between the PTO allowing a claim on gravity, as opposed to the use of gravity in a particular invention (like an elevator, for instance). Now, let's consider Epogen, which was mentioned in the Venter piece. The product as a whole, produced as it is by recombinant processes, could be patented without granting protection to the sequence itself. Let's take, for example, Epogen:

"Epoetin alfa), a 165 amino acid glycoprotein manufactured by recombinant DNA technology, has the same biological effects as endogenous erythropoietin. It has a molecular weight of 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin"

Without granting some protection on the sequence (which, let us imagine could be put to numerous other orthogonal uses), the manufacturer can protect his invention as a whole, which combines some naturally-occurring sequence, with some inventive step -- the use of recombinant technology (mammalian cells) to manufacture the end product. My examples above (I think it was in this thread, if not, then the thread from the other day) was: imagine if I developed a new way to synthesize water, or better yet, to desalinate seawater. The process I use to desalinate would be patentable, but the fresh water that emerges would not be.

There would be more patents available to get in the end, more incentive to do the basic science, and room to innovate on inventive processes using discoveries about nature produced by (better funded, as I have called for) basic science.

best,
David

David,

one of your first remarks after my previous post was that "the EPO looks to the work as a whole, and bare sequence claims do not foreclose others from utilizing the sequences in other inventions". This is incorrect in several ways. First of all the EPO only deals with pre-grant procedures, i.e. whether an invention is patentable or not. The European Patent Convention has no bearing on the scope of the patent and when infringement occurs: that is left to the various national laws. Secondly, it is incorrect that a claim to a sequence would not foreclose others from utilizing the sequence. A claim to a sequence is a product claim like any other product claim and if someone uses such a sequence - in any way - it would basically be infringement (except of course the use falls under the exceptions to infringement (like private, non-commercial use). You are right that a novel and inventive use would in itself be patentable, but this would only give you a dependent patent position.

Further, the fact that the EPC requires a function is not different from the US situation, where you have to fullfil the utility requirements. The function does not need to be stated in the claims, a claim just can be 'sequence ABC' (in the end a sequence, whether you like it or not, is just a chemical structure, and you could draft its structural formula and even follow the chemical nomenclature).

Lastly, the teaching from your example on epoietin escapes me. Are you saying that if a patent on the sequence would exist, this would block further innovation on it? If this were true, then the same thing would apply with any chemical compound, for which a patent has been filed. Patenting has never stopped research and never will. First of all because innovation is a process that is stimulated by patents (yes, I know, there is currently a debate ongoing whether this is really the case, but it has been the presumption of starting the patent system after all, so for the moment let's stick to this presumption). According to the research exemption (at least under the Dutch patent law) you are allowed to use the patented invention 'to further the art'. Secondly, if the compound (or sequence) is important enough, people will start to innovate if only to circumvent the patent(which has nicely been shown in the erythropoietin case by Transkaryotic Therapies). Also research on erythropoeitin has led to many new patented products and uses (just type erythropoietin into Espacenet).

Dutch,

I said a claim to a sequence does foreclose other inventions that use the sequence, which appears to mirror what you said above, which is precisely why I disfavor claims to sequences, but would allow claims to inventions utilizing sequences, as long as the sequence itself receives no protection (unless it's engineered).

You should also check out the claims in the Myriad case, which include claims that researches have been sent cease and desist letters for their research on the BRCA1 and 2 genes. In the US, this is legal under the Patent Act, unlike the exception for research in Europe. To see the effect in the US on basic research, you might read this study by Fiona Murray et al: http://linkinghub.elsevier.com/retrieve/pii/S0167268107000182

best,
David

those silly scientists:
http://jnci.oxfordjournals.org/cgi/content/full/95/1/8

Myriad patent scope limited in Europe:
http://www.genomeweb.com/myriad-wins-brca1-patent-appeal-europe-scope-limited

Dear David:

No one ever said you were alone in your opinions. But that doesn't make you right.

David,
as far I could read the docuemnts that you cited, I read that Myriad does not contest research on the BRCA genes itself, it only sent cease-and-desist letters to 'researchers' that used the invention for performing clinical diagnostic tests, i.e. an economic activity.

Dear Dutch:

That is the hypocrisy of at least some of the plaintiffs in the ACLU case and in the anti-gene patenting crowd in general - it isn't that patentees are restricting "philosophical" or basic reaearch, it's that they (justifiably) don't want infringers using high-minded "principles" to mask their infringement.

Thanks for the comments.

Dutch and Kevin,

That is what Myriad claims. That doesn't mean they're right either. When I was a litigator, I noted that not everyone tells the whole truth. Perhaps, as you suggest, it's the hypocritical researchers, or perhaps it's the greedy corporations. Maybe it's somewhere in between.

We shall see what comes of it all.

I have enjoyed and even learned from the debate with you gentlemen (and any women who might have chimed in under pseudonyms).

best,
David

I realize commentators have been going back and forth with David Koepsell, but this book review by Chris Holman absolutely obliterates Koepsell's book:

http://ndpr.nd.edu/review.cfm?id=17005

Holman does an excellent job of exposing Koepsell's utter lack of knowledge on molecular biology and patent law. Unfortunately, as Holman points out, the average Joe is more likely to read Koepsell's muck and become incensed and entrenched than to read quality blogs like this one and become informed.

I should probably find some copy-pasted text I wrote about the same issue although most of it was covered by the above comments.

Businesses and intellectual properties are impossible to enforce in todays world without significant destruction of civil liberties.
no one is forcing any party to do any research and benefit from it , they can work in manual labor while the shareholders can go invest in sweatshops in china to leech off the work reservoir of those who let them so far.

I support civil disobedience that will force the patent holders resort to force and make fall their(ivory) card tower.
It pretty much happens with software now and you could make the thought experiment yourself , however you are likely mentally and financially bound to certain interests that don't benefit the world per-se

Locke,

Holman's review would have been more convincing had he actually read my book. My detailed response, where I also make clear he skipped a critical chapter altogether and only concentrated on about 10 pages, can be found here: http://whoownsyou-drkoepsell.blogspot.com/2009/08/methodical-response-to-chris-holmans.html and here's a patent attorney who rises to my defense: http://www.stephankinsella.com/2009/08/26/comment-on-david-koepsells-why-i-believe-gene-patenting-is-wrong/

and finally, here's a summary of the critical argument that Holman and others keep missing: http://whoownsyou-drkoepsell.blogspot.com/2009/08/summary-of-argument.html

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