maggiekb — 2013-07-31T10:45:10-04:00 — #1
hystericblue — 2013-07-31T11:53:52-04:00 — #2
Nice article in an attempt to explain this complex case. However, I have 2 bones to pick.
DNA is made of up of sequences of amino acid base pairs.
DNA is made up of sequences of nucleotide base pairs.
If you took a bacteria and gave it the foreign DNA, it would run into
those introns and just get confused — kind of like what would happen
if you took somebody who only spoke English and gave them a set of
instructions written in a mixture of English and Japanese.
The metaphor is weird. In that if introns are in Japanese and the bacteria only read English, the bacteria would have no problem assembling the protein. Since only the English part is coding the protein.
maggiekb — 2013-07-31T14:53:27-04:00 — #3
I fixed the first thing. That was a mistake on my part and thanks for pointing it out in a polite way.
With the second thing, my understanding from talking to my source was that the bacteria in question would have been tripped up by the presence of introns. Even though the introns don't code for the protein, they would have gotten in the way of the bacteria's ability to understand what its protein-coding instructions were.
fenudel — 2013-07-31T15:19:10-04:00 — #4
@maggiekb Thanks for the fix; that was very important. And thanks for spending some time on the subject.
To adequately present the position of the SCOTUS, you have to explain their rationale. I think it is incorrect (at least in spirit, see below), but it is not mysterious. They single out cDNA because it is synthetically produced in the lab by human manipulations. Ian Bosdet and Science on Google+ had an excellent Hangout On Air recently to explain this issue (https://plus.google.com/events/cb8gdd8olcclfkcnmp1787uu8a8).
The synthetic origins of cDNA, according to the SCOTUS may render it patentable for the same reason that synthetic drugs (as substances) are patentable. This makes some sense, but ignores the fact that not all cDNA is synthetic, which makes the decision short-sighted (to say the least).
There is also the big picture: people fail to recognize that what is being patented is information. This is not done in a straightforward way (the synthetic cDNA molecule is the disguise here), but that is what's happening. The primary role that nucleic acids play in cells is information storage. Therefore, when you patent genomic DNA, or cDNA, or RNA you are (in effect) patenting information that can be interpreted by the cell (or, since we all share the same genetic code—roughly speaking—information that can be interpreted by biological systems on Earth). I think this is the big problem, not the arbitrary picking of cDNA as a potentially patentable entity.
In fact, imo, the outstanding question is the same here as with the software patents: how (and if) can we patent information?
faendryl — 2013-07-31T17:08:39-04:00 — #5
I am so very not a lawyer, but when you read the decision the Court ruled that cDNA is patentable under the first clause of Title 35 (subject matter), but explicitly expressed no opinion on whether it is patentable under clauses 2 (novelty) or 3 (obviousness). This is contained in footnote 9. It sounds to me, and is the opinion of more legally-educated people that I've spoken with, as though cDNA patent claims on natural genes are likely to be ruled invalid on grounds of obviousness. I haven't seen this discussed much in articles concerning the significance of cDNA patents, and I'm curious whether there's something wrong with the argument or whether it's simply been overlooked?
l_mariachi — 2013-08-01T02:46:20-04:00 — #6
Wintermute made a pathway of enzymes
I can’t see what could possibly go wrong with it doing that.
prestonsturges — 2013-08-01T23:20:34-04:00 — #7
Actually the central point in the conclusion is fundamentally wrong:
When you’re looking for potentially deadly mutations, only the exons
matter. The Court said that Myriad can’t patent the DNA that contains
both introns and exons, but the company can patent the exon-only cDNA.
And you're going to want to be careful never to make that mistake again!
Actually, there are a couple different kinds of mutations that can occur in the introns that prevent synthesis of the protein by either causing synthesis of the RNA to terminate prematurely or by interfering with the subsequent splicing of the intron. This is particularly relevant to the BRCA genes which have lot of introns
Alternative mRNA variants and regulation: The gene contains
61 distinct gt-ag introns. Transcription produces 45 different mRNAs, 38
alternatively spliced variants and 7 unspliced forms. There are 5
probable alternative promotors, 9 non overlapping alternative last
exons and 7 validated alternative polyadenylation sites (see the
diagram). The mRNAs appear to differ by truncation of the 5' end,
truncation of the 3' end, presence or absence of 42 cassette exons,
overlapping exons with different boundaries, splicing versus retention
of one intron. 653 bp of this gene are antisense to spliced gene
NBR2andNBR1.aAug10, raising the possibility of regulated alternate
And that's not even counting all mutations that have been identified. The real gripe with Myraid is that their tests were based on the cDNA sequences without the introns, so the Myriad patents were preventing other labs from testing for the dangerous intron mutations that Myriad was ignoring.
prestonsturges — 2013-08-04T16:56:52-04:00 — #8
Having given the issue some thought, I think the courts decision was sound in general. Genomic DNA (with the introns) is the form found in vivo (in live organisms) so that remains a public domain resource. cDNA is the derivative work made by the inventive efforts of private parties. that can be patented. Perhaps the use of "introns" and "exons" is more technical and specific than it needs to be, but the precedent it sets is pretty clear.
In the specific case of the BRCA diagnostics, it breaks Myriads lock on these genes. Their original patents were way too broad in that they had patented genomic sequences that were not fully characterized (in a population statistics sense), nor was the utility of these sequences known. So when other labs discovered dozens of additional mutations, many of them in the introns, they could not offer to test for these mutations. Also, it became clear that new technologies needed to be developed to test for these mutations, but there was no financial incentive to develop these new diagnostic platforms.
maggiekb — 2013-08-05T10:45:11-04:00 — #9
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