The Supreme Court just ruled on the Myriad gene patentability case. To recap, Myriad holds patents on the BRCA1 and BRCA2 genes, for which they offer testing to help determine breast cancer risk.
To summarize the decision, the Court held that naturally-occurring DNA, even if it is isolated, is not patentable. However, they also state that “[f]or the reasons that follow,” complementary DNA (cDNA) is patentable. What are those reasons?
In section I.A., the court walks through the Central Dogma and does a fine job with it. DNA is transcribed to RNA. RNA gets the introns spliced out and (largely) keeps exons. Processed RNA is then translated by the ribosome into a sequence of amino acids, i.e., a protein. Note that there are a great many functions that RNA serves (tRNA, rRNA, RNA interference, etc). These omissions may become important later. Nevertheless, the Court’s description of how genetic information goes from DNA to protein is essentially right. Importantly, they clearly define cDNA as having come from reverse transcription of cDNA. In other words, they correctly define cDNA.
In I.B., the court dismisses Myriad’s claims that isolated naturally-occurring BRCA1/2 sequences are patent eligible. Just because you have broken two chemical bonds to free the BRCA1/2 sequence from the rest of the genome, you have not “invented” anything.
Section I.C. starts off with a bang:
cDNA does not present the same obstacles to patentability as naturally occurring, isolated DNA segments. As already explained, creation of a cDNA sequence from mRNA results in an exons-only molecule that is not naturally occurring.
From a scientific standpoint, these opening sentences are hard to reconcile with reality. cDNA naturally occurs quite frequently: it is created by cells infected with retroviruses. The way that we make cDNA is by using reverse transcriptase–which we discovered thanks to retroviruses that exist in the wild–to reverse transcribe RNA to its reverse complement (hence the “c” in cDNA). Is natural cDNA accidentally omitted, intentionally omitted, or is the Court re-defining cDNA to only be artificially reverse transcribed DNA? (Probably not the latter.)
[…] the lab technician unquestionably creates something new when
cDNA is made.
Is putting an isolated enzyme (reverse transcriptase) in a test tube with mRNA the “magic juice” that triggers the Court’s deference to the technician’s “creation”? If it weren’t for the splicing work that nature did to remove introns from the mRNA, the technician’s work would simply reproduce already-existent DNA, introns and all.
As a result, cDNA is not a “product of nature” and is patent eligible under §101, except insofar as very short series of DNA may have no intervening introns to remove when creating cDNA. In that situation, a short strand of cDNA may be indistinguishable from natural DNA.
Any cDNA may plausibly be found in nature thanks to retroviruses; therefore, literally any cDNA may be indistinguishable from natural DNA.
I am not convinced by the Court’s reasoning for permitting cDNA patents on otherwise non-modified genetic sequences. If the Court does not extend this analogy beyond cDNA synthesis, one can imagine ways to show natural occurrence of many important cDNAs, or to alter or create new mRNA sequencing techniques to avoid cDNA intermediates in many RNA applications. However, if the Court extends its analogy beyond the reverse transcription step, then it has stepped into territory that seems quite hazardous for the progress of science and the useful arts.
In no particular order:
Would the discovery of naturally-occurring cDNA invalidate a company’s patents?
Would the discovery of individuals with gene duplications (that have had introns removed–this happens) invalidate the relevant cDNA patents for that particular gene?
By analogy with the logic here, should any PCR’ed product become patentable, because the technician put an isolated enzyme (DNA polymerase) in a test tube with DNA? (Since the intron splicing step in cDNA construction occurs before the mRNA is reverse transcribed, it’s not needed in this analogy.) If not, should any Sanger sequencing product be patentable (since instead of being made entirely of DNA, it’s made of DNA plus a modified cap that includes a fluorophor, and therefore differs from the natural DNA template)?
If someone develops a technique that performs artificial DNA intron splicing without a mRNA step, thus yielding DNA indistinguishable from cDNA created in the normal way, should that DNA be patent eligible as if it were cDNA? Should it be considered infringing on patented cDNA of the same sequence?
Should DNA strands created by completely artificial synthesis of DNA–with no RNA step–be patentable? Should they be considered infringing on patented cDNA of the same sequence?
Should we focus on the Court’s special emphasis on the reverse transcription of spliced mRNA as the definitive act of human invention? What does this mean for rtPCR? RNA-seq? How can we prevent potential patents on cDNAs in this realm from hindering scientific research?
Will this cause greater interest in mRNA sequencing that avoids a DNA step? One could imagine a variant on Sanger sequencing that uses a mixture of mRNA, non-holoenzyme RNA-dependent RNA polymerases, and RNA nucleotides, along with a small concentration of ddNTPs attached to fluorophores and DNA polymerase for chain termination / sequencing of mRNA without any cDNA stage.
Alternatively, one could imagine a discovered (or artificially created) RNA-dependent RNA polymerase that occasionally incorporates fluorophoric ddNTPs.
Recall that the average length of exons in the human genome is >100 nucleotides. Does this ruling mostly harm splice-variant and splice-site research?