"Where there is no vision, the people perish: but he that keepeth the law, happy is he."
-- Proverbs 29:18, King James Bible (KJV)

Tuesday, October 26, 2021

Patents and Human Genes incl. A Nature Magazine Book Review by Heidi Ledford of The Genome Defense: Inside the Epic Legal Battle to Determine Who Owns Your DNA by Jorge L. Contreras

We are happy to report that Nature magazine has a timely book review by Heidi Ledford, reviewing The Genome Defense: Inside the Epic Legal Battle to Determine Who Owns Your DNA, a book authored by Jorge L. Contreras, Algonquin books, Workman.com, 2021. See also, e.g. Amazon.com.

As Nature writes about the book:

""Ably and affectingly detailed . . . This story stands as a guide to the forces that shape an increasingly important industry—and to the vexed influence of patents.” — Nature"

The book author, Jorge L. Contreras, has a seminal opinion editorial ("op-ed") at CNN, Don't let gene patents make a comeback, in which he writes that "gene patenting" was ended in 2013 by a unanimous U.S. Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, a decision that has since come under intense pressure by moneyed interests. As Contreras writes at CNN:

"The current prohibition on gene patents, however, could change. The biotechnology industry criticized the Myriad decision when it was released and has worked tirelessly to overturn it, along with other key Supreme Court decisions limiting patents. These opponents claim that unless the reach of patents is expanded, biomedical innovation will be stifled, research will not be funded and lives will be lost. But, as the unprecedented effort to analyze the virus responsible for Covid-19 has shown, this is not true. "

Contreras in that same CNN op-ed correctly writes about the great advantages of patent-free zones in the health and biomedical field:

"In January 2020, when the SARS-CoV-2 virus was first identified, researchers quickly sequenced its genome and uploaded it to the GenBank public database. They then raced to develop vaccines and treatments to combat Covid-19. One thing that enabled them to do so in record time was the absence of patents covering the virus and the hundreds of thousands of genetic variants that have emerged since. Without a doubt, this patent-free zone contributed to the speed at which the scientific community was able to respond to this global threat."

The treatment of human genes in patent law is a topic that -- in our opinion -- has thus far not been adequately covered by mainstream law school journals or legal scholars, although there are signs that they may be awakening out of their slumber. See Book Talk: The Genome Defense: Inside the Epic Legal Battle to Determine Who Owns Your DNA, "Co-sponsored by the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law SchoolHarvard Law School Library, and Harvard Book Store, which is a locally owned, independently run Cambridge landmark since 1932."

Sometimes it seems to us that mainstream law has preferred to focus on what some may consider to be "politically correct" dialogue on various human rights issues involving minorities of every description, ignoring much of the rest of the legal spectrum that applies to both minorities AND majorities. To put it differently, the law also has the duty to protect the rights of average citizens, genes included.

While we do not deny the importance of human rights issues, there are many other important topics in our era that also deserve proper legal attention. The state of patent law as regards human genes is one such deserving topic. Indeed, we have been posting at LawPundit about the sad state of patent law in general for many years, and have specifically argued that human genes are an invention of "the Almighty" (insert the God of your belief here) and should not be patentable in any form, since human genes are not a human invention by any means.

We posted about the Myriad case already early in the court decision process. See Myriad Human Gene Patent Case Vacated and Remanded by U.S. Supreme Court in Light of Prometheus, writing:

"The logic we suggest is: if you cleave an orange in two, you can not claim the two orange halves as inventions, and so it is also with human genes."

In Are Human Genes Patentable? Their Patentability is Once Again on the U.S. Supreme Court Agenda we wrote about the patentability of genes as follows:

"“Are human genes patentable?”

How can the answer be anything but NO?

As posted by Dennis Crouch of Patently-O, Supreme Court has Granted Cert in the Myriad Case, Question: Are Human Genes Patentable.

Timothy B. Lee also has the story at Ars Technica in Supreme Court to rule on patentability of human genes.

We posted previously at LawPundit about this sordid legal farce of greedy companies trying to cash in commercially by claiming “patent” ownership of your genes and mine, as if the two halves of a cleaved orange would be an “invention”‘:

It is time for the U.S. Supreme Court to put an end to this nonsense.

The Almighty, whoever that might be or have been, in whatever shape or form, according to whatever religion you preach or not, “invented” the genes, whether via evolution, or creation, or intelligent design, whatever you believe,

it makes no difference,

but the inventor was NOT some human in a laboratory.

We hope the Supremes get that and make it clear to the recalcitrant judges on the Federal Circuit who think everything is a human invention worthy of monopolistic ownership for the profit of the few."

We also discussed the alleged difference between DNA and cDNA in Can Human Genes Be Patented? U.S. Supreme Court Answer Likely to Be "No", but the Ultimate Issue Down the Road is the Patentability of cDNA (Complementary DNA) viz. Is a Split Hair viz. Split Gene an Invention?, writing:

"Is an orange, a lemon, a fig or a tomato split in half and “peeled”, “a patentable invention”? How about a tree split by a logger into firewood? Patent-eligible? How about the patentability of a split hair?
Or is the excerpt of a paragraph of text taken from a book “a new patentable invention” just because it has been “lifted” from the original whole?

What will be the U.S. Supreme Court decision concerning the patentability of human genes and “split genes” in a case currently before the Court as Association for Molecular Pathology v. Myriad Genetics, Inc., Docket No., 12-398, Argument Date: TBD (“to be determined”), which presents the following question:

“QUESTION PRESENTED:
Many patients seek genetic testing to see if they have mutations in their
genes that are associated with a significantly increased risk of breast or ovarian cancer.  Respondent Myriad Genetics obtained patents on two human genes that correlate to this risk, known as BRCA1 and BRCA2. These patents claim every naturally-occurring version of those genes, including mutations, on the theory that Myriad invented something patent–eligible simply by removing (“isolating”) the genes from the body.  Petitioners are primarily medical professionals who regularly use routine, conventional genetic testing methods to examine genes, but are prohibited from examining the human genes that Myriad claims to own. This case therefore presents the following questions:

1. Are human genes patentable?

2. Did the court of appeals err in upholding a method claim by Myriad that
is irreconcilable with this Court’s ruling in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289 (2012)?

3. Did the court of appeals err in adopting a new and inflexible rule,
contrary to normal standing rules and this Court’s decision in MedImmune, Inc. v. Genentech, Inc., 549 U.S. 118 (2007), that petitioners who have been indisputably deterred by Myriad’s “active enforcement” of its patent rights nonetheless lack standing to challenge those patents absent evidence that they have been personally threatened with an infringement action?”

What has been invented by man? and what by God?

James D. Watson was the co-discoverer of genetic DNA together with Francis Crick, and both he and Crick and Maurice Wilkins won the 1962 Nobel Prize in Medicine “for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material“.

Watson has filed an amicus (“friend of the court”) brief in this case and has written there as follows:

“Human genes should not be patented…. First, a human gene is fundamentally unique–unlike any ordinary “composition of matter.” A gene conveys information–the instructions for life. As a product of nature, a human gene’s primary purpose is to encode the information for creating proteins, enzymes, cells, and all the other components that make us who we are…. Life’s instructions ought not be controlled by legal monopolies created at the whim of Congress or the courts.

Second, much of what we known about human genes traces back to the Human Genome Project, which was structured as a public works project, intended to benefit everyone by deciphering our genetic code… [M]uch but not all of the human genome was dedicated to the public…. It was a mistake by the Patent Office to issue patents on human genes and a mistake by those who filed for those patents.

Third, human gene patents are not necessary to encourage scientists…. Innovation will be rewarded based on [developments in technologies using human genes], not the patenting of the human gene….

“Human genes…are useful because they convey vital information…..”

In our view, awarding ANYONE any kind of patent or other monopoly on this information, in whole or in part, is simply theft of that universal information. What belongs to all is being stolen for the benefit of the few.

In terms of the law and the patentability of inventions and discoveries, when we talk about any form of human genes, we must ask: where is “the inventive step” or the “non-obvious” human discovery involved when “splitting” genes or “splitting” DNA that already exists? Cutting things apart is not “a discovery”. Imagine if firewood were patentable. Whatever is found was already there.

Andrew Torrance at SCOTUSblog in Nothing under the sun that is made of man suggests that the U.S. Supreme Court “likely” will reject the patenting of human genes in Association for Molecular Pathology v. Myriad Genetics, Inc.
[recommended citation at SCOTUSblog: Andrew Torrance, Nothing under the sun that is made of man, SCOTUSblog (Feb. 7, 2013, 12:24 PM), http://www.scotusblog.com/2013/02/nothing-under-the-sun-that-is-made-of-man/ ]

We agree. See our previous postings on this topic here and here.

Alas, however, that may not solve the “actual” practical legal problem presented in this case, where a finding that human genes are not patentable may not really resolve the real issue in this case.

One must fear, in fact that the U.S. Supreme Court could follow the simplistic and errant line of argumentation of the United States Government in its amicus brief which concludes that:

“The judgment of the court of appeals should be affirmed insofar as it holds that cDNA is patent-eligible, and reversed insofar as it holds that isolated but otherwise unmodified DNA is patent-eligible.”

The U.S. Government is thus urging that unmodified DNA be seen as a product of nature, but “modified” DNA be seen as “an invention”, even if that invention consists primarily of using and monopolizing code information that has always been there in the original product of nature.

We ourselves would never tolerate such an illogically split result, but it is a result which might be seen to provide Supreme Court Justices with “an easy out” in this case, replacing individual critical thinking by the judges.

In this manner they could issue a holding meeting “popular” demand that human genes are not patentable, but could at the same time then nevertheless carve out a large and significant “hair-splitting” viz. “gene-splitting” patent exception for “split-off” DNA. We might compare this to a teaspoon of sugar spread on a split lemon. NOT found in nature. Or we might compare it to a clipped paragraph from a book to which proprietary introductory and closing texts are newly appended to create “a new invention”.

If such a terrible decision on the law were to issue from the current U.S. Supreme Court, one would subsequently have no recourse but to argue that even if cDNA were found patent-eligible (as “split” from original human genes) it would nevertheless not be patentable because the “splitting” is obvious.

Making patentability in this field dependent on the obviousness of the splitting would, however, be a very unsatisfactory standard. To government institutions such as the USPTO and the U.S. Court of Appeals for the Federal Circuit, apparently virtually “NOTHING” appears to be obvious.

The U.S. Government writes in its amicus brief about cDNA as follows:

“Petitioners contend (Br. 49-53) that cDNAs are not patent-eligible because they contain the same protein-coding information — i.e., exon sequences — as DNA in the body. But the properties of any product originally derived from nature, including the bacterium in Chakrabarty, can be traced to the operation of natural principles. While the coding properties of cDNA molecules’ exons are determined by nature, those properties operate within a molecule (a DNA strand with the regulatory and intron regions spliced out) that does not exist in nature and that has increased utility relative to naturally occurring genetic materials or isolated but unmodified DNA. The fact that a cDNA incorporates nucleotide sequences whose significance is derived from nature therefore does not mean that the molecule as a whole is a product of nature.5 See Diehr, 450 U.S. at 187.”
__________
5 It is possible that, given the prevailing level of knowledge in biotechnological fields, future patent applications directed to cDNAs and other synthesized DNA molecules may rejected as obvious. 35 U.S.C. 103; see In re Kubin, 561 F.3d 1351, 1358-1361 (Fed. Cir. 2009).”

If cDNA code information were found to be patent eligible in general as being “split” from an original non-patentable gene (as if the coded part were more patentable than the coded whole), the patent approach pointed out in footnote 5 would then be the correct one as a patent defense.

It would then in fact be the ONLY defense remaining, since “creating” cDNA’s
— for those who want to call it “creating” rather than “splitting away from” —
is child’s play these days if you have the right kit.

Indeed, creating cDNA is so simply done that it has already generated a lively market for “cDNA Synthesis Kits”. Just plug that term into Google to view links to any number of them.

We quote from the SMART cDNA Synthesis Kit description online:

“SMART (Switching Mechanism at 5’ End of RNA Template) is a unique technology that allows the efficient incorporation of known sequences at both ends of cDNA during first strand synthesis, without adaptor ligation. The presence of these known sequences is crucial for a number of downstream applications including amplification, RACE, and library construction. While a wide variety of technologies can be employed to take advantage of these known sequences, the simplicity and efficiency of the single-step SMART process permits unparalleled sensitivity and ensures that full-length cDNA is generated and amplified.“

As written at the Wikipedia:

“In genetics, complementary DNA (cDNA) is DNA synthesized from a messenger RNA (mRNA) template in a reaction catalysed by the enzymes reverse transcriptase and DNA polymerase.[1] cDNA is often used to clone eukaryotic genes in prokaryotes. When scientists want to express a specific protein in a cell that does not normally express that protein (i.e., heterologous expression), they will transfer the cDNA that codes for the protein to the recipient cell. cDNA is also produced by retroviruses (such as HIV-1, HIV-2, Simian Immunodeficiency Virus, etc.) which is integrated into its host’s genome where it creates a provirus….

Though there are several methods for doing so, cDNA is most often synthesized from mature (fully spliced) mRNA using the enzyme reverse transcriptase. This enzyme operates on a single strand of mRNA, generating its complementary DNA based on the pairing of RNA base pairs (A, U, G and C) to their DNA complements (T, A, C and G respectively).
To obtain eukaryotic cDNA whose introns have been removed:
  1. A eukaryotic cell transcribes the DNA (from genes) into RNA (pre-mRNA).
  2. The same cell processes the pre-mRNA strands by removing introns, and adding a poly-A tail and 5’ Methyl-Guanine cap.
  3. This mixture of mature mRNA strands is extracted from the cell. The Poly-A tail of the post transcription mRNA can be taken advantage of with oligo(dT) beads in an affinity chromatography assay.
  4. A poly-T oligonucleotide primer is hybridized onto the poly-A tail of the mature mRNA template, or random hexamer primers can be added which contain every possible 6 base single strand of DNA and can therefore hybridize anywhere on the RNA (Reverse transcriptase requires this double-stranded segment as a primer to start its operation.)
  5. Reverse transcriptase is added, along with deoxynucleotide triphosphates (A, T, G, C). This synthesizes one complementary strand of DNA hybridized to the original mRNA strand.
  6. To synthesize an additional DNA strand, you need to digest the RNA of the hybrid strand, using an enzyme like RNase H, or through alkali digestion method.
  7. After digestion of the RNA, a single stranded DNA (ssDNA) is left and because single stranded nucleic acids are hydrophobic, it tends to loop around itself. It is likely that the ssDNA forms a hairpin loop at the 3′ end.
  8. From the hairpin loop, a DNA polymerase can then use it as a primer to transcribe a complementary sequence for the ss cDNA.
  9. Now, you should be left with a double stranded cDNA with identical sequence as the mRNA of interest.

The reverse transcriptase scans the mature mRNA and synthesizes a sequence of DNA that complements the mRNA template. This strand of DNA is complementary DNA.“

In other words, cDNA is simply a modified form of mRNA that is “created” from KNOWN coded information according to fixed rules that are essentially the same for all cDNAs. There is NO INVENTION as such. Unpatentable coded information is simply “reformatted”. That does not make the info patentable.

We ourselves would not find cDNA itself patent eligible in ANY form. Rather, if anything should be patented here, it is the cDNA synthesis kits — and ONLY these.

The correct decision in this case is to view human genes — as explained by James D. Watson previously — as living strands of coded information. The innumerable parts of that coded information make up a gigantic book, i.e. the book of the coded instructions for life, for making a human being. Taking a clip of that information out of that book and perhaps cutting off the chapter heading or dropping the ending period of a sentence still does not make that text or information a new “invention” of any man or commercial undertaking.

It remains at all times the SAME coded original information of nature, and hence is NOT patentable, in ANY form. So our opinion."