2013 marek vácha your-genes/?pagination=false

2013Marek Vácha

http://www.nybooks.com/articles/archives/2013/mar/07/can-they-patent-your-genes/?pagination=falsehttp://www.nature.com/news/the-great-gene-patent-debate-1.11044http://www.genome.gov/19016590

http://www.nybooks.com/articles/archives/2013/mar/07/can-they-patent-your-genes/?pagination=false

http://www.nybooks.com/articles/archives/2013/mar/07/can-they-patent-your-genes/?pagination=false

http://www.nature.com/news/the-great-gene-patent-debate-1.11044

BRCA

BRCA 1 is a tumor suppressor gene

In the patent law of 1793, Congress defined eligibility partly in language that Jefferson provided and that remains at the heart of the statutory code (USC Title 35, Section 101) for the subject.

According to the statute, patents could be obtained for “any new and useful art”—the word was replaced in 1952 by “process”—“machine, manufacture, or composition of matter [Jefferson’s phrase], or any new and useful improvement…[thereof].”

During the following two centuries, these exclusions from patent eligibility came to be explicitly articulated in a body of federal court decisions holding, for example, that

natural elements taken from the earth, even if they had to be chemically isolated from other substances, did not constitute patentable subject matter under Section 101, if only because they were not new.

Discovery or Invention?

Thus products of nature such as the naturally occurring elements in the periodic table or the creatures of the earth, being neither new in the world nor made by man, were taken to be ineligible for patents.

So, tacitly, were laws of nature, natural manifestations, abstract ideas, thought.

Patent on Adrenalin

1911: patent on adrenalin, which a chemist had isolated from the body, purified, and produced in concentrated form

having been extracted, purified, and thus made useful, the adrenalin “became for every practical purpose a new thing commercially and therapeutically.”

Patent on a GMO

1980: a landmark case that allowed patents on a genetically modified bacterium—they had “markedly different characteristics from any found in nature.”

Patent and Trademark Office (PTO)

1980s: the PTO began issuing patents on DNA—not DNA in the body, which was indisputably a product of nature—but on three different versions of DNA isolated from the body. cDNA isolated fragments DNA the whole of the raw DNA in a gene.

BRCA 1 and BRCA 2

1990: a geneticist at Berkeley announced that her laboratory had tracked the location of BRCA1 to somewhere on chromosome number 17.

A transatlantic race then ensued to find the exact position of the gene

major competitor was Mark Skolnick, a geneticist at the University of Utah and a cofounder of Myriad Genetics. Mark Skolnick

BRCA 1 (1994) and BRCA 2 (1995)

Skolnick and his colleagues won the race in 1994, finding BRCA1 and isolating it from the rest of the DNA and the tangle of protein that form chromosome 17.

In 1995, Myriad’s scientists also identified and isolated BRCA2, which resides on chromosome number 13.

Shortly before November 1995, the ICR team found a mutation from one of their breast cancer families that looked as though it might very well sit in the BRCA 2 gene. Within two weeks of the sequence being available, they not only confirmed this mutation but found five more.

There was no doubt: they had found the gene. Mike moved fast to publish the group´s discovery in Nature, while keeping it secret even from his collaborators until the last possible minute.

But despite his efforts, enough information about the discovery reached Skolnick to enable him to locate the gene himself and bang in a patent application – the day before the ICR paper came out in Nature.

Sulston, J., Ferry, G., (2003) The Common Thread. A Story of Science, Politics, Ethics and the Human Genome. Gorgi Books, London

In 1994, Myriad, applied for patents on both the isolated DNA that makes up the BRCA1 gene

and also on a set of diagnostic tests to detect its presence.

In 1995, it did the same for the isolated DNA of BRCA2.

In 1997 and 1998, the PTO awarded a total of seven patents on the two isolated genes, various DNA fragments within them, and the diagnostic tests to find them.

Myriad’s patents extended to all three types of DNA extracted from the two BRCA genes.

the patents give Myriad exclusive rights to conduct diagnostic tests on the genes.

Women who test positive using Myriad's gene test, BRCA Analysis, have an 82 percent higher risk of breast cancer and 44 percent higher risk of ovarian cancer in their lifetimes.

Myriad Genetics filed for and received a patent on the BRCA1 and BRCA 2 genes, and this patent gave the company a monopoly on diagnostic uses of these discoveries.

Myriad has aggressively protected its patent right by posing legal challenges to any other laboratory that has tried to offer testing.

As a result, all competing diagnostic efforts for BRCA 1/2 in the United States have been driven out of business.

Although Myriad has offered a test that is highly accurate, the absence of any market competition has kept the price quite high (about $ 3 500), placing it outside the reach of many individuals who would like to have the information.

Collins, F., (2010) The Language of Life. Profile Books LTD. London, GB. p. 199

January 2001: The PTO issued “Utility Examination Guidelines” to clarify the criteria that patent claims on DNA would have to satisfy. products of nature can become eligible for

patents if they had “markedly different characteristics from any found in nature.”

2001, PTO: cDNA, which is made by scientists outside the body, differs markedly from the DNA inside it.

So does the raw DNA extracted from the body, whether the whole of a gene or a fragment of it. when it is chemically disentangled from its

chromosomal housing it becomes a new composition of matter.

2005: 4,382 human genes (~20% of the total number in our genome) are covered by patents or other intellectual property claims.

„BRCA CASE“: Defendants and Plaintiffs

Defendants the Myriad Genetics

Corporation Patent and Trademark

Office (PTO) the University of Utah

Research Foundation

Plaintiffs medical geneticists, pathologists advocates for women’s

health biomedical

researchers genetic counselors several women with

breast cancer or at risk for it.

May 2009: Plaintiffs contended that

BRCA DNA—and by implication all human DNA—should not be eligible for patents as a matter of law

Myriad’s enforcement of its patents interfered with the progress of science and the delivery of medical services.

The plaintiffs contended that the patents should never have been granted on either the DNA or the tests

Myriad’s diagnostic methods boiled down to comparing the base-pair sequence in the DNA taken from a patient with the sequence in a version of the gene that will dispose the person to cancer. the comparison did not require any particular process but

only the act of looking at one sequence and seeing whether or not it matched the other.

The “claim” was therefore to abstract ideas and thought and as such was excluded from patentability.

Plaintiffs:

the raw DNA and the cDNA forms embodied the same sequences of cancer- disposing base pairs—the same defining genetic information—as did the native genes.

The extracted raw DNA differed in material composition only trivially from the native version.

It was no more transformed from the natural DNA than was gold upon removal from a stream bed or the yolk after separation from the rest of the egg.

Myriad

The patents gave Myriad a virtual lock on research and diagnostics on the workings of the BRCA1 and BRCA2 genes because, such research and diagnostics required analysis and

manipulation of the DNA in isolated form.

Myriad reserved to itself the performance of all diagnostic analyses of a patient’s DNA that might be disclosed to her.

Myriad

The legal argument in favor of patenting is that the gene being patented is not being claimed in its natural state, but is a product of experimental investigation in which the gene has been spliced into a recombinant DNA vector, sequenced, and analyzed.

The United States Patent and Trademark Office has chosen to accept the argument, based on an analogy with chemical patents, that this is „composition of matter“ appropriate for patent protection.


Plaintiffs:

Myriad’s policy enabled it to charge prices for the tests that put them beyond the reach of some women.

It also prevented patients from obtaining a second diagnostic opinion from an independent laboratory.

Plaintiffs:

DNA is not just another chemical. Even in isolated form, it embodies the gene’s

natural repository of genetic information and its ability to express laws of nature.

genes are not only special natural products; each is also unique in its composition and function. No one can invent another BRCA1 or BRCA2 any

more than someone can devise a different hydrogen or oxygen..

March 2010, Judge Sweet struck down Myriad’s patents on the isolatedBRCA DNA and the diagnostic methods that Myriad used to determine whether a patient possesses the genes herself.

the isolation of the BRCA DNA, in whichever form, did not alter its “essential characteristic”—the sequence of base pairs that made it a carrier of genetic information.

Myriad’s BRCA DNA was thus not eligible for a patent as a new composition of matter

Court of Appeals

July 29, 2011, a three-judge panel of the court partially reversed Judge Sweet by upholding Myriad’s claim that the BRCA DNA is eligible to be patented.

Court of Appeals

August 16, 2012, a Court of Appeals panel, composed of the same three judges who had dealt with the case the year before, affirmed Judge Sweet’s ruling against the patentability of Myriad’s diagnostic methods, finding them tantamount to a law of nature,

but overturned his decision once again. The panel held that cDNA itself is patent-eligible because it is markedly different from the DNA in the body,

they ruled that the other forms of isolated BRCA DNA, whether the fragments or the whole of the gene, are also eligible to be patented.

Plaintiffs:

the isolated BRCA DNA is fundamentally the same in structure and function as the DNA in the body.

It is no more a human invention because it had been isolated from the chromosome than was a kidney taken from the body, a limb removed from the tree, or a mineral or plant extracted from the earth.

Plaintiffs:

James Watson: "Life's instructions ought not be controlled by legal monopolies created at the whim of Congress or the courts."

John Sulston

„My first response is that the genome sequence is a discovery, not an invention.

Like a mountain or a stream, it is a natural object that was here, if not before we were, at least before we were aware of its existence.“

„You can´t ever say that you own a gene, because then you´d be owning one of my genes as well.


Anyone who wants to make a better mousetrap has to invent around existing mousetrap patents.

You can´t invent around discovery; you can only invent around other inventions.

Defendants

Venture capitalists would be reluctant to invest in a small biotechnology firm if there was no secure patent protection

On September 25, 2012, the plaintiffs asked the Supreme Court to review the Court of Appeals’s August decision and on November 30 the Court accepted the case, confining its review solely to the fundamental question of whether genes are patentable…

If the court decides that the patents are invalid, that ruling would reverse more than 20 years of precedent, during which companies and academic researchers have patented thousands of genes.

November 2012 The Supreme Court agreed to decide

whether human genes can be patented Myriad shares fell as much as 9 percent after

the Supreme Court agreed to hear the appeal

cca more than 4,000 of the roughly 22,000 genes in the human genome have U.S. patents.

January 25, 2013 For the second time, the US Supreme

Court has agreed to hear a lawsuit that challenges patents on the BRCA1 andBRCA2 genes...

Questions remain...

Are genes part of our collective heritage that should not be patentable at all?

Should the isolation and purification of genes from their natural state be a sufficient basis for a patent?

should the applicant be required to demonstrate a use for the discovery?

Francis Collins

„Recognizing these principles, my own laboratory and that of Lap-Chee Tsui insisted that the discovery of the CF gene, in 1989, be available on a nonexclusive basis to any laboratory that was interested in offering testing.

Many legal scholars have pointed to this as a better example of how to ensure public benefit.

Francis Collins

Furthemore, I donated all my own patent royalties from the CF gene discovery to the Cystic Fibrosis Foundation, to support further research into treatment. As director of HGP, I took further steps to discourage unwarranted gene patenting, insisting that all information about the human DNA sequence be placed immediately in the public domain.“


Francis Collins

The information contained in our shared instruction book is so fundamental and requires so much further research to understand its utility, that patenting it at the earliest stage is like putting up a whole lot of unnecessary toll booths on the road to discovery.


John Sulston

Patents (or so I had always believed) are designed to protect inventions. There are three essential criteria for an invention: it has to be novel (no-one has published the

idea before) useful (in that it could be developed for

commercial or other uses) and non-obvious

The ESTs met none of these criteria

John Sulston

There was no „invention“ involved in finding them, so how could they be patentable?

Yet the 1991 patentn application claimed exclusive rights not only to the ESTs, but to the whole genes they represented and even the proteins encoded by these genes. It was crazy.


EST

= expressed sequence tag A unique stretch of DNA within a coding

region of a gene that is useful for identifying full-length genes and serves as a landmark for mapping.

krátká sekvence cDNA délka 500 – 800 nukleotidů je komplementární k mRNA EST je tedy část exprimovaného genu

When Craig announced at a public briefing on genome research for the US Senator Pete Domenici in July 1991 that the patents had been filed, Watson burst out that the movewas „sheer lunacy“, and said he would be „horrified“ if it were true that random bits of sequence could be patented. He argued that there was no invention involved, asserting that the automation of sequencing meant that the work could be done by „virtually any monkey“.


Despite these protests in February 1992 the NIH added a further 2 375 ESTs to the patent application, although this time they dropped their claim to the proteins encoded by the genes they represented. Their action set off a fresh round of criticism.

Berg spoke for many when he said, „It makes a mockery of what most people feel is the right way to do the Genome Project.“


The US Patent Office roundly rejected the firs application in August 1992, but the NIH ppealed against the rejection and applied for patents on another 4 448 ESTs. After the election of Bill Clinton as US President in

November 1992 Healy resigned (the NIH head is a plitical appointment and she was a Republican appointee). Her replacement, the highly respected cancer researcher and Nobel prizewinner Harold Varmus, decided not to pursue the patent issue any further and withdrew all outstanding applications in early 1994.

Not until 2000 did the Patent Office produce a set of guidelines that tightened up the definition of „utility“ to prevent people giving uses as vague as „a gene probe“ in their applications.

It is still permissible to patent a gene sequence as long as you can show how it might be used to diagnose diseases, for example.


John Sulston

The goal of the genome project, as I saw it, was to provide as much information as possible that could be freely used by everyone, public and private, to adfvance our understanding and develop new treatments.

I didn´t have a problem, and still don´t, with the companies protecting their rights to the inventions they sell – drugs or diagnostic kits, for exemple – but I thought there was a real danger if they were able to gain exclusive rights to the information contained in the sequence itself.


In 1994, Merck funded a massive drive to generate ESTs and place them in the public databases, where they would be freely avilable to all.

Bob Watersoin and Rick Wilson received a grant from Merck to generate 4 000 ESTs a week for two years, starting in January 1995

by doing this, Merck not only gave the entire research community, public and private, free access to valuable genomic data; it also made those sequences (and possibly the whole genes from which they came) much more difficult to patent.

Once the sequences had been in the public domain for a year they could not be patented and it would be tough for any company to identify the most

promisisng genes out of so many and understand their function in such a short space of time

JNCI J Natl Cancer Inst (2000) 92(8): 594-597.doi: 10.1093/jnci/92.8.594

http://jnci.oxfordjournals.org/content/92/8/594.full

Rok 2000Clinton-Blair

Clinton – Blair Statement

On the day of th stataement CBS Radio News reported that Clintona adn Blair had agreed to „ban patents on individual genes“, following an easrly morning White House press briefing.

That proved to be the last straw for an already jumpy and still overvalued stock market.

The Nasdaq, the index of biotechnology and other high technlology stocks,k suffered the second biggest fall in its history, more than 200 points.


„The good guys won“

any constraints no patents filed on the raw sequences no licenses no documents to be signed all you need is an internet connection we produced a sequence, put it in the public

domain and made it impossible for any individual or company to control access to it.


The guidelines on patenting genes in the US have recently been clarified to give a somewhat tighter definition of utility – the use must be „substantial, specific and credible“

The European Patent Directive, approved by the European Parliament in 1998, accepts that a sequence or partial sequence of a gene is eligible for a „cmposition of matter“ patent once it has been replicated outside the human body – say, copied in bacteria as we do for sequencing. This argument has always seemed to me absurd. The essence of a gene is the information – the sequence – and copying it into another format makes no difference.

It is as though I took a hardback book that you had written, published it in paper-back, and called it mine because the binding is different.


SUPPLEMENT(NON-MANDATORY FOR THE TEST)

June 13, 2013

Justices, 9-0, Bar Patenting Human Genes

Human genes may not be patented, the Supreme Court ruled unanimously on Thursday. After the ruling, at least three companies

and two university labs said that they would begin offering genetic testing in the field of breast cancer.

http://www.nytimes.com/2013/06/14/us/supreme-court-rules-human-genes-may-not-be-patented.html

June 13, 2013

Held: A naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated, but cDNA is patent eligible because it is not naturally occurring cDNA is not a “product of nature,” so it is

patent eligible under §101. http://www.supremecourt.gov/opinions/

12pdf/12-398_8njq.pdf

June 13, 2013

“The Supreme Court got it exactly right,” “It’s a great decision for patients, it’s a

great decision for science, and I think it’s a great decision for the biotechnology industry.” (Eric Lander)

It is often said that patents cover 4,000 human genes, or about 20 percent of all human genes, meaning the decision could have a large impact.

2013 marek vácha your-genes/?pagination=false

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