The end of DNA patents in the United States?

Abstract

For over 20 years, the US Patent & Trademark Office (USPTO) has been granting patents to DNA sequences. But on 13 June 2013, the US Supreme Court decided that genomic DNA sequences are unpatentable because they are products of nature. This article discusses the effect that this will have on DNA patents in the Unites States and in other countries.

Keywords::

• DNA sequences
• Myriad
• patents
• United States
• USPTO

1. Background

The patentability of inventions which are based on DNA sequences is judged using the same basic criteria that apply to all other inventions: such inventions must be novel and must be non-obvious. Novelty is generally achieved if the DNA sequence has been isolated from an organism's genome, for example, a single gene that has been physically excised from one of the organism's chromosomes, thus creating a new chemical entity. The DNA must also be non-obvious or inventive. Before the advent of automated gene sequencing, it was generally not easy to identify and sequence a specific new gene; and hence, the inventive step hurdle used to be a relatively easy one to overcome. However, during the DNA sequencing revolution of the 1990s, the Patent Offices around the world had to deal with a sudden tidal wave of patent claims to DNA sequences and expressed sequence tags (ESTs) in particular. In many cases, kilobases of raw unannotated DNA sequence was being claimed, where the patent applications gave no indication of what the DNA actually coded for. This lead the Patent Offices to reassess how they treated patent applications to DNA sequences.

In Europe, the result was the publication in 1998 of an EU Directive (generally known as the ‘Biotech Directive'), which endorsed the practice of the European Patent Office (EPO) in granting patents to DNA sequences [1].

A similar decision was reached in 2001 in the United States by the publication of new Examination Guidelines from the USPTO. The EU Directive and US Examination Guidelines both agreed that the standard criteria for patentability (i.e., novelty and non-obviousness/inventive step) should be applied to DNA sequences, but that an additional criteria should be added: the function of the claimed DNA sequence must be disclosed in the patent application, and some indication must be given of a commercial use for that DNA sequence. The US courts have also developed the concept of an enhanced ‘written description' requirement for biotech patents which requires the Applicant to demonstrate that he was in possession of the claimed invention [2].

This has therefore been the practice of the US and European Patent Offices since that time.

2. Myriad's patents

In 1994 – 1995, Myriad Genetics, Inc., found and sequenced two genes that are associated with human breast cancer; these genes are now known as BRCA1 and BRCA2. Myriad filed a series of patent applications to these genes. The patent claims were judged by the USPTO to satisfy the necessary novelty and non-obviousness criteria; and three US patents were granted in 1997 – 1998 (US Patent Nos. 5747282, 5693473 and 5837492).

Myriad's patents included claims to isolated DNA sequences that were defined in terms of the nucleotide sequences or corresponding amino acid sequences which they encoded. Examples of these patent claims are given below:

• US Patent No. 5,747,282

• 1. An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO: 2.

• 2. The isolated DNA of claim 1, wherein said DNA has the nucleotide sequence set forth in SEQ ID NO: 1.

(Patent claims do not usually include nucleotide or amino acid sequences unless they are very short. The actual sequences are usually placed in a separate part of the patent application called a Sequence Listing, where the sequences are given Sequence Identifier Numbers such as SEQ ID NO: 1, 2, etc.)

After Myriad learnt that some US entities were offering genetic screening for breast cancer, Myriad filed patent infringement actions in the US courts against those entities, forcing the defendants to stop their genetic testing using the BRCA genes.

In 2008, a group of patients, doctors and other interested groups (including the Association for Molecular Pathology, AMP) joined the American Civil Liberties Union (ACLU) in their US District Court lawsuit requesting that Myriad's US patents be declared invalid. Whilst the District court ruled that Myriad's US patents were invalid, this decision was reversed on appeal to the US Court of Appeal of the Federal Circuit (US CAFC). The issue was then passed in 2012 to the US Supreme Court for a final ruling on this matter.

3. US Supreme Court decision

The issues which the US Supreme Court deliberated upon were nothing to do with whether or not the claimed BRCA genes were novel or non-obvious, or whether enough information was contained in the patent application about the commercial use of the BRCA genes. The sole issue at hand was more fundamental than this: it was whether or not the genes should be considered to be patentable subject matter in the United States. The law under which this was judged is 35 U.S.C. 101 which states as follows:

Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefore, subject to the conditions and requirements of this title.

The US courts have previously decided that laws of nature, natural phenomena and abstract ideas should generally be excluded from the above because they are basic tools of scientific and technological work which should lie beyond the domain of patent protection. The key question which the US Supreme Court was asked to decide upon in this case was whether or not genes – and genomic DNA or cDNA in particular - should be considered to be products of nature and hence unpatentable subject matter under 35 U.S.C. 101 in the United States.

4. Result of decision

The US Supreme Court reviewed the decisions of the lower courts and the numerous comments that had been filed by other interested parties. They dismissed arguments that the isolation of the BRCA1 and BRCA2 genes from chromosomes 17 and 13, respectively, created new patentable chemical entities. They also made it clear that they had the power to decide against the years of standard practice of the USPTO practice in allowing gene patents. The Supreme Court ruled that:

“Myriad did not create anything. To be sure, it found an important and useful gene, but separating that gene from its surrounding genetic material is not an act of invention.

Groundbreaking, innovative or even brilliant discovery does not by itself satisfy the § 101 enquiry.

Myriad's claims are simply not expressed in terms of the chemical composition, nor do they rely in any way on the chemical changes that result from the isolation of a particular stretch of DNA. Instead, the claims understandably focus on the genetic information encoded in the BRCA1 and BRCA2 genes.”

To the author (a European patent attorney) and many others, the Supreme Court's justification is difficult to follow because Myriad's patent claims do refer directly to ‘isolated' DNA, thus making it clear that what it being claimed is indeed a new chemical entity compared to chromosomal DNA, and it is not merely ‘genetic information'.

The Supreme Court went on, however, to distinguish between genomic DNA and cDNA. Due to the fact that cDNA has had introns removed and hence it is an artificial entity, they ruled that:

“cDNA does not present the same obstacles to patentability as naturally occurring, isolated [genomic] DNA segments”.

“... the lab technician unquestionably creates something new when cDNA is made”.

Consequently, the US Supreme Court ruled that genomic DNA as it exists in nature is unpatentable in the United States because it is a product of nature, but cDNA is patentable because it is an artificial creation. This leaves the door open, therefore, for ways to get around the decision. For example, an expression vector comprising genomic DNA is an artificial construct and hence this should avoid the ban. Additionally, any nonnatural changes to a genomic sequence should also take the sequence outside the ban. On the contrary, the patentability of PCR primers might now be questionable if their sequences correspond directly to (any) natural genomic DNA sequence.

5. Impact of the US Supreme Court decision

The first point to emphasise is that because this is a decision of a US court, based on their interpretation of a US law, then the decision is only binding on the US courts and USPTO. It will not have a direct impact on other courts or Patent Offices around the world.

In particular, as mentioned earlier, biotech patent law in Europe is largely governed by the Biotech Directive which confirms the patentability of isolated DNA sequences, whether they are genomic or cDNA. Despite this, DNA patents in some European countries have been restricted to the particular uses which are identified in the patents. Additionally, a decision of the Court of Justice of the European Union ruled in 2010 that products (such as transgenic seeds) containing or consisting of genetic material would only be covered by patents whilst the genetic material was performing its function [3]. Hence, although the US Supreme Court decision is unlikely to have much impact in Europe, patent protection for DNA sequences is gradually being eroded in other ways.

The decision, does not, however, affect the validity of Myriad's patent claims to methods of diagnosing breast cancer; and Myriad has already started enforcing such method claims with renewed vigour [4].

There are further concerns as to whether the US Supreme Court decision might have an impact on the patentability of biotech inventions in areas other than genomic DNA sequences. For example, on 2 July 2013, the US Court of Appeal of the Federal Circuit was asked by certain public interest groups to invalidate some of WARF's human embryonic stem cell patents on grounds that such stem cells were products of nature [5].

6. Conclusions

Whilst the US Supreme Court's decision will be welcomed by many academics and public interest groups who oppose patents on DNA, the commercial biotech sector in the United States will be dismayed by the reversal of the stance of the United States on this issue. Companies seek to patent DNA sequences in order to develop diagnostic and therapeutic products for the US healthcare market, and hence any reduction in protection for such products will not be welcomed by investors.

Whilst the immediate impact of the ban will largely be felt in the United States, the ripples of this decision might well be felt elsewhere in due course as public interest groups cite this decision in other countries in support of their desire to see DNA patents overturned in those countries also.

For US biotech companies, one key concern will be how far the ban will extend. Proteins and stem cells are also arguably ‘products of nature', as are many natural chemicals. Is the ban going to be extended to them also? Only time will tell.

Declaration of interest

The authors state no conflict of interest and have received no payment in preparation of this manuscript.