Late last week the Federal Circuit issued its much anticipated opinion – Assn. Molec. Path. et al. v. USPTO et al. - which addressed, inter alia, the issue of whether and to what extent is genetic material patent-eligible. Judge Lourie, writing for the majority, held that isolated genetic material is patent-eligible. Judge Moore concurred-in-part that isolated DNA can be patent-eligible while Judge Bryson dissented and opined that cDNA, but not isolated DNA, is patent-eligible.

Myriad Genetics, Inc. and the Directors of the University of Utah Research Foundation (“Myriad” or “Defendants”) appealed from the decision of the U.S. District Court for the Southern District of New York, which held that: 1) Plaintiffs had standing under the Declaratory Judgment Act to challenge Defendant’s patents; 2) the patent claims to isolated DNA molecules are invalid because they cover patent-ineligible products of nature under Section 101 of the Patent Act; 3) patent claims to screening potential cancer therapeutics via changes to potential growth rates are invalid because they are directed to a patent-ineligible scientific principle; and 4) patent claims to methods directed to “comparing” or “analyzing” DNA sequences also are patent-ineligible for being directed to a scientific principle.

This posting will only review the issue of patent-eligibility of the DNA claims.  Jackie Wright Bonilla’s prior post on the Personalized Medicine Bulletin and Courtenay Brinckerhoff’s PharmaPatent blog post provide succinct reviews of all issues decided on appeal.

The Claims At Issue

The DNA claims at issue cover two isolated human genes having an association with a predisposition to breast and ovarian cancers: BRCA1 and BRCA2 (identified by the court as “BRCA1/2” or “BRCA”) and certain alterations or mutations in these genes.  Claims 1, 2 and 5 of U.S. Patent No 5,747,282 were identified by the court as representative:

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.

5. An isolated DNA having at least 15 nucleotides of the DNA of claim 1.

SEQ ID NO:1 is the nucleotide sequence of the BRCA1 DNA coding region and SEQ ID NO:2 is the amino acid sequence of the BRCA1 protein.

The Federal Circuit began its analysis by focusing on the plain language of Section 101 of the patent statute by noting that 35 U.S.C. Section 101 recites:

“[w]hoever 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 court noted that while the U.S. Supreme Court has consistently construed Section 101 broadly, the Section does not cover everything and is not without limits.  Laws of nature, physical phenomena, and abstract ideas are judicially created exceptions to Section 101’s broad patent-eligibility principles, as explained by the Supreme Court in Funk Brothers Seed Co. v. Kalo Innoculant Co., 333 U.S. 127 (1948); Gottschalk v. Benson, 409 U.S. 63 (1972); Diamond v. Chakrabarty, 447 U.S. 303 (1980); and Bilski v. Kappos, 130 S. Ct. 3218 (2010).

Isolated DNA, cDNA And A Magic Microscope

Plaintiffs had argued that isolated DNA in any form was not patent-eligible because it covers natural phenomena and products of nature, relying on Supreme Court precedent that a product of nature is not patent-eligible even if, as claimed in the patents at issue, it has undergone some highly useful change from its natural form.  Rather, to be patent-eligible, a composition including isolated DNA must also have a distinctive name, character, and use, making it “markedly different” from the natural product.  Plaintiffs argued that isolated DNA retains the same nucleotide sequence as native DNA and it does not have any markedly different characteristics.  Plaintiffs also argued that as a matter of policy, patents to DNA are preemptive and exclude anyone from working with the same DNA or gene.

Myriad argued that isolated DNA is patent-eligible because it is a nonnaturally occurring composition of matter with a distinctive name, character and use.  Isolated DNA does not exist in nature and its isolation provides it new uses that are unavailable to the native material, e.g., for use as primers and probes for diagnosing cancer.  Myriad also noted that all composition of matter is composed of natural materials.  Moreover, the U.S. patent office has consistently allowed such claims.

The U.S. Department of Justice (“DOJ” as amicus curie) argued that DNA molecules that are engineered by man, such as cDNAs, are patent-eligible compositions of matter because, with rare exceptions, they do not occur in nature, either in isolation or as contiguous sequences within a chromosome.  However, isolated and unmodified DNAs are not patent-eligible since their nucleotide sequences exist because of evolution, not man.  At oral argument, the DOJ constructed a “magic microscope” test for patent-eligibility: if an imaginary microscope could focus on the claimed DNA molecule as it exists in the human body, the claim covers unpatentable subject matter.  Thus, under this test, isolated DNA as it exists in nature in any form, would be patent-ineligible.

Purified DNA Is Not Isolated DNA

Judge Lourie in his opinion stated that the key distinction between a patent-ineligible product of nature and a patent-eligible man made invention for the purpose of Section 101 turns on a change in the claimed composition’s identity compared with what exists in nature.  He stated that the Supreme Court has drawn a line between compositions that, even if combined or altered in a manner not found in nature, have similar characteristics as in nature, and compositions that human intervention has given markedly different, or distinctive, characteristics.  He concluded that thus, the claims are patentable because the claimed subject matter is markedly different in it has a distinctive chemical identity and nature from the naturally occurring form.  Isolated DNA, the court reasoned, is a free-standing portion of a native DNA molecule.  It has been cleaved (covalent bonds chemically cleaved) or synthesized to consist of just a fraction of a naturally occurring DNA molecule.

Judge Lourie then contrasted isolated and purified DNA.  Purification, he noted, makes pure what was the same material, but was previously impure.  Isolated DNA is distinct from purified DNA in that is must be removed from its native cellular environment and chemically manipulated to produce a molecule that is markedly different from that which exists in the body.  As an aside, he noted that purified molecules have been determined to be patent-eligible.

He also dismissed Plaintiffs’ arguments that the similarity between isolated DNA and DNA in its native environment – to transmit information- is controlling.  Uses of chemical substances may be relevant to the non-obviousness of the composition but does not control whether or not the composition is patent-eligible.  Judge Lourie stated that the claimed isolated DNA molecules are distinct from their natural existence as portions of larger entities, and their informational content is irrelevant to that fact.  Genes, he noted, are chemical in nature and therefore best described in patents by their structures rather than their functions.

In rejecting the DOJ’s magic microscope test, Judge Lourie stated that the test misunderstands the difference between science and invention and fails to take into account the existence of molecules as separate chemical entities.  The ability to visualize a DNA molecule through a microscope or any other means is worlds apart from possessing an isolated DNA molecule that is in hand and usable.  “It is the difference between knowledge of nature and reducing a portion of nature to concrete form, the latter activity being what the patent laws seek to encourage and protect…Visualization does not cleave and isolate the particular DNA; that is the act of human invention.”

Judge Moore’s Concurrence-In-Part

Judge Moore agreed for the most part with Judge Lourie’s opinion but noted that patentability of DNA does not ride solely on the issue of whether or not the DNA is “isolated.”  Rather, to be patent-eligible, the isolated DNA must possess markedly different properties that are directly responsible for a new and significant utility.  Applying her test, Judge Moore concluded that smaller isolated genomic DNA fragments (e.g., probes) and cDNA are clearly patent-eligible, but claims that encompass longer isolated full-length genes present “a more difficult issue.”  Ultimately, she joined the majority result for policy reasons, i.e., because “Congress has, for centuries, authorized an expansive scope of patentable subject matter.”

She also remarked that even purified compositions, such as a purified protein (e.g., adrenaline) or a purified vitamin (e.g., B12), can be patent-eligible if the end product has “’markedly different characteristics,’ as compared to the impure products, which resulted in ‘the potential for significant utility’.”  In contrast, mere purification of a naturally occurring element (e.g., vanadium or uranium) is typically insufficient to make it patentable because the step of purifying the element does not change (or add to) its inherent qualities or result in an element with new properties.

Judge Bryson’s Opinion

Judge Bryson stated that isolated genomic DNA, in any form, should not be patentable but that cDNA is patent-eligible.  Analogizing DNA and genes to naturally occurring minerals, the judge noted that while the process of extraction and isolation may be difficult and could impart new qualities to the resulting product, is insufficient to impart patentability.  Judge Bryson also analogized the isolation of the gene to the snapping of a leaf from a tree.  Plucking a leaf from the tree does not, in Judge Bryson’s opinion, turn it into a human-made invention.  In contrast, a cDNA molecule is patent-eligible because it must be created in the laboratory and therefore requires human intervention.

Looking Ahead

All members of this panel appear to support patent-eligibility of cDNA and any other material where human intervention is required to produce a final product that is “markedly different” from any naturally occurring material. The judges’ divergent views, and particularly the different analysis applied by Judges Lourie and Moore who agree on the ultimate holding, may make it difficult to extrapolate this decision to other non-DNA subject matter. Still, it is likely that the impact of this decision will be felt beyond the world of genes and genetic diagnostics, and could impact other nascent technologies, such as regenerative stem cell technologies, which rely on isolated or purified products for new products and therapies.