Tag Archives: BRCA

Are Claims of Isolated DNA Eligible Subject Matter under Section 101 of the Patent Act or Is It Simply A Cloak to Patent A Human Gene?

The American College of Legal Medicine 1st Place Orr Award Winning Post-Doctoral Student Writing Competition, January 2013. 

Copyright 2013, Ellia Ciammaichella. All Rights Reserved.

Fair use only please.

I. Introduction

Since most genetic disorders are due to a mutation in one or more human protein-coding genes, the study of the sequence of both mutated and wild type genes have been the cornerstone of research in patterns of inheritance, drug and therapy development, disease susceptibility and diagnosis, and cancer risk. Thus, it is no surprise that scientists have diligently identified more than 12,000 of the 30,000 human protein-coding genes.[1]

One such set of genes that have been identified and sequenced are the BRCA1 and BRCA2 genes (hereinafter “BRCA gene”). A woman with certain BRCA gene mutations has more than a six fold greater breast cancer risk than the average woman, with up to an 80% lifetime risk of developing breast cancer.[2] Due to these overwhelming statistics, it is important that high risk women are screened early for possible BRCA gene mutations. With these screenings, a high risk patient can be diagnosed with a BRCA gene mutation even before symptoms arise, resulting in better prognosis and greater options personalized to the specific mutations involved. Thus, the identification and sequence of the BRCA gene has been of paramount importance in the care and treatment of women with BRCA gene mutations.

The discovery of the location and sequence of the BRCA gene or any other gene has insurmountable possible applications but this does not come without the expenditure of considerable resources.[3] Thus, to recoup these resources, the United States had granted 40,000 DNA-related patents spanning about 20 percent of the human genes.[4]

While patent protection is meant to provide monetary incentive to invent and disclose significant advances in ideas, by its nature patent protection is a double-edged sword as it also necessarily raises the price of using the inventive idea and could possibly impede further research.[5] Thus, the Patent Act is interpreted to allow the patenting of subject matter of “anything under the sun that is made by man . . . [except] laws of nature, physical phenomena, and abstract ideas.”[6] Such limitation on eligible subject matter protects “part of the storehouse of knowledge . . . free to all men and reserved exclusively to none.”[7] Therefore, although the DNA sequence of the BRCA gene is not patentable subject matter under Section 101, the application of the DNA sequence may be patentable.[8]

Considering this, is isolated DNA a sufficient inventive application of the DNA sequence to warrant patentability? In light of the resources invested in discovering a gene and its DNA sequence and the state of the art of genetics at the time of discovery, does the U.S. Patent Act permit a limited time monopoly on isolated DNA of a discovered gene? This is the issue pending on writ of certiorari in the U.S. Supreme Court in Association for Molecular Pathology v. Myriad Genetics, Inc.[9]

To understand the issues involved in analyzing whether an isolated DNA is patent eligible, Part II of this article reviews the history of the BRCA gene and current proceedings over the BRCA gene-related patents. Part III analyses the current law associated with the eligibility of patentable subject matter, proposes clarification to the current law, and attempts to use this framework to determine whether isolated DNA as it relates to the BRCA gene is eligible subject matter under Section 101 of the Patent Act. Finally, Part IV concludes with possible outcomes of the pending writ of certiorari at the Supreme Court.

II. History and Review of Proceedings Related to the BRCA Genes

In 1990, scientists from the University of California, Berkeley, announced the location of the BRCA1 gene.[10] In 1994, scientists from Myriad Genetics, University of Utah, the U.S National Institutes of Health (NIH), and McGill University published the sequence for the BRCA1 and BRCA2 gene, which they had isolated.[11]

That same year, these scientists filed a patent application for the isolated DNA coding for the BRCA gene polypeptide. Prototypical examples of the composition claims, such as patent 5,747,282, include:

“1. An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2.”[12]

“5. An isolated DNA having at least 15 nucleotides of the DNA of claim 1.”[13]

The patent specification defined “isolated DNA” as “a segment of DNA nucleotides existing separate from other cellular components normally associated with native DNA, including proteins and other DNA sequences comprising the remainder of the genome, and includes both DNA originating from a cell as well as DNA synthesized through chemical or heterologous biological means.”[14] Thus, isolated DNA encoding the BRCA gene encompasses both cleaved native DNA and synthesized cDNA.

In 2009, after having received a cease and desist letter from Myriad Genetics, the Association for Molecular Pathology and several other parties (collectively, “AMP”) filed a complaint against Myriad Genetics and several other defendants (collectively, “Myriad”). AMP’s complaint alleged that Myriad’s fifteen claims from seven different patents are invalid as ineligible subject matter under Section 101 of the Patent Act.

During the history of the litigation, all parties agreed that:

  1. Isolated DNA is a composition of matter;[15] and
  2. DNA sequences and native DNA are laws or products of nature that is excepted from patentable subject matter.[16]

Thus, the fundamental disagreement is whether isolated DNA, as claimed in Myriad’s patents, is patentable subject matter under Section 101 of the Patent Act.

The U.S. District Court for the Southern District of New York agreed with AMP, held Myriad’s composition claims unpatentable, and granted summary judgment.[17]

Myriad appealed. On appeal Myriad was vindicated as the U.S. Court of Appeals for the Federal Circuit (“Federal Circuit”) held that Myriad’s composition claims were patentable and reversed the District Court’s decision.[18]

Unhappy with the Federal Circuit’s decision, AMP petitioned for a writ of certiorari. The Supreme Court granted the petition, vacated the Federal Circuit’s judgment, and remanded the case “for further consideration in light of Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. __ (2012).”[19]

On remand the Federal Circuit upheld Myriad’s composition claims.[20]

Subsequently, AMP filed a second petition for writ of certiorari, which was granted on November 30, 2012, and is awaiting further disposition.[21]

III. Eligible Subject Matter under Section 101 of the Patent Act

Under section 101 of the U.S. Patent Act, “[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 therefor, subject to the conditions and requirements of this title.”[22] This entails “anything under the sun that is made by man . . . [except] laws of nature, physical phenomena, and abstract ideas.”[23] Such limitation on eligible subject matter protects “part of the storehouse of knowledge . . . free to all men and reserved exclusively to none.”[24]

However, since inventions, at some level, exploit the laws of nature, a claim “is not unpatentable simply because it contains a law of nature . . . .”[25] Rather, an “application” of a law of nature that is “novel and useful” may be patentable subject matter.[26] For compositions of matter, the Supreme Court has held that the claimant must claim compositions with “markedly different characteristics from any found in nature and one having the potential for significant utility” to be eligible subject matter.[27] This requirement of an “inventive concept,”[28] prevents the monopoly of laws of nature by simply limiting its use “to a particular technological environment” or by adding “insignificant postsolution activity.”[29]

In relation to the isolated DNA coding for a BRCA gene polypeptide, since all parties agreed that the DNA sequence and native DNA of the BRCA gene was unpatentable as a product or law of nature, the issue is whether isolated DNA has “markedly different characteristics” than native DNA and whether isolated DNA has “potential for significant utility.”

A. “Markedly Different Characteristics” Between Native and Isolated DNA

The first step in determining whether isolated DNA is patentable subject matter is to determine if it has “markedly different characteristics” than native DNA. The word “different” as it relates to a composition of matter requires any structure variance between native and isolated DNA.

In addition, in light of the policy of granting patents to spur innovation, the adjective “markedly” requires that sufficient ingenuity is applied to create the different characteristics between the product of nature, i.e. native DNA, and the claimed invention, i.e. isolated DNA. Ingenuity is not present if an ordinary person skilled in the art would have created the isolated DNA. This follows from the idea that “‘basic tools of scientific and technological work’. . . is treated as though it were a familiar part of the prior art.”[30] Furthermore, if an ordinary person skilled in the art could have created the structural differences, such differences would be nothing but “insignificant postsolution activity” used to cloak a law or product of nature under the guise of invention and thereby monopolize the “storehouse of knowledge. . . free to all men and reserved exclusively to none.”[31]

Defining “markedly” in terms of an ordinary person skilled in the art prevents patent eligibility from simply being contingent on “the draftsman’s art.”[32] In fact, in determining whether the subject matter was patentable in Mayo Collaborative Services v. Prometheus Laboratories, Inc. (hereinafter “Mayo”), the Supreme Court asked: “[D]o the patent claims add enough to their statements of the correlations to allow the processes they describe to qualify as patent-eligible processes that apply natural laws?”[33] The Supreme Court answered in the negative, stating that “any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.”[34] Thus, the Supreme Court implicitly required that claims incorporating laws of nature have something added that an ordinary person skilled in the art would not have included.

The fact that Mayo applied subject matter patentability on method claims rather than composition claims and laws of nature rather than products of nature does not make Mayo inapplicable to isolated DNA. The Supreme Court’s concern in Mayo was to prevent the “law of nature” exception to §101 patentability from becoming “a dead letter.”[35] Thus, if any addition to a law of nature was patentable subject matter, then the “law of nature” exception could be evaded by any skilled draftman. Such concern applies equally well to both method and composition claims. In addition, while native DNA is a product of nature, the DNA sequence encoded in the native DNA codes basic genetic information and therefore embodies laws of nature. Accordingly, since Mayo applies to whether isolated DNA is patentable, isolated DNA must have an additional quality over its DNA sequence that an ordinary person skilled in the art would not have created.

Therefore, as it relates to a composition of matter, it is proposed that the requirement of “markedly different characteristics” include two elements:

  1. The presence of any structural difference between the product of nature and the claimed composition of matter; and
  2. An ordinary person skilled in the art would not have created the claimed composition of matter.

The first element, the presence of any structural difference, was correctly analyzed by the Federal Circuit. In its explanation, the Federal Circuit noted that isolated DNA “is a free-standing portion of a larger, natural DNA molecule. Isolated DNA has been cleaved (i.e., had covalent bonds in its backbone chemically severed) or synthesized to consist of just a fraction of a naturally occurring DNA molecule.”[36] The Federal Circuit explained that “human intervention in cleaving or synthesizing a portion of a native chromosomal DNA imparts on that isolated DNA a distinctive chemical identity from that possessed by native DNA.”[37] Furthermore, native DNA must be “chemically cleaved from their chemical combination with other genetic material”[38] to form the isolated DNA. Thus, there is a structural difference between native and isolated DNA.

The District Court, on the other hand, considered the presence of a structural difference as a mere factor in the entire analysis. Although some leaps are required, one can presume that the District Court did consider isolated DNA as structurally different since it mentioned that isolated DNA lacks “nucleotide sequences” present in native DNA.[39] Since the absent nucleotide sequences are bonded to native DNA but not present in isolated DNA, isolated DNA necessarily has a different structure than native DNA. However, instead of explicitly acknowledging any structural difference, the District Court placed great weight on the similarities between native and isolated DNA. As such, the District Court concluded that the absence of “proteins and other nucleotide sequences . . . does not alter its essential characteristic – its nucleotide sequence – that is defined by nature and central to both its biological function within the cell and its utility as a research tool in the lab.”[40] Unfortunately, when a product of nature, i.e. native DNA, is used to create a purported new invention, i.e. isolated DNA, the purported new invention will necessarily be similar to the product of nature. Thus, comparing the similarity between native and isolated DNA does not necessarily provide useful information as to whether native and isolated DNA has any structural difference. In addition, such an analysis may result in deeming a purported invention “unpatentable simply because it contains a law of nature.” [41]

Considering that native DNA and isolated DNA are structurally different, the second element of the analysis must be met: would the claimed composition of matter have been created by an ordinary person skilled in the art? The District Court implicitly answered this in the positive as the structural difference between native and isolated DNA is simply due to “technical skill and considerable labor [that] was simply the application of techniques well-known to those skilled in the art.”[42] Thus, while the District Court acknowledged that Myriad deserves recognition for the identification of the BRCA gene sequences, this accomplishment does not necessarily entitle Myriad to a patent.[43]

The Federal Circuit, however, did not consider whether the second element was satisfied, namely that the claimed composition of matter would have been created by an ordinary person skilled in the art. Instead, the Federal Circuit reasoned that because a structural difference existed, isolated DNA was “markedly different” from native DNA and therefore patentable. This presumes that any artificial composition of matter that has any structural difference to products of nature is patentable, contradicting the analysis in Cochrane v. Badische Anilin & Soda Fabrik.[44] Furthermore, had this been the standard in determining patent eligibility, any slight change to products of nature would be a patentable composition of matter. On the contrary, an “insignificant” change cannot make what was unpatentable now patentable.

B. Potential for Significant Utility

If isolated DNA could not have been created by an ordinary person skilled in the art, then the next step is to determine whether isolated DNA has “potential for significant utility.”[45] This requirement was clearly established as Myriad claimed that isolated DNA, unlike native DNA, can be used as a primer or molecular probe.[46]

The Federal Circuit, however, noted that the “markedly different characteristics” of isolated DNA depends on the structure of the molecule of the isolated DNA rather than the “physiological use or benefit” of the isolated DNA,[47] and, thus, failed to acknowledge that the “potential for significant utility” was a separate requirement set forth in Diamond v. Chakrabarty (hereinafter “Chakrabarty”).[48] Thus, even if the purported invention and the product of nature had “markedly different characteristics,” the purported invention would also need “potential for significant utility.”

IV. Conclusion

Considering the current state of the law, on writ of certiorari, the Supreme Court could very well stand behind Chakrabarty and require that compositions of matter that incorporate products of nature have “markedly different characteristics from any found in nature and . . . potential for significant utility” to be eligible subject matter under Section 101. However, to provide clear guidance, the Supreme Court needs to clarify the standards set in Chakrabarty, which is proposed to be:

  1. The claimed composition must be “markedly different from any found in nature,” which is defined as:
    1. The presence of any structural difference between the product of nature and the claimed composition of matter; and
    2. The claimed composition of matter would not have been created by an ordinary person skilled in the art; and
  2. These differences must have a “potential for significant utility.”

Without clear guidance of what exactly Chakrabarty dictates, the law will remain unclear and unpredictable and will necessarily chill innovation in the area of isolated DNA and any downstream research related to the isolated DNA.

With that said, having applied these elements to the current pending case and the current information presented, the composition of matter claims for isolated DNA coding for the BRCA genes do not have “markedly different characteristics” to its corresponding native DNA. This is because the state of genetic technology in 1994 was such that an ordinary person skilled in the art would have had the ability and incentive to create the isolated DNA, given the location and DNA sequence of the BRCA gene, which was conceded to be laws or products of nature. Therefore, under this analysis isolated DNA coding for the BRCA gene is not patentable subject matter under Section 101 of the Patent Act.

 

[1] National Center for Biotechnology Information. Genes and Disease. Introduction to Genes and Disease, available at http://www.ncbi.nlm.nih.gov/books/NBK22185/ (last visited Jan. 4, 2012); Johns Hopkins University and National Center for Biotechnology Information, Online Mendelian Inheritance in Man, available at http://www.ncbi.nlm.nih.gov/omim?db=omim (last visited Jan. 4, 2013).

[2] While the average woman has about a 12.38 percent risk of developing breast cancer in her lifetime, a woman with a BRCA gene mutation has as high as an 80 percent risk of developing breast cancer. U.S. National Institutes of Health, National Cancer Institute, Seer Cancer Statistics Review, 1975–2009, Breast Cancer, tbl.4.18, available at http://seer.cancer.gov/csr/1975_2009_pops09/browse_csr.php?section=4&page=sect_04_table.18.html (last revised Apr. 2012); American Cancer Society, Breast Cancer, What are the Risk Factors for Breast Cancer?, available at http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-risk-factors

(last updated Dec. 5, 2012) (describing BRCA gene mutations, as well as other factors, as significant genetic risk factors for breast cancer).

 

In addition to breast cancer, certain BRCA gene mutations are associated with an increased risk of Fanconi anemia, ovarian cancer, prostate cancer, pancreatic cancer, fallopian tube cancer, male breast cancer, and melanoma. National Institute of Health, U.S. National Library of Medicine, Genetics Home Reference, Genes: BRCA1, available at http://ghr.nlm.nih.gov/gene/BRCA1 (last reviewed Aug. 2007); National Institute of Health, U.S. National Library of Medicine, Genetics Home Reference, Genes: BRCA2, available at http://ghr.nlm.nih.gov/gene/BRCA2 (last reviewed Aug. 2007).

[3] Br. in Opposition for Myriad Genetics, Inc., et.al, as Respondents 4, Ass’n for Molecular Pathology v. Myriad Genetics, Inc., No. 12-398 (writ of cert. granted Nov. 30, 2012) [hereinafter Br. in Opposition] (explaining that discovering and sequencing the BRCA gene required considerable private funding).

[4] Eric J. Rogers, Can You Patent Genes? Yes and No, 93.1 J. Patent & Trademark Office Soc’y 19 (2011).

[5] Mayo Collaborative Servs. v. Prometheus Labs., Inc., No. 10–1150, 566 U. S. _, slip op. at 23 (Mar. 20, 2012) (stating that “[p]atent protection is, after all, a two-edged sword. On the one hand, the promise of exclusive rights provides monetary incentives that lead to creation, invention, and discovery. On the other hand, that very exclusivity can impede the flow of information that might permit, indeed spur, invention, by, for example, raising the price of using the patented ideas once created, requiring potential users to conduct costly and time-consuming searches of existing patents and pending patent applications, and requiring the negotiation of complex licensing arrangements.”).

[6] Diamond v. Chakrabarty, 447 U.S. 303, 309 (1980).

[7] Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U. S. 127, 130 (1948).

[8] Br. in Opposition, supra note 4, at 14 (admitting that the BRCA gene sequence itself is “the genetic material naturally existing in every human being” and is not eligible for patent protection).

[9] Ass’n for Molecular Pathology v. Myriad Genetics, Inc., No. 12-398, 568 U.S. __, slip op. at 1 (Nov. 30, 2012) (granting petition for a writ of certiorari limited to the patentability of isolated DNA).

[10] J.M. Hall, M.K. Lee, B. Newman, J.E. Morrow, L.A. Anderson, B. Huey, & M.C. King, Linkage of Early-Onset Familial Breast Cancer to Chromosome 17q21, 250 Science Magazine 1684 (1990), available at http://www.sciencemag.org/content/250/4988/1684 (last visited Jan. 4, 2013).

[11] Y. Miki, J. Swensen, D. Shattuck-Eidens, P.A. Futreal, K. Harshman, S. Tabtigian, Q. Liu, C. Cochran, L.M. Bennett, W. Ding, A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1, 266 Science Magazine 66 (1994), available at http://www.sciencemag.org/content/266/5182/66 (last visited Jan. 4, 2013); R. Wooster, S.L. Neuhausen, J. Mangion, Y. Quirk, D. Ford, N. Collins, K. Nguyen, S. Seal, T. Tran, D. Averill, Localization of a Breast Cancer Susceptibility Gene, BRCA2, to Chromosome 13q12-13, 265 Science Magazine 2088, available at http://www.sciencemag.org/content/265/5181/2088 (last visited Jan. 4, 2013).

[12] Ass’n for Molecular Pathology v. U.S. Patent & Trademark Office, No. 09 Civ. 4515, 702 F. Supp.2d 181, 2010 WL 1233416, at *28 (S.D.N.Y. 2010).

[13] Id.

[14] Id. at 216 – 17 (quoting the patent specification’s definition of “isolated DNA”). Method claims were also in dispute. However, because this does not add to the issue of this article, it is not explained further.

[15] See Br. in Opposition, supra note 4, at 14 (stating that “molecules of isolated BRCA1 and BRCA2 DNA are chemical ‘composition[s] of matter’”); Pet. for Writ of Cert. for the Ass’n for Molecular Pathology as Pet., Ass’n for Molecular Pathology v. Myriad Genetics, Inc., No. 12-398 (writ of cert. granted Nov. 30, 2012) [hereinafter Pet. for Writ of Cert.] (repeatedly referring to the challenged claims as “composition claims”).

[16] See Pet. for Writ of Cert., supra note 16, at 3 (stating that “[g]enes are fragments of DNA that uniquely embody laws of nature that determine, in part, the structure and functions of the body”); Br. in Opposition, supra note 4, at 14 (stating that “genetic material naturally existing in every human being is not an ‘invention,’ i.e., it is not the product of human ingenuity. But this case does not involve claims to such ‘native’ human genes.”).

[17] See Ass’n for Molecular Pathology, 2010 WL 1233416. Prior to any summary judgment motion, Myriad moved to dismiss the complaint on the grounds that AMP lacked standing but the district court denied the motion based on the district court’s finding that Myriad took affirmative acts to enforce its patents on AMP. See MedImmune, Inc. v. Genetech, Inc., 549 U.S. 118 (2007) (holding that standing in patent cases are analyzed like any non-patent case).

 

In addition, the U.S. Patent and Trademark Office, a defendant in the case, moved for judgment on the pleadings, and subsequently, the district court dismissed the constitutional claims against them based on the doctrine of constitutional avoidance. Ass’n for Molecular Pathology, 2010 WL at *50.

[18] Ass’n for Molecular Pathology v. U.S. Patent & Trademark Office, 653 F.3d 1329 (Fed. Cir. 2011), vacated 132 S. Ct. 1794 (2012), on remand 2012 WL 3518509 (Fed. Cir. Aug. 16, 2012).

[19] Ass’n for Molecular Pathology v. Myriad Genetics, Inc., No. 11-725, 566 U.S. __, slip op. (Mar. 26, 2012).

[20] Ass’n for Molecular Pathology, 653 F.3d 1329.

[21] Ass’n for Molecular Pathology v. Myriad Genetics, Inc., No. 12-398, 568 U.S. __, slip op. at 1 (Nov. 30, 2012) (granting petition for a writ of certiorari limited to Question 1 presented by the petition).

[22] 35 U.S.C. § 101 (1946).

[23] Chakrabarty, 447 U.S. at 309.

[24] Funk Brothers Seed Co., 333 U. S. at 130.

[25] Diamond v. Diehr, 450 U.S. 175, 187 (1981).

[26] Id. at 188 (quoting Mackay Radio & Tel.Co. v. Radio Corp. of Am., 306 U.S. 86, 94 (1939)).

[27] Chakrabarty, 447 U.S. at 310.

[28] Mayo Collaborative Servs., No. 10–1150, slip op. at 3.

[29] Diehr, 450 U.S. at 191-92.

[30] Parker v. Flook, 437 U.S. 584, 591-92 (1978).

[31] Funk Brothers Seed Co., 333 U. S. at 130.

[32] Mayo Collaborative Servs., No. 10–1150, slip op. at3 (quoting Parker, 437 U.S. at 593).

[33] Id.at 8.

[34] Id. at 11.

[35] Id. at 21.

[36]Ass’n for Molecular Pathology, 653 F.3d, slip op. at 42.

[37]Id.

[38]Id. at 43.

[39] Ass’n for Molecular Pathology, 2010 WL at *45.

[40] Id.

[41] Diehr, 450 U.S. at 187.

[42] Ass’n for Molecular Pathology, 2010 WLat *45.

[43] Id.

[44] 111 U.S. 293, 311 (1884) (determining that despite the claimed invention was artificial and produced a brighter hue, “[c]alling it artificial alizarine did not make it a new composition of matter, and patentable . . . .”).

[45] Chakrabarty, 447 U.S. at 310.

[46] Ass’n for Molecular Pathology, 2010 WLat *44.

[47] Id.

[48] 447 U.S. at 310. The District Court also did not determine whether isolated DNA has “potential for significant utility.” Instead, the District Court reasoned that the use of isolated DNA as a primer or molecular probe is proof that isolated and native DNA are so similar as to be merely one in the same. As stated earlier, however, similarities do not necessarily point out the differences between two objects.