Myriad Genetics Research Articles

Free the Data: The End of Genetic Data as Trade Secrets

For patients and their clinicians, broad access to information about DNA sequence variation is critical. The information is essential to interpreting the clinical significance of genetic variants, but it is not always readily available. At the present time, genetic test providers have the ability to create private databases containing information they have collected through testing and to restrict access to this vital information. A case study of BRCA1/2 testing by Myriad Genetics reveals the implications of creating a private database of clinical information and the importance of open access of this information. Until the June 2013 U.S. Supreme Court ruling that invalidated patents on isolated, naturally occurring human DNA, Myriad Genetics provided the only commercially available test for BRCA1/2 diagnostic testing in countries where patents were filed (for example, the United States). Myriad has tested over 1 million people and has gained valuable experience and information. A particularly significant consequence of being the sole provider of the BRCA1/2 diagnostic tests is that Myriad has collected a vast number of the genetic variants associated with the BRCA1 and BRCA2 genes, along with the accompanying interpretation of each variant. If this testing becomes available elsewhere, this information will not be available to researchers, clinicians, and patients. Some BRCA1/2 test results have a clear-cut interpretation. Perhaps the most clear-cut is a negative result upon testing a relative of someone with a known mutation. A negative result could be uncertain unless the negative result occurs in a person with a known mutation in the family and that mutation was not detected. A positive result, or detection of a known deleterious mutation, is also clear-cut when that mutation has been disclosed. However, some variants are particularly difficult to interpret because the effect of the variation is not yet known. These BRCA variations are aptly named “variants of unknown significance” (VUS). Myriad's patent exclusivity on the BRCA1/2 genes allowed the company to be the sole distributors of the genetic test, and thus it has been the largest collector of any clinically discovered VUS. Through the information gained from this collection, Myriad reports it was able to reduce the frequency of reporting a VUS. Furthermore, when a patient receives a test result with a VUS, Myriad offers free testing to the family members in an effort to gain more information and help determine the clinical significance of the variant. The ability to include additional data on the VUS and expand the proprietary database is a clear incentive for Myriad to offer free testing to the family members of the patient with the VUS. Patients also benefit from this practice. However, other providers of the BRCA1/2 tests will face unnecessary challenges due to the lack of transparency of data. The practice of privatizing clinical data obstructs the scientific community from independently verifying the data's clinical significance and accuracy. The ideal course of action to mitigate this problem would be to require every laboratory that tests for BRCA1/2 to register each test in the National Center for Biotechnology Information (NCBI), National Institutes of Health, Genetic Testing Registry, and deposit all BRCA1/2 variants in the NCBI ClinVar database. Another powerful way of liberating the BRCA1/2 variants is for the very people who have been tested to “free the data” and independently submit their BRCA1/2 report to directly contribute to an open-access database. Current projects that have undertaken this effort include the Sharing Clinical Reports Project (www.sharingclinicalreports.org), where physicians are encouraged to submit their patients' de-identified report to be uploaded to the ClinVar database, and the complementary Free the Data! Campaign (www.free-the-data.org), where the individuals are empowered to share the information themselves. The Sharing Clinical Reports Project avoids violating the Health Insurance Portability and Accountability Act by the de-identification of the patient's personal information, but the Free the Data! Campaign goes one step further in individual autonomy by enabling tested individuals to share their variant in ClinVar and to set their own sharing, privacy, and data access preferences. They can also share phenotypic information, thus providing researchers with information to help advance an understanding of these variants. BRCA1/2 is just an example of the clinical trade secret issue. Allowing public access to variants and associated phenotypes on all genes is essential for the accelerated understanding of health and disease that everyone desires. Private databases thwart progress and slow understanding of the contribution of genetics to health and disease. Laboratories need to share clinical variants for the public good; it cannot be held as a proprietary interest. Individuals need to exert their influence and “free the data” to let the data speak.

Patent portfolios after myriad, how to fit in those new genes?

The recent US Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc. clarified what is considered patentable subject matter. Patent claims limited to the composition of isolated nucleic acid sequences are now considered a product of nature and not patent eligible, while man-made variants of nucleic acid sequences may still be patentable. The decision is consistent with an earlier ruling in Mayo Collaborative Services v. Prometheus Laboratories., Inc. related to diagnostic methods. In Prometheus, the Court held that a method simply reciting known steps used to observe a natural event is not patentable subject matter. Taken together, the Court's decisions provide guidance as to what constitutes a natural phenomenon outside patent protection and what is considered a man-made creation worthy of protection. Despite misgivings, both decisions will provide impetus for increased genetic research and development of new therapeutics and diagnostics, especially in genomic and personalized medicine.

AMP v. Myriad : A Surgical Strike on Blockbuster Business Models

The U.S. Supreme Court’s decision in the Myriad Genetics case will promote translation of genetics-based diagnostics while preserving patent protection for other biomedical products.

Supreme Court Rules Out Patents on 'Natural' Genes

Genes are a product of nature and not an invention, the Supreme Court said in invalidating Myriad Genetics' patents on two breast cancer genes.

Annotated Supreme Court Decision in Association for Molecular Pathology v. Myriad Genetics

Annotated Supreme Court Decision in Association for Molecular Pathology v. Myriad Genetics.

Gene Patents and Personalized Cancer Care: Impact of the Myriad Case on Clinical Oncology

Genomic discoveries have transformed the practice of oncology and cancer prevention. Diagnostic and therapeutic advances based on cancer genomics developed during a time when it was possible to patent genes. A case before the Supreme Court, Association for Molecular Pathology v Myriad Genetics, Inc seeks to overturn patents on isolated genes. Although the outcomes are uncertain, it is suggested here that the Supreme Court decision will have few immediate effects on oncology practice or research but may have more significant long-term impact. The Federal Circuit court has already rejected Myriad's broad diagnostic methods claims, and this is not affected by the Supreme Court decision. Isolated DNA patents were already becoming obsolete on scientific grounds, in an era when human DNA sequence is public knowledge and because modern methods of next-generation sequencing need not involve isolated DNA. The Association for Molecular Pathology v Myriad Supreme Court decision will have limited impact on new drug development, as new drug patents usually involve cellular methods. A nuanced Supreme Court decision acknowledging the scientific distinction between synthetic cDNA and genomic DNA will further mitigate any adverse impact. A Supreme Court decision to include or exclude all types of DNA from patent eligibility could impact future incentives for genomic discovery as well as the future delivery of medical care. Whatever the outcome of this important case, it is important that judicial and legislative actions in this area maximize genomic discovery while also ensuring patients' access to personalized cancer care.

Are Human Genes Patentable?

This commentary reviews the events leading to the Supreme Court decision regarding Myriad Genetics patents on the BRCA1 and BRCA2 genes. Those developing molecular diagnostics will have to comport ...

Association for Molecular Pathology v. Myriad Genetics: A Scientific Approach to Not Just an Isolated Instance, But a Myriad of Dilemma

I attempt to apply the scientific model to legal reasoning, parsing through in a step-wise fashion both scientific and legal principles. This veers from traditional legal thought; I am avoiding precedent, and analyzing the case in a vacuum, in light of definitions and working knowledge. This article will mainly address the issue of 35 U.S.C. § 101 patentability, leaving the issue of patenting methods of utilizing the sequences for further writing.

Application of pharmacokinetic (PK)-guided 5-fluorouracil (FU) in clinical practice.

2595 Background: Body surface area (BSA)-based dosing of FU results in up to 100-fold inter-individual PK variability. PK-guided FU compared to BSA-based dosing resulted in higher response rates and decreased rate of toxicities in two randomized clinical trials. A paucity of data exists on PK-guided FU dosing in the clinical setting. Methods: A total of 70 colorectal cancer (CRC) patients (pts) from 6 academic and community sites received mFOLFOX6 (FU 2,400 mg/m2over 46 h every 2 wks) +/- bevacizumab. Peripheral blood was obtained 2-44 h after start of FU infusion and AUCs were estimated using an immunoassay at Myriad Genetics. FU doses for cycles 2-4 (C2-4) were adjusted algorithmically to target an area under the concentration-time curve (AUC) of 20-25 mg*h/L. The primary outcome was the % of pts within target AUC by C4, with a secondary outcome of toxicity rates compared to historical data. Comparisons between cycles were made using generalized linear models, accounting for repeated observations within pt. Results: The % of pts within target AUC post C1 and C4 was 30% (17/57, 95%CI: 18-43%) and 46% (24/52, 95%CI: 32-61%), respectively (OR=2.16, p=0.05). For each subsequent cycle, the odds of a pt being within range increases by 28% (p=0.04) (Table). The median dose needed to achieve target AUC at C4 was 2,580 (range 1,920-3,484) mg/m2. The median AUC post C1 and C4 was 19 and 21 mg*h/L, respectively. Less grade 3/4 mucositis and diarrhea were seen compared to historical data (3 v 15% and 6 v 12%, respectively); however, no difference in grade 3/4 neutropenia was noted (27 v 33%). Nine pts were non-evaluable by protocol for PK analysis, largely due to sampling/processing errors. Conclusions: PK-guided FU resulted in a greater number of pts achieving the targeted AUC and fewer pts under-dosed at C4 compared to C1. Individualization of FU dosing in the front-line, community and academic, setting is achievable for the treatment of CRC; however, larger clinical trials are needed to define the clinical utility of PK-guided FU. Clinical trial information: NCT01164215. [Table: see text]

Gene Patents at Home and Abroad: Should the WTO Take Action in Light of Myriad?

In 2012 the U.S. Supreme Court granted certiorari to the Myriad case. In doing so, the Court created an opportunity to harmonize U.S. patent law with global patent law norms regarding patents for composition claims of isolated human gene segments. The domestic importance of this case is high: it is estimated that as of 2005, 40,000 patents in the U.S encompass approximately twenty percent of the human genome.While the decision of the Myriad case is uncertain, the current global operating environment for gene patents poses a veritable minefield for practitioners in relevant industries. This article will attempt to address three questions. First: Is there a practical difference between allowing a patent on isolated genes and disallowing a patent on the method used with the isolated genes to diagnose patients? Second: Should the World Trade Organization (WTO) consider adopting a uniform approach on this issue, or is it too controversial? Third: Does a U.S. Supreme Court decision to disallow Myriad Genetics’ isolated gene sequence patents violate Article 27 of the WTO Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS Agreement)?In part IIA, this article will examine the current posture of the Myriad case. In part IIB, the article will examine the background of international laws regarding patent law as relevant to the issue of isolated human gene segments. In part IIC, the article will examine the international law regarding patent law and human gene patents. In part IID, the article will examine the relevant U.S. domestic precedent affecting the validity of Myriad’s composition claims.In part IIIA, the article will analyze the differences between allowing a patent on isolated genes and disallowing a patent on the method used with the isolated genes to diagnose patients. In part IIIB, this article will analyze the considerations facing the WTO in considering whether to adopt a uniform approach to human gene patents.The article concludes that there is a difference between allowing a patent composition claim for on an isolated gene patent while disallowing an associated method claim. The WTO should not consider incorporating the World Intellectual Property Organization (WIPO) Substantive Patent Law Treaty into WTO TRIPS. Rather, there are existing mechanisms in the WTO TRIPS agreement that may be amended to facilitate a uniform, global treatment of human gene patents.Finally, a U.S. Supreme Court decision that disallows Myriad Genetics’ isolated gene sequence patents likely would not violate the current WTO TRIPS Agreement Article 27 because of the principle of nationality present in WTO TRIPS and other international patent agreements.

Commercial Opportunities and Ethical Pitfalls in Personalized Medicine: A Myriad of Reasons to Revisit the Myriad Genetics Saga

In 1996, the US-based biotechnology company Myriad Genetics began offering genetic diagnostic tests for mutations in the genes BRCA1 and BRCA2, which are linked to hereditary breast and ovarian cancer. Since that time, Myriad has been a forerunner in the field of personalized medicine through the use of effective commercialization strategies which have been emulated by other commercial biotechnology companies. Myriad’s strategies include patent acquisition and active enforcement, direct-to-consumer advertising, diversification, and trade secrets. These business models have raised substantial ethical controversy and criticism, often related to the company’s focus on market dominance and the potential conflict between private sector profitability and the promotion of public health. However, these strategies have enabled Myriad to survive the economic challenges that have affected the biotechnology sector and to become financially successful in the field of personalized medicine. Our critical assessment of the legal, economic and ethical aspects of Myriad’s practices over this period allows the identification of the company’s more effective business models. It also discusses of the consequences of implementing economically viable models without first carrying out broader reflection on the socio-cultural, ethical and political contexts in which they would apply.

Should the New Zealand Parliament Allow the Intellectual Property Office of New Zealand to Continue to Grant Patents for Isolated Human Genes?

It is time for New Zealanders to decide whether we want to allow patents over isolated human genes. In making this decision, we should take heed of the pitfalls other jurisdictions have encountered in this area. In this article, I determine the approach New Zealand intellectual property law should take to the patenting of isolated human genes, with reference to the arguments and issues raised by the Myriad Genetics litigation in the United States of America. I conclude that a nuanced approach should be adopted. Isolated human genes are not patentable subject-matter from a legal perspective; however, patents in the field of gene therapeutics should be allowed on policy grounds.

The Changing Relationship Between Patent Owners and Researchers

Pharmaceutical Patent AnalystVol. 2, No. 2 CommentaryThe changing relationship between patent owners and researchersJake M Holdreith & Jamie R KurtzJake M Holdreith* Author for correspondenceRobins, Kaplan, Miller & Ciresi LLP, 601 Lexington Avenue, Suite 3400, NY 10022–14611, USA. Search for more papers by this authorEmail the corresponding author at jmholdreith@rkmc.com & Jamie R KurtzRobins, Kaplan, Miller & Ciresi LLP, 800 LaSalle Avenue, 2800 LaSalle Plaza, MN 55402–52015, USASearch for more papers by this authorPublished Online:26 Feb 2013https://doi.org/10.4155/ppa.13.12AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleKeywords: §271(e)basic researchlaboratory methods and materialsresearch exemptionsafe harborReferences1 Association for Molecular Pathology, et al. v. USPTO & Myriad Genetics, Inc., 689 F.3d 1303 (Fed. Cir. 2012).Google Scholar2 35 U.S.C. §271(e).Google Scholar3 Momenta Pharma. v. Amphastar Pharma., 686 F.3d 1348 (Fed. Cir. 2012).Google Scholar4 Monsanto v. E.I. DuPont De Nemours and Pioneer Hi-Bred International, Civ. No. 4:09-cv-686, Dkt. No. 1661 (E.D. Mo.) (2012).Google Scholar5 Madey v. Duke, 266 F.Supp.2d 420, 425 (M.D.N.C. 2001) (citing Deuterium Corp. v. United States, 19 Cl. Ct. 624, 630 (1990).Google Scholar6 Madey v. Duke, 307 F.3d 1351, 1362 (Fed. Cir. 2002).Google Scholar7 Alzheimer’s Inst. of Am. v. Avid Radiopharmaceuticals, Civ. No. 10–6908 (E.D. Penn.) (2010).Google Scholar8 Alzheimer’s Inst. of Am. v. Elan Pharmas., Civ. No. 3:10-cv-482 (N.D. Cal.) (2010).Google Scholar9 Harvard College v. Kappos, Case No. 1:12-CV-1034, Dkt. No. 1. (E.D. Va.).Google Scholar101 Nine points to consider in licensing university technology. www.autm.net/Nine_Points_to_Consider1.htmGoogle Scholar102 Wisconsin alumni research foundation exclusive license agreement. www.warf.org/uploads/media/LicenseExclusive_with_right_to_sublicense_010412.pdfGoogle ScholarFiguresReferencesRelatedDetails Vol. 2, No. 2 Follow us on social media for the latest updates Metrics Downloaded 113 times History Published online 26 February 2013 Published in print March 2013 Information© Future Science LtdKeywords§271(e)basic researchlaboratory methods and materialsresearch exemptionsafe harborFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

Men with Low Preoperative Sexual Function May Benefit from Nerve Sparing Radical Prostatectomy

We determined the effect of nerve sparing radical prostatectomy on sexual and urinary function in men at various levels of pretreatment sexual function. Men in the CaPSURE™ (Cancer of the Prostate Strategic Urologic Research Endeavor) database who underwent radical prostatectomy and had baseline and 2-year posttreatment UCLA-PCI sexual function and urinary function scores were selected. Nerve sparing was categorized as bilateral, unilateral or none and the level of pretreatment sexual function was divided into quartiles. The cohort was divided into subgroups of nerve sparing technique and pretreatment sexual function. Differences between sexual function and urinary function among subgroups were determined. A test of interaction was performed between preoperative sexual function and degree of nerve sparing on postoperative sexual function and urinary function scores. A total of 1,322 patients met the study inclusion criteria. Median patient age was 61 years (range 41 to 79). Bilateral, unilateral and no nerve sparing procedures were performed in 899, 200 and 223 men, respectively. The effects of nerve sparing on sexual function differed among the quartiles of preoperative sexual function (p <0.01). Nerve sparing did not have an effect on the sexual function of men in the lowest quartile of preoperative sexual function score (p = 0.15) but did have a significant beneficial effect on sexual function in the higher 3 quartiles (p = 0.04, p <0.01 and p <0.01, respectively). Alternatively, nerve sparing improved urinary function in men in the lowest quartile of baseline sexual function. Nerve sparing radical prostatectomy results in better sexual function outcomes than no nerve sparing in most men except those with little baseline function. Urinary function was positively impacted in all men. Men who are suitable candidates for nerve preservation may benefit from nerve sparing surgery. Poorer baseline sexual function should not exclude these men from such surgery.

A 2-Stage Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms Associated with Development of Urinary Symptoms After Radiotherapy for Prostate Cancer

We identified single nucleotide polymorphisms associated with change in the AUA Symptom Score after radiotherapy for prostate cancer. A total of 723 patients treated with brachytherapy with or without external beam radiation therapy were assessed at baseline and annually after radiotherapy using the AUA Symptom Score. A 2-stage genome-wide association study was performed with the primary end point of change in AUA Symptom Score from baseline at each of 4 followup periods. Single nucleotide polymorphism associations were assessed using multivariable linear regression adjusting for pre-radiotherapy AUA Symptom Score severity category and clinical variables. Fisher's trend method was used to calculate combined p values from the discovery and replication cohorts. A region on chromosome 9p21.2 containing 8 single nucleotide polymorphisms showed the strongest association with change in AUA Symptom Score (combined p values 8.8×10(-6) to 6.5×10(-7) at 2 to 3 years after radiotherapy). These single nucleotide polymorphisms form a haplotype block that encompasses the inflammation signaling gene IFNK. These single nucleotide polymorphisms were independently associated with change in AUA Symptom Score after adjusting for clinical predictors including smoking history, hypertension, α-blocker use and pre-radiotherapy AUA Symptom Score. An additional 24 single nucleotide polymorphisms showed moderate significance for association with change in AUA Symptom Score. Several of these single nucleotide polymorphisms were more strongly associated with change in specific AUA Symptom Score items, including rs13035033 in the MYO3B gene, which was associated with straining (beta coefficient 0.9, 95% CI 0.6-1.2, p = 5.0×10(-9)). If validated, these single nucleotide polymorphisms could provide insight into the biology underlying urinary symptoms following radiotherapy and could lead to development of an assay to identify patients at risk for experiencing these effects.

Isolated human genes and related therapeutic treatment methods held patent-eligible

Patents on isolated genes are big business. In the past three decades, the United States Patent and Trademark Office (USPTO) has issued over 2500 patents claiming isolated DNA, and 40000 DNA-related patents in nonnative form, for genes in the human genome. Thus in 2010, when a US district court judge found claims to isolated DNA and related method claims patent-ineligible, the industry was shocked and mobilized to respond: see Ass’n for Molecular Pathology v US Patent & Trademark Office, 702 F Supp 2d 181, 220–37 (SDNY 2010) (‘Myriad I’). At first, on appeal, the majority of a three-judge panel of the US Court of Appeals for the Federal Circuit reversed the district court decision and found all of the composition claims, as well as one method claim directed to screening potential cancer therapies based upon changes in the growth rates of transformed cells, patent-eligible: Ass’n for Molecular Pathology v US Patent & Trademark Office, 653 F 3d 1329 (Fed Cir 2011) (‘Myriad II’). This result was shortlived: the US Supreme Court, in Mayo Collaborative Services v Prometheus Laboratories, Inc, 132 S Ct 1289 (2012) (‘Mayo’), granted certiorari, vacated Myriad II and remanded for further consideration in view of Mayo. Ass’n for Molecular Pathology v Myriad Genetics, Inc, 132 S Ct 1794 (2012) (‘Myriad III’). This past August, in Myriad IV, the Federal Circuit, on remand, quickly set a new briefing schedule to address the impact of Mayo on its prior Myriad II decision, held oral argument, and then the same panellists reissued a substantively similar decision. While each of the panellists considered Mayo, it had little impact on their ultimate conclusions as to whether isolated DNA claims and related method claims were patent-eligible.

Journeys into the genome of cancer cells

I come from a family in which there have been no scientists or doctors. I was interested, however, in biology at school and started my scientific career by training in medicine at Oxford University and Guys Hospital, London. Practising as a doctor reinforced my curiosity about the biological processes underlying human disease. As a consequence, I pursued a clinical vocation in histopathology, a discipline that couples exposure to the sights and smells of the autopsy room with a daily journey into the often beautiful, sometimes ugly world of healthy and diseased human tissues under the microscope. After an introduction to general histopathology in Nick Wright's department at the Hammersmith Hospital, London, I completed my postgraduate medical training in neuropathology with Peter Lantos at the Maudsley Hospital, London.Peering at the nuclei of cancer cells under the microscope, for me it was a matter of fascination that hidden within them were the key events converting normal cells into cancer cells, and frustration because they were out of reach. Many of the tissue samples examined by pathologists are from cancers. The clonal theory of cancer development and the general role of DNA mutations in generating cancer cell clones had been established by 1986 when I was working as a junior pathologist. Indeed, the first mutated cancer gene, HRAS , had recently been identified through application of the, then new, technologies of recombinant DNA technology. Peering at the nuclei of cancer cells under the microscope, for me it was a matter of fascination that hidden within them were the key events converting normal cells into cancer cells, and frustration because they were out of reach. So, I took 3 years break from medicine to study for a PhD, learning the methods and thinking of molecular oncology in Colin Cooper's laboratory at the Institute …

Pervasive sequence patents cover the entire human genome

The scope and eligibility of patents for genetic sequences have been debated for decades, but a critical case regarding gene patents (Association of Molecular Pathologists v. Myriad Genetics) is now reaching the US Supreme Court. Recent court rulings have supported the assertion that such patents can provide intellectual property rights on sequences as small as 15 nucleotides (15mers), but an analysis of all current US patent claims and the human genome presented here shows that 15mer sequences from all human genes match at least one other gene. The average gene matches 364 other genes as 15mers; the breast-cancer-associated gene BRCA1 has 15mers matching at least 689 other genes. Longer sequences (1,000 bp) still showed extensive cross-gene matches. Furthermore, 15mer-length claims from bovine and other animal patents could also claim as much as 84% of the genes in the human genome. In addition, when we expanded our analysis to full-length patent claims on DNA from all US patents to date, we found that 41% of the genes in the human genome have been claimed. Thus, current patents for both short and long nucleotide sequences are extraordinarily non-specific and create an uncertain, problematic liability for genomic medicine, especially in regard to targeted re-sequencing and other sequence diagnostic assays.

Progress in genomics according to bingo: 2013 edition

Progress in genomics according to bingo: 2013 edition

After Prometheus, Are Human Genes Patentable Subject Matter?

On November 30, 2012, the U.S. Supreme Court granted certiorari in Association for Molecular Pathology v. Myriad Genetics, Inc. on the question, “Are human genes patentable?” For over 150 years Supreme Court decisions have excluded from the federal patent power laws of nature and physical phenomena. The words invention, new and useful in §101 are consistent with these exclusions from the federal patent power, so they are not the result of a judicially active court limiting the will of Congress. The conclusions of Judges Lourie and Moore in Myriad Genetics that the isolated DNA segments of claim 1 constitute patentable subject matter disregard the Supreme Court's decisions in Chakrabarty and Funk Brothers on products derived from nature. “Isolation” is not an inventive step to change an unpatentable physical phenomenon into patentable subject matter. Turning to claim 2, even if the isolated cDNA segments do not under Chakrabarty and Funk Brother constitute a patentable product, under Prometheus the isolated cDNA segments capture an unpatentable law of nature - the genetic code. Since no inventive step has been added to the genetic code in claim 2, the cDNA of claim 2 constitutes unpatentable subject matter under Prometheus. The Federal Circuit’s disregard in Myriad Genetics of the laws of nature threatens to eviscerate the public domain of basic scientific knowledge.