. Wolters Kluwer law & Business. Mayo v. Prometheus: Natural Law or Mental Step?... 3

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1 nte ectua roperty Edited by the Technology and Proprietary Rights Group of Wei I, Gotshal & Manges LLP VOLUME 24 NUMBER I 2 DECEMBER 20 I 2 Mayo v. Prometheus: Natural Law or Mental Step? Tamsen Valoir, of Boulware & Valoir, discusses the recent U.S. Supreme Court decision in Mayo Collaborative Services v. Prometheus Laboratories, Inc., and ponders whether the United States should consider eliminating medical patents altogether. Dr. Valoir observes that other countries have already eliminated certain medically related patents in the interests of public health. Recognizing that such an important decision may be better made in the halls of Congress (where interested parties can all contribute to the debate) and not in the closed chambers of the Supreme Court, she concludes her article by noting that only time and further opinions will elucidate the full impact of the Mayo case. Her analysis provides a methodology for thinking about Section 101 issues in. the medical context until the courts or Congress make greater : determinations about Section 101 patent eligibility criteria. Federal Circuit Changes the Standard for Induced Infringement of Method Pat.ents Kirk T. Bradley and Christopher L. McArdle of Alston & Bird LLP discuss a recent en bane decision wherein the Federal Circuit ruled that inducement of patent infringement no longer requires proof that a single entity directly infringes the patent. As Messrs. Bradley and McArdle observe, the court, overruling a 2007 decision and limiting its analysis to method patents, held "that all the steps of a claimed method must be performed in order to find induced infringement, but that it is not necessary to prove that all the steps were committed by a single entity." They note that this new rule eases a patentee's burden for proving induced infringement and is already having an immediate and dramatic impact on patent litigation. They conclude that the new standard will affect claim drafting as well as earlier concerns about structuring method claims to capture infringement by a single party are now less worrisome. Federal Trade Commission Continues to Put a Spotlight on Pharmaceutical Patent Agreements The Federal Trade Commission (FTC) recently demonstrated that it is becoming more proactive in its efforts to scrutinize the competitive effects of pharmaceutical industry agreements regarding patents. First, as Barbara H. Wootton and Matthew Shultz of Arnold & Porter LLP point out, the FTC announced that it was proposing to amend the Hart-Scott-Rodino (HSR) premerger notification rules to broaden the types of exclusive patent rights transfers, in the pharmaceutical industry only, that are reportable under the HSR Act. Second, the FTC also announced that it moved for leave to file an amicus brief with U.S. District Court in New Jersey for In re Effexor XR Antitrust Litigation, arguing that a branded company's commitment not to launch an authorized generic in competition with a generic company as part of a patent settlement constitutes a "payment" for delayed generic entry under the Third Circuit's recent decision in In re K-Dur Antitrust Litigation which adopted the FTC's position on the standard for antitrust review of pharmaceutical patent settlements. Bankruptcy's (mis )Treatment of Intellectual Pr..operty: Why 365(n) Is Not Enough-Part II This is the second part of a two part article by Alex Thcker exploring the intersection of intellectual property and bankruptcy law. Part I, which appeared in the last issue, dealt with the development of the Countryman Functional and Hypothetical-Actual circuit splits. Part I concluded with an assessment of a debtor's statutory power to reject, assume, and assign intellectual property licenses. In this issue, Part II concludes the analysis and suggests legislative and judicial changes that would provide non-debtor licensors much needed certainty and predictability over the future of their licenses.. Wolters Kluwer law & Business

2 I Mayo v. Prometheus: Natural Law or Mental Step? By Tamsen Valoir In the recent Mayo Collaborative Services v. Prometheus Laboratories, Inc. 1 case, the Supreme Court unanimously held that methods of treatment optimization claims were ineligible for patent protection on the basis that the claims recited a law of nature. Section 101 of the Patent Act defines patent eligible subject matter. It provides: 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 therefor, subject to the conditions and requirements of this title.z This section has been interpreted by the courts very broadly, and indeed includes anything "made by man."j While a very expansive grant of subject matter eligibility is provided by Section 101, its scope is not infinite. The Supreme Court has long held that there are certain exceptions to what is patentable-one important exception is that "natural laws" are not patentable. Thus, "Einstein could not patent his celebrated law that E = mc2; nor could Newton have patented the law of gravity."4 Chemical elements, mental processes and abstract concepts are similarly exempted from patent protection.s The claims at issue in the Mayo case related to optimizing drug dosage levels by determining the levels of a metabolite of that drug. Certain drugs, such as 6-mercaptopurine (6-MP), are converted to 6-thioguanine (6-TG) in the body, and the inventors discovered how much 6-TG is too much, thus indicating a need to lower the dosage of 6-MP. Tamsen Valoir is a co-founder of the Intellectual Property boutique law firm of Boulware & Valoir. She practices patent, trademark, and copyright law, as well as licensing and FDA regulatory law. This article does not reflect the official opinion of the firm, and may not even reflect the opinions of the author. Dr. Valoir can be reached at tvaloir@boulwarevaloir.com. Claim 1 is illustrative: 1. A method of optimizing therapeutic efficacy for treatment of an inunune-mediated gastrointestinal disorder, comprising: (a) administering a drug providing [6-TG) to a subject having said inunune-mediated gastrointestinal disorder; and (b) determining the level of[ 6-TG) in said subject having said immune-mediated gastrointestinal disorder, wherein the level of [6-TG) less than about 230 pmol per 8 x 10 8 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject and wherein the level of [6-TG) greater than about 400 pmol per 8X10 8 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.6 The claim requires two active steps: (1) "administering" a drug and (2) "determining" the level of metabolite. The "wherein" clauses that follow merely identify optimal dosage levels. However, no active step of changing the dosage is affirmatively recited in the claim. According to the Supreme Court's opinion, w ritten by Justice Breyer, the fault with the claims was that they were "tying up the use of the underlying natural laws, inhibiting their use in the making of further discoveries.''? No natural law is readily apparent from reading the claims. In fact, F = MA and E = mc 2 are still free to be used by anyone on the planet, as are all of the other physical laws. However, the Court also said: The claims purport to apply natural laws describing the relationships between the concentration in the blood of certain thiopurine metabolites and the likelihood Volume 24 Number 12 December 2012 Intellectual Property & Technology Law journal 3

3 that the drug dosage will be ineffective or induce harmful side-effects. s The "natural law" thus relates to the metabolic process of converting 6-MP to 6-TG and to the levels of 6-TG that are considered toxic. Of course, this is not a "law" in the sense that a scientist would typically think of, since every human both metabolizes the drug a bit differently and has a different tolerance for toxic side effects. Even the 6-TG cutoff levels can vary from disease to disease, since higher toxicity levels are acceptable for more deadly diseases. Nonetheless, the conversion of 6-MP to 6-TG and toxic levels thereof is arguably a natural process or correlation (although 6-MP is wholly man made)9 and what the Court considers to be the underlying "natural law." The Supreme Court appears concerned with overly broad claims covering the correlation and preventing further research and discovery. However, the metabolic conversion of 6-MP to 6-TG can still be practiced by any patient taking 6-MP. In taking such drug, the patient is practicing the "administering" step, but since the "determining" step is not practiced by most patients, they are free to take 6-MP and internally convert it to 6-TG without risking patent infringement. The claim may, however, prevent doctors from both prescribing such a drug and then ordering a diagnostic test for determining the 6-TG levels.1o The claim might also reduce clinical research in developing new assays for determining 6-TG levels since clinical research will require "administering" a drug to a patient and any following assay of a blood sample from that patient will involve "determining" metabolite levels. The patent statute already has an infringement exception for medical practitioners and would appear to alleviate most of the Court's concerns. Section 287(c) provides in part: (1) With respect to a medical practitioner's performance of a medical activity that constitutes an infringement under section 271 (a) or (b) of this title, the provisions of sections 281, 283, 284, and 285 of this title shall not apply against the medical practitioner or against a related health care entity with respect to such medical activity. (2) For the purposes of this subsection: (A) the term "medical activity" means the performance of a medical or surgical procedure on a body, but shall not include (i) the use of a patented machine, manufacture, or composition of matter in violation of such patent, (ii) the practice of a patented use of a composition of matter in violation of such patent, or (iii) the practice of a process in violation of a biotechnology patent. Therefore, the law already appears to provide a medical exception for patent infringement, unless the medical practitioner is using a patented machine, manufacture, or composition of matter, or a biotechnology process patent. The treatment optimization claims above, do not require the use of a patented drug (those patents have expired), and there is no patented biotech process, machine or manufacture needed to practice the claim either. Thus, no medical practitioner could be found liable for infringing the claims at issue. In addition to the infringement exception under Section 287(c), the claim may also be anticipated or obvious. In fact, the drugs and the metabolite were both known and assays for determining 6-TG had long been in use (e.g., with inflammatory bowel diseases such as Crohn's disease).11 If the claim's offense was that it blocked medical treatments and basic research, it could possibly have been invalidated under the usual anticipation or obviousness analysis. Although declining to analyze the claim under traditional prior art precedent, 12 the Supreme Court's analysis of the patent eligibility introduced novelty and non-obviousness concepts into the Section 101 analysis: To put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist 4 Intellectual Property & Technology Law journal Volume 24 Number 12 December 2012

4 of well-understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing signiftcant beyond the sum of their parts taken separately.n Many have criticized this portion of the analysis in particular because it appears to conflate patent eligibility under Section 101 with novelty and non-obviousness requirements under Sections 102 and 103. Indeed, more than one commentator has noted that any law student would receive a failing grade for an analysis that imports novelty and non-obviousness criteria into a patent eligibility analysis.14 Yet, the Supreme Court apparently intentionally conflated these different concepts: We recognize that, in evaluating the significance of additional steps, the 101 patent-eligibility inquiry and, say, the 102 novelty inquiry might sometimes overlap. IS Another interesting feature of the Court's analysis, is that a patent claim that consisted only of the administering step (a) was patent eligible (though the patent has long since expired),16 but now that the inventors added another step, it is no longer patent eligible. It becomes difficult (if not impossible) to analyze pending or issued claims under the Supreme Court's analysis. One would have to determine what the Court considers a "natural law" and even if it could be done, there are no inventions that fail to use natural laws. Mayo shows that medical correlations are at least good candidates for a "natural law," but this is singularly unhelpful for any art outside of medicine. Further, the analysis seems to say if the steps other than the natural law step are conventional (a Section 102 or Section 103 question), a claim that recites such a natural law is not patent eligible. However, most inventions are directed to conventional steps if the so-called nugget of patentability is ignored and the approach contravenes the long established rule that claims are to be analyzed "as a whole," not element-by-element.17 In order to provide a way to move forward out this mire, we will step outside of the comfortable boundaries of a logical analysis and try to guess what the real drivers in the Mayo case were. An unconventional approach to be sure, but struggling to understand the Mayo opm10n may lead practitioners down less trodden paths. To review the claim again, it consists of two steps: (1) a drug is "administered," and (2) 6-TG levels are "determined." The remainder of the claim is a "wherein" clause, reciting those 6-TG levels that are too high or too low. However, no change in dosing levels is actually required. The claim seems to read on doctors even thinking about the optimal dosage levels, even where they do not take the next step of changing the dosage. In fact, Mayo repeatedly asserted that a dermatologist using the drug and testing for 6-TG levels would infringe the patent by merely thinking about the correlation between levels and toxicity. IS Further, the same issue arose in the LabCorp case, where the Supreme Court initially granted certiorari to consider the question of "[w]hether a method patent... directing a party simply to 'correlate' test results can validly claim a monopoly over a basic scientific relationship... such that any doctor necessarily infringes the patent merely by thinking about the relationship after looking at a test result."19 A similar "mental step" issue arose with the invalidated claims in the recent Myriad case.zo The Myriad patents relate to the breast cancer genes BRCA1 and BRCA2, where having certain mutations gives a woman a higher chance of developing breast cancer. The Federal Circuit held that method claims relating to screening tumors which recited only "analyzing" or "comparing" steps to be patent ineligible mental steps.21 For example, one of the claims at issue in Myriad read as follows: 1. A method for detecting a germline alteration in a BRCA1 gene, said alteration selected from the group consisting of the alterations set forth in Tables 12A, 14, 18 or 19 in a human which comprises analyzing a sequence of a BRCA1 gene or BRCA1 RNA from a human sample or analyzing a sequence of BRCA1 edna made from mrna from said human sample with the proviso that said germline alteration is not a deletion of 4 nucleotides corresponding to base numbers ofseq ID NO:t.zz Volume 24 Number 12 December lntelleaual Property & Technology Law Journal 5

5 The only verb in the body of this claim is "analyzing." Typically, one determines whether a patient has a given mutation by either "sequencing" the gene in question or by "hybridizing" the gene to a probe that is specific for the mutation in question. In contrast, this claim assumes that the sequence or hybridization information is already available and all one need to do is to "analyze" that information. Therefore, one could review a sheet of paper providing the nucleotide sequences in question, see if the recited mutations are present, and thereby infringe the claim. Even though such an action would normally be performed by a computer, the claims are not so limited, and merely reading the sequence and thinking about the mutations would be an infringement. Thus, the method claim recites only a mental step. 23 This suggests that in spite of the Supreme Court's "natural law" analysis, the real driver and problem with the Mayo claims may have been that they recited a mental step. Indeed Mayo itself wrote extensively in its Petition for Certiorari that doctors would infringe the claims by merely thinking.24 If true, then companies should review their pending or patented claims directed to diagnostic methods, treatment optimization methods, and biomarker related claims to ensure that the claims are not so broadly worded as to be potentially infringed by a merely mental step. Instead, the claims should recite active verbs that require actual physical actions. If any patents lack sufficient specificity of verbs, reissue should be sought to obtain narrower claims reciting verbs that describe physical, as opposed to mental, actions. Under this analysis, the Mayo claim should recite something like the following: 1. A method of optimizing therapeutic efficacy for the treatment of disease D, comprising: (a) administering a dosage of 6-MP to a patient having disease D; (b) collecting a sample of body fluid fi om said patient at least 24 hours after said administration; (c) measuring the level of 6-TG in said sample; and (d) raising said dosage if 6-TG is less than X, or lowering said dosageif 6-TG is greater than y2s Additional claims should also recite specific methods of measuring 6-TG levels, although we may ultimately discover that even the basic claims should recite a particular method to pass Section 101 muster. Of course, under the Supreme Court's analysis, which conflates Section 102/103 issues with Section 101 issues, many have opined that the proposed claim recites no more than conventional steps. Furthermore,Justice Breyer in both the Mayo opinion and in the LabCorp dissent makes it clear that he is greatly troubled by diagnostic claims that only recite naturally occurring correlations. 26 Indeed, it is probably not unreasonable to conclude that Justice Breyer has signaled a desire to eliminate diagnostic and medical treatments patents altogether. Perhaps as a society we should consider eliminating medical patents altogether. Certainly, other countries have already eliminated certain medically related patents in the interests of public health.27 However, such an important decision may be better made in the halls of Congress, where interested parties can all contribute to the debate, and not in the closed chambers of the Supreme Court. Although the proposed claim still might not survive Supreme Court analysis, most claims never get to the Supreme Court. Further, because the claim avoids reciting any steps that can be performed mentally, it has at least a chance of escaping the Mayo scrutiny at the USPT02s and lower court levels. Only time and many more written opinions will elucidate the full import of the Mayo v. Prometheus case, but this analysis should provide some rational way of thinking about Section 101 issues in the medical context until the courts or Congress sort out the Section 101 patent eligibility criteria. Notes U.S._, 132 S. Ct (2012), see Slip Opinion at I opinions/ 11 pdf/ pdf (hereinafter Mayo Slip Op.) U.S. C Diamond v. Chakrabarty, 447 U.S. 303, 309 (1980) ("Congress intended statutory subject matter to 'include anything under the sun that is made by man.'") (citation omitted). 4. Mayo Slip Op. at p. 1-2 (citation omitted). 5. ld. ("a new mineral discovered in the earth or a new plant found in the wild is not patentable subject matter... Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are 6 Intellectual Property & Technology Law journal Volume 24 Number 12 December 20 12

6 not patentable, as they are the basic tools of scientific and technological work.") (citations omitted). 6. U.S. Patent No. 6,355,623. There was an additional patent and additional claims at issue, but for simplicity only a single claim is discussed. 7. Mayo Slip Op. at p Mayo Slip Op. at p Gertrude B. Elion and George H. Hitchings invented 2-amino-6-mercaptopurine in U.S. Patent No. 2,884, "Prescribing" is different from "administering," and there are potential issues with different parties practicing the two different steps. However, the Supreme Court did not get caught up with such technicalities and we may gloss over such issues herein as well. 11. Cuffari C, et al., 6-M ercaptopurine metabolism in Crohn's disease: correlation with efficacy and toxicity, Gut Sep.39(3):401-6 ("blood was obtained prior to daily administration of 6-MP in 25 adolescent Crohn's disease patients... [and] 6-thioguanine (6-TG) and 6-methyl-mercaptopurine (6-MMP) were measured... "). 12. The Court specifically rejected using a approach. Mayo Slip Op. at p. 22 ("These considerations lead us to decline the Government's invitation to substitute 102, 103, and 112 inquiries for the better established inquiry under 101."). 13. Mayo slip op. at p See e.g., http: I lwww.ipwatchdog.com/ supremecourt-mayo-v-prometheuslid= ("If a student were to write such nonsense in a patent law paper or on a patent law final exam they would receive little, if any, credit."). 15. Mayo Slip Op. at p. 21 (en"lphasis added). 16. U.S. Patent No. 4,443,435 ("12. The method of eliciting the corresponding therapeutic response in a warmblooded animal, which comprises administering to such animal an effective amount of a compound as defined by claim 1 [reciting prodrugs of6-mp)"). 17. Diamond v. D iehr, 450 U.S. 175, 188 (1981) ("'n determining the eligibility of respondents' claimed process for patent protection under 101, their claims must be considered as a whole. It is inappropriate to dissect the claims into old and new elements and then to ignore the presence of the old elements in the analysis."). 18. Mayo Petition for a Writ of Certiorari, 2011 WL (U.S. 2011), available at http: I lwww.patentlyo.com I mayocertpet.pdf, at p. 15 ("Dermatologist Dr. ei-azhary cannot stop thinking about Prometheus's ranges once she learns of them, even if her goal in reviewing a patient's test results is to find entirely different numbers relating only to dermatology.") (hereinafter Mayo Petition for Cert.). 19. The Supreme Court initially granted certiorari to hear the LabCorp case, but later dismissed the case without comment. See Lab. Corp. of Am. Holdings v. Metabolite Labs., Inc.,548 U. S. 124 (2006) (Breyer, J., dissenting) (hereinafter Lab Corp). 20. Ass'n For Molecular Pathology v. USPTO and Myriad Genetics Inc., 689 F.3d 1303 (2012) (holding isolated DNA claims patent eligible, but stating "We affirm the court's decision, however, that Myriad's method claims directed to "comparing" or "analyzing" DNA sequences are patent ineligible; such claims include no transformative steps and cover only patent-ineligible abstract, mental steps.") (hereinafter Myriad). 21. Id. at 1309 ("We affirm the court's decision, however, that Myriad's method claims directed to "comparing" or "analyzing" DNA sequences are patent ineligible; such claims include no transformative steps and cover only patent-ineligible abstract, mental steps."). 22. U.S. Patent No. 5,709,999 (paragraph breaks inserted for the readers' convenience). 23. See also Lab Corp, 548 U.S. at (suggesting that the claims do not cover a process for transforming a bodily sample, but rather merely instruct the user to obtain test results and "think" about them). 24. Mayo Petition for Cert., at p. 7 ("Dr. el-azhary cannot resume her dermatological research unless and until she rids her memory of the correlations that Prometheus observed in gastro-intestinal patients, regardless of how she ultimately may use any test results. She infringes whenever she recognizes the correlations, no matter what else she thinks or does."). 25. Actors will attempt to avoid infringement by separating the various steps amongst different parties, but at least the claim might pass the 101 hurdle. 26. LabCorp, 548 U.S. at 136 (Breyer, ]., dissenting) ("Claim 13's process instructs the user to (1) obtain test results and (2) think about them. Why should it matter if the test results themselves were obtained through an unpatented procedure that involved the trans-formation of blood? Claim 13 is indifferent to that fact, for it tells the user to use any test at all."). 27. See, e.g., Article 53(c) EPC excludes methods for the treatment of the human or animal body by therapy or surgery from being patent eligible. See also 35 U.S.C. 287(c). 28. See 2012 Interim Procedure for Subject Matter Eligibility Analysis of Process Claims Involving Laws of Nature, available at exam _interim_guidance.pdf (hereinafter PTO Guidance). T he Guidance provides examples of claims Volume 24 Number 12 December Intellectual Property & Technology Law Journal 7

7 covering the "natural principle" that white light positively affects a persons' mood. Claims 1 and 2 are too broad to be patent eligible, and but claim 3 would be allowable according to the PTO Guidance: 1. A method for treating a psychiatric behavioral disorder of a patient, the disorder associated with a level of neuronal activity in a neural circuit within a brain of the patient, the method comprising: exposing the patient to sunlight to alter the level of neuronal activity in the neural circuit to mitigate the behavioral disorder. 2. A method for treating a psychiatric behavioral disorder of a patient, the disorder associated with a level of neuronal activity in a neural circuit within a brain of the patient, the method comprising: exposing the patient to a source of white light to alter the level of neuronal activity in the neural circuit to mitigate the behavioral disorder. 3. A method for treating a psychiatric behavioral disorder of a patient, the disorder associated with a level of neuronal activity in a neural circuit within a brain of the patient, the method comprising: providing a light source that emits white light;jiltering the ultraviolet (UV) rays from the white light; positioning the patient adjacent to the light source at a distance between em for a predetermined period ranging from minutes to expose photosensitive regions of the brain of the patient to the filtered white light to mitigate the behavioral disorder. 8 lntelleaual Property & Technology Law journal Volume 24 Number 12 December 2012