Ex Parte Niewczas et alDownload PDFPatent Trial and Appeal BoardMar 16, 201713130711 (P.T.A.B. Mar. 16, 2017) Copy Citation United States Patent and Trademark Office UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O.Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 13/130,711 08/09/2011 Monika A. Niewczas JDP-131US 1023 35859 7590 Pierce Atwood LLP 100 Summer Street Suite 2250 Boston, MA 02110 EXAMINER HIBBERT, CATHERINE S ART UNIT PAPER NUMBER 1636 NOTIFICATION DATE DELIVERY MODE 03/20/2017 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): Patent @pierceatwood. com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte MONIKA A. NIEWCZAS and ANDRZEJ S. KROLEWSKI1 Appeal 2015-001681 Application 13/130,711 Technology Center 1600 Before JOHN G. NEW, JOHN E. SCHNEIDER and TIMOTHY G. MAJORS, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL SUMMARY 1 Appellants state the real party-in-interest is Joslin Diabetes Center, Inc. App. Br. 3. Appeal 2015-001681 Application 13/130,711 Appellants file this appeal under 35 U.S.C. § 134(a) from the Examiner’s Non-Final Rejection of claims 17—20 which stand rejected as unpatentable under 35 U.S.C. §101 as being directed to unpatentable subject matter. Claims 17—20 also stand rejected as unpatentable under 35 U.S.C. §103 (a) as being obvious over the combination of C. Keller et al., Association of Kidney Function with Inflammatory and Procoagulant Markers in a Diverse Cohort: A Cross-sectional Analysis from the Multi- Ethnic Study of Atherosclerosis (MESA), 9:9 BMK Nephrology 1—8 (2008) (“Keller”), E.L. Knight et al., Kidney Dysfunction, Inflammation, and Coronary Events: A Prospective Study, 15 J. Am. Soc. Nephrol., 1897—1903 (2004) (“Knight”), and M. Tonelli et al., Biomarkers of Inflammation and Progression of Chronic Kidney Disease, 68 Kidney Int’l 237-45 (2005) (“Tonelli”). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. NATURE OF THE CFAIMED INVENTION Appellants’ invention is directed to methods of diagnosing and predicting renal disease, using one, two, or more biomarkers, including sTNFR-I, sTNFR-II, sFAS, TNF, and IL-6. Abstract. GROUPING OF CLAIMS Claim 17 is representative and recites: 2 Appeal 2015-001681 Application 13/130,711 17. A method of determining whether a human subject has an increased risk of developing chronic kidney disease (CKD), or end stage renal disease (ESRD), or both, the method comprising: obtaining a sample from a human subject who has proteinuria; measuring the level of soluble TNF receptor type I (sTNFRI) in the subject sample; comparing the subject levels of sTNFRI with reference levels of sTNFRI; and determining whether the subject has an increased risk of developing CKD or ESRD, or both, based on the comparison of the subject levels with the reference levels App. Br. 18-19. ISSUE AND ANALYSIS We agree with, and adopt, the Examiner’s reasoning and conclusion that the claims are both directed to nonstatutory subject matter and obvious over the cited prior art references. We address Appellants’ arguments below. A. Rejection of the claims as being directed to nonstatutory subject matter Issue Appellants argue that the Examiner erred in finding that the claims are directed to nonstatutory subject matter under 35U.S.C. § 101. App. Br. 6. Analysis Appellants argue the Examiner has failed to analyze the claims “as a whole” by including each and every element of the invention including the element(s) directed to the alleged “law of nature,” as required by the Supreme Court in Mayo Collaborative Services v. Prometheus 3 Appeal 2015-001681 Application 13/130,711 Laboratories, Inc., 566 U.S. 66, 90 (2012). App. Br. 8—9. According to Appellants, the alleged “natural law” must be considered in combination with the other elements of the claimed invention when determining whether a claimed invention is directed towards patent-eligible subject matter. Id. at 9. Appellants contend the allegedly non-patent eligible subject matter was excluded by the Examiner from the analysis and the remaining elements of the invention were considered separately, with little consideration given to an analysis of the claim “as a whole.” App. Br. 9. According to Appellants, the standards employed by the Examiner in the rejection were overly stringent and go well beyond the criteria that the Supreme Court’s holding in Prometheus established. Id. Appellants argue that the claims, when taken as a whole, provide a patent-eligible method to determine the likelihood of a subject having, or being susceptible to, developing chronic kidney disease (“CKD”) or end-stage renal disease (“ESRD”). Id. at 10. Appellants argue the claimed method combines several elements into what constitutes a significant advance beyond the elements when taken separately. App. Br. 10. Appellants assert that the recognition and use of the level of soluble TNF receptor type I (“sTNFRI”) in a subject is effective for determining a specific medical condition is analogous to the use of an algorithm effective for determining when to adjust molding temperature, as in Diamond v. Diehr, 450 U.S. 175 (1981). Id. Appellants contend the added elements of the present invention, when taken as a whole in combination with the alleged natural law, provide, as in Diehr, that “the process as a whole does not thereby become unpatentable subject matter,” 4 Appeal 2015-001681 Application 13/130,711 merely for containing an alleged law of nature. Id. (quoting Diehr, 450 U.S. at 187). Appellants assert that, as was the case in Diehr, they do not seek to patent a level of sTNFRI in a subject, nor the relationship of the level of sTNFRI to a medical condition. Id. (quoting Diehr, 450 U.S. at 187). Rather, Appellants assert that they seek to patent a method of determining the likelihood of a subject of having an “increased risk of developing CKD, or ESRD, or both. Id. Appellants argue further that the Supreme Court’s Prometheus analysis drew a distinction between claims that were overly preemptive versus claims that were not overly preemptive in a given field, with the latter being claims that are more likely drawn to patent eligible subject matter. App. Br. 10—11. Appellants argue that their claims on appeal, like the claims in Diehr, are not overly preemptive and are therefore drawn to patent eligible-subject matter and that they seek only to “foreclose from others the use of that [relationship] in conjunction with the other steps in the claimed process.” Id. at 10 (quoting Diehr, 450 U.S. at 187). Appellants assert further that, rather than being preemptive, the pending claims provide a teaching to the public that will facilitate research, further investigation, and further invention with regards to the discovery of new treatments and the discovery of novel drugs and their use. Id. Finally Appellants argue that their invention adds matter “significant beyond the sum of their parts taken separately” because the contribution of function of the presently claimed invention when taken “as a whole” was not considered. App. Br. 11. According to Appellants, when the functional aspects of the claimed invention are considered, it should be evident that the claimed invention provides a functionally significant difference beyond 5 Appeal 2015-001681 Application 13/130,711 merely reciting a law of nature and, therefore, is drawn to patent eligible subject matter. Id. at 11—12. We are not persuaded. When performing an analysis of whether the claims are directed to patent-eligible subject matter, we perform a two-step analysis as reflected in the Supreme Court’s Alice and Mayo precedents,2 and as set forth by the Director in the 2014 Interim Guidance on Patent Subject Matter Eligibility, December 10, 2014 (79(241) Fed Reg. 74618— 33 (December 16, 2014)) (the “Interim Guidance) for claims involving phenomenon of nature and subsequently updated in 2015 and 2016 (the “Interim Guidance”). We agree with the Examiner that the limitations of the claims on appeal, as exemplified by claim 17, are analogous to the claims at issue in Mayo and, consequently, dictate the same outcome. See Non-Final Act. 3. In performing the analysis, we first determine whether the claims on appeal are directed to a statutory category. See Interim Guidance 76422. In this instance, we conclude that they are: the claims are explicitly directed to a method or process of determining whether a human subject has an increased risk of developing CKD or ESRD, or both. See claim 17. Next, we determine whether the claims are directed to a judicially- created exception, in this instance, a natural law or phenomenon of nature. See Interim Guidance 76422—23. Although the claims require a non-novel (and unspecified) assay to determine the phenomenon, the phenomenon itself, the relationship between levels of sTNFRI and the likelihood of 2 Alice Corp. Pty. Ltd. v. CLSBankInt’l, 134 S.Ct. 2347, 2355 (2014); Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S.Ct. 1289, 1297 (2012). 6 Appeal 2015-001681 Application 13/130,711 developing CKD and ESRD, occurs naturally within the body, whether detected or not. See Spec. 5—6. Consequently we find that the claims are directed to a phenomenon of nature and therefore falls within one of the judicially-created exceptions. See Alice, 134 S.Ct. at 2355; Mayo, 132 S.Ct. at 1293. Having determined that the claims are directed to a phenomenon of nature, we next look to the claim as a whole to determine whether any element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the exception. See Interim Guidance 76423-23. The claims are directed to a specific audience, i.e., physicians treating patients for their likelihood of developing CKD or ESRD, and directs them to “measure[e] the level of soluble TNF receptor type I (sTNFRI) in the subject sample; and compar[e] the subject levels of sTNFRI with reference levels of sTNFRI.” See claim 17. It has been well settled by our reviewing court that claim steps that require “assaying” and “comparing” do not add significantly more to a claim than the recitation of the phenomenon of nature: In recent cases, we found claims “directed to” a patent-ineligible concept when they amounted to nothing more than observing or identifying the ineligible concept itself. For example, in Genetic Technologies, the claim recited methods for detecting a coding region of DNA based on its relationship to non-coding regions. Genetic Techs., Ltd. v. MerialL.L.C., 818 F.3d at 1369, 1373—74 (Fed. Cir. 2016). Because the relationship between coding and non-coding sequences was a law of nature, the claim amounted to nothing other than identifying “information about a patient’s natural genetic makeup.” Id. at 1375. Fikewise in Ariosa, the claims recited methods for detecting paternally inherited cffDNA in the blood or serum of a pregnant female. Ariosa Diagnostics, 7 Appeal 2015-001681 Application 13/130,711 Inc. v. Sequenom, Inc., 788 F.3d 1371, 1373—74 (Fed. Cir. 2015), cert, denied, No. 15—1102,----- U.S.-------- , 136 S.Ct. 2511,----- L.Ed.2d------- , 2016 WL 1117246 (June 27, 2016). The existence and location of cffDNA is a natural phenomenon; identifying its presence was merely claiming the natural phenomena itself. Id. at 1376. And in In re BRCA, the claims recited methods for screening human germline for an altered BRCA1 gene by comparing the target DNA sequence with wild-type sequence. In re BRCA1— & BRCA2—Based Hereditary Cancer Test Patent Litig., 774 F.3d 755, 761—62 (Fed. Cir. 2014). But comparing two sequences to detect alterations is a patent-ineligible “abstract mental process.” Id. at 763. Although the claims in each of these cases employed method steps, the end result of the process, the essence of the whole, was a patent-ineligible concept. See also Genetic Techs. Ltd. v. Merial L.L.C., 818 F.3d 1369 (Fed. Cir. 2016). Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc., 827 F.3d 1042, 1048 (Fed. Cir. 2016) (emphasis added). Similarly, in this case the recited steps of the claims require determining the level of sTNFRI in a subject and comparing it to reference levels. As such, these “functional” steps consist of nothing more than “observing or identifying” the ineligible concept (i.e., the relationship between sTNFRI and “comparing” them with a reference to determine the likelihood of developing CKD or ESRD. These steps, therefore, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately. The claims therefore do not amount to significantly more than the natural law itself. Appellants may have discovered the relationship between sTNFRI levels and the likelihood of developing CKD and/or ESRD, but the discovery of a phenomenon of nature is not, by itself, an invention, and is consequently not directed to patentable subject matter. See Association for 8 Appeal 2015-001681 Application 13/130,711 Molecular Pathology v. Myriad Genetics, Inc., 133 S.Ct. 2107, 2117 (2013) (“Groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the § 101 inquiry.”); Mayo, 132 S.Ct. at 1293 (‘“Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable.’”) (quoting Gottschalk v. Benson, 409 U.S. 63, 67 (1972)) (emphasis added). We therefore affirm the Examiner’s rejection of the claims on this ground. B. Rejection of the claims as obvious under 35 U.S.C. $ 103(a) Issue Appellants argue that the Examiner erred in: (1) not identifying in the cited prior art all of the elements of the claimed invention; (2) not showing why a person of ordinary skill in the art would have combined the teachings of the prior art without the benefit of the teachings of the present invention; and (3) not showing that a person of ordinary skill would have reasonably expected to succeed in combining the teachings of the cited prior art to arrive at Appellants’ claimed invention. App. Br. 14. Analysis Appellants argue Keller neither teaches nor suggests proteinuria and does not specifically identify which, if any, of the subjects taught therein may have had proteinuria. App. Br. 15. According to Appellants, proteinuria is determined in the art by measuring either total protein in urine or albumin in protein, neither of which is taught by Keller. Id. Appellants assert Keller teaches a correlation between cystatin C and TNF-aRl, however, Appellants argue, cystatin C levels and proteinuria (total protein 9 Appeal 2015-001681 Application 13/130,711 levels) are not the same. Id. Appellants therefore argue that Keller fails to teach determining if a significantly higher level of sTNFRI in subjects with proteinuria have an increased risk of developing chronic kidney disease. Id. Appellants argue Knight, which teaches that “kidney dysfunction is associated with increased risk of coronary events and inflammation, as assessed by the levels of higher sTNFRI and sTNFRII which may be correlated to the increased risk.” App. Br, 15 (quoting Non-Final Act. 6). Appellants assert Knight concludes “kidney dysfunction is associated with an increased odds of coronary events, and inflammation, as assessed by higher sTNFRI and II levels, may mediate some of this risk.” Id. (quoting Knight, Abstr.). However, Appellants argue, Knight teaches no association or prediction at all about the levels of sTNFRI and the risk of progression to CKD/ESRD. Id. Appellants argue that Tonelli is cited as teaching biomarkers of inflammation and progression of chronic kidney disease, and explicitly correlates a relationship between sTNFR-II and the rate of kidney function loss. App. Br. 15—16. However, Appellants argue, Tonelli only presents teachings with respect to sTNFRII and not sTNFRI. Id. at 16. The Examiner responds that Keller teaches that the measurement of albumin in the urine, as proteinuria, was well known in the art. Ans. 12 (citing Keller 8) (“The participants in the MESA study were more likely ... to have diabetes and a higher urine albumin to creatinine ratio,” which the Examiner asserts is known in the art as proteinuria). The Examiner finds Keller also teaches obtaining a serum sample from a human subject having proteinuria and measuring the level of differential gene expression compared to a reference control level to determine if the subject has an 10 Appeal 2015-001681 Application 13/130,711 increased risk of developing chronic kidney disease (CKD), where significantly higher sTNFRI levels indicate the increased risk. Id. at 12—13 (citing Keller Table 2). The Examiner finds Knight teaches that kidney dysfunction is associated with increased risk of coronary events and inflammation, as assessed by the levels of higher sTNFRI and sTNFRII which may be correlated to the increased risk. Non-Final Act. 6. The Examiner finds the increased levels of inflammation biomarkers, and specifically the markers: hs-CRP, IL-6, and sTNFR-I and sTNFR-II are significantly correlated with coronary events. Id. The Examiner next finds Tonelli teaches biomarkers of inflammation and progression of chronic kidney disease and explicitly correlates TNFRII and the rate of kidney function loss. Non-Final Act. 7. The Examiner finds Tonelli teaches that serum TNF-a levels are associated with the severity of proteinuria in diabetic nephropathy. Id. The Examiner concludes that a person of ordinary skill in the art would realize from the teachings of the cited references that assays showing levels of sTNFRI in serum samples from patients having proteinuria, and particularly Type II diabetes, would correlate with an increased risk of chronic kidney disease, including end stage renal failure. Non-Final Act. 7. The Examiner further concludes it would have been obvious in view of the cited references because the TNFRII marker was already known to be associated with chronic kidney disease, including end stage renal failure and soluble TNFR biomarkers were already known to be associated with decreased renal function in patients with Type II diabetes having proteinuria. Id. 11 Appeal 2015-001681 Application 13/130,711 We are not persuaded by Appellants’ arguments. Keller teaches: “After adjustment for age, sex, ethnicity, and BMI, cystatin C had statistically significant partial correlations with all six biomarkers in participants both with and without CKD (Table 2, p <0.01 for all). However, the associations with TNF-aRl and fibrinogen were significantly stronger among participants with CKD.” Keller 3. Keller concludes that: While the strong association between kidney function and TNF- aRl levels may be simply attributable to renal clearance of TNF- aRl, TNF-a itself may also play a more complex role in the mediation of kidney damage. A future study should evaluate whether TNF-a and its soluble receptors predict the longitudinal progression of kidney disease. Keller 5 (emphasis added). Keller thus teaches the likelihood that soluble TNF1 may play an important role in kidney disease and suggests its use as a predictive marker of kidney disease, providing explicit motivation for a person of ordinary skill in the art to pursue this course. Moreover, Knight teaches: Reduced kidney function may result from and cause a state of chronic inflammation, and inflammation may lead to coronary artery disease. In terms of the relation between kidney function and inflammatory biomarkers, our results are consistent with previous reports that CRP, IL-6, and sTNFR levels are higher in individuals with reduced kidney function. These levels may be higher because of increased production in individuals with kidney disease. Knight 1901 (emphasis added, internal references omitted). Knight thus teaches that it was known in the art that elevated levels of sTNFR are indicative of reduced kidney function. 12 Appeal 2015-001681 Application 13/130,711 Finally, Tonelli is directed to the association between pravastatin use, levels of C-reactive protein (CRP), soluble tumor necrosis factor receptor II (sTNFrll), and the rate of kidney function loss. Tonelli, Abstr. Tonelli teaches: Tumor necrosis factor-a (TNF-a) is a central proinflammatory agonist mediator that is generated in a wide variety of innate and adaptive immune responses, including some forms of chronic kidney disease. TNF-a binds to cell surface receptors on target cells and induces expression of adhesion molecules, chemokines for leukocytes, and apoptosis in susceptible cells. Soluble TNF receptors are elevated in the setting of inflammation and chronic kidney disease. TNF-a also appears to have multiple roles that could mediate progressive renal injury, and both soluble TNF receptor II (sTNFrll) and CRP may be used as markers of inflammation. Tonelli 237—38 (emphases added). Tonelli thus explicitly teaches that sTNFs are indicators of chronic kidney disease. We agree with the Examiner that the combined cited prior art references teach that elevated levels sTNFRs were known in the art to be associated with chronic kidney disease and that, in view of the prior art, it would have been obvious to a person of ordinary skill to use an assay for sTNFRs as an indicator of CKD. Appellants also argue that the Examiner failed to provide prima facie findings and conclusions as to why a person of ordinary skill in the art would have combined the teachings of the prior art without the benefit of the teachings of the present invention or why a person of ordinary skill would have reasonably expected to succeed in combining the teachings of the cited prior art to arrive at Appellants’ claimed invention. See App. Br. 14. However, Appellants have presented no arguments, nor adduced any 13 Appeal 2015-001681 Application 13/130,711 evidence, to support these arguments or to show that the Examiner must have relied upon impermissible hindsight reasoning. As such, these arguments amount to little more than attorney argument and we consequently accord them little weight. See In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984) (Arguments and conclusions unsupported by factual evidence carry no evidentiary weight). We therefore affirm the Examiner’s rejection of claims 17—20 on this ground. DECISION The Examiner’s rejection of claims 17—20 under 35 U.S.C. § 101 is affirmed. The Examiner’s rejection of claims 17—20 under 35 U.S.C. § 103(a) is affirmed. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R. § 1.136(a)(l)(iv). AFFIRMED 14 Copy with citationCopy as parenthetical citation