Ex Parte Andersen et alDownload PDFPatent Trial and Appeal BoardMay 25, 201613316733 (P.T.A.B. May. 25, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 13/316,733 12/12/2011 93599 7590 Eric P, Mirabel, JD, LLM 3783 Darcus Street Houston, TX 77005 05/27/2016 FIRST NAMED INVENTOR Lars Dyrskjot Andersen 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 ATTORNEY DOCKET NO. CONFIRMATION NO. SORGE-COL4A3BP 1064 EXAMINER HIBBERT, CATHERINE S ART UNIT PAPER NUMBER 1636 NOTIFICATION DATE DELIVERY MODE 05/27/2016 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): emirabel@comcast.net PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte LARS DYRSKJOT ANDERSEN, TORBEN FALCK ORNTOFT, JOSEPH A. SORGE, and ALEXEY NOVORADOVSKY1 Appeal2013-008021 Application 13/316,733 Technology Center 1600 Before ERIC B. GRIMES, ROBERT A. POLLOCK, and JACQUELINE T. HARLOW, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims to a method of predicting the likelihood of bladder cancer progression, which have been rejected as indefinite, anticipated, and directed to patent-ineligible subject matter. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. STATEMENT OF THE CASE The Specification states that bladder cancer can take the form of either recurring superficial tumors (stages Ta and T 1 ), or it can progress to a 1 Appellants identify the Real Parties in Interest as Catalyst Assets LLC and Aros Applied Biotechnology A/S. (Appeal Br. 3.) Appeal2013-008021 Application 13/316,733 muscle invasive form (stages T2 and up). (Spec. 1.) "The ability to predict which tumors are likely to recur or progress would have great impact on the clinical management of patients with superficial disease, as it would be possible to treat high-risk patients more aggressively (e.g. with radical cystectomy or adjuvant therapy)." (Id. at 2.) The Specification states that "increased expression of mRNAs or other gene products from COL4A3BP, optionally in combination with increased expression of MBNL2, F ABP4, and/or NEKl (protective markers), correlates with lack of progression of a subject's bladder cancer." (Id. at 4.) The Specification also states that increased expression of certain other markers ("harmful markers" correlates with progression of a subject's bladder cancer. (Id.) Claims 30-37 are on appeal. Claim 36 is illustrative and reads as follows: 36. A method of using a quantitative PCR ("QPCR") machine to determine gene expression levels of the protective bladder cancer progression marker COL4A3BP to generate a record of the likelihood of an individual's bladder cancer progression, said method comprising: a. Using QPCR to assay nucleic acids in a bladder cancer tumor sample from an individual to obtain a COL4A3BP Ct value representing the gene expression level of the protective marker COL4A3BP; b. Comparing said COL4A3BP Ct value to a COL4A3BP Ct value associated with a control; and c. Recording the individual's likelihood of bladder cancer progression as increased if the comparison indicates decreased expression of COL4A3BP in the sample from the individual relative to expression of COL4A3BP in said control, or recording the individual's likelihood of bladder cancer progression as decreased if the comparison indicates increased expression of COL4A3BP in the sample from the individual relative to expression of COL4A3BP in said control. 2 Appeal2013-008021 Application 13/316,733 The claims stand rejected as follows: Claims 30-37 under 35 U.S.C. § 112, second paragraph, as indefinite (Ans. 2); Claims 30-37 under 35 U.S.C. § 101 as directed to patent-ineligible subject matter (Ans. 3); and Claims 30-37 under 35 U.S.C. § 103(a) as obvious based on Mack (US 2004/0076955 Al, published Apr. 22, 2004) (Ans. 8). I The Examiner has rejected claims 30-37 as indefinite, for two reasons. (Ans. 2-3.) First, the Examiner concludes that the claims "provide for the 'using' of QPCR, but, since the claims do not set forth any active, positive steps delimiting how this use is actually practiced, it is unclear what method/process applicant is intending to encompass by the term 'using QPCR' ." (Id. at 2.) Appellants argue that "[t]he using of the QPCR machine and of QPCR is [] clearly set forth in steps in these claims to provide a clear definition of the term 'using QPCR. "' (Appeal Br. 11.) On this point, we agree with Appellants. The Examiner has not pointed to evidence showing that those skilled in the relevant art would not understand what process is referred to as quantitative PCR (QPCR) and in fact argues, in the context of the§ 101 rejection, that QPCR is a routine, conventional activity engaged in by the scientific community. (See Ans. 6- 7.) The Examiner notes that "the Mack et al reference discloses the use of QPCR for performing differential gene expression analysis is routine and 3 Appeal2013-008021 Application 13/316,733 conventional activity." (Id. at 7.) Thus, the evidence supports Appellants' position that those skilled in the art would know the scope of a step of "using QPCR" to determine the expression level of a particular gene. The second basis for the rejection is that claim 33 recites "the harmful markers in the sample" in part ( c ), but "[t ]here is insufficient antecedent basis for this limitation in the claim because there is no prior reference to a harmful marker in the claims and one of ordinary skill in the art would not be able to determine what markers would be encompassed or excluded." (Id. at 3.) On this point, we agree with the Examiner. Claim 33 recites "[u]sing QPCR to assay nucleic acids in said bladder cancer tumor sample from said individual to obtain a harmful Ct value representing the gene expression level of the harmful markers in the sample." (Claim 33, step ( c ).) However, the claim does not define which or how many harmful markers are assayed. Thus, the scope of what is required by the claim language is unclear, and the claim is indefinite. Appellants argue that "[a]lthough there is no prior reference to a harmful marker in claim 33, the term is a defined term, as shown in the specification at page 14, lines 7-9 from the bottom." (Appeal Br. 11.) The cited passage reads as follows: "Harmful markers" are indicator genes or indicator gene products for which increased expression levels indicate a less favorable prognosis, i.e., increased expression levels correlate with higher risk of progression; and decreased expression levels correlate with lower risk of progression. (Spec. 14, 3rd full i-f.) 4 Appeal2013-008021 Application 13/316,733 This definition of what markers qualify as "harmful," however, does nothing to clarify which set of harmful markers must be assayed in order to practice the method defined by claim 33. We therefore affirm the rejection of claim 33, and dependent claims 34 and 35, under 35 U.S.C. § 112, second paragraph. II The Examiner has rejected all of the claims on appeal under 35 U.S.C. § 101 as being directed to patent-ineligible subject matter. The Examiner finds that "claim(s) 30-37 are determined to be directed to a law of nature/natural principle." (Ans. 3.) The Examiner reached this conclusion by applying the test set out in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 132 S. Ct. 1289 (2012), as directed in a 2012 guidance memo. (Ans. 3-7.) Appellants argue that the claims require the use of QPCR, which is an additional element that is significantly more than the natural principle of correlating COL4A3BP gene expression levels with the likelihood of bladder cancer progression. (Appeal Br. 14--15.) Appellants also argue that the claims do not preempt the natural principle, because "[ n Jo one is foreclosed from correlating gene expression with bladder cancer progression by other processes or means." (Id. at 15.) Finally, Appellants argue that the calculations recited in the claims are not conventional and routine steps because no reference has been cited that teaches these steps. (Id. at 17-18.) We agree with the Examiner that, under the two-step test of Mayo, the claims are not directed to patent-eligible subject matter. The Mayo court applied its test to claims that are similar to those of the instant application. 5 Appeal2013-008021 Application 13/316,733 In Mayo, the claimed invention was a "method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder" comprising administering a certain class of drug and then determining the level of 6-thioguanine ( 6-TG) in a patient, where a level of 6-TG below or above certain amounts indicated a need to increase or decrease, respectively, the drug dosage. Mayo, 122 S. Ct. at 1295. Claim 3 6 of the instant application is similar, in that it is directed to a method of predicting whether a given patient's bladder cancer is or is not likely to progress from an early, superficial stage to a muscle-invasive stage, by measuring the expression of the COL4A3BP gene and comparing the result to a control. The Mayo Court concluded that the claims at issue in that case "set forth laws of nature-namely, relationships between concentrations of certain metabolites in the blood and the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm." Id. at 1296. Similarly here, claim 36 on appeal sets forth a law of nature-namely, a relationship between the level of expression of COL4A3BP and the likelihood that a bladder cancer will progress to a more invasive form. Under the first step of the Mayo test claim 36 on appeal is directed to a law of nature or natural phenomenon. The Mayo Court next turned to the question "[ w ]hat else is there in the claims before us?" Id. at 1297. The claims in Mayo included an "administering" step, a "determining" step, and a "wherein" clause. Id. The Court concluded that "[t]he upshot is that the three steps simply tell doctors 6 Appeal2013-008021 Application 13/316,733 to gather data from which they may draw an inference in light of the correlations." Id. at 1298. In other words, the claims inform a relevant audience about certain laws of nature; 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. Id. The Court concluded that "the steps are not sufficient to transform unpatentable natural correlations into patentable applications of those regularities." Id. Like the steps of the claims in Mayo, the manipulative steps of claim 36 on appeal also "consist of well-understood, routine, conventional activity already engaged in by the scientific community." Id. "Using QPCR" to measure the expression level of a given gene is conventional, as shown by Mack: "Often, amplification-based assays are performed to measure the expression level of bladder cancer-associated sequences .... Methods of quantitative amplification are well known to those of skill in the art." (Mack ii 153.) The step of comparing gene expression levels is also routine, as also shown by Mack, which states that its "invention provides nucleic acid and protein sequences that are differentially expressed in bladder disease or cancer relative to normal tissues." (Id. at ii 104.) The final step of claim 36, recording the result, simply preserves and informs others of the correlation. Thus, when claim 3 6 is considered as an ordered combination, it informs a relevant audience of certain laws of nature: specifically, that the expression level of COL4A3BP can be used to distinguish between bladder 7 Appeal2013-008021 Application 13/316,733 cancer patients whose cancer is more likely or less likely to progress. All of the additional steps of claim 36 consist of well-understood, routine, conventional activity already engaged in by the scientific community such as Mack. We conclude that, under the Mayo test, claim 36 is directed to patent- ineligible subject matter. The rejection of claim 36 under 35 U.S.C. § 101 is affirmed. Independent claims 30 and 33 add more data manipulation steps, but those steps merely determine the level of COL4A3BP expression relative to other (protective or harmful) markers, in order to determine the likelihood of bladder cancer progression. Although the specific natural principle of claims 30 and 33 involves expression levels of genes in addition to COL4A3BP, these claims also add nothing more than routine and conventional steps of data manipulation that are required to inform the relevant audience of the natural principle itself. We therefore conclude that all of the claims on appeal are directed to patent-ineligible subject matter. III The Examiner has rejected claims 30-37 as obvious based on Mack. The Examiner finds that Mack "measure[s] the gene expression level of the marker COL4A3BP using QPCR" and calculates Ct values to determine whether the gene is up- or down-regulated in bladder cancer. (Ans. 9.) The Examiner also finds that Mack includes COL4A3BP in its "Table 9A, entitled 'Genes predictive of no bladder cancer progression.'" (Id.) The Examiner finds that steps (b) and ( c) of claim 36 "are directed to mental steps and/or recording steps" and therefore are not entitled to patentable weight. (Id. at 11.) 8 Appeal2013-008021 Application 13/316,733 As Appellants point out (Appeal Br. 20), however, Mack includes COL4A3BP (or "collagen IV, type 3 (Goodpasture)") both in its Table 8A of genes that are predictive of bladder cancer progression and in its Table 9 A of genes that are predictive of no bladder cancer progression. (Mack, pages 135 and 144). In view of this contradictory data, the Examiner has not adequately explained what result would be expected from determining a patient's COL4A3BP expression level that would lead a skilled artisan to select COL4A3BP for quantitating a patient's gene expression level. Thus, we conclude that the Examiner has not shown that it would have been obvious to measure the expression level of COL4A3BP as a gene predictive progression of bladder cancer or predictive of no progression of bladder. We therefore reverse the rejection under 35 U.S.C. § 103(a). SUMMARY We affirm the rejection of claims 33-35 under 35 U.S.C. § 112, second paragraph, but reverse the rejection of claims 30-32, 36, and 37. We affirm the rejection of claims 30-37 under 35 U.S.C. § 101. We reverse the rejection of claims 30-37 under 35 U.S.C. § 103(a). TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED 9 Copy with citationCopy as parenthetical citation