DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Currently, claims 1-20 are pending in the instant application. Claims 3-9 and 20 are withdrawn from consideration as directed to a non-elected invention. Claims 1-2 and 11-19 are currently under examination. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are either newly applied, as necessitated by amendment, or are reiterated. They constitute the complete set being presently applied to the instant Application. Response to Applicant's arguments follow. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.
Claim Rejections - 35 USC § 101
Claims 1, 2, and 10-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation/law of nature and an abstract idea without significantly more. This judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, 561 U.S. 593, 601 (June 28, 2010) and Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014). See also Myriad v Ambry, CAFC 2014-1361, -1366, December 17, 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Dia-mond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. at 601 (2010).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1).
The instant claims are directed to methods and therefore are directed to one of the four statutory categories of invention.
The claims are then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)].
The claimed invention recites a method of assessing an individual’s risk for metastatic colorectal cancer by performing a detection assay to detect genetic aberrations in PTPRT, TCF7L2, AMER1 (FAM123B), APC, SMAD4, TP53 and KRAS. However, this recitation is a natural correlation between the presence of genetic aberrations in the recited genes and metastatic colorectal cancer. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. The claimed invention also recites “assessing an individual’s risk”, “determining that each gene … exhibits a genetic abnormality”, which are directed to abstract ideas because they encompasses conclusions and determinations, as well as reading a report that lists genetic aberrations, respectively, which can occur entirely within the mind. It is therefore determined that the claims are directed to judicial exceptions.
The claims are then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)].
The claims recite steps of performing a detection assay to detecting genetic aberrations the recited genes, however this does not integrate the JE into a practical application because it is a mere data gathering step to use the correlation and does not add a meaningful limitation to the method.
Although dependent claims recite “administering to the individual a treatment based upon that each gene… exhibits a genetic abnormality…which is further based upon the clinical stage of the cancer progression…”, such treatments include “prolonged monitoring” which requires nothing more than further data gathering. The Supreme Court does acknowledge that it is possible to transform an unpatentable law of nature, but one must do more than simply state the law of nature while adding the words "apply it.” CLS BankInt’l, 134 S.Ct. at 2358; Prometheus, 132 S. Cl, at 1294.
In the absence of steps or elements that integrate the JE into a practical application, the additional elements/steps are considered to determine whether they add significantly more to the JE either individually or as an ordered combination, to “’transform the nature of the claim’ into a patent eligible application” [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)] (STEP 2B).
In the instant situation, the steps of examining genetic material of a biopsy are generally recited and do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This is not only directed to data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). The administering steps also encompass further data gathering which are well understood routine and conventional. Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[t]o put the matter more succinctly, 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.” Therefore these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
When viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
Response to Arguments
The response traverses the rejection and asserts that claim 1 is subject matter eligible under step 2A prong 2 because it is directed to an improved application of assessing metastatic colon cancer risk, where the assessment yields a risk prognosis based on identifying genetic aberrations within a distinct set of genes. The response asserts that the step of “performing a detection assay” allows identification of genetic aberrations which implicates treatment regimens for increased metastatic risk. This argument has been thoroughly reviewed but was not found persuasive. The claims do not recite any particular risk prognosis, however even if they did, such a risk prognosis is itself a natural correlation. The mere recitation of a judicial exception itself is not sufficient to render the claims subject matter eligible. The response further asserts that under step 2B, the claim recites additional elements that are not well understood, routine, and conventional. This argument has been thoroughly reviewed but was not found persuasive because the steps are generally recited. The mere recitation of a “detection assay” broadly encompasses any of the many routine sequencing techniques which are commonly used in the field of cancer genetics to detect mutations in particular genes. This is also evidenced by the teachings in the specification, the references cited in applicants IDS, as well as the references cited in this office action below. The response also asserts that there is a direct connection between the limitations that perform the detection assay and the determination from the results of the assay that genes in the recited gene combination sets exhibit a genetic abnormality that confers a pathogenic effect on gene function. This argument has been thoroughly reviewed but was not found persuasive because this is also directed to the natural correlation between the gene mutations and their effect on gene function. The arguments that the claims do not recite insignificant extra solution activity because the performance of the detection assay is not incidental is not found persuasive because the general recitation of detection of mutations in known genes is considered well understood, routine, and conventional. For these reasons and the reasons already made of record, the rejection is maintained.
Claim Rejections - 35 USC § 103
Claims 1, and 11-18 are rejected under 35 U.S.C. 103 as being unpatentable over Oliveira (Oliveira et al; Oncotarget, vol 9; May 18, 2018; pp 23960-23974).
With regard to claims 1, 11-15, Oliveira teaches (see whole document) obtaining biopsies from colorectal tumors of patients with colorectal cancer (page 23970, col 2), extracting DNA from the pathological tissues, and performing next generation sequencing (page 23971, col 1). Oliveira teaches detecting mutations in each of PTPRT, TCF7L2, AMER1 (FAM123B), APC, SMAD4, TP53, and KRAS (page 23963, col 2-page 23964; figure 3; supplementary figure 11; see also supplemental table S2 included as an appendix to the office action). With regard to claim 13, Oliveira teaches detecting single nucleotide variants (see supplementary figures). With regard to claims 16-18, Oliveira teaches analysis and detection of mutations that were previously known oncogenic mutations from the COSMIC database, as well as novel mutations (page 23964, col 2; supplementary figure 11). With regard to claim 19, Oliveira teaches that the damaging effects of the identified variants were evaluated through prediction algorithms (page 23971, col 2). Although Oliveira does not teach detecting mutations in these genes in the same biopsy of an individual, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date, that the presence of mutations in the same sample would be associated with colorectal cancer.
Claims 1, 2, and 10-19 are rejected under 35 U.S.C. 103 as being unpatentable over Oliveira, as applied to the claims above, and further in view of Huang (Huang et al; Cancer and Metastasis Reviews, January 2018; vol 37, pages 173-187) and Bianchi (Bianchi et al; The Lancet; vol 17; 2016, pages 738-746).
The teachings of Oliveira are set forth above and incorporated herein. Oliveira does not teach administration of treatment based on that each gene contains a genomic abnormality, or on stage, where the stage of cancer is stage IV. However, Huang teaches that mutations in SMAD4, KRAS, and TP53 are known to be driver mutations in colorectal cancer metastasis, while Oliveira teaches detection of mutations in all of the genes recited. Further, Bianchi teaches targeted adjuvant chemotherapy treatment in patients with stage IV colorectal cancer. Therefore it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to treat patients with mutations in the recited genes, as taught by Oliveira and Huang, and with stage IV disease, with targeted adjuvant chemotherapy for the obvious benefit providing treatment for colorectal cancer as taught by Bianchi.
Response to Arguments
The response traverses the rejection. The arguments directed to the assertions that Oliveira does not teach
“performing a detection assay on genetic material ... to detect genetic aberrations within a set of genes comprising PTPRT, TCF7L2, AMER1, APC, KRAS, TP53, and SMAD4;
detecting genetic aberrations occurring within the genes PTPRT, TCF7L2, AMER1, APC, KRAS, TP53, or SMAD4; and
determining from the results of the detection assay that each gene of one of the following combinations of gene sets exhibits a genetic abnormality that confers a pathogenic effect on gene function.” are not found persuasive because Oliveira does in fact teach performing a detection assay and detecting mutations in all of the recited genes. Supplemental table 2 of Oliveira describes in detail, all of the mutations that were found in colorectal cancer patients, including in patients with poor prognosis (metastasis). This table is available on the internet as a downloadable excel spreadsheet, a portion of which has been included as an appendix to the office action. The recitation of “determining … that gene sets exhibit a genetic abnormality that confers a pathogenic effect on gene function” requires nothing more than recognizing that the mutations are found in genes known to be associated with cancer. The only active steps required by the claims are to perform a detection assay, detect genetic aberrations, and determine that the mutations are pathogenic. These steps are not only taught by Oliveira, but the pathogenicity of the mutations is inherent to the mutations themselves. The claim is so generally recited, that no particular analysis is actually required other than performing the assay and detecting aberrations. The response also asserts that “ Claim 1 is based on the discovery that metastatic competence within colon cancer is based on whether certain gene combinations exhibit a genetic abnormality (Specification, 0167-0168 and Figs. 43 & 44). When each gene of the combination was determined to exhibit a genetic abnormality, the cancer had greater metastatic cancer potential, resulting in greater risk.” This argument has been thoroughly reviewed but was not found persuasive because these arguments are directed to an intended use and do not distinguish the active steps required by the claims from the teachings of the cited prior art. The rejections are maintained and applied the newly amended claims.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682