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. Currently, claims 1-3, 6-13, 20-23, 25, and 28-31 are pending and under consideration in the instant application. Information Disclosure Statement The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. Claim Rejections - 35 USC § 101 35 U.S.C. 101 reads as follows: 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. Claims 1-3, 6-13, 20-23 and 25 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); s ee 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 method s of evaluating the prognosis of HPV associated head and neck cancer patients or predicting response to treatment based on detecting defects in the genes recited in the claims, or their expression products, or changes in expression levels of mRNA expression products of the genes recited (eg claim 20). This recitation is a natural correlation between defects (mutations) in the genes or changes in expression levels of genes and prognosis /response to treatment of HPV associated head and neck cancer patients. 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 “evaluating prognosis”, “predicting response”, “develop a treatment strategy”, and “normalizing” mRNA expression levels, which are r ecitation of abstract idea s because they encompasses conclusions and determinations which can occur entirely within the mind , as well as describing mathematical relationships and calculations . 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 detecting defects or mRNA expression of combinations of genes, however th ese steps do not integrate the JE into a practical application because they are mere data gathering step s to use the correlation and do not add a meaningful limitation to the method. Although dependent claims recite “develop” a treatment strategy, this is itself an abstract idea because it encompasses just thinking about appropriate treatments. Additionally, th is generally recited element is considered nothing more than instructions to apply the law of nature . 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 step of detecting defects or mRNA expression levels are g enerally 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. Not only are these steps directed to data gathering, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). 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. Claims 28-31 are rejected under 35 U.S.C. 101 because the claimed invention is directed to product s of nature without significantly more. This judicial exception is not integrated into a practical application and the claims 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, part II. The unpatentability of natural products was confirmed by the U.S. Supreme Court in Association for Molecular Pathology v. Myriad Genetics, Inc., , 133 S. Ct. 2107, 2116, (2013). 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 claims were 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 claims were 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) ]. In the absence of a step(s) or element(s) that integrate the JE into a practical application, the additional elements/steps have been considered to determine whether they add significantly more to the JE ( STEP 2B ) [ 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) ]. It was found that the present claims fail to meet the elements required for patent eligibility . The claims are directed to nucleic acid probes, which also encompass PCR primers, and as such , are directed to products. Accordingly, the claims are directed to one of the four statutory cat e gories of invention. The claims are drawn to nucleic acid primers or probes which detect naturally occurring mutations, including those which hybridize to naturally occurring sequences. These include SEQ ID NOS 1-4 and those that can detect SEQ ID NO: 6 or 8. However, these sequences are directed to fragments of naturally occurring sequences. As such the claims are directed to a product of nature which is a judicial exception. This judicial exception is not integrated into a practical application because the nucleic acid molecules encompassed by the claims convey the same genetic information as their naturally occurring counterparts . The Supreme Court has made clear "separating [DNA] from surrounding genetic material is not an act of invention" Myriad , 133 S. Ct. at 2117. In Myriad v. Ambry CAFC 2014-1361,1366, December 17, 2014, the CAFC further (regarding a claim directed to a pair of primers) stated “In fact, the naturally occurring genetic sequences at issue here do not perform a significantly new function. Rather, the naturally occurring material is used to form the first step in a chain reaction—a function that is performed because the primer maintains the exact same nucleotide sequence as the relevant portion of the naturally occurring sequence. One of the primary functions of DNA’s structure in nature is that complementary nucleotide sequences bind to each other. It is this same function that is exploited here—the primer binds to its complementary nucleotide sequence. Thus, just as in nature, primers utilize the innate ability of DNA to bind to itself.” The claims do not recite any additional limitations that add significantly more to the JE’s recited. None of these molecules or cells are patent eligible, whether isolated or not, pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics Inc ., US (June 13, 2013). Accordingly, the claims are rejected as being directed to non - patentable subject matter. Claim Rejections - 35 USC § 112 112(a) The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. Claims 1-3, 6-13, and 25 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim s contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention. Relevant to the lack of particular structural limitations in the rejected claims drawn to any defects in TRAF3, CYLD, TRAF2, MYD88, NFKBIA, TNFAIP3, TRAF6, BIRC2, BIRC3, and MAP3K14 which are associated with prognosis of HPV associated head and neck cancer, MPEP 2163 states: The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art. Additionally, at 2163IIA3(a), the MPEP states: “…describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly , 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene “because it is only an indication of what the gene does, rather than what it is.”); see also Fiers , 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co ., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co ., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”). The claims are broadly drawn to methods of evaluating prognosis or treatment response of HPV associated head and neck cancer patients by detecting any defect in any of the genes comprising TRAF3, CYLD, TRAF2, MYD88, NFKBIA, TNFAIP3, TRAF6, BIRC2, BIRC3, and MAP3K14 , or their expression products. In the case of the instant claims, the functionality of identifying defects, such as non coding SNPs, missense, nonsense, frameshift, inversions, translocations, or deletions in the genes listed which are associated with prognosis or treatment response in HPV associated head and neck cancer patients is a critical feature of the claimed methods. The specification teaches analysis of clinical data from TCGA HNSCC cohort for analysis of gene mutations in patients. Although the specification teaches at figure 1, that mutations occurred in the genes recited in the claims, the specification does not identify the mutations, other than CYLD N300S or D618A, nor does the specification teach which of the many possible mutations that are found in the recited genes are capable of predicting HPV associated head and neck cancer prognosis or treatment response. While the skilled artisan may be capable of detecting defects in the recited genes, or their expression products, poss ession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rocheste r, 358 F.3d at 927, 69 USPQ2d at 1895. The claims encompass a n enormous genus of structurally undefined defects, such as non coding SNPs, missense, nonsense, frameshift, inversions, translocations, or deletions , in the genes listed or their expression products. For claims drawn to a genus, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc ., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem , 323 F.3d at 966, 63 USPQ2d at 1615. Further, University of California v. Eli Lilly and Co ., 43 USPQ2d 1398, 1404, 1405 held that: To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“ [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966. Thus considering the breadth of the mutations required by the claimed methods, their specific required functionalities, and the teachings of the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter. Claim Rejections - 35 USC § 102 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale , or otherwise available to the public before the effective filing date of the claimed invention. Claims 1-3, 8, 10, 13, 20-23 and 25 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Hayes (Hayes et al; WO2013/192089; cited in the IDS dated 12/9/2023) . With regard to claims 1-3, 8, 13, 20-23, and 25, Hayes teaches methods of prognosing head and neck cancer. Hayes teaches analysis of copy number variations using Affymetrix Genomewide SNP6.0 chips and mRNA expression using Agilent 44K microarrays (claim 8) , which contain probes for analysis of each of the genes listed in the claims. It is noted that the claims do not require that a defect be found in each gene listed. Therefore, the broadest reasonable interpretation of the claims encompasses analysis of the genes recited in claims 1, 13, and 20-22 (para 00226-00239). It is further noted that this is the only active step required by the claims. With regard to claim 12, Hayes teaches analysis of frozen surgically extracted tumors (para 00226). With regard to claim 10, Hayes teaches developing treatment regimen (see claim 26 of Hayes). Accordingly, the teachings of Hayes anticipates in the instant claims. Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claims 1-3, 6-13, 20-23, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Spetzler (Spetzler et al; WO2016/141169; cited in the IDS filed 12/9/2023) in view of Hayes. Spetzler teaches mutational analysis of genes in patient for analysis of cancer, including HPV associated head and neck carcinoma and oropharyngeal HNSCC (abstract, whole document, para 0055). Spetzler teaches analysis of expression compared to control (para 0037, 00438, 00148). Spetzler teaches mutations include Missense, nonsense, frameshift, etc (para 0046, 00208). Spetzler teaches analysis includes RT-PCR, and NGS (para 0043, 0089, 00117, 00201, 00208), etc. Spetzler teaches analysis of medical and family history (para 00310, 00346) . Spetzler teaches analysis including in formalin fixed paraffin embedded samples (0050). Although Spetzler does not specifically list all of the genes recited in the claims, Hayes teaches analysis of gene mutations and expression analysis in patients with HPV associated head and neck cancer using Affymetrix and Agilent microarrays which contain probes for analysis of all of the genes listed in the claims. Therefore it would have bene prima facie obvious to the ordinary artisan prior to the effective filing date to have used the arrays taught by Hayes in the method of Spetzler with a reasonable expectation of success. Claims 28-31 are rejected under 35 U.S.C. 103 as being unpatentable over Hajek (Hajek et al; Cancer, vol 123, pages 1778-1790, 2017; cited in the IDS dated 12/9/2023) in view of Morten (Morten. J.; US 6,316,196; 2001) . Hajek teaches detecting the N300S and D618A mutation in CYLD in patients with HPV associated head and neck cancers (see table 1). Hajek does not teach probes for primers for detecting the mutations, however Morten provides a review of methods of detecting missense mutations in DNA (see whole document). Morten teaches performing PCR following by the use of allele specific primers (probes) to detect nucleotide substitutions. Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have constructed primers, including allele specific primers, for detecting the known N300S and D618A mutations in the known CYLD gene with a reasonable expectation of success. The ordinary artisan would have been motivated to construct oligonucleotides to detect these mutations because Hajek teaches they are associated with HPV associated head and neck cancer and Morten teaches and exemplifies the routine nature of designing primers for detecting known mutations. Absent secondary considerations, the SEQ ID NOS in claim 30 are considered obvious in view of the teachings of the cited prior art. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner is a hoteling examiner and can normally be reached Mondays-Fridays from 8:00 AM to 2 :00 PM Eastern Time Zone . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Winston Shen, can be reached on (571) 272-3157. The fax phone number for organization where this application or proceeding is assigned is (571) 273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /JEHANNE S SITTON/ Primary Examiner, Art Unit 1682