DETAILED ACTION
The amendment filed on 11/07/2025 has been entered. No new matter has been added.
Applicant’s election without traverse of Group I (Claims 1-2, 6, 8-11, 14-15, 17-18) in the reply filed on 04/03/2025 is acknowledged. Claims 24-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/03/25.
Claims 1 and 11 were amended in the claim set filed on 11/07/2025.
Claim 2 was canceled.
Claim 32 was added.
Claims 1, 6, 8-11, 14-15, 17-18, and 32 in the claim set filed on 11/07/2025 are pending and currently under examination.
Response to the Arguments
Objections to the Specification in the previously mailed non-final has been withdrawn in light of applicants Specification amendment and filing of an additional IDS.
Applicant’s arguments regarding previous rejection(s) of claim(s) 11 under 35 U.S.C. 112 have been fully considered and are persuasive. The 35 U.S.C. 112 rejections documented in the previously mailed non-final have been withdrawn in light of applicants claim amendments and arguments on Pg. 7.
Applicant’s arguments regarding previous rejection(s) of claim(s) 1-2, 6, 8-11, 14-15, and 17-18 under 35 U.S.C. 101 have been fully considered and are not persuasive. The 35 U.S.C. 101 rejections documented in the previously mailed non-final have been maintained and revised (documented below on Pg. 4-8) in light of applicants claim amendments and arguments on Pg. 8-10.
Applicant’s arguments regarding previous rejection(s) of claim(s) 1-2, 8-11, 14-15, 17-18 under 35 U.S.C. 103 have been fully considered and are not persuasive. Applicant’s argument on Pg. 10-14, states that “none of the cited documents provide any motivation for a person of ordinary skill in the art to combine the teachings of the cited prior art to arrive at a method of testing for, screening for or diagnosing cancer with improved sensitivity and specificity comprising determining the expression level of the specific combination of biomarkers, as required by the presently amended claims.” The 35 U.S.C. 103 rejections documented in the previously mailed non-final have been maintained and revised (documented below on Pg. 8-14) in light of applicants claim amendments, newly added claim 32, and arguments on Pg. 10-14.
Applicant’s arguments regarding previous rejection(s) of claim(s) 6 under 35 U.S.C. 103 have been fully considered and are not persuasive. The 35 U.S.C. 103 rejections documented in the previously mailed non-final have been maintained (documented below on Pg. 16-17) in light of applicants claim amendments and arguments on Pg. 7-8.
The rejections for claims 1-2, 6, 8-11, 14-15, 17-18 and 32 are documented below in this Final Office Action are necessitated by claim amendments filed on 11/07/2025.
Priority
This application is a U.S. National Phase Application filed under 35 U.S.C. § 371 claiming benefit to International Patent Application No. PCT/EP2020/070689, filed July 22, 2020, which claims the benefit of priority from United Kingdom Application No. GB 1910444.7, filed July 22, 2019. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy of GB 1910444.7 has been filed on Jan. 21, 2022. The priority date of claim set filed on Nov. 7, 2025, is determined to be July 22, 2019.
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, 6, 8-11, 14-15, 17-18 and 32 are rejected under 35 U.S.C. 101 because the claimed invention is directed towards a natural phenomenon of gene expression in cancer and routine and conventional biomarkers for gene expression in cancer, without significantly more. The claim(s) recite(s) natural phenomena and routine and conventional methods. This judicial exception is not integrated into a practical application because no additional elements integrate the judicial exceptions into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because no additional elements are considered significantly more than the judicial exceptions.
Claim analysis
The instant claim 1 is directed towards: A method of testing for, screening for or diagnosing cancer, comprising: a) determining the level of expression of: i) all of NEK2, FOXM1, TOP2A, MMP13, NR3C1, and S100A16; and at least 7 biomarkers selected from the group consisting of HOXA7, CENPA,DNMT1, INHBA, BIRC5, CXCL8, IVL, AND CBX7; or ii) all of HOXA7, CENPA, NEK2, FOXM1, TOP2A, BIRC5, MMP13, CXCL8, IVL, CBX7, AND S100A16; and at least 1 of the biomarkers selected from the group consisting of DNMT1 and INHBA or iii) HOXA7, CENPA, NEK2, INHBA, FOXM1, TOP2A, BIRC5, MMP13, CXCL8, NR3C1, IVL, CBX7, and S100A16; or iv) HOXA7, CENPA, NEK2, DNMT1, INHBA, FOXM1, TOP2A, BIRC5, MMP13, CXCL8, NR3C1, IVL, CBX7, AND S100A16; in a sample obtained from a patient; and b) administering a cancer therapy to the patient.
The instant claim 32 is directed towards: A method of testing for, screening for or diagnosing cancer, comprising: a) determining the level of expression of HOXA7, CENPA, NEK2, DNMT1, 1NHBA, FOXM1, TOP2A, BIRC5, MMP13, CXCL8, NR3C1, IVL, CBX7 and S100A16 in a sample obtained from a patient; and b) administering a cancer therapy to the patient.
The correlation of gene expression biomarkers to cancer is a natural phenomenon.
The determining the level of expression in step a) is considered to be an active step requiring the analysis of a sample. The active step is routine and conventional as demonstrated by Zhang et al. (“Zhang”; (2019). Co-Expression Network Analysis Identified Gene Signatures in Osteosarcoma as a Predictive Tool for Lung Metastasis and Survival. Journal of Cancer, 10(16), 3706–3716.).
Zhang teaches a method comprising “A metastasis signature was constructed according to the expression level and association with the metastasis status of genes” (Pg 3707, Lasso Cox Regression and Metastasis Signature, Para. 1). Zhang teaches a method comprising “a microarray dataset containing gene expression patterns of 19 OS cell lines and 6 normal samples (osteoblasts and bones). The platforms of these datasets are the GPL10295 Illumina human-6 v2.0 expression beadchip and GPL6102 Illumina human-6 v2.0 expression beadchip.” (Pg. 3707, Material and Methods, Para. 1). Zhang teaches a method comprising “In clinical circumstances, if we apply the signature to OS patients, we can detect the expression levels of specific genes from biopsies or surgically procured samples and predict metastasis progression. For patients with a high score or at a high risk, more frequent follow-ups and active treatment may greatly improve their survival and quality of life, corresponding with the concept of precision medicine.” (Pg. 3713, Last para.) “microarray dataset containing gene expression patterns … Illumina human-6 v2.0 expression beadchip” reads on step a). Thus, Zhang teaches a method where in determining the level of expression of the claimed combinations of biomarkers in a sample obtained from a patient.
The administering a cancer therapy to the patient is considered not particular, and is instead merely instructions to "apply" the exception in a generic way. See MPEP 2106.04(d)(2).
Dependent claims set forth further limitations about the reference markers, method of detecting and quantifying gene expression, sample, cancer, expression regulation of biomarker(s).
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case, the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, natural phenomena.
With regard to claim 1, the claim recites” A method of testing for, screening for or diagnosing cancer, comprising: a) determining the level of expression of: i) all of NEK2, FOXM1, TOP2A, MMP13, NR3C1, and S100A16; and at least 7 biomarkers selected from the group consisting of HOXA7, CENPA,DNMT1, INHBA, BIRC5, CXCL8, IVL, AND CBX7; or ii) all of HOXA7, CENPA, NEK2, FOXM1, TOP2A, BIRC5, MMP13, CXCL8, IVL, CBX7, AND S100A16; and at least 1 of the biomarkers selected from the group consisting of DNMT1 and INHBA or iii) HOXA7, CENPA, NEK2, INHBA, FOXM1, TOP2A, BIRC5, MMP13, CXCL8, NR3C1, IVL, CBX7, and S100A16; or iv) HOXA7, CENPA, NEK2, DNMT1, INHBA, FOXM1, TOP2A, BIRC5, MMP13, CXCL8, NR3C1, IVL, CBX7, AND S100A16;in a sample obtained from a patient; and b) administering a cancer therapy to the patient.” The method of determining the level of expression of a cancer biomarker is routine and conventional. Cancer cells naturally express these genes that are considered biomarkers and is thus a natural phenomenon.
With regard to claim 32, the claim recites” A method of testing for, screening for or diagnosing cancer, comprising: a) determining the level of expression of HOXA7, CENPA, NEK2, DNMT1, 1NHBA, FOXM1, TOP2A, BIRC5, MMP13, CXCL8, NR3C1, IVL, CBX7 and S100A16 in a sample obtained from a patient; and b) administering a cancer therapy to the patient.” The method of determining the level of expression of a cancer biomarker is routine and conventional. Cancer cells naturally express these genes that are considered biomarkers and is thus a natural phenomenon.
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? No, there are no additional steps that integrate the claims into a practical application.
The administering a cancer therapy to the patient is considered not particular, and is instead merely instructions to "apply" the exception in a generic way. See MPEP 2106.04(d)(2).
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No, there are no additional elements that are significantly more than the judicial exceptions.
Regarding claims 1 and 32, the claim requires the routine and conventional active steps of determining the level of expression of a cancer biomarker to determine, test or screen for or diagnose cancer similar to that of Zhang et al. (“Zhang”; (2019). Co-Expression Network Analysis Identified Gene Signatures in Osteosarcoma as a Predictive Tool for Lung Metastasis and Survival. Journal of Cancer, 10(16), 3706–3716.).
Zhang teaches a method comprising “A metastasis signature was constructed according to the expression level and association with the metastasis status of genes” (Pg 3707, Lasso Cox Regression and Metastasis Signature, Para. 1). Zhang teaches a method comprising “a microarray dataset containing gene expression patterns of 19 OS cell lines and 6 normal samples (osteoblasts and bones). The platforms of these datasets are the GPL10295 Illumina human-6 v2.0 expression beadchip and GPL6102 Illumina human-6 v2.0 expression beadchip.” (Pg. 3707, Material and Methods, Para. 1). Zhang teaches a method comprising “In clinical circumstances, if we apply the signature to OS patients, we can detect the expression levels of specific genes from biopsies or surgically procured samples and predict metastasis progression. For patients with a high score or at a high risk, more frequent follow-ups and active treatment may greatly improve their survival and quality of life, corresponding with the concept of precision medicine.” (Pg. 3713, Last para.) “microarray dataset containing gene expression patterns … Illumina human-6 v2.0 expression beadchip” reads on step a). Thus, Zhang teaches a method where in determining the level of expression of the claimed combinations of biomarkers in a sample obtained from a patient. Thus, the claim does not provide additional steps which are significantly more.
Dependent claims require reference marker(s), methods of detecting and quantifying gene expression, sample distinction, cancer type, expression regulation of biomarker(s) which are all routine and conventional based on Teh, Muy, Teck ("Teh", Patent App. Pub. No. WO 2012013931 A1, Feb. 2, 2012) in view of Zhang et al. (“Zhang”; (2019). Co-Expression Network Analysis Identified Gene Signatures in Osteosarcoma as a Predictive Tool for Lung Metastasis and Survival. Journal of Cancer, 10(16), 3706–3716.), Spetzler et al. (“Spetzler”, Patent App. Pub. No. WO 2016141169 A1, Sept. 09, 2016), Mongan et al. (“Mongan”, Patent App. Pub. No. WO 2018057971 A1, March 29, 2018), Kim et al. (“Kim”, (2012). Biomarker detection for the diagnosis of lymph node metastasis from oral squamous cell carcinoma. Oral oncology, 48(4), 311-319), Wang et al. (“Wang”, (2015). An eleven gene molecular signature for extracapsular spread in oral squamous cell carcinoma serves as a prognosticator of outcome in patients without nodal metastases. Oral oncology, 51(4), 355-362) and Sapkota et al. (“Sapkota”, S100A16 promotes differentiation and contributes to a less aggressive tumor phenotype in oral squamous cell carcinoma. BMC cancer, 15, 1-14.).
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.
Claims 1, 8-11, 14-15, 17-18 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Teh, Muy, Teck ("Teh", Patent App. Pub. No. WO 2012013931 A1, Feb. 2, 2012) in view of Spetzler et al. (“Spetzler”, Patent App. Pub. No. WO 2016141169 A1, Sept. 09, 2016), Mongan et al. (“Mongan”, Patent App. Pub. No. WO 2018057971 A1, March 29, 2018), Kim et al. (“Kim”, (2012). Biomarker detection for the diagnosis of lymph node metastasis from oral squamous cell carcinoma. Oral oncology, 48(4), 311-319), Wang et al. (“Wang”, (2015). An eleven gene molecular signature for extracapsular spread in oral squamous cell carcinoma serves as a prognosticator of outcome in patients without nodal metastases. Oral oncology, 51(4), 355-362) and Sapkota et al. (“Sapkota”, S100A16 promotes differentiation and contributes to a less aggressive tumor phenotype in oral squamous cell carcinoma. BMC cancer, 15, 1-14.).
Teh discloses methods for diagnosing cancer in a patient or for identifying a patient at risk of developing cancer. The methods comprise determining the amount of five or more biomarkers selected from HOXA7, AURKA, NEK2, FOXMIB, CCNBI, CEP55, CENPA, DNMT3B, DNMTI, HELLS, MAPKS, BMII, ITGBl, IVL and CTNNBI in a sample obtained from a patient and comparing the amount of the determined biomarkers in the sample from the patient to the amount of the biomarkers in or of a normal control (Abstract).
Regarding claims 1 and 32, Teh teaches a method comprising, determining the amount of one or more, … biomarkers selected from HOXA7, AURKA, NEK2, FOXM1B, CCNBl, CEP55, CENPA, DNMT3B, DNMT1 , HELLS, MAPK8, BMIl, ITGBl , IVL and CTNNB in a sample obtained from a patient (e.g., Pg. 1, Para 4. -Pg. 2. Para. 1, Summary of Invention). FOXM1B is interpreted as FOX1M isoform B. Teh teaches a method “comprising Prognosis and choice of treatment are dependent upon the stage of the cancer and the patient's general state of health.” (Pg. 5, Para. 6) Thus, Teh teaches a method of testing for, screening for or diagnosing cancer, comprising: a) determining the level of expression of HOXA7, CENPA, NEK2, DNMT1, and FOXM1 in a sample obtained from a patient; and b) administering a cancer therapy to the patient.
Teh does not explicitly teach INHBA, TOP2A, BIRC5, MMP13, CXCL8, NR3C1, IVL, CBX7, and S100A16 that are recited in claims 1 and 32.
Spetzler discloses methods and systems of molecular profiling of diseases, such as cancer (Abstract).
Regarding claims 1 and 32, Spetzler teaches a method wherein the cancer comprises a …, head and neck squamous cell carcinoma (HNSCC), … (e.g., Para. 55). Table 2 provides a listing of gene and corresponding protein symbols and names of many of the molecular profiling targets that are analyzed according to the methods of the invention (Para. 271, Table 2). Spetzler teaches BIRC5 and TOP2A in Table 2. Spetzler teaches “Genes and gene products that are known to play a role in cancer and can be assayed by any of the molecular profiling techniques of the invention include without limitation … MMP13...” (Para. 273). Spetzler teaches “the panel of genes assessed as part of the MI molecular profiling is expanded to include additional biomarkers... INHBA…” (Para. 471). Thus, Spetzler teaches a method comprising, determining the level of expression of one or more biomarkers selected from the group consisting of BIRC5, TOP2A, MMP13, and/or INHBA.
Mongan discloses methods and compositions that are useful for assessing gene expression for tumor immune response profile of a sample.
Regarding claims 1 and 32, Mongan teaches a method directed to a plurality of target sequences to measure the expression levels of the targets in the sample wherein the target genes are selected from immune response genes… In some embodiments, the target genes are selected from immune response genes consisting of one or more function of Table A” ( Para. 56) “CXCL8” (Pg. 27, Table A). Thus, Mongan teaches a method comprising determining the level of expression of CXCL8.
Kim discloses the gene set detected from the combined dataset classified the lymph node status more accurately in the validation dataset and clear expression patterns classifying the lymph node status based on chromosomal location were observed. The combined dataset holds promise for use as a more accurate candidate gene set for the diagnosis of lymph node metastasis and the selected gene set could be used for biological validation in further studies (Summary).
Regarding claims 1 and 32, Kim teaches a method comprising, “the selected genes from the combined dataset are summarized in Table 3” (e.g., Pg. 316) and “NR3C1” (e.g., Pg. 314, Table 3, 43rd symbol). Kim teaches a method wherein, “examined the expression patterns of genes selected from the combined dataset” and “NR3C1 on chromosome 5 was up regulated” (Pg. 319, Expression patterns of the selected genes on the chromosomal location). Thus, Kim teaches a method comprising determining the level of expression of NR3C1.
Wang discloses an 11 gene signature (GGH, MTFR1, CDKN3, PSRC1, SMIM3, CA9, IRX4, CPA3, ZSCAN16, CBX7 and ZFP3) which was robust in segregating tumors by ECS status. In node negative patients, patients harboring this ECS signature had a significantly worse overall survival (Summary-Results).
Regarding claims 1 and 32, Wang teaches a method comprising “gene expression profiling was performed using the Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform” (e.g., Pg. 356, Gene expression profiling data). Wang teaches a method comprising “identify a set of genes consistently differentially expressed between node-positive patients with ECS and those without” and “the 11 gene set included … CBX7…” (e.g., Pg. 356, Results). Thus, Wang teaches a method comprising determining the level of expression of CBX7.
Sapkota discloses both S100A16 mRNA and protein levels were found to be progressively down-regulated from normal human oral mucosa (NHOM) to oral dysplastic lesions (ODL) and oral squamous cell carcinoma (OSCC) (Abstract-Results).
Regarding claims 1 and 32, Sapkota teaches a method wherein “in the current study for the expression analysis of S100A16 by immunohistochemistry (IHC) and/or quantitative RT-PCR (qRT-PCR).” (e.g., Pg. 2, Human tissue specimens, col 2 ). Thus, Sapkota teaches a method comprising determining the level of expression of S100A16.
Teh, Spetzler., Mongan, Kim, Wang and Sapkota are all considered to be analogous to the claimed invention because they are in the same field of molecular profiling of cancer with implications in SCC. Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method comprising determining the level of expression of one or more biomarkers selected from the group consisting of HOXA7, CENPA, NEK2, DNMT1, FOXM1, IVL, … in a sample obtained from a patient and treatment of cancer as taught by Teh to incorporate the method comprising BIRC5, TOP2A, MMP13, and/or INHBA as taught by Spetzler, CXCL8 as taught by Mongan, NR3C1 as taught by Kim, CBX7 as taught by Wang, and S100A16 as taught by Sapkota and provide a method for testing screening or diagnosing cancer. Teh teaches that “there is an imperative need for a cost-effective, fast, reproducible, objective and quantitative molecular method to alleviate cancer classification dilemmas shrouding clinicians and scientists” (Pg. 1, Para. 2) and suggests that “it should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. (Pg. 42, Para. 2). Thus, one of ordinary skill in the art would be motivated to further determine the expression of INHBA, TOP2A, BIRC5, MMP13, CXCL8, NR3C1, IVL, CBX7, and S100A16 disclosed in Spetzler, Mongan, Kim, Wang and Sapkota, respectively, to further optimize the multi-target profiling of a sample for SCC if the need remained, with no change in their respective functions, and the combination would have yielded the predictable outcome of improving the classification of cancer harboring of the characteristic biomarkers and reproducibility of the testing, screening, or diagnosing method. A person of ordinary skill in the art would have had a reasonable expectation of success in incorporating the other biomarkers because determining the expression of the biomarkers in cancers such as SCC is already known in the art.
The teachings of Teh, Spetzler, Mongan, Kim, Wang and Sapkota, are documented above in the rejection of claims 1 and 32 under 35 U.S.C. 103. Claims 8-11, 14-15 and 17-18 depend on claim 1.
Regarding claim 8, Teh teaches a method wherein “The mRNA expression levels of each of the 128 genes in the transduced cells were measured” (e.g., Pg. 18, Detailed description of the invention, Figure 1). Thus, Teh teaches a method wherein determining the level of expression of one or more biomarkers comprises determining the amount of mRNA or protein corresponding to each of the biomarkers in the sample.
Regarding claim 9, Teh teaches a method wherein “the cancer is a squamous cell carcinoma (SCC)” (e.g., Pg. 5, SUMMARY OF THE INVENTION). Thus, Teh teaches a method wherein the cancer is squamous cell carcinoma (SCC), optionally wherein the SCC is head and neck SCC (HNSCC).
Regarding claim 10, Teh teaches a method wherein “the sample comprises biological … tissue obtained from the patient” (e.g., Pg. 8, para. 3-4). Thus, Teh teaches a method wherein the sample is a tissue sample.
Regarding claim 11, Teh teaches a method wherein “(b) comparing the amount of the determined biomarkers in the sample from the patient to the amount of the biomarkers in or of a normal control” (e.g., Pg. 2, para. 2). Thus, Teh teaches a method wherein the method further comprises comparing the level of expression of the one or more biomarkers to one or more control biomarkers, optionally wherein the level of expression of the one or more control biomarkers is represented by the level of expression of one or more biomarkers selected from the group consisting of YAPI, POLR2A, ACTB, GAPDH, ANDHPRTQ, further optionally wherein the level of expression of the one or more control biomarkers is the level of expression of the corresponding biomarkers from a sample obtained from a healthy patient.
Regarding claim 14, Teh, M.T., Spetzler et al., Mongan et al., Kim et al., Wang et al. and Sapkota et al. is documented above. Teh teaches a “method for diagnosing cancer in a patient or for identifying a patient at risk of developing cancer” ( Pg. 1, para. 3, Summary of Invention). Teh teaches method wherein “(HOXA7, … NEK2, FOXM1B, …, CENPA, …, DNMTI, …) show progressive upregulation and … IVL) showed progressive downregulation across the cell panel (Figure 2C)” (Pg., 32, para. 1). Teh teaches a method wherein “qPCR for each of the target genes and 2 reference genes across a training panel of 8 independent primary NHOKs (isolated from oral mucosa tissues donated by healthy disease-free individuals), 5 oral premalignant and 11 malignant oral SCC cell types” The up- or downregulation regulation of expression of target genes in cancer cells compared to normal cell is interpreted as indicative or predictive of cancer. Thus, Teh teach a method wherein upregulation of any of HOXA7, CENPA, NEK2, DNMT1, and FOXM1 and downregulation of IVL is indicative or predictive of cancer.
Regarding claim 15, Teh teaches a method wherein “All qPCR primers … associated with each biomarker panel used in this study for oral SCC (14 biomarkers plus 2 reference genes) and skin SCC (6 biomarkers and 2 reference genes) are listed in Table 1 and 2” (e.g., Pg. 26, Real-time absolute quantitative RT-PCR; Table 1-2). Primers are interpreted as a binding molecule. Thus, Teh teaches a method wherein the step of determining the level of expression of the one or more biomarkers comprises the use of a binding molecule or binding molecules specific for the biomarker or biomarkers whose level of expression is being determined, optionally wherein the binding molecule or binding molecules are oligonucleotides or antibodies.
Regarding claim 17, Teh teaches a method wherein the sample is “primary human oral cells” (e.g., Pg. 26, Real-time absolute quantitative RT-PCR, last sentence). Thus, Teh teaches a method wherein the sample is from a human.
Regarding claim 18, Teh teaches a method wherein “samples obtained from a patient
suffering from or suspected of suffering from cancer” (e.g., Pg. 13, para. 3). Thus, Teh teaches a method wherein the sample is from a patient having or suspected of having cancer.
Response to Arguments
Applicant' s arguments filed 11/07/2025 (Pg.10-13) with respect to claim 1, 8-11, 14-15, 17-18 have been considered but are not persuasive. To clarify some instances argued in the response filed 11/07/2025 see responses to each argument made by Applicant below:
Applicants’ argument: “there is nothing in any of the cited references that would motivate one of ordinary skill in the art to combine the teachings of these references to produce the presently claimed invention. Moreover, there is nothing in any of the cited references that would provide one of ordinary skill in the art with a reasonable expectation of success in making the combination in the presently claimed invention.” (Pg. 11)
Response: Applicant's argument filed 11/07/2025 has been fully considered but is not persuasive. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, as stated in the revised rejection under 35 U.S.C. 103 (documented above) towards claim 1, Teh, Spetzler., Mongan, Kim, Wang and Sapkota are all considered to be analogous to the claimed invention because they are in the same field of molecular profiling of cancer with implications in SCC. Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method comprising determining the level of expression of one or more biomarkers selected from the group consisting of HOXA7, CENPA, NEK2, DNMT1, FOXM1, IVL, … in a sample obtained from a patient and treatment of cancer as taught by Teh to incorporate the method comprising BIRC5, TOP2A, MMP13, and/or INHBA as taught by Spetzler, CXCL8 as taught by Mongan, NR3C1 as taught by Kim, CBX7 as taught by Wang, and S100A16 as taught by Sapkota and provide a method for testing screening or diagnosing cancer. Teh teaches that “there is an imperative need for a cost-effective, fast, reproducible, objective and quantitative molecular method to alleviate cancer classification dilemmas shrouding clinicians and scientists” (Pg. 1, Para. 2) and suggests that “it should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. (Pg. 42, Para. 2). Thus, one of ordinary skill in the art would be motivated to further determine the expression of INHBA, TOP2A, BIRC5, MMP13, CXCL8, NR3C1, IVL, CBX7, and S100A16 disclosed in Spetzler, Mongan, Kim, Wang and Sapkota, respectively, to further optimize the multi-target profiling of a sample for SCC if the need remained, with no change in their respective functions, and the combination would have yielded the predictable outcome of improving the classification of cancer harboring of the characteristic biomarkers and reproducibility of the testing, screening, or diagnosing method. A person of ordinary skill in the art would have had a reasonable expectation of success in incorporating the other biomarkers because determining the expression of the biomarkers in cancers such as SCC is already known in the art as cited in the prior art.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Teh, M.T. , Spetzler et al., Mongan et al., Kim et al., Wang et al., and Sapkota et al. as applied to claim 1 above, and further in view of Gresner et al. (“Gresner”, (2011). Selection of reference genes for gene expression studies in astrocytomas. Analytical biochemistry, 408(1), 163-165.).
The teachings of Teh, Spetzler, Mongan, Kim, Wang and Sapkota, are documented above in the rejection of claim 1 under 35 U.S.C. 103. Claims 6 depends on claim 1.
Regarding claim 6, Teh teaches a method comprising “the expression level of the one or more reference genes, for example YAP1 and/or POLR2A” (e.g., Pg. 3, para. 3, Summary of Invention).
Additionally, with regard to “reference markers” recited in claim 6, Gresner discloses a test a panel of six housekeeping genes (GAPDH, HPRT1, POLR2A, RPLP0, ACTB, and H3F) so as to identify and validate the most suitable reference genes for expression studies in astrocytomas (Abstract).
Gresner teaches a method comprising “the expression levels of six commonly used HKGs (glyceraldehyde-3-phosphate dehydrogenase [GAPDH]; hypoxanthine phosphoribosyl transferase [HPRT1] ; polymerase (RNA) II (DNA-directed) polypeptide A, 220 kDa [POLR2A] …” Thus, Gresner teaches a method comprising determining the level of expression of one or more reference biomarkers, optionally wherein the one or more reference biomarkers are selected form the group consisting of YAP1, POLR2A, ACTB, GAPDH, and HPRT1.
Gresner, Teh, Spetzler., Mongan, Kim, Wang and Sapkota are all considered to be analogous to the claimed invention because they are in the same field of expression profiling in cancer. Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method comprising determining the level of expression of the biomarkers HOXA7, CENPA, NEK2, DNMT1, FOXM1, IVL, INHBA, TOP2A, BIRC5, MMP13, CXCL8, NR3C1, IVL, CBX7, and S100A16 as well as the expression level of example YAP1 and/or POLR2A, in a sample obtained from a patient, treatment of cancer as taught by Teh, Spetzler, Mongan, Kim, Wang and Sapkota to incorporate the method of as taught by Gresner and provide determining the level of expression of one or more reference biomarkers. Doing so would allow for a more accurate interpretation of experimental results.
Response to Arguments
Applicant's arguments filed 11/7/2025 have been fully considered but they are not
persuasive. Arguments against Teh, Spetzler, Mongan, Kim, Wang, and Sapkota on Pg. 10-14 are not persuasive as discussed above.
Conclusion of Response to Arguments
In view of the amendments, revised rejections and responses to arguments are documented above in this Final Office Action. No claims are in condition for allowance.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KENDRA R VANN-OJUEKAIYE whose telephone number is (571)270-7529. The examiner can normally be reached M-F 9:00 AM- 5:00 PM.
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/KENDRA R VANN-OJUEKAIYE/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682