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 .
Claims 1-20 are pending and are being examined on the merits.
Information Disclosure Statement
The Information Disclosure Statements submitted October 30, 2024, January 29, 2025, May 14, 2025, October 16, 2025 and August 25, 2026 have each been considered. However, the Examiner notes that none of the references in any of the IDSs seem to relate to the instantly claimed subject matter. For example, US Patent No. 11,085,663 (10/30/2024 IDS, No. 10) is directed to “[a]n environmental control system for a building including … HVAC equipment”, while US Patent App. Pub. No. 2019/0331802 (8/25/2026, No. 7) is directed to “[a] method [for] obtaining barometric data … and sound intensity data”.
Drawings
The drawings are objected to because 2 different figures are labeled as “7A” – 1 on p. 7 of the drawings and 1 on p. 8 of the drawings.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Specifically, an embedded hyperlink appears at para. 97.
The disclosure is objected to because of the following informalities: the specification refers to Fig. 8 (para. 73), but there is no Fig. 8 in the drawings.
Appropriate correction is required.
Claim Objections
Claims 3 and 15 are objected to because of the following informalities:
In each of claims 3 and 15, the limitation “head & neck” should be “head and neck”.
Appropriate correction is required.
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 1-15 and 20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Eligibility is considered in light of MPEP 2106 III, which incorporates the 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG) published on January 17, 2019 (84 Fed. Reg. 50) and clarified in the October 2019 Update.
As can be seen in the MPEP 2106 III Figure, eligibility analysis requires one to address the following questions: (i) Step 1 – Is the claim directed to one of the four statutory categories (i.e., process, machine, manufacture or composition of matter); (ii) Step 2A – Is the claim directed to a judicial exception (i.e., a natural phenomenon, law of nature or abstract idea); and (iii) Step 2B – does the claim recite additional elements that amount to significantly more than the judicial exception. In addition, as can be seen in the MPEP 2106.04 II Figure, Step 2A is a two-prong inquiry, with Prong One asking whether the claims recite a judicial exception (i.e., an abstract idea, natural phenomenon or law of nature) and Prong Two asking whether the claims recite additional elements that integrate the judicial exception into a practical application.
In this case, as to Step 1, claims 1, 8 and 14 are directed to one of the four statutory categories since they are drawn to a process.
The analysis cannot be streamlined, so the claims are considered with respect to Step 2A.
With respect to Prong One of Step 2A, claims 1, 8 and 14 recite a judicial exception. Specifically, the correlation between the elevated copy numbers of the MYC and HSF1 genes and the sample having an increased susceptibility to a therapeutic inhibitor is a law of nature. In addition, in claim 8, the step of determining whether the biological sample has reduced cell viability is an abstract idea, and the correlation between the reduced cell viability and the increased susceptibility to the epigenetic inhibitor is a law of nature. Further, in claim 14, the correlation between the elevated copy numbers of the MYC and HSF1 genes and the subject having cancer is a law of nature.
With respect to Prong Two of Step 2A, the claims do not recite additional elements that integrate the judicial exception into a practical application for the following reason. In particular, the claims do not recite additional elements that integrate the judicial exception into a practical application because the elements in the claims other than the judicial exception (i.e., obtaining biological samples, measuring for gene copy numbers and measuring cell viability) constitute insignificant extra-solution activity as described in the 2019 PEG and MPEP 2106.05(g). Further, regarding the step of “administering … an inhibitor to the subject” in claim 14, this limitation does not integrate the judicial exception into a practical application because the “inhibitor” treatment is not a “particular treatment” in that the term “inhibitor” is general enough that it can be construed to cover any possible treatment of the subject (i.e., “administer[] [a] [cancer] inhibitor to the subject [with cancer]” is essentially equivalent to reciting “treat the cancer”).
Thus, the answer to step 2A is “Yes, the claims are directed to a judicial exception”, and the analysis mover to Step 2B, which asks if the additional elements in the claim amount to significantly more than the judicial exception.
In this case, claims 1-15 and 20 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because only routine and conventional elements are recited in combination with the judicial exceptions. As evidenced by Cyran, Martins, Brusselaers and Hansen (cited below in conjunction with the prior art rejections), the steps obtaining biological samples, measuring gene copy numbers and measuring cell viability, were performed routinely prior to the effective filing date of the claimed invention. Further, claims 4 and 20 only recite additional features of the judicial exceptions themselves. Therefore, the additional elements in claims 1-3 and 5-15 are not non-routine or unconventional.
In view of the foregoing, claims 1-15 and 20 are rejected under 35 U.S.C. 101 as being drawn to a judicial exception without significantly more.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1, 4 and 8 each recite the limitation “indicates increased susceptibility to the
[therapeutic/epigenetic] inhibitor”, the meaning of which is unclear. Specifically, the increase is relative to what metric? Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite.
Claims 2-7 depend directly or indirectly from claim 1, and consequently incorporate the
indefiniteness issues of claim 1.
Claims 9-13 depend directly or indirectly from claim 8, and consequently incorporate
the indefiniteness issues of claim 8.
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 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Cyran (Heat Shock Proteins and HSF1 in Cancer, Front. Oncol., 12, 1-21, 2022) in view of Brusselaers (Copy number of 8q24.3 drives HSF1 expression and patient outcome in cancer: an individual patient data meta-analysis, Human Genomics, 13:54, 1-12, 2019) and Martins (Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer, Nature Communications, 13:6330, 1-14, 2022).
Regarding independent claims 1 and dependent claims 2-3 and 5, Cyran teaches …
A method of determining in a biological sample, optionally a tumor, optionally
breast cancer, endometrial cancer, esophageal cancer, liver cancer or pancreatic cancer, obtained from a human … comprising the steps of: a) measuring copy number of the MYC gene in the biological sample and determining that the copy number of the MYC gene is elevated; and b) measuring copy number of the HSF1 gene in the biological sample and determining that the copy number of the HSF1 gene is elevated (Sections 5, 5.1.2; Fig 3A).
As noted, Cyran teaches elevated copy numbers for each of MYC and HSF1 in various cancers. Cyran also teaches that MYC and HSF1 are both at chromosome locus 8q24.3 (p. 10, left col., para. 2). Cyran does not teach determining that the elevated copy number is greater than or equal to three. Cyran also does not teach that the samples with such elevated copy numbers have increased susceptibility to a therapeutic inhibitor.
Martins teaches MYC gene amplifications in ovarian cancer, and in particular, identified gains (3 or 4 copies) and amplifications (5 or more copies) in the MYC gene (Fig. 3B; p. 4, right col., para. 1). Martins teaches measuring copy number using next-generation sequencing (p. 4, left col., para. 2). Martins also teaches an association between MYC copy number and response to therapy (Figs. 3B, 3H; p. 4, right col., para. 1 through p. 5, left col., para. 1; p. 5, left col., para. 5).
Brusselaers teaches HSF1 copy number alterations in various cancers and also teaches that HSF1 copy number alteration strongly correlates with copy number alterations of the other genes on 8q24.3 (p. 6, left col., para. 2), which includes MYC, as taught by Cyran.
Thus, the combination of Cyran, Martins and Brusselaers teaches or suggests all of the limitations of claims 1-3 and 5.
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Cyran method to incorporate the copy number alterations of MYC (i.e., an increase of at least 3), as taught by Martins. The ordinary artisan would have been motivated to do so to achieve the expected advantage of a more precise assay for characterizing a tumor. The ordinary artisan would have been motivated to further incorporate into the Cyran method the copy number alterations of HSF1 (i.e., an increase of at least 3) as taught or suggested by the combination of Cyran and Brusselaers, which teaches that MYC and HSF1 are both at chromosome locus 8q24.3, and that HSF1 copy number alteration strongly correlates with copy number alterations of the other genes on 8q24.3. The ordinary artisan would have been motivated to do so to achieve the expected advantage of a more precise assay for characterizing a tumor. The ordinary artisan would have had an expectation of success as the design and modification of biomarker assays is well-known in the art.
It would have been additionally obvious to incorporate the step of determining an increase in susceptibility to a therapeutic inhibitor, as taught by Martins. The ordinary artisan would have been motivated to do so to achieve the expected advantage of an assay with the additional capability of selecting an appropriate therapeutic inhibitor. The ordinary artisan would have had an expectation of success as the design and modification of biomarker assays is well-known in the art.
Finally, it would have been further obvious to measure the gene copy numbers using next-generation sequencing, as such a technique is known in the art as being suitable for that intended purpose. MPEP 2144.07. Further, the ordinary artisan would have been motivated to optimize the assay as needed through routine experimentation. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid assays is well-known in the art.
Regarding dependent claim 4, Martins teaches that the copy number of MYC is greater than or equal to five (Fig. 3B; p. 4, right col., para. 1), while Brusselaers teaches HSF1 copy number alterations in various cancers and also teaches that HSF1 copy number alteration strongly correlates with copy number alterations of the other genes on 8q24.3 (p. 6, left col., para. 2), which includes MYC, as taught by Cyran. Further, Martins suggests that at least 5% of the cells in the sample have such a copy number. Specifically, Martins teaches deriving spheroids from (ovarian) cancer samples and determining the copy number data for each spheroid (Fig. 3E: shows MYC copy numbers in various spheroids of 5 or above, including 7, 16 and 20 copies). Martins also teaches that the prevalence of chromosomal alterations across in the genome in the spheroid cohort is approximately 80% for MYC (Fig. 2A). Thus, Martins at least suggests that at least some of the spheroids have large copy number increases and that these alterations occur across the majority of their genomes.
Prior to the effective filing date of the instant invention, it would have been prime facie obvious to further modify the modified Cyran assay, discussed above, to incorporate the copy number alterations of MYC (i.e., an increase of at least 5), as taught by Martins, and to incorporate the copy number alterations of HSF1 (i.e., an increase of at least 5) as taught or suggested by the combination of Cyran and Brusselaers, which teaches that MYC and HSF1 are both at chromosome locus 8q24.3, and that HSF1 copy number alteration strongly correlates with copy number alterations of the other genes on 8q24.3. The ordinary artisan would have been motivated to do so to achieve the expected advantage of a more precise assay for characterizing a tumor. It would have been further obvious to limit the sample to those with at least 5% of the cells in the sample have such a copy number as doing so would result in the expected advantage of increasing the sensitivity and specificity of the assay by removing non-target samples. The ordinary artisan would have had an expectation of success as the design and modification of biomarker assays is well-known in the art.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Cyran (Heat Shock Proteins and HSF1 in Cancer, Front. Oncol., 12, 1-21, 2022) in view of Brusselaers (Copy number of 8q24.3 drives HSF1 expression and patient outcome in cancer: an individual patient data meta-analysis, Human Genomics, 13:54, 1-12, 2019) and Martins (Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer, Nature Communications, 13:6330, 1-14, 2022)as applied to claim 1 above, and further in view of Valinciute (Class 1 HDAC Inhibitors and PLK1 Inhibitors Synergize in MYC-Amplified Medulloblastoma, Neuro-Oncology, 23, Supplement 1, p. i5, 2021).
Regarding dependent claim 6, Valinciute teaches treating MYC-amplified tumors with PLK1 inhibitors and HDAC inhibitors.
Prior to the effective filing date of the instant invention, it would have been prime facie obvious to further modify the modified Cyran assay, discussed above, to incorporate the PLK1 inhibitors and HDAC inhibitors, as taught by Valinciute, as such inhibitors are known in the art as being suitable for that intended purpose. MPEP 2144.07. Further, it would have been obvious to try the inhibitors in order optimize the assay as needed through routine experimentation. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid assays is well-known in the art.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Cyran (Heat Shock Proteins and HSF1 in Cancer, Front. Oncol., 12, 1-21, 2022) in view of Brusselaers (Copy number of 8q24.3 drives HSF1 expression and patient outcome in cancer: an individual patient data meta-analysis, Human Genomics, 13:54, 1-12, 2019) and Martins (Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer, Nature Communications, 13:6330, 1-14, 2022) and Valinciute (Class 1 HDAC Inhibitors and PLK1 Inhibitors Synergize in MYC-Amplified Medulloblastoma, Neuro-Oncology, 23, Supplement 1, p. i5, 2021) as applied to claims 1 and 6 above, and further in view of Solca (US Patent App. Pub. No. 2013/0004481 A1).
Regarding dependent claim 7, Solca teaches anticancer therapies of the PL1 inhibitor
volasertib (para. 241) and the HDAC inhibitors of panobinostat, vorinostat, romidepsin, belinostat and entinostat (para. 229).
Prior to the effective filing date of the instant invention, it would have been prime facie obvious to further modify the modified Cyran assay, discussed above, to incorporate the PLK1 inhibitors and HDAC inhibitors, as taught by Solca, as such inhibitors are known in the art as being suitable for that intended purpose. MPEP 2144.07. Further, it would have been obvious to try the inhibitors in order optimize the assay as needed through routine experimentation. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid assays is well-known in the art.
Claims 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Cyran (Heat Shock Proteins and HSF1 in Cancer, Front. Oncol., 12, 1-21, 2022) in view of Brusselaers (Copy number of 8q24.3 drives HSF1 expression and patient outcome in cancer: an individual patient data meta-analysis, Human Genomics, 13:54, 1-12, 2019), Martins (Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer, Nature Communications, 13:6330, 1-14, 2022), Valinciute (Class 1 HDAC Inhibitors and PLK1 Inhibitors Synergize in MYC-Amplified Medulloblastoma, Neuro-Oncology, 23, Supplement 1, p. i5, 2021) and Hansen (US Patent App. Pub. No. 2013/0324570 A1).
Regarding independent claim 8 and dependent claims 9 and 11-12, Cyran teaches …
A method for screening an therapeutic agent against a biological sample comprising cancer cells, comprising: a) contacting the biological sample with the therapeutic agent; b) measuring cell viability of the biological sample following contact with the therapeutic agent; and c) determining whether the biological sample has reduced cell viability following contact with the therapeutic agent relative to an untreated portion of the biological sample, wherein reduced cell viability indicates increased susceptibility to the therapeutic agent (section 7.3: cell viability measured by tumor volume, cell cycle arrest and/or apoptosis).
Cyran teaches that the sample has elevated copy numbers of the MYC gene and elevated copy numbers of the HSF1 gene (Sections 5, 5.1.2; Fig 3A).
Martins teaches that the copy number of MYC is greater than or equal to three (Fig. 3B; p. 4, right col., para. 1). Martins suggests that at least 5% of the cells in the sample have such a copy number. Specifically, Martins teaches deriving spheroids from ovarian cancer samples and determining the copy number data for each spheroid (Fig. 3E: shows MYC copy numbers in various spheroids of 5 or above, including 7, 16 and 20 copy numbers). Martins also teaches that the prevalence of chromosomal alterations across in the genome in the spheroid cohort is approximately 80% for MYC (Fig. 2A). Thus, Martins at least suggests that at least some of the spheroids have large copy number increases and that these alterations occur across the majority of their genomes.
Brusselaers teaches HSF1 copy number alterations in various cancers and also teaches that HSF1 copy number alteration strongly correlates with copy number alterations of the other genes on 8q24.3 (p. 6, left col., para. 2), which includes MYC, as taught by Cyran.
Valinciute teaches epigenetic inhibitors, specifically PLK1 inhibitors and HDAC inhibitors, as therapeutic agents for treating MYC-amplified tumors.
Cyran does not teach average cell viability. However, Hansen teaches this limitation and teaches measuring it with a colorimetric (MTT) assay (para. 61).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Cyran method to incorporate the copy number alterations of MYC (i.e., an increase of at least 3), as taught by Martins. The ordinary artisan would have been motivated to do so to achieve the expected advantage of a more precise assay for characterizing a tumor. The ordinary artisan would have been motivated to further incorporate into the Cyran method the copy number alterations of HSF1 (i.e., an increase of at least 3) as taught or suggested by the combination of Cyran and Brusselaers, which teaches that MYC and HSF1 are both at chromosome locus 8q24.3, and that HSF1 copy number alteration strongly correlates with copy number alterations of the other genes on 8q24.3. The ordinary artisan would have been motivated to do so to achieve the expected advantage of a more precise assay for characterizing a tumor. The ordinary artisan would have had an expectation of success as the design and modification of biomarker assays is well-known in the art.
It would have been further obvious to limit the sample to those with at least 5% of the cells in the sample having such a copy number as doing so would result in the expected advantage of increasing the sensitivity and specificity of the assay by removing non-target samples. The ordinary artisan would have had an expectation of success as the design and modification of biomarker assays is well-known in the art.
It would have been additionally obvious to further modify the modified Cyran assay, discussed above, to incorporate the PLK1 inhibitors and HDAC inhibitors, as taught by Valinciute, as such inhibitors are known in the art as being suitable for that intended purpose. MPEP 2144.07. Further, it would have been obvious to try the inhibitors in order optimize the assay as needed through routine experimentation. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid assays is well-known in the art.
Finally, it would have been further obvious to measure the average cell viability using a colorimetric assay, as such a technique is known in the art as being suitable for that intended purpose. MPEP 2144.07. Further, the ordinary artisan would have been motivated to optimize the assay as needed through routine experimentation. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid assays is well-known in the art.
Regarding dependent claim 10, Cyran additionally teaches breast cancer, esophageal cancer, lung cancer, colorectal cancer and prostate cancer (section 5).
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Cyran (Heat Shock Proteins and HSF1 in Cancer, Front. Oncol., 12, 1-21, 2022) in view of Brusselaers (Copy number of 8q24.3 drives HSF1 expression and patient outcome in cancer: an individual patient data meta-analysis, Human Genomics, 13:54, 1-12, 2019), Martins (Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer, Nature Communications, 13:6330, 1-14, 2022), Valinciute (Class 1 HDAC Inhibitors and PLK1 Inhibitors Synergize in MYC-Amplified Medulloblastoma, Neuro-Oncology, 23, Supplement 1, p. i5, 2021) and Hansen (US Patent App. Pub. No. 2013/0324570 A1) as applied to claims 8 and 12 above, and further in view of Solca (US Patent App. Pub. No, 2013/0004481 A1).
Regarding dependent claim 13, Solca teaches anticancer therapies of the PL1 inhibitor
volasertib (para. 241).
Prior to the effective filing date of the instant invention, it would have been prime facie obvious to further modify the modified Cyran assay, discussed above, to incorporate the PLK1 inhibitors, as taught by Solca, as such inhibitors are known in the art as being suitable for that intended purpose. MPEP 2144.07. Further, it would have been obvious to try the inhibitors in order optimize the assay as needed through routine experimentation. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid assays is well-known in the art.
Claims 14-15 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Cyran (Heat Shock Proteins and HSF1 in Cancer, Front. Oncol., 12, 1-21, 2022) in view of Brusselaers (Copy number of 8q24.3 drives HSF1 expression and patient outcome in cancer: an individual patient data meta-analysis, Human Genomics, 13:54, 1-12, 2019) and Martins (Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer, Nature Communications, 13:6330, 1-14, 2022).
Regarding independent claim 14, Cyran teaches …
A method of treating a cancer in a mammalian subject comprising administering a therapeutically effective amount of an inhibitor to the subject, wherein at least one cell in a sample of cancer cells obtained from the mammalian subject has elevated gene copies of MYC and elevated gene copies of HSF1 (Sections 5, 5.1.2, 7.3; Fig 3A).
Martins teaches that the copy number of MYC is greater than or equal to three (Fig. 3B; p. 4, right col., para. 1).
Brusselaers teaches HSF1 copy number alterations in various cancers and also teaches that HSF1 copy number alteration strongly correlates with copy number alterations of the other genes on 8q24.3 (p. 6, left col., para. 2), which includes MYC, as taught by Cyran.
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Cyran method to incorporate the copy number alterations of MYC (i.e., an increase of at least 3), as taught by Martins. The ordinary artisan would have been motivated to do so to achieve the expected advantage of a more precise assay for characterizing a tumor. The ordinary artisan would have been motivated to further incorporate into the Cyran method the copy number alterations of HSF1 (i.e., an increase of at least 3) as taught or suggested by the combination of Cyran and Brusselaers, which teaches that MYC and HSF1 are both at chromosome locus 8q24.3, and that HSF1 copy number alteration strongly correlates with copy number alterations of the other genes on 8q24.3. The ordinary artisan would have been motivated to do so to achieve the expected advantage of a more precise assay for characterizing a tumor. The ordinary artisan would have had an expectation of success as the design and modification of biomarker assays is well-known in the art.
Regarding dependent claim 15, Cyran additionally teaches breast cancer, endometrial cancer, esophageal cancer, liver cancer and pancreatic cancer (section 5).
Regarding dependent claim 20, Martins teaches that the copy number of MYC is greater than or equal to five (Fig. 3B; p. 4, right col., para. 1), while Brusselaers teaches HSF1 copy number alterations in various cancers and also teaches that HSF1 copy number alteration strongly correlates with copy number alterations of the other genes on 8q24.3 (p. 6, left col., para. 2), which includes MYC, as taught by Cyran. Further, Martins suggests that at least 5% of the cells in the sample have such a copy number. Specifically, Martins teaches deriving spheroids from ovarian cancer samples and determining the copy number data for each spheroid (Fig. 3E: shows MYC copy numbers in various spheroids of 5 or above, including 7, 16 and 20 copies). Martins also teaches that the prevalence of chromosomal alterations across in the genome in the spheroid cohort is approximately 80% for MYC (Fig. 2A). Thus, Martins at least suggests that at least some of the spheroids have large copy number increases and that these alterations occur across the majority of their genomes.
Prior to the effective filing date of the instant invention, it would have been prime facie obvious to further modify the modified Cyran assay, discussed above, to incorporate the copy number alterations of MYC (i.e., an increase of at least 5), as taught by Martins, and to incorporate the copy number alterations of HSF1 (i.e., an increase of at least 5) as taught or suggested by the combination of Cyran and Brusselaers, which teaches that MYC and HSF1 are both at chromosome locus 8q24.3, and that HSF1 copy number alteration strongly correlates with copy number alterations of the other genes on 8q24.3. The ordinary artisan would have been motivated to do so to achieve the expected advantage of a more precise assay for characterizing a tumor. It would have been further obvious to limit the sample to those with at least 5% of the cells in the sample have such a copy number as doing so would result in the expected advantage of increasing the sensitivity and specificity of the assay by removing non-target samples. The ordinary artisan would have had an expectation of success as the design and modification of biomarker assays is well-known in the art.
Claims 16 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Cyran (Heat Shock Proteins and HSF1 in Cancer, Front. Oncol., 12, 1-21, 2022) in view of Brusselaers (Copy number of 8q24.3 drives HSF1 expression and patient outcome in cancer: an individual patient data meta-analysis, Human Genomics, 13:54, 1-12, 2019) and Martins (Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer, Nature Communications, 13:6330, 1-14, 2022) as applied to claim 14 above, and further in view of Valinciute (Class 1 HDAC Inhibitors and PLK1 Inhibitors Synergize in MYC-Amplified Medulloblastoma, Neuro-Oncology, 23, Supplement 1, p. i5, 2021).
Regarding dependents claims 16 and 18, Valinciute teaches treating MYC-amplified tumors with PLK1 inhibitors and HDAC inhibitors.
Prior to the effective filing date of the instant invention, it would have been prime facie obvious to further modify the modified Cyran assay, discussed above, to incorporate the PLK1 inhibitors and HDAC inhibitors, as taught by Valinciute, as such inhibitors are known in the art as being suitable for that intended purpose. MPEP 2144.07. Further, it would have been obvious to try the inhibitors in order optimize the assay as needed through routine experimentation. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid assays is well-known in the art.
Claims 17 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Cyran (Heat Shock Proteins and HSF1 in Cancer, Front. Oncol., 12, 1-21, 2022) in view of Brusselaers (Copy number of 8q24.3 drives HSF1 expression and patient outcome in cancer: an individual patient data meta-analysis, Human Genomics, 13:54, 1-12, 2019), Martins (Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer, Nature Communications, 13:6330, 1-14, 2022) and Valinciute (Class 1 HDAC Inhibitors and PLK1 Inhibitors Synergize in MYC-Amplified Medulloblastoma, Neuro-Oncology, 23, Supplement 1, p. i5, 2021) as applied to claims 14, 16 and 18 above, and further in view of Solca (US Patent App. Pub. No, 2013/0004481 A1).
Regarding dependent claims 17 and 19, Solca teaches anticancer therapies of the PLK1
inhibitor volasertib (para. 241) and the HDAC inhibitors of panobinostat, vorinostat, romidepsin, belinostat and entinostat (para. 229).
Prior to the effective filing date of the instant invention, it would have been prime facie obvious to further modify the modified Cyran assay, discussed above, to incorporate the PLK1 inhibitors and HDAC inhibitors, as taught by Solca, as such inhibitors are known in the art as being suitable for that intended purpose. MPEP 2144.07. Further, it would have been obvious to try the inhibitors in order optimize the assay as needed through routine experimentation. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid assays is well-known in the art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-7 and 14-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7 and 14-20 of copending Application No. 18/418,110 (hereinafter, the ‘110 application).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the claims at issue are not identical, they are not patentably distinct from each other because …
Claims 1-5, 7 and 15 of the ‘110 application teach or suggest all of the limitations of instant claims 1-7, although in different embodiments.
Claims 14-20 of the ‘110 application teach or suggest all of the limitations of instant claims 14-20, although in different embodiments.
It would have been prima facie obvious to modify the method of the ‘110 application to arrive at different embodiments. The ordinary artisan would have been motivated to do so to optimize the assay as desired through routine experimentation. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid assays is well-known the art.
Conclusion
Claims 1-20 are being examined and are rejected. Claims 3 and 15 are objected to. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
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, Gary Benzion can be reached at 571-272-0782. The fax phone number for the 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.
/CAROLYN L GREENE/Primary Examiner, Art Unit 1681
