DETAILED ACTION
The amendment filed on 02/03/2026 has been entered (Note, some amendments were not properly documented in the claim set of 02/03/2026, such as the removal of the dash bullets before “determining” in lines 3, 9, 15 and 20 of claim 1).
Claims 1-10 were amended in the claim set filed on 02/03/2026.
Applicant's election with traverse of Group I (claims 1-10) and the species comprising the immune defense response gene IFI16, the T-Cell receptor signaling gene PRKACA, and the PDE4D7 correlated gene RAP1GAP2, in the reply filed on 10/22/2025 is acknowledged.
Claims 12 and 18-24 have been canceled.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Claims 29-36 have been added.
Election/Restrictions
Newly submitted claim 36 is directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: claim 36 is drawn to the non-elected Group III, drawn to the use of a computer program. User interface is interpreted as use of a computer program.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claim 36 is withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims 2-4, 11, 13-17 and 36 are withdrawn.
Claims 1, 5-10, and 25-35 are currently pending and under examination.
Response to the Arguments
Claims 2-4 remain withdrawn from consideration as being directed to a non-elected specie, as the specie elected in claim 1 would require one immune defense response gene IFI16, one T-Cell receptor signaling gene PRKACA, and one PDE4D7 correlated gene RAP1GAP2, while claims at least two or three or more of genes from each group of genes.
Applicant’s arguments regarding previous rejections of claims 1, 5-10 and 25-28 under Improper Markush have been fully considered and are persuasive. The Improper Markush documented in the previously mailed non-final has been withdrawn in light of arguments on Pg. 16-17.
Applicant’s arguments regarding previous rejections of claims 1, 5-10 and 25-28 under 35 U.S.C. 112(b) have been fully considered and are partially persuasive based on claim amendments. The 35 U.S.C. 112(b) rejections documented in the previously mailed non-final have been withdrawn in light of applicants claim amendments and arguments on Pg. 18-19.
Applicant’s arguments regarding previous rejections of claims 1, 5-10 and 25-28 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 in light of applicants claim amendments and arguments on Pg. 20-24. As necessitated by amendment, new grounds of rejection are made for claims 29-35 under 35 U.S.C. 101 rejections in this office action on Pg. 5-9.
Applicant’s arguments regarding previous rejections of claims 1, 5-10 and 25-28 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 and revised in light of applicants claim amendments and arguments on Pg. 24-29. As necessitated by amendment, revised rejections for claims 1, 5-10 and 25-28 are made, as documented below, under the 35 U.S.C. 103 rejections in this office action on Pg. 3-7. A new ground of rejections is made for claims 29-35 under 35 U.S.C. 103 rejections in this office action on Pg. 10-22.
Applicant’s arguments regarding previous rejections of claim 1 under Nonstatutory Double Patenting have been fully considered and are not persuasive. The Nonstatutory Double Patenting rejection documented in the previously mailed non-final have been maintained.
The rejections for claims 1, 5 and 25-35 are documented below in this Final Office Action are necessitated by claim amendments filed on 02/03/2026.
Priority
This application is the U.S. National Phase application under 35 U.S.C. §371 of International Application No. PCT/EP2021/073 149, filed on August 20, 2021, which claims the benefit of European Patent Application No. 20193653.1, filed on August 31, 2020. The certified copy of EP 20193653.1 has been filed on February 22, 2022. Accordingly, the priority date of claim set filed on February 3, 2026, is determined to be August 31, 2020.
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, 5-10, 25-29, 31, and 33 are rejected under 35 U.S.C. 101 because the claimed invention is directed towards abstract ideas/mental processes determining or receiving results of a profile and determining dose based on profiles, natural phenomenon of gene expression to prostate cancer, and routine and conventional methods without significantly more. The claim(s) recite(s) abstract ideas, 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 for treating a prostate cancer subject with radiotherapy, comprising: determining or receiving the result of a determination of a first gene expression profile for each of one or more immune defense response genes selected from the group consisting of:AIM2, APOBEC3A, CIAO1, DDX58, DHX9, IFI16, IFIH1, IFIT1,IFIT3, LRRFIP1, MYD88, OAS1, TLR8, and ZBP1, said first gene expression profile(s) being determined in a biological sample obtained from the subject; and determining or receiving the result of a determination of a second gene expression profile for each of one or more T-Cell receptor signaling genes selected from the group consisting of: CD2, CD247, CD28, CD3E, CD3G, CD4, CSK, EZR, FYN, LAT, LCK, PAG1, PDE4D, PRKACA, PRKACB, PTPRC, and ZAP70, said second gene expression profile(s) being determined in a biological sample obtained from the subject; and determining or receiving the result of a determination of a third gene expression profile for each of one or more PDE4D7 correlated genes selected from the group consisting of: ABCC5, CUX2, KIAA1549, PDE4D, RAP1 GAP2, SLC39All, TDRD1, and VWA2, said third gene expression profile(s) being determined in a biological sample obtained from the subject; determining the selection of a radiotherapy dose to treat the subject based on one of: the first gene expression profile(s); the second gene expression profile(s); the third gene expression profile(s); and the first, second, and third gene expression profile(s); and treating the subject with the determined radiotherapy dose.
The correlation of gene expression to prostate cancer is a natural phenomenon.
The determining or receiving the result of a determination of a first gene expression profile, determining or receiving the result of a determination of a second gene expression profile, determining or receiving the result of a determination of a third gene expression profile are considered abstract ideas (mental process) related to organizing or analyzing information in a way that can be performed mentally or is analogous to human mental work. See MPEP 2106.4 (a)(2).
The determining the selection of a radiotherapy dose to treat the subject based on one of: the first gene expression profile(s); the second gene expression profile(s); the third gene expression profile(s); and the first, second, and third gene expression profile(s) are considered abstract ideas (mental process) related to organizing or analyzing information in a way that can be performed mentally or is analogous to human mental work and is considered to be active steps requiring the analysis of a sample. The active step is routine and conventional as demonstrated by the 35 USC § 103 rejections stated below.
The treating the subject with the determined radiotherapy dose is of great generality being routine and conventional as demonstrated in the prior art rejections documented below and is not a particular treatment.
Dependent claims set forth further limitations about number of immune defense response genes, T-Cell receptor genes, and PDE4D7 correlated genes, method of determining the selection of the radiotherapy dose, clinical parameters, sample, radiotherapy, radiotherapy level of dose, determining subject risk level, and first, second, or third expression profile.
The instant claim 33 is directed towards: The method of claim 1, further comprising: determining, based on the first gene expression, the second gene expression, and the third gene expression profile, that the subject is in a high risk cohort or a low risk cohort.
The determining, … that the subject is in a high risk cohort or a low risk cohort is considered an abstract idea (mental process) related to organizing or analyzing information in a way that can be performed mentally or is analogous to human mental work.
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, abstract ideas and natural phenomena.
With regard to claim 1, the claim recites “A method for treating a prostate cancer subject with radiotherapy, comprising: determining or receiving the result of a determination of a first gene expression profile for each of one or more immune defense response genes selected from the group consisting of:AIM2, APOBEC3A, CIAO1, DDX58, DHX9, IFI16, IFIH1, IFIT1,IFIT3, LRRFIP1, MYD88, OAS1, TLR8, and ZBP1, said first gene expression profile(s) being determined in a biological sample obtained from the subject; and determining or receiving the result of a determination of a second gene expression profile for each of one or more T-Cell receptor signaling genes selected from the group consisting of: CD2, CD247, CD28, CD3E, CD3G, CD4, CSK, EZR, FYN, LAT, LCK, PAG1, PDE4D, PRKACA, PRKACB, PTPRC, and ZAP70, said second gene expression profile(s) being determined in a biological sample obtained from the subject; and determining or receiving the result of a determination of a third gene expression profile for each of one or more PDE4D7 correlated genes selected from the group consisting of: ABCC5, CUX2, KIAA1549, PDE4D, RAP1 GAP2, SLC39All, TDRD1, and VWA2, said third gene expression profile(s) being determined in a biological sample obtained from the subject; determining the selection of a radiotherapy dose to treat the subject based on one of: the first gene expression profile(s); the second gene expression profile(s); the third gene expression profile(s); and the first, second, and third gene expression profile(s); and treating the subject with the determined radiotherapy dose.”.
The determining or receiving the result of a determination of a … gene expression profile and determining the selection of the radiotherapy dose based on the … gene expression profile(s) are considered abstract ideas (mental process) related to organizing or analyzing information in a way that can be performed mentally or is analogous to human mental work.
Prostate cancer cells naturally express these genes that are considered in the expression profiles and is thus considered natural phenomena.
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. Although the independent claim 1 recites “treating the subject with the determined radiotherapy dose”, which is of great generality being routine and conventional as demonstrated in the prior art rejections documented below and is not a particular treatment.
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 claim 1, the claim requires the routine and conventional active steps of determining the result of a gene expression profile(s) requiring the analysis of a sample similar to that of Davicioni et al. (“Davicioni”; Patent App. Pub. No. WO 2019028285 A2, Feb. 07, 2019).
Davicioni discloses “Methods, systems, and kits for the diagnosis, prognosis and the determination of cancer progression of prostate cancer in a subject are disclosed. In particular, the disclosure relates to the use of immune cell-specific gene expression in determining prognosis and identifying individuals in need of treatment for prostate cancer who will be responsive to radiation therapy.” (Abstract). Thus, the claim does not provide additional steps which are significantly more.
Dependent claims require further limitations about clinical parameters, sample, radiotherapy, radiotherapy level of dose, determining subject risk level, and first, second, or third expression profile, which are all routine and conventional based on Davicioni et al. (“Davicioni”; Patent App. Pub. No. WO 2019028285 A2, Feb. 07, 2019) in view of Bosquet et al. (“Bosquet”; Patent App. Pub. WO 2016004387 A1, Jan. 7, 2016) and Ganswindt et al. (“Ganswindt”; (2005). 70 Gy or more: which dose for which prostate cancer?, Journal of cancer research and clinical oncology, 131(7), 407–419.).
Response to Arguments
Applicant’s arguments have been fully considered and found unpersuasive because applicants amendments do not overcome the lack of patentably matter under U.S.C. 35 101. The previously presented and amended claims recite abstract ideas/mental process, natural phenomena and routine and conventional steps of clinical parameters, sample, radiotherapy treatment, radiotherapy level of dose, determining subject risk level, and first, second, and/or third expression profile minimum composition. The judicial exceptions are not integrated into a practical application because the claim limitations do not appear to improve the current technology or technical field beyond well-understood, routine, conventional activity. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims provide no specific limitations that provide significantly more.
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.
Claim(s) 1, 5-10, 25-29, 31 and 33 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Davicioni et al. (“Davicioni”; Patent App. Pub. No. WO 2019028285 A2, Feb. 07, 2019) in view of Bosquet et al. (“Bosquet”; Patent App. Pub. WO 2016004387 A1, Jan. 7, 2016).
Claim Interpretation: Regarding claim 7, the limitation of “one or more of: (i) … (iv) is interpreted to end after the clause “and the combination of the third gene expression profiles”. Regarding claim 7, “combining one or more of” is interpreted “as at least one of (i-iv)”.
Davicioni discloses “Methods, systems, and kits for the diagnosis, prognosis and the determination of cancer progression of prostate cancer in a subject are disclosed. In particular, the disclosure relates to the use of immune cell-specific gene expression in determining prognosis and identifying individuals in need of treatment for prostate cancer who will be responsive to radiation therapy.” (Abstract).
Regarding claim 1, Davicioni teaches a method comprising “use of immune cell-specific gene expression in determining prognosis and identifying individuals in need of treatment for prostate cancer who will be responsive to radiation therapy” (Para. 2). Davicioni teaches a method comprising “levels of immune cell-specific gene expression; d) determining the prognosis of the patient based on the levels of the one or more immune cell types in the biological sample” and “the immune cell-specific gene is one or more genes… IFI16” (Para. 10). Davicioni teaches a method comprising “In some embodiments, the immune cell-specific gene comprises or consists of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 225, or 250 genes” (Para. 10). Moreover, Davicioni teaches a method comprising “Human Exon 1.0 ST microarray (Thermo-Fisher, Carlsbad, CA)” (Para. 192). “Human Exon 1.0 ST microarray” reads on any gene in the human genome. “Immune cell-specific” reads on T-cell signaling genes.
Davicioni also teaches a method comprising determining a therapeutic regimen may comprise modifying, recommending, continuing or discontinuing an anti-cancer regimen… In some instances, if the sample expression patterns are consistent with the expression pattern for a known disease or disease outcome, the expression patterns can be used to designate one or more treatment modalities (e.g., therapeutic regimens, anti-cancer regimen). An anti-cancer regimen may comprise one or more anti -cancer therapies. Examples of anticancer therapies include surgery, chemotherapy, radiation therapy, immunotherapy/biological therapy, and photodynamic therapy” (Para. 139). “determining a therapeutic regimen” reads on selecting a dose for radiotherapy. “modifying, recommending… an anticancer regimen” read on selecting a dose for radiotherapy. “continuing or discontinuing an anticancer regimen” also read on selecting a dose for radiotherapy, rather it is the same or none at all. “therapeutic regimen” reads on radiation therapy and dose. “expression patterns can be used to designate one or more treatment modalities (e.g., therapeutic regimens, anti-cancer regimen)” reads on determining the selection of the radiotherapy dose based on the first gene expression profile(s), or on the second gene expression profile(s), or on the third gene expression profile(s), or on the first, second, and third gene expression profile(s).
Furthermore, Davicioni teaches a method comprising “e) administering a treatment to the subject based on the prognosis” (Para. 10).
Davicioni teaches “While some embodiments of the disclosure have been illustrated and described, it will be appreciated that various changes can be made”. Davicioni does not explicitly teach expression profile of IFI16, PRKACA and RAP1GAP2 determined in a biological sample.
Bosquet discloses “The current invention pertains to a method for determining whether a subject suffering from a cancer is a good candidate for a chemotherapy for the cancer, and a method of treating a subject suffering from a cancer based on the identification of the subject as a good candidate or a bad candidate for the chemotherapy. The methods comprise the steps of identifying the subject as a good candidate for a chemotherapy or a bad candidate for the chemotherapy. The methods may further include administering the chemotherapy to the subject if the subject is identified as a good candidate for the chemotherapy, or withholding the administration of the chemotherapy to the subject identified as the bad candidate for the chemotherapy. In addition to withholding the chemotherapy from the bad candidate, an alternative treatment may be administered. The current invention also provides microarray chips useful in practicing the claimed invention of identifying a subject suffering from a cancer as a good candidate for a chemotherapy.” (Abstract).
Regarding claim 1, Bosquet teaches a method comprising “Cancers suitable for practicing the methods of the claimed invention include... prostate” (Pg. 8 ln 12 and ln 16). Bosquet teaches “IFI16” (Table 3, Pg. 41). Bosquet teaches “PRKACA” (Table 4, Pg. 102). Bosquet teaches “RAP1GAP2” (Table 4, Pg. 104). Furthermore, Bosquet teaches a method comprising “… Table 3 summarize whole genome significant somatic gains and losses determined by the genomic identification of significant targets in cancer (GISTIC) analysis” (Pg. 30, ln 6). Bosquet also teaches a method wherein “The differential copy number alterations (CNA), mutations, DNA methylation, and miRNA expression between patients that responded to standard treatment and those who did not or recurred prematurely was also identified. These significant parameters were correlated to gene expression to create a signature of genes associated with chemo-response” (Pg. 5, ln 16-20). Thus, Bosquet also teaches a method comprising using signature genes that were identified from significant targets in cancer between patients that respond and patients that do not respond to therapeutic treatment to a predict response to the therapeutic treatment.
Thus, Davicioni and Bosquet teach A method for treating a prostate cancer subject with radiotherapy, comprising: determining or receiving the result of a determination of a first gene expression profile for each of one or more immune defense response genes selected from the group consisting of:AIM2, APOBEC3A, CIAO1, DDX58, DHX9, IFI16, IFIH1, IFIT1,IFIT3, LRRFIP1, MYD88, OAS1, TLR8, and ZBP1, said first gene expression profile(s) being determined in a biological sample obtained from the subject; and determining or receiving the result of a determination of a second gene expression profile for each of one or more T-Cell receptor signaling genes selected from the group consisting of: CD2, CD247, CD28, CD3E, CD3G, CD4, CSK, EZR, FYN, LAT, LCK, PAG1, PDE4D, PRKACA, PRKACB, PTPRC, and ZAP70, said second gene expression profile(s) being determined in a biological sample obtained from the subject; and determining or receiving the result of a determination of a third gene expression profile for each of one or morePDE4D7 correlated genes selected from the group consisting of: ABCC5, CUX2, KIAA1549,PDE4D, RAP1 GAP2, SLC39All, TDRD1, and VWA2, said third gene expression profile(s) being determined in a biological sample obtained from the subject; determining the selection of a radiotherapy dose to treat the subject based on one of: the first gene expression profile(s); the second gene expression profile(s); the third gene expression profile(s); and the first, second, and third gene expression profile(s); and treating the subject with the determined radiotherapy dose.
Davicioni and Bosquet are both considered to be analogous to the claimed invention because they are in the same field of gene expression related to cancer diagnosis, prognosis, and therapeutic response. 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 a gene expression profile for one or more immune defense response genes or T-Cell receptor signaling genes selected from the group comprising :IFI16; determining a selection of the radiotherapy response based on the gene expression profiles for the one or more genes, and treating the subject with the determined radiotherapy dose as taught by Davicioni to incorporate the method comprising the expression profile of genes comprising IFI16, PRKACA and/or RAP1GAP2 as taught by Bosquet and provide a method of determining a gene expression profile for one or more immune defense response genes, T-Cell receptor signaling genes, and/or PDE4D7 correlated genes comprising: IFI16, PRKACA and/or RAP1GAP2, selecting a radiotherapy dose to treat a subject based on a first, second and/or third expression profile and treating the subject with the determined radiotherapy dose. Davicioni provides the enabling methodology, a suggestion to modify the claimed method and evidence suggesting the modification would be successful (Example 1). It would be obvious to the ordinary artisan to try other biomarkers not specifically disclosed in Davicioni and that have been identified in prostate cancer and have documented radiotherapy treatment response data to choose the specific set of genes to determine the expression profiles and base selection of radiotherapy dose upon. Doing so would improve the prognosis of prostate cancer based on the expression profile(s) for one or more biomarkers, predictions of radiotherapy responses based on expression profiles, and treatment regimen selected and administered based on prostate cancer prognosis. (Para. 2; Para. 190)
The teachings of Davicioni and Bosquet are documented above in the rejection of claim 1 under 35 U.S.C. 103. Claims 5-10 and 25-28 depend on claim 1.
Regarding claim 5-6, Davicioni teaches a “Standard clinical parameters such as tumor size, grade, lymph node involvement and tumor- node-metastasis (TNM) staging (American Joint Committee on Cancer) may correlate with outcome and serve to stratify patients with respect to (neo)adjuvant chemotherapy, immunotherapy, antibody therapy and/or radiotherapy regimens.” (Para. 4). Davicioni teaches a method wherein “CAPRA-S” (Para. 200) and “Subset analyses for each pre-specified variable with respect to PSA, Gleason score … margin status, and lymph node involvement (LNI)…” (Para. 201). Thus, Davicioni and Bosquet teach a method wherein the determining of the selection of the radiotherapy dose is further based on one or more clinical parameters obtained from the subject; and wherein the clinical parameters comprise one or more of: (i) a prostate-specific antigen (PSA) level; (ii) a pathologic Gleason score (pGS); (iii) a clinical tumour stage; (iv) a pathological Gleason grade group (pGGG); (v) a pathological stage; (vi) one or more pathological variables, for example, a status of surgical margins and/or a lymph node invasion and/or an extra-prostatic growth and/or a seminal vesicle invasion; (vii) CAPRA; (viii) CAPRA-S; (ix) EAU-BCR risk groups, and; (x) another clinical risk score
Regarding claim 7, Davicioni teaches a method wherein “b) measuring levels of immune cell-specific gene expression in the biological sample; c) calculating levels of one or more immune cell types in the biological sample based on the levels of immune cell-specific gene expression…d) determining the prognosis of the patient based on the levels of the one or more immune cell types in the biological sample; and e) administering a treatment to the subject based on the prognosis, wherein the treatment is selected from the group consisting of.., radiation therapy” (Para. 11). Davicioni also teaches a method wherein “regression was utilized to analyze” (Para. 200). Davicioni teaches a method wherein the clinical parameters comprise “CAPRA-S” (Para. 200) and “Subset analyses for each pre-specified variable with respect to PSA, Gleason score … margin status, and lymph node involvement (LNI)…” (Para. 201). Thus, Davicioni and Bosquet teach a method wherein the determining of the selection of the radiotherapy dose comprises combining one or more of: (i) the first gene expression profile(s) for the one or more immune defense response genes; (ii) the second gene expression profile(s) for the one or more T-Cell receptor signaling genes; (iii) the third gene expression profile(s) for the one or more PDE4D7 correlated genes, and; (iv) the combination of the first gene expression profiles, the combination of the second gene expression profiles, and the combination of the third gene expression profiles, and the one or more clinical parameters obtained from the subject with a regression function that had been derived from a population of prostate cancer subjects.
Regarding claim 8, Davicioni teaches a method wherein “obtaining a biological sample comprising cancer cells from the patient…and e) administering a treatment to the subject based on the prognosis. In some embodiments, the cancer is prostate cancer.” (Para. 10). Davicioni teaches a method wherein “the anti-cancer treatment may comprise radiation therapy” (Para. 147). Thus, Davicioni and Bosquet teach a method wherein the biological sample(s) is/are obtained from the subject before the start of the radiotherapy.
Regarding claims 9-10, Davicioni also teaches a method wherein “For patients with high test scores consistent with systemic disease outcome after prostatectomy, additional treatment modalities such as … systemic radiation therapy (e.g., samarium or strontium) and/or anti-androgen therapy (e.g., surgical castration, finasteride, dutasteride) can be designated.” (Para. 182). Davicioni teaches a method wherein “For patients with intermediate test scores consistent with biochemical recurrence only (BCR-only or elevated PSA that does not rapidly become manifested as systemic disease only localized adjuvant therapy (e.g., radiation therapy of the prostate bed)” (Para.183; Para.188). Thus, Davicioni and Bosquet teach a method wherein the radiotherapy is radical radiotherapy or salvage radiotherapy; and wherein the prostate cancer subject is a prostate cancer subject undergoing salvage radiotherapy (SRT) after post-surgical disease recurrence.
Regarding claim 25, Bosquet teaches “IFI16” (Table 3, Pg. 41). Thus, Davicioni and Bosquet teach a method wherein the first gene expression profile comprises IFI16.
Regarding claim 26, Bosquet teaches “PRKACA” (Table 4, Pg. 102). Thus, Davicioni and Bosquet teach a method wherein the second gene expression profile comprises PRKACA.
Regarding claim 27, Bosquet teaches “RAP1GAP2” (Table 4, Pg. 104). Thus, Davicioni and Bosquet teach a method wherein the third gene expression profile comprises RAP1GAP2.
Regarding claim 28, Bosquet teaches “Affymetrix Human Genome U133 Plus 2.0 and U133A arrays” (Pg. 23, Materials and Methods, ln 21-22). “Affymetrix Human Genome U133 Plus 2.0 and U133A arrays” read on any gene in the human genome. Thus, Davicioni and Bosquet teach a method wherein the first gene expression profile comprises IFI16, the second gene expression profile comprises PRKACA, and the third gene expression profile comprises RAP1GAP2.
Regarding claim 29, Davicioni teaches a method wherein “deliver one or more high doses of radiation” (Para. 152) and “brachytherapy can be… high-dose-rate treatment” (Para. 158). Thus, Davicioni and Bosquet suggest a method wherein the determined radiotherapy dose is a high dose.
Regarding claim 31, Davicioni teaches a method wherein “brachytherapy can be… low-dose-rate… treatment” (Para. 158). Thus, Davicioni and Bosquet suggest a method wherein the determined radiotherapy dose is a low dose.
Regarding claim 33, Davicioni teaches a method wherein “determining if the patient as at risk of developing metastatic cancer or not at risk of developing metastatic cancer, based on the level of expression of one or more immune cell- specific genes in the biological sample” (Para. 37). Davicioni teaches a method wherein “assaying the expression level for a plurality of targets in the sample; and (c) subtyping the cancer based on the expression level of the plurality of targets” (Para. 50). “at risk of developing metastatic cancer” is interpreted as high risk. “not at risk of developing metastatic cancer” is interpreted as low risk. Thus, Davicioni and Bosquet suggest a method further comprising: determining, based on the first gene expression, the second gene expression, and the third gene expression profile, that the subject is in a high risk cohort or a low risk cohort.
Response to Arguments
Applicant' s arguments filed 02/03/2026 (Pg.6) with respect to claims 1, 5-10, 25-29, 31 and 32 have been considered but are not persuasive. To clarify some instances argued in the response filed 02/03/2026 see responses to each argument made by Applicant below:
Applicants’ argument: “However, there is no teaching or disclosure in paragraph [00139] or elsewhere in Davicioni- alone or in combination with Bosquet - of determining a radiotherapy dose to treat a subject, much less determining a dose based on the claimed determined gene profiles.” (Pg. 25)
Response: Applicant's arguments filed 02/03/2026 have been fully considered but they are not persuasive. As recited on Pg. 13 of the Non-final office action and highlighted in the arguments of the response (Pg. 25), “Davicioni also teaches a method comprising determining a therapeutic regimen may comprise modifying, recommending, continuing or discontinuing an anti-cancer regimen... In some instances, if the sample expression patterns are consistent with the expression pattern for a known disease or disease outcome, the expression patterns can be used to designate one or more treatment modalities (e.g., therapeutic regimens, anti-cancer regimen). An anti-cancer regimen may comprise one or more anti -cancer therapies. Examples of anticancer therapies include surgery, chemotherapy, radiation therapy, immunotherapy/ biological therapy, and photodynamic therapy. “determining a therapeutic regimen” reads on selecting a dose for radiotherapy. “modifying, recommending… an anticancer regimen” read on selecting a dose for radiotherapy. “continuing or discontinuing an anticancer regimen” also read on selecting a dose for radiotherapy, rather it is the same as a previously determined dose or modified to none at all. “therapeutic regimen” reads on radiation therapy and dose. “expression patterns can be used to designate one or more treatment modalities (e.g., therapeutic regimens, anti-cancer regimen)” reads on selecting a dose for radiotherapy based on the claimed determined gene profiles. Thus, Davicioni and Bosquet do suggest determining a radiotherapy dose to treat a subject, based on the claimed determined gene profiles.
Applicants’ argument: “Applicant further asserts that one of skill in the art would not have generated the specific modification/combination proposed by the Patent Office” and “Without the benefit of Applicant's disclosure, why would one want to increase the number of immune cell-specific genes monitored and evaluated for the selection of radiotherapy dose response? More specifically, why would one of skill in the art select the very specific list of genes to increase the number of immune cell-specific genes monitored and evaluated for the selection of radiotherapy dose response? There is no support in the provided disclosures for this combination.” (Pg. 28-29)
Response: Applicant's arguments filed 02/03/2026 have been fully considered but they are not persuasive. First, the combination is not necessarily required for the claim limitations of the instant claim set. Furthermore, as recited in the revised 103 rejection documented above, “Davicioni and Bosquet are both considered to be analogous to the claimed invention because they are in the same field of gene expression related to cancer diagnosis, prognosis, and therapeutic response. 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 a gene expression profile for one or more immune defense response genes or T-Cell receptor signaling genes selected from the group comprising :IFI16; determining a selection of the radiotherapy dose to treat a subject based on the gene expression profiles for the one or more genes, and treating the subject with the determined radiotherapy dose as taught by Davicioni to incorporate the method comprising the expression profile of genes comprising IFI16, PRKACA and/or RAP1GAP2 as taught by Bosquet and provide a method of determining a gene expression profile for one or more immune defense response genes, T-Cell receptor signaling genes, and/or PDE4D7 correlated genes comprising: IFI16, PRKACA and/or RAP1GAP2, selecting a radiotherapy dose to treat a subject based on a first, second and/or third expression profile and treating the subject with the determined radiotherapy dose. Davicioni provides the enabling methodology, a suggestion to modify the claimed method and evidence suggesting the modification would be successful (Example 1). It would be obvious to the ordinary artisan to try other biomarkers not specifically disclosed in Davicioni and that have been identified in prostate cancer and have documented radiotherapy treatment response data to choose the specific set of genes to determine the expression profiles and base selection of radiotherapy dose upon. Doing so would improve the prognosis of prostate cancer based on the expression profile(s) for one or more biomarkers, predictions of radiotherapy responses based on expression profiles, and treatment regimen selected and administered based on prostate cancer prognosis. (Para. 2; Para. 190)”.
Claim(s) 30, 32, 34 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Davicioni et al. (“Davicioni”; Patent App. Pub. No. WO 2019028285 A2, Feb. 07, 2019) in view of Bosquet et al. (“Bosquet”; Patent App. Pub. WO 2016004387 A1, Jan. 7, 2016), as applied to claims 1, 5-10, 25-29, 31 and 33 above and further in view of Ganswindt et al. (“Ganswindt”; (2005). 70 Gy or more: which dose for which prostate cancer?, Journal of cancer research and clinical oncology, 131(7), 407–419.).
The teachings of Davicioni and Bosquet are documented above in the rejection of claims 1, 5-10, 25-29, 31 and 33 under 35 U.S.C. 103. Claims 29, 31, and 33 depend on claim 1. Claim 30 depends on claim 29, which depend on claim 1. Claim 32 depends on claim 31, which depends on claim 1. Claims 34 and 35 depend on claim 33, which depends on claim 1.
Ganswindt discloses “Introduction: Radical prostatectomy and radiotherapy are currently accepted treatment modalities for localized prostate cancer. Regarding radiotherapy, current evidence suggests that favorable treatment outcome critically depends on adequate radiation doses. However, the exact role of dose in relation to the individual risk profile is complex. In order to evaluate available data on radiation dose response relationships, in prostate cancer, a thorough and critical literature analysis was performed.” (Abstract-Introduction)
Regarding claim 30, Ganswindt teaches a method wherein “Higher radiation dose (>66 Gy)” (Table 3, Results, ln 1-2). Thus, Davicioni, Bosquet, and Ganswindt suggest a method wherein the determined high radiotherapy dose is above 66 Gy.
Davicioni, Bosquet, and Ganswindt are considered to be analogous to the claimed invention because they are in the same field of prostate cancer and treatment prognosis. 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 methods of treating a prostate cancer as taught by Davicioni et al. and Bosquet et al. to incorporate the method wherein high radiotherapy dose is above 66 Gy as suggested by Ganswindt and provide a method for treating a prostate cancer with radiotherapy according to the limitations of claims 1, 29 and 30. These claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome according to the limitations of claims 1, 29 and 30. Doing so would allow for better disease-specific survival and overall survival for patients (Table 3).
Regarding claim 32, Ganswindt teaches a method wherein “<66 Gy” (Table 3, Results, ln 9). “<66 Gy” is interpreted as a low dose in comparison to the high dose >66 Gy. “Thus, Davicioni, Bosquet, and Ganswindt suggest a method wherein the determined low radiotherapy dose is equal to or less than 66 Gy.
Regarding claim 34, Davicioni teaches a method wherein “d) administering a treatment to the patient if the patient is determined to be at risk of developing metastatic cancer based on the level of expression of one or more immune cell-specific genes in the biological sample” (Para. 37). Ganswindt teaches a method wherein “patients with Gleason scores from 8 to 10 had a significant benefit in terms of disease-specific and overall survival when receiving radiation doses above 66 Gy.” (Pg. 413, Population-based, retrospective or pooled data analyses, Para. 2) “patients with Gleason scores from 8 to 10” are interpreted as high risk. “radiation doses above 66 Gy” is interpreted as high dose. Thus, Davicioni, Bosquet, and Ganswindt suggest a method wherein a high dose is selected for the radiotherapy dose when the subject is determined to be in the high-risk cohort.
Regarding claim 35, Ganswindt teaches a method wherein “dose groups of <66 Gy versus 66.6 Gy versus >66.6 Gy in 264 low risk prostate cancer patients. Neither significant differences in (5 years) bNED rates between the three dose groups (79.2% vs 78.4% vs 84.5%)” (Pg. 415, Col. 1, Para. 3). “<66 Gy” reads on low dose. Furthermore, other studies analyzed suggested a method wherein a lower dose would have decreased toxicity “Toxicity after 3D conformal radiation therapy was dose dependent. Actuarial (5 year) rate of grade 2 rectal toxicity: 14% (95% CI±2) after ≥75.6 Gy. and 5% (95% CI±2) after ≤75.6 Gy (P<0.001)” (Table 2). Thus, Davicioni, Bosquet and Ganswindt suggest a method wherein a low dose is selected for the radiotherapy dose when the subject is determined to be in the low-risk cohort.
Response to Arguments
Applicant's arguments filed 02/03/2026 with respect to claims 1, 29-32 and 33-35 have been fully considered but they are not persuasive. Arguments against Davicioni and Bosquet on Pg. 24-28 are not persuasive as discussed above.
Conclusion of Response to Arguments
In view of the amendments, revised and new grounds of rejections, and responses to arguments are documented 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.
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/KENDRA R VANN-OJUEKAIYE/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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