DETAILED ACTION
The amendment filed on 03/16/2026 has been entered. No new matter has been added.
Claims 1-5,7,11-15,17-20,22,24, 26 and 29 are pending.
Applicant’s election without traverse of Group I (claims 1-5 and 7), drawn to a method of determining susceptibility and response to an immune checkpoint therapy in a subject in need in the reply filed on 11/11/2025 is acknowledged. Claim 29 was amended to be a dependent claim within Group I.
Claims 11-15,17-20,22 and 24-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/11/2025.
Claims 1 and 4 are amended in the claim set filed on 03/16/2026.
Claim 30 is added in the claim set filed on 03/16/2026.
Claim 25 is canceled in the claim set filed on 03/16/2026.
Claims 1-5, 7 and 29-30 in the claim set filed on 03/16/2026 are currently under examination.
Response to the Arguments
Objections to the Drawings and Specification in the previously mailed non-final are withdrawn in light of the Drawings and Specification amendments.
Applicant’s arguments regarding previous rejection(s) of claim 4 under 35 U.S.C. 112 (b) has been fully considered but is not persuasive. The 35 U.S.C. 112 rejections documented in the previously mailed non-final have been maintained and revised (documented below on Pg. 3-4) in light of applicants claim amendments and arguments on Pg. 10-11.
The arguments for claims 1 and 4 do not address the rejection of claims 5 and 29 under 35 U.S.C. 112 (b). However, after further consideration previous rejection(s) of claims 5 and 29 under 35 U.S.C. 112 (b) have been withdrawn.
Applicant’s arguments regarding previous rejection(s) of claim(s) 1-5, 7 and 29 under 35 U.S.C. 101 have been fully considered and are persuasive. The 35 U.S.C. 101 rejections documented in the previously mailed non-final have been withdrawn in light of applicants’ amendments and arguments on Pg. 12-14.
Applicant’s arguments regarding rejection(s) of claim(s) 1-5, 7 and 29-30 under 35 U.S.C. 103 have been fully considered but are not persuasive. The 35 U.S.C. 103 rejections documented in the previously mailed non-final have been revised and maintained (documented below on Pg. 4-12) in light of applicants’ amendments and arguments on Pg. 11-12.
The rejections for claims 1-5, 7 and 29-30 are documented below in this Final Office Action are maintained and revised.
Priority
This application is the U.S. National Stage of PCT/US2021/0451991 with international filing date of August 9, 2021, and which claims the benefit of priority under 35 U.S.C. § 119(e) of United States Provisional Application No. 63/066,079, filed August 14, 2020.The priority date of claim set filed on November 11, 2025, is determined to be August 14, 2020.
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.
Claim 4 is 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.
Claim 4 is indefinite over the limitation “wherein one or more genes comprise TREM2, secreted phosphoprotein 1 (SPP1), and ribonuclease A family member 1, pancreatic (RNASE1)”. It is unclear if the “one or more genes comprise… and” is indicating any one or more genes as long as they comprise at least one the genes listed, or if the genes comprise at least the combination of the genes listed.
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, 7, and 30 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Davicioni et al. (“Davicioni”; Patent App. Pub. CA 3072061 A1, Feb. 07, 2019).
The inclusion of claim 30 is necessitated by claim amendments filed on 03/16/2026.
Claim interpretations: Regarding claim 4, the limitation “one or more genes comprise at least” is interpreted as minimum requirement of one gene which is comprised of TREM2 as recited in claim 1.
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 claims 1 and 30, Davicioni teaches a method comprising” Incorporation of molecular markers in clinical practice may define tumor subtypes that are more likely to respond to targeted therapy” (Para. 4). Davicioni teaches a method comprising “In some embodiments, the disclosure includes a method for determining a prognosis and treating a patient for cancer, the method comprising: a) obtaining a biological sample comprising cancer cells from the patient; 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” (Para. 10). Davicioni teaches a method comprising “In some embodiments, the treatment is …immunotherapy….” (Para. 10). Davicioni teaches a method comprising “Table 2. In some embodiments, the immune cell-specific gene comprises or consists of at least 1, 2, 3, … or 250 genes selected from Table 2. In some embodiments, the immune cell-specific gene is one or more genes selected from …TREM2…” (Para. 10). Davicioni teaches a method comprising “based on the levels of immune cell-specific gene expression… patient compared to reference value ranges for a control subject” (Para. 23). Furthermore, Davicioni teaches a method comprising “immune checkpoint molecules that are targets of clinically utilized drugs (anti-CTLA-4, anti-PD-1, anti-PD-L1” (Para. 199; Para. 201) and “Immune checkpoint inhibitors target CTLA-4 and PD-1” (Para. 206). “;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” reads on “b) identifying the subject as likely to respond to the ICT; and (c) administering the ICT to the subject identified as likely to respond to the ICT”. Thus, Davicioni suggests a method of identifying a subject as likely to respond to an immune checkpoint therapy (ICT) , the method comprising: (a) detecting an expression level of one or more genes associated with an immune cell gene expression signature (ImmuneCells.Sig), wherein the one or more genes comprise at least triggering receptor expressed on myeloid cells 2 (TREM2) and where in the expression levels of the one or more genes are reduced as compared to control expression levels; (b) identifying the subject as likely to respond to the ICT; and (c) administering the ICT to the subject identified as likely to respond to the ICT.
Furthermore, Davicioni suggests a method of identifying a subject as likely to respond to an immune checkpoint therapy (ICT), the method comprising:(a) detecting an expression level of one or more genes comprising triggering receptor expressed on myeloid cells 2 (TREM2), ADAM21, ALDH1L2, APBB2, APOC2, ARSF, ASAH2, ASPM, BIRC5, C6orf223, CACNG1, CCL18, CD177, CD244, CDCA5, CDH1, CEACAM6, CILP2, CLDN7, CLNK, CORO7, CR2, CRTAM, CYTL1, DHRS9, DLK1, DUSP13, EIF4A2, ENTHD1, FBLN1, FBLN2, FMOD, FOLR2, FOXI1, GBP1P1, GDF1, GIMAP4, GPR31, GRIA1, GRM7, ITGA3, JMJD7, KIR2DL4, KIRREL2, KLHDC8B, KRT4, LALBA, LEF1, LINC00243, LYSMD2, MAEL, MAP2K5, MATN3, MFAP2, MKI67, MMP12, MMP9, MT1G, MUSK, MXRA8, MYL1, MYOIG, NACA2, NACA3P, NUDT10, NUPR1, OTOF, PCLAF, PKDCC, PLA2G2D, PPA2, PPP4R3C, PRPH, PRUNE2, RASL12, RIMS2, RNASE1, ROR1, RPL36AP41, RRM2, SCGB2A2, SELENOP, SH2D2A, SHC3, SLC16A3, SPATA13, SPC24, SPP1, STC1, STC2, STOML3, SYT6, TDRD15, TEAD2, TK1, TM4SF19, TMEM171, TRAF3IP2, TRPC4, TSHZ3, TUBA8, TYMS, UBE2C, UNC80, ZNF219, ZNF462, and ZNF610, ZNF880; (b) identifying the subject as likely to respond to the ICT based on the expression levels of the one or more genes; and (c) administering the ICT to the subject identified as likely to respond to the ICT.
The teachings of Davicioni are documented above in the rejection of claim 1 under 35 U.S.C. 103. Claims 1 and 30 are independent claims. Claims 2-3 and 5 depend on claim 1. Claim 4 depends on claim 3, which depends on claim 1. Claim 7 depends on claim 5, which depends on claim 1.
Regarding claim 2, Davicioni teaches a method wherein “the cancer is selected from the list consisting of…melanoma” (Para. 38). Thus, Davicioni teaches a method wherein the subject has a cancer selected from basal cell carcinoma (BCC) and melanoma.
Regarding claim 3, Davicioni teaches a method wherein “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.” (Para. 10) and “In some embodiments, the treatment is … immunotherapy” (Para. 10). Steps c) and d) read on “if the expression level of one or more genes is lower than the expression levels of the control expression levels. ”Thus, Davicioni teaches a method wherein the method comprises treating the subject with an immune checkpoint therapy if the expression level of one or more genes is lower than the expression levels of the control expression levels.
Regarding claim 4, Davicioni teaches a method wherein “TREM2” (Para. 10, Table 2). Thus, Davicioni suggests a method wherein the one or more genes comprise at least TREM2, secreted phosphoprotein 1 (SPP1), and ribonuclease A family member 1, pancreatic (RNASE1).
Regarding claim 5, Davicioni teaches a method wherein “RRM2” (Para. 10; Table 2). Thus, Davicioni teaches a method wherein the one or more genes further comprise ribonucleotide reductase regulatory subunit M2 (RRM2).
Regarding claim 7, Davicioni teaches a method wherein “immune checkpoint molecules that are targets of clinically utilized drugs (anti-CTLA-4, anti-PD-1, anti-PD-L1” (Para. 199; Para. 201) and “Immune checkpoint inhibitors target CTLA-4 and PD-1” (Para. 206). Thus, Davicioni teaches a method wherein the immune checkpoint therapy is a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA4 inhibitor, or any combination thereof.
Therefore, the invention as recited in claims 1-5 and 7 are prima facie obvious over the prior art Davicioni et al. One of ordinary skill in the art would have had a reasonable expectation of success as the claim are prima facia obvious. It would have been obvious to provide a method of identifying a subject as likely to respond to an immune checkpoint therapy (ICT) according to the limitations of the instant application claims 1-5 and 7 based on Davicioni et al. (Patent App. Pub. No. CA 3072061 A1).
Response to Arguments
Applicant' s arguments filed 03/16/2026 (Pg. 11-12) with respect to claim 1-5 ,7 and 30 have been considered but are not persuasive. To clarify some instances argued in the response filed 03/16/2026 see responses to each argument made by Applicant below:
Applicants’ argument: “Davicioni does not teach or suggest identifying a subject as likely to respond to immune checkpoint therapy, as recited in claims 1 and 30.”(Pg. 11)
Response: In response to the applicants’ arguments above, the revised rejection under 35 U.S.C. 103 (documented above) does suggest identifying a subject as likely to respond to immune checkpoint therapy, as recited in claims 1 and 30. As stated above, briefly, “Davicioni teaches a method comprising… 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” (Para. 10). “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” reads on “b) identifying the subject as likely to respond to the ICT; and (c) administering the ICT to the subject identified as likely to respond to the ICT”.
Applicants’ argument: “More broadly, Davicioni does not teach or suggest predicting responsiveness to immune checkpoint therapy (ICT) nor does the reference teach that TREM2 is associated in any way with predicting subject response to ICT)” (Pg. 11)
Response: In response to the applicants’ argument above, “predicting responsiveness to immune checkpoint therapy (ICT)” is not an actual limitation examined as it is stated. Furthermore, Davicioni suggests that limitation as well, as stated in Para. 139 “Diagnosing, predicting, or monitoring a status or outcome of a cancer may comprise treating a cancer or preventing a cancer progression. In addition, diagnosing, predicting, or monitoring a status or outcome of a cancer may comprise identifying or predicting responders or non-responders to an anticancer therapy.”
Applicants’ argument: “In addition, a person of ordinary skill in the art would not have had a reasonable expectation of success in identifying a subject as likely to respond to an ICT based on Davicioni, because the reference does not teach or suggest that TREM2 is associated with ICT responsiveness.” (Pg. 12)
Response: In response to the applicants’ argument above, Davicioni does suggest TREM2 is associated with ICT responsiveness, as stated in the revised rejection above, “Davicioni teaches a method comprising “Incorporation of molecular markers in clinical practice may define tumor subtypes that are more likely to respond to targeted therapy“ (Para. 4). Davicioni teaches a method comprising “In some embodiments, the disclosure includes a method for determining a prognosis and treating a patient for cancer, the method comprising: a) obtaining a biological sample comprising cancer cells from the patient; 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” (Para. 10). Davicioni teaches a method comprising “In some embodiments, the treatment is …immunotherapy….” (Para. 10). Davicioni teaches a method comprising “Table 2. In some embodiments, the immune cell-specific gene comprises or consists of at least 1, 2, 3… or 250 genes selected from Table 2. In some embodiments, the immune cell-specific gene is one or more genes selected from …TREM2…” (Para. 10).” Thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to associate TREM2 with immune checkpoint therapy responsiveness as suggested by Davicioni.
Claims 1, 5 and 29 is rejected under 35 U.S.C. 103 as being unpatentable over Davicioni et al. (“Davicioni”; Patent App. Pub. CA 3072061 A1, Feb. 07, 2019) in view of Rhodes et al. (“Rhodes”; Patent App. Pub. AU 2010326066 A1, Jun. 21, 2012).
The teachings of Davicioni are documented above in the rejection of claims 1-5 and 7 under 35 U.S.C. 103. Claim 29 depends on claim 5, which depends on claim 1.
Regarding claim 29, Davicioni teaches a method wherein “CDCA5...TREM2…RRM2” (Para. 10; Table 2). Davicioni teaches “While some embodiments of the disclosure have been illustrated and described, it will be appreciated that various changes can be made therein without departing from the spirit and scope of the disclosure” (Para. 210).
Davicioni does not explicitly teach the limitations of claim 29 “wherein the one or more genes further comprises baculoviral IAP repeat containing 5 (BIRC5), SPC24 component of NDC80 kinetochore complex (SPC24), ubiquitin conjugating enzyme E2 C (UBE2C)…”
Rhodes discloses “a system for classifying a patient's cancer as belonging to one or more Cancer Modules of 1 of 15 different cancer types is provided. The Cancer Modules are useful to identify patient populations and individual patients demonstrating specific prognosis, risk of metastasis and/or recurrence, response or lack of response to drugs, and the like.” (Abstract)
Regarding claim 29, Rhodes teaches a method wherein “The patient's prognosis, including response to therapy, recurrence, and/or metastasis, can be predicted based on the Cancer Module identified, for example using microarray analysis and the expression profiles of the Cancer Modules set forth in Tables 1-161” (Para. 81) and “UBE2C... BIRC5…SPC24” (Table 86; Table 10). Thus, Davicioni and Rhodes teach a method wherein the one or more genes further comprises baculoviral IAP repeat containing 5 (BIRC5), SPC24 component of NDC80 kinetochore complex (SPC24), ubiquitin conjugating enzyme E2 C (UBE2C), and cell division cycle associated 5 (CDCA5).
Davicioni and Rhodes are both considered to be analogous to the claimed invention because they are in the same field of cancer patient's prognosis, including response to therapy. 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 of identifying a subject as likely to respond to an immune checkpoint therapy (ICT) according to the limitations of the instant application claims 1 and 5; and wherein the genes further comprise CDCA5...TREM2…RRM2 as taught by Davicioni to incorporate the method of determining the expression of BIRC5, SPC24 and UBE2C as taught by Rhodes and provide a method of identifying a subject as likely to respond to an immune checkpoint therapy (ICT) comprising detecting the expression level of one or more genes comprising TREM2 and further comprises RRM2, BIRC5, SPC24, UBE2C and CDCA5. 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, 5 and 29. Doing so would allow for assessment of genes in a subject for useful to prediction of patients’ prognosis, including response to therapy (e.g. immune checkpoint inhibitors), recurrence, and/or metastasis.
Response to Arguments
Applicant' s arguments filed 03/16/2026 (Pg.12) with respect to claim 1, 5 and 29 have been considered but are not persuasive. To clarify some instances argued in the response filed 03/16/2026 see responses to each argument made by Applicant below:
Applicants’ argument: “Rhodes does not teach that any of these markers are predictive of responsiveness to immune checkpoint therapy, nor does Rhodes suggest that BIRC5, SPC24, or UBE2C are relevant to determining susceptibility or response to ICT in any context.”(Pg. 12) and “the combination of references does not teach or suggest each and every element of claims 1, 5, and 29, nor would a person of ordinary skill in the art have had a reasonable expectation of success” (Pg. 12).
Response: In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Furthermore, Rhodes does suggest analysis and the expression profiles of BIRC5, SPC24, or UBE2C to predict the patient's prognosis, including response to therapy, recurrence, and/or metastasis, as stated in the U.S.C. 103 rejection above. As stated in the 103 rejection above, these claim elements were taught by Davicioni and Rhodes before the effective filing date 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, 5 and 29 with a reasonable expectation of success.
Conclusion of Response to Arguments
In view of the amendments, documented above in this Final Office Action are maintained and revised rejections as necessitated by amendment as well as responses to arguments. No claims are in condition for allowance.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's
disclosure: Patent App. Pub. No: WO 2019070755 A1 (RNASE1-Para. 46, Table 4, Table 27C; SPP1-Para. 78, Table 4, Table 27C; TREM2- Para. 68, Table 3, and Claim 4).
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