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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/09/2026 has been entered.
Response to Amendment/Status of Claims
Receipt of Arguments/Remarks filed on 03/09/2026 is acknowledged. Claims 1-6,8,9,11 and 13 stand cancelled. No claims were amended. Claims 7,10,12 and 14 are pending and under examination.
Priority
Applicant has provided an English translation of the Foreign Priority Application JP2019-105500 with a statement that the translation of the certified copy is accurate. The priority application has a filing date of June 5, 2019 and therefore the instant claims receive the priority date of June 5, 2019.
Response to Arguments
The Declaration under 37 CFR 1.132 filed 03/09/2026 is insufficient to overcome the rejection of claims 7,10,12 and 14 based upon 35 U.S.C. 103 as set forth in the last Office action because: the Declaration points to Figure 1 and Example 2 of the present specification to show results of proliferation assays conducted using 41 miRNAs in colorectal cancer cell lines (DLD1, HCT116 and HT29). The Declaration states the miRNA identified as No. 20 in Figure 1 corresponds to miR-4711-5p and demonstrates markedly superior inhibitory effects on colorectal cancer cell proliferation compared to the other tested miRNAs, and that the remaining 40 miRNAs shown in Figure 1 are the miRNAs listed in the table appended herewith, and each of these miRNAs is also disclosed in Table 1 of Lee et al. The Declaration states that Figure 1 of the present application clearly demonstrates that miR-4711-5p exhibits significantly greater inhibitory effect on colorectal cancer cell proliferation than the other miRNAs taught by Lee et al. which was completely unexpected.
This was not found persuasive, because nothing in the Declaration points to any unexpected effects regarding the activity of miR-4711-5p with regards to pancreatic cancer. The Declaration points to Figure 1 and Example 2 and only pertains to colorectal cancer, however the claims also recite treating pancreatic cancer. Therefore, no unexpected results have been explained or cited in regards to treating pancreatic cancer. In addition, Figure 1 in the instant application that applicant cites for unexpected results, does not appear to show unexpected effects in the DLD1 cells. miR-4711-5p does not even show the best inhibitory effect in DLD1 cells, as while it is below 40% cell viability, there are numerous other miRs with superior inhibitory activity, including many with 20% or less cell viability. Therefore, no unexpected effect has been shown for miR-4711-5p with regards to the DLD1 cells. With regards to the HCT116 cells in Figure 1, there does appear to be a superior inhibitory effect on cell viability for miR-4711-5p. However, the claims are not limited to this cell line. Regarding HT29, there is another miR (No. 26) that appears to have almost the same effect on cell viability as miR-4711-5p.
Therefore, the results shown are not commensurate in scope with the claims. Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003); In re Grasselli, 713 F.2d 731, 741, 218 USPQ 769, 777 (Fed. Cir. 1983). Note: MPEP 716.02(d).
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 7 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (US 20190218555), Published 18 July 2019, cited on an IDS.
Claim Interpretation: Claims 7 and 10 recite “comprising administering a therapeutically effective amount of miR-4711-5p to a cancer patient”, and therefore do not limit the claims to only administering a therapeutically effective amount of miR-4711-5p to a cancer patient, and encompasses administering other agents as well.
Regarding claims 7 and 10, Lee et al. recite a method for treating colorectal cancer or pancreatic cancer, comprising administering a pharmaceutical composition comprising miR-8078 as an active ingredient to a patient/subject in need of cancer treatment (claim 6), and teaches a composition for treating cancer which comprises the miRNA of the present invention and a pharmaceutically acceptable carrier, and includes parenteral formulations (paragraph 0063). Lee et al. teach that studies have revealed that expression patterns of miRNAs in cancer cells greatly differ from expression patterns in normal cells, as well as expression patterns differing depending on the primary organs in which cancer occurred (paragraph 0011), and based on the deep connection of miRNA in cancer, it has recently been attempted to use miRNAs as anticancer therapeutic agents (paragraph 0012). Lee et al. teach an object of the invention is to identify miRNA having excellent abilities to inhibit cancer cell proliferation and induce cancer cell apoptosis, and provide a pharmaceutical composition for treatment of cancer comprising the miRNA as an active ingredient (paragraph 0014).
Lee et al. teach a screening library of 1700 miRNAs and their sequences, including miR-4711 having SEQ ID NO: 1887 below (Table 1, page 32):
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25
658
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SEQ ID NO: 1887 of miR-4711 of Lee et al. is the same sequence as the instantly claimed miR-4711-5p, which based on the instant specification the sequence is:
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29
421
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Lee et al. does not teach administering the miR-4711 of SEQ ID NO: 1887 to a colorectal or pancreatic cancer patient.
However, it would have been obvious to one of ordinary skill in the art before the effective filing date, to pick the miR-4711 of SEQ ID NO: 1887 from the miRNA screening library and intravenously administer to a colorectal cancer patient or pancreatic cancer patient with a reasonable expectation of success, to treat colorectal cancer or pancreatic cancer, respectively. Alternatively, it would have been obvious to one of ordinary skill in the art to select any of the specifically taught miRNAs, including the miR-4711 of SEQ ID NO: 1887 and combine with miR-8078 and administer them both together, with a reasonable expectation of success, for an additive effect on treating colorectal cancer or pancreatic cancer. Administering the miR-4711 of SEQ ID NO: 1887 to a colorectal cancer patient or pancreatic cancer patient would have been obvious to try based on choosing from a finite number of identified, predictable solutions with a reasonable expectation of success (the miRNA screening library) for treating cancer. One of ordinary skill in the art would have been motivated to administer the miR-4711 of SEQ ID NO: 1887, or the combination of miR-8078 and miR-4711 to a colorectal cancer patient or pancreatic cancer patient, because Lee et al. teach the need to identify miRNA having excellent abilities to inhibit cancer cell proliferation and induce cancer cell apoptosis, and provide a pharmaceutical composition for treatment of cancer, including colorectal cancer and pancreatic cancer, and would make obvious the limitations of claims 7 and 10.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Response to Arguments
Applicant's arguments filed 03/09/2026 have been fully considered but they are not persuasive.
Applicant argues on page 4 that the second Rule 132 Declaration by Hirofumi Yamamoto, dated March 4, 2026 explains that miR-4711 exhibits a superior inhibitory effect on colorectal cancer cell proliferation compared with the other miRNAs taught by Lee and Test Example 2 and Figure 1 of the present specification shows the results of proliferation assays conducted using 41 different miRNAs in colorectal cancer cell lines, DLD1, HCT116 and HT29. miR-4711-5p corresponds to No. 20 in Figure 1, and as shown in Figure 1, demonstrates markedly superior effect on colorectal cancer cell proliferation compared to the other tested miRNAs. The remaining 40 miRNAs in Figure 1 are the miRNAs listed in Mr. Hirofumi Yamamoto’s Rule 132 Declaration, and each of these miRNAs is listed in Table 1 of Lee. Applicant argues that Figure 1 of the present application thus clearly demonstrates that miR-4711-5p exhibits a significantly greater inhibitory effect on colorectal cancer cell proliferation than other miRNAs taught by Lee, and there was no way of knowing that miR-4711-5p would stand out from all of the other miRNAs including those taught by Lee, and therefore the present methods are not prima facie obvious over Lee.
This is not found persuasive. The Declaration does not point to any unexpected effects regarding the activity of miR-4711-5p with regards to pancreatic cancer. The Declaration points to Figure 1 and Example 2 and only pertains to colorectal cancer, however the claims also recite treating pancreatic cancer. Therefore, no unexpected results have been explained or cited in regards to treating pancreatic cancer. In addition, Figure 1 in the instant application that applicant cites for unexpected results, does not appear to show unexpected effects in the DLD1 cells. miR-4711-5p does not even show the best inhibitory effect in DLD1 cells, as while it is below 40% cell viability, there are numerous other miRs with superior inhibitory activity, including many with 20% or less cell viability. Therefore, no unexpected effect has been shown for miR-4711-5p with regards to the DLD1 cells. With regards to the HCT116 cells in Figure 1, there does appear to be a superior inhibitory effect on cell viability for miR-4711-5p. Regarding HT29, there is another miR (No. 26) that appears to have almost the same effect on cell viability as miR-4711-5p.
Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. An unexpected property or result must actually be unexpected and of statistical and practical significance. The burden is on the applicant to establish the results are in fact unexpected, unobvious and of statistical and practical significance. See MPEP 716.02.
For these reasons, the 35 U.S.C 103 rejection of claims 7 and 10 over Lee et al. is maintained.
Claims 12 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. as applied to claims 7 and 10, and further in view of Yamamoto et al. (US 20170073686), Published 16 March 2017.
The teachings of Lee et al. as applicable to claims 7 and 10 are described above.
Lee et al. does not teach miR-4711-5p is complexed to a carbonate apatite particle.
However, before the effective filing date, Yamamoto et al. teach a therapeutic agent for colorectal cancer including microRNA (paragraph 0001). Yamamoto et al. recites a therapeutic agent comprising either one or both of miR4689 and miR4685-3p in the form of a complex with carbonate apatite particles (claim 4) and recites a method of treating a colorectal cancer comprising a step of administering a therapeutically effective amount of one or both of miR4689 and miR4685-3p to a patient with the colorectal cancer (claim 6). Yamamoto et al. teach a preparation of complex particles of miR4689 and carbonate apatite particles were injected into the caudal vein at amount of 40ug of the miR (Example 9, paragraph 0131), and results showed when the complex particles of miR4689 and carbonate apatite particles were administered into the caudal vein, proliferation of DLD1 cells was significantly suppressed and when administered in the form of the complex particles of carbonate apatite particles, miR4689 exhibited significantly excellent antitumor effect on colorectal cancer cells (paragraph 0133), and apoptosis of cancer cells (Example 10, paragraph 0136). Additionally, Yamamoto et al. teach one or both of the miR4689 and miR4685-3p as the complex with the carbonate apatite particles enables either one or both of the miRs to be efficiently accumulated on the colorectal cancer cells within a living organism by the action of carbonate apatite, and after introduction into the cells, the miR is released from the carbonate apatite particles within the cells and as a result an antitumor effect of one or both of the miRs can be efficiently exhibited (paragraph 0088).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the miR-4711 of SEQ ID NO: 1887 used in the method of Lee et al. for treating colorectal cancer or pancreatic cancer, by forming a complex with carbonate apatite particles based on the teaching of Yamamoto et al. with a reasonable expectation of success. There would be a reasonable expectation of success, as both Lee et al. and Yamamoto teach methods of treating colorectal cancer with miRNA based therapeutics. One of ordinary skill in the art would have been motivated to provide the miR-4711 of SEQ ID NO: 1887 of Lee et al. in a complex with carbonate apatite particles to administer to a colorectal cancer patient or pancreatic cancer patient, because Yamamoto et al. teach efficient accumulation of the miR(s) on colorectal cancer cells within a living organism by action of carbonate apatite (paragraph 0088) and when complex particles of miR4689 and carbonate apatite particles were administered into the caudal vein, proliferation of DLD1 cells was significantly suppressed and when administered in the form of the complex particles of carbonate apatite particles, miR4689 exhibited significantly excellent antitumor effect on colorectal cancer cells (paragraph 0133), and apoptosis of cancer cells (Example 10, paragraph 0136), and would make obvious the limitations of claims 12 and 14.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Response to Arguments
Applicant's arguments filed 03/09/2026 have been fully considered but they are not persuasive.
Applicant states that they have not addressed all of the issues on the dependent claims, and does not necessarily agree with the characterization and assessment of the dependent claims made by the Examiner and believes each claim is patentable on its own merits.
This is not found persuasive. No additional arguments have been made regarding Yamamato et al. and the examiner has responded to the rejection of claims 7 and 10 as unpatentable over Lee et al. above regarding the obviousness of the instant claims and Applicant’s arguments regarding the Declaration, Figure 1 and Example 2, and therefore maintains the 103 rejection of claims 12 and 14 as obvious over Lee et al. and Yamamato et al.
Conclusion
Claims 7,10,12 and 14 are rejected.
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/STEPHANIE L SULLIVAN/Examiner, Art Unit 1635
/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636