DETAILED ACTION
The present application is a national stage entry of PCT/JP2022/006831, filed 21 February 2022, which claims foreign priority to JP2021-026848, filed 23 February 2021.
Claims 1-5, 9-12 and 14-37 are pending in the current application. Claims 1-5, 9-12, 14-16, and 29-37 are withdrawn as being drawn to a non-elected invention. Claims 17-28 are examined on the merits herein.
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 .
Election/Restrictions
Applicant’s election of Group II, claims 17-28 in the reply filed on 28 January 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-5, 9-12, 14-16, and 29-37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant’s election of imatinib as a first species of tyrosine kinase inhibitor in the reply filed on 28 January 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Objections
Claim 17 is objected to because they include limitations from a withdrawn claim. In accordance with MPEP 2173.05(h), “Where possible, claims are to be complete in themselves.”. The claim should be amended to include all the limitations from the withdrawn claim.
Appropriate correction is required.
Applicant is advised that should claim 19 be found allowable, claim 20 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing the claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 706.03(k). Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 28 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.
The recitation “for preventing the recurrence of chronic myeloid leukemia that occurs after treatment with a tyrosine kinase inhibitor is discontinued…” in claim 28 renders the claim herein indefinite. Claim 28 depends from claim 17, which does not recite the use of a tyrosine kinase inhibitor. It’s not clear if the method requires the previous administration of a tyrosine kinase inhibitor, or if it’s referring to a future use of a tyrosine kinase inhibitor.
Since no tyrosine kinase inhibitor is positively administered, the recitation above is interpreted as an intended use.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 17-20 and 28 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Sako et al. (US Patent Application Publication No. 2018/0179246, cited in PTO-892).
Sako et al. teach the use of 5-azacytidine or 2’-deoxy-5-azacytidine prodrug for treating myelomas, including myelodysplastic syndrome (abstract). The prodrugs are represented by formula (1):
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228
162
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, wherein R is OR3 or a hydrogen atom, R1, R2, and R3 are each independently hydrogen atom or silyl group represented by formula (2):
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102
94
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, wherein R4, R5 and R6 are each independently alkyl group (para [0051]-[0054]). Sako et al. teach using the compound to treat chronic myeloid leukemia (CML), (para [0086]). Compound B is identified as 5’-O-trimethylsilyl-2’-deoxy-5-azacytidine (para [0110]). Compound K is 5’-O-triethylsilyl-2’-deoxy-5-azacytidine (para [0155]). Sako et al. teach the prodrug shows stability against cytidine deaminase (abstract). The prodrugs can be administered orally (para [0048], [0083], [0089]).
The recitation “wherein the method prevents the recurrence of chronic myeloid leukemia based on the effect of inhibiting stem cells of chronic myeloid leukemia” in claim 17 necessarily occurs upon performing the positively recited step.
The recitation “for preventing the recurrence of chronic myeloid leukemia that occurs after treatment with a tyrosine kinase inhibitor is discontinued followed by amelioration due to the treatment of chronic myeloid leukemia” in claim 28 is an intended use of the method claim.
Sako et al. exemplify a compound that reads on the present claims, and identifies treating CML from a small list of possible conditions.
Thus, the disclosure of Sako et al. anticipates claims 17-20 and 28 of the present application.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 17-26 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Sako et al. (cited above) in view of Jiang et al. (Oncology Letters, 2017, vol. 14, pp. 1295-1302, cited in PTO-892).
Sako et al. teach as discussed above.
Sako et al. do not expressly disclose administering imatinib (present claims 21-24).
Jiang et al. teach administering 2’-deoxy-5-azacytidine (also known as decitabine) in combination with a tyrosine kinase inhibitor (TKI) to treat CML (abstract). The decitabine functions as a DNA methylation inhibitor, and is known to be effective in patients with CML (p.1295, last para). Jiang et al. found decitabine demonstrated a dose-dependent proliferation inhibition in an in vitro CML model (p.1298, last para). A significant difference in cell proliferation was identified from the combination of using 0.1 µM imatinib and 5 µM decitabine (figure 1). Jiang et al. suggest decitabine recovers SHP-1 expression through demethylation, thereby enhancing the therapeutic effect of TKIs (p.1301, last para). Thus, decitabine combined with TKIs provides another strategy for managing TKI tolerance and the progression of CML in patients.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer 5’-O-trimethylsilyl-2’-deoxy-5-azacytidine or 5’-O-triethylsilyl-2’-deoxy-5-azacytidine in combination with imatinib to treat CML.
From the teaching of Jiang et al., one having ordinary skill in the art would have been motivated to administer 2’-deoxy-5-azacytidine (decitabine), including in combination with imatinib to treat a patient having CML. The ordinary artisan would have been motivated to substitute 2’-deoxy-5-azacytidine (decitabine) with a prodrug of 2’-deoxy-5-azacytidine with a reasonable expectation of success, because the prior art teach the active drug and prodrug are each useful in treating CML.
The skilled artisan would have been motivated to administer 5’-O-trimethylsilyl-2’-deoxy-5-azacytidine or 5’-O-triethylsilyl-2’-deoxy-5-azacytidine as the prodrug in combination with imatinib, because Jiang et al. identified these prodrugs as having remarkable stability against cytidine deaminase for treating myelomas, including CML.
With respect to the route of administration, Jiang et al. teach the prodrug can be administered orally. Thus, one of ordinary skill in the art would have been motivated to administer the prodrug orally.
With respect to the order of administration, one having ordinary skill in the art would have been motivated to administer the combination of active agents at the same time, or sequentially. Sequential administration would either involve administering the prodrug and then the TKI, or the TKI and then the prodrug.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claim(s) 25-27 are rejected under 35 U.S.C. 103 as being unpatentable over Sako et al. in view of Jiang et al. as applied to claims 17-24 and 28 above, and further in view of Abaza et al. (Am. J. Hematol., 2020, vol. 95, pp. 1288-1295, cited in PTO-892).
Sako et al. teach as discussed above.
Sako et al. do not expressly disclose the order of administration, or the route of administration (present claims 25-27).
Jiang et al. teach as discussed above.
Abaza et al. teach administering a combination of decitabine with dasatinib, a TKI, to patients suffering from advanced-phase chronic myeloid leukemia (CML), (abstract). Two different dosing schedules were investigated, both of which involved administering decitabine intravenously and the tyrosine kinase inhibitor orally (also see Table 2). Abaza et al. found the combination was effective to achieve myelosuppression (p.1294, second para). Survival probability among responders was better than what would have been expected with either agent alone (p.1294, last para).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer 5’-O-trimethylsilyl-2’-deoxy-5-azacytidine or 5’-O-triethylsilyl-2’-deoxy-5-azacytidine in combination with imatinib to treat CML.
In addition to the reasons discussed above, the ordinary artisan would have had a reasonable expectation of success because Abaza et al. found the combination of decitabine with a tyrosine kinase inhibitor achieved myelosuppression, and increased survival probability in patients with advanced-phase CML.
The ordinary artisan would have been motivated to administer the prodrug of formula (I) orally and the tyrosine kinase inhibitor orally because Sako et al. teach the prodrugs can be formulated for oral delivery, and Abaza et al. teach administering the TKI orally.
With respect to the order of administration, one having ordinary skill in the art would have been motivated to administer the combination of active agents at the same time, or sequentially. Since Abaza et al. teach administering the decitabine intravenously, and the TKI orally, the reference suggests administering the drugs sequentially. Sequential administration would either involve administering the prodrug and then the TKI, or the TKI and then the prodrug.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699