FINAL 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 08/19/2025 has been entered.
Status of the Claims
This action is in response to papers filed 08/19/2025 in which claims 7-10 and 12-14 were previously canceled; claims 1-6 were previously withdrawn; and no claim was amended.
Claims 11 and 15 are under examination.
Maintained Rejection
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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) 11 and 15 are is/are rejected under 35 U.S.C. 103 as being unpatentable over Green et al (US 2009/0274773 A1) in view of Baba et al (US 2015/0011499 A1), Yonemura et al (Cancer Sci., January 2007, Vol. 98, No. 1, pages 11-18), and Dilruba et al (Cancer Chemother Pharmacol, 2016, 77: 1103-1124; cited in IDS filed 04/12/2021).
Regarding claims 11 and 15, Green teaches a method of treating a tumor or cancer comprising administering to a subject in need thereof a pharmaceutical combination of a cytosine nucleoside analogue and platinum antineoplastic such as cisplatin (Abstract; [0003], [0007]-[0008], [0011], [0025], [0027], [0029]-[0031], [0047], [0049], [0054], [0067]-[0069], [0070]-0075], [0079]-[0080], [0082], [0102]-[0109] and [0164]-[0182]; claims 1, 10-19, and 29-35). Green teaches the tumor or cancer include ovarian cancer ([0079]). Green teaches cisplatin is known to be used for the treating of ovarian cancer ([0079]). Green teaches the cytosine nucleoside analogue and platinum antineoplastic are administered to the subject separately, simultaneously or sequentially ([0029]-[0031], [0047], [0070]-[0075] and [0079]-[0082]; claims 1, 10-19, and 29-35).
However, Green does note teach the cytosine nucleoside analogue as 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine of claims 11 and 15.
Regarding 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine of claims 7, 11 and 15, Baba teaches a method of treating tumor or cancer comprising administering to a subject in need thereof 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine as an antitumor agent (Abstract; [0009]-[0015], and [0036]; claims 1 and 7-11). Baba teaches the antitumor agent can be used in combination with other therapeutic drugs containing a known antitumor agent conventionally used in this field ([0036]). Baba teaches 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine is effective in treating tumors of various types including ovary, testis, prostate gland, pancreas, stomach, small intestine, and other organs ([0036]).
It would have been obvious to one of ordinary skill in the art incorporate or substitute 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine as the cytosine nucleoside analogue in the method of treating tumor or cancer of Green, and produce the claimed invention of treating pancreatic cancer, ovarian cancer, cholangiocarcinoma or breast cancer. One of ordinary skill in the art would have been motivated to do so because Yonemura establishes that both 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine of Baba and 2'-cyano-2'-deoxy-N'- palmitoyl-1-B-D-arabinofuranosyl-cytosine (CYC682), or a metabolite thereof (1-(2-C-Cyano-2-deoxy-B-D-arabino-pentafuranosyl)-cytosine, CNDAC) of Green are known antitumor nucleoside analogues that can be used in combination with other antitumor agents such as cisplatin, as combination therapies in cancer chemotherapy provides promising and superior results than either compounds individually, especially in resistant cancer cells (Yonemura: pages 11 and 16). Green also suggested that cytosine nucleoside analogue when used in combination with antitumor platinum drug such as cisplatin provided synergist activities, and such synergistic interaction may allow for lower doses of each component to be administered to a patient, thereby decreasing the toxicity of chemotherapy, whilst producing and/or maintaining the same therapeutic effect (Green: [0054]).
One ordinary skill in the art would have reasonable expectation of success of incorporate or substitute 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine as the cytosine nucleoside analogue in the method of treating tumor or cancer of Green, and arrive at claimed invention of treating pancreatic cancer, ovarian cancer, cholangiocarcinoma or breast cancer because i) Baba indicated that 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine can be used in combination with other therapeutic drug containing a known antitumor agent conventionally used in this field, and cisplatin is conventionally know antitumor agent in the field of cancer chemotherapy that can be used in combination with nucleoside analogue to provide enhanced treating of tumor or cancer; ii) Baba further indicated that the cytosine nucleoside analogue is effectively used to treat tumors of various types including ovary, prostate gland, and pancreas; and iii) Green and Dilruba established that it is well-known in the prior art that platinum drug such as cisplatin are widely used in therapy of human neoplasm, as well as, cisplatin is known for their effective treatment against ovarian cancer (Green: [0079]; Dilruba: pages 1103 and 1106). Thus, an ordinary artisan seeking to maximize the therapeutic effect of treating of tumor or cancer such as pancreatic cancer, ovarian cancer, or breast cancer, while also decreasing the toxicity of chemotherapy, would have looked using combination therapy of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with a known antitumor platinum drug such as cisplatin, and achieve Applicant’s claimed invention with reasonable expectation of success, as it would have been simply substitution of one known cytosine nucleoside analogue for another to achieve predictable results of enhanced treatment of tumor or cancer such as pancreatic cancer, ovarian cancer, or breast cancer when used in combination with a known antitumor platinum drug such as cisplatin.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 08/19/2025 have been fully considered but they are not persuasive.
Applicant’s arguments on pages 3-16 of the Remarks filed 08/19/2025 relied on the Declarations from Simon Green and William Plunkett, submitted on 08/19/2025 as the rebuttal for nonobviousness. Thus, Applicant’s arguments in view of the Declarations will be address together as set forth below.
The “Simon Green” and “William Plunkett” Declarations under 37 C.F.R. §1.132 filed 08/19/2025 are considered, but found insufficient to overcome the 103 rejection as set forth in this office action for the reasons set forth below.
Applicant argues:
“The biological activity of a nucleoside analog cannot be predicted from the biological activity of another nucleoside analog that has a different mechanism of action (Plunkett Declaration, para 4; Green Declaration, para 4).
The prodrug CYC682 and its active metabolite CNDAC have a unique mechanism of action among nucleoside analogs. The Examiner has not presented any reason for a person of ordinary skill in the art to believe that 4'-thio-FAC has the same mechanism of action (Plunkett Declaration, para 3 and 4; Green Declaration, para 2 and 3).1 Based on chemical structure, one skilled in the art would not select CYC682 and CNDAC for comparison to 4'-thio-FAC. Both declarants state that gemcitabine is closer in chemical structure and the more relevant nucleoside mechanistically for comparison to 4'-thio- FAC. The Plunkett Declaration describes the critical role of the cyano group in the mechanism of action of CYC-682 and CNDAC, which is lacking in both gemcitabine and 4'-thio-FAC (Plunkett Declaration, para 6; Green Declaration para 3).
When combined with a platinum drug, one skilled in the art would more likely compare the activity of 4'-thio-FAC to gemcitabine rather than to the combination with CYC682 and CNDAC. Gemcitabine is a drug approved in combination with cisplatin. CYC682 and CNDAC have never been approved (Plunkett Declaration, para 6; Green Declaration, para 1 and 3).
The biological activity of a nucleoside analog against one tumor type does not mean that the same biological activity will be seen against a different tumor type (Plunkett Declaration, para 5; Green Declaration, para 6).” (Remarks, pages 4-5).
In response, the Examiner disagrees. The Green and Plunkett's Declarations were considered above and while providing expert testimonies, such expert testimonies are not persuasive to obviate the 103 rejection over the combined teachings of Green, Baba, Yonemura, and Dilruba.
As previously discussed, Green and Baba directs an ordinary artisan to use cytosine nucleoside analogue including 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine in combination with a known antitumor agent, particularly an antitumor platinum drug such as cisplatin, and Baba established that 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine is effectively used to treat tumors of various types including ovary, prostate gland, and pancreas, and likewise, Green and Dilruba established cisplatin is known in the art are platinum-based drugs effective in the treatment ovarian cancer. Thus, 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine and platinum-based drug such as cisplatin is individually known in the prior art to be effective in the treatment of ovarian cancer, and synergistic effects of treatment using a combination of cytosine nucleoside analogue and platinum-based drugs is also taught and recognized by the cited prior art. As such, it is maintained that claimed the combination of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with cisplatin, would have been an obvious combination from a finite number of combinations of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with platinum-based drug, and such combination would have been reasonably predictive and expected to be effective in treating cancer such as ovarian cancer. See Non-Final Rejection dated 12/04/2024, pages 9-12.
As previously discussed, the Examiner has also made clear that the Courts from MPEP §716.02(d)-(e), any allegation of unexpected results would also have to be compared to the closest cited prior art. The Declarants opined comparison to gemcitabine is not pertinent to the 103 rejection, the obviousness analysis, and the closest cited prior art. As previously discussed, it is reiterated that Applicant’s alleged unexpected synergistic results would need to be compared with Green, is indeed the closest cited prior art. To date, Applicant’s arguments, evidence shown in the Specification, and all the 132 Declarations of record including the recent Declarations from Green and Plunkett, have failed to provide objective evidence comparing to Green. An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).
As previously discussed, it is also reiterated that while to Azuma et al. and Liu et al. disclosed that mechanism of action differ among cytosine nucleoside analogs (Applicant’s previously presented evidence of nonobviousness in which the fact pattern also applies here with respect to the Green and Plunkett's expert testimonies): there was no showing that CYC682, CNDAC, and 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine were not effective in treating ovarian cancer. As previously discussed, it is reiterated that it was shown in the cited prior art, while CYC682 and CNDAC may differ in their mechanism of action from 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine, all three cytosine nucleoside analogs was taught to be effective in treating ovarian cancer, which was the only objective of the claimed method … to treat pancreatic cancer, ovarian cancer, cholangiocarcinoma or breast cancer. It is noted the claim method only requires the combination of 4-thio-β-D-arabinofuranosyl)cytosine with a platinum complex to treat pancreatic cancer, ovarian cancer, cholangiocarcinoma or breast cancer. Thus, it is maintained that such combination of a cytosine nucleoside analog including 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with cisplatin, would have been an obvious combination from a finite number of combinations of a cytosine nucleoside analog such as 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with a platinum-based drug, and such combination would have been reasonably predictive and expected to be effective in treating cancer such as ovarian cancer, as 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine and platinum-based drug such as cisplatin is individually taught in the prior art supra, to be effective in the treatment of ovarian cancer, and combination therapy have shown and known in the prior to provide synergistic results, particularly cytosine nucleoside analogue are advantageously known to be used in combination with platinum-based drugs to treat cancer.
As previously discussed, it is reiterated that the combination of a cytosine nucleoside analog including 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with cisplatin is an obvious combination from a finite number of combinations of a cytosine nucleoside analog such as 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with a platinum-based drug, and such combination would have been reasonably predictive and expected to be effective in treating cancer such as ovarian cancer, as 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine and platinum-based drug such as cisplatin is individually taught in the cited prior arts of the standing 103 rejection, to be effective in the treatment of ovarian cancer, and combination therapy have shown and known in the prior art to provide synergistic results, particularly cytosine nucleoside analogue are advantageously known to be used in combination with platinum-based drugs to treat cancer such as ovarian cancer.
The preponderance of evidence of record to establish obviousness of the claimed method have been discussed in the Non-Final Rejection dated 12/04/2024, pages 8-20, said discussion being incorporated herein in its entirety.
The Examiner reiterates that a strong prima facie case of obviousness has been established by the Examiner for the reason discussed above, of record, and in the standing 103 rejection. Thus, [t]he submission of objective evidence of patentability does not mandate a conclusion of patentability in and of itself. In re Chupp, 816 F.2d 643, 2 USPQ2d 1437 (Fed. Cir. 1987). Although the record may establish evidence of secondary considerations which are indicia of nonobviousness, the record may also establish such a strong case of obviousness that the objective evidence of nonobviousness is not sufficient to outweigh the evidence of obviousness. Newell Cos. v. Kenney Mfg. Co., 864 F.2d 757, 769, 9 USPQ2d 1417, 1427 (Fed. Cir. 1988), cert. denied, 493 U.S. 814 (1989); Richardson-Vicks, Inc., v. The Upjohn Co., 122 F.3d 1476, 1484, 44 USPQ2d 1181, 1187 (Fed. Cir. 1997).
Applicant argues:
“The teachings of Yonemura are limited to gastric cancer. Both Declarations make clear that the activity of a nucleoside analogue in one tumor type does not predict the activity in a different tumor type, especially with respect to synergistic activity. Moreover, the only mention of gastric cancer in Green is in connection with docetaxel and is without supporting data [paragraph 0084]. Therefore, there is no reason to combine Green and Yonemura.” (Remarks, page 6).
In response, the Examiner disagrees. As discussed in the 103 rejection, Yonemura was used to establish that both 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine of Baba and 2'-cyano-2'-deoxy-N'- palmitoyl-1-B-D-arabinofuranosyl-cytosine (CYC682), or a metabolite thereof (1-(2-C-Cyano-2-deoxy-B-D-arabino-pentafuranosyl)-cytosine, CNDAC) of Green are known antitumor nucleoside analogues that can be used in combination with other antitumor agents such as cisplatin, as combination therapies in cancer chemotherapy provides promising and superior results than either compounds individually, especially in resistant cancer cells (Yonemura: pages 11 and 16). This establishment from Yonemura is in lined with Green, which also suggested that cytosine nucleoside analogue when used in combination with antitumor platinum drug such as cisplatin provided synergist activities, and such synergistic interaction may allow for lower doses of each component to be administered to a patient, thereby decreasing the toxicity of chemotherapy, whilst producing and/or maintaining the same therapeutic effect (Green: [0054]). Accordingly, Yonemura is properly combined with Green in the 103 rejection.
Applicant argues:
“There is no reason based on the Dilruba disclosure to connect it to Baba. Dilruba is merely a review article of platinum-based drugs. In fact, Dilruba offers cautions regarding the use of cisplatin. Specifically, Dilruba teaches the toxicity limitations of cisplatin. "[C]isplatin therapy ... is accompanied by severe side effects including dose-limiting nephrotoxicity, cumulative peripheral sensory neuropathy, ototoxicity due to irreversible damage of the hair cells in Corti organ, as well as nausea and vomiting." (page 1103). Further, the Dilruba review article is largely about efforts to overcome the toxicity issues of cisplatin with modified platinum drugs and formulations. There is mention of PARP inhibitors and EGFR inhibitors. It is noteworthy that Dilruba points to only one nucleoside for use in combination with cisplatin. That nucleoside is gemcitabine. While Dilruba points to gemcitabine as a combination, it makes no mention of CNDAC or 4'-thio-FAC.” (Remarks, pages 7-8).
In response, the Examiner disagrees. As discussed in the standing 103 rejection, Dilruba is also in lined with Green, in that both Dilruba and Green established that it is well-known in the prior art that platinum such as cisplatin is widely used in therapy of human neoplasm, as well as, cisplatin is known for their effective treatment against ovarian cancer (Green: [0079]; Dilruba: pages 1103 and 1106). Accordingly, Dilruba is properly combined with Green in the 103 rejection.
As discussed above, it is reiterated that Green and Baba directs an ordinary artisan to use cytosine nucleoside analogue including 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine in combination with a known antitumor agent, particularly an antitumor platinum drug such as cisplatin, and Baba established that 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine is effectively used to treat tumors of various types including ovary, prostate gland, and pancreas, and likewise, Green and Dilruba established cisplatin is known in the art are platinum-based drugs effective in the treatment ovarian cancer. Thus, 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine and platinum-based drug such as cisplatin is individually known in the prior art to be effective in the treatment of ovarian cancer, and synergistic effects of treatment using a combination of cytosine nucleoside analogue and platinum-based drugs is also taught and recognized by the cited prior art. See entire obviousness analysis in the 103 rejection, pages 4-6 of this office action.
As such, it is maintained that claimed the combination of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with cisplatin, would have been an obvious combination from a finite number of combinations of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with platinum-based drug, and such combination would have been reasonably predictive and expected to be effective in treating cancer such as ovarian cancer.
Applicant argues:
“The Declaration of Dr. William Plunkett is by a leading expert in the cancer biology of nucleoside analogues. Furthermore, he has studied and published on the mechanism of action of CNDAC. Dr. Plunkett clearly states that one cannot predict the activity of 4'-thio-FAC based on the activity of CNDAC (Plunkett Declaration, para 2 and 4). In his Declaration, Dr. Plunkett explains that CNDAC is a unique cytosine nucleoside analog that is not representative of that class of compounds (Plunkett Declaration, para 3 and 4). He states that gemcitabine is the better comparator (Plunkett Declaration, para 6). He also states that one cannot predict that a drug combination will have synergistic activity against a certain cancer based on its activity in a different cancer (Plunkett Declaration, para 5 and 7). Dr. Plunkett further states that the superiority of 4'-thio-FAC versus gemcitabine when combined with cisplatin is surprising (Plunkett Declaration, para 10). Furthermore, the result is meaningful because, as Dilruba makes abundantly clear, cisplatin is a toxic agent.
Dr. Simon Green, the first-named inventor on the cited Green patent application, also distinguishes CNDAC from other cytosine nucleoside analogues. Like Dr. Plunkett, Dr. Green disagrees with the Examiner's notion that the activity of CNDAC is predictive of the activity of 4'-thio-FAC, in combination with cisplatin. Dr. Green also states that gemcitabine is the proper comparator drug, and he too would not have expected the superior results of 4'-thio-FAC relative to gemcitabine.” (Remarks, pages 8-9).
In response, the Examiner disagrees. As discussed above, Green and Baba directs an ordinary artisan to use cytosine nucleoside analogue including 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine in combination with a known antitumor agent, particularly an antitumor platinum drug such as cisplatin, and Baba established that 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine is effectively used to treat tumors of various types including ovary, prostate gland, and pancreas, and likewise, Green and Dilruba established cisplatin is known in the art are platinum-based drugs effective in the treatment ovarian cancer. Thus, 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine and platinum-based drug such as cisplatin is individually known in the prior art to be effective in the treatment of ovarian cancer, and synergistic effects of treatment using a combination of cytosine nucleoside analogue and platinum-based drugs is also taught and recognized by the cited prior art. As such, it is maintained that claimed the combination of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with cisplatin, would have been an obvious combination from a finite number of combinations of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with platinum-based drug, and such combination would have been reasonably predictive and expected to be effective in treating cancer such as ovarian cancer. See Non-Final Rejection dated 12/04/2024, pages 9-12.
As previously discussed, it is also reiterated that while to Azuma et al. and Liu et al. disclosed that mechanism of action differ among cytosine nucleoside analogs (Applicant’s previously presented evidence of nonobviousness in which the fact pattern also applies here with respect to the Green and Plunkett's expert testimonies): there was no showing that CYC682, CNDAC, and 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine were not effective in treating ovarian cancer. As previously discussed, it is reiterated that it was shown in the cited prior art, while CYC682 and CNDAC may differ in their mechanism of action from 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine, all three cytosine nucleoside analogs was taught to be effective in treating ovarian cancer, which was the only objective of the claimed method … to treat pancreatic cancer, ovarian cancer, cholangiocarcinoma or breast cancer. It is noted the claim method only requires the combination of 4-thio-β-D-arabinofuranosyl)cytosine with a platinum complex to treat pancreatic cancer, ovarian cancer, cholangiocarcinoma or breast cancer. Thus, it is maintained that such combination of a cytosine nucleoside analog including 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with cisplatin, would have been an obvious combination from a finite number of combinations of a cytosine nucleoside analog such as 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with a platinum-based drug, and such combination would have been reasonably predictive and expected to be effective in treating cancer such as ovarian cancer, as 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine and platinum-based drug such as cisplatin is individually taught in the prior art supra, to be effective in the treatment of ovarian cancer, and combination therapy have shown and known in the prior to provide synergistic results, particularly cytosine nucleoside analogue are advantageously known to be used in combination with platinum-based drugs to treat cancer.
As previously discussed, it is also reiterated that the alleged evidence of unexpected results drawn to synergistic activities, would have been reasonably expected in view of the showing from Green, particularly at least from Figure 6, in which Green showed that the cytosine nucleoside analogue when used in combination with antitumor platinum drug such as oxaliplatin showed synergistic activities, as Figure 6 showed a very low C.I. value, which appeared to be comparably as low as the C.I. value (i.e., 0.4, 0.3, and 0.2) shown in Table 7 of Applicant’s specification (see instant specification, paragraphs [0076]-[0077]). MPEP §716.02(c) states "[e]xpected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967) (resultant decrease of dental enamel solubility accomplished by adding an acidic buffering agent to a fluoride containing dentifrice was expected based on the teaching of the prior art); Ex parte Blanc, 13 USPQ2d 1383 (Bd. Pat. App. & Inter. 1989).
As discussed above, the preponderance of evidence of record to establish obviousness of the claimed method have been discussed in the Non-Final Rejection dated 12/04/2024 on pages 8-20, said discussion being incorporated herein in its entirety.
As discussed above, the Examiner had also made clear that the Courts from MPEP §716.02(d)-(e), any allegation of unexpected results would also have to be compared to the closest cited prior art. The Declarants (Green and Plunkett) opined comparison to gemcitabine is not pertinent to the 103 rejection, the obviousness analysis, and the closest cited prior art. As previously discussed, it is reiterated that Applicant’s alleged unexpected synergistic results would need to be compared with Green, is indeed the closest cited prior art. To date, Applicant’s arguments, evidence shown in the Specification, and all the 132 Declarations of record including the recent Declarations from Green and Plunkett, have failed to provide objective evidence comparing to Green. An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).
The Examiner reiterates that a strong prima facie case of obviousness has been established by the Examiner for the reason discussed above, of record, and in the standing 103 rejection. Thus, [t]he submission of objective evidence of patentability does not mandate a conclusion of patentability in and of itself. In re Chupp, 816 F.2d 643, 2 USPQ2d 1437 (Fed. Cir. 1987). Although the record may establish evidence of secondary considerations which are indicia of nonobviousness, the record may also establish such a strong case of obviousness that the objective evidence of nonobviousness is not sufficient to outweigh the evidence of obviousness. Newell Cos. v. Kenney Mfg. Co., 864 F.2d 757, 769, 9 USPQ2d 1417, 1427 (Fed. Cir. 1988), cert. denied, 493 U.S. 814 (1989); Richardson-Vicks, Inc., v. The Upjohn Co., 122 F.3d 1476, 1484, 44 USPQ2d 1181, 1187 (Fed. Cir. 1997).
Applicant argues:
“Both declarants, Drs. Green and Plunkett, state that superior results would not be expected based on the gemcitabine comparison. Furthermore, both declarants opine that the superior results were noted over a wide dose range. Superior results are seen early on in the dose response curves starting at about 10-30 nM to about 300-1000 nM, as shown in the various Tables. The range in doses is 10-fold to 100-fold. Accordingly, the claims are commensurate in scope.” (Remarks, pages 9-10).
In response, the Examiner disagrees. As previously discussed, the claimed combination of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine and antitumor platinum complex (cisplatin) is dose dependent among other criticalities shown in Applicant’s alleged unexpected results. Thus, as previously discussed, claims 11 and 15 remain not commensurate in scope with the concentrations of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine and cisplatin, as well as, the CI values as shown and used in Applicant’s alleged unexpected results.
As previously discussed, it is further reiterated that with any allegation of unexpected results would also have to be compared to the closest prior art. In this instant case, Applicant’s alleged unexpected synergistic results would need to be compared with Green. In this instant case, Applicant’s alleged unexpected synergistic results would need to be compared with Green. However, Applicant’s argument and evidence shown in the specification failed to show a comparison to Green. See MPEP §716.02(d)-(e). For the reasons discussed above, the claimed invention remains obvious and unpatentable over the combined teachings of Green, Baba, Yonemura, and Dilruba, as independent claims 11 and 15 are not sufficiently commensurate in scope with Applicant’s alleged evidence of unexpected results, as well as, Applicant’s alleged evidence of unexpected results have not been compared to the closest prior art of Green.
Nevertheless, as previously discussed, even if said independent claims 11 and 15 were to be amended so as they are reasonably commensurate in scope to Applicant’s evidence of unexpected results, the alleged evidence of unexpected drawn to synergistic activities, would have been reasonably expected in view of the showing from Green, particularly at least from Figure 6, in which Green showed that the cytosine nucleoside analogue when used in combination with antitumor platinum drug such as oxaliplatin showed synergistic activities, as Figure 6 showed a very low C.I. value, which appeared to be comparably as low as the C.I. value (i.e., 0.4, 0.3, and 0.2) shown in Table 7 of Applicant’s specification (see instant specification, paragraphs [0076]-[0077]). As such, for the above reason, the claimed invention remains obvious and unpatentable over the combined teachings of Green, Baba, Yonemura, and Dilruba, because MPEP §716.02(c) states "[e]xpected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967) (resultant decrease of dental enamel solubility accomplished by adding an acidic buffering agent to a fluoride containing dentifrice was expected based on the teaching of the prior art); Ex parte Blanc, 13 USPQ2d 1383 (Bd. Pat. App. & Inter. 1989).
As previously discussed, to the extent that Figure 6 of Green used a combination of a cytosine nucleoside analogue and oxaliplatin on colon cancer cell lines showed synergistic activities of providing a very low C.I. value, this combination on colon cancer cell lines does not teach away from the use of claimed combination in treating pancreatic cancer, ovarian cancer, choloangiocarcinoma or breast cancer because the broader disclosures from Green in combination with the teachings from Baba, Yonemura, and Dilruba remains to provide a reasonable expectation that combination of a cytosine nucleoside analogue such as 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with an antitumor platinum drug such as cisplatin, would provide synergistic activities against other cancers such as pancreatic cancer, ovarian cancer, choloangiocarcinoma or breast cancer, or at least be effective in the treatment of pancreatic cancer, ovarian cancer, choloangiocarcinoma or breast cancer as claimed. This is because as discussed above in the pending 103 rejection, i) Baba indicated that 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine can be used in combination with other therapeutic drugs containing a known antitumor agent conventionally used in this field, and cisplatin is conventionally know antitumor agent in the field of cancer chemotherapy that can be used in combination with nucleoside analogue to provide enhanced treating of tumor or cancer; ii) Baba further indicated that the cytosine nucleoside analogue is effectively used to treat tumors of various types including ovary, prostate gland, and pancreas; and iii) Green and Dilruba established that it is well-known in the prior art that platinum such as cisplatin is widely used in therapy of human neoplasm, as well as, cisplatin is known for their effective treatment against ovarian cancer (Green: [0079]; Dilruba: pages 1103 and 1106). Thus, there is reasonable expectation in the prior art that it would have been obvious to use for example, a combination of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with cisplatin in the treatment of breast cancer because Green and Baba directs an ordinary artisan to use cytosine nucleoside analogue including 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine in combination with a known antitumor agent, particularly an antitumor platinum drug such as cisplatin, and Baba established that 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine is effectively used to treat tumors of various types including ovary, prostate gland, and pancreas, and likewise, Green and Dilruba established cisplatin is known in the art are platinum-based drugs effective in the treatment ovarian cancer. As such, such combination of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with cisplatin, would have been an obvious combination from a finite number of combinations of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with platinum-based drug, and such combination would have been reasonably predictive and expected to be effective in treating cancer such as ovarian cancer, as 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine and platinum-based drug such as cisplatin is individually known for use in the treatment of ovarian cancer, and combination therapy have shown and known in the prior to provide synergistic results, particularly cytosine nucleoside analogue are advantageously known to be used in combination with platinum-based drugs to treat cancer.
As discussed above, the Examiner had made clear that the Courts from MPEP §716.02(d)-(e), any allegation of unexpected results would also have to be compared to the closest cited prior art. The Declarants (Green and Plunkett) opined comparison to gemcitabine is not pertinent to the 103 rejection, the obviousness analysis, and the closest cited prior art. As previously discussed, it is reiterated that Applicant’s alleged unexpected synergistic results would need to be compared with Green, which is indeed the closest cited prior art. To date, Applicant’s arguments, evidence shown in the Specification, and all the 132 Declarations of record including the recent Declarations from Green and Plunkett, have failed to provide objective evidence comparing to Green. An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).
Applicant argues:
“The Plunkett and Green Declarations make clear that CNDAC is not the closest prior art. As explained in each Declaration, gemcitabine is the better comparator for cytosine nucleoside analogs, especially when combined with cisplatin. As shown, 4'-thio-FAC is closer in chemical structure. The cyano group in CNDAC is not present in the other compounds. Dr. Plunkett declares that the cyano group distinguishes the mechanism of action of CNDAC from other nucleoside analogs (Plunkett Declaration, para 6). Gemcitabine is widely used with cisplatin while that combination was never developed for CYC-682. In the Dilruba reference cited by the Examiner, it is gemcitabine that is mentioned in combination with cisplatin, not CNDAC.” (Remarks, page 10).
In response, the Examiner disagrees. As discussed above, the Examiner had made clear that the Courts from MPEP §716.02(d)-(e), any allegation of unexpected results would also have to be compared to the closest cited prior art. The Declarants (Green and Plunkett) opined comparison to gemcitabine is not pertinent to the 103 rejection, the obviousness analysis, and the closest cited prior art. As previously discussed, it is reiterated that Applicant’s alleged unexpected synergistic results would need to be compared with Green, which is indeed the closest cited prior art. To date, Applicant’s arguments, evidence shown in the Specification, and all the 132 Declarations of record including the recent Declarations from Green and Plunkett, have failed to provide objective evidence comparing to Green. An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).
Applicant argues:
“Drs. Plunkett and Green make clear that the activity of 4'-thio-FAC is not at all predictable based on the activity of CNDAC disclosed in Green. To the extent that the Examiner continues to dismiss the mechanistic uniqueness of CNDAC that underlies the lack of predictability, Applicant urges the Examiner to reconsider based on the Declarations of the two experts, Drs. Green and Plunkett.” (Remarks, bottom of page 10 to page 11).
In response, the Examiner disagrees. As discussed above, the Examiner had made clear that the Courts from MPEP §716.02(d)-(e), any allegation of unexpected results would also have to be compared to the closest cited prior art. The Declarants (Green and Plunkett) opined comparison to gemcitabine is not pertinent to the 103 rejection, the obviousness analysis, and the closest cited prior art. As previously discussed, it is reiterated that Applicant’s alleged unexpected synergistic results would need to be compared with Green, which is indeed the closest cited prior art. To date, Applicant’s arguments, evidence shown in the Specification, and all the 132 Declarations of record including the recent Declarations from Green and Plunkett, have failed to provide objective evidence comparing to Green. An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).
Applicant argues:
“No prediction of activity for 4'-thio-FAC can be made based on the activity of CNDAC, especially against other cancer cell lines” and “[t]he Plunkett and Green Declarations emphasize that predictions of activity cannot be made based on activity against a different cell type.” (Remarks, pages 11 to 12).
In response, the Examiner disagrees. Plunkett and Green Declarations are expert testimonies without actual proof of unexpected results when compared to the closest prior art of Green.
As discussed above, the Examiner had made clear that the Courts from MPEP §716.02(d)-(e), any allegation of unexpected results would also have to be compared to the closest cited prior art. The Declarants (Green and Plunkett) opined comparison to gemcitabine is not pertinent to the 103 rejection, the obviousness analysis, and the closest cited prior art. As previously discussed, it is reiterated that Applicant’s alleged unexpected synergistic results would need to be compared with Green, which is indeed the closest cited prior art. To date, Applicant’s arguments, evidence shown in the Specification, and all the 132 Declarations of record including the recent Declarations from Green and Plunkett, have failed to provide objective evidence comparing to Green. An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).
Applicant argues:
“The closest prior art cannot be a compound which is reported to have a mechanism of action that is unique among nucleoside analogues. Furthermore, a compound with such a unique mechanism of action as shown by Liu et al. and Azuma et al., cannot serve as the basis for any predictability with respect to 4'-thio-FAC. As the two Declarations show, mechanism of action does matter when it comes to predictability or lack thereof. Mechanism of action matters not only when a drug is used alone, but especially in a combination therapy. Furthermore, one cannot expect synergistic activity based on that of a compound having a different mechanism of action (Plunkett Declaration, para 4; Green Declaration, para 2) because the effect of modulating multiple pathways in a cell is not predictable.
The Plunkett and Green Declarations clearly caution against the reliance on CNDAC activity in Green because it has a different mechanism of action. A basic understanding in the field of cancer research is that the activity of a compound depends in large part on its mechanism of action.
Because of the unique mechanism of action of CNDAC, due to the cyano group in its chemical structure, which contributes to its unique mechanism of action, and because gemcitabine is widely used with cisplatin, CNDAC is not the closest prior art.” (Remarks, pages 12-13).
In response, the Examiner disagrees. As discussed above, the Examiner had made clear that the Courts from MPEP §716.02(d)-(e), any allegation of unexpected results would also have to be compared to the closest cited prior art. The Declarants (Green and Plunkett) opined comparison to gemcitabine is not pertinent to the 103 rejection, the obviousness analysis, and the closest cited prior art. As previously discussed, it is reiterated that Applicant’s alleged unexpected synergistic results would need to be compared with Green, which is indeed the closest cited prior art. To date, Applicant’s arguments, evidence shown in the Specification, and all the 132 Declarations of record including the recent Declarations from Green and Plunkett, have failed to provide objective evidence comparing to Green. An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).
Applicant argues:
“the presently claimed invention is not based merely on the combination of two known antitumor agents. Instead, the presently claimed invention is based on the discovery that the particular combination of 4'-thio-FAC and cisplatin is superior and unexpected, i.e., the claimed combinations are synergistic.
First, the mechanism of action of 4'-thio-FAC is different from that of CNDAC. Second, the claimed tumor types are different from the ones where synergy was reported in Green. Further, the proper comparator is gemcitabine, and the present application shows 4'-thio-FAC in combination with cisplatin to be clearly superior against the claimed cancers.
The discussion above and the Declarations submitted with this response clearly explain why there is no expectation of synergy for 4'-thio-FAC and cisplatin based on Green. On the other hand, the Examiner has not articulated a clear reason why a person of ordinary skill in the art would extend the teaching of Green to the present application.
The Declarations of Drs. Plunkett and Green clearly state that the synergistic activity reported in Green for CNDAC and CYC682 in combination with platinum against colon cancer and NSCLC does not predict the synergistic activity for the combination with 4'-thio-FAC against pancreatic, breast, cholangiocarcinoma and ovarian cancers.” (Remarks, pages 13-16).
In response, the Examiner disagrees. As discussed above, Green and Baba directs an ordinary artisan to use cytosine nucleoside analogue including 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine in combination with a known antitumor agent, particularly an antitumor platinum drug such as cisplatin, and Baba established that 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine is effectively used to treat tumors of various types including ovary, prostate gland, and pancreas, and likewise, Green and Dilruba established cisplatin is known in the art are platinum-based drugs effective in the treatment ovarian cancer. Thus, 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine and platinum-based drug such as cisplatin is individually known in the prior art to be effective in the treatment of ovarian cancer, and synergistic effects of treatment using a combination of cytosine nucleoside analogue and platinum-based drugs is also taught and recognized by the cited prior art. As such, it is maintained that claimed the combination of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with cisplatin, would have been an obvious combination from a finite number of combinations of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with platinum-based drug, and such combination would have been reasonably predictive and expected to be effective in treating cancer such as ovarian cancer. See Non-Final Rejection dated 12/04/2024, pages 9-12.
As previously discussed, it is also reiterated that while to Azuma et al. and Liu et al. disclosed that mechanism of action differ among cytosine nucleoside analogs (Applicant’s previously presented evidence of nonobviousness in which the fact pattern also applies here with respect to the Green and Plunkett's expert testimonies): there is no showing that CYC682, CNDAC, and 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine were not effective in treating ovarian cancer. As previously discussed, it is reiterated that it was shown in the cited prior art, while CYC682 and CNDAC may differ in their mechanism of action from 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine, all three cytosine nucleoside analogs was taught to be effective in treating ovarian cancer, which is the only objective of the claimed method … to treat pancreatic cancer, ovarian cancer, cholangiocarcinoma or breast cancer. It is noted the claim method only requires the combination of 4-thio-β-D-arabinofuranosyl)cytosine with a platinum complex to treat pancreatic cancer, ovarian cancer, cholangiocarcinoma or breast cancer. Thus, it is maintained that such combination of a cytosine nucleoside analog including 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with cisplatin, would have been an obvious combination from a finite number of combinations of a cytosine nucleoside analog such as 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine with a platinum-based drug, and such combination would have been reasonably predictive and expected to be effective in treating cancer such as ovarian cancer, as 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine and platinum-based drug such as cisplatin is individually taught in the prior art supra, to be effective in the treatment of ovarian cancer, and combination therapy have shown and known in the prior to provide synergistic results, particularly cytosine nucleoside analogue are advantageously known to be used in combination with platinum-based drugs to treat cancer such as ovarian cancer.
As previously discussed, it is also reiterated that the alleged evidence of unexpected results drawn to synergistic activities, would have been reasonably expected in view of the showing from Green, particularly at least from Figure 6, in which Green showed that the cytosine nucleoside analogue when used in combination with antitumor platinum drug such as oxaliplatin showed synergistic activities, as Figure 6 showed a very low C.I. value, which appeared to be comparably as low as the C.I. value (i.e., 0.4, 0.3, and 0.2) shown in Table 7 of Applicant’s specification (see instant specification, paragraphs [0076]-[0077]). MPEP §716.02(c) states "[e]xpected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967) (resultant decrease of dental enamel solubility accomplished by adding an acidic buffering agent to a fluoride containing dentifrice was expected based on the teaching of the prior art); Ex parte Blanc, 13 USPQ2d 1383 (Bd. Pat. App. & Inter. 1989).
As discussed above, the preponderance of evidence of record to establish obviousness of the claimed method have been discussed in the Non-Final Rejection dated 12/04/2024 on pages 8-20, said discussion being incorporated herein in its entirety.
As discussed above, the Examiner has also made clear that the Courts from MPEP §716.02(d)-(e), any allegation of unexpected results would also have to be compared to the closest cited prior art. The Declarants (Green and Plunkett) opined comparison to gemcitabine is not pertinent to the 103 rejection, the obviousness analysis, and the closest cited prior art. As previously discussed, it is reiterated that Applicant’s alleged unexpected synergistic results would need to be compared with Green, is indeed the closest cited prior art. To date, Applicant’s arguments, evidence shown in the Specification, and all the 132 Declarations of record including the recent Declarations from Green and Plunkett, have failed to provide objective evidence comparing to Green. An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).
The Examiner reiterates that a strong prima facie case of obviousness has been established by the Examiner for the reason discussed above, of record, and in the standing 103 rejection. Thus, [t]he submission of objective evidence of patentability does not mandate a conclusion of patentability in and of itself. In re Chupp, 816 F.2d 643, 2 USPQ2d 1437 (Fed. Cir. 1987). Although the record may establish evidence of secondary considerations which are indicia of nonobviousness, the record may also establish such a strong case of obviousness that the objective evidence of nonobviousness is not sufficient to outweigh the evidence of obviousness. Newell Cos. v. Kenney Mfg. Co., 864 F.2d 757, 769, 9 USPQ2d 1417, 1427 (Fed. Cir. 1988), cert. denied, 493 U.S. 814 (1989); Richardson-Vicks, Inc., v. The Upjohn Co., 122 F.3d 1476, 1484, 44 USPQ2d 1181, 1187 (Fed. Cir. 1997).
As a result, for the reasons discussed above and of record, as well as, the preponderance of evidence, claims 11 and 15 stand rejected as being obvious and unpatentable over the combined teachings of Green, Baba, Yonemura, and Dilruba in the standing 103 rejection as set forth in this of action.
Conclusion
No claim is allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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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/DOAN T PHAN/ Primary Examiner, Art Unit 1613