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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/22/2026 has been entered.
Status of the Claims
This action is in response to papers filed 04/22/2026 in which claims 7-10 and 12-14 were canceled; claims 1-6 were withdrawn; claims 11 and 15 were amended; and claims 16-18 were newly added. All the amendments have been thoroughly reviewed and entered.
Claims 11 and 15-18 are under examination.
Withdrawn Rejection
The Examiner has re-weighted all the evidence of record. Any rejection and/or objection not specifically addressed below is hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
New Rejection
Necessitated by Applicant’s Claim Amendments
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 15-18 are is/are rejected under 35 U.S.C. 103 as being unpatentable over Janku (US 2020/0352973; effective filing date 29 January 2018) in view of Valle et al (The New England Journal of Medicine, 8 April 2010, 362(14): 1273-1281), Zajchowski et al (Int. J. Cancer, 2005, 114: 1002-1009), and Macbeth et al (US 2015/0216886 A1).
Regarding claim 11, Janku teaches a method of treating biliary tract cancer (cholangiocarcinoma) comprising administering a therapeutically effective dose of 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine or a salt thereof in a subject in need of said treatment (Abstract; [0005]-[0076]; claims 1-7).
While Janku does not particularly teach the 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine is administered in combination with an antitumor platinum complex, it would have been obvious to use a combination therapy of -(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine and an antitumor platinum complex in view of the guidance from Valle, Zajchowski, and MacBeth.
Valle teaches treatment of biliary tract cancer (cholangiocarcinoma) using a combination therapy of cisplatin (a platinum drug) and gemcitabine (a cytidine analog) (pages 1273-1274 and 1278-1280). Valle teaches that combination therapy of cisplatin and gemcitabine was associated with a significant survival advantage without the addition of substantial toxicity in patients with advanced biliary cancer (page 1273).
Zajchowski teaches 1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine (4’-thio-FAC) is a deoxycytidine analog that has shown to be 100-fold more potent than gemcitabine (a deoxycytidine analog) in inhibiting DNA polymerase α and also significantly inhibits DNA polymerase β with 10-fold less potency than for the α enzyme (pages 1002 and 1007-1008). Zajchowski also teaches 4’-thio-FAC demonstrated superior activity to gemcitabine with respect to efficacy and tolerability in solid tumors, especially 4’-thio-FAC being low toxicity in vivo when compared to gemcitabine (pages 1002 and 1008).
Macbeth teaches a method of treating a solid tumor where the solid tumor is a cancer of the gastrointestinal system, the method comprising administering a cytidine analog in combination with an anticancer agent such as platinum agents such as cisplatin and oxaliplatin (Abstract; [0010]-[0019], [0045]-[0046], [0064], [0186]-[0187], and [0212]-[0215]).
It would have been obvious to one of ordinary skill in the art to administer 4’-thio-FAC of Janku in combination with a platinum drug for the treatment of cholangiocarcinoma, and arrived at the claimed method. One of ordinary skill in the art would have been motivated to do so because Valle established that a platinum drug such as cisplatin can be used in combination with a cytidine analog (gemcitabine) to provide improved treatment of cholangiocarcinoma, especially in patients with advanced biliary cancer. Zajchowski established that 4’-thio-FAC demonstrated superior activity to gemcitabine with respect to efficacy and tolerability in solid tumors, especially 4’-thio-FAC being low toxicity in vivo when compared to gemcitabine. Thus, an ordinary artisan seeking to provide superior efficacy against cholangiocarcinoma while also reducing toxicity during treatment, would have looked to using a combination of 4’-thio-FAC and a platinum drug such as cisplatin. One of ordinary skill in the art would have reasonable expectation of success in doing so because Macbeth established that cytidine analogs are suggested to be used in combination with platinum drugs such as cisplatin and oxaliplatin to provide effective treatment in relapsed or refractory solid tumors, or regionally advanced cancer, and Janku suggested that before the administration of 4’-thio-FAC, a patient having cholangiocarcinoma can be pretreated with a cisplatin regimen, thereby suggesting a reasonable expectation of success of using a combination of a platinum drug (cisplatin) and a cytidine analog (4’-thio-FAC) in the effective treatment of cholangiocarcinoma.
Regarding claim 15, Valle and Macbeth teach the cytidine analog is administered separately or sequentially from platinum drug (Valle: pages 1273-1274 and 1278-1280; Macbeth: [0046], [0186], [0257], and [0313]), where Janku suggested that a platinum drug (cisplatin) can be administered as a pretreatment followed by the administration of 4’-thio-FAC (Janku: [0063]-[0076]; Example 1 and Table 1), thereby rendering obvious the administration of 4’-thio-FAC (1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine) and a antitumor platinum complex separately or sequentially in the treatment of cholangiocarcinoma.
Regarding claims 16-18, Macbeth teaches and provide guidance for using a combination of platinum drug such as cisplatin or oxaliplatin with cytidine analog (Macbeth: Abstract; [0010]-[0019], [0045]-[0046], [0064], [0186]-[0187], and [0212]-[0215]), where Valle established that combination therapy of a platinum drug (cisplatin) and a cytidine analog is effective in providing superior treatment of cholangiocarcinoma, especially in patient having advanced biliary cancer (advanced cholangiocarcinoma) (Valle: pages 1273-1274 and 1278-1280), thereby rendering obvious the use of a combination therapy of 4’-thio-FAC (1-(2-deoxy-2-fluoro-4-thio-β-D-arabinofuranosyl)cytosine) with cisplatin or oxaliplatin in the treatment of cholangiocarcinoma.
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 with respect to claim(s) 11 and 15 on pages 5-13 of the Remarks filed on 04/22/2026 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claim is allowed.
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/DOAN T PHAN/ Primary Examiner, Art Unit 1613
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