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 .
Application Status
The preliminary amendment filed on 9/26/2025 is acknowledged. Claims 1-12 are currently pending and under consideration.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements filed on 10/14/2022, 1/26/2023, 3/14/2023, 12/16/2024 and 8/27/2025 have been considered except where lined though.
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.
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.
Claim(s) 1-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Albertella et al. (US2019/0091246A1, 2019-03-28) in view of Al-Salama et al. (Drugs (2019); 79:665-674).
Albertella et al. teach a method of treating liver cancer or liver metastasis, comprising administering to a subject in need thereof a targeted therapeutic agent, wherein the targeted therapeutic agent is sorafenib in combination with a phosphoramidate prodrug of troxacitabine having the formula
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(claim 1 of Albertella et al). Specifically, the PGPub teaches Sorafenib and a phosphoramidate prodrug of troxacitabine having the formula
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were assayed in a combinatorial cell culture assay and had a log volume of 40 at 95% confidence calculated by MacSynergy II, which corresponds to strong-antiproliferative synergy (paragraph 0331-0333, Example 4). With regards to the liver cancer and/or liver metastasis, the PGPUB teaches that the liver cancer is HCC or intra-hepatic cholangiocarcinoma and the liver metastasis is derived from colorectal cancer, breast cancer, esophageal cancer, lung cancer, melanoma, pancreatic cancer or stomach cancer (claims 12-14 of Albertella et al). With regards to the treatment, Albertella et al. teach that sorafenib and the prodrug are each administered on the same day either co-delivered in a common, orally administered dosage form or administered as separate orally administered dosage units, wherein the dosage units of each drug are administered at least 6 hours apart on any given day (claims 6-9 of Albertella et al.). Moreover, Albertella et al. teach that sorafenib and the prodrug are alternatively administered in monotherapy treatment cycles of 1-28 days, wherein the treatment commences with a sorafenib cycle and includes 4 or 3 consecutive weeks with 1 week, 2 weeks or 3 consecutive weeks off (claim 10-11 of Albertella et al and paragraph 0225). Additionally, Albertella et al. teach that sorafenib and the prodrug are each administered daily as QD, BID or TID on the same day (claim 15 of Albertella et al.).
Albertella et al. does not specifically teach Lenvatinib in combination with the phosphoramidate prodrug of troxacitabine having the formula
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for treating liver cancer or liver metastasis.
Al-Salama et al. teach Lenvatinib is an oral small molecule inhibitor of multiple receptor tyrosine kinases, and is approved for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC) in the USA, EU, Japan and China (Abstract). Moreover, Al-Salama et al. teach that given its non-inferior efficacy to sorafenib and manageable tolerability profile, Lenvatinib represents a long-awaited alternative option to sorafenib for the first-line systemic treatment of patients with unresectable HCC (abstract).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute sorafenib as taught by Albertella et al. with Lenvatinib in view of the teachings of Al-Salama et al.. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Al-Salama et al. teaches that Lenvatinib efficacy is non-inferior to sorafenib, and represents a long-awaited alternative to sorafenib.
Moreover, "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) see MPEP 2144.06.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 10,960,017 to Albertella et al. (2021-03-30) in view of Al-Salama et al. (Drugs (2019); 79:665-674).
US Patent No 10,960,017 claims a method of treating liver cancer or liver metastasis, comprising administering to a subject in need thereof a targeted therapeutic agent, wherein the targeted therapeutic agent is an isotope of sorafenib in combination with a phosphoramidate prodrug of troxacitabine having the formula
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(claim 1 of the US Patent). Specifically, the US Patent No 10,960,017 claims Sorafenib and a phosphoramidate prodrug of troxacitabine having the formula
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(claim 4). With regards to the liver cancer and/or liver metastasis, the US Patent No 10,960,017 claims that the liver cancer is HCC or intra-hepatic cholangiocarcinoma and the liver metastasis is derived from colorectal cancer, breast cancer, esophageal cancer, lung cancer, melanoma, pancreatic cancer or stomach cancer (claims 11-13). With regards to the treatment, US Patent No 10,960,017 claims that sorafenib and the prodrug are each administered on the same day either co-delivered in a common, orally administered dosage form or administered as separate orally administered dosage units, wherein the dosage units of each drug are administered at least 6 hours apart on any given day (claims 5-8). Moreover, US Patent No 10,960,017 claims that sorafenib and the prodrug are alternatively administered in monotherapy treatment cycles of 1-28 days, and interspersed with treatment-free periods of 1-28 days(claim 9-10, 15). Additionally, US Patent No 10,960,017 claims that sorafenib and the prodrug are each administered daily as QD, BID or TID on the same day (claim 14).
US Patent No 10,960,017 does not specifically claim Lenvatinib in combination with the phosphoramidate prodrug of troxacitabine having the formula
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for treating liver cancer or liver metastasis.
Al-Salama et al. teach Lenvatinib is an oral small molecule inhibitor of multiple receptor tyrosine kinases, and is approved for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC) in the USA, EU, Japan and China (Abstract). Moreover, Al-Salama et al. teach that given its non-inferior efficacy to sorafenib and manageable tolerability profile, Lenvatinib represents a long-awaited alternative option to sorafenib for the first-line systemic treatment of patients with unresectable HCC (abstract).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute sorafenib as claimed by the US Patent with Lenvatinib in view of the teachings of Al-Salama et al.. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Al-Salama et al. teaches that Lenvatinib efficacy is non-inferior to sorafenib, and represents a long-awaited alternative to sorafenib.
Moreover, "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) see MPEP 2144.06.
Claims 1 and 8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 9 of U.S. Patent No. 12,303,521 to Albertella et al. (2025-05-20) in view of Al-Salama et al. (Drugs (2019); 79:665-674).
US Patent No 12,303,521 claims a method of treating liver cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a compound having the formula
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in combination with monoclonal antibody which blocks binding of PD-L1 (claim 1). With regards to the liver cancer, US Patent No 12,303,521 claims that the liver cancer is HCC (claim 9).
US Patent No 12,303,521 does not specifically claim Lenvatinib in combination with the phosphoramidate prodrug of troxacitabine having the formula
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for treating liver cancer or liver metastasis.
Al-Salama et al. teach Lenvatinib is an oral small molecule inhibitor of multiple receptor tyrosine kinases, and is approved for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC) in the USA, EU, Japan and China (Abstract). Moreover, Al-Salama et al. teach that given its non-inferior efficacy to sorafenib and manageable tolerability profile, Lenvatinib represents a long-awaited alternative option to sorafenib for the first-line systemic treatment of patients with unresectable HCC (abstract).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the antibody as claimed by the US Patent with Lenvatinib in view of the teachings of Al-Salama et al.. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Al-Salama et al. teaches that Lenvatinib efficacy is non-inferior to sorafenib, and represents a long-awaited alternative to sorafenib.
Moreover, "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) see MPEP 2144.06.
Conclusion
Therefore, No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626