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 .
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.
Current Status of 17/833,095
This Office Action is responsive to the amendments and arguments received 1 December 2025.
Claims 1-2, 4, 6-8, and 11-20 are currently pending.
Priority
Applicant’s claim for the benefit of the prior-filed patent applications PCT/KR2020/018271 (filed 14 December 2020), KR 10-2019-0166966 (filed 13 December 2019), and KR 10-2020-0174443 (filed 14 December 2020) under 35 U.S.C. 119(e), 120, 121, 365(c), or 386(c) is acknowledged.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Response to Amendments
The objections to the drawings, present in the previous office action, are hereby withdrawn due to the replacement drawing sheets.
The objection to the specification, present in the previous office action, is hereby withdrawn, due to Applicant’s amendments.
The objections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments.
The 35 U.S.C. 112 rejections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments, but new rejections are presented herein as necessitated by Applicant’s amendments.
The 35 U.S.C. 102(a)(1) and/or 35 U.S.C. 102(a)(2) rejections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments.
The 35 U.S.C. 103 rejections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments. However, new rejections are presented herein, as necessitated by Applicant’s amendments.
Response to Arguments
Applicant argues that the requirement for a pharmaceutical composition, which is now present in the claims, no longer allows the Examiner to use the GAO reference to reject the instant claims. Applicant argues that the instant specification shows evidence of synergistic effects of the claimed combination.
The Examiner no longer relies upon GAO in the instant action. The Examiner is not disregarding Applicant’s assertion of synergistic effects of the claimed combination. However, the combination of two drugs that have been previously used for the exact same condition, and for the exact same mouse model as shown in the references below, is sufficiently strong evidence of obviousness to outweigh the findings of synergistic effects.
Claim Rejections - 35 USC § 112
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.
Claims 19 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.
Claim 19 recites “The method of claim 11, wherein the cancer is at least one compound selected from the group consisting of…”. This phrase is unclear for multiple reasons. Firstly, it appears that Applicant inserted the word “compound”, which doesn’t make any sense, where they most likely intended to place “cancer”. However, even if the phrase was amended to recite “wherein the cancer is at least one cancer”, this would still be unclear, because the phrase “the cancer” treats cancer as a singular condition and then provides a list of that single item. This wording is confusing to the reader and renders claim 19 indefinite. Applicant may choose to amend the beginning of claim 19 as follows “The method of claim 11, wherein the cancer is
Claim Interpretation
Paragraph [035] of the instant specification provides some examples of “benzimidazole-based” compounds, but these examples do not constitute a closed definition. The Examiner interprets the broadest reasonable meaning of a “benzimidazole-based” compound to be: any compound having a benzimidazole moiety with any number of substituents, excluding any compounds wherein additional rings have been added directly to the benzimidazole moiety (fused, bridged, or spiro).
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.
Claims 1, 4, 11-14, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over:
LIU (Liu, H.; Xu, H.; Zhang, Y.; et al. “Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice” World J Gastroenterol 2015 September 28; 21(36): 10367-10374)
in view of:
YOUNIS (Younis, N.S.; Ghanim, A.M.H.; Saber, S. “Mebendazole augments sensitivity to sorafenib by targeting MAPK and BCL-2 signalling in n-nitrosodiethylamine-induced murine hepatocellular carcinoma” Scientific Reports | (2019) 9:19095 | https://doi.org/10.1038/s41598-019-55666-x).
LIU teaches the administration of ursodeoxycholic acid (UDCA) to treat hepatocellular carcinoma (HCC) in a mouse model (abstract). LIU teaches that this therapeutic use was successful in decreasing the volume of xenograft tumors in the mouse model (abstract). LIU teaches that the anti-cancer effect reported therein was, at least partially, due to increased apoptosis (discussion section). LIU does not teach any benzimidazole-based drugs therein.
YOUNIS teaches that mebendazole was administered to a mouse model of HCC (abstract). YOUNIS teaches that the mebendazole treatment, especially when combined with sorafenib, improved liver function and increased survival in the HCC mouse model (abstract). YOUNIS teaches that the mebendazole also provided additional beneficial effects, such as decreasing angiogenesis and metastases (page 11).
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to combine the UDCA, taught by LIU to treat hepatocellular carcinoma, with the mebendazole-sorafenib cocktail taught by YOUNIS to treat hepatocellular carcinoma, for the purpose of increasing the efficacy of the anti-cancer therapy. The artisan would have expected success in this combination, because both agents are taught to treat the same disease.
This is an example of combining equivalent therapeutic agents known to be useful for the same purpose. “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” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06.
Regarding claims 4 and 14: LIU teaches the administration of 50 mg/kg/day of UDCA (abstract). YOUNIS teaches the administration of 100 mg/kg/day of mebendazole (abstract). The combination of these two dosages represents a molar ratio of 1:2.
Claims 1-2, 11-13, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over:
LIU (Liu, H.; Xu, H.; Zhang, Y.; et al. “Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice” World J Gastroenterol 2015 September 28; 21(36): 10367-10374)
in view of:
SON (Son, D.; Lee, E.; Adunyah, S.E. “The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs” Immune Netw. 2020 Aug;20(4):e29).
LIU teaches the administration of ursodeoxycholic acid (UDCA) to treat hepatocellular carcinoma (HCC) in a mouse model (abstract). LIU teaches that this therapeutic use was successful in decreasing the volume of xenograft tumors in the mouse model (abstract). LIU teaches that the anti-cancer effect reported therein was, at least partially, due to increased apoptosis (discussion section). LIU does not teach any benzimidazole-based drugs therein.
SON is a review that teaches the use of benzimidazole antihelminthics to treat cancer (title and abstract). The list of antihelminthics that SON focuses on is as follows: albendazole, parbendazole, fenbendazole, mebendazole, oxibendazole, oxfendazole, ricobendazole, and flubendazole (abstract). SON teaches that mebendazole was successfully used to treat HCC in a mouse model (page 7). SON also teaches that albendazole was successfully used to treat HCC in a human patient (Table 1). SON also teaches that fenbendazole was effective in inhibiting the growth of multiple HCC cell lines (page 3, 1st paragraph).
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to combine the UDCA, taught by LIU to treat hepatocellular carcinoma, with the each of mebendazole, albendazole, and fenbendazole taught by SON to treat hepatocellular carcinoma, for the purpose of increasing the efficacy of the anti-cancer therapy. The artisan would have expected success in this combination, because both agents are taught to treat the same disease.
This is an example of combining equivalent therapeutic agents known to be useful for the same purpose. “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” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06.
Claims 1, 4, 11-15, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over:
VANDEWYNCKEL (Vandewynckel, Y.; Laukens, D.; Devisscher, L. “Tauroursodeoxycholic acid dampens oncogenic apoptosis induced by endoplasmic reticulum stress during hepatocarcinogen exposure” Oncotarget, Vol. 6, No. 29, 2015)
in view of:
YOUNIS (Younis, N.S.; Ghanim, A.M.H.; Saber, S. “Mebendazole augments sensitivity to sorafenib by targeting MAPK and BCL-2 signalling in n-nitrosodiethylamine-induced murine hepatocellular carcinoma” Scientific Reports | (2019) 9:19095 | https://doi.org/10.1038/s41598-019-55666-x).
VANDEWYNCKEL teaches the administration of tauroursodeoxycholic acid (TUDCA) to a mouse model of HCC (abstract). VANDEWYNCKEL teaches that TUDCA administration reduced the tumor burden within the mouse model (discussion section). VANDEWYNCKEL also teaches that the TUDCA administration decreased inflammation within the liver of the HCC mouse model (discussion section).
YOUNIS teaches that mebendazole was administered to a mouse model of HCC (abstract). YOUNIS teaches that the mebendazole treatment, especially when combined with sorafenib, improved liver function and increased survival in the HCC mouse model (abstract). YOUNIS teaches that the mebendazole also provided additional beneficial effects, such as decreasing angiogenesis and metastases (page 11).
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to combine the TUDCA, taught by VANDEWYNCKEL to treat hepatocellular carcinoma, with the mebendazole-sorafenib cocktail taught by YOUNIS to treat hepatocellular carcinoma, for the purpose of increasing the efficacy of the anti-cancer therapy. The artisan would have expected success in this combination, because both agents are taught to treat the same disease.
This is an example of combining equivalent therapeutic agents known to be useful for the same purpose. “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” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06.
Regarding claims 4 and 14: VANDEWYNCKEL teaches the administration of 60 mg/kg/day of TUDCA (discussion section). YOUNIS teaches the administration of 100 mg/kg/day of mebendazole (abstract). The combination of these two dosages represents a molar ratio of 1:1.67.
Allowable Subject Matter
Claims 1-2, 4, 11-15, and 19-20 are herein rejected under 35 U.S.C. 103. Claims 6-8 and 16-18 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: The closest prior art is that of LIU (Liu, H.; Xu, H.; Zhang, Y.; et al. “Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice” World J Gastroenterol 2015 September 28; 21(36): 10367-10374) and YOUNIS (Younis, N.S.; Ghanim, A.M.H.; Saber, S. “Mebendazole augments sensitivity to sorafenib by targeting MAPK and BCL-2 signalling in n-nitrosodiethylamine-induced murine hepatocellular carcinoma” Scientific Reports | (2019) 9:19095 | https://doi.org/10.1038/s41598-019-55666-x).
LIU teaches the administration of ursodeoxycholic acid (UDCA) to treat hepatocellular carcinoma (HCC) in a mouse model (abstract). YOUNIS teaches that mebendazole was administered to a mouse model of HCC (abstract). While it would have been obvious for one of ordinary skill in the art to combine these two therapies to treat HCC, it is not clear why the artisan would also have added vitamin E tocopherol, vitamin E succinate, or an omega-3 fatty acid.
Conclusion
Claims 1-2, 4, 11-15, and 19-20 are herein rejected under 35 U.S.C. 103, and claims 6-8 and 16-18 are objected to as being dependent upon a rejected base claim.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625