DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
Receipt is acknowledged of Applicants’ amendment and remarks, filed on 09/19/2025, in which claims 10 and 14-16 are amended and claims 1-9 and 12-13 are canceled.
Applicant’s declaration of Taoka, filed on 09/19/2025, is acknowledged and further discussed below.
Claims 10-11 and 14-18 are pending and are examined on the merits herein.
Priority
The instant application is a 371 of PCT/JP2021/012054, filed on 03/23/2021, which claims foreign priority to JP 2020-051807, filed on 03/23/2020.
Information Disclosure Statement
The information disclosure statements (IDS) dated 06/13/2025 and 12/10/2025 comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the information disclosure statements have been considered by the examiner.
Objections and Rejections Withdrawn
Applicant’s amendment and remarks, filed 09/19/2025, with respect that claims 15-16 are objected to because of informalities has been fully considered and is persuasive, as claims have been corrected. This objection has been withdrawn.
Applicant’s amendment and remarks, filed 09/19/2025, with respect that claims 10-11 and 13-18 are rejected under 35 U.S.C. 112(a), because the specification, while being enabling for treating renal cell carcinoma, does not reasonably provide enablement for preventing renal cell carcinoma, has been fully considered and is persuasive, as the claims have been amended to limit the scope of the claim to exclude prevention. This rejection has been withdrawn
Applicant’s amendment and remarks, filed 09/19/2025, with respect that claims 13-14 are rejected under 35 U.S.C. 112(d), as being of improper dependent form has been fully considered and is persuasive, as claim 13 has been canceled and claim 14 has been amended to clarify the scope of the claim. This rejection has been withdrawn
The following are modified grounds of rejection necessitated by Applicant’s amendment.
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.
Claims 10-11 and 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over Matsuoka et al. (The Nishinihon Journal of Urology, 2019; IDS 09/22/22) in view of Tokuda et al. (WO 2016/152293 A1; IDS 09/22/22).
Matsuoka teaches the administration of rare sugars for the treatment of renal cell carcinoma. Matsuoka teaches that renal cell carcinoma is known to display high expression of the glucose transporter, which prompted the investigation of whether rare sugars could inhibit the proliferation of renal cell carcinoma cells. Matsuoka discloses the incorporation of the rare sugar D-allose into renal cell carcinoma cells and shows that D-allose gave the highest anti-tumor effect (page 135, left column). Matsuoka also discloses intraperitoneal injection of D-allose into a xenograft mouse model of renal cell carcinoma (page 135, left column) where the mice were dosed with alternatively 100mg/kg or 400mg/kg every day (page 135, right column). The results demonstrate that D-allose inhibits cancer cell growth and can be a new treatment strategy for treating renal cell carcinoma (page 135, right column).
Matsuoka does not teach the intro-intestinal administration of a composition containing D-allose (instant claim 1).
Tokuda teaches that D-allose is known to promote the expression of the cancer suppressor gene TXNIP, which in turn inhibits cell division and stops the proliferation of cancer cells. D-allose is also known to inhibit the expression of glucose transporter (GLUT1), thereby inhibiting the supply of glucose to cancer cells that require energy to proliferate, starving the cancer cells and thereby inhibiting the proliferation of cancer or causing cell death [0006].
Tokuda provides a method for using D-allose as a therapeutic agent for treatment of cancers by inhibiting expression of Glucose Transporter-1 (GLUT1) by cancer cells (abstract). Tokuda discloses a composition comprising D-allose for inhibiting the expression of glucose transporter 1 in cancer cells (claim 1). The composition may be administered orally as a food (claim 14), including as a health food, which may be a food with specified health uses or a food with nutritional functions, or as a dietary supplement (claims 15-16). In addition, Tokuda teaches a preferred oral dosage formulated as a pill, capsule, powder, and tablet, among others [0021]. Tokuda is thus interpreted as teaching that the composition comprising D-allose may be administered orally as a drug.
It would have been prima facie obvious to combine the teachings of Matsuoka and Tokuda before the effective filing date of the claimed invention by formulating the D-allose composition of Matsuoka according to the oral formulations of Tokuda to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to apply the oral formulation of Tokuda to the D-allose compositions of Matsuoka because it would have been prima facie obvious to apply the known technique of formulating the D-allose anti-cancer compositions taught by Tokuda for administration in the D-allose anti-cancer treatment method of Matsuoka. One of ordinary skill in the art would have a reasonable expectation of success because Matsuoka teaches the inhibition of cancer cell proliferation in renal cell carcinoma by D-allose and suggests the inhibition of glucose transport and Tokuda teaches that D-allose comprising compositions provide inhibition of cancer cell proliferation and glucose transporter expression.
Regarding instant claim 14, the claim is dependent on claim 10, which recites “D-allose and/or a derivative thereof and/or a mixture of the same.” Claim 14 provides additional limitations on the derivative of D-allose, but does not require the presence of a D-allose derivative. Therefore, the additional limitations of claim 14 are considered met by any prior art meeting the limitations of claim 10 in the form of a composition comprising D-allose.
Claims 10-11 and 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over Izumori et al. (US 8,420,606 B2; PTO-892) in view of Noguchi et al. (Tohoku J. Exp. Med., 2016; PTO-892) and Chan et al. (Science Translational Medicine, 2011; PTO-892).
Izumori discusses methods of utilizing the physiological activity of a variety of rare saccharides, and teaches that D-allose is an example of a rare saccharide (col. 1, lines 19-40). Izumori demonstrates that D-allose inhibits proliferation of cancer cells. D-allose may be applied through oral administration among other routes of administration (col. 11, lines 33-35). The dose of the rare saccharide used as medicines is not limited to a particular value, but it is preferably, per 1 kg of patient weight, about 0.01 to 2,000 mg in the case of oral administration (col. 14, lines 33-36). The composition may be administered as a functional food (col. 14, lines 45-59), or as a drug (col. 14, lines 60-62). Izumori also teaches that D-allose may be mixed in foods (col. 14, line 19). Izumori states that because the exact dose of the drug product or the drug composition changes depending on the intended usage and the treatment time a proper dose is decided by a doctor (col. 15, lines 4-6). Izumori also teaches methods of determining cancers susceptible to inhibition by rare saccharide compositions, including a method to determine the effect of rare saccharide upon proliferation of cultured cells (Example 1 on col. 15, line 61 - col. 17, line 20) and a method to demonstrate the concentration dependency of the inhibitory effect of D-allose on cancer cell proliferation for a given cancer type (Example 2 on col. 17, lines 22-52).
Izumori does not teach the treatment of renal cell carcinoma (instant claim 1).
Noguchi teaches the inhibition of cancer cell growth by D-allose through the inhibition of GLUT1 expression and increased TXNIP expression (abstract). In particular, Noguchi teaches that over-expression of GLUT1 has been reported in many cancer cell lines (page 131, paragraph 1). Kock-down of thioredoxin interacting protein (TXNIP) expression is known to increase GLUT1 expression and TXNIP expression is down-regulated in many cancer cells (paragraph bridging pages 131-132). The rare sugar D-allose strongly induces TXNIP and thereby inhibits cancer cell growth (page 132, paragraph 1). Noguchi teaches that that the TXNIP induction by D-allose may cause down-regulation of GLUT1 expression at the transcriptional level (page 138, paragraph 4). D-allose likely affects cancer cell growth via a reduction in GLUT1 expression (paragraph bridging pages 138-139). Noguchi concludes that as GLUT1 is over-expressed in various types of cancer cells and D-allose is a strong inducer of TXNIP, D-allose may inhibit GLUT1 expression in cancer cells and may thus be an effective treatment for cancer (page 140, paragraph 5).
Chan teaches treatment of renal cell carcinoma (RCC) by targeting GLUT1 and the Warburg effect by administration of a small molecular which selectively kills RCCs by specifically targeting glucose uptake through GLUT1 and exploiting the unique dependence of these cells on GLUT1 for survival (abstract). RCC, the most common type of kidney cancer, is a particularly challenging, intractable disease, resistant to both radiation therapy and standard systemic chemotherapies. Less than 10% of metastatic RCC patients respond to immunotherapy, and the agents that are standard of care for RCC treatment are not curative. In most RCCs, the von Hippel–Lindau (VHL) tumor suppressor gene is inactivated, driving tumor development. VHL deficiency imparts distinct characteristics on tumor cells, such as reliance on the high affinity glucose transporter 1 (GLUT1) and aerobic glycolysis, also known as the Warburg effect. Chan teaches that a strategy to specifically target RCC includes targeting cells that have lost functional VHL and display these characteristics (page 1, paragraph 2). Chan states that specific inhibition of GLUT1, either pharmacologically or genetically with RNA interference, leads to necrosis of cells lacking VHL (page 6, paragraph 1). Chan teaches that targeting of GLUT1 in human renal cell cancers is a feasible approach that displayed no toxicity to normal tissue in these studies (page 6, paragraph 2).
It would have been prima facie obvious to combine the teachings of Izumori, Noguchi, and Chan before the effective filing date of the claimed invention by administering a composition comprising D-allose as an active ingredient in a method of treating RCC to arrive at the instantly claimed invention. One of ordinary skill in the art would have been motivated to apply the anti-cancer D-allose formulations and administration methods of Izumori to the treatment of RCC because Chan teaches that RCC has limited treatment options and is sensitive to the targeting of GLUT1, and Noguchi teaches that D-allose targets GLUT1 in cancer cells. One of ordinary skill in the art would have a reasonable expectation of success in doing so because Chan teaches that targeting of GLUT1 in human renal cell cancers is a feasible approach and Izumori teaches methods for testing the cancer cell proliferation inhibitory effect of D-allose on various cancer types.
Regarding the dosage of the D-allose in instant claim 10, it would have been prima facie obvious to optimize the dosage of D-allose oral administration taught by Izumori within the taught range of 0.01 to 2,000 mg/kg of body weight because Izumori teaches that the dosage of the composition changes depending on the intended usage and the treatment time. One of ordinary skill in the art would have a reasonable expectation of success because Izumori, a proper dose is decided by a doctor, thus indicating that optimizing the dosage would have been accomplished by a practitioner.
Regarding instant claim 14, the instant claim is dependent on claim 10, which recites “D-allose and/or a derivative thereof and/or a mixture of the same.” This indicates that a derivative of D-allose may be included in the composition, but is not required to be included. Claim 14 provides additional limitations on the derivative of D-allose, but does not require the presence of a D-allose derivative. Therefore, the additional limitations of claim 14 are considered met by any prior art meeting the limitations of claim 10 in the form of a composition comprising D-allose.
Regarding instant claim 18, Izumori teaches that the composition may be administered as a functional food (col. 14, lines 45-59) and that D-allose may be mixed in foods (col. 14, line 19). Because Izumori teaches administration of D-allose for inhibiting the proliferation of cancer cells and teaches that D-allose may be mixed in food, it would be prima facie obvious to administer D-allose as a health functional food which is a specified health food for the inhibition of the proliferation of cancer cells.
Response to Arguments
Applicant's arguments filed 09/19/2025 have been fully considered but they are not persuasive.
Applicant argues that because Matsuoka teaches the use of D-allose intraperitoneally (Remarks, page 5, paragraph 4 and page 6, paragraph 2) and Izumori' s range is extremely broad and is not functionally demonstrated (Remarks, page 6, paragraph 5), one of ordinary skill in the art would not be able to use the teachings of the prior art to determine the dosage for oral administration. This is not persuasive.
As established in the above grounds of rejection, Izumori teaches that the recommended dosage of the composition changes depending on the intended usage and the treatment time and thus a practitioner would have optimized the dosage for oral administration.
Applicant further argues that the range taught by Izumori is essentially a blanket range that would require extensive experimentation (Declaration, paragraph 18) and that there was no way to predict, from the teachings of the cited references, that oral D-allose would reach tumors in RCC in sufficient concentration to be effective, especially at the claimed level of dosing (Declaration, paragraph 19). Applicant also argues that D-allose is taken up by RCC cells to a greater degree than other types of cancer cells, citing support in paragraph 14 of the Declaration. Applicant’s arguments amount to an argument from unexpected results. This is not persuasive.
The closest prior art is Matsuoka, which teaches administration of D-allose as a strategy for treatment of renal cell carcinoma. Matsuoka discloses the incorporation of rare sugars, including D-allose, into RCC cells, including Caki-1, Caki-2, and ACHN cells. Matsuoka shows that of the rare sugars D-allose gave the highest anti-tumor effect. Matsuoka also discloses intraperitoneal injection of D-allose into a xenograft mouse model of renal cell carcinoma where D-allose inhibits cancer cell growth.
Because the closest prior art teaches administration of D-allose to RCC cells, as well as intraperitoneal administration of D-allose in RCC treatment, Applicant must demonstrate a significant difference in outcome of transintestinal versus intraperitoneal administration of D-allose in treatment RCC in order to show unexpected results. Applicant provides data comparing tumor volumes in mice administered intraperitoneal injections of D-allose, saline, or cabozantinib (Declaration, paragraph 15), but this does not provide a comparison using the claimed transintestinal route of administration. Applicant provides data showing the change in tumor D-allose concentration after oral versus intraperitoneal administration of D-allose to a renal cell carcinoma xenotransplantation mouse model (instant specification [0047]). Applicant demonstrates that with oral administration of 400 mg/kg body weight, D-allose was detected in the tumors at about 80% of the D-allose concentration with intraperitoneal administration of 400 mg/kg body weight (instant specification [0049] and figures 1(c) and 1(d)). However, Applicant does not demonstrate that the result of an 80% comparative concentration of D-allose is unexpected. Although Applicant states that the expectation of one of reasonable skill in the art would be that D-allose would be extensively metabolized prior to delivery to the renal cells if it was administered orally (Declaration, paragraph 17), Applicant does not demonstrate that a difference of 20% would be considered unexpected for this dosage. Similarly, Applicant does not demonstrate that the difference in D-allose uptake by RCC cells is significant as compared to the amount up taken by the other tested cancer types (Declaration, Tables 1-9). MPEP 716.02(b)(I) states that the evidence relied upon should establish that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance. MPEP 716.02(b)(II) states that Applicants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness.
Because Applicant’s arguments are not persuasive, the instant claims are rejected for the reasons of record with modifications made to account for the claim amendments filed 09/19/2025.
Conclusion
No claims are allowed.
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 extension fee 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 date of this final action.
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/S.G.H./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693