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 .
DETAILED ACTION
2. This Office Action is responsive to Applicant’s Amendment and Remarks, filed January 30, 2026. The amendment, filed January 30, 2026, is entered, wherein claims 24 and 29 – 31 are amended and claims 32 – 39 are new and withdrawn.
Claims 24 – 39 are pending in this application and claims 24 – 31 are currently examined.
Priority
3. This application is a domestic application, filed November 28, 2022, which claims benefit of provisional application 63/283,800, filed November 29, 2021.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/283,800, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The domestic application 63/283,800 does not provide support for the limitations of “orientin”, “vitexin”, and “bergenin concentration of between about 25 micromoles per liter to 100 micromoles per liter” recited in claims 24 – 31. Thus, the priority date of claims 24 – 31 is November 28, 2022.
The following are maintained / modified grounds of rejection necessitated by Applicant’s Amendment and Remarks, filed January 30, 2026, wherein claims 24 and 29 – 31 are amended. Previously cited references have been used to establish the maintained / modified grounds of rejection.
Maintained / Modified 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:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. Considering objective evidence present in the application indicating obviousness or
nonobviousness.
Claims 24 – 25, 29, and 30 – 31 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et al. (Journal of Molecular Neuroscience, 2019, Vol. 69, Issue 2, page 246 – 253, cited in the previous Office Action mailed September 30, 2025), in view of Yahaya et al. (Journal of Immunology Research, 2020, cited in the previous Office Action mailed September 30, 2025), Shal et al. (International Journal of Molecular Sciences, June 2021, Vol. 22, Issue 12, cited in the previous Office Action mailed September 30, 2025), and Barai et al. (Behavioural Brain Research, 2019, Vol. 356, page 18 – 40, cited in the previous Office Action mailed May 16, 2025).
a. Regarding claims 24 – 25, 29, and 30 – 31, Zhong et al. teach that orientin can enhance autolysosome clearance, decrease brain Aβ deposition, and improve learning and memory in AD mice (Abstract). The subject is treated with 10 mg/kg orientin in 0.5 mL saline daily (page 247, Left Col., para. 3).
However, Zhong et al. do not teach combining orientin with vitexin and bergenin as well as the concentration of bergenin. Zhong et al. also do not teach the reduction of tau protein.
Yahaya et al. teach that vitexin is an active compound found in abundance in most medicinal plant species such as pearl millet. The compound is said to possess a number of pharmacological properties including anticancer, antinociceptive, antiviral, and anti-inflammatory, and anti-AD. Yahaya et al. disclose that vitexin has shown its ability to limit the formation of Aβ via the inhibition of BACE1 enzyme (page 4, Left Col., para. 3 – 4).
Shal et al. teach studies performed in 5xFAD Tg mouse model, which bergenin is administered orally in the amounts of 1, 20, and 60 mg/kg. The results show that bergenin significantly attenuate the memory deficit observed in the Y-maze and Morris water maze test. The differential scanning calorimeter suggests an absence of Aβ aggregation in bergenin-treated mice (Abstract). Shal et al. teach the working concentrations of bergenin to be 1, 10, 50, and 100 μM (page 20, para. 5).
Barai et al. teach that bergenin possess efficacious antioxidant, antiulcerogenic, anti-HIV, hepatoprotective, neuroprotective, anti-inflammatory and immunomodulatory activity along with antinociceptive effect and wound healing properties. The bergenin treatment at 80 mg/kg leads to significant abatement of the raised Aβ-1-42 levels and alleviated the perturbed p-tau levels to significantly low levels of p-tau in brain homogenates of rats. The observed effects might be attributed to the cholinesterase inhibitory activity of bergenin coupled with its antioxidant effect, anti-inflammatory activity and reduction of Aβ-1-42 and p-tau levels which could have collectively helped in the attenuation of cognitive deficits (Abstract). Barai et al. disclose that the reports on inhibition of carrageenan-induced edema in rats, hPTP1B inhibitory activity and reduction of various inflammatory and pro-inflammatory mediators, like IL-1β, TNF-α, IFN γ, COX-1, COX-2, phospholipase A2, etc. indicate that anti-inflammatory activity of bergenin might have also contributed its part for the improvement of the morphology of neurons by reducing neuroinflammation (page 38, Left Col., para. 1). Barai et al. further demonstrate bergenin’s dose-dependent inhibition of AChE and BuChE in vitro and found to be safe up to 50 µM (Abstract).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine orientin as taught by Zhong et al. with vitexin and bergenin in view of Yahaya et al. and Shal et al. to administering the combination of orientin, vitexin, and bergenin to reduce Aβ protein. It would have been obvious for one of ordinary skill in the art to do this because orientin, vitexin, and bergenin are known separately in the art for the purpose of reducing Aβ protein, and it would have been obvious to combine them for the same purpose. Each of the references identifies orientin, vitexin, and bergenin as the essential active agents responsible for reducing Aβ/tau proteins. The references do not teach other components. Therefore, the combination of Zhong et al., Yahaya et al. and Shal et al. met the recitation of “consisting of”. Barai et al. teach that bergenin is able to reduce tau protein, said combination containing orientin, vitexin, and bergenin will achieve the intended purpose when administered to a patient. One of ordinary skill in the art would have had a reasonable expectation of success to modify Zhong et al. with the teachings of Yahaya et al. and Shal et al. because it is well known to combine drugs to treat the same condition.
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Zhong et al. (Journal of Molecular Neuroscience, 2019, Vol. 69, Issue 2, page 246 – 253, cited in the previous Office Action mailed September 30, 2025), in view of Yahaya et al. (Journal of Immunology Research, 2020, cited in the previous Office Action mailed September 30, 2025) and Shal et al. (International Journal of Molecular Sciences, June 2021, Vol. 22, Issue 12, cited in the previous Office Action mailed September 30, 2025) as applied to claims 24 – 25 and 29 above, and further in view of Varshney et al. (Critical Reviews in Food Science and Nutrition, 2021, cited in the previous Office Action mailed May 16, 2025).
b. Regarding claim 26, the references teach the limitations discussed above.
However, these references do not teach the claimed concentration of vitexin.
Varshney et al. teaches 10 μM of vitexin was used in zebrafish larvae model (page 1760, Right Col., para. 1). About 50 μM of vitexin was found to inhibit aggregation of Aβ25-35 on Neuro-2a cells significant and restored the cell viability up to 92.86 ± 5.57% via inhibition of caspase-3 activation, and Bax protein expression. It has been reported that vitexin has low cytotoxicity and is able to reduce the releases of TNF-α, IL-1β, NO, etc (page 2760, Left Col., para. 2).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings as taught by Zhong et al., Yahaya et al., and Shal et al. with the effective dose of vitexin in view of Varshney et al. because Varshney et al. disclose that 50 μM vitexin is able to inhibit aggregation of Aβ25-35 on Neuro-2a cells. One would have been motivated to combine the teachings as taught by Zhong et al., Yahaya et al., and Shal et al. with the effective dose of vitexin in view of Varshney et al. because of the therapeutic effects of vitexin against Aβ protein. One of the ordinary skill in the art would have had a reasonable expectation of success to combine the teachings as taught by Zhong et al., Yahaya et al., and Shal et al. with the effective dose of vitexin in view of Varshney et al. as Varshney et al. disclose the therapeutic effects of vitexin.
Claims 27 – 28 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et al. (Journal of Molecular Neuroscience, 2019, Vol. 69, Issue 2, page 246 – 253 cited in the previous Office Action mailed September 30, 2025), in view of Yahaya et al. (Journal of Immunology Research, 2020, cited in the previous Office Action mailed September 30, 2025) and Shal et al. (International Journal of Molecular Sciences, June 2021, Vol. 22, Issue 12, cited in the previous Office Action mailed September 30, 2025) as applied to claims 24 – 25 and 29 above, and further in view of Lam et al. (Advances in Pharmacological Sciences, 2016, Vol. 2016, page 1 – 9, cited in the previous Office Action mailed November 28, 2023).
c. Regarding claims 27 – 28, the references teach the limitations discussed above.
However, these references do not teach the claimed concentration of orientin.
Lam et al. disclose various medicinal properties of orientin (page 3 – 6). In one of the in vivo studies, 3, 10, and 30 μmol/L have been used to evaluate the cardioprotective effects in rats (page 4, Right Col., para. 4). Lam et al. further disclose that the use of orientin is able to produce neuroprotective effects in Amyloid β-protein induced mitochondrial dysfunction oxidative stress (Alzheimer’s disease, AD) mice. Moreover, Lam et al. find that orientin will improve cognitive impairment of the AD mice (page 5, Right Col., para. 3).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings as taught by Zhong et al., Yahaya et al., and Shal et al. with the dosing amount of orientin in view of Lam et al. because Lam et al. disclose that it has been safe to treat rat with 3, 10, and 30 μmol/L. One would have been motivated to combine the teachings as taught by Zhong et al., Yahaya et al., and Shal et al. with the dosing amount of orientin in view of Lam et al. because it is known in the art that it is safe to use up to 30 μmol/L in treatment. The dosage disclosed by Lam et al. is able to act as a guidance to establish a safe dose in other animals, such as human. The dose would be optimized by routine experimentation to discover the best effective amount for optimal Aβ protein reduction. One of the ordinary skill in the art would have had a reasonable expectation of success to combine the teachings as taught by Zhong et al., Yahaya et al., and Shal et al. with the dosing amount of orientin in view of Lam et al. as Lam et al. teach the safety dosage for subject to administered.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed January 30, 2026, have been fully considered and is found to be not persuasive.
Regarding the rejections, Applicant argues that the amended claim with the transitional phrase “consisting of” overcome the rejection. However, the argument is not persuasive. The rejection properly relies on multiple references and the cited references teach each of the orientin, vitexin, and bergenin without the addition of other components. Zhong et al. teach orientin is useful for reducing Aβ protein in an Alzheimer’s disease model; Yahaya et al. teach that vitexin exhibits the inhibitory activity against Aβ protein; and Shal et al. teach that bergenin is useful in a transgenic Alzheimer’s mouse model with attenuation of memory deficit and absence of Aβ aggregation. Therefore, one of ordinary skill in the art would have been motivated to combine the three known compounds for treating Alzheimer’s disease by reducing Aβ protein because it is known in the art that these three compounds are effective in reducing Aβ protein. One of ordinary skill in the art would have had a reasonable expectation of success to combine the three known compounds for treating Alzheimer’s disease by reducing Aβ protein because each compound is known to be effective against Alzheimer’s disease.
Applicant argues that the combination of orientin, vitexin, and bergenin in a composition yields an unexpected synergistic benefit beyond any of the individual components of the composition. However, the argument is not persuasive because the results are not commensurate in scope with the claims. For example, the examples only test on a limited concentration of orientin, vitexin, and bergenin. Claims 24 and 29 – 31 encompass compositions consisting of orientin, vitexin, and bergenin in any effective dose for reducing Aβ protein , tau protein, or both, and claims 25 – 27 further encompass concentration ranges for the recited components. The evidence shown in Figure 29 is limited to a small number of tested compositions with specific concentrations for each components and Applicant does not establish that those tested concentrations are representative of the entire claimed ranges or that the ranges are critical. Additionally, the data do not demonstrate a dose-response relationship or any trend from which one of ordinary skill in the art would reasonably conclude that the synergistic effect would occur throughout the full scope of the claimed invention. Therefore, the examiner is not able to determine the unexpected results based on the results currently provided.
Conclusion
No claim is found to be allowable.
Applicant's amendment necessitated the maintained / modified 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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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693