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 18/376,982
This Office Action is responsive to the amended claims received 6 February 2026.
Claims 1 and 6 are currently pending.
Priority
Applicant’s claim for the benefit of the prior-filed applications JP 2022-162718 (filed 7 October 2022) 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).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application. For the purposes of the instant office action, the Examiner has determined that the priority date of the instant claims is 10 May 2024.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Response to 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The 35 U.S.C. 112 rejections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments.
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U.S.C. 102(a)(1) and/or 35 U.S.C. 102(a)(2) rejections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments.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 maintained herein.
Response to Arguments
Applicant argues that WIEDENHOEFT focuses on mice, not humans. Applicant argues that drugs effective in animal experiments may not be equally effective in humans. Applicant argues that WIEDENHOEFT does not teach the following limitations of instant claim 1: a human subject and a dosage of 10 to 50 mg per day of resveratrol. Applicant argues that the Examiner proposed an 80 kg VCI patient, which would correspond to a daily dose of 13 mg (based upon WIEDENHOEFT and NAIR). Applicant argues that the standard body weight for a human is 60 kg. Applicant argues that the Examiner should have used this standard body weight to calculate the dosage, and would have arrived at 9.78 mg/day, which Applicant argues is less than the required 10-50 mg/day range of instant claim 1.
Applicant argues that WIEDENHOEFT does not teach the oral administration of resveratrol instant claim 6, but instead intravenous injection. Applicant argues that, even through WIEDENHOEFT does teach the use of resveratrol as a dietary supplement, “its tissue distribution after oral absorption is low, and high efficacies in vitro cannot be sufficiently translated to in vivo applications”. Applicant argues that WIEDENHOEFT teaches away from oral administration in favor of the fusogenic liposome technology therein.
Applicant’s arguments are not persuasive. The Examiner agrees that the outcome of administration of a therapeutic compound to a mouse model does not guarantee the same or a similar outcome in the average human patient. However, the Examiner is arguing that it would have been obvious to one of ordinary skill in the art, reading the teachings of WIEDENHOEFT, to administer the therapy of WIEDENHOEFT to human patients. WIEDENHOEFT clearly intends for the findings therein to be applied to human patients. That would be clear to one of ordinary skill in the art, but additional evidence follows. The discussion section of WIEDENHOEFT states “Age-related impairment of neurovascular coupling responses manifests in older adults (Zaletel et al. 2005; Topcuoglu et al. 2009; Stefanova et al. 2013) and has been causally linked to cognitive decline (Sorond et al. 2013; Sorond et al. 2011)”. The title of the Topcuoglu reference in the quoted sentence above is present on page 725 of WIEDENHOEFT, and mentions findings from human patients.
Applicant’s dosage arguments suffer from two problems. Firstly, Applicant argues that the Examiner should have used a “standard” body weight for a human patient, but one of ordinary skill in the art would immediately envisage patients having a wide weight range, as patients in reality have a wide weight range. In other words, the Examiner does not understand why one of ordinary skill in the art would only envisage human patients weighing 60 kg. Secondly, Applicant argues that the Examiner should have arrived at a dosage of 9.78 mg/day. Because the value of 10 mg/day within the instant claims lacks additional significant figures, one of ordinary skill in the art would interpret 9.78 mg/day and 10 mg/day as reasonably being synonymous values.
The Examiner agrees that WIEDENHOEFT argues for the benefits of their fusogenic liposome administration. WIEDENHOEFT also states “Using FL-RSV, we could show that the pharmacological effect of resveratrol in the cerebral microcirculation was comparable to previous data of orally applied resveratrol (Toth et al. 2014), yet the treatment period and dose could be reduced for comparable rescue of neurovascular responses”. WIEDENHOEFT does not appear to teach away from oral administration of resveratrol and specifically states that oral administration produces a comparable pharmacological effect.
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 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over:
WIEDENHOEFT (Wiedenhoeft, T.; Tarantini, S.; Nyul-Toth, A.; et al. “Fusogenic liposomes effectively deliver resveratrol to the cerebral microcirculation and improve endothelium-dependent neurovascular coupling responses in aged mice” GeroScience (2019) 41:711–725)
in view of:
NAIR (Nair, A.B.; Jacob, S. “A simple practice guide for dose conversion between animals and human” Basic Clin Pharma 2016; 7:27-31.).
WIEDENHOEFT teaches resveratrol-containing liposomes that can be used for the prevention and/or treatment of vascular cognitive impairment (VCI) during aging (abstract). WIEDENHOEFT teaches that mice were retro-orbitally injected with 2 mg/kg/day of resveratrol within liposomes (last sentence on Pg. 714). WIEDENHOEFT teaches that oral administration of resveratrol was comparable, in terms of its cerebral effect, with the lipid-based dosing technique (last sentence in the left column of Pg. 718).
The teaching of WIEDENHOEFT within the abstract, that resveratrol-containing liposomes can be used to prevent or treat VCI would clearly be understood by one of ordinary skill in the art to indicate the treatment of human patients having VCI. The mice model used by WIEDENHOEFT is referred to as a model organism, within the discussion section therein, because the mice are a “model” intended to predict the outcome of the same therapy within human patients.
WIEDENHOEFT does not directly teach a dosage of 10 to 50 mg per day of resveratrol.
NAIR is a guide that teaches how to convert a pharmaceutical dosage between animals and humans when the dosage for a particular species is not available (title, introduction). Table 1 of NAIR teaches that to convert between a mouse pharmaceutical dose and the equivalent human dose, the mouse dose in mg/kg should be divided by 12.3.
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to apply the mouse-to-human dose conversion, already known in the art, to the method of treating vascular cognitive impairment taught by WIEDENHOEFT. Because WIEDENHOEFT teaches the administration of resveratrol to human patients, but does not provide a specific dosage for humans, the artisan would have sought out teachings to fill this gap and come across the teachings of NAIR.
Dividing the daily mouse dosage taught by WIEDENHOEFT (2 mg/kg) by 12.3, as taught by NAIR, results in a human-equivalent daily dose of 0.163 mg/kg. One of ordinary skill in the art, applying this to an 80 kg patient with VCI, would calculate a daily dose for that patient of 13 mg. The artisan would have success in the application of the teachings of NAIR to the method of WIEDENHOEFT, because NAIR provides a practical way to convert pharmaceutical dosages from a mouse dosage to a human dosage when the dosage for a particular species is not yet available, and this is the case with the teachings of WIEDENHOEFT.
Conclusion
No claims are currently allowable.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN D MCANANY whose telephone number is (571)270-0850. The examiner can normally be reached 8:30 AM - 5:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, ANDREW D KOSAR can be reached at (571)272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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