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 .
Status of the Application
This Office Action is in response to Applicant's arguments filed on December 19, 2025. Claim(s) 16-30 are pending and examined herein.
Response to Arguments
In view of applicant’s amendments, the 112(a) rejection over claim 30 for being enabled for treatment of Alzheimer’s disease, but not the prevention or prophylaxis thereof is hereby withdrawn.
Applicant’s arguments with respect to the following rejections have been fully considered.
Claims 16, 18, 19, 20, 21, and 30 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml?id=68ea55e7444c4c12a32ec6baa2e7ebc1 (referred to as China Drug Trials).
Claims 17 and 22-29 are rejected under 35 U.S.C. 103 as being unpatentable over http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml?id=68ea55e7444c4c12a32ec6baa2e7ebc1 (referred to as China Drug Trials) as applied to claims 16, 18, 19, 20, 21, and 30 in the 102(a) rejection above.
The arguments are not persuasive as applicant is arguing base on amended claims. In view of the amendments, said rejections are hereby withdrawn.
Applicant further argues:
In particular, as is disclosed in the Examples of the subject application, the present application discloses the results of randomized and placebo-controlled studies demonstrating for the first time that the combined administration of benfotiamine and donepezil achieves a synergistic effect in the treatment of Alzheimer's disease. This is clear e.g., from the data contained in Table 1 of the specification which substantiate that the combined administration of benfotiamine (BTMP) and donepezil hydrochloride produces effects matching the blank control group. That these results elicit a surprising synergistic effect would be apparent to one skilled in the pharmaceutical art based on the analysis below.
Examiner respectfully notes that “a greater than expected result is an evidentiary factor pertinent to the legal conclusion of obviousness of the claims at issue.” In re Corkill, 711 F.2d 1496, 226 USPQ 1005 (Fed. Cir. 1985). In Corkhill, the claimed combination showed an additive result when a diminished result would have been expected. This result was persuasive of nonobviousness even though the result was equal to that of one component alone. Evidence of a greater than expected result may also be shown by demonstrating an effect which is greater than the sum of each of the effects taken separately (i.e., demonstrating “synergism”). Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). However, a greater than additive effect is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected. Applicants must further show that the results were greater than those which would have been expected from the prior art to an unobvious extent, and that the results are of a significant, practical advantage. Ex parte The NutraSweet Co., 19 USPQ2d 1586 (Bd. Pat. App. & Inter. 1991) (Evidence showing greater than additive sweetness resulting from the claimed mixture of saccharin and L-aspartyl-L-phenylalanine was not sufficient to outweigh the evidence of obviousness because the teachings of the prior art lead to a general expectation of greater than additive sweetening effects when using mixtures of synthetic sweeteners.).
Moreover, Applicant contends:
By contrast, the claimed invention unexpectedly achieves 99%, which significantly exceeds the hypothetical "best-case" additive scenario of 94%. Based on this result, one skilled in the art would necessarily conclude that the claimed invention elicits a synergistic effect on the progression of Alzheimer's disease. Moreover, Applicant submits that such synergy is highly surprising and not reasonably suggested by any information in the cited China Drug Trials disclosure, especially taking into account the current lack of effective treatments for reversing or preventing the progression of Alzheimer's disease. Further based on these synergistic results Applicant submits that the claimed treatment combination is non-obvious. Applicant further submits that the claimed treatment combination is non-obvious based on the improved ADAS-cog score of subjects treated with the claimed combination which is also supported by the subject application.
With respect to the arguments above, examiner notes that they are not commensurate in scope of the claimed invention. There is no limitation recited in the claims limited to the effective concentration of benfotiamine and donepezil which demonstrates discussed synergy, nor the improved ADAS-cog score associated therewith.
Applicant’s arguments with respect to the 103 rejection of claims 16-30 as being unpatentable over CN 108904739 (referred to as Patent ‘739) of record in view of Pan (Brain, 2010) have been fully considered, but not persuasive for the reasons discussed above. Said rejection is hereby maintained.
Applicant argues:
Moreover, and contrary to the stated rationale for the obviousness rejection, the '739 Patent does not state the purpose of including vitamin B1 in their composition. More particularly, the '739 Patent does not state whether the inclusion of vitamin B1 provides for enhanced therapeutic effects or whether it provides nutritional supplementation.
Examiner notes, the reason or motivation to modify a reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. While there must be motivation to make the claimed invention, there is no requirement that the prior art provide the same reason as the applicant to make the claimed invention. MPEP 2144 Sources of Rationale Supporting a Rejection Under 35 U.S.C. 103. /www.uspto..qov/web/offices/pac/mpep/documents/2100 2144.htm>.
Any rejection from the previous Office action not set forth on record below is hereby withdrawn.
The maintained/modified/new rejections are made in the Final Office action below as necessitated by 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 16-30 are rejected under 35 U.S.C. 103 as being unpatentable over http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml?id=68ea55e7444c4c12a32ec6baa2e7ebc1 (referred to as China Drug Trials).
China Drug Trials teaches phase II clinical trial to evaluate the efficacy and safety of benfotiamine tablets added to donepezil hydrochloride tablets in the treatment of mild to moderate Alzheimer's disease.
China Drug Trials teaches dosing of 50 mg/tablet, orally twice a day, 3 tablets each time, for a total of 18 months for the low-dose group. Additional doing is taught with 50 mg/tablet, orally twice a day, 6 tablets each time, for a total of 18 months in the high-dose group.
China Drug Trials does not specifically teach a single formulation of the two components nor the ratios as required by the limitations of the instant claims.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have varied the concentration of the benfotiamine and Donepezil, absent secondary considerations (i.e., unexpected results). Generally, mere optimization of ranges will not support the, patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimal or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also In re Peterson, 315 F. 3d at 1330, 65 USPQ 2d at 1382 "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." MPEP 2114.04.
Thus, based on the foregoing reasons, the instant claims are deemed unpatentable over the cited reference.
Claims 16-30 are rejected under 35 U.S.C. 103 as being unpatentable over CN 108904739 (referred to as Patent ‘739) of record in view of Pan (Brain, 2010).
Patent ‘739 teaches a Chinese-Western preparation composed of the following components：1-1.5 parts of piracetam, 1-1.5 parts of Donepezil Hydrochloride, 0.5-1 parts of vitamin B1, useful in improving cranial nerve, the cerebrovascular and brain blood circulation function, improve and treat insomnia forgetfulness caused by senile dementia, failure of memory, cognitive ability decline (abstract; claim 1).
Patent ‘739 does not teach benfotiamine, a synthetic derivative of vitamin B1 (thiamine).
Pan teaches thiamine (vitamin B1)-dependent processes are critical in glucose metabolism and have been found to be impaired in brains from patients with Alzheimer’s disease. Further, Pan teaches benfotiamine, a thiamine derivative with better bioavailability than thiamine, exhibits beneficial effects on cognitive impairment and pathology alterations in a mouse model of Alzheimer’s disease (abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have employed the composition of Donepezil Hydrochloride and thiamine for the treatment of senile dementia, failure of memory, cognitive ability decline, as taught by Patent ‘739, and employed the synthetic thiamine analog, benfotiamine. The motivation, provided by Pan, teaches that benfotiamine, a thiamine derivative, exhibits beneficial effects on cognitive impairment and pathology alterations in a mouse model of Alzheimer’s disease. Additionally, Pan teaches benfotiamine exhibits better bioavailability than thiamine further motivating the skilled artisan to improve the composition, as taught by Patent ‘739, by replacing thiamine with that of benfotiamine.
Moreover, the skilled artisan would have found it obvious to vary the concentration of benfotiamine and Donepezil, absent secondary considerations (i.e., unexpected results). Generally, mere optimization of ranges will not support the, patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimal or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also In re Peterson, 315 F. 3d at 1330, 65 USPQ 2d at 1382 "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." MPEP 2114.04.
Thus, based on the foregoing reasons, the instant claims are deemed unpatentable over the cited reference.
Conclusion
Claims 16-30 are not 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 mailing date of this final action.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sahar Javanmard whose telephone number is (571)270-3280. The examiner can normally be reached on Monday-Friday, 9:00-5:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/SAHAR JAVANMARD/Primary Examiner, Art Unit 1622