DETAILED ACTION
Claims 13-16 and 19 are currently pending in the instant application and are rejected.
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 .
Election/Restrictions
Applicant's election with traverse of Group IV and the species of nebivolol as a beta blocker and donepezil as a cholinesterase inhibitor in the reply filed on 3 February 2026 has been previously acknowledged.
As claims 13-16 and 19 are drawn solely to the elected species, claims 13-16 and 19 have been searched and examined in their entirety.
Response to Amendment and Arguments
Applicant's amendment and arguments filed 15 June 2026 have been fully considered and entered into the instant application. Applicant’s amendment has overcome the 35 USC 112(d) rejection as claims 17 and 18 have been canceled. In regards to the 35 USC 103 rejection, applicant argues unexpected results, evidence of synergy with reference to Figures 1-3 providing nebivolol and donepezil exhibiting synergistic effects at a molar ratio of 1:0.5 to 1:2. While the Figures 1-3 provide synergistic effects at a molar ratio of 1:0.5 to 1:2, it is noted that the molar ratio of 1:0.5 to 1:2 is not a claim limitation in any of the pending claims. Instant claims 13, 14, and 16 do not have any molar ratio limitation. Claims 16 and 19 have molar ratios of 1:01 to 20 and 1:0.5 to 20, which are much larger molar ratio variations than the molar ratio of 1:0.5 to 1:2 of nebivolol and donepezil provided in Figures 1-3. Please see MPEP 2145 VI:
VI. ARGUING LIMITATIONS WHICH ARE NOT CLAIMED
Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993) (Claims to a superconducting magnet which generates a “uniform magnetic field” were not limited to the degree of magnetic field uniformity required for Nuclear Magnetic Resonance (NMR) imaging. Although the specification disclosed that the claimed magnet may be used in an NMR apparatus, the claims were not so limited.); Constant v. Advanced Micro-Devices, Inc., 848 F.2d 1560, 1571-72, 7 USPQ2d 1057, 1064-1065 (Fed. Cir.), cert. denied, 488 U.S. 892 (1988) (Various limitations on which appellant relied were not stated in the claims; the specification did not provide evidence indicating these limitations must be read into the claims to give meaning to the disputed terms.); Ex parte McCullough, 7 USPQ2d 1889, 1891 (Bd. Pat. App. & Inter. 1987) (Claimed electrode was rejected as obvious despite assertions that electrode functions differently than would be expected when used in nonaqueous battery since “although the demonstrated results may be germane to the patentability of a battery containing appellant’s electrode, they are not germane to the patentability of the invention claimed on appeal.”).
The 35 USC 103 rejection is therefore maintained as synergy has not been shown for any and all molar ratios as covered by the instant claims and the data provided for molar ratios of 1:0.5 to 1:2 cannot be extrapolated to any and all molar ratios as only three ratios have been shown, 1:0.5, 1:1, and 1:2.
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.
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.
Claim(s) 13-6 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shigeta et al. (attached 892) in view of Wang et al. (IDS filed 8/21/2023, Cite No. 1 Non-Patent Literature).
Determining the scope and contents of the prior art (See MPEP 2141.01)
Shigeta et al. provides Donepezil, which is approved for the treatment of mild to moderate Alzheimer’s disease with new indications for donepezil in psychiatric and neurologic diseases, other than AD, which includes dementia with Lewy bodies, brain injury, attention deficit hyperactivity, multiple sclerosis, Down’s syndrome, delirium, mood disorders Huntington’s disease and sleep disorders, pages 353-354. Figure 1, page 357, provides treatment of mild to moderate Alzheimer’s disease in US phase III trials with 5mg and 10mg/day.
Wang et al. provides nebivolol as treatment of AD at very early stages of the disease, page 1147. Page 1148 provides that nebivolol was shown to interfere with amyloid-B protein precursor processing in neuronal-like cells and exert estrogen-like neuroprotective effects. Page 1150 provides that mice were treated with 1, 3, 10, and 30mg/kg/day. Page 1151 provided that 2 months of chronic treatment with 1mg/kg/day nebivolol significantly improved short term memory function.
Ascertaining the differences between the prior art and the claims at issue (See MPEP 2141.02)
The prior art does not teach an explicit embodiment where the donepezil and nebivolol are administered together for the treatment of a neurodegenerative disease.
Finding of prima facie obviousness---rationale and motivation (See MPEP 2142-2143)
As Shigeta et al. provides the administration of donepezil for the treatment of mild to moderate Alzheimer’s disease and Wang et al. provides the administration of nebivolol for the treatment of AD at very early stages of the disease, it would have been prima facie obvious for a person having ordinary skill in the art to administer a combination of donepezil and nebivolol a as both were known in the art to be efficacious in treating mild or early stage Alzheimer’s disease Per MPEP 2144.06, I. “"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.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted)”. In regards to applicant’s instant claim 15 required molar ratio of administration of 1:0.1-20, donepezil has a calculated molecular mass of about 379.5 g/mol and nebivolol has a calculated molar mass of about 405.4 g/mol. The administration of 5mg daily of donepezil would equate to 0.005g X 1mol/369.5g which is about 1.35 x 10-5 moles. For 10mg daily of donepezil, the moles would be about 2.71 x 10-5 moles. For nebivolol, the administration is performed in mice with 1, 3, 10, and 30mg/kg/day. As the weight of mice can vary, for example, from 18-40 grams, the administration of 30mg/kg/day in an 18 gram mouse would be about 0.54mg per day and the administration 30mg/kg/day in a 40gram mouse would be about 1.2mg per day. The administration of 0.54mg daily of nebivolol would equate to 0.00054g X 1mol/405.4g which is about 1.33 X 10-6 moles whereas the administration of 1.2mg daily of nebivolol would equate to 0.0012g X 1mol/405.4g which is about 2.96 X 10-6 moles. These exemplified moles would provide molar ratios within 1:0.1-20. Additionally, as seen in MPEP 2144.05, In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In reWertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In reWoodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of Americav.Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) “The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties.”. See also In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%). "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005). In regards to applicant’s instant claim 16 administration simultaneously, separately or sequentially, as both prior art references provide administration, it would be obvious to select the most advantageous administration route of both donepezil and nebivolol by routine experimentation. Additionally, simultaneous, separate or sequential administration are all the possible administration routes.
Conclusion
THIS ACTION IS MADE FINAL. 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 REBECCA L ANDERSON whose telephone number is (571)272-0696. The examiner can normally be reached Monday-Friday from 6am-2pm.
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/REBECCA L ANDERSON/Primary Examiner, Art Unit 1626 ____________________ 13 August 2026
Rebecca Anderson
Primary Examiner
Art Unit 1626, Group 1620
Technology Center 1600
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