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 .
Current Status
This action is responsive to the amended claims of 10/27/2025. Claims 1, 4-5, 8-9, 12-13, and 16-20 are pending. Claims 1, 4-5, 8-9, 12, and 17 are withdrawn. Claims 17-20 are new. Claims 13, 16, and 18-20 have been examined on the merits.
Election/Restrictions
The reply of 10/27/2025 did not overcome all of the prior art rejections of the previous action (07/25/2025). Thus, the Markush search will not be extended unnecessarily in this action.
The elected species sodium valproate retrieved prior art (see SEARCH 6 of the attached search notes) and reads on claims 13, 16, and 18-20.
Claim 17 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/16/2025.
Claims 1, 4-5, 8-9, and 12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/16/2025.
Note: Applicant has elected Group II drawn to a method of treatment administering the compound of Formula I, thus, the Group I claims drawn to a compound of Formula I, a medicament thereof, and a method of making the medicament thereof cannot be rejoined since these claims do not require all limitations of the elected method claims (See MPEP 821.04). Thus, Applicant is encouraged to cancel all Group I claims (claims 1, 4-5, 8-9, and 12). This will expedite allowance.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The effective filing date remains 09/30/2020.
Response to Arguments
Examiner acknowledges receipt of and has reviewed the remarks and amendments of 10/27/2025, no new matter is found.
The objections to claims 13 and 16 are withdrawn since Applicant has amended in line with Examiner’s suggestions.
The 112(a) scope of enablement rejection of claims 13 and 16 is withdrawn since Applicant has struck the word “preventing” from the claims.
The 112(b) rejections of claims 13 and 16 (¶15-17 of prev. action) are withdrawn since Applicant has struck the cited instances of parentheses, “preferably”, and “more preferably”.
The 102 rejection of claims 13 and 16 as anticipated by SINISCALCHI is withdrawn. Applicant’s arguments are persuasive, in part. Applicant argues that SINISCALCHI does not teach treatment or amelioration of the symptom/Down Syndrome (DS), but that treatment with sodium valproate induced a tremor. Upon further review of the reference, Examiner agrees that SINISCALCHI does not teach or suggest relief of DS and any of its symptoms by administration of the sodium valproate. It merely teaches administration of the sodium valproate to the DS patient. For this reason, the rejection is withdrawn.
Note, however, that Applicant’s other argument was not found persuasive. Applicant argues that claim 13 is directed to a method of treating DS which can improve cognitive function, neurodevelopment, and synaptic plasticity. Examiner respectfully disagrees, because the current drafting of claim 13 is not so narrow. The current drafting does encompass treatment of those symptoms, but at its broadest encompasses the treatment of any and all symptoms associated with DS. If Applicant wishes for the claim to be drawn to treatment of just these symptoms, Examiner suggests Applicant incorporate the limitation of claim 16 into claim 13. This may become relevant to any art found in future Markush search extensions.
The 103 rejection of claims 13 and 16 over GALLAGHER and LOCKROW is maintained below, and is further modified to include the new claims 18-20. Applicant's arguments filed 10/27/2025 have been fully considered but they are not persuasive. Applicant argues that GALLGHER does not teach treatment of DS and LOCKROW, while teaching pathological phenomena (including age-related memory impairment) of DS, does not teach treatment methods. Thus, the artisan would have no motivation to combine the references. Examiner respectfully disagrees. GALLAGHER is drawn to treating age-related cognitive/memory impairment and teaches sodium valproate treatment increases glutamate reuptake to improve memory in memory-impaired rats; LOCKROW teaches age-related memory deficits in DS which are similar to Alzheimer’s and are reversed in mouse models by blocking glutamate receptors (see teachings on Pg. 15 of prev. action). As explained on Pg 16-17 of the prev. action, the references are both drawn to improvement of age-related memory deficits by inhibiting/decreasing glutamate signaling. Based on this overlap, the artisan would recognize the method of GALLAGHER (treating memory-impairment by decreasing glutamate signaling) as applicable to treatment of DS based on the symptoms and mouse model (improved memory upon blocking glutamate receptor) taught by LOCKROW.
Applicant further argues that Alzheimer’s and DS exhibit different etiologies and would not be motivated to use a method of treating Alzheimer’s to treat DS. Applicant admits late-stage DS has similar pathology to Alzheimer’s. However, the prev. action did not state that the two diseases have the same etiology, LOCKROW’s teaching that Alzheimer’s-like neuropathology develops in DS (Pg. 1 Abstract) was cited as a way to characterize the cognitive and memory/learning issues that are known to develop in DS and connect them to the age-related memory impairment taught by GALLAGHER. Further, under the broadest reasonable interpretation of the claims treatment or amelioration of DS is not limited to treatment of the root cause of DS (i.e., etiology) but is also drawn to treatment of the symptoms (i.e., pathology). Since the pathology of late-stage DS and Alzheimer’s are similar, the artisan would recognize the cognitive, memory, and learning deficits of late-stage DS as age-related memory impairments analogous to those taught by GALLAGHER.
Finally, Applicant argues that GALLAGHER teaches valproic acid can enhance synaptic plasticity and, “on the other hand”, LOCKROW discloses the memory impairment of late-stage DS is characterized by decreased synaptic density. Examiner fails to see how these teachings are contradictory or lead the artisan away from the combination of references. Examiner believes these teachings complement each other: i.e., 1) valproic acid improves synaptic health; 2) late-stage DS synaptic health is poor; 3) thus, the artisan would have a reasonable expectation of success that treatment of DS with valproic acid would improve synaptic health and improve memory/cognitive function.
Moreover, MPEP 2145(I) states “An argument by the applicant is not evidence unless it is an admission… Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.").” Here, Applicant has not provided any evidence of secondary consideration, e.g., unexpected results (see MPEP 716.02(a)), affidavit, or secondary references/teachings which teach away from the claimed limitations. Thus, for all of the reasons stated above, the rejection is maintained.
Response to 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.
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 13, 16, and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over GALLAGHER (US 2011/0065674, cited by Examiner 07/25/2025) in view of LOCKROW (Lockrow, J.P., et al., Current Gerontology and Geriatrics Research, 2012, 2012, 1-13, provided by Examiner 07/25/2025).
Determining the Scope and Contents of the Prior Art:
GALLAGHER teaches a method of treating age-related cognitive impairment in a subject in need comprising administering a valproate or the pharmaceutically acceptable salt thereof (Pg. 9 Claim 1). GALLAGHER further teaches the method is directed to subjects having or at risk for Mild Cognitive Impairment (MCI), Age-Associated Memory Impairment (AAMI) or Age-Related Cognitive Decline (ARCD) (Pg. 1 P1). GALLAGHER teaches the valproate is sodium valproate, a medication which modifies excitatory-inhibitory functions by increasing glutamate reuptake and GABA concentrations (Pg. 4 P50). GALLAGHER further teaches memory-impaired rats treated with sodium valproate showed less forgetting, i.e., memory savings or retention, compared to the saline treatment group (Pg. 8 P92). Sodium valproate reads on instant claims 13, 16, and 18-20.
LOCKROW teaches Down syndrome (DS) is a condition that causes variable intellectual disability, and progressive memory loss and neurodegeneration with age; DS leads to pathological hallmarks of Alzheimer’s disease (AD) by age 40 or 50 and progressive age-related memory deficits occurring in both AD and in DS have been connected to degeneration of several neuronal populations (Pg. 1 Abstract). LOCKROW further teaches a mouse model of DS shows consistent learning and memory deficits, such as deficits in novel object tasks, which are reversed by blocking the glutamate receptor, suggesting that glutamate and GABA signaling are affected in the mouse model (Pg. 3 Left col. P2-Right col. P1). LOCKROW teaches the cognitive impairment observed over time in the mouse model of DS parallels cognitive impairment in adults with DS (Pg. 4 Left Col. P1).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
GALLAGHER does not teach the subject in need has Down’s syndrome.
LOCKROW does not teach the administration of sodium valproate to the subject with Down’s syndrome.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of learning, memory, and cognitive impairment and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the method for treatment of Down’s syndrome. Said artisan has also reviewed the problems in the art regarding learning, memory, and cognitive impairment in Down’s syndrome and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references GALLAGHER and LOCKROW.
The artisan would find it obvious to treat a subject with age-related cognitive decline caused by Down’s syndrome according to the method of GALLAGHER, i.e., by administering sodium valproate. The artisan would be motivated to do so in order to treat/ameliorate memory and cognitive impairment since LOCKROW teaches Down’s syndrome causes progressive memory loss and neurodegeneration in line with the pathological hallmarks of Alzheimer’s disease (Pg. 1 Abstract).
The artisan would have an expectation of success, since GALLGHER teaches administration of sodium valproate resulted in memory savings or retention (Pg. 8 P92), i.e., treatment/amelioration of learning, memory, and cognitive impairment. Thus, the artisan would recognize GALLGHER’s method of treating subjects having or at risk for Mild Cognitive Impairment (MCI), Age-Associated Memory Impairment (AAMI) or Age-Related Cognitive Decline (ARCD) (Pg. 1 P1) as applicable to Down’s syndrome patients with age-related memory loss and neurodegeneration.
The artisan would have further expectation of success that administration of sodium valproate would treat/ameliorate the learning/memory/cognitive impairment caused by Down’s syndrome since GALLAGHER teaches sodium valproate increases glutamate reuptake (Pg. 4 P50) and LOCKROW teaches learning and memory deficits in a mouse model of Down’s syndrome are reversed by blocking the glutamate receptor (Pg. 3 Left col. P2-Right col. P1). Thus, the artisan would recognize the ability of sodium valproate to increase memory savings or retention (GALLAGHER Pg. 8 P92) is likely connected to glutamate reuptake enacted by the sodium valproate, which in view of LOCKROW (Pg. 3), would likely treat/ameliorate deficits in learning and memory caused by Down’s syndrome.
Thus, the instant claims 13, 16, and 18-20 are made obvious by the combined references.
Conclusion
Claims 13, 16, and 18-20 are rejected.
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.
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/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625