DETAILED ACTION
The Examiner inherited this application from another.
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 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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/27/2026, has been entered.
Current Status of 18/497,386
Claims 1, 7, 11, 13-14, 17, 19-20, 23-24, 26, 45-46, 49 and 51-52 are currently amended and have been examined on the merits..
Information Disclosure Statement
The information disclosure statement (IDS) and the supplemental Information Disclosure Statement under 37 CFR 1.56 submitted on 01/18/2025, were filed before the mailing of a first Office action after the filing of RCE. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
The Examiner acknowledges receipt of Applicants’ claim amendments and Reply
of 02/27/2026.
The Examiner has reviewed the claim amendments and Reply of 02/27/2026.
Applicants’ arguments filed 2/27/2026 have been fully considered, but they are not persuasive. Applicants argue that the Office didn’t articulate why a POSITA would have reasonably expected fasoracetam to successfully treat Conduct Disorder (CD), not merely why such treatment was conceivable. Applicants further content Turgay, as the only cited reference that addresses CD, doesn’t provide a reasonable expectation of success. However, Turgay teaches that monotherapy has been used successfully in one instance to treat Attention Deficit/Hyperactive Disorder (ADHD) comorbid with CD. While Applicants argue that this single successful case implies existence of many unsuccessful cases, no evidence has been presented to support applicant’s inference and assertion (see MPEP 2145, e.g. “The arguments of counsel cannot take the place of evidence in the record”. 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)). Likewise, although Applicants criticize Turgay’s disclosure of a single successful case of treating ADHD comorbid with CD, there is no evidence demonstrating successful treatment of ADHD and CD with fasoracetam. For example, the open-label Phase Ib clinical trial described in Example 3, eight of the 30 ADHD subjects exhibited symptoms of obsessive compulsive-disorder (OCD), and that these OCD symptoms improved during therapy with NFC-1 ([00121], p 226). These data are related to ADHD comorbid with OCD, not ADHD comorbid with CD recited in claim 1.
Applicants also argue that a POSITA would not have motivated to modify the method of Glessner in view of Turgay, Barlow, Niswender, or Oka so as to arrive at the presently claimed method with a reasonable expectation of success.
On this point, as discussed below, the prior art provides additional teachings suggesting ADHD with comorbid disruptive behaviors warranted further investigation. Specially, VILLODAS teaches that stimulant medications and atomoxetine, a selective noradrenergic reuptake inhibitor, are well-established treatments for children and adolescents with ADHD, demonstrating reduce comorbid problems, including aggressive behavior and symptoms of Oppositional Defiant Disorder (ODD). Moreover, stimulant medications have been shown to significantly reduce aggression in children with ADHD comorbid with CD (p.3).
VILLODAS further explains that, despite the nearly universal recognition of the overlap in etiology and development of ADHD and ODD/CD, there has been a lack of interventions that specifically focus on simultaneously addressing the symptoms and impairments associated with both disorders. Individuals with comorbid ADHD and conduct problems represent a particularly high-risk subgroup and have unique risk factors and impairments requiring targeted treatment. Additionally, while medication algorithms for ADHD are well developed, algorithms for comorbid disruptive behavior have not been well studied and therefore represent an important opportunity for future research (p. 12).
In the interest of compact prosecution, the examiner withdraws the previous rejections and references.
Response to Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 26 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 26 recites the limitation “… wherein symptoms of aggression, antisocial behavior, inattentiveness, hyperactivity, and/or impulsiveness are reduced… " in claim 1. There is insufficient antecedent basis for this limitation in claim 1, even though the cited disorders in claim 26 are co-morbid with CD.
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, 7, 11, 13-14, 17, 19-20, 23-24, 26, 45-46, 49, 51-52 are rejected under 35 U.S.C. 103(a) as being unpatentable over:
GLESSNER (WO2012/027491 A1, presented previously), in view of
BARLOW (US 2010/0216734 A, presented previously) and
VILLODAS (Villodas et al ”Prevention of Serious Conduct Problems in Youth with Attention Deficit/Hyperactivity Disorder” Expert Rev Neurother. 2012 October; 12(10): 1253–1263), and further in view of
KUMAGAI (Kumagai et al “Comparison of pharmacokinetics of NS-105, a novel agent for cerebrovascular disease, in elderly and young subjects” Int J Clin Pharmacol Res 1999;19(1):1-8), and evidenced by
GHOSH (Ghosh et al. “ADHD, ODD, and CD: Do They Belong to a Common Psychopathological Spectrum? A Case Series” Case Reports in Psychiatry Volume 2012, Article ID 520689, 4 pages. doi:10.1155/2012/520689).
Determining the scope and contents of the prior art
GLESSNER teaches methods of the genetic diagnosis and treatment of ADHD patients. The methods include isolating, analyzing and detecting at least one CNV in mGluR genes of ADHD patients. The treatment is by administration of one member of piracetam nootropic agents, and a particularly preferred agent being NS-105 (aka, fasoracetam monohydrate) ([0167], p 27; claim 26). The method has the advantage of using a patient's genetic profile to personalize treatment by administering drugs targeted towards specific neurological defects and may benefit up to 50% of patients with ADHD with greater efficacy and fewer side effects than non-personalized treatment. Thus, any of the patients exhibiting an alteration in glutaminergic signaling can be tested for the presence of such a genetic alteration and then treated with the appropriate pharmaceutical (para [0009]).
BARLOW teaches a composition comprising one or more nootropic agents, optionally with a neurogenic agent or anti-astrogenic agent, for treating affective disorders including anxiety and depression, psychosis, learning and memory disorders, (para [0006]). Other disorders are abnormal behavior, abnormal movement, hyperactivity, combativeness, hostility, negativism, withdrawal, cognitive defects, tension, irritability, poor impulse control, distractibility, aggressiveness (para [0059]). The nootropic agents, including pharmaceutically acceptable salts and solvates thereof, are four racetams one of which is fasoracetam (lines 4-7, para [0007]), the dose is 0.001ng/kg/day to 200mg/kg/day (para[0139]) and the dosage may be optimized for the measurable relief of a particular disease condition (para [0058]). Fasoracetam is exemplified in concentration response curves (CRC) (Figures 19-23) and in claims 14-15 and 30-31.
GHOSH teaches ADHD, ODD and CD shared risk factors and overlapping symptoms especially in domains of aggression, hostility, and emotionality in the developmental pathway from ADHD to ODD and CD (last paragraph before Reference, p 3).
VILLODAS teaches ADHD has high comorbidity rates with a number of disorders, including ODD, its comorbidity rates being estimated to be approximately 60% and CD, its estimated comorbidity rate of approximately 16-20% (p. 2). For medical intervention, stimulant medication and atomoxetine, a selective noradrenergic reuptake inhibitor, are well-established treatments for children and adolescents with ADHD, demonstrating reduce comorbid problems, such as aggressive behavior and symptoms of ODD. Moreover, stimulant medications have been shown to significantly reduce aggression in children with comorbid ADHD and CD (p.3). Despite the nearly universal recognition of the overlap in etiology and development of ADHD and ODD/CD, there has been a lack of interventions that specifically focus on simultaneously addressing the symptoms and impairments inherent to each disorder. VILLODAS further teaches that individuals with comorbid ADHD and conduct problems represent a particularly high-risk subgroup and have unique risk factors and impairments that will need to be targeted specifically. Moreover, although detailed medication algorithms for ADHD are well developed, algorithms for comorbid disruptive behavior have not been well studied and thus represent an opportunity for future research (p. 12).
KUMAGAI discloses a pharmacokinetics study of NS-105 on adults of ages of 20-79.
Ascertaining the differences between the prior art and the claims at issue
The instant claims are generally drawn to a method of treating CD comorbid with ADHD in a subject comprising administering an effective amount of fasoracetam to the subject, wherein the subject has at least one copy number variation (CNV) in a metabotropic glutamate receptor (mGluR) network gene. The genetic alterations in mGluR network genes link both diagnosis and treatment, and the genetic testing helps identify conduct disorder or confirm a prior diagnosis. Genetic alterations include copy number variations, deletions, duplications, and single-nucleotide changes in mGluR-network genes. The fasoracetam treatment may reduce aggression, antisocial behavior, inattention, hyperactivity, and impulsiveness.
GLESSNER teaches methods of isolating, analyzing and detecting at least one CNV in mGluR genes and treatment of ADHD patients by administration of NS-105 (fasoracetam monohydrate) after they are identified with the genetic diagnosis. But, GLESSNER doesn’t teach treating CD.
BARLOW teaches a composition of fasoracetam treating diseases, disorders, and conditions of the central nervous systems including, but not limited to, disorders of anxiety and depression, psychosis, learning and memory disorders, abnormal behavior, abnormal movement, hyperactivity, combativeness, hostility, negativism, withdrawal, cognitive defects, tension, irritability, poor impulse control, distractibility, aggressiveness, etc (paras [0006] and [0059]).
Although BARLOW doesn’t cure the GLESSNER’s defect of lacking CD outright, it provides a clear path to reach CD for the treatment as it has shown many symptoms overlapped with CD being treatable with fasoracetam (paras [0006] and [0059]). The symptoms overlap among ADHD, ODD and CD is evidenced by GHOSH, who teaches ADHD, ODD and CD shared risk factors and overlapping symptoms especially in domains of aggression, hostility, and emotionality (last paragraph before Reference, p 3).
Furthermore, VILLODAS teaches that not only a nearly universal recognition exists for the overlap in etiology and development of ADHD and ODD/CD, there has also been a lack of interventions that specifically focus on simultaneously addressing the symptoms and impairments inherent to each disorder, study on the comorbid disruptive behaviors of ADHD represent an opportunity for future research (p 12).
VILLODAS, combined with the teachings of BARLOW and evidenced by GHOSH, cures the GLESSNER defect on connecting CD to ADHD.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Regarding claim 1, GLESSNER teaches methods of isolating, analyzing and detecting at least one CNV in mGluR genes and treatment of ADHD patients by administration of NS-105 (fasoracetam monohydrate) after they are identified with the genetic diagnosis. GLESSNER’s teaching meets the limitations of claim 1, except lacking CD. The artisan would be motivated to extend GLESSNER’s teaching on analyzing and detecting the CNVs in mGluR genes in the treatment of ADHD patients to CD patents with reasonable confidence of success since BARLOW teaches many of CD symptoms shared with CD (such as aggression, hostility, and emotionality evidenced by GHOSH) are treatable with fasoracetam (see above). The motivation is taught by VILLODAS, who teaches simultaneously addressing the symptoms and impairments of CD/COD/ADHD and that individuals with comorbid ADHD and conduct problems have unique risk factors and impairments that will needs to be targeted specifically (p.12).
Regarding claims 7 and 13, GLESSNER teaches identification of 228 genes within 2 degrees of relation to 8 GRM genes based on the merged human interactome ([0138], p.16) and CNV is used herein to refer to a nucleic acid that hybridizes to sequences comprising a duplication on a chromosome ([0033], p. 3; Table 11, p. 20).
Regarding claims 11 and 26, BARLOW teaches the dose is 0.001ng/kg/day to 200mg/kg/day (para[0139]), which is 0.06ng-12000mg/day for a 60kg subject, embraced 50-400mg of claim11. BARLOW also teaches the dosage and dosing regimen may be optimized for the measurable relief of a particular disease condition (para [0058]). The artisan would be motivated to establish the dosage and dosing regimen of fasoracetam to treat CD using it as a reference following BARLOW’s suggestion.
Regarding claims 14, 17, 49 and 51 of routine steps in the art, the artisan performs routine and conventional activity. Claim17 is inherent to claim14, the sample is coming out from the screen either with one or more CNVs (claim 14) or without CNV (claim17).
MPEP 2144.05(II)(A) provides guidance about the routine optimization of
prior art conditions. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). "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.” In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
Regarding claims 23, 24 and 52, BARLOW teaches the combinations may be a racetam such as fasoracetam, … in combination with clozapine, a non-limiting representative of an antipsychotic. Claim 52 covers different types of brain stimulation therapies.
Regarding claim 26, it’s related to inherent property of fasoracetam, and its onset of action time is mainly determined by its ADME for a given delivery route. The ADME is also a routine optimization in the art (see above).
Regarding claims 19-20 and 45-46, on the intended subject of claim 19, KUMAGAI discloses a pharmacokinetics study of NS-105 on adults of ages of 20-79. Claims 20 and 45-46 are related to symptoms of CD and other disorders that are subjected to routine medical diagnostic examinations. See MPEP 2144.05(II)(A).
Therefore, the instant claims are prima facie obvious in light of the combination of references GLESSNER, BARLOW, and VILLODAS and further in view of KUMAGAI and evidenced by GHOSH.
Conclusion
No claims are presently allowable as written.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BIN TAO whose telephone number is (571)272-0398. The examiner can normally be reached Monday-Friday 8-5PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/B.T./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
Prosecution Insights