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 .
Claims 1, 7, 11, 13-14, 17, 19-20, 23-25, 29, 49-50, 53-56, are pending.
Claims 2-6, 8-10, 12, 15-16, 18, 21-22, 26-28, 30-48, 51-52, are deleted.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 1, 7, 11, 13-14, 17, 19-20, 23-25, 29, 49-50, 53-56, are rejected under 35 U.S.C. 103(a) as being unpatentable over Barlow et al., US 2010/0216734 A1, in view of Niswender et al., Ann. Rev. Pharmacol. Toxicol. (2010), Vol. 50, pp. 295-322; Glessner et al., WO 2012/027491 A1; Braaten et al., Soc. Biol. Psych. (2003)53:93-99, and Oka et al., Nauuyn-Schmiedeberg’s Arch. Pharmacol. (1997), 356:189-196, XP009192623.
Barlow et al., teaches a composition comprising one or more nootropic agents, optionally with a neurogenic agent or anti-astrogenic agent ([0007] and [0014], lines 1-2) for treating affective disorders, which are anxiety disorder (AD) and depression, [0007]. The nootropic agents are four racetams one of which is fasoracetam ([0007], lines 4-6), the dose is 0.001ng/kg/day to 200mg/kg/day, and the dose and dosing regimen may be adjusted (optimize) for the relief of a particular disease, [0058], [0139]. Barlow et al., exemplifies fasoracetam in concentration response curves (CRC), figures 19-23, and suggests performing diagnosis before treatment and prognosis after treatment [0088].
Niswender et al., teaches isolation and analysis of metabotropic glutamate receptors (mGluRs). Niswender et al., teaches mGluRs are family of G-protein-coupled receptors and are part of the modulation of synaptic transmission and neuronal excitability throughout the CNS. Niswender et al., further teaches the widespread expression of mGluRs makes them attractive targets for drugs in the treatment of neurological and psychiatric disorders. See the abstract.
Glessner et al., teaches methods for isolating, analyzing and detecting at least one CNV in mGluR genes of ADHD patients. Glessner et al., also teaches treatment of ADHD patients after they are identified. The treatment is by administration of a piracetam (a racetam as fasoracetam). The invention has the advantage of using a patient’s genetic profile to personalize treatment by administering drugs targeted towards specific neurological defects. Summary of invention, particularly pp. 2, line 32 to pp. 3, line 3 and lines 16-23. See also, pp, 16-19, and 64-66. Glessner et al., teaches accurate diagnosis of disorders based on associated genetic alterations is highly desirable, (pp. 2, lines 9-10). The prior art teaches any patient who has alteration in glutaminergic signaling can be tested for the genetic alteration and treated with the appropriate pharmaceutical agent (pp. 3, lines 24-27) e.g. a piracetam (a racetam as fasoracetam).
Braaten et al., teaches familial association between ADHD and AD. That the incidence of AD is significantly high in ADHD patients and their relatives than in non ADHD subjects and their relatives. See Results, pp. 93.
Oka et al., teaches NS-105 (fasoracetam monohydrate) modulates adenylate cyclase activity by stimulating mGluR. Oka et al., further teaches NS-105 is a more potent mGluR agonist than other mGluR agonists tested (fig. 1, pp. 193); it is a nonselective mGluR activator (col. 2, p. 194, ¶ 1-2); has a unique pharmacological features as agonist of mGluRs and that the activation is concentration dependent (p. 195, ¶ 1, line 30). See also the abstract, col. 1, pp. 190; col. 2, pp.191 to col. 2, pp. 193 and col. 1, pp. 194 to col. 2, pp. 195.
“[R]eason, suggestion, or motivation to combine may be found explicitly or implicitly: 1) in the prior art references themselves; 2) in the knowledge of those of ordinary skill in the art that certain references, or disclosures in those references, are of special interest or importance in the field; or 3) from the nature of the problem to be solved.” Ruiz v. A.B. Chance Co., 234 F.3d 654, 665; 57 USPQ2d 1161 (Fed. Cir. 2000); see In re Dembiczak, 175 F.3d 994, 999; 50 USPQ2d 1614 (Fed. Cir. 1999). Also, KSR 550 US 398, 82 USPQ2d 1385 (2007), instructs courts to take a more “expansive and flexible approach” in determining whether a patented invention was obvious at the time it was filed. 550 U.S. at 415. In particular, the Court emphasized the role of “common sense”. “Rigid preventative rules that deny fact finders recourse to common sense … are neither necessary under our case law nor consistent with it.” Id. at 421. See Wyers v. Master Lock Co, 95 USPQ2d 1525, (Fed. Cir. 2010).
None of the prior arts above teaches the combination of the instant steps of diagnosing AD patient and treatment with fasoracetam. However, the invention is obvious from the combined prior arts and knowledge well-known in the art, because a POSA who wants to practice targeted treatment of AD patients would have known and be motivated to use the process by Glessner et al., in AD patients, with reasonable expectation of success, because Glessner et al., teaches the process provides advantages of targeted treatment of neurological and psychiatric disorders; that accurate diagnosis of disorders based on associated genetic alterations is highly desirable and that any patient who has alteration in glutaminergic signaling can be tested for the genetic alteration and treated with the appropriate pharmaceutical agent, e.g. a piracetam drug (a racetam as in the instant). Therefore, a POSA would have known and be motivated to administer a racetam with reasonable expectation of success. The selection of fasoracetam is motivated by Barlow, Niswender and Oka.
As held in KSR Int. Co. v. Teleflex Inc, 550 U.S. 82 USPQ2d 1385 (2007), “when a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field (ADHD), or a different one (AD). If a person of ordinary skill can implement a predictable variation, 103 likely bars its patentability. For the same reason if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill.”
In the instant, it is not beyond the ordinary skill of a scientist to repeat the process by Glessner et al., in AD patients. Such is deemed invention of reasoning, not of creativity, KSR.
Anxiety disorder by Barlow et al., and Niswender et al., embraced the different ADs in claim 19. There is no negative teachings by the prior arts away from the ADs in claim 19.
When fasoracetam is administered per Barlow et al., patients who have no CNV in mGluR genes and those who have at least one CNV in mGluR genes will be treated. Such is inherent property of fasoracetam. “An inherent structure, composition or function is not necessarily known . . . or obvious.” Schering Corp. v. Geneva Pharm. Inc., 67 USPQ2d 1664, 1667 (Fed. Cir. 2003). “Insufficient prior understanding of inherent properties of known composition does not defeat finding of [inherency]; insufficient scientific understanding does not defeat showing of inherency; [invention] is no more than showing that [Barlow] did not recognize function inherently present” in [the drug].” Atlas Powder Co. v IRECO Inc., 51 USPQ2d 1943 (Fed Cir, 1999). “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for prior art composition, does not render the old composition patentably new to the discoverer, Atlas Powder Co. v IRECO Inc., 51 USPQ2d 1943 (Fed Cir, 1999). A new use, new function or new property which is inherent in prior art is not patentable. In re Best, 195 USPQ 430 (CCPA, 1977).
Applicant claims treatment of patients who have no CNV in mGluR genes (claim 17) and those who have at least one CNV in mGluR genes. Those patients who have at least one CNV in mGluR genes may show better treatment outcomes as alleged by applicant. Having known the study by Glessner et al., one of ordinary skill in the art would have known and be motivated to perform a similar study in AD patients because Glessner et al., teaches accurate diagnosis of disorders based on associated genetic alterations is highly desirable; that any patient who has alteration in glutaminergic signaling can be tested for the genetic alteration and treated.
Since there is familial association between ADHD and AD patients resulting in significant high incidence of AD in ADHD subjects (Braaten et al.) and applicant wanted to reduce ADHD symptoms in AD patients (claims 29, 49-50) specification, [0031]-[0032]), applicant would have known and be motivated to treat AD by using the data from the study by Glessner et al., with reasonable expectation of success because, the patients are the same. The motivation for treating the disorders in claims 29, 49-50, is from Niswender et al., which teaches widespread expression of mGluRs makes them attractive targets for drugs in the treatment of neurological and psychiatric disorders.
The steps in claims 14, 53, are conventional steps, claimed at the highest level of generality. The steps are invitations to a POSA to perform them using any means and/or procedures known to the artisan. For example, Glessner et al. Claim 56, is drawn to conventional knowledge in the art. Hence, not applicant’s invention.
The selection of fasoracetam is motivated by Barlow et al., that the drug is one of four racetams useful for treating AD. It was used in CRC studies (figs. 19-23) and claimed (claims 22, 25). The claims are what Barlow et al., regards as the inventions and are deemed most preferred embodiments. Therefore, one of ordinary skill in the art would have been motivated to select from the most preferred embodiments. Such selection is an obvious modification available for the preference of an artisan.
The selection of fasoracetam is further motivated by Oka et al., that NS-105 is a more potent mGluR agonist than other mGluR agonists tested (fig. 1, pp. 193), it is a nonselective mGluR activator (col. 2, p. 194, ¶ 1-2), has a unique pharmacological features as agonist of mGluRs and that the activation is concentration dependent (pp. 195, ¶ 1, line 30).
Establishing the range of a dose is not significant. In re Aller, 105 USPQ 232, 235; 220F.2d 454, 456 (CCPA, 1955). “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum workable ranges”. In re Aller, 105 USPQ 232, 235 (CCPA, 1955), In re Russell, 169 USPQ 426, 439 F2d 1228 (CCPA, 1971).
A dose of 0.001ng/kg/day to 200mg/kg/day by Barlow et al., e.g. for a 60kg subject, embraced 40-400mg by applicant, claim 11, wherein weight is non-limiting, and therefore embrace 60kg by Barlow. With the expectation that any of the four racetams may be selected, Barlow et al., teaches the dose and dosing regimen may be adjusted for the relief of a particular disorder [0058] and [0139]. Therefore, a POSA would have known and be motivated to establish the dose of fasoracetam for AD patients. One way of doing so is to start with 0.001ng/kg/day to 200mg/kg/day and change the dose and dosing regimen as suggested by Barlow et al.
The expected outcomes in claim 29, 59-50, are due to inherent properties of fasoracetam. They are not applicant’s inventions, can be read from medical record, ascertain by observing the subject or through routine prognostic procedures.
Combination therapy allows for synergy, possible administration of lower doses of drugs in the combination, which provides avoidance of overdose, toxicity or other negative effects of each drug. Hence, the motivation for combination therapy in medicine. The treatments and drugs in claims 24-25, are well-known in the art. Assuming their combination with fasoracetam produce an effect somewhat greater than the sum of their separate effects, the idea of combining them flows logically from the teachings by prior arts. Therefore, a claim to their joint use is not patentable. In re Crockett, 126 USPQ 186 (CCPA, 1960).
The invention is still obvious from the combination of the prior arts and knowledge well-known in the art.
Response
Applicant's arguments filed 8/27/25 have been fully considered but they are not persuasive. Applicant contends the rejection fails to show a POSA would have reasonable expectation “the role of a CNV in a mGluR network is functionally equivalent in ADHD and AD; thus the clinical manifestation and treatment” with fasoracetam would be expected to work; that the references fail to teach such. This contention is not dispositive of the issue in the instant, because claim 17 is drawn to treatment of subjects who do not have a CNV in a mGluR network. Also, absolute predictability is not required by the Patent Statues. Section 103 of the Statute merely requires that there be a "reasonable expectation, or some predictability"’. In re Kratz, 592 F.2d 1169 , 201 USPQ 71 ; and In re Kronig, 539 F.2d 1300 , 190 USPQ 425.
Glessner et al., teaches personalize and targeted treatment is applicable for any neurological defect. A POSA who wants to practice targeted treatment in AD patients would have known and be motivated to repeat the study by Glessner et al., in AD patients because, the prior art teaches methods for isolating, analyzing and detecting at least one CNV in mGluR genes; targeted treatment and its advantages in the treatment of neurological and psychiatric disorders. The prior art teaches accurate diagnosis of disorders based on associated genetic alterations is highly desirable; that any patient who has alteration in glutaminergic signaling can be tested for the genetic alteration and treated with the appropriate pharmaceutical agents, such as a piracetam (a racetam as fasoracetam). Glessner teaches targeted treatment is highly desirable and the study by Glessner allows applicant to take advantage of targeted treatment in AD patients. Glessner provides the solution for what applicant wanted to do. There is no negative teaching by Glessner or any of the prior arts away from AD.
Braaten et al., teaches familial association between ADHD and AD. That the incidence of AD is significantly high in ADHD patients and their relatives than in non ADHD subjects and their relatives. Niswender et al., teaches widespread expression of mGluRs makes them attractive targets for drugs in the treatment of neurological and psychiatric disorders. Braaten and Niswender provide further motivation for a POSA to try the process and treatment by Glessner in AD subjects, with reasonable expectation of success.
Oka et al., teaches NS-105 (fasoracetam monohydrate) modulates adenylate cyclase activity by stimulating mGluR. Oka et al., further teaches NS-105 is a more potent mGluR agonist than other mGluR agonists tested (fig. 1, pp. 193); it is a nonselective mGluR activator (col. 2, p. 194, ¶ 1-2); has a unique pharmacological features as agonist of mGluRs and that the activation is concentration dependent (p. 195, ¶ 1, line 30). Oka et al., further provides the motivation for a POSA to try fasoracetam in the treatment of AD subjects, with reasonable expectation of success.
In the instant, it is not beyond the ordinary skill of a scientist to repeat the process by Glessner et al., in AD patients. Such is deemed invention of reasoning, not of creativity, KSR.
Applicant’s argument is mere argument, and does not take the place of evidence, In re Schulze, 145 USPQ 716 (CCPA, 1965), Cole, 140 USPQ 230 (CCPA, 1964). Applicant must provide scientific evidence why a POSA who wants to practice targeted treatment in subjects who present with AD or comorbidity thereof will not or cannot repeat the study by Glessner.
Applicant must provide scientific evidence why fasoracetam treats AD in the instant subject but does not in Barlow’s subject. Under the US patent practice the Examiner is not allowed to discount the invention by a prior art and Applicant is not allowed to disparage it. Applicant’s claims affirm treatment of AD with fasoracetam by Barlow. Applicant cannot have it both ways. Selective combination of the treatments by Barlow, alone or in combination with Glessner or other prior arts, is deemed invention of reasoning not of creativity, KSR. There is reasonable expectation of success because applicant did as taught by the prior arts.
When fasoracetam is administered per Barlow the drug must necessarily treat AD due to its inherent property. “An inherent structure, composition or function is not necessarily known.” Schering Corp. v. Geneva Pharm. Inc., 67 USPQ2d 1664, 1667 (Fed. Cir. 2003). “Insufficient prior understanding of inherent properties of known composition does not defeat finding of [inherency]; insufficient scientific understanding does not defeat showing of inherency; [Applicant’s contention] is no more than showing that [Krauss] did not recognize function inherently present” in [the drug].” Atlas Powder Co. v IRECO Inc., 51 USPQ2d 1943 (Fed Cir, 1999). “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for prior art composition, does not render the old composition patentably new to the discoverer, Atlas Powder Co. v IRECO Inc., 51 USPQ2d 1943 (Fed Cir, 1999). A new use, new function or new property which is inherent in prior art is not patentable. In re Best, 195 USPQ 430 (CCPA, 1977).
This is a RCE of applicant's earlier Application No. 18/497,338. All claims are identical to, patentably indistinct from, or have unity of invention with the invention claimed in the earlier application (that is, restriction (including lack of unity) would not be proper) and have been finally rejected on the grounds and art of record. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action in this case. See MPEP § 706.07(b). 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.
Telephone Inquiry
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Taofiq A. Solola, whose telephone number is (571) 272-0709.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Andy Kosar, can be reached on (571) 272-0913. The fax phone number for this Group is (571) 273-8300.
Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to the Group receptionist whose telephone number is (571) 272-1600.
/TAOFIQ A SOLOLA/ Primary Examiner, Art Unit 1625
September 7, 2025