DETAILED ACTION
This action is in response to papers filed on 01/16/2026. Claims 8-11 and 15-19 of Inoue et al., 17771136 (04/22/2022) are pending examination on the merits: claims 1-7 were previously cancelled, claim 8 is withdrawn. Claims 9-11 and 15-19 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 .
Priority
This application is a 371 of PCT/JP2020/039450 (10/20/2020) and claims Foreign Priority JAPAN 2019-194758 (10/25/2019).
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 07/21/2022, 11/06/2023, and 01/16/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Election/Restriction
In a response filed on 01/16/2026, Applicant elected:
Group II, claims 9-11, and 15-19, drawn to a method for preventing or treating tauopathy in a mammal comprising administering an effective amount of an inhibitor of α2δ to the mammal.
Group I, claim 8, drawn to a method of screening for a prophylactic or therapeutic agent for tauopathy is hereby withdrawn.
Applicant also elected the following species:
Pregabalin as the species of inhibitors of α2δ represented by formula (I) as per claim 9, and as per claim 11. Applicant’s Remarks at page 6.
MPEP 818.01 discloses that Election in reply to a requirement for restriction may be made either with or without an accompanying traverse of the requirement. The absence of any statement indicating whether the requirement to restrict is traversed or the failure to provide reasons for traverse will be treated as an election without traverse. Applicant’s response is therefore treated as an election without traverse.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 9-11 and 15-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the treatment of tauopathy, does not reasonably provide enablement for the prevention of tauopathy using the multitude of compounds encompassed by formula (I) (c.f., claim 10). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to A method for preventing or treating tauopathy in a mammal, comprising administering an effective amount of an inhibitor of α2δ to the mammal, wherein the inhibitor is an array of compounds of represented by formula (I) (c.f., claim 10).
Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to the treatment or prevention of tauopathy in a mammal, wherein the tauopathy is Alzheimer's disease or frontotemporal lobar degeneration showing tauopathy (FTLD-Tau) per claim 18, using compounds of formula (I) per claim 10, and encompassing hundreds of compounds with mutually exclusive properties based on the wide range of variables of R1-R10.
State of the prior art:
The claims recite prevention, and prevention is suggested to include a level of protection against, up to and including complete protection against the development of a disease or condition which is unsupported by the disclosure. Giving the claims their broadest reasonable interpretation, the term “prevention” includes any measure taken prior to the onset or occurrence of a disease or condition which precludes its coming into existence, absolutely and in all cases. There is no evidence in the prior art that the instant genus of compounds would be usable as a preventative composition, particularly for preventing tauopathy wherein the tauopathy is Alzheimer's disease or frontotemporal lobar degeneration showing tauopathy (FTLD-Tau).
Alzheimer’s disease has traditionally been very difficult or impossible to treat effectively. See e.g., the Journal of Alzheimer’s Disease, Vol. 29, Issue 2 wherein Korczyn et al., states that “Attempts to find cures for Alzheimer’s disease (AD) have, however, failed so far, in spite of enormous investments, intellectual and financial,” (Abstract, line 1-2).
Those of ordinary skill in the art know that it is not possible to accurately predict drug activity, especially in terms of prevention, when substantial variations in structure are made (c.f., Wermuth et al., The Practice of Medicinal Chemistry, 4th ed. (2015), 763 pages, for example p. 142). The variations of R1 to R10 of the instant claims cover a large number of substituents that are not enabled by the Specification, and no nexus has been established between the prevention of tauopathy and the genus of compounds claimed (c.f., claim 10). The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F. 2d 833, 839, 166, USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
Beginning at Page 37 of the instant specification, the Applicant has provided disclosure on cell culture, immunocyte chemistry, Western blot analysis, and a cell survival assay. The results are discussed beginning on page 43.
No working examples have been provided that would enable the instant invention for treatment tauopathy wherein the tauopathy is Alzheimer's disease or frontotemporal lobar degeneration showing tauopathy (FTLD-Tau) using the multitude of compounds claimed, much less its prevention.
Quantity of experimentation needed to use the invention based on the content of the disclosure:
The quantity of experimentation needed is undue experimentation. A person having ordinary skill in the art would need not only to develop metrics, but also to formulate and evaluate compositions of the instantly claimed compounds for their efficacy in treating a broad scope of conditions associated tauopathy, with no assurance of success.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation.
Genentech Inc. V Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person having ordinary skill in the art would have to engage in undue experimentation to determine the efficacy of disclosed compounds in treating and preventing conditions associated with tauopathy such as Alzheimer’s disease as recited, with no assurance of success.
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.
Claims 9-11, and 15-19 are rejected under 35 U.S.C. 103 as being unpatentable over Supasitthumrong et al., (2018) Br. J. Clin. Pharmacol. 85, 690–703 (first published 21 December 2018) (“Supasitthumrong”) in view of Sałat et al., Naunyn-Schmiedeberg's Arch Pharmacol 389, 613–623 (2016).
Regarding claims 9-11, and 15-19, Supasitthumrong teaches gabapentin and pregabalin (c.f., instant claim 11) as treatment for aggressivity in dementia, where their mechanism of action is by “… binding to the α2δ protein, an auxiliary subunit of presynaptic voltage-gated calcium channels…” resulting in “… The decrease in presynaptic calcium is linked to a reduction in the liberation of excitatory neurotransmitters such as glutamate…” (page 691, Pharmacodynamics of pregabalin and gabapentin). Supasitthumrong teaches the mechanism of pregabalin as inhibiting the α2δ protein.
Supasitthumrong also teaches that there is evidence based on case series and case reviews suggests possible benefit of gabapentin and pregabalin in patients with behavioral and psychological symptoms of dementia in Alzheimer's disease. (c.f., Results).
Salat teaches “Effect of pregabalin on contextual memory deficits and inflammatory state-related protein expression in streptozotocin-induced diabetic mice” (STZ) (Title). Salat also teaches in the Abstract: “There is also a link between diabetes mellitus and vascular dementia or Alzheimer’s disease ... Pregabalin is widely used for the treatment of diabetic neuropathic pain, but little is known about its impact on cognition or inflammation-related proteins in diabetic patients...”. Salat also states in the Conclusion that “… pregabalin does not aggravate memory deficits induced by STZ injection. Moreover, this drug has anti-inflammatory and antioxidant properties in STZ-treated mice. The results obtained in the present study might be relevant when considering the increasing use of pregabalin for epileptic and non-epileptic medical indications.”
In the present application, gabapentin and pregabalin are used as therapeutic agents for treating tauopathy, wherein the tauopathy is Alzheimer's disease (AD) or frontotemporal lobar degeneration showing tauopathy (FTLD-Tau) (per claim 18), by administering an effective amount of the inhibitor of α2δ to the mammal. Applicant has not disclosed any criticality regarding effective amount of the inhibitor.
Consistent with these teachings about gabapentin and pregabalin use as therapeutic agents for treating Alzheimer's disease (AD), it would have been prima facie obvious to one of ordinary skill in the art, to combine the teachings of Supasitthumrong and Salat, at the time of filing, and arrive at the claimed invention with a reasonable expectation of success. Supasitthumrong teaches the benefit of using gabapentin and pregabalin in patients with behavioral and psychological symptoms of dementia in Alzheimer's disease by “… binding to the α2δ protein, an auxiliary subunit of presynaptic voltage-gated calcium channels…”, and Salat teaches that Pregabalin is widely used for the treatment of diabetic neuropathic pain, but little is known about its impact on cognition or inflammation-related proteins in diabetic patients...”, that there is a link between diabetes mellitus and vascular dementia or Alzheimer’s disease, and that “… pregabalin does not aggravate memory deficits, and that this drug has anti-inflammatory and antioxidant properties.”. The claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). MPEP § 2112(I).
Conclusion
No claims are allowed.
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/C A/Examiner, Art Unit 1622 August 20, 2026
/JAMES H ALSTRUM-ACEVEDO/
Supervisory Patent Examiner, Art Unit 1622
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