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 .
Status of Claims
The amendments to the claims filed September 18, 2025 are acknowledged and entered. Claims 1-15 and 22-25 are pending.
Priority
This application is a 371 of PCT/KR2023/005773, filed April 27, 2023, which claims benefit of 63/335,779, filed April 28, 2022.
Information Disclosure Statement
Acknowledgement is made of the Information Disclosure Statements filed on October 28, 2024 and June 11, 2026. All references have been considered except where marked with a strikethrough.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which applicant may become aware of in the specification.
Claim Objections
Claims 1-15 and 22-25 are objected to because of the following informalities:
Claim 1 and Claim 7 show structures of Formula (I) and Formula (II), respectively, which are difficult to read because atoms and variables (e.g. R2, R1, R3, NH…) are displaced from the general structure. Claims 2-13, 15 and 22-25 depend from claim 1. Claims 7-13 require Formula (II).
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Claim 1 and Claim 7 should be amended to provided clear structures of Formulae (I) and (II). Support for these amendments can be found at paragraphs [45] and [58] of the specification.
Claim 1 is objected to for reciting “R2 is hydrogen”. Presently, the claim requires that variable n can be 0 to 4; however, this limitation permits that there are no atoms attached to the carbon atoms of the phenyl ring which is not possible (i.e. carbon must have 4 bonds). Claims 2-3, 5, 7-9 and 11 depend from claim 1 and explicitly recite “R2 is hydrogen”. Examiner suggests deleting “hydrogen” from the definitions of R2 in each of the claims.
Claims 14 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112a
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 23 and 25 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 pain, does not reasonably provide enablement for a method of generally treating or preventing a disease or condition mediated by sodium channels.
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. When a compound or composition claim is limited by a particular use, enablement of that claim should be evaluated based on that limitation. See In re Vaeck, 947 F.2d 488, 495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991) (claiming a chimeric gene capable of being expressed in any cyanobacterium and thus defining the claimed gene by its use).
In the instant case, the claims are drawn to a method of treatment or prevention of disease, and a composition which recites the intended use “for treating or preventing pain”. Applicant teaches that the instant compound of Formula (I) is an inhibitor of hNav1.7 (see paragraph [482] and Table 1, hNav1.7 channel assay). However, this activity is not known to be correlated with the treatment of the entire scope of conditions embraced by the claims or prevention of any condition embraced by the claims. Applicant’s disclosure is only enabling for the treatment of conditions which Applicant has demonstrated may be treated by the instant compound, and of conditions which the prior art is already aware may be treated by a compound with the disclosed activity (e.g. an inhibitor of Nav1.7) and for which Applicant has written support. Case law is clear on this point. In an unpredictable art, such as drug therapy to treat disease, models may be used for enablement only if there is a reasonable correlation between the activity in question and the asserted utility. Given the guidance provided by Applicant, one skilled in the art would not be able to practice the full scope of the invention without undue experimentation.
In evaluating the enablement question, several factors are to be considered. Note In re Wands, 8 USPQ2d 1400 and Ex parte Forman, 230 USPQ 546. The factors include: 1) The nature of the invention, 2) the state of the prior art, 3) the predictability or lack thereof in the art, 4) the amount of direction or guidance present, 5) the presence or absence of working examples, 6) the breadth of the claims, and 7) the quantity of experimentation needed. The determination that “undue experimentation” would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations.
Nature of the Invention and Breath of the Claims
Instant claim 1 is drawn to a compound of Formula (I). As noted above, Formula (I) is an inhibitor of Nav1.7.
Instant claim 23 is drawn to a composition comprising an active ingredient which is effective for preventing pain.
Instant claim 25 depends from claim 1 and recites a method of treating or preventing a disease or condition mediated by sodium channels, comprising: administering a therapeutically effective amount of the compound, or optical isomer, stereoisomer or isotopic variant thereof, or a pharmaceutically acceptable salt thereof as defined in claim 1 to a mammal in need thereof.
“Mammal” is not defined by the specification. In view of the specification “mammal” would be understood by a person of ordinary skill in the art as including humans.
“Preventing” is not defined in the specification. Merriam-Webster dictionary defines prevention as to keep from happening or existing. In view of this definition, prevention of disease as claimed would be understood by a person of ordinary skill in the art to mean the disease is kept from occurring or existing.
The scope of a “disease or condition” mediated by sodium channels is not provided in the specification. However, the specification teaches:
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The nature of the invention is thus a method of treating or preventing a disease or disorder mediated by sodium channels in a mammal, including humans, by administration of a Nav1.7 inhibitor (Formula (I)). The scope of diseases embraced by the claims is not defined; however, in view of the specification a person of ordinary skill in the art would understand the method includes the treatment or prevention of those conditions disclosed at paragraph [158]-[169] of the specification. The scope of the claims therefore is very broad.
The state of the prior art
State of the prior art reference Blass (J Med Chem Lett March 2022, 13, 532-533) teaches pain sensation has been linked to Nav 1.7 and that blocking Nav 1.7 activity may be a viable method of treating pain (Title, col 1).
The state of the prior art thus appears to recognize that inhibition of Nav 1.7 could have the effect of treating pain.
The state of the prior art, however, is not aware that a Nav 1.7 inhibitor has any use in the treatment of all conditions embraced by the claims which would include the general treatment neurological disorders, neurodegenerative disorders, inflammatory disorders, gastrointestinal (GI) tract disorders, disorders of the genito-urinary tract, psychiatric disorders, cardiovascular disorders and neuromuscular disorders (see [163] above). The state of the prior art is not aware of any condition which is prevented by a Nav 1.7 inhibitor.
The Level of One of Ordinary Skill
The level of skill in the art is high. The artisan using the claimed invention would be a person with medical training such as a medical doctor or physician with an MD degree or the equivalent.
Predictability in the art
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F. 2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved”. 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 a 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.
Amount of guidance/working examples
Applicant teaches that the instant compound of Formula (I) is an inhibitor of hNav1.7 (see paragraph [482] and Table 1, hNav1.7 channel assay), thus suggesting that the claimed invention may have use in the treatment of pain.
However, no experimental or other data is provided to show the instant compounds may have use
in the treatment of the full scope of diseases claimed.
The specification does not provide any guidance to one of ordinary skill in the art to extrapolate the in vitro data provided by Applicant to the treatment of the many different forms of disease included in the scope of the method.
As per “preventing”, there is no evidence in the record to suggest the claimed invention prevents any condition claimed. It is presumed “prevention” of the claimed disease would require a method of identifying those individuals who will develop the claimed diseases before they exhibit symptoms. Nothing in the specification teaches how one skilled in the art identifies a subject who’s disease will be prevented.
The quantity of experimentation needed:
MPEP 2164.01(a) states, "A conclusion of lack of enablement means that, based on theevidence 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. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)."
That conclusion is clearly justified here and one skilled in the art could not practice the full scope of the claimed invention without undue experimentation.
This rejection could be overcome by amending claim 25 to recite a method of treating pain; and amending claim 23 to delete “preventing”.
Claim Rejections - 35 USC § 112b
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.
Claims 23-24 are 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. The claims are indefinite for the reasons that follow:
Regarding claim 23, the phrase "including" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. See MPEP § 2173.05(d).
Claim 24 recites the limitation “the active ingredient" in line 1. There is insufficient antecedent basis for this limitation in the claim because claim 24 depends from claim 22 which does not recite an active ingredient.
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 1-4, 6-10, 12-13, 15 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Bayliss et al. (Journal of Medicinal Chemistry 2017, 60, 9790-9806)(hereinafter “Bayliss”) in view of Ascenzi et al. (IUBMB Life 2003, 55(10-11), 573-578)(hereinafter “Ascenzi”) and Mfuh et al. (Current Medicinal Chemistry 2015, 22, 2819-2857)(hereinafter “Mfuh”).
Bayliss teaches compounds 12 (Table 1; pictured below for convenience) which corresponds to instant Formula (I) wherein R1 and R3 are hydrogen and R2 is 6 membered heterocycloalkyl comprising one N atom. Bayliss teaches a composition comprising compound 12 (page 9805, Test compound (0.4 µL in DMSO) was transferred) which is not an oral formulation. Bayliss teaches compounds 12 has use in the treatment parasitic infections (Table 1, TbNMT IC50; Introduction: TbNMT is one of the few druggable targets to be validated in both in vitro and rodent models of Human African trypanosomiasis (HAT))).
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The only difference between Bayliss and the instant claims is that the claims require a pyridyl N-oxide ring. Bayliss does not teach wherein the N in the pyridyl ring of compound 12 is oxidized; however, Ascenzi teaches nitric oxide (NO) is an anti-parasitic agent (Title; page 1, col 2: NO is an anti-parasitic agent) and Mfuh provides that heterocyclic N-oxides, including pyridyl N-oxides, can function as NO mimics and elicit NO like effect (Page 2819-2820, 2.2 Nitric Oxide (NO) Mimics; See Table 1 and page 2827, the best results were obtained for compound 26 that contains pyridyl N-oxide).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the instant application to modify compound 12 of Bayliss into the claimed invention because heterocyclic N-oxides, including pyridyl N-oxides, were known to mimic NO and elicit NO like effects.
One would have been motivated to make the modification because the at the time it was known that the pyridyl N-oxide functioned as an NO mimic which would have been anticipated to have NO like effects. NO was known to be anti-parasitic and so one would have made the modification to install an NO mimic as a matter of making an additional compound for treating Human African trypanosomias.
One would have had a reasonable expectation of success because at the time NO was known to be anti-parasitic (Ascenzi) and pyridyl N-oxide was a known NO mimic that would have been presumed to have NO like effects (Mfuh). One thus would have made the modification because they would have anticipated that modifying compound 12 with an NO mimic by simply oxidizing the pyridyl N of compound 12 may produce a compound with anti-parasitic properties.
Allowable Subject Matter
Claims 14 is objected to as noted above.
Claims 5 and 11 would be allowable if amended to overcome the above objections.
Claim 24 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims, and if rewritten to overcome the objection above.
The following is a statement of reasons for the indication of allowable subject matter: The closest reference to the instant claims is Bayliss which was discussed in the rejection herein. Bayliss does not teach the limitations of instant claims. There is no teaching which would have motivated a person of ordinary skill in the art before the effective filing date of the instant application to modify Bayliss into the claimed invention with any reasonable expectation of success.
Conclusion
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August 6, 2026
/KEVIN S MARTIN/Examiner, Art Unit 1624
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