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 .
Election/Restrictions
Applicant elected, with traverse, Group I, claims 1-15 and 18-19, drawn to a compound/composition represented by formula I, or a pharmaceutically acceptable salt or isotopically substituted form thereof. Applicant further elected, with traverse, the single compound species depicted in the reply, identified by Applicant as one of the compounds recited in claim 13:
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. The election in the reply filed on June 10 2026 is acknowledged.
Claims 16-17 are drawn to the non-elected Group II method of treating a mineralocorticoid-related disease or disorder using the compound/composition and are withdrawn from further consideration. Claims 1-15 and 18-19 are examined only to the extent they read on the elected invention and the elected compound species. Non-elected species encompassed by the pending claims are not presently examined.
Applicant’s traverse has been fully considered but is not persuasive. Applicant argues that the pending claims are linked by a common formula I core, namely a 1,4-dihydro-1,6-naphthyridine amide structure that functions as a mineralocorticoid receptor antagonist. The Office acknowledges that a product and a process of use of that product may, in appropriate circumstances, satisfy the unity requirement. However, unity requires more than a common product/use relationship. Under PCT Rule 13.2 and 37 CFR 1.475(a), the claimed inventions must share the same or corresponding special technical feature, meaning a technical feature that defines a contribution over the prior art.
Here, the feature relied upon by Applicant, namely the formula I 1,4-dihydro-1,6-naphthyridine amide structure and its mineralocorticoid receptor antagonist activity, does not constitute such a special technical feature. As set forth in the restriction requirement, Wang et al. (CN113214248A) teaches 1,4-dihydro-1,6-naphthyridine-3-carboxamide compounds, including deuterated compounds such as Example 3, and teaches that such compounds modulate steroid nuclear receptors, including the mineralocorticoid receptor. Wang further teaches pharmaceutical compositions comprising such compounds and use of the compounds/compositions for preparation of a medicament for diseases or disorders mediated by or associated with steroid nuclear receptor activity, including mineralocorticoid receptor activity. Accordingly, the common formula I core and mineralocorticoid receptor antagonist use relied upon by Applicant were already known in the prior art and do not define a contribution over the prior art. Therefore, the asserted common feature is not a special technical feature within the meaning of the unity requirement. The claimed inventions are not so linked as to form a single general inventive concept.
Applicant’s further argument that examination of the elected compound species necessarily encompasses the remaining inventions is also not persuasive. The claims encompass multiple species within the formula I genus, including different substituent patterns, salts, and isotopically substituted forms. Search and examination of the elected species does not necessarily address the patentability of each non-elected species or the withdrawn method claims unless and until an allowable generic or elected product claim is found.
For the reasons above, the restriction/election requirement is maintained and is made FINAL. Applicant’s right to petition is governed by 37 CFR 1.144.
Claims 16-17 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 with traverse in the reply filed on June 10 2026.
Status of the Claims
Claims 1-10, 13-15 and 18-19 are elected and are examined to the extent they read on the elected compound species.
Claims 16-17 are withdrawn from consideration as being directed to a non-elected invention.
Claims 11-12 do not read on the elected species, therefore, the Examiner has determined that claims 11-12 are drawn to a non-elected species and are not examined on the merits at this time.
Priority
The instant application 18/691,820 filed on March 13, 2024 is a 371 national stage application of PCT/CN2022/119209, filed on September 16, 2022, which claims priority to CN202111324281.2 filed on November 10, 2021, CN202111636982.X filed on December 29, 2021, CN202111104458.8 filed on September 16, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on March 13, 2024 and February 26, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
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 6 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 6 recites “for example” language in defining the substituent R5. This language renders the metes and bounds of the claim unclear because it is uncertain whether the preferred or exemplary substituent lists are intended to further limit the claim.
Appropriate correction would include deleting “for example” language from the claims or rewriting the claims to clearly recite the intended limitations.
Claim Rejections - 35 USC § 112(a)
Written Description
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 1-10, 15, and 18-19 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claim 1 recites a broad genus of compounds represented by formula I, including broad and variable definitions for R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, Z1, and Z2, as well as pharmaceutically acceptable salts and isotopically substituted forms thereof. The claim encompasses numerous structurally distinct species, including compounds having different heteroatom arrangements, alkyl, alkoxy, thioalkyl, cycloalkyl, heterocycloalkyl, perfluoroalkyl, amino, cyano, nitro, hydroxy, ester, and amide substituent patterns.
The specification discloses and appears to show possession of certain specifically exemplified compounds, including the elected compound species and closely related compounds having the disclosed 4S 1,4-dihydro-1,6-naphthyridine-3-carboxamide scaffold, a 4-cyano-2-alkoxyphenyl substituent, a 5-ethoxy substituent, 2,8-dimethyl substitution, a 3-carboxamide group, and mineralocorticoid receptor antagonist activity. However, the specification provides working examples and biological data for only a limited subset of compounds having those relatively narrow structural features. The exemplified compounds do not represent the full breadth of the claimed genus, and the specification does not identify structural features common to the entire claimed genus that would reasonably convey possession of all claimed compounds as mineralocorticoid receptor antagonists
For example, the claims encompass broad alternatives for R3, including sulfur-containing substituents, oxygen-linked alkyl groups substituted by multiple different substituent classes, perfluoroalkyl groups, cycloalkoxy groups, heterocycloalkyl groups, and heterocycloalkoxy groups. The specification does not provide representative examples across these categories sufficient to show possession of the entire genus. Similarly, the claims encompass broad alternatives at R1, R2, R5, and R7-R11, but the specification does not provide sufficient representative species or structure-activity correlation showing that Applicant possessed the full scope of the claimed compounds.
Accordingly, although the specification may describe certain specific compounds, including the elected species, it does not reasonably convey possession of the full scope of claims 1-10, 15, and 18-19. To overcome this rejection, Applicant should amend the claims to correspond to the compounds and subgenera actually described in the specification, such as the elected compound species or a subgenus supported by representative disclosed examples, or provide persuasive evidence or explanation showing possession of the full claimed genus at the time of filing.
Claim 15 recites a pharmaceutical composition comprising the broadly claimed compound genus and is deficient for the same reasons to the extent it encompasses unsupported compounds outside the described and exemplified subgenera. Applicant may overcome this rejection by amending claim 15 to depend from, or otherwise require, a compound or subgenus that is adequately described in the specification.
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 1-10, 13-15, and 18-19 are rejected under 35 U.S.C. §103 as being unpatentable over Barfacker et al. (US 8,436,180 B2) in view of Knutson et al. (J Med. Chem. 2018, 61(6):2422-2446).
Regarding claim 1, Barfacker et al. teaches substituted 4-aryl-1,4-dihydro-1,6-naphthyridine-3-carboxamide compounds useful as selective mineralocorticoid receptor antagonists (see e.g., col. 3, line 1-25). Barfacker et al. teaches that potent, non-steroidal antagonists selective for the mineralocorticoid receptor provide therapeutic advantages and that the compounds are useful for treating disorders, especially cardiovascular disorders (see col. 2, line 64). Barfacker et al. further teaches pharmaceutical compositions comprising such compounds and pharmaceutically acceptable excipients (see e.g., col. 70, claim 7).
Barfacker et al. specifically teaches 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide
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in Example 4 (see e.g., col. 52, line 50). Barfacker et al. further teaches resolution of the racemate into enantiomers in Example 5 and identifies the S-configuration enantiomer(finerenone) (see col. 53, line 55). Thus, Barfacker et al. teaches the non-deuterated parent compound corresponding to the elected species, namely the 4S compound having the same 1,4-dihydro-1,6-naphthyridine-3-carboxamide core, the same 4-cyano-2-methoxyphenyl substituent, the same 5-ethoxy group, the same 2,8-dimethyl substitution pattern, and the same mineralocorticoid receptor antagonist use.
Barfacker et al. alco teaches the same R1 methyl group corresponding to claim 2; the same R6 carboxamide group corresponding to claim 3; the same aryl cyano substituent corresponding to claim 4; the same narrowed naphthyridine-amide framework corresponding to claims 5 and 8; the same substituent selections corresponding to claims 6, 7, 9, 10, 18, and 19; and the same pharmaceutical composition subject matter corresponding to claim 15.
Barfacker et al. does not expressly teach replacement of the three hydrogen atoms of the aryl methoxy group with deuterium, i.e., replacement of —OCH3 with —OCD3. The elected species differs from Barfacker et al.’s parent compound is that replacement of the three hydrogen atoms of the aryl methoxy group with deuterium, i.e., replacement of —OCH3 with —OCD3.
Knutson et al. teaches deuterated ligands in which deuterium was incorporated into methoxy substituents. Knutson et al. teaches that incorporation of deuterium into methoxy substituents increased duration of action through improved metabolic stability and bioavailability while retaining receptor selectivity (see e.g. p. 2423 col. 2, last paragraph). Thus, Knutson et al. teaches the missing —OCD3 modification and provides motivation to replace the hydrogens of a methoxy group with deuterium in a biologically active ligand where improved metabolic stability and pharmacokinetic properties are desired.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Barfacker et al.’s 4S finerenone parent compound by replacing the hydrogens of the aryl methoxy group with deuterium to form the corresponding trideuteriomethoxy analog, as taught by Knutson et al. One of ordinary skill in the art would have been motivated to make the modification to improve metabolic stability and/or pharmacokinetic properties while retaining the same overall size, shape, and electronic character of the methoxy substituent. One of ordinary skill in the art would have had a reasonable expectation of success because the modification involved a known conservative isotope substitution, namely hydrogen-to-deuterium replacement at a methoxy methyl group, in a known active mineralocorticoid receptor antagonist scaffold, and deuterium substitution generally preserves the steric and electronic characteristics of hydrogen while altering the rate of metabolic C—H bond cleavage.
Accordingly, claim 1-10, 13-15, and 18-19 are unpatentable over Barfacker et al. in view of Knutson et al. In particular, claim 1 is met Barfacker et al.’s teaching except for —OCD3 group, which is taught by Knutson et al.; claims 2-10, 18, and 19 recite narrower structural limitations taught by Barfacker et al. in the corresponding parent compound; claim 13 recites the elected —OCD3 analog of Barfacker et al.’s 4S finerenone parent compound; claim 14 recites deuterium abundance that would result from preparing the OCD3 analog with isotopically enriched deuterated reagents; and claim 15 recites a pharmaceutical compositions taught by Barfacker et al..
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Rejoinder
Claims 11-12 do not read on the elected compound species and are not examined on the merits at this time. Claims 16-17 remain withdrawn from further consideration as being directed to the non-elected invention of Group II.
Applicant’s request for rejoinder of claims 16-17 is noted. Rejoinder is premature at this time. Claims 16-17 will be considered for rejoinder if all elected product claims are found allowable and the withdrawn method claims require all limitations of an allowable elected product claim.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GENBIN SHI whose telephone number is (571)272-8796. The examiner can normally be reached Mon-Fri, 8:00am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/G.S./ Examiner, Art Unit 1628 /AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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