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 .
DETAILED ACTION
1. This application is a CON of PCT/IB21/00862 12/10/2021; PCT/IB21/00862 has PRO 63/124,395 12/11/2020.
Claims 1-5, 9-11, 17, 25-28, 30-32, 34 are pending.
Response to Restriction Election
2. Applicant’s election of group I and the species, N-(2-Benzyl-1H-benzimidazol-5-yl)-2-cyclohexyl-acetamide (Example 1.1), in the reply filed on February 19, 2026 is acknowledged. The election was made without traverse. According to applicants’ representative claims 1, 4, 5, 9 and 34 read on the elected species. As detailed in the following rejections, the generic claim encompassing the elected species was not found patentable. Therefore, the provisional election of species is given effect, the examination is restricted to the elected species only, and claims not reading on the elected species are held withdrawn. Accordingly, claims 2-3, 10-11, 17, 25-28, 30 which do not read on the elected species are withdrawn.
Claim Interpretation
3. While represented as one tautomer the compounds of Formula (I) exist as both a 1H and 3H form. The specification explains on page 9 that the additional form is part of the invention:
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Claim 9, which depends upon claim 1, is drawn to examples of both the compounds. Two pair are claimed 2.2.6 and 2.2.5 on page 5 as the last two compounds:
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In order to have antecedent basis the claim 1 would have to be drawn to both tautomers. Typically the two tautomers are simultaneously present since they rapidly interconvert, although one may predominate and many factors contribute to the equilibrium, including substituents on the ring, solvent, crystal form, etc.1 For purposes of examination the two tautomers will be treated as the same compound.
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.
4. Claims 1 and 34 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 1 defines Y “Y is selected from -CH2- and CH(CH3)-; or Y combines with R2 as defined below…Y and R2 together form an unsubstituted C3-8 alkyl group” in the proviso B, section ii. the “Y and R2 do not combine to form C3-10 alkyl”. There is a lack of antecedent basis in the claim for this limitation.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
5. Claim(s) 1 and 34 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Collingwood WO 2020249957 (cited on the IDS). Collingwood teaches a number of anticipatory compounds of general formula IA on page 14 including but not limited to compounds on pages 23 ff. which includes Example 2 on page 65 line 10 ff
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This compound reads on claim 1 where R1 is ii. CH(R11)(R12), R11 is H, R12 is phenyl or alternatively is iv. where R1 is benzyl2, R3-R5 are H, R2 is adamantane (a 10 membered carbocyclic ring system), Z is either definition3, and Y is CH2.
6. Claim(s) 1, 34 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Goeker Eur. J. Med Chem 2005, 40, 1062-1069 (cited on the IDS). Table 1 on page 1063 teaches anticipatory compounds 63-64 where in claim 1 R1 is iv. 6 membered aryl, phenyl substituted with chloro or fluoro, R3-R5 are H, Y combines with R2 to form an unsubstituted alkyl group (C3 or C4), Z is either definition. The compounds were placed in solution for testing, see section 5.7 page 1068 meeting claim 34.
7. Claim(s) 1, 4 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by the STN-Chemical Database Registry for N-Cyclohexyl-2-(phenylmethyl)-1H-benzimidazole-6-carboxamide, RN 2199776-37-7 entered into STN: 27 Mar 2018. This compound reads on claim 1 where R1 is R1 is ii. CH(R11)(R12), R11 is H, R12 is phenyl or alternatively is iv. where R1 is benzyl, R3-R5 are H, where Y combines with R24, and R2 is cyclohexyl (a 6 membered carbocyclic ring system) Z is either definition. This compound was entered into Registry and is listed as being commercially available by the company Aurora Fine Chemicals. The on sale bar is also met since the following documentation shows that this material was subject to an offer for sale by a foreign manufacturer which was communicated to a prospective purchaser in the United States. (See CTS Corp. v. Piher Int 'l Corp., 593 F.2d 777, 201 USPQ 649 (7th Cir. 1979). This information was communicated to the prospective purchaser in the United States via the internet as shown by the following, which was dated by the internet archive to April 6, 2007: "http://web.archive.org/web/20070406205858/http://www.aurorafinechemicals.com/english/order.html" dated April 6, 2007, accessed February 19, 2015.
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.
8. Claim(s) 5 and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Collingwood WO 2020249957 as applied to claims 1, 4, 34 above and further in view of Wislicenus, J. “Adolph Strecker’s Short Textbook of Organic Chemistry” 1881, Spottiswoode: London, pages 38-39.
The applied reference has a common assignee and some inventors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art:
The compound in claim 9,
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is a position isomer of the compound Example 2 cited in the 102 rejection. This compound only differs by the point of attachment of the adamantane as 1 or 2.
Collingwood also teaches a number of additional compounds that are similar to those of claims 5 and 9 including:
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This compound is simply an alkyl homolog of the claimed compound in claim 9:
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,
where the size of the ring was extended by one methylene unit. The elected species is a compound where the ring has contracted by one methylene as compared to prior art compound Example 24.2 as shown below:
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The lower homolog where the ring is cyclopentyl is also disclosed by Collingwood on page 114:
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Ascertaining the differences between the prior art and the claims at issue.
The instant claims are drawn to minor variations of the disclosed species of the prior art including position isomers and alkyl homologs.
Resolving the level of ordinary skill in the pertinent art and Considering objective evidence present in the application indicating obviousness or nonobviousness:
Positional isomers, having the same radical on different positions of the molecule, are prima facie obvious, and require no secondary teaching. The experienced Ph.D. synthetic organic chemist, who would make the compounds, would be motivated to prepare these position isomers based on the expectation that such close analogues would have similar properties and upon the routine nature of such position isomer experimentation in the art of medicinal chemistry. It would be routine for the chemist to vary the point of attachment in order to increase potency. Homologs have long been known to exhibit similar properties as evidenced by page 38 of Wislicenus:
HOMOLOGY AND HOMOLOGOUS SERIES,
48. In opposition to the remarkable differences between organic bodies of like molecular formulae, is the fact that bodies of different molecular composition frequently exhibit great similarity in all their chemical and physical properties. The compounds in which these analogies are most marked are those whose formulae differ by CH2, or a whole multiple thereof, nCH2, and whose molecular weights differ therefore by ± 14n.…This analogy of structure is especially shown in the fact that like reagents produce like changes, and further that the resulting products of such changes agree in properties, but differ in composition by CH2. Such bodies are termed homologous compounds. They form members of a natural family of bodies which can be arranged according to their increasing contents of carbon. The similarity of physical properties between the members of a homologous series is greater the nearer they stand to one another on such a list that is, the less they differ in chemical composition.
Analogs differing only in a single methylene, are prima facie obvious, and require no secondary teaching, see In re Coes, Jr. (CCPA 1949) 173 F2d 1012, 81 USPQ 369. In re Shetty, 195 USPQ 753, In re Wilder, 195 USPQ 426, and Ex parte Greshem, 121 USPQ 422 all feature a compound with a two carbon link rejected over a compound with a one carbon link. Similarly In re Chupp, 2 USPQ 2nd 1437 and In re Coes, 81,USPQ 369 have a one-carbon link unpatentable over a two-carbon link. Ex parte Ruddy, 121 USPQ 427 has a three-carbon link unpatentable over a one-carbon link. Ex parte Nathan, 121 USPQ 347 found the insertion of an ethylene linkage obvious. The variation was per se obvious in all these cases and did not require a specific teaching. In this case Collingwood made various homologs and the species claimed just fill additional gaps in the disclosed homologous series.
9. Claims 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over STN-Chemical Database Registry for N-Cyclohexyl-2-(phenylmethyl)-1H-benzimidazole-6-carboxamide, RN 2199776-37-7 entered into STN: 27 Mar 2018 as applied to claim 1 and 4 above. This compound reads on claim 1 as discussed above. This compound was entered in the database Chemcats, and is listed as being commercially available by the company Aurora Fine Chemicals. The on sale bar is also met. This compound was sold for high throughput screening purposes. Typically such compounds are also sold as solutions in DMSO for cell screening purposes, however no evidence of a solution offered for sale has been obtained. It would be obvious to place the compound in DMSO to facilitate such screening. Similar companies offer the compounds for sale in solution in DMSO. Online: "http://web.archive.org/web/20070630171813/http://www.enamine.net/index.php?option=com_content&task=view&id=22&menuid=51&PHPSESSID=64a4f248f69d671a413f487bb62c4d90" dated June 30, 2007, accessed April 1, 2015. "Format dry powders / DMSO solutions in ENAMINE's or your vials / plates".
It would be obvious to place such a compound in a solution with a solvent. Ex parte Douros et al. (POBA 1968) 163 USPQ 667; “It is clearly obvious to add a carrier or solvent to an unpatentable compound. This combination does not become new and patentable because of the presence of the solvent or carrier, Ex parte Billman, 71 USPQ 253 ; In re Riden et al., 50 CCPA 1411, 318 F.2d 760, 1963 C.D. 794, 796 O.G. 863, 138 USPQ 112 ; In re Pieroh et al., 50 CCPA 1471, 319 F.2d 248, 797 O.G. 6, 138 USPQ 238 ; In re Rosicky, 47 CCPA 859, 276 F.2d 656, 755 O.G. 929, 125 USPQ 341, 1960 C.D. 197.”
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
10. Claims 1, 34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-7 of U.S. Patent No. 12,552,770. Although the claims at issue are not identical, they are not patentably distinct from each other because the species of the patent claims anticipated the claimed genus including but not limited to the second compound in claim 1 which reads on claim 1 where R1 is ii. CH(R11)(R12), R11 is H, R12 is phenyl or alternatively is iv. where R1 is benzyl , R3-R5 are H, R2 is adamantane (a 10 membered carbocyclic ring system), Z is either definition , and Y is CH2. The additional compounds of claim 2-6 read on claim 1 where the phenyl is substituted with hydroxy, fluoro chloro, and/or alkyl or where
11. Claims 5, 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-7 of U.S. Patent No. 12,552,770 as applied to claims 1 and 34 above and further in view of Wislicenus, J. “Adolph Strecker’s Short Textbook of Organic Chemistry” 1881, Spottiswoode: London, pages 38-39. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims are drawn to position isomers and alkyl homologs and are obviousness type double patenting for the same reasons as set forth in the 103 rejection over Collingswood.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Rejections Under the Judicially Created Doctrine of Improper Markush Grouping
12. Claims 1, 34 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: The only non-variable atoms in Formula I is a benzimidazole. This structure is insubstantial to the disclosure of the compounds in the specification. According to the specification the compounds are inhibitors of TMEM16A. Channel TMEM16A (Transmembrane member 16A), also known as Anoctamin-1 (ANO1), is a calcium-activated chloride channel (CaCC) encoded by the ANO1 gene. Roh “Distinct modulation of calcium- activated chloride channel
TMEM16A by drug- binding sites” PNAS 2024 Vol. 121 No. 51 e2314011121 1-11 discusses ligand binding and ”reveals a mechanism for the structural characteristics and pharmacological regulation of TMEM16A and offers a structure-based rational background…” “Our findings on electrostatic interactions in the outer pore region identified residues important for TMEM16A function: R515 and K603. These residues have been earlier identified to be important for anion selectivity ( 13 , 22 ), which is in line with our results that these residues may directly interact with the permeating anion. Moreover, we observed electrostatic regulation of R515 and K603 by E623 and E633 ( Fig. 6 ); E623A or E633A mutants increased the energy barrier for ion permeation. In addition, nonpore blocker-binding caused TM3 and TM4 to move away from the center of the pore, resulting in disrupted electrostatic interactions in R515, K603, E623, and E633 ( Fig. 5 ). Therefore, the pore and nonpore blockers modulate outer pore residues in a different manner, yet their ultimate result is the same: TMEM16A inhibition ( Fig. 6D).” The structure of the inhibitor molecule governs its ability to interact with the binding site. These intermolecular interactions between the inhibitor molecule and residues of the protein are highly specific and subtle and include van der Waals forces, cation-dipole interactions and hydrogen bonding. The specification discloses only a few compounds that have the property of binding inhibition. These compounds are relatively homogenous. The core disclosed has a cycloalkyl as R2 and typically an aromatic R1 group.
The claims do not reflect these nuanced molecular interactions and are so expansive that a common utility cannot be expected. All of the compounds, have a very specific structure absent from the instant claims. In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1) (emphasis provided).
Conclusion
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID K O'DELL whose telephone number is (571)272-9071. The examiner can normally be reached on Monday - Friday 9:30 - 7:00 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached on 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DAVID K O'DELL/Primary Examiner, Art Unit 1621
1 See García-Báez, E.V.; “ 13C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion.” Molecules 2022, 27, 6268.
2 THE VAN NOSTRAND CHEMIST'S DICTIONARY 1953, entry for “aryl” Pg. 44. “ARYL. A radical derived from an aromatic hydrocarbon by the elimination of one atom of hydrogen, so producing a univalent unit. Examples are phenyl C6H5- derived from benzene; tolyl (or benzyl) C7H7. derived from toluene, etc.”
3 Since the point of attachment of either Z is ambiguous any of the two definitions can create the prior art compounds.
4 The manner “Y combines with R2” is ambiguous and is open to a number of interpretations. This interpretation has Y subsumed by R2 which is part of the “defined below”. Other interpretations include where part of “Y and R2 together form”. It is not clear that the combining is limited to the forming language.
Prosecution Insights