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/Restriction
In view of instant claim amendments, the initial search wherein R1 was limited to -NHMe was found to be allowable for claims 15-16, therefore, the search was expanded to encompass the instant compounds wherein R1 is -NHMe, alkyl, or cycloalkyl.
Claims 15 and 16 are allowable. The restriction requirement between Groups I-XIV, as set forth in the Office action mailed on 05/22/2025, has been reconsidered in view of the allowability of claims to the elected invention pursuant to MPEP § 821.04(a). The restriction requirement is hereby withdrawn as to any claim that requires all the limitations of an allowable claim. Specifically, the restriction requirement of 05/22/2025 is withdrawn. Claims 18-20, 24-25, 55-57, and 61-71, directed to methods of treatment comprising administration of the compounds of claim 15, are no longer withdrawn from consideration because the claims require all the limitations of an allowable claim. For the purposes of compact prosecution, claims 43-52 are also rejoined, despite there being no allowable linking claim. However, claims 4-5, 58-60, directed to methods of treating comprising administration of the pharmaceutical compositions of claim 1, are withdrawn from consideration because they do not require all the limitations of an allowable claim.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Status of the Claims
Claims 1-3, 6-13, 15-37, 39-40, 42-57, and 61-71 are under examination herein. Claims 14, 38, and 41 have been cancelled by Applicant. Claims 4-5 and 58-60 remain withdrawn from consideration.
Claim Objections
In claims 1-2 and 15-16, since m is limited to 0 now, in view of claim amendments, the definitions of R6 and m in the claims are redundant and should be deleted. The figures of Formula A, II, A1-3, and II-b should all be amended to remove the –(R6)m groups for clarity and conciseness.
Claim 63 is objected because it is missing the term “is” in “…disorder a cardiac dysfunction.” to read “…disorder is a cardiac dysfunction.”
In claims 65-66, 69, and 71 “disorderis” should read “disorder is”.
Appropriate correction is required.
Claims 44-45 and 52 are 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.
Claims 17-37, 39-40, 42, 54-57, and 61-71 are objected to as being dependent upon an objected base claim. Claims are free of the prior art.
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 57 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.
Regarding claim 57, the phrase "(e.g., KCNT1)" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Furthermore, A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Examiner suggests removing parentheses and limitations therein.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 42 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 42 is rejected for failing to further limit claim 15, from which it depends. Claim 15 speaks to the compounds of Formula II wherein t is not 0. Claim 42, however, claims the compounds below, for example, which correspond to t being 0.
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Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1-3, 6-13, 42, and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Dean et al. (US 5,378,703 A – previously cited) (“Dean”); in view of Meanwell et al. (J. Med. Chem. 2011, 54, 2529–2591) (“Meanwell”).
While claim 42 depends upon claim 15, which is not rejected herein, claim 42 is broader than claim 15. Therefore, as it pertains to the limitations that fall outside the scope of claim 15, the rejection herein applies.
Regarding claims 1-3, 6-13, 42, and 53, Dean discloses their compounds of Formula I below (col. 2-3), which render the instant compounds of Formulae A and A-3 obvious when: R3 (corresponding to instant R6) is H etc. (corresponding to m = 0); R1 (corresponding to instant R2) can be H or C1-4 alkyl; G can be C=O; and R2 (corresponding to instant
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) can be C1-3 alkyl substituted with phenyl or R10, wherein R10 can be pyridine, pyrrole, pyrimidine, etc. (corresponding to ring A) either of which can be substituted with C1-3 alkyl/ haloalkyl/ alkoxy, halogen, etc. (all corresponding to instant R5).
While Dean does not teach their sulfonamide having an alkyl group (corresponding to instant R1 being -NHRa, wherein Ra can be C1-6 alkyl, or methyl – as in the elected compound); Applicant is advised that H vs. Me is considered an obvious modification in the absence of superior, unexpected results. Note In re Wood 199 USPQ 137; In re Lohr 187 USPQ 548 and In re Bowers 149 USPQ 573. Note also In re Fauque 121 USPQ 425 in which differences were 2H’s vs 2 methyl groups. Also see MPEP 2144.09.
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Dean discloses their preferred embodiment below (Example 14, col. 38). While their example 14 does not show substitution on the phenyl ring (corresponding to R5 when t is not 0); Dean specifically teaches that their phenyl or heteroaryl ring (corresponding to instant ring A) can be substituted with C1-3 alkyl or halogen, etc. Table 2 of Dean (shown below, compounds 14a-j from col. 40) shows additional embodiments that demonstrate substitution of the phenyl and thiophene rings. Thus Dean discloses a small genus of compounds, which encompass the instant invention.
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Dean’s Table 2 (compounds below are referenced herein as 14a-e in descending order)
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Furthermore, while Dean’s preferred embodiments 14 and 14a-e above do not show: (i) the group corresponding to instant R5 as a halogen, C1-3 alkyl, etc. (claims 1-3, 6-8, 9-13, 42, and 53); the teachings of Meanwell are relied upon to leverage these differences.
Meanwell teaches that the design of bioisosteres frequently introduces structural changes that can be beneficial depending on the context, with size, shape, electronic distribution, polarizability, dipole, polarity, lipophilicity, and pKa potentially playing key contributing roles in molecular recognition and mimicry. In the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates (abstract). Meanwell also teaches -OH, Cl, Br, and -CH3 also as classical monovalent bioisosteres; and H and F as classical monovalent bioisosteres; as well as -NH2 and -Me (see Table 1, page 2530, col. 1).
Therefore, regarding the compounds of instant claims 1-3, 6-8, 9-13, 42, and 53, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Dean’s disclosed formula I and preferred embodiment of Example 14 and 14a-e in Table 2 above; In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). See MPEP 2144.08. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by Dean and their teaching that their group corresponding to instant R5 can be C1-3 alkyl or halogen, etc.; further in view of Meanwell’s teachings that exploration of bioisosteres leads to improved properties such as lipophilicity, potency, etc. in drugs or lead compounds; further because Meanwell discloses Cl, Br, and -CH3 are monovalent bioisosteres of -OH, and F is a monovalent bioisostere for H. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of Dean’s compounds, substituting the -OH substituent on phenyl with Cl or Br (halogen) or -CH3 (C1 alkyl) in view of Meanwell; or substituting H in Example 14 for F (halogen) to arrive at the instant invention.
Further regarding claims 42 and 53, the compounds below, for example, are obvious for the reasons above:
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Further regarding claims 1-3, 6-8, and 9-13, Dean discloses pharmaceutical compositions comprising their compounds and pharmaceutically acceptable carriers (Examples 15-26). Therefore, it would have been prima facie obvious to one of ordinary skill to prepare pharmaceutical compositions comprising the instant compounds of Formula A or A-3. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Dean’s disclosure of their compounds of Formula I and the preferred embodiment of Example 14, further in view of Dean’s disclosure of pharmaceutical compositions comprising their compounds and acceptable carriers.
Claims 43 and 46-51 are rejected under 35 U.S.C. 103 as being unpatentable over Dean et al. (US 5,378,703 A – previously cited) (“Dean”).
Regarding claims 43, 46-51, Dean discloses their below (col. 36), which render the instant compounds of Formula III obvious when: R3 (corresponding to instant R6) is H (corresponding to m = 0), or Me; R1 (corresponding to instant R2) is H; G is C=O; and R2 (corresponding to instant
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) can be C1-3 alkyl substituted with pyridine, etc., which can be substituted with C1-3 alkyl/ haloalkyl/ alkoxy, halogen, etc. (all corresponding to instant R5). Thus, Dean’s compounds are encompassed by the instant claims.
Examples from Dean’s Table 2
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Therefore, regarding claims 43, 46-51, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Dean’s compounds above. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by Dean. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
While Dean does not teach their sulfonamide having an alkyl group (corresponding to instant R1 being -NHRa, wherein Ra can be C1-6 alkyl, or methyl – as in the elected compound); Applicant is advised that H vs. Me is considered an obvious modification in the absence of superior, unexpected results. Note In re Wood 199 USPQ 137; In re Lohr 187 USPQ 548 and In re Bowers 149 USPQ 573. Note also In re Fauque 121 USPQ 425 in which differences were 2H’s vs 2 methyl groups. Also see MPEP 2144.09.
Regarding claims 48-50, while Dean’s preferred embodiments above do now show substitution on the pyridine, Dean teaches their group pyridine can be substituted with C1-3 alkyl/ haloalkyl/ alkoxy, halogen, etc. (reading on t = 1 also).
Further regarding claim 51, Dean teaches their R3 (corresponding to instant R6) can be H (corresponding to m = 0).
Response to Arguments
Claims
Claim amendments are acknowledged. No new matter has been introduced.
Claim Rejections - 35 USC § 103
Applicant’s arguments, see pages 23-25, filed 01/23/2026, with respect to the rejection(s) of claim(s) 15-37, 39-40, 42, 54-57, and 61-71 under 35 USC § 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, claims 1-3, 6-13, 42-43, 46-51, and 53 stand rejected over Dean or Dean in view of Meanwell, as outlined in this office action.
Applicant cites MPEP 2143. Applicant states Dean does not teach the sulfonamide wherein Ra is alkyl, and that Dean fails to suggest embodiments in which t = 1-4, m = 0, and R1 is phenyl or pyridine, as recited in amended claims. Applicant argues the office has failed to establish a teaching or suggestion to elect amongst “the myriad of possibilities provided by Dean…and that the possibilities encompassed by Dean’s disclosure are enormous, encompassing millions of possible variations. Applicant asserts the only manner one would arrive at the present invention is by use of hindsight reconstruction, absent any teaching to do so. Applicant argues Dean’s compounds are “carbonic anhydrase inhibitors useful for lowering [intraocular pressure]” while the instant compounds are meant for the treatment of neurological diseases, and that therefore, a person of ordinary skill would not have reasonable basis to expect that applicant’s compounds would have properties similar to Dean’s.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Dean discloses their compounds of Formula I below (col. 2-3), which render the instant compounds of Formulae A and A-3 obvious when: R3 (corresponding to instant R6) is H etc. (corresponding to m = 0); R1 (corresponding to instant R2) can be H or C1-4 alkyl; G can be C=O; and R2 (corresponding to instant
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) can be C1-3 alkyl substituted with phenyl or R10, wherein R10 can be pyridine, pyrrole, pyrimidine, etc. (corresponding to ring A) either of which can be substituted with C1-3 alkyl/ haloalkyl/ alkoxy, halogen, etc. (all corresponding to instant R5).
While Dean does not teach their sulfonamide having an alkyl group (corresponding to instant R1 being -NHRa, wherein Ra can be C1-6 alkyl, or methyl – as in the elected compound); Applicant is reminded that H vs. Me is considered an obvious modification in the absence of superior, unexpected results.
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Dean discloses their preferred embodiment below, wherein m = 0 (Example 14, col. 38). While their example 14 does not show substitution on the phenyl ring (corresponding to R5 when t is not 0); Dean specifically teaches that their phenyl or heteroaryl ring (corresponding to instant ring A) can be substituted with C1-3 alkyl or halogen, etc. Table 2 of Dean (shown below, compounds 14a-j from col. 40) shows additional embodiments that demonstrate substitution of the phenyl and thiophene rings. Thus, Dean discloses a small genus of compounds, which encompass the instant invention.
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Dean’s Table 2 (compounds below are referenced herein as 14a-e in descending order)
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Furthermore, while Dean’s preferred embodiments 14 and 14a-e above do not show: (i) the group corresponding to instant R5 as a halogen, C1-3 alkyl, etc.; the teachings of Meanwell are relied upon to leverage these differences.
Meanwell teaches that the design of bioisosteres frequently introduces structural changes that can be beneficial depending on the context, with size, shape, electronic distribution, polarizability, dipole, polarity, lipophilicity, and pKa potentially playing key contributing roles in molecular recognition and mimicry. In the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates (abstract). Meanwell also teaches -OH, Cl, Br, and -CH3 also as classical monovalent bioisosteres; and H and F as classical monovalent bioisosteres; as well as -NH2 and -Me (see Table 1, page 2530, col. 1).
Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Dean’s disclosed formula I and preferred embodiment of Example 14 and 14a-e in Table 2 above. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by Dean and their teaching that their group corresponding to instant R5 can be C1-3 alkyl or halogen, etc.; further in view of Meanwell’s teachings that exploration of bioisosteres leads to improved properties such as lipophilicity, potency, etc. in drugs or lead compounds; further because Meanwell discloses Cl, Br, and -CH3 are monovalent bioisosteres of -OH, and F is a monovalent bioisostere for H. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of Dean’s compounds, substituting the -OH substituent on phenyl with Cl or Br (halogen) or -CH3 (C1 alkyl) in view of Meanwell; or substituting H in Example 14 for F (halogen) to arrive at the instant invention.
In response to Applicant arguments that Dean’s compounds are “carbonic anhydrase inhibitors useful for lowering [intraocular pressure]” while the instant compounds are meant for the treatment of neurological diseases, Applicant is advised that the discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. See MPEP 2112.02 (II). Applicant is further advised that similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Grabiak, 769 F.2d 729, 731, 226 USPQ 870, 871 (Fed. Cir. 1985) (“When chemical compounds have very close structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563 F.2d 457, 461, 195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d 1013, 1016, 173 USPQ 560, 562 (CCPA 1972) (see MPEP 2144.08(d)).
In the present case, Applicant would need to demonstrate that Dean’s compounds, wherein the group corresponding to instant R1 is -NH2, are inferior compared to the instant compounds of claim 1, wherein R1 is -NHMe, in the context of the intended use of the instant application.
Rejoinder
See Election/Restriction section in this office action.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627