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 .
Information Disclosure Statement
Two information disclosure statement (IDS) submitted: One on August 9th, 2024; one on December 13th, 2024. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The use of the terms Axura®, Akatimol®, Namenda®, etc. which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
While the Examiner has made every attempt to check the Specification for trade mark compliance, Applicant is required to carefully check the entire Specification for any and all issues regarding trade mark use compliance.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see for example page 365, [0755] line 3). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
While the Examiner has made every attempt to check the Specification for hyperlink incorporation compliance, Applicant is required to carefully check the entire Specification for any and all issues regarding hyperlink incorporation compliance.
Status of the Claims
Claims 1, 3-4, 7-8, 11, 14, 17, 20, 22-25, 30, 45-46, 61-62, 64-65 and 67-68 are pending in this application. Claims 2, 5-6, 9-10, 12-13, 15-16, 18-19, 21, 26-29, 31-44, 47-60, 63, 66, and 69-75 have been cancelled by applicant.
Claim Objections
Claims 1, 3-4, and 7-8 are objected to because of the following informalities:
Claims 1, 3-4, and 7-8 read: “when two R7 groups bound to the same atom . . .” Claims should read: “when two R7 groups are bound to the same atom . . .”
Appropriate correction is required.
Claim Interpretation
The specification doesn’t define the term “isomer,” only provides that examples of isomers include stereoisomers, E/Z isomers, and tautomers in [0085]. The term “isomers” as used in the art includes stereoisomers and constitutional isomers, which differ in the connectivity of atoms. Obtained from chem.libretexts.org [Retrieved on 11/02/2025] <URL: https://chem.libretexts.org/Courses/Thompson_Rivers_University/CHEM_1500%3A_Chemical_Bonding_and_Organic_Chemistry/08%3A_Organic_Chemistry_II_-_Stereochemistry/8.01%3A_Types_of_Isomers>).
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.
Claims 1, 3-4, 7-8, 11, 14, 17, 20, 22-25, 30, 45-46, 61-62, 64-65 and 67-68 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 regards as the invention.
Regarding claim 1, the term “in particular” is a relative term which renders the claim indefinite. The term “in particular” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Further regarding claim 1, the phrase "in some aspects" 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).
Claims 45, 61-62, 64, and 67 recites the limitation "the step". There is insufficient antecedent basis for this limitation in the claim. Claim 1 from which these claims depend makes no mention of a step. It is suggested that as one possible way to overcome this rejection the claims could be amended to read “…comprising
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.
Claims 3-4, 7-8, 11, 14, 17, 20, and 22 are 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.
Claims 3-4, 7-8, 11, 14, 17, and 20, are rejected for failing to further limit the limitations of claim 1, from which they depend. In the present case, claim 1 defines the position corresponding to R13/ 14 in the structures below as always being H, while in the present claims this limitation is expanded so that the position corresponding to R13/ 14 can be H, C1-3 aliphatic, or C-3-6 cycloalkyl.
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Claim 22 is rejected for failing to further limit claim 1, from which it depends. This is the case in the example shown below (and other cases not shown), where the position indicated with a circle (always corresponding to a carbon in Formula I of claim 1) is shown as a nitrogen. Furthermore, some compounds (an example shown below with a box around the group of interest) lack the X and W groups, which are defined in claim 1 as always being present and representing either -O-, -N-, -NR3, or -C(R4)1-2. Compounds that fail to further limit claim 1 are compounds 25-32.
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Further regarding claim 22, if the term “isomers” is intended to be limited to stereoisomers only (see claim interpretation), then the compound 58 below fails to further limit the limitations of claim 1, wherein the circled position is always a carbon.
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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 § 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.
Claims 1, 3-4, 7-8, 14, 22-25, 30, 45-46, 62, 64 and 67-68 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by MeKonnen et al. (US 2019/0055258 A1 – cited in IDS – Pub. Date: Feb. 21st, 2019) (“MeKonnen”).
To the extent that the term “isomers” encompasses constitutional isomers and stereoisomers – see claim interpretation – the rejections below apply:
Regarding claims 1, 3-4, 7-8, 14, and 22-23, MeKonnen teaches the compound of Formula I below [0010], in methods for treating cognitive impairment associated with central nervous system (CNS) disorders [0002] – which is the same application as in the instant claims. Their compounds anticipate the instant claims when U forms a 6 membered aryl ring with carbons α and β; R1 (corresponding to instant R1) is H, halogen, C1-6 alkyl, -OH, CF3, etc.; A is C; E is N; D is CR6, wherein R6 (corresponding to instant R6) can be H or C1-6 alkyl; F is N; B is C; R4/ 5 is H; Y and Z can be C or N as long as they were not both nitrogens – meaning that they can both be carbons [0019]; and X, W, V (corresponding to instant X, W, V) can be N, C, or O.
R3 (corresponding to instant R2) can be
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etc.
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(I)
MeKonnen discloses the compounds II, III, and IV below ([0154]-[0158]) as preferred embodiments, which represent constitutional isomers of the instant structures.
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(II)
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Regarding claim 24, MeKonnen discloses a pharmaceutical composition comprising their compounds and an acceptable carrier, adjuvant, or vehicle (MeKonnen’s claim 6).
Regarding claim 25, MeKonnen discloses a pharmaceutical composition comprising a second therapeutic agent (MeKonnen’s claim 7).
Regarding claim 30, MeKonnen discloses a pharmaceutical composition comprising a second therapeutic agent, wherein the second therapeutic agent is an acetylcholine esterase inhibitor, like Donepezil (MeKonnen’s claims 8 and 11).
Regarding claim 45, MeKonnen claims a method of treating a cognitive impairment disorder associated with the CNS comprising administration of their compounds or pharmaceutical compositions thereof, such as their composition comprising a second therapeutic agent, as recited in MeKonnen’s claim 12.
Regarding claim 46, MeKonnen claims a method of treating wherein the CNS disorder is age-related, like MCI, AMCI, Alzheimer’s disease, etc. (MeKonnen’s claims 13-26).
Regarding claim 62, MeKonnen speaks to treatment of cognitive impairment associated with brain cancer (abstract, last 4 lines).
Regarding claim 64, MeKonnen claims a method of treating schizophrenia and bipolar disorder comprising administration of their compounds of pharmaceutical compositions or combinations thereof (MeKonnen’s claims 12 and 18).
Regarding claims 67-68, MeKonnen claims a method of treating wherein the CNS disorder stems from age-related risk factors, like MCI, AMCI, Alzheimer’s disease, etc. (MeKonnen’s claims 13-26).
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, 3-4, 7-8, 11, 14, 17, 20, 22-25, 30, 45-46, 62, 64-65 and 67-68 are rejected under 35 U.S.C. 103 as being unpatentable over MeKonnen et al. (US 2019/0055258 A1 – cited in IDS) (“MeKonnen”).
To the extent that the term “isomers” encompasses only stereoisomers:
Regarding claims 1, 3-4, 7-8, 11, 14, 17, 20, and 22-23, MeKonnen teaches the compound of Formula I below [0010], in methods for treating cognitive impairment associated with central nervous system (CNS) disorders [0002] – which is the same application as in the instant claims. Their compounds render the instant compounds obvious when U forms a 6 membered aryl ring with carbons α and β; R1 (corresponding to instant R1) can be H, halogen, C1-6 alkyl, -OH, CF3, etc.; A is C; E can be N; D can be CR6, wherein R6 (corresponding to instant R6) can be H or C1-6 alkyl; F can be N; B can be C; R4/ 5 can be H; Y and Z can be C or N; and X, W, V (corresponding to instant X, W, V) can be N, C, or O.
R3 (corresponding to instant R2) can be
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(I)
MeKonnen discloses the compounds II, III, and IV below ([0154]-[0158]) as preferred embodiments, which differ from the instant structures only by the nitrogen corresponding to MeKonnen’s Y and Z, which is the instant claim always correspond to carbon.
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(IV)
MeKonnen discloses in their general formula I that their groups Y and Z can independently be C or N, as long as they were not both nitrogens – meaning that they can both be carbons [0019]. Furthermore, MeKonnen discloses that their X, W, V (corresponding to instant X, W, V) can be N, C, or O, as in the instant claims. MeKonnen specifically discloses their group corresponding to X, Y, Z, V, W may be:
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; etc. (see [0468] to [0478]), reading on the instant claims. Thus, MeKonnen discloses a fairly broad genus of compounds, which encompass the instantly claimed subgenus.
Therefore, regarding claims 1, 3-4, 7-8, 11, 14, 17, 20, and 22-23, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by MeKonnen’s disclosed formula I, wherein their X, Y, Z, V, and W groups can be:
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; etc., (in which Y and Z are both carbon – which is the main structural difference between MeKonnen’s Formulae II, III, and IV above and instant Formulae I, I-a, I-aa, I-b, I-ba, I-c, I-d, I-e, and I-f); 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 MeKonnen. 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.
Further regarding claims 3-4, 7-8, 11, 14, 17, and 20, MeKonnen discloses their compound of Formula I above, and preferred embodiments II, III, and IV, wherein Y and Z can be C and X, W, V (corresponding to instant X, W, V) can be N, C, or O. Mekonnen specifically discloses the preferred embodiments below, which read on the present claims when instant R2 is
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substituted with 1 R7 group, wherein R7 is C3 alkyl; R1 is F (halogen); R4 is alkyl.
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([1123] page 112)
Applicant is advised that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. In re Norris, 179 F.2d. 970, 84 USPQ 458 (CCPA 1970). Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results. In re Finely, 81 USPQ 383 (CCPA 1949); 84 USPQ 458 (CCPA 1950).
Regarding claim 24, MeKonnen discloses a pharmaceutical composition comprising their compounds and an acceptable carrier, adjuvant, or vehicle (MeKonnen’s claim 6).
Regarding claim 25, MeKonnen discloses a pharmaceutical composition comprising a second therapeutic agent (MeKonnen’s claim 7).
Regarding claim 30, MeKonnen discloses a pharmaceutical composition comprising a second therapeutic agent, wherein the second therapeutic agent is an acetylcholine esterase inhibitor, like Donepezil (MeKonnen’s claims 8 and 11).
Regarding claim 45, MeKonnen claims a method of treating a cognitive impairment disorder associated with the CNS comprising administration of their compounds or pharmaceutical compositions thereof, such as their composition comprising a second therapeutic agent, as recited in MeKonnen’s claim 12.
Regarding claim 46, MeKonnen claims a method of treating wherein the CNS disorder is age-related, like MCI, AMCI, Alzheimer’s disease, etc. (MeKonnen’s claims 13-26).
Regarding claim 62, MeKonnen speaks to treatment of cognitive impairment associated with brain cancer (abstract, last 4 lines).
Regarding claim 64, MeKonnen claims a method of treating schizophrenia and bipolar disorder comprising administration of their compounds of pharmaceutical compositions or combinations thereof (MeKonnen’s claims 12 and 18).
Regarding claim 65, MeKonnen defines “treating” as comprising alleviation, amelioration, or slowing the progression of one or more symptoms [0215]. Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer MeKonnen’s treatment for a cognitive impairment disorder associated with the CNS and expect alleviation, amelioration, or slowing the progression of one or more symptoms. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of MeKonnen’s disclosure.
Regarding claims 67-68, MeKonnen discloses methods of treating cognitive impairment associated with the CNS in a subject in need or at risk thereof (abstract, line 9-11; [0002]; [0006], last line; and [0164] first 4 lines), such as age-related risks (reading on risk factors associated with aging in instant claim 68) (MeKonnen’s claim 13).
Further regarding claims 25, 30, 45-46, 62, 64-65 and 67-68, Applicant is 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)).
Claim 61 is rejected under 35 U.S.C. 103 as being unpatentable over MeKonnen et al. (US 2019/0055258 A1 – cited in IDS) (“MeKonnen”); as applied to claims 1, 3-4, 7-8, 11, 14, 17, 20, 22-25, 30, 45-46, 62, 64-65 and 67-68; in view of Sengupta et al. (Acta Neuropathol., 2014, 127:593–603 – cited in IDS) (“Sengupta”).
The teachings of MeKonnen are disclosed above and incorporated herein.
MeKonnen discloses their compounds as α5-GABAA receptor agonists (abstract and [0009]).
While MeKonnen does not specifically teach their compounds for the treatment of brain cancers, the teachings of Sengupta are relied upon for these disclosures.
Sengupta discloses that targeting α5-GABAA receptors in MYC-driven medulloblastomas with a specific α5-GABAA agonist results in decreased cell viability and sanitization to cisplatin (page 601, col. 2, Discussion).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of claimed invention to administer MeKonnen’s compounds for the treatment of brain cancers, such as medulloblastomas. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because MeKonnen discloses their α5-GABAA receptor agonists; and Sengupta teaches that targeting α5-GABAA receptors in MYC-driven medulloblastomas with specific α5-GABAA agonist results in decreased cell viability and sensitization to cisplatin (reading on combination therapy). The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). See MPEP 2744.07.
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
For the purposes of all the NSDP rejections presented below, the term “isomers” was interpreted as encompassing stereoisomers only.
Claims 1, 3-4, 7-8, 11, 14, 17, 20, 22-25, 30, 45-46, 62, 64-65 and 67-68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. US 10,329,301 B2 (US ‘301); in view of MeKonnen et al. (US 2019/0055258 A1 – cited in IDS).
Regarding instant claims 1, 3-4, 7-8, 11, 14, 17, 20, and 22-23, US ‘301 discloses the compounds of Formula II, which read on the instant compounds when instant R2 (US ‘301’s R3) is –(5 to 10- membered) heteroaryl etc.; R6 (US ‘301’s R6) is H or C1-6 alkyl; R1 (US ‘301’s R1) is H, halogen, C1-6 alkyl, -OH, CF3, etc.; US ‘301’s R4/ 5 are H; X is N; W is N; and V is -CR4, wherein R4 (US ‘301’s R2) is C1-6 alkyl (US ‘301’s claim 3).
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(150)
US ‘301 also discloses compound 150, which reads on the instant claims when instant X and W are N; V is CR4; R4 is alkyl; R2 is
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substituted with 1 R7 group, wherein R7 is C3 alkyl; and R1 is F (halogen).
Regarding claim 24, US ‘301 discloses a pharmaceutical composition comprising their compounds and an acceptable carrier, adjuvant, or vehicle (US ‘301’s claim 24).
Regarding claim 25, US ‘301 discloses a pharmaceutical composition comprising a second therapeutic agent (US ‘301’s claim 25).
Regarding claim 30, US ‘301 discloses a pharmaceutical composition comprising a second therapeutic agent, wherein the second therapeutic agent is an acetylcholine esterase inhibitor, like Donepezil (US ‘301’s claim 25).
Regarding claim 45, US ‘301 claims a method of treating a cognitive impairment disorder associated with the CNS comprising administration of their compounds or pharmaceutical compositions thereof (US ‘301’s claim 27).
Regarding claim 46, US ‘301 claims a method of treating wherein the CNS disorder is age-related, like MCI (US ‘301’s claims 27-29).
Regarding claim 62, US ‘301 speaks to treatment of cognitive impairment associated with brain cancer (US ‘301’s claim 35).
Regarding claim 64, the instant specification doesn’t define “neuropsychiatric conditions”. Thus, the claim has been given the broadest reasonable interpretation. US ‘301 claims a method of treating schizophrenia and bipolar disorder comprising administration of their compounds of pharmaceutical compositions or combinations thereof (US ‘301’s claim 32).
Regarding claim 65, US ‘301 defines “treating” as comprising alleviation, amelioration, or slowing the progression of one or more symptoms (col. 16, lines 18-22). Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘301’s treatment for a cognitive impairment disorder associated with the CNS and expect alleviation, amelioration, or slowing the progression of one or more symptoms. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘301’s disclosure and claims.
Regarding claims 67-68, US ‘301 claims a method of treating wherein the CNS disorder is age-related, like MCI (US ‘301’s claims 27-29).
Further regarding instant claims 25, 30, 45-46, 62, 64-65 and 67-68, Applicant is reminded that similar properties may normally be presumed when compounds are very close in structure. (“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.
While US ‘301 does not disclose their compounds wherein the group circled in II and 150 is a carbon, or wherein the positions corresponding to instant X, W, and V are anything other than N, N, and C, respectively, (such as C, N, and O in the instant claims); the teachings of MeKonnen et al. are relied upon for these disclosures.
MeKonnen teaches the compound of Formula I below [0010], in methods for treating cognitive impairment associated with central nervous system (CNS) disorders [0002] – which is the same application as in the instant claims and the claims from US ‘301. MeKonnen’s compounds render the instant compounds obvious when U forms a 6 membered aryl ring with carbons α and β; R1 (corresponding to instant R1) can be H, halogen, C1-6 alkyl, -OH, CF3, etc.; A is C; E can be N; D can be CR6, wherein R6 (corresponding to instant R6) can be H or C1-6 alkyl; F can be N; B can be C; R4/ 5 can be H; Y and Z can be C or N; and X, W, V (corresponding to instant X, W, V) can be N, C, or O.
R3 (corresponding to instant R2) can be
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MeKonnen discloses in their general Formula I that their groups Y and Z can independently be C or N, as long as they were not both nitrogens – meaning that they can both be carbons, as in the instant claims, and still function for the same purpose of treating cognitive impairment associated with the CNS [0019]. Furthermore, MeKonnen discloses that their X, W, V (corresponding to instant X, W, V) can be N, C, or O, as in the instant claims. MeKonnen specifically discloses their group corresponding to X, Y, Z, V, W may be:
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; etc. (see [0468] to [0478]), reading on the instant claims.
Therefore, regarding claims 1, 3-4, 7-8, 11, 14, 17, 20, and 22-23, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by US ‘301’s and MeKonnen’s disclosed formulae. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by US ‘301 in view of MeKonnen et al. 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.
Applicant is reminded that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results.
Claim 61 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. US 10,329,301 B2 (US ‘301); in view of MeKonnen et al. (US 2019/0055258 A1 – cited in IDS); as applied to claims 1, 3-4, 7-8, 11, 14, 17, 20, 22-25, 30, 45-46, 62, 64-65 and 67-68; further in view of Sengupta et al. (Acta Neuropathol., 2014, 127:593–603 – cited in IDS).
The teachings of US ‘301 and MeKonnen et al. are disclosed above and incorporated herein.
US ‘301 discloses their compounds as α5-GABAA receptor agonists (abstract).
MeKonnen discloses their compounds as α5-GABAA receptor agonists (abstract and [0009]).
While US ‘301 in view of MeKonnen does not specifically teach their compounds for the treatment of brain cancers, the teachings of Sengupta et al. are relied upon for these disclosures.
Sengupta discloses that targeting α5-GABAA receptors in MYC-driven medulloblastomas with a specific α5-GABAA agonist results in decreased cell viability and sanitization to cisplatin (page 601, col. 2, Discussion).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘301 in view of MeKonnen’s compounds for the treatment of brain cancers, such as medulloblastomas. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘301’s disclosure of their compounds, which are taught to be α5-GABAA receptor agonists; MeKonnen’s disclosure of their related α5-GABAA receptor agonists; and Sengupta’s teachings that targeting α5-GABAA receptors in MYC-driven medulloblastomas with a specific α5-GABAA agonist results in decreased cell viability and sanitization to cisplatin (reading on combination therapy).
Claims 1, 3-4, 7-8, 11, 14, 17, 20, 22-25, 30, 45-46, 62, 64-65 and 67-68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. US 10,815,242 B2 (US ‘242); in view of MeKonnen et al. (US 2019/0055258 A1 – cited in IDS).
Regarding instant claims 1, 3-4, 7-8, 11, 14, 17, 20, and 22-23, US ‘242 discloses the compounds of Formula II, which read on the instant compounds when instant R2 (US ‘242’s R3) is –(5 to 10- membered) heteroaryl etc.; R6 (US ‘242’s R6) is H or C1-6 alkyl; R1 (US ‘242’s R1) is H, halogen, C1-6 alkyl, -OH, CF3, etc.; US ‘242’s R4/ 5 are H; X is N; W is N; and V is -CR4, wherein R4 (US ‘242’s R2) is C1-6 alkyl (US ‘242’s claim 2).
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(II)
Regarding claim 24, US ‘242 discloses a pharmaceutical composition comprising their compounds and an acceptable carrier, adjuvant, or vehicle (US ‘242’s claim 5).
Regarding claim 25, US ‘242 discloses a pharmaceutical composition comprising a second therapeutic agent (US ‘242’s claim 6).
Regarding claim 30, US ‘242 discloses a pharmaceutical composition comprising a second therapeutic agent, wherein the second therapeutic agent is an acetylcholine esterase inhibitor, like Donepezil (US ‘242’s claim 10).
While US ‘242 does not disclose: (i) their compounds wherein the group circled in II is a carbon, or wherein the positions corresponding to instant X, W, and V are anything other than N, N, and C, respectively, (such as C, N, and O in the instant claims); (ii) a method of treating cognitive impairment (CI) associated with the CNS by administering their compounds (claim 45); (iii) a method wherein the CI is age related and is MCI, etc. (claim 46); (iv) a method of treating CI related to cancer-therapy (claim 62); (v) a method of treating CI associated with neuropsychological conditions (claim 64); (vi) wherein treatment comprises alleviation (claim 65); (vii) a method of treating CI associated with a risk factor, such as aging (claims 67-68); the teachings of MeKonnen et al. are relied upon for these disclosures.
MeKonnen teaches the compound of Formula I below [0010], in methods for treating cognitive impairment associated with central nervous system (CNS) disorders [0002] – which is the same application as in the instant claims and the claims from US ‘242. MeKonnen’s compounds render the instant compounds obvious when U forms a 6 membered aryl ring with carbons α and β; R1 (corresponding to instant R1) can be H, halogen, C1-6 alkyl, -OH, CF3, etc.; A is C; E can be N; D can be CR6, wherein R6 (corresponding to instant R6) can be H or C1-6 alkyl; F can be N; B can be C; R4/ 5 can be H; Y and Z can be C or N; and X, W, V (corresponding to instant X, W, V) can be N, C, or O.
R3 (corresponding to instant R2) can be
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(I)
MeKonnen discloses in their general Formula I that their groups Y and Z can independently be C or N, as long as they were not both nitrogens – meaning that they can both be carbons, as in the instant claims, and still function for the same purpose of treating cognitive impairment associated with the CNS [0019]. Furthermore, MeKonnen discloses that their X, W, V (corresponding to instant X, W, V) can be N, C, or O, as in the instant claims. MeKonnen specifically discloses their group corresponding to X, Y, Z, V, W may be:
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; etc. (see [0468] to [0478]), reading on the instant claims.
Therefore, regarding claims 1, 3-4, 7-8, 11, 14, 17, 20, and 22-23, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by US ‘242’s and MeKonnen’s disclosed formulae. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by US ‘242 in view of MeKonnen et al. 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.
Applicant is reminded that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results.
Regarding claim 45, MeKonnen claims a method of treating a cognitive impairment disorder associated with the CNS comprising administration of their compounds or pharmaceutical compositions thereof, such as their composition comprising a second therapeutic agent, as recited in MeKonnen’s claim 12.
Regarding claim 46, MeKonnen claims a method of treating wherein the CNS disorder is age-related, like MCI, AMCI, Alzheimer’s disease, etc. (MeKonnen’s claims 13-26).
Regarding claim 62, MeKonnen speaks to treatment of cognitive impairment associated with brain cancer (abstract, last 4 lines). Therefore, it would have been prima facie obvious to one of ordinary skill to treat cognitive impairment associated with brain cancer by administering MeKonnen’s compounds or pharmaceutical compositions thereof. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of MeKonnen’s disclosure.
Regarding claim 64, MeKonnen claims a method of treating schizophrenia and bipolar disorder comprising administration of their compounds of pharmaceutical compositions or combinations thereof (MeKonnen’s claims 12 and 18).
Regarding claim 65, MeKonnen defines “treating” as comprising alleviation, amelioration, or slowing the progression of one or more symptoms [0215]. Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer MeKonnen’s treatment for a cognitive impairment disorder associated with the CNS and expect alleviation, amelioration, or slowing the progression of one or more symptoms. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of MeKonnen’s disclosure.
Regarding claims 67-68, MeKonnen discloses methods of treating cognitive impairment associated with the CNS in a subject in need or at risk thereof (abstract, line 9-11; [0002]; [0006], last line; and [0164] first 4 lines), such as age-related risks (reading on risk factors associated with aging in instant claim 68) (MeKonnen’s claim 13).
Further regarding claims 25, 30, 45-46, 62, 64-65 and 67-68, Applicant is reminded that similar properties may normally be presumed when compounds are very close in structure. (“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.
Claim 61 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. US 10,815,242 B2 (US ‘242); in view of MeKonnen et al. (US 2019/0055258 A1 – cited in IDS); as applied to claims 1, 3-4, 7-8, 11, 14, 17, 20, 22-25, 30, 45-46, 62, 64-65 and 67-68; further in view of Sengupta et al. (Acta Neuropathol., 2014, 127:593–603 – cited in IDS).
The teachings of US ‘242 and MeKonnen et al. are disclosed above and incorporated herein.
US ‘242 discloses their compounds as α5-GABAA receptor agonists (abstract).
MeKonnen discloses their compounds as α5-GABAA receptor agonists (abstract and [0009]).
While US ‘242 in view of MeKonnen does not specifically teach their compounds for the treatment of brain cancers, the teachings of Sengupta et al. are relied upon for these disclosures.
Sengupta discloses that targeting α5-GABAA receptors in MYC-driven medulloblastomas with a specific α5-GABAA agonist results in decreased cell viability and sanitization to cisplatin (page 601, col. 2, Discussion).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘242 in view of MeKonnen’s compounds for the treatment of brain cancers, such as medulloblastomas. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘242’s disclosure of their compounds, which are taught to be α5-GABAA receptor agonists; MeKonnen’s disclosure of their related α5-GABAA receptor agonists; and Sengupta’s teachings that targeting α5-GABAA receptors in MYC-driven medulloblastomas with a specific α5-GABAA agonist results in decreased cell viability and sanitization to cisplatin (reading on combination therapy).
Claims 1, 3-4, 7-8, 11, 14, 17, 20, 22-25, 30, 45-46, 61-62, 64-65 and 67-68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-37 of U.S. Patent No. US 12,291,535 B2 (US ‘535); in view of MeKonnen et al. (US 2019/0055258 A1 – cited in IDS).
Regarding instant claims 1, 3-4, 7-8, 11, 14, 17, 20, and 22-23, US ‘535 discloses the compounds of Formula X, which read on the instant compounds when instant R2 (US ‘535’s R3) is
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; R6 (US ‘535’s R6) is H or C1-6 alkyl; R1 (US ‘535’s R1) is H, halogen, C1-6 alkyl, -OH, CF3, etc.; US ‘535’s R4/ 5 are H; X is N; W is N; and V is -CR4, wherein R4 (US ‘535’s R2) is C1-6 alkyl (US ‘535’s claim 1).
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(X)
Regarding claim 24, US ‘535 discloses a pharmaceutical composition comprising their compounds and an acceptable carrier, adjuvant, or vehicle (US ‘535’s claim 9).
Regarding claims 25 and 30, US ‘535 discloses a pharmaceutical composition comprising a second therapeutic agent, wherein the second therapeutic agent is an acetylcholine esterase inhibitor, like Donepezil (US ‘535’s claim 10).
Regarding claim 45, US ‘535 claims a method of treating a cognitive impairment disorder associated with the CNS comprising administration of their compounds or pharmaceutical compositions thereof (US ‘535’s claim 14).
Regarding claim 46, US ‘535 claims a method of treating wherein the CNS disorder is age-related, like MCI (US ‘535’s claim 15).
Regarding claim 61, US ‘535 claims a method of treatment of brain cancer comprising administration of their compounds, wherein the brain cancer is medulloblastoma (US ‘535’s claim 21).
Regarding claim 62, US ‘535 speaks to treatment of cognitive impairment associated with brain cancer (US ‘535’s claim 22).
Regarding claim 64, US ‘535 claims a method of treating schizophrenia and bipolar disorder comprising administration of their compounds of pharmaceutical compositions or combinations thereof (US ‘535’s claim 20).
Regarding claim 65, US ‘535 defines “treating” as comprising alleviation, amelioration, or slowing the progression of one or more symptoms (col. 42, lines 11-16). Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘535’s treatment for a cognitive impairment disorder associated with the CNS and expect alleviation, amelioration, or slowing the progression of one or more symptoms. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘535’s disclosure and claims.
Regarding claims 67-68, US ‘535 claims a method of treating wherein the CNS disorder is age-related, like MCI (US ‘535’s claim 15).
Further regarding instant claims 25, 30, 45-46, 61-62, 64-65 and 67-68, Applicant is reminded that similar properties may normally be presumed when compounds are very close in structure. (“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.
While US ‘535 does not disclose their compounds wherein the group circled in X is a carbon, or wherein the positions corresponding to instant X, W, and V are anything other than N, N, and C, respectively, (such as C, N, and O in the instant claims); the teachings of MeKonnen et al. are relied upon for these disclosures.
MeKonnen teaches the compound of Formula I below [0010], in methods for treating cognitive impairment associated with central nervous system (CNS) disorders [0002] – which is the same application as in the instant claims and the claims from US ‘535. MeKonnen’s compounds render the instant compounds obvious when U forms a 6 membered aryl ring with carbons α and β; R1 (corresponding to instant R1) can be H, halogen, C1-6 alkyl, -OH, CF3, etc.; A is C; E can be N; D can be CR6, wherein R6 (corresponding to instant R6) can be H or C1-6 alkyl; F can be N; B can be C; R4/ 5 can be H; Y and Z can be C or N; and X, W, V (corresponding to instant X, W, V) can be N, C, or O.
R3 (corresponding to instant R2) can be
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MeKonnen discloses in their general Formula I that their groups Y and Z can independently be C or N, as long as they were not both nitrogens – meaning that they can both be carbons, as in the instant claims, and still function for the same purpose of treating cognitive impairment associated with the CNS [0019]. Furthermore, MeKonnen discloses that their X, W, V (corresponding to instant X, W, V) can be N, C, or O, as in the instant claims. MeKonnen specifically discloses their group corresponding to X, Y, Z, V, W may be:
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