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 .
Status of the Application
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/05/2026 has been entered.
Claims 2, 25, 27, 35-36, 68, 77 and 89-104 are pending as of the response filed on 02/05/2026. Claims 1, 3-24, 26, 28-34, 37-67, 69-76 and 78-88 are cancelled. Claims 93-104 are newly added. Claims 2, 25, 27, 35-36, 68, 77 and 89-104 are examined herein.
The 35 U.S.C. § 112(b) rejection of previous record is withdrawn in consideration of the claim amendments.
The nonstatutory double patenting rejection of record is updated to address the claim amendments.
Double Patenting – Updated
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 93-104 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5, 20, 36, 41, 52, 61, 67, 77, 81, 83-84, 87 and 112 of co-pending Application No 18/201,885 in view of Fleming et al. (Nitrile-Containing Pharmaceuticals: Efficacious Roles of the Nitrile Pharmacophore, 25 November 2011, hereinafter Fleming, of previous record).
Although the claims at issue are not identical, both sets of claims are drawn to compounds having similar core structures.
The instant application is drawn to compounds of Formula I-a with variables as defined in instant claim 93, or a pharmaceutically acceptable salt thereof.
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The claims of the co-pending ‘885 application are drawn to compounds of Formula I with variables as defined in claim 1, or a pharmaceutically acceptable salt thereof. Claim 4 of the reference ‘885 application teaches Formula I-a-1 with variables R1, ring B and ring A that substantially overlap in scope with the instant claims.
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Claim 84 of the reference ‘885 application teaches a species of compound that is very similar to the following non-elected species of instant claim 100.
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Compound of claim 84 of reference application Compound of instant claim 100
The above compound of the reference ‘885 application differs in the presence of a fluoro group versus a nitrile group attached to the piperidinyl nucleus. Looking into the specification of the reference ‘885 application for the utility of the compounds, the compounds are taught to act as CYP46A1 inhibitors (Para. [0003]), having similar utility to the instantly claimed compounds.
Fleming teaches nitrile-containing compounds as an important pharmacophore in pharmaceuticals (Pg. 1, first paragraph). Fleming teaches the nitrile group to be robust and not readily metabolized, including nitriles attached to fully substituted carbons (Pg. 1, third paragraph – Pg. 2, continued paragraph). Fleming teaches the nitrile mimics the polarization of the halides and is often an excellent halogen bioisostere (Pg. 6, bullet point 6). Fleming teaches improving ADME-Tox profiles by replacing a halogen with a nitrile (Pg. 9, bullet point 7).
According to MPEP 2144.09 (I), A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
According to MPEP 2144.09 (III), “Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979). See also In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (claimed and prior art compounds used in a method of treating depression would have been expected to have similar activity because the structural difference between the compounds involved a known bioisosteric replacement)”.
In the instant case, the cited compounds are so close in structure that, correspondingly, the instant compounds are expected to have very similar or identical utilities and functional properties, rendering them prima facie obvious in view of the claims of the reference ‘885 application. A person of ordinary skill in the art at the time the application was effectively filed would have been motivated to produce the claimed closely-structurally-related compounds in order to provide additional candidates for further pharmacological and/or commercial development. The co-pending ‘ 885 application provides a substantial chemical and functional roadmap for Applicants to utilize without the need for expending additional time and resources, in screening alternative core compounds having CYP46A1 inhibitory activity.
Further, this renders the limitations of instant claims 94-99, prima facie obvious.
Claim 87 of the reference ‘885 application is drawn to a pharmaceutical composition comprising the compound of claim 1 of the reference application or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. This renders the pharmaceutical compositions of instant claims 91-92 and 102-104, prima facie obvious, in view of the above discussion.
Thus claims 1, 4-5, 20, 36, 41, 52, 61, 67, 77, 81, 83-84, 87 and 112 of co-pending application 18/201,885, renders the instant claims 93-104 prima facie obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
The compounds of Formula I-a as in instant claim 2 and instant claim 93 have been found to be free of prior art. Except for the nonstatutory double patenting rejection, all claims would be allowable.
The following is a statement of reasons for the indication of allowable subject matter:
The instant application relates to a compound of general Formula I-a, with variables as defined in instant claim 2 and instant claim 93 and a pharmaceutical composition thereof.
The closest prior art of record is Koike et al. (WO 2013/054822 A1, publication date 18 April 2013, hereinafter Koike).
Koike teaches heterocyclic compounds or a salt thereof, having a cholesterol 24-hydroxylase inhibitory action and pharmaceutical compositions comprising the same (Abstract; Para. [0001]; Para. [0300]; Table 15) (cholesterol 24-hydroxylase is also known as CYP46A1, as evidenced by Para. [0002] of the instant specification). Koike teaches compounds of formula (I), with variables as defined (Paras. [0029]-[0030]). Koike teaches the following exemplary compound, compound 14 (Para. [0289]; Table 7) shown below.
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Compound 54 of Koike overlaps the scope of Formula I-a of instant claim 2 and instant claim 93, wherein
B is
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; three R6 being independently CR6a, R6a is H, the fourth R6 is N (pyridinyl);
A is pyrimidinyl;
m is 0;
n is 1.
Compound 54 of Koike differs from the compounds of Formula I-a of instant claim 2 in the presence of a hydroxyl group versus a nitrile group attached to the piperidinyl nucleus and R1 being a C6 aryl (phenyl) versus the instantly claimed C3-C7 cycloalkyl.
Compound 54 of Koike overlaps the scope of Formula I-a of instant claim 93, wherein
B is
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; three R6 being independently CR6a, R6a is H, the fourth R6 is N (pyridinyl);
A is pyrimidinyl;
m is 0;
n is 1.
Compound 54 of Koike differs from the compounds of Formula I-a of instant claim 93 in the presence of a hydroxyl group versus a nitrile group attached to the piperidinyl nucleus and R1 being an unsubstituted C6 aryl (phenyl). Claim 93 requires R1 to be substituted with 1-4 substituents independently selected from C1-C6 alkyl, C1-C6 alkoxy, and C3-C7 cycloalkyl.
There are at least two changes in going from the compounds of Koike to the compounds of instant Formula I-a as in claim 2 or claim 93, rendering it non-obvious. Therefore, the instant compounds are novel and non-obvious variants of the compounds taught by the prior art.
Conclusion
Claims 93-104 are rejected.
Claims 2, 25, 27, 35-36, 68, 77 and 89-92 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PADMAJA S RAO whose telephone number is (571) 272-9918. The examiner can normally be reached 9:00-5:30 pm EDT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L Klinkel can be reached on (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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/PADMAJA S RAO/Examiner, Art Unit 1627
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