DETAILED ACTION
Continued Examination Under 37 CFR 1.114
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 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6/05/2026 has been entered.
AIA Status of the Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Newly submitted claims 65 and 67-73 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: the claims are drawn to a non-elected compound species.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 65 and 67-73 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Response to Arguments
Applicant’s arguments, filed 6/05/2026, have been fully considered.
The rejection of claims 1 and 57-58 under 35 U.S.C. 112(b) is WITHDRAWN in view of Applicant’s amendments to the claims.
Applicant traverses the rejection of claims on the grounds of nonstatutory double patenting over copending Application No. 17/776,531 in view of Williams et al (Foye’s Principles of Medicinal Chemistry, 5th Edition, Pages 59-63, 2002; of record) and Wipf (Pharmacy Lecture Notes on Bioisosterism, Pages 43-49, 2/14/2008 - available online at https://www.yumpu.com/en/document/view/18242742/pharmacy-lecture-08-ccc as of 7/17/2013l; of record).
As argued by Applicant, “[c]laim 1 is directed to compounds of Formula (I’), which contain a spirocyclic lactam core” as follows:
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whereas “the claims of the ‘531 application contain compounds with a spirocyclic lactone core” (Applicant Arguments, Page 30) as follows:
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.
As further argued by Applicant, “the claimed lactam compounds are non-obvious, and therefor patentably distinct over, the lactone containing compounds claimed in the ‘531 application” (Applicant Arguments, Page 31).
In particular, Applicant notes that “receptors display a high degree of selectivity, and that small variations in ligand structure can have a significant effect on receptor-ligand binding” (Applicant Arguments, Page 31). Applicant additionally points out that “[t]his is particularly challenging when a receptor is part of a family of proteins that are related and have a high degree of homology yet sill have differences in their amino acid sequences that impart small changes in a binding site” as is the case of “the 5-HT receptor family... with at least seven (7) family members, each with various subfamilies and subpopulations which are expressed in various tissues” (Applicant Arguments, Page 31). And, as further argued by Applicant, “[a]mides, such as those contained by the instantly claimed lactams, exhibit double bond character due to the resonance of the nitrogen atoms. This results in subtle, but important differences in rigidity, conformation, and hydrogen bonding capacity as compared to esters” (Applicant Arguments, Page 32).
None of this is disputed.
Based on all of the foregoing, Applicant argues that “contrary to the Office’s assertion, replacement of a lactone with a lactam is not obvious” and “the Office has provided no basis for a person of ordinary skill the expect the claimed compounds to act as inhibitors of the 5-HT7 receptor, particularly when structural modifications can impact the ability of the compound to bind to the receptor” (Applicant Arguments, Page 32).
Applicant’s arguments have been considered but are not found persuasive. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413 (CCPA 1981); In re Merck & Co., 800 F.2d 1091 (Fed. Cir. 1986). In the instant case, the rejection is based further on Williams et al and Wipf. As discussed in the previous Action:
As taught by Williams et al “[w]hen a lead compound is first discovered for a particular disease state, it often lacks the required potency and pharmacokinetic properties suitable for making it a viable clinical candidate… The medicinal chemist therefore must modify the compound to reduce or eliminate these undesirable features without losing the desired biological activity. Replacement or modification of functional groups with other groups having similar properties is known as isosteric or bioisosteric replacement” (Page 59). Although it is clear that "the use of bioisosteric replacement (classical or nonclassical) in drug development is highly dependent upon the biological system being investigated” and that “[n]o hard and fast rules exist to determine what bioisosteric replacement is going to work with a given molecule” it is also clear that “some generalizations have been possible” (Page 60). Notably, one such generalization is that -O- and -NH- can replace each other (Page 59, Table 2.8).
Indeed, as similarly taught by Wipf, discussing bioisosteres wherein “substituents or groups which chemical or physical similarities that produce similar biological properties” to “attenuate toxicity, modify activity of lead, and/or alter pharmacokinetics of lead” (Page 43 of 64), the replacement of -O- for -NH-, including in rings to replace tetahydrofuran with pyrrolidine, is a classical isostere (Page 45 of 64).
Accordingly, based further on Williams et al and Wipf, it would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was made to replace -O- in Compound 6 of the ‘531 application with -NH- (i.e., replace the tetrohydrofuran ring with a pyrrolidine ring) to arrive at the instantly claimed compound. The person of ordinary skill in the art at the time the invention was made would have been motivated to make the bioisosteric modifications in an effort to synthesize similar compounds that retain biological activity, but have improved physiochemical properties and better pharmacokinetic behavior, with a reasonable expectation of success.
As such, the nonstatutory double patenting rejection of claims is MAINTAINED.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 1, 54-58 and 66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 6-10, 41-42, 48-49 of ALLOWED Application No. 17/776,531 in view of Williams et al (Foye’s Principles of Medicinal Chemistry, 5th Edition, Pages 59-63, 2002; of record) and Wipf (Pharmacy Lecture Notes on Bioisosterism, Pages 43-49, 2/14/2008 - available online at https://www.yumpu.com/en/document/view/18242742/pharmacy-lecture-08-ccc as of 7/17/2013l; of record).
Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘531 claims are drawn to compound of Formula (1*) (claim 1) and compositions thereof (claim 42), including, for example, the following compound species:
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(claim 41, Compound 6);
which differs from the instantly claimed compounds in comprising -O- in place of -NH- (i.e., comprising a tetrohydrofuran ring as opposed to a pyrrolidine ring), as indicated by arrow.
Yet, as taught by Williams et al “[w]hen a lead compound is first discovered for a particular disease state, it often lacks the required potency and pharmacokinetic properties suitable for making it a viable clinical candidate… The medicinal chemist therefore must modify the compound to reduce or eliminate these undesirable features without losing the desired biological activity. Replacement or modification of functional groups with other groups having similar properties is known as isosteric or bioisosteric replacement” (Page 59). Although it is clear that "the use of bioisosteric replacement (classical or nonclassical) in drug development is highly dependent upon the biological system being investigated” and that “[n]o hard and fast rules exist to determine what bioisosteric replacement is going to work with a given molecule” it is also clear that “some generalizations have been possible” (Page 60). Notably, one such generalization is that -O- and -NH- can replace each other (Page 59, Table 2.8).
Indeed, as similarly taught by Wipf, discussing bioisosteres wherein “substituents or groups which chemical or physical similarities that produce similar biological properties” to “attenuate toxicity, modify activity of lead, and/or alter pharmacokinetics of lead” (Page 43 of 64), the replacement of -O- for -NH-, including in rings to replace tetahydrofuran with pyrrolidine, is a classical isostere (Page 45 of 64).
Accordingly, based further on Williams et al and Wipf, it would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was made to replace -O- in Compound 6 of the ‘531 application with -NH- (i.e., replace the tetrohydrofuran ring with a pyrrolidine ring) to arrive at the instantly claimed compound. The person of ordinary skill in the art at the time the invention was made would have been motivated to make the bioisosteric modifications in an effort to synthesize similar compounds that retain biological activity, but have improved physiochemical properties and better pharmacokinetic behavior, with a reasonable expectation of success.
Conclusion
All claims are drawn to the same invention claimed in the application prior to the entry of the submission under 37 C.F.R. 1.114 and could have been finally rejected on the grounds and art of record in the next Office Action if they had been entered in application prior to entry under 37 C.F.R. 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a Request for Continued Examination and the submission under 37 C.F.R. 1.114. See MPEP 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 C.F.R. 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 extension fee pursuant to 37 C.F.R. 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 CRAIG D RICCI whose telephone number is (571) 270-5864. The examiner can normally be reached on Monday through Thursday, and every other Friday, 7:30 am - 5:00 pm ET.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached on (571) 272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CRAIG D RICCI/Primary Examiner, Art Unit 1611
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