Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Response to Amendment
The response filed 6/23/2026 has been entered. Claims 21-40 and 42-44 are pending in the application. Claims 21-40 and 42 remain withdrawn. Claims 43-44 are examined herein.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied and constitute the complete set presently being applied to the instant application.
Response to Applicant’s Arguments
Regarding the rejection over Forman in view of Pellicciari, applicant argues that the modification taught in Pelliciarri is only described as “comparable” and not “superior” with respect to the results of Figure 1. Further, Forman and Palliciarri fail to teach the elected species or its use as a synthetic intermediate and there is no suggestion that applicant’s compound would find use as an FXR activator. Applicant’s arguments are fully considered but not persuasive. First, the terms “comparable” and “superior” are not mutually exclusive. It is clear from Fig. 1 that the Pellicciarri compounds resembling the bile acid core of the Forman and claimed compounds are in fact comparable in effect but also the compound possessing the beta-hydroxyl is superior (Compound 100). See particularly both compounds compared at 1uM where the error bars of each compound do not overlap:
PNG
media_image1.png
634
543
media_image1.png
Greyscale
.
Further, examiner in the referenced rejection does not state or necessarily rely on the Forman teaching of “superior” FXR activity resulting from the added hydroxyl. Examiner describes the motivation for performing the modification suggested by Pellicciari as the formation of a “a potent, selective FXR modulator” (Action: Page 5). To improve upon the potency is implied by the obviously superior results and only provides further motivation to make the obvious modification. Second, although the exact elected species is not taught in either reference alone, both references are cited in combination in a single rejection and must be considered in view of each other rather than in isolation. Both references teach the same bile acid core; Forman teaches a synthetic route for forming an FXR agonist and a preceding intermediate resembling the intermediate of the examined claims differing only by a hydroxyl; Pellicciari teaches the addition of the same, a hydroxyl in the beta position, results in comparable—yet superior as assessed and depicted in Figure 1—FXR agonists. Therefore, it is obvious to modify the Forman synthesis in view of Pellicciarri to add a beta-hydroxyl to achieve a similar potent FXR agonist, which also exhibits superior activity. The described modification at any point in the Forman synthesis necessarily yields the examined compound. The resulting intermediate is also in fact an intermediate in the synthesis of an FXR agonist, the intended use which applicant ascribes to the elected compound and those of Claims 43-44. Further, there is no requirement that the modified Forman compound (which is the elected compound) possessing an oxo as compared to the C-11 hydroxyl of the final Forman product (unmodified or modified in view of Pellicciari) be an FXR agonist because it is taught as a synthetic intermediate, satisfying the concerns raised by applicant with respect to the use of the elected and prior art compounds. Both the lead compound and elected intermediate are employed for the same use.
Regarding the double patenting rejection previously issued, applicant argues the claims in the ‘533 application are directed to methods and kits for therapeutic use. Applicant also requests the rejection be held in abeyance. Applicant’s arguments are considered but not persuasive. The particular use of the compounds employed in methods and kits does not limit the structure of said compounds so as to distinguish (them and obvious variants thereof) encompassed by the general formula from the claimed compounds. Therefore, the rejection stands and is reissued below. The rejection over ‘533 will not be held in abeyance. See MPEP 804 (I) (B) (1).
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 43-44 are rejected under 35 U.S.C. 103 as being unpatentable over Forman (Steroids 77 (2012) 1335–1338) in view of Pellicciari (WO2014184271, 9/5/2023 IDS).
Forman teaches methods of synthesizing a potent selective FXR agonist as follows (Abstract; Page 1336, Fig. 2):
PNG
media_image2.png
308
706
media_image2.png
Greyscale
.
Intermediate 3 differs from the claimed intermediate in that Int 3 lacks a C11 beta hydroxy group.
Forman does not suggest the addition of a beta hydroxy at the C11 position before or after the synthesis of Int 3.
Pellicciari teaches Compound 100,
PNG
media_image3.png
154
220
media_image3.png
Greyscale
, which differs from Compound 4, the product of Forman, by the addition of a beta hydroxy at the C11 position (Page 30). Pellicciari teaches the particular addition of the beta hydroxy group yields a potent, and selective FXR agonist, the same result desired in Forman (Page 32, Table 1). Pellicciari specifically compares Compound 100 to Forman Compound 4/Obeticholic Acid/INT-747/Pellicciari Compound A, noting increased potency (Figure 1):
PNG
media_image4.png
498
534
media_image4.png
Greyscale
.
Said compounds differ only by the presence of a beta hydroxyl at position C11, the same difference between the Forman intermediate and elected species. One of ordinary skill in the art seeking to form a potent, selective FXR modulator as described by both Forman and Pellicciari, would find it obvious to modify the Forman synthesis through the addition of the beta hydroxy at the C11 to any of the intermediates or starting material of Fig. 2 at any step of the synthesis. Such a modification would yield applicant’s elected species as an intermediate when forming the selective, potent FXR agonist of Forman modified in view of Pellicciarri. One would expect success in forming the intermediate for the synthesis of the potent end product of Pellicciari before the effective filing date of the instant application because the synthetic route deployed in Forman only serves to add an ethyl group to C6 and hydrogenate the oxo group at C7 rather than (de)hydroxylate, leaving the hydroxy groups in tact or preserved by a protecting group.
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.
PROVISIONAL:
Claims 43-44 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1, 4-5, 10-20, 24-25 of copending Application No. 18878533 (hereinafter referred to as intercept).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a genus of bile acid derivatives.
Intercept teaches methods which require the compounds of the instant claims.
Formula (B) of
PNG
media_image5.png
155
272
media_image5.png
Greyscale
and the elected species
PNG
media_image6.png
195
291
media_image6.png
Greyscale
differ in that the elected species possesses an oxo substituent at C7. Intercept explicitly teaches the hydroxy and hydrogen at C7 may instead be a single oxo.
One of skill in the art, in view of Intercept teaching oxo as an alternative embodiment to OH and H, would find it obvious to modify formula (B) accordingly and expect the resulting compound, within the scope of formula (I), to treat cognitive impairment as taught by Intercept.
Since both applications teach bile acid derivatives, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Intercept.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowable.
THIS ACTION IS MADE FINAL. 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 extension fee 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.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Richard G. Peckham whose telephone number is (703)756-4621. The examiner can normally be reached 7:30am - 4:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
Prosecution Insights