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 Claims
Claims 17-35 are pending in this application. Claims 1-16 have been cancelled by Applicant.
Allowable Subject Matter
Claim 26 is allowed.
Claim Objections
Claim 17 is objected to because of the following informalities: In view of claim amendments, each of the variables E1-6 and U1-3 has been narrowed to encompass a single option, therefore, Applicant should substitute these variables from each bicyclic ring A below with the corresponding options, for simplicity and clarity.
PNG
media_image1.png
75
307
media_image1.png
Greyscale
Appropriate correction is required.
Claims 22-23 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.
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 17-21, 24-25, and 27-35 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (WO 2020/123827 A1 – Int. Filing Date: Dec. 12th, 2019) (“Yu”); in view of Meanwell et al. (J. Med. Chem. 2011, 54, 2529–2591) (“Meanwell”).
Regarding instant claims 17, Yu discloses their compounds of Formula I and III below as THRα and THRβ inhibitors (abstract; and pages 3 and 5) – which is the same intended use of the instant compounds. Yu’s compounds read on the instant structures when R1 (corresponding to instant R1) is H, CN, alkyl, etc.; R2-3 (corresponding to instant R3d, 3a) are halogen or alkyl; and R4 is H.
PNG
media_image2.png
197
265
media_image2.png
Greyscale
PNG
media_image3.png
168
351
media_image3.png
Greyscale
(III)
Yu specifically discloses their preferred embodiments 10 and 14 below (page 7), which read on the instant compounds when instant ring A is
PNG
media_image4.png
92
112
media_image4.png
Greyscale
; R3a, 3d are Cl; R3b, 3c are H; R1 is H or CN; and Ry is Cl.
PNG
media_image5.png
118
196
media_image5.png
Greyscale
PNG
media_image6.png
117
172
media_image6.png
Greyscale
While Yu’s compound a have different connectivity compared to the instant compounds, (in instant compounds the Y group connects to the phenyl corresponding to A-ring, while in Yu’s compounds Y connects to the position corresponding to instant E4), 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).
While Yu’s preferred embodiments have a =N in the position corresponding to instant E5 (which is limited to =CR4h in the instant claims), 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 C=C and C=N as classical divalent bioisosteres (see Table 1, page 2530).
Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Yu’s disclosed formulae; 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 THRα and THRβ inhibitor compounds disclosed by Yu; in view of Meanwell’s teaching that, 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, and their disclosure that C=C and C=N as classical divalent bioisosteres. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, by replacing Yu’s N (corresponding to instant E5) for a C to arrive at the instant invention.
Regarding claim 18, Yu discloses their preferred embodiments 10 and 14 above, wherein the group corresponding to instant R3a, 3d are Cl; R3b, 3c are H.
Regarding claim 19, Yu discloses their preferred embodiments 10 and 14 above, wherein the group corresponding to instant R1 is H or CN.
Regarding claims 20-21, Yu discloses their preferred embodiments 10 and 14 above, wherein the group corresponding to instant Rc is H. Furthermore, 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. Therefore, the instant compounds wherein Rc is Me are obvious in view of Yu.
Regarding claim 24, Yu in view of Meanwell discloses their preferred embodiments 10 and 14 above, wherein the group corresponding to instant E5 is =CR4h (after substitution of Yu’s =N with its bioisostere =CR4h, as taught by Meanwell), reading on the instant claim when R4h is H.
Regarding claim 25, Yu discloses their compounds of Formula III above, wherein the group R4 can be -OCF3 (corresponding to instant Ry being C1 alkoxy substituted with 3 Ry4 groups, wherein the Ry4 groups are F).
Regarding claim 27, Yu claims a pharmaceutical composition comprising their compounds and a pharmaceutically acceptable adjuvant (Yu’s claim 18).
Regarding claims 28-35, Yu discloses their compounds for the treatment of diseases related to thyroid hormone receptors in humans (mammal) ([0004]-[0005]). Yu claims methods for the treatment of diseases like hyperlipidemia, non-alcoholic steatohepatitis (NASH) comprising administration of their compounds or pharmaceutical compositions thereof.
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer Yu in view of Meanwell’s compounds for the treatment of conditions related to thyroid hormone receptors in mammals. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Yu discloses their compounds and pharmaceutical compositions thereof in methods of treating THR related diseases, such as hyperlipidemia and non-alcoholic steatohepatitis (NASH).
Furthermore, the courts have found 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)).
Response to Arguments
Claims
Claim amendments are acknowledged and have been entered. No new matter has been introduced.
Claim Rejections - 35 USC § 112(a)
Applicant’s arguments, see pages 15-16, filed 02/05/2026, with respect to 35 USC § 112(a) rejections have been fully considered and are persuasive. The 35 USC § 112(a) rejection of the claims has been withdrawn.
Claim Rejections - 35 USC § 103
Applicant’s arguments, see pages 15-16, filed 02/05/2026, with respect to 35 USC § 103 rejections have been fully considered and are persuasive. The 35 USC § 103 rejection of the claims has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Yu in view of Meanwell.
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.
Examiner interviews are available via telephone 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 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.
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.
/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
Prosecution Insights