SMALL MOLECULE STING ANTAGONISTS

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 . 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. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 16 September 2026, has been entered. Election/Restrictions Applicants’ claim amendments render moot the prior art rejection of record. Therefore, the Examiner extended the Markush search to the full scope of instant claim 1 but did not find any prior art. Thus, the Election of Species Requirement of 24 April 2025, is withdrawn, as all claims are free of the prior art. All claims have been examined on the merits. Current Status of 17/798,552 This Office Action is responsive to the amended claims of 16 September 2026. Claims 1, 4, 9, 12-13, 17, 19-20, 27, 35-36, and 42-45 have been examined on the merits. Claims 1, 13, 17, 19-20, 27, 35, and 45 are currently amended. Claims 4, 9, 36, and 42-44 are previously presented. Claim 12 is original. Priority The effective filing date is 12 February 2020. Information Disclosure Statement The information disclosure statement (IDS) submitted on 16 September 2026, was filed after the mailing date of the Final Office Action on 16 June 2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Response to Arguments The Examiner acknowledges receipt of and has reviewed Applicants’ claim amendments and Reply of 16 September 2026. Applicants canceled claim 33 thereby rendering moot the 35 USC 112(d) rejection of record. Applicants amended claim 1 by removing -CH2- as an alternative embodiment for variable X7 which renders moot the anticipatory prior art rejection of record. Response to Amendment Claim Objections Claim 13 is objected to for the poor resolution of the 1H-indolyl: PNG media_image1.png 136 178 media_image1.png Greyscale . The artisan cannot discern its point of attachment (should be denoted with a squiggly mark) and the missing N heteroatom in the 5-membered ring of the indolyl. Appropriate corrections are required. Note: Please review all claims to expedite allowance and verify that illustrated moieties in lists are 1) clearly visible and discernible and 2) include a discernible point of attachment. Claim Rejections - 35 USC § 112 The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claims 43-44 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification and/or prior art, while being enabling for treating and/or ameliorating the diseases of claims 43-44, do not reasonably provide enablement for preventing the diseases of claims 43-44. The specification and/or prior art do not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. The Wands Factors used in an (scope of) enablement rejection include (per MPEP 2164.01(a)): The breadth of the claims: The method claims 43-44 are each drawn to a method of treating, ameliorating, or preventing the diseases of the claims 43-44 by administering the compound of formula I of claim 1. The nature of the invention: The invention belongs to biotechnology, more specifically, immunotherapy involving pharmaceutical compositions comprising: the compounds of genus formula I of instant claim 1 which modulate STING receptors. As stated in the Background section of the Specification, the STING receptors are involved in innate immune cell signaling. Therefore, the Examiner is interpreting the broadest reasonable interpretation (BRI) of the method claims 43-44 to include treating, ameliorating, or preventing any disease of claims 43-44. The state of the prior art: A review of STN’s Registry, HCaplus, and Casreact databases does not find prior art for genus formula I of instant claim 1. Furthermore, there is no known prior art that would support preventing the diseases of claims 43-44. For example, the reference LUPUS (Lupus Research Alliance. “What is Lupus?”. Available to the public: 3 May 2017. Accessed 25 September 2026. Available from: < https://www.lupusresearch.org/about-lupus/what-is-lupus/ >), discloses that lupus is unpredictable in nature (see page 4 of 7 under the heading “Why is lupus so complex?”). This begs the question: If we cannot predict who will get lupus, how can we prevent it? Moreover, the reference T1D (Monzavi, Roshanak. “Symptoms, Treatment and Prevention of Type 1 Diabetes.” Available to the public: 13 July 2015. Accessed: 25 September 2026. Available from: < https://www.chla.org/blog/advice-experts/symptoms-treatment-and-prevention-type-1-diabetes > ), discloses that there are no known therapies that can alter the immune system and prevent it from destroying beta cells; hence, there is no known way to prevent Type 1 diabetes (page 4 of 7). The level of one of ordinary skill: The level of one of ordinary skill includes the knowledge/skill to engage in a reasonable amount of experimentation to make and use the pharmaceutical compositions of claim 1 based on the disclosure in the Specification (pages 1-5, 64-206, and Biological Assay data pages 206-209). The one of ordinary skill also has the knowledge to engage in a reasonable amount of experimentation to treat some diseases, such as cardiovascular disease. However, no one has skill to engage in the undue burdensome level of experimentation required to provide guidance/enablement for treating or preventing the diseases/disorders of the claims 43-44. The level of predictability in the art: The art is predictable to make the instantly claimed compounds and pharmaceutical compositions. However, the art does not provide predictability as to which diseases and disorders can be prevented. To generate this level of guidance, one has to engage in undue burdensome experimentation (since no predictability in the art) to test the pharmaceutical composition against every disease of claims 43-44. This level of experimentation would be required to match the scope of instant claims 43-44. The amount of direction provided by the inventor: Inventors have provided direction as to making the pharmaceutical compound and composition (pages 64-206 of the instant Specification). Inventors have also provided direction as to using the pharmaceutical composition to treat (but not prevent) immune-related diseases involving STING (see pages 1-5; and see “Biological Assay” data pages 206-209 of the instant Specification). The existence of working examples; and Applicants’ Specification provides guidance/enablement with working examples of how Applicants synthesized their compounds of genus formula I (claim 1). See, for example, pages 64-206 of the instant Specification). Moreover, Applicants have guidance/enablement in their Specification for treating STING/immune-related diseases of claims 43-44 by administering the instant pharmaceutical compositions of the instant claims (see pages 1-5 and “Biological Assay” data pages 206-209 of the Specification). This guidance does not support preventing any of the diseases of the claims 43-44. The quantity of experimentation needed to make or use the invention based on the content of the disclosure: Applicants’ invention requires a high level/quantity of experimentation to make/use the invention in order to ascertain what diseases of claims 43-44 can be prevented by administering a compound of instant claim 1. While Applicants have provided guidance in their Specification for making the pharmaceutical compound and composition of claim 1, they have not provided enough evidence that said pharmaceutical composition can be used to prevent the scope of diseases or disorders per the BRI of instant claims 43-44. At best, the Specification does provide enablement/guidance for using the instantly claimed pharmaceutical composition to treat (not prevent) the diseases of claims 43-44 (see Specification pages 206-209). Therefore, claims 43-44 are both rejected under 35 USC 112(a) for lacking scope of enablement for the scope of preventing the diseases or disorders of claims 43-44. To render moot this scope of enablement rejection: Applicants should delete “prevent” and/or “prevention”/”preventing” from the claims. 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, 4, 9, 12-13, 17, 19-20, 27, 35-36, and 42-45 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 (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 1 recites the limitation “R12" (see first line page 3). There is insufficient antecedent basis for the limitation “R12” in the claim. The variable R12 in the claim 1 narrative (see first line page 3) renders the metes and bounds of claim 1 undefined (hence rendering claim 1 indefinite under 35 USC 112(b)). The artisan does not know where antecedent basis for R12 is found now since Applicants deleted CR11R12 as an alternative embodiment for variable X7. There are no previous (antecedent) bases for variable R12. Please delete variable R12 from the claim 1 narrative (and any other occurrence within the claim-set) to render moot this rejection. Claims 4, 9, 12-13, 17, 19-20, 27, 35-36, and 42-45 are similarly rejected as indefinite under 35 USC 112(b) since these claims refer back to claim 1 but do not remedy the rationale underpinning the basis for rejecting claim 1. Claims 42-44, each drawn to a method involving administering a compound of claim 1 to a subject in need thereof, are rejected as indefinite under 35 USC 112(b). The metes and bounds of these method claims are undefined since the artisan does not know how it is physically possible to administer “a compound” (meaning “one compound”) to a subject in need thereof. This rejection can be rendered moot if Applicants revise claims 42-44 to say -- administering the pharmaceutical composition of claim 36 to a subject in need thereof -- . 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. Claim 9 is 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. Dependent claim 9 is rejected under 35 USC 112(d) as it does not further narrow/limit the alternative embodiment choices of variable L4 from parent claim 1. In fact, it presents the same 8 choices as variable L4 of parent claim 1. 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. Conclusion No claims are presently allowable as written. There is no known prior art reference that either teaches or anticipates a compound of formula I according to instant claim 1. The reference ACS (American Chemical Society. Chemical Abstract Service. RN 2230497-18-2. Entered into STN: 11 July 2018, previously provided to Applicants in previous Office Action), discloses the compound: PNG media_image2.png 136 406 media_image2.png Greyscale (previously provided to Applicants during the previous Office Action), wherein: X2 is -CR2, wherein R2 is -L1-L2-L3-L4-R15, wherein R17 and R18 are each H; L4 is absent; R15 is phenyl substituted with -NR20R21, wherein R20 and R21 are each H; X3 is -CR3; R1, R3, R4, R5 are each H; X6 is -C(=O); “n” is 1; Z is -CR9R10, wherein each of R9 and R10 are H; X7 is -CR11R12, wherein R11 and R12 are H. However, Applicants removed the embodiment CR11R12 from the list of choices of alternative embodiments for variable X7 of independent instant claim 1. Therefore, ACS is no longer considered a prior art reference. Furthermore, the co-pending 18/682,878 is drawn to a distinct invention and therefore cannot be a double patent reference. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN S KENYON whose telephone number is (571)270-1567. The examiner can normally be reached Monday-Friday 10a-6p. 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, Andrew D Kosar can be reached at (571) 272-0913. 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. /JOHN S KENYON/Primary Patent Examiner, Art Unit 1625