NOVEL BENZOTHIOPHENE DERIVATIVES AND USE AS BET INHIBITORS

§102 §112

Detailed Action The present office action is in response to the reply filed on 21 Sep 2026. 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 Claims 1-15 of the pending application have been examined on the merits. Claims 16-20 are withdrawn (see “Response to Applicant Election” below). Priority Applicants identify the instant application, Serial #: 18/853,963, filed 03 Oct 2024, as a National Stage Entry of International Application #: PCT/KR2023/003859, filed 23 Mar 2023, which claims priority from Foreign Application #: KR10-2022-0042469, filed 05 Apr 2022. Information Disclosure Statement The information disclosure statement(s) (IDS) submitted on 03 Oct 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Response to Applicant Election Acknowledgement is made of the remarks filed 21 Sep 2026. Applicant election without traverse of Group I in the reply filed on 21 Sep 2026 is acknowledged. Applicant further elected BBC1115 (below) as the species of Formula 1. PNG media_image1.png 449 764 media_image1.png Greyscale After a search, the elected compound was found free of prior art. Examiner has expanded the Markush search to include the following species of Formula 1: PNG media_image2.png 357 471 media_image2.png Greyscale A search for this species returned prior art. Claims 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 21 Sep 2026. Examiner notes that the relevant anticipation rejection below is based upon art which was found incidental to the search for the elected species. The additional art found is relevant to the claims addressing species which have the same core structure as the instant claims. This is not indicative that the entire scope of the claims has been examined; however, the following art is being applied in an effort to promote compact prosecution of the case. Drawings The drawings are objected to because the sheets of drawings are not numbered. 37 C.F.R. 1.84 states: (t) Numbering of sheets of drawings. The sheets of drawings should be numbered in consecutive Arabic numerals, starting with 1, within the sight as defined in paragraph (g) of this section. These numbers, if present, must be placed in the middle of the top of the sheet, but not in the margin. The numbers can be placed on the right-hand side if the drawing extends too close to the middle of the top edge of the usable surface. The drawing sheet numbering must be clear and larger than the numbers used as reference characters to avoid confusion. The number of each sheet should be shown by two Arabic numerals placed on either side of an oblique line, with the first being the sheet number and the second being the total number of sheets of drawings, with no other marking. Further, Fig. 6 and Fig. 8 are of low-resolution verging on illegible. Examiner requests a higher resolution sheet be submitted for both figures. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance. Specification The abstract of the disclosure is objected to because the abstract contains a reference to chemical formula 1 without including the formula. Further, the last phrase of the abstract, “a pharmaceutical composition comprising same for preventing or treating BET protein-associated diseases” does not make grammatical sense and correction is required. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b). The disclosure is objected to because of the following informalities: The images found on pg. 5, line 17; pg. 6, line 2; pg. 16, line 1; pg. 16, line 6; pg. 16, line 13; pg. 17, line 2; pg. 18, whole page; pg. 22, line 1; pg. 23, line 1; pg. 24, line 2; pg. 26, line 1; pg. 27, line 1; pg. 28, line 4; pg. 29, line 2; pg. 30, Table 2; and pg. 31, Table 31 are of low resolution verging on illegible. Examiner requests that new images be uploaded in higher resolution in black and white to replace the lower quality images. Appropriate correction is required. Claim Objections Claims 1-2 and 4-5 objected to because of the following informalities: The images found in the claims are of low-resolution verging on illegible. Examiner requests new images for each chemical structure be uploaded in higher resolution in black and white. Claim 1 is objected to because of the following informalities: The phrase “X or Y is each…” should be “X and Y are each…” Appropriate correction is required. Claim Rejections - 35 USC § 112(b) 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 1-15 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. Regarding claims 1-2 and 4-5, the claims are directed towards compounds of Chemical Formula 1: PNG media_image3.png 121 254 media_image3.png Greyscale The claims further include the phrase, “Z is the same or different one or more selected from the group…” However, the structure only includes one instance of Z attached to the benzothiophene core while the wording of the claims implies multiple Z substituents may be attached to this core. Further, claim 5 includes the following structures which have more than one Z substituent: PNG media_image4.png 128 188 media_image4.png Greyscale PNG media_image5.png 132 216 media_image5.png Greyscale PNG media_image6.png 162 191 media_image6.png Greyscale PNG media_image7.png 123 175 media_image7.png Greyscale and PNG media_image8.png 113 154 media_image8.png Greyscale The structures and the limitations of the claims therefore lack clarity as to what the scope of the claims entail. Claims 3 and 6-15 are rejected for failing to remedy the deficiencies of the rejected claims. Applicant may overcome this rejection by amending the claims to have a consistent definition of Z. Regarding claim 3, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Regarding claim 5, claim 5 is dependent on claim 1. Claim 1 is directed to compounds of Chemical Formula 1: PNG media_image3.png 121 254 media_image3.png Greyscale Claim 1 defines variables X and Y as each being independently H, halo, cyano, alkyl, alkenyl, alkynyl, -(Ra)C(=O)Rb, -(Ra)C(=O)N(Rb)(Rc), -(Ra)C(=O)ORb, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, pyridine, alkyl pyridine, piperidine, piperidinopyridine, indazole, or PNG media_image9.png 52 72 media_image9.png Greyscale . It is unclear how the following structures in Claim 5 meet the limitations of X and Y: PNG media_image4.png 128 188 media_image4.png Greyscale PNG media_image5.png 132 216 media_image5.png Greyscale PNG media_image7.png 123 175 media_image7.png Greyscale PNG media_image8.png 113 154 media_image8.png Greyscale PNG media_image10.png 183 128 media_image10.png Greyscale Specifically, there is no limitation found in claim 1 which allows for the alkyl aryl or alkyl heteroaryl attachments of claim 5. Further, it is unclear how the following structures found in claim 5: PNG media_image10.png 183 128 media_image10.png Greyscale and PNG media_image11.png 140 124 media_image11.png Greyscale can have a methyl group attached to the thiophene ring when only the amide group is attached to the thiophene ring in Formula 1. Applicant may overcome this rejection by amending the claims to allow for all structures of claim 5 to be included in claim 1. Claim Rejections - 35 USC § 112(d) 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. Claims 7-11 are 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. Claims 7-11 are dependent claims of claim 6 which is directed to a pharmaceutical composition “for preventing or treating bromodomain extra-terminal (BET) protein-associated diseases, comprising the compound or pharmaceutically acceptable salt thereof according to claim 1.” The phrase “for preventing or treating bromodomain extra-terminal (BET) protein-associated diseases” is interpreted as an intended use and is of no consequence to the claim construction. See MPEP § 2111.02(II). Claims 7-11 only include further limitations of the intended use and therefore do not effectively further limit claim 6. 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. Claim Rejections - 35 USC § 102 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. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chemical Abstracts Service (“N-(3-Amino-3-oxopropyl)-N-phenylbenzo[b]thiophene-2-carboxamide,” (CAS 1017105-45-1) CAS Registry File Accessed 07 Oct 2026 from STN, entered into STN 24 Apr 2008), hereinafter CAS. The instant claims are directed to compounds of Formula 1: PNG media_image3.png 121 254 media_image3.png Greyscale Examiner has expanded the Markush search to the following compound: PNG media_image2.png 357 471 media_image2.png Greyscale Which is a species of Formula 1 when X is –(Ra)C(=O)N(Rb)(Rc); Y is PNG media_image9.png 52 72 media_image9.png Greyscale ; R1 is H; and Z is H. CAS teaches the following compound: PNG media_image2.png 357 471 media_image2.png Greyscale This compound anticipates the instant claims. The following anticipation rejections below are based upon art which was found incidental to the search for the elected species. The additional art found is relevant to the claims addressing species which have the same core structure as the instant claims. This is not indicative that the entire scope of the claims has been examined; however, the following art is being applied in an effort to promote compact prosecution of the case. Claim(s) 1 and 6-11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by ElHady et al. (J Med Chem, 2017, 60:5377-5391), hereinafter ElHady. ElHady Teaches Compounds 5a, 6a, 12a, 13a, 14a, and 15a which are derivatives of methoxybenzothiophene-2-carboxylamides where R is PNG media_image12.png 37 63 media_image12.png Greyscale , PNG media_image13.png 39 63 media_image13.png Greyscale , PNG media_image14.png 41 71 media_image14.png Greyscale , PNG media_image15.png 47 66 media_image15.png Greyscale , PNG media_image16.png 47 86 media_image16.png Greyscale , or PNG media_image17.png 52 83 media_image17.png Greyscale , respectively (pg. 5379, Table 1). ElHady further teaches Compound 18b and Compound 19b which are N-methylated derivatives of the reference compounds with the following formula: PNG media_image18.png 50 108 media_image18.png Greyscale Where R is PNG media_image19.png 53 65 media_image19.png Greyscale for Compound 18b and PNG media_image20.png 60 49 media_image20.png Greyscale for Compound 19b (pg. 5381, Scheme 2). ElHady further teaches administering the compounds in pharmaceutically acceptable compositions to T24, MDA-MB-231, and HepG2 cells (pg. 5389, column 1). These compositions are created using the compounds and DMEM medium (pg. 5389, column 1). Pertinent Prior Art The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. U.S. Patent No. 5,712,304 is considered pertinent for teaching compounds with the same core structure as the instant claims. WO 2010/081904 is considered pertinent for teaching compounds with the same core structure as the instant claims. Conclusion No claim is allowed. Correspondence Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F. 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 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. /J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625