CTNF 18/554,403 CTNF 87582 DETAILED ACTION This Office action details a first action on the merits for the above referenced application No. Claims 1-9, 25, 33, 37-40, and 43-47 are pending in this application. Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Priority This application is a 35 USC 371 National Stage filing of international application No. PCT/US2022/023904 filed on 7 Apr. 2022 and claims benefit under 35 USC 119(e) to US provisional application No. 63/172,181 filed on 8 Apr. 2021. Claim Rejections - 35 USC § 112 07-30-02 AIA 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. Claim 6 is 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. In claim 6, the recitations of “(p-toluenesulfonamide)”, “(trichloroethyl chloroformatate)”, and “(4-nitrobenzenesulfonyl chloride)” are indefinite because it is not clear if the recitations are required limitations or merely examples. Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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. 07-20-aia AIA 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. 07-23-aia AIA The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. 07-20-02-aia AIA This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. 07-21-aia AIA Claim (s) 1-3, 8, 33, 37-40, and 43-46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sankaranarayanan et al. (J. Clin. Med.; published 6 Jul. 2020; see attached 892), in view of Wang et al. (J. Med. Chem.; published 2016; see attached 892) . Sankaranarayanan et al teach advancements in PARP1 targeted nuclear imaging and theranostic probes (see title). Sankaranarayanan et al. teach that to assess PARP1 levels several imaging probes with beta/gamma emitting radionuclides have been proposed. Sankaranarayanan et al. teach diagnostic value in detection of primary tumors as well as metastases (see abstract). Sankaranarayanan et al. teach that various PARP inhibitors such as talazoparib have been clinically approved by the FDA and EMA. Radiohalogens such as 18 F, 123 I, and 131 I are favored for radiolabeling PARPis (pg. 2). Sankaranarayanan et al. teach a schematic representation of PARP1 imaging approaches including PARP expression imageable via PET/SPECT (Fig. 1). Combination therapy of PARPi with chemotherapy and immunotherapy is being assessed to improve cytotoxicity (pg. 2). Sankaranarayanan et al. teach that clinically approved PARPi core structures or their derivatives have been used for labeling with radionuclides (pg. 3). Sankaranarayanan et al. teach 18 F-olaparib (pg. 4). The PET radionuclide 18 F is one of the most favored diagnostic radionuclides in PARP imaging probes. 18 F-PARPi was used to quantify target engagement of clinical PARPis (Olaparib and talazoparib) in NSCLC (pg. 7). PARP1 imaging in emerging as a novel tool for assessing PARP1 expression in tumor and monitoring PARP inhibitor therapy response in the clinic (pg. 11). PARP1 overexpression is various cancers can be exploited as a molecular target in the clinic. Some tracers are fast approaching clinical translation (pg. 12). Sankaranarayanan et al. teach intravenous administration (pgs. 10-11). Sankaranarayanan et al. teach mutated breast cancer (BRCA1/2 mut ) (pg. 2). Sankaranarayanan et al. do no teach the structure of talazoparib or a compound of formula (I) PNG media_image1.png 229 292 media_image1.png Greyscale wherein R 1 is a 18 F or the compound PNG media_image2.png 199 252 media_image2.png Greyscale or an imaging method for diagnosis and treating a patient having cancer comprising (a) administering to a subject a compound of formula (I) and optionally (b) detecting the compound in the subject using an imaging technique such as PET and wherein the compound inhibits PARP1/2 activity optionally further comprising quantifying an amount of the compound in a subject and optionally wherein the method is used to obtain pharmacokinetic data and/or monitor chemotherapy response in a subject optionally wherein the subjected has at least one mutation in BRC1 or BRC2 or the cancer is breast cancer or ovarian cancer and wherein the compound is administered intravenously. Wang et al. teach the discovery and characterization of BMN 673, talazoparib a highly potent and orally efficacious PARP-1/2 inhibitor as an anticancer agent (see title). Wang et al. teach the structure PNG media_image3.png 155 218 media_image3.png Greyscale (see abstract, Fig. 1). Talazoparib demonstrates excellent potency inhibiting PARP1 and PARP2 enzyme activity. Talazaoparib displays favorable PK properties and remarkable antitumor efficacy in BRCA1 mutant MX-1 breast cancer xenograft model following oral administration (see abstract). It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the compound of Sankaranarayanan et al. (talazoparib) by substituting the -F-Ph with 18 F-Ph to arrive at a compound of instant formula (I) wherein R 1 = 18 F ([ 18 F]talazoparib) as taught by Sankaranarayanan et al. and Wang et al. because the [ 18 F]talazoparib would have been expected provide an 18 F-labeled PARP inhibitor approved by FDA and EMA and capable of targeting and PET imaging PARP expressing cancers such as ovarian and breast cancers. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Sankaranarayanan et al. by further intravenously administering the obvious [ 18 F]talazoparib to a subject in need thereof such as a subject having at least one mutation in BRCA1 such as a breast cancer and detect that compound using PET and quantify the amount of the compound in the subject or to obtain pharmacokinetic data or monitor chemotherapy response in the subject and wherein the administration is done prior to, concurrent with or subsequent to immunotherapeutic treatment as taught by Sankaranarayanan et al. and Wang et al. because the administering would have been expected to advantageously enable in vivo PET imaging and quantitation of PARP associated cancer including mutated breast cancer and the monitoring of PARP inhibitor therapy including combination therapy with immunotherapeutic treatment in the clinic and/or assessment of the in vivo pharmacokinetics of [ 18 F]talazoparib . 07-21-aia AIA Claim (s) 1-9, 25, 33, 37-40, and 43-46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sankaranarayanan et al. (J. Clin. Med.; published 6 Jul. 2020; see attached 892), in view of Wang et al. (J. Med. Chem.; published 2016; see attached 892), in further view of Gouverneur et al. (WO 2019/186135 A1; published 3 Oct. 2019; see attached 892) and Zhou et al. (Tetrahedron Lett.; published 2018; see attached 892) . Sankaranarayanan et al. teach as discussed above. Sankaranarayanan et al. do not further teach a compound of instant formula (I) wherein R 1 is 76 Br or 77 Br or a compound wherein amino protecting group is acetyl or Boc or wherein R 1 is pinacolboronate or the compound PNG media_image4.png 366 363 media_image4.png Greyscale . Wang et al. teach as discussed above. Gouverneur et al. teach radiolabeled compounds (see title). Gouverneur et al. teach that there are over 100 clinical trials ongoing using Olaparib as a single drug or in combination with other chemotherapy, immunotherapy or radiation therapies (pg. 2). Gouverneur et al. teach the direct 18 F-radiolabeled analogue of the FDA approved PARP inhibitor [ 18 F]Olaparib (pg. 4). Gouverneur et al. teach 76 Br radiolabeled analogues of Olaparib (pgs. 7-8). Gouverneur et al. teach evaluation the suitability of PARP inhibitor for treating cancer (pg. 13). Gouverneur et al. teach protecting groups (pg. 30). Gouverneur et al. teach the precursor compound PNG media_image5.png 193 274 media_image5.png Greyscale obtained by reacting methyl-2-bromo-5-((4-oxo-((2-trimethylsilyl)ethoxy) methyl)-3,4-dihydrophthalazin-1-yl)methyl)benzoate, bis(pinacolator)diboron, Pd(dppf)Cl 2 and potassium acetate (pg. 70). Gouverneur et al. teach the Boc protecting group (pg. 84). Gouverneur et al. teach the copper mediated 18 F-fluorodeboronation of aryl pinacol boronic esters (pgs. 81-82). Gouverneur et al. teach an ant-PARP-1 monoclonal antibody (pg. 88). Gouverneur et al. teach talazoparib (see pgs. 13, 16, 58, 87, 89, 99) Zhou et al. teach copper-mediated nucleophilic radiobromination of aryl boron precursors: convenient preparation of a radiobrominated PARP-1 inhibitor (see title). Zhou et al. teach 77 Br for radiation therapy (see pg. 1963). Zhou et al. teach copper mediated radiobromination of model compounds containing a boronic acid or boronic ester (see fig. 2). It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Sankaranarayanan et al. so that the talazoparib is radiolabeled with 76 Br or 77 Br as taught Gouverneur et al. and Zhou et al. because those radiolabels would have been expected to advantageously enable PET imaging and radiotherapy of PARP expressing cancers. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Sankaranarayanan et al. so that instant R 2 and R 3 are an amine protecting group and the amine protecting group is a Boc protecting as taught by Gouverneur et al. because the BOC protecting group would have been expected to advantageously enable radiohalogenation by protection and deprotection strategy. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Sankaranarayanan et al. so that the instant R 1 is a pinacol borane as taught by Gouverneur et al. and Zhou et al. that compound would have been expected to advantageously enable radiohalogenation by radiohalodeboronation reaction. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Sankaranarayanan et al. so that the compound is further defined as PNG media_image4.png 366 363 media_image4.png Greyscale as taught by Gouverneur et al. because that compound would have been expected to advantageously enable the preparation of [ 18 F]talazoparib by copper mediated 18 F-fluorodeboronation reaction. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Sankaranarayanan et al. so that the obvious radiolabeled talazoparib gets produced comprising a) providing methyl -2-(4-bromophenyl)-7-fluoro-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-1,2,3,4-tetrahydro-quinoline-5-carboxylate, b) protecting the pyridazinone α-amine and the piperidine amine with amine protecting groups, c) substituting the phenyl 4-bromo group with a boronic acid or a boronate ester, and d) substituting the 4-boronic acid or 4-boronate ester with halogen isotope and e) removing the amine protecting groups to provide the radiolabeled talazoparib derivative as taught by Gouverneur et al. because that method of preparation would have been expected to advantageously enable preparation of a radiolabeled talazoparib derivative by radiohalodeboronation reaction . 07-21-aia AIA Claim (s) 1-4, 6-9, 25, 33, 37-40, and 43-47 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sankaranarayanan et al. (J. Clin. Med.; published 6 Jul. 2020; see attached 892), in view of Wang et al. (J. Med. Chem.; published 2016; see attached 892), and Gouverneur et al. (WO 2019/186135 A1; published 3 Oct. 2019; see attached 892), in further view of Hinchcliff et al. (In J. Gynecol. Cancer; published 22 May 2019; see attached 892) . Sankaranarayanan et al. teach as discussed above. Sankaranarayanan et al. do not further teach the claimed imaging method wherein the immunotherapeutic treatment is an immune checkpoint inhibitor. Wang et al. teach as discussed above. Gouverneur et al. teach as discussed above. Hinchcliff et al. teach PARP inhibitor use in ovarian cancer: expanding indications and novel combination strategies (see title). Hinchcliff et al. teach talazoparib has the strongest DNA binding ability (pg. 956). Hinchcliff et al. teach checkpoint inhibition combination strategies, including immune checkpoint inhibitors such as anti-CTL4 and anti-PD1/PD-L1. Such agents are attractive targets for combination regimens with PARPi (pg. 960). It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Sankaranarayanan et al. so that the administration is done with an immunotherapeutic treatment wherein the immune therapeutic treatment is an immune checkpoint inhibitor as taught by Wang et al., Gouverneur et al. and Hinchcliff et al. because the immune checkpoint inhibitor would have been expected to advantageously enable improved efficacy in patients being treated for a PARP expressing cancer. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN R DONOHUE whose telephone number is (571)270-7441. The examiner can normally be reached on Monday - Friday, 8:00 - 5:00 EST. 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, Michael Hartley can be reached on (571)272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618 / SEAN R. DONOHUE/ Examiner, Art Unit 1618 Application/Control Number: 18/554,403 Page 2 Art Unit: 1618 Application/Control Number: 18/554,403 Page 3 Art Unit: 1618 Application/Control Number: 18/554,403 Page 4 Art Unit: 1618 Application/Control Number: 18/554,403 Page 5 Art Unit: 1618 Application/Control Number: 18/554,403 Page 6 Art Unit: 1618 Application/Control Number: 18/554,403 Page 7 Art Unit: 1618 Application/Control Number: 18/554,403 Page 8 Art Unit: 1618 Application/Control Number: 18/554,403 Page 9 Art Unit: 1618 Application/Control Number: 18/554,403 Page 10 Art Unit: 1618
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