PROCESS OF MAKING APOPTOSIS-INDUCING AGENTS

§102 §103 §DP

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 Claim Status Claims 1-23 are pending. Claims 1-23 are under examination. Claims 1-12, 16-17 and 19-23 are rejected. Claim 18 is objected to. Claims 13-15 are allowed. Election/Restrictions A restriction was not mailed. Reasoning for doing so is as follows. Group I, claims 1-12 and 16-21, Group II claim 13, Group III claim 14, Group IV claim 22. Group V claim 23. Claims 1, 10, 13, 14, 15, 16, 22, and 23 are independent claims. Claims 2-9 depend from claim 1, claims 11-12 depend on claim 10 and claims 17-21 depend from claim 16. Claims 1 and 10 overlap in scope with claim 20. Claim 14 overlaps in scope with claim 16. Claim 15 overlaps in scope with claim 18. Claims 13 and 14 overlap in scope with regards to compound (2-6). Hypothetically, upon election of Group I, a large portion of the claims would have necessarily been examined. Leaving only claims 13-14 and 22-23. Filing Receipt PNG media_image1.png 170 998 media_image1.png Greyscale PNG media_image2.png 120 992 media_image2.png Greyscale PNG media_image3.png 144 1002 media_image3.png Greyscale PNG media_image4.png 94 996 media_image4.png Greyscale Claim Rejections - 35 USC § 102 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 person shall be entitled to a patent unless – (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. Claim(s) 1-12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Harper et al. 2021 (Commercial-Scale Visible-light Trifluoromethylation of 2-Chlorothiophenol using CF3I gas., ChemRxiv, 16 pages, Published 10/14/2021) or Harper et al. 2022 (Commercial-Scale Visible Light Trifluoromethylation of 2-Chlorothiophenol Using CF3I Gas. Org. Process Res. Dev., 26(2), Pages A-I, Published 02/07/2022). MPEP 2153.01(a) Grace Period Inventor-Originated Disclosure Exception AIA 35 U.S.C. 102(b)(1)(A) first provides that a disclosure which would otherwise qualify as prior art under AIA 35 U.S.C. 102(a)(1) is excepted as prior art if the disclosure is made: (1) one year or less before the effective filing date of the claimed invention; and (2) by the inventor or a joint inventor or by another who obtained the subject matter disclosed directly or indirectly from the inventor or a joint inventor (i.e., an inventor-originated disclosure). Thus, a disclosure that would otherwise qualify as prior art under AIA 35 U.S.C. 102(a)(1) may not be used as prior art by Office personnel if the disclosure is made one year or less before the effective filing date of the claimed invention, and the evidence shows that the disclosure is an inventor-originated disclosure…… . Specifically, Office personnel may not apply a disclosure as prior art under AIA 35 U.S.C. 102(a)(1) if the disclosure: (1) was made one year or less before the effective filing date of the claimed invention; (2) names the inventor or a joint inventor as an author or an inventor; and (3) does not name additional persons as authors on a printed publication or joint inventors on a patent. This means that in circumstances where an application names additional persons as joint inventors relative to the persons named as authors in the publication Current Applicant: AbbVie Inc. Current inventors: PNG media_image5.png 98 283 media_image5.png Greyscale PNG media_image6.png 91 294 media_image6.png Greyscale PNG media_image7.png 70 284 media_image7.png Greyscale Authors of references: Harper et al. 2021 underlined names identical to current inventors. Kaid Harper1, Timothy Grieme1, Timothy Towne1, Daniel Mack1, Moiz Diwan1, Yi-Yin Ku1, Jeremy Griffin1, Robert Miller1, En-Xuan Zhang2, Zhi-qing Liu2, Song-yuan Zheng2, Ning-ning Zhang2, Srinivas Grangula2, Jia-long Yuan2, Ping zhong Huang2, James Gage Companies: AbbVie and Asymchem Harper et al. 2022 underlined names identical to current inventors. Kaid C. Harper,* En-Xuan Zhang,* Zhi-Qing Liu, Timothy Grieme, Timothy B. Towne, Daniel J. Mack, Jeremy Griffin, Song-Yuan Zheng, Ning-Ning Zhang, Srinivas Gangula, Jia-Long Yuan, Robert Miller, Ping-Zhong Huang, James Gage, Moiz Diwan, and Yi-Yin Ku Companies: AbbVie and Asymchem Harper et al. 2021 disclose the following reaction (p. 3) PNG media_image8.png 218 809 media_image8.png Greyscale Compound 2 being current compound (1-2), 1 being current compound (1-1), CF3I being CF3I and the current alkylation with CF3, irradiation with 450nm reads on claims 1-4 and the Ru catalyst is the catalyst in current claim 5. Concerning the two feed system in current claims 6-8, Harper et al. 2021 disclose the following on page 9. PNG media_image9.png 376 850 media_image9.png Greyscale Concerning the feed make-up, claims 6-8, Harper et al. 2021 disclose the following on page 6. “A system which combined the photocatalyst and thiophenol 1 in a feed and TMG and CF3I in another feed met the criteria of being stable over long periods of time, gave consistent reaction performance, and was amenable to the available processing equipment”. The TMG is the amine base 1, 1,3,3-tetramethylguanidine (TMG) (par. 69, page 31 of the spec.). Concerning claim 9, the above photoreactor is post the mixing of the two feeds. Concerning claim 10, Harper et al. 2021 disclose the following on page 10. PNG media_image10.png 275 687 media_image10.png Greyscale Compounds 2 and 8 above are current compounds (1-2) and (1-3) respectively. The above H5IO6 is the current oxidizing agent. Concerning claim 12 and the continuous production of (1-2) from (1-1) and (1-3) from (1-2), Harper et al. 2021 disclose the following on page 12. PNG media_image11.png 336 914 media_image11.png Greyscale PNG media_image12.png 463 915 media_image12.png Greyscale This anticipates the claims. Harper et al. 2022 disclose the following reaction (p. B) PNG media_image8.png 218 809 media_image8.png Greyscale Compound 2 being current compound (1-2), 1 being current compound (1-1), CF3I being CF3I and the current alkylation with CF3, irradiation with 450nm reads on claims 1-4 and the Ru catalyst is the catalyst in current claim 5. Concerning the two feed system in current claims 6-8, Harper et al. 2022 disclose the following on page D. PNG media_image9.png 376 850 media_image9.png Greyscale Concerning the feed make-up, claims 6-8, Harper et al. 2022 disclose the following on page D lower left column. “A system which combined the photocatalyst and thiophenol 1 in a feed and TMG and CF3I in another feed met the criteria of being stable over long periods of time, gave consistent reaction performance, and was amenable to the available processing equipment”. The TMG is the amine base 1, 1,3,3- tetramethylguanidine (TMG) (par. 69, page 31 of the spec.). Concerning claim 9, the above photoreactor is post the mixing of the two feeds. Concerning claim 10, Harper et al. 2022 disclose the following on page F. PNG media_image10.png 275 687 media_image10.png Greyscale Compounds 2 and 8 above are current compounds (1-2) and (1-3) respectively. The above H5IO6 is the current oxidizing agent. Concerning claim 12 and the continuous production of (1-2) from (1-1) and (1-3) from (1-2), Harper et al. 2022 disclose the following on page F. PNG media_image11.png 336 914 media_image11.png Greyscale PNG media_image12.png 463 915 media_image12.png Greyscale This anticipates the claims. Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Orlova et al. (GLP (Good Laboratory Procedure) for SCF3 construction: Useful procedure for trifluoromethylation of thiols by reaction with trifluoromethyliodide, Journal of Fluorine Chemistry, 261-262, pp. 1-8, Published 06/13/2022). Orlova et al. disclose the following reaction (p. 2). Wherein, compound 2h is PNG media_image13.png 133 580 media_image13.png Greyscale PNG media_image14.png 218 595 media_image14.png Greyscale current compound (1-2), current compound (1-1) is compound 1h in the above Scheme 1. The current alkylating agent being CF3I. This anticipates the claims. Claim(s) 10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Muller et al. (US Patent 2,108,606, Patent date 02-1938) Muller et al. disclose the oxidation of current compound (1-2) to (1-3) in column 2 lines 20-30 seen immediately below. PNG media_image15.png 134 478 media_image15.png Greyscale The ortho-chlorotrifluoromethylphenylsulfide is current compound (1-2). The ortho-chlorotrifluoromethylphenylsulphone is current compound (1-3). The oxidation agent is disclosed in column 2, lines 1-10 as chromic anhydride. This anticipates the 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. 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. 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. Claim(s) 1-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (Silver-catalyzed fluoroalkylation of thiols using fluoroalkanesulfinates, Journal of Fluorine Chemistry, 193, pp. 113-117, Published 2017) and Straathof et al. (A mild and fast photocatalytic trifluoromethylation of thiols in batch and continuous-flow, Chem. Sci.,5, pp. 4768-4773, Published 2014). Examiner’s Note: claims 6-9 are not being rejected over the combinational teachings of Straathof et al. and Ma et al. because Straathof et al. teach the CF3I in gaseous form (p. 4771) as opposed to a solution in current claim 6. PNG media_image16.png 325 598 media_image16.png Greyscale Scope of the Prior Art Ma disclose the following reaction on page 115. Wherein, compound 3l is PNG media_image17.png 139 506 media_image17.png Greyscale PNG media_image18.png 90 469 media_image18.png Greyscale PNG media_image19.png 91 464 media_image19.png Greyscale PNG media_image20.png 94 431 media_image20.png Greyscale PNG media_image21.png 136 508 media_image21.png Greyscale current compound (1-2), current compound (1-1) is compound 1 in the above Table 1. Additional teachings of Ma et al. are as follows. Ma teach the following (p.113). PNG media_image22.png 188 514 media_image22.png Greyscale PNG media_image23.png 125 505 media_image23.png Greyscale Ascertain the Differences Ma et al. does not teach the alkylating agent CF3I, nor visible light nor any irradiation, nor the photoredox catalyst nor the current Ru photoredox catalyst. Secondary References Straathof et al. teach the immediate below reaction (p. 4770). PNG media_image24.png 218 1028 media_image24.png Greyscale PNG media_image25.png 333 1026 media_image25.png Greyscale Straathof et al. teach overlapping aryl thiols as taught by Ma et al. with yields above those reported by Ma et al. See Straathof et al. page 4770 and immediately below. PNG media_image26.png 122 946 media_image26.png Greyscale PNG media_image27.png 124 1030 media_image27.png Greyscale Straathof et al. similarly to Ma et al. teach the incorporation of the S-CF3 motif in pharmaceuticals. See Straathof et al. page 4768 and immediately below. PNG media_image28.png 172 511 media_image28.png Greyscale PNG media_image29.png 238 512 media_image29.png Greyscale The above teachings of Straathof et al. overlap with the teachings of Ma et al. and are deemed to be analogous art to the invention. Obviousness It would have been prima facie obvious for an ordinary artisan before the effective filing date of the claimed invention to have tried the alkylation procedures taught by Straathof et al. on current compound (1-1) taught by Ma et al. to prepare current compound (1-2) and arrive at the current invention of claims 1-5 with a reasonable expectation of success. The ordinary artisan would have done so to achieve the higher yields taught by Straathof et al. MPEP 2141 (E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. Additionally, obviousness and a reasonable expectation of success is gained from just substituting one alkylation method for another. In other words substituting the methods taught by Ma et al. with those taught by Straathof et al. The ordinary artisan would have done so to substitute one known method for another to obtain predictable results. See MPEP 2141 III (B). The ordinary artisan would have looked to Straathof et al. from the perspective of Ma et al. due to the overlapping compounds and due to the overlapping interest in incorporation of the S-CF3 motif in pharmaceuticals. The reasonable expectation of success because both Straathof et al. and Ma et al. teach overlapping compounds that are alkylated with the CF3 group. Claim(s) 10-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Muller et al. (US Patent 2,108,606, Patent date 02-1938) and Orlova et al. (GLP (Good Laboratory Procedure) for SCF3 construction: Useful procedure for trifluoromethylation of thiols by reaction with trifluoromethyliodide, Journal of Fluorine Chemistry, 261-262, pp. 1-8, Published 06/13/2022). Scope of the Prior Art The disclosure of Muller et al. is written in the above 102 rejection and is incorporated by reference. Additional teachings of Muller et al. are as follows. Muller et al. teach the trifluoromethylphenylsulphones are valuable parent materials for manufacturing pharmaceutical products (page 1, right column lines 1-10). Muller et al. teach methods to prepare current compound (1-2) via fluorination of the trichloromethylphenylsulfides (page 1, left column, lines 25-45). This is not the currently claimed method. Ascertain the Differences Muller et al. does not teach the current preparation of compound (1-2) from compound (1-1), nor the CF3I. Secondary References Orlova et al. teach the deficiencies of Muller et al. See the disclosure of Orlova et al. in the above 102 rejection which is incorporated by reference. Orlova et al. goes on to teach overlapping subject matter to Muller et al. in that trifluoromethyl sulfides are starting compounds useful for further transformation into S(O)CF3 and SO2CF3 derivatives (page 1, Introduction left column). The above teachings render Orlova et al. analogous art to the invention. Obviousness It would have been prima facie obvious for an ordinary artisan before the effective filing date of the claimed invention to have obtained current compound of (1-2) via the methods taught by Orlova et al. from current compound (1-1). Next the ordinary artisan would have utilized current compound (1-2) obtained from the teachings Orlova et al. as the starting reagent to prepare (1-3) as taught by Muller et al. Substitution of the method to prepare the starting material (1-2) as taught by Muller et al. with the method taught by Orliva et al. is obvious. The ordinary artisan would have done so to substitute one known method for another to obtain predictable results. See MPEP 2141 III (B). The ordinary artisan would have looked to Orlova et al. from the perspective of Muller et al. due to the overlapping subject matter and because Orlova et al. is analogous art to the invention. Concerning claim 12 and the continuous production, “the court held that continuous operation would have been obvious in light of a batch process in the prior art. See In re Dilnot, 319 F.2d 188, 138 USPQ (CCPA 1963)”. MPEP 2144.04 V. E. Claim(s) 16, 19 and 22-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (Discovery of an Orally Bioavailable Small Molecule Inhibitor of Prosurvival B-Cell Lymphoma 2 Proteins, J. Med. Chem., 51, 6902–6915, Published 2008) and Muller et al. (US Patent 2,108,606, Patent date 02-1938) Scope of the Prior Art In interest of the confluence of the rejection, claim 19 will be addressed first. Concerning claim 19 and the preparation of compound (1-4) (current claim 22), Park et al. teach the use of aqueous ammonia with a Fluorinated compound and not the current Chlorinated compound (1-4). (p 6905 and 6904 and 6909). See compound 17 and 18 of Park et al. below wherein fluorine is present. Additionally, see Scheme 2 of Park et al. (p. 6905) immediately below wherein the fluorine version of (1-4) is made. PNG media_image30.png 275 1021 media_image30.png Greyscale PNG media_image31.png 232 574 media_image31.png Greyscale PNG media_image32.png 112 557 media_image32.png Greyscale PNG media_image33.png 216 577 media_image33.png Greyscale PNG media_image34.png 214 566 media_image34.png Greyscale The aqueous ammonium hydroxide being the current aqueous ammonia. Now returning to claim 16. Concerning claim 16, Park et al. teach current compound (3-8) (p. 6903, left column, Figure 1 compound 2). See immediately below. PNG media_image35.png 437 576 media_image35.png Greyscale Parke et al. teach the process to prepare current compound (3-8) via the coupling of current compounds (3-7) and (2-7) (page 6907, Scheme 6, and page 6906, Scheme 5). See immediately below. PNG media_image36.png 316 890 media_image36.png Greyscale PNG media_image37.png 317 568 media_image37.png Greyscale PNG media_image38.png 49 1176 media_image38.png Greyscale PNG media_image39.png 359 500 media_image39.png Greyscale Concerning, the preparation of current compound (2-7) via the current free base, Parke et al. teach the immediately below reaction (p. 6905). Wherein compound 19 of Park et al. is the current free base and compound 20b of Park et al. is current compound (2-7). PNG media_image40.png 272 1035 media_image40.png Greyscale The difference between the teachings of the prior art to the instant invention being compounds 16, 17 and 18 of Park et al. have a fluorine instead of the current chlorine. Note: compound 18 of Park et al. is the fluorinated version of current compound (1-5) in claims 16 and 23. Park et al. does however suggest other benzene derivatized compounds having chlorine or bromine undergo coupling reactions with amines. See Park et al. Scheme 1, page 6904 immediately below. PNG media_image41.png 198 490 media_image41.png Greyscale PNG media_image42.png 172 478 media_image42.png Greyscale PNG media_image43.png 121 484 media_image43.png Greyscale PNG media_image44.png 93 487 media_image44.png Greyscale Ascertain the Differences However, Park et al. does not teach current compounds (1-4) and (1-5), the chlorinated versions of the compounds in Schemes 1 and 2 of Park et al. Secondary References Muller et al. teach the oxidation of current compound (1-2) to (1-3) in column 2 lines 20-30 seen immediately below. PNG media_image15.png 134 478 media_image15.png Greyscale The ortho-chlorotrifluoromethylphenylsulfide is current compound (1-2). The ortho-chlorotrifluoromethylphenylsulphone is current compound (1-3). The oxidation agent is taught in column 2, lines 1-10 as chromic anhydride. Note: current compound (1-2) and (1-3) are the chlorine versions of compounds 16 and 17 of Park et al. Obviousness It would have been prima facie obvious for an ordinary artisan before the effective filing date of the claimed invention to have simply substituted the fluorine in the compounds taught by Park et al. with chlorine to arrive at the current invention. The ordinary artisan would have done so to substitute one known method for another to obtain predictable results. See MPEP 2141 III (B). Additional motivation to utilize a chlorine in place of the fluorine compounds of Park et al. with an expectation of success is from Park et al. Wherein the halogenated aryls with Br and Cl are shown to undergo coupling reactions with amines. The ordinary artisan in need of the chlorine versions of compounds 16 and 17 of Park et al. would have found these compounds in Muller et al. Upon substituting the current compounds (1-2) to (1-3) in column 2 lines 20-30 of Muller et al. into the place of compounds 16 and 17 of Park et al., current compounds (1-4) and (1-5) would have been made. Additionally, the coupling of current compound (1-5) with the current free base to achieve current compound (2-7) would have occurred. In other words the pertinent compounds in Scheme 2 of Park et al. (p. 6905) having the F in ortho position to the SO2CF3 position would have been the chlorine versions. Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (Discovery of an Orally Bioavailable Small Molecule Inhibitor of Prosurvival B-Cell Lymphoma 2 Proteins, J. Med. Chem., 51, 6902–6915, Published 2008) and Muller et al. (US Patent 2,108,606, Patent date 02-1938) as applied to claim 16, 19 and 22-23 in the above 103 rejection and further in view of Hoffman (page 1, Published 2019 (7 years ago)) and/or TeachersCollegesj (5 pages, Published 2020). Scope of the Prior Art The combinational teachings of Park et al. and Muller et al. are in the above 103 rejection and are incorporated herein by reference. Concerning the hydrolysis reaction of claim 17. Park et al. teach preparing the compound (3-7) via the hydrolysis of (3-6) with a LiOH hydroxide base in a solvent composition comprising water (p. 6906, 6913 right column). Concerning the hydrolysis procedures in the current specification, the current hydrolysis is described as a saponification as follows. “Saponification with sodium hydroxide in a heated mixture of ethanol and water transforms a compound of formula (3-6) to a compound of formula (3-7)” (p. 28, par. 60). Ascertain the Differences Park et al. and/or Muller et al. do not teach the use of ethanol in the current hydrolysis/saponification. Secondary References Hoffman teach the use of ethanol in a saponification reaction to assist contact of reactants in saponification reactions due to the solubility of the reactants. TeachersCollegesj teach use of ethanol in a saponification reaction to provide more contact…. and to speed up the reaction, reduce the polarity and increases catalyst solubility, thus accelerating the saponification reaction (p. 2 of 5). TeachersCollegesj teach use NaOH or KOH (p. 3 of 5). Obviousness It would have been prima facie obvious for an ordinary artisan before the effective filing date of the claimed invention to have utilized the ethanol taught by Hoffman and/or TeachersCollegesj in the hydrolysis/saponification reactions arrived at by the ordinary artisan via the combinational teachings of Park et al. and Muller et al. with an expectation of success. The ordinary artisan would have done so to assist in the contact of reactants in saponification reactions and/or speed up the reaction, reduce the polarity and/or increase catalyst solubility. In doing so the ordinary artisan would have arrived at the current invention. The ordinary artisan would have tried the KOH and/or the NaOH in place of the base taught by Park et al. The ordinary artisan would have done so to substitute one known method for another to obtain predictable results. See MPEP 2141 III (B). MPEP 2141 (E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. Claim(s) 20-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (Discovery of an Orally Bioavailable Small Molecule Inhibitor of Prosurvival B-Cell Lymphoma 2 Proteins, J. Med. Chem., 51, 6902–6915, Published 2008) and Muller et al. (US Patent 2,108,606, Patent date 02-1938) as applied to claim 16, 19 and 22-23 in the above 103 rejection and further in view of Ma et al. (Silver-catalyzed fluoroalkylation of thiols using fluoroalkanesulfinates, Journal of Fluorine Chemistry, 193, pp. 113-117, Published 2017), Straathof et al. (A mild and fast photocatalytic trifluoromethylation of thiols in batch and continuous-flow, Chem. Sci.,5, pp. 4768-4773, Published 2014) and Ciba Limited (GB918,635, Published 1963). Scope of the Prior Art The combinational teachings of Park et al. and Muller et al. are in the above 103 rejection and are incorporated herein by reference. Concerning the current compound of (1-4), as argued in the above 103 rejection of claim 16, current compounds (1-4) and (1-5) are obvious over Park et al. and Muller et al. Concerning the irradiation of current (1-1) in the presence of a photoredox catalyst and CF3I, thereby producing (1-2), Park et al. teach contacting compound 15 with methyl viologen dichloride (amine base) and CF3I to prepare 16 (p. 6910). PNG media_image45.png 99 254 media_image45.png Greyscale PNG media_image46.png 46 254 media_image46.png Greyscale Concerning the chlorosulfonic acid in step (c) of claim 20, Park et al. teach chlorosulfonic acid is utilized when preparing sulfonamides. See Park et al. Scheme 1, page 6904, step (a) immediately below. PNG media_image41.png 198 490 media_image41.png Greyscale PNG media_image44.png 93 487 media_image44.png Greyscale Ascertain the Differences Neither Park et al. and/or Muller et al. teach the use of a photoredox catalyst nor thionyl chloride. Secondary References The individual and combinational teachings of Ma et al. and Straathof et al. as written in the 103 rejection of claims 1-5, which are incorporated by reference, successfully argued the obviousness of the current irradiation of (1-1) in the presence of a photoredox catalyst and CF3I to produce (1-2). To tie Ma et al. to Muller et al., Ma et al. teach overlapping compounds with respect to Muller et al. See Ma et al. compound 3I (p. 115, left) and Muller et al. compound ortho-chlorotrifluoromethylphenylsulfide, current compound (1-2). PNG media_image47.png 116 149 media_image47.png Greyscale PNG media_image48.png 125 181 media_image48.png Greyscale Concerning the thionyl chloride, Ciba Limited teach the use of chlorosulphonic acid and thionyl chloride as a halogenation agent when preparing arylsulphochlorides (p. 2, left column, lines 1-20). This teaching overlaps in scope with Park et al. with regards to preparing arylsulphochlorides using chlorosulphonic acid, and renders Ciba Limited analogous art to the invention. Obviousness As argued in the above 103 rejection of claim 16, it would have been prima facie obvious for an ordinary artisan before the effective filing date of the claimed invention to have obtained current compound (1-4) and (1-5) via the combinational teachings of Park et al. and Muller et al. When preparing current compound (1-4), the ordinary artisan would have been in possession of the chlorinated versions of compounds 16-18 in Park et al. via the combinational teachings of Park et al. and Muller et al. PNG media_image49.png 247 943 media_image49.png Greyscale In need of the chlorinated version of compound 15 of Park et al. the ordinary artisan would have substituted the fluorine for chlorine with the reasons argued in the above 103 rejection of claim 16 of which are incorporated by reference. As a reminder Park et al. taught chlorine and bromine undergoing coupling reactions with amines. Next, in need of the chlorinated version of compound 15 of Park et al. the ordinary artisan would have looked to the trifluoromethylation methods taught by the combinational teachings of Ma et al. and Straathof et al. and would have found the chlorinated version of compound 15 of Park et al., current compound (1-1). Also, with in the combinational teachings of Ma et al. and Straathof et al., the ordinary artisan would have found the current process to prepare compound (1-2) via irradiating a mixture comprising compound ( 1-1 ), a photoredox catalyst, and trifluoroiodomethane. The ordinary artisan would then have substituted the methods of trifluoromethylation taught by Park et al. with those arrived at by the combinational teachings of Ma et al. and Straathof et al. to arrive at the current invention of claim 20. See MPEP 2141 III (B). The ordinary artisan would have looked to Ma et al. and Straathof et al. due to the teaching of the incorporation of the S-CF3 motif in pharmaceuticals of which is also a part of the teachings of Park et al. Concerning the thionyl chloride, Ciba Limited teach the use of thionyl chloride as a halogenation agent when preparing arylsulphochlorides (p. 2, left column, lines 1-20). Therefore, it would have been obvious to have incorporated the thionyl chloride taught by Ciba Limited into the above arrived at synthesis to prepare current compound (1-4) from current compound (1-3). The ordinary artisan would have done so with a reasonable expectation of success because Ciba Limited teach the use of thionyl chloride as a halogenation agent when preparing arylsulphochlorides. The ordinary artisan would have looked to Ciba Limited due to the overlapping subject matter compared to Park et al. and being analogous art to the invention. Concerning claim 22 and the continuous production, “the court held that continuous operation would have been obvious in light of a batch process in the prior art. See In re Dilnot, 319 F.2d 188, 138 USPQ (CCPA 1963)”. MPEP 2144.04 V. E. 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. Claims 1-5, 10-12, 16-17, and 19-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 8,624,027 (027) in view of Park et al. (Discovery of an Orally Bioavailable Small Molecule Inhibitor of Prosurvival B-Cell Lymphoma 2 Proteins, J. Med. Chem., 51, 6902–6915, Published 2008) and Muller et al. (US Patent 2,108,606, Patent date 02-1938), Ma et al. (Silver-catalyzed fluoroalkylation of thiols using fluoroalkanesulfinates, Journal of Fluorine Chemistry, 193, pp. 113-117, Published 2017), Straathof et al. (A mild and fast photocatalytic trifluoromethylation of thiols in batch and continuous-flow, Chem. Sci.,5, pp. 4768-4773, Published 2014), Ciba Limited (GB918,635, Published 1963), Hoffman (page 1, Published 2019 (7 years ago)) and/or TeachersCollegesj (5 pages, Published 2020). Note: the limitations of current claims 1-5 and 10-12 overlap with current claim 20-21 which is currently being rejected. 027 claims the following. PNG media_image50.png 68 494 media_image50.png Greyscale PNG media_image51.png 418 427 media_image51.png Greyscale PNG media_image52.png 154 495 media_image52.png Greyscale PNG media_image53.png 217 211 media_image53.png Greyscale PNG media_image54.png 71 495 media_image54.png Greyscale The above claims of 027 encompass current compound (3-8) in current claim 16. However, 027 does not claim the specific specie of current compound (3-8) nor the current method to prepare current compound (3-8). Park et al. teach the current compound (3-8) seen immediately below (page 6903, Figure 1, item 2). PNG media_image55.png 370 500 media_image55.png Greyscale Park et al. teach overlapping cancer treatment subject matter as claimed in reference patent 027 (claim 1). See Park et al. abstract, page 6905 right column, bridging pages 6906 and 6907. For the current methods of preparation, the combination of the prior art of record, which is incorporated by reference, successfully argued the current methods obvious. Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the patented subject matter. Claims 6-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 8,624,027 (027) in view of Park et al. (Discovery of an Orally Bioavailable Small Molecule Inhibitor of Prosurvival B-Cell Lymphoma 2 Proteins, J. Med. Chem., 51, 6902–6915, Published 2008) and Muller et al. (US Patent 2,108,606, Patent date 02-1938), Ma et al. (Silver-catalyzed fluoroalkylation of thiols using fluoroalkanesulfinates, Journal of Fluorine Chemistry, 193, pp. 113-117, Published 2017), Straathof et al. (A mild and fast photocatalytic trifluoromethylation of thiols in batch and continuous-flow, Chem. Sci.,5, pp. 4768-4773, Published 2014), Ciba Limited (GB918,635, Published 1963), Hoffman (page 1, Published 2019 (7 years ago)) and/or TeachersCollegesj (5 pages, Published 2020) as applied to claims 1-5, 10-12, 16-17, and 19-23 and in further view of Harper et al. 2021 (Commercial-Scale Visible-light Trifluoromethylation of 2-Chlorothiophenol using CF3I gas., ChemRxiv, 16 pages, Published 10/14/2021) or Harper et al. 2022 (Commercial-Scale Visible Light Trifluoromethylation of 2-Chlorothiophenol Using CF3I Gas. Org. Process Res. Dev., 26(2), Pages A-I, Published 02/07/2022). The combinational teachings of the previous recited prior art are incorporated by reference. The reference patent and the previous recited prior art do not teach the limitations of 6-9. However, in the above 102 rejections, the disclosure Harper et al. 2021 and/or Harper et al. 2022, which are incorporated by reference, were utilized to successfully argue claims 1-12 being anticipated. Harper et al. 2021 and/or Harper et al. 2022 disclose overlapping subject matter to the methods arrived at by the ordinary artisan when combining the prior art utilized to reject claims 1-5, 10-12, 16-17, and 19-23. For instance, the prior art utilized to reject claims 1-5, 10-12 overlap in scope with Harper et al. 2021 and Harper et al. 2022 with respect to adding a CF3 group. Thus, the ordinary artisan would have looked to Harper et al. 2021 and Harper et al. 2022. Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the patented subject matter. Allowable Subject Matter Claims 13-15 are allowed. Claim 18 is 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. The following is a statement of reasons for the indication of allowable subject matter: The closest prior art to claims 13 and 14 is STN (STN, pages 1-2, Published 03 19 2010). STN discloses current Compound (2-6) (p. 1). However, STN does not disclose or fairly suggest the current process to prepare current Compound (2-6) in claim 13 nor the method to prepare current Compound (2-7) utilizing current Compound (2-6) in claim 14. It would not have been obvious to have modified the prior art to arrive at the current invention. There being no motivation to do so. The closest prior art to claims 15 and 18 is Park et al. (Discovery of an Orally Bioavailable Small Molecule Inhibitor of Prosurvival B-Cell Lymphoma 2 Proteins, J. Med. Chem., 51, pp. 6902–6915, Published 2008). Concerning claim 15 and 18 and the process to prepare current compound (3-6), Park et al. teach the following synthesis to prepare 30e seen immediately below (p. 6906). PNG media_image56.png 321 909 media_image56.png Greyscale Park et al. does not disclose or fairly suggest the use of current compound (3-5) in above process. It would not have been obvious to have modified the prior art to arrive at the current invention. There being no motivation to do so. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to BLAINE G DOLETSKI whose telephone number is (571)272-2766. The examiner can normally be reached M-F 7-4 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, Scarlett Goon can be reached at (571)270-5241. 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 /B.G.D/Examiner, Art Unit 1692 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625