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. Claim Rejections - 35 USC § 112 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 appl icant regards as his invention. Claims 1, 3, 5, 7, 9-11, 13-20, 22, 24-27, 29, 32 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. The term “the synthetic route” in claim 1 lacks antecedent basis. It is unclear what structures Applicant intends to cover by the recited “derivatives”. The criteria of the term “appropriate” or “sufficient” within the context of recited reagent s, organic bases, solvent amounts and reaction times is unclear . Specifically, t he se terms are merely relative which renders the claim indefinite. The term “ appropriate ” or “sufficient” is not generically defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The relative amounts of solvents, when use together, e.g., steps, C, D, E, F, J, K, is not defined. The term “the filtrate” in claim 1, step s B, I, lacks antecedent basis. The term “the filter cake” in claim 1, steps C, D, K , lacks antecedent basis. The intended structure s of “triazole -based compound”, step G, are unclear. The intended pH’s or pH range in step H is not defined. The required steps to “catalyze the reaction” are not defined in step H. The required steps for “preparing ” are not defined in step L . The term “ the concentrate ” in step N lacks antecedent basis. In claim 32, it is unclear as to what amounts or concentrations or partial pressures of nitrogen qualify as “under the protection of nitrogen”. Claim 1, step B recites obtaining a filtrate or filter cake by suction filtration, but step A does not recite production of a solid. Step E recites dissolving the filter cake and obtaining a filter cake, but does not recite how a solid is re-obtained from the dissolved filter cake. In step E, it is unclear how acetic acid, methanol and water dissolve the solid product, but the same solvents only wash (but not dissolve) the solid in step F. 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. Claim s 1, 3, 5, 7, 9-11, 13-20, 22, 24-27, 29-32 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Publication No 20220056147 based on an application by Fang et al. ( Fang ) in view of Thin Layer Chromatography: A Complete Guide to TLC , 2020, downloaded 12 March 2026 from https://chemistryhall.com/thin-layer-chromatography/ ( TLC ) and Shields et al., Nature , Vol 590 , 202 1, pp. 89-100 ( Shields ). Regarding claims 1, 10, 11, 16 and 22 , Fang teaches the preparation of antibody conjugate intermediates covered by the rejected claims, see pages 14-15: Synthesis of Compound 6 (Mc-Val-Cit-PAB-PNP) Compound 5 (Mc-Val-Cit-PAB, 4.58 g, 8.0 mmol) was dissolved in DMF (100 mL), added with NPC (di(p-nitrophenyl) carbonate, 3.65 g, 12.0 mmol) and DIPEA (1.70 mL, 9.6 mmol), reacted for 5 hours at room temperature, and the reaction progress was monitored by TLC. After the reaction was completed, the reaction mixture was poured into petroleum ether (1000 mL), stirred and filtered, and the obtained filter cake was washed with petroleum ether (60 mL×3) and dried by suction to give a off-white solid powder (5.04 g, 85.2%). Note: DIPEA = diisopropylethylamine. Synthesis of Compound 7 (Mc-Val-Cit-PAB-MMAE) Compound 6 (1.19 g, 1.6 mmol) was dissolved in 12 mL of DMF, and added with MMAE (1.08 g, 1.5 mmol), HOBt (0.21 g, 1.5 mmol), DIPEA (0.55 mL, 3.0 mmol) and pyridine (2.5 mL) under the protection of nitrogen gas. Under stirring at room temperature for 24 hours, the reaction progress was monitored by TLC . After the reaction was completed, purification was carried out by preparative high-performance chromatography , and the resultant solution was rotary evaporated under reduced pressure to give Compound 7 (white solid powder, 0.891 g, 45.1%). LC-MS m/z (ES+), 1316.18 (M+ H)+ . Synthesis of Compound 8 (Mc-Val-Cit-PAB-MMAD) Compound 6 (0.74 g, 1.1 mmol) was dissolved in 10 mL of DMF, and added with MMAD (0.77 g, 1.0 mmol), HOBt (0.14 g, 1.0 mmol), DIPEA (0.35 mL, 2.0 mmol) and pyridine (2 mL) under the protection of nitrogen gas. Under stirring at room temperature for 24 hours, the reaction progress was monitored by TLC. After the reaction was completed, purification was carried out by preparative high-performance chromatography , and the resultant solution was rotary evaporated under reduced pressure to give Compound 8 (white solid powder, 0.59 g, 42.8%). LC-MS m/z (ES+), 1369.38 (M+ H)+ . Note : HOBt = hydroxybenzotriazole ( claim 22 ). While Fang t each es that the product is washed , Fang may not teach this solid purification technique by washing with ethyl acetate and hexanes, or H2O/ EtAc /MeOH . However, choosing the optimal solvent system s to purify or wash a product is routine and depends on the chemical properties of the desired product. Specifically, optimizing the washing solvent system solvent involves choosing a liquid in which the target product is insoluble (or poorly soluble) . In particular, t he ethyl acetate ( EtOAc ) and hexane solvent system was known as a versatile, standard mixture for silica gel chromatography (TLC and column), balancing polarity ( EtOAc ) and non-polarity (hexane) to separate organic compounds , based on relative amounts of each, see TLC (“ classical mixtures of apolar solvent (hexane, pentane or cyclohexane) and polar solvent (ethyl acetate or diethyl ether), as a combination of these solvents will be usually enough to deal with most organic compounds … Hexane/ EtOAc is usually the standard mixture for organic separations. ”). In this manner, in the absence of unexpected results, the recited wash solvents would have been within the optimization of those of ordinary skill, and in particular, using the recited EtOAc /Hexane systems would have been obvious since this system solvent was known as a versatile and standard mixture for product separations. Regarding claims 3, 5, 7, 9 , 13- 15, 17- 20, 24-27, 29 and 32 , these claims recite results effective-variables such amounts, times, pH, temperature, etc., and are thus subject to optimization. In this regard, these parameters are subject to optimization by those of ordinary skill, see Shields (“ Optimization of a chemical reaction is a complex, multidimensional challenge that requires experts to evaluate various reaction parameters, such as substrate, catalyst, reagent, additive, solvent, concentration, temperature and reactor type … Modern advances in high-throughput experimentation (HTE) have extended experimental capabilities to the collection of a few thousand data points under a limited set of conditions ”) . In this way, in the absence of an unexpected result, routine optimization of the recited parameters methods by everyday laboratory practices facilitate more efficient synthesis of functional chemicals , and are therefore prima facie oblivious . Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645 . The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m. If attempts to reach the examiner by telephone are unsuccessful, the examiner's acting supervisor, Gregory Emch , can be reached at telephone number 571-272-8149. 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). /KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646