A SOLID PHARMACEUTICAL COMPOSITION

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 Claims 20, 21, 24, 25 and 27-39 are currently pending and an amendment to the claims filed on 07/20/2026 is acknowledged. Information Disclosure Statement The information disclosure statement (IDS) submitted on 09/02/2026 was filed before the mailing date of the instant first action on the merits. The submission thereof is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner, and signed and initialed copy is enclosed herewith. New Grounds of Rejection --- as necessitated by amendment Claim Rejections - 35 USC § 103 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 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. Claims 20, 21, 24, 25, 27 and 36-39 are rejected under 35 U.S.C. 103 as being unpatentable over Spyvee et al. (CN103097358A, IDS of 06/28/204, citation is obtained from its corresponding US2014/0155452A1) in view of Bao et al. (US2017/0182003A1, IDS of 05/13/2026) or further in view of Muller et al. (US2010/0129352A1). Applicant claims claim 20 filed on 07/20/2026: A solid pharmaceutical composition in the form of tablet comprising a compound of formula 1 or its salt in an amount of about 30 to about 80% and carrier comprising specific species of a filler, a binder, a disintegrant, a lubricant and glidant and amounts thereof. Level of Ordinary Skill in the Art (MPEP 2141.03) MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a medical/pharmaceutical composition research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from medicine, pharmacy, physiology and chemistry— without being told to do so. In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)). Determination of the scope and content of the prior art (MPEP 2141.01); Ascertainment of the difference between the prior art and the claims (MPEP 2141.02) and Finding of prima facie obviousness Rational and Motivation (MPEP 2142-2143) Spyvee discloses a pharmaceutical composition in the form of tablet ([0072]) which reads on the claimed solid dosage form containing a compound ER886046 “4-{(1S)-1-[({3-(difluoromethyl)-1-methyl-5-[3-(trifluoromethyl)phenoxy]-4-1H-pyrazolyl} carbonyl)amino]ethyl}benzoic acid” (Example 21) which reads on the claimed formula I, and a pharmaceutical carrier including diluent (=filler) lactose and corn starch, lubricating agent such as magnesium stearate (e.g., [0072]), polyvinylpyrrolidone, sodium carboxymethylcellulose ([0049]) that reads on the claimed disintegrating agent as supported by the instant publication at [0070], cellulose-based substance (e.g., [0049]) that reads on the claimed binder as supported by the instant publication at [0071], colloidal silica (e.g., [0049]) that reads on the claimed glidant as supported by the instant publication at [0073] (instant claims 20-21 and 24-25, in part, and claim 27); therapeutically effective amount of the active compound to be administered in the composition will vary depending upon the host treated, and the particular route of administration, and preferably, a dosage is between 0.01-100mg/kg body and e.g., a dosage can be between 0.01 mg and 50mg ([0107]) and for example, in case of 60kg adult, the dosage will be 0.6mg-6000mg which overlaps the instant range of about 50mg to about 500mg or about 100mg to about 300mg. MPEP2144.05: “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).” (instant claims 36-37); and the composition containing ER886046 and carrier is effective to treat multiple sclerosis, rheumatoid arthritis, cancer including skin cancer, breast cancer, colorectal cancer, prostate cancer, kidney cancer, ovarian cancer, cervical cancer, endometrial cancer, glioblastoma, lung cancer, head and neck cancer, medulloblastoma, and urinary tract cancer (e.g., [0017]-[0018], [0080], [0360], [0115]-[0125], and claim 48 of prior art) (instant claims 38-39). However, Spyvee does not expressly teach the ranges of compound, filler, binder, disintegrant, lubricant and glidant as claimed. The deficiencies are cured by Bao or with Muller. Bao discloses compositions for treating cancer by administering an EP4 antagonist with chemotherapy and radiation (abstract) wherein the EP4 antagonist includes compound ER-88046 (see 5th compound recited in claim 11 of prior art) that reads on the claimed compound formula I: PNG media_image1.png 509 682 media_image1.png Greyscale ;the compound ER-886046 is administered in an amount of 150mg/kg ([0026]-[0028]) or 0.01mg/kg to 200mg/kg ([0070]-[0071]); the compound is present in an amount of 0.01 or 0.5% to 95% ([0066]) which overlaps the ranges of about 30% to about 80% of instant claim 20 or about 40% to about 60% of instant claim 21 (instant claims 20-21: the amount of compound). Although this prior art does not expressly teach the amounts of carrier including fillers, binders, lubricants, disintegrants and glidants of instant claims of 20 and 24-25, they would be present in remaining balanced amount relative to the active agent, unless criticality of the carrier ranges is shown. In the alternative, Muller discloses a pharmaceutical composition in the form of tablet ([0035]) containing active ingredient olamine, filler (=diluent) such as microcrystalline cellulose or mannitol, binder such as polyvinylpyrrolidone (=povidone), lubricant such as magnesium stearate, colloidal silica, disintegrant such as crospovidone, sodium croscarmellose, flow aids (=glidant) such as talc, fumed silica, etc. (e.g., [0045], [0047], [0050], [0069] and [0082]) wherein a) from about 2% to about 65% active ingredient; b) from about 25% to about 89% of diluent (=filler) that overlaps the ranges of about 5% to about 60% of instant claim 20, about 10% to about 50% of instant claim 24, or about 20% to about 40% of instant claim 25; c) up to about 8% binder that overlaps the range of about 0% to about 8% of instant claim 1, about 2% to about 6% of instant claim 24 or about 3% to about 5% of instant claim 25; d) up to about 2% of lubricant that overlaps the range of about 0.1% to about 10% of instant claim 20, about 0.5% to about 8% of instant claim 24 or about 1% to about 6% of instant claim 25; and e) from 4% to about 12% of disintegrant that overlaps the range of about 0% to about 30% of instant claim 20, about 0.1% to about 25% of instant claim 24 or about 1% to about 25% of instant claim 25. Colloidal silica and silica as a lubricant in up to 2% (e.g., [0046]) could also be used as glidant that overlaps the instant range of about 0% to about 1% or “about 0%” as claimed embraces absence of glidant. MPEP 2144.05 noted above (instant claims 20, 24, and 25: carriers and their amounts). It would have been obvious to optimize the ranges of carriers of the applied art Spyvee and Bao with the claimed ranges because the applied art teaches a pharmaceutical composition containing EP4 antagonist compound ER886046 and typical pharmaceutical carriers including fillers, binders, disintegrants, lubricants and/or glidants; and in the alternative, it would have been obvious to a person of ordinary skill in the art to formulate the EP4 antagonist from Spyvee and Bao using the carriers disclosed in Muller because Muller teaches such typical carriers are suitable for delivering pharmaceutically active compound, and the selection of known carrier(s) for known active agent(s) is a routine formulation optimization wherein Muller teaches overlapping amounts of carriers. Unless the criticality is shown, the ranges of carrier would be obvious and optimized from the skill and knowledge of an ordinary artisan. In light of the foregoing, instant claims 20, 21, 24, 25, 27 and 36-39 are obvious over Spyvee in view of Bao or further in view of Muller. Claims 28-35 are rejected under 35 U.S.C. 103 as being unpatentable over Spyvee et al. (CN103097358A, IDS of 06/28/204, citation is obtained from its corresponding US2014/0155452A1) and further in view of Xu et al., (US2019/0231783A1). Applicant claims the below claims 30-32 filed on 07/20/2026: PNG media_image2.png 403 827 media_image2.png Greyscale For examination purpose, claims 30-32 are product-by-process limitation, but those limitations are not seen as structurally limiting the instant composition because the “patentability of a product does not depend on its method of production.” In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP 2113 reads “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.” Further, as a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972). Accordingly, in the instant case, it is interpreted that claims 30-32 recites “granules”. However, Spyvee does not expressly teach instant claims 28-35 and but the deficiency is cured by Xu. Xu discloses pharmaceutical composition in the form of tablet for treating cancer comprising a compound, i.e., A2A receptor antagonist or its salt and pharmaceutically acceptable carrier; the composition containing the compound, excipient such as a polymer, surfactant or combination thereof is initially provided in granules, optionally with an outer coating layer and then compressed into a tablet ([0016]) wherein the compound is formulated into nanoparticles by dry milling or wet milling, either alone or with one or more pharmaceutically acceptable excipients ([0251]-[0252]) (instant claims 28-32); the compound has a particle size distribution of D90 of about 500nm or less ([0015])or about one micron or less ([0075]) which is within the claimed range of less than 200 microns or less (instant claims 33-34); and the tablet can further have an outer coating layer ([0015])(instant claim 35). That is, Spyvee discloses tablet of EP996046 compound, and remains silent about granule and however, to prepare tablet, granule should be compressed. Xu teaches that granule (see [0016] of Xu). Further, Spyvee discloses ER886046 compound and Xu teaches reducing the particle size of active ingredient to a D90 of less than one micron or 500nm improves bioavailability, and therefore it would have been obvious to modify teachings of Spyvee with D90 particle size distribution and protective coating of Xu in order to enhance the properties of the obtained composition including e.g., dissolution, bioavailability, predictable therapeutic performance, and protection of tablet. Please note that such D90 particle size distribution is formulation-dependent, not drug-class-specific and thus the teachings of Xu can be applied to the teachings of Spyvee. In light of the foregoing, instant claims 28-35 are obvious over Spyvee in view of Xu. Response to Arguments Applicant’s arguments have been fully considered, but are not persuasive. Applicant argues that the claimed tablet containing formula I and carrier provides unexpected results including reduced RSD, particle-size independent dissolution, improved stability, and more consistent in-vivo exposure compared to capsules containing the same as demonstrated in Examples 1, 4 and 4a and Comparative Examples 1-2; and the applied art does not recognize the problem of capsule and solution to overcome; and the ranges of carrier cannot be optimized; Xu obtains nanoparticles by nano-milling while the claimed invention does not; and the instant application was granted in foreign countries. The Examiner responds that as noted in the body of Action, Spyvee discloses specific selection of compound ER886046-contraining oral composition and its method of use, and tablet (e.g., Example 21 and [0072]). Since the combined art teaches the claimed invention, the claimed properties may be expected because Spyvee discloses when the composition is provided in the form of tablet for oral use, carriers commonly used include lactose and corn starch, and lubricating agent such as magnesium stearate ([0072]) and Muller teaches tablet and carriers therefor as noted above. That is, the claimed carriers and amounts thereof are commonly used, as taught by Spyvee and Muller and thus optimization of carrier is within the knowledge and skill of the ordinary artisan; even further, such properties applicant argues are not found in the claims; concerning failure of recognition of problems, please see MPEP 2144(IV): “The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006)”; the claimed amount (about 30 to about 80%) of the compound may overlap the prior art amount ([0107] of Spyvee and [0066] and [0070]-[0071] of Bao); and the claimed amounts of the carries are field of use in the pharmaceutical field unless criticality evidence is shown. In this regard, please see MPEP 2144.05 (II)(A): Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Also, see, “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The prior art provides overlapping amounts of the carriers, See MPEP 2144.05 I. OVERLAP OF RANGES In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990), and the ordinary artisan would optimize the overlapping ranges with the claimed ranges, and applicant did not show criticality of the claimed carrier range; the claimed invention is directed to a composition not to a method to refer how to obtain D90 nanoparticles, and Xu is relied for disclosing D90 that overlaps the claimed D90. It is noted that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In reKeller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In reMerck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). MPEP 2145; and lastly, US examination practice is independent of other countries’ patent practice. In light of the foregoing, applicant’s arguments are not persuasive. Suggestion To make the claimed tablet distinct, Applicant may consider additionally incorporating tablet properties (reduced RSD, particle-size independent dissolution, improved stability, and more consistent in-vivo exposure compared to capsule) into claim 20, and D90 particle size of claim 33 into claim 20. Conclusion All claims examined are rejected. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYUNG S CHANG whose telephone number is (571)270-1392. The examiner can normally be reached M-F 8-5. 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, Yong (Brian-Yong) S Kwon can be reached at 571-272-0581. 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. /KYUNG S CHANG/Primary Examiner, Art Unit 1613