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 .
Status of Claims
Amendments to filed on 04/16/2026 is acknowledged.
Claims 8 and 10 remain cancelled. Claims 1, 6-7, and 11 are amended.
Claims 13-20 are new.
Claims 1-7, 9, and 11-20 are pending and being examined on the merits herein.
Priority
This instant application, filed 01/26/2023, claims domestic benefit to US provisional application 63/303250, filed 01/26/2022.
Information Disclosure Statement
The information disclosure statement (IDS), filed on 11/14/2025, is in compliance with the
provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the
Examiner.
Withdrawn Objections/Rejections
All previous claim Objection(s) / Rejection(s) as set forth in the previous Office action (mailed 12/16/2025) that are not repeated and/or maintained in the instant Office action are withdrawn, in light of applicant’s amendment and remark filed on 04/16/2026.
Claim Objections
Claims 6-7 and 18-19 are objected to because of the following informalities:
Claims 6-7 and 18-19 each recites “ a weight of the pharmaceutical composition”, the word “a” has to be changed to “the”, because the pharmaceutical composition only has one weight and “the” is proper to define it.
Claim 19 recites “containing from of 3β-hydroxyurs-12-en-28-oic acid”, wherein the phrase “from of” appear to be unnecessary and should be removed.
Appropriate correction is required.
Claim Interpretation
The limitations of “3β-hydroxyurs-12-en-28-oic acid (same as ursolic acid) is in an amorphous state in the solid dispersion pharmaceutical composition” and “the solid dispersion pharmaceutical composition has irreversible stability of the amorphous state after storage …” in Claims 15-17 and Claim 20 are interpreted as the property or intended use of ursolic acid and/or the pharmaceutical composition, because they do not materially contribute to the composition matter in the preparation process.
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 applicant regards as his invention.
Claims 1-7, 9, and 11-20 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.
Claim 1 recites “wherein a temperature of the heating zone” in ii). It is unclear whether the heating zone meant to be the previous mentioned temperature “from about 50 C to about 200 C”, or it is meant to be some other heating zone with different temperature range. Because “a temperature of the heating zone” does not appear to refer to the temperature from about 50 C to about 200 C, the phrase is interpreted as the latter meaning, as such, there is insufficient antecedent basis for this limitation in the claim, for “heating zone” was not previously mentioned. Claim 1 also recites “passes sequentially through the at least four heating zones”. There is insufficient antecedent basis for this limitation in the claim, because “at least four heating zones” was not previously defined in the claim. For the purpose of compact prosecution, the limitation is interpreted as the blend passes through at least four heating zones wherein temperature of the heating zones is sequentially lowered.
Claim 11 recites “in the melt extrusion, the blend … is melted while the blend passes through at least four heating zones connected in series”. There is insufficient antecedent basis for the limitation of “the melt extrusion” in the claim, because claim 1, which claim 11 depends upon, does not mention “melt extrusion”, and it is unclear whether this melt extrusion belongs to step ii) or other steps. Furthermore, it is unclear whether “at least four heating zones connected in series” refers to the same “at least four heating zones” in claim 1, because definite article “the” is not present in front of this phrase of claim 11, and “at least four heating zones connected in series” in claim 11 represents differently, which can be connected in series with temperature either rising or falling, while temperature of the at least four heating zones in claim 1 is “sequentially lowered … through the at least four heating zones”. It is also unclear of the language “the blend … is melted while the blend passes through”, whether the blend is already melted before the blend passes through the zones, or the blend is being melted while passing through the zones. All the issues as addressed above render claim 11 indefinite. For the purpose of compact prosecution, claim 11 is interpreted as further defining claim 1 step ii), melt extruding the mixture at a temperature from about 50 C to about 200 C, after the blend is melted, the blend passes through the at least four heating zones with sequentially lowered temperatures.
Claims 16 and 17 each recites “the solid pharmaceutical composition has irreversible stability of the amorphous state”, however, the amorphous state corresponds to 3β-hydroxyurs-12-en-28-oic acid compound in claim 15, which claim 16 depends upon, not as the composition stability of amorphous state as expressed in claim 16. Based on the context, “the amorphous state” for the composition in claims 16 and 17 lacks sufficient antecedent basis and it renders the claims indefinite.
Claim 20 recites “the solid pharmaceutical composition has irreversible stability of the amorphous state”, while previously in the claim mentions “3β-hydroxyurs-12-en-28-oic acid is in an amorphous state in the solid dispersion pharmaceutical composition”. Therefore, the irreversible stability of the amorphous state of the composition lacks sufficient antecedent basis, because amorphous state referred to the acid, not the composition previously in the claim.
Claims 2-7, 9, 12-15, and 18-19 are rejected accordingly because they are directly or indirectly depending on claim 1, and they do not further clarify the issue addressed above in claim 1.
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 19-20 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.
Claim 19 recites “… of claim 1, wherein the mixture includes an extract containing …”. Because in claim 1, which claim 19 depends upon, defines the mixture as “3β-hydroxyurs-12-en-28-oic acid, and a water-soluble polymer”, while claim 19 rather expands or changes the mixture in claim 1 to include an extract containing 3β-hydroxyurs-12-en-28-oic acid. Therefore, claim 19 fails to further limit the subject matter of claim 1 which it depends.
Claim 20 is rejected accordingly because it depends on claim 19 and it does not further clarify the issue addressed above in claim 19.
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 § 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.
Claims 1-7, 9 and 11-20 are rejected under 35 U.S.C. 103 as being unpatentable over to Allegrini et al. (WO2021089433, 05/14/2021, Record of 11/18/2024) in view of Williams et al. (WO2019051440, 03/14/2029, Record of 11/18/2024) and Baek at al. (WO2014073889, 05/15/2014, Record of 12/16/2025).
Allegrini throughout the reference directs to a solid dispersion comprising a salt of ursolic acid (same as 3β-hydroxyurs-12-en-28-oic acid, Pg. 1, top paragraph), a phospholipid (a biological polymer), and one or more pharmaceutical or nutraceutical excipients (e.g., Abstract; Page 3, Lines 11-19).
Regarding instant claim 1, Allegrini points out that ursolic acid is classified as class IV molecule based on Biopharmaceutics Classification System (BCS) with poor water solubility and low membrane permeability, resulting in scarce bioavailability (Background, Page 1, Lines 11-14), although ursolic acid constitutes many bioactivities as a promising candidate for the nutraceutical market (Page 1, Lines 8-11) and pharmaceutical applications (Page 2, Lines 7-15). Allegrini indicates the solid dispersion process aims to improve ursolic acid solubility and bioavailability (Page 2, Lines 1-9). Thus, Allegrini teaches a process for preparing a solid dispersion of ursolic acid for improved therapeutic use.
Allegrini specifies that soluble and insoluble diluents, such as cellulose or cellulose ether polymers can be used as a type of excipients in the composition (e.g., Claim 4; Page 3, Lines 21-23) as shown in two exemplary embodiments containing a salt of ursolic acid, a phospholipid, cellulose or cellulose ether (e.g., Claim 4; Claim 6; Page 4, Line 4-Page 5, Line 4), while cellulose is a straight chain polymer, cellulose ether is known as a major class of water-soluble polymer. Therefore, Allegrini teaches instant claim 1 i) blending ursolic acid and a water-soluble polymer.
Allegrini describes the solid dispersion through a process comprises of: a-1) mixing the ursolic acid salt and a phospholipid in an alcohol to provide a suspension, b-1) heating the suspension obtained in previous step, c-1) removing the solvent (alcohol) to provide a solid dispersion SD. When the composition comprises adding one more excipient, the excipients can be added during step a-1) or optionally, at the end of step c-1) (Page 6, Lines 7-14; Page 8 Line 3-16).
Allegrini demonstrates the solubility of solid dispersion ursolic acid increases 2-13 folds in gastrointestinal fluids tested (Page 8 bottom-Page 9 top), thus the solid dispersion of ursolic acid has an increased bioavailability of at least two-folds over unprocessed material as instantly claimed.
Regarding instant claim 2, Allegrini discloses the exact same chemical structure of ursolic acid (Page 1, Lines 1-5) as recited.
Regarding instant claim 3, Allegrini states that salts of ursolic acid with alkali metals gain higher solubility than ursolic acid in solid dispersion (Page 3, Lines 3-10).
Regarding instant claims 6-7 and 18-19, Allegrini specifies the ursolic acid salt weight percentage as 16%-75% in the solid dispersion, preferably from 33% to 66%, or from 33-50%, or 50% (Page 6, Lines 3-6); Allegrini exemplifies using 2.5g ursolic acid (as 33.3% ursolic acid of the final product), 1.25 g microcrystalline cellulose for the 7.5 g final ursolic acid solid dispersion product (Example 2, Pg. 11, Lines 10-19), overlapping to ursolic acid amount about 5% to about 50% in instant claims 6 and 19. Allegrini also indicates that weight ratio between one or more excipient and the salt of ursolic acid ranges from 0.5:1 to 2:1 in the solid dispersion (e.g., Claim 5), wherein the one or more excipients can be cellulose (e.g., Claims 4 and 6), corresponding to water soluble polymer can be at range 0.5/1.5 to 2/3, or approx. 22.2% to 66.7% (calculation based upon cellulose as the only one excipient in the ursolic acid blend composition), overlapping with the water-soluble polymer amount from about 5% to about 50% in instant claim 7 and overlapping with range from about 30% to about 90% in instant claims 18-19.
Regarding instant claim 9, Allegrini demonstrates the solubility of solid dispersion ursolic acid increases 2-13 folds in gastrointestinal fluids tested (Page 8 bottom-Page 9 top), overlapping with bioavailability improved at least four folds over unprocessed material in instant claim 9.
Although Allegrini teaches solid dispersion of ursolic acid improves solubility, it does not teach the steps of ursolic acid solvent-free solid dispersion as recited in instant claim 1, and it does not expressly teach a water-soluble polymer with a glass transition temperature lower than 284 °C in the composition as recited in instant claim 1, or the species of water-soluble polymers as recited in instant claims 4-5 and its amount about 5% to about 50% as recited in instant claim 7. Allegrini does not teach the mixture passes through four heating zones with sequentially lowed temperatures as interpreted in instant claim 1, and does not specify the blend has been melted before passing through the at least four heating zones as interpreted in claim 11, each zone specific temperature range as recited in instant claim 12, the melt extruding temperature ranges as recited in instant claims 13-14, ursolic acid in amorphous state in the composition as recited in instant claim 15, the amorphous stability as defined in instant claims 16-17, water-soluble polymer is polyvinylpyrrolidone-vinyl acetate copolymer as in instant claim 19, or the ursolic acid is in an irreversible stable amorphous state in the composition after storage for 15 months as recited in instant claim 20.
Williams throughout the reference teaches amorphous solid dispersion (ASD) [0003] method through hot melt extrusion (HME) or fusion-based process free of solvent [0008, 0015] for improving compound solubility including BCS class IV molecules [0002-0003, 0009; Claims 15-16], such as poorly water-soluble lipophilic therapeutic agents [0065], while as evidenced by instant specification (Spec., Lines 9-10) ursolic acid is a naturally-derived lipophilic pentacyclic triterpene therapeutic agent.
Williams points out the increased risk of drug degradation when thermolabile drugs are processed above their melting point during the hot melt extrusion process (Page 2, Lines 24-26). It specifies that the thermal process is carried out at a temperature below the melting point of the therapeutic agent in some embodiments [0008, 0017]. Williams describes the hot melt extrusion (solid dispersion) method steps as following: the formulations were mixed until uniform using a mortar and pestle then heated at 150 °C for 10 minutes. The cooled sample was prepared by using a mortar and pestle to a uniform granule size. Then the formulation was processed utilizing the same conditions but then milled with a grinder to size the granulated/aggregated material obtained during the hot melt technique [0085]. These processes of solvent-free solid dispersion result in the four following steps: i) mixing the formulation (corresponding to instant claim 1 i), ii) melt extruding the mixture at 150 °C (corresponding to instant claim 1 ii), overlapping with the melt extruding temperature about 50 °C to about 200 °C, iii) grinding the melt extrudate (corresponding to instant claim 1 iii), then iv) blending the milled extrudate (corresponding to blending the milled extrudate in instant claim 1 iv)).
Williams indicates that the extrudate comprising the therapeutic agent, mesoporous carrier, and polymer may be dried, formed, milled, sieved, or any combination of these processes to obtain a final composition, as routine and known processes in the art. Additionally, the extrudate may be milled and combined with one or more additional excipients to form the final composition [0081]. In other words, when there is additional excipient in the composition, step iv) above can be modified as following: iv) blending the milled extrudate with excipients to form a pharmaceutical composition (corresponding to blending the milled extrudate with excipients to form solid dispersion pharmaceutical composition in instant claim 1 iv)).
Williams specifies that heating and melting temperature of the composition can be 60-250 °C and many other temperatures can be used [0080], such as, 25-200 °C [0086], 50-180 °C [0097], overlapping with melt extruding temperature ranges from about 50-160C or from about 70-160 C in instant claims 13-14. Williams describes the barrel configuration for processing the extrudates constituting four zones: a feed zone, closed barrel, closed venting zone, and a closed zone, mentioning the feeding zone is maintained at room temperature, while zones 1-3 for the barrel with temperatures at 160 °C before the extrudates are cooled to room temperature [0085, Table 2], which would naturally constitute the at least four heating zones with sequentially lowering temperatures as recited in instant claims 1 ii) and 11-12. It is apparent that the mixture has been melted before the blend passes through this heating zone in order to cool down the melt extrude, corresponding to interpreted claim 11. Since the highest melting temperature designated in solid dispersion taught by Williams is 250 °C as described above, the melting point of all the polymers mentioned in the list herein logically fall below 250 °C, lower than ursolic melting point 284 °C, corresponding to polymer glass transition temperature in instant claim 1 i).
Williams specifies that ASDs typically necessitate a high polymer ratio compared to the active compound to maintain amorphicity, and polymer selection is a critical aspect to form stable ASD formulations and can affect the amount of drug that is loaded and its ability to maintain amorphicity (e.g., [0003]). Williams indicates that the pharmaceutical acceptable polymer in the pharmaceutical composition is cellulosic polymer (e.g., Claims 21-23), and lists numerous proper cellulosic and non-cellulosic polymers for the composition including water-soluble polymers such as, polyvinylpyrrolidone-vinyl acetate copolymer, polyethylene glycol, hypromellose acetate succinate (same as hydroxypropyl methyl cellulose acetate succinate), and polymethacrylate or polyacrylate such as Eudragit® (e.g., [0072], [0073]), which read into instant claims 4-5 and 19. Williams explicitly teaches about 1-49% polymer amount in the composition [0012, 0019] (overlapping to polymer amount about 5% to about 50% in instant claims 7, or from about 30% to about 90% in instant claims 18-19).
Williams indicates that the therapeutic agent in the ASD (amorphous solid dispersion) is a therapeutic agent, e.g., BCS class IV compound such as ursolic acid, is substantially or essentially present as an amorphous form in the pharmaceutical composition (e.g., Claims 16 and 19-20) (corresponding to ursolic acid amorphous status in instant claims 15-17 and 20). Williams exemplifies that therapeutic agent indomethacin after HME process exhibits amorphous status of all samples processed with XDP (e.g., [00102]).
Baek throughout the reference teaches solid dispersions of insoluble drug and preparation method comprising active drug, carbamic acid 3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl ester, and a water-soluble polymer having a glass transition temperature lower than the melting point of the active ingredient as a carrier and it is prepared via melt extrusion. The solid dispersion remarkably increases the solubility and dissolution rate of the active ingredient which is an insoluble drug to efficiently improve the bioavailability (e.g. Abstract).
Baek teaches that the active ingredient is prepared in a solid dispersion with water soluble polymer having the glass transition temperature lower than the melting point of the active ingredient as a carrier (e.g., Claim 1; Claim 9), such as polyvinylpyrrolidone, hydromellose acetate succinate and their combination (Claim 3), wherein the water-soluble polymer is at 30 wt % or more (Claim 4) and the active ingredient is 10 to 50% of the total weight of the composition (Claim 7). Baek specifies that the step of melt-extruding the mixture at a temperature lower than the melting point of the active ingredient (Claim 13), and the melted mixture of the composition passes through four or more heating blocks whose temperature is sequentially lowered (Claim 15) (corresponding to the melted blend passes through at least four heating zones connected in series as recited in instant claim 1 ii) and 11), wherein the heating blocks consist of the first to the fourth heating blocks wherein the melting temperature of the first heating block is controlled to 160 to 145°C, that of the second heating block to 144 to 120°C, that of the third heating block to 119 to 80°C, and that of the fourth heating block to 79 to 70°C (Claim 16), corresponding to a temperature of the heating zone is sequentially lowered while the blend passes sequentially through the at least four heating zones as recited in instant claim 1 ii), with all temperature ranges exactly into the ranges in instant claim 12.
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective
filing date to incorporate specific water-soluble polymers and steps taught in Williams and Baek into the ursolic acid solid dispersion composition from Allegrini to arrive at current invention. It would have been prima facie obvious for one of ordinary skill in the art to combine the prior art elements to modify the ursolic acid solid dispersion preparation with the known solvent-free solid dispersion method because ursolic acid belongs to lipophilic agents suitable for the method as taught by Williams and the solvent-free method taught by Williams and Baek do not require tedious solvent removal step in Allegrini method. One of ordinary skill in the art would have a reasonable expectation of success because all solid dispersion methods taught by prior art yield predictable results of increased solubility and bioavailability, while Williams and Baek provide step by step process with specific water-soluble polymers and temperature ranges in solvent-free solid dispersion process that would facilitate the process of solvent-free solid dispersion. This renders obviousness as “use of known technique to improve similar devices (methods, or products) in the same way” or as “applying a known technique to a known device (method, or product) ready for improvement to yield predictable results”. See MPEP §2143. (I)(C) and (I)(D). Moreover, Williams specifies that ASDs typically necessitate a high polymer ratio compared to the active compound to maintain amorphicity, and polymer selection is a critical aspect to form stable ASD formulations and can affect the amount of drug that is loaded and its ability to maintain amorphicity (e.g., [0003]). It is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (MPEP §2144.07). See Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
Further regarding amorphous status of ursolic acid or pharmaceutical composition amorphous status in storage life, in light of claim interpretation, it is interpreted as property or intended use of ursolic acid and/or the pharmaceutical composition in the process of preparation, which prior art has already taught ursolic acid in the pharmaceutical composition of the ADS process, therefore, such property would necessarily present, or would be capable of being achieved.
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. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP §2144.05(I) states that “A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.” See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003), "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” Also see 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). For this instance, melt extruding the mixture temperature, ursolic acid weight amount, polymer weight amount overlap with those taught in prior art. Furthermore, “[i]t would have been prima facie obvious for one of ordinary skill in the art to optimize additive amount through nothing more than “routine experimentation,” because of a reasonable expectation of success resulting from the optimization for desirable features of intended use of the composition (MPEP §2144.05 (II)). See Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969).
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 1-7, 9 and 11-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over at least claims 1, 3, 6-8 10-13, 16-18 and 20 of copending Application No. 19274778 (hereafter App’778) in view of Allegrini et al. (WO2021089433, 05/14/2021, Record of 11/18/2024), Williams et al. (WO2019051440, 03/14/2029, Record of 11/18/2024) and Baek at al. (WO2014073889, 05/15/2014, Record of 12/16/2025).
App’778 directs to a method for preparing a pharmaceutical composition comprising blending ursolic acid and salts thereof with a water-soluble polymer having a glass transition temperature lower than 170C, melt extruding the blend at a temperature about 60 C to about 180 C (corresponding to instant claims 1 and 13-14) to obtain an extrusion product, grinding and mixing the extrusion product with excipient to produce the composition, wherein the method is free from solvent-associated processing steps (Claims 1 and 12, corresponding to instant claim 1), ursolic acid is in amorphous state (Claim 3) (corresponding to instant claims 15-17), water-soluble polymer is selected from the group as defined in claims 6 and 16 (corresponding to instant claim 4) such as polyvinylpyrrolidonevinyl acetate polymer (Claims 7 and 17) (corresponding to instant claim 5), ursolic acid is about 1% to 50% of the weight of the composition (Claims 8 and 18) (corresponding to instant claims 6 and 19), water-soluble polymer is about 5% to about 90% (Claims 10 and 20) (corresponding to instant claims 7 and 18-19), blend is melted while it passes through at least four heating zones with sequentially lowered temperature (Claim 11) (corresponding to instant claims 1 and 11). App’778 shows the compound ursolic acid formula (Claim 13) (corresponding to instant claim 2).
App’778 does not indicate the solid dispersion pharmaceutical composition has an increase of at least two folds over unprocessed material as recited in instant claim 1, or at least four folds in instant claim 9, the four heating zone temperature ranges as recited in instant claim 12.
As discussed above in great detail, combined prior art Allegrini, Williams and Baek teaches the solid dispersion of ursolic acid can improve bioavailability, and the preparation method can have the defined four heating zones with temperature sequentially lowered for the blend to pass through.
It would have been prima facie obvious to implement the teachings from Allegrini, Williams and Baek into the method and composition of App’778 to arrive at current invention. This renders obviousness as combining prior art elements according to known methods to yield predictable results, see In Supreme Court KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). It is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (MPEP §2144.07). See Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
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. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP §2144.05(I) states that “A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.” See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003).
Furthermore, “[i]t would have been prima facie obvious for one of ordinary skill in the art to optimize additive amount through nothing more than “routine experimentation,” because of a reasonable expectation of success resulting from the optimization for desirable features of intended use of the composition (MPEP §2144.05 (II)). See Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant’s remarks/arguments filed on 04/16/2026 have been fully considered.
35 U.S.C. 112 rejections
Applicant mentions that previous office action has rejected claims 1-9 for “a solid dispersion” on line 7 of claim 1.
This rejection was present NOT in the most recent office action mailed on 12/26/2025. Applicant might have mistaken from earlier office actions that do not direct to current prosecution status. However, amended claims filed on 04/16/2026 have generated new 112 rejections as presented in this office action above.
Art rejections
Applicant asserts each prior art reference, Allegrini, Williams, or Baek does not teach all the claimed elements, for instance, Allegrini does not teach melt-extruding, Williams or Baek shows melt-extrusion temperature is not far from melting temperature of the active ingredient, Williams or Baek does not involve ursolic acid.
One cannot show nonobviousness by attacking references individually where the rejections are
based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck
& Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Because "[T]he test for obviousness is what
the combined teachings of the references would have suggested to [a PHOSITA]." In re Mouttet, 686
F.3d 1322, 1333, 103 USPQ2d 1219, 1226 (Fed. Cir. 2012). The rejection is based on combined teachings of references, thus, each reference does not have to contain all claimed elements, because it is obviousness rejection, not anticipated rejection. The combined prior art Allegrini, Williams, and Baek teaches current invention as a whole.
Applicant asserts that the melt-extrusion temperature in Williams is generally broad, while the working example as practical guidance for the person of the art in Williams shows that indomethacin (IND) is melt extruded at temperature 150 C, right below its active ingredient melting temperature of about 160C; Baek’s working example is using 145-160C right beneath (at least about 88% as close) the active ingredient melting temperature at 165 C, while in instant claim, ursolic acid melting temperature is 283 C, the melt extrusion temperature is performed at most 200 C (as most about 70%) as close to melting temperature.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., melt extrusion temperature at most about 70% as close to melting temperature of active ingredient) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Regarding Williams and Baek does not directly teach ursolic acid, “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983), and "A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments." Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), and "Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments." In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971).
Williams and Baek each presents the melt extrusion temperature which happens to be not far from the melting temperature of the active ingredient in each working example, that does not constitute a teaching away from the broader disclosure of the melt-extrusion temperature ranges disclosed in prior art. Moreover, there is no evidence that prior art teaches that ursolic acid melt extrusion temperature MUST BE CLOSELY beneath its melting temperature. Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). It is applicant’s imaginative deduction based on the working examples in prior art to conclude that the melt extrusion temperature has to be closely beneath melting temperature of the active ingredient, while prior art on the contrary teaches otherwise. The most relevant paragraph from the office action is copied below for reference:
Williams specifies that heating and melting temperature of the composition can be 60-250 °C and many other temperatures can be used [0080], such as, 25-200 °C [0086], 50-180 °C [0097], overlapping with melt extruding temperature ranges from about 50-160C or from about 70-160 C in instant claims 13-14. Williams describes the barrel configuration for processing the extrudates constituting four zones: a feed zone, closed barrel, closed venting zone, and a closed zone, mentioning the feeding zone is maintained at room temperature, while zones 1-3 for the barrel with temperatures at 160 °C before the extrudates are cooled to room temperature [0085, Table 2], which would naturally constitute the at least four heating zones with sequentially lowering temperatures as recited in instant claims 1 ii) and 11-12. It is apparent that the mixture has been melted before the blend passes through this heating zone in order to cool down the melt extrude, corresponding to interpreted claim 11. Since the highest melting temperature designated in solid dispersion taught by Williams is 250 °C as described above, the melting point of all the polymers mentioned in the list herein logically fall below 250 °C, lower than ursolic melting point 284 °C, corresponding to polymer glass transition temperature in instant claim 1 i).
Applicant asserts that Williams results in solid dispersion in which the active ingredient has low stability of the amorphous state, while Allegrini does not involve melt-extruding and Baek is expected of deficiency in the stability of the amorphous state due to melt-extrusion temperature being close to melting temperature of the active ingredient, same as Williams.
The combined prior art teaches the current invention as presented in the office action as presented above in detail. Williams explicitly teaches that the active ingredient in the composition is in amorphous state (see below the copied paragraph). Even though working examples in Baek and Williams use extrusion temperature closely beneath melting temperature of the active ingredient, there is no evidence that the ingredient is not in amorphous state, moreover, there is no evidence in prior art teaching that ursolic acid in ADS has to use melt extrusion temperature closely beneath its melting temperature, as applicant asserts. Again, Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965).
Here is the most relevant paragraph from office action showing prior art teaching the stable amorphous state of the active ingredient:
Williams indicates that the therapeutic agent in the ASD (amorphous solid dispersion) is a therapeutic agent, e.g., BCS class IV compound such as ursolic acid, is substantially or essentially present as an amorphous form in the pharmaceutical composition (e.g., Claims 16 and 19-20) (corresponding to ursolic acid amorphous status in instant claims 15-17 and 20). Williams exemplifies that therapeutic agent indomethacin after HME process exhibits amorphous status of all samples processed with XDP (e.g., [00102]).
In conclusion, the arguments are not persuasive.
Please refer to the entire office action as a complete response to the remarks/arguments.
Conclusion
No claim is allowed.
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.
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/DX.Z./Examiner, Art Unit 1616
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616
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