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 .
Priority
The instant application is a 371 National Stage Entry of PCT/CN2020/135369 filed on December 10, 2020 which claims priority to foreign application No. App CN202011243436.5 filed on November 9, 2020.
English Translation
Examiner notes that a certified translation of the Foreign Application CN202011243436.5 (filed November 9, 2020) has been placed on record.
Status of Claims
Acknowledgement is made of previously presented (1, 7, 9-11, 18), amended (3-5, 8, 12-17), and cancelled (2, 6) claims filed January 20, 2026. Claims 1, 3-5, 7-18 are pending in instant application.
Response to Arguments
In light of Applicant’s amendments filed January 20, 2026, the rejection of claims 7-8 under 35 U.S.C. 112(b) has been withdrawn.
Applicant's arguments filed January 20, 2026 have been fully considered but they are not persuasive.
Regarding teaching a combination (see 1/20/26 Remarks at p. 6), the prior art provides motivation to combine because each component is known to treat substance abuse relapse (see 9/17/25 Office Action at p. 6).
Regarding unexpected effect (see 1/20/26 Remarks at p. 7),
It is the Examiner’s understanding that Applicant alleges the existence of unexpected results commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02, wherein such results are sufficient to rebut prima facie obviousness.
However, to establish unexpected results, the evidence must establish that the expected results occur to an unexpected extent (see, e.g., MPEP § 716.02(a)(I)), on the basis of statistically and practically significant evidence (see, e.g., MPEP § 716.02(b)(I)), which is fully explained (see, e.g., MPEP § 716.02(b)(II)), commensurate in scope with the claimed invention (see, e.g., MPEP § 716.02(d)), and wherein a comparison of the claimed invention with the closest prior art of record is provided (see, e.g., MPEP § 716.02(e)). Furthermore, even if evidence satisfying MPEP §§ 716.02, 716.02(a), 716.02(b), 716.02(d), and 716.02(e) is set forth on record, such evidence may not be sufficient to rebut prima facie obviousness because the evidence of expected and unexpected results must be weighed (see, e.g., MPEP § 716.02(c)(I)) and the totality of the record considered (see, e.g., MPEP § 716.02(f)), including teachings in the prior art and evidence of expected results which weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)).
If Applicant means to allege the existence of unexpected results commensurate in scope with the requirements of MPEP § 716.02 based upon instant sustained release and stability over 90 days (see 1/20/26 Remarks at p. 7 ¶1 and at Figure 8), and a reduction in mice spontaneous activities (see Figure 9), this is also not persuasive because the requirements of MPEP § 716.02 have not been satisfied. Specifically, MPEP § 716.02(d) is not satisfied because such proffered evidence is not commensurate in scope with the instant claims with respect to parts of naltrexone, parts of risperidone, method of making risperidone microsphere (including solvents, concentrations, additives, polymers), and method of making naltrexone microsphere (including solvents, concentrations, additives, polymers) (see instant claim 1); rather the examples are highly limited to two specific embodiments of the instant invention (see instant spec. at pp. 9-10 Example 1 and Figures 6, 8, and pp. 10 – 12 Example 2 and Figure 7). Notably these embodiments require static concentrations, fully defined component species, and fail to establish that the observed results persist within the full scope and ranges of compositions presently claimed (see, e.g., MPEP § 716.02(d)).
In addition, the instant specification states "to achieve the synchronous release of the two sustained-release microspheres, the parameters need to be limited within the ranges by the present disclosure" (see instant spec. at p. 17 par 1) which indicates unpredictability in the art. Furthermore, the prior art teaches microspheres of each component within the instantly claimed ranges. One would thus expect that combining the compositions taught by the prior art would exhibit the same beneficial properties. Applicant is stating the parameters must be limited, but only shows a small range to be superior, it is unclear how such specific data can be extrapolated over the entire claimed range and show the same unexpected effect.
Either i) there are specific, superior embodiments/ranges, in which case Applicant must support the scope of such embodiments/ranges, and amend the claims to reflect such, or ii) compositions of the ranges disclosed all display the beneficial properties, so any composition taught by the prior art that falls within the range must also have the beneficial properties.
Claim Interpretation
Claim 8 recites 0-10 wt% sodium chloride or 0-20 wt% sucrose which optionally reads on no sodium chloride or sucrose present.
Maintained/Modified Rejections
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.
Claims 1, 3-5, 7-8, 10-17 are rejected under 35 U.S.C. 103 as being unpatentable over Dinarvand et. al.1 and CN106474070 A to Yao2 in view of Smelson et. al.3 and Vogel et. al.4 as exemplified by STN5.
Regarding claim 1 and naltrexone, Dinarvand teaches an emulsification/solvent-evaporation method for preparing naltrexone microspheres (see Dinarvand at p. 2 “Microsphere Preparation”).
Regarding claim 1 and risperidone, Yao teaches a method of making microspheres comprising a hydrophobic drug, optionally risperidone, with a double emulsion-evaporation strategy (see Yao claim 1).
Regarding claims 3, 11-13, Yao teaches dissolving the hydrophobic drug (risperidone) and a polymer, optionally polylactic acid-co-glycolic acid, polylactic acid, or polycaprylactone (all fat-soluble polymers, see instant spec at p. 4 lines 1-3) in an organic solvent (corresponding to claim 3 step 2) and adding the mixture to an inner aqueous phase which is water or an aqueous solution (corresponding to claim 3 step 1) optionally with additives such as NaCl, sucrose, or mannitol (compare Yao claim 7 with instant spec. at p. 3 lines 33-34), then adding the mixture to a surfactant aqueous solution, optionally the surfactant is polyvinyl alcohol (see Yao claim 4, a water-soluble polymer see instant spec. at p. 4 line 5), ultrasonically treating (see Yao at claim 6) to form a double emulsion, then stirring until the organic solvent evaporates (corresponding to claim 3 step 4) (see Yao claim 1).
Regarding claims 4-5, 14, Yao teaches adding 1% NaCl to the inner aqueous phase (see Yao at p. 48 [0090]). Yao does not specify the drug concentration in mg/mL units, but does teach the amount of organic solvent is 2 – 25 g per gram of the hydrophobic drug (Yao claim 2), and an embodiment where 1.25 g of risperidone is dissolved in 15 mL of dichloromethane, 83 mg/mL (Yao p. 36 [0056] and p. 40 ¶[0066]). Yao teaches the organic solvent may be dichloromethane or ethyl acetate (Yao claim 1). Yao teaches an embodiment wherein 1.8 g of 7525DLG7E (PLGA, see Yao at p. 19 ¶[0026]) is dissolved in 15 mL of dichloromethane, 120 mg/mL (see Yao at p. 36 ¶[0056]). Yao does not specify the volume ratio of primary emulsion to aqueous solution, but does teach embodiments of volume ratios for forming the first emulsion (see Yao at p. 10 ¶[0013]). Yao does not specify the amount of water-soluble polymer in wt% units, but does teach the water-soluble polymer (e.g. PVA) surfactant aqueous solution having a concentration of 0.005-0.05 g/mL.
Regarding claim 7, 15-16, Dinarvand teaches adding PLA (polylactic acid, a fat-soluble polymer, see instant spec. at p. 4 lines 1-2) to methylene chloride (an organic solvent also known as dichloromethane as explained by STN, see instant spec. at p. 5 line 24), dissolving naltrexone, then drop-wise adding the solution to an aqueous phase comprising PVA (polyvinyl alcohol, a water-soluble polymer, see instant spec. at p. 4 line 5), then stirring to evaporate the methylene chloride (see id).
Regarding claim 8, 17, Dinarvand does not specify mg/mL units but teaches naltrexone was dissolved to provide 1-2.5% wt/vol drug solutions, PLA in methylene chloride provided concentrations of 2.5, 3, 3.5 and 4% wt/vol, and 200 mL aqueous phase containing 0.5% wt/vol PVA (see Dinarvand at p. 2 “Microsphere Preparation”).
Regarding claim 10 and naltrexone, Dinarvand teaches naltrexone is an opiate antagonist used to prevent relapse in opioid-dependent patients currently with patient self-administered forms, with a new focus in the field of preparing naltrexone injectable microparticles or implants as delivery methods (see Dinarvand at p. 1-2 “Introduction”).
Regarding claim 10 and risperidone, Smelson teaches that risperidone treats substance abuse relapses and cocaine dependence (see Smelson at Title and Results).
Regarding differences in ratios or concentrations, Vogel teaches reaction yields may be optimized by varying time, temperature, solvent mixtures, or molar ratios of reactants (see Vogel at p. 34 ¶2).
The prior art differs from the instant claims as follows: While Dinarvand, Yao, and Smelson teach naltrexone microsphere and risperidone microspheres for treating drug addiction, they do not specify a combination of the two.
However, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reasons:
Regarding a combination, per MPEP § 2144.06(I), "[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Combining the naltrexone microsphere composition for treating addiction taught by Dinarvand with the risperidone microsphere composition taught by Yao to treat addiction as taught by Smelson would have a reasonable expectation of success because each composition was known to treat addiction on its own.
Regarding differences in ratios or concentrations, the final microsphere products taught by Dinarvand and Yao are the same as those instantly claimed absent evidence that the claimed steps result in a structurally distinct product (see MPEP § 2113(I-II)).
In addition or in the alternative, per MPEP § 2144(II)(A) differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. In addition, it would have been obvious to one skilled in the art to optimize ratios in a method of preparing microspheres taught by Dinarvand or Yao through routine experimentation as taught by Vogel (see also MPEP § 2144.05(II)).
Accordingly claims 1, 3-5, 7-8, 10-17 are obvious over Dinarvand and Yao in view of Smelson and Vogel as exemplified by STN.
Claims 9, 18 are rejected under 35 U.S.C. 103 as being unpatentable over Dinarvand and Yap in view of Smelson and Vogel as exemplified by STN as applied to claims 1, 3-5, 7-8, 10-17, and in further view of Paul et. al.6
The prior art differs from the claims as follow: While Dinarvand teaches tableting of the PLA microspheres containing naltrexone (see Dinarvand at p. 7 left col. ¶2), Dinarvand does not specify the presence of a lubricant.
However,
Paul teaches magnesium stearate, sodium stearyl fumerate, and stearic acid are commercially available tablet lubricants (see Paul at Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2143(I)(A), a prima facie case of obviousness exists for combining prior art elements according to known methods to yield predictable results. It would have been obvious to combine Dinarvand’s teaching of tableting naltrexone microspheres with the teachings of Paul’s lubricants for tableting to arrive at the instant invention because Paul teaches the lubricants are commonly used, efficient, and tailorable for tablet formulation.
Accordingly claims 9, 18 are obvious over Dinarvand, Yao, Smelson, Vogel, as exemplified by STN and in further view of Paul.
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, 3-5, 7-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 19/115,6317 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The copending claims are drawn to combination of risperidone and naltrexone microspheres for treating addiction (compare App’631 claims 1, 10 with instant claims 1, 10), wherein App’631 “degradable material A” and “degradable material B” are indistinct from or substantially overlap with instant “fat-soluble polymer” (compare App’631 claim 3 with instant claims 12, 15), App’631 “additive” is indistinct from instant “additive” (compare App’631 claim 3 with instant claim 11), App’631 “lubricant” is indistinct from instant “lubricant” (compare App’631 claim 3 with instant claims 9, 18). App’631’s process of preparing risperidone microspheres is a double-emulsion solvent evaporation method and naltrexone microsphere is an emulsion-solvent evaporation method with the substantially overlapping or indistinct steps (compare App’631 claims 4-9, 11-13 with instant claims 3-5, 7-9, 11-18).
The copending claims differ from instant claims as follows: App’631 claims an implant comprising instant compositions.
Per MPEP § 804(II)(B)(1), it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim (see, e.g., MPEP § 804(II)(B)(1)). App’631 states that the naltrexone implant was prepared by blending microspheres with a lubricant and tableting (see App’631 at pp. 23-24 Steps 4 and 5) and risperidone implant was prepared by blending microspheres with a lubricant and tableting (see App’631 pp. 24-25 Steps 3 and 4). This appears substantially overlapping with instant claims 9, 18 detailed a tablet comprising microspheres and a lubricant selected from the same as those in App’631 claim 1.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 3-5, 7-18 are rejected.
THIS ACTION IS MADE FINAL. 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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/S.R./ Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Dinarvand et. al. "Preparation of Biodegradable Microspheres and Matrix Devices Containing Naltrexone", AAPS PharmSciTech 2003, 4, 3, 34, 1-10. DOI: 10.1208/pt040334
2 Published March 8, 2017, cite No. 4 in the IDS filed 5/22/23. Citations herein refer to Machine Translation of CN 106474070 A, Translated by Patent Translate Espacenet.org on 9/10/25, 75 pages. Hereinafter Yao.
3 Smelson et. al. "Risperidone Decreases Craving and Relapses in Individuals with Schizophrenia and Cocaine Dependence" Can J Psychiatry, 2002, 47, 7, 671-675. DOI: 10.1177/070674370204700710
4 Vogel et. al. "Vogel's Textbook of Practical Organic Chemistry" 5th Ed; Longman Scientific & Technical: London, 1989. Select Pages.
5 Dichloromethane (CAS 75-09-2) CAS Registry File Accessed September 11, 2025 from STN, entered into STN November 16, 1984. Hereinafter STN.
6 Paul et. al. "Systematic evaluation of common lubricants for optimal use in tablet formulation" European Journal of Pharmaceutical Sciences 2018, 117, 118-127, DOI: 10.1016/j.ejps.2018.02.013. Hereinafter Paul.
7 371 of PCT/CN2023/122253 filed September 27, 2023, claiming foreign priority to CN202211195550.4 filed September 28. 2022.