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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-7 and 9-10, drawn to a pharmaceutical composition; and the following species:
castor oil as the species of liquid oil;
glyceryl monostearate as the species of pharmaceutically acceptable gelator;
SPC as the species of pharmaceutically acceptable stabilizer;
a combination of ropivacaine and meloxicam as the species of the pharmaceutically active ingredients; and
DMSO as the species non-aqueous solvent
are maintained.
Claim 8 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and species, there being no allowable generic or linking claim.
Newly added claims 15-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Expansion of Election of Species Requirement
A reasonable and comprehensive search of the elected species conducted by the Examiner
discover a prior art by Wang et al. that renders obvious the claimed invention, wherein the prior art teaches anhydrous ethanol and benzyl alcohol as a non-aqueous solvent in the working example. In light of this discovery, the search is expanded to the subject matter of the non-aqueous solvent to include the combination of anhydrous ethanol and benzyl alcohol in addition to the elected dimethyl sulfoxide, such that it does not encompass the full scope of the claims.
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on March 2, 2026, wherein claims 1, 3-7, 10-11 and 13-14 are amended; claims 2 and 8 are unchanged; claims 9 and 12 are cancelled; and claims 15-20 are newly added.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-8, 10-11, 13-20 are pending.
Claim 8 remain withdrawn. Claims 15-20 are withdrawn.
Claims 1-7, 10-11, and 13-14 are under examination in accordance with the elected invention and species.
Priority
The instant application 18/253,429 filed on May 18, 2023 is a 371 of PCT/CN2022/071928 filed
on January 14, 2022, which claims priority to, and the benefits of Foreign Application No. CN202110051096.4 filed on January 14, 2021.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Action Summary
Acknowledgement is made of the receipt and entry of the amendment to the specification filed on March 2, 2026. Applicant’s amendment to the specification and claims overcome each and every objection previously sets forth in the Non-Final Office Action mailed on December 1, 2025.
Claim 11 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 are withdrawn in light of the claim amendments.
Claim 12 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 are withdrawn in light of the claim amendments. Said claim is now cancelled.
Claims 1-7 and 9-14 rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 2021/129635 A1; cited in the IDS filed on 10/22/2025), in view of Shen et al. (WO 2019/113366 A1), as evidenced by Kumar et al. (Renewable and Sustainable Energy Reviews, 2010. Vol. 14 (7): 1830-1844) are withdrawn in light of the claim amendments that added the new limitation of “the pharmaceutical composition is an oleogel”. Upon further consideration, the prior arts have been reapplied for the reasons set forth herein.
Declarations
The declarations under 37 CFR 1.132 filed on March 2, 2026 is insufficient to overcome the rejection of claims 1-7 and 9-14 based upon Wang et al. (WO 2021/129635 A1; cited in the IDS filed on 10/22/2025) in view of Shen et al. (WO 2019/113366 A1), as evidenced by Kumar et al. (Renewable and Sustainable Energy Reviews, 2010. Vol. 14 (7): 1830-1844), under 35 U.S.C. 103 as set forth in the last Office action because of the reasons shown below:
In Summary, the declarant conducted Supplemental Experiments I and II to investigate gel formation and stability using different ingredients. The declarant argues compositions containing castor oil and some excipients that are common materials of sustained-release formulation cannot form an ideal stable gel, because Supplemental Experiment I demonstrates compositions of Table I are not suitable for industrial production as they fail to form a gel or demand high temperature or long time for solidification. The declarant further argues commonly used stabilizer, such as anti-oxidants or surfactants, formed gels with various deficiencies, because Supplemental Experiment II demonstrate compositions C2-C3 of Table III, compositions C4-C8 of Table IV, and compositions C9-C11 of Table V are significantly darker.
In response, according to MPEP 716.02 (E) “[a]n affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). ’A comparison of the claimed invention with the disclosure of each cited reference to determine the number of claim limitations in common with each reference, bearing in mind the relative importance of particular limitations, will usually yield the closest single prior art reference." In re Merchant, 575 F.2d 865, 868, 197 USPQ 785, 787 (CCPA 1978) (emphasis in original). Where the comparison is not identical with the reference disclosure, deviations therefrom should be explained, In re Finley, 174 F.2d 130, 81 USPQ 383 (CCPA 1949), and if not explained should be noted and evaluated, and if significant, explanation should be required. In re Armstrong, 280 F.2d 132, 126 USPQ 281 (CCPA 1960) (deviations from example were inconsequential).’”. In the present case, the Examiner respectfully noted that none of the compositions described in Table I of Supplemental Experiment I is a claimed pharmaceutical composition or a composition taught by the cited prior art(s); therefore, the compositions of Table I, drawn to compositions not specifically claimed, are considered incomparable and irrelevant to the claimed invention.
Additionally, Composition C1 of Table III shown below (see Table III of the declaration):
PNG
media_image1.png
216
614
media_image1.png
Greyscale
does not fall within the scope of the pharmaceutical composition instantly claimed. Compositions C2-C11 described in Table III, IV and V of Supplemental Experiment I are not a claimed pharmaceutical composition nor a composition taught by the cited prior art(s). In other words, these results do not appear to be a true comparison to demonstrate unexpected results.
Additionally, according to MPEP 716.02(d), “whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the ‘objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.’ In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)”. It is respectfully noted that Composition C1 contains 58.6 wt% of castor oil (CO), 22.2 wt% of glyceryl monostearate (IMWITOR® 900K), 2.5 wt% of ropivacaine (ROP), 0.19 wt% of meloxicam (MLX), 3.51 wt% of N-methylpyrrolidone (NMP), 3 wt% of soybean phosphatidylcholine (SPC), and 10 wt% of benzyl alcohol (BA). In contrast, instant claim 1 recites “[a] pharmaceutical composition, comprising … a pharmaceutically acceptable gelator selected from glyceryl monostearate, glyceryl distearate, and mixtures thereof; a pharmaceutically acceptable stabilizer selected from soybean phosphatidylcholine, palmitoyloleoylphosphatidylcholine, dierucoylphosphatidylcholine, egg yolk phospholipid, dioleoylphosphatidylcholine, and combinations thereof… the pharmaceutically acceptable gelator accounts for 5 w/w% to 20 w/w% of the total amount of the composition; the pharmaceutically acceptable stabilizer accounts for 4 w/w% to 12 w/w% of the total amount of the composition”. In other words, the weight-by-weight percentage of glyceryl monostearate in the composition(s), including Composition C1, provided by the declarant exceeds the upper limit of 20 w/w%, and that does not provide adequate basis to support the claimed invention demonstrate unexpected results. In addition, the weight-by-weight percentage of SPC in composition C1 is lower than the lower limit of 4 w/w%, and that does not provide adequate basis to support the claimed invention demonstrate unexpected results.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
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.
Claim 10 is 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 (newly applied as necessitated by amendments).
Regarding claim 10, the claim recites "[a] sustained-release formulation" and further recites "wherein the formulation comprises a packaging filled with the sustained-release formulation”; therefore, it is not clear whether the "sustained-release formulation" refers to the formulation itself or to a packaged article including both the packaging and the formulation contained therein. The claim thus presents an internally inconsistent and circular recitation regarding the relationship between the formulation and the packaging. The lack of clarity renders the claim indefinite as one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The claim may be amended the following ways if proper support is established: (i) a packaged sustained-release formulation comprising the pharmaceutical composition according to claim 1, wherein the packaging is selected from the group consisting of a vial, a pre-filled syringe, and a cartridge; or (ii) A package comprising the pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is a sustained-release formulation, and wherein the package is selected from the group consisting of a vial, a pre-filled syringe, and a cartridge.
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 1-7, 10-11, and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 2021/129635 A1; cited in the IDS filed on 10/22/2025), in view of Shen et al. (WO 2019/113366 A1; cited in the previous Office Action), as evidenced by Kumar et al. (Renewable and Sustainable Energy Reviews, 2010. Vol. 14 (7): 1830-1844; cited in the previous Office Action) (newly reapplied as necessitated by amendments).
Please note Wang et al. cited in the IDS filed on 10/22/2025 is written in foreign language and the legible copy provided therein only has an English translation of the abstract; therefore, a machine translation of said foreign patent application has already been provided in the previous Office Action, the specific portions cited in this instant Office Action will refer to the sections of the machine translated copy.
Wang et al. teaches a pharmaceutical composition labeled as “Composition 14“ in Table 16-1 shown below (see shaded):
PNG
media_image2.png
142
734
media_image2.png
Greyscale
, and
PNG
media_image3.png
30
196
media_image3.png
Greyscale
(see page 9, line 25 of Wang et al. in foreign language). According to the machine translation, the compositions of Table 16-1 are:
PNG
media_image4.png
227
1084
media_image4.png
Greyscale
, in which composition 14 comprises 46.3% (w/w) of castor oil, 5% (w/w) of hydrogenated soybean phospholipids, 10% (w/w) of soybean phospholipids, 5% (w/w) of ropivacaine, 3.7% (w/w) of meloxicam solution (dissolved in N-methyl pyrrolidone), 10% (w/w) of anhydrous ethanol, and 20% (w/w) of benzyl alcohol (see e.g., Table 16-1; [0207]); and EtOH stands for anhydrous ethanol (see e.g., [0082]). Please note the anhydrous ethanol taught by Wang et al. is an absolute ethanol, as evidenced by Kumar et al. (see e.g., p. 1831, right column, “1.1 Anhydrous ethanol”). Wang et al. further teaches after cooling to room temperature, the resulting composition was a liquid that could be gelled by adding water (see e.g., [0207]). Wang et al. further teaches a pharmaceutical composition comprising a liquid oil selected from, inter alia, castor oil; at least one compound represented by formula I selected from phosphatidylcholine compounds; at least one pharmaceutically active ingredient; may further comprises at least one pharmaceutically acceptable solvent selected from organic solvent or a mixture of water and organic solvent, and preferably, the organic solvent is selected from one or more combination of, inter alia, dimethyl sulfoxide and alcohols selected from, inter alia, ethanol (see e.g., claims 1-2 and 7); may further comprises a pharmaceutically acceptable release modifier and/or a gelling agent. Preferably, the pharmaceutically acceptable release modifier is selected from one or more combinations of unsaturated phospholipids and other surfactants (see e.g., claim 4). Wang et al. further teaches the liquid oil accounts for about 20% to about 99.5% (w/w) of the total composition (see e.g., claim 6; [0036]); the compound represented by Formula I accounts for 0.5 to 40% (w/w) of the total composition; the pharmaceutically active ingredient comprises 0.1% to 50.0% (w/w) of the total composition; the total solvent comprises 0% to 50% (w/w) of the total composition; the release modifier comprises 0.1% to 40% (w/w) of the total composition; the gelling agent comprises 1% to 40% (w/w) of the total composition; and the surfactant comprises 0.1% to 5% (w/w) of the total composition (see e.g., claim 6). Wang et al. further teaches the unsaturated phospholipids are, inter alia, soybean phospholipids (see e.g. claim 4). Wang et al. further teaches the pharmaceutically acceptable gelling agent is selected from one or more combinations of, inter alia, fatty acid glycerides (see e.g., claim 4). Wang et al. further teaches a formulation comprising the pharmaceutical composition, wherein the formulation further comprises a packaging material filled with the formulation, and the packaging material is selected from one or more of the following: vials, pre-filled syringes, and cartridge vials (see e.g., claims 9-10). Wang et al. further teaches the pharmaceutical composition can be used in a sustained-release preparation system, so that the drug is in the form of a semi-solid or solution at room temperature (see e.g., abstract). Wang et al. further teaches as the ambient temperature decreases, the gelling agents can trap the liquid oil through self-assembly or crystallization to form a three-dimensional network structure, preventing the flow of the lipophilic liquid and thus solidifying the entire system into a gel. Compared to hydrogels, oil gels have unique advantages, such as simple preparation and high manipulability; they can encapsulate different types of drugs; and as the oil gel degrades in vivo, it can achieve slow drug release, prolonging the drug release cycle (see e.g., [0007]). Wang et al. further teaches oil gels are thermally reversible viscoelastic semi-solid substances composed of a lipophilic liquid (mainly liquid oil) and a small amount of gelling agents (see e.g., [0007]).
Wang et al. does not teach the elected pharmaceutically acceptable gelator (glyceryl monostearate).
Shen et al. teaches suitable gelling agents can be, inter alia, solid partial glyceride of fatty acids (see e.g., [0055]); and the solid partial glycerides of fatty acids that can be added to castor oil to form a semi-solid gel include GELEOLTM, a glyceryl monostearate with a melting point of 54°C to 64 °C (see e.g., [0058]). Shen et al. further teaches the rate of release may be increased or decreased by using different level of gelling agents; and it may also be altered by selecting different gelling agents or by changing their amount, or the combination thereof (see e.g., [0073]). Shen et al. further teaches the castor oil mixed with the gelling agents (the final delivery vehicle), and the delivery vehicle with the active ingredients can form a defined long-lasting depot once administered into the body at 37° C, and will gradually degrade/erode, and be dissolved into the body liquids, and the semi-solid lipids will eventually be hydrolyzed to natural free glycerol and free fatty acids by lipase through a process called lipolysis (see e.g., [0062]).
According to MPEP §2144.05, “[i]n 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). In the present case, Wang et al. clearly teaches composition 14 can be used in a sustained-release preparation system, so that the drug is in the form of a semi-solid or solution at room temperature; and the use of gelling agents can trap the liquid oil, prevent the flow of the lipophilic liquid, and solidify the entire system into a gel known as oil gels; reading on the “oleogel”. The difference between the composition 14 of Wang et al. (composition 14 comprises 46.3 w/w% of castor oil, 10 w/w% of soybean phospholipids, 5 w/w% of ropivacaine, 3.7 w/w% of meloxicam solution [dissolved in N-methyl pyrrolidone], 10 w/w% of anhydrous ethanol, and 20 w/w% of benzyl alcohol) and the claimed pharmaceutical composition is that the prior art composition contains 46.3 w/w% of castor oil rather than 50 w/w% to 70 w/w%, and the prior art composition does not contain 5 w/w% to 20 w/w% of the elected pharmaceutically acceptable gelator (glyceryl monostearate) as the gelling agent; and the prior art composition contains 10 w/w% of absolute ethanol and 20 w/w% of benzyl alcohol rather than 5 w/w% to 20 w/w%. Please note the soybean phospholipids taught by Wang et al. is a soybean phosphatidylcholine according to page 4, line 28-29 of the specification; and the anhydrous ethanol taught by Wang et al. is an absolute ethanol, as evidenced by Kumar et al. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by modifying the composition 14 of Wang et al. by further incorporating 1% to 40% (w/w) of fatty acid glycerides as the gelling agent, then selectively choose to incorporate glyceryl monostearate taught by Shen et al. as the fatty acid glycerides, and then modifying the weight-by-weight percentage of the castor oil to the range of about 20% to about 99.5% (w/w) of the total composition, and modifying the weight-by-weight percentage of the total solvent (absolute ethanol + benzyl alcohol) to the range of about 0% to 50% (w/w) of the total composition. One would have been motivated to do so, because Wang et al. teaches the pharmaceutical composition may further comprises a pharmaceutically acceptable gelling agent selected from fatty acid glycerides that accounts 1% to 40% (w/w) of the total composition, and the weight-by-weight percentage of castor oil can be in the range of about 20% to about 99.5%, and the weight-by-weight percentage of total solvent can be in the range of about 0% to 50% (w/w); and Shen et al. teaches glyceryl monostearate is an exemplary solid partial glyceride of fatty acids and a suitable gelling agent that can be added to castor oil to form a semi-solid gel. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by incorporating 1% to 40% (w/w) of glyceryl monostearate taught by Shen et al. as the gelling agent into the pharmaceutical composition of Wang et al. would have successfully solidify castor oil; and by modifying the w/w % of castor oil starting from 46.3 w/w% to the range of about 20% to about 99.5% (w/w), and modifying the w/w % of total solvent staring from 10 w/w% of absolute ethanol and 20 w/w% of benzyl alcohol to the range of 0% to 50% (w/w) would have successfully arrive at a pharmaceutical composition that can be employed in the sustained-release preparation system to give an oil gel.
Regarding the limitation of “[a] sustained-release formulation comprising the pharmaceutical composition according to claim 1, wherein the formulation comprises a packaging filled with the sustained-release formulation, wherein the packaging is selected from…pre-filled syringe ” in claim 10, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by packaging the modified composition 14 of Wang et al. and Shen et al. set forth above in a pre-filled syringe. One would have been motivated to do so, because Wang et al. teaches the formulation can be employed in the sustained-release preparation system, and can be filled into a packaging material including a pre-filled syringe. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the modified composition 14 of Wang et al. and Shen et al. set forth above can be in sustained-release formulation, and successfully fill into a pre-filled syringe for packaging.
Regarding the limitation as claimed in claim 11, according to MPEP §2144.05, “[i]n 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). In the instant case, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by modifying the weight-by-weight percentage of ropivacaine and meloxicam to the range of 0.1% to 50.0% (w/w) in the modified composition 14 of Wang et al. and Shen et al. set forth above, because Wang et al. teaches the pharmaceutically active ingredient can be in the range of 0.1% to 50.0% (w/w) of the total composition. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by modifying the weight-by-weight percentage of ropivacaine and meloxicam, starting from 5 w/w % of ropivacaine and 3.7 w/w% of meloxicam, to the range of 0.1% to 50.0% (w/w) would have successfully arrive at a pharmaceutical composition that can be employed in the sustained-release preparation system to give an oil gel.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Response to Arguments
Applicant's arguments filed on March 2, 2026 with respect to the rejection of claims 1-7 and 9-14 under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 2021/129635 A1; cited in the IDS filed on 10/22/2025), in view of Shen et al. (WO 2019/113366 A1), as evidenced by Kumar et al. (Renewable and Sustainable Energy Reviews, 2010. Vol. 14 (7): 1830-1844) have been fully considered but they are not persuasive.
Applicant amends claim 1 that changes the scope of the claims. Specifically, Applicant amends claim 1 by adding a new limitation “the pharmaceutical composition is an oleogel”; amending the recitation of “a non-aqueous solvent” to the recitation of “a non-aqueous solvent selected from benzyl alcohol, absolute ethanol, N-methylpyrrolidone, benzyl benzoate, dimethyl sulfoxide, and mixtures thereof”, which is previously recited in claim 12; deleting the recitation of “dipalmitoyloleoylphosphatidylcholine (DPPC)” and adding the new limitation “palmitoyloleoylphosphatidylcholine” to the list of pharmaceutically acceptable stabilizer; and amending the recitation of “a pharmaceutically acceptable gelator selected from glyceryl monostearate, glyceryl distearate, glyceryl tristearate, glyceryl monobehenate, glyceryl dibehenate, glyceryl monopalmitate stearate, glyceryl dipalmitate stearate, glyceryl monopalmitate, glyceryl dipalmitate, and glyceryl palmitate stearate” to the recitation of “ a pharmaceutically acceptable gelator selected from glyceryl monostearate, glyceryl distearate, and mixtures thereof”, and “mixtures thereof” is a new limitation. Applicant further amends claim 10, from the recitation of “[t]he sustained-release formulation according to claim 9, further comprising a packaging filled with the formulation, wherein the packaging is selected from a vial, a pre-filled syringe, and a cartilage” to the recitation of “[a] sustained-release formulation comprising the pharmaceutical composition according to claim 1, wherein the formulation comprises a packaging filled with the sustained release formulation, wherein the packaging is selected from a vial, a pre-filled syringe, and a cartridge”. Each of these findings demonstrate that the amendment changes the scope of the claims, and necessitated a modification of the rejection on the record.
In Summary, Applicant argues saturated phospholipid is an essential component for the pharmaceutical composition of Wang et al. for achieving the desired formulation properties, and further argues the claimed invention does not involve a saturated phospholipid. Specifically, applicant cites paragraph [0116], [0117], [0123], Example 3 and Example 16 of Wang et al. to support said argument. In sum, paragraph [0116], [0117], [0123] of Wang et al. teaches compositions containing unsaturated phospholipids (SPC and EPC) are in solution form at room temperature and cannot be used to obtain semi-solid formulations; Example 3 of Wang et al. teaches the composition containing unsaturated phospholipids fails to form a depot; and Example 16 of Wang et al. teaches the presence of a saturated phospholipid to form a gel depot is ensured, the formulation can further contain an unsaturated phospholipid as a release modulator. Applicant further argues the formulation taught by Wang et al. is a liquid that undergoes a phase transition in vivo after injection to form a gel depot, and formulation containing only unsaturated phospholipid cannot undergo this phase transition to form a semi-solid; and therefore, applicant argues one would have no motivation to incorporate compositions lacking saturated phospholipids to be used as a starting point for further research and development.
In response, applicant’s argument is not found persuasive. It may well be true that the compositions of Wang et al., including Composition 14, contains saturated phospholipid; However,
it is respectfully noted that the instant claim(s) recites the transitional term “comprising”. According to MPEP 2111.03, “[t]he transitional term ‘comprising’, which is synonymous with ‘including,’ ‘containing,’ or ‘characterized by,’ is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004)”. In other words, the instant claims do not exclude “saturated phospholipid” as an additional, unrecited element(s); and therefore, said argument is not found persuasive.
In response to applicant’s argument that the formulation(s) disclosed by Wang et al. is a liquid that undergoes a phase transition in vivo after injection to form a gel depot, this appears to be a mere argument without factual evidence. It is noted that the feature of “gel depot” addressed in the argument is 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). To the extent that “gel depot” is referring to the “oleogel” instantly claimed, the Examiner noted Wang et al. clearly teaches the composition 14 was a liquid that could be gelled by adding water after cooling to room temperature (see e.g., [0207]); and said prior art also teaches the gelling agents is capable of trapping the liquid oil, preventing the flow of the lipophilic liquid, and solidifying the entire system into a gel, also known as oil gels (see e.g., [0007]). If applicant premises the formulation disclosed by Wang et al., specifically, the composition 14 sets forth in the rejection above, with or without the incorporation of the gelling agent(s) cannot arrive at an oleogel, supporting evidence is respectfully requested.
Applicant further argues the teachings of Wang et al. and Shen et al. cannot be combined, because Shen et al. fails to teach the performance properties, such as the oil-retention property, emphasized in the present invention, and fails to teach component (b) and the specific combination (castor oil + unsaturated phospholipid + API) instantly claimed.
In response to applicant's argument that Shen et al. fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “the performance properties”) 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).
Additionally, the rejection on the record is formed using the combination of Wang et al. and Shen et al., rather than each prior art individually. It is respectfully noted that the claimed castor oil, the claimed pharmaceutical acceptable stabilizer and the claimed active ingredients are taught by Wang et al. (see rejection above); therefore, the argument is not found persuasive.
Applicant further argues the claimed invention demonstrate unexpected results by directing attention to the Examples summarized on page 12-14 of the reply, including Example 1-3, 5, 9, 11, 12, and other examples (Example 4, 6, 7, 10); and further argues the declaration under 1.132 filed on March 2, 2026 further demonstrates the unpredictability in obtaining a stable gel.
In response, Applicant’s argument is not found persuasive for the reasons set forth below:
According to MPEP 716.02(d), “whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the ‘objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.’ In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)”.
In the present case, Applicant argues unexpected results are demonstrated in Example 1-3, 5, 9, 11, 12, and other examples (Example 4, 6, 7, 10). All of these examples have been fully considered by the Examiner; However, it is respectfully noted that these unexpected results are not commensurate in scope with the claimed invention.
For example, none of the compositions shown in Example 1 (No. 1001-1008) and Example 12 (No. 1079) is a pharmaceutical composition instantly claimed. It may well be true that Example 1 demonstrates the addition of 10 w/w% soybean phosphatidylcholine (SPC) or 10 w/w% hydrogenated soybean phosphatidylcholine (HSPC) are both capable of minimizing color change for 20 months; However, ”hydrogenated soybean phosphatidylcholine” is not recited in the rejected claim(s). In addition, applicant only exemplified 10% of soybean phosphatidylcholine as the only species of pharmaceutically acceptable stabilizer. In contrast, instant claim 1 broadly recites “a pharmaceutically acceptable stabilizer selected from soybean phosphatidylcholine, palmitoyloleoylphosphatidylcholine, dierucoylphosphatidylcholine, egg yolk phospholipid, dioleoylphosphatidylcholine, and combinations thereof… the pharmaceutically acceptable stabilizer accounts for 4 w/w% to 12 w/w% of the total amount of the composition”. In other words, the disclosure of Example 1 is not a claimed pharmaceutical composition, and structurally distinct pharmaceutical compositions cannot use to provide adequate basis for concluding that similar results (“color changes were significantly smaller”, see page 12 of the reply) would be obtained for the full scope of pharmaceutical composition instantly claimed, including those that comprises other species of pharmaceutically acceptable stabilizer in any other weight-by-weight percentage.
Another example is the Example 2, which applicant asserts the results of Example 2 demonstrate “certain stabilizer” shows excellent oil holding properties (see page 12-13 of the reply). It is noted that only composition no. 1012, 1016, 1017 and 1039-1042 in Example 2 is a pharmaceutical composition instantly claimed. As disclosed therein, composition no. 1012, 1016, 1017 contain soybean phosphatidylcholine (SPC, a pharmaceutically acceptable stabilizer), in the amount of 10%, 5%, and 8% (w/w), respectively; and they do not have oil separation at 25°C and 40°C; However, when the weight-by-weight percentage of soybean phosphatidylcholine is in 1% or 3% (w/w) (see Composition No. 1014-1015 in Table 2-3), oil separation occurs at 25°C. In other words, the oil holding properties upon which applicant relies is concentration-dependent. All of these compositions (composition no. 1012, 1016 and 1017) use 15 w/w% of glyceryl distearate (ATO5) as the pharmaceutically acceptable gelator, a combination of bupivacaine (BUP) and meloxicam (MLX) as the pharmaceutically active ingredient (composition 1012 contains 6 w/w% of BUP and 0.18 w/w% of MLX; and compositions 1016-1017 contains 5 w/w% of BUP and 0.15 w/w% of MLX), and 10 w/w % of n-methylpyrrolidone (NMP) as the non-aqueous solvent.
Additionally, composition no. 1039-1042 in Example 2 each uses 5% (w/w) of a pharmaceutically acceptable stabilizer. Specifically, composition no. 1039 uses 5 w/w% of palmitoyloleoylphosphatidylcholine (POPC), no. 1040 uses 5 w/w% of dierucoylphosphatidylcholine (DEPC), no. 1041 uses 5 w/w% of egg yolk phospholipid (EPC), and no. 1042 uses 5 w/w% of dioleoylphosphatidylcholine (DOPC) (see Table 2-7). It is further noted that when the composition 1043 uses a different pharmaceutically acceptable stabilizer, 5 w/w% of cholesterol (CHO), marginal oil separation was observed. In other words, the oil holding properties upon which applicant relies not only depends on concentration, it also depends on the selection of pharmaceutically acceptable stabilizer. All of these compositions (composition no. 1039-1042) uses 61.76 w/w% of castor oil, 5.44 w/w of benzyl alcohol (BA) and 4.56% of dimethyl sulfoxide (DMSO) as the non-aqueous solvent, a combination of 8 w/w% of bupivacaine (BUP) and 0.24 w/w% of meloxicam (MLX) as the pharmaceutically active ingredient, and 15 w/w% of glyceryl distearate (ATO5) as the pharmaceutically acceptable gelator.
In contrast, instant claim 1 broadly recites “[a] pharmaceutical composition, comprising: a castor oil; a pharmaceutically acceptable gelator selected from glyceryl monostearate, glyceryl distearate,
and mixtures thereof; a pharmaceutically acceptable stabilizer selected from soybean phosphatidylcholine, palmitoyloleoylphosphatidylcholine, dierucoylphosphatidylcholine, egg yolk phospholipid, dioleoylphosphatidylcholine, and combinations thereof; a pharmaceutically active ingredient that is a combination of ropivacaine and meloxicam, or a combination of bupivacaine and meloxicam; and a non-aqueous solvent selected from benzyl alcohol, absolute ethanol, N-methylpyrrolidone, benzyl benzoate, dimethyl sulfoxide, and mixtures thereof, wherein:
the pharmaceutical composition is an oleogel; the castor oil accounts for 50 w/w% to 70 w/w% of a total amount of the composition; the pharmaceutically acceptable gelator accounts for 5 w/w% to 20 w/w% of the total amount of the composition; the pharmaceutically acceptable stabilizer accounts for 4 w/w% to 12 w/w% of the total amount of the composition; the pharmaceutically active ingredient accounts for 2.0 w/w% to 12.0 w/w% of the total amount of the composition; and the non-aqueous solvent accounts for 5 w/w% to 20 w/w% of the total amount of the composition”. In short, the instant claim(s) promises a broad genus of pharmaceutical compositions that includes other species of pharmaceutically acceptable gelator, other species of pharmaceutically acceptable stabilizer, other species of pharmaceutically active ingredient, and other species of non-aqueous solvent. The claim(s) also include a wide range of weight-by-weight percentage other than the one exemplified in Example 2.
In other words, Applicant only exemplified unexpected results using 5%, 8%, and 10% (w/w) of SPC, and that does not provide adequate basis for concluding that similar results would be obtained using other weight-by-weight percentage of SPC. Applicant only exemplified unexpected result using 5 w/w% of POPC, DEPC, EPC, and DOPC, and that does not provide adequate basis for concluding that similar results would be obtained using other weight-by-weight percentage of POPC, DEPC, EPC, DOPC, and combinations thereof. Applicant only exemplified a single species of pharmaceutically acceptable gelator (15 w/w% of glyceryl distearate [ATO5]), and that is not commensurate to encompass the full scope of pharmaceutically acceptable gelator (including glyceryl monostearate, glyceryl distearate, and the combination of glyceryl monostearate and glyceryl distearate) that accounts for 5 w/w% to 20 w/w % of the total amount of the composition. Applicant only exemplified three combination species of bupivacaine (BUP) and meloxicam (MLX) (8 w/w% BUP + 0.24 w/w% MLX; 5 w/w% BUP + 0.15 w/w% MLX; and 6 w/w% BUP + 0.18 w/w% MLX), and that is not commensurate to encompass the full scope of pharmaceutically active ingredients (including the combination of bupivacaine and meloxicam, and the combination of ropivacaine and meloxicam) that accounts for 2.0 w/w% to 12 w/w% of the total amount of the composition. Applicant only exemplified two species of non-aqueous solvent (10 w/w% NMP; and 4.56 w/w% DMSO + 5.44 w/w% BA), and that is not commensurate to encompass the full scope of non-aqueous solvent (including benzyl alcohol, absolute ethanol, N-methylpyrrolidone, benzyl benzoate, dimethyl sulfoxide, and mixtures thereof) that accounts for 5 w/w% to 20 w/w% of the total amount of the composition. Same logics is applicable to other Examples.
Please note applicant’s argument with respect the experimental results demonstrated in the declaration under 1.132 filed on March 2, 2026 have been addressed in the declaration section above.
In view of these findings, it demonstrates that applicant’s assertion of unexpected results is not commensurate in scope with the claimed invention; therefore, applicant’s argument is not persuasive.
Conclusion
No claims are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Chihyi Lee whose telephone number is (571)270-0663. The examiner can normally be reached Monday - Friday 8:30 am - 5:00 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L. Clark can be reached at (571) 272-1310. 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.
/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628
Prosecution Insights