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 Application
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/31/2026 has been entered.
Receipt of Applicant’s Remarks and Amendments filed on 07/31/2026 is acknowledged. Claims 1-3, 6-9 and 11-14 are pending.
Claim 4, 5 and 10 are cancelled.
Claims 1, 2, and 3 are amended.
Claims 7-8 and 11-14 remain withdrawn pursuant to the restriction requirement.
Claims 1-3, 6 and 9 are pending and under examination in this application.
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.
Claims 1-3 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 "0.5-0.63 g of the sodium carboxymethyl cellulose" in line 4. There is insufficient antecedent basis for this limitation in the claim. Claim 1 does not previously recite "sodium carboxymethyl cellulose"; the preamble and body of the claim refer only to "a pharmaceutically acceptable excipient" in generic terms. Use of the definite article "the" before a term that has not been previously introduced renders it unclear whether "the sodium carboxymethyl cellulose" is intended to refer back to the previously recited "pharmaceutically acceptable excipient" or is intended to introduce a new, separate element, rendering the metes and bounds of the claim indefinite. Claims 2 and 3 depend from claim 1 and are rejected for incorporating the same deficiency. Appropriate correction is required, e.g., by amending the claim to recite "a sodium carboxymethyl cellulose" or by amending the preamble to positively recite sodium carboxymethyl cellulose as the pharmaceutically acceptable excipient.
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.
Claims1-3, 6 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Ye (WO 2017036408 A1) in view of Zhang et al. (US 11,084,790 B2, hereinafter "Zhang").
Ye teaches a sustained-release suspension formulation for ropivacaine comprising (A) ropivacaine; (B) a carrier comprising one or more surfactants, one or more suspending agents, one or more fillers, one or more preservatives, one or more isotonic agents, one or more buffers; and (C) water for injection (page 3, top ¶). Ye further teaches ropivacaine in an amount of 1 to 40% by weight, more preferably 2 to 20%, still more preferably 2 to 8% by weight (page 3, ¶5); a surfactant in an amount of 0.01% to 20% by weight (page 4, ¶2), including poloxamer 188 as a preferred surfactant; an isotonicity adjusting agent, including sodium chloride, in an amount of 0.05% to 20% by weight (page 4, ¶8); and 0.1% to 2% by weight of a suspending agent, including sodium carboxymethylcellulose as a preferred suspending agent (page 2, middle, ¶C). Applicant's claimed concentrations of ropivacaine (2-3.5 g/100 mL), sodium carboxymethyl cellulose (0.5-0.63 g/100 mL), sodium chloride (0.6-0.7 g/100 mL), and poloxamer 188 (0.4-0.6 g/100 mL) each fall within Ye's disclosed ranges for the reasons set forth in the Final Office Action mailed 05/05/2026, which reasoning is incorporated herein and has not been disputed by Applicant.
Regarding the particle size distribution limitation newly recited in claim 1 (D10 of 4 µm to 10 µm, D50 of 12 µm to 37 µm, and D90 of 30 µm to 90 µm), Ye teaches that the primary suspension of ropivacaine is mechanically ground or homogenized to reduce the particle size of ropivacaine to a desired level, such as 0.1 to 50 microns, to prepare a sterile ropivacaine suspension formulation having a desired average particle size (page 5, ¶3). Ye's own working examples report particle size distribution at the D10/D50/D90 level of granularity now claimed (e.g., Example 14: D10 <5.92 µm, D50 <12.3 µm, D90 <20.6 µm), demonstrating both that Ye's disclosed process is capable of controlling particle size at this level of specificity and that a person of ordinary skill in the art would have recognized particle size distribution as a result-effective variable affecting the sustained-release behavior of the suspension. See MPEP 2144.05(II) (discovering an optimum or workable range by routine experimentation is not ordinarily inventive where the prior art recognizes that a result-effective variable affects the property of interest).
While Ye's disclosed working examples do not themselves extend to a D90 as high as the claimed 30 µm to 90 µm, Zhang establishes that a person of ordinary skill in the art would have had reason to extend particle size beyond Ye's disclosed examples, with a reasonable expectation of success. Zhang is directed to sustained-release local anesthetic suspension injections, including ropivacaine-based formulations (see Zhang, Preparation Example 9, mono(ropivacaine) pamoate), employing the same classes of excipients relied upon in Ye and recited in the instant claims (a cellulosic suspending agent, a surfactant, an isotonic adjusting agent such as mannitol, and a phosphate buffer). Zhang expressly teaches that particle size is a result-effective variable governing sustained-release duration in this type of formulation, reporting that half-life "prolonged along with the particle size increased, and the time of sustained release and the time of maintaining the analgesic efficacy could be controlled by adjusting the particle size" (Zhang, Test Example 6, Table 29). Table 29 of Zhang reports pharmacokinetic data for particle size distributions of D50 2.845 µm, D50 5.873 µm, and D50 25.088 µm (Groups 17A-C), showing t1/2 increasing with increasing particle size. Consistent with this teaching, Formulation Example 7 of Zhang (the unpulverized preparation used in Group 19 of Test Example 6) discloses a suspension with a measured particle size distribution of D10 5.314 µm, D50 25.088 µm, and D90 70.305 µm — within the D50 range and squarely within the D90 range recited in instant claim 1 — prepared using the same excipient classes as Ye and as claimed.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to extend Ye's disclosed particle size reduction process to reach a D10 of 4 µm to 10 µm, a D50 of 12 µm to 37 µm, and a D90 of 30 µm to 90 µm, as claimed, because: (i) Ye discloses a process for controlling particle size, including at the D10/D50/D90 level of specificity, and expressly contemplates a target range (0.1 to 50 microns) that encompasses the claimed distribution; (ii) Zhang establishes that particle size is a recognized result-effective variable for controlling sustained-release duration in local anesthetic suspensions employing the same classes of excipients; (iii) Zhang demonstrates that increasing particle size within and beyond the range exemplified by Ye predictably prolongs sustained-release duration; and (iv) Zhang's own working example achieves a D50 and D90 within the claimed ranges using conventional homogenization processing of the same general type already taught by Ye and practiced in the instant specification's examples. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 416-17 (2007) (a combination of familiar elements according to known methods that does no more than yield predictable results is likely obvious); In re Applied Materials, Inc., 692 F.3d 1289, 1295 (Fed. Cir. 2012). Such a modification amounts to no more than the application of a known technique (particle size optimization to control sustained-release duration) to a known formulation (Ye's ropivacaine suspension) ready for improvement, to yield predictable results.
Regarding claims 2 and 3, which further narrow the D50 recited in claim 1, from 12 µm to 34.5 µm and 12 µm to 20 µm, respectively: these narrower ranges fall entirely within the D50 range of claim 1 (12 µm to 37 µm) already addressed above, and it is prima facie obvious to select a narrower range that lies wholly within a range rendered obvious by the prior art combination, absent a showing of criticality. In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003); MPEP 2144.05(I). Moreover, Zhang's own working example within the claimed range (Formulation Example 7: D50 25.088 µm) falls within both narrower ranges recited in claims 2 and 3, further supporting that a person of ordinary skill in the art would have arrived at a suspension having a D50 within these narrower ranges with a reasonable expectation of success, for the same reasons discussed above with respect to claim 1. Applicant has not presented evidence of criticality specific to the narrower D50 ranges of claims 2 and 3 distinct from the arguments already addressed above with respect to claim 1.
Regarding claim 6, Ye teaches to adjust the pH of the suspension to a range of 6 to 8.5 (page 4, ¶ 4-5), which falls within and overlaps the claimed range of 5-9.
Regarding claim 9, Ye teaches Freeze-drying (page 5, ¶ 5-6).
Response to Arguments
Applicant's arguments, filed 07/31/2026, have been fully considered but are not persuasive for at least the following reasons.
Regarding Applicant's argument that Ye does not disclose the particle size distribution now recited in claim 1: this argument does not address the combination of Ye with Zhang set forth above. As explained above, Ye discloses a particle-size-control process expressly encompassing the claimed range and recognizes particle size as a variable affecting suspension performance, and Zhang supplies both a specific working example within the claimed D50/D90 ranges and an express teaching that increasing particle size in this class of local anesthetic suspension predictably prolongs sustained-release duration. The rejection is not based on Ye's disclosed working examples alone.
Regarding Applicant's argument of no reasonable expectation of success: this argument is not persuasive in view of Zhang, which directly and quantitatively demonstrates the relationship between increasing particle size and prolonged half-life in a local anesthetic suspension formulated with the same classes of excipients relied upon in Ye and in the instant claims. Zhang 's teaching provides an express, data-supported basis for a reasonable expectation of success in extending Ye's particle size reduction process to the claimed range, rather than relying on unpredictability in the art generally.
Regarding Applicant's unexpected results argument (comparing a Cmax of 605.31 and 479.58 ng/mL for Examples III and IV of the instant application against a Cmax of 990±394 ng/mL for Ye's 2% ropivacaine suspension, Example 35): this argument remains unpersuasive for the reasons set forth in the Final Office Action mailed 05/05/2026, which are incorporated herein. First, no declaration under 37 CFR 1.132 has been filed; attorney argument cannot take the place of evidence. In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997). Second, the comparison is not made against the closest prior art with all other variables held constant — Applicant's Example III/IV formulations and Ye's Example 35 differ in excipient identity, excipient concentration, particle size, and preparation method simultaneously, making it impossible to attribute any Cmax difference to particle size specifically. In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991).
Further, Applicant's own specification data does not support a showing of unexpected results commensurate in scope with the newly claimed D90 range. Specification Example 2 (Experimental Group II: D50 9.07 µm, D90 20.6 µm — near Ye's own largest disclosed example, Example 14, D90 <20.6 µm) exhibits a Cmax of 768.97 ng/mL, the highest Cmax among Experimental Groups I-IV. By contrast, Experimental Group I (Example 1: D50 3.80 µm, D90 7.80 µm — well below Ye's disclosed range) exhibits the lowest Cmax of the four groups, 456.03 ng/mL, comparable to or lower than Experimental Group IV (Example 4: D50 34.5 µm, D90 85.5 µm, within the newly claimed range), which exhibits a Cmax of 479.58 ng/mL. This non-monotonic relationship among Applicant's own working examples is inconsistent with Applicant's position that a reduced Cmax is a criticality-establishing consequence of the newly claimed D90 range; the data show no reliable trend correlating increasing D90 with decreasing Cmax across Applicant's own examples. Applicant has therefore not established that any Cmax reduction is attributable to, or commensurate in scope with, the claimed particle size distribution as opposed to the other variables that differ between the compared formulations.
Regarding written description support for the amended claims: the Advisory Action mailed 07/08/2026 noted that the D10/D50/D90 profile added to claim 1 and the D50 ranges added to claims 2 and 3 should be scrutinized for new matter. Upon review, the D10/D50/D90 distribution recited in claim 1 (D10: 4 µm to 10 µm; D50: 12 µm to 37 µm; D90: 30 µm to 90 µm) finds express, verbatim support in the specification. The D50 range recited in claim 2 (12 µm to 34.5 µm) is supported by the same disclosed D50 range of about 12 µm to about 37 µm together with the specification's disclosure of a D50 of 34.5 µm in Example 4, and by the specification's statement that every numerical range disclosed includes every narrower range falling within it. The D50 range recited in claim 3 (12 µm to 20 µm) draws its lower bound from the same 12-37 µm embodiment and its upper bound from the specification's separately disclosed D50 range of about 5 µm to about 20 µm; in view of the specification's express statement that its various disclosed embodiments and preferences may be combined with each other, this range is considered supported. No new matter has been introduced by the amendment.
Accordingly, Applicant's arguments are not persuasive, and claims 1-3, 6, and 9 stand rejected as set forth above.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDRE MACH whose telephone number is (571)272-2755. The examiner can normally be reached 0800 - 1700 M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A Wax can be reached at 571-272-0323. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANDRE MACH/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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