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 .
Claim Status/Prosecution History
Claims 1-4, 7-20, 23-24, and 29 were previously pending and claims 7-8 and 12-20 remained withdrawn from consideration as a result of a previous Restriction/Election Requirement.
A Non-Final Rejection office action was mailed 30 July 2025.
In response to that 30 July 2025 office action, Applicant filed an Amendment/Request for Reconsideration on 01 December 2025.
In the 01 December 2025 Amendment/Request for Reconsideration, Applicant amended claims 1-4, 9-11, 23-24, and 29. No claims were cancelled or added. Claims 7-8 and 12-20 remain withdrawn from consideration in accordance with 37 CFR §1.142(b).
Therefore, claims 1-4, 9-11, 23-24, and 29 are under examination.
Priority
Applicant has claimed the following priority:
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Information Disclosure Statement (IDS)
The IDSs (2) filed on 03 September 2025 and 20 April 2026 have been considered by the examiner. Signed copies are enclosed.
Applicant is reminded of their duty to disclose to the Office all information known to the
person to be material to patentability as defined in 37 CFR 1.56. As stated therein, “[e]ach
individual associated with the filing and prosecution of a patent application has a duty of candor
and good faith in dealing with the Office, which includes a duty to disclose to the Office all
information known to that individual to be material to patentability as defined in this section.”
Affidavit/Declaration Under 37 CFR § 1.132 of Dr. Zhiwen Tang
Examiner acknowledges the Declaration of Dr. Zhiwen Tang was received on 01 December 2025. Examiner has fully considered Dr. Tang’s Declaration and addresses its contents below.
Withdrawn Claim Objections/Rejections
Claim objections/rejections not reiterated from previous office actions are hereby withdrawn. The following objections/rejections are either reiterated or newly applied and constitute the complete set of objections/rejections presently being applied to the examined claims.
Claim Objections
Claim 9 is objected to for the following reason:
Claim 9 was amended from the previous claim set, yet the status identifier is “(Previously Presented).” See 37 CFR §1.121. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-4, 9-11, 23-24, and 29 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 the at least one biocompatible solvent does not substantially dissolve the biocompatible polymer excipient.” The term ‘substantially’ renders this claim indefinite as neither the claims nor the specification identifies what would constitute ‘substantially.’ In addition, there is no broadly accepted meaning of ‘substantially dissolved’ in the art. Therefore, one of ordinary skill in the art (POSITA) could not determine the metes and bounds of this claim as it relates to infringement.
Claim 1 also recites “…at least one active pharmaceutical ingredient(s) that is undissolved and micronized to a particle size distribution DV50 of about 0.5 µm to about 20.0 µm. Using terms of degree such as ‘substantial’ and ‘about’ are not necessarily indefinite if the specification provides some standard of measurement or a POSITA could ascertain the scope of the claim. However, similar as to what was discussed above, the specification does not define ‘about’ or the amount +/- the claimed range that would be included in the range defined by ‘about.’ Furthermore, there is no standard recognized in the art for measuring the term of degree as claimed. The disclosure is wholly silent on the matter and only lists API particle size distribution data (µm, DV50) and does not disclose how this data was obtained (p. 14, Table 1). A POSITA would recognize the DV50 value can fluctuate depending upon the instruments or methods used to obtain such value. Therefore, the DV50 value is not an intrinsic property of the sample alone and is a method-dependent parameter. Because of this, it is critical to specifically define the range without terms of degree and disclose and/or claim the method used in obtaining the value. See MPEP 2173.05(b) citing Ex parte Oetiker, 23 USPQ2d 1641 (Bd. Pat. App. & Inter. 1992), where the phrases “relatively shallow,” “of the order of,” “the order of about 5mm,” and “substantial portion” were held to be indefinite because the specification lacked some standard for measuring the degrees intended.
Claims 2-4, 9-11, 23-24, and 29 are included in this rejection because of their dependence upon, and requiring every limitation of, rejected claim 1.
Claims 23 and 24 are further rejected under 35 U.S.C. 112(b) for lack of antecedent basis in the claims. Claims 23 and 24 both recite the limitation “wherein the sustained release formulation” in claim 1. However, claim 1 was amended to no longer include the sustained release formulation. Therefore, there is insufficient antecedent basis for this limitation in the claim.
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.
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 1-2, 4, 9-11, and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Jain (US PGPub. No. 2010/0015195 A1; published: 21 January 2010) and further in view of Khadka (“Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability”; published: 13 June 2014).
Jain discloses novel injectable depot compositions comprising at least one active agent in the form of a biphasic suspension (abstract). When the composition of Jain is administered to a subject, an in-situ gel depot or implant at the site of injection is formed upon contact with body fluid (abstract).
Regarding claim 1 – “an injectable sustained release suspension formulation, the sustained release formulation comprising…”
Jain discloses the novel depot injectable compositions are able to provide a sustained release of the active agent for a prolonged duration ([0035]). Jain further discloses obtaining a parenteral suspension, which when injected intramuscularly or subcutaneously, forms a hydrogel at injection site that acts as a depot from which the active agent(s) is released in a sustained manner for prolonged time period ([0057]).
Regarding claim 1 – “at least one active pharmaceutical ingredient(s) that is undissolved and micronized to a particle size distribution Dv5o of about 0.5 µm to about 20.0 µm…”
Jain discloses the injectable depot compositions comprising at least two components, where component-1 is in the form of biodegradable microparticles comprising at least one active agent, at least one biodegradable polymer, and at least one viscosity enhancing agent ([0042]). Jain further discloses the microparticle is partially or entirely embedded in the viscosity enhancing agent and released upon contact with body fluids by becoming hydrated and forming a gel around the biodegradable microparticles ([0042]). Jain describes a process of obtaining the microparticles resulting in a suspension of microparticles ([0104]), which indicates the API is not dissolved in the polymer excipient. Finally, Jain describes the microparticle size containing the API has a mean particle size in a range of 1 µm to 250 µm ([0093]). This range overlaps with the currently claimed range. See MPEP 2144.
While Jain discloses producing API microparticles by spray drying or lyophilization technique and further discloses microparticles in a size that overlaps with the instantly claimed range ([0092]-[0093]), Jain does not expressly teach micronization of the API. However, this limitation is made obvious in view of Khadka as addressed below.
Jain teaches preparing API particles by spray drying or lyophilization to obtain particles having controlled particle size in the range of 1 to 250 µm suitable for suspension/formulation. While this technique is not inherently micronization as it can produce larger particle sizes, it is a bottom-up particle engineering technique that is capable of achieving micronization of the API. As disclosed by Jain, spray drying can be used to produce micronized particles if the process parameters are set to achieve fine, uniform particle sizes.
The specification discloses methods of micronizing the API include jet milling, grinding, ball-milling, or homogenizing ([0037]), which are considered top-down particle engineering approaches. However, the specification also discloses these methods are non-limiting.
Khadka discloses particle technologies for drugs with poor aqueous solubility (p. 306). Khadka discloses two known methods for achieving reduced API particle size: 1) mechanical micronization such as jet milling, ball milling, and homogenization; and 2) engineered particle size control such as cryogenic spray process (p. 305). Therefore, it would have been obvious to a POSITA, before the effective filing date of the claimed invention, to substitute micronization in place of the spray drying process taught by Jain. A POSITA would be motivated to make this substitution because Khadka teaches both techniques were recognized in the art as suitable for controlling API particle size (art-recognized equivalence). A POSITA would therefore have a reasonable expectation of success in using micronization to obtain API particles of desired size for the same formulation purpose.
Regarding claim 1 – “at least one biocompatible polymer excipient…” and claim 4 –
“wherein the at least one biocompatible polymer excipient is chosen from hyaluronic acid, sodium hyaluronate, cross-linked derivatives of hyaluronic acid, polyethylene oxide (PolyOX), methylcellulose, hydroxypropyl methylcellulose, collagen, carboxymethyl cellulose, or a combination thereof.”
Jain discloses the viscosity enhancing agent of component-1 is selected from: cellulose derivatives such as methylcellulose and hydroxypropyl methylcellulose; and poly(ethylene oxide) ([0052]). While claims 1 and 4 are drawn to “at least one biocompatible polymer excipient” and Jain discloses these claimed excipients as viscosity enhancing agents, products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Regarding claim 1 – “water present in an amount of at least 15 wt percent and less than 30 wt percent based on the total weight of the sustained release suspension…”
Jain discloses formulations comprising component-1 and component-2 ([0100]-[0163]). Jain discloses water may be present in component-2 ([0100]). This limitation, when included in the drug formulation for its functional role and not therapeutic effect, is considered a pharmaceutically acceptable excipient with which Jain discloses in an amount from 0.1% to 99.8% w/w based upon the total weight of the formulation ([0014] and p. 16, claim 35). This range encompasses the currently claimed range. See MPEP 2144.
Regarding claim 1 – “at least one biocompatible solvent chosen from the group consisting of PEG300, PEG400, NMP, and DMSO…”
Jain discloses component-2 of the invention can include solvents such as PEG300 and PEG400 ([0055]).
Regarding claim 1 – “wherein the at least one biocompatible solvent does not substantially dissolve the biocompatible polymer excipient.”
Jain discloses the biodegradable solvent of the invention (disclosed as PEG300 or PEG400) at least partially solubilizes the viscosity enhancing agent (disclosed as methylcellulose, hydroxypropyl methylcellulose, and poly(ethylene oxide)) ([0018]).
Regarding claim 2 – “wherein the one or more pharmaceutical ingredient(s) is an anesthetic drug, an anti-inflammatory drug, an antiemetic drug, or a combination thereof.”
Jain discloses the active agent of the invention is selected from an anti-inflammatory, anesthetic, or anti-emetic drug ([0045]).
Regarding claim 9 – “wherein the at least one active pharmaceutical ingredient(s) ranges from about 0.01 wt% to about 20.0 wt% w/w of the total sustained release formulation.”
Jain discloses the active agent is present from 0.1% w/w to 95% w/w based on the total weight of the formulation ([0014] and p. 16, claim 35). This range encompasses the currently claimed range. See MPEP 2144.
Regarding claim 10 – “wherein the at least one biocompatible polymer excipient ranges from about 0.01 wt% to about 20.0 wt% of the total sustained release formulation.”
Jain discloses the biocompatible polymer excipient (or viscosity enhancing agent) ranges from 0.1% w/w to 95% w/w ([0014] and p. 16, claim 35). This range encompasses the currently claimed range. See MPEP 2144.
Regarding claim 11 – “wherein the at least one biocompatible solvent ranges from about 10.0 wt% to about 90.0 wt% the total sustained release formulation.”
Jain discloses the addition of a solvent, selected from PEG 300 or PEG 400, whereby the choice of solvent and its quantity primarily depends on the solubility of the API ([0055]). Jain further notes that when the composition is formulated with a water-soluble solvent such as ethanol, the solvent will diffuse rapidly out of the injected volume leaving a high viscosity depot that is well-suited for long-term drug deliver ([0055]).
While Jain does not expressly disclose a particular range of solvent, Jain discloses the amount of solvent can be modified depending upon the API solubility and desired release properties. Jain’s disclosure lays the foundation for routine optimization (see MPEP 2144.05(II)). Since Jain discloses ranges of the other claimed components of the composition, and further specifically discloses the solvent is selected from solvents identical to the currently claimed solvent, arriving at the claimed range of biocompatible solvent in claim 11 amounts to nothing more than routine optimization. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results) and In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). It is not outside the capabilities of a POSITA to manipulate ranges through routine experimentation. This routine experimentation is made easier by Jain, who discloses: 1) ranges of the other claimed component variables in the composition; 2) a solvent identical to the claimed solvent; and 3) motivation to manipulate the amount of solvent depending upon API solubility and desired pharmacodynamics (result-effective variable).
Regarding the in vitro pharmacodynamic release properties as recited in claims 23 and 24:
Jain discloses the injectable compositions are in the form of an in-situ gelling composition or an implant composition which form a depot upon in vivo administration upon contact with body fluids thereby providing a prolonged release of the active agent for extended periods of time ([0040]). The compositions disclosed by Jain are capable of producing a prolonged release of the active agent for at least 7 days ([0040]). While Jain does not expressly disclose the in vitro release properties of instant claims 23 and 24, Jain discloses the structural features required by the claims (API, solvent, polymer excipient) and thus, it would necessarily follow that the claimed release profiles would be met as an inherent characteristic of the suspension.
Therefore, the combination of Jain and Khadka disclose the currently claimed invention in instant claims 1-2, 4, 9-11, and 23-24. Jain discloses a bi-phasic, injectable API suspension with extended-release properties capable of in vitro swelling upon contact with bodily fluid. Jain further discloses the claimed components in ranges that encompass the claimed ranges, allowing a POSITA to pick and choose from Jain’s disclosure to arrive at the instantly claimed invention with a reasonable expectation of success. In addition, Khadka discloses various methods of controlling API particle size, making obvious the micronization technique of instant claim 1 substituted in the spray drying technique of Jain. For the reasons discussed above, Jain in further view of Khadka makes obvious the sustained-release suspension of instant claims 1-2, 4, 9-11, and 23-24.
While the declaration under 37 C.F.R. 1.132 of Dr. Zhiwen Tang addresses the previous 35 USC 103 rejection of record (30 July 2025) pertaining to the references of Gennari (US 2013/0230594 A1), Shoichet (US 2022/0202793 A1), Van Hove (US 2022/0040201 A1), Voigt (US 2016/0166701 A1), Lim (US 2006/0188583 A1), and Ottoboni (US 2017/0035777 A1), Examiner believes the newly cited references address features of the claimed suspension cited in Dr. Tang’s declaration including:
Biphasic suspension prior to injection (Declaration, p. 1);
Polymer excipient present as solid particulates dispersed in PEG 300 or PEG 400, described by Jain as a viscous mixture (Declaration, p. 2);
Upon injection, suspension undergoes a structural transition (in-situ gelation) upon contact with surrounding bodily fluid (Declaration, p. 2).
Therefore, in light of the newly cited references, while the Declaration of Dr. Tang was considered, it was not found to be persuasive.
Furthermore, Applicant’s arguments pertain to the previously cited references of record. Examiner believes the newly cited references overcome Applicant’s arguments. Therefore, Applicant’s remarks have been considered, but in light of the newly cited references, are not found to be persuasive.
Claims 3 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Jain and Khadka as applied to claims 1-2, 4, 9-11, and 23-24 above, and further in view of Lyons (US PGPub. No. US 2008/0044476 A1; published: 21 February 2008).
The disclosures of Jain and Khadka are discussed above.
As it relates to claim 3, Jain discloses a sustained-release formulation comprising an active agent selected from a broad therapeutic genus which encompasses the claimed API species of instant claim 3 (e.g., local anesthetics, analgesic/opioid, NSAIDs/COX inhibitors, corticosteroids at [0045]). Jain does not expressly disclose the species of API as required by instant claim 3, but this limitation is made obvious in view of Lyons.
As it relates to claim 29, Jain discloses a sustained release formulation comprising a viscosity enhancing agent such as PEG 300 or PEG 400. Jain further discloses the viscosity enhancing agent can be selected from the broad genus of glycosaminoglycans ([0052]), which encompasses the claimed sodium hyaluronate species of instant claim 29. Jain does not expressly disclose the species of sodium hyaluronate as required by instant claim 29, but this limitation is made obvious in view of Lyons.
Lyons discloses viscous formulations for intra-articular and intramuscular injections to treat peripheral conditions (abstract). The suspension ([0041]) of Lyons comprises undissolved API triamcinolone acetonide particles, polymeric hyaluronate in which the triamcinolone particles are suspended, sodium chloride, dibasic sodium phosphate heptahydrate, monobasic sodium phosphate monohydrate, and water ([0051]). Lyons further discloses contact with water is necessary for the API to be released from its carrier in vitro ([0038]).
Regarding claim 3, Lyons discloses the API as triamcinolone acetonide ([0068]).
Regarding claim 29, Lyons discloses the viscosity inducing component is a hyaluronic acid polymer component such as sodium hyaluronate ([0036]).
Jain discloses the genus of API as a steroid ([0045]) and the genus of viscosity enhancing agent as glycosaminoglycans ([0052]), but does not disclose the species of each as required by instant claims 3 and 29. However, these limitations are made obvious over Lyons, who teaches an injectable gel suspension formulation comprising suspended triamcinolone acetonide particles and sodium hyaluronate, wherein sodium hyaluronate forms a viscous polymeric matrix capable of swelling upon contact with water.
It would have been obvious to a POSITA, before the effective filing date of the claimed invention, to substitute the species disclosed by Lyons with the representative genus disclosed by Jain. One of ordinary skill would have both motivation and a reasonable expectation of success in making these substitutions because Jain teaches the corresponding genus as suitable and Lyons confirms that the species was a known member of the genus used in similar injectable suspension formulations. For the reasons discussed above, Jain (suspension and genus components) and Khadka (micronization), in further view of Lyons (suspension and genus components) makes obvious the sustained-release suspension of instant claims 3 and 29.
Conclusion
Claims 1-4, 9-11, 23-24, and 29 are rejected. No claim is in condition for allowance.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Julia A. Rossi whose telephone number is (571)272-0138. The examiner can normally be reached M-Th 7:30-5:30 (MST).
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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)272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JULIA A. ROSSI/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
Prosecution Insights