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 . Claims 1-2 and 4-10 are pending; claims 1-2 and 4-7 are examined and claims 8-10 are currently withdrawn from further consideration pursuant to Applicant’s election on 10 November 2025.
Applicant’s arguments, filed 02 April 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103
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 1-2, 4 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (CN 115382026 A, 11/25/2022) (hereinafter Zhang).
Zhang discloses a drug-containing coating material made of three-layer shell-core structure microspheres with the particle size of 5-30 µm, the innermost layer is an inner core containing a main drug, the middle layer is a micron-sized capsule formed by slow-release polymers, and the outermost layer is a lipid shell containing amphiphilic lipid (abs, claim 6). The inner core comprises the main medicine and a hydrophobic or hydrophilic micelle material including polyvinyl alcohol and polyethylene glycol (PEG) (p. 5, ¶¶ 6-8); and the interlayer comprises a sustained release polymer including polylactic-co-glycolic acid (PLGA) (p. 5, ¶ 9). In an embodiment, the innermost layer is 10 to 45 percent, the intermediate layer is 35 to 55 percent, and the outermost layer is 10 to 35 percent by mass percent (p. 5, ¶ 2).
The prior art discloses shell-core structure microspheres containing a shell-core microsphere with the inner core containing a main drug and a micelle material (i.e. claimed wrapped by a copolymer), including polyvinyl alcohol and PEG, and a shell comprising an interlayer comprising PLGA (i.e. a claimed chain polymer and hydrophilic chain polymer of claim 4) and an outermost lipid-containing layer.
The prior art is not anticipatory insofar as this combination must be selected from various lists/locations in the reference. It would have been obvious, however, to make the combination since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. See MPEP § 2143 (I)(A).
Regarding claim 1 reciting wherein the copolymer and the chain polymer layer is each of a net structure, since the inner core of Zheng comprises substantially the same structure (i.e. core comprising a plurality of drug molecules surrounded by a copolymer) comprising substantially the same ingredients as the claimed invention, one of ordinary skill in the art would reasonably expect the micelle material and interlayer of Zhang to be of a net structure like the claimed invention.
Regarding claim 1 reciting an orientation of the amphiphilic lipid, Zhang does not explicitly disclose specific orientation of the hydrophilic end and the lipophilic end. However, since Zhang discloses substantially the same structure (i.e. core-shell structure comprising drug core surrounded by a micelle material; a polymer layer; and an outermost layer comprising amphiphilic lipids) comprising substantially the same ingredients as the claimed invention, one of ordinary skill in the art would reasonably expect the outermost lipid layer of Zhang to arrange such that the hydrophilic end faces into the shell and lipophilic end faces out the shell like the claimed invention.
Regarding claim 2, the claimed size of the core-shell micelle microsphere (i.e. 1-10 µm) would have been obvious to one ordinary skill in the art since they overlap with the ranges of the prior art (i.e. 5-30 µm). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP § 2144.05(I).
Regarding claim 7, the claimed mass ratio of lipid layer to chain polymer layer would have been obvious to one of ordinary skill in the art since they overlap with the mass ratios of the prior art (i.e. 10-35 mass % : 35-55 mass %). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP § 2144.05(I).
Response to Arguments
Applicant mainly asserts on pp. 5-6 that the core-shell microspheres of Zhang only have 3 layers while the instant claims have 4. Applicant further asserts that the sustained release polymer of Zhang includes PLA, PLGA, or PGA, all of which are hydrophobic compounds, thus the hydrophobic end would point inward rather and outward in its outermost layer.
The Examiner does not find Applicant’s argument to be persuasive. Although the prior art does not disclose verbatim the structure as recited in the instant claims, Zhang discloses wherein the core-shell structure microspheres comprise an inner core containing a drug and hydrophilic or hydrophobic micelle material (i.e., instantly claimed drug molecules “wrapped” by a copolymer). Moreover, the instant claims merely require “a plurality of drug molecules” wrapped by a copolymer, therefore the core of Zhang, disclosing both hydrophilic and hydrophobic micelle material options, reasonably appears to meet the limitations as instantly claimed. Finally, Zhang discloses wherein the drug molecules may be dissociated in gaps of polymer macromolecular chains, but the drug molecules do not penetrate through the outer layer of the polymer. The drug molecules can be physically embedded, or can be combined by electrostatic adsorption (p. 5, line 11). Thus it appears Zhang discloses or at least suggests a net-like structure.
Regarding the alleged orientation of the hydrophobic end, although Zhang discloses wherein the interlayer comprises polylactic-co-glycolic acid (PLGA), substantially the same description is disclosed as an instantly claimed chain polymer in para. [0015] of the instant Specification and instant claim 4. Thus it is not clear to the Examiner how the structure of Zhang differs from the instantly claimed structure in its current scope (i.e. comprising a chain polymer, or wherein the chain polymer comprises PLGA). As such, it would have been obvious to one of ordinary skill in the art that Zhang does not limit its shell-core structures to only a lipid layer with hydrophilic end facing outside as Applicant alleges. As such, Applicant’s assertion is unpersuasive.
It is also noted that the features upon which Applicant relies (i.e. high drug utilization rate, providing a wide application range in the long-term sustained release of drugs) 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 MPEP 2111.01.
Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (CN 115382026 A, 11/25/2022) (hereinafter Zhang) in view of Avgoustakis et al. (“Effect of copolymer composition on the physicochemical characteristics, in vitro stability, and biodistribution of PLGA–mPEG nanoparticles”, 2003).
The disclosure of Zhang is discussed in detail in the rejection supra.
Zhang differs from the instant claims insofar as not explicitly disclosing wherein the PLGA is a mPEG-PLGA block copolymer.
However, Avgoustakis discloses monomethoxypoly(ethyleneglycol) (mPEG) (p.116, col. 2, ¶ 3) covalently bound to poly(lactide-co-glycolide) (PLGA) confers long circulation properties and sterically stabilizes a surface of a nanoparticle against opsonization and phagocytosis, probably due to its high hydrophilicity, chain flexibility, electrical neutrality and absence of functional groups, which prevent interactions with biological components in vivo (p. 115, col. 2 – p. 116, col. 1, ¶ 1). Moreover, PLGA particles followed non-linear and dose-dependent pharmacokinetics whereas PLGA-mPEG nanoparticles followed linear and dose-independent pharmacokinetics, have prolonged drug residence time in systemic blood circulation (p.116, col. 2, ¶ 2).
Accordingly, it would have been obvious to one of ordinary skill in the art to have included mPEG-PLGA in the material of Zhang since it is a known and effective particle suitable for sterically stabilizing a surface of PLGA containing particles as taught by Avgoustakis.
Response to Arguments
Applicant further asserts on pp. 6-7 that Avgoustakis fails to teach or suggest any four-layered microsphere, in which a core shell is formed from the combination of both a chain polymer and an amphiphilic lipid, as a whole, nor any orientation of the lipid layer as the present invention. In fact, Avgoustakis teaches away from the disclosure of Zhang since it is focused on a different retention property.
The Examiner does not find the Applicant’s assertion to be persuasive. As this is a 103 obviousness rejection, no one piece of prior art is required to teach each and every claim limitation. See MPEP 2141(III). As discussed in the rejection, Zhang discloses the structure as instantly claimed in the current scope. Avgoustakis teaches a known and effective modification to PLGA that is suitable for stabilizing a surface of PLGA containing particles. Thus it would have been obvious to one of ordinary skill in the art to have included such modification in formulating the microspheres.
Regarding the alleged teaching away, the Examiner disagrees. The disclosure of Zhang does not explicitly disclose wherein the polymers may not be modified. As acknowledged by the Applicant, Zhang discloses adjusting the proportion of the polymers and controlling the release period of the drug components. Thus the disclosure of Avgoustakis, providing a modification to PLGA resulting in changes to the release time, does not teach away from Zhang. As such, Applicant’s assertion is unpersuasive.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Hu et al. (CN 111317907 A, 06/23/2020), directed to a composite drug coating comprising a middle layer containing medicament coated by a coating agent and hydrophilic excipient/lipophilic excipient/amphiphilic excipient.
Chen et al. (CN 114796811A, 07/29/2022), directed to drug-loaded nano-microspheres comprising medicine, excipient and slow-release material.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUCY TIEN whose telephone number is (571)272-8267. The examiner can normally be reached Monday - Thursday 8:30 AM - 6:30 PM EST.
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/LUCY M TIEN/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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