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 Claims 1-10 are pending; claims 1-7 are examined and claims 8-10 are currently withdrawn.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-7 in the reply filed on 10 November 2025 is acknowledged. The traversal is on the ground that the feature of “a core-shell micelle microsphere” is common to all the claims and therefore any search and examination relating to the subject matter of elected claims 1-7 would necessarily result in a search and examination relating to the subject matter of withdrawn claims 8-10. This is not found persuasive because claim 8 is drawn to a method of making the microsphere, which involves steps not encompassed by claims 1-7, such as solvent choices or standing time. Claims 9 and 10 is drawn to how the microspheres are intended to be used, which can encompass a broad subject matter not encompassed by claims 1-7. As such, claims 8-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The requirement is still deemed proper and is therefore made FINAL.
Claim Objections
Claim 1 is objected to because of the following informalities: “the chain polymer” in the last line should be recited as --- a chain polymer ---. Appropriate correction is required.
Claim 4 is objected to because of the following informalities: “PEG” and “PLGA” should each be preceded with their non-abbreviated terms, with abbreviations immediately after and in parentheses. Appropriate correction is required.
Claim 5 is objected to because of the following informalities: “mPEG” should be preceded with its non-abbreviated terms, with abbreviations immediately after and in parentheses. Appropriate correction is required.
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 1-4 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 including polyvinyl alcohol and PEG (i.e. claimed wrapped by a copolymer), 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 and the interlayer of Zheng comprises substantially the same structure (i.e. core: a plurality of drug molecules wrapped by a copolymer; and a shell comprising a chain polymer layer formed by the chain polymer) 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 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 3, 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 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).
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.
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
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUCY M TIEN whose telephone number is (571)272-8267. The examiner can normally be reached Monday - Friday 10:00 AM - 6:00 PM EST.
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/LUCY M TIEN/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612