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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/09/2026 has been entered.
Response to Amendment
The amendment filed on 06/09/2026 has been entered. Claims 1-14 and 17-18 are pending in the application. Claims 1-8 are withdrawn.
Applicant’s amendments to the claims have not introduced new matter and are supported in the specification in at least [0006] and [0065]-[0066] of the instant specification.
The amendments have not overcome the 35 USC 112(b) rejection set forth in the action dated 03/09/2026 and that is maintained and presented again below for claims 17-18.
Response to Arguments
Applicant’s arguments, see Pg. 4-5 filed 06/09/2026 with respect to claims 9, 11, and 13, have been fully considered however are solely directed to the amendment requiring only “poly(lactide-co-glycolide)-b- poly(ethylene glycol)-maleimide (PLGA-PEG-Mal)” as the polymer matrix introduced in the amendment filed 06/09/2026, which postdates the final rejection mailed 03/09/2026.
Upon further search and consideration and as necessitated by the amendment, the 35 U.S.C. 102(a)(1) rejection of 03/09/2026 is withdrawn and a new grounds of rejection is made under 35 U.S.C. 103 as being unpatentable over Shapiro et al. (US20210228746A1) in view of Gao et al. (J. Photochem. Photobio. B, Bio. 2018, 187, 184-189).
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.
Claims 17-18 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.
Regarding claim 17, the metes and bounds of the claim are indefinite because claim 17 is directed to the use of the hybrid nanoparticle of claim 9 in “a therapeutically effective amount for treatment of a central neuronal system disease”. The person of ordinary skill in the art before the effective filing date of the claimed invention would not be apprised of when infringement of claim 17 would begin because Applicant has not provided a definition of what a ‘therapeutically effective’ amount would be and the specification does not permit the ordinarily skilled artisan to determine the ‘therapeutically effective amount’ when the claim is read in light of the supporting disclosure (see MPEP 2173.05(c)(III) which describes that the phrase “therapeutically effective amount” may or may not be indefinite and that “a therapeutically effective amount” may be definite “when read in light of the supporting disclosure”).
Turning to Applicant’s specification, Examiner has located [0050] which discusses the terms “therapeutically effective” and “sufficient” but does not provide a particular definition of these terms.
Additionally, Examiner has considered [0053] which discusses “treating” and “treatment” but notes that a particular definition of these terms is not provided such that an ordinarily skilled artisan could reasonably resolve the ambiguity in claim 17 as to what a ‘therapeutically effective amount’ of the hybrid nanoparticle of claim 9 would be for the treatment of any type of CNS disease.
Claim 18 depends from claim 17 and is thus also rendered indefinite.
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 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 9 and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Shapiro et al. (US20210228746A1) in view of Gao et al. (J. Photochem. Photobio. B, Bio. 2018, 187, 184-189).
Regarding claim 9, Shapiro teaches a nanoparticle construct that includes a magnetic nanocrystal carried by the nanoparticle and a coupling agent extending from the outer surface of the nanoparticle (Abstract). Shapiro teaches the nanoparticle includes a polymer matrix within which the nanocrystal is embedded, where the polymer matrix includes poly
(lactic-co-glycolic acid) (PLGA), a polyethylene glycol (PEG) linker, and a maleimide functionality connected to the linker (i.e. forming a PLGA-PEG-maleimide polymer matrix) ([0010]-[0015]). Shapiro further teaches the magnetic nanocrystal comprises a metal oxide that can include oxides selected from Fe3O4 (magnetite) and Fe2O3 (maghemite)), aluminum (Al), titanium (Ti), zinc (Zn), nickel (Ni), copper (Cu), tin (Sn), cobalt (Co), magnesium (Mg), cerium (Ce), bismuth (Bi), yttrium (Y), gadolinium (Gd), and combinations thereof ([0069]).
While Shapiro teaches cerium oxide can be present, Shapiro does not explicitly motivate selection of cerium oxide from the list of metal oxides while the instant claim requires cerium oxide.
Gao teaches a nano-CeO2 (cerium oxide) particle loaded co-polymer matrix, where the cerium oxide nanoparticles are encapsulated on poly-(lactide-co-glycolide)-polyethylene glycol (PEG-PLGA) copolymer matrix (Abstract).
Advantageously, cerium oxide has been shown to defend against blood brain barrier damage and acts as an effective antioxidant (Abstract).
Thus, prior to the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to include cerium oxide in the product of Shapiro in order to provide a metal oxide that defends against blood brain barrier damage and acts as an efficient antioxidant as taught by Gao.
Regarding claim 11, Shapiro in view of Gao teach the product of claim 9 and Shapiro further teaches the nanoparticles can be about 0.5 to about 50 nm ([0071]). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. MPEP 2144.05 (I). In the instant case, the range taught by Shapiro (nanoparticles of about 0.5 to 50 nm) overlaps with the claimed range (2-10 nanometers). Therefore, the range in Shapiro renders obvious the claimed range.
Regarding claim 12, Shapiro in view of Gao teach the product of claim 9 and Shapiro further teaches the nanoparticle constructs can be about 100-1000 nm ([0107]; Table 1). Subtracting the maximum metal oxide size of 50 nm from the construct range provides a polymer PLGA-PEG-maleimide matrix size of about 50 to 950 nm taught in Shapiro. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. MPEP 2144.05 (I). In the instant case, the range taught by Shapiro (polymer matrix about 50 to 950 nm) overlaps with the claimed range (50-300 nm). Therefore, the range in Shapiro renders obvious the claimed range.
Regarding claim 13, Shapiro in view of Gao teach the product of claim 9 and the claim further requires the cerium oxide exhibits antioxidant/anti-inflammatory effects, to which Shapiro doesn’t specifically state this property for the metal oxides. Gao teaches the cerium oxide nanoparticle act as antioxidants (Pg. 188, left col. “The biological results of CeO2 nanoparticles with polymer groups are acted as antioxidants…”).
Advantageously, cerium oxide nanoparticles acting as effective antioxidants allows for permeability across the blood brain barrier that helps defend against blood brain barrier damage (Abstract).
Thus, prior to the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to include cerium oxide as an antioxidant in the product of Shapiro in order to provide a metal oxide that defends against blood brain barrier damage by acting as an efficient antioxidant as taught by Gao.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Shapiro et al. (US20210228746A1) in view of Gao et al. (J. Photochem. Photobio. B, Bio. 2018, 187, 184-189), with evidentiary support provided by Kuo et al. (J. Mater. Res. Tech. 2019, 8, 1, 887-895).
Regarding claim 10, Shapiro in view of Gao teach the product of claim 9 and the claim further requires the cerium oxide is encapsulated by “hydrophobic interaction”. Shapiro teaches the magnetic metal oxide is embedded within the polymer matrix such that some particles are completely embedded within the matrix ([0072]).
While Shapiro does not explicitly describe “hydrophobic interaction,” Shapiro teaches an identical metal oxide can be used (cerium) and that the identical polymer matrix comprised of PLGA-PEG-maleimide can be used ([0069]; [0076]). Incorporation of the CeO2 nanoparticles with the hydrophobic cores of the copolymer matrix sufficiently describes a hydrophobic interaction, as evidenced by Kuo, who describes hydrophobic interactions as interactions between metal oxide nanoparticles and the surface of PLGA nanoparticles (Pg. 888, right col.). Therefore, the PLGA-PEG-maleimide embedded metal oxide nanoparticles of Shapiro would be expected to display a hydrophobic interaction and meet the limitation required by the claim. See MPEP 2112.II.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Shapiro et al. (US20210228746A1) in view of Gao et al. (J. Photochem. Photobio. B, Bio. 2018, 187, 184-189) and further in view of Danhier et al. (J. Cont. Rel. 2012, 161, 505-522).
Regarding claim 14, Shapiro in view of Gao teach the product of claim 9 and the claim further requires “a targeting ligand bonded to the hybrid nanoparticle,” to which Shapiro and Gao do not explicitly state.
Danhier teaches the functionality of PLGA nanoparticles where targeting ligands are grafted onto the nanoparticle surface via PEG chains (Pg. 506, right col.).
Advantageously, incorporating targeting ligands into PLGA nanoparticles comprising PEG chains increases selective cellular binding and internalization through receptor-mediated endocytosis, while allowing the affinity of binding receptors to be matched with ligands (Pg. 506, right col.; Fig. 3). Note, Gao teaches the cerium oxide nanoparticles are encapsulated on poly-(lactide-co-glycolide)-polyethylene glycol (PEG-PLGA) copolymer matrix, lending feasibility to the combination with Danhier of PEG chains incorporated with PLGA.
Thus, prior to the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to include a targeting ligand in the product of Shapiro in order to increase selective cellular binding and internalization through receptor-mediated endocytosis as taught by Danhier.
Claims 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (J. Photochem. Photobio. B, Bio. 2018, 187, 184-189) in view of Shapiro et al. (US20210228746A1).
Regarding claims 17, Gao further teaches the cerium oxide particles can be used to defend and have a biological result against cerebral ischemic brain stroke and/or brain injury related to Cerebral ischemic stroke (Pg. 188, left col.; Abstract). Gao teaches a nano-CeO2 (cerium oxide) particle loaded co-polymer matrix, where the cerium oxide nanoparticles are encapsulated on poly-(lactide-co-glycolide)-polyethylene glycol (PEG-PLGA) copolymer matrix (Abstract). Gao teaching that the Ce nanoparticles have a ‘biological result’ of reducing ischemic brain injury meets the broadest reasonable interpretation of at least the recited options of stroke and/or brain injury.
The claim further requires “the hybrid nanoparticle of claim 9”, which requires PLGA-PEG-maleimide (Mal) to which Gao teaches poly-(lactide-co-glycolide)-polyethylene glycol (PEG-PLGA) copolymer.
Shapiro teaches a nanoparticle construct that includes a magnetic nanocrystal carried by the nanoparticle and a coupling agent extending from the outer surface of the nanoparticle (Abstract). Shapiro teaches the nanoparticle includes a polymer matrix within which the nanocrystal is embedded, where the polymer matrix includes poly (lactic-co-glycolic acid) (PLGA), a polyethylene glycol (PEG) linker, and a maleimide functionality connected to the linker (i.e. forming a PLGA-PEG-maleimide polymer matrix) ([0010]-[0015]).
Advantageously, the PLGA-PEG-maleimide agent allows the nanoparticle construct to be attached to cell surfaces of proteins or peptides, allowing effective binding to specifically thiolated moieties ([0075]-[0077]).
Thus, prior to the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to include PLGA-PEG-maleimide matrix in the product of claim 9 in order to allow for attachment of the nanoparticle construct to cell surfaces of proteins or peptides, as taught by Shapiro.
Regarding claim 18, Gao in view of Shapiro teach the method of claim 17 and Gao teaches the hybrid particles defend against strokes (Abstract).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jordan Wayne Taylor whose telephone number is (571)272-9895. The examiner can normally be reached Monday - Friday, 7:30 AM - 5 PM EST; Second Fridays Off.
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/JORDAN W TAYLOR/Examiner, Art Unit 1738
Prosecution Insights