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 .
Acknowledgement of Receipt
Applicant’s Response, filed 6/23/2026, in reply to the Office Action mailed 4/1/2026, is acknowledged and has been entered. Claims 1 and 20 have been amended. Claims 1, 3-14, 20 and 22-25 are pending and are examined herein on the merits for patentability.
Response to Arguments
Applicant’s arguments have been fully considered. Any rejection not reiterated herein has been withdrawn. The Examiner’s response to Applicant’s arguments is incorporated below.
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.
Claim(s) 1, 3, 4, 6-9, 12-14, 20 and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Chakravarty et al. (US 2022/0048788) in view of Hwan et al. (KR 20130114346), for reasons set forth in the previous Office Action.
Claim(s) 1, 3-9, 12-14, 20 and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Chakravarty et al. (US 2022/0048788) in view of Hwan et al. (KR 20130114346), in further view of Uvdal (WO 08/096279), for reasons set forth in the previous Office Action.
Claim(s) 1, 3-4, 6-14, 20 and 22-25 are rejected under 35 U.S.C. 103 as being unpatentable over Chakravarty et al. (US 20220048788) in view of Hwan et al. (KR 20130114346), in further view of Khoee et al. (J Nanostruct Chem, 2014, 4, 111), for reasons set forth in the previous Office Action.
Response to arguments
Applicant argues that none of Chakravarty, Hwan, Uvdal, or Khoee, alone or in combination, teaches or suggests the features of previously presented claims 2 and 21, noting that none of the cited references teach or suggest a coated magnetic nanoparticle (or method of producing one) in which "no primary amines can be detected on the surface of the nanoparticle using a standard assay," as recited in amended independent claim 1. Applicant asserts that as amended, claim 1 defines a structural and functional endpoint of the coated magnetic nanoparticle: primary amines on the surface of the nanoparticles have been backfilled below the detection threshold of a standard assay, which may include 3-(4-carboxybenzoyl)quinoline-2- carboxaldehyde (CBQCA) or o-phthaldialdehyde (OPA) based assays, citing the instant Specification at [0052], [0090], and [0107]. Applicant assert that as explained in the Specification, backfilling the primary amines on the surface of the nanoparticles to a point at which no primary amines can be detected on the surface of the nanoparticle using a standard assay improves the stability of the nanoparticles See e.g. id. at " [0090] and [0107]. Applicant contends that in contrast to amended claim 1, Chakravarty defines its tantalum oxide nanoparticle variants (e.g., TaOx NC1, NC2, and NC3) by the ratios of surface modifiers (e.g., PEG-Silane, APTMS, and m-PEG-SG) used during synthesis to tune hydrophilicity/hydrophobicity. For example, Chakravarty explains that "[b]y controlling the surface modifier 16, its concentration and/or the ratio of at least two surface modifiers 16, the hydrophobicity or hydrophilicity of the resulting nanoparticles 10, 10a, 10b can be manipulated." Chakravarty 1 [0125]. Applicant asserts that nowhere does Chakravarty quantify surface primary amines on its nanoparticles, much less describe backfilling primary amines below the detection threshold of a standard assay.
Applicant further argues that Hwan does not cure the deficiencies of Chakravarty. Applicant asserts that no portion of Hwan contemplates quantification of unreacted surface amines after performing the conjugation. Moreover, no portion of Hwan contemplates how conjugating the PEG to the residual amine groups impacts the stability of its nanoparticles. Applicant further argues that Uvdal and Khoee are likewise silent on the quantification of surface primary amines and that Uvdal and Khoee, alone or in combination, do not cure the deficiencies of Chakravarty and Hwan.
Applicant’s arguments have been fully considered but are not found to be persuasive. It is respectfully submitted that Chakravarty teaches coating a nanoparticle with a combination of PEG-Silane and APTMS and/or APTES and then further contacting the now partially-coated NC with methoxy polyethylene glycol-succinimidyl glutamate ester (mPEG-SG) results in the nanoparticles having the covalent coating comprising the surface modifiers of PEG-Silane and APTMS-m-PEG-glutarate and/or APTES-m-PEG-glutarate, which after the dialysis, is highly hydrophilic (paragraph 0125). As set forth in the previous Office Action, Chakravarty teaches the surface modifier being selected from the group consisting of an emulsifier, (3-aminopropyl)triethoxy silane (APTMS), APTMS-methoxy-poly(ethylene- glycol)-succinimidyl glutarate (APTMS-m-PEG-glutarate), 2-[methoxy (polyethyleneoxy)- 9-12-propyl]trimethoxysilane (PEG-Silane), fluorescein isothiocyanate-APTMS (FITC- APTMS), hexadecyltriethoxy silane, and combinations thereof (paragraph 0019). It is noted that the surface modifiers are recited in the alternative, including combinations. A nanoparticle having APTMS-m-PEG-glutarate as a coating doe not require free amine.
With regard to arguments directed to backfilling primary amines, it is respectfully submitted that the arguments are not commensurate in scope with the claims, which do not require a backfilling component.
With regard to arguments directed to the coating in Hwan, it is noted that Hwan is incorporated to show obviousness of providing a magnetic core in the tantalum oxide nanoparticles, as for the benefit of bimodal NMR/optical imaging, rather than the coating itself. The Uvdal and Khoee references are included to demonstrate known use of a targeting ligand and PEG structure, respectively. Applicant’s arguments have been fully considered but the rejections are maintained.
Conclusion
No claims are allowed at this time.
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.
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/LHS/
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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