DETAILED ACTION
Claims 1-5, 8, and 10-23 are pending.
Status of Claims
Claims 1-5, 8, and 10-23 are pending. Claim 1 has been amended. Claims 8, and 10-23 are under examination.
Withdrawn Claim Objections and/or Rejections
The rejection of claims 1, 4-8, 11-13, and 14 under 35 USC 102 as being anticipated by Lin et al., as set forth on pp. 2-5 of the previous office action (mailed on 04/06/2026) has been withdrawn in view of the amended claims (filed on 06/30/2026).
The rejection of claim 22-23 under 35 USC 103 as being unpatentable over Lin et al., as set forth on p. 6 of the previous office action (mailed on 04/06/2026) has been withdrawn in view of the amended claims (filed on 06/30/2026).
The rejection of claims 2-3 and 13 under 35 USC 103 as being unpatentable over Lin and Li et al., as set forth on pp. 6-7 of the previous office action (mailed on 04/06/2026) has been withdrawn in view of the amended claims (filed on 06/30/2026).
The rejection of claim 9 under 35 USC 103 as being unpatentable over Lin and Park et al., as set forth on pp. 7-8 of the previous office action (mailed on 04/06/2026) has been withdrawn in view of the cancelled claim (filed on 06/30/2026).
The rejection of claims 15-16 under 35 USC 103 as being unpatentable over Lin and Mrowczynski et al., as set forth on pp. 8-9 of the previous office action (mailed on 04/06/2026) has been withdrawn in view of the amended claims (filed on 06/30/2026).
The rejection of claims 10 and 17-21 under 35 USC 103 as being unpatentable over Lin and Jiang et al., as set forth on pp. 9-11 of the previous office action (mailed on 04/06/2026) has been withdrawn in view of the amended claims (filed on 06/30/2026).
Maintained 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 (i.e., changing from AIA to pre-AIA ) 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.
1.Claims 1, 4-5, 8, 11-12, 14, and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Lin et al. “Multifunctional Fe₃O₄@polydopamine core-shell nanocomposites for intracellular mRNA detection and imaging-guided photothermal therapy.” ACS nano vol. 8,4 (2014): 3876-83. doi:10.1021/nn500722y (IDS filed on 08/17/2023), in view of Draz et al., “Applications of gold nanoparticles in virus detection.” Theranostics vol. 8,7 1985-2017. 15 Feb. 2018, doi:10.7150/thno.23856.
Lin teaches a nanoparticle complex for detecting or isolating a target material from a
biological sample (see page 2 “In this work, we fabricated multifunctional
Fe3O4@polydopamine core–shell nanocomposites (Fe3O4@PDA NCs) consisting of a Fe3O4
core surrounded by a thin PDA shell, which can be utilized for intracellular mRNA detection and
multimodal imaging-guided photothermal therapy (PTT).”),
wherein the nanoparticle complex is a complex in which the surface of nanoparticles is
coated with a polymer material (see abstract “Multifunctional nanocomposites have the
potential to integrate sensing, diagnostic, and therapeutic functions into a single nanostructure.
Herein, we synthesize Fe3O4@polydopamine core–shell nanocomposites (Fe3O4@PDA NCs)
through an in situ self-polymerization method. Dopamine, a melanin-like mimic of mussel
adhesive proteins, can self-polymerize to form surface-adherent polydopamine (PDA) films onto
a wide range of materials including Fe3O4 nanoparticles used here.”), and
the polymer material is any one or more selected from the group consisting of
polydopamine (see abstract) (instant claim 1). Lin teaches wherein the bond is in the form of
a bond by a linker, and the bond by a linker is a thiol group (see page 6 “PDA can react with
thiol- and amino-terminated molecules via the Michael addition or Schiff base reactions,15,17–
20 which can facilitate the surface functionalization of the nanocomposites with biomolecules for
targeting specific cell”, thiol-terminated molecules are known linkers) (instant claims 4-5). Lin teaches the nanoparticle being iron oxide nanoparticles (see page 6 “Water-soluble iron
oxide (Fe3O4) nanoparticles with carboxylic acid group (ca. 15 nm) were obtained from Ocean
NanoTech (Springdale, AR, USA).”) (instant claim 8).
Lin teaches a method for preparing the nanoparticle complex of claim 1, the method
comprising the following steps: a) preparing polydopamine-coated nanoparticles by adding and
dispersing nanoparticles and an acid-base catalyst in a polydopamine solution (see page 2 “In
this work, we fabricated multifunctional Fe3O4@polydopamine core–shell nanocomposites
(Fe3O4@PDA NCs) consisting of a Fe3O4 core surrounded by a thin PDA shell, which can be
utilized for intracellular mRNA detection and multimodal imaging-guided photothermal therapy
(PTT). Although the synthesis of Fe3O4@PDA NCs has been reported,33,34 to the best of our
knowledge, the theranostic applications of Fe3O4@PDA NCs have not been explored until now.
The modification of the Fe3O4 nanoparticles (Fe3O4 NPs) with PDA was achieved by in situ
polymerization of DA onto the surface of the Fe3O4 NPs (Figure 1a). Furthermore, we
demonstrated that PDA can adsorb dye-labeled single-stranded DNA (ssDNA) probe and
effectively quench the fluorescence of the dye”. Fe3O4 is known as magnetite, which is a known
acid-base catalyst); and
b) adding a receptor to the polydopamine-coated nanoparticles and reacting the
resulting mixture to prepare a receptor-bound polydopamine-coated nanoparticle complex (see
page 3 “The adsorption and fluorescence quenching abilities of the Fe3O4@PDA NCs toward
the dye-labeled ssDNA were evaluated via measurements made while mixing the fluorescent
DNA probe and the prepared Fe3O4@PDA NCs. Since hairpin ssDNA (hpDNA) can provide
increased target recognition specificity than the linear ssDNA, we chose a FAM-labeled hairpin
ssDNA (FAM-hpDNA) containing a 21-base single-stranded loop and a 6-base-pair stem as the recognition probe (all sequences are shown in the Supporting Information Table S1).” (instant
claim 11). Lin teaches the nanoparticle being iron oxide nanoparticles (see page 6 “Water-
soluble iron oxide (Fe3O4) nanoparticles with carboxylic acid group (ca. 15 nm) were obtained
from Ocean NanoTech (Springdale, AR, USA).”) (instant claim 14). Lin teaches wherein the
nanoparticles and polydopamine in Step a) are mixed at a weight ratio of 1:0.01 to 1:1.5 (see
page 7 “In a typical synthesis of Fe3O4@PDA NCs with 4 nm thickness of PDA shell, 6 mg of
dopamine was added to 50 mL of 10 mM PBS (pH 8.5) containing 5 mg of Fe3O4 NPs. After
shaking at room temperature for 4 h, Fe3O4@PDA NCs were obtained by centrifugation and
washed with water for three times.”) (instant claim 12). Lin teaches the use of nanoparticle complex (see page 6 “In summary, we have synthesized Fe3O4@PDA NCs as multifunctional theranostic agents for intracellular mRNA detection and multimodal imaging-guided photothermal therapy.”). While Lin does not explicitly teach the use of a kit, it would have been obvious to one of ordinary skill in the art at the time of the instant invention to combine the nanoparticle complex as the active ingredient in a kit. The use of a kit is widely known in the art (instant claims 22-23).
Lin does not teach the receptor being one or more selected from the group consisting of an antibiotic, an antibody, and a lectin, which specifically bind to a target material, wherein the target material, wherein the target material is one or more selected from the group consisting of a pathogen and a virus, and wherein the nanoparticle complex has a diameter of 200 to 1,000 nm.
Draz teaches a complex with a receptor that is an antibody which binds specifically to a target material, the target material being a virus (see figure 4), and the nanoparticle complex having a diameter of 200 to 1,000 nm (see page 1988 “AuNPs are a leading class of metal nanostructures that is widely known for its chemical stability, water solubility, and broad size and shape controllability. AuNPs can range from 1 to 800 nm in size”) (instant claim 1). Draz teaches the sample being blood (see page 1987 “The main working principle of these techniques is the use of specific antibodies in conjugation with different signal reporting systems, such as red blood cells, enzymes, and radioactive or fluorescent materials”) (instant claim 10).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the polydopamine nanoparticle complex taught by Lin with the methods of using nanoparticles in virus detection taught by Draz. Draz teaches that one of the most common approaches for exploiting nanostructures in virus detection is in the development of nanobio hybrid systems that contain an antibody derived from viruses conjugated to the surface of different nanoparticle forms (see page 1988). Draz further teaches that using nanoparticles to detect viruses allows for improvements in designs, detection performance, sensitivity, specificity and stability (see page 2010). The artisan would have reasonable expectation of success based on the cumulative disclosures of these prior art references.
2.Claims 2-3 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Lin and Draz as applied to claims 1, 4-5, 8, 11-12, 14, and 22-23 above, in view of Li et al., “Specific Immobilization of Escherichia coli Expressing Recombinant Glycerol Dehydrogenase on Mannose-Functionalized Magnetic Nanoparticles”. Catalysts. 2019; 9(1):7. https://doi.org/10.3390/catal9010007 (IDS filed on 08/17/2023).
The teachings of Lin and Draz as they pertain to claims 1, 4-5, 8, 11-12, 14, and 22-23 are discussed in the 35 USC 103 rejection above.
Lin does not teach the coating being a mixture of a monosaccharide for lectin binding and a polymer material and the monosaccharide being mannose, mannose-functionalized nanoparticles for the immobilization of E.coli cells, indicating that mannose is immobilize on the surface of Fe3O4@OA@DP, nor the monosaciaride is added to the polydopamine solution at a weight ration of 1:05 to 1:15.
Li teaches wherein the coating is a mixture of a monosaccharide for lectin binding and a
polymer material and the monosaccharide being mannose (see abstract, see page 3 “The
mannose-functionalized nanoparticles were then used to immobilize E. coli cells. To investigate
the morphological changes and dispersional stabilization of the Fe3O4@OA@DP,
Fe3O4@OA@DP–mannose, and Fe3O4@OA@DP–mannose–E. coli nanoparticles,
transmission electron microscopy (TEM) was conducted (Figure 2)”) (instant claims 2-3). Li
teaches mannose-functionalized nanoparticles for the immobilization of E.coli cells, indicating
that mannose is immobilize on the surface of Fe3O4@OA@DP (see abstract, see pages 1-2).
One of ordinary skill in the art would have considered optimizing the numerical range of the
weight ratio of monosaccharide to polydopamine, in the methods of Li because the
concentration of materials when working with nanoparticles are routinely optimized (instant
claim 13).
It would have been obvious to one of ordinary skill in the art at the time of the instant
application to modify the nanoparticle complex of Lin with the methods of using nanoparticles in virus detection taught by Draz, with the use of monosaccharides with nanoparticles taught by Li. Li teaches that mannose-functionalized magnetic nanoparticles can be used for the specific recognition of gram-negative bacteria, which gives them great potential in applications such as preparation of biocatalysts and biosensors and clinical diagnosis (see abstract). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed.
3.Claims 15-16 are under 35 U.S.C. 103 as being unpatentable over Lin and Draz as applied to claims 1, 4-5, 8, 11-12, 14, and 22-23 above, in view of Mrowczynski et al., “Assessment of polydopamine coated magnetic nanoparticles in doxorubicin delivery” RSC Advances, 2016, pp.5936-5943, Vol. 6. DOI: 10.1039/c5ra24222c (IDS filed on 08/17/2023).
The teachings of Lin and Draz as they pertain to claims 1, 4-5, 8, 11-12, 14, and 22-23 are discussed in the 35 USC 103 rejection above.
Lin does not teach that the nanoparticles and the acid-base catalyst are dispersed in polydopamine solution for 4 to 26 hours in step a) nor does Lin teach the resulting mixture instep b) reacts for 1-5 hours.
Mrowczynski teaches the magnetite nanoparticles being mixed with dopamine hydrochloride and the acid-base catalyst for 6 hours (see page 5937) (instant claims 15-16).
It would have been obvious to one of ordinary skill in the art at the time of the instant
application to modify the nanoparticle complex of Lin with the methods of using nanoparticles in virus detection taught by Draz, with the polydopamine-coated nanoparticle preparation method of Mrowczynski. Mrowczynski teaches that magnetite (an acid-base catalyst) have been supplied as supports to drug delivery systems, multifunctional nanomaterials, preparation of gene and nucleic acids, nano-carriers, supports for metalo and organocatalysts as well as analytical methods (see page 5936). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed.
4.Claims 10 and 17-21 are rejected under 35 U.S.C. 103 as being unpatentable over Lin and Draz as applied to claims 1, 4-8, 11-12, and 14 above, in view of Jiang et al., “PEG-coated and Gd-loaded fluorescent silica nanoparticles for targeted prostate cancer magnetic resonance imaging and fluorescence imaging.” International journal of nanomedicine vol. 14 5611-5622. 23 Jul. 2019, doi:10.2147/IJN.S207098 (IDS filed on 08/17/2023).
The teachings of Lin and Draz as they pertain to claims 1, 4-5, 8, 11-12, 14, and 22-23 are discussed in the 35 USC 103 rejection above.
Lin teaches a method for preparing the nanoparticle complex of claim 1, the method
comprising the following steps: b) adding a receptor to the coated nanoparticles and reacting
the resulting mixture to prepare a receptor-bound polymer material-coated nanoparticle complex
bound (see page 3 “The adsorption and fluorescence quenching abilities of the Fe3O4@PDA
NCs toward the dye-labeled ssDNA were evaluated via measurements made while mixing the
fluorescent DNA probe and the prepared Fe3O4@PDA NCs. Since hairpin ssDNA (hpDNA) can
provide increased target recognition specificity than the linear ssDNA, we chose a FAM-labeled
hairpin ssDNA (FAM-hpDNA) containing a 21-base single-stranded loop and a 6-base-pair stem
as the recognition probe (all sequences are shown in the Supporting Information Table S1). Lin
teaches the nanoparticles having a thiol group and dispersing the same (see page 6 “PDA can react with thiol- and amino-terminated molecules via the Michael addition or Schiff base
reactions,15,17–20 which can facilitate the surface functionalization of the nanocomposites with
biomolecules for targeting specific cell”, thiol-terminated molecules are known linkers) (instant
claim 17). Lin teaches wherein the nanoparticles and polydopamine in Step a) are mixed at a
weight ratio of 1:0.01 to 1:1.5 (see page 7 “In a typical synthesis of Fe3O4@PDA NCs with 4
nm thickness of PDA shell, 6 mg of dopamine was added to 50 mL of 10 mM PBS (pH 8.5)
containing 5 mg of Fe3O4 NPs. After shaking at room temperature for 4 h, Fe3O4@PDA NCs
were obtained by centrifugation and washed with water for three times.”) (instant claim 19).
Lin does not teach a) preparing polymer material-coated nanoparticles by adding a
polymer material to silica shell nanoparticles having a thiol group and dispersing the same,
the type of polymer material, the biological sample being blood, nor does Lin teach the polymer material being mixed and dispersed for 4 to 36 hours, or the resulting mixture reacting for 1 to 5 hours.
Jiang teaches a) preparing polymer material-coated nanoparticles by adding a polymer
material to silica shell nanoparticles (see page 5613 under “Preparation of silica-based NPs”),
wherein the polymer material is any one or more selected from the group consisting of
polyethylene glycol (see abstract “The Gd@Cy5.5@SiO2-PEG-Ab NPs had a spherical
morphology with a relatively uniform size distribution and demonstrated high efficiency for Gd
loading.”, see page 5613) (instant claim 17). Jiang teaches wherein in Step b), 1-ethyl-3-(3-
dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) are added along
with the receptor (see figure 1, see abstract, see page 5612 “Triton X-100 (TX-100),
cyclohexane and n-hexyl alcohol were obtained from Alfa Aesar (Ward Hill, MA, USA). 1-Ethyl-
3-(3-dimethylaminopropyl) carbodiimide/ N-hydroxysuccinimide (EDC/NHS)”, see page 5613
“Gd@Cy5.5@SiO2-PEG-Ab NPs were prepared using the carbodiimide method. Briefly, a mixture of Gd@Cy5.5@SiO2-PEG-COOH(30 mg), EDC (10 mg), NHS (15 mg) and MES
solution (2 mL, 0.1 mol/L, pH =5.5) was stirred for 1 h at 4 °C.”) (instant claim 18). Jiang
teaches saline-PEG-COOH is added to silica nanoparticles and mixed for 8 hours (see page
5613) (instant claim 20). Jiang teaches YPSMA-1 (a receptor) which is a monoclonal antibody
against PSMA is added to the coated nanoparticles and mixed for 1 hour (see page 5613)
(instant claim 21). Jiang teaches the samples being blood samples (see page 5615) (instant
claim 10).
It would have been obvious to one of ordinary skill in the art at the time of the instant
application to modify the nanoparticle complex of Lin with the methods of using nanoparticles in virus detection taught by Draz, with the method of nanoparticle preparations taught by Jiang. Jiang teaches that nanoparticles display great promise in biomedical applications due to advantages such as high colloidal stability, adjustable particle size, high biocompatibility, low toxicity, and transparency to light and magnetism (see page 5612). Jiang teaches that silica has and contains a large number of hydroxyl groups, which can be modified with various chemical moieties for loading of antibodies and drugs (see page 5612). Jiang teaches that PEG has been used to increase the circulation times of nanoparticles in vivo by reducing the aggregation of opsonins and proteins from blood serum on the surface of NPs that lead to endocytosis (see page 5612). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed.
Response to Arguments
Applicant's arguments filed on 06/30/2026 have been fully considered but they are not persuasive.
On p. 6 applicant argues that Lin does not teach the nanoparticle complex diameter being 200 to 1,000 nm. Applicant argues that the Lin’s core objective would be unsuitable for its intended purpose if the particle diameter had to be 200-1,000 nm.
However, the 103 rejection is based on the combination of Lin and Draz. Draz supplies the teaching of the particle diameter being 200-1,000 nm. Draz explicitly teaches the nanoparticle complex having a diameter of 200 to 1,000 nm.
On p. 6 applicants argue that Li, Mrowczynski, and Jiang fail to remedy the deficiencies of Lin.
However, Draz teaches the deficiencies of Lin, by teaching the nanoparticle complex diameter being 200 to 1,000 nm.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 MCKENZIE A DUNN whose telephone number is (571)270-0490. The examiner can normally be reached Monday-Tuesday 730 am -530pm, Wednesday-Friday 730 am-430 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch can be reached at (571)272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MCKENZIE A DUNN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
