DETAILED ACTION
Claims 1-23 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 08/17/2023 has been considered by the examiner.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
1.Claims 1, 4-8, 11-12, and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by 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).
Instant claim 1 recites a nanoparticle complex for detecting or isolating a target material from a biological sample, wherein the nanoparticle complex is a complex in which the surface of nanoparticles is coated with a polymer material, and comprises a receptor for detecting or isolating a target material bound to the polymer material, and the polymer material is any one or more selected from the group consisting of polydopamine, polyethylene glycol, polyetherimide, polyvinyl alcohol, casein, dextran, and chitosan.
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
comprises a receptor for detecting or isolating a target material bound to the polymer material, wherein the receptor is a nucleic acid (see page 2 “Furthermore, we demonstrated that PDA can adsorb dye-labeled single-stranded DNA (ssDNA) probe and effectively quench the fluorescence of the dye.”) (instant claim 6), 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 target being a nucleic acid (see page 4 “These results demonstrated that the Fe3O4@PDA-based nanoprobe is useful for detecting intracellular mRNA.”) (instant claim 7). 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).
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.
2.Claims 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Lin as applied to claims 1, 4-8, 11-12, and 14 above.
The teachings of Lin as it pertains to claims 1, 4-8, 11-12, and 14 are discussed in the 35 USC 102 rejection above.
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).
One of ordinary skill in the art would have been motivated to use the methods of Lin because Lin teaches PDA has numerous functional group such as amino and catechol, which can facilitate the further functionalization of PDA-based nanocomposites with biomolecules (see page 3).
3.Claims 2-3 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Lin as applied to claims 1, 4-8, 11-12, and 14 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 as it pertains to claims 1, 4-8, 11-12, and 14 are discussed in the 35 USC 102 rejection above.
Lin does not teach the coating being a mixture of a monosaccharide for lectin binding, nor does Lin teach the monosaccharide being mannose.
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 use of monosaccharides with nanoparticles taught by Li. Li provides motivation by teaching 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.
4.Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Lin as applied to claims 1, 4-8, 11-12, and 14 above, in view of Park et al., (US 10465184 B2) (IDS filed on 08/17/2023).
The teachings of Lin as it pertains to claims 1, 4-8, 11-12, and 14 are discussed in the 35 USC 102 rejection above.
Lin does not teach the nanoparticle complex diameter being between 200 to 1,000 nm.
Park teaches the nanoparticle complex having a diameter of 200 to 1,000 nm (see claim 1 of Park) (instant claim 9).
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 nanoparticle complex sizing of Park. Park provides motivation by teaching that the particle size that is used for isolation and purification of DNA, RNA, and proteins is preferably in the range from about 100 nm to about 10 µm (10 µm is equal to 10,000 nm) (see column 1 lines 52-56). 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.
5.Claims 15-16 are under 35 U.S.C. 103 as being unpatentable over Lin as applied to claims 1, 4-8, 11-12, and 14 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 as it pertains to claims 1, 4-8, 11-12, and 14 are discussed in the 35 USC 102 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 in step b) reacts fir 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 polydopamine-coated nanoparticle preparation method of Mrowczynski. Mrowczynski provides motivation by teaching that magnetite (an acid-base catalyst) have been supplied as supports to drug delivcery 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.
6.Claims 10 and 17-21 are rejected under 35 U.S.C. 103 as being unpatentable over Lin 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 as it pertains to claims 1, 4-8, 11-12, and 14 are discussed in the 35 USC 102 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. Lin does not teach the claimed polymer material of claim 17. Lin does not teach the claimed biological sample of claim 10, 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 nanoparticle preparations taught by Jiang. Jiang provides motivation by teaching that silica 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 provides further motivation by teaching 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.
Conclusion
No claim is allowed.
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/MCKENZIE A DUNN/ Examiner, Art Unit 1678
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678
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