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 .
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.
Status of Claims
Claims 15-16 and 21-36 are pending and under examination.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 15-16 and 21-34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The newly added limitation of “contacting the bound antigen detection reagent with a substrate for 10 minutes or less, thereby producing a product” is new matter. Applicant has indicated in the Remarks dated 07/24/2025 that the amendments can be found throughout the filed specification and, in the particular, paragraphs [0003], [0108], [0110], [011], [0144], [0152], [0157], [0175], and [0201].
Even though the specification discloses the peroxidase-like activity of Pt-Pd NPs, the catalysis to peroxidase substrate TMB or oPD was tested in the presence of H2O2 and it was observed that Pt-Pd NPs could catalyze H2O2-induced oxidization of TMB or oPD, resulting in a deep blue color and yellow color solution within 10 min. The examiner was not able to find support in the instant specification a reaction with a single substrate without hydrogen peroxide and the reaction produces a product in 30 seconds or 1 minute (i.e., 10 minutes or less).
For the reasons above, the specification fails to provide direction or blaze marks to the limitations of contacting the bound antigen detection reagent with a substrate for 10 minutes or less, thereby producing a product.
Written description
Claims 15-16 and 21-36 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that, for a claimed genus, the written description requirement may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus:
The amended claims are drawn to a method of rapidly detecting the presence of an antigen of interest by contacting a sample with an antigen detection reagent comprises an antigen-binding molecules conjugated to the claimed mesoporous bimetallic nanoparticle and contacting the bound antigen detection reagent with a substrate for 10 minutes or less (e.g., 10 seconds), thereby producing a product and detecting rapidly the presence of the product, thereby indicating the presence of the antigen of interest.
The claims as a whole cover broad genuses of substrates and the antigen detection reagents. The antigen detection reagents as claimed are broad because (1) the antigen detection reagents may comprise a wide range of chemical structures by reciting comprises (open-ended) and (2) structural orientation of the bimetallic nanoparticles. Explicit in the claims is that such combination must possess certain functional characteristics; namely, the contacting bound antigen detection reagent comprising the mesoporous bimetallic nanoparticle and a substrate would produce a detectable signal for 10 minutes or less.
As filed, the specification only discloses the antigen detection reagent is one or more antigen-binding molecules conjugated to the claimed bimetallic mesoporous nanoparticles wherein the pores are made of fine Pt NPs that are forming several branched structure on the surface and the Pt nanoparticles had an average diameter of 3-4 nm and were distributed evenly on the surface of the nanocore with hydrogen peroxide (H2O2) by adding TMB or oPD solution for 10 mins to produce a detectable (see pg. 51, lines 19-25; and pg. 52, lines 5-13, filed dated 03/14/2022). Noted that the specification discloses a specific structural orientation between the Pt element and the nanocore forming mesoporous bimetallic nanoparticles.
Meanwhile, Gao et al. teach that in an assay format of irregular-shaped platinum nanoparticles with specific H2O2 and TMB took 15 min on a plate shaker for color development (see abstract and pg. 81, left col., second 2.4). (“Irregular-shaped platinum nanoparticles as peroxidase mimics for highly efficient colorimetric immunoassay” Analytica Chimica Acta, vol. 776, 2013, pgs. 79-86, published 03/21/2013, of record dated 03/24/2025). Additionally, Masud et al. teach mesoporous γ-Fe2O3 shows high nanozyme activities (and magnetism) toward the catalytic oxidation of chromogenic substances such as TMB (see abstract). Masud teaches the Fe2O3 nanoparticles catalyze with TMB and H2O2 and the reaction was conducted in the dark for 10 min, and the nanozyme catalyzed the oxidation of the colourless TMB solution to a blue-coloured (see pg. 5414, left col., para. 1). (“Nanoarchitectured peroxidase-mimetic nanozymes: mesoporous nanocrystalline α- or γ-iron oxide?”, J. Mater. Chem. B, 2019, vol. 7, pgs. 5412-5422).
As discussed above, the MPEP has stated that written description for a genus can be achieved by a representative number of species within a broad generic limitation. However, it is unquestionable that the pending claims are broad and generic with respect to the substrates and the antigen detection reagents used to produce a detectable product within 10 minutes or less. The possible structural variations are limitless. Therefore, the person would not be able to envision performing a reaction using the claimed antigen detection reagent with any substrate or a single substrate to produce a product in 10 mins or less, as claimed. In particular, Masud teaches to produce peroxidase-like activity, TMB and H2O2 are used in the reaction for 10 minutes to produce a product that is detectable.
In light of the specification, the person skilled in the art would face an undue burden of examination in extrapolating from the myriad of combinations of the claimed ingredients that would not meet the functional characteristics of producing a detectable product in 10 minutes or less. The person cannot envision the detailed chemical reactions until reduction to practice has occurred, regardless of the simplicity of the product.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed agents.
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 15-16 and 21-34 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.
Claim 15 recites the limitation of contacting the bound antigen detection reagent with a substrate for 10 minutes or less, thereby producing a product is unclear to the metes and bounds of what is the product produced in 10 minutes or less. As stated in the written description, the structures are specific to meet the function of producing a product with 10 minutes. Therefore, it is unclear to what is the product in 10 minutes or less that is detectable. Claims 16 and 21-34 are being rejected as being dependent from claim 15.
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.
Claims 15-16, 21-24, 26-27, and 31-36 are rejected under 35 U.S.C. 103 as being unpatentable over Hamed et al. (“All-Metal Mesoporous Nanocolloids: Solution-Phase Synthesis of Core–Shell Pd@Pt Nanoparticles with a Designed Concave Surface”, Angew. Chem. Int. Ed., vol. 52, pgs. 13611-13615, published 2013, of record dated 06/22/2023, of record), Gao et al. (“Irregular-shaped platinum nanoparticles as peroxidase mimics for highly efficient colorimetric immunoassay” Analytica Chimica Acta, vol. 776, 2013, pgs. 79-86, published 03/21/2013, of record) and Liu et al. (Microchim Acta, vol., 182, pgs. 1143–1151, published 12/9/2014, of record dated 06/22/2023, of record).
With respect to claims 15, 27 and 35-36, Hamed teaches bimetallic nanoparticles have often shown superior catalytic activity (see pg. 13611, left col., middle of para. 1). Hamed teaches mesoporous metal nanoparticles with high indexed facets, which can provide many catalytically active sites for catalytic reactions (see pg. 13611, left col., bottom of para. 1 and pg. 13614, left col., bottom of para. 3). Hamed further teaches the mesoporous nanoparticles are highly useful in important applications such as adsorption, catalysis, and drug delivery (see pg. 13611, left col., para. 2). Hamed teaches the mesoporous structures in the Pd@Pt nanoparticles provide a high surface area and many catalytically active sites on a concave surface (see pg. 13611, right col., bottom of para. 2). Hamed teaches in Fig. 1 that the size distribution of the nanocolloids has an average size of 45 nm and uniform mesopores were confirmed on the nanoparticle surface (also see pg. 13611, right col., para. 4). Hamed further teaches that TEM and SEM images clearly show that nanocolloids are remarkably uniform in size and shape without any formation of by-products, demonstrating the high-yield (100%) synthesis of the Pd@Pt nanoparticles (see pg. 13612, right col., bottom of para. 2). Hamed teaches visibly monitor color reactions of the formation of nanoparticles (see pg. 13613, right col., para. 1). Hamed teaches that the Pt-Pd alloy heterointerface, of which the Pd (as an oxophilic element) can enhance the removal of adsorbed CO on neighboring Pt atoms by adsorbing oxygen-containing species (see pg. 13613, left col., para. 1). Hamed also teaches that the electrocatalytic activity was normalized by the surface area, the activity of mesoporous Pd@Pt nanoparticles was still around twice that of Pt black and from the enhanced activity observed here is attributable to the increase of active sites and as seen in Fig. 2d, the mesoporous structure provides not only high surface area but also rich atomic steps with concave surface topology (see pg. 13614, middle of para. 2).
Hamed does not teach detecting the presence of an antigen of interest comprising contacting a sample with an antigen detection reagent comprising one or more antigen-binding molecules with a substrate for 10 minutes or less to produce a product, and detecting the presence of the product, thereby indicating the presence of the antigen of interest.
Gao teaches ELISA methods based on natural enzyme-labeled probes have been applied in the immunoassays, but most have some inevitable limitations (e.g., harsh preparation, purification and storage) and are unsuitable for routine use. Gao teaches synthesizing a new class of irregular-shaped platinum nanoparticles (ISPtNP) (see abstract and Scheme 1). Gao teaches the catalytic mechanism of the ISPtNP toward TMB/H2O2 through a sandwich-type assay format, two types of colorimetric immunoassay protocols were designed and developed for the detection of IgG by using the synthesized ISPtNP and conventional HRP as the labeling of detection antibodies and similar results were obtained (see abstract and Scheme 1). Gao teaches that TMB and H2O2 are used as the substrates of natural enzymes for visible color development and irregular-shaped platinum nanoparticles were used as peroxidase mimics to catalyze the color (see pg. 81, right col., section 3.1 of Results and discussion and Scheme 1). Gao teaches that platinum nanoparticles are especially interesting in catalysis, since platinum is one of the most important materials used in catalytic techniques because hydrogen, oxygen and other gases become bound to platinum and in the form of nanoparticles, platinum has a substantially higher effectiveness because of the increased specific surface area (see pg. 80, left col., top of last para.). Gao also teaches that when platinum nanoparticles are modified with the antigens or antibodies, the functional nanoparticles may be carried with certain charges on the surface of nanoparticles, thus resulting in mutual repulsion in the solution and so the protein molecules make platinum nanoparticles become stabilize and less coagulated (see pg. 80, left col., bottom of last para.). Gao teaches that the smaller the Km value is, the stronger the affinity of the mimic toward the enzyme substrate (see pg. 83, left col., bottom of section 3.3 Optimization of catalytic conditions). Gao concluded that the results indicated that the synthesized irregular-shaped platinum nanoparticles displayed strong peroxidase-like catalytic activity, high catalytic efficiency and low Km value toward TMB (see pg. 85, right col., Conclusions).
Liu teaches porous platinum nanoparticles and PdPt nanocages in immunoassay and said PdPt nanocages display excellent catalytic property and high loading capacity (see abstract and Scheme 1). Liu teaches that porous platinum nanoparticles also have excellent catalytic performance (see pg. 1144, left col., middle of para. 1). Liu teaches that PdPt nanoparticles not only immobilize lots of antibodies and redox probes, but also catalyze H2O2 to improve the electrochemical signal due to their porous walls and excellent catalytic properties (see pg. 1145, right col., bottom of para. 1). Liu teaches that in order to further amplify the signal and increase detection sensitivity, catalytic performance of the immunoprobes is the further demand for conducting ultrasensitive electrochemical sensing interface and Pt-based bimetallic nanomaterials Pt-M wherein M = Pd, Co, Ni, and Au) in place of pure Pt will not only retain the beneficial features of both but also can optimize the binding energy between Pt and oxygen and thus enhance the catalytic performance (see pg. 1144, left col., para. 2). Liu also teaches signal amplification for enhanced sensitivity is achieved by catalytic oxidation of H2O2 using PdPt nanoparticles (see pg. 1144, right col., para. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the mesoporous core-shell Pd@Pt nanocolloids as taught by Hamed with antibodies and substrates as taught by Gao et al. for immunoassay analysis because Hamed teaches the mesoporous core-shell Pd@Pt nanoparticles provide a high surface area and these mesoporous nanoparticles (irregular-shaped, see Fig. 1) have many catalytic active sites on a concave surface of said nanoparticles and Gao teaches that irregular-shaped Pt nanoparticles produce a strong peroxidase-like catalytic activity from catalytic efficiency to develop colorimetric immunoassays in the presence of TMB/H2O2 substrates (scheme 1). Thus, it would have been obvious to the person to have incorporated the mesoporous core-shell Pd@Pt having many catalytic active sites of Hamed with antibodies and TMB/H2O2 substrates for assay detection because said mesoporous nanoparticles have the characteristics that are recognized in the art to produce a strong peroxidase-like catalytic activity with TMB/H2O2 substrates as taught by Gao et al.
Additionally, it would have been obvious to the person to have used the mesoporous core-shell Pd@Pt combination as taught by Hamed to produce catalytic activity for immunoassays as taught by Liu because Liu teaches the immunoassay with core-shell Pd-Pt combination displays excellent catalytic properties and high loading capacity. Because Hamed teaches that the mesoporous core-shell Pd-Pt nanoparticles having the characteristic properties of containing many catalytic active sites on a concave surface and Liu and Gao have recognized that Pt containing nanoparticles have strong catalytic activities, it would have been obvious to have used said mesoporous nanoparticles for the purpose of producing catalytic properties from Pt nanoparticles for immunoassays.
With respect to contacting for 10 minutes or less, thereby producing a product, because Hamed teaches the mesoporous Pd-Pt nanoparticles and Gao teaches using TMB + H2O2 solution to develop a colorimetric immunoassay (i.e., as disclosed in the instant specification), it would have been obvious that the reaction containing said mesoporous nanoparticles and TMB+ H2O2 would produce a detectable product within 10 minutes of contacting.
The person would have reasonably expected success in using the mesoporous palladium-platinum (Pd@Pt) nanoparticles for immunoassays because it has been well recognized in the art to have attached antibodies to irregular-shaped or porous Pt nanoparticles, as taught by Liu and Gao. Additionally, the person would have expected success using the mesoporous Pd@Pt nanoparticles to produce a reaction because Hamed, Liu, and Gao all recognize the importance of producing catalytic activity through Pt nanoparticles and Hamed teaches that mesoporous Pd@Pt nanoparticles contain an abundance of catalytic sites.
With respect to claim 16, Hamed does teach color produced from the mesoporous nanoparticles (see pg. 13613, right col., para. 1), but does not teach antigen-binding molecules and substrate. However, Gao and Liu teach at least one substrate (see above). As discussed above, it would have been obvious to the person to have incorporated the mesoporous nanoparticle having many catalytic active sites with antibodies and TMB/H2O2 substrates for assay detection because said mesoporous nanoparticles have the characteristics that are recognized in the art to produce a strong peroxidase-like catalytic activity with TMB/H2O2 substrates, as taught by Gao et al.
With respect to claims 21-22, Hamed teaches bimetallic nanoparticles have often shown superior catalytic activity (see pg. 13611, left col., middle of para. 1). Hamed teaches mesoporous metal nanoparticles with high indexed facets, which can provide many catalytically active sites for catalytic reactions (see pg. 13611, left col., bottom of para. 1 and pg. 13614, left col., bottom of para. 3). Thus, Hamed’s bimetallic Pd@Pt nanoparticles would produce a peroxidase-like activity as it has catalytic active sites and the mesoporous bimetallic nanoparticle reads all the structural limitations of the claimed mesoporous bimetallic Pt/Pd nanoparticles.
With respect to claims 23-24, Hamed does not teach a peroxidase substrate and the product is a peroxidase product. Gao teaches that TMB + H2O2 are used as the substrates and irregular-shaped platinum nanoparticles were used as peroxidase mimics to catalyze the color (see pg. 81, right col., section 3.1 of Results and discussion and Scheme 1). As discussed above, it would have been obvious to the person to have incorporated the mesoporous nanoparticle having many catalytic active sites with antibodies and TMB/H2O2 substrates for assay detection because said mesoporous nanoparticles have the characteristics that are recognized in the art to produce a strong peroxidase-like catalytic activity with TMB/H2O2 substrates, as taught by Gao et al.
With respect to claim 26, as stated above, Hamed does not teach detecting the presence of an antigen of interest in a sample. Liu teaches immunoassay for two tumor markers (CEA and AFP) (see abstract). Gao teaches ELISA is an important analytical method commonly used for diagnoses in medicine and plant pathology (see pg. 79, left col., para. 1). Thus, it would have been obvious to have used the mesoporous Pd@Pt nanoparticles with antibodies for immunoassay detection as taught by Gao or Liu because Gao and Liu recognized the use of Pt containing nanoparticles for immunoassay detection through catalytic activities.
With respect to claim 27, as stated above claim 15.
With respect to claims 31-32, as stated above, Hamed does not teach the antigen-binding molecules and covalently or noncovalently conjugated to the mesoporous bimetallic nanoparticles. Gao teaches that biofunctionalized peroxidase-like nanostructures and biomolecules including fluorogen-labeled biomolecules are covalently conjugated onto the nanomaterials (see pg. 80, left col., bottom of para. 2). Gao teaches the ISPtNP-anti-RIgG conjugation (see pg. 80, right col., section 2.3 and Scheme 1). Liu teaches antibodies bound non-covalently onto the Pd@Pt nanoparticles (see pg. 1145, Scheme 1). Thus, it would have been obvious to have conjugated the antibodies covalently or noncovalently to the Pt containing nanoparticles for the purpose of immunoassay detection.
With respect to claim 33, Hamed does not teach quantifying the antigen of interest in the sample, comprising a detectable signal intensity from the product to a reference standard. Liu also teaches the analytical data obtained from the porous platinum nanoparticles with diluent serum samples were in good agreement with references values obtained via a standard ELISA (see abstract). Gao teaches ISPtNP-based colorimetric immunoassays for testing of real samples, diluted rabbit serum specimens were evaluated by using developed immunoassays and the results were compared with those obtained by using the commercialized ELISA kit (see pg. 85, right col., para. 2; and Fig. 5). Thus, it would have been obvious to have compared the modified assay against the conventional or standard ELISA for a colorimetric evaluation of the modified assay.
With respect to claim 34, Hamed does not teach the antigen of interest is immobilized directly or indirectly to the substrate. Gao teaches that the substrate TMB + H2O2 are immobilized to the nanoparticles (see Scheme 1). Thus, it would have been obvious to have immobilized the substrate onto the nanoparticles for a rapid and colorimetric reaction.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Hamed et al., Gao et al. and Liu et al., as applied to claim 23 above, and further in view of He et al. (“Au@Pt nanostructures as oxidase and peroxidase mimetics for use in immunoassays”, Biomaterials, vol. 32, pgs. 1139-1147, published 2011, IDS submitted 3/14/2022, NPL cite # 5).
Hamed, Liu, and Gao have been discussed above. Gao teaches that TMB and H2O2 are used as the substrates of natural enzymes for visible color development and irregular-shaped platinum nanoparticles were used as peroxidase mimics to catalyze the color (see pg. 81, right col., section 3.1 of Results and discussion and Scheme 1). However, the references do not teach the peroxidase substrate is o-phenylenediamine dihydrochloride (oPD).
He teaches Au nanorods coated with a shell composed of Pt nanodots (Au@Pt nanostructures) exhibited intrinsic oxidase-like, peroxidase-like and catalase-like activity, catalyzing oxygen and hydrogen peroxide reduction and Au@Pt nanostructure-based enzyme linked immunosorbent assay ELISA for the detection (see abstract). He teaches activity of the nanostructures as oxidase and peroxidase mimetics was evaluated using the typical HRP substrates of o-phenylenediamine (OPD) and 3,3’,5,5’-tetramethylbenzidine (TMB) (see pg. 1140, left col., para. 3 and section 2.1) and kinetic reaction of TMB and OPD (see pg. 1140, right col., section 2.4).
Thus, it would have been obvious to have used the mesoporous nanoparticles with o-phenylenediamine (OPD) to mimetic ELISA because He teaches that o-phenylenediamine (OPD) and 3,3’,5,5’-tetramethylbenzidine (TMB) are typical HRP substrates for catalytic reaction of ELISA. The person would have reasonably expected success because it has been understood in the art to use either o-phenylenediamine (OPD) or 3,3’,5,5’-tetramethylbenzidine (TMB) to react with specific catalytic enzyme reaction for ELISA.
Claims 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Hamed et al., Gao et al. and Liu et al., as applied to claim 27 above, and further in view of Qian et al. (Nature Biotechnology, vol. 26 (no 1), pgs. 83-90, published January 2008, of record dated 06/22/2023).
Hamed, Liu, and Gao have been discussed above but the references do not explicitly teach the claimed antibody-like molecules.
Qian teaches conjugated to tumor-targeting ligands such as single-chain variable fragment (ScFv) antibodies and the conjugated nanoparticles were able to target tumor biomarkers (see abstract and Fig. 3). Fig. 3 teaches covalent conjugate of an EGFR-antibody fragment (also see caption).
Thus, it would have been obvious to the person to have used the used the modified immunoassay of Hamed et al., Gao et al., and Liu et al. with antibody fragments such as single-chain variable fragments of Qian because Liu and Gao each recognizes that Fab regions of the IgG antibodies bind to target antigens. The person would reasonably expected success in using ScFv fragments with the mesoporous nanoparticles because it has been well understood in the art to conjugate said fragments to nanoparticles for detection, as taught by Qian.
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Hamed et al., Gao et al. and Liu et al., as applied to claim 27 above, and further in view of Quay et al. (US2008/0318837A1, published 12/25/2008, of record dated 06/22/2023).
Hamed, Liu, and Gao have been discussed above but the references do not teach the antigen binding molecule is a lectin.
Quay teaches lectin binding agent (see para. [0128]). Quay further teaches lectin conjugated to gold nanoparticles (see bottom of para. [0128]). Quay teaches lectins are plant proteins that bind to specific sugars found on the surface of glycoproteins and glycolipids of eukaryotic cells (see bottom of para. [0128]). Quay teaches study samples, standards, and quality control samples and further teaches a reference curve using reference standards of known concentration (see para. [0270]).
Therefore, it would have been obvious to the person to have used or incorporated the modified immunoassay of Hamed et al., Liu et al., and Gao et al. with concanavalin A lectin in assay detection of Quay because Quay teaches that lectin binds to specific sugar molecules found on the surface of the targeted antigen. The person would have used or incorporated lectins, as lectins have been recognized in the art to bind to a specific sugar structure for detection. The person would reasonably expected success in using the lectin in the modified assay because it has been well understood by Quay that lectin conjugates to nanoparticles for assay detection.
Response to Arguments
Applicant's arguments filed 07/24/2025 have been fully considered but they are not persuasive. The 103 rejections have been modified and maintained.
Applicant argues on page 9, second full paragraph, that the claims are patentable over Hamed, Liu, and Gao. Applicant argues that Liu and Gao are fundamentally different from those disclosed and recited in the pending claims. Liu discloses the use of both porous platinum nanoparticles and Pd@Pt nanocages in an electrochemical assay, while Gao discloses irregular-shaped platinum nanoparticles. None of these nanostructures are the same as or are used in the same way as those disclosed and recited in the pending claims. Applicant argues on page 10 that there is nothing in Liu’s reference is relevant to the pending claims. Therefore, there is little in Liu to provide guidance or motivation to one of ordinary skill in the art to combine the teachings of Liu with those of Hamed. With respect to Gao, the Office has provided no basis for ascribing any characteristic associated with the disclosed nanoparticle with the bimetallic mesoporous nanoparticles recited in the pending claims. It is well known in the art that particles of many different types can be used in a colorimetric immunoassay; however, the there is no link or motivation between Gao and Hamed. Applicant argues on pages 10-11 that the amended claims are patentable over the teachings of Hamed, Liu, and Gao.
The arguments are not found persuasive for the following reasons. The claims recite a method “comprising” which is an open-ended limitation. Thus, the claimed method does not limit to only using bimetallic nanoparticles in the detection. As stated above, although Liu and Gao do not explicitly teach the claimed mesoporous bimetallic nanoparticles for its methods, these references recognize the use of platinum (Pt) element in immunoassays because Pt containing nanoparticles possess the catalytic properties to produce a product in the presence of a substrate. In particular, Liu teaches using two forms of Pt nanoparticles, therefore, Pt has been a well-recognized element for immunoassays. Meanwhile, Gao also teaches that irregular-shaped Pt nanoparticles (i.e., similar to the structure of mesoporous nanoparticles) produce catalytic reaction with TMB/H2O2 substrates. Thus, the linking element in using is the use of Pt element for catalytic properties. Because Hamed teaches that the mesoporous core-shell Pd-Pt nanoparticles containing many catalytic active sites on a concave surface and Liu and Gao recognize that strong catalytic activities from Pt for immunoassays, it would have been obvious to have incorporated said mesoporous nanoparticles with antibodies and TMB/H2O2 substrates for immunoassays.
With respect to arguments related to claims 25 and 28-30, Applicant argues that these claims are dependent from claim 15 and in view of the amendments in claim 15 and arguments above, a request to reconsider and withdraw the rejections. The arguments are not found persuasive for the reasons stated in claim 15 (see above).
Conclusion
No claim is 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.
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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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