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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/28/2025 has been entered.
Priority
The present application filed on 02/15/2022, claims foreign priority under 35 U.S.C. 119(b) and 37 CFR 1.55 to Japanese Patent Application No. JP2022010495, filed on 01/26/2022, and Japanese Patent Application No. JP2021031241, filed on 02/26/2021.
The contents of this application are supported in the original disclosure provided in Japanese Patent Application No. JP2021031241, filed on 02/26/2021, thus examined instant claims 4-5, 9, and 11-23 have an effective filing date of 02/26/2021.
Information Disclosure Statement
Five Information Disclosure Statement(s) (IDSs), filed on 02/15/2022, 04/27/2022, 07/21/2022, 08/20/2024, and 12/09/2025, are acknowledged and considered.
Claim Status
Claims 4-23 are pending. Claims 1-3 are canceled. Claims 6-8 and 10 are withdrawn. Claims 4-5, 9, and 11-23 are examined herein below.
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.
Claim(s) 4-5, 9, 11-22 are rejected under 35 U.S.C. 103 as being unpatentable over Michiya et al., (Michiya et al., (JPH02257063A, Pub. Date:10/17/1990, provided in IDS filed on 12/09/2025 as FOR Cite No. 1), in view of Koshkina et al., (Koshkina et al., Temperature-Triggered Protein Adsorption on Polymer-Coated Nanoparticles in Serum, 2015, Langmuir, 31, 8873-8881), as evidenced by Millipore Sigma, [Properties for PEG and polyoxazoline (POx) site information provided as NPL], and Luxenhofer et al., (Luxenhofer et al., Poly(2-oxazoline)s (POx) in Biomedical Applications, 2016, Material Matters, 8.3, 70, 1-11).
Throughout the disclosure, Michiya teaches a method of measuring antigens and antibodies using an immunoassay and immunoassay reagent comprising an immunoagglutination, also referred to as a latex agglutination, reaction comprising an insoluble carrier having a low detection sensitivity and high non-specific binding (JPH02257063A, Espacenet Translation: pgs. 2-3). Michiya teaches the insoluble carrier is a latex particle wherein the latex particle may include polystyrene, among other options (JPH02257063A, Espacenet Translation: pg. 5, lines 16-18). Michiya teaches measuring trace amounts of target analyte, in a body fluid, supported on the insoluble latex carrier and measuring the degree of agglutination of the insoluble latex carrier in the immunoassay, which is proportional to the amount of target analyte present (JPH02257063A, Espacenet Translation: pgs. 2-3). Michiya further teaches adding an agglutination sensitizer, poly(ethylene glycol) (PEG), to the immunoagglutination /latex agglutination reaction for promoting antigen-antibody binding and improving sensitivity. Michiya teaches a suitable molecular weight for the agglutination sensitizer (PEG) is an average molecular weight of 50,000 to 2,000,000 (JPH02257063A, Espacenet Translation: pg. 5, lines 4-5).
Regarding claim 4, Michiya teaches a latex agglutination reagent comprising a latex agglutination sensitizer having an average molecular weight of 50,000 to 1,000,000; and a latex particle that carries an antibody or an antigen, the latex particle dispersed in the agglutination reagent solution (JPH02257063A, Espacenet Translation: pg. 1, Abstract; pg. 2, lines 17-24; pg. 3, lines 2-9; pg. 5, lines 4-7). Michiya does not teach a latex agglutination reagent comprising polyoxazoline (sensitizer) dissolved in an aqueous medium, wherein polyoxazoline has a repeating unit represented by formula (1).
However, Koshkina, in the same field of endeavor, throughout the disclosure, teaches nanoparticles (NPs) coated with poly-2-isopropyl-2-oxazoline (PiPOx) in serum. Koshkina teaches that heating PiPOx-coated NPs above their phase separation temperature of ~ 31 ºC and up to 37 ºC induces formation of agglomerates. Koshkina teaches that during phase separation, protein adsorption on NPs is induced. When heated, Koshkina teaches that the agglomerated PiPOx-coated NPs, in serum, were loosely packed, an indication that binding of adsorbed proteins between NPs contributed to the agglomeration of NPs.
Koshkina teaches the limitation(s) of claim 1 reciting a polyoxazoline solution comprising polyoxazoline dissolved in an aqueous medium, wherein the polyoxazoline has a repeating unit represented by formula 1 (Koshkina et al., 2015, Langmuir, 31, pg. 8873; pg. 8874, full para 4 [serum = water-based medium]; pg. 8875, "Results" and Fig. 1 [POx has repeating units of formula (1)].
It would have been prima facie obvious, at the time of filing, to combine the latex agglutination reagent in the method for measuring target antigen or antibody comprising the latex agglutination reaction and an agglutination sensitizer (poly(ethylene glycol) (PEG), as taught by Michiya, with the teachings of the POx polymer shown to promote/induce agglomeration between particles via protein-protein interactions, as taught by Koshkina, in order to substitute the PEG agglutination sensitizer taught by Michiya with the POx polymer taught by Koshkina. Agglutination is a form of biological or chemical agglomeration. As discussed above, Koshkina teaches that POx promotes the agglomeration of POx-coated particles via protein-protein interactions on the surface of the POx-coated particles. In the art, it is known that POx polymers have been studied and suggested as an equal or superior alternative/ substitute for PEG in drug delivery and therapeutic applications because non-specific protein binding is equally low on POx-modified surfaces and POx offers the following advantages over PEG: structural control (linear, branched, start, etc.) with R group/side chain substitutions; tunable properties by varying size and type of R group/side chain functional group to modulate solubility and hydrophobic/hydrophilic properties; and increased structural stability under physiological conditions where PEG is prone to oxidative degradation (see Luxenhofer et al., 2016, Material Matters, 8.3, 70, 1-11). Though the claimed invention is not a drug delivery system or a therapeutic application, due to the prior art suggestion of POx as a substitute for PEG based on both their similarities and the added advantages of POx, at the time of filing, a skilled artisan would have been motivated to substitute the PEG agglutination sensitizer taught by Michiya with the POx polymer taught by Koshkina because it would enhance the latex agglutination reactions by promoting low non-specific binding leading to improved antigen-antibody binding on the latex particle and increased measurement sensitivity. At the time of filing, the latex agglutination method using an agglutination sensitizer, POx as an equal or superior substitute for PEG, the capability of POx to promote agglomeration and promote low non-specific protein binding were all already known in the art. Thus, a person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings amounts to a simple substitution between known components/elements, with each of their functions known in the art at the time of filing, to yield expected and predictable results.
It would have been further prima facie obvious, at the time of filing, to combine the latex agglutination method of measuring target antigen or antibody comprising the latex agglutination reaction and an agglutination sensitize (poly(ethylene glycol) (PEG), as taught by Michiya, with the POx polymer shown to promote/induce agglomeration between particles via protein-protein interactions, as taught by Koshkina, and try the higher optimal average molecular weight range, of 50,000 to 1,000,000 for the agglutination sensitizer taught by Michiya, with the agglutination sensitizer substitute POx, that is taught by Koshkina, as part of routine optimization. Michiya teaches increasing the molecular weight of the agglutination sensitizer to optimize viscosity of the agglutination reagent and optimize measurement sensitivity for target antibody or antigen. Thus, at the time of filing, a person having ordinary skill in the art would have been motivated to try the optimal and finite range for agglutination sensitizer molecular weight taught by Michiya to determine the optimal size/molecular weight for the agglutination sensitizer POx that would yield the optimal viscosity for the agglutination reagent to arrive at the claimed invention. At the time of filing, a skilled artisan would have a reasonable expectation of success because the prior art teaches an optimal, finite range of average molecular weight for the agglutination sensitizer that optimizes viscosity of the agglutination reagent and improves sensitivity; thus a skilled artisan would be trying a finite number of known, predictable solutions to yield expected and predictable results.
Regarding claim 5, Michiya and Koshkina teach all the limitations of claim 4. Michiya teaches a concentration range for the agglutination sensitizer (PEG) in the agglutination reagent is 0.05-3.0% (w/w). The density of the agglutination sensitizer (PEG), taught by Michiya, is 1.13 g/mL, therefore, the reference concentration range taught by Michiya for an agglutination sensitizer is 0.057-3.39% (w/v), since (%w/v) = (%w/w) x density in units of g/mL or g/cm3, thus (0.05%) x (1.13 g/mL) = 0.057 % and (3.0%) x (1.13 g/mL) = 3.39 % (see Millipore Sigma Properties for PEG and polyoxazoline (POx) NPL provided). Thus, using the broadest reasonable interpretation, Michiya further teaches the limitation(s) of claim 5 reciting wherein a concentration of the agglutination sensitizer is 0.01 w/v% to 2.0 w/v% (JPH02257063A, Espacenet Translation: pg. 7. lines 7-11). Michiya does not teach the agglutination sensitizer is polyoxazoline (POx).
Koshkina teaches that polyoxazoline (POx) is capable of functioning as an agglutination sensitizer (Koshkina et al., 2015, Langmuir, 31, pg. 8873; pg. 8874, full para 4; pg. 8875, "Results" and Fig. 1).
It would have been prima facie obvious, at the time of filing, to combine the latex agglutination reagent in the method for measuring target antigen or antibody comprising the latex agglutination reaction and an agglutination sensitizer PEG present within an optimal concentration range in (%w/v), as taught by Michiya, with the teachings of the POx polymer shown to promote/induce agglomeration between particles via protein-protein interactions, as taught by Koshkina, in order to substitute the PEG agglutination sensitizer taught by Michiya, with the POx polymer taught by Koshkina, which has nearly the same density as PEG (see Millipore Sigma, [Properties for PEG and polyoxazoline (POx) site information provided as NPL). Agglutination is a type of biological or chemical agglomeration. As discussed above, Koshkina teaches that POx promotes the agglomeration of PiPOx-coated particles via protein-protein interactions on the surface of the PiPOx-coated particles. In the art, it is known that POx polymers have been studied and suggested as equal or superior alternatives/ substitutes for PEG in drug delivery and therapeutic applications because non-specific protein binding is equally low on POx-modified surfaces and POx offers the following advantages over PEG: structural control (linear, branched, start, etc.) with R group/side chain substitutions; tunable properties by varying size and type of R group/side chain functional group to modulate solubility and hydrophobic/hydrophilic properties; and improved structural stability under physiological conditions where PEG is prone to oxidative degradation (see Luxenhofer et al., 2016, Material Matters, 8.3, 70, 1-11). Though the claimed invention is not a drug delivery system or a therapeutic application, due to the prior art suggestion of POx as a substitute for PEG based on both their similarities and the added advantages of POx, at the time of filing, a skilled artisan would have been motivated to substitute the PEG agglutination sensitizer taught by Michiya with the POx polymer taught by Koshkina because the versatility and tunability of POx and its capability to promote agglomeration with low non-specific binding would enhance the latex agglutination reaction, improve antigen-antibody binding on the latex particle, and improve measurement sensitivity. At the time of filing, the latex agglutination method using an agglutination sensitizer at a concentration within the range recited in the claimed invention, POx as an equal or superior substitute for PEG with a similar density, and the capability of POx to promote agglomeration with low non-specific protein binding were all already known in the art. Thus, a person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings amounts to a simple substitution between known components/elements, with each of their functions known in the art at the time of filing, to yield expected and predictable results.
Regarding claim 9, Michiya and Koshkina teach all the limitations of claim 4 and Michiya further teaches a method for measuring a target substance in a specimen by a latex agglutination reaction using a latex particle that carries an antibody or an antigen, the method comprising: mixing of the specimen and, the latex agglutination reagent according to claim 4; and detecting the agglutination of the latex particles (JPH02257063A, Espacenet Translation pg. 1, Abstract; pg. 3, lines 1-9).
Regarding claim 11, Michiya and Koshkina teach all the limitations of claim 4, Michiya teaches the limitations of claim 9. Michiya teaches a concentration range for the agglutination sensitizer (PEG) in the agglutination reagent is 0.05-3.0% (w/w). The density of the agglutination sensitizer (PEG), taught by Michiya, is 1.13 g/mL, therefore, the reference concentration range taught by Michiya for an agglutination sensitizer is 0.057-3.39% (w/v), since (%w/v) = (%w/w) x density in units of g/mL or g/cm3, therefore, (0.05%) x (1.13 g/mL) = 0.057 % and (3.0%) x (1.13 g/mL) = 3.39 % (see Millipore Sigma Properties for PEG and polyoxazoline (POx) NPL provided). Thus, using the broadest reasonable interpretation, Michiya further teaches performing the latex agglutination reaction in which a concentration of the agglutination sensitizer in the latex agglutination reagent is 0.005 w/v% to 1.9 w/v% (JPH02257063A, Espacenet Translation: pg. 7. lines 7-11). Michiya does not teach the agglutination sensitizer is polyoxazoline (POx).
However, Koshkina teaches that polyoxazoline (POx) is capable of functioning as an agglutination sensitizer (Koshkina et al., 2015, Langmuir, 31, pg. 8873; pg. 8874, full para 4; pg. 8875, "Results" and Fig. 1).
It would have been prima facie obvious, at the time of filing, to combine the latex agglutination method for measuring target antigen or antibody comprising the latex agglutination reaction and an agglutination sensitizer PEG present within an optimal concentration range in (w/v%), as taught by Michiya, with the POx polymer shown to promote/induce agglomeration between particles via protein-protein interactions, as taught by Koshkina, in order to substitute the PEG agglutination sensitizer taught by Michiya, with the POx polymer taught by Koshkina, which has nearly the same density as PEG (see Millipore Sigma, [Properties for PEG and polyoxazoline (POx) site information provided as NPL]). Agglutination is a type of biological or chemical agglomeration. As discussed above, Koshkina teaches that POx promotes the agglomeration of PiPOx-coated particles via protein-protein interactions on the surface of the PiPOx-coated particles. In the art, it is known that POx polymers have been studied and suggested as equal or superior alternatives/substitutes for PEG in drug delivery and therapeutic applications because non-specific protein binding is equally low on POx-modified surfaces and POx offers the following advantages over PEG: structural control (linear, branched, start, etc.) with R group/side chain substitutions; tunable properties by varying size and type of R group/side chain functional group to modulate solubility and hydrophobic/hydrophilic properties; and structural stability under physiological conditions where PEG is prone to oxidative degradation (see Luxenhofer et al., 2016, Material Matters, 8.3, 70, 1-11). Though the claimed invention is not a drug delivery system or a therapeutic application, due to the prior art suggestion of POx as a substitute for PEG based on both their similarities and the added advantages of POx, at the time of filing, a skilled artisan would have been motivated to substitute the PEG agglutination sensitizer taught by Michiya with the POx polymer taught by Koshkina because the versatility and tunability of POx and its capability to promote agglomeration with low non-specific binding would enable a skilled artisan to enhance latex agglutination reactions, improve antigen-antibody binding on the latex particle, and improve measurement sensitivity. At the time of filing, the latex agglutination method using an agglutination sensitizer at a concentration within the range recited in the claimed invention, POx as an equal or superior substitute for PEG with a nearly identical density, and the capability of POx to promote agglomeration and non-specific protein binding were all already known in the art. Thus, a person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings amounts to a simple substitution between known components/elements, with each of their functions known in the art at the time of filing, to yield expected and predictable results.
Regarding claim 12, Michiya and Koshkina teach all the limitations of claim 4, Michiya teaches the limitations of claim 9. Michiya further teaches wherein the latex particle is any one of a polystyrene particle, a polystyrene particle containing siloxane, and a polystyrene particle containing polyglycidyl (meth)acrylate (JPH02257063A, Espacenet Translation: pg. 5, lines 16-18).
Regarding claim 13, Michiya and Koshkina teach all the limitations of claim 4. Michiya further teaches wherein the average molecular weight of the agglutination sensitizer is 50,000 to 400,000, wherein the latex particle includes a polystyrene particle or a polystyrene particle containing polyglycidyl (meth)acrylate, and wherein a concentration of the agglutination sensitizer in the latex agglutination reagent is 1.5 w/v% to 1.75 w/v% (JPH02257063A, Espacenet Translation: pg. 5, lines 4-5 and 16-18; and pg. 7, lines 10-14 [reference lower limit is 0.05% (w/w%)= 0.057% (w/v%) and upper limit is 3% (w/w%) = 3.39% (w/v%) for PEG, see detailed calculation herein above]). Michiya does not teach the agglutination sensitizer is polyoxazoline (POx).
However, Koshkina teaches that a polyoxazoline (POx) is capable of functioning as an agglutination sensitizer (Koshkina et al., 2015, Langmuir, 31, pg. 8873; pg. 8874, full para 4; pg. 8875, "Results" and Fig. 1).
Regarding claim 14, Michiya and Koshkina teach all the limitations of claim 4. Michiya further teaches wherein the average molecular weight of the agglutination sensitizer is 50,000 to 400,000 (JPH02257063A, Espacenet Translation: pg. 5, lines 4-5), wherein the latex particle includes a polystyrene particle or a polystyrene particle containing polyglycidyl (meth)acrylate (JPH02257063A, Espacenet Translation: pg. 5, 16-18), and wherein a concentration of the agglutination sensitizer in a reaction solution is 0.743 w/v% to 0.866 w/v% (JPH02257063A, Espacenet Translation: pg. 7, lines 9-14, [reference lower limit is 0.05% (w/w%)= 0.057% (w/v%) and upper limit is 3% (w/w%) = 3.39% (w/v%) for PEG, see detailed calculation herein above]). Michiya does not teach the agglutination sensitizer is polyoxazoline (POx).
However, Koshkina teaches that a polyoxazoline (POx) is capable of functioning as an agglutination sensitizer (Koshkina et al., 2015, Langmuir, 31, pg. 8873; pg. 8874, full para 4; pg. 8875, "Results" and Fig. 1).
Regarding claims 15-16, Michiya and Koshkina teach all the limitations of claim 4. Michiya further teaches wherein the average molecular weight of the agglutination sensitizer is 200,000 to 1,000,000 [claim 15] and wherein the average molecular weight of the polyoxazoline is 400,000 to 1,000,000 [claim 16] (JPH02257063A, Espacenet Translation: pg. 5, lines 4-5). Michiya does not teach the agglutination sensitizer is polyoxazoline (POx).
However, Koshkina teaches that a polyoxazoline (POx) is capable of functioning as an agglutination sensitizer (Koshkina et al., 2015, Langmuir, 31, pg. 8873; pg. 8874, full para 4; pg. 8875, "Results" and Fig. 1).
Regarding claims 13-16, It would have been prima facie obvious, at the time of filing, to combine the latex agglutination reagent in the method for measuring target antigen or antibody comprising the latex agglutination reaction and an agglutination sensitizer (PEG) present with an optimal concentration range in (w/v%), as taught by Michiya, with the POx polymer shown to promote/induce agglomeration between particles via protein-protein interactions, as taught by Koshkina, in order to substitute the PEG agglutination sensitizer taught by Michiya, with the POx polymer taught by Koshkina, which has nearly the same density as PEG (see Millipore Sigma, [Properties for PEG and polyoxazoline (POx) site information provided as NPL]). Agglutination is a form of biological or chemical agglomeration. As discussed above, Koshkina teaches that POx promotes the agglomeration of PiPOx-coated particles via protein-protein interactions on the surface of the PiPOx-coated particles. In the art, it is known that POx polymers have been studied and suggested as equal or superior alternatives/ substitutes for PEG in drug delivery and therapeutic applications because non-specific protein binding is equally low on POx-modified surfaces and POx offers the following advantages over PEG: structural control (linear, branched, start, etc.) with R group/side chain substitutions; tunable properties by varying size and type of R group/side chain functional group to modulate solubility and hydrophobic/hydrophilic properties; and improved structural stability under physiological conditions where PEG is prone to oxidative degradation (see Luxenhofer et al., 2016, Material Matters, 8.3, 70, 1-11). Though the claimed invention is not a drug delivery system or a therapeutic application, due to the prior art suggestion of POx as a substitute for PEG based on both their similarities and the added advantages of POx, at the time of filing, a skilled artisan would have been motivated to substitute the PEG agglutination sensitizer taught by Michiya with the POx polymer taught by Koshkina because the versatility and tunability of POx and its known capability to induce agglomeration with low non-specific binding would enable a skilled artisan to enhance latex agglutination reactions, improve antigen-antibody binding on the latex particle, and improve measurement sensitivity. At the time of filing, the latex agglutination method using an agglutination sensitizer at a concentration within the range recited in the claimed invention, agglutination sensitizer with the optimal molecular weight range recited in the claimed invention, POx as an equal or superior substitute for PEG, and the capability of POx to promote agglomeration with low non-specific protein binding were all already known in the art. Thus, a person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings amounts to a simple substitution between known components/ elements, with each of their functions known in the art at the time of filing, to yield expected and predictable results.
It would have been further prima facie obvious, at the time of filing, to combine the latex agglutination method of measuring target antigen or antibody comprising the latex agglutination reaction and an agglutination sensitize (poly(ethylene glycol) (PEG), as taught by Michiya, with the POx polymer shown to promote/induce agglomeration between particles via protein-protein interactions, as taught by Koshkina, and try the higher optimal average molecular weight range of 50,000 to 400,000, 200,000 to 1,000,000, and 400,000 to 1,000,000 for the agglutination sensitizer, as taught by Michiya, with the agglutination sensitizer substitute POx taught Koshkina as part of routine optimization. Michiya teaches increasing and varying the molecular weight of the agglutination sensitizer to optimize the viscosity of the agglutination reagent and improve measurement sensitivity. Thus, at the time of filing, a person having ordinary skill in the art would have been motivated to try the optimal and finite range for the molecular weight of the agglutination sensitizer taught by Michiya to determine the optimal molecular weight that optimizes the viscosity of the agglutination reagent using the substitute agglutination sensitizer POx to arrive at the claimed invention. At the time of filing, a skilled artisan would have a reasonable expectation of success because the prior art teaches an optimal, finite range of average molecular weight for the agglutination sensitizer to optimize viscosity of the agglutination reagent, thus a skilled artisan would be trying a finite number of known, predictable solutions to yield expected and predictable results.
Regarding claim 17, Michiya and Koshkina teach all the limitations of claim 4 and Michiya further teaches wherein an average particle size of the latex particle is 0.05 µm to 1 µm (JPH02257063A, Espacenet Translation: pg. 8, lines 10-11; pg. 9, lines 20-22; pg. 10, lines 22-23).
Regarding claim 18, Michiya and Koshkina teach all the limitations of claim 4 and Michiya further teaches wherein the latex particle is any one of a polystyrene particle, a polystyrene particle containing siloxane, and a polystyrene particle containing polyglycidyl (meth)acrylate (JPH02257063A, Espacenet Translation: pg. 5, lines 16-18).
Regarding claim 19, Michiya and Koshkina teach all the limitations of claim 4 and Michiya further teaches wherein the latex particle comprises a copolymer of styrene, glycidyl (meth)acrylate, and divinylbenzene (JPH02257063A, Espacenet Translation: pg. 5, lines 16-18).
Regarding claim 20, Michiya and Koshkina teach all the limitations of claim and Michiya further teaches wherein the aqueous media is any of purified water, a phosphate buffer, a glycine buffer, a Good's buffer, a tris buffer, and an ammonia buffer (JPH02257063A, Espacenet Translation: pg. 3, lines 12-13; pg. 7, lines 16-18).
Regarding claim 21, Michiya and Koshkina teach all the limitations of claim 4 and Michiya further teaches latex agglutination reagent further comprising any of salts, bovine serum albumin, surfactants, immunoglobulins, and sodium chloride (JPH02257063A, Espacenet Translation: pg. 8, lines 16-21).
Regarding claim 22, Michiya and Koshkina teach all the limitations of claim 4 and Michiya further teaches wherein the latex particle carries the antibody, and wherein the antibody is an anti-human CRP polyclonal antibody or an anti- human ferritin antibody (JPH02257063A, Espacenet Translation: pg. 8, lines 8-16).
Claim(s) 23 is rejected under 35 U.S.C. 103 as being unpatentable over Michiya et al., (Michiya et al., (JPH02257063A, Pub. Date:10/17/1990, provided in IDS filed on 12/09/2025 as FOR Cite No. 1), in view of Koshkina et al., (Koshkina et al., Temperature-Triggered Protein Adsorption on Polymer-Coated Nanoparticles in Serum, 2015, Langmuir, 31, 8873-8881), as applied to claim 4 above, and further in view of Koshkina et al., (Koshkina et al., Tuning the Surface of Nanoparticles: Impact of Poly(2-ethyl-2-oxazoline, 2016, Macromol. Biosci., 16, 1287-1300, provided in IDS filed on 12/09/2025 as NPL Cite No. 1), and as evidenced by Luxenhofer et al., (Luxenhofer et al., Poly(2-oxazoline)s (POx) in Biomedical Applications, 2016, Material Matters, 8.3, 70, 1-11).
Regarding claim 23, the teachings of Michiya and Koshkina in the 2015 article are discussed herein above. Michiya and Koshkina’s 2015 article teach all the limitations of claim 4, but do not teach wherein R in the formula (1) is an ethyl group.
Throughout the 2016 article, Koshkina teaches poly(2-ethyl-2-oxazoline) (PEtOx) as an effective alternative to PEG on surface-modified nanoparticles (NP) because PEtOx offers the following advantages: low non-specific protein adsorption on PEtOx-modified particles and non-specific cellular uptake is reduced.
Koshkina in the 2016 article teaches the limitation(s) of claim 23 reciting a POx wherein the R in the formula (1) is an ethyl group (Koshkina et al., 2016, Macromol. Biosci., 16, pg. 1287).
It would have been prima facie obvious, at the time of filing, to combine the latex agglutination reagent in the method for measuring target antigen or antibody comprising the latex agglutination reaction and an agglutination sensitizer (poly(ethylene glycol) (PEG), as taught by Michiya, in view of Koshkina’s teachings in the 2015 article, with the POx R group, in formula (1), substituted with an ethyl group substituent to generate PEtOx, as taught by Koshkina in the 2016 article, in order to substitute the poly(ethylene glycol) (PEG) agglutination sensitizer taught by Michiya, with the PEtOx polymer taught by Koshkina. Agglutination is a type of biological or chemical agglomeration. As discussed above, Koshkina’s 2015 article teaches that POx promotes the agglomeration of POx-coated particles via protein-protein interactions on the surface of the POx-coated particles. In the art, it is known that POx polymers have been studied and suggested as an equal or superior alternatives/ substitutes for PEG in drug delivery and therapeutic applications because non-specific protein binding is equally low on POx-modified surfaces and POx offers the following advantages over PEG: structural control (linear, branched, start, etc.) with R group/side chain substitutions; tunable properties by varying size and type of R group/side chain functional group to modulate solubility and hydrophobic/hydrophilic properties; structural stability under physiological conditions where PEG is prone to oxidative degradation (see Luxenhofer et al., 2016, Material Matters, 8.3, 70, 1-11). Further, Koshkina’s 2016 article teaches PEtOx in particular reduces non-specific protein adsorption on particles. Though the claimed invention is not a drug delivery system or a therapeutic application, due to the prior art suggestion of POx as a substitute for PEG based on both their similarities and the added advantages of POx and PEtOx in particular, at the time of filing, a skilled artisan would have been motivated to substitute the PEG agglutination sensitizer taught by Michiya with the PEtOx polymer taught by Koshkina because it would enhance the latex agglutination reactions by promoting low non-specific binding leading to improved antigen-antibody binding on the latex particle and increased measurement sensitivity. At the time of filing, the latex agglutination method using an agglutination sensitizer, POx including PEtOx as an equal or superior substitute for PEG, the capability of POx to promote agglomeration, and teachings that PEtOx promotes low non-specific protein binding were all already known in the art. Thus, a person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings amounts to a simple substitution between known components/elements, with each of their functions known in the art at the time of filing, to yield expected and predictable results.
Response to Arguments
Applicant’s arguments with respect to claim(s) 4-23 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
All examined claims (4-5, 9, and 11-23) are rejected. No claims are allowed.
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/MELISSA LIZETTE LIRIANO-NG/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 June 3, 2026
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