The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to Applicants’ amendments/remarks received May 29, 2026.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 6-7, 9-20, 23-27 are canceled. Claims 1-5, 8, 21-22, 28-38, 39-42, 43-45 are under consideration.
Priority: This application claims benefit of provisional applications 62/877188, filed July 22, 2019, and 63/040159, filed June 17, 2020.
Objections and Rejections
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.
Claims 1-2, 4-5, 8, 21, 28-30, 32-38, 39-42, 44-45 are rejected under 35 U.S.C. 103 as being unpatentable over Qian et al. (US 20050255453; previously cited) in view of Taniguchi et al. (US 20070154976; previously cited) and Depa et al. (WO 2019152508; previously cited), and evidenced by Ferri et al. (2009 Journal of Diabetes Science and Technology 3(3): 585-592; previously cited).
Qian et al. disclose an assay for quantitating glycated protein, the assay comprising multilayer reagent test strips, where the reagent test strips include a plurality of different layers, where the layers are in sequential fluid communication (at least paragraph 0024). Qian et al. disclose the distinct layers range from about 2 to 10, usually 3 to 7, including a minimum of three layers in sequential order a blood filter layer, a protease layer, and a ketoamine oxidase signal producing layer (at least paragraph 0025). Qian et al. disclose the layers are polymers comprising porous matrices (at least paragraph 0056), where it is known polymers comprise cross-linked chains (at least paragraph 0040), where the protease layer comprises a protease enzyme (at least paragraph 0056-0057), the signal producing layer comprises a ketoamine oxidase, an indicator dye (detection agent), a peroxidase enzyme (at least paragraphs 0059-0064). Qian et al. disclose that agents to remove interference can also be included in the matrix (at least paragraph 0046). Qian et al. also disclose that the multiple layers of the polymers or porous matrices can comprise a buffered solution (at least paragraph 0041). As noted above, Qian et al. disclose that one or more additional layers that provide for additional functionality are also present (at least paragraph 0025), where additional layers include additional polymeric layers (at least paragraphs 0077-0079). Qian et al. also disclose in the art, ketoamines are generally known as “fructosamines” (at least paragraph 0006). Therefore, Qian et al. can reasonably be deemed to disclose an assay comprising a stack of film layers comprising from bottom to top, a first film layer comprising a cross-linked polymeric matrix (or gel) comprising a detection agent, a ketoamine oxidase (or fructosyl oxidase), an agent that prevents interference, and a peroxidase enzyme; a second film layer comprising a polymeric matrix (or gel); and a third film layer comprising a protease. Qian et al. do not explicitly teach a lysing agent and denaturing agent in the protease layer.
Taniguchi et al. disclose reagents for determining a substrate in a hemoglobin-containing sample, the substrate being glycated hemoglobin (at least abstract, paragraphs 0003, 0020). Taniguchi et al. disclose a surfactant, i.e. Triton X-100, can be used in combination with other anionic surfactants (at least paragraph 0040) with whole blood samples, and in combination with protease (at least paragraph 0044), where protease acts to release glycated amino acid from hemoglobin A1c (at least paragraph 0038), and its action is combined with the surfactants used for hemolysis (at least paragraph 0044). Taniguchi et al. disclose the oxidase include fructosyl amino acid oxidase, ketoamine oxidase, fructosyl peptide oxidase (at least paragraph 0032). Taniguchi et al. also disclose that the oxidase is used in combination with another enzyme for treating interfering substance (at least paragraph 0034). Taniguchi et al. disclose a first reagent comprising the surfactants for hemolysis and a second reagent comprising fructosyl peptide oxidase, peroxidase, TPM-PS (at least examples). The fructosyl peptide oxidase acts on fructosyl valylhistidine or fructosyl valine (at least paragraph 0041). Taniguchi et al. disclose the reagent can be provided in dry or gel form; may be placed in a glass vial, etc. or applied to or impregnated into an insoluble carrier; insoluble carriers include particle/sphere carriers such as latex, glass, and colloid; flat plate carriers such as semiconductor and glass; film-like carriers (at least paragraph 0049).
Depa et al. disclose a test strip comprising multiple film layers for measuring analytes, where the analyte comprises glycated hemoglobin (at least abstract). Depa et al. disclose that any layer underneath a porous layer when it is wetted becomes semi-transparent, and the layer underneath is colored, could potentially interfere with the optical apparatus during analysis with the optical measuring apparatus (at least p. 7 lines 13-15). Depa et al. disclose impregnating into the layer a filler or whitening agent such as titanium oxide to provide opacity to reduce background signal for a better reflectance signal and test accuracy for the optical measuring apparatus (at least p. 7 lines 15-18).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the references and arrive at the claimed slide comprising a stack of film layers, from bottom to top, a first film layer comprising a cross-linked polymeric matrix (or gel) comprising a detection agent, a fructosyl oxidase that is specific for Fru-ValHis peptide or a glycated amino acid, an agent that prevents interference, and a peroxidase enzyme; a second film layer comprising a polymeric matrix (or gel) for additional functionality including minimizing interference comprising a buffered solution; and a third film layer comprising a lysing agent (Triton X-100), a denaturing agent (anionic surfactant), and a protease (instant claims 1-2, 21, 34-36, 45). The motivation to do so is given by Taniguchi et al., which disclose that Triton X-100 (lysing agent) and an anionic surfactant (denaturing agent) can be combined with protease in a reagent to release hemoglobin, hemoglobin A1c, and hemoglobin A1c specific glycated peptide from the blood sample. Therefore, one of ordinary skill would have a reasonable motivation to incorporate the Triton X-100 and anion surfactant disclosed in Taniguchi et al. in the protease layer of the assay comprising a stack of film layers of Qian et al., thereby arriving at the claimed invention. One of ordinary skill would have a reasonable expectation of success because an assay for measuring glycated hemoglobin comprising multilayer reagent strips was disclosed in the prior art and the reagents for measuring glycated hemoglobin were also known.
Regarding the limitation that the second layer comprising the polymeric matrix (gel) or hardened gel comprises at least one buffer and a reflective material portion comprising titanium dioxide that functions as a sieve for the glycated product (Fru-ValHis peptide) to pass through while excluding larger molecular weight proteins including hemoglobin from passing through to the first layer (detection region) (instant claims 1, 45), as noted above, Depa et al. disclose that any layer underneath a porous layer when it is wetted becomes semi-transparent, and the layer underneath is colored, could potentially interfere with the optical apparatus during analysis with the optical measuring apparatus (at least p. 7 lines 13-15). Depa et al. disclose impregnating into the layer a filler or whitening agent such as titanium oxide to provide opacity to reduce background signal for a better reflectance signal and test accuracy for the optical measuring apparatus (at least p. 7 lines 15-18). As also noted, Qian et al. also disclose that the multiple layers of the polymers or porous matrices can comprise a buffered solution (at least paragraph 0041); in addition, agents to remove interference can also be included in the matrix (at least paragraph 0046). Qian et al. disclose that one or more additional layers that provide for additional functionality are also present (at least paragraph 0025), where additional layers include additional polymeric layers (at least paragraphs 0077-0079). Qian et al. disclose the matrix material is one that is porous and provides for flow of sample fluid through the material; a number of different porous matrices have been developed and are available; where the matrix may have a porosity gradient, with larger pores near or at the sample application region and smaller pores at the detection region (at least paragraph 0056). Therefore, it would have been obvious to one of ordinary skill in the art to incorporate a layer comprising titanium oxide as suggested in Depa et al. and a buffered solution as suggested in Qian et al. into the assay comprising a stack of film layers, such as a layer comprising a polymeric matrix (or hardened gel) having a porosity gradient that allows the smaller molecules for detection (fructosyl valylhistidine) to flow through to the detection region while excluding the larger molecular weight biomolecules, including hemoglobin, from flowing through to the detection region, where the noted layer is above the layer comprising the cross-linked polymeric matrix (or gel) comprising the detection agent, fructosyl oxidase, agent that prevents interference, and peroxidase enzyme disclosed in the multi-layer assay of Qian et al. and Taniguchi et al. noted above (instant claim 1) because doing so would reduce background signal for a better reflectance signal and test accuracy. Since Depa et al. suggest incorporating a reflective material (titanium oxide) that is materially the same and has the same functional purpose as the recited reflective material and Qian et al. disclose materially the same polymers or polymeric matrices for incorporating into a multiple layer assay may be optimized to have a porosity gradient with larger pores near or at the sample application region and smaller pores at the detection region, it would be obvious that the noted layer comprising a polymeric matrix (or hardened gel) for additional functionality comprising titanium oxide as suggested in Depa et al. and a buffered solution as suggested in Qian et al. above can be optimized or designed to have a porosity that allows the glycated molecules for detection (fructosyl valylhistidine) to flow through to the detection region while excluding the larger molecular weight biomolecules, including hemoglobin, from flowing through to the detection region.
Additionally, regarding the instant limitation wherein the second layer is configured to generate a signal of the noted wavelength(s) (instant claims 1, 45), since Depa et al. suggest incorporating a reflective material (titanium oxide) that is materially the same and has the same functional purpose as the recited reflective material and Qian et al. disclose materially the same polymers or polymeric matrices for incorporating into a multiple layer assay also for the same purpose as the claimed multilayer film slide, it would be obvious that the layer comprising a reflective material portion has the configuration to generate the recited signals.
Regarding instant claim 4, Qian et al. disclose the protease is any convenient protease, including proteinase K, chymotrypsin, trypsin, and the like (at least paragraph 0057).
Regarding instant claims 5, 30, Qian et al. disclose the indicator dye is DA-67 (at least paragraph 0073) and Taniguchi et al. also disclose the color producing compound is DA-67 (at least paragraph 0035).
Regarding instant claims 5, 28, 29, Taniguchi et al. disclose the color producing compound is also selected from DA-64, TPM-PS (at least paragraph 0035).
Regrading instant claims 8, 33, Qian et al. disclose the polymer matrices are porous (at least paragraph 0056). Qian et al. disclose pore sizes in multilayer reagent strips include among others about 30 µm (at least paragraph 0053). Taniguchi et al. also disclose the reagent can be immobilize in an insoluble carrier, including particle/sphere carriers such as latex (at least paragraph 0049). Therefore, it would be obvious that the protease layer in the multilayer reagent strips noted above can comprise a layer with particles, where the particles have a diameter of about 25 µm, because the prior art discloses the polymeric layers comprise pores and/or particles having sizes similar to the claimed particle diameters. Additionally, regarding instant claim 33, Taniguchi et al. disclose particles carriers such as latex (at least paragraph 0049).
Regarding instant claim 32, Taniguchi et al. disclose an interference prevention agent is ascorbic acid oxidase (at least paragraph 0034).
Regarding instant claims 34-36, as noted above, Taniguchi et al. disclose the fructosyl peptide oxidase acts on fructosyl valylhistidine or fructosyl valine (at least paragraph 0041).
Regarding instant claims 37-38, it is known that fructosyl oxidase enzymes have a FAD cofactor (evidenced by Ferri et al. p. 586-587). Further, Taniguchi et al. has disclosed that in methods for determining glycated hemoglobin, the presence of a surfactant helps to reduce interference of hemoglobin which coexists in the sample (at least paragraph 0020). Taniguchi et al. disclose incorporating a surfactant with a protease in a reagent to release glycated peptide or amino acid from the glycated hemoglobin and then the release glycated peptide/amino acid is further treated with fructosyl peptide oxidase or fructosyl amino acid oxidase, i.e. in steps i-iii (at least paragraphs 0038-0041). Taniguchi et al. disclose that the steps including i-iii may be performed sequentially or simultaneously (at least paragraph 0044); therefore, it would be obvious that the layer comprising a fructosyl oxidase of Qian et al./Taniguchi et al. in the 103 rejection above has a FAD cofactor and can further be incorporated with a surfactant.
Regarding instant claims 39-42, Qian et al. disclose an upper guard piece and a support element above the blood separation and protease layers and a support element below the fructosyl oxidase bottom layer and polymer layers (at least paragraphs 0080-0085, see also Fig. 1).
Regarding instant claim 44, Depa et al. also disclose that the incorporation of a titanium oxide portion is optional (at least p. 7 lines 15-18); therefore, it would be an obvious design choice that an area of the functionalized second layer noted above does not have titanium oxide.
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive. The reasons for maintaining the 103 rejection are the same as previously noted and are incorporated herein.
Applicants assert that the office action relies on Qian et al. for porous multilayer structures. Applicants assert that however, the office action does not identify any disclosure demonstrating that these layers are configured to discriminate between peptides and proteins or possess a molecular weight cutoff consistent with exclusion of hemoglobin while permitting Fru-α-ValHis diffusion. Applicants assert that the specification of Qian et al. provides evidence of the contrary. Applicant asserts that Qian et al. recite separating blood cells from plasma (Qian et al. 0025-0028 and that a representative matrix with pores to separate red blood cells range from about 0.1 µm to about 5 µm (Qian et al. paragraph 0048). Applicant asserts that the smallest pore recited 0.1 µm or 100 nm is incapable of separating hemoglobin from a peptide. Applicants assert that furthermore, description of the protease layer notes that the matrix provides sufficient void space for the proteases to exert its activity on proteins present in fluid that passes through the matrix (Qian et al. 0050), implying the matrix does not act as sieve for proteins.
Applicants’ remarks are not persuasive.
Qian et al. disclose an assay comprising a stack of film layers comprising from bottom to top, a first film layer comprising a cross-linked polymeric matrix (or gel) comprising a detection agent, a ketoamine oxidase (or fructosyl oxidase), an agent that prevents interference, and a peroxidase enzyme; a second film layer comprising a polymeric matrix (or gel); and a third film layer comprising a protease.
Qian et al. disclose that the multiple layers of the polymers or porous matrices can comprise a buffered solution (at least paragraph 0041); in addition, agents to remove interference can also be included in the matrix (at least paragraph 0046). Qian et al. disclose that one or more additional layers that provide for additional functionality are also present (at least paragraph 0025), where additional layers include additional polymeric layers (at least paragraphs 0077-0079). Qian et al. disclose the matrix material is one that is porous and provides for flow of sample fluid through the material; a number of different porous matrices have been developed and are available; where the matrix may have a porosity gradient, with larger pores near or at the sample application region and smaller pores at the detection region (at least paragraph 0056).
Qian et al. disclose that when the sample is applied onto the multilayer test strip, the sample is allowed to flow sequentially through the various layers of the strip, such that it separates in the separation element, is digested in the protease layer and reacts with the members of the signal producing system in the system producing system layer (detection region) to produce a detectable product; the amount of detectable product, i.e. the signal produced by the signal producing system is determined and related to the amount of glycated protein in the initial sample (at least paragraph 0092).
Therefore, even if Qian et al. disclose an initial separation element layer for the red blood cells having a minimum pore size 0.1 µm (or 100 nm) which Applicants assert is incapable of separating hemoglobin from a peptide, Qian et al. has expressly disclosed that downstream of that initial separation element layer, which includes at least the protease layer, any additional functional layers, and the detection layer or region, the matrices of the layers may have a porosity gradient, i.e. wither larger pores near at or at the sample application region and smaller pores at the detection region (paragraph 0056). Therefore, it would be obvious that the functional layer(s) downstream from the initial separation element layer and the protease layer, are closer to the detection region, can be designed to have smaller pores as suggested by Qian et al. to create a porosity gradient having decreasing pores, that function to separate larger biomolecules, which includes hemoglobin, from the cleaved peptides since the purpose of the multilayer test strip is to allow the cleaved product (or peptides) to flow through to the detection region to be detected.
Since the purpose of the multistrip test strip of Qian et al. is to detect cleaved peptides (the detection region is downstream of the protease layer), and Qian et al. disclose functional layers of the multilayer test strip may have a porosity gradient, and Depa et al. disclose the advantage of incorporating a titanium oxide into a layer under a porous layer to provide opacity to reduce background signal for a better reflectance signal and test accuracy for the optical measuring apparatus (see above), it would an obvious design choice that the noted layer comprising a polymeric matrix (or hardened gel) for additional functionality comprising titanium oxide as suggested in Depa et al. and a buffered solution as suggested in Qian et al. above can be optimized to have a porosity that allows the smaller molecules for detection (fructosyl valylhistidine) to flow through to the detection region while excluding the larger molecular weight biomolecules, including hemoglobin, to flow through to the detection region.
As previously noted, Depa et al. disclose a test strip having multiple film layers for measuring analytes, including the glycated hemoglobin of Qian et al./Taniguchi et al. (Depa et al. abstract). Depa et al. disclose that any layer underneath a porous layer when it is wetted becomes semi-transparent, and the layer underneath is colored, could potentially interfere with the optical apparatus during analysis with the optical measuring apparatus (at least p. 7 lines 13-15). Depa et al. disclose impregnating into the layer a filler or whitening agent such as titanium oxide to provide opacity to reduce background signal for a better reflectance signal and test accuracy for the optical measuring apparatus (at least p. 7 lines 15-18).
In the multilayer assay of Qian et al. and Taniguchi et al. above, the blood sample flows through the protease layer before reaching the fructosyl oxidase bottom layer (see above). Qian et al. disclose that one or more additional layers that provide for additional functionality are also present (at least paragraph 0025).
Therefore, it would have been obvious to one of ordinary skill in the art to incorporate a layer comprising titanium oxide as suggested in Depa et al. and a buffered solution as suggested in Qian et al. into the assay comprising a stack of film layers, such as a layer comprising a polymeric matrix (or hardened gel) having a porosity gradient that allows the smaller molecules for detection (fructosyl valylhistidine) to flow through to the detection region while excluding the larger molecular weight biomolecules to flow through to the detection region, where the noted layer is above the layer comprising the cross-linked polymeric matrix (or gel) comprising the detection agent, fructosyl oxidase, agent that prevents interference, and peroxidase enzyme disclosed in the multi-layer assay of Qian et al. and Taniguchi et al. noted above (instant claims 1, 45) because doing so would reduce background signal for a better reflectance signal and test accuracy. Since Depa et al. suggest incorporating a reflective material (titanium oxide) that is materially the same and has the same functional purpose as the recited reflective material and Qian et al. disclose materially the same polymers or polymeric matrices for incorporating into a multiple layer assay may be optimized to have a porosity gradient with larger pores near or at the sample application region and smaller pores at the detection region, it would be obvious that the noted layer comprising a polymeric matrix (or hardened gel) for additional functionality comprising titanium oxide as suggested in Depa et al. and a buffered solution as suggested in Qian et al. above can be optimized to have a porosity that allows the smaller molecules for detection (fructosyl valylhistidine) to flow through to the detection region while excluding the larger molecular weight biomolecules to flow through to the detection region.
Regarding Applicants’ remarks that the cited references do not teach or suggest a slide “configured to generate a signal above the reflective material portion including a first wavelength at 540…” and so forth, the remarks are not persuasive.
As previously noted, the instant claims are product claims drawn to a system comprising multiple reagent layers (or multilayer reagent test strips) and not to a method for measuring Hb or glycated Hb.
Since Depa et al. suggest incorporating a reflective material (titanium oxide) that is materially the same and has the same functional purpose as the recited reflective material and Qian et al. disclose materially the same polymers or polymeric matrices for incorporating into a multiple layer assay also for the same purpose as the claimed multilayer film slide, it would be obvious that the layer comprising a reflective material portion has the configuration to generate the recited signals.
Taniguchi et al. has also disclosed wavelengths of 546 nm and 542 nm and 600 to measure hemoglobin and fructosyl peptide (examples).
Regarding Applicants’ previous remarks that Depa et al.’s porous membrane does not include at least one buffer and a hardened gel and rather Depa et al. utilize a soft and/or hard membrane, the remarks are not persuasive. Depa et al. is cited with at least Qian et al. and Taniguchi et al. above, which disclose the layer(s) of the multilayer reagent test strips are in polymeric matrix (i.e. gel form (Qian et al.)) and that the reagents can be provided in gel form (Taniguchi et al.).
Regarding Applicants’ previous remarks that the subject application discusses the advantages of using titanium oxide and a hardened gel to create a sieve small enough to allow Fru-alpha-ValHis to pass through while excluding larger molecular weight proteins, the remarks are not persuasive. MPEP 2145 notes that “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
In this instance, Depa et al. disclose the advantage of incorporating a titanium oxide into a layer under a porous layer to provide opacity to reduce background signal for a better reflectance signal and test accuracy for the optical measuring apparatus (see above).
In the multilayer assay of Qian et al. and Taniguchi et al. above, the blood sample flows through the protease layer before reaching the fructosyl oxidase bottom layer (see above). Qian et al. disclose that one or more additional layers that provide for additional functionality are also present (at least paragraph 0025).
Qian et al. disclose the matrix material is one that is porous and provides for flow of sample fluid through the material; a number of different porous matrices have been developed and are available; where the matrix may have a porosity gradient, with larger pores near or at the sample application region and smaller pores at the detection region (at least paragraph 0056).
Since Depa et al. suggest incorporating a reflective material (titanium oxide) that is materially the same and has the same functional purpose as the recited reflective material and Qian et al. disclose materially the same polymers or polymeric matrices for incorporating into a multiple layer assay may be optimized to have a porosity gradient with larger pores near or at the sample application region and smaller pores at the detection region, it would be obvious that the noted layer comprising a polymeric matrix (or hardened gel) for additional functionality comprising titanium oxide as suggested in Depa et al. and a buffered solution as suggested in Qian et al. above can be optimized to have a porosity that allows the smaller molecules for detection (fructosyl valylhistidine) to flow through to the detection region while excluding the larger molecular weight biomolecules to flow through to the detection region.
Therefore, Applicants’ recognized advantage of titanium oxide and a gel matrix to create a sieve would flow from following the teachings of the prior art.
See also the reasons noted on at least 8-11 of the August 19, 2025 final office action, p. 7-11 of the October 17, 2024 final office action, p. 6-11 of the April 19, 2024 non-final office action, and p. 6-10 of the October 30, 2023 final office action.
For at least these reasons, the 103 rejection is maintained.
Claims 1-2, 4-5, 8, 21, 22, 28-30, 32-38, 39-42, 44-45 are rejected under 35 U.S.C. 103 as being unpatentable over Qian et al. (US 20050255453; previously cited) in view of Taniguchi et al. (US 20070154976; previously cited), Depa et al. (WO 2019152508; previously cited), and Yuan et al. (US 20130078664; previously cited). The teachings of Qian et al. in view of Taniguchi et al. and Depa et al. over at least instant claims 1-2, 4-5, 8, 21, 28-30, 32-38, 39-42, 44-45 are noted above. As noted above, Qian et al. in view of Taniguchi et al. and Depa et al. reasonably disclose an assay comprising a stack of film layers, from bottom to top, a first film layer comprising a cross-linked polymeric matrix (or gel) comprising a detection agent, a fructosyl oxidase, an agent that prevents interference, and a peroxidase enzyme; a second film layer comprising a polymeric matrix (or gel) and a titanium oxide; and a third film layer comprising a lysing agent (Triton X-100), a denaturing agent (anionic surfactant), and a protease.
Yuan et al. also disclose assays and/or methods for measuring glycated hemoglobin (at least abstract). Similar to Taniguchi et al., Yuan et al. also discloses a composition comprising a lysing buffer comprising protease (at least p. 11 claims 7-8) and a composition comprising fructosyl amino acid oxidase, peroxidase, and a color forming substance (p. 11 claim 13). Yuan et al. disclose lysing buffers generally contain a detergent, including Triton X-100, Tween 20, SDS, CTAB, TTAB, POEs, and NP-40 (at least paragraph 0048).
Therefore, it would have been obvious to one of ordinary skill to substitute and/or incorporate a detergent selected from Tween 20, SDS, CTAB, TTAB, POEs, and NP-40 as suggested in Yuan et al. for the Triton X-100 (lysing agent) in the layer comprising a lysing agent, a denaturing agent (anionic surfactant), and a protease, in the assay comprising a stack of film layers of Qian et al. and Taniguchi et al. and Depa et al. noted above (instant claim 22).
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive. The reasons for maintaining Qian et al., Taniguchi et al. and Depa et al. are the same as noted above.
Claims 1-2, 4-5, 8, 21, 28-30, 31, 32-38, 39-42, 43, 44-45 are rejected under 35 U.S.C. 103 as being unpatentable over Qian et al. (US 20050255453; previously cited) in view of Taniguchi et al. (US 20070154976; previously cited), Depa et al. (WO 2019152508; previously cited), and JP ‘919 (JP5870919B2 translation provided by EPO: 35 pages; previously cited). The teachings of Qian et al. in view of Taniguchi et al. over instant claims 1-2, 4-5, 8, 21, 28-30, 32-38, 39-42, 44-45 are noted above. As noted above, Qian et al. in view of Taniguchi et al. and Depa et al. reasonably disclose an assay comprising a stack of film layers, from bottom to top, a first film layer comprising a cross-linked polymeric matrix (or gel) comprising a detection agent, a fructosyl oxidase, an agent that prevents interference, and a peroxidase enzyme; a second film layer comprising a polymeric matrix (or gel) and a titanium oxide; and a third film layer comprising a lysing agent (Triton X-100), a denaturing agent (anionic surfactant), and a protease.
JP ‘919 also discloses methods and reagent compositions for measuring glycated hemoglobin (at least p. 1). Similar to Qian et al. and Taniguchi et al. also disclose leuco compounds for the color producing compounds (at least paragraph 0057-0060). In addition to DA-67 disclosed in Qian et al. and Taniguchi et l., JP ‘919 also disclose 2-(3,5-dimethoxy-4-hydroxyphenol)-4,5-bis(4-diethylaminophenyl) imidazole (at least paragraph 0058).
Therefore, it would have been obvious to substitute and/or incorporate a 2-(3,5-dimethoxy-4-hydroxyphenol)-4,5-bis(4-dimethylaminophenyl) imidazole as recited in instant claim 31 for the detection agent (indicator dye) in the layer comprising a cross-linked polymeric matrix (or gel) comprising a detection agent, a fructosyl oxidase, an agent that prevents interference, and a peroxidase enzyme, in the assay comprising a stack of film layers of Qian et al. and Taniguchi et al. and Depa et al. noted above (instant claim 31) because JP ‘919 also disclose a leuco compound 2-(3,5-dimethoxy-4-hydroxyphenol)-4,5-bis(4-diethylaminophenyl) imidazole that is similar to the claimed detection agent.
Regarding instant claim 43, JP ‘919 discloses that the protease activity occurs in the presence of metal ions , including sodium chloride, potassium chloride (at least paragraph 0070). JP ‘919 discloses other metal salts including aluminum chloride and calcium chloride (at least paragraph 0074). Therefore, it would have been obvious to incorporate a calcium chloride as suggested in JP ‘919 with the protease in the layer comprising protease of the assay comprising a stack of film layers of Qian et al. and Taniguchi et al. and Depa et al. noted above.
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive. The reasons for maintaining Qian et al., Taniguchi et al. and Depa et al. are the same as noted above.
Claims 1-2, 3, 4-5, 8, 21, 28-30, 32-38, 39-42, 44-45 are rejected under 35 U.S.C. 103 as being unpatentable over Qian et al. (US 20050255453; previously cited) in view of Taniguchi et al. (US 20070154976; previously cited), Depa et al. (WO 2019152508; previously cited), and Bhairi et al. (2017 Sigma-Aldrich Detergents: A guide to the properties and uses of detergents in biological systems: 20 pages; previously cited). The teachings of Qian et al. in view of Taniguchi et al. and Depa et al. over instant claims 1-2, 4-5, 8, 21, 28-30, 32-38, 39-42, 44-45 are noted above. As noted above, Qian et al. in view of Taniguchi et al. and Depa et al. reasonably disclose an assay comprising a stack of film layers, from bottom to top, a first film layer comprising a cross-linked polymeric matrix (or gel) comprising a detection agent, a fructosyl oxidase, an agent that prevents interference, and a peroxidase enzyme; a second film layer comprising a polymeric matrix (or gel) and a titanium oxide; and a third film layer comprising a lysing agent (Triton X-100), a denaturing agent (anionic surfactant), and a protease. Additionally, as noted above, Taniguchi et al. disclose a surfactant, i.e. Triton X-100, can be used in combination with other anionic surfactants (at least paragraph 0040) with whole blood samples, where protease can also be combined with the surfactants used for hemolysis (at least paragraph 0044).
Bhairi et al. disclose known detergents including the detergents and/or surfactants disclosed in Taniguchi et al., including Triton X-100 (p. 5). Bhairi et al. disclose other known anionic detergents include N-lauroylsarcosine (p. 6).
Therefore, it would have been obvious to one of ordinary skill to substitute and/or incorporate an anionic detergent including N-lauroylsarcosine as suggested in Bhairi et al. for the anionic surfactant (denaturing agent) in the layer comprising a lysing agent, a denaturing agent (anionic surfactant), and a protease, in the assay comprising a stack of film layers of Qian et al. and Taniguchi et al. and Depa et al. noted above (instant claim 3).
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive. The reasons for maintaining Qian et al., Taniguchi et al. and Depa et al. are the same as noted above.
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Marsha Tsay whose telephone number is (571)272-2938. The examiner can normally be reached M-F.
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, Manjunath N. Rao can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Marsha Tsay/Primary Examiner, Art Unit 1656
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