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 .
Status of the Rejections pending since the Office Action
Mailed on July 08, 2025
All of the rejections under 35 U.S.C. 103 are withdrawn, but have been rewritten below in light of Applicant’s latest Amendment.1
Response to Arguments
Applicant's arguments filed October 08, 2025 have been fully considered but they are not persuasive.
On page 11, continuing onto page 12, of Applicant’s latest Amendment, Applicant argues that the Examiner has employed hindsight reasoning. In particular, Applicant comments
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As a first matter the Examiner would like to point out that Applicant’s application disclosure makes no mention of the problem of air bubbles possibly forming in the claimed biosensor, let alone that a polysaccharide would be useful in preventing or reducing the presence of such bubbles. Applicant’s reliance upon Pamidi paragraph [0103] is misplaced as the Examiner does not refer to it in any of the previously pending claim rejections. Moreover, this paragraph describes the reference electrode assembly (64 (reference solution inlet), 106 (reference electrode), 66 (reference capillary (liquid junction))), not the assembly of any of the enzymatic electrodes, especially that of the creatine electrode (118) or the creatinase electrode (116), which are quite different in design (see Pamidi Figures 2 and 3A, and paragraphs [0095], [0096], [0102], and [0103]). Last, Pamidi paragraph [0103] actually supports the Examiner's rejection as it deals with a second source of air bubbles in the biosensor (the first being the calibration solutions. See Pamidi parapgrjhs [0068]-[0070]).
In any event, Applicant’s argument is now largely moot in light of newly cited Vladislav Dolnik US 2007/0051628 A1 (hereafter “Dolnik”) and Wang et al., “Dissolution-Guided Wetting for Microarray and Microfluidic Devices,” Lab Chip, 2012, 12, 3036–3039 (hereafter “Wang”). Dolnik discloses “. . . .a method of preparation of a neutral wall coating made of thermally immobilized polysaccharides. The coating suppresses electroosmotic flow and adsorption [of analytes] on the wall under acidic, neutral, and basic conditions in capillary electrophoresis.” See the Abstract and paragraph [0001]. Wang discloses using a monosaccharide, such as D-glucose or D-sorbitol, to eliminate trapped air bubbles (from microwells, traps, dead ends, and corners) from microarrays and microfluidic devices. See the abstract. Dolnik and Wang2 along with previous applied Winarta, Cai, Zhao, and Dalton together disclose at least five benefits of polysaccharides pertinent to the Pamidi biosensor:
1) preventing adsorption of analytes3 along the flow path of the sample through the biosensor;
2) preventing or removing air bubbles;
3) stabilizing enzymes;
4) improving cross-linking properties of and providing additional mechanical strength to an enzyme matrix; and
5) altering the porosity of photo-formed membranes.
One of ordinary skill in the art would recognize that in order to best realize these benefits polysaccharide would have to be located at or in different regions of the Pamidi biosensor, namely as claimed.
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 35, 38-40, 42, 43, 45, 47, 50, 51, 53-57, 59, and 60 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. Independent claims 35, 45, and 54 each require
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The scope of these claims allows for the any of the first polysaccharide, second polysaccharide, or third polysaccharide to be different from the other two polysaccharides, which may be the same, or each of the polysaccharides to be different from the other two, which themselves are different from each other (such interpretations are implied by dependent claims 36 and 48 as the appear to narrow respective claims 35 and 45 by excluding such interpretations). No support has been found such embodiments in Applicant’s originally filed application. So, these embodiments falling within the scope of claims 35 and 45 introduce new matter.
Claims 35, 36, 38-40, 42-45, 47, 48, 50, 51, 53-57, 59, and 60 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. Independent claims 35 and 45 each require
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No support has been found for this limitation in Applicant’s originally filed application. So, this feature introduces new matter. Note that the only mention of the word “structure” in Applicant’s specification is in regard to biological or biochemical structure , for example, “enzyme structure “and “protein structure”. See Applicant’s pre-grant publication US 20220187234 A1 (hereafter “Applicant’s PG-PUB”) paragraphs [0014], [0015], and [0035].
Claims 40 and 50 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. Claim 40 requires
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Claim 50 similarly requires
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These claims allow for the polysaccharide in any of the first polysaccharide, second polysaccharide, or third polysaccharide to be different from one or both of the other two polysaccharides. For example, the first polysaccharide may comprise sucrose, the second polysaccharide may comprise trehalose, and the third polysaccharide may comprise raffinose. Additionally, though the use of the transitional phrase “comprises” (see MPEP 2111.03(I)) each of the first polysaccharide, second polysaccharide, or third polysaccharide may contain or more or all of sucrose, trehalose, raffinose, or lactitol. Moreover, “comprises” allows other polysaccharides to be present in any of the first polysaccharide, second polysaccharide, or third polysaccharide in addition to those listed. No support has been found such embodiments in Applicant’s originally filed application. So, these embodiments falling within the scope of claims 40 and 50 introduce new matter.
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.
Note that dependent claims will have the deficiencies of base and intervening claims.
Claims 35, 36, 38-40, 42-45, 47, 48, 50, 51, 53-57, 59, and 60 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:
a) Independent claims 35, 45, and 54 each require
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The scope of the word structure is indefinite as the only mention of the word “structure” in Applicant’s specification is in regard to biological or biochemical structure , for example, “enzyme structure “and “protein structure”.4 See Applicant’s PG-PUB paragraphs [0014], [0015], and [0035].
b) claim 60 requires “immersing the biosensor in a solution comprising about 10% to about 25% of the same polysaccharide for thirty minutes or longer…” This phrase is indefinite because there is no concentration unit (such as mol% or weight %) associated with the percentage range (nor does there appear to be any unit mentioned in the specification). Additionally, it is not clear what the concentrations of the resulting first polysaccharide, second polysaccharide, and third polysaccharide will be.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 35, 36, 38, 39, 40, 42, 43, 44, 45, 47, 48, 50, 51, 53-57, and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Pamidi et al. US 2004/0211666 A1 (hereafter “Pamidi”) in view of Winarta US 2007/0131548 A1 (hereafter ‘Winarta”), Cai et al. US 6,767,441 B1 (hereafter “Cai”), Zhao et al. 2014/0262777A1 (hereafter “Zhao”), Dalton et al. WO 2009/053370 A1 (hereafter “Dalton”), Dolnik, and Wang.
Addressing claims 35 and 39, Pamidi discloses a biosensor (116; see Figure 2, the Abstract, and paragraphs [0002] and [0095]) configured to measure at least one of creatine or creatinine in a fluid sample in a flow path (Figure 2), the biosensor comprising:
a structure (the bottom layer or substrate of card 50 in which the biosensor has been formed. This layer may be inferred from Figure 3A (57 extends though this layer. See annotated Figure 3A at the end of this claim rejection.) ) comprising:
an electrode (57; Figures 3A and 3B, and paragraph [0130]);
a plurality of enzymes (53) over the electrode (
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The creatininase, creatinase, and sarcosine oxidase disclosed in paragraphs [0096] and [0097] are understood by the Examiner to be located in enzyme layer 53.),
a polyionic compound among the plurality of enzymes (see Pamidi paragraph [0025], noting especially, “In another embodiment, the enzyme stabilizer present in the matrix may include one or more of the compounds, polyethyleneimine, polypropyleneimine, poly(N-vinylimidazole), polyallylamine, polyvinylpiridine, polyvinylpyrollidone, polylysine, protamine and their derivatives.“. Note that Dalton discloses that many of the polyionic compounds suggested by Pamidi as enzyme stabilizers (paragraph [0025]) act as protective agents for enzyme reagent on an electrode (see Dalton page 10, line 23, to page 11, line 15). So, there is also a separate reason to include a polyionic compound in the modified Pamidi biosensor than as an enzyme stabilizer.);
a diffusion barrier (51) over the structure (see annotated Figure 3A at the end of this claim rejection), and
wherein the diffusion barrier is configured to receive the fluid sample from the flow path (note that in Pamidi the diffusion barrier (51) is configured to receive the fluid sample from the flow path (56). See Pamidi Figure 3B.).
Pamidi, though, does not disclose the following newly added limitations
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Winarta discloses an electrochemical biosensor comprising a reagent over an electrode. See the title, Abstract, and paragraphs [0032] and [0034]. This reagent comprises creatinine amidohydrolase (creatininase), creatine amidonohydrolase (creatinase), and sarcosine oxidase. See in Cai5 the title, Abstract, and col. 6:17-46. Winarta further discloses that this reagent may also comprise a bulking reagent, which may be a polysaccharide, such as trehalose or sucrose. See Winarta paragraphs [0044], [0111], and [0112]. Note
(1) in both Pamidi and Winarta the enzymes are located in a well (see in Pamidi Figure 3A. See in Winarta Figure 3 and paragraph [0093]),
(2) Pamidi clearly expresses concern over the possible presence of bubbles in the biosensor, which would adversely affect the accuracy of the measurements:
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Zhao discloses “[a] sugar or sugar alcohol, such as sucrose, sorbitol, or mannitol, may also be included in the formulation to alter the porosity of the photoformed matrix and to help stabilize the enzymes. In accordance with some aspects of the invention, the one or more proteins may comprise SOX, CRH, CNH, catalase, lactate oxidase (LOX), glucose oxidase (GOX), and/or bovine serum albumin (BSA) mixed to obtain the enzymatic activities, water uptake and diffusional properties desired in each biolayer.[italicizing and underlining by the Examiner]”6 See in Zhao the title, Abstract, and paragraph [0047]. Note in this regard that Pamidi discloses that more than one enzyme stabilizer may be included in the biosensor7 and that Pamidi discloses photoforming membranes (for example, see paragraph [0148], noting especially “The cross-linking reaction can be initiated by a photoinitiator . . . .” and paragraph [0150], the last sentence).
Dalton explains that enzyme stabilizers, such as trehalose, when present in an enzyme matrix “. . . . can inhibit denaturation, improve cross-linking properties and provide additional mechanical strength.[italicizing by the Examiner]” See Dalton
page 10, line 30 to page 11, line 5.
Dolnik discloses “. . . .a method of preparation of a neutral wall coating made of thermally immobilized polysaccharides. The coating suppresses electroosmotic flow and adsorption [of analytes] on the wall under acidic, neutral, and basic conditions in capillary electrophoresis.” See the Abstract and paragraph [0001].
Wang discloses using a monosaccharide8, such as D-glucose or D-sorbitol, to eliminate trapped air bubbles (from microwells, traps, dead ends, and corners) from microarrays and microfluidic devices. See the abstract.
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to provide one or more polysaccharides as taught by Winarta, Cai, Zhao, Dalton, Dolnik, and Wang in the biosensor of Pamidi because
together they disclose at least five benefits of polysaccharides pertinent to the Pamidi biosensor:
1) preventing adsorption of analytes9 along the flow path of the sample through the biosensor;
2) preventing or removing air bubbles;
3) stabilizing enzymes;
4) improving cross-linking properties of and providing additional mechanical strength to an enzyme matrix; and
5) altering the porosity of photo formed membranes.
As for the claimed placements of the first polysaccharide, second polysaccharide, or third polysaccharide, one of ordinary skill in the art would recognize that in order to best realize these benefits polysaccharide would have to be located at or in different regions of the Pamidi biosensor, namely as claimed. For example, to obtain the polysaccharide benefit of stabilizing enzymes it would be obvious to include polysaccharide among the plurality of enzymes. To obtain the polysaccharide benefit of preventing or removing air bubbles and preventing adsorption of analytes (and other blood components) from the sensor well (Figure 3A) and the flow channel region neighboring the biosensor it would be obvious to provide polysaccharide covering the structure and also covering the diffusion barrier10.
As for the claim 35 limitation “ . . . ., and wherein the biosensor maintains a biosensor sensitivity after a storage period and a use life period…”, this limitation may be viewed as just expressing a property that is inherently present in the prior art. It is well established that something which is old (here including polysaccharide in a biosensor) does not become patentable upon discovery of a new property and that an inherent feature need not be recognized at the relevant time. See MPEP 2112(I) and 2112(II). Also, claimed properties are presumed to be inherent in a prior art device or composition otherwise the same as claimed. See MPEP 2112.01(I) and 2112.02(II). This is especially so here as Applicant’s specification attributes the newly added “storage” claim features to the presence of a polysaccharide on a part of the biosensor (see, for example, Applicant’s pre-grant application publication (US 20220187234 A1) paragraphs [0033], [0034], [049], and [0052]), With polysaccharide both on the diffusion barrier and in the immobilized enzymes as just argued, there is a reasonable expectation that the polysaccharide will be present in sufficient amount to maintain the biosensor sensitivity as claimed. Also, it should be noted that Pamidi discloses several ways to extend the shelf-life of the biosensor-
“ It is also desirable that the ion plasticizer be substantially non-volatile to provide extended shelf-life for the electrode…” ( Pamidi paragraph [0121]),
“As also described in greater detail below, the uniformity of thickness of the ion selective membrane plays an important role in the optimum utilization of electrodes of the type described herein. Thus, if maximum advantage in terms of storage capability is to be obtained, the ion-selective membrane should be of relatively uniform thickness as defined above….” ( Pamidi paragraph [0123]), and
“Cross-linking of the enzyme molecules and the use of the polyionic stabilizers and inert proteins in the enzyme matrix can significantly extend the shelf-life and the use-life of the enzyme electrodes…” ( Pamidi paragraph [0137]).
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Addressing claim 36, as for the electrode comprising one of the listed materials note the following in Pamidi
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As for the claim 36 limitation “. . . .; and wherein the first polysaccharide, the second polysaccharide, and the third polysaccharide are a same polysaccharide…”, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have this be so as it will simplify manufacture of the biosensor as additional polysaccharide dispensing means (and chemicals (polysaccharides)) will not be needed.
Addressing claim 38, for the additional limitation of this claim note the following in Pamidi
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Addressing claim 40, for the additional limitation of this claim note the following in Winarta
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Additionally, one of ordinary skill in the art would know how to select one or more suitable polysaccharides from those disclosed by Winarta, Cai, Zhao, Dalton, Dolnik, and Wang depending on factors such the benefit to be achieved and chemical compatibility with the ,material it will be in contact with (namely, the electrode reagent, sample, analyte, flow channel surface, diffusion barrier). Put another way the choice of polysaccharide(s) from those disclosed or suggested by Winarta, Cai, Zhao, Dalton, Dolnik, and Wang is prima facie obvious as simple substitution of one known element (polysaccharide)for another to obtain predictable results. See MPEP 2143(I)(B).
Addressing claim 42, for the additional limitation of this claim note the following in Pamidi
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Addressing claim 43, for the additional limitation of this claim see in Pamidi paragraphs [0008], [0019], and [0132].
Additionally, one of ordinary skill in the art would know how to select one or more suitable polysaccharides from those disclosed by Winarta, Cai, Zhao, Dalton, Dolnik, and Wang depending on factors such the benefit to be achieved and chemical compatibility with the ,material it will be in contact with (namely, the electrode reagent, sample, analyte, flow channel surface, diffusion barrier). Put another way the choice of polysaccharide(s) from those disclosed or suggested by Winarta, Cai, Zhao, Dalton, Dolnik, and Wang is prima facie obvious as simple substitution of one known element (polysaccharide)for another to obtain predictable results. See MPEP 2143(I)(B).
Addressing claim 44, Pamidi as modified in the rejection of underlying claim 35 above does disclose having the first polysaccharide, second polysaccharide, and third polysaccharide comprise sucrose.
Addressing claim 45, Pamidi discloses a biosensor (116; see Figure 2, the Abstract, and paragraphs [0002] and [0095]) configured to measure at least one of creatine or creatinine in a fluid sample in a flow path (Figure 2), the biosensor comprising:
a structure (the bottom layer or substrate of card 50 in which the biosensor has been formed. This layer may be inferred from Figure 3A (57 extends though this layer. See annotated Figure3A at the end of this claim rejection.) ) comprising:
an electrode (57; Figures 3A and 3B, and paragraph [0130]);
a plurality of enzymes (53) over the electrode (
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The creatininase, creatinase, and sarcosine oxidase disclosed in paragraphs [0096] and [0097] are understood by the Examiner to be located in enzyme layer 53.),
a polyionic compound among the plurality of enzymes (see Pamidi paragraph [0025], noting especially, “In another embodiment, the enzyme stabilizer present in the matrix may include one or more of the compounds, polyethyleneimine, polypropyleneimine, poly(N-vinylimidazole), polyallylamine, polyvinylpiridine, polyvinylpyrollidone, polylysine, protamine and their derivatives.“. Note that Dalton discloses that many of the polyionic compounds suggested by Pamidi as enzyme stabilizers (paragraph [0025]) act as protective agents for enzyme reagent on an electrode (see Dalton page 10, line 23, to page 11, line 15). So, there is also a separate reason to include a polyionic compound in the modified Pamidi biosensor than as an enzyme stabilizer.);
a diffusion barrier (51) over the structure (see annotated Figure 3A at the end of this claim rejection), and
wherein the diffusion barrier is configured to receive the fluid sample from the flow path (note that in Pamidi the diffusion barrier (51) is configured to receive the fluid sample from the flow path (56). See Pamidi Figure 3B.).
Pamidi, though, does not disclose the following newly added limitations
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Winarta discloses an electrochemical biosensor comprising a reagent over an electrode. See the title, Abstract, and paragraphs [0032] and [0034]. This reagent comprises creatinine amidohydrolase (creatininase), creatine amidonohydrolase (creatinase), and sarcosine oxidase. See in Cai11 the title, Abstract, and col. 6:17-46. Winarta further discloses that this reagent may also comprise a bulking reagent, which may be a polysaccharide, such as trehalose or sucrose. See Winarta paragraphs [0044], [0111], and [0112]. Note
(1) in both Pamidi and Winarta the enzymes are located in a well (see in Pamidi Figure 3A. See in Winarta Figure 3 and paragraph [0093]),
(2) Pamidi clearly expresses concern over the possible presence of bubbles in the biosensor, which would adversely affect the accuracy of the measurements:
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Zhao discloses “[a] sugar or sugar alcohol, such as sucrose, sorbitol, or mannitol, may also be included in the formulation to alter the porosity of the photoformed matrix and to help stabilize the enzymes. In accordance with some aspects of the invention, the one or more proteins may comprise SOX, CRH, CNH, catalase, lactate oxidase (LOX), glucose oxidase (GOX), and/or bovine serum albumin (BSA) mixed to obtain the enzymatic activities, water uptake and diffusional properties desired in each biolayer.[italicizing and underlining by the Examiner]”12 See in Zhao the title, Abstract, and paragraph [0047]. Note in this regard that Pamidi discloses that more than one enzyme stabilizer may be included in the biosensor13 and that Pamidi discloses photoforming membranes (for example, see paragraph [0148], noting especially “The cross-linking reaction can be initiated by a photoinitiator . . . .” and paragraph [0150], the last sentence).
Dalton explains that enzyme stabilizers, such as trehalose, when present in an enzyme matrix “. . . . can inhibit denaturation, improve cross-linking properties and provide additional mechanical strength.[italicizing by the Examiner]” See Dalton
page 10, line 30 to page 11, line 5.
Dolnik discloses “. . . .a method of preparation of a neutral wall coating made of thermally immobilized polysaccharides. The coating suppresses electroosmotic flow and adsorption [of analytes] on the wall under acidic, neutral, and basic conditions in capillary electrophoresis.” See the Abstract and paragraph [0001].
Wang discloses using a monosaccharide14, such as D-glucose or D-sorbitol, to eliminate trapped air bubbles (from microwells, traps, dead ends, and corners) from microarrays and microfluidic devices. See the abstract.
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to provide one or more polysaccharides as taught by Winarta, Cai, Zhao, Dalton, Dolnik, and Wang in the biosensor of Pamidi because
together they disclose at least five benefits of polysaccharides pertinent to the Pamidi biosensor:
1) preventing adsorption of analytes15 along the flow path of the sample through the biosensor;
2) preventing or removing air bubbles;
3) stabilizing enzymes;
4) improving cross-linking properties of and providing additional mechanical strength to an enzyme matrix; and
5) altering the porosity of photo formed membranes.
As for the claimed placements of the first polysaccharide, second polysaccharide, or third polysaccharide, one of ordinary skill in the art would recognize that in order to best realize these benefits polysaccharide would have to be located at or in different regions of the Pamidi biosensor, namely as claimed. For example, to obtain the polysaccharide benefit of stabilizing enzymes it would be obvious to include polysaccharide among the plurality of enzymes. To obtain the polysaccharide benefit of preventing or removing air bubbles and preventing adsorption of analytes (and other blood components) from the sensor well (Figure 3A) and the flow channel region neighboring the biosensor it would be obvious to provide polysaccharide covering the structure and also covering the diffusion barrier16.
As for the claim 45 limitation “ . . . ., and wherein the biosensor maintains a biosensor sensitivity after a storage period and a use life period…”, this limitation may be viewed as just expressing a property that is inherently present in the prior art. It is well established that something which is old (here including polysaccharide in a biosensor) does not become patentable upon discovery of a new property and that an inherent feature need not be recognized at the relevant time. See MPEP 2112(I) and 2112(II). Also, claimed properties are presumed to be inherent in a prior art device or composition otherwise the same as claimed. See MPEP 2112.01(I) and 2112.02(II). This is especially so here as Applicant’s specification attributes the newly added “storage” claim features to the presence of a polysaccharide on a part of the biosensor (see, for example, Applicant’s pre-grant application publication (US 20220187234 A1) paragraphs [0033], [0034], [049], and [0052]), With polysaccharide both on the diffusion barrier and in the immobilized enzymes as just argued, there is a reasonable expectation that the polysaccharide will be present in sufficient amount to maintain the biosensor sensitivity as claimed. Also, it should be noted that Pamidi discloses several ways to extend the shelf-life of the biosensor-
“ It is also desirable that the ion plasticizer be substantially non-volatile to provide extended shelf-life for the electrode…” ( Pamidi paragraph [0121]),
“As also described in greater detail below, the uniformity of thickness of the ion selective membrane plays an important role in the optimum utilization of electrodes of the type described herein. Thus, if maximum advantage in terms of storage capability is to be obtained, the ion-selective membrane should be of relatively uniform thickness as defined above….” ( Pamidi paragraph [0123]), and
“Cross-linking of the enzyme molecules and the use of the polyionic stabilizers and inert proteins in the enzyme matrix can significantly extend the shelf-life and the use-life of the enzyme electrodes…” ( Pamidi paragraph [0137]).
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As for performing the claim 45 steps of
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, in light of the biosensor of modified Pamidi as described above it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to perform them because it is just a matter of using the biosensor as intended to be used.
Addressing claim 47, for the additional limitation of this claim see Pamidi paragraph [0025].
Addressing claim 48, as for the electrode comprising one of the listed materials note the following in Pamidi
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As for the claim 48 limitation “. . . .; and wherein the first polysaccharide, the second polysaccharide, and the third polysaccharide are a same polysaccharide…”, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have this be so as it will simplify manufacture of the biosensor as additional polysaccharide dispensing means (and chemicals (polysaccharides)) will not be needed.
Addressing claim 50, for the additional limitation of this claim note the following in Winarta
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Additionally, one of ordinary skill in the art would know how to select one or more suitable polysaccharides from those disclosed by Winarta, Cai, Zhao, Dalton, Dolnik, and Wang depending on factors such the benefit to be achieved and chemical compatibility with the ,material it will be in contact with (namely, the electrode reagent, sample, analyte, flow channel surface, diffusion barrier). Put another way the choice of polysaccharide(s) from those disclosed or suggested by Winarta, Cai, Zhao, Dalton, Dolnik, and Wang is prima facie obvious as simple substitution of one known element (polysaccharide)for another to obtain predictable results. See MPEP 2143(I)(B).
Addressing claim 51, for the additional limitation of this claim note the following in Pamidi
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Also see Pamidi paragraphs [0095]-[0099], which describe the measurements made by the Creatine and Creatinine sensors.
Addressing claim 53, for the additional limitation of this claim see Pamidi paragraphs [0024], [0025], and [0136].
Addressing claim 54, Pamidi discloses a system (Figure 1) comprising
a flow path configured to receive a fluid sample to be tested (Figure 2); and a biosensor configured to measure at least one of creatine or creatinine in the fluid sample in the flow path (
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), the biosensor comprising:
a structure (the bottom layer or substrate of card 50 in which the biosensor has been formed. This layer may be inferred from Figure 3A (57 extends though this layer. See annotated Figure 3A at the end of this claim rejection.) ) comprising:
an electrode (57; Figures 3A and 3B, and paragraph [0130]);
a plurality of enzymes (53) over the electrode (
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The creatininase, creatinase, and sarcosine oxidase disclosed in paragraphs [0096] and [0097] are understood by the Examiner to be located in enzyme layer 53.),
a polyionic compound among the plurality of enzymes (see Pamidi paragraph [0025], noting especially, “In another embodiment, the enzyme stabilizer present in the matrix may include one or more of the compounds, polyethyleneimine, polypropyleneimine, poly(N-vinylimidazole), polyallylamine, polyvinylpiridine, polyvinylpyrollidone, polylysine, protamine and their derivatives.“. Note that Dalton discloses that many of the polyionic compounds suggested by Pamidi as enzyme stabilizers (paragraph [0025]) act as protective agents for enzyme reagent on an electrode (see Dalton page 10, line 23, to page 11, line 15). So, there is also a separate reason to include a polyionic compound in the modified Pamidi biosensor than as an enzyme stabilizer.);
a diffusion barrier (51) over the structure (see annotated Figure 3A at the end of this claim rejection), and
wherein the diffusion barrier is configured to receive the fluid sample from the flow path (note that in Pamidi the diffusion barrier (51) is configured to receive the fluid sample from the flow path (56). See Pamidi Figure 3B.).
Pamidi, though, does not disclose the following newly added limitations
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Winarta discloses an electrochemical biosensor comprising a reagent over an electrode. See the title, Abstract, and paragraphs [0032] and [0034]. This reagent comprises creatinine amidohydrolase (creatininase), creatine amidonohydrolase (creatinase), and sarcosine oxidase. See in Cai17 the title, Abstract, and col. 6:17-46. Winarta further discloses that this reagent may also comprise a bulking reagent, which may be a polysaccharide, such as trehalose or sucrose. See Winarta paragraphs [0044], [0111], and [0112]. Note
(1) in both Pamidi and Winarta the enzymes are located in a well (see in Pamidi Figure 3A. See in Winarta Figure 3 and paragraph [0093]),
(2) Pamidi clearly expresses concern over the possible presence of bubbles in the biosensor, which would adversely affect the accuracy of the measurements:
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Zhao discloses “[a] sugar or sugar alcohol, such as sucrose, sorbitol, or mannitol, may also be included in the formulation to alter the porosity of the photoformed matrix and to help stabilize the enzymes. In accordance with some aspects of the invention, the one or more proteins may comprise SOX, CRH, CNH, catalase, lactate oxidase (LOX), glucose oxidase (GOX), and/or bovine serum albumin (BSA) mixed to obtain the enzymatic activities, water uptake and diffusional properties desired in each biolayer.[italicizing and underlining by the Examiner]”18 See in Zhao the title, Abstract, and paragraph [0047]. Note in this regard that Pamidi discloses that more than one enzyme stabilizer may be included in the biosensor19 and that Pamidi discloses photoforming membranes (for example, see paragraph [0148], noting especially “The cross-linking reaction can be initiated by a photoinitiator . . . .” and paragraph [0150], the last sentence).
Dalton explains that enzyme stabilizers, such as trehalose, when present in an enzyme matrix “. . . . can inhibit denaturation, improve cross-linking properties and provide additional mechanical strength.[italicizing by the Examiner]” See Dalton
page 10, line 30 to page 11, line 5.
Dolnik discloses “. . . .a method of preparation of a neutral wall coating made of thermally immobilized polysaccharides. The coating suppresses electroosmotic flow and adsorption [of analytes] on the wall under acidic, neutral, and basic conditions in capillary electrophoresis.” See the Abstract and paragraph [0001].
Wang discloses using a monosaccharide20, such as D-glucose or D-sorbitol, to eliminate trapped air bubbles (from microwells, traps, dead ends, and corners) from microarrays and microfluidic devices. See the abstract.
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to provide one or more polysaccharides as taught by Winarta, Cai, Zhao, Dalton, Dolnik, and Wang in the biosensor of Pamidi because
together they disclose at least five benefits of polysaccharides pertinent to the Pamidi biosensor:
1) preventing adsorption of analytes21 along the flow path of the sample through the biosensor;
2) preventing or removing air bubbles;
3) stabilizing enzymes;
4) improving cross-linking properties of and providing additional mechanical strength to an enzyme matrix; and
5) altering the porosity of photo formed membranes.
As for the claimed placements of the first polysaccharide, second polysaccharide, or third polysaccharide, one of ordinary skill in the art would recognize that in order to best realize these benefits polysaccharide would have to be located at or in different regions of the Pamidi biosensor, namely as claimed. For example, to obtain the polysaccharide benefit of stabilizing enzymes it would be obvious to include polysaccharide among the plurality of enzymes. To obtain the polysaccharide benefit of preventing or removing air bubbles and preventing adsorption of analytes (and other blood components) from the sensor well (Figure 3A) and the flow channel region neighboring the biosensor it would be obvious to provide polysaccharide covering the structure and also covering the diffusion barrier22.
As for the claim 35 limitation “ . . . ., and wherein the biosensor maintains a biosensor sensitivity after a storage period and a use life period…”, this limitation may be viewed as just expressing a property that is inherently present in the prior art. It is well established that something which is old (here including polysaccharide in a biosensor) does not become patentable upon discovery of a new property and that an inherent feature need not be recognized at the relevant time. See MPEP 2112(I) and 2112(II). Also, claimed properties are presumed to be inherent in a prior art device or composition otherwise the same as claimed. See MPEP 2112.01(I) and 2112.02(II). This is especially so here as Applicant’s specification attributes the newly added “storage” claim features to the presence of a polysaccharide on a part of the biosensor (see, for example, Applicant’s pre-grant application publication (US 20220187234 A1) paragraphs [0033], [0034], [049], and [0052]), With polysaccharide both on the diffusion barrier and in the immobilized enzymes as just argued, there is a reasonable expectation that the polysaccharide will be present in sufficient amount to maintain the biosensor sensitivity as claimed. Also, it should be noted that Pamidi discloses several ways to extend the shelf-life of the biosensor-
“ It is also desirable that the ion plasticizer be substantially non-volatile to provide extended shelf-life for the electrode…” ( Pamidi paragraph [0121]),
“As also described in greater detail below, the uniformity of thickness of the ion selective membrane plays an important role in the optimum utilization of electrodes of the type described herein. Thus, if maximum advantage in terms of storage capability is to be obtained, the ion-selective membrane should be of relatively uniform thickness as defined above….” ( Pamidi paragraph [0123]), and
“Cross-linking of the enzyme molecules and the use of the polyionic stabilizers and inert proteins in the enzyme matrix can significantly extend the shelf-life and the use-life of the enzyme electrodes…” ( Pamidi paragraph [0137]).
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Addressing claim 55, for the additional limitation of this claim see the first sentence of each of Pamidi paragraphs [0049] and [0056].
Addressing claims 56 and 59, the additional limitations of these claims only express desired results of using (storing). The biosensor. As discussed in the rejection of underlying claim 35,
It is well established that something which is old (here including polysaccharide in a biosensor) does not become patentable upon discovery of a new property and that an inherent feature need not be recognized at the relevant time. See MPEP 2112(I) and 2112(II). Also, claimed properties are presumed to be inherent in a prior art device or composition otherwise the same as claimed. See MPEP 2112.01(I) and 2112.02(II). This is especially so here as Applicant’s specification attributes the newly added “storage” claim features to the presence of a polysaccharide on a part of the biosensor (see, for example, Applicant’s pre-grant application publication (US 20220187234 A1) paragraphs [0033], [0034], [049], and [0052]), With polysaccharide both on the diffusion barrier and in the immobilized enzymes as just argued, there is a reasonable expectation that the polysaccharide will be present in sufficient amount to maintain the biosensor sensitivity as claimed.
Claim 60 is rejected under 35 U.S.C. 103 as being unpatentable over Pamidi in view of Winarta, Cai, Zhao, Dalton, Dolnik, and Wang as applied to claims 35, 36, 38-40, 42-45, 47, 48, 50, 51, 53-57, 59, and 60 above, and further in view of Feldman et al. US 2005/0173245 A1 (hereafter “Feldman”) and Brister et al. US 2006/0020192 A1 (hereafter “Brister”) .
Addressing claim 60, as a first matter the additional limitation of this claim expresses a product-by-process limitation. As such the claim is not limited to the manipulation of the recited step (“immersing’), only the structure implied by the steps. See MPEP 21113. As the there is no apparent material difference between the resulting biosensor form claim 60 and that of modified Pamiri as described in the rejection of claim 35, claim 60 may be said to be met by the claim 35 rejection. Additionally, one of ordinary skill in the art would know how to select an appropriate manufacturing technique to deposit the first polysaccharide, second polysaccharide, and third polysaccharide. In particular, it will be noted that dip-coating (immersing) was utilized in the biosensor art to form certain biosensor coatings. See, for example, Feldman paragraph [0021], and Brisker paragraphs [0134] and [0141]. As for the claim 60 phrase “immersing the biosensor in a solution comprising about 10% to about 25% of the same polysaccharide”, as a first matter it is not clear how it further limits the product (biosensor/electrode) as there is no unit associated with the percentage range and, more importantly perhaps, there is no way to determine what the concentrations of the first polysaccharide, second polysaccharide, and third polysaccharide on the product will be as they will depend on factors intrinsic to the biosensor, such as wettability and coating adhesion, and on the solution used, such as its viscosity, temperature, and the presence of any reactive substances. In any event, barring a showing of unexpected results, depending on the desired polysaccharide benefit to be obtained (see the five benefits listed in the rejection of claim 35) and the intended sample and analytes one of ordinary skill in the art would be able to determine through routine trial and error effective concentrations for the polysaccharides.
Other Relevant Prior Art
The Office Action received for European Patent Application No. 19734963.2, mailed on July 09, 2025, 5 pages, does not reject any claims over prior art. Additionally, the subject matter addressed in this Office action seems only tangentially related to the claimed subject matter in U.S. application 17/680487.23
The Office Action received for Chinese Patent Application No. 201980103233.5, mailed on March 08, 2025, 11 pages (6pages of English Translation and 5 pages of Original Document), also seems only tangentially related to the claimed subject matter in U.S. application 17/680487.24
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER STEPHAN NOGUEROLA whose telephone number is (571)272-1343. The examiner can normally be reached on Monday - Friday 9:00AM-5:30 PM EST.
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/ALEXANDER S NOGUEROLA/Primary Examiner, Art Unit 1795 November 7, 2025
1 Received October 08, 2025.
2 Although Wang only mentions monosaccharides, there is a reasonable expectation of a similar benefit that polysaccharides will eliminate air bubbles also (see MPEP 2144.09), especially as Zhao already discloses this benefit for polysaccharides.
3 Note that the main sample disclosed in Pamidi is blood.