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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 June 8th, 2026 has been entered.
Status of the Claims
Claims 1 and 39 have been amended; Claims 43-45 have been added. Claims 6-7, 13-14, 16-19, 27, 31, 37-38, and 40-42 have been previously cancelled; and Claims 15, 20-26, 28-30, and 32-36 have previously been withdrawn. Claims 1-5, 8-12, 39, and 43-45 are currently examined herein.
Status of the Rejection
Applicant’s amendments to the claims have overcome the 35 U.S.C. § 103 rejections previously set forth in the Final Office Action mailed February 6th, 2026.
New grounds of claim objection, 35 U.S.C. § 112(f), and rejection under 35 U.S.C. § 112(a), 35 U.S.C. § 112(b), and 35 U.S.C. § 103 are necessitated by Applicant’s amendments.
Claim Objections
Claims 1, 39, and 45 are objected to because of the following informalities:
Claim 1, please amend “higher affinity than dsDNA,;” to “higher affinity than dsDNA[[,]];”; “binds the target” to “binds the ssDNA target”.
Claim 39, please amend “electrode, wherein the channel layer a channel layer” to “electrode, wherein the channel layer
Claim 45, please amend “electrical parameter” to “electrical parameters”.
Appropriate correction is required.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier.
Such claim limitations are: Claim 1, “a data analyzer configured to detect a change in a concentration of the ssDNA target in the sample solution via a change in an electrical parameter of the FET”, is being interpreted under 35 U.S.C. 112(f). Prong 1: a data analyzer (uses a generic placeholder), prong 2: configured to detect a change in a concentration of the ssDNA target in the sample solution via a change in an electrical parameter of the FET (functional language), prong 3: sufficient structure for performing the function not recited. Therefore, claim 1 invokes 112(f). The corresponding structure for performing the functions is described in the specification. For example, the data analyzer may be a semiconductor parameter analyzer equipped with a probe station [para. 0153].
Claim 39, “a data analyzer configured to detect a level of the ssDNA primers by detection of a change in a FET electrical parameter”, is being interpreted under 35 U.S.C. 112(f). Prong 1: a data analyzer (uses a generic placeholder), prong 2: configured to detect a level of the ssDNA primers by detection of a change in a FET electrical parameter (functional language), prong 3: sufficient structure for performing the function not recited. Therefore, claim 39 invoke 112(f). The corresponding structure for performing the functions is described in the specification. For example, the data analyzer may be a semiconductor parameter analyzer equipped with a probe station [para. 0153].
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 43-45 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 43 recites the data analyzer is configured to “compare the baseline and the post-amplification FET electrical parameter values; and identify a presence of the target polynucleotide via a statistically significant difference between the baseline and the post-amplification FET electrical parameter values”, which is not supported in the specification/figures. The specification does not disclose that the “data analyzer” performs these functions, as the data analyzer recited in paras. 0123, 0153, and 0350 is a semiconductor parameter analyzer equipped with a probe station that records the data from the FET biosensor and does not perform the functions of “comparing the baseline” and “identify a presence of the target polynucleotide”. Although Applicant claims support from original claims 25-27, these claims were directed to the method of detecting amplification comprising steps of “comparing the baseline…” and “identifying presence of the target polynucleotide” not using a data analyzer but could, for instance, be performed by a person interpreting the data output by the data analyzer. Therefore, claim 43 is a new matter. Claims 44-45 are further rejected by virtue of their dependence upon and because they fail to cure the deficiencies of indefinite claim 43.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 39, and 43-45 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.
Regarding Claim 39, the limitation “the crumpled semiconductor material” lacks antecedent basis. Claims 43-45 are further rejected by virtue of their dependence upon and because they fail to cure the deficiencies of indefinite claim 39.
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 1-5, 8, and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Hoffman (US 2018/0315750 A1) in view of Hwang 2016 (Highly specific SNP detection using 2D graphene electronics and DNA strand displacement. PNAS 2016; 113(26), 7088-7093), Hwang 2018 (DNA Nanotweezers and Graphene Transistor Enable Label-Free Genotyping. Adv. Mater. 2018; 30, 1-9), Nam (US 2015/0340436 A1), and Cranford (Packing efficiency and accessible surface area of crumpled graphene. Physical Review B. 2011; 84, 205451-1 to 205451-7). Tang (Constraint of DNA on Functionalized Graphene Improves its Biostability and Specificity. Small 2010; 6(11), 1205-1209) is used as evidence for claim 1.
Regarding Claim 1, Hoffman teaches a biosensor (a system for analysis of biological and/or chemical materials [para. 0280]) comprising:
a field effect transistor (FET) (chemically-sensitive field-effect transistor 1 in Figs. 4A-4C [para. 0281]) comprising:
a source electrode (source 22 in Figs. 4A-4C [para. 0282]);
a drain electrode (drain 24 in Figs. 4A-4C [para. 0282]), wherein the source and drain electrodes are separated from each other by an electrode separation distance (source 22 and drain 24 are separated from one another and positioned relative to the graphene layer 30 so as to form a gate structure 26 [para. 0282]);
a channel layer between the source electrode and the drain electrode (graphene layer 30 between the source 22 and drain 24 in Fig. 4A-4C [para. 0282]),
a sample reservoir (well 28, which is formed by gate structure 26 and chamber walls 29a and 29b in Fig. 4A [para. 0280]) in fluidic contact with the channel layer (fluid may be delivered in well 28, which is in contact with graphene channel layer 30 as illustrated in Figs. 4A-4C [para. 0282]);
a sample solution (fluid may include one or more reactants, such as analytes, in addition to a nucleic acid template [para. 0065, 0004]) that is an ionic solution (fluid may include one or more reactants, such as analytes, in addition to a nucleic acid template [para. 0065, 0004]; polynucleotide solutions for sequencing are in ionic solution), wherein the sample solution is positioned in the sample reservoir (fluid is delivered into well 28 [para. 0282]);
a gate electrode (gate structure 26 [para. 0282]) configured to electrically contact the sample solution in the sample reservoir (FET sensor detects a change when a solution containing reactants is added to the gate region [para. 0282]); the limitation “wherein the channel layer is configured to bind ssDNA at a higher affinity than dsDNA” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Hoffman teaches the channel is made of graphene (graphene layer 30 [para. 0282]), and, as evidenced by Tang, double-stranded DNA in the presence of graphene suggests that double-stranded DNA has a weaker interaction with graphene than single-stranded DNA (Tang, first para. col. 2, page 1206). Thus, the channel of Hoffman is capable of performing the claiming function above.
Hoffman is silent on wherein the channel layer has a crumpled geometry having a crumpled ratio of between 50% and 55%; a sample solution comprising a ssDNA target in the presence of dsDNA; a probe anchored to the channel layer, wherein the probe binds the target in the ionic solution to form a probe-target complex; and a data analyzer configured to detect a change in a concentration of the ssDNA target in the sample solution via a change in an electrical parameter of the FET.
Hwang 2016 teaches a graphene FET with a DNA probe (abstract), and teaches a sample solution having a ssDNA target (ssDNA, such as perfect match or single mismatch ssDNA, targeted to dsDNA probe attached to graphene layer [third para. col. 2, page 7091]); a probe anchored to the channel layer (graphene is functionalized with dsDNA probe [second and third para. col. 2, page 7090], dsDNA probe is anchored to graphene via 1-pyrenebutanoic acid (PASE) [first para. col. 2, page 7090]), wherein the probe binds the target in the ionic solution to form a probe-target complex (ssDNA binds with dsDNA via strand displacement [second para. col. 2, page 7091]); and a data analyzer (a semiconductor parameter analyzer equipped with a probe station [first para. col. 2, page 7093]) configured to detect a change in a concentration of the ssDNA target in the sample solution via a change in an electrical parameter of the FET (analyzer measures Dirac voltage of various concentrations of ssDNA probes [see Fig. 4 on page 7092]).
Hwang 2016 and Hoffman are considered analogous art to the claimed inventions because they are in the same field of graphene FET sensors. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the FET sensor of Hoffman to include a sample solution having a ssDNA target; a probe anchored to the channel layer, wherein the probe binds the target in the ionic solution to form a probe-target complex; and a data analyzer configured to detect a change in a concentration of the ssDNA target in the sample solution via a change in an electrical parameter of the FET, as taught by Hwang 2016, as detecting a ssDNA target from a sample opens development of diagnostic tools, including early detection of human diseases (Hwang 2016, [Conclusion, page 7092]).
Modified Hoffman is silent on wherein the sample solution comprises the presence of dsDNA; the channel layer has a crumpled geometry having a crumpled ratio of between 50% and 55%.
Hwang 2018 teaches a graphene FET to get ssDNA targets (abstract), and teaches the sample solution comprises the presence of dsDNA (ssDNA target in plasma circulating DNA, which contains dsDNA [second para. col. 2, page 7]).
Hwang 2018 and modified Hoffman are considered analogous art to the claimed inventions because they are in the same field of graphene FET sensors. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the sample solution of modified Hoffman to include the presence of dsDNA, as taught by Hwang 2018, as detecting a ssDNA target in the presence of dsDNA allows for early prognosis of diseases in real samples (Hwang 2018, [second para. col. 2, page 7 to first para. col. 1, page 8]).
Modified Hoffman is silent on the channel layer has a crumpled geometry having a crumpled ratio of between 50% and 55%.
Nam teaches wherein the channel layer has a crumpled geometry (graphene channel layer is crumpled by thermally-induced texturing [para. 0063])
Modified Hoffman and Nam are considered analogous art to the claimed inventions because they are in the same field of graphene FET sensors. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the channel layer of modified Hoffman to have a crumpled geometry, as taught by Nam, as increased surface area of textured graphene may enhance the degree of functionalization of the material and alter its chemical reactivity (Nam, [para. 0004]).
Modified Hoffman is silent on the channel layer has a crumpled geometry “having a crumpled ratio of between 50% and 55%.
Cranford teaches packing efficiency and surface area of crumpled graphene (abstract), and teaches the crumpling the graphene affects many properties of the graphene for sensors, such as increasing electrolyte contact with the graphene surface as well as other properties including variation in bands structure and electronic properties of the curvature (second para. col. 1, page 205451-5).
As the crumpled ratio of the crumpled graphene channel layer is made to have different crumpling ratios to increase electrolyte contact, as well as other properties including variation in bands structure and electronic properties of the curvature (Cranford, [second para. col. 1, page 205451-5]), the crumpled ratio affects the amount of electrolyte contact of the graphene layer, band structure, and electronic properties of the graphene (Cranford, [second para. col. 1, page 205451-5]). As amount of electrolyte contact in contact with the graphene surface is a variable that can be modified, among others, by adjusting the crumpled ratio of the graphene layer, the precise crumpled ratio would have been considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed crumpled ratio of the graphene channel cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, the crumpled ratio of the graphene channel of modified Hoffman to obtain crumpled ratio of between 50% and 55%. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Regarding Claim 2, modified Hoffman teaches the biosensor of claim 1.
Hoffman teaches wherein the channel layer is formed of a two-dimensional layer of material selected from the group consisting of graphene, silicene, germanane, MoS2 (2D material may be graphene, silicene, germanane, and MoS2 [para. 0026]).
Regarding Claim 3, modified Hoffman teaches the biosensor of claim 1.
Hoffman teaches wherein the channel layer is formed of graphene (graphene layer 30 [para. 0282]).
Regarding Claim 4, modified Hoffman teaches the biosensor of claim 1.
Hoffman teaches a support substrate layer that supports the source electrode, the drain electrode and the channel layer (silicon substrate 10 in Figure 4A [para. 0281], on which the FET can be fabricated on [para. 0021]).
Hoffman is silent on wherein the support substrate is formed of a material capable of undergoing shrinkage transformation to thereby crumple the channel layer that is supported by the support substrate.
Nam teaches wherein the support substrate is formed of a material capable of undergoing shrinkage transformation to thereby crumple the channel layer that is supported by the support substrate (polymer 12, such as polystyrene, which shrinks when exposed to heat to buckle the monolayer 10 to become crumples 14 [paras. 0029. 0031]).
It would be obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to substitute the support substrate of modified Hoffman with a support substrate material capable of undergoing shrinkage transformation to thereby crumple the channel layer that is supported by the support substrate, as taught by Nam, as adding a support capable of shrinking is one method for crumpling the FET channel layer (Nam, [para. 0029]).
Regarding Claim 5, modified Hoffman teaches the biosensor of claim 1, and teaches a probe anchored to the channel by a linker molecule (as outlined in the claim 1 rejection, Hwang 2016 teaches 1-pyrenebutanoic acid (PASE) was used to link graphene and the amine group at the N side of the DS probe (Hwang 2016, [first para. col. 2, page 7090]).
Regarding Claim 8, modified Hoffman teaches the biosensor of claim 1;
the limitation “wherein during use with the sample solution, a Debye length at the surface of the crumpled geometry is greater than a Debye length of an equivalent channel having a flat geometry” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, as outlined in the claim 1 rejection above, as the crumpled ratio of modified Hoffman is in the range of 50% to 55% and the structure of modified Hoffman is substantially identical to the apparatus of the instant application, it is capable of performing the claimed functions above.
Regarding Claim 10, modified Hoffman teaches the biosensor of claim 1.
Hoffman is silent on wherein the crumpled geometry corresponds to a multi-axial deformation or a uniaxial deformation of the channel layer.
Nam teaches wherein the crumpled geometry corresponds to a uniaxial deformation of the channel layer (the crumpled graphene geometry on polystyrene can be uniaxial [para. 0058]).
It would be obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the crumpled channel of modified Hoffman to correspond to a uniaxial deformation of the channel layer, as taught by Nam, as increased surface area of textured graphene may enhance the degree of functionalization of the material and alter its chemical reactivity (Nam, [para. 0004]).
Regarding Claim 11, modified Hoffman teaches the biosensor of claim 1.
Hoffman is silent on wherein the crumpled geometry corresponds to an average periodicity ranging between 1 nm and 100 nm and an average amplitude ranging between 1 nm and 100 nm.
Nam teaches that the crumples may be arranged with a predetermined spacing with a pitch of about 500 nm or less [para. 0036], and a root-mean-square roughness of about 500 nm or less [para. 0037]. The Examiner interprets the pitch and the root-mean-square roughness of the crumpled channel of Nam as average periodicity and average amplitude of the instant application, respectively.
Given the teachings of Nam regarding channel crumples with a pitch of about 500 nm or less, and a root-mean-square roughness of about 500 nm or less, it would be obvious to one or ordinary skill in the art prior to the effective filing date of the claimed invention to modify the channel geometry of modified Hoffman to have selected and utilized an average periodicity and an average amplitude within the disclosed respective range, including those amounts that overlap within the claimed range, as the electrical properties of graphene can be modulated via bending and shaping the graphene layer (Nam, [para. 0004]). It has been held that obviousness exists where the claimed ranges overlap or lie inside ranges disclosed by the prior art. See MPEP 2144.05 (I).
Regarding Claim 12, modified Hoffman teaches the biosensor of claim 1.
Hoffman is silent on wherein the channel layer is in continuous or discontinuous contact with a support substrate layer.
Nam teaches wherein the channel layer is in continuous or discontinuous contact with a support substrate layer (polystyrene [PS] substrate may conform to arbitrary geometries of the crumpled graphene [para. 0046], or can be transferred onto a different polymer substrate while maintaining the crumpled morphology [para. 0046]).
It would be obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to substitute the silicon substrate layer of modified Hoffman with polystyrene so that the channel layer is in continuous or discontinuous contact with a support substrate layer, as taught by Nam, as using a substrate that can conform to the channel layer allows for facile integration with other materials in unconventional ways (Nam, [para. 0046]).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Hoffman Hwang 2016, Hwang 2018, Nam, and Cranford, as applied to claim 1 above, and in view of Chin (Microfluidics-based diagnostics of infectious diseases in the developing world. Nature Medicine, 2011; 17(8), 1015-1020).
Regarding Claim 9, modified Hoffman teaches the biosensor of claim 1;
Hoffman teaches that the sample comprises a DNA sequence (DNA is isolated from a biological sample [para. 0009].
Hoffman is silent on the sample solution is unprocessed whole blood, plasma, saliva or sputum; the biosensor having a detection limit down to 600 nucleic acid molecules.
Chin teaches a biosensor microchip assay with easier handling of samples (abstract), and teaches the sample solution is unprocessed whole blood (<1 µL of unprocessed whole blood [first para. col. 1, page 1018]).
Modified Hoffman and Chin are considered analogous art to the claimed inventions because they are in the same field of biosensors with immobilized surface layers. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the sample solution of modified Hoffman to be unprocessed whole blood, as taught by Chin, as using unprocessed bloods allows for simplistic user use and the use of the biosensor in resource-limited settings (Chin, [first para. col. 2, page 1015);
the limitation “the biosensor having a detection limit down to 600 nucleic acid molecules” is a functional recitation of the biosensor of modified Hoffman. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, as the apparatus of modified Hoffman is identical to the apparatus outlined in claim 9 of the instant application, and Chin teaches the sample solution is unprocessed whole blood (Chin [first para. col. 1, page 1018]), the biosensor of modified Hoffman is configured to perform the claimed function above.
Claims 39 and 43-45 are rejected under 35 U.S.C. 103 as being unpatentable over Hoffman in view of Hwang 2016 and Nam. Georgakilas (Noncovalent Functionalization of Graphene and Graphene Oxide for Energy Materials, Biosensing, Catalytic, and Biomedical Applications 2016. Chem. Rev. 116, 5464-5519) and Tang are used as evidence for claim 39.
Regarding Claim 39, Hoffman teaches a system (a system for analysis of biological and/or chemical materials [para. 0280]) comprising:
a field effect transistor FET (chemically-sensitive field-effect transistor 1 in Figs. 4A-4C [para. 0281]) having:
a source electrode (source 22 in Figs. 4A-4C [para. 0282]);
a drain electrode (drain 24 in Figs. 4A-4C [para. 0282]), wherein the source and drain electrodes are separated from each other by an electrode separation distance (source 22 and drain 24 are separated from one another and positioned relative to the graphene layer 30 so as to form a gate structure 26 [para. 0282]);
a channel layer between the source electrode and the drain electrode (graphene layer 30 in Fig. 4A-4C [para. 0282]),
a channel layer receiving surface that forms part of a sample reservoir (well 28, is formed by the graphene channel 30 and chamber walls 29a and 29b, as illustrated in Fig. 4A [para. 0280]);
wherein the amplifiable sample solution (fluid may include one or more reactants, such as analytes, in addition to a nucleic acid template [para. 0065, 0004]) is an ionic solution having the target polynucleotide (fluid may include one or more reactants, such as analytes, in addition to a nucleic acid template [para. 0065, 0004]; polynucleotide solutions for sequencing are in ionic solution), wherein the amplifiable sample solution is positioned in the sample reservoir (fluid is delivered into well 28 [para. 0282]);
the amplifiable sample solution comprising ssDNA primers and amplification reagents to amplify the target polynucleotide (fluid may include one or more reactants, such as analytes, in addition to a nucleic acid template [para. 0065, 0004]),
the limitations “for detecting a target polynucleotide in an amplifiable sample solution; wherein during use the amplification sample solution contacts the channel layer receiving surface of the sample reservoir” are functional limitations. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Hoffman teaches that the FET sensor may use DNA hybridization [para. 0032]; that the fluid, or sample, is delivered into well 28 [para. 0282], and that binding or synthesis steps can be used to amplify the bound DNA [para. 0011]. Thus, the chemically-sensitive field-effect transistor 1 and the electrical detector (processor) are configured to performed the claimed functions above;
Hoffman is silent on wherein ssDNA primers during use bind to the channel layer receiving surface by a noncovalent π-π interaction between the crumpled semiconductor material and an aromatic ring of the ssDNA at a higher affinity than dsDNA; and a data analyzer configured to detect a level of the ssDNA primers by detection of a change in a FET electrical parameter.
Nam teaches wherein the channel layer comprises a crumpled semiconductor material (graphene channel layer is crumpled by thermally-induced texturing [para. 0063], which can be two dimensional [para. 0026]).
Hoffman and Nam are considered analogous art to the claimed inventions because they are in the same field of graphene FET sensors. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the channel layer of Hoffman to channel layer a two-dimensional crumpled semiconductor material, as taught by Nam, as increased surface area of textured graphene may enhance the degree of functionalization of the material and alter its chemical reactivity (Nam, [para. 0004]);
the limitation “wherein ssDNA primers during use bind to the channel layer receiving surface by a noncovalent π-π interaction between the crumpled semiconductor material and an aromatic ring of the ssDNA at a higher affinity than dsDNA” is a functional limitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Nam teaches that a channel with a crumpled channel can be made of graphene [para. 0041], which as evidenced by Georgakilas, has favorable π-π interactions with DNA ([entire page 5477 and Figure 6, page 5477]), and, as evidenced by Tang, double-stranded DNA in the presence of graphene suggests that double-stranded DNA has a weaker interaction with graphene than single-stranded DNA (Tang, first para. col. 2, page 1206). Thus, the crumpled geometry channel of the FET biosensor of modified Hoffman is capable of performing the claimed function above.
Hoffman is silent a data analyzer configured to detect a level of the ssDNA primers by detection of a change in a FET electrical parameter.
Hwang 2016 teaches a data analyzer (a semiconductor parameter analyzer equipped with a probe station [first para. col. 2, page 7093]) configured to detect a level of the ssDNA primers by detection of a change in a FET electrical parameter (analyzer measures Dirac voltage of various concentrations of ssDNA probes [see Fig. 4 on page 7092]).
Hwang 2016 and modified Hoffman are considered analogous art to the claimed inventions because they are in the same field of graphene FET sensors. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the FET sensor of Hoffman to include a data analyzer configured to detect a level of the ssDNA primers by detection of a change in a FET electrical parameter, as taught by Hwang 2016, as detecting a ssDNA target from a sample opens development of diagnostic tools, including early detection of human diseases (Hwang 2016, [Conclusion, page 7092]).
Regarding Claim 43, modified Hoffman teaches the system of claim 39; the limitations “wherein the data analyzer is configured to: receive the FET electrical parameter prior to amplification of the sample solution to obtain a baseline FET electrical parameter value; receive the FET electrical parameter after the step of conducting the amplification to obtain a post-amplification FET electrical parameter value; compare the baseline and the post-amplification FET electrical parameter values; and identify a presence of the target polynucleotide via a statistically significant different between the baseline and the post-amplification FET electrical parameter values” are functional recitations. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, as detailed in Fig. 4 of Hwang 2016 on page 7092, the data analyzer of Hwang 2016 generates Dirac voltages for a target DNA stand including a probe without the target DNA strand to generate a baseline. The Dirac voltages generated can be compared to the probe baseline to identify a presence of the target DNA, and, depending on a statistical difference between the baseline and perfect match Dirac voltages, which is the difference in Dirac voltage function comparing the baseline to the perfect match, allows for identification of the target ssDNA strand. Note that the baseline can also be prior to amplification and the Dirac voltages can be measured after post-amplification FET electrical parameter values. Thus, the data analyzer of modified Hoffman is capable of performing the claimed functions above.
Regarding Claim 44, modified Hoffman teaches the system of claim 43, and teaches wherein the FET electrical parameter is a Dirac point shift voltage (as outlined in the claim 43 rejection above, Hwang 2016 teaches the data analyzer measures Dirac voltage of various concentrations of ssDNA probes [see Fig. 4 on page 7092]).
Regarding Claim 45, modified Hoffman teaches the system of claim 43;
the limitation “wherein the statistically significant difference corresponds to an at least 10% difference of the baseline and post-amplification FET electrical parameter” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, as detailed in Fig. 4 of Hwang 2016 on page 7092, the minimum Dirac voltage of the probe baseline compared to the 10 µM perfect match in Fig. 4 is ~80% different (at the minimum Dirac voltage of ~0.35 V, the difference between the probe baseline and 10 µM perfect match is (4.5-2.5)/2.5 x 100% = 80%). As the statistical difference is at least 10% from the baseline compared to the target DNA, the data analyzer of modified Hoffman is capable of performing the claimed function above.
Response to Arguments
Applicant's arguments, see Remarks Pgs. 9-11, filed 06/08/2026, with respect to the 35 U.S.C. § 103 rejections have been fully considered.
Applicant’s Argument #1
Applicant has amended independent claim 1 to recite “a data analyzer configured to detect a change in a concentration of the ssDNA target in the sample solution via a change in an electrical parameter of the FET”, which is not taught by the cited prior art. Claim 39 has been similarly amended to recite “a data analyzer”. Applicant notes that computer-implemented functional claim limitations may not be ignored as merely statements of intended use.
Examiner’s Response #1
Applicant argues have been fully considered, but are moot in terms of the new grounds of rejection above. The Examiner notes that the functions of the data analyzer for claims 43-45 appear to be new matter. Thus, the data analyzer for claims 43-45 is not being interpreted as having controller limitations.
Conclusion
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/R.L.G./Examiner, Art Unit 1795
/SHIZHI QIAN/Primary Examiner, Art Unit 1795
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