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 .
Response to Amendment
The Amendment filed 08/27/2026 has been entered. Claims 1, 4, 6-10, and 13-22 remain pending in the application. Claims 16-22 are withdrawn. New grounds of rejections necessitated by amendments are discussed below.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 4, 6-10, and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Kinz-Thompson et al. (US 20130294972 A1; cited in the IDS filed 03/24/2022) in view of Rothberg et al. (US 20150141268 A1) and Ronaghi et al. (US 20090032401 A1).
Regarding claim 1, Kinz-Thompson teaches an apparatus (Fig. 1; abstract) for sensing a molecule (interpreted as an intended use, see MPEP 2114; abstract; Fig. 1 shows biomolecule of interest 160), the apparatus comprising:
a substrate layer (substrate 120);
a sample interface layer (side wall 110) having a sample interface side (top side of side wall 110 opposite of element 130) and a substrate layer facing side (bottom side of side wall 110 adjacent to element 130);
an electrically conductive layer (Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, i.e. electrically conductive layer) disposed between the substrate layer facing side of the sample interface layer and the substrate layer (Fig. 1 shows adhesion layer 130 is between elements 110 and 120);
wherein a side wall portion of the sample interface layer and a sidewall portion of the electrically conductive layer each define a respective opening therethrough that, aligned, each compose at least a portion of a side wall of a well (Fig. 1 shows side wall portions of elements 110 and 130 define a respective opening that are aligned and compose a side wall of nano-well 101), wherein a bottom boundary of the well is defined by the substrate layer (Fig. 1 shows nano-well 101 with a bottom boundary defined by substrate 120),
the side wall portion of the electrically conductive layer being positioned in a bottom half of the side wall of the well (Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, i.e. electrically conductive layer, is positioned in a bottom half of the sidewall of the nano-well 101);
the electrically conductive layer (Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, i.e. electrically conductive layer), when energized with a given polarity relative to an electrically conductive element, producing an electric field from the electrically conductive layer through the well to the electrically conductive element (interpreted as a functional limitation of the adhesion layer 130; Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, thus the titanium or metallic adhesion layer 130 is structurally capable of being energized with a given polarity to produce an electric field to produce an electric field as claimed since the layer is made of titanium or another metal, which is at least partially conductive), the electric field sufficient to draw the molecule, the molecule being of polarity opposite from the given polarity, from the sample at the sample interface side through the well toward the electrically conductive layer (interpreted as a functional limitation of the adhesion layer 130; Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, thus the titanium or metallic adhesion layer 130 is structurally capable of producing an electric field of a polarity as claimed to draw or attract the molecule from the top side of the side wall 110, through the nano-well 101 and towards the adhesion layer 130, i.e. bottom of the wall of the well; note that “molecule” is not positively recited structurally);
wherein the substrate layer is a transparent material at visible and near-infrared wavelengths (paragraph [0026] teaches the substrate 120 is a transparent material, such as glass; therefore, the glass is transparent at visible and near-infrared wavelengths) and the sample interface layer is an optically reflective layer for the visible and near-infrared wavelengths (paragraph [0026] teaches side wall 101 is made from gold, wherein gold is a structurally material that is capable of optically reflecting visible and near-infrared wavelengths, i.e. optically reflective layer);
an optical sensor system (Figs. 1 and 8 and paragraph [0040], arrangement of the laser, collection optics, dichroic beam splitter, and objective), the optical sensor system having an arrangement (Figs. 1 and 8 and paragraph [0040], arrangement of the laser, collection optics, dichroic beam splitter, and objective) to direct a wavelength to the well via the substrate layer (interpreted as an intended use of the arrangement, see MPEP 2114; Figs. 1 and 8 and paragraph [0040], teach the arrangement of the laser, dichroic beam splitter, and objective directs a wavelength of light 180 to nano-well 101 via substrate 120) and collect a response from the molecule via the substrate layer (interpreted as an intended use of the arrangement, see MPEP 2114; Figs. 8-9 and paragraphs [0040],[0042] teaches fluorescence is collected from a molecule from the apparatus), the optically reflective layer limiting transmission of the wavelengths to the sample above the sample interface layer (interpreted as a functional limitation of the optically reflective layer, see MPEP 2114; paragraph [0026] teaches side wall 101 is made from gold, wherein gold is a structurally material that is capable of optically reflecting wavelengths; therefore, the gold side wall is capable of limiting transmission of wavelengths as claimed);
wherein the visible wavelengths range from about 400 nm to about 800 nm (note that “visible wavelengths” is interpreted as a functional limitation of the substrate layer and optically reflective layer; paragraph [0026] teaches the substrate 120 is a transparent material, such as glass; therefore, the glass is structurally transparent at visible wavelengths range from about 400 nm to about 800 nm; paragraph [0026] teaches side wall 101 is made from gold, wherein gold is a structurally material that is capable of optically reflecting the visible wavelengths range from about 400 nm to about 800 nm), and wherein the well is a zero-mode waveguide relative to the visible wavelengths (paragraph [0026] teaches the zero-mode waveguide, ZMW, includes the nano-well 101; thus, the nano-well 101 is a ZMW relative to the visible wavelengths);
an organic matter (Fig. 1, target molecule 150; paragraph [0029] teaches the target biomolecule can be streptavidin, i.e. organic matter), fixedly located in the well (Fig. 1 shows target molecule 150 is fixed in the nano-well 101 via elements 125 and 126), that is selected based on a property that enables the molecule to chemically couple thereto (paragraph [0030] teaches target biomolecule 150 can bind to the biomolecule of interest), wherein the molecule is DNA or RNA (note that “the molecule” is not positively recited structurally; paragraph [0026] teaches the biomolecule of interest includes DNA or RNA).
While Kinz-Thompson teaches biomolecules of interest may include those which associate with other molecules such as polymerases, enzymes, or ribozymes (paragraph [0026]), Kinz-Thompson fails to teach:
an electrically conductive element positioned in a sample that is in contact with the sample interface side of the sample interface layer;
the electrically conductive layer being in electrical connection with a voltage potential source configured to apply a voltage potential difference between the electrically conductive element and the electrically conductive layer;
the electrically conductive layer, when energized with a given polarity relative to the electrically conductive element, producing an electric field from the electrically conductive layer through the well to the electrically conductive element, the electric field sufficient to draw the molecule, the molecule being of polarity opposite from the given polarity, from the sample at the sample interface side through the well toward the electrically conductive layer; and
wherein the organic matter is a complex comprising a DNA or RNA-processing enzyme to which the molecule binds.
Rothberg teaches devices and systems capable of sequencing single nucleic acid molecules with high accuracy (paragraph [0161]), wherein a DNA polymerase, i.e. DNA processing enzyme, is immobilized or attached to a sample wall, such as the bottom of a sample well (paragraph [0161]). Rothberg teaches a sample well contains enzymes such as a polymerase needed for nucleic acid synthesis (paragraph [0161]). Rothberg teaches nucleic acid sequencing of a plurality of single-stranded target nucleic acid templates may be completed where multiple sample wells are available, wherein each sample well is contacted with appropriate reagents, such as polymerase (paragraph [0166]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the organic matter of Kinz-Thompson to incorporate the teachings of DNA or RNA-processing enzymes of Rothberg (paragraphs [0161],[0166]) to provide: wherein the organic matter is a complex comprising a DNA or RNA-processing enzyme to which the molecule binds. Doing so would have a reasonable expectation of successfully improving processing of a desired molecule such as DNA by providing an appropriate reagent to the well as taught by Rothberg (paragraphs [0161],[0166]).
Modified Kinz-Thompson fails to teach: an electrically conductive element positioned in a sample that is in contact with the sample interface side of the sample interface layer;
the electrically conductive layer being in electrical connection with a voltage potential source configured to apply a voltage potential difference between the electrically conductive element and the electrically conductive layer;
the electrically conductive layer, when energized with a given polarity relative to the electrically conductive element, producing an electric field from the electrically conductive layer through the well to the electrically conductive element, the electric field sufficient to draw the molecule, the molecule being of polarity opposite from the given polarity, from the sample at the sample interface side through the well toward the electrically conductive layer.
Ronaghi teaches a method and apparatus that use an electric field for improved biological assays; the electric field is applied across a device having wells; and by controlled use of the electric field charged species in a fluid in a fluid channel are directed into or out of the well by an electric field between the electrodes; wherein the electric-field induced movement is involved in DNA sequencing and synthesis (abstract). Ronaghi teaches one of the main challenges in sequencing by synthesis is to deliver the nucleotide to the vicinity of DNA to enable rapid incorporation and to remove the nucleotide efficiently to enhance the read-length ([0008]). Ronaghi teaches the device is designed to enhance the overall quality of signals obtained from the light generating reactions and to improve the read-length ([0022]). Ronaghi teaches an electrically conductive layer (Fig. 2B, electrodes 119) disposed between a substrate layer facing side of a sample interface layer (Figs. 1 and 2B, photoresist layer 110 above electrodes 119) and a substrate layer (Fig. 2B, transparent layer 117; Fig. 2B shows electrodes 119 is between photoresist layer 110 and transparent layer 117); wherein a side wall portion of the electrically conductive layer define a respective opening therethrough (Fig. 2B); and that, aligned, each of the side wall portion of the sample interface layer and electrically conductive layer compose at least a portion of a sidewall of a well (Fig. 2B); the side wall portion of the electrically conductive layer (119) being positioned in a bottom half of the side wall of the well (Fig. 2B; [0061]), and the electrically conductive layer being in electrical connection with a voltage potential source configured to apply a voltage potential difference between an electrically conductive element and the electrically conductive layer (Fig. 2B and [0069] teach electrodes 119 connected to voltage source 118 to apply a voltage between electrodes 112 and electrodes 119); the electrically conductive layer, when energized with a given polarity relative to the electrically conductive element, producing an electric field from the electrically conductive layer through the well to the electrically conductive element, the electric field sufficient to draw a molecule, the molecule being of polarity opposite from the given polarity, from the sample at a sample interface side through the well toward the electrically conductive layer (Fig. 2B and [0022],[0069] teaches applying a voltage across the electrodes to produce an electric field to draw nucleotides in the wells towards electrodes 119 and depending on polarity of the field, nucleotides concentrate or repel away from the DNA beads in the wells). Ronaghi teaches the applying a voltage to the bottom and top slide achieves concentration of molecules near the bottom of the well ([0097]-[0098]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the apparatus of modified Kinz-Thompson to incorporate Ronaghi’s teachings of an electrically conductive layer between a sample interface layer and substrate layer (Fig. 2B) and applying a voltage potential difference between an electrically conductive element and the electrically conductive layer to draw molecules towards the bottom of a well (Fig. 2B; [0022],[0069],[0097]-[0098]) to provide: an electrically conductive element positioned in a sample that is in contact with the sample interface side of the sample interface layer; the electrically conductive layer being in electrical connection with a voltage potential source configured to apply a voltage potential difference between the electrically conductive element and the electrically conductive layer; the electrically conductive layer, when energized with a given polarity relative to the electrically conductive element, producing an electric field from the electrically conductive layer through the well to the electrically conductive element, the electric field sufficient to draw the molecule, the molecule being of polarity opposite from the given polarity, from the sample at the sample interface side through the well toward the electrically conductive layer. Doing so would have a reasonable expectation of successfully improving rapid incorporation and removal of molecules in the well to enhance read-length and to enhance overall quality of signals obtained from light generating reactions of the apparatus as taught by Ronaghi ([0008],[0022],[0097]-[0098]).
Note that the “molecule” is not positively recited structurally and the limitations of the sample interface layer and electrically conductive layer are interpreted as functional limitations of the claimed apparatus. The inclusion of the material or article, i.e. “molecule”, worked upon by a structure, i.e. the sample interface layer and electrically conductive layer, being claimed does not impart patentability to the claims (see MPEP 2115).
Regarding claim 4, Kinz-Thompson further teaches wherein the sample interface layer, electrically conductive layer, and substrate layer define multiple wells (paragraph [0027] teaches the device can include arrays or matrix of nano-wells separated by side walls 110), and wherein the sensor system is configured to sense a respective molecule in the multiple wells in a parallel manner (interpreted as a functional limitation of the sensor system, see MPEP 2114; paragraphs [0021],[0043] teaches measurement of fluorescence in different nano-wells, thus the sensor system is structurally capable of sensing a respective molecule in the wells in a parallel manner at a later time).
Regarding claim 6, Kinz-Thompson further teaches wherein the wells (Figs. 1 and 6, nano-well 101) are cylindrically shaped holes (paragraphs [0027], [0037] teach the nano-wells have circular cross sections, i.e. cylindrically shaped holes). Kinz-Thompson fails to explicitly teach the cylindrically shaped hole of about 100nm to about 150nm in diameter and at least 100 nm in length.
Kinz-Thompson teaches the nano-well can have a diameter of 25-500 nm (paragraph [0027]) and a height, i.e. length, of 50-500 nm (paragraph [0027]).
Since Kinz-Thompson teaches the nano-well can have a diameter of 25-500 nm (paragraph [0027]) and a height, i.e. length, of 50-500 nm (paragraph [0027]), wherein the taught diameter range of 25-500 nm overlaps with the claimed diameter range of 100-150 nm and the taught length range of 50-500 nm overlaps with the claimed length range of at least 100 nm, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the wells of Kinz-Thompson to provide where the cylindrically shaped hole of about 100nm to about 150nm in diameter and at least 100 nm in length. I.e., it would have been prima facia obvious to have selected the overlapping portion of the range (i.e. diameter of 100-150 nm; length of at least 100 nm) from the taught diameter of 25-500 nm (paragraph [0027]) and a height, i.e. length, of 50-500 nm (paragraph [0027]) (In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); see MPEP 2144.05 (I)).
Regarding claim 7, Kinz-Thompson further teaches wherein the transparent material includes fused silica, quartz, or glass (paragraph [0026] teaches the substrate 120 is a transparent material, such as glass).
Regarding claim 8, Kinz-Thompson further teaches wherein the sample interface layer is a metal (paragraph [0026] teaches side wall 101 is made from gold). Modified Kinz-Thompson fails to teach the apparatus of claim 1 further comprising an electrically non-conductive layer positioned between the sample interface layer and the electrically conductive layer, wherein a side wall portion of the electrically non-conductive layer defines a respective opening aligned with the opening of the side wall portion of the sample interface layer and the opening of the side wall portion of the electrically conductive layer.
Rothberg teaches a device capable of performing biomolecule detection and/or analysis, such as single-molecule nucleic acid sequencing, wherein the device includes a sample well (abstract). Rothberg teaches a sample well may be formed as a nanohole and may be formed as a zero-mode waveguide having a cylindrical shape (paragraph [0208]). Rothberg teaches an embodiment of the device (Fig. 3-7F) comprising a sample interface layer (3-230), substrate layer (3-235), and an electrically conductive layer (Fig. 3-7F and paragraph [0225], first layer 3-232 which is a semiconducting or conducting material) between the sample interface layer and substrate layer (Fig. 3-7F). Rothberg teaches the sample interface layer is a metal (paragraph [0225], first layer 3-230 which is a conductor or semiconductor; paragraph [0298] teaches top layer 3-230 is a conductive metal; paragraph [0364] teaches conductive material 3-230), and further comprising an electrically non-conductive layer (Fig. 3-7F and paragraph [0225], second layer 3-234 which is an insulator or dielectric, i.e. electrically non-conductive layer) positioned between the sample interface layer (3-230) and the electrically conductive layer (3-232), wherein a side wall portion of the electrically non-conductive layer defines a respective opening aligned with a side wall portion of the opening of the sample interface layer and the opening of the side wall portion of the electrically conductive layer (Fig. 3-7F shows aligned openings of elements 3-230, 3-234, 3-232). Rothberg teaches conductive materials include gold and aluminum (paragraph [0364]). Rothberg teaches multi-layer materials used for forming a sample well may be selected to suppress excitation radiation from propagating beyond the sample well and multi-layer structure into the bulk specimen (paragraph [0225]).
Since Rothberg teaches wells for sensing a molecule, similar to Kinz-Thompson, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the apparatus of modified Kinz-Thompson to incorporate the teachings of multi-layer materials used to for a sample well of Rothberg (Fig. 3-7F; paragraphs [0225],[0298],[0364]) to provide: the apparatus of claim 1 further comprising an electrically non-conductive layer positioned between the sample interface layer and the electrically conductive layer, wherein a side wall portion of the electrically non-conductive layer defines a respective opening aligned with the opening of the side wall portion of the sample interface layer and the opening of the side wall portion of the electrically conductive layer. Doing so would have a reasonable expectation of successfully improving insulation of the electrically conductive layer and suppressing excitation radiation from propagating beyond a sample well as taught by Rothberg (paragraph [0225]).
Furthermore, the claimed limitations are obvious because all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements (i.e. and the claimed electrically non-conductive layer) by known methods with no change in their respective functions (i.e. sensing and analyzing a molecule in a well while insulating the electrically conductive layer), and the combinations yielded nothing more than predictable results (i.e. providing the claimed electrically non-conductive layer would yield nothing more than the obvious and predictable result of enabling molecule sensing and analysis within a well while insulating the electrically conductive layer). See MPEP 2143(A).
Regarding claim 9, modified Kinz-Thompson fails to teach wherein the electrically non-conductive layer is made of a material including silicon dioxide, aluminum oxide, or silicon nitride.
Rothberg teaches an insulating layer may comprise an oxide, such as silicon dioxide (paragraph [0298]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the electrically non-conductive layer of modified Kinz-Thompson to incorporate the teachings of a silicon dioxide insulating layer of Rothberg (paragraph [0298]) to provide wherein the electrically non-conductive layer is made of a material including silicon dioxide, aluminum oxide, or silicon nitride. Doing so would have a reasonable expectation of successfully insulating desired layers of the apparatus.
Regarding claim 10, Kinz-Thompson further teaches wherein the metal includes platinum, gold, silver, titanium, aluminum, or combination thereof (paragraph [0026] teaches side wall 101 is made from gold).
Regarding claim 13, Kinz-Thompson further teaches wherein the organic matter (Fig. 1, target molecule 150) is attached to an electrically non-conductive layer in the well (Fig. 1 shows target molecule 150 attached to substrate 120 in the nano-well 101 via elements 125 and 126; paragraph [0026] teaches the substrate is glass, which is an electrically non-conductive layer; note that the BRI of “electrically non-conductive layer” includes the interpretation that the substrate layer is the electrically non-conductive layer) through biotinylated polyethylene glycol silane-based functionalization of the substrate layer (Fig. 1 and paragraph [0029] teaches target molecule 150 is attached to the glass substrate 120 through second functional molecule 125 comprising polyethylene glycol, wherein the second functional molecule includes a silane end group that is biotinylated, thus the substrate 120 is functionalized with biotinylated polyethylene glycol silane).
Regarding claim 14, Kinz-Thompson further teaches wherein the well forms the shape of a cylinder, truncated cone, or any polygonal prism (Fig. 1 and paragraphs [0027], [0037] teach the nano-wells have circular cross sections, i.e. cylindrically shaped holes).
Regarding claim 15, Kinz-Thompson further teaches wherein an opening at the sample interface side of the sample interface layer (opening of nano-well 101 at the top side of side wall 110 opposite of element 130) has a diameter from about 20 nm to about 250 nm (paragraph [0027] teaches the nano-well has a diameter of 200-250 nm).
Claims 1, 4, 7, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Larkin et al. (Larkin, J.; et al., "Length-independent DNA packing into nanopore zero-mode waveguides for low-input DNA sequencing," Nature nanotechnology 2017, 12 (12), 1169l; cited in the IDS filed 04/28/2022; Additionally, see Supplemental Information of Larkin) in view of Ronaghi et al. (US 20090032401 A1).
Regarding claim 1, Larkin teaches an apparatus for sensing a molecule (abstract; Fig. 1), the apparatus comprising:
a substrate layer (Fig. 1 and Supplemental Information, Supplementary Figure 1, interpreted as the SiO2 layer, i.e. silicon dioxide layer);
a sample interface layer (Fig. 1 and Supplemental Information, Supplementary Figure 1, interpreted as the aluminum layer and SiO2 layer on top of the base SiO2 layer) having a sample interface side (Fig. 1, top of the aluminum layer and SiO2 layer) and a substrate layer facing side (Fig. 1, bottom of the aluminum layer and SiO2 layer facing the SiO2 layer);
an electrically conductive element positioned in a sample that is in contact with the sample interface side of the sample interface layer (Figs. 1 and 4a teaches a voltage is applied using at least an electrically conductive element positioned in the upper area of a sample solution that is in contact with the top of the aluminum layer and SiO2 layer);
wherein a side wall portion of the sample interface layer define a respective opening therethrough (Figs. 1 and 4a shows an opening through the aluminum layer and SiO2 layer on top of the base SiO2 layer) that compose at least a portion of a sidewall of a well (Figs. 1b and 4a shows the aluminum layer and SiO2 layer on top of the base SiO2 layer compose a portion of a sidewall of a well), wherein a bottom boundary of the well is defined by the substrate layer (Figs. 1b and 4a shows the bottom of boundary of the well is defined by the SiO2 layer);
wherein the substrate layer (Fig. 1 and Supplemental Information, Supplementary Figure 1, interpreted as the SiO2 layer, i.e. silicon dioxide layer) is a transparent material at visible and near-infrared wavelengths (Fig. 1 and Supplemental Information Supplementary Figure 1 teaches SiO2, which is a transparent material at visible and near-infrared wavelengths; Fig. 1d) and the sample interface layer is an optically reflective layer for the visible and near-infrared wavelengths (Fig. 1 and Supplemental Information Supplementary Figure 1, interpreted as including an aluminum layer, which is an optically reflective layer for the visible and near-infrared wavelengths);
an optical sensor system (Fig. 1b, fluorescence microscope), the optical sensor system having an arrangement to direct a wavelength to the well via the substrate layer (Fig. 1b teaches three-laser illumination that directs wavelengths to the well via the SiO2 layer) and collect a response from the molecule via the substrate layer (Figs. 1b-d teaches collecting response from a molecule via the SiO2 layer of the NZMW), the optically reflective layer limiting transmission of the wavelengths to the sample above the sample interface layer (interpreted as a functional limitation; Fig. 1 and Supplemental Information Supplementary Figure 1, interpreted as including an aluminum layer, which is an optically reflective layer for the visible and near-infrared wavelengths; therefore, the optically reflective layer including aluminum is structurally identical to the claimed optically reflective layer, and would have the ability to perform the function recited in the claim, see MPEP 2112.01 (I));
wherein the visible wavelengths range from about 400 nm to about 800 nm (Fig. 1d), and wherein the well is a zero-mode waveguide relative to the visible wavelengths (Fig. 1 teaches the well is a nanopore of the nanopore zero-mode waveguide, i.e. NZMW); and
an organic matter, fixedly located in the well (Figs. 1b and 4a teaches DNA/polymerase complex bound to the surface in the well; wherein “organic matter” is interpreted as the polymerase), that is selected based on a property that enables the molecule to chemically couple thereto (page 1172, section “Efficient DNA binding to NZMW surface”, first paragraph teaches DNA is bound to a DNA polymerase, therefore the polymerase is selected based on a property that enables DNA to couple to the polymerase), wherein the molecule is DNA or RNA (Fig. 4a and page 1172, section “Efficient DNA binding to NZMW surface” teaches the molecule is “DNA”), and wherein the organic matter is a complex comprising a DNA or RNA- processing enzyme to which the molecule binds (Fig. 4a and page 1172, section “Efficient DNA binding to NZMW surface” teaches polymerase, i.e. DNA-processing enzyme, to which DNA binds).
Larkin fails to teach: an electrically conductive layer disposed between the substrate layer facing side of the sample interface layer and the substrate layer; wherein a side wall portion of the electrically conductive layer define a respective opening therethrough; and that, aligned, each of the side wall portion of the sample interface layer and electrically conductive layer compose at least a portion of a sidewall of a well; the side wall portion of the electrically conductive layer being positioned in a bottom half of the side wall of the well, and the electrically conductive layer being in electrical connection with a voltage potential source configured to apply a voltage potential difference between the electrically conductive element and the electrically conductive layer; the electrically conductive layer, when energized with a given polarity relative to the electrically conductive element, producing an electric field from the electrically conductive layer through the well to the electrically conductive element, the electric field sufficient to draw the molecule, the molecule being of polarity opposite from the given polarity, from the sample at the sample interface side through the well toward the electrically conductive layer.
Larkin teaches a voltage potential source configured to apply a voltage potential difference to the electrically conductive element to produce an electric field to draw a DNA/polymerase complex from the sample at the sample interface side through the well towards the bottom of the well (Fig. 4a and page 1173, right column teaches application of voltage draws the DNA into the NZMWs; Fig. 2 teaches electrical field simulation of the NZMW; page 1170, left column, section “Voltage-driven…” teaches electric field generated by voltage application provides DNA with energy for DNA packing).
Ronaghi teaches a method and apparatus that use an electric field for improved biological assays; the electric field is applied across a device having wells; and by controlled use of the electric field charged species in a fluid in a fluid channel are directed into or out of the well by an electric field between the electrodes; wherein the electric-field induced movement is involved in DNA sequencing and synthesis (abstract). Ronaghi teaches one of the main challenges in sequencing by synthesis is to deliver the nucleotide to the vicinity of DNA to enable rapid incorporation and to remove the nucleotide efficiently to enhance the read-length ([0008]). Ronaghi teaches the device is designed to enhance the overall quality of signals obtained from the light generating reactions and to improve the read-length ([0022]). Ronaghi teaches an electrically conductive layer (Fig. 2B, electrodes 119) disposed between a substrate layer facing side of a sample interface layer (Figs. 1 and 2B, photoresist layer 110 above electrodes 119) and a substrate layer (Fig. 2B, transparent layer 117; Fig. 2B shows electrodes 119 is between photoresist layer 110 and transparent layer 117); wherein a side wall portion of the electrically conductive layer define a respective opening therethrough (Fig. 2B); and that, aligned, each of the side wall portion of the sample interface layer and electrically conductive layer compose at least a portion of a sidewall of a well (Fig. 2B); the side wall portion of the electrically conductive layer (119) being positioned in a bottom half of the side wall of the well (Fig. 2B; [0061]), and the electrically conductive layer being in electrical connection with a voltage potential source configured to apply a voltage potential difference between an electrically conductive element and the electrically conductive layer (Fig. 2B and [0069] teach electrodes 119 connected to voltage source 118 to apply a voltage between electrodes 112 and electrodes 119); the electrically conductive layer, when energized with a given polarity relative to the electrically conductive element, producing an electric field from the electrically conductive layer through the well to the electrically conductive element, the electric field sufficient to draw a molecule, the molecule being of polarity opposite from the given polarity, from the sample at a sample interface side through the well toward the electrically conductive layer (Fig. 2B and [0022],[0069] teaches applying a voltage across the electrodes to produce an electric field to draw nucleotides in the wells towards electrodes 119 and depending on polarity of the field, nucleotides concentrate or repel away from the DNA beads in the wells). Ronaghi teaches the applying a voltage to the bottom and top slide achieves concentration of molecules near the bottom of the well ([0097]-[0098]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the apparatus of Larkin to incorporate Larkin’s teachings of applying a voltage potential to produce an electric field to draw a molecule towards the bottom of the well (Fig. 4a and page 1173, right column; page 1170, left column, section “Voltage-driven…”) and Ronaghi’s teachings of an electrically conductive layer between a sample interface layer and substrate layer (Fig. 2B) and applying a voltage potential difference between an electrically conductive element and the electrically conductive layer to draw molecules towards the bottom of a well (Fig. 2B; [0022],[0069],[0097]-[0098]) to provide for each well of Larkin (Fig. 1b): an electrically conductive layer disposed between the substrate layer facing side of the sample interface layer and the substrate layer; wherein a side wall portion of the electrically conductive layer define a respective opening therethrough; and that, aligned, each of the side wall portion of the sample interface layer and electrically conductive layer compose at least a portion of a sidewall of a well; the side wall portion of the electrically conductive layer being positioned in a bottom half of the side wall of the well, and the electrically conductive layer being in electrical connection with a voltage potential source configured to apply a voltage potential difference between the electrically conductive element and the electrically conductive layer; the electrically conductive layer, when energized with a given polarity relative to the electrically conductive element, producing an electric field from the electrically conductive layer through the well to the electrically conductive element, the electric field sufficient to draw the molecule, the molecule being of polarity opposite from the given polarity, from the sample at the sample interface side through the well toward the electrically conductive layer. Doing so would have a reasonable expectation of successfully improving rapid incorporation and removal of molecules in the well to enhance read-length and to enhance overall quality of signals obtained from light generating reactions of the apparatus as taught by Ronaghi ([0008],[0022],[0097]-[0098]).
Note that the “molecule” is not positively recited structurally and the limitations of the sample interface layer and electrically conductive layer are interpreted as functional limitations of the claimed apparatus. The inclusion of the material or article, i.e. “molecule”, worked upon by a structure, i.e. the sample interface layer and electrically conductive layer, being claimed does not impart patentability to the claims (see MPEP 2115).
Regarding claim 4, modified Larkin further teaches wherein the sample interface layer, electrically conductive layer, and substrate layer define multiple wells (see above claim 1, modified Larkin includes the electrically conductive layer for each well; Larkin, Fig. 1b shows the aluminum and SiO2 layers defining multiple wells; therefore, the combination of the sample interface layer, electrically conductive layer, and substrate layer of modified Larkin define multiple wells), and wherein the sensor system (Larkin, Fig. 1b, fluorescence microscope) is configured to sense a respective molecule in the multiple wells in a parallel manner (Larkin, Fig. 3 teaches parallel sensing of respective molecules in each NZMW).
Regarding claim 7, Larkin further teaches wherein the transparent material includes fused silica, quartz, or glass (Fig. 1 and Supplemental Information Supplementary Figure 1 teaches SiO2).
Regarding claim 14, Larkin further teaches wherein the well forms the shape of a cylinder, truncated cone, or any polygonal prism (Fig. 1a-1b and Supplemental Information, page 2, last paragraph, “array of circles”; therefore the well forms the shape of a cylinder).
Claims 6, 13, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Larkin in view of Ronaghi as applied to claim 1 above, and further in view of Kinz-Thompson et al. (US 20130294972 A1; cited in the IDS filed 03/24/2022).
Regarding claim 6, Larkin further teaches wherein the well is a cylindrically shaped hole (Fig. 1a-1b; Supplemental Information, page 2, last paragraph, “array of circles”) of at least 100 nm in length (Supplemental Information, supplementary Figure 3 teaches a 100 nm high ZMW; Supplemental Information, supplementary Figure 1 teaches 100 nm of aluminum that is etched to create the nanopores).
Larkin fails to teach the cylindrically shaped hole of about 100nm to about 150nm in diameter.
Kinz-Thompson teaches an apparatus for sensing a molecule (Fig. 1; abstract), the structure comprising: a substrate layer (substrate 120); a sample interface layer (side wall 110) having a sample interface side (top side of side wall 110 opposite of element 130) and a substrate layer facing side (bottom side of side wall 110 adjacent to element 130); an electrically conductive layer (Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, i.e. electrically conductive layer) disposed between the substrate layer facing side of the sample interface layer and the substrate layer (Fig. 1 shows adhesion layer 130 is between elements 110 and 120); and wherein the sample interface layer and electrically conductive layer each define a respective opening therethrough that, aligned, compose a wall of a well (Fig. 1 shows an opening through elements 110 and 130 that are aligned and compose a wall of nano-well 101) with a bottom boundary defined by the substrate layer (Fig. 1 shows nano-well 101 with a bottom boundary defined by substrate 120). Kinz-Thompson teaches zero-mode waveguides (ZMWs) includes apertures in a metal film that allows for observation of single-molecule phenomena to allow light to be shown through the waveguide; thus ZMWs can provide improved signal-to-noise ratio of single-molecule fluorescence, permitting single fluorophore-labeled biomolecules to be observed in imaging buffers containing physiologically relevant, micromolar concentrations of fluorophore-labeled ligands (paragraphs [0004],[0044]). Kinz-Thompson teaches the nano-well can have a diameter of 25-500 nm (paragraph [0027]) and a height, i.e. length, of 50-500 nm (paragraph [0027]).
Since Kinz-Thompson teaches the nano-well can have a diameter of 25-500 nm (paragraph [0027]), wherein the taught diameter range of 25-500 nm overlaps with the claimed diameter range of 100-150 nm, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the well of modified Larkin to provide wherein the well is a cylindrically shaped hole of about 100nm to about 150nm in diameter. I.e., it would have been prima facia obvious to have selected the overlapping portion of the range (i.e. diameter of 100-150 nm) from the taught diameter of 25-500 nm (Kinz-Thompson, paragraph [0027]) (In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); see MPEP 2144.05 (I)).
Regarding claim 13, modified Larkin fails to teach wherein the organic matter is attached to an electrically non-conductive layer in the well through biotinylated polyethylene glycol silane-based functionalization of the substrate layer.
Kinz-Thompson further teaches wherein the organic matter (Fig. 1, target molecule 150) is attached to an electrically non-conductive layer in the well (Fig. 1 shows target molecule 150 attached to substrate 120 in the nano-well 101 via elements 125 and 126; paragraph [0026] teaches the substrate is glass, which is an electrically non-conductive layer; note that the BRI of “electrically non-conductive layer” includes the interpretation that the substrate layer is the electrically non-conductive layer) through biotinylated polyethylene glycol silane-based functionalization of the substrate layer (Fig. 1 and paragraph [0029] teaches target molecule 150 is attached to the glass substrate 120 through second functional molecule 125 comprising polyethylene glycol, wherein the second functional molecule includes a silane end group that is biotinylated, thus the substrate 120 is functionalized with biotinylated polyethylene glycol silane). Kinz-Thompson teaches a nano-well functionalized with at least one second molecule comprising a silane-PEG molecule, wherein the second molecule can further include a moiety, such as biotin, which is capable of binding a target biomolecule, which in turn can bind to a biomolecule of interest for single molecule fluorescence imaging analysis (abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the organic matter of modified Larkin to incorporate the teachings of biotinylated polyethylene glycol silane-based functionalization of the substrate layer for attachment of an organic matter of Kinz-Thompson (Fig. 1; abstract; paragraphs [0026],[0029]) to provide wherein the organic matter is attached to an electrically non-conductive layer in the well through biotinylated polyethylene glycol silane-based functionalization of the substrate layer. Doing so would have a reasonable expectation of successfully functionalizing a desired organic matter to the substrate for proper analysis of a molecule as taught by Kinz-Thompson (Fig. 1; abstract; paragraphs [0026],[0029]).
Regarding claim 15, modified Larkin fails to teach: wherein an opening at the sample interface side of the sample interface layer has a diameter from about 20 nm to about 250 nm.
Kinz-Thompson teaches an apparatus for sensing a molecule (Fig. 1; abstract), the structure comprising: a substrate layer (substrate 120); a sample interface layer (side wall 110) having a sample interface side (top side of side wall 110 opposite of element 130) and a substrate layer facing side (bottom side of side wall 110 adjacent to element 130); an electrically conductive layer (Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, i.e. electrically conductive layer) disposed between the substrate layer facing side of the sample interface layer and the substrate layer (Fig. 1 shows adhesion layer 130 is between elements 110 and 120); and wherein the sample interface layer and electrically conductive layer each define a respective opening therethrough that, aligned, compose a wall of a well (Fig. 1 shows an opening through elements 110 and 130 that are aligned and compose a wall of nano-well 101) with a bottom boundary defined by the substrate layer (Fig. 1 shows nano-well 101 with a bottom boundary defined by substrate 120). Kinz-Thompson teaches zero-mode waveguides (ZMWs) includes apertures in a metal film that allows for observation of single-molecule phenomena to allow light to be shown through the waveguide; thus ZMWs can provide improved signal-to-noise ratio of single-molecule fluorescence, permitting single fluorophore-labeled biomolecules to be observed in imaging buffers containing physiologically relevant, micromolar concentrations of fluorophore-labeled ligands (paragraphs [0004],[0044]). Kinz-Thompson teaches the nano-well can have a diameter of 25-500 nm (paragraph [0027]).
Since Kinz-Thompson teaches the nano-well can have a diameter of 25-500 nm (paragraph [0027]), wherein the taught diameter range of 25-500 nm overlaps with the claimed diameter range of 100-250 nm, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the well of modified Larkin to provide: wherein an opening at the sample interface side of the sample interface layer has a diameter from about 20 nm to about 250 nm. I.e., it would have been prima facia obvious to have selected the overlapping portion of the range (i.e. diameter of 100-250 nm) from the taught diameter of 25-500 nm (Kinz-Thompson, paragraph [0027]) (In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); see MPEP 2144.05 (I)).
In an alternative interpretation of claim 7, claim 7 rejected under 35 U.S.C. 103 as being unpatentable over Larkin in view of Ronaghi as applied to claim 1 above.
Regarding claim 7, if it is determined that modified Larkin fails to explicitly teach wherein the transparent material (Fig. 1 and Supplemental Information Supplementary Figure 1 teaches SiO2) includes fused silica, quartz, or glass, Ronaghi teaches a transparent layer (Fig. 2B, layer 117) forming the bottom of a well (Fig. 2B). Ronaghi teaches a substrate may be made of borosilicate glass or quartz ([0056]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the transparent material of modified Larkin to incorporate Ronaghi’s teachings of transparent materials including glass or quartz to provide: the transparent material includes fused silica, quartz, or glass. Doing so would have a reasonable expectation of successfully utilizing known transparent materials to allow for transparency of the substrate layer and to allow for optical analysis.
Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Larkin in view of Ronaghi as applied to claim 1 above, and further in view of Rothberg et al. (US 20150141268 A1).
Regarding claim 8, Larkin further teaches wherein the sample interface layer is a metal (Fig. 1 and Supplemental Information Supplementary Figure 1, interpreted as including aluminum).
Modified Larkin fails to teach the sample interface layer further comprising an electrically non-conductive layer positioned between the sample interface layer and the electrically conductive layer, wherein a side wall portion of the electrically non-conductive layer defines a respective opening aligned with the opening of the side wall portion of the sample interface layer and the opening of the side wall portion of the electrically conductive layer.
Rothberg teaches a device capable of performing biomolecule detection and/or analysis, such as single-molecule nucleic acid sequencing, wherein the device includes a sample well (abstract). Rothberg teaches a sample well may be formed as a nanohole and may be formed as a zero-mode waveguide having a cylindrical shape (paragraph [0208]). Rothberg teaches an embodiment of the device (Fig. 3-7F) comprising a sample interface layer (3-230), substrate layer (3-235), and an electrically conductive layer (Fig. 3-7F and paragraph [0225], first layer 3-232 which is a semiconducting or conducting material) between the sample interface layer and substrate layer (Fig. 3-7F). Rothberg teaches the sample interface layer is a metal (paragraph [0225], first layer 3-230 which is a conductor or semiconductor; paragraph [0298] teaches top layer 3-230 is a conductive metal; paragraph [0364] teaches conductive material 3-230), and further comprising an electrically non-conductive layer (Fig. 3-7F and paragraph [0225], second layer 3-234 which is an insulator or dielectric, i.e. electrically non-conductive layer) positioned between the sample interface layer (3-230) and the electrically conductive layer (3-232), wherein a sidewall portion of the electrically non-conductive layer defines a respective opening aligned with the opening of the sidewall portion of the sample interface layer and the opening of the sidewall portion of the electrically conductive layer (Fig. 3-7F shows aligned openings of elements 3-230, 3-234, 3-232). Rothberg teaches conductive materials include gold and aluminum (paragraph [0364]). Rothberg teaches multi-layer materials used for forming a sample well may be selected to suppress excitation radiation from propagating beyond the sample well and multi-layer structure into the bulk specimen (paragraph [0225]).
Since Rothberg teaches wells for sensing a molecule, similar to Larkin, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the apparatus of modified Larkin to incorporate the teachings of multi-layer materials used to for a sample well of Rothberg (Fig. 3-7F; paragraphs [0225],[0298],[0364]), to provide: the sample interface layer further comprising an electrically non-conductive layer positioned between the sample interface layer and the electrically conductive layer, wherein a side wall portion of the electrically non-conductive layer defines a respective opening aligned with the opening of the side wall portion of the sample interface layer and the opening of the side wall portion of the electrically conductive layer. Doing so would have a reasonable expectation of successfully improving insulation of the electrically conductive layer and suppressing excitation radiation from propagating beyond a sample well as taught by Rothberg (paragraph [0225]).
Regarding claim 9, modified Larkin fails to teach: wherein the electrically non-conductive layer is made of a material including silicon dioxide, aluminum oxide, or silicon nitride.
Rothberg teaches an insulating layer may comprise an oxide, such as silicon dioxide (paragraph [0298]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the electrically non-conductive layer of modified Larkin to incorporate the teachings of a silicon dioxide insulating layer of Rothberg (paragraph [0298]) to provide wherein the electrically non-conductive layer is made of a material including silicon dioxide. Doing so would have a reasonable expectation of successfully insulating desired layers of the apparatus.
Regarding claim 10, Larkin further teaches wherein the metal includes platinum, gold, silver, titanium, aluminum, or combination thereof (Fig. 1 and Supplemental Information Supplementary Figure 1, interpreted as including aluminum).
Response to Arguments
Applicant’s arguments, see pages 7-8, filed 08/27/2026, with respect to the rejection under 35 U.S.C. 112(b) have been fully considered and are persuasive. The rejection under 35 U.S.C. 112(b) of 03/27/2026 has been withdrawn.
Applicant’s arguments, see pages 8-12, filed 08/27/2026, with respect to the rejection(s) of claims 1, 4, 6, 7, and 13-15 under 35 U.S.C. 103 over of Bashir in view of Kinz-Thompson, claims 1, 4, 6-10, and 13-15 under 35 U.S.C. 103 over of Kinz-Thompson in view of Rothberg and Hanes, and claims 8-10 over Bashir in view of Kinz-Thompson and further in view of Rothberg, specifically regarding amended claim 1, have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Kinz-Thompson et al. (US 20130294972 A1; cited in the IDS filed 03/24/2022) in view of Rothberg et al. (US 20150141268 A1) and Ronaghi et al. (US 20090032401 A1); and Larkin et al. (Larkin, J.; et al., "Length-independent DNA packing into nanopore zero-mode waveguides for low-input DNA sequencing," Nature nanotechnology 2017, 12 (12), 1169l; cited in the IDS filed 04/28/2022; Additionally, see Larkin Supplemental Information) in view of Ronaghi et al. (US 20090032401 A1).
In response to applicant’s arguments that Kinz-Thompson does not teach “sidewall portion of the electrically conductive layer” is “positioned in a bottom half of the side well” (Remarks, page 11), the examiner disagrees. Kinz-Thompson teaches: the side wall portion of the electrically conductive layer being positioned in a bottom half of the side wall of the well (Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, i.e. electrically conductive layer, is positioned in a bottom half of the sidewall of the nano-well 101).
In response to applicant’s argument that Kinz-Thompson does not teach the electrically conductive layer is “in electrical connection with a voltage potential source…” (Remarks, page 11), the examiner agrees. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Kinz-Thompson et al. (US 20130294972 A1; cited in the IDS filed 03/24/2022) in view of Rothberg et al. (US 20150141268 A1) and Ronaghi et al. (US 20090032401 A1); and Larkin et al. (Larkin, J.; et al., "Length-independent DNA packing into nanopore zero-mode waveguides for low-input DNA sequencing," Nature nanotechnology 2017, 12 (12), 1169l; cited in the IDS filed 04/28/2022; Additionally, see Larkin Supplemental Information) in view of Ronaghi et al. (US 20090032401 A1).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Kaisha et al. (US 20190285579 A1) teaches a fluorescent testing system (abstract; Fig. 19) including an electrically conductive layer (201) between a substrate (glass board) and sample interface layer (210); wherein the electrically conductive layer (201) and sample interface (210) each include a side wall portion that define an opening therethrough and are aligned to define a well (211), wherein a bottom boundary of the well is defined by the substrate (glass board). Kaisha teaches a molecule is drawn to the bottom of the well towards electrically conductive layer (Fig. 19). Kaisha teaches by changing whether the electric field is applied to the dielectrophoresis electrode pair or an amplitude or frequency of the electric field, an attractive force is able to be acted on the capture material, and a repulsive force or the like is also able to be acted thereon ([0222]).
Tsai et al. (US 10875023 B2) teaches an oriented loading system (abstract) including a plurality of well (Fig. 2, wells 14) including an electrically conductive layer (metal layer 28) between a substrate (12) and sample interface layer (18); wherein the electrically conductive layer (metal layer 28) and sample interface (18) each include a side wall portion that define an opening therethrough and are aligned to define a well (14), wherein a bottom boundary of the well is defined by the substrate (12).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HENRY H NGUYEN whose telephone number is (571)272-2338. The examiner can normally be reached M-F 7:30A-5:00P.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached at (571) 270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HENRY H NGUYEN/Primary Examiner, Art Unit 1758
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