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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-17, in the reply filed on 08/19/2026, is acknowledged.
Claims 18-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/19/2026.
Drawings
The drawings are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims. Therefore, the “wherein the solid cover structure comprises a peripheral circumferential edge structure and at least one connecting rod within the peripheral circumferential edge structure” (claim 11 must be shown or the feature(s) canceled from the claim(s). No new matter should be entered.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: Figs. 1-2, reference character 6. Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 2 is objected to because of the following informalities: It is suggested to delete “(5)” in line 2. Appropriate correction is required.
Claim 7 is objected to because of the following informalities: It is suggested to recite “the solid cover structure cover” in line 2 as “the solid cover structure”. Appropriate correction is required.
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 5, 10, and 12 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 5, claim 5 recites the limitation "the total well opening surface" and “the effective top surface” in lines 2-3. There is insufficient antecedent basis for these limitation in the claim. It is suggested to recite "the total well opening surface" as “a total well opening surface” and “the effective top surface” as “an effective top surface”.
Regarding claim 10, claim 10 recites “each through-hole” in line 2. There is insufficient antecedent basis for this limitation in the claim. It is unclear which element includes the “through-hole”.
Regarding claim 12, claim 12 recites “the at least one gap” in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 4 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Sato et al. (US 20090053773 A1; cited in the IDS filed 03/19/2024).
Regarding claim 1, Sato teaches a sample holder (Fig. 1; abstract) for use in an analytical method involving thermocycling (interpreted as an intended use, see MPEP 2114; paragraphs [0035],[0043],[0047] teach the holder used for PCR amplification with a heat cycle, therefore is capable of being used for an analytical method involving thermocycling), wherein the sample holder comprises:
a. a base plate (Fig. 1, base plate 1), wherein the base plate is made of a base plate material (Fig. 1, material of base plate 1) and comprises a top surface (Fig. 1, top surface of base plate 1), wherein the base plate comprises an array of wells (Fig. 1, elements 11, 122, and 13), wherein each well is configured for receiving a sample (Fig. 1, elements 11, 122, and 13 are structurally capable of receiving a sample); and
b. a solid cover structure (Fig. 1, examination chamber protecting film 4) being made of a material having a melting point which is lower than the melting point of the base plate material (paragraphs [0014], [0073] teach the examination chamber protecting film 4 are heat sealed to the base plate, therefore element 4 has a lower melting point than the base plate material since it can be heat sealed to the base plate); wherein the solid cover structure is arranged on the top surface of the base plate such that at least some of the wells are uncovered (Fig. 1, some wells are uncovered, e.g. elements 122).
Regarding claim 4, Sato further teaches wherein 40% - 100% of the top surface of the base plate and/or of an effective top surface of the base plate is covered by the solid cover structure (Fig. 1, teaches examination chamber protecting film 4 covers an area of the top surface of the base plate including chambers 13, i.e. an effective top surface; therefore, 40% - 100% of “an effective top surface” of the base plate is covered by examination chamber protecting film 4).
Claims 1, 3-4, 8-9, and 13 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Kelso et al. (US 20110306109 A1).
Regarding claim 1, Kelso teaches a sample holder (Fig. 4, cartridge that includes chambers capable of holding a sample) for use in an analytical method involving thermocycling (interpreted as an intended use, see MPEP 2114; [0085] teaches the present invention is used for sample preparation prior to analysis using thermocyclers; [0185] teaches the cartridge is used with thermal cycling; therefore, the cartridge is capable of being used in an analytical method involving thermocycling), wherein the sample holder comprises:
a. a base plate (Fig. 4, plastic frame and foil chambers), wherein the base plate is made of a base plate material (Fig.4, plastic frame and foil chambers are made of a material; [0099] teaches the cartridge uses plastic) and comprises a top surface (Fig. 4, interpreted as the top surface of the foil chamber), wherein the base plate comprises an array of wells (Fig. 4 teaches the foil chambers and plastic frame forms an array of chambers, i.e. array of wells), wherein each well is configured for receiving a sample (interpreted as a functional limitation, see MPEP 2114; Fig. 4 teaches the foil chambers and plastic frame forms an array of chambers, which are structurally capable of receiving a sample; [0099] teaches the cartridge includes wells for sample preparation or analysis); and
b. a solid cover structure (Fig. 4, wax channel) being made of a material having a melting point which is lower than the melting point of the base plate material ([0100]-[0103] teach the wax is a either liquid at room temperature or solid at room temperature and a liquid at a temperature suitable for reactions; [0099] teaches the cartridge uses plastic; [0103] teaches examples including Chill-Out 14 wax and paraffin waxes such as IGI 1070A; therefore, the wax channel is made of a material with a melting point lower than that of the plastic frame and foil chamber in order for the wax channel to melt at desired temperature while the base plate does not melt); wherein the solid cover structure is arranged on the top surface of the base plate such that at least some of the wells are uncovered (Fig. 4 teaches the wax channel with a rectangular cut out is on top of the foil chamber via the adhesive tape such that the chambers are uncovered by the solid cover structure; Fig. 4 shows the chambers of the foil chamber and plastic frame are not covered by the wax channel and therefore the chambers, i.e. wells, are interpreted as “uncovered”).
Regarding claim 3, Kelso further teaches wherein the solid cover structure is made of wax (Fig. 4, wax channel).
Regarding claim 4, Kelso further teaches wherein 40% - 100% of the top surface of the base plate and/or of an effective top surface of the base plate is covered by the solid cover structure (Fig. 4 teaches 40-100% of the base plate or effective top surface of the plastic frame and foil chamber layers are covered by the wax channel; with the interpretation that the “effective top surface” is the area of the base plate covered by the wax channel, the wax channel covers 100% of the effective top surface).
Regarding claim 8, Kelso further teaches wherein the solid cover structure (Fig. 4, wax channel) is arranged such that the uncovered wells are surrounded by the solid cover structure (Fig. 4 teaches the wax channel with a rectangular cut out that surrounds the chambers of the foil chambers and plastic frame).
Regarding claim 9, Kelso further teaches wherein the solid cover structure (Fig. 4, wax channel) has a shape defining at least one gap, cut-out or sectional opening (Fig. 4 teaches the wax channel has a gap, cut-out or sectional opening).
Regarding claim 13, Kelso teaches wherein the solid cover structure is translucent at 40 °C - 99 °C ([0185] teaches a top plate is transparent in order to make optical readings during thermal cycling; Fig. 2 and [0097] teaches that during the assay, the wax is melted on to be on the wells; therefore, it is inherent that the wax channel is translucent at thermocycling temperatures that would include temperatures in the range of at 40 °C - 99 °C in order to allow for optical readings through the melted wax during thermal cycling).
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.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Kelso as applied to claim 1 above, and further in view of Bloch et al. (US 5411876 A).
Regarding claim 2, Kelso fails to explicitly teach: wherein the melting point of the solid cover structure is between 38 °C - 55°C .
Kelso teaches the wax is solid at room temperature and a liquid at a temperature suitable for reactions ([0100]-[0103]) and can include materials such as Chill-Out 14 wax and paraffin waxes such as IGI 1070A [0103]).
Bloch teaches improvements to PCR including a vapor barrier, comprising grease or wax, to minimize solvent evaporation (abstract). Bloch teaches reagent segregation with a layer of wax that is solid at room temperature; wherein thermal cycling turns the solid barrier into liquid (column 4, lines 33-43). Bloch teaches the melted wax creates a vapor barrier to minimize solvent evaporation during thermal cycling and, upon cooling after amplification is complete, re-forms a solid barrier which, among other things, reduces the ease of PCR product dispersal into the environment when reaction tubes are opened, thereby reducing the likelihood of back-contaminating later reactions (column 4, lines 56-53). Bloch teaches the wax can include paraffin (column 11, lines 22-31). Bloch teaches wax such as paraffin with a melting range of 55-61°C (column 15, lines 9-15). Bloch teaches in general, almost any wax melting between 40-80°C might serve as both a barrier layer and vapor barrier for thermocycling (column 15, lines 25-30). Bloch teaches to minimize extraction of an aqueous layer during casting of the barrier, the preferable melting point is 40-50°C (column 20, lines 63-65).
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 solid cover structure of Kelso to incorporate Bloch’s teachings of known wax layers for PCR including temperature ranges of 55-61°C (column 15, lines 9-15), 40-80°C (column 15, lines 25-30), and 40-50°C (column 20, lines 63-65) to provide: wherein the melting point of the solid cover structure is between 38 °C - 55°C . Doing so would have a reasonable expectation of successfully improving and optimizing the solid cover structure for serving as a barrier during thermocycling as taught by Bloch.
Additionally, since Bloch teaches known ranges of melting points of wax, i.e. of 55-61°C (column 15, lines 9-15), 40-80°C (column 15, lines 25-30), and 40-50°C (column 20, lines 63-65), that overlaps with the claimed range of 38 °C - 55°C, 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 solid cover structure of Kelso to provide wherein the melting point of the solid cover structure is between 38 °C - 55°C. I.e., it would have been prima facia obvious to have selected the overlapping portion of the range from the taught range of 55-61°C (Bloch, column 15, lines 9-15), 40-80°C (column 15, lines 25-30), and 40-50°C (column 20, lines 63-65) (In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); see MPEP 2144.05 (I)).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Kelso as applied to claim 1 above, and further in view of Goto et al. (US 20230201826 A1; effectively filed 09/02/2020).
Regarding claim 5, Kelso fails to explicitly teach: wherein the ratio of the total well opening surface relative to the effective top surface of the base plate is 0.1 - 0.9.
Goto teaches a fluidic device including a substrate having a well array (abstract; Fig. 1). Goto teaches the ratio of the total area of the openings of the wells of the well array, i.e. the total well opening surface, to the area of the well array on the surface, i.e. effective top surface of the base plate, is preferably 30% or more and 90% or less, i.e. 0.3-0.9 ([0043]).
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 ratio of the total well opening surface relative to the effective top surface of the base plate of Kelso to incorporate Goto’s teachings of ratios of well openings to area of a well surface ([0043]) to provide: wherein the ratio of the total well opening surface relative to the effective top surface of the base plate is 0.1 - 0.9. Doing so would have a reasonable expectation of successfully optimizing the size and number of openings of the wells in relation to the area of the plate.
Additionally, since Goto teaches a ratio of the total well opening surface relative to the effective top surface of the base plate of 0.3 - 0.9 ([0043]), wherein the range of 0.3 - 0.9 overlaps with the claimed range of 0.1-0.9, i.e. 0.3 - 0.9, 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 Kelso to provide wherein the ratio of the total well opening surface relative to the effective top surface of the base plate is 0.1 - 0.9. I.e., it would have been prima facia obvious to have selected the overlapping portion of the range (i.e. 0.3 - 0.9) from the taught range of 0.3 - 0.9 (Goto, [0043]) (In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); see MPEP 2144.05 (I)).
Claim 6 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Kelso as applied to claim 1 above.
Regarding claim 6, Kelso fails to explicitly teach: wherein the ratio of the volume of the solid cover structure relative to the total volume of the array of wells is 0.1-50.
Kelso teaches a liquid wax covering a volume of liquids in an array of wells (Fig. 2).
MPEP 2144.05 (II)(B) holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. In the design and fabrication of a sample holder with a wells and a cover structure, the selection of optimal experimental conditions including structural geometry and dimensions of the solid cover structure, such as a wax channel, and wells affect the volume of each wells and the volume of the solid cover structure and therefore, affect the amount of wax that will used to cover the wells. Thus, the volumes of the solid cover structure and array of wells are a result effective variables. 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 volume of the solid cover structure relative to the total volume of the array of wells of Kelso to provide: wherein the ratio of the volume of the solid cover structure relative to the total volume of the array of wells is 0.1-50 through routine experimentation (MPEP 2144.05 (II)). I.e., it would have been obvious to design and fabricate the solid cover structure and/or wells to have modified the result-effective variables, i.e. the volumes of the solid cover structure and array of wells, to arrive at the claimed invention through routine optimization of workable volumes for the solid cover structure and/or wells to optimize the volume of the wells for proper sample processing and analysis and the volume of the solid cover structure to ensure proper covering of the wells of the cartridge during use as desired by Kelso (Fig. 2).
Regarding claim 16, Kelso fails to teach: wherein each uncovered well has a maximum distance of 0.1 mm - 20 mm from the solid cover structure.
Kelso teaches the wax channel surrounding the chambers (Fig. 4) and is melted before the experiment to create a phase change plug ([0200]; Fig. 2). Kelso teaches a liquid wax covering a volume of liquids in an array of wells (Fig. 2). Kelso teaches distance between chambers is preferably 6mm to allow for proper sealing ([0185]).
MPEP 2144.05 (II)(B) holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. In the design and fabrication of a sample holder with a wells and a cover structure, the selection of optimal experimental conditions including dimensions and location, such as a wax channel, and wells affect the volume of the solid cover structure and distance between the solid cover structure and the wells. Thus, the dimensions and location of the solid cover structures and/or wells are a result effective variables. 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 dimensions and location of the solid cover structures and/or wells to provide: wherein each uncovered well has a maximum distance of 0.1 mm - 20 mm from the solid cover structure through routine experimentation (MPEP 2144.05 (II)). I.e., it would have been obvious to design and fabricate the solid cover structure and/or wells to have modified the result-effective variables, i.e. dimensions and location of the solid cover structures and/or wells, to arrive at the claimed invention (i.e. each uncovered well has a maximum distance of 0.1 mm - 20 mm from the solid cover structure) through routine optimization of workable dimensions and location of the solid cover structures and/or wells to optimize the volume of the solid cover structure and/or wells for proper sample processing and analysis and to ensure proper covering of the wells of the cartridge during use as desired by Kelso (Fig. 2).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Kelso as applied to claim 1 above, and further in view of Whitesides et al. (US 20130034869 A1).
Regarding claim 7, Kelso fails to explicitly teach: wherein the solid cover structure cover has a thickness of 0.5 mm - 5 mm.
Kelso teaches thicknesses of common plastics for carrying out chemical assays include thicknesses of 3.5-10mm ([0179]-[0181], table 3). Kelso teaches a liquid wax covering a volume of liquids in an array of wells (Fig. 2).
Whitesides teaches a device for performing multiplexed assays (abstract). Whitesides teaches the device includes a fluid impervious barrier including a wax material deposited onto paper and melted onto the paper ([0041]). Whitesides teaches the wax can be printed onto paper at a thickness, such as about 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9mm, and 1 mm or thicker ([0047]). Whitesides teaches thickness of the wax to be printed can be determined by, e.g., analyzing the extent to which the wax permeates through the thickness of the substrate after heating ([0042]).
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 thickness of the solid cover structure cover of Kelso to incorporate Kelso’s teachings of layers being 3.5-10 mm ([0179]-[0181], table 3) and Whitesides’ teachings of depositing wax on a paper to be melted, the wax having a thickness such as about 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9mm, and 1 mm or thicker ([0041],[0042],[0047]) to provide: wherein the solid cover structure cover has a thickness of 0.5 mm - 5 mm. Doing so would have a reasonable expectation of successfully optimizing the amount of solid cover structure available to ensure adequate volume of the solid cover structure to properly cover of the wells of the cartridge during use as desired by Kelso (Fig. 2).
Additionally, since Whitesides teaches thicknesses of wax ([0047]) that overlaps with the claimed range of 0.5 mm-5 mm, 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 solid cover structure cover of Kelso to provide wherein the solid cover structure cover has a thickness of 0.5 mm - 5 mm. I.e., it would have been prima facia obvious to have selected the overlapping portion of the range (i.e. 0.5-1mm) from the taught range of about 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9mm, and 1 mm or thicker (Whitesides, [0047]) (In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); see MPEP 2144.05 (I)).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Kelso as applied to claim 8 above, and further in view of Goldman et al. (US 20030072685 A1).
Regarding claim 10, Kelso fails to teach: the sample holder according to claim 8, wherein each through-hole has an open surface area of 1 mm2-400 mm2.
Kelso teaches sample preparation prior to modification and analysis using thermocyclers ([0085]); and the device suitable for carrying out PCR ([0107]). Kelso teaches cartridges prepared using a 96 well plate ([0149]).
Goldman teaches a heat-conducting sample block including a top plate and base plate (Figs. 1-2; abstract), the block is for use in heating and cooling of reaction vessels for PCR and a thermal cycler ([0001],[0011]). Goldman teaches the top plate includes through-holes (Figs. 1-2, recesses 102). Goldman teaches the recesses conform to industry standards, such as a standard 96-well microplate in which sample wells are arranged ([0020]). Goldman teaches the base plate includes 96 4.5 mm counterbores, with a 4.5 mm starting diameter and 5.0 mm ending diameter ([0045]), and the through-holes have a circular opening (Figs. 1-2); therefore, a circular opening having a 5 mm diameter would have an open surface area of about 19.6 mm2 . Goldman teaches notches in the base plate have circular cross sections ([0029]).
Since Goldman teaches sample blocks for PCR and thermal cycling, similar to Kelso, 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 sample holder of Kelso to incorporate Kelso’s teachings of 96 well plates ([0149]) and Goldman’s teachings of circular wells with an opening having a 5 mm diameter, i.e. about 19.6 mm2 surface area, (Figs. 1-2; [0020],[0029],[0045]) to provide: the sample holder according to claim 8, wherein each through-hole has an open surface area of 1 mm2-400 mm2. Doing so would have a reasonable expectation of successfully optimizing the size of the wells to desired diameters and volumes.
Additionally, since Goldman teaches circular wells having a diameter of 5 mm and therefore surface area of 19.6mm2 (Figs. 1-2; [0020],[0029],[0045]), which overlaps with the claimed range of at 1 mm2-400 mm2, 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 sample holder of Kelso to provide the sample holder according to claim 8, wherein each through-hole has an open surface area of 1 mm2-400 mm2. I.e., it would have been prima facia obvious to have selected the overlapping portion of the range from the taught range of about 19.6mm2 (Goldman, Figs. 1-2; [0020],[0029],[0045]) (In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); see MPEP 2144.05 (I)).
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Kelso as applied to claim 8 above, and further in view of Sandell (US 20040018610 A1).
Regarding claim 11, Kelso further teaches the sample holder according claim 8, wherein the solid cover structure (Fig. 4, wax channel) comprises a peripheral circumferential edge structure (Fig. 4, interpreted as the peripheral circumferential edge of the wax channel). Kelso fails to teach: the solid cover structure comprises at least one connecting rod within the peripheral circumferential edge structure.
Kelso teaches sample preparation prior to modification and analysis using thermocyclers ([0085]); and the device suitable for carrying out PCR ([0107]). Kelso teaches the wax channel surrounding the chambers (Fig. 4) and is melted before the experiment to create a phase change plug ([0200]; Fig. 2). Kelso teaches a liquid wax covering a volume of liquids in an array of wells (Fig. 2).
Sandell teaches a heated plate assembly (abstract; Figs. 1-2) including a plurality of sample wells (12) and a cover structure (40,50), the cover structure comprises a cover (40) and peripheral circumferential edge structure (Figs. 1-2, frame member 50) encompassing the cover structure (Figs. 1-2 teach frame member surrounds or forms an edge of cover 40). Sandell teaches the peripheral frame is used to assist in holding the cover in place ([0048]-[0049]). Sandell teaches at least one connecting rod within the peripheral circumferential edge structure (Fig. 1 and [0049] teaches holes 52 including a screw, i.e. connecting rod, inserted through the hole to hold the frame member 50 in place) in order to hold the peripheral circumferential edge structure in place ([0049]). Sandell teaches the assembly is used for thermal cycling and real-time detection of nucleic acid amplification during thermal cycling ([0042]).
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 solid cover structure of Kelso to incorporate Kelso’s teachings of performing PCR and thermocycling ([0085],[0107]) and Sandell’s teachings of a peripheral frame with screws to assist in holding a cover for an assembly for thermal cycling (Figs. 1-2; [0042], [0048]-[0049]) to provide: the solid cover structure comprises a peripheral circumferential edge structure and at least one connecting rod within the peripheral circumferential edge structure. Doing so would have a reasonable expectation of successfully improving supporting and holding sample holder including the solid cover structure in place during thermocycling procedures and analysis.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Kelso as applied to claim 8 above.
Regarding claim 12, Kelso fails to explicitly teach: the sample holder according to claim 8, wherein the at least one gap is configured such that each uncovered well has a maximum distance to the solid cover structure of 0.1 mm - 20 mm.
Kelso teaches the wax channel surrounding the chambers (Fig. 4) and is melted before the experiment to create a phase change plug ([0200]; Fig. 2). Kelso teaches a liquid wax covering a volume of liquids in an array of wells (Fig. 2). Kelso teaches distance between chambers is preferably 6mm to allow for proper sealing ([0185]).
MPEP 2144.05 (II)(B) holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. In the design and fabrication of a sample holder with a wells and a cover structure, the selection of optimal experimental conditions including dimensions and location, such as a wax channel, and wells affect the volume of the solid cover structure and separation distance between the solid cover structure and the wells. Thus, the dimensions and location of the solid cover structures and/or wells are a result effective variables. 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 dimensions and location of the solid cover structures and/or wells to provide: the sample holder according to claim 8, wherein the at least one gap is configured such that each uncovered well has a maximum distance to the solid cover structure of 0.1 mm - 20 mm through routine experimentation (MPEP 2144.05 (II)). I.e., it would have been obvious to design and fabricate the solid cover structure and/or wells to have modified the result-effective variables, i.e. dimensions and location of the solid cover structures and/or wells, to arrive at the claimed invention (i.e. each uncovered well has a maximum distance to the solid cover structure of 0.1 mm - 20 mm) through routine optimization of workable dimensions and location of the solid cover structures and/or wells to optimize the volume of the solid cover structure and/or wells for proper sample processing and analysis and to ensure proper covering of the wells of the cartridge during use as desired by Kelso (Fig. 2).
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Kelso as applied to claim 1 above, and further in view of Manage et al. (US 20150240289 A1).
Regarding claim 13, Kelso fails to teach: wherein the solid cover structure is translucent at 40 °C - 99 °C.
Kelso teaches a top plate is transparent in order to make optical readings during thermal cycling ([0185]). Kelso teaches wax melting at 60°C ([0200]).
Manage teaches a system for amplification and detection of nucleic acids (abstract). Manage teaches a wax that is optically transparent and an enclosing structure to contain the wax in a molten state ([0010]). Manage teaches a wax that encloses capillaries; and when PCR cycling beings, the wax melts and creates a vapor barrier; said wax chosen specifically to be solid at expected transport temperatures, liquid at expected PCR temperatures and optically transparent to wavelengths used to monitor or detect the effects of the PCR ([0035]). Manage teaches PCR performed with steps at temperatures of 74, 60, 72, 94, and 70-95°C ([0081]-[0083]). Manage teaches heating the cassette from 70-95°C ([0085]).
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 solid cover structure of Kelso to provide: wherein the solid cover structure is translucent at 40 °C - 99 °C. Doing so would have a reasonable expectation of successfully improving optically monitoring the wells during thermal cycling as taught by Manage ([0010],[0035],[0081]-[0083],[0085]) and desired by Kelso ([0185]).
Claims 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Kelso as applied to claim 1 above, and further in view of Joseph et al. (US 20080176290 A1).
Regarding claim 14, Kelso fails to teach: wherein the base plate is made of a material with a thermal conductivity of 10 W/(m*K) - 300 W/(m*K).
Kelso teaches sample preparation prior to modification and analysis using thermocyclers ([0085]); and the device suitable for carrying out PCR ([0107]). Kelso teaches cartridges prepared using a 96 well plate ([0149]). Kelso teaches devices comprising wells utilizes plastic or other material ([0099]).
Joseph teaches apparatus for performing large number of simultaneous reactions, such as PCR (abstract). Joseph teaches in order to sequence thousands of genes from a relatively small sample, a thermal cycling apparatus needs to adapt to range of different temperatures ([0005]). Joseph teaches a chip comprising a substrate and an array of nanowells ([0008]), and a heating element for heating and cooling the nanowells ([0009]). Joseph teaches selection of a suitable chip substrate includes a substrate with a good thermal conductor having a thermal conductivity of higher than 100 W/(m*K), such as 250 W/(m*K) or higher, and usually does not exceed 500 W/(m*K) ([0129]). Joseph teaches exemplary materials includes metals, polymers, or plastics ([0129]).
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 base plate of Kelso to incorporate Joseph’s teachings of chips with wells having a good thermal conductivity, such as higher than 100 W/(m*K) ([0005],[0008]-[009],[0129]) to provide: wherein the base plate is made of a material with a thermal conductivity of 10 W/(m*K) - 300 W/(m*K). Doing so would have a reasonable expectation of successfully improving thermal conductivity of the base plate to improve heating and cooling of the wells for thermocycling procedures.
Regarding claim 15, Kelso fails to teach: wherein the base plate is made of metal.
Kelso teaches sample preparation prior to modification and analysis using thermocyclers ([0085]); and the device suitable for carrying out PCR ([0107]). Kelso teaches cartridges prepared using a 96 well plate ([0149]). Kelso teaches devices comprising wells utilizes plastic or other material ([0099]).
Joseph teaches apparatus for performing large number of simultaneous reactions, such as PCR (abstract). Joseph teaches in order to sequence thousands of genes from a relatively small sample, a thermal cycling apparatus needs to adapt to range of different temperatures ([0005]). Joseph teaches a chip comprising a substrate and an array of nanowells ([0008]), and a heating element for heating and cooling the nanowells ([0009]). Joseph teaches selection of a suitable chip substrate includes a substrate with a good thermal conductor having a thermal conductivity of higher than 100 W/(m*K), such as 250 W/(m*K) or higher, and usually does not exceed 500 W/(m*K) ([0129]). Joseph teaches exemplary materials includes metals, polymers, or plastics ([0129]).
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 base plate of Kelso to incorporate Joseph’s teachings of chips with wells having a good thermal conductivity, such as higher than 100 W/(m*K) ([0005],[0008]-[009],[0129]) and substrate materials including metals ([0129]) to provide: wherein the base plate is made of metal. Doing so would have a reasonable expectation of successfully improving thermal conductivity of the base plate to improve heating and cooling of the wells for thermocycling procedures.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Kelso as applied to claim 1 above, and further in view of Sandell (US 20040018610 A1).
Regarding claim 17, Kelso fails to teach: the sample holder according to claim 1, further comprising a peripheral frame encompassing the solid cover structure, wherein the peripheral frame is made of a material with a melting point which is higher than the melting point of the solid cover structure.
Kelso teaches sample preparation prior to modification and analysis using thermocyclers ([0085]); and the device suitable for carrying out PCR ([0107]). Kelso teaches the wax channel surrounding the chambers (Fig. 4) and is melted before the experiment to create a phase change plug ([0200]; Fig. 2). Kelso teaches a liquid wax covering a volume of liquids in an array of wells (Fig. 2).
Sandell teaches a heated plate assembly (abstract; Figs. 1-2) including a plurality of sample wells (12) and a cover structure (40). Sandell teaches the assembly includes a peripheral frame (Figs. 1-2, frame member 50) encompassing the cover structure (Figs. 1-2 teach frame member surrounds or encompasses cover 40). Sandell teaches the peripheral frame is used to assist in holding the cover in place ([0048]-[0049]). Sandell teaches the peripheral frame may be made of any suitable material, for example sheet metal or any other material suitable for withstanding operating temperatures of approximately 80 C or higher, and appropriately suited for biological testing using a heated plate ([0048]). Sandell teaches the assembly is used for thermal cycling and real-time detection of nucleic acid amplification during thermal cycling ([0042]).
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 sample holder of Kelso to incorporate Kelso’s teachings of performing PCR and thermocycling ([0085],[0107]) where the wax channel melts ([0200]) and Sandell’s teachings of a peripheral frame to assist in holding a cover for an assembly for thermal cycling (Figs. 1-2; [0042], [0048]-[0049]) to provide: the sample holder according to claim 1, further comprising a peripheral frame encompassing the solid cover structure, wherein the peripheral frame is made of a material with a melting point which is higher than the melting point of the solid cover structure. Doing so would have a reasonable expectation of successfully improving supporting and holding sample holder including the solid cover structure in place during thermocycling procedures and analysis.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Wojtowicz (US 20190022657 A1) teaches a thermal block for a plurality of reaction sites (abstract). Wojtowicz a substrate and sample block having improved thermal isolation throughout the devices for desired performance of bio-analysis instrumentation utilizing such devices, such as PCR ([0034]-[0035]). Wojtowicz teaches substrate materials including metals such as Aluminum, Copper, Gold and Silver exhibit thermal conductivities from 205 W/mK to 406 W/mK ([0040]).
Atrazhev (US 20130078616 A1) teaches a system for amplification of nucleic acids within a hydrogel (abstract; Fig. 4) including a base plate (403) including wells (401), and a solid cover structure (406) on top of the base plate (Fig. 4), the solid cover structure is made of wax ([0042]).
Jebrail et al. (US 20210069714 A1) teaches an air-matrix digital microfluidic apparatus (abstract). Jebrail teaches a wax material in a solid state at room temperature and below, but may selectively and controllably combined with a reaction droplet within the air gap when the wax structure is heated ([0015]); the wax including paraffin wax ([0017]). Jebrail teaches a wall formed by the wax body, and upon heating to a temperature above the melting point of the wax, the wax body may melt and cover or surround the reaction droplet; wherein paraffins typically have melting points between 50 and 70 degrees Celsius ([0203]; Figs. 60A-60B).
Glauser et al. (US 20180221875 A1) teaches reversible sealing of a microfluidic chip including a sealing agent having a melting point above room temperature (abstract). Glauser teaches a sealing agent is held to the inner wall of a port (Figs. 3-3B, sealing agent 30) and is heated to melt and form an immiscible layer upon a surface of fluid of the port (Fig. 3D; [0017]). Glauser teaches the sealing agent has a melting temperature of 25° C -90° C, or between about 35° C- 80° C, or between about 45° C - 75° C ([0030]) and the wax includes paraffin wax ([0030]). Glauser teaches the instrument conducts thermal cycling ([0104]).
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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/HENRY H NGUYEN/Primary Examiner, Art Unit 1758
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