DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Objections
Claims 2, 6, 7, 17 and 20 are objected to because of the following informalities:
In claim 2, the term “or 0.2 mm dw ≤ 2 mm” should be written as “or 0.2 mm ≤ dw ≤ 2 mm”. Appropriate correction is required.
In claim 6, the term “nu-cleic” should be written as “nucleic”.
In claim 7, the term “re-verse” should be written as “reverse”.
In claim 17, the term “plu-rality” should be written as “plurality”.
In claim 20, the term “run-ning” should be written as “running”.
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.
Claims 8-10, 19, 22 and 23 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 8 recites the limitation "the first nucleic acid" and the limitation “the second nucleic acid” in lines 3 and 5. There is insufficient antecedent basis for these limitations in the claim. It is unclear if these limitations are intended to refer back to the “first dried nucleic acid amplification test kit” and the “second dried nucleic acid amplification test kit” previously recited in claim 1.
Claim 9 recites the limitation "the first nucleic acid" and the limitation “the second nucleic acid” in lines 3 and 5. There is insufficient antecedent basis for these limitations in the claim. It is unclear if these limitations are intended to refer back to the “first dried nucleic acid amplification test kit” and the “second dried nucleic acid amplification test kit” previously recited in claim 1.
Claim 10 recites the limitation "the first set of primers" and the limitation “the second set of primers” in line 2. There is insufficient antecedent basis for these limitations in the claim. It is believed that claim 10 should be made dependent on claim 4.
Claim 19 recites the limitation "the thermal interface conductance" in line 3. There is insufficient antecedent basis for these limitations in the claim.
Claim 22 recites the limitation "the first nucleic acid" and the limitation “the second nucleic acid” in lines 2 and 4. There is insufficient antecedent basis for these limitations in the claim. It is unclear if these limitations are intended to refer back to the “first dried nucleic acid amplification test kit” and the “second dried nucleic acid amplification test kit” previously recited in claim 1.
Claim 23 recites the limitation "the first nucleic acid" and the limitation “the second nucleic acid” in lines 2 and 4. There is insufficient antecedent basis for these limitations in the claim. It is unclear if these limitations are intended to refer back to the “first dried nucleic acid amplification test kit” and the “second dried nucleic acid amplification test kit” previously recited in claim 1.
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. lymp
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-7, 10-21, 24 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Stark (WO 2019122217) in view of Dunne (US 20170136458) and Lovell (US 20040033610).
With respect to claim 1, Stark discloses a metallic sample holder (Figure 1:1) comprising an array of wells (Figure 2a:11). Each well of the array is adapted to capture a sample volume (“The indentations correspond preferably to so called sample wells, wherein each indentation corresponds to one sample well for PCR detection” and “The light sources were directed to the sample holder for exciting the sample volumes captured in the indentations of the sample holder array”). Furthermore, each well is loaded with a freeze-dried nucleic acid amplification test kit. The wells are in thermal connection, and the sample holder is adapted to have the same temperature across the entire holder when exposed to a temperature change. Stark teaches that temperature changes occur across all wells rapidly and uniformly (“As mentioned above, in regard of the inventive apparatus, this change of temperature is accelerated by thermally coupling the sample holder to the body of the apparatus that serves as a heat sink. Quickly switching between the target temperature and therefore quickly going through the thermal cycle, raises several advantages”). Stark, however, does not appear to teach that the wells are divided between first and second sectors, wherein the first sector is loaded with a first dried nucleic acid amplification test kit and the second sector is loaded with a second dried nucleic acid amplification test kit.
Dunne discloses a multi-well sample holder (Figure 1:25) that may be constructed from metal materials. See paragraph [0056]. Each of the wells (Figure 1:28) are adapted to capture a sample volume. Paragraphs [0032]-[0034] and [0042] describe how the wells may be divided into any number of sectors (e.g., first and second sectors), wherein each sector receives a different dried nucleic acid amplification reagent test kit. See also paragraphs [0083] and [0084]. Fig. 6 shows one example in which each column is designated as a unique sector (1-10) such that all wells along a common column receive the same primer, while each row is similarly designated as a unique sector (A-F) such that all wells along a common row receive the same primer.
Lovell discloses a multi-well sample holder (Figure 1a:100) comprising an array of wells. Each well is configured to capture a sample volume. Furthermore, each well may retain a plurality of reagents. Paragraphs [0036]-[0047] indicate that the sample holder may be divided into essentially any number of sectors (Figure 1a:110) (e.g., first and second sectors), such that each sector may be provided with a different group of reagent test kits. See especially Figs. 2a-e.
Before the effective filing date of the claimed invention, it would have been obvious to arrange the wells of Stark in any pattern so that at least first and second sectors are loaded, respectively, with first and second dried nucleic acid amplification reagent test kits. Dunne teaches that this strategy is useful when it is necessary to evaluate a number of different samples using a number of different primers (“uniquely labelling the nucleic acids in a large number of discrete sample volumes to enable tracking, monitoring, result-correlation, etc. of the nucleic acids and experiments and assays performed”). Although Dunne focusses on a more complicated dual barcoding and pooling strategy, Dunne teaches the fundamental notion that it is desirable to load different PCR primers/reagents into different well sectors for the purpose of performing and tracking different PCR operations in the different sectors. Likewise, Lovell shows how it is logical to subdivide a standard well plate into a plurality of regions/sectors based on shared chemical and/or physical characteristics, and that this facilitates detection and analysis of individual wells. It would therefore have been obvious to strategically (or even arbitrarily) divide the Stark array of wells into designated first and second sectors that receive first and second PCR reagents.
With respect to claim 2, Stark, Dunne and Lovell disclose the combination as described above. Stark additionally shows in Fig. 6a that the wells 11 are all less than 0.9 mm apart from neighboring wells. Accordingly, any first and second sectors designated in Stark would have wells less than 0.9 mm apart.
With respect to claim 3, Stark, Dunne and Lovell disclose the combination as described above. As previously discussed, Stark, Dunne and Lovell each teach wells adapted for capturing sample volumes for nucleic acid amplification test reactions.
With respect to claim 4, Stark, Dunne and Lovell disclose the combination as described above. As previously discussed, Dunne teaches in paragraphs [0032]-[0034] and [0042] first and second primers are utilized for identifying and quantifying first and second nucleic acids.
With respect to claim, 5 Stark, Dunne and Lovell disclose the combination as described above. Stark and Dunne each indicate that PCR requires a nucleic acid amplification enzyme (i.e., a DNA polymerase), dNTPs and a buffer.
With respect to claim 6, Stark, Dunne and Lovell disclose the combination as described above. Stark further teaches an identifying and/or quantifying step includes the provision of a nucleic acid detection probe and a fluorescent dye (“In a typical fluorescent assay system, a fluorescent probe or fluorophore assay system, a fluorescent probe or fluorophore absorbs light having a wavelength or range of wavelengths”).
With respect to claim 7, Stark, Dunne and Lovell disclose the combination as described above. Dunne further teaches in at least paragraphs [0010] and [0032] that a reverse transcriptase enzyme is provided in each well.
With respect to claims 10 and 11, Stark, Dunne and Lovell disclose the combination as described above. It is well within the ability of one of ordinary skill to select primers having the same or similar annealing temperature and the same or similar length. See, for example, paragraph [0049] of Dunne (“The exact length of the primer will depend upon many factors, including temperature, source of the primer, and the method used. For example, for diagnostic and prognostic applications, depending on the complexity of the target sequence, the oligonucleotide primer typically contains at least 10, or 15, or 20, or 25 or more nucleotides, although it may contain fewer nucleotides or more nucleotides. The factors involved in determining the appropriate length of primer are readily known to one of ordinary skill in the art”).
With respect to claim 12, Stark, Dunne and Lovell disclose the combination as described above. Stark further states that the metallic sample holder consists of aluminum, silver, gold, copper or alloys thereof (“the sample holder is made of aluminum, silver, gold, copper, or alloys thereof”).
With respect to claim 13, Stark, Dunne and Lovell disclose the combination as described above. Any of the Stark wells may be used (“is adapted”) as a positive or negative control.
With respect to claim 14, Stark, Dunne and Lovell disclose the combination as described above. Stark, Dunne and Lovell each teach wells that have a cylindrical shape and a flat bottom area. Start especially teaches that the bottom area is configured to reflect an optical signal by means of a flat metallic layer (“the indentations 11 have an at least partially flat bottom area 111. The essentially flat bottom area 111 serves for reflecting an optical signal. In particular because the sample holder 1 is made of metal, the reflected optical signal is very strong and can be detected by an optical detector 4”).
With respect to claims 15 and 16, Stark, Dunne and Lovell disclose the combination as described above. Dunne additionally teaches that each well includes a unique molecular identifier and/or a plurality of barcoded oligonucleotides that are configured to provide information about the method of detection.
With respect to claims 17 and 18, Stark, Dunne and Lovell disclose the combination as described above. Stark additionally shows an apparatus (Figure 3:200) for receiving the metallic sample holder. The apparatus includes a thermal setting element (Figure 3:3) thermally coupleable to the sample holder. A controller (Figure 3:6) controls a thermal cycle of the thermal setting element, and an optical detector (Figure 3:4) is arranged in a line of sight of the array of wells. The optical detector is configured to detect, assign and record a plurality of signals from the sample volume of each well of the array of the metallic sample holder.
With respect to claim 19, Stark, Dunne and Lovell disclose the combination as described above. Stark further states that the controller is configured to steer the thermal setting element to produce a net effective heating ramp equal to or higher than 5°C/s and a net effective cooling ramp equal to or lower than -5°C/s (“Preferably, the thermal setting element heats the sample holder with a net effective heating ramp equal or higher than 5.0°C/s (net effective heating ramp 5.0°C/s), preferably with a net effective heating ramp equal or higher than 8.0°C/s (net effective heating ramp 8.0°C/s), or very preferably with a net effective heating ramp equal or higher than 10.0°C/s (net effective heating ramp 10.0°C/s) . Wherein a higher heating ramp corresponds to faster heating. Preferably, the thermal setting element cools down the sample holder with a net effective cooling ramp equal or lower than -5.0°C/s (net effective cooling ramp < -5.0°C/s), preferably with a net effective cooling ramp equal or lower than -8.0°C/s (net effective cooling ramp -8.0°C/s), or very preferably with a net effective cooling ramp equal or lower than -10.0°C/s (net effective cooling ramp -10.0°C/s) . Wherein a lower cooling ramp corresponds to faster cooling”).
With respect to claims 20 and 21, Stark, Dunne and Lovell disclose the combination as described above. Stark and Dunne each teach corresponding methods for operating the previously discussed PCR systems. Stark and Dunne each indicate that a sample holder comprising an array of wells is provided. Stark teaches that the sample holder is adapted to have the same temperature across its entire body when exposed to a temperature change. Stark and Dunne teach that dried nucleic acid amplification test kits (“reagents”) are added to each well, and that a sample is then applied to each well to dissolve the dried reagents. PCR is conducted and target nucleic acids are detected. Dunne and Lovell further disclose that the array of wells may be divided into at least first and second sectors, wherein the first sector is loaded with a first dried nucleic acid amplification test kit, and the second sector is loaded with a second dried nucleic acid amplification test kit. Detection is accomplished using a camera operated by a controller comprising a feedback loop (“the temperature sensor is connected to the controller and the thermal setting element for providing a feedback loop for controlling the temperature of the sample holder. In such an embodiment, the controller e.g. predefines a specific temperature value and sends respective commands to the thermal setting element for heating or cooling the sample holder, wherein the temperature sensor informs the controller as soon as the sample holder reaches the respective temperature”).
With respect to claim 24, Stark, Dunne and Lovell disclose the combination as described above. Dunne further states that the identifier provides information about the nucleic acid target, and, accordingly, allows one to tailor a PCR operation to the needs of a particular assay.
With respect to claim 25, Stark, Dunne and Lovell disclose the combination as described above. Stark and Dunne each teach that PCR is conducted.
Claims 8, 9, 22 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Stark (WO 2019122217) in view of Dunne (US 20170136458) and Lovell (US 20040033610) as applied to claims 1 and 7, and further in view of Tanner (US 10968493).
Stark, Dunne and Lovell disclose the combination as described above, however do not appear to expressly teach that the assay tests for DNA or RNA isolated from a virus.
Tanner discloses an apparatus and method comprising a plurality of test wells for performing multiplex LAMP reactions. Tanner specifically mentions in the Background and in column 4, lines 23-43 that the target nucleic acid is derived from a corona virus, an influenza virus, and/or SARS-CoV-2.
Before the effective filing date of the claimed invention, it would have been obvious to use the modified Stark device to screen for infectious agents, such as a corona virus, an influenza virus, and/or SARS-CoV-2. Tanner teaches that it is of critical importance to screen for potential cases of infections from patients in a clinical setting to improve individual care and prevent disease spread. Tanner shows how the detection of corona virus, influenza virus, and/or SARS-CoV-2 is accomplished using standard amplification and analysis techniques utilizing traditional multi-well plates.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The Tan (US 20080274511) reference teaches the state of the art regarding multi well sample holders divided into at least first and second sectors.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN ANDREW BOWERS whose telephone number is (571)272-8613. The examiner can normally be reached M-F 7am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached at (571) 272-1374. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NATHAN A BOWERS/ Primary Examiner, Art Unit 1799