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 .
Claims 10-27 are pending and are being examined on the merits.
Information Disclosure Statement
The Information Disclosure Statements submitted June 4, 2024 and December 9, 2024 have each been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete. Specifically, the size of the XML file should be listed in bytes, not kilobytes.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because of the following informalities: Paragraph [0001] should be updated to indicate that the parent application, US Serial No. 17/508,359, has issued into US Patent No. 12,037,635.
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 10-15 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.
Indefiniteness rejections
Claim 13 recites “a solid form reverse transcriptase”, the meaning of which is unclear. Specifically, “solid form” could be interpreted to mean a reverse transcriptase solution that has been dried, by any technique, to create a solid form. However, the specification recites “the reverse transcriptase can be a lyophilized or solid form reagent” (e.g., para. 152). Therefore, it is unclear if “solid” in claim 13 is intended to exclude a lyophilized form of the enzyme, and only refer to non-lyophilized solid forms of the reagent, or if “solid” in the claims should be construed as any solid form of the reagent, including one that has been created through lyophilization. Since the ordinary artisan would not be able to determine the metes and bounds of the claims, and it is indefinite.
Lack of antecedent basis rejections
Claim 10 recites the limitation "the input solution" in l. 9. There is insufficient antecedent basis for this limitation in the claim. Claim 10 previously recites an input volume and an amplification solution, but not an input solution.
Claims 11-15 depend from claim 10, and consequently incorporate the lack of
antecedent basis issues of claim 10.
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.
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 16 is rejected under 35 U.S.C. 103 as being unpatentable over Andreyev1 (US Patent App. Pub. No. 2016/0186240) in view of Vermesh (US 2009/0053732 A1).
Regarding independent claim 16, Andreyev teaches …
An apparatus, comprising: (para. 83: “an apparatus … configured to perform … molecular diagnostic tests … including … nucleic acid … detection”);
a housing (para. 6: “device includes a housing”);
a sample preparation module within the housing (para. 97: “conveying a sample into a sample preparation module … [which] is disposed within a housing”);
the sample preparation module defining an input reservoir configured to receive a blood sample, the sample preparation module configured to prepare the sample, the sample containing a target RNA molecule (para. 180: “sample preparation module … is disposed at least partially within the sample preparation portion of the lower housing … and is configured to receive an input sample”; para. 181: “the sample preparation module … is configured to accept and allow for spill-proof containment of a volume of liquid”; para. 315: “sample prep module has been shown to isolate the desired [target]”; para. 105: “sample … can be … blood”; para. 317: RNA target);
a reverse transcription module within the housing, the reverse transcription module configured to heat the sample to produce a target cDNA molecule associated with the target RNA molecule thereby producing an amplification solution (para. 317: “[f]or viral RNA targets, reverse transcription takes place in the heating chamber prior to PCR”);
and an amplification module disposed within the housing, the amplification module including a flow member and a heater, the flow member defining a reaction volume configured to receive the amplification solution, the heater configured to convey thermal energy into the reaction volume to amplify the target cDNA molecule within the amplification solution to produce an output containing a target amplicon. (Fig. 2; para. 116: “[t]he amplification module … includes a flow member … and a heater … and is configured to perform a … PCR on the input sample”; para. 317: “[a]fter PCR amplification, the amplicons are captured by sequence specific hybridizing probes”; para. 87: “detection module is configured to receive an output [i.e., a detection solution] from the amplification module”).
Andreyev does not teach that the sample is blood and that plasma is separated from blood. However, Vermesh teaches these limitations. Specifically, Vermesh teaches a microfluidic device configured to separate plasma from blood and then detect target analytes, e.g., oligonucleotides, in the plasma (paras. 16, 41, 43).
Prior to the effective filing date of the present invention, it would have been prima facie obvious to modify the Andreyev device with the Vermesh plasma separator. Andreyev teaches the need for point-of-care testing devices that provide fast and accurate results. Andreyev also teaches blood as being a useful target sample. The ordinary artisan would have been motivated to modify the Andreyev device to incorporate the Vermesh plasma separator with the expectation that doing so would result in the advantage of a device with improved speed and accuracy as it would eliminate the need for a separate, additional device to separate plasma from blood, and would eliminate the possibility of contamination while transferring the plasma from a separate plasma separation device to the microfluidic device. The ordinary artisan would have had an expectation of success because the design and modification of microfluidic devices is well-known in the art, and because Vermesh teaches a microfluidic device with such a component.
Claims 19-22 and 24-27 are rejected under 35 U.S.C. 103 as being unpatentable over Andreyev (US Patent App. Pub. No. 2016/0186240) in view of Sobek (Processing Protocols for High Quality Glass-Based Microarrays. In: Rampal, J.B. (eds) Microarrays. Methods in Molecular Biology, vol. 382. 2007. Humana Press. https://doi.org/10.1007/978-1-59745-304-2_4).
Regarding independent claim 19, Andreyev teaches …
A method of detecting a nucleic acid using a molecular diagnostic test device,
comprising: conveying at a first time a first volume of a first reagent solution from a reagent module within the molecular diagnostic test device to a detection module within the molecular diagnostic test device (paras. 93, 160; also see discussion below regarding the first reagent solution components);
the detection module including a detection surface configured to capture a target amplicon associated with the nucleic acid (paras. 91, 160);
conveying at a second time a sample solution containing the target amplicon into the detection module such that the target amplicon is captured on the detection surface (para. 91);
conveying after the second time a second reagent solution into the detection module, the second reagent solution formulated to cause a signal that indicates a presence of the target amplicon within the sample solution to be produced (para. 91, 93, 97, 100, 108);
and conveying after the second time a second volume of the first reagent solution into the detection module, the second volume of the first reagent solution containing an amount of the wash buffer sufficient to remove an unbound constituent from at least one of the sample solution or the second reagent solution from the detection module (paras. 160, 161).
Further, regarding the limitations reciting that the first reagent solution includes a blocking agent and a wash buffer, and that the first volume of the first reagent solution contains an amount of the blocking solution sufficient to adsorb to a surface within the detection module, Andreyev teaches “the detection module 5800 includes a detection surface 5821 with a read lane or flow channel. The detection surface 5821 is spotted and/or covalently bonded with a specific hybridizing probe 5870, such as an oligonucleotide … The bonding of the hybridizing probe 5870 to the detection surface 5821 can be performed using any suitable procedure or mechanism” (para. 160). Andreyev does not explicitly teach a procedure for attaching the probe to the detection surface. However, Sobeck teaches methods of preparing oligonucleotide arrays and teaches incubating the detection surface with blocking solutions and wash buffers just prior to incubation with the oligonucleotide probes (section 3.1.1). The ordinary artisan would thus understand from the combined teachings of Andreyev and Sobek that, prior to probe hybridization, the detection surface can be prepared by blocking and washing the detection surface with a reagent solution comprising a blocking solution and a wash buffer (i.e., any suitable method of bonding the hybridizing probe to the detection surface). The ordinary artisan would also be able to optimize the amount of blocking solution.
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Andreyev method to incorporate the Sobeck wash buffer and blocking solutions. Andreyev teaches that attaching the probe to the detection surface can be performed using any suitable technique. Sobek teaches such a technique and teaches that the reagents include wash buffer and blocking solutions. The selection of a known material based on its suitability for its intended purpose supports a prima facie obviousness determination. MPEP 2144.07. The ordinary artisan would have been additionally motivated to optimize the reagents used in the method to customize the assay as needed through routine experimentation. The ordinary artisan would have had an expectation of success as the design and optimization of microfluidic device configurations is well-known in the art.
Regarding dependent claim 20, Andreyev additionally teaches that the molecular diagnostic test device is a stand- alone molecular diagnostic test device and the method of detecting is performed without any external instrument (e.g., para. 108).
Regarding dependent claim 21, Andreyev additionally teaches that the reagent module includes a first reagent container, the first reagent solution being sealed within the first reagent container before the conveying at the first time, the method further comprising: releasing the first reagent solution from the first reagent container within the molecular diagnostic test device (para. 136).
Regarding dependent claim 22, Andreyev additionally teaches that the method further comprises storing, before the releasing, the molecular diagnostic test device including the sealed first reagent container for at least six months (para. 136).
Regarding dependent claim 24, Andreyev additionally teaches that the conveying the first volume of the first reagent solution at the first time, the conveying the sample solution at the second time, and the conveying the second volume of the first reagent solution after the second time are each performed by a fluid pump within the housing (paras. 84, 158, 235, 309, 311, 371).
Regarding dependent claims 25-26, Sobek additionally teaches or suggests that the blocking agent includes bovine serum albumin and the wash buffer includes a detergent (section 3.1.1 and 3.2: e.g., BSA and SDS), as recited in claim 25, and that the first reagent solution includes between 0.02 percent and 5 percent bovine serum albumin and between 0.05 percent and 10 percent of the detergent (section 3.1.1 and 3.2: e.g., 1-3% BSA and 0.2% SDS), as recited in claim 26.
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to further modify the modified Andreyev method, discussed above, to incorporate the specific components and percentages of the Sobeck wash buffer and blocking solutions. Andreyev teaches that attaching the probe to the detection surface can be performed using any suitable technique. Sobek teaches that BSA in specified amounts and SDS in specified amounts can be used to do so. The selection of a known material based on its suitability for its intended purpose supports a prima facie obviousness determination. MPEP 2144.07. The ordinary artisan would have been additionally motivated to optimize the reagents used in the method to customize the assay as needed through routine experimentation. The ordinary artisan would have had an expectation of success as the design and optimization of microfluidic device configurations is well-known in the art.
Regarding dependent claim 27, Andreyev additionally teaches that the method further comprises conveying before the second time an input sample to an amplification module within the molecular diagnostic test device, the amplification module defining a reaction volume; and heating the input sample within the reaction volume to amplify the nucleic acid within the input sample thereby producing the sample solution containing the target amplicon (paras. 91, 93, 97, 231, 256-257, 259).
Prior Art
Independent claim 10 and dependent claims 11-15 are free of the art. The closest prior art is Andreyev (US Patent App. Pub. No. 2016/0186240), Katz2 (IL 242807), Silverbrook3 (US Patent App. Pub. No. 2011/0312787) and Mahony4 (US Patent App. Pub. No. 2017/0173585).
The teachings of Andreyev are discussed above. Silverbrook is directed to a
lab-on-a-chip device for analyzing nucleic acids isolated from a biological sample. Silverbrook teaches devices with a single action actuation of a switch (para. 205), but does not teach that the actuation occurs as a result of moving or closing a lid of a molecular diagnostic device. Katz teaches a lid which is capable of being actuated (p. 13, claims 1 and 2), but does not teach that the lid actuation provides power to a heater. In addition, Mahony teaches a point-of-care device for detecting a target nucleic acid. Mahony additionally suggests activating a heater by closing the lid of a point-of-care device (para. 31; para. 32: “heater is activated when the lid of the extraction chamber is closed, thereby completing a circuit which connects the heater to a power supply”). However, Mahony does not teach at least a lid with a switch portion, wherein the actuation of switch provides power to a heater.
Dependent claims 17 and 18 are free of the art. The closest prior art is Andreyev (US Patent App. Pub. No. 2016/0186240), Vermesh (US 2009/0053732 A1), Liu (A high-efficiency superhydrophobic plasma separator, Lab on a Chip, 6(3): 553-560, 2016) and Wright (WO 2015/095853 A1).
The teachings of Andreyev and Vermesh are discussed above. Liu teaches a hydrophobic
plasma separator (e.g., Fig. 1), while Wright teaches a spiral filter configured to separate the plasma sample (Fig. 2). However, Liu hydrophobic plasma separator and the Wright spiral filter are standalone devices configured to separate plasma from blood samples that have a larger volume than what would be input into a microfluidic device. There does not appear to be any reason to modify the Andreyev microfluidic device to incorporate such components, nor does there appear to be a reasonable expectation of success in modifying the size of the Liu hydrophobic plasma separator and the Wright spiral filter and altering their respective configurations to make them compatible with the Andreyev device.
Dependent claim 23 is free of the art. The closest prior art is Andreyev (US Patent App. Pub. No. 2016/0186240) and Sobek (Processing Protocols for High Quality Glass-Based Microarrays. In: Rampal, J.B. (eds) Microarrays. Methods in Molecular Biology, vol. 382. 2007. Humana Press. https://doi.org/10.1007/978-1-59745-304-2_4).
The teachings of Andreyev and Sobek are discussed above. While Andreyev teaches that
the reagent module includes a reagent housing defining a reagent reservoir, and that the releasing of the first reagent solution includes releasing the first reagent solution into the reagent reservoir (para. 93), it does not teach returning at least a portion of the first volume of the first reagent solution from the detection module back to the reagent reservoir and then including at least a portion of he first volume in the second volume. Nor does there appear to be any reason to modify Andreyev to do so as it is not clear that the Andreyev device can be modified in this way and because re-using at least a portion of the first volume of first reagent solution may result in undesirable components or impurities being introduced into the second volume of the first reagent solution.
Allowable Subject Matter
Claims 17-18 and 23 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 10-27 are being examined. Claims 10-16, 19-22 and 24-27 are rejected. Claims 17-18 and 23 are objected to, but are otherwise directed to allowable subject matter. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CAROLYN L GREENE/Primary Examiner, Art Unit 1681
1 Andreyev was cited in the Information Disclosure Statement submitted June 4, 2024.
2 Katz was cited in the Information Disclosure Statement submitted June 4, 2024.
3 Silverbrook was cited in the Information Disclosure Statement submitted June 4, 2024.
4 Mahony was cited in the Information Disclosure Statement submitted June 4, 2024.
Prosecution Insights