DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/09/2025 has been entered.
Applicant's response, filed on 09/09/2025, have been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Status of claims
Canceled:
2-3, 6, 8-9, 13, 18-20, 23
Pending:
1, 4-5, 7, 10-12, 14-17, 21-22
Amended:
1, 4, 10-12, 14, 16-17, 21-22
Withdrawn:
none
Examined:
1, 4-5, 7, 10-12, 14-17, 21-22
Independent:
1, 21
Allowable:
none
Priority
As detailed on the 11/14/2019 filing receipt, this application claims priority to PCT/KR2017/0053230 filed 05/19/2017. As a National stage filing, all claims have been interpreted as being accorded this priority date.
Withdrawn Rejections/Objections
The rejection of claims 1, 4-5, 7, 10-12, 14 and 16-17 under 35 U.S.C. §102(a)(1) over Wong, in the Office action mailed 05/09/2025 is withdrawn in view of the amendments filed 09/05/2025. However, a new rejection is applied as discussed below.
The rejection of claims 15 and 21-22 under 35 U.S.C. §103 over Wong in view of Gunstream 2011, in the Office action mailed 05/09/2025 is withdrawn in view of the amendments filed 09/05/2025. However, a new rejection is applied as discussed below.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 4-5, 7, 10-12, 14-17, and 21-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 (page 3, line 12) and 21 (page 7, line 10) recite “wherein the method does not comprise the use of any passive dye for the transformation of the amplification curve.” The specification discloses “A wide variety of the signal-generating means have been known to one of skill in the art. Examples of the signal-generating means may include oligonucleotides, labels and enzymes. The signal-generating means include both labels per se and oligonucleotides with labels. The labels may include a fluorescent label, a luminescent label, a chemiluminescent label, an electrochemical label and a metal label. The label per se like an intercalating dye may serve as signal-generating means. Alternatively, a single label or an interactive dual label containing a donor molecule and an acceptor molecule may be used as signal-generating means in the form of linkage to at least one oligonucleotide. The signal-generating means may comprise additional components for generating signals such as nucleolytic enzymes (e.g., 5′-nucleases and 3′-nucleases).” (page 13, para. 4) and “According to an embodiment, the plurality of signal-generating processes may be a plurality of signal-generating processes for the same-typed target analyte performed in different reaction environments. Signal-generating processes in different reaction environments comprise various embodiments. Particularly, the signal-generating processes in different reaction environments may be a signal-generating processes performed on different instruments, performed in different wells or reaction tubes, performed for different samples, performed with target analytes of different concentrations, performed with different primers or probes, performed with different signal-generating dyes or performed by different signal-generating means. According to an embodiment, the plurality of the signal-generating-processes is performed on different instruments from each other.” (page 22, Para. 4). The specification does not disclose not using passive dye for the transformation of the amplification curve of claims 1 and 21. Therefore, this limitation is new matter.
Dependent claims are rejected for depending on rejected claim.
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 21-22 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.
Claim 21 recites “A non-transitory computer readable storage medium containing instructions to configure a processor to perform a method for detecting a target analyte in a sample, the method comprising:(a) performing a real-time polymerase chain reaction (RT-PCR) for the target analyte…” The “non-transitory computer readable storage medium” and “processor” cannot directly recite process steps such as performing a real-time polymerase chain reaction because a single claim which claims both an apparatus and the method steps of using the apparatus is indefinite (see MPEP 2173.05(p).II).
Claim 22 recites “A device for of detecting a target analyte in a sample, comprising (a) a computer processor and (b) the computer readable storage medium of claim 21 coupled to the computer processor. …” The “computer readable storage medium and processor” cannot directly recite process steps such as detecting a target analyte in a sample because a single claim which claims both an apparatus and the method steps of using the apparatus is indefinite (see MPEP 2173.05(p).II).
Dependent claims are rejected for depending on rejected claims.
Claim rejections - 101
35 USC 101 reads:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
For each rejection below, dependent claims are rejected similarly as not remedying the rejection, unless otherwise noted.
Judicial exceptions (JEs) to 101 patentability
Claims 1, 4-5, 7, 10-12, 14-17, 21-22 are rejected under 35 USC 101 because the claimed inventions are not directed to patent eligible subject matter. After consideration of relevant factors with respect to each claim as a whole, each claim is directed to one or more judicially-recognized exceptions to patentability (JEs), i.e. an abstract idea, a natural phenomenon, a law of nature and/or a product of nature, as identified below. As set forth below, it is not clear that any element or combination of elements in addition to the JE(s), i.e. and "additional elements," either integrate the identified JE(s) into a practical application and/or is a non-conventional additional element, such that it is not clear that any claim is directed to significantly more than the identified JE(s).
MPEP 2106 organizes JE analysis into Steps 1, 2A (1st prong & 2nd prong) and 2B as analyzed below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: www.uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Analysis of claims 1, 4-5, 7, 10-12, 14-17, 21-22
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Independent claim 1 is directed to a 101 process, here a “method for detecting a target analyte in a sample …," with process steps such as "performing …, transforming… and detecting…"
Independent claim 21 is directed to a 101 machine or manufacture, here a “non-transitory computer readable storage medium containing instructions to configure a processor to perform a method for detecting a target analyte in a sample," with non-transitory elements such as "computer readable storage medium and processor."
[Step 1: claims 1, 4-5, 7, 10-12, 14-17, 21-22: YES]
Step 2A, 1st prong: Do the claims recite a judicially-recognized exception (JE), e.g. a law of nature, a natural phenomenon or product, or an abstract idea (MPEP 2106.04.II.A.1 & .04(a))?
The MPEP at 2106.I, 2nd para. explains that JEs have been court-recognized as occurring in at least four types: abstract ideas, laws of nature and natural phenomena (including natural products).
MPEP § 2106.04(a)(2) further explains that abstract ideas may be grouped as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations);
• certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people);
and/or
• mental processes (procedures for observing, evaluating, analyzing/ judging and
organizing information).
Regarding the instant claims and with respect to Step 2A, 1st prong, at least preliminarily these claims recite JEs in the form of abstract ideas, mathematical concepts and certain methods of organizing human activity as follows.
Mental processes and mathematical concepts recited include:
Claims 1 and 21 recite: “Step (b) transforming the amplification curve into a calibrated amplification curve by replacing a signal value at each of the cycles in the amplification curve with a calibrated signal value; Step (c) detecting the target analyte in a sample qualitatively or quantitatively using the calibrated amplification curve.” The process of transforming the amplification curve and detecting the target analyte ‘qualitatively or quantitatively’ involves analyzing, evaluating, judging, observing and organizing data to adjust the amplification curve and to determine whether the analyte is present in the sample, which could be performed with the human mind and/or with pen and paper.
Claim 11 recites: “wherein the reference cycle is selected from a reference cycle group of each amplification curve, wherein the reference cycle group of each amplification curve is provided in the same manner to each other.” The process of selecting could be performed with the human mind or with pen and paper, which involves selecting a value from a list and assigning it as the reference cycle.
Claim 12 recites: “wherein an identical reference cycle is provided for calibrating each amplification curve of the plurality of amplification curves.” The process of providing could be performed with the human mind or with pen and paper, which involves selecting and assigning a reference cycle.
Claim 22 recites: “...detecting a target analyte in a sample...” The process of detecting involves analyzing, evaluating, observing and judging data that could be performed with the human mind or with pen and paper.
Mathematical concepts recited include:
Claims 1 and 21 recite: Step (b) “wherein the calibrated signal value is obtained by dividing the signal value at each of the cycles in the amplification curve by an analyte-insusceptible signal value,...; Step (b)(ii) a total signal change value of a standard amplification curve; for a standard material of the target analyte…; Step (c) detecting the target analyte in a sample qualitatively or quantitatively.” The process of quantitating, dividing and a total signal change requires carrying out a series of mathematical calculations and are involved with mathematical concepts and formulas.
Claim 12 recites: an identical reference cycle is provided for calibrating each amplification curve of the plurality of amplification curves. The process of calibrating requires carrying out a series of mathematical calculations and are involved with mathematical concepts and formulas.
Claim 14 recites: “wherein a total signal change value of a representative standard amplification curve is provided identically for calibrating each of the plurality of the amplification curves.” This process requires carrying out a series of mathematical calculations to calibrate and determine the total signal change and are involved with mathematical concepts and formulas.
Claim 17 recites: “wherein the amplification curve of the step (a) is a amplification curve of which a blank signal value is removed.” This process requires carrying out a series of mathematical calculations to remove blank signal value and are involved with mathematical concepts and formulas.
[Step 2A, 1st prong: claims 1, 4-5, 7, 10-12, 14-17, 21-22: YES]
Step 2A, 2nd prong: Are the above-identified JEs integrated into a practical application (MPEP 2106.04.II.A.2 & .04(d))?
Generally regarding Step 2A, 2nd prong
MPEP 2106.04(d).I lists the following considerations for evaluating whether additional elements integrate a judicial exception into a practical application:
An improvement in the functioning of a computer, or an improvement to other technology or technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a);
Applying or using a judicial exception to affect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2);
Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c); and
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
Additionally, the courts have also identified limitations that did not integrate a judicial exception into a practical application:
Merely reciting a phrase such as "apply it" (or an equivalent) along with the judicial exception, or merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, as discussed in MPEP 2106.05(f);
Adding insignificant extra-solution activity to the judicial exception, as discussed in MPEP 2106.05(g); and
Generally linking the use of a judicial exception to a particular technological environment or field of use, as discussed in MPEP 2106.05(h).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies or uses the recited judicial exception in some other meaningful way. Rather, the instant claims recite additional elements that equate to mere instructions to implement an abstract idea or insignificant extra solution activity. Specifically, the instant claims recite the following additional elements:
claim 1: the recited Step (a) "performing a real-time polymerase chain reaction (RT-PCR) for the target analyte to obtain a amplification curve" and Step (b) "... calibrated signal values is obtained..." step/element, as evidenced by MPEP 2106.05(g), e.g. "insignificant extra solution activity" since the recitation is a conventional element of a laboratory and/or computing environment, conventional data gathering/input elements, and/or conventional post-processing or output elements.
claim 5: the recited "…RT-PCR generates signals..." step/element, as evidenced by MPEP 2106.05(g), e.g. "insignificant extra solution activity" since the recitation is a conventional element of a laboratory and/or computing environment, conventional data gathering/input elements, and/or conventional post-processing or output elements.
claim 10: the recited "amplification curve comprises a plurality of amplification curves obtained from the plurality of RT-PCRs" step/element, as evidenced by MPEP 2106.05(g), e.g. "insignificant extra solution activity" since the recitation is a conventional element of a laboratory and/or computing environment, conventional data gathering/input elements, and/or conventional post-processing or output elements.
claim 14: the recited "...representative standard amplification curve is provided" step/element, as evidenced by MPEP 2106.05(g), e.g. "insignificant extra solution activity" since the recitation is a conventional element of a laboratory and/or computing environment, conventional data gathering/input elements, and/or conventional post-processing or output elements.
claim 21: the recited "A non-transitory computer readable storage medium containing instructions to configure a processor to perform...," Step(a) "performing a real-time polymerase chain reaction (RT-PCR) for the target analyte to obtain a amplification curve" and Step(b) "... calibrated signal values is obtained..."step/element, as evidenced by MPEP 2106.05(g), e.g. "insignificant extra solution activity" since the recitation is a conventional element of a laboratory and/or computing environment, conventional data gathering/input elements, and/or conventional post-processing or output elements.
claim 22: the recited "(a) a computer processor and (b) the computer readable storage medium of claim 21 coupled to the computer processor." step/element, as evidenced by MPEP 2106.05(g), e.g. "insignificant extra solution activity" since the recitation is a conventional element of a laboratory and/or computing environment, conventional data gathering/input elements, and/or conventional post-processing or output elements.
Claims 4, 7 and 15-16 do not recite additional elements.
Claims 4, 7 and 15-16 are providing information on what the data represents and do not change the character of the data obtaining step beyond mere data gathering activity.
The additional elements of claims 1, 5, 10 and 14, as discussed above, equate to mere data gathering and outputting, which amounts to insignificant extra solutional activity (see MPEP 2106.05(g)). The additional elements of claims 21-22 equate to mere data gathering and outputting via generic computer components, such as receiving data at a computer or outputting data, amount to insignificant extra-solution activity as set forth by the courts in Mayo, 566 U.S. at 79, 101 USPQ2d at 1968 and OIP Techs., Inc, v, Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015). Also, the additional elements of computer readable storage media include storing and retrieving information, such as computer program instructions in memory. Storing and retrieving information in memory were identified by the courts as well-understood, routine and conventional in Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93. The use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not integrate a judicial exception into a practical application or provide significantly more as identified by the courts in Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit). As such, as currently recited, the claims do not appear to recite an improvement to technology or apply or use the recited judicial exception in some other meaningful way.
At this point in examination it is not yet the case that any of the Step 2A, 2nd prong considerations enumerated above clearly demonstrates integration of the identified JE(s) into a practical application. Referring to the considerations above, none of 1. an improvement, 2. treatment, 3. a particular machine or 4. a transformation is clear in the record.
For example, regarding the first consideration at MPEP 2106.04(d)(1), the record does not yet clearly disclose an explanation of improvement over the previous state of the technology field. An explanation of improvement requires detailed explanation applicable to all embodiments reasonably within the claim scope. In particular, such an explanation of improvement over the previous state of technology may include: identification of the technology field, the particular improvement, as particular as possible identification of any asserted improvements, explanation of a clear difference from the technology field, explanation that reasonably all embodiments within the claim scope result in the asserted improvement, and an extension of the explanation as far as possible to include the result of an identified practical application. The claims do not yet clearly result in such an improvement. See MPEP 2106.04(d) and (d)(1).
[Step 2A, 2nd prong: claims 1, 4-5, 7, 10-12, 14-17, 21-22: NO]
Step 2B: Do the claims recite a non-conventional arrangement of additional elements (i.e. elements in addition to any identified JE) (MPEP 2106.05)?
All elements of claims 1, 4-5, 7, 10-12, 14-17, 21-22 are part of one or more identified JEs (as described above), except for elements identified here as conventional elements in addition to the above JEs:
Elements of the following claims are additional elements but nonetheless are conventional elements of a laboratory or computing environment, conventional data gathering elements or conventional post-processing elements:
claim 1: the recited Step(a) "performing a real-time polymerase chain reaction (RT-PCR) for the target analyte to obtain a amplification curve" and Step (b) "... calibrated signal values is obtained..." step/element, as evidenced by MPEP 2106.05(g), e.g. "insignificant extra solution activity" since the recitation is a conventional element of a laboratory and/or computing environment, conventional data gathering/input elements, and/or conventional post-processing or output elements.
claim 5: the recited "…RT-PCR generates signals..." step/element, as evidenced by MPEP 2106.05(g), e.g. "insignificant extra solution activity" since the recitation is a conventional element of a laboratory and/or computing environment, conventional data gathering/input elements, and/or conventional post-processing or output elements.
claim 10: the recited "amplification curve comprises a plurality of amplification curves obtained from the plurality of RT-PCRs" step/element, as evidenced by MPEP 2106.05(g), e.g. "insignificant extra solution activity" since the recitation is a conventional element of a laboratory and/or computing environment, conventional data gathering/input elements, and/or conventional post-processing or output elements.
claim 14: the recited "...representative standard amplification curve is provided" step/element, as evidenced by MPEP 2106.05(g), e.g. "insignificant extra solution activity" since the recitation is a conventional element of a laboratory and/or computing environment, conventional data gathering/input elements, and/or conventional post-processing or output elements.
claim 21: the recited "A non-transitory computer readable storage medium containing instructions to configure a processor to perform...," Step(a) "performing a real-time polymerase chain reaction (RT-PCR) for the target analyte to obtain a amplification curve" and Step(b) "... calibrated signal values is obtained..."step/element, as evidenced by MPEP 2106.05(g), e.g. "insignificant extra solution activity" since the recitation is a conventional element of a laboratory and/or computing environment, conventional data gathering/input elements, and/or conventional post-processing or output elements.
claim 22: the recited "(a) a computer processor and (b) the computer readable storage medium of claim 21 coupled to the computer processor." step/element, as evidenced by MPEP 2106.05(g), e.g. "insignificant extra solution activity" since the recitation is a conventional element of a laboratory and/or computing environment, conventional data gathering/input elements, and/or conventional post-processing or output elements.
Claims 4, 7 and 15-16 do not recite additional elements.
Claims 4, 7 and 15-16 are providing information on what the data represents and do not change the character of the data obtaining step beyond mere data gathering activity.
Data gathering steps are not an abstract idea, they are extra-solution activity, as they collect the data needed to carry out the abstract idea. Data gathering does not impose any meaningful limitation on the abstract idea, or how the abstract idea is performed. Data gathering steps are not sufficient to integrate an abstract idea into a practical application. (MPEP 2106.05(g)). Furthermore, limitations that equate to mere data gathering and outputting via generic computer components, such as receiving data at a computer or outputting data, amount to insignificant extra-solution activity as set forth by the courts in Mayo, 566 U.S. at 79, 101 USPQ2d at 1968 and OIP Techs., Inc, v, Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015). Also, the use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not integrate a judicial exception into a practical application or provide significantly more as identified by the courts in Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit). Additionally, RT-PCR processes and obtaining amplification curves are well understood and conventional activity in the field as discussed by Wong (published 2005, cited on the 08/21/2024 “Notice of References Cited” form 892). Wong teaches "Real-time PCR has become one of the most widely used methods of gene quantitation because it has a large dynamic range, boasts tremendous sensitivity, can be highly sequence-specific, has little to no post-amplification processing, and is amenable to increasing sample throughput" (Abstract) and PCR amplification curve is discussed in Figure 2, page 78.
[Step 2B: claims 1, 4-5, 7, 10-12, 14-17, 21-22: NO]
Summary and conclusion regarding claims 1, 4-5, 7, 10-12, 14-17, 21-22
Summing up the above 101 JE analysis of claims 1, 4-5, 7, 10-12, 14-17, 21-22, each viewed as a whole and considering all elements individually and in combination, no claim recites limitations that transform the claim, finally interpreted as directed to the above-identified JE(s), into patent eligible subject matter.
The claims have all been examined to identify the presence of one or more judicial exceptions. Each additional element in the claims has been addressed, alone and in combination, to determine whether the additional elements integrate the judicial exception into a practical application. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether those additional limitations provide an inventive concept which provides significantly more than those exceptions. Individually, the limitations of the claims and the claims as a whole have been found to be patent ineligible under 35 U.S.C. 101.
Response to 35 USC § 101 Arguments (Remarks 09/09/2025, pages 8-10)
Applicant amended claims 1, 4, 10-12, 14, 16-17, 21-22.
Applicant argues that under Step 2A, Prong Two claims 1 and 21 integrate the alleged judicial exception into a practical application. Applicant states that Claim 1 is directed to a "method for detecting a target analyte in a sample," and claim 21 is directed to "a non transitory computer readable storage medium containing instructions to configure a processor to perform a method for detecting a target analyte in a sample." Applicant further states that claims 1 and 21 recite the following additional elements of (a) performing a real-time polymerase chain reaction (RT-PCR) to obtain an amplification curve; (b) transforming the amplification curve into a calibrated amplification curve; and (c) detecting the target analyte using the calibrated amplification curve. Applicant argues that the combination of these additional elements integrates the JEs into a practical application.
Applicant provides an overview of the disadvantages of RT-PCR. Applicant states that the reliability of the results of real-time PCR is compromised by inter-instrument variation, intra-instrument variation, and instrument blank signals, which lead to inaccuracies such as false positives or false negatives in the field of molecular diagnostics. Applicant discusses hardware adjustment methods and dye calibration methods used to address the issues.
Applicant discusses the methods of claims 1 and 21. Applicant states that transforming an amplification curve into a calibrated amplification curve effectively reduce the inter- and intra-instrument signal variations because the methods of claims 1 and 21 do not require conventional hardware adjustment or the use of passive dye. Applicant states that the methods of claims 1 and 21 enable accurate detection of a target analyte in the field of molecular diagnostics.
In response, Applicant’s arguments under Step 2A Prong 2 regarding improvement have been fully considered and are not persuasive. It is understood that the Applicant asserts that the improvement of the invention is in an accurate detection of a target analyte in the field of molecular diagnostics. Applicant’s argument of improvement is not persuasive because the argument is a bare assertion of an improvement without the detail necessary to be apparent to a person of ordinary skill in the art. From the asserted improvement, it is not clear how the claimed invention improves over existing technology and it is also not clear how one would gauge the improvement since there are no metrics for comparison between the claimed technology and previous technology. Overall, one of ordinary skill in the art cannot gauge whether the improvements asserted are delivered by the claims because the details provided in the specification do not provide sufficient details such that the improvement would be apparent, do not explain the details of an unconventional technical solution expressed in the claim, or identify technical improvements realized by the claim over the prior art. As stated in MPEP 2106.05(a) and MPEP 2106.04(d), the disclosure must provide sufficient details such that one of ordinary skill in the art would recognize the claimed invention as providing an improvement. Furthermore, if the specification explicitly sets forth an improvement but in a conclusory manner (i.e., a bare assertion of an improvement without the detail necessary to be apparent to a person of ordinary skill in the art), the examiner should not determine the claim improves technology. An indication that the claimed invention provides an improvement can include a discussion in the specification that identifies a technical problem and explains the details of an unconventional technical solution expressed in the claim, or identifies technical improvements realized by the claim over the prior art. (see MPEP 2106.05(a) and MPEP 2106.04(d)). Also, the claim limitation of detecting the target analyte using the calibrated amplification curve is a mental process JE because it requires analyzing, evaluating, judging and observing data which could be practically perform by the human mind and/or with pen and paper (MPEP 2106.04).
Applicant argues under Step 2B of the 101 analysis that claims 1 and 21 recite non-conventional arrangement of additional elements. Applicant discusses that the use of passive dyes requires complex experimental setup and concentration optimization, and if not used properly, may lead to inaccurate calibration or misinterpretation of results. In contrast, the methods of claims 1 and 21 exclude the use of passive dyes, thereby improving efficacy and efficiency in the detection of target analytes. Applicant mentions Examples 1-4 of the instant specification. Applicant states that the methods of claims 1 and 21 are effective in reducing the inter- instrument signal variations as well as intra-instrument signal variations in amplification curves and melting curves (see also Tables 3-4, 7-8, and 12-15 of the present specification). Applicant asserts that the features of claims 1 and 21, i.e., recitation of transforming an amplification curve into a calibrated amplification curve using an analyte-insusceptible signal value, and then detecting the target analyte using the calibrated amplification curve constitute an unconventional step, are more than a mere instruction to "apply" the abstract idea using well-understood, routine or conventional technique in the field.
In response, Applicant’s arguments under step 2B of the 101 analyses have been fully considered and are not persuasive. Under step 2B of the 101 analysis the claims are evaluated to determine whether the claims recite a non-conventional arrangement of additional elements (i.e. elements in addition to any JE). The additional elements of claims 1, 5, 10 and 14, as discussed above in the 101 claim rejection section, equate to mere data gathering and outputting, which amounts to insignificant extra solutional activity (see MPEP 2106.05(g)). The additional elements of claims 21-22 equate to mere data gathering and outputting via generic computer components, such as receiving data at a computer or outputting data, amount to insignificant extra-solution activity as set forth by the courts in Mayo, 566 U.S. at 79, 101 USPQ2d at 1968 and OIP Techs., Inc, v, Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015). Also, the additional elements of computer readable storage media include storing and retrieving information, such as computer program instructions in memory. Storing and retrieving information in memory were identified by the courts as well-understood, routine and conventional in Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93. The use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not integrate a judicial exception into a practical application or provide significantly more as identified by the courts in Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit). Additionally, RT-PCR processes and obtaining amplification curves are well understood and conventional activity in the field as discussed by Wong (published 2005, cited on the 08/21/2024 “Notice of References Cited” form 892). Wong teaches "Real-time PCR has become one of the most widely used methods of gene quantitation because it has a large dynamic range, boasts tremendous sensitivity, can be highly sequence-specific, has little to no post-amplification processing, and is amenable to increasing sample throughput" (Abstract) and PCR amplification curve is discussed in Figure 2, page 78. Overall, the additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception.
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.
Claim(s) 1, 4-5, 7, 10-12, 14 and 16-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wong ("Real-time PCR for mRNA quantitation." Biotechniques 39.1 (2005): 75-85, published 2005; cited on the 08/21/2024 “Notice of References Cited” form 892) in view of Mason (US 2007/0237716 A1; published Oct. 11, 2007, cited on the attached “Notice of References Cited” form 892).
Regarding independent claim 1, Wong teaches the claim limitation of transforming the amplification curve into a calibrated amplification curve by replacing a signal value at each of the cycles in the amplification curve with a calibrated signal value to reduce the inter- and intra-instrument signal variations with “…pipet calibration are also essential for preventing cumulative error. Running a standard curve during every reaction can help alleviate this issue because the standard will be affected to the same extent as the unknowns” (page 83, col. 2, para. 1).
Wong teaches the claim limitation of wherein the calibrated amplification curve comprises cycles and calibrated signal values at the cycles, wherein the calibrated signal value is obtained by dividing the signal value at each of the cycles in the amplification curve by an analyte-insusceptible signal value with “During relative quantitation, changes in sample gene expression are measured based on either an external standard or a reference sample, also known as a calibrator (21). When using a calibrator, the results are expressed as a target/reference ratio.” (Page 77, col. 1, para. 2).
Wong teaches the claim limitation of wherein the analyte-insusceptible signal value is (i) a background-representing signal at a reference cycle selected within a background region of the amplification curve is insusceptible to the presence or absence of the target analyte in the sample;
or (ii) a total signal change value of a standard amplification curve; for a standard material of the target analyte; and (c) detecting the target analyte in a sample qualitatively or quantitatively using the calibrated amplification curve, wherein the method does not comprise the use of any passive dye for the transformation of the amplification curve with “During relative quantitation, changes in sample gene expression are measured based on either an external standard or a reference sample, also known as a calibrator (21). When using a calibrator, the results are expressed as a target/reference ratio. There are numerous mathematical models available to calculate the mean normalized gene expression from relative quantitation assays.” (Page 77, col. 1, para. 2) and with “The quantity of each experimental sample is first deter-mined using a standard curve and then expressed relative to a single calibrator sample (31). The calibrator is designated as 1-fold, with all experimentally derived quantities reported as an n-fold difference relative to the calibrator.” (page 77 col. 3, para. 2). Wong’s teachings correspond to the claim limitation option of a total signal change value of a standard amplification curve; for a standard material of the target analyte. Wong teaches that the calibrator is an external standard or a reference sample that corresponds to the recited the method does not comprise the use of any passive dye for the transformation of the amplification curve.
Although Wong teaches PCR amplification curves, Wong does not explicitly teach the claim limitation of (a) performing a real-time polymerase chain reaction (RT-PCR) for the target analyte of claim 1. However, Mason teaches this claim limitation.
Mason teaches the claim limitation of (a) performing a real-time polymerase chain reaction (RT-PCR) for the target analyte to obtain an amplification curve, wherein the amplification curve comprises cycles and signal values at the cycles with “The present invention provides compositions, methods and kits useful for the amplification of nucleic acid molecules from human β-retrovirus by reverse transcriptase-polymerase chain reaction (RT-PCR). Specifically, the invention provides compositions and methods for the amplification of nucleic acid molecules in a one or two-step real time RT-PCR procedure using reverse transcriptase, DNA polymerase, or a combination of both enzymes. The invention provides for the rapid and efficient amplification, detection and quantification of human β-retrovirus nucleic acids.” (abstract) and “The present invention relates to compositions, methods and kits for performing reverse transcriptase polymerase chain reaction (RT-PCR).” ([0002]). The recited targeted analyte corresponds to the nucleic acid molecules from human β-retrovirus as taught by Mason.
Mason teaches amplification curve for targeted analyte with Figure 3. Fig. 3 the depicts the number of cycles and fluorescence values. Mason teaches “FIG. 3 shows the detection of human β-retrovirus RNA in samples derived from patients with PBC versus those from control non-PBC subjects. In panel (a), Ct values from 6 PBC patients' serum samples varied from 34.83 and 35.86 to Ct<=37, or negative. In panel (b) Ct values from liver sample of PBC patients (n=2, Ct=28.49 and 30.06) and non-PBC subjects (n=6, Ct<=37, or negative) and not in control samples.” (Para. [0046]).
It would have been prima facia obvious to combine the teachings of Wong and Mason to arrive at the claimed invention. Mason’s method provides for rapid and efficient amplification, detection and quantification of human β-retrovirus nucleic acids (abstract). Therefore, a person of ordinary skill in the art would have been motivated to modify the method of Wong to include performing a real-time polymerase chain reaction (RT-PCR) for the target analyte as taught by Mason to rapidly and efficiently detect and quantify target analytes. Furthermore, there would have been a reasonable expectation of success, since both Wong and Mason teaches methods that pertain to RT-PCR.
Regarding claims 4, Wong teaches the recited the amplification curve of the target analyte has information indicating the presence or absence of the target analyte in the sample at least with "At the early exponential phase, the amount of fluorescence has reached a threshold where it is significantly higher (usually10 times the standard deviation of the baseline) than background levels. The cycle at which this occurs is known as Ct in ABI Prism® literature (Applied Biosystems, Foster City, CA, USA) or crossing point (CP) in LightCycler® literature (Roche Applied Science, Indianapolis, IN, USA) (2,10). This value is representative of the starting copy number in the original template and is used to calculate experimental results (2). During the log-linear phase, PCR reaches its optimal amplification period with the PCR product doubling after every cycle in ideal reaction conditions" (Page 75, Col. 3, Para. 2).
Regarding claims 5, Wong teaches the recited the RT-PCR generates signals in a dependent manner on the presence of the target analyte in the sample at least with "At the early exponential phase, the amount of fluorescence has reached a threshold where it is significantly higher (usually10 times the standard deviation of the baseline) than background levels. The cycle at which this occurs is known as Ct in ABI Prism® literature (Applied Biosystems, Foster City, CA, USA) or crossing point (CP) in LightCycler®literature (Roche Applied Science, Indianapolis, IN, USA) (2,10). This value is representative of the starting copy number in the original template and is used to calculate experimental results (2). During the log-linear phase, PCR reaches its optimal amplification period with the PCR product doubling after every cycle in ideal reaction conditions" (Page 75, Col. 3, Para. 2).
Regarding claims 7, Wong teaches the recited the target analyte is a target nucleic acid molecule at least with "...the greater the quantity of target DNA in the starting material, the faster a significant increase in fluorescent signal will appear..." (Page 75, Col. 1, Para. 1).
Regarding claims 10, Wong teaches the recited the RT-PCR comprises a plurality of RT-PCRs for the same-typed target analyte performed in different reaction vessels; wherein the amplification curve comprises a plurality of amplification curves obtained from the plurality of RT-PCRs with "During the validation of microarray results, which tends to have only a few samples and several target genes, it is reasonable to use a DNA binding dye" (Page 83, Col. 3, Para. 2) and with “Intra-assay variation quantifies the amount of error seen within a single assay when the same template is run multiple times on the same plate with the same reagents. Intra-assay variation can be calculated for every single sample of every reaction if the real-time PCR experiments are performed in triplicate, with a pooled variance for all sets of PCR triplicates representing statistical power (41).” (page 82, col. 2, para. 3).
Regarding claims 11, Wong teaches the recited the reference cycle is selected from a reference cycle group of each amplification curve, wherein the reference cycle group of each amplification curve is provided in the same manner to each other at least with "During the linear ground phase (usually the first 10–15 cycles), PCR is just beginning, and fluorescence emission at each cycle has not yet risen above background. Baseline fluorescence is calculated at this time. At the early exponential phase, the amount of fluorescence has reached a threshold where it is significantly higher (usually10 times the standard deviation of the baseline) than background levels. The cycle at which this occurs is known as Ct in ABI Prism® literature (Applied Biosystems, Foster City, CA, USA) or crossing point (CP) in LightCycler® literature (Roche Applied Science, Indianapolis, IN, USA) (2,10). This value is representative of the starting copy number in the original template and is used to calculate experimental results (2). During the log-linear phase, PCR reaches its optimal amplification period with the PCR product doubling after every cycle in ideal reaction conditions" (Page 75, Col. 3, Para. 2).
Regarding claims 12, Wong teaches the recited an identical reference cycle is provided for calibrating each amplification cu