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 .
Information Disclosure Statement
The IDS filed 6/08/2021 has been considered by the Examiner.
Priority
Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to KR10-2018-0162444 filed 12/14/2018.
Status of Claims
Amendments to the claims are acknowledged.
Claims 9, 11 and 20 are cancelled.
Claims 1-8, 10, and 12-19 are under examination.
Claim Rejections - 35 USC § 101
The instant rejection is maintained in view of Applicant’s amendments filed 7/29/2025, and modified to address the newly introduced amendments.
35 U.S.C. 101 reads as follows:
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.
Claims 1-8, 10, and 12-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Step 1: Process, Machine, Manufacture or Composition
Claims 1-8, 10, and 11-17 are drawn to a method, so a process.
Claim 19 is drawn to a device comprising a computer, so a machine.
Claim 18 is drawn to a non-transitory computer readable medium, so a machine.
Step 2A Prong One: Identification of an Abstract Idea
The claim(s) recite(s):
1. receiving a first data set representing a real-time amplification curve wherein said first data set includes a plurality of data points, each having a cycle number and a signal value at the cycle number.
This step reads on a process of receiving information by the human mind such as a mental process of looking at data that represents a growth curve. The step can be performed with the human mind or by paper/pen by recording data representing an amplification process. The step is therefore an abstract idea.
2. transforming a signal value at each cycle number in the first data set into a slope value at each number to obtain a second data set, wherein said second data set include a plurality of data points each having a cycle number and slope value at the cycle number.
This step reads on doing math because calculating slops of a multi-point data set is an entirely mathematical process. The step is therefore an abstract idea.
3. transforming the second data set into an S-shaped function by approximating the S-shaped function using a selected portion of the second data set wherein the S-shaped function is selected from the group consisting of a sigmoid function, a logistic function, a Gompertz function, and a Chapman function.
The step reads on the math of fitting data to an S-shaped function. The step is therefore an abstract idea.
4. determining a threshold cycle (Ct) value from the S-shaped function and detecting the target analyte in the sample based on the Ct value.
This step reads on analyzing the S-shaped function to determine the slope in the exponential region of the function (specification, page 35-36, connecting par.) which is a process that can be performed by the human mind and/or with further mathematics. The step is therefore an abstract idea.
Dependent claims 2-8, 10, 12-17 are further drawn to data manipulation steps with mathematics, and are therefore also abstract ideas.
Step 2A Prong Two: Consideration of Practical Application
The claims are drawn to determining a Ct value of an amplification process through mathematical data analysis of an S-shaped function. The claims do not recite any additional elements that integrate the abstract idea into a practical application.
This judicial exception is not integrated into a practical application because the claims do not meet any of the following criteria:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses 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.
Step 2B: Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea. The recited additional elements are drawn to:
1. performing a real-time amplification reaction for a target analyte, as in claim 1.
a computer readable storage medium, as in claim 18
a computer processor, as in claim 19.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the step of performing a real-time amplification is a well-known, routine and conventional data gather step. Real-time PCR is well known routine and conventional. The recited step also serves as an extra solution data gathering activity, as described in MPEP 2106.05(g). Furthermore, the computer readable storage medium and processor are a recitation of generic computer structure that serves to perform generic computer functions that are well-understood, routine, and conventional activities previously known to the pertinent industry. Viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself. Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Response to Arguments
Applicant's arguments filed 7/28/2025 have been fully considered but they are not persuasive.
Applicants argue (Remarks, page 8, par. 2) that analysis of real-time amplification curves require a complex baseline subtraction (baselining) process while the instantly claimed process does not require a baseline subtraction process as the method is characterized by using an S-shaped function of a selected portion of the first derivation for detecting a target analyte in real-time PCR.
In response, the instantly claimed method is drawn to an entirely mathematical process and is therefore an abstract idea. Improving or simplifying a preexisting mathematical procedure to arrive at an alternate, more convenient mathematical calculation does not change the nature of the procedure which is math. Without additional elements that practically apply the judicial exception (i.e. abstract idea), the claims as a whole continue to be drawn to the judicial exception. Categories of practical application are cited above under Step 2A Prong Two.
Applicants argue (page 9, par. 1) that the claimed process recites unconventional steps including the features of transforming a first data set representing a real-time amplification into a second data set and then into an S-shaped function. Applicants argue that the steps are “more than mere instructions to ‘apply’ the abstract idea using well-understood, routine and conventional technique in the field.”
In response, the analysis of well-understood, routine and conventional is applied to “additional elements” which are limitations recited in addition to the abstract idea. Currently the claims only recite routine data gathering by real-time amplification in claim 1, and a tangential computer readable storage medium and processor in claims 18 and 19. The analysis of unconventionality are not applied to the steps argued by Applicant because these steps ( i.e. transforming a first data into an S-shaped curve) read on math and mental processes which are abstract ideas.
The claimed method steps are entirely drawn to performing mathematical and mental process steps on routine amplification data. The claims as a whole are drawn to an abstract idea and therefore the 35 USC 101 rejection is maintained.
Claim Rejections - 35 USC § 112-2nd paragraph
The rejection of claims 1-20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn in view of Applicant’s amendments filed 7/28/2025.
Claim Rejections - 35 USC § 103
The rejection of claims 1-9 and 11-20 under 35 U.S.C. 103(a) as being unpatentable over Wittwer et al. (US 2002/0042051) is withdrawn in view of Applicant’s arguments.
The following rejection is necessitated by Applicant’s amendments 7/28/2025.
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-8, 10, and 12-19 are rejected under 35 U.S.C. 103(a) as being unpatentable over Li et al. (US 2013/0273547) in view of Zhao et al. (Journal of Computational Biology vol. 12 (2005) pgs. 1047-1064), and as evidenced by Wittwer et al. (US 2002/0042051)
Li et al. teach performing real-time PCR to determine the Ct value (threshold cycle number) for target nucleic acids (par. 0001 ad 0007) and applying a flat or sloped baseline (par. 0003-0005); (i.e. performing real time amplification for a target analyte to obtain a first data set representing a real-time amplification curve); the obtained curve includes cycle numbers and a plurality of points (Figure 3) (i.e. wherein the data set includes a plurality of data points each having a cycle number and a signal value at the cycle number), as in claim 1, step (a).
Li et al. teach performing a baseline fitting to determine the slope of the baseline (par. 0015 and Figure 4) and rotating the curve to flatten the baseline according to the slope of the base line (par. 0018 and Figure 5)(i.e. transforming a signal value in the first data set into a slope value to obtain a second data set), as in claim 1, step (b).
Li et al. teach that the corrected baseline plot can be fitted to a sigmoid function, Chapman function, Gompertz function (par. 0145 ) or a logistic model applied to an S-shaped curve (par. 0146-0147)(i.e. transforming the second data set into an S-shaped function by approximating the S-shaped function using a selected portion of the second data set, wherein the S-shaped function is a sigmoid, logistic, Gompertz, or Chapman function), as in claim 1, step (c).
Li et al. does not specifically teach all of claim 1, step (b) which requires transforming a signal value into a slope at each cycle number. Claim 1, step (b) reads on taking the first derivative of the amplification curve.
Li et al. does not specifically teach determining a Ct value from the S-shaped function and detecting the analyte in the sample based on the Ct value.
Zhao et al. however teach calculating mRNA levels with cycle numbers at the Ct value (Abstract). Zhao et al. teach taking the first derivative of the amplification curve (Table 2, caption) and calculating the CT from the first derivative maximum (page 1058, par. 2).
Zhao et al. also teach fitting S-shaped curves to Logistic, Sigmoidal, Gompertz, and Chapman functions (Table 2)
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teachings of Li et al. for measuring raw data of a nucleic acid amplification process and fitting the raw data to an S-shaped model with the process of Zhao et al. who teach taking a first derivative of the amplification curve to determine Ct value. Wittwer et al. evidence (Figure 3) that the first derivative curve is a distribution with an S-shape (when considered sideways) which is consistent with the description in the instant specification (page 25, par. 1):
Typically a slope data set such as the second data set represents a “bell-shaped curve” known as the normal distribution in the presence of the target analyte. The left side of the bell-shaped curve with respect to the axis of symmetry (central axis) shows an increasing pattern like an amplification curve or growth curve, that is, a pattern in which a slope value increases as the cycle number increases, whereas the right side of the bell-shaped curve shows a pattern in which a slope value decreases as the cycle number increases. Thus, the left side in a slope data set representing a bell-shaped normal distribution may be selected as the “portion” to be approximated by an S-shaped function according to the method of the present invention.
The combination of Li et al. for fitting amplification data with a sigmoid, logistic, Gompertz, or Chapman function with Zhao et al. for taking the first derivative of the amplification data, as well as also fitting amplification data with a sigmoid, logistic, Gompertz, or Chapman function to determine Ct value is a combination of known teachings which would yield a predictable result. One of ordinary skill would be motivated to fit any S-shaped data to known functions representing an S-shape to achieve a smoothed representation of the original data for analysis including Ct determination. One of skill in the art would have had a reasonable expectation of success at combining Li et al. and Zhao et al. because both teach amplification data analysis with S-shaped functions.
Regarding dependent claims 2-8, 10 and 12-19
Li et al. teach a raw data set from an amplification process (Abstract and par. 0148), and normalizing the data with a baseline correction (Figures 4-6), as in claim 2.
Li et al. teach taking a first and second derivative (par. 0003,0024, 0039)(i.e. differentiation, a ratio, a difference), as in claim 3.
Zhao et al. teach taking a first derivative maximum of sigmoid model fitting (page 1048, par. 4) which suggest that the first derivative function which is peak-like is fit until the maximum and has an S-like shape on its side and can therefore be fit with the S-models in Table 4, as in claim 4.
Zhao et al. teach teaches a start period that spans at least the first to 10th cycle (page 1053, panel (A)); Li et al. also teach a start period that spans at least the 1st and 10th cycle (Figure 3), as in claim 5.
Both Zhao et al. and Li et al. teach a first derivative curve where the maxim of the first derivative represents the maximum slope of the original amplification curve, as evidenced by Wittwer et al. (Figure 6). Therefore selecting the S-shape of the first derivative curve would inherently include up to the maximum of the first derivative curve and could include additional points at the maximum which represent the same slope, as in claims 6 and 17.
Both Li et al. (Figure 3) and Zhao et al. (page 1053, panel (A) teach an exponential phase with more than 5 cycles, as in claim 7.
Zhao et al. make teach determining parameters of S-shaped functions by determining the corresponding exponential phase (page 1053, panel (A)) and wherein the S-shaped models include parameters (Table 2, column 2), as in claim 8.
Zhao et al. teach equations corresponding to Logistic, Sigmoidal, Gompertz, and Chapman functions (Table 2) and would therefore read on equations II to V, as in claim 10.
Zhao et al. teach CT determination with the first derivative maximum method and second derivative maximum method (page 1058, par. 2), as in claim 12.
Zhao et al. teach that CT is determined within the exponential phase which reads on a parameter of the S-shaped function, as in claim 13.
Zhao et al. teach fitting the amplification curve to a perfect exponent (page 1053, panels (A) and (B)0 which makes obvious fitting the raw and first derivative data to a perfect exponential function before proceeding to fit the first derivative to an S-shape model, as in claims 14-15.
Li et al. (par. 0001) and Zhao et al. (Abstract) both teach nucleic acids, as in claim 16.
Li et al. teach computer programs (par. 0080) which suggest a computer processor and storage, as in claims 18-19.
E-mail communication Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anna Skibinsky whose telephone number is (571) 272-4373. The examiner can normally be reached on 12 pm - 8:30 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Ram Shukla can be reached on (571) 272-7035. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Anna Skibinsky/
Primary Examiner, AU 1635