Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of group I, claims 1-10 in the reply filed on 06/24/2026 is acknowledged.
Claims 11-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/24/2026.
Claims 1-10 are under examination.
Claim Rejections - 35 USC § 101
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 1-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract idea without significantly more.
Claim 1 recites determining a ratio of Ct values (A) and (B), correcting a Ct value on the basis of the ratio of Ct values (A) and (B), and measuring amount of DNA from calibration curve and corrected Ct value. These step encompasses a data analysis process which can be practiced in the method. Additionally the step of determining a ratio and correcting a Ct value includes mathematical concepts. The recitation of determining a ratio is a mathematical concept that can encompass a mathematical calculation. The recitation of correcting a Ct value on the basis of ratio of Ct value A and B encompasses a mathematical calculation. Additionally the determining a ratio, correcting a Ct value and measuring amount of DNA could be performed entirely in the mind and is also a mental process. Neither the claims nor the specification set forth limiting definitions for determining, correcting, or measuring and the claims do not set forth how the ratio is accomplished, the Ct is corrected and how the amount of DNA is measured. The broadest reasonable interpretation of each of these steps is a step that can be accomplished mentally by evaluating data and critical thinking process wherein one mentally reads information regarding Ct values and determines a ratio, corrects Ct value and measuring DNA mentally in one’s mind. Additionally each of these steps can include a step that encompasses mathematical calculation, because a ratio is a mathematical concept and correcting a Ct value and measuring DNA includes a mathematical calculation.
This judicial exception is not integrated into a practical application because the claims do not recite additional steps or elements that integrate the recited judicial exception into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps in addition to the judicial exception are data gathering steps recited at a high level of generality employing techniques that were well-established, routine and conventional at the time of the invention. For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
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.
While claim 1 recite as step of performing PCR with an internal control DNA, PCR primers, fluorescent labeled probe, and PCR buffer solution, the claims generically recites performing PCR. Additionally performing PCR with internal controls and Ct values were well known routine and conventional in the art taught by Haugland (Method 1609, EPA, March 2013, pp. 1-72).
Claims 2-5 further limit the specimen, thus is a field of use limitation which does not amount to significantly more.
Claims 6, further limit the internal control, which is a field of use limitation and does not amount to significantly more.
Claim 7-10 further limit the PCR buffer. However, it was routine in the art to determine perform PCR using the buffer limitations recited in claims 7-10, as taught by Haugland (Method 1609, EPA, March 2013, pp. 1-72).
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 1-10 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 1 recites a method for quantifying DNA in a specimen with a step of measuring a Ct value (A) for the internal control in the first container in the PCR and a Ct value (B) for the internal control DNA contained in the second container in the PCR and determining a ratio of Ct values (A) and (B). The recitation of determining a ratio of Ct values (A) and (B) renders the claim indefinite. It is unclear if the ratio to be determined is the ratio of Ct values (A) to Ct values (B), if each Ct values (A) and Ct values (B) have their own determined ratios, or if the ration is ratio of Ct values (B) to Ct value (A). The recitation of ratio of Ct value (A) and Ct value (B) does not clearly indicate what the ratio is that is determined and thus renders the claim indefinite. The metes and bounds of a ratio of Ct values A and B is unclear and indefinite. Because it is unclear what the ratio encompasses, one of skill in the art canoe determine the metes and bounds of the claimed subject matter.
Claim 1 recites a step of correcting a Ct value for the DNA in the specimen contained in the first container on a basis of the ratio of the Ct values (A) and (B). This recitation renders the claim indefinite. It is unclear how a Ct value is corrected based on the basis of the ratio of Ct values of A and B. It is unclear what is encompassed by the correction and on what basis. It is unclear if the ratio is A:B, a ratio value for each CtA and CtB, or B:A and how this corrects a Ct value for the DNA in the specimen. The metes and bounds of a correcting a Ct value…on the basis of the ratio is unclear and indefinite. Because it is unclear what the ratio encompasses and how one corrects a Ct value on the basis of an unclear ratio, one of skill in the art canoe determine the metes and bounds of the claimed subject matter.
Claim 1 recites a step of measuring DNA in the specimen from the calibration curve and corrected Ct value, this recitation is indefinite. It is unclear how the corrected Ct value is obtained and how this results in measuring DNA in a specimen from the calibration curve and corrected Ct value. The metes and bounds of a measuring DNA from a calibration curve and corrected Ct value when the correcting a Ct value…on the basis of the ratio which is unclear and indefinite is further indefinite. Because it is unclear what the ratio encompasses and how one corrects a Ct value on the basis of an unclear ratio, the step of measuring is unclear and one of skill in the art canoe determine the metes and bounds of the claimed subject matter.
Regarding claim 10, the phrase "i.e." renders the claim(s) indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by "i.e."), thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(d). The term “i.e.” means that is or in other words and is used to clarify or explain. Therefore, the use of “i.e.” is an express admission that the prior phrase, a substance that is bound to PCR-inhibiting substances is not clear. Additionally the phrase following i.e. does not clarify or explain the substance that is bound to PCR-inhibiting substances and it is unclear the scope of substance that is bound to PCR-inhibiting substances recited in the claim.
Claim Rejections - 35 USC § 102
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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2, 4-5 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Haugland (Method 1609, EPA, March 2013, pp. 1-72).
Haugland teaches measuring Enterococcus in recreational water samples (pg. 8) (environmental specimen containing a bacteria) (claims 2, 4-5). Haugland teaches qPCR analysis of a calibrator and water sample extracts should be performed in parallel (see 11.7.5) (standard sample and specimen sample). Haugland teaches a sample process control sequence (SPC) that is a 77 bp segment of rRNA gene operon of chum salmon, salmon DNA (internal control). Haugland teaches SPC are added is equal quantities to all water samples and calibrator samples. This control is added to determined if the sample was processed correctly and identify sample matrix effects on total DNA recovery (see 3.3). Haugland teaches a DNA standard that is used to generate a standard curve for qPCR and quantify target sequences (see 3.4). Haugland teaches a calibrator sample which is calculated using ΔΔCT, comparative cycle threshold calibration (see 3.5) (standard DNA). The calibrator sample provides correction for variation in cell lysis, target sequence recovery and PCR efficiency (see 3.5). Haugland teaches the ΔΔCT method calculates ratio of target sequences in two samples, calibrator sample and water sample that normalizes for differences in total DNA recovery from samples using values for reference sequence, SPC (internal control) present in equal quantities prior to DNA extraction (see 3.7). Haugland teaches performing PCR by adding primers and probes comprising labels 6-FAM and TAMRA (see 7.17), PCR master mix (buffer), BSA (see 7.15-7.17, table 4, table 8) (claim 10).
Haugland teaches calculating ratio of target sequences in two DNA samples by qPCR. Haugland teaches calculating ratio of target sequence in calibrator sample (standard DNA in second container) and water filtrate sample (first container containing a specimen). Haugland teaches normalizing differences in total DNA recovery using qPCR analysis values for reference SPC (measuring Ct values and ratios for internal control (SPC) in both samples, correcting Ct on basis of internal control, SPC) (see 3.6 and 12.4-5). Haugland teaches preparing a standard curve (calibration curve) based on known amounts of E. faecilus genomic DNA (see 9.10).
Claim Rejections - 35 USC § 103
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.
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.
Claims 3, 7, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Haugland (Method 1609, EPA, March 2013, pp. 1-72) in view of Exner (US20200340068A1).
Haugland teaches a method of measuring Enterococcus in recreational water samples (pg. 8) (environmental specimen containing a bacteria). Haugland teaches qPCR analysis of a calibrator and water sample extracts should be performed in parallel (see 11.7.5) (standard sample and specimen sample). Haugland teaches a sample process control sequence (SPC) that is a 77 bp segment of rRNA gene operon of chum salmon, salmon DNA (internal control). Haugland teaches SPC are added is equal quantities to all water samples and calibrator samples. This control is added to determine if the sample was processed correctly and identify sample matrix effects on total DNA recovery (see 3.3). Haugland teaches a DNA standard that is used to generate a standard curve for qPCR and quantify target sequences (see 3.4). Haugland teaches a calibrator sample which is calculated using ΔΔCT, comparative cycle threshold calibration (see 3.5) (standard DNA). The calibrator sample provides correction for variation in cell lysis, target sequence recovery and PCR efficiency (see 3.5). Haugland teaches the ΔΔCT method calculates ratio of target sequences in two samples, calibrator sample and water sample that normalizes for differences in total DNA recovery from samples using values for reference sequence, SPC (internal control) present in equal quantities prior to DNA extraction (see 3.7). Haugland teaches performing PCR by adding primers and probes comprising labels 6-FAM and TAMRA (see 7.17), PCR master mix (buffer), BSA (see 7.15-7.17, table 4, table 8).
Haugland teaches calculating ratio of target sequences in two DNA samples by qPCR. Haugland teaches calculating ratio of target sequence in calibrator sample (standard DNA in second container) and water filtrate sample (first container containing a specimen). Haugland teaches normalizing differences in total DNA recovery using qPCR analysis values for reference SPC (measuring Ct values and ratios for internal control (SPC) in both samples, correcting Ct on basis of internal control, SPC) (see 3.6 and 12.4-5). Haugland teaches preparing a standard curve (calibration curve) based on known amounts of E. faecilus genomic DNA (see 9.10). Haugland does not teach a specimen that is excrement, PCR buffer solution that comprises KCl and surfactant.
However, Exner teaches a method for identifying the presence or absence of target nucleic acid from a microorganism by direct amplification of a sample without nucleic acid extraction (see para 9-10). Exner teaches contacting sample with DNA polymerase and buffer for amplification of target and detecting amplified target nucleic acid wherein the buffer comprises KCl, bovine serum albumin and a surfactant (claim 7, 9. Exner teaches the sample comprises stool sample (excrement sample) (para 14) (claim 2-3) and target nucleic acid comprises virus or bacteria (para 16). Exner teaches using dual labeled fluorescent probes for PCR (see para 54). Exner exemplifies a stool sample for detection of C. difficile (See para 75).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to improve the method of detecting microorganisms in water samples as taught by Haugland to include improve stool samples as taught by Exner to allow for more comprehensive analysis of bacteria in different samples. The ordinary artisan would have been motivated to improve the method of detecting bacteria from water samples using standard DNA, calibration curves, and internal controls as taught by Haugland to include stool samples using PCR buffer conditions include KCl and surfactant as taught by Exner in the method of Haugland because Exner teaches methods that allow for direct analysis of samples without extract nucleic acid and teaches detecting bacteria from stool sample. The ordinary artisan would have had a reasonable expectation of success that the use of detecting bacterial sequences in stool samples could be used in the method of Haugland et al. because Exner teaches the analysis of C. diff species in stool samples by RT-PCR using internal controls. Because both Haugland and Exner et al. teach amplification assays to detect bacteria in samples, it would have been obvious to one skilled in the art to substitute one element of the method by Haugland, the method of PCR amplification of bacterial species in environmental samples as taught by Haugland for the method of PCR amplification of bacterial species in stool samples as taught by Exner in order to achieve the predictable result of detecting bacterial sequences in samples by using internal controls and standard curves for measuring the total amount of bacteria.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Haugland (Method 1609, EPA, March 2013, pp. 1-72) in view of Pionzio (Forensic Science International, Genetics, (2014) 9:55-60).
Haugland teaches a method of measuring Enterococcus in recreational water samples (pg. 8) (environmental specimen containing a bacteria). Haugland teaches qPCR analysis of a calibrator and water sample extracts should be performed in parallel (see 11.7.5) (standard sample and specimen sample). Haugland teaches a sample process control sequence (SPC) that is a 77 bp segment of rRNA gene operon of chum salmon, salmon DNA (internal control). Haugland teaches SPC are added is equal quantities to all water samples and calibrator samples. This control is added to determine if the sample was processed correctly and identify sample matrix effects on total DNA recovery (see 3.3). Haugland teaches a DNA standard that is used to generate a standard curve for qPCR and quantify target sequences (see 3.4).
Haugland teaches calculating ratio of target sequences in two DNA samples by qPCR. Haugland teaches calculating ratio of target sequence in calibrator sample (standard DNA in second container) and water filtrate sample (first container containing a specimen). Haugland teaches normalizing differences in total DNA recovery using qPCR analysis values for reference SPC (measuring Ct values and ratios for internal control (SPC) in both samples, correcting Ct on basis of internal control, SPC) (see 3.6 and 12.4-5). Haugland teaches preparing a standard curve (calibration curve) based on known amounts of E. faecilus genomic DNA (see 9.10). While Haugland teaches the internal control, SPC is 77bp and GC content of 68%, Haugland does not teach the internal control DNA has a GC content of 40-60%.
However, Pionzio analyzes difference in internal control sequences for PCR. Pionzio teaches as amplicon size increased and amplicon GC content decreased inhibitory effects become more detectable. Pionzio teaches the use of long, low GC content DNA amplicon as an internal PCR control will provide increased ability to detect inhibition during RT-PCR amplification (see conclusion).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to improve the method of detecting microorganisms in water samples using an internal control sequence that is 77bp and 68% GC content as taught by Haugland to include a longer amplicon size with decreased GC content for the internal control sequence of SPC as taught by Pionzio. The ordinary artisan would have been motivated to improve the internal salmon DNA sequence in Haugland and include a longer amplicon with decreased GC content between 40-60% because Pionzio teaches a longer amplicon with decreased GC content allows for higher detection of inhibitory effects during RT-PCT. The ordinary artisan would have had a reasonable expectation of success that the use of increased sequence size and reduced GC content to 40% of the internal control as taught Pionizi could be used for the internal control salmon DNA as taught by Haugland because Pionzio teaches use of long, low GC content DNA amplicon for internal PCR control allows for an increased ability to detect inhibition during real time PCR quantification step and Haugland teaches using internal control during real time PCR quantification step.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Haugland (Method 1609, EPA, March 2013, pp. 1-72) in view of Shimizu (US20180087106 A1) and Bennis (GateScientific, 2020, pp. 1-8)
Haugland teaches a method of measuring Enterococcus in recreational water samples (pg. 8) (environmental specimen containing a bacteria). Haugland teaches qPCR analysis of a calibrator and water sample extracts should be performed in parallel (see 11.7.5) (standard sample and specimen sample). Haugland teaches a sample process control sequence (SPC) that is a 77 bp segment of rRNA gene operon of chum salmon, salmon DNA (internal control). Haugland teaches SPC are added is equal quantities to all water samples and calibrator samples. This control is added to determine if the sample was processed correctly and identify sample matrix effects on total DNA recovery (see 3.3). Haugland teaches a DNA standard that is used to generate a standard curve for qPCR and quantify target sequences (see 3.4).
Haugland teaches calculating ratio of target sequences in two DNA samples by qPCR. Haugland teaches calculating ratio of target sequence in calibrator sample (standard DNA in second container) and water filtrate sample (first container containing a specimen). Haugland teaches normalizing differences in total DNA recovery using qPCR analysis values for reference SPC (measuring Ct values and ratios for internal control (SPC) in both samples, correcting Ct on basis of internal control, SPC) (see 3.6 and 12.4-5). Haugland teaches preparing a standard curve (calibration curve) based on known amounts of E. faecilus genomic DNA (see 9.10). Haugland does not teach the use of surfactant in PCR amplification buffer.
Using a surfactant in PCR amplification was known in the art. Shimizu teaches PCR amplification buffer for quantifying target nucleic acid using internal controls. Shimizu teaches surfactant comprising Tween in amplification buffer (see para 99). Bennis teaches addition of Tween can nullify the inhibitory effect of ionic detergents and results in higher yields and better specificity in samples containing inhibitors (see detergents, pg. 4).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to improve the method of detecting microorganisms in water samples using amplification buffers as taught by Haugland to include well-known surfactant, Tween in amplification buffer as taught by Shimizu and Bennis. The ordinary artisan would have been motivated with a reasonable expectation of success to include a surfactant, Tween as taught by Shimizu and Bennis in the PCR amplification buffer of Haugland for the expected benefit of neutralizing inhibitors, increasing higher yield and better specificity of samples.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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/SARAE L BAUSCH/Primary Examiner, Art Unit 1699
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