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 .
Election/Restrictions
Applicant’s election of Group I, claims 1-6 in the reply filed on January 21, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Objections
Claim 6 is objected to under 37 CFR 1.75 as being a duplicate of claim 2. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a duplicate of the allowed claim. See MPEP § 608.01(m). Thus, it is suggested to delete claim 6.
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 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 is/are rejected under 35 U.S.C. 103 as being unpatentable over Knopfmacher (US 2020/0224241) in view of Piletsky (US 2021/0239643), supported by Cady (US 2021/0147898) as an evidence.
Regarding claim 1, Knopfmacher teaches a multiplexed (¶19: a multiplex system) electrochemical antibiotic susceptibility method (Fig. 5; ¶76: a method 500 for determining the susceptibility of one or more infectious agents 102; ¶146: the sensor can be an electrochemical cell), comprising:
disposing a non-inoculated solution in one or more sample wells arranged in an array (Fig. 6; Fig. 2B, ¶54: sample receiving surface 204; ¶55: the sample receiving surface 204 can be a concave surface of a well), wherein the non-inoculated solution in the one or more sample wells is configured with a pathogen (Fig. 5; ¶79: the infectious agents 102);
measuring a multiplexed number of control signal responses (¶95: the sensors can be oxidation reduction potential ORP sensors configured to respond to a change in a solution characteristic (e.g., the ORP); ¶7: ORP is oxidation reduction potential) of the non-inoculated solution disposed in the one or more sample wells of the array (Fig. 5; ¶94: the control solution 504 measured by the second sensor 510 in step 5F(ii); Fig. 6: in channel 610);
inoculating a set number of solutions in the one or more sample wells with an antibiotic (Fig. 5C; ¶87: introducing and mixing an anti-infective 502);
measuring a multiplexed number of inoculated response signals (¶95: the sensors can be oxidation reduction potential ORP sensors configured to respond to a change in a solution characteristic (e.g., the ORP); ¶7: ORP is oxidation reduction potential) from the inoculated set number of solutions in the one or more sample wells of the array (Fig. 5; ¶94: the test solution 506 measured by the first sensor 508 in step 5F(i); Fig. 6: e.g., in channels 608, 612, 614, 616); and
analyzing with a computer control and data system/processor (Fig. 5; ¶100: the reader 120; ¶101: a laptop or desktop computer), the multiplexed number of control signal responses and the multiplexed number of inoculated response signals to provide a susceptibility index assessment indicative of the susceptibility or resistance of the pathogen to the antibiotic (¶100: Comparing the ORP of the test solution 506 with the ORP of the control solution 504 to determine the susceptibility of the infectious agent 102 to the anti-infective 502).
Knopfmacher does not disclose the control signal responses or the inoculated response signals are current or the analyzed signals are current signals.
However, Piletsky teaches the electrochemical sensor has the signal response that is a change in potential difference, impedance, capacitance and/or current between the first and second electrodes (¶25). For example, the electrochemical sensor may comprise a voltmeter configured to measure the potential difference between the first and second electrodes or an amperometer configured to measure the current between the first and second electrodes (¶25).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Knopfmacher by substituting the ORP measurements with current measurements as taught by Piletsky because they are alternative electrochemical signals for detecting and determining the analyte concentrations by the electrochemical sensors ([Abstract]; ¶25). Here, the substitution of one known element for another would yield nothing more than predictable results. MPEP 2141(III)(B). Further, applying a known technique to a known method ready for improvement to yield predictable results is prima facie obvious. MPEP 2141(III)(D). The combined Knopfmacher and Piletsky would necessarily result in comparing the electrochemical signals, e.g., current, for determining the susceptibility of the infectious agent to the anti-infective.
Knopfmacher does not disclose wherein the inoculating step includes a range of concentrations of up to about 24 times a breakpoint of the antibiotic or the analyzing is over the range of concentrations of up to about 24 times a breakpoint of the antibiotic.
However, Knopfmacher teaches the incubation period 114 can be adjusted based on the type of anti-infective 502, the mechanism of action of the anti-infective 502, the amount of the sample 104, or a combination thereof (¶93), or can be start-delayed or a pre-incubation time period can be added before the start of the incubation period 114 (¶93). The start-delayed or the pre-incubation time period is particularly useful for instances where higher innoculums or a higher concentration of infectious agents and where the signal is generated relatively fast (¶93). Thus, Knopfmacher teaches the concentration of infectious agent is a result-effective variable for incubation period, one parameter for the antibiotic susceptibility method. As evidenced by Cady, microbroth dilution is performed by incubating a given bacteria in the presence of multiple concentrations of antimicrobial; following incubation, growth/no growth of the bacteria is observed at each concentration of antimicrobial. The lowest concentration at which no growth is observed is the Minimum Inhibitory Concentration (MIC), and the “breakpoint” is the experimentally determined MIC values for specific bacterial groups or species interpreted as susceptible, intermediate, or resistant to the given antimicrobial (¶7). In another word, the concentration of the anti-infective agent must be above its breakpoint to enable the comparison between the control sample (without anti-infective) and the test sample (with effective anti-infective, i.e., above its breakpoint).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Knopfmacher by adjusting the concentration of the antibiotic within the claimed range and above its breakpoint as suggested because the antibiotic concentration is a result-effective variable when above its breakpoint to be effective and can be optimized through routine experimentation to adjust the incubation period as one of the parameters for the antibiotic susceptibility method. MPEP 2144.05 (II)(B). Thus, the combined Knopfmacher and Piletsky would necessarily result in comparing the electrochemical signals between the control sample and test sample, over the claimed concentration range above its breakpoint, for determining the susceptibility of the infectious agent to the anti-infective.
Claim(s) 2 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Knopfmacher in view of Piletsky, and further in view of Bond (US 2014/0004578).
Regarding claims 2 and 6, Knopfmacher and Piletsky disclose all limitations of claim 1, but fail to teach wherein the electron transfer mediator is at least one or an exogeneous mediator and an endogenous mediator.
However, Bond teaches various strains of E. coli have been tested in electrochemical systems and significant current was generated upon addition of exogenous redox mediators, e.g., thionine, neutral red, or ferricyanide (¶111).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Knopfmacher and Piletsky by substituting the mediator with one exogenous mediator because it generates significant current for electrochemical measurement (¶111). Here, the substitution of one known element for another would yield nothing more than predictable results. MPEP 2141(III)(B).
Allowable Subject Matter
Claim(s) 3-5 is/are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: The prior art does not disclose nor render obvious all of the cumulative limitations of claims 3-5 with particular attention to the limitations:
wherein the susceptibility index assessment includes measuring a time frame at an inflection point of an exponential growth of a number of current response and a saturated number of current responses (claim 3).
Here, Knopfmacher teaches a multiplex (Fig. 6; ¶19) method for determining the antibiotic (¶145) susceptibility based on the ORP (¶7: ORP is oxidation reduction potential) measurements (¶94) by electrochemical sensors (¶146). The susceptibility is determined by comparing the ORP of the test solution 506 with the ORP of the control solution 504 (¶100), as shown in Fig. 5F(i) and (ii) (¶94). Fig. 7A shows the sensor output (V) decreases over time during “NOT SUSCEPTIBLE” to a relatively constant value as “SUSCEPTIBLE” (Fig. 7A-B; ¶¶140, 142). The pertinent art, Piletsky, teaches the measured electrochemical signals can be either potential difference or current between the electrodes (¶25). Neither Knopfmacher nor Piletsky teaches calculating the susceptibility index by measuring a time frame at an inflection point of the exponential growth of the current signals, let alone a threshold value, e.g., 0.4, of the susceptibility index as recited in claims 4-5.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAITLYN M SUN whose telephone number is (571)272-6788. The examiner can normally be reached M-F: 8:30am - 5:30pm.
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/C. SUN/Primary Examiner, Art Unit 1795