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 .
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 5, 6 and 14 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 5 recites that the mass reporter is not generated and 14 recites that the mass reporter is generated. It is unclear how the mass reporters can be generated or not generated.
Claim 5 recites that mass reporters are not generated upon oxidation at non-reducing voltages of > -0.1. Claim 14 recites that mass reporters are generated upon reduction at non-reducing voltages of <-0.1.
Applicant’s disclosure only refers to voltages of > -0.1 in reference to electrochemical signals being generated upon oxidation at non-reducing voltages of > -0.1 not mass reporters being generated or not generated.
There is no disclosure of mass reporters associated with non-reducing voltages and no disclosure of non-reducing voltages of < -0.1.
Claim 6 recites “the mass reporter” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
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.
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.
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.
1. Claims 1, 4, 5, 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication No. 2021/0333248 to Chen (relying on publication date of WO2018/08228, cited by applicant) in view of U.S. Patent Application Publication No. 2020/0072823 to Dill.
Chen teaches a method of analyzing target compounds in complex mixtures that involves applying an oxidation/reduction potential to an electrochemical cell containing a target compound; measuring an electrochemical current during the application of the oxidation/reduction potential; ionizing and directing the target compound before and after the application of the oxidation/reduction potential to a mass spectrometer that measures a target compound ion intensity; determining a target compound ion intensity change due to the application of the oxidation/reduction potential; and determining a total amount of the target compound in the sample using the measured electrochemical current and the target compound ion intensity change. [0004]
In an example using dopamine Chen notes by examining the recorded EC current response, a sharp peak was generated, which corresponded to the oxidation of dopamine (Fig. 5B). The peak area was integrated by importing data point to the potentiostat software to determine the amount of dopamine that was oxidized (Fig. 5B). The relative intensity change of dopamine before and after oxidation was measured using the protonated arginine at m/z 175.1 as the reference peak. All measurements were repeated three times and averaged values were used for calculation. The data is summarized in Table 1 above. By integrating the measured current peak areas, the calculated amount of the oxidized dopamine was 23.29 pmol and the relative intensity change for DA (based on the DA fragment peak at m/z 137) was 14.85%, which tells the measured amount for DA to be 156.82 pmol. In comparison to the actual injection amount of DA (150 pmol), the measurement error is small (4.54%). [0046]
Chen does not specifically teach introducing an affinity agent with an attached catalyst capable of forming an electrochemical signal.
Dill teaches a microarray for detecting target molecules comprising introducing an affinity agent with an attached catalyst capable of forming an electrochemical signal.
Dill teaches a process for reading micro array devices having addressable electrodes to determine binding between a capture probe and a target molecule comprising: (a) providing an array having a plurality of addressable electrodes and a plurality of capture molecules at sites corresponding to the addressable electrodes; (b) non-specifically attaching an oxidation/reduction enzymatic moiety to one or more target molecules; (c) administering the one or more target molecules to the array and allowing for binding of the one or more target molecules to the plurality of capture molecules; (d) adding a substrate to the array that will create a local voltage signal or a current signal when catalyzed by the oxidation/reduction enzymatic moiety through local generation of electrochemical reagents; (e) waiting a period of time for the current signal to level off; and (f) measuring for the presence or absence of a voltage signal or a current signal generated locally by electrochemical reagents at one or more of the plurality of addressable electrodes. (claim 1 and [0075[-[0080])
Dill teaches a microarray for detecting target molecules comprising introducing an affinity agent with an attached catalyst capable of forming an electrochemical signal. In particular, Dill teaches a process for reading micro array devices having addressable electrodes to determine binding between a capture probe and a target molecule comprising: (a) providing an array having a plurality of addressable electrodes and a plurality of capture molecules at sites corresponding to the addressable electrodes; (b) non-specifically attaching an oxidation/reduction enzymatic moiety to one or more target molecules; (c) administering the one or more target molecules to the array and allowing for binding of the one or more target molecules to the plurality of capture molecules; (d) adding a substrate to the array that will create a local voltage signal or a current signal when catalyzed by the oxidation/reduction enzymatic moiety through local generation of electrochemical reagents; (e) waiting a period of time for the current signal to level off; and (f) measuring for the presence or absence of a voltage signal or a current signal generated locally by electrochemical reagents at one or more of the plurality of addressable electrodes. [0023] and [0075]-[0080]
Figure 1 of Dill shows the chemical reaction scheme when using horseradish peroxidase (HRP) as the oxidation/reduction enzyme. Specifically, the targeted molecule is AGP (alpha-1 acid glycoprotein) that has been complexed with HRP by adding a biotin-labeled antibody specific for an epitope of AGP. The target molecule is complexed with HRP by adding an avidin-labeled HRP enzyme. The microarray site used for detecting AGP as the target molecule has another antibody binding to a different epitope on AGP as the capture molecule. Moreover, the first antibody (labeled "Ab 1") is bound to an oligonucleotide microarray through a tag array capture probe. [0023]
It would have been obvious to one of ordinary skill in the art to modify Chen to include an affinity agent and the catalyst as taught by Dill for purposes of making the method of detecting target molecules more accurate, given that the target molecules can be isolated with capturing affinity reagent.
As for the step of measuring the electrochemical signal that is capable of being electronically coupled to optical, genetic, or mass spectrometric results, Chen in view of Dill is “capable” of being electronically coupled to optical, genetic, or mass spectrometric results.
I.) Regarding applicant’s claim 1, as noted above Chen in view of Dill teaches all the elements of claim 1.
Therefore, Chen in view of Dill renders claim 1 obvious.
II.) Regarding applicant’s claim 4, as noted above Chen in view of Dill renders claim 1 obvious from which claim 4 depends.
Claim 4 recites processing reagents for electrochemical, optical, and mass spectrometric detection in a common electrochemical sensor microwell with a size exclusion filter, electrodes, and affinity agents for analyte reagent capture and analyte detection.
Dill teaches that the micro array is coated with a porous matrix that blocks diffusion of oxidation/reduction activity products. [0016] This porous matrix is interpreted as being a size exclusion filter.
Therefore, Chen in view of Dill renders claim 4 obvious.
III.) Regarding applicant’s claim 5, as noted above Chen in view of Dill renders claim 1 obvious from which claim 5 depends.
Claim 5 recites mass reporters are not generated upon oxidation at non-reducing voltages of > -0.1.
In Chen in view of Dill mass reporters are not “generated.”
Therefore, Chen in view of Dill renders claim 5 obvious.
IV.) Regarding applicant’s claim 8, as noted above Chen in view of Dill renders claim 1 obvious from which claim 8 depends.
Claim 8 recites introducing a catalyst, wherein the catalyst is an enzyme to generate the electrochemical signal.
As noted above, Dill teaches introducing a catalyst, wherein the catalyst. is an enzyme to generate the electrochemical signal. [0023]
Figure 1 of Dill shows the chemical reaction scheme when using horseradish peroxidase (HRP) as the oxidation/reduction enzyme.
Therefore, Chen in view of Dill renders claim 8 obvious.
V.) Regarding applicant’s claim 9, as noted above Chen in view of Dill renders claim 1 obvious from which claim 9 depends.
Claim 9 recites that an affinity agent contains a fluorescent label for optical detection.
Dill teaches an affinity agent that contains a fluorescent label for optical detection. [0081], [0224]
Therefore, Chen in view of Dill renders claim 9 obvious.
2. Claims 2 and 16-19 are rejected under 35 USC 103 as being unpatentable over Chen in view of Dill as applied to claim 1 above and further in view of Applicant’s Admitted Prior Art (found in [0004]).
I.) Regarding applicant’s claim 2, as noted above Chen in view of Dill renders claim 1 obvious from which claim 2 depends.
Claim 2 recites that the method contains no interference with optical, genetic, or mass spectrometric detection.
Chen in view of Dill does not teach that method contains no interference with optical, genetic, or mass spectrometric detection.
Applicant discloses in [0004] that “Bio-analysis by combining results from multiple methodologies, namely electrochemical, optical, imaging, genetic, and mass spectrometric analysis, is becoming increasing more common for measurements of complex in-vitro, cell and tissue samples.
In the method of Chen in view of Dill it would be obvious that the method would not cause interference with optical, genetic or mass spectrometric detection as evidenced by Applicant’s Admitted Prior Art.
Therefore, Chen in view of Dill renders claim 2 obvious
II.) Regarding applicant’s claim 16, as noted above Chen in view of Dill renders claim 1 obvious from which claim 16 depends.
Claim 16 recites further analyzing analyte by downstream optical methods.
As noted above, Applicant discloses in [0004] that “Bio-analysis by combining results from multiple methodologies, namely electrochemical, optical, imaging, genetic, and mass spectrometric analysis, is becoming increasing more common for measurements of complex in-vitro, cell and tissue samples.
It would have been obvious to modify Chen in view if Dill to perform further downstream analysis by optical methods in view of Applicant’s Admitted Prior Art for purposes of performing further analysis.
Therefore, Chen in view of Dill and Applicant’s Admitted Prior Art renders claim 16 obvious.
III.) Regarding applicant’s claim 17, as noted above Chen in view of Dill renders claim 1 obvious from which claim 17 depends.
Claim 17 recites further analyzing analyte by downstream mass spectrometric methods.
As noted above, Applicant discloses in [0004] that “Bio-analysis by combining results from multiple methodologies, namely electrochemical, optical, imaging, genetic, and mass spectrometric analysis, is becoming increasing more common for measurements of complex in-vitro, cell and tissue samples.
It would have been obvious to modify Chen in view if Dill to perform further downstream analysis by mass spectrometric methods in view of Applicant’s Admitted Prior Art for purposes of performing further analysis.
Therefore, Chen in view of Dill and Applicant’s Admitted Prior Art renders claim 17 obvious.
IV.) Regarding applicant’s claim 18, as noted above Chen in view of Dill renders claim 1 obvious from which claim 18 depends.
Claim 18 recites further analyzing analyte by downstream immunoassay methods.
As noted above, Applicant discloses in [0004] that “Bio-analysis by combining results from multiple methodologies, namely electrochemical, optical, imaging, genetic, and mass spectrometric analysis, is becoming increasing more common for measurements of complex in-vitro, cell and tissue samples.
It would have been obvious to modify Chen in view if Dill to perform further downstream analysis by other known analysis methodologies including immunoassay methods in view of Applicant’s Admitted Prior Art for purposes of performing further analysis.
Therefore, Chen in view of Dill and Applicant’s Admitted Prior Art renders claim 18 obvious.
V.) Regarding applicant’s claim 19, as noted above Chen in view of Dill renders claim 1 obvious from which claim 19 depends.
Claim 19 recites further analyzing analyte by downstream genetic method.
As noted above, Applicant discloses in [0004] that “Bio-analysis by combining results from multiple methodologies, namely electrochemical, optical, imaging, genetic, and mass spectrometric analysis, is becoming increasing more common for measurements of complex in-vitro, cell and tissue samples.
It would have been obvious to modify Chen in view if Dill to perform further downstream analysis by genetic methods in view of Applicant’s Admitted Prior Art for purposes of performing further analysis.
Therefore, Chen in view of Dill and Applicant’s Admitted Prior Art renders claim 19 obvious.
3. Claims 3, 6, 7 and 14 are rejected under 35 USC 103 as being unpatentable over Chen in view of Dill as applied to claim 1 above and further in view of U.S. Patent Application Publication No. 2002/0168644 to Aebersold et al.
I.) Regarding applicant’s claim 3, as noted above Chen in view of Dill renders claim 1 obvious from which claim 3 depends.
Claim 3 recites that a mass reporter measures the integrity and identity of an analyte by mass spectrometric detection.
Chen teaches electrochemical mass spectrometry (Title), but Chen in view of Dill does not teach a mass reporter.
Aebersold et al. teaches that mass tags (“mass reporters”) are well known for use in conjunction with mass spectrometry for quantitative detection and analysis. [0063]
It would have been obvious to one of ordinary skill in the art to modify Chen in view of Dill to use a mass tag (mass reporter) as taught by Aebersold et al. for purposes of measuring the integrity and identity of an analyte by mass spectrometric detection.
Therefore, Chen in view of Dill and Aebersold et al. renders claim 3 obvious.
II.) Regarding applicant’s claim 6, as noted above Chen in view of Dill renders claim 1 obvious from which claim 6 depends.
Claim 6 recites that the mass reporter causes production of the optical, genetic, or mass spectrometric results for an analyte.
Chen in view of Dill does not teach a mass reporter.
As noted above Aebersold et al. teaches that mass tags (“mass reporters”) are well known for use in conjunction with mass spectrometry for quantitative detection and analysis. [0063]
It would have been obvious to one of ordinary skill in the art to modify Chen in view of Dill to use a mass tag (mass reporter) as taught by Aebersold et al. and select a mass tag that causes production of the optical, genetic, or mass spectrometric results for an analyte for analysis purposes.
Therefore, Chen in view of Dill and Aebersold et al. renders claim 6 obvious
III.) Regarding applicant’s claim 7, as noted above Chen in view of Dill renders claim 1 obvious from which claim 7 depends.
Claim 7 recite that mass reporter measurements allow electronical coupling of electrochemical analyte detection to optical, genetic, or mass spectrometric results.
As noted above, Aebersold et al. teaches that mass tags (“mass reporters”) are well known for use in conjunction with mass spectrometry for quantitative detection and analysis. [0063]
It would have been obvious to one of ordinary skill in the art to modify Chen in view of Dill to use a mass tag (mass reporter) as taught by Aebersold et al. and select a mass tag that allows electronical coupling of electrochemical analyte detection to optical, genetic, or mass spectrometric results. for analysis purposes.
Therefore, Chen in view of Dill and Aebersold et al. renders claim 7 obvious.
IV.) Regarding applicant’s claim 14, as noted above Chen in view of Dill renders claim 1 obvious from which claim 14 depends.
Claim 14 recites that mass reporters are generated upon reduction at non-reducing voltages of < -0.1.
Chen in view of Dill does not teach mass reporters.
As noted above, Aebersold et al. teaches that mass tags (“mass reporters”) are well known for use in conjunction with mass spectrometry for quantitative detection and analysis. [0063]
It would have been obvious to one of ordinary skill in the art to modify Chen in view of Dill to use a mass tag (mass reporter) as taught by Aebersold et al. for analysis purposes.
However, such mass tags would not be “generated” or created upon oxidation at non-reducing voltages of <-0.1.
Therefore, Chen in view of Dill and Aebersold et al. renders claim 5 obvious.
4. Claim 15 is rejected under 35 USC 103 as being unpatentable over Chen in view of Dill as applied to claim 1 above, further in view of Applicant’s Admitted Prior Art (found in [0006]) and International Patent Application Publication No. WO 2015/184321 to Pugia et a. (using U.S. Patent No. 10,809,264 as an English equivalence).
I.) Regarding applicant’s claim 15, as noted above Chen in view of Dill renders claim 1 obvious from which claim 15 depends.
Claim 15 recites introducing a catalyst, wherein the catalyst is a nanoparticle to generate the electrochemical signal.
Chen in view of Dill teaches a catalyst, but does not teach a catalyst that is a nanoparticle to generated the electrochemical signal.
Applicant discloses in [0006] that “Recently, the Signal Jon Emission Reactive Releasee Amplification GSIERRA) method for MA-IA (as described in, for example, Pugia US-10,809,264, US-11,061,035, Analytical Chem 2016, 2019, 2021) was developed using releasable organic compounds as the mass label attached to the affinity agents.”
Pugia 10,809,264 teaches catalyst label that can be nanoparticle sized (column 16, line 56 through column 17, line 16).
It would have been obvious to one of ordinary skill in the art to modify Chen in view of Dill to use a catalyst that is a nanoparticle to generated the electrochemical signal as taught by Applicant’s Admitted Prior Art and Pugia et al. for purposes of labeling target materials.
Therefore, Chen in view of Dill, Applicant’s Admitted Prior Art and Pugia et al. renders claim 15 obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL S. GZYBOWSKI whose telephone number is (571)270-3487. The examiner can normally be reached M-F 8:30-5:00.
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/M.S.G./Examiner, Art Unit 1798
/JILL A WARDEN/Supervisory Patent Examiner, Art Unit 1798