DETAILED ACTION
The Final Office Action of 02/26/2026 is hereby VACATED in favor of the following.
Status of the Claims
Claims 90-94, 96, 99, 101-103, 105, and 108-114 are currently pending.
Claims 1-89, 95, 97-98, 100, 104, and 106-107 were canceled by Applicant.
Claims 90-94, 96, 99, 101-103, 105, and 108-110 are amended.
Claims 111-114 are new.
Claims 90-94, 96, 99, 101-103, 105, and 108-114 are the subject of this Office Action.
The following Office Action is in response to Applicant’s communication dated 11/24/2025. Rejection(s) and/or objection(s) not reiterated from previous office actions are hereby withdrawn. The following rejection(s) and/or objection(s) are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Terminal Disclaimer
The terminal disclaimer filed on 11/24/2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. 11,209,412 and any patent granted on Application 18/837,354 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/24/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Abstract
The replacement abstract is accepted and the previous objection to the specification is withdrawn.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application, Application No. 62/116,888 filed 02/16/2015 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for claims 90-94, 96, and 111 of this application. Specifically, the provisional applications do not support the breadth of the instant claims, at least because the provisional application does not recite SEQ ID NO: 1-43.
Therefore 02/12/2016 is the date for the purposes of prior art concerning claims 90-94, 96, and 111.
New Claim Rejections - 35 USC § 112(b)
Necessitated by Amendments
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 90-94, 96, 99, 101-103, 105, and 108-114 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 pre-AIA the applicant regards as the invention.
Claim 90 has been newly amended to recite a plurality of recombinant microbial cell strains, each strain comprising a different expression cassette comprising a biosensor or promoter operably linked to a polynucleotide encoding a detectable agent, wherein the promoter comprises a polynucleotide having a 90% sequence identity to a polynucleotide of SEQ ID NO: 1-43. This can reasonably be interpreted to mean that (1) each and every one of the plurality of cell strains must have the same promoter (i.e., “the promoter”), or (2) each cell strain comprises a promoter, and each promoter may be independently 90% identical with one selected from SEQ ID NO: 1-43. As per MPEP § 2173.02(I), “if the language of a claim, given its broadest reasonable interpretation, is such that a person of ordinary skill in the relevant art would read it with more than one reasonable interpretation, then a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph is appropriate”. Claims 91-94, 96, and 114 depend from claim 90 and are therefore similarly rejected.
Claim 96 depends from claim 95, which has been cancelled by Applicant. Accordingly, the metes and bounds of the claim are unascertainable.
Claim 105 depends from claim 104, which has been cancelled by Applicant. Accordingly, the metes and bounds of the claim are unascertainable.
Claim 99 recites the limitation "the plurality of recombinant microbial cells" in step (a) at line 3. There is insufficient antecedent basis for this limitation in the claim. Claims 101-103, and 108-113 depend from claim 99 and are therefore similarly rejected.
As per MPEP 2173: It is of utmost importance that patents issue with definite claims that clearly and precisely inform persons skilled in the art of the boundaries of protected subject matter. Therefore, claims that do not meet this standard must be rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph as indefinite. Further, as per MPEP 2173.02: If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112, second paragraph, would be appropriate. As currently written, the metes and bounds of the rejected claims are unascertainable for the reasons set forth above, thus the above claim(s) and all dependent claims are rejected under 35 USC 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
New Claim Rejections – 35 U.S.C. 102
Necessitated by Amendments
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Merulla et al.
Claims 90-94, 96, and 114 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Merulla et al. (WO 2015/177711 A1).
Regarding claim 90, Merulla discloses a plurality of recombinant microbial cell strains (e.g., different strains as per Fig. 6-7 and pp. 16-18), each strain comprising a different expression cassette comprising a biosensor or promoter operably linked to a polynucleotide encoding a detectable agent (e.g., linked to eGFP as per Fig. 5),
wherein the promoter comprises a polynucleotide having a sequence identity of at least about 90% to a polynucleotide sequence selected from the group consisting of SEQ ID NOs: 1-43 (e.g., SEQ ID NO: 4 is the naturally occurring arsR found in R773 of E. coli as per Merulla on p. 52, which is a 100% match to SEQ ID NO: 4 as per the “Merulla SEQ ID NO 1 match” document attached), and
wherein transcription of the biosensor or promoter is modulated by the presence of one or more heavy metal analytes (e.g., Fig. 5-7).
Regarding claim 91, Merulla discloses the above, wherein the heavy metal analyte is selected from the group consisting of arsenic, cadmium, chromium VI, cobalt, copper, lead, mercury, and zinc (e.g., arsenic as per p. 52 and Fig. 5-7).
Regarding claim 92, Merulla discloses the above, wherein the biosensor or promoter comprises ParsR (arsenic) (e.g., as per p. 52 and Fig. 5-7).
Regarding claim 93, Merulla discloses the above, wherein the detectable agent is a nucleic acid, detectable protein, antibody-linked reporter protein, enzymatic assay product, or electrochemical reaction product (e.g., eGFP as per Fig. 5-7).
Regarding claim 94, Merulla discloses the above, wherein the detectable agent is a fluorescent protein or a luminescent protein (e.g., eGFP as per Fig. 5-7).
Regarding claim 96, Merulla discloses the above, wherein the bacterium is selected from the group consisting of Escherichia coli (e.g., E. coli as per p. 52 and Fig. 5-7).
Regarding claim 114, Merulla discloses the above, wherein one or more recombinant microbial cell strains of the plurality of recombinant microbial cell strains are lyophilized (e.g., as per p. 29).
Jouanneau et al.
Claims 99, 101-103, 105, 108-110, and 112 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Jouanneau et al. (Environ. Sci. Technol., 2011, 45:2925–2931).
Regarding claim 99, Jouanneau discloses a method of detecting the presence of one or more heavy metal analytes of interest, comprising:
(a) culturing, in a defined array (e.g., microwell plate as per the 2.5. Lyophilization Procedure section on p. 2926), the plurality of recombinant microbial cell strains (e.g., five bacterial strains as per the 2.1. Bacterial Strains section on p. 2926), each strain of the plurality of recombinant microbial cell strains, comprising a different expression cassette comprising a biosensor or promoter (e.g., as per the supplementary materials, page 1) operably linked to a polynucleotide encoding a detectable agent, wherein transcription of the biosensor or promoter is modulated by the presence of one or more heavy metal analytes of interest (e.g., as per Fig. 1);
(b) delivering an aqueous sample suspected of comprising the one or more heavy metal analytes of interest to each strain of the plurality of recombinant microbial cell strains in the defined array under environmental conditions permitting modulated expression of the detectable agent in the presence of the one or more heavy metal analytes of interest (e.g., as per the 2.6. Bioassay and Luminescence Measurements section on p. 2926);
(c) measuring in the defined array, expression of an amount of the detectable agent which provides a sensor-detectable signal, corresponding to a quantifiable level of the one or more heavy metal analytes of interest (e.g., as per the 2.6. Bioassay and Luminescence Measurements section on p. 2926);
(d) detecting the signal with a sensor and applying one or more machine learning algorithms to the signal, to detect the one or more heavy metal analytes of interest and to distinguish from each other different heavy metal analytes of interest, if present in the aqueous sample (e.g., as per the 2.7. Data Acquisition and Data Analysis section on pp. 2926-2927); and
(e) quantifying the quantifiable levels of the one or more heavy metal analytes of interest, based on the detected signal provided by the expression of the amount of the detectable agent (e.g., as per the 2.6. Bioassay and Luminescence Measurements section and 2.7. Data Acquisition and Data Analysis section on pp. 2926-2927);
wherein the one or more heavy metal analytes of interest are selected from the group consisting of arsenic, cadmium, chromium (VI), cobalt, copper, lead, mercury, and zinc, or is more than one of these members (e.g., zinc, copper, mercury, and arsenic as per the 2.1. Bacterial Strains section on p. 2926).
Regarding claim 101, Jouanneau discloses the above, wherein the biosensor or promoter is selected from the group consisting of ParsR (arsenic), PcadC (cadmium), PcadR (cadmium), PzntA (cadmium), PchrB (chromium VI), PchrS (chromium VI), PrecN (chromium VI), PsulA (chromium VI), PumuD (chromium VI), PdadA (cobalt), Phmp (cobalt), PilvB (cobalt), PlipA (cobalt), PmmuP (cobalt), PnmtR (cobalt), PsoxR (cobalt), PtehA (cobalt), PygbA (cobalt), PyjbJ (cobalt), PyqfA (cobalt), PcopA (copper), PcusC (copper), PcusR (copper), PpbrR (lead), PmntH (lead), PshiA (lead), PybiI (lead), PyjjZ (lead), PmerR (mercury), PmntH (zinc), PshiA (zinc), PyjjZ (zinc), PzntA (zinc) and PzraP (zinc) (parsR, pmerR, pzntA, pcopA as per Fig. SI-1).
Regarding claim 102, Jouanneau discloses the above, wherein the detectable agent is a nucleic acid, detectable protein, antibody-linked reporter protein, enzymatic assay product, or electrochemical reaction product (e.g., bioluminescence as per the Abstract).
Regarding claim 103, Jouanneau discloses the above, wherein the detectable agent is a fluorescent protein or a luminescent protein (e.g., bioluminescence as per the Abstract).
Regarding claim 105, Jouanneau discloses the above, wherein the bacterium is Escherichia coli (as per the 2.1. Bacterial Strains section on p. 2926).
Regarding claim 108, Jouanneau discloses the above, wherein the step of measuring in the defined array, the expression of an amount of the detectable agent comprises measuring a transcription level and/or an activation level of the detectable agent (e.g., as per the 2.6. Bioassay and Luminescence Measurements section and 2.7. Data Acquisition and Data Analysis section on pp. 2926-2927).
Regarding claim 109, Jouanneau discloses the above, wherein the transcription level and/or the activation level of the detectable agent corresponds to the quantifiable level of the heavy metal analyte of interest (e.g., as per the 2.6. Bioassay and Luminescence Measurements section and 2.7. Data Acquisition and Data Analysis section on pp. 2926-2927).
Regarding claim 110, Jouanneau discloses the above, wherein the step of measuring in the defined array, the expression of an amount of the detectable agent comprises measuring a detectable fluorescence and/or a luminescence signal of the detectable agent (e.g., as per the 2.6. Bioassay and Luminescence Measurements section and 2.7. Data Acquisition and Data Analysis section on pp. 2926-2927).
Regarding claim 112, Jouanneau discloses the above, wherein, the one or more recombinant microbial cell strains have been stored in lyophilized form, and the method further comprises the step of reviving the lyophilized one or more recombinant microbial cell strains in resuspension medium prior to the step of culturing, in a defined array, the plurality of recombinant microbial cell strains (as per the 2.5. Lyophilization Procedure section on p. 2926).
New Claim Rejections – 35 U.S.C. 103
Necessitated by Amendments
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.
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.
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.
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.
Jouanneau et al. and Merulla et al.
Claims 90-94, 96, 99, 101-103, 105, 108-112, and 114 are rejected under 35 U.S.C. 103 as being unpatentable over Jouanneau et al. (Environ. Sci. Technol., 2011, 45:2925–2931) in view of Merulla et al. (WO 2015/177711 A1).
Jouanneau and Merulla are relied on as above, however, it is noted that the references are individually silent on the limitation of a promoter or biosensor with at least 90% sequence identity to one or more of SEQ ID NO: 1-43, as set forth in claim 111.
Regarding claim 111, Jouanneau discloses the use of parsP, but is silent as to the source thereof. Merulla discloses a parsP that is identical to SEQ ID NO: 4, as detailed above.
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to use the parsP as per Murella in the biosensor array of Jouanneau. In accordance with MPEP 2141 citing KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385,1395 (2007), "[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results”, and as per MPEP 2143(I)(A), the rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art.
One of ordinary skill in the art would have had a reasonable expectation of success as of the application’s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since parsP from R773 as per Merulla is known to work.
Conclusion
No claims are allowed.
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.
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/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684