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 without traverse of Group I, drawn to hyperspectral reporter cells, in the reply filed on 09/08/2025 is acknowledged.
Claims 22-24, 28, 34, 38, 42, 49, and 51 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 09/08/2025.
Claims Status
Claims 3-4, 8-9, 11-12, 14-16, 18, 20-21, 25-27, 29-33, 35-37, 39-41, 43-48, 50, 52, 54, 57-59, 61-63 is/are cancelled. Claims 1-2, 5-7, 10, 13, 17, 19, 22-24, 28, 34, 38, 42, 49, 51, 53, 55-56, and 60 is/are currently pending with claims 22-24, 28, 34, 38, 42, 49, and 51 withdrawn. Claims 1-2, 5-7, 10, 13, 17, 19, 53, 55-56, and 60 is/are under examination.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(4) because reference character “Fig. 4A” has been used to designate both Fig. 4A and Fig. 9A. Likewise, the reference character “Fig. 4B” has been used to designate both Fig. 4B and Fig. 9B. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Interpretation
The claims contain limitations preceded by the term “optional”. All claim limitations recited as “optional” are interpreted as not required. As such, prior art can be applied to teach these limitations, but does not need to be applied.
Claim Objections
Claims 1 and 55 are objected to because of the following informalities:
The phrasing of the limitations in lines 2-4 of claim 1 and lines 2-3 of claim 55 can be clearer. The examiner recommends rephrasing “comprising a DNA molecule having a regulatory element responsive to a target input operatively linked to a DNA sequence encoding a signaling protein” to “comprising a DNA molecule comprising a regulatory element responsive to a target input, wherein the regulatory element is operatively linked to a DNA sequence encoding a signaling protein”.
Claims 1 and 55 should also be amended to include “and” preceding the final “wherein” clause to indicate that the “wherein” clauses of claims 1 and 55 are not alternative limitations.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
112(b):
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.
Claim 1, 6-7, 13, 19, 53, 55, and 60 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.
Claims 1, 6-7, 13, 19, 53, 55, and 60 recite the term “unique” in reference to a “unique hyperspectral signature” (claims 1, 6-7, 13, 53, 55, 60) and a “unique DNA molecule (claim 19). The specification does not provide a definition of the term “unique”, thus the definition of the term “unique” as used in the claims is unclear. As such, the metes and bounds of the limitations “unique hyperspectral signature” and “unique DNA molecule” are unclear, and claims 1, 6-7, 13, 19, 53, 55, and 60 are rendered indefinite.
Claim 6 recites that “the signaling protein comprises the unique hyperspectral signature” and “a compound comprising the unique hyperspectral signature”. From the specification, it is clear that a “hyperspectral signature” is a signal that can be captured by hyperspectral imaging techniques, and the detectable signal is what comprises the unique hyperspectral signature (page 9 lines 18-24; page 20 lines 13-18). Such signals are emitted by molecules, such as proteins, but are not comprised by molecules. It is unclear how a molecule, such as a protein, can comprise, instead of emit, a hyperspectral signal or signature. Based on the specification, claim 6 is interpreted as reciting signaling proteins and compounds which emit a unique hyperspectral signature.
112(a):
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 5-7, 10, 13, 17, 19, 53, 55-56, and 60 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it”).
According to the MPEP § 2163, "The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutsch land GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.")."
Claims 1, 53, and 55 recite hyperspectral reporters comprising any type of engineered cell (not limited to bacteria, plant cells, and fungi), any type of transducer which comprises a DNA molecule, any target input, any regulatory element, and any signaling protein. These are enormous genera of cells, transducer elements, regulatory elements, inputs, and signaling proteins.
The disclosure does not provide a definition of a “transducer”. It is unclear what structures are associated with or required by a “transducer”, as a “transducer” is not defined. The only description of a transducer in the claims and the disclosure provides that a transducer comprises a DNA sequence and that a transducer generally fulfills “signaling roles within the engineered cell hyperspectral reporter system (page 14 lines 6-7); no other structure or function is described. It is not clear what additional structures or functions are required for a DNA sequence or a structure comprising a DNA sequence to be considered a “transducer”. As no claim recites sufficient structure and function to describe a “transducer”, claims 1-2, 5-7, 10, 13, 17, 19, 53, 55-56, and 60 are rejected for not sufficiently describing a “transducer”.
On page 2 lines 8-9, the specification teaches that the cell can be “a bacterium or fungi…a plant cell”. This does not limit the engineered cell to a bacterium, fungus, or plant cell, and thus “engineered cell” as recited in claims 1, 53, and 55 encompasses cells that are not bacteria, fungi, or plant cells. However, the disclosure only describes engineered bacterial, fungal, and plant cells. As such, the disclosure fails to describe the full scope of the recited genus of engineered cells.
The specification teaches that the signaling protein can be an enzyme or a regulator of an enzyme (pages 17-18). The broad categories of “enzyme” and “regulator of an enzyme” are not limiting definitions of a signaling protein. As such, “signaling protein” is sufficiently broad to encompass any protein which can itself produce a hyperspectral signal or which through the function of the protein can result in the production of a hyperspectral signal by a molecule, compound, or different protein downstream of the activity of the protein. The disclosure does not describe a number of species representative of the full scope of the genus of “signaling protein”.
Claim 13, dependent on claim 1, recites particular species and types of target inputs, but fails to fulfill the written description requirement for the following reasons. Claim 13 recites “E. coli metabolites” and “volatile metabolites” which produce detectable signals with unique hyperspectral signatures. However, no specific E. coli metabolites or volatile metabolites are described in the claim or specification, nor are any such metabolites described through structural characteristics. The functional limitation that the metabolites produce a detectable signal with a unique hyperspectral signature, and that the metabolites have 6 or more conjugated π bonds or produce a detectable signal which absorbs light at 290-460nm or 790-810nm do not sufficiently describe the E. coli metabolites and volatile metabolites, as by Applicant’s own definition of these genera, all species would have this functional characteristic. An artisan would not be able to determine, based on the information provided in the disclosure, that the applicants were in possession of hyperspectral reporter cells comprising E. coli metabolites or volatile metabolites which produce a detectable signal with a unique hyperspectral signature.
Claim 17 recites multiple classes of target inputs: toxins, radiation, pollutants, nucleic acids, explosives, bacteria, fungi, viruses, and nutrients. However, in order for these to be target inputs, a corresponding regulatory element responsive, directly or indirectly, to the target input must exist. However, the disclosure only describes a limited number of species of cellular elements (regulatory sequences, receptors) which bind to a target input and produce a detectable signal or trigger a signaling cascade which downstream produces a detectable signal. The specification describes zinc-, dexamethasone-, tetracycline-, RU486-, and rapamycin-inducible promoters (page 15), and inducible promoters ParaBAD, PrhaBAD, Plac, Ptac, Plux, Ptet, Psa1, Ptrp, PA1lacO1, and Ppho (page16 lines 15-19). These inducible promoters are not representative of the entire scope of the genus of inducible promoters. The specification also describes that “the cell expresses a receptor capable of recognizing the target input” (page 2 lines 18-20). However, the disclosure does not provide a representative number of such receptors. These species of promoters and the broad description of receptors are not a representative number of species of cellular elements which are capable of binding or recognizing any target input selected from a toxin, radiation, pollutant, nucleic acid, explosive, bacterium, fungus, virus, and nutrient. As described above, a description of a representative number of species of such cellular elements is required in order to describe a representative number of species of target inputs as recited in claim 17. Furthermore, the disclosure does not describe a representative number of species of target inputs. The specification teaches the specific species of target inputs vanillate, IPTG, aTc, cuminic acid, DAPG, salicylic acid, 3,4-dihydroxybenzoic acid, 3OC6HSL, and 3OC14HSL (page 24 lines 5-7; page 30 “Example 1”). These are not representative of the full scope of the genera of toxins, radiation, pollutants, nucleic acids, explosives, bacteria, fungi, viruses, and nutrients.
Claim 60 recites a cell comprising a DNA molecule having a regulatory element responsive to a first target input, wherein the regulatory element is operatively linked to a DNA sequence encoding a first signaling protein, wherein the target input produces a physiological response (claim 55) which physiological response makes the cell responsive to a second target input (claim 60). However, the disclosure does not describe any target inputs or downstream structures (such as proteins activated or expressed because of the presence of the first target input) which render the cell responsive to a second target input. On page 15 lines 10-14, the specification teaches that “a first target may trigger the production of a sensor for a second target. Thus, a reporter cell can conditionally report on the presence of a second molecule only when a first molecule is present, thus increasing the complexity of the detection process.” However, no species of target inputs, sensors, or signaling proteins which could fulfill the functional requirements of claim 60 are described in the disclosure. As such, an artisan would not be able to determine, based on the disclosure, what structures could fulfill the required functions of claim 60 or that the applicants were in possession of structures which could fulfill the structural requirements of claim 60, and thus in possession of the hyperspectral reporter cell of claim 60.
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.
(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.
Claim(s) 1-2, 5-7, 13, 17, 19, 55-56 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Maeda (JP2009159862A, English machine translation provided, obtained from J-PlatPat OPD machine translation function).
MPEP §2131.01 provides guidance as to 35 U.S.C. 102 rejections over multiple references. Such rejection has been held to be proper when the extra references are cited to: (C) Show that a characteristic not disclosed in the reference is inherent.
The MPEP states: “To serve as an anticipation when the reference is silent about the asserted inherent characteristic, such gap in the reference may be filled with recourse to extrinsic evidence. Such evidence must make clear that the missing descriptive matter is necessarily present in the thing described in the reference, and that it would be so recognized by persons of ordinary skill.” Continental Can Co. USA v. Monsanto Co., 948 F.2d 1264, 1268, 20 USPQ2d 1746, 1749 (Fed. Cir. 1991) (The court went on to explain that “this modest flexibility in the rule that 'anticipation' requires that every element of the claims appear in a single reference accommodates situations in which the common knowledge of technologists is not recorded in the reference; that is, where technological facts are known to those in the field of the invention, albeit not known to judges.” 948 F.2d at 1268, 20 USPQ at 1749-50.). Note that the critical date of extrinsic evidence showing a universal fact need not antedate the filing date. See MPEP §2124.
Regarding claim 1, Maeda teaches an engineered cell (a freshwater purple bacterium) comprising a DNA molecule having a regulatory element (promoter Pars) responsive to a target input (arsenic), wherein the promoter is operatively linked to a DNA sequence encoding a signaling protein (phytoene desaturase CrtI), wherein the cell produces a detectable signal in response to the target input by producing the signaling protein, and wherein the detectable signal features a unique hyperspectral signature (claims 1-9).
Regarding claim 2, Maeda teaches that the cell is a bacterium (claims 1-9), and optionally Rubrivivax gelatinosus (paragraph [0017]).
Regarding claim 5, Maeda teaches that the promoter is an inducible promoter (claims 1, 5-6, 8-9).
Regarding claim 6, Maeda teaches that activation of expression of CrtI in response to arsenic results in production of red lycopene from colorless phytoene, wherein red lycopene produces a unique hyperspectral signature (paragraph [0010]; claim 6).
Regarding claim 7, Maeda teaches that the signaling protein is an enzyme (phytoene desaturase, CrtI), which catalyzes the production of a metabolite (red lycopene) which produces a unique hyperspectral signature, and wherein the metabolite is produced from a substrate that is naturally occurring in the cell (phytoene) (paragraph [0010]; claim 6).
Regarding claim 17, Maeda teaches that the target input is a toxin (arsenic) (claims 5-6, 8).
Regarding claim 19, Maeda teaches that the cell comprises one sensor plasmid (transducer) (paragraph [0043]).
Regarding claims 55-56, Maeda teaches an engineered cell (bacterial cell) comprising a DNA molecule having a regulatory element (promoter Pars) responsive to a target input (arsenic), wherein the regulatory element is operatively linked to a DNA sequence encoding a signaling protein (CrtI, arsR, see Fig. 4), wherein the cell produces a detectable signal in response to the target input by producing the signaling protein (claims 1-9). The signaling protein CrtI is an enzyme which produces a physiological response; this physiological response consists of the production of carotenoids in the spirilloxanthin pathway, which produce a detectable signal (paragraph [0017]; claim 6).
Claim(s) 1-2, 5-7, 10, 17-18, 55-56, 60 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Contag (WO1997040381A1, provided with IDS filed 05/23/2025).
Regarding claim 1, Contag teaches a hyperspectral reporter (a biodetector) comprising an engineered cell (e.g., a Salmonella cell, Fig. 5; page 13 lines 14-22) comprising an extracellular receptor which selectively recognizes a target input (ligand), a transducer which is activated by the ligand-bound receptor, and a responsive element which produces a detectable signal after activation by the activated transducer (claim 1; Figs. 1-2, 4). Fig. 4 shows that the “responsive element” can be a promoter region; on activation by the active transducer, luciferase is expressed, producing bioluminescence (a detectable signal with a unique hyperspectral signature). This responsive element, or regulatory element, is indirectly responsive to the target input (the target input does not directly bind to or interact with the regulatory element, but the target input binds to elements upstream in the created pathway, which activate the regulatory element). The components are introduced to the cell encoded in DNA molecules (pages 24-25).
Regarding claim 2, Contag teaches that the engineered cell is a bacterium (page 13 lines 14-22).
Regarding claim 5, Contag teaches that the regulatory element can be an inducible promoter (see Fig. 4; page 9 lines 25-26).
Regarding claim 6, Contag teaches that the expression of the signaling protein (luciferase) produces a unique hyperspectral signature (Fig. 4).
Regarding claim 7, Contag teaches that the signaling protein luciferase is an enzyme that catalyzes the production of a metabolite producing a unique hyperspectral signature from a substrate (page 17 lines 20-33).
Regarding claim 10, Contag teaches that the cell expresses a receptor capable of recognizing the target input (Fig. 4).
Regarding claim 17, Contag teaches that the target input can be bacteria, fungus, virus, pollutants, or toxins (pages 22-24).
Regarding claim 18, Contag teaches that the cell comprises 1 unique transducer (Fig. 4).
Regarding claims 55-56, Contag teaches an engineered cell comprising a DNA molecule comprising a regulatory element responsive to a target input (a ligand), wherein the regulatory element is operatively linked to a DNA sequence encoding a signaling protein (luciferase), wherein the cell produces a detectable signal in response to the target input by producing the signaling protein, wherein the signal is a unique hyperspectral signature, and wherein the target input also produces a physiological response (the target input triggers the activation of a transducer molecule, such as PO4, which in turn binds to and activates a promoter, which drives expression of the luciferase operon, see Fig. 4). Contag teaches that the physiological response is induced by an enzyme expressed as a result of the target input (luciferase is expressed as a result of the presence of the target input), wherein the physiological response produces additional substrates used to produce the detectable signal (proteins A, B, C, D< and E of the luciferase operon, which interact with the luciferase to produce bioluminescence) (Fig. 4).
Regarding claim 60, Contag teaches that expression of the signal protein and activation of the inducible promoter triggers a physiological response which makes the cell responsive to a second target input (chloramphenicol: Fig.4 shows that activation of the inducible promoter downstream of the first target input triggers expression of a lambda repressor, which represses expression of Chl, the chloramphenicol resistance gene, rendering the cell sensitive to chloramphenicol).
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.
Claim(s) 1-2, 5-7, 13, 17, 19, 55-56 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Maeda (JP2009159862A, English machine translation provided, obtained from J-PlatPat OPD machine translation function), as evidenced by Suyama (1999).
Regarding claim 1, Maeda teaches an engineered cell (a freshwater purple bacterium) comprising a DNA molecule having a regulatory element (promoter Pars) responsive to a target input (arsenic), wherein the promoter is operatively linked to a DNA sequence encoding a signaling protein (phytoene desaturase CrtI), wherein the cell produces a detectable signal in response to the target input by producing the signaling protein, and wherein the detectable signal features a unique hyperspectral signature (claims 1-9).
Regarding claim 2, Maeda teaches that the cell is a bacterium (claims 1-9), and optionally Rubrivivax gelatinosus (paragraph [0017]).
Regarding claim 5, Maeda teaches that the promoter is an inducible promoter (claims 1, 5-6, 8-9).
Regarding claim 6, Maeda teaches that activation of expression of CrtI in response to arsenic results in production of red lycopene from colorless phytoene, wherein red lycopene produces a unique hyperspectral signature (paragraph [0010]; claim 6).
Regarding claim 7, Maeda teaches that the signaling protein is an enzyme (phytoene desaturase, CrtI), which catalyzes the production of a metabolite (red lycopene) which produces a unique hyperspectral signature, and wherein the metabolite is produced from a substrate that is naturally occurring in the cell (phytoene) (paragraph [0010]; claim 6).
Regarding claim 13, Maeda teaches that the detectable unique hyperspectral signal produced by the engineered cell is produced by the combined hyperspectral signatures produced by bacteriochlorophyll (paragraphs [0010], [0017], [0026], [0027]) and the carotenoids lycopene, dehydrorhodopin, anhydrorhodovibrin, rhodovibrin, hydroxyspirilloxanthin, and spirilloxanthin (paragraph [0010]; Fig. 1). As the bacteriochlorophyll synthesis pathway is endogenous (Maeda teaches that the freshwater purple bacterium “has a spirilloxanthin pathway and a bacteriochlorophyll synthesis pathway”, paragraph [0017]), the bacteriochlorophyll produced by Rubrivivax gelatinosus is bacteriochlorophyll a (Suyama, page 49). It would have been obvious to an artisan, based on the information provided by Maeda and Suyama regarding the spirilloxanthin synthesis pathway and bacteriochlorophyll a synthesis pathway, that the reporter cell of Maeda could be modified such that the Bchl gene was placed under the control of the inducible promoter, instead of the Crtl gene. In such a modified cell, the unique hyperspectral signature produced by the products of the endogenous spirilloxanthin pathway would be constant (whereas the cell as described by Maeda constantly produces the hyperspectral signature of bacteriochlorophyll a), and the unique hyperspectral signature of the endogenously-synthesized bacteriochlorophyll a would be produced in the presence of a target input (whereas the cell as described by Maeda produces the hyperspectral signature of spirilloxanthin synthesis pathway products in response to the presence of a target input).
Regarding claim 17, Maeda teaches that the target input is a toxin (arsenic) (claims 5-6, 8).
Regarding claim 19, Maeda teaches that the cell comprises one sensor plasmid (transducer) (paragraph [0043]).
Regarding claims 55-56, Maeda teaches an engineered cell (bacterial cell) comprising a DNA molecule having a regulatory element (promoter Pars) responsive to a target input (arsenic), wherein the regulatory element is operatively linked to a DNA sequence encoding a signaling protein (CrtI, arsR, see Fig. 4), wherein the cell produces a detectable signal in response to the target input by producing the signaling protein (claims 1-9). The signaling protein CrtI is an enzyme which produces a physiological response; this physiological response consists of the production of carotenoids in the spirilloxanthin pathway, which produce a detectable signal (paragraph [0017]; claim 6).
Claim(s) 1-2, 5-7, 10, 17-18, 53, 55-56, 60 is/are rejected under 35 U.S.C. 103 as being unpatentable over Contag (WO1997040381A1).
Regarding claim 1, Contag teaches a hyperspectral reporter (a biodetector) comprising an engineered cell (e.g., a Salmonella cell, Fig. 5; page 13 lines 14-22) comprising an extracellular receptor which selectively recognizes a target input (ligand), a transducer which is activated by the ligand-bound receptor, and a responsive element which produces a detectable signal after activation by the activated transducer (claim 1; Figs. 1-2, 4). Fig. 4 shows that the “responsive element” can be a promoter region; on activation by the active transducer, luciferase is expressed, producing bioluminescence (a detectable signal with a unique hyperspectral signature). This responsive element, or regulatory element, is indirectly responsive to the target input (the target input does not directly bind to or interact with the regulatory element, but the target input binds to elements upstream in the created pathway, which activate the regulatory element). The components are introduced to the cell encoded in DNA molecules (pages 24-25).
Regarding claim 2, Contag teaches that the engineered cell is a bacterium (page 13 lines 14-22).
Regarding claim 5, Contag teaches that the regulatory element can be an inducible promoter (see Fig. 4; page 9 lines 25-26).
Regarding claim 6, Contag teaches that the expression of the signaling protein (luciferase) produces a unique hyperspectral signature (Fig. 4).
Regarding claim 7, Contag teaches that the signaling protein luciferase is an enzyme that catalyzes the production of a metabolite producing a unique hyperspectral signature from a substrate (page 17 lines 20-33).
Regarding claim 10, Contag teaches that the cell expresses a receptor capable of recognizing the target input (Fig. 4).
Regarding claim 17, Contag teaches that the target input can be bacteria, fungus, virus, pollutants, or toxins (pages 22-24).
Regarding claim 18, Contag teaches that the cell comprises 1 unique transducer (Fig. 4).
Regarding claim 53, Contag teaches an engineered reporter cell comprising a signaling molecule (a receptor which binds a target ligand and triggers a signaling cascade, see Fig. 4). The expression of this protein is required for the downstream production of a detectable signal (thus the cell produces a detectable signal by producing the signaling protein). As the signaling protein is a receptor which binds to the target input, as shown in Fig. 4, an artisan would interpret that a constitutive promoter would be optimal for driving expression of the receptor, as this would allow the cell to always be able to sense the target input.
Regarding claims 55-56, Contag teaches an engineered cell comprising a DNA molecule comprising a regulatory element responsive to a target input (a ligand), wherein the regulatory element is operatively linked to a DNA sequence encoding a signaling protein (luciferase), wherein the cell produces a detectable signal in response to the target input by producing the signaling protein, wherein the signal is a unique hyperspectral signature, and wherein the target input also produces a physiological response (the target input triggers the activation of a transducer molecule, such as PO4, which in turn binds to and activates a promoter, which drives expression of the luciferase operon, see Fig. 4). Contag teaches that the physiological response is induced by an enzyme expressed as a result of the target input (luciferase is expressed as a result of the presence of the target input), wherein the physiological response produces additional substrates used to produce the detectable signal (proteins A, B, C, D< and E of the luciferase operon, which interact with the luciferase to produce bioluminescence) (Fig. 4).
Regarding claim 60, Contag teaches that expression of the signal protein and activation of the inducible promoter triggers a physiological response which makes the cell responsive to a second target input (chloramphenicol: Fig.4 shows that activation of the inducible promoter downstream of the first target input triggers expression of a lambda repressor, which represses expression of Chl, the chloramphenicol resistance gene, rendering the cell sensitive to chloramphenicol).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFRICA M MCLEOD whose telephone number is (703)756-1907. The examiner can normally be reached Mon-Fri 9:00AM-6:00PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached on (571) 272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
For those applications where applicant wishes to communicate with the examiner via Internet communications, e.g., email or video conferencing tools, the following is a sample authorization form which may be used by applicant:
"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."
To facilitate processing of the internet communication authorization or withdraw of authorization, the Office strongly encourages use of Form PTO/SB/439, available at www.uspto.gov/patent/patents-forms. The form may be filed via EFS-Web using the document description Internet Communications Authorized or Internet Communications Authorization Withdrawn to facilitate processing. See MPEP 502.03(II).
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/RAM R SHUKLA/ Supervisory Patent Examiner, Art Unit 1635