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 .
Claims 1-2, 6-9, 11-17, 20-23, 32, and 34-35 are pending and examined on their merit herein.
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 8, 11, 12, 22 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 8, 11, 12, 22, are rejected as being indefinite for reciting “residues in parentheses” because there is no residue indicated in parenthesis in the recited Sequence Identifiers in the Sequence Listing.
Claims 8, 11, 12, 22 are also rejected as being indefinite for the recitation “may”. It is not clear whether the limitation following “may” is part of claim limitation or not.
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.
Claims 1-2, 6-7, 9, 13-15, 20-21, 23, 32, and 34-35 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Feng (CN 108486024 A, published on 2018-09-04).
Claim 1 is drawn to a recombinant microbial cell displaying on its surface a non-native protein capable of degrading an organophosphate, wherein the recombinant microbial cell has inhibited replication.
Regarding claim 1, Feng discloses recombinant Escherichia coli (bacterium) cells expressing an “OPH signal sensing module” which comprises an INPNC-OPH fusion protein for expressing on the cell surface (Section 2.1, e.g). OPH is organophosphate hydrolase (OPH), an efficient organic phosphorus degrading enzyme (Section “background technology”). Feng discloses the OPH-containing gene engineered bacteria lyophilized on the filter paper under sterile condition (Claim 9, e.g.). As understood by skilled artisan and defined by the instant Application (e.g., instant claim 2), lyophilization (or drying) is an effective means to inhibit bacterial replication. Therefore, instant claim 1 is anticipate by Feng.
Regarding claim 2, Feng discloses lyophilization. See above.
Regarding claims 6-7, Feng discloses the enzyme being OPH, a phosphate hydrolase (see above).
Regarding claim 9, Feng discloses the enzyme OPH linked to the signal peptide INPNC for expression in the cell surface (see above).
Regarding claim 13, Feng discloses controlling the expression of the OPH gene with a promoter, such as inducible tac promoter (Section 2.1, e.g.).
Regarding claims 14-15, Feng discloses the bacterium as E. coli (see above).
Claim 20 is drawn to a recombinant microbial cell engineered to be capable of expressing a non-native transcription factor that activates a non-native promoter in response to an organophosphate degradation product; wherein the non-native promoter is operatively linked to a nucleic acid encoding a reporter protein, wherein activity of the reporter protein can be detected.
Regarding claim 20, Feng discloses, as the signal generation module, engineered E. coli comprising 1) a LacZ gene (reads on the reporter protein), controlled by 2) pnpC promoter –which reads on the non-native promoter responsive promoter to organophosphate degradation product p-nitrophenol (pNP) by organophosphate hydrolase (OPH) which is in turn controlled by 3) pnpR transcription activator (which reads on the non-native transcription factor) (Section 2.2; see also for evidence regarding the pnpR-pnpC in Wang et al., Front Microbiol. 2017 Sep 14;8:1714). Feng discloses, PnpR protein, which combines with the PNP produced by the OPH module to sense organophosphorus pesticides, and stimulates the expression of β-galactosidase, and the catalytic signal indicates the molecule X-gal Decomposition produces a blue signal; PNP binds to the corresponding pnpC promoter to induce the expression of the downstream b-galactase gene, and decomposes X-gal to produce blue (Section 2.2).
Therefore, claim 20 is anticipated by Feng.
In claim 21, the alternative limitation is drawn to “or wherein the non-native transcription factor comprises any small molecule-responsive transcription factor”. Regarding claim 21, the above mentioned pnpR protein is responsive to PNP which is a small molecule.
Regarding claim 23, Feng discloses the plasmids (see above).
Regarding claim 32, Feng discloses the system (kit) “sensor-based system based on flora” comprising both modules described above in Sections 2.1 and 2.2, which reads on claim 32.
Regarding claim 34, Feng discloses the step of contacting the engineered E. coli containing the OPH protein with organophosphate compounds (Ops) such as paraoxon ethyl, ethyl parathion, etc., and the degradation of the Ops (Section 4, for example); or paraoxon ethyl from soil or apple samples (Experiment 4, e.g.).
Furthermore, regarding claim 35, Feng discloses the method of using the system comprising both modules, contacting with Ops and detecting the resulted blue signal. See relevant parts cited above, or additionally in Claims 1-9; Sections 2-4; and Experiment 4, or 5, and so on.
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.
Claims 8, 12, 16, 17, are rejected under 35 U.S.C. 103 as being unpatentable over Feng Feng (CN 108486024 A, 2018-09-04), in view of Tang (Tang, Xiangjiang, et al. "Cell surface display of organophosphorus hydrolase for sensitive spectrophotometric detection of p-nitrophenol substituted organophosphates." Enzyme and Microbial Technology 55 (2014): 107-112) with evidence from Genbank sequence P0A434.1 (sumitted by Applicant in IDS of 12/31/2024).
Claim 8 is drawn to the recombinant microbial cell of claim 1, wherein the protein comprises an amino acid sequence at least 75% identical to SEQ ID NO:1 or 3-5;
Claim 12 is drawn to the recombinant microbial cell of claim 1, wherein the protein comprises an amino acid sequence at least 75% identical to SEQ ID NO:2;
Claims 16-17 are drawn to the recombinant microbial cell of claim 1, wherein the cell is E. coli displaying an enzymatically active portion of parathion hydrolase from Pseudomonas diminuta on its surface; or wherein the cell displays an enzymatically active portion of the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2 on its surface.
Claim 1 and the teachings of Feng regarding the recombinant microbial cell of claim 1 are discussed above.
Although Feng teaches the E. coli cell surface displaying organophosphate hydrolase, including parathion hydrolase, Feng does not explicitly teach the amino acid sequence of the hydrolase, or specifically hydrolase with at least 75% identity with any of SEQ ID NO:1-5 or more specifically SEQ ID NO: 1 or 2.
Tang teaches cell surface display of organophosphorus hydrolase for sensitive spectrophotometric detection of p-nitrophenol substituted organophosphates (Title). Tang teaches organophosphorus hydrolase (EC 3.1.8.1, OPH) which was initially isolated from Pseudomonas diminuta MG in 1980s by way of citing Serdar (Bio/technology 7.11 (1989): 1151-1155) which has cloned Parathion hydrolase gene from Pseudomonas diminuta and also taught expression of the mature portion of the enzyme in Escherichia coli. Tang teaches construction of INP–OPH fusion with the OPH-coding opd. The sequence of the OPH cloned as Parathion hydrolase gene from Pseudomonas diminuta by Sedar et al is 100% identical to the instant SEQ ID NO: 1. See sequence alignment below between the instant SEQ ID NO: 1 and the Genbank sequence P0A434.1 from Sedar. Note that regarding the instant SEQ ID NO: 2, the instant SEQ ID NO: 1 is the enzymatically active portion of SEQ ID NO: 2 (mature portion).
Therefore, it would have been prima facie obvious and within the scope of ordinary skill in the art at the time of filing of the instant application, to have utilized the Pseudomonas diminuta parathion hydrolase of sequence P0A434.1, which is 100% identical to the instant SEQ ID NO: 1 and the enzymatically active portion of SEQ ID NO: 2, in the detection method and apparatus of Feng, thereby arriving at the instantly claimed invention. It is also likely that Feng has used the same OPH or something highly similar. The ordinary skilled artisan with have been motivated to do so given the teachings of Feng regarding the detection for toxic compounds such as parathion, and Tang’s teaching that OPH can catalyze the hydrolysis reaction of p-nitrophenol (PNP) substituted organophosphorus compounds (OPs) such as paraoxon, parathion, and the cell surface display of the OPH in recombinant E. coli cell for the sensitive detection system, as well as Feng’s optimization with the two-part system. The artisan would have reasonable expectation of success given the teachings and success of both Feng and Tang.
The claimed invention as a whole is prima facie obvious in view of the combined teachings of the prior art.
Alignment of instant Seq ID NO: 1 with Sequence P0A434.1
Score:734 bits(1895), Expect:0.0,
Method:Compositional matrix adjust.,
Identities:364/364(100%), Positives:364/364(100%), Gaps:0/364(0%)
Query 1 QTRRVVLKSAAAAGTLLGGLAGCASVAGSIGTGDRINTVRGPITISEAGFTLTHEHICGS 60
QTRRVVLKSAAAAGTLLGGLAGCASVAGSIGTGDRINTVRGPITISEAGFTLTHEHICGS
Sbjct 2 QTRRVVLKSAAAAGTLLGGLAGCASVAGSIGTGDRINTVRGPITISEAGFTLTHEHICGS 61
Query 61 SAGFLRAWPEFFGSRKALAEKAVRGLRRARAAGVRTIVDVSTFDIGRDVSLLAEVSRAAD 120
SAGFLRAWPEFFGSRKALAEKAVRGLRRARAAGVRTIVDVSTFDIGRDVSLLAEVSRAAD
Sbjct 62 SAGFLRAWPEFFGSRKALAEKAVRGLRRARAAGVRTIVDVSTFDIGRDVSLLAEVSRAAD 121
Query 121 VHIVAATGLWFDPPLSMRLRSVEELTQFFLREIQYGIEDTGIRAGIIKVATTGKATPFQE 180
VHIVAATGLWFDPPLSMRLRSVEELTQFFLREIQYGIEDTGIRAGIIKVATTGKATPFQE
Sbjct 122 VHIVAATGLWFDPPLSMRLRSVEELTQFFLREIQYGIEDTGIRAGIIKVATTGKATPFQE 181
Query 181 LVLKAAARASLATGVPVTTHTAASQRDGEQQAAIFESEGLSPSRVCIGHSDDTDDLSYLT 240
LVLKAAARASLATGVPVTTHTAASQRDGEQQAAIFESEGLSPSRVCIGHSDDTDDLSYLT
Sbjct 182 LVLKAAARASLATGVPVTTHTAASQRDGEQQAAIFESEGLSPSRVCIGHSDDTDDLSYLT 241
Query 241 ALAARGYLIGLDHIPHSAIGLEDNASASALLGIRSWQTRALLIKALIDQGYMKQILVSND 300
ALAARGYLIGLDHIPHSAIGLEDNASASALLGIRSWQTRALLIKALIDQGYMKQILVSND
Sbjct 242 ALAARGYLIGLDHIPHSAIGLEDNASASALLGIRSWQTRALLIKALIDQGYMKQILVSND 301
Query 301 WLFGFSSYVTNIMDVMDRVNPDGMAFIPLRVIPFLREKGVPQETLAGITVTNPARFLSPT 360
WLFGFSSYVTNIMDVMDRVNPDGMAFIPLRVIPFLREKGVPQETLAGITVTNPARFLSPT
Sbjct 302 WLFGFSSYVTNIMDVMDRVNPDGMAFIPLRVIPFLREKGVPQETLAGITVTNPARFLSPT 361
Query 361 LRAS 364
LRAS
Sbjct 362 LRAS 365
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Feng Feng (CN 108486024 A, 2018-09-04), as discussed above, and further in view of Cha (US9051586B2, 2015).
Claim 11 is drawn to the recombinant microbial cell of claim 9, wherein the domain comprises an amino acid sequence at least 75%, identical to the amino acid sequence of SEQ ID NO:6 or 7.
Claim 1 and 9 and the teachings of Feng regarding the recombinant microbial cell of claims 1 and 9 are discussed above.
While Feng teaches using the ice-nucleation protein signal peptide for the surface display of the OPH protein, Feng does not explicitly teach the sequence of the INP peptide.
Cha teaches expressing a recombinant enzyme in the Escherichia coli cell surface by fusing an ice nucleation protein sequence as a surface anchoring motif for secretion, and the ice nucleation protein having the sequence of SEQ ID NO: 5 The prior art INP signal peptide is 100% identical with the instant SEQ ID NO: 6 (See sequence alignment below).
Therefore, it would have been prima facie obvious and within the scope of ordinary skill in the art at the time of filing of the instant application, to have utilized the INP of Cha, which is 100% identical to the instant SEQ ID NO: 6, in the detection method and apparatus of Feng as the required INP, thereby arriving at the instantly claimed invention. The ordinary skilled artisan with have been motivated to do so given the teachings of Feng regarding the detection for toxic compounds such as parathion by surface displaying OPH enzymes via INP peptide, and Cha’s teaching of successful cell surface display in recombinant E. coli cell. The artisan would have reasonable expectation of success given the teachings and success of both Feng and Cha.
The claimed invention as a whole is prima facie obvious in view of the combined teachings of the prior art.
RESULT 1
US-13-817-468A-5
Sequence 5, US/13817468A
Patent No. 9051586
GENERAL INFORMATION
APPLICANT: POSTECH ACADEMY-INDUSTRY FOUNDATION
TITLE OF INVENTION: Method for converting and producing carbonate minerals from
TITLE OF INVENTION: carbon dioxide using recombinant biocatalyst
FILE REFERENCE: LPP20124765US
CURRENT APPLICATION NUMBER: US/13/817,468A
CURRENT FILING DATE: 2013-02-18
PRIOR APPLICATION NUMBER: PCT/KR2012/002816
PRIOR FILING DATE: 2012-04-13
PRIOR APPLICATION NUMBER: KR10-2012-0023429
PRIOR FILING DATE: 2012-03-07
PRIOR APPLICATION NUMBER: KR10-2011-0063729
PRIOR FILING DATE: 2011-06-29
NUMBER OF SEQ ID NOS: 25
SEQ ID NO 5
LENGTH: 462
TYPE: PRT
ORGANISM: Neisseria gonorrhoeae
FEATURE:
NAME/KEY: PEPTIDE
LOCATION: (1)..(462)
OTHER INFORMATION: carbonic anhydrase (cell surface expression)
Query Match 99.6%; Score 1188; Length 462;
Best Local Similarity 100.0%;
Matches 228; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MALDKALVLRTCANNMADHCGLIWPASGTVESRYWQSTRRHENGLVGLLWGAGTSAFLSV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MALDKALVLRTCANNMADHCGLIWPASGTVESRYWQSTRRHENGLVGLLWGAGTSAFLSV 60
Qy 61 HADARWIVCEVAVADIISLEEPGMVKFPRAEVVHVGDRISASHFISARQADPASTSTSTS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 HADARWIVCEVAVADIISLEEPGMVKFPRAEVVHVGDRISASHFISARQADPASTSTSTS 120
Qy 121 TSTLTPMPTAIPTPMPAVASVTLPVAEQARHEVFDVASVSAAAAPVNTLPVTTPQNLQTR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 TSTLTPMPTAIPTPMPAVASVTLPVAEQARHEVFDVASVSAAAAPVNTLPVTTPQNLQTR 180
Qy 181 SRLWDGKRYRQLVARTGENGVEADIPYYVNEDDDIVDKPDEDDDWIEV 228
||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SRLWDGKRYRQLVARTGENGVEADIPYYVNEDDDIVDKPDEDDDWIEV 228
Claims 21 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Feng Feng (CN 108486024 A, 2018-09-04), as discussed above, in view of Chong (ACS synthetic biology 5.11 (2016): 1290-1298).
Claims 21 and 22 are drawn to the recombinant microbial cell of claim 20, wherein the non-native transcription factor comprises DmpR, or variants thereof, or wherein the transcription factor comprises an amino acid sequence at least 75% identical to the amino acid sequence of SEQ ID NO: 8, or optionally modified with mutations Q10R/K117M.
Claim 20 and the teachings of Feng are discussed above.
While Feng teaches using a transcriptional regulatory factor in the biosensor system, Fang does not explicitly teach the sequence of SEQ ID NO: 8.
Chong also teaches whole-cell biosensors for detecting organophosphorus compounds (OP) that are neurotoxic chemicals that can be used as nerve agents (e.g., Sarin) or agricultural pesticides (e.g., parathion), comprising a sensing module and an OPH module. (Fig. 1). The sensing module comprises a dmpR under the control of weak constitutive promoter J23114. DmpR is activated by effector 4-nitrophenol that can be produced from hydrolysis of organophosphates (input) by organophosphorus hydrolase (OPH). (Fig. 1 and legend). Chong teaches the DmpR is from modified from the wild type DmpR from Pseudomonas sp. CF600, wherein the Q10R/K117M mutant is activated by 4-nitrophenol.
Although Chong does not list the sequence of the wild type DmpR from Pseudomonas sp. CF600, however, it is nonetheless the same as the instant SEQ ID NO: 8, as evidenced from the instant disclosure that SEQ ID NO: 8 is a modified version with mutations Q10R and K117M from Pseudomonas spp. CF600.
Therefore, it would have been prima facie obvious and within the scope of ordinary skill in the art at the time of filing of the instant application, to have utilized the DmpR or variants of Chong, which near 100% identical to the instant SEQ ID NO: 8 except the few amino acid substitutions, in the detection method and apparatus of Feng as the required a sensitive sensing module, thereby arriving at the instantly claimed invention. The ordinary skilled artisan with have been motivated to do so given the teachings of Feng and Chong regarding the detection for toxic compounds such as parathion by a system comprising the sensing module and the OPH module. The artisan would have reasonable expectation of success given the teachings and success of both Feng and Chong.
The claimed invention as a whole is prima facie obvious in view of the combined teachings of the prior art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WEIHUA FAN whose telephone number is (571)270-0398. The examiner can normally be reached Monday-Friday, 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad A Abraham can be reached at (571) 270-7058. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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WEIHUA . FAN
Primary Examiner
Art Unit 1663
/WEIHUA FAN/Primary Examiner, Art Unit 1663