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 .
DETAILED ACTION
Status of the Application
1. Claims 1-10 are pending and considered for examination.
Priority
2. This application filed on May 16, 2023 is a 371 of PCT/CN2021/118280 which claims foreign priority benefit to CN202011278709X filed on November 16, 2020.
Objection to the Specification
3. The disclosure is objected to because of the following informalities:
The use of the term (fluorophores, page 8, line 6-11), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The fluorophores are not followed by generic names. Appropriate correction is required.
Claim Rejections - 35 USC § 112
4. 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 4-6 and 8 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 4-6 and 8 recite ‘preferably’. The limitations followed by preferably are unclear and indefinite because it is not clear if the limitations followed by preferably are required limitations or do, they refer to an example or a preferred limitation.
Claim Rejections - 35 USC § 102
5. 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.
Claims 1-4, 6 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Teng et al. (Genome Biology, Vol. 20, 132, page 1-7, (2019), published online July 2019).
Teng et al. teach a method for detecting a target nucleic acid in a sample: comprising reacting the sample with a mixed reaction system consisting of a sgRNA-Cas system and isothermal amplification system and detecting a detectable signal generated by the reaction after the reaction is completed; wherein the sgRNA-Cas system comprises a Cas12b protein and sgRNA targeting the target nucleic acid and the isothermal amplification system comprises a primer and a single-stranded DNA reporter molecule that generates a detectable signal after being cleaved (page 4-6, paragraphs under the subheading ‘Methods’ and page 4, paragraph 1 right-hand side column and table S1-S2).
With reference to claim 2-4, Teng et al. teach that the concentration of sgRNA is 2-80ng/ ul; primer concentration is 300-1200 nM and the DNA reporter concentration is 200-2000 nM (page 6, paragraph under subheading ‘fluorescence quencher (FQ)-labeled reporter assays).
With reference to claim 6, Teng et al. teach that the reaction system further comprises a divalent cation at a concentration of 8-25 mM, wherein the divalent cation is magnesium ion (page 6, paragraph under the subheading ‘fluorescence quencher (FQ)-labeled reporter assays comprising NEBuffer and table S2 comprises a magnesium ion).
With reference to claim 10, Teng et al. teach that the sample is a whole blood, plasma, (page 6, paragraphs under subheading ‘nucleic acid preparation and page 4, paragraph 1 right-hand side column: indicating human plasma sample). For all the above the claims are anticipated.
Claim Rejections - 35 USC § 103
6. 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.
A. Claims 1-6 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (ACS Synth. Biol., Vol.8, 2228-2237, (2019 (published online September, 2019)).
Li et al. teach a method of claim 1, for detecting a target nucleic acid in a sample: comprising reacting the sample with a mixed reaction system consisting of a sgRNA-Cas system and isothermal amplification system and detecting a detectable signal generated by the reaction after the reaction is completed; wherein the sgRNA-Cas system comprises a Cas12b protein and sgRNA targeting the target nucleic acid and the isothermal amplification system comprises a primer and a single-stranded DNA reporter molecule (labeled probe) that generates a detectable signal after being cleaved (page 2236, paragraphs under the subheading ‘One-step HOLMESv2’).
With reference to claim 2-4, Li et al. teach that the concentration of sgRNA is 2-80ng/ul; primer concentration is 300-1200 nM and the DNA reporter concentration is 200-2000 nM (page 2236, paragraphs under the subheading ‘One-step HOLMESv2’).
With reference to claim 5, Li et al. teach that the reaction is performed at a first temperature and inactivated at a second temperature and the second temperature is greater than the first temperature, or greater than 460 C (page 2235, paragraph 2 under subheading ‘HOLMESv2 method’).
With reference to claim 6, Li et al. teach that the reaction system further comprises a divalent cation at a concentration of 8-25 mM, wherein the divalent cation is magnesium ion (page 2236, paragraphs under the subheading ‘One-step HOLMESv2’: indicating WarmStart LAMP kit which comprises magnesium ion).
With reference to claim 10, Li et al. teach that the sample is a urine sample (page 2236, paragraph under the subheading ‘detection of urine spike-ins of target DNA or target RNA with HOLMESv2).
Although Li et al. teach that the method can be conveniently coupled with any nucleic acid amplification method, including the isothermal LAMP or recombinase polymerase amplification to improve the detection sensitivity (page 2234, paragraph 4 on the righthand side column), however Li et al. did not specifically teach recombinase -aid isothermal amplification.
It would have been prima facie obvious to one skilled in the art before the effective filing date of the invention to modify the method of Li et al. with recombinase-aid amplification to develop an improved method for detecting a target nucleic acid. The ordinary person skilled in the art would have motivated to combine the method of Li et al. with recombinase polymerase amplification and have a reasonable expectation of success that the combination would improve detection of a target nucleic acid in a sample because Li et al. explicitly taught that the isothermal amplification is conveniently applicable to LAMP or recombinase polymerase amplification to improve the sensitivity of the detection (page 2234, paragraph 4 on the righthand side column) and such a modification of the method is considered obvious over the cited prior art.
B. Claims 1-8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (ACS Synth. Biol., Vol.8, 2228-2237, (2019 (published online September, 2019)) in view of Nautiyal et al. (J Antimicrob Chemother, Vol. 69, page 1834-1843, (2014)).
Li et al. teach a method for detecting a target nucleic acid in a sample as discussed above in section 6A. However, Li et al. did not teach suramin in the reaction mixture.
Nautiyal et al. teach a method for recombinase protein (recA protein) mediated process and use of suramin, an antimicrobial agent in said process, wherein suramin is added to the reaction mixture comprising recA protein, wherein the concentration of suramin is 3-30 ng/ul (page 1835-1836, paragraphs under ‘materials and methods’ section).
It would have been prima facie obvious to one skilled in the art before the effective filing date of the invention to modify the method of Li et al. with suramin as taught by Nautiyal et al. to develop a sensitive method for detecting a target nucleic acid. The ordinary person skilled in the art would have motivated to combine the method of Li et al. with suramin as taught by Nautiyal et al. and have a reasonable expectation of success that the combination would improve the sensitivity of detecting a target nucleic acid in a sample because Nautiyal et al. explicitly taught suramin in recA (recombinase) protein mediated process that would bind to the recA protein and reduces secondary structure of the peptide backbone of recA and antibacterial activity of suramin improves the sensitivity of the target detection (page 1842, paragraphs under conclusion section; page 1839, line 1-12 on the right-hand side column)) and such a modification of the method is considered obvious over the cited prior art.
C. Claims 1-7 and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (ACS Synth. Biol., Vol.8, 2228-2237, (2019 (published online September, 2019)) in view of Kober et al. (Biosensors and Bioelectronics, Vol. 100, p. 49-55, (2018).
Li et al. teach a method for detecting a target nucleic acid in a sample as discussed above in section 6A. However, Li et al. did not teach suramin in the reaction mixture.
Kober et al. teach a method for heterogeneous asymmetric RPA wherein method comprises tRNA in RPA reaction, wherein the concentration of tRNA is 10-20 ng/ul (page 52, paragraph under ‘heterogeneous asymmetric RPA (haRPA) on the MCR 3’ subheading).
It would have been prima facie obvious to one skilled in the art before the effective filing date of the invention to modify the method of Li et al. with tRNA as taught by Kober et al. to develop a sensitive method for detecting a target nucleic acid. The ordinary person skilled in the art would have motivated to combine the method of Li et al. with tRNA as taught by Kober et al. and have a reasonable expectation of success that the combination would improve the sensitivity of detecting a target nucleic acid in a sample because Kober et al. explicitly taught RPA reaction comprising tRNA that would increase the yield of the amplification product (page 53, paragraph under section 2.5) and such a modification of the method is considered obvious over the cited prior art.
Conclusion
No claims are allowable.
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/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681
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