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 .
Claim Status
The preliminary amendment filed September 01, 2023 has been entered. Claims 8-10 are new. Thus, claims 1-10 as amended are examined on the merits herein.
Claim Interpretation
Claim 1, line 3, recites the phrase “naked” when referring to the nucleic acids contained within the liquid recited in line 3 of claim 1. The Specification does not clearly define the term “naked” when referring to the term “nucleic acid”. Nor does the Examiner find anything in the Specification that would limit the term “naked” when referring to “nucleic acid”.
Therefore, the Examiner will reasonably interpret the meaning of the word “naked” when referring to “nucleic acid” to mean the nucleic acid itself (e.g. the nucleic acid on its own) which is not protected or packaged by or within other molecules.
Thus, the Examiner reasonably interprets the meaning as discussed above for the term “naked” when referring to “nucleic acid” to be the broadest reasonable interpretation.
Claim Objections
Claims 1-2 and 4 are objected to because of the following informalities:
(I) Claim 1, line 4, recites “a volume ratio of 1:(1-11)” when referring to the liquid and the alkali metal salt solution;
Claim 1, line 9, recites “a volume ratio of (1-4.4):1” when referring to the isopropanol and the supernatant;
Claim 1, line 15, recites “a volume ratio of (1-4.4):1” when referring to the isopropanol and the supernatant;
Claim 1, line 16, recites “equivalent to (0.0714-0.1348)” when referring to the added distilled water”;
Claim 1, line 22, recites “a volume ratio of (1.5-1.76):1” when referring to the isopropanol and the supernatant; and
Claim 1, pg. 4 of 6; lines 8-9, recites “the ratio of the supernatant to distilled water is 1:(0.125-0.1705)”, the Examiner respectfully notes and reasonably interprets in each instance as discussed above that the recitation within the parentheses is optional and thus not required by the claim. Thus, to promote clarity the Examiner suggests deleting the parentheses within each line of claim 1 as discussed above.
(II) Claim 1, line 9, recites “RT” which is an uncommon abbreviation. Thus, to promote clarity the Examiner suggests inserting the phrase “(RT)” immediately after the phrase “room temperature” in lines 4-5 of claim 1.
(III) Claim 1, line 5, recites “pouring the supernatant into a new centrifuge tube” which is clearly missing the conjunction “and” immediately before the word “pouring”. Thus, to promote clarity the Examiner suggests inserting the word “and” immediately before the word “pouring” as discussed above.
(IV) Claim 2, line 2, recites “is prepared by following” which is clearly missing the article “the” immediately before the word “following”. Thus, to promote clarity the Examiner suggests inserting the word “the” immediately before the word “following” as discussed above.
(V) Claim 2, line 4, recites “to obtain a liquid containing naked nucleic acid” which the Examiner respectfully notes is the second recitation of this limitation as claim 2 depends from claim 1. Additionally, claim 1, line 3, already recites “a liquid containing naked nucleic acids”. Thus, to promote clarity the Examiner suggests replacing the word “a” recited immediately before “liquid” with the word “the”.
(VI) Claim 4, line 2, recites “an aqueous solution of alkali metal salts” which is the second recitation of this limitation as claim 4 depends on claim 2; and wherein the Examiner respectfully notes that claim 2, line 6, already recites “an aqueous solution of alkali metal salts”. Thus, to promote clarity the Examiner suggests replacing the word “an” recited immediately before “aqueous” with the word “the”.
(VII) Claim 4, lines 3-4, recite “a compound for removing cellular secondary metabolites” which is the second recitation of this limitation as claim 4 depends on claim 2; and wherein the Examiner respectfully notes that claim 2, lines 6-7, already recite “a compound for removing cellular secondary metabolites”. Thus, to promote clarity the Examiner suggests replacing the word “a” recited immediately before “compound” with the word “the”.
Appropriate correction is required.
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 7 and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 7, line 2, and Claim 10, line 2, each recite the phrase “wherein the compound that removes secondary metabolites of cells comprises at least one of casein, polyvinylpyrrolidone 40 and cetyltrimethylammonium bromide”.
However, the Examiner respectfully notes that there are two reasonable interpretations for this limitation:
(a) the compound is casein, polyvinylpyrrolidone 40 or cetyltrimethylammonium bromide; or
(b) given the recitation of “comprises at least one of” preceding the Markush group is reasonably interpreted by the Examiner to mean that the compound includes at least one of casein, polyvinylpyrrolidone 40 or cetyltrimethylammonium bromide as a component within the compound.
Therefore, it’s unclear and indefinite if (a) the compound is casein, polyvinylpyrrolidone 40 or cetyltrimethylammonium bromide; or (b) includes a component within the compound which is casein, polyvinylpyrrolidone 40 or cetyltrimethylammonium bromide.
Thus, in the interest of compact prosecution the Examiner will interpret that the compound that removes secondary metabolites of cells is either casein, polyvinylpyrrolidone 40 or cetyltrimethylammonium bromide.
Finally, the Examiner respectfully notes that the recitation of “comprising at least one of” that refers to the compound that removes secondary metabolites of cells seems to improperly refer to the Markush group in claim 7 and claim 10 as discussed above.
Claim Rejections - 35 USC § 103
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.
Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (Published 23 April 2015, US-20150112054-A1, PTO-892) in view of Goldrick et al. (Published 06 June 1995, US-5422241-A, PTO-892) and Callahan et al. (Published 31 October 2019, WO-2019209600-A1, PTO-892).
Regarding claims 1-10, Yang teaches a method for extracting, isolating and purifying RNA (e.g. the solid nucleic acids, required in claim 1, line 1) from mouse liver (e.g. the animal organ, required in claim 3), see pg. 5, right column, example 6 and pg. 6, left column, example 7.
Yang teaches the method includes the following steps:
(1) Add 2 mL formamide (e.g. the formamide, required in claim 2, line 5) and 200 mg of fresh mouse liver to the Downce homogenizer on ice and homogenize for 20 seconds (e.g. the homogenizing, required in claim 2, line 3), see paragraph [0085];
(2) Add 200 µL mouse liver formamide homogenate solution obtained from step (1) and 50 µL 5M NaCl (e.g. the aqueous solution of alkali metal salts with a concentration of 5M-14M, required in claim 2, line 6 and the alkali metal salt, required in claims 8-9), see paragraph [0085], pg. 6, left column, paragraph (2).
(3) Add 700 µL 3.57M NaCl, 1.14 M KCl aqueous solution which has a precipitation effect (e.g. the alkali metal salt solution with a precipitation effect, required in claim 1, lines 3-4 and the alkali metal salt required in claim 5) to the 200 µL product obtained in step (2); after vortex blending and centrifugation at 16000 g for 5 minutes at room temperature (e.g. centrifugation at room temperature, required in claim 1, lines 4-5), and pour this supernatant into another centrifuge tube (e.g. the centrifuge tube, required in claim 1, line 5), see paragraph [0085], pg. 6, left column, paragraph (3).
The Examiner notes that the ratio of 200 µL product obtained in step (2) and 700 µL 3.57M NaCl, 1.14 M KCl aqueous solution as taught by Yang in (3) above meets the volume ratio of 1: 1-11 as required in claim 1, line 4.
(4) Add 500 µL isopropanol to the supernatant; mix them; centrifuge at 16000 g for 5 minutes at room temperature; discard the upper phase liquid, the lower phase liquid and visible residual impurities between the upper and lower phase; thus the white RNA precipitate can be obtained (e.g. generating a white precipitate, required in claim 1, line 10), see paragraph [0085], pg. 6, left column, paragraph (4).
Yang teaches washing the white RNA precipitate using 1 mL aqueous ethanol solution with a volume percentage concentration of 70% (e.g. the ethanol water solution, required in claim 6, line 2), centrifuging at 16000 at room temperature for 10 seconds (e.g. the centrifuge step, required in claim 6, lines 2-3); discarding the washing liquid (e.g. pouring off the washing solution, required in claim 6, line 3), adding 1 mL aqueous ethanol solution with a volume percentage concentration of 95% to soak the RNA precipitate, centrifuge, discard the ethanol solution, and put the centrifuge tube on the filter paper to dry the RNA precipitate (e.g. air-drying, required in claim 6, line 4), see paragraph [0094].
The Examiner notes the teachings of step (4) and the washing step of Yang when combined meet the limitations of way 1 as recited in claim 1, lines 7-12.
Yang teaches extracting RNA through homogenization of the mouse liver using formamide and 5M NaCl aqueous solution at 4:1 in volume (e.g. the ratio of formamide to aqueous solution of alkali metal salts, required in claim 2, line 7-8 and claim 4, line 2), see paragraph [0107].
Although, Yang does not teach (a) the standing at room temperature for 1-30 minutes after adding the isopropanol, required in claims 1-10 and (b) casein, required in claims 2, 4, 7 and 10.
However, in the same field of endeavor of isolating nucleic acids from a sample, with respect to limitation (a), Goldrick teaches a method for the recovery of nucleic acids from a reaction mixture where an alcohol (ethanol or isopropanol) is used for the precipitation of the nucleic acids, see abstract.
Goldrick teaches the method will typically include a step of incubating the reaction mixtures at reduced temperature for an appropriate length of time (e.g., 5 to 60 minutes, particularly 15 minutes) to effect the quantitative precipitation of nucleic acid in the reaction mixture, see Col. 5, lines 40-46.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have added limitation (a) into the method of Yang as discussed above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to incubate the reaction mixtures for 5-60 minutes, particularly 15 minutes, in order effect the quantitative precipitation of nucleic acids in the reaction mixture as taught by Goldrick above. One of ordinary skill in the art would have had a reasonable expectation of success to have included limitation (a) into the method of Yang above, as both Yang and Goldrick are directed to the isolation and recovery of nucleic acids from reaction mixtures where isopropanol is used as the precipitating agent.
With respect to limitation (b), Callahan teaches DNA and RNA separation and/or isolation, see pg. 1, technical field, lines 1-2. Callahan teaches blocking agents that block or reduce the interaction between contaminants in a sample and biomolecules liberated during lysis and solubilization, wherein exemplary blocking agents include casein (e.g. the compound, required in claim 7 and 10). Callahan teaches such blocking agents are useful in blocking electrostatic interactions between particles in a sample having positively charged groups and DNA or RNA released from a sample. Such interactions, if not disrupted, can lead to significant decreases in biomolecule yields from the sample. See pg. 16, lines 20-29.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have added limitation (b) into the method of Yang as discussed above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to add casein as a blocking agent into the solution of formamide and 5M NaCl taught by Yang above in order to disrupt the electrostatic interactions between RNA and particles in the sample liberated during solubilization in order to minimize any significant decrease in biomolecule yields from the sample as taught by Callahan above; which is particularly important as Yang teaches extraction, isolation and purification of RNA from mouse liver samples as discussed above. One of ordinary skill in the art would have had a reasonable expectation of success to have included limitation (b) into the method of Yang above, as both Yang and Callahan are directed to the isolation and recovery of nucleic acids.
With respect to limitations (c) “the volume ratio of 1-4.4: 1” when referring to the ratio of isopropanol and the supernatant obtained in (1), as required in claim 1, lines 8-9; (d) the 16.27-162.8 mg of biomaterial and 1 mL of homogenization-dissociation reagent in proportion, required in claim 2, lines 2-3; and (e) the absolute ethanol, required in claim 6, line 4; the above limitations are all reasonably interpreted by the Examiner to be physical limitations that are well within the scope of the artisan by using the method of Yang as a starting point, and through routine experimentation and optimization by one of ordinary skill in the art, would arrive at the claimed limitations (c)-(e) above.
As Yang teaches using mouse liver (e.g. the biomaterial as discussed above); mixing it with formamide and 5M NaCl, in addition to casein as taught by Callahan, which the Examiner respectfully notes meets all structural limitations of the homogenization-dissociation reagent as discussed above; adding isopropanol to precipitate the RNA as taught by Yang; and wherein the RNA precipitate is soaked using a 95% ethanol aqueous solution before drying the RNA precipitate as taught by Yang above; therefore the Examiner respectfully notes that the combination of Yang and Callahan teach all structural limitations as recited in limitations (c)-(e) above, and thus the physical limitations recited in limitations (c)-(e) will be met.
Additionally, the Examiner respectfully notes that MPEP 2144.05(II)(A) states “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have included limitations (a)-(b) into the method of RNA extraction, isolation and purification as taught by Yang above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to have included limitation (a) into the method of Yang as discussed above in order to effect the quantitative precipitation of nucleic acids in the reaction mixture as taught by Goldrick above and to have included limitation (b) into the method of Yang as discussed above in order to minimize any significant decrease in biomolecule yields from the sample as taught by Callahan above. One of ordinary skill in the art would have had a reasonable expectation of success to have included limitations (a)-(b) into the method of Yang as discussed above, as Yang, Goldrick and Callahan are all drawn to methods of isolating and recovering nucleic acids as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
Conclusion
No claims are allowed in this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARET J CREWS whose telephone number is (571)270-0962. The examiner can normally be reached Monday-Friday: 9:00am-5:30pm EST.
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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691