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
Applicant’s amendment and remarks, filed on 9/19/2025, in which claims 3, 7, 9, and 10 were amended, claims 1, 2, 4-6, and 8 were cancelled, and claim 11 is newly added, is acknowledged.
Claims 3, 7, and 9-11 are pending, and are examined on the merits herein.
Priority
This application is a National Stage entry of PCT/CN2022/075964 filed on 2/11/2022 and claims priority to China foreign application CN202011547374.7 filed on 12/23/2020. A certified copy of the foreign priority document in Chinese has been received. No English translation has been received.
Information Disclosure Statement
The information disclosure statement (IDS) dated 9/19/2025 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits.
Rejections Withdrawn
Applicant’s amendment and arguments, dated 9/19/2025, with respect to the rejection of claims 8 and 10 as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or joint inventor regards as the invention, has been carefully considered, and is found persuasive. Claim 8 has been cancelled. Claim 10 has been amended to remove the “preferably” language. This rejection is withdrawn.
Applicant’s amendment and arguments, dated 9/19/2025, with respect to the rejection of claim 8 as being unpatentable over CN207567206 to Gao, in view of CN111548918 to Feng, and PG Pub No. US2013/0084606 in view of Sugimoto, has been carefully considered, and is found persuasive. Claim 8 has been cancelled. This rejection is withdrawn.
The following are modified/new grounds of rejections necessitated by applicant’s amendment.
Claim Rejections - 35 USC § 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.
Claims 7 and 9-11 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 is drawn to a method as suggested in the preamble reciting “method for separating a nucleic acid amplification.” Claim 7 further recites “a separating agent utilized as a separating layer to separate the nucleic acid amplification system in a same container; wherein the separating layer can be ruptured by applying a centrifugal force, so as to realize mixing of the nucleic acid amplification system.” The claim is indefinite because none of the limitations recite an active, positive step delimiting how the utilization is practiced. For purposes of compact prosecution, the claim is being interpreted as including an active step. Claims 9-11 are rejected for being dependent from a rejected base claim.
Response to Arguments
Applicant’s amendment and remarks, dated 9/19/2025, with respect to the rejection of claims 7-11, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention, has been carefully considered but is not found persuasive. Applicant argues that the term “applying an external force” is amended to “applying a centrifugal force” in claim 7, in which a person having ordinary skill in the art would know that “applying a centrifugal force” is able to realize mixing of the nucleic acid amplification system. This argument is not found persuasive. Although one of ordinary skill in the art would recognize that applying a centrifugal force would realize in mixing of the nucleic acid amplification system, the claim specifically recites “wherein the separating layer can be ruptured…” (emphasis added). Thus, contrary to Applicant’s argument, the claim does not necessarily require application of a centrifugal force, but rather, merely requires the separately layer to having the ability to, or property of, be ruptured.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
As set forth under 35 U.S.C. 112(d), a claim in dependent form shall contain (i) a reference to a claim previously set forth, and (ii) then specify a further limitation of the subject matter claimed. Claim 3 fails under this statute as it depends from a later claim, not “a claim previously set forth,” as required under 35 35 U.S.C. 112(d).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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 3 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over CN207567206 to Gao (IDS 2/6/2023; English translation attached on PTO-892 7/16/2025), in view of CN111548918 to Feng (IDS 2/6/2023; English translation attached as PTO-892 7/16/2025), PG Pub No. US2013/0084606 to Sugimoto (PTO-892 7/16/2025), Wax-Emulsions.com (PTO-892 7/16/2025), and “Paraffin Hydrocarbon” by Encyclopoedia Britannica (PTO-892 7/16/2025).
Gao teaches a reaction tube pre-stored with a freeze-dried reagent, which has a good sealing effect, and can effectively isolate the freeze-dried reagent from contact with air. The reaction tube pre-stored with freeze-dried reagents comprises a reaction tube body with a conical structure that is larger at the top and smaller at the bottom, the freeze-dried reagent is placed at the bottom of the inner cavity of the reaction tube, a low-melting point sealing paraffin layer is arranged above the freeze-dried reagent, and a coating is arranged at the edge of the reaction tube body (paragraph 0011). According to the melting point of the sealing paraffin used, which is 37-60 °C, the thickness of the sealing paraffin can be adjusted within the range of 0.5-5mm (paragraph 0012). Gao teaches adding the extracted sample to the surface of the sealing paraffin layer, and then centrifuge it instantaneously before testing on the machine (paragraph 0022). Before machine experiment, the nucleic acid extract is directly added to the surface of the paraffin layer, and after instantaneous centrifugation, the nucleic acid extract and the PCR freeze-dried reagent can be evenly mixed and tested on the machine, which is very convenient and practical (paragraph 0014).
The teachings of Gao differ from that of the instantly claimed invention in that Gao does not teach a sealing layer that comprises polyethylene wax, that the paraffin comprises liquid and solid paraffin, or the mass ratio of polyethylene wax to solid paraffin to liquid paraffin. Additionally, Gao differs from that of the instantly claimed invention in that Gao does not teach a molecular weight of polyethylene wax, or the number of carbon atoms for paraffin.
Feng teaches a fully enclosed integrated reaction tube capable of achieving multi-system compatibility, which is effective to prevent component evaporation and leakage of nucleic acid amplification products and avoid aerosol contamination. The reaction tube comprises a temperature-changing phase solid isolation layer located in the middle of the tube body, dividing the tube body into a first chamber and a second chamber (paragraph 0010). The temperature-change phase solid isolation layer is disclosed as including, but is not limited to, composite paraffin wax, rosin, polyethylene wax, palm wax, ozokerite, hot melt adhesive, and polyvinyl fluoride (paragraph 0018). The reaction tube is taught to have the beneficial effect that it is fully closed and completed under the cover of the temperature-changing phase solid isolation layer, no heating is required, and no additional sealing liquid is required, and can effectively prevent component evaporation and leakage of nucleic acid amplification products, avoid aerosol contamination, and effectively avoid contamination during nucleic acid amplification and detection (paragraph 0027).
Sugimoto teaches a composition for preventing evaporation of a nucleic acid amplification reaction solution during nucleic acid amplification reaction. The melting point of the composition is 0-15 °C. The composition may contain mineral oil, silicone oil, other chemically synthesized oil or a combination thereof (paragraph 0055). Mineral oil is disclosed as being a petroleum derived oil, and specific examples thereof include liquid paraffin and solid paraffin (paragraph 0056). Sugimoto teaches that in order for the composition to be a liquid during reaction and to become a solid through chemical changes after completion of the reaction, the constitution of components of the composition may be adjusted to give a melting point that is either at room temperature or below the reaction temperature, e.g. about 50 °C, and in addition a solidifying agent may be used (paragraph 0058). Specific examples of compositions whose melting point is either at room temperature or below the reaction temperature include liquid paraffin and mineral oil (paragraph 0059). Specific examples of the solidifying agent include a high melting point paraffin, such as a solid paraffin with a melting point of 44-46 °C (paragraph 0060). In order for the composition to be a liquid during reaction and to be a solid through thermal changes after completion of the reaction, the constitution of components of the composition may be adjusted to give a melting point of 0-15 °C (paragraph 0061). It is possible to give the composition a melting point of -10 to 40 °C by adding 5-15 mass percent of solid paraffin to liquid paraffin taken as unity.
Wax-Emulsions.com teaches that polyethylene waxes are basically low molecular weight polymers with a molecular weight that varies roughly between 300 and 10,000, and melting points starting at 90 °C, and going up to 140 °C (subheading “Properties,” paragraph 1).
Britannica teaches that paraffin hydrocarbons containing fewer than 5 carbon atoms are usually gaseous at room temperature, those having 5 to 15 caron atoms are usually liquids, and the straight-chain paraffins having more than 15 carbon atoms per molecule are solids.
Thus, it would have been prima facie obvious for one of ordinary skill in the art to combine the teachings of Gao, Feng, Sugimoto, Wax-Emulsions.com, and Britannica by modifying the sealing paraffin layer of Gao to include a combination of polyethyelene wax, liquid paraffin, and solid paraffin, as suggested from the teachings of Feng and Sugimoto, to arrive at the instantly claimed invention. One of ordinary skill in the art would have been motivated to make the combination with a reasonable expectation of success as both Feng and Sugimoto teach that polyethyelene wax and paraffin can be used to prevent component evaporation and leakage during nucleic acid amplification. Furthermore, one of ordinary skill in the art would have a reasonable expectation of success in combining polyethylene wax with liquid paraffin and solid paraffin as Sugimoto teaches that the melting point can be adjusted based on the combination of paraffins, and Feng teaches that the waxes are used as temperature change phase solids. One of ordinary skill in the art would have a reasonable expectation of success as all the cited references teach the use of the indicated components as sealants that are compatible for use with amplification reagents.
With regards to the mass ratio of polyethylene wax to solid paraffin to liquid paraffin, Sugimoto teaches the addition of 5-10% solid paraffin to liquid paraffin to achieve a melting point of -10 to 40 °C. Thus, absent any evidence to the contrary, it would have been prima facie obvious for one of ordinary skill in the art to optimize the amount of polyethylene wax, liquid paraffin, and solid paraffin, as Sugimoto teaches that the addition of different concentrations can adjust the melting point temperature of the composition.
With regards to the molecular weight of the polyethylene wax, it would have been prima facie obvious to use a polyethylene wax having a molecular weight of between 300 and 10,000, as taught by Wax-Emulsions.com, with a reasonable expectation of success, as these are recognized molecular weights of polyethylene wax. It is prima facie obvious to combine prior art elements according to known methods to yield predictable results. See MPEP 2143(I).
With regards to the number of carbons for solid and liquid paraffin, it would have been prima facie obvious to use paraffin having the indicated number of carbon atoms as taught by Britannica for liquid and/or solid paraffin, with a reasonable expectation of success, as these are recognized carbon atoms for liquid and solid paraffin. It is prima facie obvious to combine prior art elements according to known methods to yield predictable results. See MPEP 2143(I).
Claims 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over over CN207567206 to Gao (IDS 2/6/2023; English translation attached on PTO-892 7/16/2025), in view of CN111548918 to Feng (IDS 2/6/2023; English translation attached as PTO-892 7/16/2025), PG Pub No. US2013/0084606 to Sugimoto (PTO-892 7/16/2025), Wax-Emulsions.com (PTO-892 7/16/2025), and “Paraffin Hydrocarbon” by Encyclopoedia Britannica (PTO-892 7/16/2025), as applied to claim 7, further in view of “Procedure for PCR Amplification with PowerPlex® Fusion” by DNA Database Forensic Scientist Manager and Technical Leader (hereinafter “Procedure”; PTO-892 7/16/2025).
The combined teachings of Gao, Feng, Sugimoto, Wax-Emulsions.com, and Brittanica are as discussed above.
The combined teachings of Gao, Feng, Sugimoto, Wax-Emulsions.com, and Britannica differ from that of the instantly claimed invention in that the combined teachings of Gao, Feng, Sugimoto, Wax-Emulsions.com, and Britannica do not expressly teach a centrifugal force of not less than 5,000 g and centrifugation for 5 to 60 seconds.
The Procedure teaches amplification process that uses the Promega PowerPlex® Fusion kit. The process involves several centrifugation steps, including a 1-2 sec pulse spin in step 5.4.4, a 15 second vortex spin to bring contents to the bottom of the microcentrifuge at step 5.4.8, a 2000 rpm centrifuge to bring reagents to the bottom of the centrifuge and no bubbles are present in step 5.4.14.
Thus, it would have been prima facie obvious for one of ordinary skill in the art to combine the teachings of Gao, Feng, Sugimoto, Wax-Emulsions.com, and Britannica, with that of the Procedure to arrive at the instantly claimed invention. Since Gao expressly teaches centrifugation to combine the samples prior to testing on the machine, it would have been prima facie obvious for one of ordinary skill in the art to optimize the centrifugal force and time of centrifugation to optimally mix the components prior to testing. One of ordinary skill in the art would have a reasonable expectation of success since the Procedure teaches that various centrifugal forces and time periods of centrifugation are recognized in the art for different purposes. It is prima facie obvious to combine prior art elements according to known methods to yield predictable results. See MPEP 2143(I). Furthermore, it would have been prima facie obvious for one of ordinary skill in the art to optimize the centrifugation conditions since Gao teaches the purpose is to mix the components.
Response to Arguments
Applicant’s amendment and arguments, dated 9/19/2025, with respect to the rejection of claims 7 and 8 under 35 U.S.C. 103 as being unpatentable over Gao, in view of Feng and Sugimoto, and the rejection of claims 9 and 10 under 35 U.S.C. 103 as being unpatentable over Gao, Feng and Sugimoto, further in view of Procedure, has been carefully considered, but are moot in view of the modified grounds of rejection.
Insofar as applicant’s arguments are applicable to the modified grounds of rejections set forth above, applicant argues that because Gao does not teach a sealing layer that comprises polyethylene wax, or that the paraffin comprises liquid and solid paraffin, Gao cannot disclose the specific material composition of the separating agent of the separating layer in amended claim 7. This argument has been carefully considered, but is not persuasive. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The rejection relies on additional secondary references to cure the deficiencies of Gao.
Applicant further argues that although the Examiner relied on Feng and Sugimoto to cure the deficiencies of Gao, the references cannot be combined. With regards to Feng, applicant argues that Feng discloses a temperature-change phase solid isolation layer which mixing of the PCR reaction system is achieved through melting point, and the temperature-change phase solid isolation layer is not applied with centrifugal force. Therefore, Feng cannot teach the specific material composition of the separating agent of the separating layer that coordinates with the centrifugal action of Gao. Applicant’s argument has been carefully considered, but is not found persuasive. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by Applicant. See MPEP § 2144. Thus, there is no requirement that Feng must teach the use of centrifugal force in coordination with their temperature-change phase solid isolation layer since the use of centrifugal force was already disclosed by Gao. Feng was relied on in the rejection to render obvious the additional use of polyethylene wax in the paraffin layer. As set forth in the rejection above, it would have been obvious for one of ordinary skill in the art to further include polyethylene wax in the paraffin layer of Gao since Feng teaches that polyethylene wax can be used to prevent component evaporation and leaking during nucleic acid amplification. One of ordinary skill in the art would have a reasonable expectation of success because Feng teaches that their temperature-changing phase solid isolation layer is used to separate components in a nucleic acid amplification system, which corresponds to the same purpose as the sealing layer of Gao in protecting the freeze-dried reagents, but with the added benefit of preventing component evaporation during nucleic acid amplification.
With regards to Sugimoto, applicant argues that Sugimoto teaches that the material composition is adjusted to obtain the desired melting point, such that the composition may be maintained in a liquid state during the reaction and becomes a solid after the reaction. Thus, applicant argues that the purpose of adjusting the ratio of liquid paraffin to solid paraffin in Sugimoto is only to control the melting point, and nothing related to the centrifugal force is mentioned in Sugimoto. Therefore, Sugimoto cannot teach the specific material composition of the separating agent of the separating layer that coordinates with the centrifugal action of Gao. Applicant’s arguments have been carefully considered, but are not found persuasive. it is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by Applicant. See MPEP § 2144. Thus, there is no requirement that Sugimoto must teach the use of centrifugal force in coordination with their composition since the use of centrifugal force was already disclosed by Gao. Sugimoto was relied on in the rejection to render obvious the use of both liquid and solid paraffin in the disclosed paraffin composition of Gao. As set forth in the rejection above, it would have been prima facie obvious for one of ordinary skill in the art to use a combination of both liquid and solid paraffin in the sealing paraffin layer of Gao because Sugimoto teaches that the melting point can be adjusted based on the combination of paraffins. As Gao teaches the use of centrifugal force to mix the nucleic acid and PCR freeze-dried reagents, it would have been prima facie obvious to one of ordinary skill in the art that the sealing layer will be combined with the components in the amplification step, such that the melting point would be a consideration.
Furthermore, Applicant is requested to note that the test for obviousness is not that the claimed invention must be expressly taught or suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Furthermore, 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. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. As applicable to the combination of references, each of Gao, Feng, and Sugimoto are drawn to nucleic amplification systems, with Gao and Feng teaching the use of an isolating/separation layer.
The rejections are maintained, with modifications made to address applicant’s amendments.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SCARLETT Y GOON whose telephone number is (571)270-5241. The examiner can normally be reached M-F 9:00am - 5:00pm EST.
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/SCARLETT Y. GOON/
Supervisory Patent Examiner
Art Unit 1693