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 .
Priority
The instant application was filed 06/28/2024 and claims priority from provisional application 63511391 , filed 06/30/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/5/2025 is being considered by the examiner.
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 1-7, 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 1 recites, “A method of stabilizing fully functional nucleotides (ffNs), the method comprising: including the ffNs and at least one surfactant into lyophilized material.” The metes and bounds are unclear as the claims are to a method, however the claim provides no active step. Thus it is unclear what is required of the method.
Claim 2 depends from claim 1 and recites, “wherein a concentration of the ffNs is between about 10 µM and about 15,000 µM.” The metes and bounds are confusing and unclear as the independent claim requires a lyophilized material and thus suggests the absence of liquid. However, micromolar is a concentration per liter of fluid. Thus the metes and bounds are unclear how a material without liquid has a concentration in micromoles per liter.
Claim 3 recites, “herein a concentration of the at least one surfactant is between about 0.5% and about 2.5%.” The metes and bounds are unclear if “about 0.5% and about 2.5%” is volume per volume, weight per volume, weight per weight, etc.
Claim 4 recites, “wherein including the ffNs and the at least one surfactant into the lyophilized material comprises freeze-drying the ffNs.” The metes and bounds are unclear as the independent claim requires the material is lyophilized. It is unclear how claim 4 limits claim 1 which requires the material is lyophilized or freeze dried.
Claim 5 recites, “wherein the ffNs are encapsulated in a hydrophobic core of the surfactant, which inhibits or prevents hydrolysis of the ffNs.” The metes and bounds are unclear what inhibits or prevents hydrolysis of the ffNs is relative to. It is unclear if inhibits or prevents hydrolysis of the ffNs is relative to hydration, enzymatic assay, etc.
Claim 7 recites, “A method of stabilizing a fully functional nucleotides (ffNs), the method comprising: including the ffNs and at least one bulky cation compound into lyophilized material..” The metes and bounds are unclear as the claims are to a method, however the claim provides no active step. Thus it is unclear what is required of the method.
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
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.
Claim(s) 1-4 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brivio (Eleventh International Conference on Miniaturized Systems for Chemistry and Life Sciences 7 – 11 October 2007, Paris, FRANCE).
With regards to claim 1 and 7, Brivio teaches, “A premixed solution of all PCR reagents was introduced into the reaction chambers of three different polymer chips. After filling, the chips were stored overnight at –80 ºC and then transferred to a freeze-drier.” Brivio teaches PEG (Table 1) was part of the mixture.
While Brivio teaches all PCR reagents were premixed, Brivio does not teach dNTP.
However, Brivio teaches PCR was performed. (figure 4)
Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims “all PCR reagents” of the claims encompasses dNTP and PEG which were freeze dried. The artisan would be motivated as Brivio teaches the freeze dried reagents were resuspended and DNA was amplified. The artisan would have a reasonable expectation of success as the Brivio demonstrates it works.
The metes and bounds of claim 2 are unclear as they provide concentration per liter, but the claim requires the nucleotides are lyophilized or freeze dried.
Thus claim 2 is obvious over Brivio.
With regards to claim 3, Brivio teaches 1.5% or 0.5% PEG. (table 1)
With regards to claim 4, Brivio teaches, “A premixed solution of all PCR reagents was introduced into the reaction chambers of three different polymer chips. After filling, the chips were stored overnight at –80 ºC and then transferred to a freeze-drier.”
With regards to claim 6, Brivio teaches 1.5% or 0.5% PEG. (table 1)
Claim(s) 5, 7, is/are rejected under 35 U.S.C. 103 as being unpatentable over Brivio (Eleventh International Conference on Miniaturized Systems for Chemistry and Life Sciences 7 – 11 October 2007, Paris, FRANCE) as applied to claims 1-4 and 6 above, and further in view of Vincourt (Cryobiology 60 (2010) 262–270)
The teachings of Brivio are set forth above.
While Brivio teaches freeze drying of dNTP with a surfactant, Brivio does not specifically teach a bulky cation compound.
However, Vincourt teaches freeze drying of “soybean phosphatidylcholine (SPC), cholesterol (CHOL) and 1,2-dioleoyl oxypropyl-3-N,N,N-trimethylammonium chloride (DOTAP) in a 62.5/32.5/5 ratio, incorporating or not an ASGPr ligand” with ATP. (262, 1st column)
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to freeze dry nucleotides in soybean phosphatidylcholine (SPC), cholesterol (CHOL) and 1,2-dioleoyl oxypropyl-3-N,N,N-trimethylammonium chloride (DOTAP) in a 62.5/32.5/5 ratio. The artisan would have been motivated to freeze dry dNTPs in a protective liposomal to protect nucleotides. The artisan would have a reasonable expectation of success as the artisan is merely using art accepted methods.
Claim(s) 24is/are rejected under 35 U.S.C. 103 as being unpatentable over Brivio (Eleventh International Conference on Miniaturized Systems for Chemistry and Life Sciences 7 – 11 October 2007, Paris, FRANCE) as applied to claims 1-4 and 6 above, and further in view of Vincourt (Cryobiology 60 (2010) 262–270) as applied to claim 5 and 7 above, and further in view of Yang (Gene, 83 (1989) 347-354).
The teachings of Brivio and Vincourt are set forth above.
Brivio and Vincourt do not specifically teach diluting the sample.
Yang (Genes) teaches, “We began by essentially following the steps of the protocol of the GeneAmp DNA Amplification Reagent Kit from Perkin Elmer Cetus and then examined the effects of varying the concentrations of the 4 dNTPs or the PCR primers, the total volume of the reaction, the temperature, the time, etc., on the yield of product from -digested pHPT30. The results (not shown) indicated that the highest yield after 30 cycles of PCR was obtained using the 4 dNTPs at 400 PM each, PCR primers at 0.15 PM (1 ng/pl), 2.5 units of Tuq in a total volume of 50 ~1, denaturation at 94°C for 1 min, annealing at 50°C for 1 min, and polymerization at 72 “C for 2 min. Before the first cycle, the template was denatured at 94°C for 5 min and after the 30th cycle, the time for extension at 72 ’ C was 7 min. Therefore, these conditions were employed in subsequent experiments designed to optimize the conditions used for other reactions.” Thus Yang (genes) demonstrates concentrated reagents were known.
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to use concentrated dNTP and surfactant to allow for dilution of the nucleotides and surfactants from 10X to 200x. The artisan would be motivated to have stock solutions as taught by Yang(genes). The artisan would have a reasonable expectation of success as making stock solutions in molecular biology is well known.
Claim(s) 18-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang (US20200318177) and Yang (Gene, 83 (1989) 347-354).
Yang teaches, “[0001] The present invention pertains to a field of nucleic acid sequencing. Specifically, the present invention relates to a method for sequencing a nucleic acid by using an immersion reaction protocol, in which the immersion reaction protocol comprises sequentially immersing a solid support having nucleic acid molecules immobilized thereon in different reaction containers to realize nucleic acid sequencing.” Yang teaches, “[0064] In one embodiment, the immersion reaction protocol provided by the present invention further comprises: adding into the one or more reaction solutions in the step b), the regeneration solution in the step d) and/or the washing solution in the step e) an appropriate amount of a reagent for retaining the reaction solution and/or the washing solution remaining on the solid support thereon when the solid support is taken out from the reaction solution and/or the washing solution. Without being bound by any theory, it is believed that the addition of such reagent may help to avoid the drying caused by the separation of the reaction solution and/or the washing solution remaining on the solid support from the upper end of the solid support due to the gravity when the solid support is taken out from the reaction solution and/or the washing solution. As used herein, the upper end of the solid support refers to an end that is firstly exposed to air when the solid support is taken out from the solution. In a preferred embodiment, such an reagent may be, for example, a surfactant. Such surfactant may include, but is not limited to, Tween-20, stearic acid, lauric acid, sodium lauryl sulfate, sodium dioctyl succinate sulfonate (Aerosol-OT), sodium dodecylbenzenesulfonate, sodium glycocholate, benzalkonium chloride, benzalkonium bromide, lecithin, fatty glycerides and the like. It should be understood that the addition of such reagent, such as a surfactant, should not cause any adverse effects on the reaction solution and/or the washing solution, the solid supports, and the nucleic acid molecules carried on the solid supports, and should not cause a significant increase in the amount of reagents carried on the solid supports. In a preferred embodiment, an appropriate amount of Tween-20 is added to the one or more reaction solutions of the step b), the regeneration solution of the step d) and/or the washing solution of the step e). Such a reagent, for example, a surfactant, may be added in any effective amount capable of retaining the reaction solution and/or the washing solution remaining on the solid support thereon when the solid support is taken out from the reaction solution and/or the washing solution. It should be understood that such an amount should not cause any adverse effects on the reaction solution and/or the washing solution, the solid supports, and the nucleic acid molecules carried on the solid supports, and it should not cause any significant increase in the amount of reagents carried on the solid supports. The amount of such added reagent, such as a surfactant, can be, for example, at least about 0.001%, at least about 0.005%, at least about 0.01%, at least about 0.02%, at least about 0.03%, at least about 0.04%, at least about 0.05%, at least about 0.06%, at least about 0.07%, at least about 0.08%, at least about 0.09%, at least about 0.1%, at least about 0.2%, at least about 0.3%, at least about 0.4%, at least about 0.5%, at least about 0.6%, at least about 0.7%, at least about 0.8%, at least about 0.9%, at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, or more, based on the volume of the reaction solution and/or the washing solution. In a preferred embodiment, about 0.05% to 1% of Tween-20 (v/v) is added to the one or more reaction solutions of the step b), the regeneration solution of the step d) and/or the washing solution of the step e).” Paragraph 0108 teaches, “FIG. 4 shows the improvement of the drying of the upper end of the chip by adding a certain amount of surfactant to the polymerization reagent.”
Yang (Genes) teaches, “We began by essentially following the steps of the protocol of the GeneAmp DNA Amplification Reagent Kit from Perkin Elmer Cetus and then examined the effects of varying the concentrations of the 4 dNTPs or the PCR primers, the total volume of the reaction, the temperature, the time, etc., on the yield of product from -digested pHPT30. The results (not shown) indicated that the highest yield after 30 cycles of PCR was obtained using the 4 dNTPs at 400 PM each, PCR primers at 0.15 PM (1 ng/pl), 2.5 units of Tuq in a total volume of 50 ~1, denaturation at 94°C for 1 min, annealing at 50°C for 1 min, and polymerization at 72 “C for 2 min. Before the first cycle, the template was denatured at 94°C for 5 min and after the 30th cycle, the time for extension at 72 ’ C was 7 min. Therefore, these conditions were employed in subsequent experiments designed to optimize the conditions used for other reactions.” Thus Yang (genes) demonstrates concentrated reagents were known.
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to use concentrated dNTP and surfactant to allow for dilution of the nucleotides and surfactants from 10X to 100x. The artisan would be motivated to have stock solutions as taught by Yang(genes). The artisan would have a reasonable expectation of success as making stock solutions in molecular biology is well known.
With regards to claim 19, Yang (genes) teaches of 7.5 µM to 5 µM dNTP (349, 2nd column)
With regards to claims 21-22,Yang teaches, “[0064] The amount of such added reagent, such as a surfactant, can be, for example, at least about 0.001%, at least about 0.005%, at least about 0.01%, at least about 0.02%, at least about 0.03%, at least about 0.04%, at least about 0.05%, at least about 0.06%, at least about 0.07%, at least about 0.08%, at least about 0.09%, at least about 0.1%, at least about 0.2%, at least about 0.3%, at least about 0.4%, at least about 0.5%, at least about 0.6%, at least about 0.7%, at least about 0.8%, at least about 0.9%, at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, or more, based on the volume of the reaction solution and/or the washing solution. In a preferred embodiment, about 0.05% to 1% of Tween-20 (v/v) is added to the one or more reaction solutions of the step b), the regeneration solution of the step d) and/or the washing solution of the step e).”
With regards to claim 23, Yang teaches, “sequencing-by-synthesis.” (0008)
Summary
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEVEN C POHNERT PhD whose telephone number is (571)272-3803. The examiner can normally be reached Monday- Friday about 6:00 AM-5:00 PM, every second Friday off.
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/Steven Pohnert/ Primary Examiner, Art Unit 1683
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