DETAILED ACTION
The amendment filed on 11/24/2025 has been entered.
Claims 1 and 4 were amended in the claim set filed on 11/24/2025.
NOTICE: Claim 1 amendment is not compliant. Amended claim 1 ln 8-13 was not underlined in the claim set filed on 11/24/2025, to indicate that the limitations were added to claim 1. As such, the claim set filed on 11/24/2025 can be considered non-compliant, but for the sake of compact prosecution the claim amendment has been entered.
Claims 2-4 and 7-8 are canceled in the claim set filed on 11/24/2025.
Claims 21-24 were added in the claim set filed on 11/24/2025. No new matter was added.
Claims 1, 5-6, and 9-24 in the claim set filed on 11/24/2025 are currently under examination.
Response to the Arguments
Applicant’s arguments regarding previous rejection(s) of claim(s) 1-20 under 35 U.S.C. 112 (b) have been fully considered and are persuasive. The 35 U.S.C. 112 (b) rejections documented in the previously mailed non-final have been withdrawn in light of applicants claim amendments and arguments on Pg. 5.
Applicant’s arguments regarding previous rejection(s) of claim(s) 1-20 under 35 U.S.C. 103 have been fully considered but are not persuasive. The 35 U.S.C. 103 rejections documented in the previously mailed non-final have been maintained in light of applicants claim amendments and arguments on Pg. 5-7. However, upon further consideration and search, new grounds of rejections regarding claims 1, 5-6 and 9-24 are made as documented below in the 35 U.S.C. 103 rejection in this office action on Pg. 4-28.
The rejections for claims 1, 5-6, 9-24 are documented below in this Final Office Action are necessitated by claim amendments filed on 11/24/2025.
Priority
This application claims benefit of U.S. Provisional Application No. 63/132,482 filed December 31, 2020. Accordingly, the priority date of instant claims is determined to be December 31, 2020, the filing date of U.S. Provisional Application No. 63/132,482.
Claim Objections
Claim 1 is objected to because of the following informalities:
“glutamate. 0.01” (Amended Claim 1 ln 10) should be modified to “glutamate; 0.01”.
“0.20 vol. of a nonionic surfactant” (Amended Claim 1 ln 12) should be modified to “0.20 vol. % of a nonionic surfactant”.
Appropriate correction is required.
Response to Arguments
Applicant's arguments filed 11/24/2025 do not apply to the new grounds of objections, as necessitated by amendment.
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.
Claim 23 is 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 23 is indefinite over the limitation “The reagent solution of claim 22, comprising” (ln 1). It is unclear if the limitation following the statement are considered in addition to the concentrations listed in claim 1 or the summation of the concentrations in claim 22 with additional amount of the reagents potassium glutamate, polyethylene glycol having an average molecular weight of about 20K, methyl isothiazolinone, as the concentration range is broader than the claim from which it depends on.
Response to Arguments
Applicant's arguments filed 11/24/2025 do not apply to the new grounds of rejections, as necessitated by amendment.
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.
Interpretations: Regarding claim 1, 22 and 24 and any dependent claims, “reagent solution” is considered any mixture of reagents.
Claims 1, 5-6, 9-11, 13, 15-18 and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (“Liu”; Patent App. Pub. No. WO 2011/032124 A1, March 17, 2011) in view of Hogrefe et al. ("Hogrefe", PCT App. Pub., WO 2008/013885, January 31, 2008) as evidenced by DMAPS Biocompare page (https://www.biocompare.com/11119-Chemicals-and-Reagents/20799966-DMAPS/, accessed November 13,2024), Bachmann et al. ("Bachmann", NAR 1990, Vol. 18, pg. 1309) and Piepenburg et al. (“Piepenburg”, PCT App. Pub., WO 2010/141940, December 9, 2010).
Liu discloses compositions and methods for improving nucleic acid or protein recovery. (Abstract).
Regarding claim 1, Liu teaches a reagent solution comprising “detergent, an amine, and a buffering agent” (Pg. 29, Claim 12). Liu teaches a reagent solution comprising “the amine is… tris(hydroxymethyl)aminomethane” (Pg. 29, Claim 15). Liu teaches a reagent solution comprising “the amount of each amine in the… solution is selected from the group consisting of… from about 25 mM to about 200 mM” (Para. 27). Liu teaches a reagent solution comprising “the buffering agent is 4-(2-hydroxyethyl)-l-piperazine-ethanesulfonic acid ("HEPES")” (Pg. 29, Claim 17). Liu teaches a reagent solution comprising “the amount of each buffering agent in the… solution is selected from the group consisting of… from about 25 mM to about 200 mM” (Para. 30).
Regarding claim 1, [2-(methacryloyloxy) ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide reads on DMAPS. The detergent reads on “DMAPS” as evidenced by Biocompare page description of DMAPS as “Zwittergent 3-14 is a zwitterionic detergent commonly used in biochemistry and molecular biology for … solubilization and purification … which have both hydrophilic and hydrophobic moieties, so that it has good detergency properties, making it suitable for stabilizing … in reagent solutions” (para. 1).
Regarding claim 1, Liu teaches a reagent solution comprising “polysorbate surfactants (sold commercially as TWEEN). The precise type and formulation of the lysis solution can be readily determined by a person having ordinary skill in the art according to the sample type, the method of lysis, the analyte of interest, and the method of analysis to be used” (Para. 25).
Regarding claim 1, Liu teaches a reagent solution comprising “a preservative… 2-Methyl-4-isothiazolin-3-one” and “the amount of preservative in the… solution can be about 0.01 %, or about 0.02%>, or about 0.03%>, or about 0.04%, or about 0.05%, or about 0.06%, or about 0.07%, or about 0.08%, or about 0.09%, or about 0.10%” (Para. 34). “2-Methyl-4-isothiazolin-3-one” reads on methyl isothiazolinone.
Of note, "Where 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." (MPEP 2144.05).
Thus, Liu teaches a reagent solution comprising: an aqueous solution including: 20 mM to 50 mM of tris(hydroxymethyl)aminomethane; 20 mM to 50 mM of 2-[4-(2-hydroxyethyl) piperazin-1-yl] ethanesulfonic acid; [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide; a nonionic surfactant and 0.01 vol. % to vol. 0.10 % methyl isothiazolinone. Furthermore, Liu teaches “The precise type and formulation of the … solution can be readily determined by a person having ordinary skill in the art according to the sample type, the method of lysis, the analyte of interest, and the method of analysis to be used.” (Para. 25).
However, Liu does not explicitly teach “[2-(methacryloyloxy) ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide”, which is also known as a zwitterionic detergent called “DMAPS”, at a concentration of “10 mM to 120 mM”; 10 mM to 500 mM of potassium glutamate; or “a nonionic surfactant “at a concentration of “0.01 vol. % to 0.20 vol.”
Hogrefe discloses an invention that provides compositions and kits that include … a zwitterionic detergent … useful in PCR amplification (abstract).
Regarding claims 1 and 3, Hogrefe further teaches “Tris”, “buffers were supplemented with … one or more zwitterionic detergents” and “in percentage (v/v) ranging from 0.05 to 0.5%” (Pg. 26, Example 1). “0.05 to 0.5%” of DMAPS reads on 1.789 mM -17.89 mM DMAPS. It is noted the molecular weight of DMAPS (2-(Methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium) is approximately 279.35 g/mole, and a reagent solution comprises mostly water that has density at about 1.0 g/ml. Accordingly, the “0.05 to 0.5%” of DMAPS taught by Hogrefe is equivalent to 1.789 mM -17.89 mM, which overlaps with 10 mM -120 mM concentration range.
Liu and Hogrefe are both considered to be analogous to the claimed invention because they are in the same field of preparation of nucleic acids and the reagent solution can be used for rehydration. Therefore, it would have been obvious to the ordinary artisan before the effective filling date to have modified the reagent solution comprising a combination of Tris, HEPES and a detergent, and further comprising methyl isothiazolinone and a nonionic surfactant as taught by Liu to incorporate “DMAPS” as a zwitterionic detergent reagent as evidenced by Biocompare and incorporate the zwitterionic detergent reagent in the amount of 1.789 mM -17.89 mM as taught by Hogrefe with the reasonable expectation of a more soluble and stable reagent solution for nucleic acid preparation. Thus, the claim element of a detergent such as DMAPS was known in the art and one of skill in the art could have combined this element with the other known elements with no change in their respective functions, and the combination would have yielded the predictable outcome of a reagent solution comprising the reagents according to the limitations of claim 1. An ordinary artisan would be motivated to combine the reagents of Tris, HEPES, detergent of Liu with zwitterionic detergent (DMAPS) of Hogrefe for the rehydration and preparation of nucleic acids for amplification because Hogrefe suggests “product yields are dramatically higher when PCR amplification reactions are conducted in buffers containing one or more zwitterionic detergents” (e.g., Pg. 6 ln 2-3). Furthermore, a skilled artisan in life science with years of research experience will certainly understand that DNA prepared in reagent solutions taught by Liu et al. can certainly be used as the starting solution for DNA molecules to be amplified by PCR reaction taught by Hogrefe et al.
Bachmann discloses detergents that improve PCR amplified DNA sequencing (pg. 1309, para 1).
Regarding claims 1 and 5-6, Bachmann teaches “polyoxyethylene (20) sorbitan monolaurate”, also known as Tween-20, a type of “polyoxyethylene sorbitan monolaurate” or Tween, of claims 5 and 6 at the concentration of “0.5 %” (pg. 1309, para 1). As stated above, "Where 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." (MPEP 2144.05).
Liu, Hogrefe and Bachmann are considered to be analogous to the claimed invention because they are in the same field of a reagent solution used for nucleic acid assays. Therefore, it would be prima facia obvious to one of ordinary skill in the art before the effective filing date to modify a reagent solution suggested by Liu and Hogrefe to incorporate the nonionic surfactant, Tween-20 at an optimal concentration optimized from 0.5% as taught by Bachmann in order to yield a predictable result of a reagent solution with similar functionality in amplification assays and rehydration. It would be obvious to the ordinary to optimize the Tween-20 concentration to an optimal concentration of 0.01-0.2% by routine experimentation. It would be obvious to the ordinary artisan to add the detergent, Tween 20, to a reagent solution of Liu and Hogrefe, as Bachman teaches a reasonable expectation of the solution functionality having an enhanced signal intensity and reduced background when used in amplification assays.
Piepenburg discloses a kit comprising solutions for … DNA (pg. 20 ln 2-3, claim 1).
Regarding claim 1, Piepenburg teaches “potassium acetate” at the concentration of “50-150 mM”, which is within the indicated range of 10- 500 mM (pg. 21 ln 15). Piepenburg teaches “potassium acetate” while the claimed invention discloses ““potassium glutamate”. Although the claim is drawn to potassium glutamate in the same concentration, the interchange of potassium acetate as taught by Piepenburg would be an obvious interchange of potassium glutamate as both are used in assays to neutralize the negative charge on the DNA backbone.
Liu, Hogrefe, Bachmann, and Piepenburg are considered to be analogous to the claimed invention because they are in the same field of a reagent solution used for nucleic acid assays. Therefore, it would be prima facia obvious to one of ordinary skill in the art before the effective filing date to modify a reagent solution suggested by Liu, Hogrefe and Bachmann to further comprise potassium containing reagent as taught by Piepenburg et al. to yield a predictable reagent solution with similar functionality in an amplification assay. It would be obvious to the ordinary artisan to modify Liu, Hogrefe and Bachmann to further comprise the potassium containing reagent of Piepenburg in the reagent solution to make the simple substitution of potassium acetate for potassium glutamate to obtain predictable results based on the similar neutralizing functionality of potassium on the DNA backbone in an amplification process or rehydration process.
The teachings of Liu, Hogrefe, Bachmann and Piepenburg are documented above in the rejection of claim 1 and 5-6 under 35 U.S.C. 103. Claims 5, 9, 13, 15-18 and 20-21 depend on claim 1. Claim 6 depends on claim 5, which depends on claim 1. Claim 11 depends on claim 10, which depends on claim 9, which depends on claim 1.
Regarding claims 9-11, Piepenburg teaches “polyethylene glycol” at the concentration of “0.3 % - 7.5 % weight/volume”, which is similarly included in the indicated range of 0.1-7 % (pg. 21 ln 16). Piepenburg also teaches “1.5 %-5 % … polyethylene glycol” that could be added (pg. 20 ln 8-9). It would be obvious that these polyethylene glycols encompass a variety of molecular weight(s) or combination thereof in a reagent solution.
Regarding claim 13, Piepenburg teaches “dNTPs”, also known as nucleotides, at a concentration approximately within the range of “150 - 400 μM” (pg. 20 ln 13).
Regarding claim 15, Piepenburg teaches “DTT”, also known as dithiothreitol, at a concentration of “1-10 mM”, which is included within the range of the indicated “0.01 mM to 20 mM’ (pg. 20 ln 12).
Regarding claim 16, Piepenburg teaches “trehalose”, at a concentration of “2.5 % - 7.5 %”, which is included within the range of the indicated “0.1 vol. % to 20 vol. %”, (pg. 20 ln 10).
Regarding claim 17, Piepenburg teaches “ATP”, also known as “adenosine triphosphate”, at a concentration of “1.5 – 3.5 mM”, which is included within the range of the indicated “0.1 mM to 50 mM”, (pg. 20 ln 14).
Regarding claim 18, Piepenburg teaches “Magnesium Acetate” at a concentration of “8 – 16 mM or 160-320 mM”, which is included within the range of the indicated “0.1 mM to 50 mM”, (pg. 21 ln 21-22,26).
Regarding claim 20, Piepenburg teaches “phosphocreatine” to be reconstituted within the kit by the rehydration buffer to a concentration of “20 – 75 mM”, which is included within the range of the indicated “1 mM to 200 mM”, (pg. 20 ln 19).
Regarding claim 21, Liu teaches a reagent solution wherein the “solution has a pH selected from the group consisting of: from approximately 7.5 to approximately 10, from approximately 7.5 to approximately 9.5, from approximately 8.0 to approximately 9.5, … from approximately 7.5 to approximately 9.0, from approximately 8.0 to approximately 9.0, … from approximately 7.0 to approximately 8.5, from approximately 7.5 to approximately 8.5, from approximately 8.0 to approximately 8.5, from approximately 7.0 to approximately 8.0, from approximately 7.5 to approximately 8.0, from approximately 7.0 to approximately 7.5, 7.0 or greater, 7.5 or greater, 8.0 or greater, …. 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0….” (Para. 32).
Response to Arguments
Applicant's arguments filed 11/24/2025 (Pg. 5-7) with respect to claims 1, 5-6, 9-11, 13, 15-18 and 20-21 have been fully considered but are not persuasive, in light of the new grounds of rejection. To clarify some instances argued in the response filed 11/24/2025 that remains relevant to the new grounds of 103 rejection documented in this Final Office Action, examiner' s responses to each relevant argument made by Applicant are provided below:
Applicant’s arguments: “As discussed below, the pending independent claims have been amended to include specific limitations that are neither taught nor suggested by Liu, Hogrefe, Bachmann, Piepenburg, nor the additional references (alone or in combination) relied upon in the Office Action. The cited art fails to disclose, or provide any motivation to modify, the referenced compositions to arrive at the presently claimed reagent solutions. In particular, the amended claims now recite a reagent solution that functions collectively to produce rehydration and sequencing performance not predicted from the cited references individually or in any combination.” (Pg. 6)
Response: Applicant’s arguments stated above have been considered but are not persuasive because Liu, Hogrefe, Bachmann, and Piepenburg do teach the specific limitations regarding claims 1, 5-6, 9-11, 13, 15-18 and 20-21 as stated in the 35 U.S.C. 103 rejection above, Pg. 4-10. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, as stated in the 35 U.S.C. 103 rejection above (Pg. 6), Liu teaches “The precise type and formulation of the … solution can be readily determined by a person having ordinary skill in the art according to the sample type, the method of lysis, the analyte of interest, and the method of analysis to be used.” (Para. 25). Thus, the ordinary artisan would be motivated to modify, the referenced compositions to arrive at the presently claimed reagent solutions.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., reagent solution that functions collectively to produce rehydration and sequencing performance) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Furthermore, in response to applicant's argument that “reagent solution that functions collectively to produce rehydration and sequencing performance”, if the limitation was claimed, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Applicant’s arguments: “Liu fails to teach or suggest each and every element of amended claim 1. In particular, Liu does not disclose the specific concentration ranges recited for [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (DMAPS), tris(hydroxymethyl)aminomethane (Tris), 2-[4-(2-hydroxyethyl)piperazin-l -yl]ethanesulfonic acid (HEPES), potassium glutamate, nonionic surfactants, or methyl isothiazolinone. Moreover, nothing in Liu provides any teaching, suggestion, or motivation that would have led one of ordinary skill in the art to prepare a formulation comprising the particular combination and concentration ranges now claimed. Hogrefe does not cure the deficiencies of Liu. Although Hogrefe discloses high-pH enzyme buffers containing general levels of sulfobetaines, it neither discloses DMAPS at the presently claimed 10-120 mM concentration range nor describes any buffer system combining DMAPS with Tris and HEPES, preferably at a relatively neutral pH Hogrefe likewise fails to disclose or suggest the inclusion of potassium glutamate, nonionic surfactants, or methyl isothiazolinone. Rather, Hogrefe is directed to a substantially different class of enzymatic buffers and provides no teaching or suggestion to combine its components with those of Liu in the manner required by the amended claims… Bachmann discloses the use of Triton X-100 in unrelated assay mixtures but does not teach or suggest the use of a nonionic surfactant in an amount within the range of 0.01 to 0.20 vol.% in relation to the compositions of Liu or Hogrefe. Nor does Bachmann provide any teaching or rationale to incorporate such a nonionic surfactant (v/v) together with methyl isothiazolinone or any of the other claimed components of amended claim 1. Bachmann thus cannot remedy the deficiencies of Liu and Hogrefe..” (Pg. 6-7)
Response: In response to applicant's arguments against the references individually, 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). In response to the argument against providing any teaching, suggestion, or motivation that would have led one of ordinary skill in the art to prepare a formulation comprising the particular combination and concentration ranges now claimed, please see the response to the argument above and new grounds of 35 U.S.C. 103 rejection above. Furthermore, in response to the concentration ranges, as stated above in the 103 rejection, the MPEP states "Where 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." (MPEP 2144.05).Thus, Liu provides a teaching, suggestion, or motivation that would have led one of ordinary skill in the art to prepare a formulation comprising the particular combination and concentration ranges according to claimed invention.
Applicant’s arguments: “DMAPS (DMAPS Biocompare page) merely demonstrates its commercial availability and does not teach or suggest its use in sequencing reagents, nor its compatibility with Tris, HEPES, potassium glutamate, surfactants, or preservatives. As such, the evidence provides no motivation to modify Hogrefe to arrive at the presently claimed reagent solution.”(Pg. 7)
Response: In response to applicant's arguments against the evidence by DMAPS Biocompare page, the evidence provided is that “DMAPS” is a detergent “commonly used in biochemistry and molecular biology for … solubilization and purification … which have both hydrophilic and hydrophobic moieties, so that it has good detergency properties, making it suitable for stabilizing … in reagent solutions”. (para. 1). Thus, the claim element of a detergent such as DMAPS was known in the art and one of skill in the art could have used the DMAPS zwitterionic detergent with the other known elements with no change in their respective functions, and the combination would have yielded the predictable outcome of a reagent solution comprising the reagents according to the limitations of claim 1.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., its use in sequencing reagents, nor its compatibility with Tris, HEPES, potassium glutamate, surfactants, or preservatives”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Furthermore, in response to applicant's argument that “its use in sequencing reagents, nor its compatibility with Tris, HEPES, potassium glutamate, surfactants, or preservatives”, if the limitations were claimed, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Applicant’s arguments: “the experimental data presented in the Examples (i.e., [0073] and [0075]) of the present application show that the claimed combination of Tris/HEPES buffering with DMAPS and a defined concentration of potassium glutamate produces unexpected and synergistic results. Specifically, the data indicates that a 4% improvement in the percentage of valid reads, longer mean read lengths, and enhanced raw read accuracy, suggesting that the claimed formulation (i.e., the test solution) provides improved nucleotide solubility, rapid and complete rehydration of lyophilized reagents, and greater stability of sequencing components. These synergistic effects could not have been predicted from the individual performance of the components described in the cited references, which fail to suggest that this particular combination and concentration balance would achieve such improvements.”(Pg. 7)
Response: In response to applicant's argument stated above, the fact that the inventor has recognized another slight advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (“Liu”; Patent App. Pub. No. WO 2011/032124 A1, March 17, 2011) in view of Hogrefe et al. ("Hogrefe", PCT App. Pub., WO 2008/013885, January 31, 2008) as evidenced by DMAPS Biocompare page (https://www.biocompare.com/11119-Chemicals-and-Reagents/20799966-DMAPS/, accessed November 13,2024), Bachmann et al. ("Bachmann", NAR 1990, Vol. 18, pg. 1309) and Piepenburg et al. (“Piepenburg”, PCT App. Pub., WO 2010/141940, December 9, 2010), as applied to claim 1, and further in view of Yilin et al. ("Yilin", CN Patent App. Pub. 105925692, September 7, 2016).
The teachings of Liu, Hogrefe, Bachmann and Piepenburg are documented above in the rejection of claims 1, 5-6, 9-11, 13, 15-18 and 20-21 under 35 U.S.C. 103. Claim 12 depends on claim 1. However, Liu, Hogrefe, Bachmann and Piepenburg do not explicitly teach “further comprising a biocide”.
Yilin discloses a…solution that can stably exist (abstract).
Regarding claim 12, Yilin teaches “sodium azide” also known as a ”biocide” at the concentration of “0.002% -0.09% (w/w)” in the solution, which is within the indicated concentration range of 0.001-0.1% (para 12, Summary of present invention ; para 6, Background).
Yilin teaches a “biocide” in an amplification reagent solution. Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date to modify a reagent solution suggested by Liu, Hogrefe, Bachmann and Piepenburg by further comprising adding a biocide to a reagent solution, as taught by Yilin, to support preservation of a reagent solution. It would be obvious to an ordinary artisan that adding a biocide to a reagent solution would have a reasonable expectation of reagent solution preservation for amplification assays or rehydration processes.
Response to Arguments
Applicant’s arguments: “the pending independent claims have been amended to include specific limitations that are neither taught nor suggested by Liu, Hogrefe, Bachmann, Piepenburg, nor the additional references (alone or in combination) relied upon in the Office Action.”(Pg. 6)
Response: Applicants’ arguments filed 11/24/2025 have been fully considered but are not persuasive. Arguments against Liu, Hogrefe, Bachmann and Piepenburg are not persuasive as discussed above.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (“Liu”; Patent App. Pub. No. WO 2011/032124 A1, March 17, 2011) in view of Hogrefe et al. ("Hogrefe", PCT App. Pub., WO 2008/013885, January 31, 2008) as evidenced by DMAPS Biocompare page (https://www.biocompare.com/11119-Chemicals-and-Reagents/20799966-DMAPS/, accessed November 13,2024), Bachmann et al. ("Bachmann", NAR 1990, Vol. 18, pg. 1309) and Piepenburg et al. (“Piepenburg”, PCT App. Pub., WO 2010/141940, December 9, 2010), as applied to claim 1, and further in view of Galliano et al. ("Galliano", Pract Lab Med, 2021, Vol. 25, e00221).
The teachings of Liu, Hogrefe, Bachmann and Piepenburg are documented above in the rejection of claims 1, 5-6, 9-11, 13, 15-18 and 20-21 under 35 U.S.C. 103. Claim 14 depends on claim 1. However, Liu, Hogrefe, Bachmann and Piepenburg do not explicitly teach “further comprising acetic acid”.
Galliano discloses solutions to perform DNA isolation with special regard to the amount and purity of the DNA to be amplified by specific real-time PCR.(Abstract).
Regarding claim 14, Galliano teaches “acetic acid” in a solution for DNA isolation (pg. 3, Discussion, para. 2).
Therefore, it would be prima facia obvious to one of ordinary skill in the art before the effective filing date to modify a reagent solution suggested by Liu, Hogrefe, Bachmann and Piepenburg by further comprising acetic acid as taught by Galliano to yield a predictable reagent solution with the same functionality in an amplification assay or for rehydration. It would be obvious to an ordinary artisan that adding acetic acid to a reagent solution would have a reasonable expectation of neutralizing the pH of the reagent solution in amplification assays or rehydration process.
Response to Arguments
Applicant’s arguments: “the pending independent claims have been amended to include specific limitations that are neither taught nor suggested by Liu, Hogrefe, Bachmann, Piepenburg, nor the additional references (alone or in combination) relied upon in the Office Action.”(Pg. 6)
Response: Applicants’ arguments filed 11/24/2025 have been fully considered but are not persuasive. Arguments against Liu, Hogrefe, Bachmann and Piepenburg are not persuasive as discussed above.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (“Liu”; Patent App. Pub. No. WO 2011/032124 A1, March 17, 2011) in view of Hogrefe et al. ("Hogrefe", PCT App. Pub., WO 2008/013885, January 31, 2008) as evidenced by DMAPS Biocompare page (https://www.biocompare.com/11119-Chemicals-and-Reagents/20799966-DMAPS/, accessed November 13,2024), Bachmann et al. ("Bachmann", NAR 1990, Vol. 18, pg. 1309) and Piepenburg et al. (“Piepenburg”, PCT App. Pub., WO 2010/141940, December 9, 2010), as applied to claim 1, and further in view of Arslan et al. ("Arslan", US Patent App. Pub. 2021/0123911, April 29, 2021, Filed October 5, 2020).
The teachings of Liu, Hogrefe, Bachmann and Piepenburg are documented above in the rejection of claims 1, 5-6, 9-11, 13, 15-18 and 20-21 under 35 U.S.C. 103. Claim 19 depends on claim 1. However, Liu, Hogrefe, Bachmann and Piepenburg do not explicitly teach “further comprising methyl cellulose”.
Arslan discloses multivalent binding compositions allow one to localize detectable signals to active regions of biochemical interaction and can be used to identify sites of base incorporation in elongating nucleic acid chains during PCR amplification reactions and to provide improved base discrimination for sequencing and array based applications.(abstract).
Regarding claim 19, Arslan teaches the crowding agent “methyl cellulose” (pg. 9, para. 80, Compositions).
Therefore, it would be prima facia obvious to one of ordinary skill in the art before the effective filing date to modify a reagent solution suggested by Liu, Hogrefe, Bachmann and Piepenburg to further comprise methyl cellulose as taught by Arslan to yield a predictable reagent solution with the same functionality in an amplification assay and for rehydration. It would be obvious to an ordinary artisan that adding the crowding agent, methylcellulose, to a reagent solution would have a reasonable expectation of improved base discrimination in amplification assays and thickening allowing for lubricated coverage during rehydration processes.
Response to Arguments
Applicant’s arguments: “the pending independent claims have been amended to include specific limitations that are neither taught nor suggested by Liu, Hogrefe, Bachmann, Piepenburg, nor the additional references (alone or in combination) relied upon in the Office Action.” (Pg. 6)
Response: Applicants’ arguments filed 11/24/2025 have been fully considered but are not persuasive. Arguments against Liu, Hogrefe, Bachmann and Piepenburg are not persuasive as discussed above.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (“Liu”; Patent App. Pub. No. WO 2011/032124 A1, March 17, 2011) in view of Bachmann et al. ("Bachmann", NAR 1990, Vol. 18, pg. 1309) and Piepenburg et al. (“Piepenburg”, PCT App. Pub., WO 2010/141940, December 9, 2010).
Liu discloses compositions and methods for improving nucleic acid or protein recovery. (Abstract).
Regarding claim 22, Liu teaches a reagent solution comprising “detergent, an amine, and a buffering agent” (Pg. 29, Claim 12). Liu teaches a reagent solution comprising “the amine is… tris(hydroxymethyl)aminomethane” (Pg. 29, Claim 15). Liu teaches a reagent solution comprising “the amount of each amine in the… solution is selected from the group consisting of… from about 25 mM to about 200 mM” (Para. 27). Liu teaches a reagent solution comprising “the buffering agent is 4-(2-hydroxyethyl)-l-piperazine-ethanesulfonic acid ("HEPES")” (Pg. 29, Claim 17). Liu teaches a reagent solution comprising “the amount of each buffering agent in the… solution is selected from the group consisting of… from about 25 mM to about 200 mM” (Para. 30).
Regarding claim 22, Liu teaches a reagent solution comprising “polysorbate surfactants (sold commercially as TWEEN). The precise type and formulation of the lysis solution can be readily determined by a person having ordinary skill in the art according to the sample type, the method of lysis, the analyte of interest, and the method of analysis to be used” (Para. 25). ““polysorbate surfactants (sold commercially as TWEEN)” reads on polyoxyethylene sorbitan monolaurate.
Regarding claim 22, Liu teaches a reagent solution comprising “a preservative… 2-Methyl-4-isothiazolin-3-one” and “the amount of preservative in the… solution can be about 0.01 %, or about 0.02%>, or about 0.03%>, or about 0.04%, or about 0.05%, or about 0.06%, or about 0.07%, or about 0.08%, or about 0.09%, or about 0.10%” (Para. 34). “2-Methyl-4-isothiazolin-3-one” reads on methyl isothiazolinone.
Of note, "Where 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." (MPEP 2144.05).
Thus, Liu teaches a reagent solution comprising: an aqueous solution including: 20 mM to 50 mM of tris(hydroxymethyl)aminomethane; 20 mM to 50 mM of 2-[4-(2-hydroxyethyl) piperazin-1-yl] ethanesulfonic acid; polyoxyethylene sorbitan monolaurate; and 0.01 vol. % to vol. 0.10 % methyl isothiazolinone. Furthermore, Liu teaches “The precise type and formulation of the … solution can be readily determined by a person having ordinary skill in the art according to the sample type, the method of lysis, the analyte of interest, and the method of analysis to be used.” (Para. 25).
However, Liu does not explicitly teach 2.0 vol. % to vol. 3.0 % polyethylene glycol having an average molecular weight of about 20k; 50 mM to 250 mM of potassium glutamate; or “polyoxyethylene sorbitan monolaurate “at a concentration of “0.05 vol. % to 0.15 vol. %”.
Bachmann discloses detergents that improve PCR amplified DNA sequencing (pg. 1309, para 1).
Regarding claim 22, Bachmann teaches “polyoxyethylene (20) sorbitan monolaurate”, also known as Tween-20, a type of “polyoxyethylene sorbitan monolaurate” or Tween, at the concentration of “0.5 %” (pg. 1309, para 1). As stated above, "Where 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." (MPEP 2144.05).
Liu and Bachmann are considered to be analogous to the claimed invention because they are in the same field of a reagent solution used for nucleic acid assays. Therefore, it would be prima facia obvious to one of ordinary skill in the art before the effective filing date to modify a reagent solution comprising a combination of 20 mM -50 mM Tris, 20 mM -50 mM HEPES 0.01%- 0.1% methyl isothiazolinone and polyoxyethylene sorbitan monolaurate (Tween) as taught by Liu to incorporate the polyoxyethylene sorbitan monolaurate, Tween-20 at an optimal concentration optimized from 0.5% as taught by Bachmann in order to yield a predictable result of a reagent solution with similar functionality in amplification assays and rehydration. It would be obvious to the ordinary to optimize the Tween-20 concentration to an optimal concentration of 0.05-0.15 % by routine experimentation. It would be obvious to the ordinary artisan to add the Tween-20 to a reagent solution of Liu, as Bachman teaches a reasonable expectation of the solution functionality having an enhanced signal intensity and reduced background when used in amplification assays.
Piepenburg discloses a kit comprising solutions for … DNA (pg. 20 ln 2-3, claim 1).
Regarding claim 22, Piepenburg teaches “potassium acetate” at the concentration of “50-150 mM”, which is within the indicated range of 10- 500 mM (pg. 21 ln 15). Piepenburg teaches “potassium acetate” while the claimed invention discloses ““potassium glutamate”. Although the claim is drawn to potassium glutamate in the same concentration, the interchange of potassium acetate as taught by Piepenburg would be an obvious interchange of potassium glutamate as both are used in assays to neutralize the negative charge on the DNA backbone.
Regarding claim 22, Piepenburg teaches “polyethylene glycol” at the concentration of “0.3 % - 7.5 % weight/volume”, which is similarly included in the indicated range of 2-3 % (pg. 21 ln 16). Piepenburg also teaches “1.5 %-5 % … polyethylene glycol” that could be added (pg. 20 ln 8-9). “polyethylene glycol” reads on “polyethylene glycol having an average molecular weight of about 20k”. It would be obvious to the ordinary artisan that polyethylene glycol can be provided at a variety of molecular weight(s) to be used based on desired effects of the solution.
Liu, Bachmann, and Piepenburg are considered to be analogous to the claimed invention because they are in the same field of a reagent solution used for nucleic acid assays. Therefore, it would be prima facia obvious to one of ordinary skill in the art before the effective filing date to modify a reagent solution suggested by Liu and Bachmann to incorporate a potassium containing reagent and polyethylene glycol having a MW about 20K at the concentration of 2-3%, as taught by Piepenburg et al. to yield a predictable reagent solution with similar functionality in an amplification assay. It would be obvious to the ordinary artisan to modify Liu and Bachmann to further comprise the potassium containing reagent of Piepenburg in the reagent solution to make the simple substitution of potassium acetate for potassium glutamate to obtain predictable results based on the similar neutralizing functionality of potassium on the DNA backbone in an amplification process or rehydration process. Furthermore, it would be obvious to the ordinary artisan that these polyethylene glycol encompass a variety of molecular weight(s) to be used based on desired effects of the solution.
Response to Arguments
Applicant’s arguments: “the pending independent claims have been amended to include specific limitations that are neither taught nor suggested by Liu, Hogrefe, Bachmann, Piepenburg, nor the additional references (alone or in combination) relied upon in the Office Action.”(Pg. 6)
Response: Applicants’ arguments filed 11/24/2025 have been fully considered but are not persuasive. Arguments against Liu, Hogrefe, Bachmann and Piepenburg are not persuasive as discussed above.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (“Liu”; Patent App. Pub. No. WO 2011/032124 A1, March 17, 2011) in view of Bachmann et al. ("Bachmann", NAR 1990, Vol. 18, pg. 1309) and Piepenburg et al. (“Piepenburg”, PCT App. Pub., WO 2010/141940, December 9, 2010) as applied to claim 22 above, and further in view of Hogrefe et al. ("Hogrefe", PCT App. Pub., WO 2008/013885, January 31, 2008) as evidenced by DMAPS Biocompare page (https://www.biocompare.com/11119-Chemicals-and-Reagents/20799966-DMAPS/, accessed November 13,2024).
The teachings of Liu, Bachmann and Piepenburg are documented above in the rejection of claim 22 under 35 U.S.C. 103. Claim 23 depend on claim 1.
As stated above, Liu teaches a reagent solution comprising “detergent, an amine, and a buffering agent” (Pg. 29, Claim 12). Liu, Bachmann and Piepenburg do not explicitly teach the limitations of claim 23.
Regarding claim 23, [2-(methacryloyloxy) ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide reads on DMAPS. The detergent reads on “DMAPS” as evidenced by Biocompare page description of DMAPS as “Zwittergent 3-14 is a zwitterionic detergent commonly used in biochemistry and molecular biology for … solubilization and purification … which have both hydrophilic and hydrophobic moieties, so that it has good detergency properties, making it suitable for stabilizing … in reagent solutions” (para. 1). Thus, the claim element of a detergent such as DMAPS was known in the art and one of skill in the art could have used the DMAPS zwitterionic detergent with the other known elements with no change in their respective functions.
Hogrefe discloses an invention that provides compositions and kits that include … a zwitterionic detergent … useful in PCR amplification (abstract).
Regarding claims 1 and 3, Hogrefe further teaches “Tris”, “buffers were supplemented with … one or more zwitterionic detergents” and “in percentage (v/v) ranging from 0.05 to 0.5%” (Pg. 26, Example 1). “0.05 to 0.5%” of DMAPS reads on 1.789 mM -17.89 mM DMAPS. It is noted the molecular weight of DMAPS (2-(Methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium) is approximately 279.35 g/mole, and a reagent solution comprises mostly water that has density at about 1.0 g/ml. Accordingly, the “0.05 to 0.5%” of DMAPS taught by Hogrefe is equivalent to 1.789 mM -17.89 mM.
As stated above, the MPEP states "Where 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." (MPEP 2144.05). Thus, one of ordinary skill in the art would be motivated to optimize the reagent concentration through routine experimentation based on desired effects of the solution to the limitations according to claim 23.
Liu, Bachmann, and Piepenburg and Hogrefe are considered to be analogous to the claimed invention because they are in the same field of a reagent solution used for nucleic acid assays. Therefore, it would have been obvious to the ordinary artisan before the effective filling date to have modified the reagent solution of Liu, Bachmann, and Piepenburg to incorporate “DMAPS” as a zwitterionic detergent reagent as evidenced by Biocompare and incorporate the zwitterionic detergent reagent at an optimal concentration as taught by Hogrefe with the reasonable expectation of a more soluble and stable reagent solution for nucleic acid preparation. Thus, the claim element of a detergent such as DMAPS was known in the art and one of skill in the art could have combined this element with the other known elements with no change in their respective functions, and the combination would have yielded the predictable outcome of a reagent solution comprising the reagents according to the limitations of claim 1. An ordinary artisan would be motivated to combine the reagents of Liu, Bachmann, and Piepenburg and incorporate the zwitterionic detergent (DMAPS) at a concentrations of 60 to 100 mM of Hogrefe for the rehydration and preparation of nucleic acids for amplification because Hogrefe suggests “product yields are dramatically higher when PCR amplification reactions are conducted in buffers containing one or more zwitterionic detergents” (e.g., Pg. 6 ln 2-3). Furthermore, a skilled artisan in life science with years of research experience will certainly understand that DNA prepared in reagent solutions taught by Liu, Bachmann, Piepenburg and Hogrefe can certainly be used as the starting solution for DNA molecules in nucleic acid assays as taught by Hogrefe et al.
Response to Arguments
Applicant’s arguments: “the pending independent claims have been amended to include specific limitations that are neither taught nor suggested by Liu, Hogrefe, Bachmann, Piepenburg, nor the additional references (alone or in combination) relied upon in the Office Action.”(Pg. 6)
Response: Applicants’ arguments filed 11/24/2025 have been fully considered but are not persuasive. Arguments against Liu, Hogrefe, Bachmann and Piepenburg are not persuasive as discussed above.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (“Liu”; Patent App. Pub. No. WO 2011/032124 A1, March 17, 2011) in view of Bachmann et al. ("Bachmann", NAR 1990, Vol. 18, pg. 1309) and Piepenburg et al. (“Piepenburg”, PCT App. Pub., WO 2010/141940, December 9, 2010).
Liu discloses compositions and methods for improving nucleic acid or protein recovery. (Abstract).
Regarding claim 24, Liu teaches a reagent solution wherein the “solution has a pH selected from the group consisting of: from approximately 7.5 to approximately 10, from approximately 7.5 to approximately 9.5, from approximately 8.0 to approximately 9.5, … from approximately 7.5 to approximately 9.0, from approximately 8.0 to approximately 9.0, … from approximately 7.0 to approximately 8.5, from approximately 7.5 to approximately 8.5, from approximately 8.0 to approximately 8.5, from approximately 7.0 to approximately 8.0, from approximately 7.5 to approximately 8.0, from approximately 7.0 to approximately 7.5, 7.0 or greater, 7.5 or greater, 8.0 or greater, …. 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0….” (Para. 32).
Regarding claim 24, Liu teaches a reagent solution comprising “detergent, an amine, and a buffering agent” (Pg. 29, Claim 12). Liu teaches a reagent solution comprising “the amine is… tris(hydroxymethyl)aminomethane” (Pg. 29, Claim 15). Liu teaches a reagent solution comprising “the amount of each amine in the… solution is selected from the group consisting of… from about 25 mM to about 200 mM” (Para. 27).
Regarding claim 24, Liu teaches a reagent solution comprising “polysorbate surfactants (sold commercially as TWEEN). The precise type and formulation of the lysis solution can be readily determined by a person having ordinary skill in the art according to the sample type, the method of lysis, the analyte of interest, and the method of analysis to be used” (Para. 25). ““polysorbate surfactants (sold commercially as TWEEN)” reads on polyoxyethylene sorbitan monolaurate.
Regarding claim 24, Liu teaches a reagent solution comprising “a preservative… 2-Methyl-4-isothiazolin-3-one” and “the amount of preservative in the… solution can be about 0.01 %, or about 0.02%>, or about 0.03%>, or about 0.04%, or about 0.05%, or about 0.06%, or about 0.07%, or about 0.08%, or about 0.09%, or about 0.10%” (Para. 34). “2-Methyl-4-isothiazolin-3-one” reads on methyl isothiazolinone.
Of note, "Where 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." (MPEP 2144.05).
Thus, Liu teaches a reagent solution comprising: an aqueous solution including: 20 mM to 50 mM of tris(hydroxymethyl)aminomethane; polyoxyethylene sorbitan monolaurate and 0.01 vol.% to vol. 0.10% methyl isothiazolinone. Furthermore, Liu teaches “The precise type and formulation of the … solution can be readily determined by a person having ordinary skill in the art according to the sample type, the method of lysis, the analyte of interest, and the method of analysis to be used.” (Para. 25).
However, Liu does not explicitly teach 2.0 vol. % to vol. 3.0 % polyethylene glycol having an average molecular weight of about 20k; 50 mM to 250 mM of potassium glutamate; or “polyoxyethylene sorbitan monolaurate “at a concentration of “0.05 vol. % to 0.15 vol. %”.
Bachmann discloses detergents that improve PCR amplified DNA sequencing (pg. 1309, para 1).
Regarding claim 24, Bachmann teaches “polyoxyethylene (20) sorbitan monolaurate”, also known as Tween-20, a type of “polyoxyethylene sorbitan monolaurate” or Tween, at the concentration of “0.5 %” (pg. 1309, para 1). As stated above, "Where 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." (MPEP 2144.05).
Liu and Bachmann are considered to be analogous to the claimed invention because they are in the same field of a reagent solution used for nucleic acid assays. Therefore, it would be prima facia obvious to one of ordinary skill in the art before the effective filing date to modify a reagent solution comprising a pH above 7, a combination of 20 mM -50 mM Tris, 0.01%- 0.1% methyl isothiazolinone and polyoxyethylene sorbitan monolaurate (Tween) as taught by Liu to incorporate the polyoxyethylene sorbitan monolaurate, Tween-20 at an optimal concentration optimized from 0.5% as taught by Bachmann in order to yield a predictable result of a reagent solution with similar functionality in amplification assays and rehydration. It would be obvious to the ordinary to optimize the Tween-20 concentration to an optimal concentration of 0.05-0.15% by routine experimentation. It would be obvious to the ordinary artisan to add the Tween-20 to a reagent solution as taught by Liu, as Bachman teaches a reasonable expectation of the solution functionality having an enhanced signal intensity and reduced background when used in amplification assays.
Piepenburg discloses a kit comprising solutions for … DNA (pg. 20 ln 2-3, claim 1).
Regarding claim 24, Piepenburg teaches “potassium acetate” at the concentration of “50-150 mM”, which is within the indicated range of 10- 500 mM (pg. 21 ln 15). Piepenburg teaches “potassium acetate” while the claimed invention discloses ““potassium glutamate”. Although the claim is drawn to potassium glutamate in the same concentration, the interchange of potassium acetate as taught by Piepenburg would be an obvious interchange of potassium glutamate as both are used in assays to neutralize the negative charge on the DNA backbone.
Regarding claim 24, Piepenburg teaches “polyethylene glycol” at the concentration of “0.3 % - 7.5 % weight/volume”, which is similarly included in the indicated range of 2-3 % (pg. 21 ln 16). Piepenburg also teaches “1.5 %-5 % … polyethylene glycol” that could be added (pg. 20 ln 8-9). “polyethylene glycol” reads on “polyethylene glycol having an average molecular weight of about 20k”. It would be obvious to the ordinary artisan that polyethylene glycol can be provided at a variety of molecular weight(s) to be used based on desired effects of the solution.
Liu, Bachmann, and Piepenburg are considered to be analogous to the claimed invention because they are in the same field of a reagent solution used for nucleic acid assays. Therefore, it would be prima facia obvious to one of ordinary skill in the art before the effective filing date to modify a reagent solution suggested by Liu and Bachmann to incorporate a potassium containing reagent and polyethylene glycol having a MW about 20K at the concentration of 2-3%, as taught by Piepenburg et al. to yield a predictable reagent solution with similar functionality in an amplification assay. It would be obvious to the ordinary artisan to modify Liu and Bachmann to further comprise the potassium containing reagent of Piepenburg in the reagent solution to make the simple substitution of potassium acetate for potassium glutamate to obtain predictable results based on the similar neutralizing functionality of potassium on the DNA backbone in an amplification process or rehydration process. Furthermore, it would be obvious to the ordinary artisan that these polyethylene glycol encompass a variety of molecular weight(s) to be used based on desired effects of the solution.
Response to Arguments
Applicant’s arguments: “the pending independent claims have been amended to include specific limitations that are neither taught nor suggested by Liu, Hogrefe, Bachmann, Piepenburg, nor the additional references (alone or in combination) relied upon in the Office Action.”(Pg. 6)
Response: Applicants’ arguments filed 11/24/2025 have been fully considered but are not persuasive. Arguments against Liu, Hogrefe, Bachmann and Piepenburg are not persuasive as discussed above.
Conclusion of Response to Arguments
In view of the amendments, new grounds of rejections and the above responses to arguments are documented in this Final Office Action. No claims are in condition for allowance.
Conclusion
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 KENDRA R VANN-OJUEKAIYE whose telephone number is (571)270-7529. The examiner can normally be reached M-F 9:00 AM- 5:00 PM.
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/KENDRA R VANN-OJUEKAIYE/Examiner, Art Unit 1682 /WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682