DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12 November 2025 has been entered.
Status of Application
The amendments and response filed 12 November 2025 are acknowledged and have been considered in their entireties. Claims 12-20 are new, thus, claims 1-4, 6-8 and 11-20 are pending and subject to examination on the merits.
Terminal Disclaimer
As a reiteration, the terminal disclaimer filed on 26 June 2024 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patents 10633697 and 11519025 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Modified Rejection(s) – Necessitated by Amendments
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.
Claim(s) 1-4, 6-8 and 11-20 are rejected under 35 U.S.C. 103 as being unpatentable over Gelfand et al. (US 5561058 – cited previously).
Gelfand et al. teach:
Regarding claims 1-4 and 6-8 a “kit” for Reverse Transcription/PCR comprising a Thermus thermophilus DNA polymerase suitable of nucleic acid amplification (See Example 1(V)(C, D, E)), Moloney murine leukemia MMLV/MoMuLV reverse transcriptase (See Example 1(V)(A), 10x PCR Buffer comprising 100 mM Tris (pH8.3)), 18.75 mM MgCl2 and 7.5 mM EGTA (See Example 1(IV)(G)); wherein when in an amplification mixture at 1x concentration would be 1.875 mM MgCl2 and 0.75 mM EGTA.
It is also noted regarding the claims above and claim 11, that Example VII and VIII utilizes two different DNA polymerases, one with reverse transcriptase activity (Tth polymerase) and a DNA polymerase for amplification (Taq), wherein said reactions all utilized 10x nucleic amplification buffers comprising 100 mM Tris, 18.75 MgCl2, 7.5 mM EGTA and dNTP’s (See also Example VI as indicated in Example VII for RT mixture comprising said dNTP’s), wherein when in an amplification mixture at 1x concentration would be 1.875 mM MgCl2 and 0.75 mM EGTA. In addition, in Example VIII, 1mM MnCl2 is utilized in the RT reaction. In Example IX, kits are taught comprising:
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Gelfand et al., however, do not teach concentrations of EGTA at 1.5 mM to 8mM when in an amplification reaction mixture.
Gefland et al., however, do teach the following (Col. 28, lines 36-63):
The reverse transcription reaction products are suitable as templates for amplification by PCR. In one embodiment of the invention, following the high temperature reverse transcription incubation, the reverse transcription reaction is adjusted to PCR buffering conditions, and the amplification reaction is initiated following the addition of a second primer. PCR buffer is added to maintain the appropriate buffering capacity, pH, monovalent cation concentration, and to dilute the concentration of enzyme and dNTPs to within 20-200 μM each dNTP. MgCl2 is added to a final concentration of 1-3 mM. Preferably, the concentrations of dNTPs in both the reverse transciptase and PCR reaction mixes are balanced. Because Mn+2 can diminish PCR amplification when present at high concentrations, in a preferred embodiment of the invention the Mn+2 is chelated prior to the PCR amplification. The presence of high amounts of Mn+2 also may decrease fidelity during amplification, however chelating the Mn+2 avoids this problem. Accordingly, in a preferred embodiment, following the reverse transcription reaction, EGTA is added to a concentration between about 1-3 times the molar concentration of Mn+2 to chelate the Mn+2. In the presence of both Mg+2 and Mn+2, EGTA preferentially binds Mn+2. Low dNTP and Mg+2 concentrations, as described herein, may also increase fidelity of Tth DNA polymerase during amplification. Glycerol and non-ionic detergent (for example, Tween-20™) may be added to a final concentration of between 1-20% and 0.01-0.05%, respectively, to increase enzyme stability.
Therefore, it would be obvious to optimize the concentration of MgCl2 to be utilized by the skilled artisan because Gefland et al. specifically teach to do this Example IX. In addition, it would be obvious to optimize the EGTA concentration to anything that is 1-3x’s the manganese concentration, thus, for example in Example VIII, 1-3x the MnCl2 concentration for the concentration of EGTA would be 1-3 mM EGTA, as suggested by Gefland at Col. 28, lines 51-57. In addition, this concentration is also an optimizable parameter because in Example IX Gefland et al. teach to optimize the MgCl2 and the MnCl2 concentrations, which necessarily would mean optimizing the EGTA concentration as well to be 1-3x its concentration of the MnCl2.
As noted in MPEP 2144.05(I), “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)” Here, when one adjusts/optimizes the EGTA concentration to be 1-3x the concentration of MnCl2 utilized in the reaction as suggested as noted above, the concentration results in overlapping concentrations of 1-3mM EGTA, which overlaps with the claimed concentration of 1.5mM-8mM EGTA. In addition, the concentration of MgCl2 is suggested to be 1-3mM, which overlaps directly with the range as claimed in the claims, 1-4, 6-8, 12, 16 and 19, and is sufficiently close to the ranges recited in claims 17-18 and 20, wherein it would be obvious to optimize said concentration by one skilled in the art to reach the optimized reaction conditions (MPEP 2144.05(II)) as suggested to Gefland et al. in Example IX. As such, the teachings of Gefland et al. render the instant claims and concentrations as prima facie obvious.
Applicant’s Remarks and Examiner’s Rebuttal:
Applicant’s traverse the previous rejection of claims 1-4, 6-8 and 11 under 35 U.S.C. 103 as being obvious over Gelfand et al. (US 5561058 – cited previously).
It is asserted that the concentration of EGTA is used to bind Mn2+ which is required for reverse transcription but is inhibitor to PCR, and to inhibit at time prior to said PCR. With this, the EGTA concentration needs to be sufficient to bind said Mn2+ but not too high of a concentration to also bind Mg2+ - See Remarks, pp. 6 to top of p. 7.
In this regard, Gefland et al. specifically teach what the concentration of EGTA needs to be relative to the Mn2+ concentration, e.g. an EGTA concentration that is 1-3 times that of the Mn2+ concentration. As such, there is little guess work for a skilled artisan although said it would be apparent that the skilled artisan would readily optimize both concentrations.
Applicant’s also argue that EGTA is utilized differently in the instant specification/invention because it is not used to bind Mn2+ but rather it is used to bind Mg2+. It is specifically stated that “…..one of ordinary skill in the art would not have a reasonable expectation of success in modifying the cited refence to arrive at the instantly claimed method because EGTA concentration suitable for D1 may not necessarily be suitable to the instantly claimed methods” – See Remarks, p. 7, last paragraph.
This is not convincing because the instant claims are not method claims, rather product claims. While Gefland et al. teach utilizing their products/kits for a different purpose, optimizing those concentrations for their intended use would be obvious, wherein it so happens that the claimed concentrations and suggested optimization parameters happen to overlap with those specifically as claimed in the present kits. As noted in MPEP 2144(IV):
“The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) ("One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings."); In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) (discussed below); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991) (discussed below).”
As such, Applicant’s arguments are not convincing and the rejection of Gefland et al. above still applies.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUZANNE M NOAKES whose telephone number is (571)272-2924. The examiner can normally be reached on M-F (7-4).
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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 17 November 2025
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