Detailed Office 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 .
Status of the Claims
Acknowledgement is hereby made of receipt and entry of the communication filed 22 December, 2025. Claims 2, 4, 5, 7-11, 13, and 14 were canceled without prejudice or disclaimer. Claims 1, 3, 6, and 12 are pending in the instant application.
37 C.F.R. § 1.98
The information disclosure statement filed 22 December, 2025, has been placed in the application file and the information referred to therein has been considered.
35 U.S.C. § 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 previous rejection of claims 1-14 under 35 U.S.C. § 112(b) 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out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention, is hereby withdrawn in response to Applicant’s amendment.
35 U.S.C. § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. § 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless --
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
The previous rejection of claims 1-8, 13, and 14 under 35 U.S.C. § 102(a)(1) as being clearly anticipated by Smyrlaki et al. (2020), is hereby withdrawn in response to Applicant’s amendment.
Joint Inventors, Common Ownership Presumed
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 at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicant is advised of the obligation under 37 C.F.R. § 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned at the time a later invention was effectively filed 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.
Graham v. Deere Analysis
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 U.S.P.Q. 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. § 103(a) 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.
35 U.S.C. § 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 of this title, 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 previous rejection of claims 9-11 under 35 U.S.C. § 103 as being unpatentable over Smyrlaki et al. (2020), is moot in view of the cancellation of these claims.
Claims 1, 3, 6, and 12 are rejected under 35 U.S.C. § 103 as being unpatentable over Smyrlaki et al. (2020) in view of Calvez et al. (2020). The amended claims are directed toward a method for providing a preparation for detection of a target nucleic acid sequence in a specimen, the method comprising the steps of:(a) incubating a specimen stored in a transport medium at 98°C to provide a preparation, wherein the target nucleic acid is a viral nucleic acid, wherein the transport medium contains no materials for lysis of a specimen, wherein the specimen is lysed by the incubation; wherein the specimen is a swab or saliva, wherein when the specimen is a swab, the incubation is carried out for 3 minutes, wherein when the specimen is saliva, the saliva is treated with proteinase K and then the subjected to the incubation for 20 minutes; and (b) mixing the preparation with a composition for detecting a target nucleic acid wherein the mixture is used in the target nucleic acid detection reaction, wherein the target nucleic acid detection reaction includes RT-PCR (Reverse Transcription PCR), and wherein the specimen stored in the transport medium in step (a) or the preparation in step (b) is 4-fold diluted. Claim 3 further defines the source of the swab (e.g., nasopharyngeal) and claim 6 references a transport medium with a preservative. Claim 12 further specifies that heat-inactivated samples should be cooled to 2-10°C before combining with the PCR amplification mix.
Smyrlaki et al. (2020) disclose a rapid testing method for SARS-CoV-2 that involves performing RT-qPCR directly on heat-inactivated samples without RNA-extractions (see Results, Optimisation of hid-RT-qPCR and Validation of hid-RT-qPCR against standardized clinical testing, pp. 3-4; and METHODS, Sample collection, Heat inactivation, and One-step RT-qPCR, pp. 5-6). The heat-inactivation was performed optimally at 95°C for 5’ (claims 1 and 8). With respect to claims 2, 3, 6, and 7, specimens included swabs (e.g., nasopharyngeal) and saliva which were collected and deposited in transport medium (see METHODS, Sample collection, p. 5). Note that the heat-inactivated samples were not processed with the MagNA lysis buffer. With respect to claims 4, 5, 13, and 14, the heat-inactivated samples were used to detect SARS-CoV-2 viral nucleic acids using RT-qPCR (see Results, Optimisation of hid-RT-qPCR and Validation of hid-RT-qPCR against standardized clinical testing, pp. 3 and 4). The authors concluded that RNA extractions, which constitute a barrier to scale-up testing, can be circumvented by performing RT-qPCR directly on heat-inactivated samples without the use or RNA extraction kits. The authors also examined the suitability of numerous transport buffers lacking lysing reagents (see Results, Generic transport buffers optimal for direct RT-PCR testing, pp. 8-9). This teaching does not disclose a heat-inactivation step for swab samples at 98 °C for 3 minutes.
Calvez et al. (2020) disclose a direct RT-qPCR amplification procedure for the detection of SARS-CoV-2 without an RNA extraction step. Samples were subjected to heat inactivation at 95°C or 98°C for 5 minutes followed by transfer to another thermoblock set at 4°C for at least 5 minutes. Following this step the sample was combined with the RT-qPCR mix and subjected to PCR. This teaching does not disclose a heat-inactivation step for swab samples at 98 °C for 3 minutes.
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform a simple experiment to identify the optimal incubation times for any given swab or saliva sample. Smyrlaki et al. (2020) clearly state (see Results, Optimisation of SARS-CoV-2 hid-RT-PCR, p. 4) that “we conclude that inactivation before hid-RT-PCR should be performed at 95–98°C. This result is fortunate and important, since incubation at such high temperature should completely inactivate the virus.” Moreover, Calvez et al. (2020) already performed heat-inactivation steps at 98°C for 5 minutes. Thus, one of ordinary skill in the art could have reasonably determined the optimal heat-inactivation temperature and time. Moreover, Smyrlaki et al. (2020) performed sample dilutions (see Results, Development of SARS-CoV-2 hid-RT-PCR, Fig. 2f/g, p. 4) and reported that “To identify the optimal range of sample input in clinical samples, we performed dilution series (10–0.01 μl) of individual COVID-19 positive heat-inactivated nasopharyngeal swab samples, and found an input of 1–4 μl sample in a 20 μl RT-PCR reaction to be optimal” (see Results, Development of SARS-CoV-2 hid-RT-PCR, p. 3, rt. col.). The lower dilution range is approximately five-fold, which is similar to the claimed four-fold dilution. Once again, one of ordinary skill in the art could have determined the optimal dilution using routine experimentation.
Applicant traverses and submits that heat-inactivation of samples at 98°C for 3 minutes is critical for lysing the specimen without degrading target nucleic acid. It was further noted that incorporating a four-fold dilution of the specimen sample prior to subjecting it to hid-RT-PCR was also critical. The utilization of a transport buffer lacking sample lysis reagents was also critical. Applicant’s arguments have been carefully considered vbut are not deemed to be persuasive for the reasons of record set forth supra.
Applicant is reminded that a prima facie case of obviousness exists where 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 U.S.P.Q. 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). See also Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 41 U.S.P.Q.2d 1865 (1997) (under the doctrine of equivalents, a purification process using a pH of 5.0 could infringe a patented purification process requiring a pH of 6.0-9.0); In re Aller, 220 F.2d 454, 456, 105 U.S.P.Q. 233, 235 (C.C.P.A. 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%); In re Dreyfus, 73 F.2d 931, 934, 24 U.S.P.Q. 52, 55 (C.C.P.A. 1934)(the prior art, which taught about 0.7:1 of alkali to water, renders unpatentable a claim that increased the proportion to at least 1:1 because there was no showing that the claimed proportions were critical); In re Lilienfeld, 67 F.2d 920, 924, 20 U.S.P.Q. 53, 57 (C.C.P.A. 1933)(the prior art teaching an alkali cellulose containing minimal amounts of water, found by the Examiner to be in the 5-8% range, the claims sought to be patented were to an alkali cellulose with varying higher ranges of water (e.g., "not substantially less than 13%," "not substantially below 17%," and "between about 13[%] and 20%"); K-Swiss Inc. v. Glide N Lock GmbH, 567 Fed. App'x 906 (Fed. Cir. 2014)(reversing the Board's decision, in an appeal of an inter partes reexamination proceeding, that certain claims were not prima facie obvious due to non-overlapping ranges).
Moreover, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 U.S.P.Q. 233, 235 (C.C.P.A. 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 U.S.P.Q.2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 U.S.P.Q.2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 U.S.P.Q.2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 U.S.P.Q.2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); In re Williams, 36 F.2d 436, 438, 4 U.S.P.Q. 237 (C.C.P.A. 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
One of ordinary skill in the art would have been motivated to identify the optimum heat-inactivation parameters (temperature and time) ascertain the appropriate sample dilution that provides optimal results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 U.S.P.Q.2d 1385 (2007) noting that it is prima facie obvious to determine the most effective variables, particularly when there are a finite number of solutions.
Additional Prior Art
The following additional prior art, which has not been relied upon in this Office action, is relevant to the claimed invention:
1) Fomsgaard, A, and M. W. Rosenstierne, April 2020, An alternative workflow for molecular detection of SARS-CoV-2-escape from the NA extraction kit-shortage, Copenhagen, Denmark, March 2020, Euro. Surveill. 25(14):1-4.
2) Merindol, N., et al., April 2020, Optimization of SARS-CoV-2 detection by RT-QPCR without RNA extraction, bioRxiv prepreint, doi.org/10.1101/2020.04.06.028902, pp. 1-17.
Action Is Final
Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See M.P.E.P. § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 C.F.R. § 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 extension fee pursuant to 37 C.F.R. § 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.
Correspondence
Any inquiry concerning this communication should be directed to Jeffrey S. Parkin, Ph.D., whose telephone number is (571) 272-0908. The Examiner can normally be reached Monday through Friday from 10:00 AM to 6:00 PM. A message may be left on the Examiner's voice mail service. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner are unsuccessful, the Examiner's supervisor, Michael Allen, Ph.D., can be reached at (571) 270-3497. Direct general status inquiries to the Technology Center 1600 receptionist at (571) 272-1600.
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Respectfully,
/JEFFREY S PARKIN/Primary Examiner, Art Unit 1671 04 January, 2026