DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
2. A request for continued examination under 37 CFR 1.114 was filed in this application after a decision by the Patent Trial and Appeal Board, but before the filing of a Notice of Appeal to the Court of Appeals for the Federal Circuit or the commencement of a civil action. 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examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on December 2, 2025 has been entered.
Claims 1, 2, 5-15, 18-23, 25-28, and 30-32 are pending. Claims 1, 2, 5-7, 9-15, 18, 20-23, 25-28, and 30-32 are under examination. Claims 8 and 19 remain withdrawn as being drawn to a non-elected species.
Response to Arguments
3. In the last Office action, the following rejections were made:
1) Claims 1, 2, 5-7, and 9-13 were rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Harvey in view of Thompson, Hennessy, and Santos as evidenced by the “Helping you build a smarter diagnostic assay” published by GE Healthcare Life Sciences (“the GE publication”) and also as evidenced by Gustavsson;
2) Claims 14, 15, 17, 18, 20-22, 24-28, and 30 were rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Santos as evidenced by the GE publication and also as evidenced by Gustavsson and in view of Seaman;
3) Claim 23 was rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Santos as evidenced by the GE publication and also as evidenced by Gustavsson and in view of Seaman and further in view of Gunstream;
4) Claims 31 and 32 were rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Santos as evidenced by the GE publication and also as evidenced by Gustavsson and in view of Seaman and further in view of Widschwendter and Harvey;
5) Claims 1, 2, 5-7, 9-12, 14, 15, 17, 18, 21, and 22 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of US 10,053,686;
6) Claim 23 was rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of US 10,053,686 in view of Gunstream; and
7) Claims 24-28, 30, and 31 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of US 10,053,686 in view of Harvey.
Applicant’s response of December 2, 2025 does not present any arguments concerning rejections (1) and (4), nor have any of the claims included in those rejections been amended. The rejections have been reconsidered, but they are maintained since they remain applicable.
As to rejections (2) and (3), Applicant argues that independent claim 14 has been amended.1 The response does not present any additional arguments (e.g., that the previously cited references do not meet the requirements of the amended claim). These rejections have been modified to include a new reference that explicitly addresses the new requirement in independent claim 14 for the reaction vessel to be a well in a multi-well plate. The rejections have also been modified to address the cancellation of claims 17 and 24.
As to rejections (5)-(7), claim 14 has been amended. Applicant’s response does not include specific arguments concerning the non-statutory double patenting rejections, nor has a terminal disclaimer been filed. Accordingly, the rejections have been maintained, with modifications to address the amendments to claim 14 and the cancellation of claims 17 and 24, since they remain applicable.
Claim Objections
4. Claim 14 is objected to because of the following informalities. Replacing “a group consisting of” in line 4 of step (i) with “the group consisting of” is suggested to improve consistency with the language in lines 2-3 of step (i).
Claim Rejections - 35 USC § 112
5. 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 14, 15, 18, 20-23, 25-28, and 30 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 14 has been amended to recite the following in step (i): wherein the cellular sample is selected from a group consisting of eukaryotic cell, prokaryotic cell, bacteria, plant and tissue culture cells. The language “group consisting of eukaryotic cell, prokaryotic cell” is grammatically incorrect because a singular article (“an” and “a,” respectively) should precede “eukaryotic cell” and “prokaryotic cell,” respectively, or “eukaryotic cell” and “prokaryotic cell” should be plural (i.e., “eukaryotic cells” and “prokaryotic cells”). As a result of the grammatical issue, it is not clear whether the recited options in step (i) of claim 14 are intended to include analysis of cellular samples consisting of a single cell or not. Since the scope of the claim is not entirely clear, it is indefinite.
Claims 15, 18, 20-23, 25-28, and 30 are also indefinite since they depend from claim 14 and do not remedy its indefiniteness issue.
Claim Rejections - 35 USC § 103
6. The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
7. This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
8. Claims 1, 2, 5-7, and 9-13 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Harvey et al. (US 2010/0106057) in view of Thompson et al. (Methods in Molecular Biology 2012; 830: 3-16), Hennessy et al. (US 2012/0122093 A1), and Santos et al. (Brazilian Journal of Microbiology 2012; 43: 389-392) as evidenced by the “Helping you build a smarter diagnostic assay” publication by GE Healthcare Life Sciences (2013; “the GE publication” below) and also as evidenced by Gustavsson et al. (Journal of Clinical Virology 2009; 46: 112-116).2
The instant claims are drawn to a method for amplifying a nucleic acid. A cellular sample is first contacted with a solid support that comprises a chaotropic salt. Nucleic acid on the solid support is eluted from the support, amplified by qPCR, and quantified in the presence of the solid support. A short tandem repeat (STR) profile is also obtained in the presence of the solid support. Applicant has previously elected the following species for examination: (i) a guanidine salt as the chaotropic salt, and (ii) a cellulose-based support as the solid support.
Regarding claim 1, Harvey teaches a method that comprises PCR and STR profiling (see, e.g., Example 3 on page 5). The method disclosed in Example 3 of Harvey includes the following steps: (i) contacting the solid support with a cellular sample (buccal cells) that contains nucleic acids (para. 65); (ii) transferring the solid support to a reaction vessel (para. 66); (iii) incubating the nucleic acids from step (i) with a nucleic acid amplification reagent solution in the presence of the solid support (para. 66); (iv) subjecting the nucleic acids to PCR in the presence of the solid support (para. 66); and (v) analyzing the PCR products to obtain an STR profile (para. 66).
Regarding claims 6, 7, and 10-12, as evidenced by the specification of the instant application at page 5, the FTA® Elute cards disclosed by Harvey in paragraph 16 are pre-punched cellulose-based solid supports that contain guanidine thiocyanate.
Regarding claim 9, Harvey teaches that the method comprises washing the solid support with an aqueous solution following step (i) (see para. 65, which discloses washing; see also para. 54, which provides more details concerning this wash step and indicates it is conducted using an aqueous solution).
Regarding claim 13, as evidenced by the GE publication on pages 22-23, the FTA® Elute cards disclosed by Harvey in para. 16 also meet the requirements set forth in claim 13.
Harvey does not teach all of the elements of the instant claims. First, Example 3 does not clearly teach generating an eluate as required by step (iii) in independent claim 1. Instead, based on the teachings in the GE publication on page 23, it appears that DNA on the FTA cards used by Harvey in Example 3 remains bound to the solid support during the amplification reaction. Second, Harvey does not meet the requirement in claim 1 for the solid support to contain a chaotropic agent. In view of the election of species requirement, the solid support must contain a chaotropic agent—specifically a guanidine salt as recited in claims 6 and 7. As evidenced by the specification of the instant application at page 5, the FTA® Elute cards disclosed by Harvey in paragraph 16 are pre-punched cellulose-based solid supports that contain guanidine thiocyanate. This solid support was not used to conduct the method of Example 3, however, and since FTA® and FTA® Elute cards are treated with different materials and have different DNA retention properties,3 it is not clear Harvey provides a reasonable expectation of success in practicing the method disclosed in Example 3 with an FTA® Elute card rather than an FTA® card. Third, the PCR disclosed in Example 3 of Harvey is not a qPCR method as required by claim 1. Fourth, it is not clear that the STR analysis was conducted without removing the solid support from the reaction vessel as required by claim 1. Lastly, Harvey fails to meet the requirements of claims 2 and 5.
Thompson, though, discusses methods for human STR profiling and teaches that it is important to determine the amount of human DNA in a sample from which an STR profile is to be determined (page 7, section 2.2, para. 1). In particular, Thompson teaches in this portion of the reference that such a quantification step helps one avoid the poor amplification results that can occur when too much DNA or too little DNA is subjected to multiplex PCR. Thompson then states that “Currently, the best procedure for performing quantification, utilizes real-time PCR” (page 7, section 2.2, para. 2) and goes on to note that real-time PCR offers the advantages of high sensitivity, wide dynamic range, and compatibility with automation (page 8, first paragraph). Thompson further teaches that real-time PCR instruments are available (page 7, last paragraph – page 8, first paragraph).
Thompson does not discuss amplification in the presence of an FTA® Elute card, but Santos discloses a method that comprises conducting PCR in the presence of an FTA® Elute card (abstract and page 390). Further regarding claim 1, as evidenced by Gustavsson in sections 3.2 and 3.3 on page 113, the “direct PCR” of Santos, in which the FTA® Elute card is directly added to the PCR mix, includes an elution step since the heating steps in the PCR described on page 390 of Santos will release the DNA from the FTA® Elute card to generate an eluate that is amplified.4 Further regarding claim 5, Santos teaches conducting PCR in the presence of a primer, polymerase, dNTPs, and a buffer (page 390, column 1).
It would have been prima facie obvious for one of ordinary skill in the art at the time of the invention to substitute the PCR taught in Harvey with a qPCR conducted prior to the STR profiling step when conducting the method of Harvey. Thompson provides motivation to do so by teaching that such a step, which is best conducted using real-time PCR (i.e., qPCR), helps one to avoid the poor PCR results that can occur when too much or too little DNA is used for the multiplex PCR preceding capillary electrophoresis in STR profiling methods (pages 7-8, section 2.2). The ordinary artisan would have recognized that a qPCR step as disclosed in Thompson would have improved the method of Harvey by providing information as to the quantity of human DNA available for the multiplex PCR step in the STR profiling method of Example 3, and thereby, reducing the likelihood of poor amplification results stemming from the use of inappropriate amounts of DNA in the multiplex PCR. The ordinary artisan would have had a reasonable expectation of success since Thompson taught that real-time PCR instruments were available (pages 7-8, section 2.2).
It also would have been prima facie obvious for the ordinary artisan to practice the method suggested by Harvey in view of Thompson using either an FTA® card as disclosed in Example 3 of Harvey or the FTA® Elute card disclosed in para. 16 of that reference. As noted above, Harvey teaches that FTA® or FTA® Elute cards may be used to practice the invention in para. 16. This teaching motivates the use of either card in the method of Example 3, but Harvey fails to provide a reasonable expectation of success for conducting PCR in the presence of the FTA® Elute support. Santos remedies this deficiency, though, by disclosing PCR conditions that are suitable for amplifying DNA in the presence of an FTA® Elute card (page 390). And, further regarding step (iii) in claim 1, elution from the solid support and incubation with an amplification reagent solution occur in the presence of the solid support when subjecting the FTA® Elute card to amplification as taught by Santos.
Furthermore, it also would have been prima facie obvious to obtain the STR profile in the method of Harvey without removing the solid support from the reaction vessel. That is, it would have been obvious to load the CE device used by Harvey in Example 3 to obtain the STR profile directly from the reaction vessel containing the solid support at least because the ordinary artisan would have recognized that doing so would reduce the number of consumables required for the method. The ordinary artisan would have had a reasonable expectation of success since Hennessy teaches that 96-well plates may be used to conduct PCR and to load amplification products into a capillary electrophoresis device (see, e.g., paras. 88-89).
Thus, the methods of claims 1, 5-7, and 9-13 are prima facie obvious.
Further regarding claim 2, it also would have been prima facie obvious to place the solid support in the reaction vessel of Harvey prior to contacting it with the buccal cell sample. As noted in MPEP 2144.04 IV C, it is prima facie obvious to alter the order of method steps in the absence of unexpected results. In this case, there is no particular reason to not place the solid support in the reaction vessel prior to contacting it with the buccal cell sample, and no evidence of unexpected results has been presented. Thus, the method of claim 2 is prima facie obvious.
Finally, further regarding claim 5, it would have been obvious to use an amplification reagent mixture comprising a primer, polymerase, buffer, and dNTPs to conduct the qPCR step in the method suggested by the references. As discussed in MPEP 2144.07, it is prima facie obvious to select a known material based on its suitability for the intended purpose in the absence of unexpected results. In this case, the teachings of Santos on page 390 and Hennessy in para. 59 indicate that the reagents recited in claim 5 are useful for conducting PCR, and no evidence of unexpected results concerning these reagents has been presented. Accordingly, the method of claim 5 is prima facie obvious.
In view of the foregoing, the methods of claims 1, 2, 5-7, and 9-13 are prima facie obvious.
9. Claims 14, 15, 18, 20-22, 25-28, and 30 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Santos et al. (Brazilian Journal of Microbiology 2012; 43: 389-392) as evidenced by each of the “Helping you build a smarter diagnostic assay” publication by GE Healthcare Life Sciences (2013; “the GE publication” below), Gustavsson et al. (Journal of Clinical Virology 2009; 46: 112-116) and in view of Seaman et al. (Virology Journal 2010; 7: 194) and further in view of Boyle et al. (US 2012/0045751 A1).5
The instant claims are drawn to a method for amplifying a nucleic acid. A cellular sample is first contacted with a solid support that comprises a lysis reagent. Applicant has previously elected a cellulose-based support as the solid support and a guanidine salt as the lysis reagent. Nucleic acid on the solid support is then eluted, amplified by qPCR, and quantified in the presence of the solid support.
Regarding claims 14, 18, 20, 21, 25, 27, 28, and 30, Santos teaches a method that comprises performing PCR in the presence of a solid support (abstract and p. 390). In the method of Santos, a cervicovaginal sample to be screened for the presence of HPV is spotted onto an FTA® Elute card (p. 390). The card is stored overnight, and punches are added directly to a reaction vessel and subjected to PCR (p. 390). As evidenced by the specification of the instant application at page 5, FTA® Elute cards are pre-punched cellulose-based solid supports that contain guanidine thiocyanate. Also, as evidenced by the GE publication at pages 22-23, the FTA® Elute cards used by Santos also meet the requirements set forth in claim 20. Further regarding claim 14, as evidenced by Gustavsson in sections 3.2 and 3.3 on page 113, the “direct PCR” of Santos, in which the FTA® Elute card is directly added to the PCR mix, includes an elution step since the heating steps in the PCR described on page 390 of Santos will release the DNA from the FTA® Elute card to generate an eluate that is amplified.6
Further regarding claim 26, Santos suggests using the method for molecular diagnostics (p. 391, col. 2).
Santos does not teach all of the elements of the instant claims. In particular, Santos fails to teach using qPCR to quantify the amplified nucleic acid as required by independent claim 14. Santos also fails to teach that the reaction vessel is a well in a multi-well plate as required by amended independent claim 14. Further, Santos does not teach that the solid support is in the reaction vessel prior to contact with the cervicovaginal sample as required by claim 15. Lastly, regarding claim 22, Santos does not teach washing the solid support with an aqueous solution after contacting the solid support with the cervicovaginal sample.
Seaman describes using real-time PCR to detect and quantify HPV in genital samples, which include cervicovagincal samples (abstract and pp. 2-3). Seaman teaches that “Real time quantitative PCR (qPCR) allows for quantitation of DNA over 8 orders of magnitude” (p. 2, col. 1). Seaman also teaches that real-time PCR is a rapid means for quantification and detection (p. 16, col. 1). Seaman goes on to describe a real-time qPCR assay for HPV (pp. 2-3) and also cites several prior art methods for quantitative detection of HPV (p. 2). Seaman further teaches that quantifying HPV is desirable because “Increasing oncogenic viral loads have been associated with the development of malignancy” (p. 15, col. 1) and additionally hypothesizes that the viral load of non-oncogenic HPV types may be also be associated with the risk of developing warts or other non-malignant conditions associated with HPV infection (p. 15, col. 1).
Further regarding amended independent claim 14, Seaman teaches using a Lightcycler 480 to conduct the disclosed real-time PCRs (p. 3, col. 2), but the reference does not clearly teach using a multi-well plate for the real-time PCRs. Boyle, though, teaches that the Lightcycler 480 can be used with a multi-well plate (see Example 1 on pp. 21-24, esp. para. 409).
It would have been prima facie obvious for one of ordinary skill at the time of the invention to substitute conventional PCR as disclosed in Santos for real-time qPCR as described in Seaman. The ordinary artisan would have been motivated to do so since Seaman taught that real-time qPCR offers a rapid and highly sensitive means for detecting and quantifying HPV (p. 2, col. 1 and p. 16, col. 1). The ordinary artisan also would have been motivated to substitute a quantitative method since Seaman taught that the viral load of oncogenic HPV types is known to be “associated with the development of malignancy” (p. 15, col. 1). The ordinary artisan would have had a reasonable expectation of success in view of the guidance provided by Seaman throughout the reference.
Further regarding amended independent claim 14, in conducting the real-time PCR suggested by Seaman, the ordinary artisan would have been motivated to use a multi-well plate as the real-time PCR reaction vessel. Boyle provides motivation and a reasonable expectation of success by teaching that a multi-well plate is suitable for use in the real-time PCR device used by Seaman (para. 409). See also MPEP 2144.07, which notes that selecting a known material based on its suitability for the intended purpose is prima facie obvious in the absence of unexpected results. In this case, no evidence of unexpected results has been presented with respect to the use of a multi-well plate for amplification, and the cited teachings of Boyle indicate that a multi-well plate is suitable for use as the reaction vessel when conducting real-time PCR in the device used by Seaman.
Thus, the methods of claims 14, 18, 20, 21, 25-28, and 30 are prima facie obvious.
Further regarding claim 15, it also would have been prima facie obvious to place the solid support in the reaction vessel prior to contacting it with the cervicovaginal sample. As noted in MPEP 2144.04 IV C, it is prima facie obvious to alter the order of method steps in the absence of unexpected results. In this case, there is no particular reason not to place the solid support in the reaction vessel prior to contacting it with the cervicovaginal sample, and no evidence of unexpected results has been presented. Thus, the method of claim 15 are prima facie obvious.
Lastly, further regarding claim 22, it also would have been prima facie obvious to wash the solid support between the step of contacting the support with the cervicovaginal sample and placing the solid support in the reaction vessel. Santos teaches two methods for amplifying DNA spotted on FTA elute cards (p. 390). In the first method, the card is washed to remove “impurities and inhibitors”, and then the DNA is eluted and subjected to amplification (p. 390, col. 2). In the second method, punches from the card are placed in reaction vessels containing a PCR mixture and subjected to amplification (p. 390, col. 2). The ordinary artisan would have been motivated to incorporate a wash step before the step of transferring the solid support to a reaction vessel since Santos taught that washing was useful to remove impurities and inhibitors. Since heating is required to elute DNA from the cards (Santos, p. 390, col. 2), the ordinary artisan would have reasonably expected the washing to result in the removal of inhibitors and impurities and not the DNA to be amplified. Thus, the method of claim 22 is prima facie obvious.
10. Claim 23 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Santos et al. (Brazilian Journal of Microbiology 2012; 43: 389-392) as evidenced by each of the “Helping you build a smarter diagnostic assay” publication by GE Healthcare Life Sciences (2013; “the GE publication” below), Gustavsson et al. (Journal of Clinical Virology 2009; 46: 112-116) in view of Seaman et al. (Virology Journal 2010; 7: 194) and further in view of Boyle et al. (US 2012/0045751 A1) and further in view of Gunstream (US 2008/0178653 A1).7
As discussed above, the teachings of Santos as evidenced by each of the GE publication and Gustavsson in view of Seaman and further in view of Boyle render obvious the methods of claims 14, 15, 18, 20-22, 25-28, and 30.
Regarding claim 23, neither Santos nor Seaman teaches or suggests quantification using a PCR imaging system, but Gunstream teaches that real-time PCR methods can include monitoring with a PCR imaging system (para. 24).
It would have been prima facie obvious for one of ordinary skill in the art at the time of the invention to monitor the real-time PCR method suggested by the teachings of Santos in view of Seaman and Boyle with a PCR imaging system. The teachings of Gunstream provide motivation and a reasonable expectation of success since they indicate that such detection was routine and conventional at the time of the invention. Thus, the method of claim 23 is prima facie obvious.
11. Claims 31 and 32 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Santos et al. (Brazilian Journal of Microbiology 2012; 43: 389-392) as evidenced by the “Helping you build a smarter diagnostic assay” publication by GE Healthcare Life Sciences (2013; “the GE publication” below) and as also evidenced by Gustavsson et al. (Journal of Clinical Virology 2009; 46: 112-116) in view of Seaman et al. (Virology Journal 2010; 7: 194) and further in view of Widschwendter et al. (Cancer Letters 2003; 202: 231-239) and Harvey et al. (US 2008/0196517 A1).8
Claims 31 and 32 are drawn to a nucleic acid amplification method. The method uses a serum sample and comprises performing amplification and quantification steps in the presence of a solid support. As noted above, Applicant previously elected cellulose-based solid supports and a guanidine salt for examination.
Regarding claims 31 and 32, Santos teaches a method that comprises PCR in the presence of a solid support (abstract and p. 390). In the method of Santos, a cervicovaginal sample to be screened for the presence of HPV is spotted onto an FTA® Elute card (p. 390). The card is stored overnight, and punches are added directly to a reaction vessel and subjected to PCR (p. 390). As evidenced by the specification of the instant application at page 5, FTA® Elute cards are pre-punched cellulose-based solid supports that contain guanidine thiocyanate, which is a lysis reagent. Also, as evidenced by the GE publication on pages 22-23, the FTA® Elute cards used by Santos also meet the requirements set forth in claim 32. This publication also expressly states that the FTA® Elute cards of Santos contain a lysis reagent (p. 23). Further, as evidenced by Gustavsson in sections 3.2 and 3.3 on page 113, the “direct PCR” of Santos, in which the FTA® Elute card is directly added to the PCR mix, includes an elution step since the heating steps in the PCR described on page 390 of Santos will release the DNA from the FTA® Elute card to generate an eluate that is amplified.9
Santos does not teach all of the elements of the claims since the reference fails to teach a serum sample as required by claim 31. Santos also fails to teach quantifying the amplified nucleic acid in the presence of the solid support as required by claim 31.
Seaman describes using real-time PCR to detect and quantify HPV in genital samples, which include cervicovagincal samples (abstract and pp. 2-3). Seaman teaches that “Real time quantitative PCR (qPCR) allows for quantitation of DNA over 8 orders of magnitude” (p. 2, col. 1). Seaman also teaches that real-time PCR is a rapid means for quantification and detection (p. 16, col. 1). Seaman goes on to describe a real-time qPCR assay for HPV (pp. 2-3) and also cites several prior art methods for quantitative detection of HPV (p. 2). Seaman further teaches that quantifying HPV is desirable because “Increasing oncogenic viral loads have been associated with the development of malignancy” (p. 15, col. 1) and additionally hypothesizes that the viral load of non-oncogenic HPV types may be also be associated with the risk of developing warts or other non-malignant conditions associated with HPV infection (p. 15, col. 1).
Seaman does not teach detecting HPV in serum samples, but Widschwendter teaches that serum may represent a useful additional sample for HPV detection (abstract and pp. 236-238). As well, Harvey teaches that FTA® Elute cards may be used with serum samples (paras. 10, 14, and 27).
It would have been prima facie obvious for one of ordinary skill at the time of the invention to substitute conventional PCR as disclosed in Santos for real-time qPCR as described in Seaman. The ordinary artisan would have been motivated to do so since Seaman taught that real-time qPCR offers a rapid and highly sensitive means for detecting and quantifying HPV (p. 2, col. 1 and p. 16, col. 1). The ordinary artisan also would have been motivated to substitute a quantitative method since Seaman taught that the viral load of oncogenic HPV types is known to be “associated with the development of malignancy” (p. 15, col. 1). The ordinary artisan would have had a reasonable expectation of success in view of the guidance provided by Seaman throughout the reference.
It also would have been prima facie obvious for the ordinary artisan to use the method suggested by Santos in view of Seaman to analyze serum samples. Widschwendter provides motivation to do so by stating that serum samples may represent a useful addition to the traditional cervical cell samples of Santos for HPV detection (abstract and pp. 236-238). The ordinary artisan would have had a reasonable expectation of success in amplifying HPV DNA from serum samples in view of the guidance provided by Widschwendter on pages 236-238. The ordinary artisan also would have had a reasonable expectation of success in using the FTA® Elute cards of Santos with serum samples in view of the teachings of Harvey (paras. 10, 14, and 27).
In view of the foregoing, the methods of claims 31 and 32 are prima facie obvious.
Double Patenting
12. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
13. Claims 1, 2, 5-7, and 9-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,053,686 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘686 patent overlap in scope with the instant claims and teach or suggest all of their limitations.
The instant claims are drawn to a method for amplifying a nucleic acid. The nucleic acid is present in a sample that is contacted with a solid support. The solid support contains a chaotropic salt or a lysis reagent, which may also be a chaotropic salt. Nucleic acids are eluted from the solid support and amplified in the presence of the solid support.
The claims of the ‘686 patent overlap in scope in that they are also drawn to a nucleic acid amplification method that comprises (i) contacting a solid support with a sample that contains nucleic acids, (ii) eluting nucleic acids from the solid support, and (iii) amplifying the eluted nucleic acids in the presence of the solid support.
More specifically, the limitations of the instant claim 1 are recited in claims 1, 4, 8, 13, and 15 of the ‘686 patent. Thus, the instant claim 1 is not patentably distinct from the claims of the ‘686 patent.
The instant claim 2 requires the solid support to be in the reaction vessel prior to the addition of the cellular sample. The claims of the ‘686 patent recite the reverse order of operation (i.e., the solid support is transferred to a reaction vessel after addition of the cellular sample - see claims 1, 15, and 16 of the ’686 patent). As discussed in MPEP 2144.04 IV C, though, changing the order of method steps is prima facie obvious in the absence of unexpected results. In this case, no evidence of unexpected results has been presented, and there is no particular reason to place the solid support in the reaction vessel before or after contacting it with the solid support. Accordingly, the claimed order of steps is prima facie obvious, and the instant claim 2 is not patentably distinct from the claims of the ‘686 patent.
The limitations of the instant claim 5 are recited in claim 7 of the ‘686 patent.
The limitations of the instant claims 6 and 7 are recited in or met by claim 8 of the ‘686 patent.
The limitations of the instant claim 9 are recited in claim 9 of the ‘686 patent.
The limitations of the instant claims 10-12 are recited in claims 10-12, respectively, of the ‘686 patent.
Thus, the instant claims 1, 2, 5-7, and 9-12 are not patentably distinct from the claims of the ‘686 patent.
14. Claims 14, 15, 18, 21, 22, 25-28, 30, and 31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,053,686 B2 in view of Harvey et al. (US 2010/0106057 A1; cited previously).
As discussed above, the instant claims 1, 2, 5-7, and 9-12 are not patentably distinct from the claims of the ‘686 patent.
The limitations of the instant claim 14, which is an independent claim, are recited in claims 1, 4, and 8 of the ‘686 patent with two exceptions: (i) the claims of the ‘686 patent do not specify the type of cellular sample; and (ii) the claims of the ‘686 patent do not recite conducting amplification in a multi-well plate. Similarly, the limitations of the instant claim 31, which is an independent claim, are recited in claims 1 and 8 of the ‘686 patent except for the requirement that the sample is serum.
These differences between the claims of the ‘686 patent and the instant claims 14 and 31 (and also the instant claims 25 and 30, which depend from the instant claim 14 and further limit the type of cellular sample) would have been obvious. As discussed in greater detail above, Harvey discloses a method that comprises the following steps (see Example 3 on page 5): (i) contacting a solid support with a cellular sample (buccal cells, which are eukaryotic cells) that contains nucleic acids (para. 65); (ii) transferring the solid support to a reaction vessel (para. 66); (iii) incubating the nucleic acids with a nucleic acid amplification reagent in the presence of the solid support (para. 66); (iv) subjecting the nucleic acids to PCR in the presence of the solid support (para. 66); and (v) obtaining an STR profile (para. 66). Thus, the method of Harvey is similar to the method recited in the claims of the ‘686 patent since it also involves amplification in the presence of a solid support and obtaining an STR profile.
Then, since Harvey taught that useful samples for practicing this method include the serum, eukaryotic cell, virus-containing, saliva, blood, lymph fluid, buccal cells, CSF, semen, feces, bacterial, or urine samples recited in the instant claims 25, 30, and 31 (paras. 42 and 51), the ordinary artisan would have recognized that these samples would also be suitable for use in the methods recited in the claims of the ‘686 patent and would have been motivated to use them in said methods with a reasonable expectation of success.
And, further regarding the instant claim 14, the ordinary artisan would have been motivated to use any reaction vessel generally known to be useful for amplification reactions (e.g., multi-well plates), recognizing their suitability for the intended purpose. It is further noted that no evidence of unexpected results has been presented with respect to the reaction vessel used for the amplification reaction.
Thus, the instant claims 14, 25, 30, and 31 are not patentably distinct from the claims of the ‘686 patent in view of Harvey.
The limitations of the instant claim 15, which depends from the instant claim 14, are also suggested by the claims of the ‘686 patent. This claim requires the solid support to be in the reaction vessel before addition of the cellular sample. The claims of the ‘686 patent recite the reverse order of operation (i.e., the solid support is transferred to a reaction vessel after addition of the cellular sample - see claims 1, 15, and 16 of the ‘686 patent). As discussed in MPEP 2144.04 IV C, though, changing the order of method steps is prima facie obvious in the absence of unexpected results. In this case, no evidence of unexpected results has been presented, and there is no particular reason to place the solid support in the reaction vessel before or after contacting it with the solid support. Accordingly, the claimed order of steps is prima facie obvious, and the instant claim 15 is not patentably distinct from the claims of the ‘686 patent.
The limitations of the instant claim 18, which depends from the instant claim 14, are met by claim 8 of the ‘686 patent.
The limitations of the instant claims 21 and 22, which depend from the instant claim 14, are recited in claims 10 and 9, respectively, of the ‘686 patent.
Regarding the instant claim 26, which depends from the instant claim 14, the claims of the ‘686 patent do not recite using the amplified nucleic acid as a molecular diagnostics tool, a human identification tool, or a forensics tool. However, since Harvey taught that amplified nucleic acids may be used for forensics, human identification, or diagnostic purposes (see, e.g., para. 51), the ordinary artisan would have recognized these downstream applications as useful in the context of the methods recited in the claims of the ‘686 patent, and, accordingly, would have been motivated to also perform any of these applications with a reasonable expectation of success. Thus, the instant claim 26 is not patentably distinct from the claims of the ‘686 patent in view of Harvey.
Regarding the instant claims 27 and 28, which depend from the instant claim 14, the claims of the ‘686 patent do not recite storing the nucleic acid on the solid support. The ordinary artisan would have recognized, though, that the solid supports used in the methods recited in the claims of the ‘686 patent could be stored for any desired amount of time (e.g., the at least 30 minutes recited in the instant claim 28) since Harvey taught that similar solid supports could be stored prior to processing (see, e.g., the abstract and para. 16). Thus, the instant claims 27 and 28 are not patentably distinct from the claims of the ‘686 patent in view of Harvey.
15. Claim 23 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,053,686 B2 in view of Harvey et al. (US 2010/0106057 A1; cited previously) and further in view of Gunstream (US 2008/0178653 A1; cited previously).
As discussed above, the instant claims 14, 15, 18, 21, 22, 25-28, 30, and 31 are not patentably distinct from the claims of the ‘686 patent in view of Harvey.
Regarding the instant claim 23, which depends from the instant claim 14, the claims of the ‘686 patent do not teach or suggest using a PCR imaging system to quantify amplified nucleic acid. Harvey does not remedy this deficiency, but Gunstream teaches that real-time PCR methods can include monitoring with a PCR imaging system (para. 24).
It would have been prima facie obvious for one of ordinary skill in the art at the time of the invention to monitor the qPCR method suggested by the claims of the ‘686 patent (see claim 4) in view of Harvey using a PCR imaging system. The teachings of Gunstream provide motivation and a reasonable expectation of success since they indicate that such detection was routine and conventional at the time of the invention. Thus, the instant claim 23 is not patentably distinct from the claims of the ‘686 patent in view of Harvey and further in view of Gunstream.
Conclusion
16. No claims are currently allowable.
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/ANGELA M. BERTAGNA/Primary Examiner, Art Unit 1681
1 Claim 23 in rejection (3) depends from claim 14.
2 Each of these references was cited in the last Office action.
3 GE publication at pages 22-23.
4 The language in step (iii) of claim 1 does not exclude a method in which the eluate is generated during PCR. The language “generating an eluate….from the solid support, and incubating said eluate with a nucleic acid amplification reagent solution” encompasses adding the amplification reagent solution to the reaction vessel and generating the eluate in the presence of said reagent solution (e.g., during the PCR).
5 The Boyle reference is newly cited. All other references were cited in the last Office action.
6 As discussed above in the rejection of claim 1, the language in step (iii) of claim 14 does not exclude a method in which the eluate is generated during PCR.
7 The Boyle reference is newly cited. All other references were cited in the last Office action.
8 Each of these references was cited in the last Office action.
9 As noted above in the rejection of claim 1, the language in step (iii) of claim 31 does not exclude a method in which the eluate is generated during PCR.
Prosecution Insights