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 .
Applicant’s amendment filed on October 7, 2025 is acknowledged and has been entered. Claim 2-3 has been canceled. Claims 1, 13-14 have been amended. Claim 15 has been added. Claims 1 and 4-15 are pending.
Claims 1 and 4-15 are discussed in this Office action.
All of the amendments and arguments have been thoroughly reviewed and considered but are not found persuasive for the reasons discussed below. Any rejection not reiterated in this action has been withdrawn as being obviated by the amendment of the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is made FINAL as necessitated by Amendment.
New Grounds of Rejection – Necessitated by Amendment
Claim Rejections - 35 USC § 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3-6, 8, 10-12 and 14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nielsen et al (US Patent; 8894946 B2; November 2014).
With regard to claim 1, Nielsen teaches a method of amplifying nucleic acids from a direct blood sample comprising:
(a) adding the direct blood sample to a sample buffer (col. 4, line 34 to line 42; col. 7, lines 25-line 53, where the sample includes blood; see also col. 61, where the collected sample includes blood);
(b) bead beating the sample buffer (col. 7, lines 32-46, where beads are part of processing the sample; see also Fig 10, col. 16, where “four bead suspension and capture chambers 1003”; see also Fig 48, col. 9, lines 58 to col. 10, line 10, where “The sample cartridge comprises a sample receptacle to receive a sample and areas to perform functions such as cell lysis, DNA capture and wash, DNA amplification and DNA dilution”; see Fig 48, where the steps are depicted);
(c) extracting the nucleic acids from the sample buffer (col. 7, lines 32-46, where beads are part of processing the sample; see also Fig 10, col. 16, where “four bead suspension and capture chambers 1003”; see also Fig 48, col. 9, lines 58 to col. 10, line 10, where “The sample cartridge comprises a sample receptacle to receive a sample and areas to perform functions such as cell lysis, DNA capture and wash, DNA amplification and DNA dilution”; see Fig 48, where the steps are depicted);
(d) amplifying the nucleic acids (col. 7, lines 32-46, where beads are part of processing the sample; see also Fig 10, col. 16, where “four bead suspension and capture chambers 1003”; see also Fig 48, col. 9, lines 58 to col. 10, line 10, where “The sample cartridge comprises a sample receptacle to receive a sample and areas to perform functions such as cell lysis, DNA capture and wash, DNA amplification and DNA dilution”; see Fig 48, where the steps are depicted),
wherein steps (b) through (d) are performed in a closed sample vessel (col. 10, line 17-24, col. 11, line 14-21, where the vessels or chambers are closed);
wherein steps (a) through (d) are performed without centrifugation, ethanol precipitation,
and DNA digestion (col. 7, lines 32-46, where beads are part of processing the sample; see also Fig 10, col. 16, where “four bead suspension and capture chambers 1003”; see also Fig 48, col. 9, lines 58 to col. 10, line 10, where “The sample cartridge comprises a sample receptacle to receive a sample and areas to perform functions such as cell lysis, DNA capture and wash, DNA amplification and DNA dilution”; see Fig 48, where the steps are depicted and where the method steps do not include centrifugation, precipitation or digestion), and
wherein a ratio of direct blood sample to sample buffer is in a range from 1 to 8 to 1 to 1,
preferably in a range from 1 to 5 to 1 to 1.67 (col. 40 and col. 45-46, where various amounts of components of the fluids, amounts and liquids used within the cartridge).
With regard to claim 4, Nielsen teaches a method of claim 1. wherein the nucleic acids are host RNA (col. 7, lines 25-line 53, where the sample includes blood and DNA, RNA or protein).
With regard to claim 5, Nielsen teaches a method of claim 1. wherein the direct blood sample is collected in a RNA stabilized solution (col. 7, lines 25-line 53, where the sample includes blood and DNA, RNA or protein).
With regard to claim 6, Nielsen teaches a method of claim 1. wherein the direct blood sample is collected in a non-RNA stabilizing solution (col. 7, lines 25-line 53, where the sample includes blood and DNA, RNA or protein).
With regard to claim 11, Nielsen teaches a method of claim 1, further comprising washing the nucleic acids following the extracting step. wherein the washing step comprises no more than three washes (Fig 11, Fig 37 and col. 9, lines 58 to col. 10, line 10, where “The sample cartridge comprises a sample receptacle to receive a sample and areas to perform functions such as cell lysis, DNA capture and wash, DNA amplification and DNA dilution”, where wash steps and wash buffers are included).
With regard to claim 12, Nielsen teaches a method of claim 1, wherein the sample buffer includes a guanidinium compound (col. 16, line 61 to col. 17, line 29, where guanidine salts are included).
With regard to claim 14, Nielsen teaches a method of claim 1, further comprising: providing the closed sample vessel having, in fluid communication:
i. one or more ports, including an injector port for introducing the direct blood sample and the sample buffer into the closed sample vessel, wherein the one or more ports are sealable ports configured to close the closed sample vessel (Fig 15, col. 2, line 64 to col. 3, line 18, where ports are included),
ii. a cell lysis zone configured for lysing cells or spores present in the direct blood sample (see Fig 48, where the steps are depicted; col. 9, lines 58 to col. 10, line 10, where “The sample cartridge comprises a sample receptacle to receive a sample and areas to perform functions such as cell lysis, DNA capture and wash, DNA amplification and DNA dilution”),
iii. a nucleic acid preparation zone, the nucleic acid preparation zone configured for purifying a plurality of nucleic acids that may be in the direct blood sample, wherein the nucleic acid preparation zone, cell lysis zone, and the injector port are fluidically connected (see Fig 48, where the steps are depicted; col. 9, lines 58 to col. 10, line 10, where “The sample cartridge comprises a sample receptacle to receive a sample and areas to perform functions such as cell lysis, DNA capture and wash, DNA amplification and DNA dilution”);
iv. at least one amplification zone fluidically connected to the nucleic acid preparation zone, the amplification zone configured for amplification of the plurality of nucleic acids that may be in the direct blood sample (see Fig 48, where the steps are depicted; col. 9, lines 58 to col. 10, line 10, where “The sample cartridge comprises a sample receptacle to receive a sample and areas to perform functions such as cell lysis, DNA capture and wash, DNA amplification and DNA dilution”).
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.
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 as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention 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.
Claim(s) 7-8 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nielsen et al (US Patent; 8894946 B2; November 2014) as applied over claims 1, 3-6, 11-12 and 14 above and further in view of Wang et al. (Lab Chip, 2010, 10:3157-3162).
With regard to claim 7, Wang teaches a method of claim 1, wherein the direct blood sample is separated prior to step (a) and a blood fraction is used (Abstract; “plasma separation from whole blood” heading, p 3157, Fig 1, where plasma is separated).
With regard to claim 8, Wang teaches a method of claim 1. further comprising filtering the sample between steps (a) and (b) (Abstract; “plasma separation from whole blood” heading, p 3157, Fig 1, where a filter is included).
With regard to claim 15, Wang teaches a method of claim 1, wherein steps (a)-(c) are completed in 2 minutes or less (Abstract).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Nielsen to include a fractionated blood sample source as taught by Siegrist to arrive at the claimed invention with a reasonable expectation for success. First, Nielsen teaches “disclosure provides an integrated and automated
sample-to-answer system that, starting from a sample comprising biological material, generates a genetic profile in less than two hours. In certain embodiments, the biological material is DNA and the genetic profile involves determining alleles at one or a plurality of loci ( e.g., genetic loci) of a subject,” (Abstract). Nielsen also notes “need for systems that have a smaller footprint in relation to other systems and in a faster time. In addition, there is a need for systems and methods that enable genetic profiling at lower cost with less skilled operators” (col. 2, line 9-12). While Nielsen teaches samples that include blood samples, Nielsen does not specifically teach fractionation of the sample. Siegrist teaches “Direct processing of raw blood samples remains a challenge for NA diagnostics, as these samples pose large hurdles due to their high concentration of inhibitors and their very low concentration of analyte.3 For example, sepsis related microbe concentrations in blood can be <10 NA molecules per mL when directly targeting microbial DNA” (p 363, col. 2). Further, Siegrist teaches “mechanical lysis is the most effective method for breaking down cells that have thick cell walls, such as Gram positive microbes, and for successfully extracting intact DNA. One mechanical lysis method known as bead-beating is the most efficient method in this respect, and functions by combining the sample with an agitated mixture of milling beads” (p 364, col. 1). Siegrist teaches “a new system with a smaller footprint amenable to integration. By changing the experimental setup from a radial length system to one that works in the inner radius of the CD, space has been created for additional analysis steps. Several new centrifugal microfluidic functions have been implemented, and considerations for practical use in the clinic have been kept in mind” (p 371, col. 1) Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Nielsen to include a fractionated blood sample source as taught by Siegrist to arrive at the claimed invention with a reasonable expectation for success.
Claim(s) 9-10 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nielsen et al (US Patent; 8894946 B2; November 2014) as applied over claims 1, 3-6, 11-12 above and further in view of Yamada et al. (J of Clin Micro, 2011: 2552-2556).
With regard to claim 9, Yamada teaches a method of claim 1, wherein the nucleic acids are provided in high copy number (Fig 2 legend; p 2554, col. 1, where a range of copy numbers are described; p 2555, col. 2, where copy number is described in more detail).
With regard to claim 10, Yamada teaches a method of claim 1, wherein the nucleic acids are from microorganisms (Abstract).
With regard to claim 13, Yamada teaches a method of claim 1, wherein step (g) includes a first-stage multiplex PCR and a plurality of individual second-stage PCR reactions (Abstract, where multiplex nested PCR is described and includes multiple stages of PCR; p 2553, “Congenital toxoplasmosis screening method” where multiplex nested amplification is described).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Nielsen to include nested multiplex and high copy number nucleic acids as taught by Yamada to arrive at the claimed invention with a reasonable expectation for success. First, Nielsen teaches “disclosure provides an integrated and automated sample-to-answer system that, starting from a sample comprising biological material, generates a genetic profile in less than two hours. In certain embodiments, the biological material is DNA and the genetic profile involves determining alleles at one or a plurality of loci ( e.g., genetic loci) of a subject,” (Abstract). Nielsen also notes “need for systems that have a smaller footprint in relation to other systems and in a faster time. In addition, there is a need for systems and methods that enable genetic profiling at lower cost with less skilled operators” (col. 2, line 9-12) While Nielsen teaches amplification, Nielsen does not specifically teach multiplex amplification. Yamada teaches “Acute infection with Toxoplasma gondii during pregnancy can cause congenital toxoplasmosis. The aim of this study was to evaluate whether screening with the use of IgG avidity and multiplex nested PCR methods was effective to detect a high-risk pregnancy” (Abstract). Yamada also teaches “Multiplex nested PCR for T. gondii DNA on amniotic fluid, maternal blood, and umbilical cord blood were performed with informed consent” (Abstract). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Nielsen to include nested multiplex and high copy number nucleic acids as taught by Yamada to arrive at the claimed invention with a reasonable expectation for success.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1 and 4-15 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Jovanovich et al. (US 20150136602; May 2015). Eberhart et al. (US Patent 10865440 B2; December 2020).
Conclusion
No claims are allowed. All claims stand rejected.
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 STEPHANIE KANE MUMMERT whose telephone number is (571)272-8503. The examiner can normally be reached M-F 9:00-5:30.
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/STEPHANIE K MUMMERT/Primary Examiner, Art Unit 1681