DETAILED 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 Application
The Response filed December 8, 2025 is acknowledged.
Claims 33-51 were pending and are now canceled. New claims 52-62 are being examined on the merits.
Response to Arguments
Applicant’s arguments filed December 8, 2025 have been fully considered.
The following rejections are WITHDRAWN in view of Applicant’s arguments and amendments to the claims:
Rejection of claims under 35 USC § 112(b), indefiniteness
Rejection of claims under 35 USC § 112(a), written description
Prior art rejections with Selden as the primary reference
The following rejections are MODIFIED:
Rejection of claims under 35 USC § 101
Prior art rejections with Marquez as the primary reference
Response to arguments regarding 35 USC § 101 rejections
Applicant argues that the 35 USC § 101 rejections should not apply to the new claims since this instant claim set restores the claims back to a version which were not originally rejected under 35 USC § 101 (Remarks, p. 41).
The Examiner notes that the claims have been reconsidered for patent eligibility and new 35 USC § 101 rejections have been applied to some of the claims.
Response to arguments regarding prior art rejections
Applicant argues that the prior art rejections should not apply to the new claims since this instant claim set restores the claims back to the version of previous claims 41 and 51 (July 18, 2024 claim set), which were indicated as being free of the art (Remarks, p. 46).
The Examiner agrees that new claim 62 is consistent with prior claims 41 and 51, and consequently is free of the art. However, instant claim 52 is not consistent with prior claims 41 and 51. The prior claims each recited “where the primer sets anneal to a complete or partial sequence of the CR1, CR2, CR3, CR4 and CR5 conserved regions”, as does instant claim 62. However, instant claim 52 recites “where the primer sets anneal to a complete or partial sequence of one or more of the CR1, CR2, CR3, CR4 and CR5 conserved regions”. Thus, instant claim 52, which only requires annealing to one of the conserved regions is broader than instant claim 62 (and prior claims 41 and 51) which require annealing to all 5 of the conserved regions.
The prior art rejections are modified in view of the instant claim amendments.
Claim Interpretation
The claims 52, 54 and 62 recitation “for determining the presence of viable cells in an (analysis) sample” (preamble) is a statement of intended use and does not limit the claim.
When claim language recites an intended use, the claim must be evaluated to determine whether the statement of intended use results in a structural difference between the claimed invention and the prior art. If there is no such structural difference, then the intended use does not limit the claim. MPEP 2111.02 (II). Here, there is no structural difference between a kit that comprises reagents for detecting viable cells, and a kit that comprises the same reagents, but for some other use, and thus these statements do not impose a structural difference on claims.
Claims 53 and 54-61 are construed with corresponding reasoning.
The claims 52-53, 59 and 62 recitations of “short-lived … RNA [molecules/biomarker]”, and the claims 59 and 62 recitation of “short-lived RNA molecules in the analysis sample”, and the claim 62 recitations of “c) … the short-lived … biomarker that is present in viable cells with more than 300 copies per cell, and has nucleic acid sequences in more than one kingdom …, and is not abundant in non-viable cells” are functional limitations.
These limitations are construed as requiring that the detection agent binds/hybridizes to
biomarkers with the required characteristics, and in claims 52-61 specifically to one or more of the CR1, CR2, CR3, CR4 and CR5 conserved regions RPR, or specifically to all of the CR1, CR2, CR3, CR4 and CR5 conserved regions of RPR, in claim 62.
The claim 62 recitation that the detection agent/primer sets “detect[] the short-lived RNA biomarker that is present in viable cells with more than 300 copies per cell, (ii) has one or more nucleic acid sequences in more than one kingdom of life, and … which is found in viable cells and is not abundant in non-viable cells” are functional properties of the detection agent/primer sets. In the instant context of detection of nucleic acid biomarkers, the only function that the detection oligonucleotide has is to hybridize to the target biomarker oligonucleotide, which is RPR1. Thus, the criteria describe the functional ability of a detection agent/primer set to hybridize to RPR, and a detection agent/primer set that does so inherently satisfies these criteria2.
The claim 62 recitation of “wherein the primer sets anneal to a complete or partial sequence of the CR1, CR2, CR3, CR4 and CR5 conserved regions” is being interpreted as requiring that the primer sets anneal to each of CR1 and CR2 and CR3 and CR4 and CR5. Thus, claim 62 comprises an embodiment, e.g., with 5 primer sets, where primer set 1 anneals to CR1, primer set 2 anneals to CR2, primer set 3 anneals to CR3, primer set 4 anneals to CR4 and primer set anneals to CR5. However, claim 62 does not comprise an embodiment, e.g., with one primer set, where the first primer of the set anneals to CR1 and the second primer of the set anneals to CR5, thus creating an amplification product spanning CR1 through CR5 and comprising all of the intervening sequences, because such a primer set does not anneal to each of CR1, CR2, CR3, CR4 and CR5.
The claim 52 recitation of “substantially abundant” is being interpreted consistent with the teachings in the specification (para. 66).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 52-53 and 59-62 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Eligibility is considered in light of MPEP 2106 III, which incorporates the 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG) published on January 17, 2019 (84 Fed. Reg. 50) and is clarified in the October 2019 Update.
As can be seen in the MPEP 2106 III Figure, eligibility analysis requires one to address the following questions: (i) Step 1 – Is the claim directed to one of the four statutory categories (i.e., process, machine, manufacture or composition of matter); (ii) Step 2A – Is the claim directed to a judicial exception (i.e., a natural phenomenon, law of nature or abstract idea); and (iii) Step 2B – does the claim recite additional elements that amount to significantly more than the judicial exception. In addition, as can be seen in the MPEP 2106.04 II Figure, Step 2A is a two-prong inquiry, with Prong One asking whether the claims recite a judicial exception (i.e., an abstract idea, natural phenomenon or law of nature) and Prong Two asking whether the claims recite additional elements that integrate the judicial exception into a practical application.
In this case, as to Step 1, claims 52-53 and 59-62 are directed to one of the four statutory categories since they are drawn to a composition of matter.
The analysis cannot be streamlined, so the claims are considered with respect to Step 2A.
With respect to Prong One of Step 2A, claims 52-53 and 59-62 recite a judicial exception. Specifically, the primers in claims 52 and 62 are a product of nature (i.e., a natural phenomenon). The claims require oligonucleotides that each bind to a particular RNA molecule. While the primer sequences themselves are not specified, they would encompass fragments of the naturally occurring complementary genomic DNA strand. It is not clear that these primers exist in nature, but these oligonucleotides, are, nevertheless, judicial exceptions because they are derived from naturally occurring nucleic acids (see, e.g., Marquez, cited below in conjunction with the prior art rejections; Table 1: CRIV#2 sequence; p. 750, left col., para. 3) and possess no structural or functional differences relative to their naturally occurring counterpart. For example, the oligonucleotides are not required to include a label or non-naturally occurring nucleotides, nor do they have functions not possessed by naturally occurring nucleic acids. As well, MPEP 2164.04(b)(i) identifies isolated nucleic acids having no structural or functional differences from naturally occurring nucleic acids as an example of a patent-ineligible natural product.
In addition, as discussed in MPEP 2016.04(b)(II), “[P]roduct of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart.” See Ambry Genetics, 774 F.3d at 760, 113 USPQ2d at 1244. In this case, the claimed oligonucleotides have no functional differences relative to their naturally occurring counterparts since both the claimed and naturally occurring molecules hybridize to complementary nucleic acids.
Further, additional products of nature include, the conditioning reagent in claims 52 and 62, e.g., cell culture media3, the lysis reagent in claims 53, 59 and 62, e.g., lysozyme and proteases4, and the positive control of claim 61, e.g., RPR RNA5.
In view of the foregoing, claims 52-53 and 59-62 clearly recite judicial exceptions. With respect to Prong Two of Step 2A, the claims do not recite additional elements that integrate the judicial exceptions into a practical application for the following reason. In particular, the elements in the claim other than the judicial exception (i.e., reaction vessel) constitute insignificant extra-solution activity as described in the 2019 PEG and MPEP 2106.05(g). In addition, to the extent that “kit” is construed to require something additional, such as assembling the various oligonucleotides into container(s), this also constitutes insignificant extra-solution activity as described in the 2019 PEG and MPEP 2106.05(g).
Thus, the answer to step 2A is “Yes, the claims are directed to a judicial exception,” and the analysis moves to Step 2B, which asks if the additional elements in the claim amount to significantly more than the judicial exception.
In this case, claims 52-53 and 59-62 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the use of reaction vessels was routinely taught in the art prior to the effective filing date of the claimed invention, as was assembling nucleotides into kits (e.g., see Marquez and Kubit, cited below in conjunction with the prior art rejections). Therefore, the additional elements in claims 52-53 and 59-62 are not non-routine or unconventional.
In view of the foregoing, claims 52-53 and 59-62 are rejected under 35 U.S.C. 101 as being drawn to a judicial exception without significantly more.
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.
Claims 52-53 and 59-61 are rejected under 35 U.S.C. 103 as being unpatentable over Marquez6 (Structural implications of novel diversity in eucaryal RNase P RNA, RNA, 11(5):739-751, 2005) in view of Kubit7 (WO 2022/051570) and Innings8 (Multiplex Real-Time PCR Targeting the RNase P RNA Gene for Detection and Identification of Candida Species in Blood, Journal of Clinical Microbiology, 45(3): 874-880, 2007).
Regarding independent claim 52, Marquez teaches …
A composition for determining the presence of viable cells in an analysis sample, the composition comprising: a) one or more conditioning reagents that provide conditions in the analysis sample such that the viable cells present in the analysis sample possess abundant short-lived RNA molecules (p. 747, right col., para. 3: cells were grown in media; trophozoites were maintained in TYI-S-33 medium; the instant specification teaches culture media as a conditioning reagent (paras. 59, 68));
one or more RT-PCR primers which target RPR, where the primers anneal to a complete or partial sequence of the CR5 conserved region and where the RT-PCR primers are configured to produce a product which is directly or indirectly detectable to indicate the presence of the RPR RNA (p. 749, left col., para. 1; Table 1: primer used to detect RPR CRV; p. 740, right col., para. 3; Fig. 1; p. 742, right col., para. 2);
Marquez does not explicitly teach that the RPR RNA biomarker is substantially abundant in viable cells and non-abundant in non-viable cells. However, Marquez implicitly teaches this limitation, as Marquez teaches RPR, and the instant specification admits that RPR has these characteristics (e.g., paras. 46, 77)9.
Further, Kubit teaches assembling the components into a kit (e.g., paras. 11, 436-439). In addition, Innings teaches primer sets that anneal to RPR CR1 or CR5 regions (p. 875, right col., para. 4).
Regarding dependent claims 60-61, Marquez additionally teaches or suggests including one or more reaction vessels (p. 748, right col., para. 3: discusses primer extension of gel-purified RNA; the ordinary artisan understands that gel-purified RNA is placed in a reaction vessel), as recited in claim 60, and one or more positive or negative control reagents (p. 749, left col., para. 1), as recited in claim 61.
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Marquez composition by combining the various components into a kit, as taught by Kubit. The ordinary artisan would have been motivated to do so to with the expectation of achieving an advantage of a more efficient method of reagent storage and transport. The ordinary artisan would have had an expectation of success as assembling various reaction components into a kit is well-known in the art.
It would have been further obvious to incorporate primer sets that are specific to RPR conserved regions, into the Marquez composition. Marquez teaches that certain regions of RPR are conserved across various species (p. 749, right col., para. 2). Thus, the ordinary artisan would have been motivated to incorporate primer sets that anneal to conserved regions of RPR into the kit, with the expectation that doing so would result in the advantage of an assay that can detect RPR from a number of different organisms. The ordinary artisan would have had an expectation of success as modifying reagent kits and methods to detect different targets is well-known in the art.
Regarding dependent claims 53 and 59, Marquez teaches an RNA access component for providing access to a short-lived RNA molecule, present in viable cells in the analysis sample (p. 747, right col., para. 4); the components comprising: i) a capture agent to access the short-lived RNA molecules in the analysis sample (p. 747, right col., para. 4: DEAE-cellulose column).
Claims 54-58 are rejected under 35 U.S.C. 103 as being unpatentable over Marquez (Structural implications of novel diversity in eucaryal RNase P RNA, RNA, 11(5):739-751, 2005) in view of Kubit (WO 2022/051570), and Innings (Multiplex Real-Time PCR Targeting the RNase P RNA Gene for Detection and Identification of Candida Species in Blood, Journal of Clinical Microbiology, 45(3): 874-880, 2007), as applied to claim 53 above, and further in view of Selden10 (WO 2020/028273).
Independent claim 54 incorporates the kit of claim 53 (see prior art citations above). In addition, Marquez teaches or suggests one or more reaction vessels (p. 748, right col., para. 3: discusses primer extension of gel-purified RNA; the ordinary artisan understands that gel-purified RNA is placed in a reaction vessel). Further, Selden teaches areas for modifying temperature (para. 81) and manipulating the cell (paras. 118), and an area for target detection (para. 118).
Regarding dependent claims 55 and 57-58, Selden additionally teaches that the RNA access component is a hardware device (para. 119), as recited in claim 55, and that the system is at least partially automated (para. 118), as recited in claim 58. In addition, Selden teaches that the system performs real-time measurements of the target (para. 81), as recited in claim 57.
Regarding dependent claim 56, Selden additionally teaches that the area for target detection comprises a device that performs nucleic acid amplification using isothermal or changing temperatures using a single zone (para. 81; para. 118: “[a]ll the process steps required for DNA analysis are integrated in a single plastic consumable”).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Marquez composition with the various Selden system components. Marquez teaches methods for various amplification reactions (p. 748, right col., para. 3), but does not explicitly teach systems that are capable of executing the amplification reaction method steps. Selden teaches an integrated system that has the capability of executing such method steps (para. 89). The ordinary artisan would thus be motivated to try the Selden system components with the modified Marquez kit because the Selden system is known to be suitable for such a purpose. MPEP 2144.07. The ordinary artisan would do so to achieve the expected advantage of an integrated system that could be used efficiently in a point-of-care setting, and would have an expectation of success as the design and modification of systems that are capable of performing nucleic acid amplification systems is well-known in the art, and because Marquez does not limit what systems are used to perform the various methods.
Conclusion
Claims 52-62 are being examined, and are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
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/CAROLYN L GREENE/Primary Examiner, Art Unit 1681
1 See Cooper (The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. Detection of Nucleic Acids and Proteins. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9916): “[n]ucleic acid hybridization provides a means for detecting DNA or RNA sequences that are complementary to any isolated nucleic acid” (p. 1, para. 3).
2 See MPEP 2112 (I), which states that “the claiming of a new … function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable”. Also see MPEP 2112.01 (I), which states that “[w]here the claimed and prior art products are identical or substantially identical in structure or composition … a prima facie case of either anticipation or obviousness has been established”, and MPEP 2112.01 (II), which states that “[p]roducts of identical chemical composition cannot have mutually exclusive properties”. Finally, see MPEP 707 which states that the examiner may rely upon admissions by the application in rejecting claims as to any matter affecting patentability.
3 The specification teaches that the “conditioning reagent” includes “natural cell culture media” (para. 54).
4 The specification teaches that the “lysis reagent” includes “enzymes such as lysozyme or proteases” (para. 74).
5 The specification teaches that the controls can include an internal spike-in RNA (para. 66). The ordinary artisan would understand that here the spike-in RNA control would be RPR RNA.
6 Marquez was cited in the PTO-892 Notice of References Cited mailed August 8, 2025.
7 Kubit was cited in the PTO-892 Notice of References Cited mailed August 1, 2024.
8 Innings was cited in the PTO-892 Notice of References Cited mailed January 6, 2025.
9 Also see MPEP 2112 (I), which states that “the claiming of a new … function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable”. Also see MPEP 2112.01 (I), which states that “[w]here the claimed and prior art products are identical or substantially identical in structure or composition … a prima facie case of either anticipation or obviousness has been established”, and MPEP 2112.01 (II), which states that “[p]roducts of identical chemical composition cannot have mutually exclusive properties”. Finally, see MPEP 707 which states that the examiner may rely upon admissions by the application in rejecting claims as to any matter affecting patentability.
10 Selden was cited in the Information Disclosure Statement submitted July 2, 2024.