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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/12/2026 and 05/15/2026 was filed after the mailing date of the Non-final Rejection on 03/11/2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of claims / Response to Amendment
This office action is in response to an amendment filed on July 30, 2026.
Claims 1-6 were previously pending. Applicant amended claims 1-6; added new claims 7-20.
Claims 1-20 are currently pending, with claims 8-20 withdrawn.
Claims 1-7 are under consideration.
Applicant's submission of the amendment to specification obviated the previously presented objection.
All of the previously presented claim objections and rejections have been withdrawn as being addressed or obviated by the amendment of the claims, which added new limitations to the claims, that were not considered in the previous rejections.
Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
This office action contains new grounds for rejection necessitated by amendment.
Election/Restrictions
This application contains claims directed to the following patentably distinct species:
Species of blood RT-PCR assaying methods
A) A method for identifying Staphylococcus aureus, Escherichia coli, or Pseudomonas aeruginosa in a whole-blood sample, comprising a step of performing multiplex quantitative polymerase chain reaction with primer pairs that specifically amplify a plurality of RNA targets for Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa (claim 1-7);
B) A method for identifying one or more bacteria in a whole-blood sample from a patient as a cause of pneumonia in the patient (claim 8-13);
C) A method for identifying expression of antimicrobial resistance genes in a whole-blood sample from a patient having an infection, and requires performing target-specific amplification for specific antimicrobial resistance genes (claim 14-20).
The species are independent or distinct because the different species recite separate characteristics of such species, and there is no disclosure of relationship between species (see MPEP § 806.04(b)). In addition, these species are not obvious variants of each other based on the current record. The species necessitate separate searches, leading to serious search and/or examination burden (see MPEP § 808.01(a)) because the Species of blood RT-PCR assaying methods reflect distinct, independent methods that have different objectives, require different method steps for analyzing samples from independent cohorts of patients, resulting in separate searches.
There is a serious search and/or examination burden for the patentably distinct species as set forth above because at least the following reason(s) apply: The species require a different field of search (e.g., searching different classes/subclasses or electronic resources, or employing different search queries); and/or the prior art applicable to one species would not likely be applicable to another species; and/or the species are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph.
Applicant’s election without traverse of the species directed to the method of claims 1-7, in the reply filed on July 30, 2026 is acknowledged.
Claims 8-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Priority
The applicant claims priority of US provisional applications NO. 63/378,366 and 63/378,365, both have filling date on October 04, 2022.
Claim Interpretation
In evaluating the patentability of the claims presented in this application, claim terms have been given their broadest reasonable interpretation (BRI) consistent with the specification, as understood by one of ordinary skill in the art, as outlined in MPEP§ 2111.
For the purpose of applying prior art, claim 1 recites "performing multiplex quantitative polymerase chain reaction on the cDNA with a plurality of oligonucleotide primer pairs that specifically amplify a plurality of RNA targets. "
Under BRI and in light of the specification ([00131]), "primer pairs that specifically amplify a plurality of RNA targets" are understood as primer pairs capable of amplifying RNA-derived nucleic acid sequences, such as cDNA.
For the purpose of applying prior art, claim 1 recites an "RNA-stabilizing blood-collection tube," which is not defined in the application's disclosure.
Therefore, under BRI, "RNA-stabilizing blood-collection tube" is interpreted as encompassing blood collection tubes suitable for supporting downstream RNA analysis.
For the purpose of applying prior art, the recitation in claim 1 that "wherein the plurality of RNA targets were previously identified … " by the specified sequencing process is interpreted as describing how the targets were previously identified, and does not require performance of the identification process as part of the claimed RT-qPCR method.
The claim further states that the RNA targets were selected based on having "abundant reads in common across blood samples from multiple patients having positive blood cultures for the corresponding bacterium." However, the claim does not recite any threshold for "abundant,1" nor does it otherwise recite structural characteristics that distinguish the selected targets from any target sequences from the recited bacteria.
Accordingly, under BRI, the claimed amplification target is interpreted as encompassing sequence region from a recited bacteria species (Staphylococcus aureus, Escherichia coli, or Pseudomonas aeruginosa) that is capable of being detected in more than one sample comprising the bacteria species.
Claim Rejections - 35 USC § 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.
Claims 1-7 are rejected 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 (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A) Regarding claim 1, it recites that the amplification targets "were previously identified" by the specified sequencing-based identification process. As discussed in the claim interpretation section above, this language is interpreted as describing how the targets were previously identified and does not require performance of the identification process as part of the claimed RT-qPCR method.
The question of whether the target identification process impose any structural limitation on the primers used in the step of "performing multiplex quantitative polymerase chain reaction" has been considered. However, this process is indefinite.
Specifically, the target identification process includes step (iv):
(iv) selecting, for primer design, RNA target regions that have abundant reads in common across blood samples from multiple patients having positive blood cultures for the corresponding bacterium, are unique to the corresponding bacterium and distinct from other bacteria, and are selected based on expression pattern and abundance to distinguish infection from colonization.
This claim language is indefinite because:
it is unclear what qualifies as "abundant";
it is unclear what "unique" and "distinct" modify; and
it is unclear how the selection based on "expression pattern and abundance to distinguish infection from colonization" is carried out.
First, it is unclear what amount of reads constitute "abundance." It is further unclear whether "abundant reads in common" refers to frequency across samples, such as one read being present in common across then samples, or to the number of reads found in each sample, such as at least 100 common reads being present in each sample tested.
Second, it is unclear whether "unique" and "distinct" modify the read sequences themselves or the abundance of reads. For example, it is unclear whether the limitation requires a read sequence, such as "AATTCCGG," to be found only in samples positive for a single bacterial species and not in samples positive for others; or whether the limitation requires that the read sequence have a unique abundance level in one bacterial species sample compared with all others, but the presence of the read sequence is permitted in all samples.
Further, this claim language "unique to the corresponding bacterium and distinct from other bacteria," appears to implicitly require comparing reads obtained from samples positive for each of the recited bacterial species in order to determine whether they are unique or distinct. However, the sequencing step (i) only recites sequencing samples positive for one of the three bacterial species. Thus, it is unclear how the sequencing step provides the comparative data needed.
Third, it is unclear how selection based on "expression pattern and abundance to distinguish infection from colonization" is carried out. The application's disclosure does not provide clear criteria for making this selection. Further, to distinguish infection from colonization, it appears that data from at least infection-only samples and colonization-only samples would need to be obtained and compared. However, the claim does not recite such data.
The specification does not provide any objective standard for target selection process nor does it make clear what structural features, if any, are required by the recited target identification process. Accordingly, it is unclear what structural characteristics the claimed primer pairs or amplification targets are required to have in accordance with the identification process.
For the purpose of compact prosecution and applying prior art under 35 USC§ 102 and 103, in the absence of any structural features clearly imposed by the target identification process, the claim language describing the identification process is interpreted as not further limiting the claimed primer pairs or targets.
Claims 2-7 are rejected for depending from claim 1 and not remedying the indefiniteness.
B) Claim 6 recites : "wherein the RNA target regions selected according to step (iv) comprise parts of the custom genomes having the most abundant reads," which is indefinite. The phrase "the most abundance reads" is a relative term and is indefinite because it is unclear what the reads are "most abundant" compared to.
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 1-7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Independent claim 1 is drawn to a method comprising steps for performing, with a blood sample without culturing from a patient having bacteremia, a multiplex quantitative polymerase chain reaction assay for detection of bacterial RNA from Staphylococcus aureus, Escherichia coli, or Pseudomonas aeruginosa, in order to determine which bacterial species is the cause of bacteremia.
Following the analysis below the claims are not patent eligible under 35 U.S.C. 101.
Step 1 - Whether the Claim is to a Statutory Category: YES. The claims are drawn to a method, therefore to one of the four statutory categories.
Step 2A Prong 1 - Whether the Claim Recite an Abstract idea, Law of Nature, or Natural Phenomenon: Yes.
As stated in MPEP 2106.04(b)(I), laws of nature and natural phenomena, as identified by the courts, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature.
Here, the claim recites a judicial exception, namely a law of nature of natural phenomenon. Specifically, the claim recites the natural correlation between the presence of bacteria and a condition caused by the bacteria (e.g., bacteremia), observed in a subject.
In conclusion, the claims recite laws of nature and natural phenomena.
Step 2A Prong 2 - Whether the Claim Recite Additional Elements that Integrate the Judicial Exception into a Practical Application: No. The claim as a whole do not integrates the exception into a practical application of that exception.
The additional element in the claim do not integrate the recited judicial exception into a practical application of the exception.
As discussed in the claim interpretation section, the target identification process, recited in the past tense, is not required by the claimed multiplex RT-PCR method. Therefore, that process cannot impose a meaningful limit sufficient to transform the judicial exception into patent-eligible subject matter.
Claim 1 involves a natural correlation (correlation between the presence of bacteria and bacteremia caused by the bacteria), and recites steps of collecting blood, extract RNA, and performing reverse transcription multiplex qPCR to detect bacterial RNA. These steps reflect observation of the naturally occurring correlation, using well-established approaches in the art, and reflect extra-solution activities for data gathering. See MPEP §2106.04(d).
Thus, these method steps merely observe the judicial exception and do not integrate it into a practical application.
Step 2B- Whether a Claim Amounts to Significantly More: No.
According to MPEP§ 2106.05, The second part of the Alice/Mayo test is often referred to as a search for an inventive concept. Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 217, 110 USPQ2d 1976, 1981 (2014) (citing Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71-72, 101 USPQ2d 1961, 1966 (2012)). An “inventive concept” is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966).
In this instant case, the claims, when considered as a whole, do not recite any inventive concept with additional elements that amount to significantly more than the judicial exception.
The claim recites steps of collecting blood, extract RNA, and performing reverse transcription multiplex qPCR to detect bacterial RNA. However, these elements reflect extra-solution activities for data gathering, using well-known and conventional molecular biology techniques (see Thomann (US20210002715A1), discloses performing multiplex amplification (e.g., RT-PCR,[0095]) in whole blood for pathogen detection. see Abstract; [0095]-[0096]; [0098]; [0249] ; see also Savelkoul (US20170349937A1), [0097]-[0099]; [0100]-[0103]; [0114]-[0116]).
Performing a multiplex qPCR from blood without culturing, with a time-to-result being within 4 hours is also well-known in the art (see Tsalik (US20180245154A1), [0022]; [0092]"Real-time PCR may be used to quickly identify gene expression from a whole blood sample"; [0155] time to result 30-45 minutes; [0239]; Opota et al., Microbial diagnosis of bloodstream infection: towards molecular diagnosis directly from blood. Clin Microbiol Infect. 2015 Apr;21(4):323-31. doi: 10.1016/j.cmi.2015.02.005. Epub 2015 Feb 14. PMID: 25686695.; see Figure 2 ;
See also Lee et al, ; A polymer lab-on-a-chip for reverse transcription (RT)-PCR based point-of-care clinical diagnostics. Lab Chip 2008; 8 (12): 2121–2127,
Time to result is less than 35 minutes).
As recognized by the courts, determining the marker expression level through molecular biology techniques such as PCR amplification and sequencing, represents well-understood, routine, conventional activity in the life science arts. See University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014).
The dependent claims do not recite additional elements that amount to significantly more than the judicial exception, as they either further describe the judicial exception or represent mere general linkage of the judicial exception to the additional elements in the claims (MPEP § 2106.05(h)).
In conclusion, the claims 1-7 are not patent eligible under 35 U.S.C. 101.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Savelkoul (US20170349937A1- Test for Microbial Blood Infections ; published 2017-12-07), in view of Thomann (US20210002715A1- Methods and systems for amplification in complex samples; published 2021-01-07).
A) Savelkoul teaches methods for detecting microbial blood infections including sepsis in a subject, comprising real-time PCR reactions for detection of specific microorganisms (Abstract), using primers containing sequences that specifically hybridizes to target regions (e.g., gene products, such as a RNA product) ([0101]; [0081]), wherein the target nucleic acid is obtained or derived from Pseudomonas aeruginosa, Escherichia coli and/or Staphylococcus aureus ([0108]).
Regarding claim 1, Savelkoul teaches a method for identifying Staphylococcus aureus, Escherichia coli, or Pseudomonas aeruginosa in a whole-blood sample from a patient having bacteremia caused by Staphylococcus aureus, Escherichia coli, or Pseudomonas aeruginosa, without culturing the whole-blood sample ([0091]-[0095]; [0099] the disclosed RT-PCR based test does not require blood culturing ; [0206]), the method comprising the steps of:
(a) collecting the whole-blood sample in an RNA-stabilizing blood-collection tube ([0205]-[0206] Whole blood samples collected aseptically in EDTA-tubes; [0095]);
(b) extracting RNA from the whole-blood sample ([0099] lines 1-5, “a gene product such as ribonucleic acid (RNA) may be isolated from a blood sample,”);
(c) reverse transcribing the extracted RNA to cDNA ([0099] lines 5-18, “RNA is preferably converted into complementary DNA ( cDNA) prior to amplification …”); and
(d) performing multiplex quantitative polymerase chain reaction on the cDNA with a plurality of oligonucleotide primer pairs that specifically amplify a plurality of RNA targets for Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa ([0017] “Optimized primers and probes for multiplex real-time PCR are provided in Tables 1 and 2. The most common infections underlying microbial blood infections such as sepsis are caused by Pseudomonas aeruginosa, Escherichia coli … and Staphylococcus aureus”; [0129]; Table 4; [0103] “Real-time PCR, also called quantitative PCR (qPCR), is a technique which is used to amplify and simultaneously quantify a template DNA molecule”; [0199] Sequences with adequate in silico coverage and specificity were used for primer design) ,
wherein a result is obtained in fewer than four hours from collection of the whole- blood sample ([0015] “the results from this method for detecting sepsis can be available within 4 hours, while the classical blood cultures take 2-3 days. This fast detection enables fast, adequate antibiotic treatment which will significantly reduce mortality”; [0226]-[0228] “Clinical blood samples from critically ill patients admitted to the ICU were used to evaluate the multiplex BSI PCR.” “ the time-to-result time for the PCR is only 3 hours”).
Regarding the recitation
“wherein amplification, in the multiplex quantitative polymerase chain reaction, of a combination of two or more of the plurality of RNA targets selected according to step (iv) for the same bacterium, in the absence of amplification of RNA targets selected according to step (iv) for the other two bacteria, identifies Staphylococcus aureus, Escherichia coli, or Pseudomonas aeruginosa in the whole-blood sample as the cause of bacteremia in the patient”
This wherein clause is obvious in view of Savelkoul and Thomann.
As discussed in claim interpretation and 112(b) sections above, the RNA target selection process comprising step (iv) is not actively required by the claimed method.
Further, because the RNA target selection process does not recite any objective selection standard or criteria that impose any structural feature distinguishing the RNA target from other RNA targets known in the art, “the plurality of RNA targets selected according to step (iv)” is interpreted to encompass sequence regions derived from RNA (e.g., cDNA) of a recited bacterial species (Staphylococcus aureus, Escherichia coli, or Pseudomonas aeruginosa) that are detectable in samples from more than one individual.
Under the current claim interpretation, this wherein clause is understood to mean:
The amplification amplifies at least two target regions for each specific bacterial species;
The amplification is species-specific.
Savelkoul teaches multiplex real-time PCR using gene-target specific primers for specific detection of bacterial species including Pseudomonas aeruginosa, Escherichia coli, or Staphylococcus aureus, which are the most common cause for microbial blood infections such as sepsis ([0116]-[0117]); Tables 1 and 2).
" [0117] Optimized primers and probes for multiplex real-time PCR are provided in Tables 1 and 2. The most common infections underlying microbial blood infections such as sepsis are caused by Pseudomonas aeruginosa, Escherichia coli, Klebsiella species, Enterococcus faecalis, Staphylococcus spp. and Staphylococcus aureus."
The primer sequences are designed to ensure coverage in all available sequences of the target organism in whole genome database ([0199]). Accordingly, a skilled artisan would readily understand that these primers in Savelkoul are capable of amplifying common sequence regions shared by the same bacterial species across samples.
One of the aims of Savelkoul’s multiplex real-time PCR method is to determine the specific bacterial species that cause the sepsis, and apply a specific treatment based on the identified microorganism. ([0192]; see also [0185]-[0191]). Accordingly, a skilled artisan would understand that, because Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus are among the most common cause for microbial blood infections such as sepsis ([0117]), detection of one bacterial species in the absence of detection of the others, supports identifying the detected bacterial species as the likely causative microorganism.
Although Savelkoul does not explicitly teach amplifying two or more targets for the same bacterium in its multiplex PCR assay, and instead teaches amplifying one bacterial species-specific gene for detecting the presence of the bacterium in the blood sample (Tables 1 and 2), this feature would have been obvious in view of Thomann.
Thomann teaches methods for detecting pathogens in whole blood sample (Abstract), wherein the panel of pathogens individually detect one or more of Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus ([0220]).
Thomann further teaches amplification of more than one target nucleic acid characteristic of a species improves sensitivity and/or specificity of detection of the species, compared to a method that only amplifies one target per species ([0224-0225]).
“· [0224] Amplifying Multiple Amplicons Characteristic of a Species for Improved Sensitivity and/or Specificity
· [0225] In some embodiments, the methods of the invention may involve amplification and detection of more than one amplicon characteristic of a species in a biological sample containing cells and/or cell debris including but not limited to blood (e.g., whole blood, a crude whole blood lysate, serum, or plasma), bloody fluids (e.g., wound exudate, phlegm, bile, and the like), tissue samples (e.g., tissue biopsies, including homogenized tissue samples), or sputum. In some embodiments, amplification of more than one target nucleic acid characteristic of a species increases the total amount of amplicons characteristic of the species in an assay (in other words, the amount of analyte is increased in the assay). This increase may allow, for example, an increase in sensitivity and/or specificity of detection of the species compared to a method that involves amplification and detection of a single amplicon characteristic of a species. In some embodiments, the methods of the invention may involve amplifying 2, 3, 4, 5, 6, 7, 8, 9, or 10 amplicons characteristic of a species.”
Accordingly, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it prima facie obvious to modify the method of Savelkoul, which detects microbial blood infections using multiplex real-time PCR reactions and primers that specifically hybridize to one target region per bacterial species (e.g., Pseudomonas aeruginosa, Escherichia coli, or Staphylococcus aureus), to further detect more than one target nucleic acid sequence region per bacterial species, as taught by Thomann.
A skilled artisan would have been motivated to make this modification to improve detection performance. As suggested by Thomann, amplifying more than one target nucleic acid from a bacterial species improves sensitivity and specificity compared to amplifying only one target per species, as it increases the amount of analytes in the assay.
There would have been a reasonable expectation of success because both references pertain to detecting the same pathogens in blood and provide technically compatible teachings. Including primers targeting additional target sequences in a multiplex PCR assay was within the level of ordinary skill in the art (see Savelkoul in [0114]).
B) Regarding claims 2-4, each claim recites “wherein the same bacterium,” having two or more amplification targets for detection, is Staphylococcus aureus, Escherichia coli, or Pseudomonas aeruginosa, respectively.
As discussed above for claim 1, these limitations would have been obvious in view of the combined teachings of Savelkoul and Thomann. A person of ordinary skill in the art would have found it obvious to modify the method of Savelkoul, which detects microbial blood infections using multiplex real-time PCR reactions and primers that specifically hybridize to one target region per bacterial species (e.g., Pseudomonas aeruginosa, Escherichia coli, or Staphylococcus aureus), to further detect more than one target nucleic acid sequence region per bacterial species, as taught by Thomann.
Regarding claims 5-6, they are obvious in view of the combined teachings of Savelkoul and Thomann because they recite descriptive statements that do not further distinguish the claimed method from the prior art.
Claim 5 recites:
The method of claim 1,wherein the RNA target regions selected according to step (iv) are selected from conserved regions of the custom genomes.
Claim 6, recites:
The method of claim 1,wherein the RNA target regions selected according to step (iv) comprise parts of the custom genomes having the most abundant reads.
Per MPEP 2111.04, a wherein clause can limit a method claim if it contributes meaning and purpose to the manipulative steps.
Here, claims 5 and 6 each recites a wherein in clause that further describes the process by which the RNA target regions were selected. The RNA target identification process, including the selecting step (iv), is recited as occurring before the claimed method and is therefore not actively required by the claimed method. Accordingly, the "wherein" clauses do not introduce any additional steps or modify any existing step.
Further, these wherein clauses do not clearly recite any structural feature that distinguishes the primer pairs used in step (d) from other primers capable of amplifying cDNA sequences of the recited bacterial species. Therefore, they do not impose a manipulative difference to the claimed method.
Therefore, these claim languages are interpreted as descriptive statement without any associated active steps and do not distinguish the claims from the prior art.
Regarding claim 7, Savelkoul teaches primer pairs that specifically amplifies multiple genes of the same bacterium ([0024] Sa442 gene primers for detection of Staphylococcus aureus ; [0031] hsdM gene primers for detection of Staphylococcus aureus).
Prior Art
Below are relevant prior art not used in rejection but pertinent to the claims or disclosure.
Designing pathogen-strain specific primers using sequence data is a well-known approach in the art:
Hernández et al., (2020) Design of Bacterial Strain-Specific qPCR Assays Using NGS Data and Publicly Available Resources and Its Application to Track Biocontrol Strains. Front. Microbiol. 11:208. doi: 10.3389/fmicb.2020.00208;
Zhang et al. Developing a multiplex PCR-based assay kit for bloodstream infection by analyzing genomic big data. J Clin Lab Anal. 2022; 36:e24686. doi: 10.1002/jcla.24686;
Cruz-Rangel et al. End-point RT-PCR based on a conservation landscape for SARS-COV-2 detection. Sci Rep 12, 4759 (2022).
Other references also teach multiplex PCR amplification for detection of Sepsis-causing bacteria in blood:
US20160108461A1- Targeted whole genome amplification method for identification of pathogens;
Opota et al., Microbial diagnosis of bloodstream infection: towards molecular diagnosis directly from blood. Clin Microbiol Infect. 2015 Apr;21(4):323-31. doi: 10.1016/j.cmi.2015.02.005. Epub 2015 Feb 14. PMID: 25686695.; see Figure 2;
Sinha et al., Emerging Technologies for Molecular Diagnosis of Sepsis. Clin Microbiol Rev. 2018 Feb 28;31(2):e00089-17. doi: 10.1128/CMR.00089-17. PMID: 29490932; PMCID: PMC5967692;
Murugan et al., Application of six multiplex PCR's among 200 clinical isolates of Pseudomonas aeruginosa for the detection of 20 drug resistance encoding genes. Kaohsiung J Med Sci. 2018 Feb;34(2):79-88. doi: 10.1016/j.kjms.2017.09.010. Epub 2017 Nov 6. PMID: 29413231; PMCID: PMC12977118;
US20150086987A1- Real-time pcr for the detection of pathogens.
Conclusion
No claims are allowed.
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 TIAN NMN YU whose telephone number is (703)756-4694. The examiner can normally be reached Monday - Friday 8:30 am - 5:30 pm.
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/TIAN NMN YU/Examiner , Art Unit 1681 /AARON A PRIEST/Primary Examiner, Art Unit 1681
1 The lack of an objective standard for determining what constitutes "abundant read" is addressed separated under 35 U.S.C. 112(b).
