DETAILED ACTION
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
This application has PRO 63/339,291 05/06/2022
This application has PRO 63/282,947 11/24/2021
The claims of the instant application have a priority date of 11/24/2021.
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 .
Election/Restriction
Applicant’s election without traverse of Group I, claims 1-38 in the reply filed on 10/31/2025 is acknowledged.
Claims 39-72 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/31/2025.
Claims 1-38 are pending for examination.
Claim Objections
Claim 32 is objected to because of the following informalities: The terms “Enterobacter cloacae” and “Staphylococcus aureus,” are repeated twice in claim 32.
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Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-38 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.
Claims 1-2 (and those claims dependent thereon) recite:
A method of characterizing a microbial cell from a biological sample, the method comprising a) directly inoculating the microbe onto a device; b) identifying the microbe; and c) detecting susceptibility to one or more antimicrobial agents.
A method of characterizing a microbial cell from a biological sample, the method comprising a) directly inoculating the microbe onto a device; b) identifying the microbe; and c) detecting future susceptibility to one or more antimicrobial agents.
Line 1 of claims 1-2 recite: “a microbial cell,” however line 2 of these claims recite the limitation “the microbe,” two times. The term “the microbe” lacks antecedent basis, additionally the term is broader in scope with respect to the term “microbial cell.” A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 1-2 recite the term “detecting susceptibility,” or “detecting future susceptibility,” the metes and bounds of these phrases are indefinite. The phrase “detecting susceptibility” is unclear since it not certain that the “term “detecting” involves visual inspection, or requires additional steps not included in the claim. Moreover, it is unclear what level of susceptibility is encompassed by this term.
Regarding claim 2, which recites “detecting future susceptibility,” it is uncertain what criteria are used by Applicant to detect which characteristics (or changes) in the microbe are present or absent, such that the “susceptibility” of the microbe against an antimicrobial agent could be determined in the future. For prior art, the phrase will be interpreted as “detecting susceptibility,” without an assessment of future susceptibility. If susceptibility is detected for a microbe for a particular antimicrobial agent, a person of ordinary skill in the art would expect future susceptibility to that agent as well.
The term “susceptibility” in claims 1-38 is a relative term which renders the claim indefinite. The term “susceptibility” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 21 recites the following:
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Regarding claim 21, the term “(e.g.….)” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Additionally, the use of parentheses in the claim is also indefinite, because it is unclear if the claim is to be limited to the limitations within the parentheses.
Further, broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 21 recites the broad recitation of multidrug resistance proteins, membrane associated transporters, and soluble proteins, and the claim also recites limitations within parentheses, which are the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Additionally, claim 32 recites “E. coli and (including pathogenic E. coli),” this phrase is indefinite because it recites the broader limitation E. coli, and the narrower limitation “pathogenic E. coli” in the same claim. MPEP 2173.05(c).
Claims 25-27, depend from claim 1. However, these claims recite "the susceptibility or future susceptibility'" This limitation lacks antecedent basis in claim 1, claim 2 provides support for the limitation “future susceptibility” not claim 1.
Claim 33 recites “wherein the viral infection is selected from Helicobacter pylori...” This phrase is improper since H. pylori is a bacterium, not a virus.
Regarding claim 35, this claim recites multiple forms of parasitic infections, a broad range or limitation, and further recites in the same claim a narrow range or limitation (species of microbes associated with the infection, that falls within the broad range or limitation (in the same claim). This may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Additionally, the use of parentheses in claim 35 is indefinite, because it is unclear if the claim is limited to the limitations recited in the parentheses.
Claim 36 is also rejected under 35 USC 112(b) for reciting indefinite claim language. Specifically, as per MPEP § 2173.05(c), a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See for example where claim 36 recites the limitation “physiological secretions,” (broad limitation), followed by: “tears, mucus, sweat, milk, semen, seminal fluid, vaginal secretions, fluid from ulcers and other surface eruptions, blisters, and abscesses...”, which are narrower limitations, in the same claim.
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.
Claim(s) 1-10, 16-24 and 36-37 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Shi et al. (12-2020). The applied reference has a common author/inventor (Hao Shi, and Iwijn De Vlaminck) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Shi et al teaches the following method (p. 677, Figure 1):
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The method of Shi et al. comprises the use of live cell imaging techniques in combination with in-situ hybridization (HiPR-FISH) to identify microbes in a mixture of cells. (See page 677 “Proof of Principle”, reads on claims 5-7):
“[T]o test the robustness of HiPR-FISH, we characterized predefined mixtures of the 1,023 E. coli barcode isolates. We first created and imaged a mixture of all barcode strains at an equal concentration. We performed barcode decoding for a total of 65,534 cells (Fig. 1e) and determined that all barcodes were represented in the mixture, with a median fractional abundance of 8.9 × 10−4 and full width at half maximum (FWHM) of 3.7 × 10−4—close to what is expected for a multinomial distribution (median relative abundance of 9.8 × 10−4 and FWHM of 3.1 × 10−4). We next randomly divided the 1,023 aliquots into 8 groups, each comprising 127 or 128 barcodes, and mixed barcodes in the same group at varying abundance.” (claim 9)
Shi et al further teaches at page 678, the following: “The effect of antibiotic treatment on the spatial organization of the mucosa-associated gut microbiome has not been studied in detail. To fill this knowledge gap, we created HiPR-FISH maps of the mouse gut microbiome in the presence and absence of antibiotic treatment. We designed HiPR-FISH probe sets based on full-length 16S sequences that were generated using PacBio sequencing (Methods, Supplementary Tables 5, 6, Extended Data Fig. 4).” This method is interpreted as reading on a determination of susceptibility, and further characterization of the microbes tested by gene expression using in-situ hybridization. This disclosure reads on claims 1 and 3-10, 16-24, where the use of 16S RNA expression in their methods of antimicrobial susceptibility testing (AST).
Shi et al. teaches the use of a human oral microbiome, see abstract. (claim 37).
Claim(s) 1, 12-13, 26-32, 36 and 38 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dong et al. ( Anal. Chem. 2015, 87, 2410−2418).
The method of Dong et al. teaches pathogen identification with AST in personalizing antibiotic treatment of UTIs, where the method comprising the evaluation of the metabolism of the pathogen in a urine sample. See the following:
“[I]n this study, a cell-based lab-on-a-chip (LOC) system employs the immunosorbent ATP-bioluminescence assay (IATP-BLA) as a fundamental measuring method to identify and evaluate the properties of uropathogenic bacteria. The ATP bioluminescence assay (ATP-BLA) is a multistep process involving the luciferase enzyme, luciferin substrate, oxygen, magnesium cation, and adenosine triphosphate (ATP), which will induce the efficient emission of photons (550–570 nm). Target microbes in the urine sample will be captured by specific antibodies on the fiberglass membrane inside of the device and then encapsulated by the calcium alginate gel in situ. Given enough growth medium, the immobilized microbes can survive there for on-chip AST prior to the IATP-BLA quantification. Basically, the magnitude of the ATP bioluminescence signal is proportional to the amount of corresponding living microbes. The entire process is smoothly integrated in this microfluidic simulator, so the specificity of immunoassay and the ultrasensitivity of the ATP-bioluminescence assay can be perfectly integrated. Compared with traditional microbial culture, the test cycle is reduced from a few days down to hours or even minutes. The 384-chamber microfluidic simulator can simultaneously perform an AST of 8 selected antibiotics on 13 types of microbe strains. (Page 2411, 1st col., 1st full ¶). (Reads on claims 26-27).
This disclosure by Dong et al. describes a method of AST that includes a microbe containing sample taken from a urine sample of a patient having a UTI (see abstract), and further includes measuring ATP by bioluminescence signal. The method utilizes oxygen, magnesium cation, and adenosine triphosphate (ATP).
Page 2410 teaches that UTIs may be caused by:
“[The most common UTI-causing organism is Escherichia coli, with 80%−85% of the cases originating from these bacteria.3 Staphylococcus saprophyticus are responsible for 5%−10% of UTI cases,3,5 and in some rare cases, UTIs can also be caused by viral or fungal infections.3,6 Other groups of bacteria such as Klebsiella, Proteus, Pseudomonas, and Enterobacter can also cause UTIs.”
This disclosure reads on AST comprising measuring microbial metabolism, where the sample is from a patient having an infection, the infection is a UTI, and may be caused by e.g. E. coli, and anticipates claims 1, 12-13 and 28-32 and 36.
Claim(s) 1 and 11 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Jarvius et al. (US20180223327A1).
Jarvius et al. (US20180223327A1) teaches methods for AST and MIC determination comprising: [0088] “[G]enerally speaking, an AST assay is performed by monitoring the effect of an antimicrobial agent on microbial growth. A microbial culture (here the microbial culture preparation) is used to inoculate culture medium in a series of at least two culture vessels, each comprising a different concentration of an antimicrobial agent, and the microorganisms are cultured for a period of time. In this way, a series of at least two different concentrations of an antimicrobial agent is tested in order to determine the minimum inhibitory concentration (MIC) that is required in order to prevent microbial growth. The MIC value obtained thus provides an indication of whether a microorganism is resistant or susceptible to an individual antimicrobial agent.” (This disclosure read on claims 1 and 11.)
Claim(s) 1 and 14-15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al. (J Vis Exp. 2019 Feb 8:(144):10.3791/58978).
Claims 14-15 recite:
14. The method of claim 1, wherein microbial cell susceptibility is determined by a live/dead stain.
15. The method of claim 1, wherein microbial cell susceptibility is determined by cell number.
Wang et al. describe the following protocols, which include the use of viability quantification of GC aggregations of live/dead stain, fluorescence microscopic analysis of Live/Dead of GC aggregates, and image analysis in their methods of AST.
See the following (Wang pages 2-4):
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The above disclosure is interpreted as anticipating claims 1, and 14-15.
Claim(s) 1-3, 24-26 and 31-38 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Super at al. (WO2013/130875A1).
Super et al. discloses the following method (see claim 1 of the WIPO publication):
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This disclosure anticipates claims 1-3.
Regarding claims 31-36, Super et al. discloses the following:
Regarding claim 1-2, and claim 36 Super anticipates these claims in the following disclosure: (calims section)
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Regarding claims 24-26, Super teaches the following, this disclosure is considered to anticipate these claims:
[00107] In accordance with various aspects described herein, microbes in a sample need not be identified prior to incubation with one or more antibiotic agents. While Figure 1 illustrates that the optional step 1212 (microbe detection) can occur between step 1206 and optional step 1213, it should be readily appreciated that the optional step 1212 can be carried out at any time after step 1206 (microbe capture and separation). In some embodiments, step 1212 can be performed independently in parallel with any of the steps after step 1206. In some embodiments, step 1212 can be performed after step 1216 where antibiotic activity is detected in microbial cultures. For example, the captured microbes grown in the control antimicrobial/antibiotic-free matrix can be subjected to microbe identification (e.g., MALDI TOF mass spectroscopy). In some embodiments, step 1212 can be performed once or more than once throughout the process 1200.
Additionally, Super teaches simultaneous detection and AST, see the following:
[00109] In some embodiments, antibiotic susceptibility can be determined based on a collective response from a population of captured or isolated microbes, e.g., microbes bound on one or more microbe-targeting substrates, e.g., microbe-targeting magnetic particles. In some embodiments, antibiotic susceptibility can be determined based on a collective response from more than 1, more than 10, more than 25, more than 50, more than 100, more than 1000, more than 105 captured or isolated microbes, e.g., microbes bound on one or more microbe targeting substrates, e.g., microbe-targeting magnetic particles.
Regarding claim 31, Super et al. teaches: “[00126] As used herein, the term "antibiotic agent" refers to naturally occurring, semisynthetic, or fully synthetic agents which inhibit the growth of microbes (i.e., bacteria, fungi, viruses, parasites and microbial spores) thereby preventing their development and microbial or pathogenic action.
Regarding claim 32, Super teaches: “[0040] In one embodiment, the bacteria is selected from the group consisting of Acinetobacter baumannii, Bacillus anthracis, Bacillus cereus, Bordetella pertussis, Borrelia burgdorferi, Brucella aborus, Brucella canis, Brucella melitensis, Brucella suis, Campylobacter jejuni, Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium diphtherias, Enterobacter sp., Enterococcus faecalis, vancomycin-resistant Enterococcus faecalis, Enterococcus faecium, Escherichia coli, enterotoxigenic Escherichia coli (ETEC), enteropathogenic Escherichia coli, E. coli O157:H7, Francisella tularensis, Haemophilus influenzae, Helicobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Listeria monocytogenes, Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma pneumoniae, Neisseria gonorrhoeae, Neisseria meningitidis, Proteus, Pseudomonas aeruginosa, Rickettsia rickettsii, Salmonella typhi, Salmonella typhimurium, Shigella sonnei, Staphylococcus aureus, Staphylococcus epidermis, Staphylococcus saprophyticus, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VSA), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, and Yersinia pestis.”
Regarding claim 33 Super describes the microbe as Helicobacter pylori, see ¶ [0040] above. The system of Super also teaches the detection of virus, see ¶ [0094], “[17 viruses (e.g. CMV, HIV, Ebola, HSV, HepB),” are detectable using their system.
Regarding claim 34, Super also teaches where the microbe can be fungi, including Candida, Aspergillus, and Cryptococcus, see ¶ [0094].
Regarding claims 35-36, Super states that their system can be used identify and test parasites associated with Malaria and Schistosoma. Super also teaches that microbes or pathogens useful in their methods can be extracted or concentrated from blood samples or other biological fluids. ¶ [0094].
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 1-38 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (mental process) without significantly more. The claim(s) recite(s) methods for characterizing, which includes techniques such as identifying, detecting, “dynamic calculation,” measuring, counting, and visualizing. These activities can be considered mental processes or abstract ideas, which are not considered patentable subject matter. This judicial exception is not integrated into a practical application because the claims are drawn to characterizing a microbial cell, The practice of “characterizing” can occur in the human mind. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because “directly inoculating,” and detecting susceptibility, are common and routine. These elements do not apply, rely on or use the judicial exception in a manner
that imposes a meaningful limit on the judicial exception. According to 2019 PEG, limitations that are indicative of integration into a practical application when recited in a claim with a judicial exception include:
• Improvements to the functioning of a computer, or to any other technology or
technical field, as discussed in MPEP 2106.05(a);
• Applying or using a judicial exception to affect a particular treatment or
prophylaxis for disease or medical condition – see Vanda Memo
• Applying the judicial exception with, or by use of, a particular machine, as
discussed in MPEP 2106.05(b);
• Effecting a transformation or reduction of a particular article to a different state
or thing, as discussed in MPEP 2106.05(c); and
• Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP 2106.05(e) and the Vanda Memo issued in June 2018. Limitations that are not indicative of integration into a practical application when recited in a claim with a judicial exception include:
• Adding the words “apply it” (or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer, or merely uses a computer as a tool to perform an abstract idea, as discussed in MPEP 2106.05(f);
• Adding insignificant extra-solution activity to the judicial exception, as
discussed in MPEP 2106.05(g); and
• Generally linking the use of the judicial exception to a particular technological environment or field of use, as discussed in MPEP 2106.05(h).
In the instant case, measuring the susceptibility of a microbe to an antimicrobial agent in a biological sample is merely data gathering. Data gathering steps required to use the correlation do not add a meaningful limitation to the method as they are insignificant extra-solution activity. The claims also do not effect a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP 2106.05(c).
The claims also fail to meet step 2B because the additional elements were well known and conventional in the art. For example, see Dong et al. and Wang et al. cited in this action. Therefore, the additional steps/elements do not add significantly more to the judicial exception. Since the claims as a whole do not include additional elements that are sufficient to amount to significantly more than the judicial exception, the claims are not directed to eligible subject matter under 35U.S.C 101.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L EPPS-SMITH whose telephone number is (571)272-0757. The examiner can normally be reached M-F, 10:00 AM-6:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Patricia Mallari can be reached at (571)272-4729. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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JANET L. EPPS-SMITH
Supervisory Patent Examiner
Art Unit 1646
/JANET L EPPS -SMITH/
Supervisory Patent Examiner, Art Unit 1646