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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on Jan. 26, 2026.
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Jan. 26, 2026. Claims 1-8, 10-19 and 21-36 are pending and are currently examined.
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 of this title, 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.
(Previous rejection- maintained with edition based on the amendment) Claims 1-8, 10-14, 17-19 and 21-27 and 30-36 are rejected under 35 U.S.C. 103 as being unpatentable over Gil et al. (US 2017/0121688 A1, published on May 04, 2017) and in view of Alfa et al. (BMC Infect Dis. 2009 May 8;9:56) as evidenced by Nelson labs (https://www.nelsonlabs.com/testing/disinfection-validation-for-reusable-devices/, 2019).
The amended base claim 1 is directed to a method for the detection of a viable microorganism of interest in a sample in the presence of at least one high-level disinfectant, wherein the method comprises
obtaining a sample from a surface, wherein the sample comprises at least one high-level disinfectant; and
(ii) analyzing the sample in the presence of the at least one high-level disinfectant, wherein analyzing the sample comprises:
incubating the sample with an indicator cocktail composition comprising at least one recombinant bacteriophage; and
detecting an indicator protein product produced by the at least one recombinant bacteriophage, wherein positive detection of the indicator protein product indicates that the viable microorganism of interest is present in the sample.
Gil et al. describes a methods and systems for rapid detection of microorganisms using infectious agents (See Title), and teaches that the invention comprises a recombinant bacteriophage comprising an indicator gene inserted into a late gene region of a bacteriophage genome (See Abstract). Gil et al. teaches the samples can be swabs of a solid surface (See e.g., [0064]), and the compositions can include cocktails of different indicator phages that may encode and express the same or different indicator proteins (See e.g. [0013]), which teaches the limitation of claim 1 (ii)-(a). Gil et al. further teaches that the invention comprises a method for detecting a microorganism of interest in a sample comprising the steps of incubating the sample with a recombinant bacteriophage that infects the microorganism of interest (See e.g., 0014]), which teaches the limitation of claim 1 (ii)-(b). Accordingly, Gil et al. teaches a method for the detection of a viable microorganism of interest on a surface using a recombinant bacteriophage as claimed.
Gil et al. teaches using CBA120NanoLuc Indicator Bacteriophage to detect the bacteria in the “vegetable wash” (See e.g., [0213] to [0216]), which indicates that Gil’s indicator bacteriophage detection is used in a surface sample validation after a cleaning process. However, Gil et al. is silent on the sample in the presence of the at least one high-level disinfectant.
Alfa et al. teaches that the "buildup biofilm" (BBF) can be built on the Flexible endoscopes during the repeated rounds of patient-use and reprocessing (See Background). Alfa et al. uses a unique modelling approach to evaluate microbial survival in BBF formed by repetitive cycles of drying, disinfectant exposure and re-exposure to the test organism. This model mimics the cumulative effect of the reprocessing protocol on flexible endoscopes. Glutaraldehyde (GLUT) and accelerated hydrogen peroxide (AHP) were evaluated to assess the killing of microbes in TBF and BBF (See Methods and Results), where the Glutaraldehyde (GLUT) and hydrogen peroxide (AHP) are high-level disinfectant (HLD). For the surface samples, Alfa et al. teaches that all test sampling was done immediately pre- and post-treatment cycle on triplicate sample pegs (See page 3, right column, paragraphs 5-6), which indicates that tested samples contain the HDL like Glutaraldehyde (GLUT) and accelerated hydrogen peroxide (AHP) as claimed in claim 1 (i) because the samples are collected from the pegs right after the HDL treatment. For example, Figures 3 and 4 of Alfa show the TBF ad BBF are formed under the treatment of accelerated Hydrogen peroxide (See page 8 and below Figure 4.)
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In the method details, Alfa et al. teaches evaluating GLUT (HLD disinfection) efficacy under different disinfection condition (See page 4, right column, paragraph 4), and discloses a method of outgrowth testing as: following HLD, sample pegs were aseptically transferred into 10% FBS in TBS in sterile tubes that remained unopened at 35°C for 5 days. These tubes were subjected to the standard elution protocol (shaking for 2 minutes, sonication for 5 minutes, vertexing for 1 minute) however the tubes remained closed. The tubes with pegs were reintubated for 25 days at 35°C. Turbidity indicated positive growth (See page 4, left column, paragraph 5), and the result is shown as Table 3 (See page 11 and below). The results in Table 3 teaches
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that despite no detectable viable organisms for the quantitative counts (limit of detection 10 cfu/peg), there can be low- level microbial survival to GLUT in TBF and BBF (See page 6, right column, paragraph 1) and indicates the importance of the validation test after the HLD disinfection. This can also be evidenced by the Nelson Labs by teaching that disinfection validations are used to validate device manufacturer’s disinfection instructions for reusable medical devices, and validations maybe performed to support high-level disinfection, intermediate-level disinfection, and low-level disinfection processes depending on the intended use of the device (See page 1). Furthermore, the “low- level microbial survival to GLUT” of Alfa teaches a need for using a highly sensitive detection method.
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to use the method of Gil on the sample of Alfa because Alfa teaches that there can be low-level microbial survival after disinfection with GLUT in TBF and BBF and the assay of Gil can be used to detect these low levels. One of skill in the art would have been motivated to do so because the re-usable medical device needs to be disinfected by HLD. After the HLD, a validation test needs to be performed by detecting the viable microorganism. Gil teaches that the embodiments employing recombinant bacteriophage of the invention (i.e., indicator bacteriophage) allow rapid detection of specific bacterial strains, with total assay times under 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, 10.5, 11.0, 11.5, or 12 hours (See e.g., [0109]), which is a time-saving detection method comparing to the detection method taught by Alfa for 25 days to see the indicator Turbidity. Also, Gil teaches a compositions, methods and systems that demonstrate surprising sensitivity for detection of a microorganism of interest in test samples (See e.g., [0037]), and discloses that the detection sensitivity can reveal the presence of as few as 50, 20, 10, 9, 8, 7, 6, 5, 4, 3, or 2 cells of the microorganism of interest in a test sample. In some embodiments, even a single cell of the microorganism of interest may yield a detectable signal (See e.g. [0122]). Therefore, there is a motivation for collecting samples containing the HLD for performing the validation test, and there is a motivation to apply the rapid and sensitive detection of indicator bacteriophage of Gil for detecting the microorganisms after the HLD. There would be a reasonable expectation of success to develop a method for the detection of a viable microorganism of interest on a surface using bacteriophage detection method because Alfa and Nelson’s lab teach a method for collecting samples after HLD and teaches the importance for performing a validation test for HLD. At the same time, Gil teaches an indicator bacteriophage detection method to provide a more rapid, simple and sensitive detection and identification of microorganisms, such as bacteria and other potentially pathogenic microorganisms (See [0007]). Therefore, using Gil’s method to detect the samples after HLD has a reasonable expectation of success.
Regarding claims 2-5, they require the surface is from device or equipment. Gil et al. teaches that the sample may be an environmental or food or water sample. Some embodiments may include medical or veterinary samples. Samples may be liquid, solid, or semisolid. Samples may be swabs of solid surfaces (See [0064]). Although Gil et al. does not explicitly point out the samples can be from a device or equipment such the endoscope, both Alfa and Nelson Labs teach a disinfection validation for the medical device such as endoscope as described above, which include the sample collection from the surface of the devices. It would be obvious for one of ordinary skill in the art to collect samples from the surface of devices for disinfection validation just as the teaching of Nelson Labs at “Disinfection validation testing is specifically needed when a device can’t be sterilized using elevated temperatures”.
Regarding claim 6, it requires that the surface is decontaminated prior to obtaining a sample. Gil et al. teaches testing the bacteria after washing the spinach (See e.g., [0036]), which can be a similar process of ‘decontamination” prior to obtaining a sample. Nevertheless, Alfa teaches that the sample pegs were removed before and after HLD and evaluated for microbial survival (See page 4, left column, paragraph 2). It would be obvious for one of ordinary skill in the art to collect the samples after the HLD decontamination based on the needs and detect the vibrable bacteria using Gil’s indicator bacteriophage.
Regarding claims 7-8, Gil et al. teaches a clean step for washing (See [0214]). Alfa et al. teaches a disinfection step using HLD, a clean step and steam sterilized steps for the Flexible endoscope’s application (See page 2, left column, paragraph 1). It would be obvious for one of ordinary skill in the art to apply Alfa’s method into Gil’s invention if the medical device is applied.
Regarding claim 10, it requires the method comprises incubating a first aliquot of the sample with a first indicator cocktail composition and incubating a second aliquot of the sample with a second indicator cocktail composition. Gil et al, teaches that compositions of the invention may comprise one or more wild-type or genetically modified infectious agents (e.g., bacteriophages) and one or more indicator genes. In some embodiments, compositions can include cocktails of different indicator phages that may encode and express the same or different indicator proteins (See e.g. [0084]), which indicates that different bacteriophages are present in the cocktail which can be the different host-phages, and the cocktail phages can infect the bacterium of interest (See e.g. [0113]). Gil et al. also teaches that the aliquots of a test sample may be distributed directly into wells of a multi-well plate, indicator phage may be added, and after a period of time sufficient for infection (See e.g. [0116]), and the bacteriophages can be well-studied phages of E. coli. include T1, T2, T3, T4, TS, T7, and lambda; other E. coli phages available in the ATCC collection, for example, include phiX174, S13, Ox6, MS2, phiVl, fd, PR772, and ZIKl (See [0087]). Based on the description here, the sample aliquot can be added as a first aliquot and second aliquot where they can be contacted with a recombinant bacteriophage cocktail composition where one or more recombinant bacteriophage that is specific for the desired host bacteria are presented.
Regarding claims 11-14 and 17 Gil et al. teaches that compositions can include one or more wild-type or genetically modified infectious agents (e.g., bacteriophages) and one or more indicator genes and the cocktail compositions of recombinant bacteriophages can be used to detect potentially harmful bacteria. (See e.g. [0013]; Abstract), where infectious agents can be different phages T1 and T7 for the same host of Escherichia coli (E. coli). Here the descriptions teach claim 11 at the indicator cocktail composition comprising at least two recombinant bacteriophages like T1 and T7 that are specific for the same microorganism of interest such as E. coli, and it is obvious that the microorganism of interest is a bacterium (claim 12). At the same time, Gil teaches that in some embodiments, the present invention utilizes the high specificity of infectious agents such as bacteriophage (See e.g., [0042]), and the bacterial cells detectable by the present invention include Klebsiella pneumoniae (high-risk) and Bacillus (low-or moderate-risk) (See [0063]), wherein it is reasonable consider that the recombinant bacteriophage used is specific for a high-risk microorganism (claim 13), the recombinant bacteriophage used is specific for a low- or moderate-risk microorganism (claims 14). Based on the description above, it is also obvious for one skilled in the art to develop a method of the first indicator cocktail composition comprises at least one recombinant bacteriophage specific for a high-risk microorganism and the second indicator cocktail composition comprises at least one recombinant bacteriophage specific for a low- or moderate-risk microorganism that can teach claim 17.
Regarding claims 18-19, as for the claimed high-risk or low- or moderate-risk microorganism, Gil teaches the detected bacteria can be the high-risk microorganism such Escherichia coli, Klebsiella pneumonia and also can be the low- or moderate-risk microorganism such Bacillus. (See [0063]). As for the amended action steps, Gil teaches cleaning the spinach in a bag that should involve many recleaning steps. Also, Alfa teaches the flexible endoscopes undergo repeated rounds of patient-use and reprocessing (See Background). It would be obvious for one of ordinary skill in the art to include the reprocessing steps of Alfa into Gil’s invention when decontaminating the medical devices. As for the “positive detection of at least 100 CFUs of a low- or moderate-risk microorganism” in claim 19, Gil et al. teaches that using the bacteriophage detection method, about 1 million bacteria were found by CFU to reside on a single spinach leaf (1-2 g) (See [0214]), and also teaches that the bacterial cells detectable by their invention include, but are not limited to, bacterial cells that are food or water borne pathogens that can includes the low- or moderate- risk microorganism Bacillus (See e.g., [0063]).
Regarding claim 21, Gil et al. teaches that samples added to the cocktail composition may include environmental materials, such as the water samples, or the filters from air samples (See e.g. [0064]), where the test samples can be filtered before the test (See e.g. [0110]).
Regarding claims 22-23, Gil et al. teaches that in certain embodiments as little as a single bacterium is detected (See e.g. [0041]), and the in some embodiments, the total time to results is less than 12 hours, less than 11 hours, less than 10 hours, less than 9 hours, less than 8 hours, less than 7 hours, or less than 6 hours (See [0017]).
Regarding claims 24-27, Gil et al. teaches that the invention comprises a recombinant bacteriophage comprising an indicator gene inserted into a late gene region of a bacteriophage genome such that expression of the indicator gene during bacteriophage replication following infection of host bacteria (See e.g. [0009]; [0014]). Gil et al. further teaches that in certain embodiments of the infectious agent, the indicator gene does not encode a fusion protein and the exogenous promoter is a bacteriophage late promoter such as class III promoter, e.g., from T7, T4, or Vil (See [0069]; [0083]), and in some embodiments, the indicator gene is a luciferase gene (See [0010]).
Regarding claims 30-31, Gil teaches that the recombinant bacteriophage is from well-studied phages of E. coli include T1, T2, T3, T4, T5, T7, and lambda (See [0087]) and the methods and systems of the invention can be applied to detection and quantification of a variety of microorganisms (See e.g. [0045]) and a sample is maintained at a temperature that maintains the viability of any pathogen cells contained within the sample (See [0065]).
Regarding 32-34, Gil et al. teaches that the invention comprises compositions, methods, systems and kits for the detection of microorganisms (See [0008]), wherein some embodiments of the method can be performed on filter plates (See e.g. [0117]). In some embodiments of recombinant indicator bacteriophage, the indicator gene can be codon-optimized and can encode a soluble protein product that generates an intrinsic signal or a soluble enzyme that generates signal upon reaction with substrate (See [0010]). Although Gil et al. does not specifically point out a high-level disinfectant as claimed in claim 32, Alfa et al. teaches a high-level disinfectant (HLD) condition using Glutaraldehyde (GLUT) and accelerated hydrogen peroxide (AHP), where the Glutaraldehyde (GLUT) and hydrogen peroxide (AHP) are high-level disinfectant (HLD) agent (See page 4, right column, paragraph 4). It would be obvious for one of ordinary skill in the art to include a sample from? the high-level disinfectant as Alfa taught. For claim 33, Gil et al. teaches that an example kit for measuring the signal “RLU” at the detection of the reaction between luciferase and appropriate substrate (e.g., NANOLUC® with NANO-GLO®) is often reported in RLU detected (See e.g., [0059]). Gil et al. also teaches that Samples may include environmental materials, such as the water samples, or the filters from air samples or aerosol samples from cyclone collectors (See [0064}, which teaches claim 34.
Regarding claims 35 and 36, based on the description above, Gil et al. teaches that the invention comprises compositions, methods, systems and kits for the detection of microorganisms (See [0008]), wherein the systems and kits of the invention include various components. As used herein, the term "component" is broadly defined and includes any suitable apparatus or collections of apparatuses suitable for carrying out the recited method (See [0159]), and in other embodiments, various tools (e.g., a centrifuge or filter) may be used to concentrate the samples before enrichment or before testing (See [0110]). For claim 35, Gil et al. teaches (i) can be a swab of solid surface (See [0064]) and (ii) an apparatus that is suitable for carrying out the composition of the cocktail of phages (See [0159]; [0013]) and (iii) a detection apparatus of a luminometer for measuring a luciferase enzyme activity to detect the viable microorganism of interest (See e.g., [0151]). For claim 36, Gil et al. teaches that various tools (e.g., a centrifuge or filter) may be used to concentrate the samples before enrichment or before testing (See [0110]). As for the high-level disinfection, Alfa et al. teaches a high-level disinfectant (HLD) condition using Glutaraldehyde (GLUT) and accelerated hydrogen peroxide (AHP), where the Glutaraldehyde (GLUT) and hydrogen peroxide (AHP) are high-level disinfectant (HLD) agent (See page 4, right column, paragraph 4). It would be obvious for one of ordinary skill in the art to include a sample form the high-level disinfectant as Alfa taught.
(Previous rejection- maintained) Claims 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Gil et al. (US 2017/0121688 A1, published on May 04, 2017) and in view of Alfa et al. (BMC Infect Dis. 2009 May 8;9:56) as evidenced by Nelson labs (https://www.nelsonlabs.com/testing/disinfection-validation-for-reusable-devices/, 2019) as applied to claims 1-8, 10-14, 17-19 and 21-27 and 30-36 above and in view of FDA- Duodenoscope Surveillance Sampling and Culturing Protocols ( https://www.fda.gov/media/111081/download).
Claims 15 and 16 require the detected microorganism are limited to specific high-risk and low- or moderate-risk microorganism.
Gil et al. teaches some microorganism detected are high-risk microorganism such as Klebsiella pneumonia and the some of them are low- or moderate-risk microorganism such as Bacillus (See [0063]). However, it does not cover the lists as claimed in claims 15-16.
FDA releases the interim Duodenoscope Surveillance Protocol updated by CDC in March 2015, and address the concerns regarding validation of duodenoscope culturing protocols raised in ASM’s April 2015 Policy Statement on Culturing of Duodenoscopes (See page 1). In this protocol, FDA teaches the definitions of HIGH-CONCERN ORGANISM and LOW/MODERATE-CONCERN ORGANISM (See page 11), and list all the microorganism claimed in claims 15 and 16.
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to follow FDA’s protocol to add these HIGH-CONCERN ORGANISM and LOW/MODERATE-CONCERN ORGANISM into Gil’s invention to develop a method for the detection of these viable microorganism on a surface of device or instruments. One would have been motivated to do so to apply the bacteriophage-based detection methods and systems to the FDA identified microorganism and follow FDA’s protocol to conducting a risk/safety detection. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated and commonly used as evidenced by the prior art teachings.
(Previous rejection- maintained) Claims 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Gil et al. (US 2017/0121688 A1, published on May 04, 2017) and in view of Alfa et al. (BMC Infect Dis. 2009 May 8;9:56) as evidenced by Nelson labs (https://www.nelsonlabs.com/testing/disinfection-validation-for-reusable-devices/, 2019) as applied to claims 1-8, 10-14, 17-19 and 21-27 and 30-36 above and in view of Russotto et al. (J Intensive Care. 2015 Dec 10;3:54) and Chen et al. (ACS Sens. 2017 Apr 28;2(4):484-489).
Claims 28 and 29 are directed to determine the antibiotic resistance of the detected microorganism of interest and further comprises a step for contacting the sample with an antibiotic prior to contacting the sample with the indicator cocktail composition.
Relevance of Gil et al. is set forth above. However, it is silent on determining the antibiotic resistance of the detected microorganism as claimed.
Russotto et al. reviews the bacterial contamination of inanimate surfaces and equipment in the intensive care unit, and teaches that Intensive care unit (ICU)-acquired infections are a challenging health problem worldwide, especially when caused by multidrug-resistant (MDR) pathogens. In ICUs, inanimate surfaces and equipment (e.g., bedrails, stethoscopes, medical charts, ultrasound machine) may be contaminated by bacteria, including MDR isolates (See Abstract). Russotto et al. teaches the antibiotic-resistance microorganism have been identified. For example, in a retrospective study performed in eight adult ICUs at a tertiary care hospital, investigators assessed the risk of acquiring methicillin-resistant Staphylococcus aureus (MRSA) and vancomicin-resistant enterococci (VRE) from prior room occupants (See page 3, left column). Russotto et al. teaches the issue of environmental contamination has been included in a recently published bundle of recommendations aiming to reduce the incidence of ICU-acquired infections caused by MDR pathogens, and inanimate surfaces and equipment in ICU are heavily contaminated by bacteria, including MDR species (See page 2, right column; page 7, left column), which indicates an urgent need for MDR detection.
Chen et al. studies the development of engineered Bacteriophages for Escherichia coli Detection and High-Throughput antibiotic Resistance Determination. Chen et al. teaches that using their genetically modified phage to rapidly determine the antibiotic resistance profile of E. coli in 96-well plate format. This method includes the steps inoculating E. coli BLT5403 cells into LB broth containing different antibiotics at varying concentrations at 37 °C for 3 h., and then the T7lacZ phage is added to initiate a colorimetric response if an infection occurred (See page 487, right column, paragraph 2). Chen et al. teaches the advantages of the High-throughput determination format, a low limit of detection when determining bacterial antibiotic resistance profiling by LacZ gene and more sensitive and fast method such as be able to detect E. coli at a concentration of 10 CFU·mL−1 within 7 h (Seepage 488, left column, paragraph 2). Chen’s teaching indicates that T7lacZ phage bacteriophage can be used for detecting antibiotic resistance of microorganism of interest.
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Gil, Russotto and Chen to arrive at an invention as claimed. Russotto et al. teaches inanimate surfaces and equipment in ICUs are heavily contaminated by bacteria, including MDR species, and Chen teaches that the phage can be used for detection of the antibiotic-resistance bacteria contamination. Because Gil teaches that the embodiments employing recombinant bacteriophage of the invention (i.e., indicator bacteriophage) allow rapid detection of specific bacterial strains, with total assay times under 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, 10.5, 11.0, 11.5, or 12 hours (See e.g., [0109]), which is a time-saving detection method comparing with Chen’s method, one would have been motivated to develop a fast detection method for antibiotic-resistance bacteria detection by using Chen’s T7lacZ phage and Gil’s fast detection kit to develop a method for less than 7 hours than Chen taught. There would have been a reasonable expectation of success to develop a method as claimed based on the teachings of Chen and Gil.
Responses to Applicant’s Remarks
Applicant’s arguments filed on Jan. 26, 2026 has been received and fully considered.
Applicant’s arguments on rejections under 35 U.S.C. § 103 is not found persuasive as the follows:
1. Applicant argued that the ability to rapidly detect a microorganism of interest in a sample comprising a high-level disinfectant is an important technical improvement of the present invention with Example 3 to show the detection result and further argued that the amended claims are not obvious over Gil in view of Alfa and Nelson Labs (See Remarks, bridging pages 8 and 9).
The argument is not persuasive.
1). Gil teaches the amended claim 1 (ii) using the bacteriophages with indicator protein to test the microorganisms from the surface samples like a sample from the washed vegetables. Although the reagent used for washing the vegetables is different from the claimed HDL reagent, the secondary reference, Alfa, teaches modeling and detecting the microbial survival from a sample collected form the surface of the medical device after HDL treatment where the pegs containing the HDL agent and is directly used for sample collections. With the teaching of the needs of disinfection validation testing for reusable devices from Nelson, it is applicable to combine the teachings of Gil in view of Alfa and Nelson Labs for the claimed Claim 1 (i).
2). As for the Example 3 in the instant specification cited in the Remarks, the applicant alleged that it demonstrates the technical improvement by evaluating the detection of microorganisms of interest in the presence of high-level disinfectants CID EX® OP A and RAPICIDE™ OP A/28 (Published Application, Tables 11, 12, 13, 15, 16, and 17), and Applicant respectfully submits that the amended claims are not obvious over Gil in view of Alfa and Nelson Labs (See Remarks, page 2).
First, the alleged improvement is not persuasive because the improvement detection evaluation is not required in the instant claims.
Second, the base claim 1 claims a generic HDL reagent, a generic microorganism and a generic bacteriophage, thus Example 3 does not represent the full scope of the instant claims.
Third, there are studies to teach that the bacteriophage is active under HDL with different conditions. This can be evidenced by 1Agun’s study (Viruses. 2018 Feb 28;10(3):103). Agun studies the Interactions Between Bacteriophage phiIPLA-RODI and Four Chemical Disinfectants for the Elimination of Staphylococcus aureus Contamination and teaches the susceptibility of Phage phiIPLA-RODI to different disinfectants including the HDL disinfectant, Hydrogen peroxide (See page 5, 3.1.1 and Table 2 below). The method design can be found in Agun’s study at “to determine phage susceptibility to different disinfectants, a phage suspension was diluted to a final concentration of approximately 10^5 PFU/mL in TSB and different final concentrations of chemical antimicrobial agents or no antimicrobial (control) were added. These suspensions were then incubated overnight at 37 °C. The following day, the surviving phage particles in each sample were determined by the double-layer assay (See page 3, 2.2). Here Agun teaches a similar method for “Detection Assay in the Presence of Cleaning Reagents” in the instant Example 3.
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2. Applicant argued that the "vegetable wash" process of Gil is a not a disinfecting process, and the "vegetable wash" of Gil does not contain at least one high-level disinfectant. It is a fact that there is a difference between the “water” and “HDL” agents. However, the “vegetable wash” here is an example for teaching that the microorganism like E. coli O157:H7 from a sample of a surface that is “cleaned” through processing can be detected and validated by the phages with indicator. For example, Gil teaches that in an embodiment, the microorganism captured on the filter or plate surface is subsequently washed one or more times to remove excess unbound infectious agent (See [0128]). The common points between the “wash” and the “HDL” are for removing the infectious agent and then following a bacteriophage-based validation detection. Nevertheless, Alfa teaches that a sample collected from an HDL-disinfected device is detected for the present of the microorganism like “Following HLD, sample pegs were aseptically transferred into 10% FBS in TBS in sterile tubes that remained unopened at 35°C for 5 days…” (See page 4, left column). In addition, there is no evidence to show that Alfa teaches “the HLD is explicitly removed from the samples” as argued. The teaching of "Following disinfectant exposure, pegs were neutralized using 10% FBS in TSB (for 10 minutes) to eliminate the possibility of disinfectant carryover" in Alfa (See Alfa, page 4, paragraph 1) as argued is not related to the sample collection.
3. Applicant also argued against the teachings of Nelson, FDA- Duodenoscope Surveillance Sampling and Culturing Protocols, Russotto et al., Chen et al. in the 103 rejections.
The arguments are not persuasive.
Combining with the teachings of Gil and Alfa, Nelson’s lab further teaches a method for collecting samples after HLD and teaches the importance for performing a validation test after HLD disinfection. It is important to include the teachings of Nelson’s lab for showing the important to follow the Disinfection Validation standards. Also, the references of FDA- Duodenoscope Surveillance Sampling and Culturing Protocols, Russotto and Chen used in the 103 rejections are for supporting each special limitation claimed in the instant application, such as Chen teaches that the phage can be used for detection of the antibiotic-resistance bacteria contamination. They are applicable to be combined with Gile, Alfa and Nelson for teaching the instant claims in the 103 rejections.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am-4:30 pm, EST.
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/RUIXUE WANG/ Examiner, Art Unit 1672
/NICOLE KINSEY WHITE/ Primary Examiner, Art Unit 1672
1 Agun et al. is cited solely to response to applicant’s argument and not to reject any claim.