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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 May 28, 2025 has been entered.
DETAILED ACTION
Claims 3-7, 9-17, 22-23 and 26 are canceled.
The rejection of claims 1-2, 19-21, 27-28 and 32-36 under 35 U.S.C. 103 as being unpatentable under Edberg in view of Coorens et al., Rompré et al., Liu et al. and Model et al. is withdrawn in light of the amendment to claim 1 limiting the nutrient medium to 20% DMEM and 5% Fetal Calf Serum, which is not taught in the prior art, and further consideration of the declaration from Dr. Glukhman filed Nov. 22, 2024, providing evidence that a combination of 20% DMEM plus 5% fetal calf serum results in a synergism effect that is not taught in the prior art.
Claims 1-2, 8, 18-21, 24-25 and 27-37 are pending and under examination.
Priority
This application is a CON of PCT/IL2019/050064 filed on January 16, 2019, which claims priority to US provisional application 62/618,094 filed on January 17, 2018. The effective filing date of the current application is January 17, 2018.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-2, 8, 18-21, 24-25 and 27-37 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention.
Applicant is referred to MPEP 2163(II)(A)(3)(a)(i and ii), which states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure indicates that the patentee has invented species sufficient to constitute the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.
Claims 1 and 27 are drawn to a method for rapid detection and quantification of mammalian pathogenic Coliform bacteria in a sample, which requires (a) providing a detection cocktail comprising a nutrient medium comprising 20% Dulbecco’s Modified Eagle Medium (DMEM) and 5% Fetal Calf Serum, at least one fluorescent marker molecule selected from Fluorescein, Fluorescein di(β-D-glucuronide), NileRed and CY5; and at least one metabolic activator selected from X-glucuronide, B-galactose and D-glucose; and (b) contacting said sample with said detection cocktail; wherein said detection and quantification is by measuring intracellular gray levels of fluorescent intensity of said marker molecules by a sensor and determining said intracellular gray level to a predetermined threshold of metabolism and correlating said gray levels above said predetermined threshold with quantity of highly metabolically active said pathogenic Coliform bacteria in said sample. Claims 8 and 29 further require the addition of a fluorescently labelled antibody complex configured to bind to cell wall antigens specific for recognizing said Coliform bacteria, which is a “product by function” limitation. Dependent claims 2, 8, 18-21 and 28-37 do not provide additional support showing that applicant was in possession of the claimed invention. There is a failure to meet the written description requirement because the specification does not disclose a representative number of species of detection markers to support the detection of all Coliform bacteria in a sample, nor does the specification describe what structure is required for a fluorescently-labelled antibody complex to perform the desired function of recognizing cell wall antigens specific to Coliform bacteria, as described below.
The specification describes the quantification of intracellular concentration of marker molecules to differentiate recovered active cells from inactive cells (Specification p.17, lines 24-25). The specification identifies that using the marker molecules’ specific dye, it is possible to detect and quantify the rate and level of said indicators’ intracellular concentration in order to define, specify and count recovered microorganisms in the tested sample (Specification p.18, lines 1-4). The specification describes a single example of diluting a sample of wastewater sludge in PBS in concentrations of 1:10, 1:100 and 1:1000 w/v (Specification p.20, lines 1-2). The samples were treated with working solutions of CY3 membrane dyes in PBS with additions of beta-galactoside for total Coliform bacteria, stained for 6 minutes and imaged (Specification p.20, lines 22-29). The specification describes formulations of growth media that contain 100mL of DMEM and 25mL of FCS in a 500mL volume, and 200mL DMEM and 50mL of FCS in a 1000L volume (Specification p.32 Table 4; p.33 Table 5), which is equivalent to the claimed nutrient medium composition comprising 20% DMEM and 5% FCS, used in a detection assay (Specification p. 12, lines 1-3 and 10-13).
The specification does not identify examples of fluorescently labeled antibody complexes configured to bind to cell wall antigens that are conserved across all Coliform bacteria, and whether it is possible to determine and distinguish every species of Coliform bacteria using fluorescently labeled antibody complexes configured to bind to cell wall antigens.
Blanch et al. (“Characterization of bacterial coliform occurrences in different zones of a drinking water distribution system”, Journal of Applied Microbiology, 2007, Vol. 102, Issue 3, pp.711-721) teaches comparing bacterial coliforms detected from three zones of a water distribution system supplied by two separate water sources (abstract). Blanch teaches that the percentages of E. coli depended on the identification criteria, suggesting that there is uncertainty in detecting E. coli based on a specific set of identification criteria. Blanch teaches that some bacteria of the Enterobacterial group are not aerogenic, meaning they cannot use lactose with gas production, however total coliforms were only those that meet the classic definition and could ferment lactose with gas production at 37°C (p.713, 1st column 4th paragraph), suggesting that not all coliforms have the same identifying features and there is unpredictability in being able to determine all coliforms based on their metabolic activity, and further unpredictability around whether the specific metabolic activators of X-glucuronide, B-galactose and D-glucose would be able to increase the metabolism all coliforms. Blanch teaches that eight biochemical profiles for coliform populations were defined according to the results of the confirmative tests, and there was high diversity among these populations in the three zones studied (abstract), suggesting that a single metabolic activator, D-glucose, does not determine biochemical profiles for all the possible coliform populations that could be present in a sample from water, wastewater, sludge, food, beverage, air and soil.
Fiello et al. (“Variability in the Characterization of Total Coliforms, Fecal Coliforms and Escherichia coli in Recreational Water Supplies of North Mississippi, USA”, Bulletin of Environmental Contamination and Toxicology, 2014, Vol. 93, pp.133-137) teaches that the fecal coliform Escherichia coli is a historical organism for the detection of fecal pollution in water supplies, and that it is important to distinguish E. coli from other coliform bacteria (e.g. Citrobacter, Klebsiella and Enterobacter), which are present not only in fecal matter, but also in soil and runoff water and are not good indicators of fecal contamination (abstract), suggesting there is unpredictability in detecting all Coliform bacteria because these coliform bacteria have distinguishing properties from E. coli and may not be universally detectable using the same methods. Fiello further teaches that species of the coliform Kluyvera are essentially E. coli phenotypically, demonstrating β-glucuronidase activity and positive indole production, however they are citrate positive (p.133, 2nd column, last paragraph), suggesting that different coliform bacteria have different metabolism profiles, and a particular metabolic activator may not be universally applicable to all coliform bacteria.
Labadie et al. (“Selection of cell wall antigens for the rapid detection of bacteria by immunological methods”, Journal of Applied Bacteriology, 1994, Vol. 72, Issue 3, pp.220-226) teaches the selection of cell wall antigens for the rapid detection of bacteria by immunological methods (title). Labadie teaches that among the different methods of detecting and counting bacteria present in foods, immunological techniques are promising because of their sensitivity and rapidity (p.220, 1st column 1st paragraph). Labadie further teaches that for gram-negative bacteria, different proteins from the outer membranes are known to be common antigens of a genus or species (p.220, 1st column 1st paragraph), suggesting that antigens are not necessarily conserved across bacteria of different genera, and thus there is unpredictability in being able to determine what antibody complex is configured to bind to cell wall antigens specific to recognizing all Coliform bacteria.
Based on the teaching of the prior art, it is highly unpredictable as to whether a detection cocktail comprising 20% DMEM and 5% Fetal Calf Serum; at least one fluorescent marker selected from Fluorescein, Fluorescein di(β-D-glucuronide), NileRed and CY5; and at least one metabolic activator selected from X-glucuronide, B-galactose and D-glucose will be able to detect coliform bacteria in a sample from water, wastewater, sludge, food, beverage, air and soil across the genus of any coliform bacteria. It is also highly unpredictable as to whether any fluorescently labeled antibody configured to bind to cell wall antigens will be universally applicable to detecting any Coliform bacteria, as cell wall antigens can vary between genus and species of bacteria.
Conclusion
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/DEEPA MISHRA/Examiner, Art Unit 1657