DETAILED ACTION
Applicant’s amendment submitted on 1/13/2026 is acknowledged. Claims 1-2 and 5-7 are currently amended. Claims 20-21 are newly added. Claims 13-16 remain withdrawn pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention. Claims 1-2 and 4-21 are pending in the instant application.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/13/2026 has been entered.
Priority
The instant application is a U.S. national phase of PCT/IL2021/050128, filed on 2/3/2021, and claims domestic benefit to U.S. provisional application number 62/969,197, filed on 2/3/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/19/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Amendment
Applicant’s amendment to paragraph [032] of the specification overcomes the objection previously set forth in the Final Rejection mailed on 10/21/2025.
Duplicate Claims - Warning
Applicant is advised that should claim 1 be found allowable, claim 2 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Despite a slight difference in wording, claims 1 and 2 are directed to the same method for isolating a target microorganism from a sample and recite the same method steps.
Claim Objections
Claim 2 is objected to because of the following informalities:
Independent Claim 2 recites “FISH” in line 7 but should fully recite “fluorescent in situ hybridization” before the abbreviation.
Appropriate correction is required.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1-2, 4-5, 7-12, and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Tram et al. (Food Control, 2012, Vol. 24, p.23-28; of record) in view of Xiao et al. (J. AOAC Intern., 2012, Vol. 95(1), p.216-221; of record) and Bruder et al. (Systemat. Appl. Microbiol., 2016, Vol. 39, p.464-475; of record).
Regarding claims 1 and 2, Tram teaches an isolation and detection method for Campylobacter jejuni from chicken fecal samples through immunomagnetic separation combined with PCR (see Abstract). Tram teaches amino-functionalized magnetic microparticles were coated covalently with C. jejuni monoclonal and polyclonal antibodies for the isolation and detection of C. jejuni in samples prepared from chicken feces, reading on contacting said sample with an antibody having specific affinity to said target microorganism and separating at least one selected bacterial target microorganism being bound to said antibody, thereby determined to be presented in said sample, from said sample, thereby isolating a target microorganism from the sample comprising a plurality of microorganisms, as recited in claim 1 (see p.24, paragraph bridging left and right column, and right column, 1st-last paragraphs). With respect to claim 2, this teaching by Tram reads on steps (a) and (d). Tram further teaches using a PCR assay to confirm the presence of C. jejuni captured to the magnetic microparticles, reading on determining the presence of said target microorganism in said fraction of said sample, as recited in claim 1 (see p.24, right column, 2nd and last paragraphs, and Fig. 1). With respect to claim 2, this teaching by Tram reads on step (b).
Tram does not teach wherein said antibody is produced by immunizing a host organism using a selected target microorganism, and wherein said selected target microorganism is selected by contacting a fraction of said sample with one or more fluorescently labeled polynucleotide molecules each having specific affinity to one bacterial target microorganism, determining the presence of said bacterial target microorganism in said fraction of said sample using fluorescent in situ hybridization (FISH).
Xiao teaches producing a rabbit polyclonal antibody against Pseudomonas aeruginosa by inoculating New Zealand rabbits with inactivated culture of P. aeruginosa emulsified with complete Freund’s adjuvant subcutaneously and dorsally and purifying the antibody from the immunized rabbit’s blood, reading on said antibody being produced by immunizing a host organism using a selected target microorganism, as recited in claim 1 (see Abstract and p.217, left column, 3rd paragraph). With respect to claim 2, this teaching by Xiao reads on step (c).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have produced the polyclonal antibody specific to C. jejuni by immunizing rabbits with inactivated C. jejuni and purifying the antibody from the rabbit’s blood, as taught by Xiao, and substituting the polyclonal antibody specific to C. jejuni produced by immunization of the rabbit for the polyclonal antibody coated on the magnetic microparticles of Tram, to arrive at the claimed invention. One of ordinary skill in the art would have been applying known methods for producing bacteria-specific polyclonal antibodies as taught by Xiao to obtain polyclonal antibodies useful in the method of Tram, yielding predictable results. One of ordinary skill in the art would have had a reasonable expectation of success because the antibody produced in the method of Xiao is a polyclonal antibody and the method of Tram utilizes polyclonal antibody.
Xiao does not teach wherein said selected target microorganism is selected by contacting a fraction of said sample with one or more fluorescently labeled polynucleotide molecules each having specific affinity to one bacterial target microorganism, determining the presence of said bacterial target microorganism in said fraction of said sample using fluorescent in situ hybridization (FISH).
Bruder teaches a method of sorting fecal bacteria by combining fluorescence in situ hybridization (FISH) and fluorescence-activated cell sorting (FACS) (see Abstract, p.465, left column, 2nd paragraphs, right column, 1st paragraph, p.467, left column, 3rd paragraph-right column, last paragraph, p.468, left column, 1st-2nd paragraphs, p.470, left column, 1st paragraph-p.471, right column, 1st passage, Figs. 5 and 6, and Table 2). The polynucleotide ssRNA probes designed by Bruder target domain III of the 23S rRNA and are fluorescently labeled (see Abstract, p.465, left column, last paragraph, right column, last paragraph, and p.472, left column, last paragraph, and right column, 1st paragraph). Thus, Bruder teaches a method of selecting a target microorganism from a sample using a fluorescently labeled polynucleotide molecule having specific affinity to the target microorganism and determining the presence of said bacterial target microorganism in said fraction of said sample using FISH.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have isolated C. jejuni from chicken fecal samples using the combined FISH-FACS method taught by Bruder, to provide isolated C. jejuni to immunize rabbits and produce polyclonal antibodies specific to C. jejuni, as taught by Tram in view of Xiao, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated with a reasonable expectation of success to isolate C. jejuni from chicken fecal samples to provide isolated C. jejuni for the production of polyclonal antibodies specific to C. jejuni because Bruder teaches the combined FISH-FACS method is capable of sorting bacteria in complex samples such as fecal samples and Tram teaches performing their methods on chicken fecal samples. The ordinarily skilled artisan would have been using known techniques for isolating bacterial cells in order to provide isolated C. jejuni cells for immunization of rabbits and production of C. jejuni-specific polyclonal antibody.
Thus, the method of claims 1 and 2 are prima facie obvious over Tram in view of Xiao and Bruder.
Regarding claims 4-5, Tram teaches Campylobacter jejuni is a bacterial food-borne pathogen (see Abstract and p.23, left column, 1st paragraph).
Regarding claim 7, Tram further teaches performing their method of isolation and detection using 6 common food-borne bacterial species in chicken feces including Campylobacter jejuni, C. coli, Salmonella enteritidis, Escherichia coli, Clostridium perfringens, and Listeria monocytogenes (see p.24, 3rd-4th paragraphs, and Table 1). Tram teaches C. jejuni is the major food-borne pathogen implicated in human Campylobacter infections worldwide and is associated with the consumption of contaminated foods, such as poultry and poultry products (see p.23, left column, 1st paragraph).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have performed the method of Tram in view of Xiao and Bruder, on all 6 strains of pathogenic bacterial species found in chicken feces, in order to detect and isolate these pathogenic bacteria and identify and prevent the spread of food-borne illness, yielding predictable results. One of ordinary skill in the art would have had a reasonable expectation of success because Tram teaches these bacteria are found in chicken feces and the method of Bruder for isolating bacteria using combined FISH-FACS is performed in fecal samples. Thus, a plurality of fluorescently labeled polynucleotide molecules each having specific affinity to one bacterial target microorganism is prima facie obvious over Tram in view of Xiao and Bruder.
Regarding claims 8-9, Tram teaches the samples are chicken fecal samples (see p.24, right column, 2nd-3rd paragraphs).
Regarding claim 10, Tram teaches their method of isolation and detection of Campylobacter jejuni is functional without pre-enrichment (see Abstract and p.27, passage bridging left and right columns, and p.28, left column, 1st paragraph). Tram teaches 10 CFU of C. jejuni could be detecting in 1 μl of chicken stool (see p.27, right column, 1st passage). One of ordinary skill in the art would have found it obvious before the effective filing date of the claimed invention to perform the method of Tram with a step of enrichment of C. jejuni in the fecal sample to determine if there is an improvement in the CFU of C. jejuni detected, yielding predictable results.
Regarding claims 11 and 17-18, the method of Tram in view of Xiao and Bruder would necessarily deplete the sample of C. jejuni as it is being isolated (i.e. separated) from the sample, thus reading on claim 11. In separating C. jejuni from the sample, C. jejuni is being eliminated from the sample, reading on claims 17-18.
Regarding claim 12, Tram teaches testing the specificity of the assay for isolation and detection using 6 common food-borne bacterial species in chicken feces including Campylobacter jejuni, C. coli, Salmonella enteritidis, Escherichia coli, Clostridium perfringens, and Listeria monocytogenes (see p.24, 3rd-4th paragraphs, p.26, paragraph bridging left and right columns, and Tables 1 and 4).
Xiao teaches testing the specificity of the polyclonal antibody produced by immunizing rabbits using 12 strains of Pseudomonas aeruginosa and Enterobacter cloacae (see p.217, left column, 1st paragraph, paragraph bridging p.217-218, p.219, right column, 1st paragraph, Table 1, and Fig. 4).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have determined the specificity of the polyclonal antibody specific to Campylobacter jejuni produced through immunization of rabbits, as taught by Tram in view of Xiao and Bruder, against a control, as taught by Tram and Xiao, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to determine there are no off-target effects of the polyclonal antibody produced and that it is indeed specific to the target bacteria, yielding predictable results.
Claims 6 and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Tram et al. (Food Control, 2012, Vol. 24, p.23-28; of record) in view of Xiao et al. (J. AOAC Intern., 2012, Vol. 95(1), p.216-221; of record) and Bruder et al. (Systemat. Appl. Microbiol., 2016, Vol. 39, p.464-475; of record), as applied to claims 1-2, 4-5, 7-12, and 17-18 above, and further in view of Carlander et al. (Upsala J. Med. Sci., 1999, Vol. 104, pp.179-190).
Tram in view of Xiao and Bruder teach the invention of claims 1 and 2 as outlined in the rejection above.
Xiao teaches producing a rabbit polyclonal antibody against Pseudomonas aeruginosa by inoculating New Zealand rabbits with inactivated culture of P. aeruginosa emulsified with complete Freund’s adjuvant subcutaneously and dorsally and purifying the antibody from the immunized rabbit’s blood, reading on said antibody being produced by immunizing a host organism using a selected target microorganism, as recited in claim 1 (see Abstract and p.217, left column, 3rd paragraph). With respect to claim 2, this teaching by Xiao reads on step (c).
Regarding claims 6 and 20-21, Tram, Xiao, and Bruder do not teach wherein said antibody is an immunoglobulin Y (IgY) or wherein said host organism is a chicken.
Carlander teaches laying hens produce more IgY yolk antibodies than a rabbit can produce in the same time period, and the animal care costs are lower for the chicken than the rabbit (see Abstract and p.180, 1st paragraph). Carlander further teaches polyclonal antibody production is highly efficient in immunized laying hens since antibodies can be purified in large amounts from egg yolk (see Abstract, passage bridging pp.184-185, p.185, 2nd paragraph and 2nd passage, and p.186, 3rd passage).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have substituted a laying hen for IgY antibody production, as taught by Carlander, for the rabbit used for preparing polyclonal antibody, as taught by Tram in view of Xiao and Bruder, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to use laying hens instead of rabbits for IgY antibody production because Carlander teaches laying hens produce more antibodies in the same time period and the costs of care for laying hens is lower than rabbits, yielding predictable results. Thus, claims 6 and 20-21 are prima facie obvious.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Tram et al. (Food Control, 2012, Vol. 24, p.23-28; of record) in view of Xiao et al. (J. AOAC Intern., 2012, Vol. 95(1), p.216-221; of record) and Bruder et al. (Systemat. Appl. Microbiol., 2016, Vol. 39, p.464-475; of record), as applied to claims 1-2, 4-5, 7-12, and 17-18 above, and further in view of Fuller (J. Poult. Sci., 2001, Vol. 38(3), pp.189-196).
Tram in view of Xiao and Bruder teach the invention of claims 1 and 18 as outlined in the rejection above.
Regarding claim 19, Tram, Xiao, and Bruder do not teach administering a composition comprising said sample devoid of the bacterial target microorganism to a subject in need thereof.
Fuller teaches chickens are important food animals but can be responsible for public health problems due to Campylobacter infections (see Abstract). Fuller teaches that wild chickens receive their gut flora from the mother’s feces which confers protection against infection from pathogens, whereas commercial chickens hatched in clean incubators are not exposed to the microorganisms commonly found in the gut (see p.192, 3rd paragraph). Fuller further teaches that dosing day-old chicks with feces from adult chickens improved their resistance to colonization of the gut by Salmonella enteritidis and Campylobacter (see p.192, 4th paragraph). The problem that faces using raw gut contents as a feed supplement is potential pathogen transfer and has been minimized by utilizing pathogen-free flocks and culturing under in vitro conditions to eliminate protozoa and viruses (see p.192, 4th paragraph).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have administered chicken feces from chickens that have had the pathogen Campylobacter jejuni removed, as taught by Tram in view of Xiao and Bruder, to day-old chicks, as taught by Fuller, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to inoculate the day-old chicks with the healthy microflora of adult chickens having had pathogenic C. jejuni removed to provide resistance to pathogenic bacteria like Campylobacter and Salmonella, yielding predictable results. There would have been a reasonable expectation of success because chickens are known to receive gut flora inoculations from feces. Thus, claim 19 is prima facie obvious.
Response to Arguments
Applicant's arguments filed 1/13/2026 have been fully considered but they are not persuasive.
In Applicant’s Remarks, see p.7, last paragraph,-p.8, 3rd paragraph, Applicant submits that the combination of prior art fails to teach or suggest the specific integrated workflow recited in claims 1 and 2. Applicant further argues Tram does not teach producing custom antibodies by immunizing a host organism with bacteria that were first selected from the sample using polynucleotide probes. Applicant further argues the antibodies used by Tram were commercially available and specific for well-characterized known bacterial species and not bacteria that were identified and selected from the sample through FISH-based detection using polynucleotide molecules. Applicant further argues Xiao uses known bacteria strains for immunization and not bacteria that were selected from a sample using polynucleotide probes. Applicant further argues Xiao doesn’t teach or suggest first determining the presence of a bacterial target in a sample fraction using fluorescently labeled polynucleotide molecules by FISH, and then using that bacterium as an immunogen. Applicant further argues Bruder’s purpose is antithetical to the claimed invention since it is not specific to selecting bacteria to use as immunogens for antibody production. Applicant argues that there is no suggestion in Bruder to use the sorted bacteria for immunization purposes. This is not found persuasive.
With regards to the specific workflow of the claimed invention, the rejection as set forth would require that the specific workflow is carried out for the following reasons. Tram demonstrates isolation of a target bacteria, i.e., Campylobacter jejuni, from chicken fecal samples through immunogenic separation combined with PCR to confirm C. jejuni was indeed isolated. Tram utilizes monoclonal and polyclonal antibodies for isolation and detection of C. jejuni in samples prepared from the chicken fecal samples. Although Tram doesn’t teach the antibodies are produced by immunization of a host with C. jejuni, the prior art teaches methods of producing specific targeting antibodies by immunizing a host with the target bacteria. Xiao is relied upon to teach such a technique of immunizing a host with a target bacteria to produce polyclonal antibodies that target the bacteria. Specifically, Xiao teaches inoculating New Zealand rabbits with inactivated culture of P. aeruginosa emulsified with complete Freund’s adjuvant subcutaneously and dorsally and purifying the antibody from the immunized rabbit’s blood. A person of ordinary skill in the art before the effective filing date of the claimed invention, would have found it obvious to produce specific antibodies for C. jejuni useful in the method of Tram by immunizing rabbits with C. jejuni and collecting the polyclonal antibodies produced. A person of ordinary skill is a person of ordinary creativity and not an automaton and would have been able to adapt the overall process of Xiao for the purposes of producing a polyclonal antibody that targets C. jejuni to provide Tram with such polyclonal antibodies, yielding predictable results. In order to obtain isolated C. jejuni to immunize rabbits with, Bruder teaches a method of FISH-FACs that sorts bacteria from feces utilizing fluorescently-labeled ssRNA polynucleotides. Specifically, Bruder teaches sorting fecal bacteria by combining fluorescence in situ hybridization (FISH) and fluorescence-activated cell sorting (FACS). One of ordinary skill in the art would have found it obvious to isolate C. jejuni from the fecal samples of Tram since Bruder teaches a method of sorting specific bacteria from feces. Thus, the person of ordinary skill in the art, looking to Tram, Xiao, and Bruder, would have been able to adapt the relevant teachings of each to arrive at the claimed invention with a reasonable expectation of success since Tram and Bruder teach their methods involve bacteria from fecal samples, absent any impermissible hindsight, since the relevant techniques were well-known and recognized in the prior art. An obviousness rejection does not require that the purpose of each prior art specifically align with the Applicant’s, only that there would be reasonable motivation to combine the prior art to arrive at Applicant’s claimed invention. Therefore, Tram, Xiao, and Bruder need not specifically supply each of the claimed limitations independently to the render the claimed invention wholly obvious. Furthermore, the claimed invention does not require that the target bacteria not be a known bacterial species as Applicant argues. Thus, the arguments related to the bacteria of the prior art being known are not commensurate in scope with the claimed invention.
In Applicant’s remarks, see p.8, last paragraph,-paragraph bridging pp.8-9, Applicant argues the rejection relies on improper hindsight reconstruction rather than any teaching or suggestion in the prior art, since the prior art do not suggest the specific claimed workflow. Applicant further argues the motivation provided by the Office does not address why one of ordinary skill in the art would use bacteria selected by fluorescently labeled polynucleotide probes and FISH specifically as immunogens when the prior art of Tram and Xiao already had access to known bacterial strains for immunization. Lastly, Applicant submits the claimed invention provides a unique approach for isolating bacterial target microorganisms from complex samples where the identity of the target bacteria may not be known a priori, which has not been contemplated by the cited references. This is not found persuasive.
Applicant’s arguments with regards to impermissible hindsight reconstruction have been addressed in the response above. Furthermore, as discussed in the response above, the claimed invention does not require that the target bacteria is not a well-known bacterial species. Thus, Applicant’s argument is not commensurate in scope with the claimed invention, and the cited prior art do not need to satisfy this feature as stated by Applicant.
Therefore, the claimed invention remains rejected over Tram in view of Xiao and Bruder for the reasons set forth in the rejection and responses above.
Conclusion
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/J.P.S./
Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651