DETAILED ACTION
Applicant’s amendment submitted 5/31/2026 is acknowledged. Claims 2, 4, 6-7, 9, and 12 are currently amended. Claims 1, 3, 5, 8, 10-11, and 13-20 are canceled. Claims 22-25 are newly added. Claims 2, 4, 6-7, 9, 12, and 21-25 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 .
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.
Response to Amendment
Applicant’s amendment to claim overcomes the objection previously set forth in the Non-Final Rejection mailed on 3/3/2026.
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.
Maintained Rejection: Claims 2, 4, 7, 9, 12, and 23-25, 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 claim 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 fraction of said sample with an antibody having specific affinity to the pathogenic target bacteria, thereby isolating a target microorganism from the fraction of said sample comprising a plurality of microorganisms (see p.24, paragraph bridging left and right column, and right column, 1st-last paragraphs). 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 pathogenic target bacteria in said fraction of said sample (see p.24, right column, 2nd and last paragraphs, and Fig. 1).
Tram does not teach immunizing a host organism using the isolated pathogenic target bacteria, thereby producing an antibody having specific affinity to the isolated pathogenic target bacteria, contacting a fraction of said sample with one or more fluorescently labeled polynucleotide molecules each having specific affinity to one bacterial target microorganism, or 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 an isolated pathogenic target bacteria as recited in step (c), (see Abstract and p.217, left column, 3rd 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 produced the polyclonal antibody specific to C. jejuni by immunizing rabbits with inactivated isolated 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 contacting a fraction of said sample with one or more fluorescently labeled polynucleotide molecules each having specific affinity to one bacterial target microorganism, or 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 isolating a target microorganism from a sample by contacting it with a fluorescently labeled polynucleotide molecule having specific affinity to the target bacteria 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.
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 depleting the pathogenic target bacteria from the sample. In separating C. jejuni from the sample, C. jejuni is being eliminated from the sample.
Thus, the method of claim 2 is prima facie obvious over Tram in view of Xiao and Bruder.
Regarding claim 4, Tram teaches Campylobacter jejuni is a bacterial food-borne pathogen (see Abstract and p.23, left column, 1st paragraph).
Regarding claim 7, Bruder teaches the polynucleotide ssRNA probes are designed to 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). The method of hybridization utilizes a plurality of fluorescently labeled probes (see p.467, left column, last paragraph). Thus, the method rendered obvious by Tram in view of Xiao and Bruder reads on contacting said sample with a plurality of fluorescently labeled polynucleotide molecules each having specific affinity to said pathogenic target bacteria.
Regarding claim 9, Tram teaches the samples are chicken fecal samples (see p.24, right column, 2nd-3rd paragraphs).
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, a common technical practice in the field, yielding predictable results.
Regarding claims 23 and 24, Bruder teaches polynucleotide ssRNA probes are designed to target domain III of the 23S rRNA and are fluorescently labeled and hybridize to the complementary domain in the target bacteria and sorted by FACS based on the fluorescent signal (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, the limitations of claims 23-24 are obvious over Tram as modified by Xiao and Bruder.
Regarding claim 25, Bruder teaches the polynucleotide ssRNA probes are designed to 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). Bruder further teaches PCR identification of the target bacteria in the sample using a primer designed to target the 16S rRNA of the bacterium (see p.466, right column, 1st-2nd paragraphs). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to design the fluorescently labeled polynucleotide probes using the 16S rRNA rather than the 23S rRNA, to arrive at the claimed invention. One of ordinary skill in the art would have been substituting known specific targeting domains of the bacterium to serve the same purpose, yielding predictable results.
Maintained Rejection: Claims 6 and 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 2, 4, 7, 9, 12 and 23-25 above, and further in view of Carlander et al. (Upsala J. Med. Sci., 1999, Vol. 104, pp.179-190; of record).
Tram in view of Xiao and Bruder teach the invention of claim 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 an isolated pathogenic target bacteria, as recited in step (c) (see Abstract and p.217, left column, 3rd paragraph).
Regarding claims 6 and 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 21 are prima facie obvious.
Maintained Rejection: 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; of record).
Tram in view of Xiao and Bruder teach the invention of claim 2 as outlined in the rejection above.
Regarding claim 22, Tram, Xiao, and Bruder do not teach administering the sample devoid of the pathogenic target bacteria 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 22 is prima facie obvious.
Response to Arguments
Applicant's arguments filed 5/31/2026 have been fully considered but they are not persuasive.
In Applicant’s Remarks, see paragraph bridging pp.6-7,-p.8,last paragraph, Applicant argues Tram in view of Xiao and Bruder fails to teach the specific claimed workflow. Applicant further argues that none of the references teach or suggest physically isolating pathogenic target bacteria from a fraction of a sample after FISH-based detection and then using that isolated bacterium as an immunogen for antibody production. Applicant argues that Tram does not teach producing custom antibodies by immunizing a host organism with pathogenic bacteria that were first isolated from a fraction of the sample using polynucleotide probes. Applicant also argues that Xiao does not teach or suggest first determining the presence of a pathogenic target bacteria in a sample fraction using fluorescently labeled polynucleotide molecules by FISH, isolating that bacterium, and then using the isolated bacterium as an immunogen. Applicant further argues Bruder is directed to DNA recovery and metagenomic analysis and not for isolating live bacteria for use as immunogens for antibody production. Applicant further argues Bruder’s fixation of cells with paraformaldehyde (PFA) prior to FISH and sorting would render the sorted bacteria unsuitable for immunization. Applicant argues Bruder does not suggest using the sorted bacteria for immunization purposes, or to physically isolate live bacteria from a sample fraction for subsequent use as immunogens. Applicant further argues none of the cited references teaches or suggests the depleting step as claimed. Applicant further argues Tram’s method focuses on detecting the presence of the pathogen and not on depleting the pathogen using antibodies produced from FISH-isolated bacteria. Applicant further argues the motivation provided in the Office Action does not address why one of ordinary skill in the art would physically isolate bacteria from a sample fraction using FISH-based detection specifically for use as immunogens when the prior art of Tram and Xiao already had access to known bacterial strains for immunization. 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, which have been set forth above. Therefore, Tram, Xiao, and Bruder need not specifically supply each of the claimed limitations independently to the render the claimed invention wholly obvious. Furthermore, a person of ordinary skill in the art is a person of ordinary creativity, not an automaton, and would have understood how to piece together the teachings of Tram, Xiao, and Bruder in such a cohesive manner (See MPEP § 2141.03). That is, one of ordinary skill in the art would avoid the unnecessary fixation step of Bruder in order to maintain the viability of the isolated cells and their subsequent use in immunization in a host organism to generate polyclonal antibodies specific to the isolated bacteria. Thus one of ordinary skill in the art looking to fit the teachings of Tram, Xiao, and Bruder together would recognize the need to maintain the viability of the isolated cells and would understand that unnecessary cell killing steps need to be avoided.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/J.P.S./ Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
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