DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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
2. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Nov. 16, 2025 has been entered.
Claim Amendments
3. The amendment filed Nov 16, 2025 have been entered. Claims 1-10 were previously cancelled. Claims 11, 25 and 26 were amended. Claims 11-27 are under consideration in this Office Action.
Withdrawal of Rejections
4. The rejection of claims 25-27 under 35 U.S.C. 101 is withdrawn in view of Applicants amendments is withdrawn in view of Applicants amendments.
Maintained Ground of Rejection
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
5. Claims 11-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The U.S. Patent and Trademark Office recently published revised guidance on the application of § 101 [ 1] ("2019 Guidance"). Under that guidance, in determining what concept the claim is "directed to," we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e.,
mathematical concepts, certain methods of organizing human activity such as a
fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical
application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an "'inventive concept' sufficient to 'transform"' the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not "well understood, routine, conventional" in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously
known to the industry, specified at a high level of generality, to the judicial exception.
See 2019 Guidance.
Step 1 - Whether a claim is to a statutory category - YES
The instantly claimed invention is directed to a method for determining the risk of an avian pathogenic E. coli (APEC) infection in an avian flock, the method comprising obtaining a pooled environmental sample derived from the flock, quantifying by qPCR
specific virulence factors (VF), each with respect to the amount of E. coli reference gene ybbW (SEQ ID NO: 6) or functional fragments thereof, wherein the specific virulence factors include at least the genes iroN (SEQ ID NO.:1) and ompT (SEQ ID NO:2) or functional fragments thereof; and using a ratio of the quantified virulence factors to reference gene, VFs/ybbW, as an indicator of infection risk.
Step 2A Prong 1 - Whether the claim is directed to a judicial exception (i.e. Does
the claim recites an abstract idea, law of nature, or natural phenomenon?) - YES
Claims 11-24 recite the following steps which fall under the law of
nature and/or mathematical concepts grouping of abstract ideas:
Claims 11-24 are directed to a method for determining the risk of an avian pathogenic E. coli (APEC) infection in an avian flock. The limitation falls into judicial exceptions because: 1) the amount of specific virulence factors (VF), each with respect to the amount of E. coli reference gene ybbW (SEQ ID NO: 6) or functional fragments thereof, in a sample from the avian, is a natural correlation between the virulence genes of iroN and ompT and the reference gene ybbW; and 2) the broadest reasonable interpretation of determining the risk of an APEC infection in an avian is based on the amount of at least iroN and ompT virulence gene which involves a mental process determining the ratio of virulence factors with respect to the amount of reference gene.
Therefore, the claim as a whole is directed to judicial exceptions (a law of nature and an abstract idea). For purposes of examination efficiency, a law of nature is selected into the conduction of the eligibility analysis. The claim recites several nature-based product limitations including iroN and ompT and the environmental sample, which raises the question of whether the markedly different characteristics analysis should be used to determine if the nature-based product limitations are product of nature exceptions. For a process claim, the general rule is that the claim is not subject to the markedly different analysis for nature-based products used in the process. MPEP 2106.04(c)(I)(C). While there is an exception to this general rule for process claims that are drafted in such a way that they are no different in substance than a product claim, claim 11 does not invoke this exception because review of this claim indicates that it is focused on a process of determining how much iroN and ompT is present in the sample. Thus, the general rule expressed in the MPEP applies, meaning that the markedly different characteristics analysis is not Appendix 1 to the October 2019 Update: Subject Matter Eligibility Life Sciences & Data Processing Examples October 2019 4 performed on the recited nature-based product limitations, and the claim is not considered to “recite” any products of nature for purposes of further eligibility analysis. However, the claim still must be reviewed to determine if it recites any other type of judicial exception. The claim recites “…using a ratio of the quantified virulence factors to reference gene, VFs/ybbW, as an indicator of infection risk.” which has a BRI that requires performing an arithmetic calculation (division) in order to obtain the ratio of VFs/ybbW levels, and then using this ratio to determine the risk of an avian pathogenic E. coli (APEC) infection in an avian flock. This limitation therefore recites a mathematical calculation. The grouping of “mathematical concepts” in the 2019 PEG includes “mathematical calculations” as an exemplar of an abstract idea. 2019 PEG Section I, 84 Fed. Reg. at 52. Thus, limitation (a) falls into the “mathematical concept” grouping of abstract ideas. In addition, this type of simple arithmetic calculation (division) can be practically performed in the human mind, and is in fact performed in the human mind on a daily basis, for instance by school-aged children studying mathematics. Note that even if most humans would use a physical aid (e.g., pen and paper, a slide rule, or a calculator) to help them complete the recited calculation, the use of such physical aid does not negate the mental nature of this limitation. Thus, limitation (a) also falls into the “mental process” groupings of abstract ideas. In addition, limitation (a) describes a naturally occurring relationship between the ratio of VFs to ybbW, and thus may also be considered to recite a law of nature. Accordingly, the limitation recites a judicial exception (an abstract idea that falls within the mathematical concept and mental process groupings in the 2019 PEG, and a law of nature), and the analysis must therefore proceed to Step 2A Prong Two. Although the limitation falls under several exceptions (e.g., a mathematical concept-type abstract idea, a mental process-type abstract idea, and a law of nature), there are no bright lines between the types of exceptions. See, e.g., MPEP 2106.04(I). Thus, it is sufficient for the examiner to identify that limitation (a) aligns with at least one judicial exception, and to conduct further analysis based on that identification. See October 2019 Update at Section I.B n.7.
Step 2A: Prong 2 - Does the claim recite additional elements that integrate
the judicial exception into a practical application? NO
The Step 2A, Prong 2 analysis requires identifying whether there are any
additional elements recited in the claim beyond the judicial exception(s), and
evaluating those additional elements to determine whether they integrate the
exception into a practical application of the exception. There is no claim limitation integrating the recited judicial exception into a practical application to affect a particular treatment or prophylaxis for a disease or medical condition. Therefore, the claims do not apply or use the judicial exception in a specific and meaningful way.
Claims 11-24, regarding step 2A prong one; recites mathematical formulas for determining risk and are considered to be a judicial exception as they express a scientific truth (quantitated gene amounts), but have been labelled by the courts as both abstract ideas and laws of nature. MPEP 2106.04 Mathematical formulas can be performed in the human mind and are considered “mental processes” and laws of nature are the basic tools of scientific and technological work are not patentable, because the “manifestations of laws of nature" are "part of the storehouse of knowledge,” "free to all men and reserved exclusively to none." Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130, 76 USPQ 280, 281 (1948).
Step 2B; Whether the additional elements contribute an "inventive concept". In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP 2106.05. The claims include steps collecting sample, incorporating additional virulence factors which are well-known in the art. De Carli et al., (Poultry Science. Vol. 94, Issue 11, Nov 2015, pages 2635-2640) teach Virulence gene content in Escherichia coli isolates from poultry flocks with clinical signs of colibacillosis in Brazil. De Carli et al., describe samples of each gene were sequenced and compared to reference strains. Many virulence factors were detected in Brazilian E. coli isolates. Moreover, a high nucleotide similarity (over 99%) was observed between gene sequences of Brazilian isolates and reference strains. The analysis of this set of virulence factors can be used to differentiate between APEC and AFEC isolates in Brazil. This part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. As explained with respect to Step 2A Prong Two, the claim recites a single additional element in limitation (b), which does not require any particular application of the recited calculation and is at best the equivalent of merely adding the words “apply it” to the judicial exception.
Therefore, the claims do not include any additional steps appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception.
For additional guidance, applicant is directed generally to applicant is directed generally to the MPEP§ 2106.
Response to Arguments
6. Applicant's arguments filed Nov. 16, 2025 have been fully considered but they are not persuasive. The rejection of claims 11-24 under 35 U.S.C. 101 is maintained for reasons of record.
Applicants asserts that although claim 11 recites a law of nature, it also includes: a) obtaining pooled environmental samples; b) quantitative analysis of samples via qPCR, and c) using a specific set of genes (iroN, ompT, ybbW) to reflect APEC infection risk. Applicant submits that these elements, in combination, provide an inventive concept that transforms a natural observation into a useful, technological laboratory method.
Contrary to Applicants assertion, the evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. 2019 PEG Section III(A)(2), 84 Fed. Reg. at 54-55. Besides the abstract idea, the claim recites the additional element of “using a ratio of the quantified virulence factors to reference gene, VFs/ybbW, as an indicator of infection risk.”
Although this limitation indicates that a ratio is to be used, it does not provide any information as to how the ratio value is used as an indication of risk infection. The use of the ratio does not determine a risk of an APEC infection. In fact, this limitation is recited at such a high level of generality that it does not even require a specific ratio outcome into account when determining the risk of APEC infection, making the limitation’s inclusion in this claim at best nominal. Like the claims in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 78 (2012), claim 1 here tells the relevant audience about the mathematical concepts and at most adds an indicator of risk. The limitation thus fails to meaningfully limit the claim because it does not require any particular application of the recited calculation, and is at best the equivalent of merely adding the words “using” to the judicial exception. Accordingly, the limitation does not integrate the claim limitation.
Applicants argue that claim 11, as a whole, integrates the correlation between VF expression and risk of APEC into a practical, laboratory-implemented process for obtaining and analyzing biological data for infection risk. The Office’s position is that this part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. As explained with respect to Step 2A Prong Two, the claim recites a single additional element in the using limitation, which does not require any particular application of the recited calculation.
Contrary to Applicants assertion, the claims MPEP 2106.04 Mathematical formulas can be performed in the human mind and are considered “mental processes” and laws of nature are the basic tools of scientific and technological work are not patentable, because the “manifestations of laws of nature" are "part of the storehouse of knowledge,” "free to all men and reserved exclusively to none. There is no claim limitation integrating the recited judicial exception into a practical application to affect a particular treatment or prophylaxis for a disease or medical condition. Risk determination did not solve the real world problem of determining avian APEC infection. Therefore, the claims do not apply or use the judicial exception in a specific and meaningful way.
Therefore applicants arguments are not persuasive and the rejection is maintained.
Claim Rejections - 35 USC § 112
7. Claims 11-24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 11-24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are:
Claim 11 is drawn to determining the risk of an avian pathogenic E coli infection in a flock. The method step recites “…using a ratio of the quantified virulence factors to reference gene, VFs/ybbW, as an indicator of infection risk.” However the claim fails to recite how the ratio is correlated to determine infection risk. The claims do not state how the ratio value will determine avian pathogenic E coli infection risk. The claims do not teach a ratio value which determines the level of risk avian pathogenic E coli infection. There is no value for determining negative or positive likelihood of avian pathogenic E coli infection risk to the flock. There is no value which represents the odds that the flock is at risk of an avian pathogenic E coli infection. There is no ratio value that measures disease severity which is correlated to avian pathogenic E coli infection. The claim only provides a numeric value and neither the claims nor the specification provide an explanation for the ratio value. The claims do not recite a step where risk of APE infection is assessed. The claims do not recite method steps for determining the risk criteria. Disease progression is not equivalent to risk determination. There is an omission within the claims which create a gap within the claimed steps.
Response to Arguments
8. Applicant's arguments filed Nov. 16, 2025 have been fully considered but they are not persuasive. The rejection of claims 11-24 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is maintained for reasons of record.
Applicants amended the claims to overcome the rejection to recite obtaining a polled sample, quantifying by qPCR and using a ratio as an indicator of infection risk. However, the claims do not actually recite any steps for determining risk of infection. At best, the claims recite using the ratio as an indicator of infection risk. The claims still do not recite a step where risk of APE infection is assessed. The claims do not recite any steps where the risk of avian pathogenic E coli infection in an avian flock was defined or even determined. Finding an Indicator of infection risk does not equate to determining the risk of an APEC flock infection. Therefore, the rejection is maintained.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
9. Claims 25-27 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Price et al., (WO 2014008312 published Jan 2014; priority to July 2012).
The claims are drawn to an environmental screening kit, comprising probes for detecting and quantifying at least iroN (SEQ ID NO: 1), ompT (SEQ ID NO: 2), and ybbW (SEQ ID NO: 6) wherein said probes are labeled with a fluorophore.
It is noted that the broadest reasonable interpretation of the claims and in view of Applicants response, the sequence recited within the parenthesis is merely an alternative way to identify the instantly named genes.
Price et al., teach methods and assay kits useful in detecting the presence of the distinct subtype of E. coli. The method of identifies the presence of E. coli H30-Rx, comprising: providing DNA from an E. coli sample; and detecting in the DNA from the E. coli sample whether the DNA has one or more single nucleotide polymorphisms (SNP) selected from the group consisting of SNP20Q, SNP264, and SNP3729, wherein detection of one or more of the SNPs indicating the presence of E. coli H30- Rx in the E. coli sample; further comprising: detecting in the DNA from the E. coli sample whether the DNA has an SNP of G723 A in an allantoin protein-encoding ybbW gene, wherein detection of the SNP of G723Ain ybbW indicating the presence of E. coli H30-Rx in the E. coli sample. Figure 27 presents a distribution of virulence factors by subclone. Presence (black box) / absence (gray box) scores for 52 known virulence factors are grouped by hierarchical clustering adjacent to the whole genome SNP-based phylogeny to reveal clonal grouping of these genes. Virulence factors include ompT [Example 17]. See also Example 27 showing analysis of iroN, siderophore receptor and ompT as outer membrane protease T and iutA (aerobactin receptor) [Figure 18]. For the H30-Rx subclone, primers were designed to detect a subclone-specific SNP ybbW. The term “label” refers to any moiety which can be attached to a molecule and: (i) provides a detectable signal; (ii) interacts with a second label to modify the detectable signal provided by the second label, e.g. FRET; (iii) stabilizes hybridization, i.e. duplex formation; or (iv) provides a capture moiety, i.e. affinity, antibody/antigen, ionic complexation. Labelling can be accomplished using any one of a large number of known techniques employing known labels. Labels include light-emitting compounds which generate a detectable signal by fluorescence, chemiluminescence, or bioluminescence [para 58]. The probe is labeled. The probe can be an oligonucleotide that is complementary to at least a portion of an amplification product formed using two primers [para 60]. In order to facilitate real-time detection or quantification of the amplification products, one or more of the primers and/or probes used in the amplification reaction can be labeled, and various formats are available for generating a detectable signal that indicates an amplification product is present. For example, a convenient label is typically a label that is fluorescent, which may be used in various formats including, but are not limited to, the use of donor fluorophore labels, acceptor fluorophore labels, fluorophores, quenchers, and combinations thereof [para 71].
There are provided assay kits for detecting the presence of H30-R and H30-Rx. In some embodiments, the kit and assays comprise one or more primer pairs for amplification of an H30-R or H30-Rx bacteria. In some embodiments, the kit comprises one or more probes for detection of the presence of H30-R or H30-Rx bacteria. In some embodiments, the kit comprises: a) one or more primer pairs for amplification of H30-R or H30-Rx genes; and/or b) one or more probes for detection of at least one H30-R or H30-Rx gene [para 13] . Virulence factor gene distribution varied significantly in relation to both ESBL phenotype and ST131 genotype (Supplemental table 1). Overall, nearly all VF genes that were significantly associated with ESBL status were more prevalent among ESBL-negative isolates [para 277]. Within ST131, iroN, was among the more prevalent among non-H30 isolates (Table 22). The analysis of VF gene profiles associated with subclones within ST131. Price et al., identified three prevalent VF genes including iutA.
The PCR is a multiplex asymmetric PCR. In the multiplex asymmetric PCR of the present invention, DNA polymerase, dNTP, Mg2+ concentration and the compounds of the buffer are same as that in traditional PCR, and they can be optimized according to different reactions [para 104]. Thus, Price et al., disclose the components of the instantly kit.
Response to Arguments
10. Applicant's arguments filed Nov 16, 2025 have been fully considered but they are not persuasive. The rejection of claims 25-27 under 35 U.S.C. 102(a)(2) as being anticipated by Price et al., is maintained for reasons of record.
Applicants argues that Price describes iroN or ompT and these genes are presented as diagnostic markers and not as quantitative markers forming a ratio indicative of avian infections risk. In response to applicant's argument that probes and markers have different uses, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Price provided assay kits. The primers included in the kit for detection of H30-Rx and/or H30-R bacteria are those disclosed herein, for example those listed in Table 8 showing primers for genetic markers kpsM subset which includes ompT; papG allele II which includes iroN, hlyF and iss and 025b which include iutA. Price teach fluorophore labeled probes and primers. Therefore, Price et al., describes fluorophore labeled probes iroN, ompT and ybbW, and iutA.
Applicants argue that the use of use are non-overlapping and have different uses. In response to applicant's argument that the intended use of the screening kit comprising iroN, ompT and ybbW labeled with a fluorophore, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. There is no structural difference and the intended use of the probes does not make patentable when the prior art clearly teaches the probes labeled with a fluorophore.
In this case, the prior art structure is capable of performing the intended use, therefore it meets the claim., Price et al., teach probes for detecting and quantifying at least iroN (SEQ ID NO: 1), ompT (SEQ ID NO: 2), and ybbW (SEQ ID NO: 6) wherein said probes are labeled with a fluorophore. Applicants have not pointed to any structural differences between the labeled probes and the instant claims. Therefore, Applicants arguments are not found persuasive and the rejection is maintained.
Pertinent Art
11. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure. Johnson et al., (ASM Journals/J of Clinical Microbio. Vol. 46, No. 12) Johnson et al., teach E. coli isolates of known pathogenicity and serogroup were subjected to virulence genotyping and phylogenetic typing. The results were analyzed by multiple-correspondence analysis. From this analysis, five genes carried by plasmids were identified as being the most significantly associated with highly pathogenic APEC strains: iutA, hlyF, iss, iroN, and ompT. A multiplex PCR panel targeting these five genes was used to screen a collection of 994 avian E. coli isolates. APEC isolates were clearly distinguished from the avian fecal E. coli isolates by their possession of these genes, suggesting that this pentaplex panel has diagnostic applications [abstract].
De Carli et al, (Poultry Science. Volume 94, Issue 11, November 2015, pages 2635-2640) De Carli et al., teach Isolates were obtained after culture from different tissue/organ samples (spleen, liver, kidney, trachea, lungs, skin, ovary, oviduct, intestine, cloaca) and collected environmental swabs [Samples]. Thus teaching the pooled samples. De Carli et al., describe ten virulence genes (cvaC, iroN, iss, iutA, sitA, tsh, fyuA, irp-2, ompT and hlyF) were detected by PCR and real-time PCR with procedures. PCR results were directly evaluated in polyacrylamide gel (10%) stained with silver nitrate in comparison to controls and commercial molecular weight markers [PCR amplification and Analysis].
Walker et al., (Water Research. Vol. 126, December 2017, pages 101-110) teach new quantitative real-time PCR (qPCR) assay was developed to detect the ybbW gene sequence, which was found to be 100% exclusive and inclusive (specific and sensitive) for E. coli and directly compared for its ability to quantify E. coli in environmental waters against colony counts.
See also, Joseph et al., (Journal of Applied Microbiology, Volume 135, Issue 5, May 2024).
Conclusion
12. No claims allowed.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571)272-0859. The examiner can normally be reached Monday thru Thursday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor Dan Kolker, can be reached on 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANA A HINES/Primary Examiner, Art Unit 1645