DETAILED ACTION
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 .
Applicant’s arguments and amendments have been thoroughly reviewed and considered. Claim 46 has been added. Claims 27-31 and 39-45 remain withdrawn. Claims 17-18, 24-25, 32, 34-35, 38, and 46 are pending and are examined on the merits herein.
Response to Applicant’s Amendments
Claim Objections
Claims 17 and 18 were objected to due to minor informalities. In light of Applicant’s amendments to the claims submitted 3/9/2026, these objections have been withdrawn. See also new grounds of objection below.
35 USC 103 Rejections
Claims 17-18, 25, 32, 34-35, and 38 were rejected under 35 U.S.C. 103 as being unpatentable over Ai et al. (Oncotarget, 2017), in view of Bullman et al. (Science, 2017), in view of GenBank (Accession #s ADGQ01000060.1, CR626927.1, AE015928.1, and LS483440.1), in view of Ye et al. (BMC Bioinformatics, 2012), and in view of Godfrey et al. (US 2006/0068433 A1).
Claim 24 was rejected under 35 U.S.C. 103 as being unpatentable over Ai et al. (Oncotarget, 2017), in view of Bullman et al. (Science, 2017), in view of GenBank (Accession #s ADGQ01000060.1, CR626927.1, AE015928.1, and LS483440.1), in view of Ye et al. (BMC Bioinformatics, 2012), in view of Godfrey et al. (US 2006/0068433 A1), and further in view of Zhang et al. (Cancer Medicine, 2019).
Applicant’s arguments and amendments have been thoroughly reviewed and considered. These rejections have been maintained. See “Response to Applicant’s Arguments” below. See also new grounds of rejection below for newly added claim 46.
Response to Applicant’s Arguments
Regarding the 35 USC 103 Rejections, Applicant argues that the cited references do not teach all the elements of the presently amended claims, particularly the final limitation in the kit of claim 17 that states that the kit has increased specificity and/or a reduced false positive rate compared to the use of a FOBT alone (Remarks, page 10). Specifically, Applicant states that Ai, the primary reference, does not teach the specific combination of claimed bacterial markers, and argues that Ai does not combine the results of FOBT with the abundance of specific bacterial species (Remarks, page 11).
On page 12 of their Remarks, Applicant notes that Peptostreptococcus stomatis was only shown to be associated with colorectal cancer (CRC) in a single population of the two studied in Ai, and that the ordinary artisan would thus not select this bacteria as a single biomarker for CRC. Applicant also states that Ai teaches away from selecting the abundance of a specific biomarker, as the reference shows that unclassified OTUs increase test performance. Ai also allegedly teaches away from the claimed invention as the reference is directed to the use of machine learning models (Remarks, page 12).
Regarding the secondary reference Bullman, Applicant states that the reference does not disclose using the claimed Bacteroides species in isolation from Fusobacterium (Remarks, page 13).
Regarding the combination of references used to reject claim 17, Applicant states that the rationale for this rejection relies on improper hindsight reasoning and provides speculative, non-specific reasoning (Remarks, page 14).
Firstly, in considered the scope of instant claim 17, it is noted that the claim is directed to a product (i.e. the claimed kit). Though the preamble of the kit recites that said kit is “For detecting colorectal advanced neoplasia (AN), advanced adenoma (AA) and/or colorectal cancer (CRC) in a subject,” this is considered intended use, and thus, this preamble is not limiting. This is because this preamble does not impart particular structural limitations on the claimed invention. See MPEP 2111.02. Thus, whether the prior art teaches the claimed kit in the context of the diseases listed in the preamble is not relevant to the determination of patentability. Prior art which generally suggests the use of the claimed elements in some fashion (e.g. the use of each element does not have to be simultaneous) will be considered to read on the instant claims. Additionally, the claimed kit is stated to comprise the listed reagents, and so could include additional reagents, such as additional oligonucleotides for the detection of additional bacterial species.
In considering Ai, the reference teaches that their analysis of CRC in populations began by performing sample collection, DNA extraction, and sequencing, where primers were used (pages 9552-9553). Thus, though the reference does eventually utilize machine learning models, the reference also teaches analysis of genomic material with primers, which would require oligonucleotides that can bind to said genomic sequences, similar to the claimed kit. Ai also teaches the use of FOBT in conjunction with microbiome data for both populations (see Table 1, page 9549, “Fecal microbiome combined with FOBT moderately improved the prediction ability”). As noted above, the simultaneous use of oligonucleotides and FOBT is not required in instant claim 17. Figure 3 shows that when including FOBT data with bacterial genomic data, false positive rates are lower than with FOBT alone. Though this bacterial data involves a different group of bacteria than those recited in claim 17, the use of additional bacteria, as noted above, is encompassed by the claim.
In considering the specific bacteria examined by Ai, the Examiner argues that any bacteria which was shown by the reference to be strongly CRC-associated would be of interest to the ordinary artisan for additional/further examination. As the reference specifically states that Peptostreptococcus stomatis was the most CRC-associated bacteria in Population B (Figure 4C), this bacteria would thus be of interest. Regarding the OTUs discussed by Ai, this refers to a pre-processing step concerning sequencing data before it is used in a model. Though Ai states that “test performance of almost all models improved,” there were very few significant differences between classified and unclassified models (Figure 2A), and so for those that were not significantly different, it is not clear that the ordinary artisan would be motivated to use unclassified data. Figures 2B-C show data from one model that did show significant differences between classified and unclassified data, but this is not necessarily representative of patterns for all models. In Figure 3B, which shows the superior performance of FOBT combined with microbial data versus the use of FOBT alone, neither of the models represented (Random Forest and BayesNet) are those which showed significant differences in Figure 2. Thus, in situations where microbial data is used in conjunction with FOBT utilizing the guidance provided by Ai, the classification status of OTU information is not particularly relevant. Furthermore, the bacterial data shown in Figure 4 is based on “the most discriminative bacterial species that consist of default parameters in many algorithms,” and so the importance of Peptostreptococcus stomatis applies to most of the models used by the reference as a whole.
Regarding teaching away, MPEP 2145 X (D) 1 states, “Furthermore, "the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). See also UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 692, 2023 USPQ2d 448 (Fed. Cir. 2023) ("a reference does not teach away if it merely expresses a general preference for an alternative invention but does not criticize, discredit or otherwise discourage investigation into the invention claimed.") (internal quotations omitted) (quoting DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1327 (Fed. Cir. 2009)).” Ai does not discredit or discourage using FOBTs and oligonucleotides, as the reference teaches using both of these components in their invention. As noted above, no particular use is required by instant claim 17, and additional components are not restricted, so Ai utilizing these claimed components in a method that also involves modeling does not constitute teaching away. The Examiner also does not suggest using a single biomarker from Ai – para. 27 of the Non-Final Rejection simply points out the use of Peptostreptococcus stomati and the associated primer in the reference.
Regarding Bullman, the fact that the Bacteroides species taught by the reference are also taught in conjunction with the finding of Fusobacterium is irrelevant to whether the reference renders the use of oligonucleotides that can hybridize to the claimed Bacteroides species obvious, as the presence of Fusobacterium-related oligonucleotides in the claim is not restricted (i.e. the claim comprises the listed components). Furthermore, the reference, regardless of the presence of Fusobacterium, teaches that Bacteroides fragilis and Bacteroides thetaiotaomicron are microbes found in primary cancer CRC tumors that also persist in metastases (page 1, column 3, para. 4). This alone would make these bacterial species of interest to study, as not only can these bacteria be indicative of CRC, but they may also be associated with later stage cancers, furthering the potential importance/interest in these species in CRC methods.
In combining Ai in view of Bullman, para. 30 of the Non-Final Rejection specifically states, “Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to use the teachings of Bullman to inform the method of Ai. Specifically, though Ai is not specific on all the bacterial species used in their OTUs, Bullman teaches many bacterial species, such as Bacteroides fragilis, Bacteroides thetaiotaomicron, and Gemella morbillorum, that are correlated with colorectal cancer, and so would be useful in predictive models.” Thus, Ai in view of Bullman would incorporate Bacteroides fragilis and Bacteroides thetaiotaomicron into the methods of Ai, which would involve the of use primers for these species, sequencing, and model analysis. Applicant states that the rationale for this rejection is based on impermissible hindsight related to Applicant’s own disclosure, but Applicant’s own disclosure is not cited in this paragraph.
Regarding obviousness, MPEP 2144 I states, “The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992).” MPEP 2144 II states, “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-95, 217 USPQ 1, 5-6 (Fed. Cir. 1983).” MPEP 2141.03 I states, “"A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. At 418, 82 USPQ2d at 1396.” The motivation used in the present rejection (increased predictive power and accuracy that would lead to better modeling and patient outcomes) is based on knowledge the ordinary artisan would have through knowledge generally available to them in the art and scientific principles, namely that including more predictive variables in a model generally increases the predictive power of said model. Though this reasoning is not explicitly stated in either Ai or Bullman, such a statement is not required in order to properly make an obviousness rejection. It is the Examiner’s position that the ordinary artisan, with ordinary skill, creativity, and knowledge in the art, would recognize the benefits of adding additional bacteria to the methods of Ai, as described in the rejection. The reasonable expectation of success in adding these bacteria to the method of Ai is clear, as Bullman teaches sequencing analysis of Bacteroides fragilis and Bacteroides thetaiotaomicron, providing support that these bacteria can be specifically targeted.
It is noted that Ai in view of Bullman is not directed to a specific combination of the claimed biomarkers and no other biomarkers, and such a closed, specific, combination is not required by the claims. Therefore, the obviousness rejection requires no rationale or motivation to use only the biomarkers for PTST, BCTF, and BCTT and no other biomarkers.
Thus, Applicant’s arguments are not considered persuasive. Applicant’s amendments to claim 17 do not change the scope of the claim, and so the rejections presented in the Non-Final Rejection mailed 12/10/2025 are maintained. Newly added claim 46 also requires new grounds of rejection below.
Regarding newly added claim 46, the claim recites that the kit is for detecting AA in the subject with increased specificity and/or the reduced false positive rate as compared to the FOBT alone. This amounts to choosing one of the diseases from the preamble of claim 17, as the wherein clause of claim 17 makes the same specificity and/or reduced false rate statement as in claim 46. As noted above, the preamble of claim 17 is not considered limiting, as it does not impart any structure to the claim (e.g. it does not require any additional kit components, and does not impact the construction of the recited kit components). Claim 46 similarly does not add any additional components to the kit, nor does it impact the construction of the recited kit components of claim 17. Therefore, this claim is considered to recite intended use, and is not further limiting.
Claim Objections
Claim 18 is objected to because of the following informalities: the commas before “or SEQ ID NO:25” “or SEQ ID NO:27” and “or SEQ ID NO:31” should each be removed. Appropriate correction is required.
Claim Interpretation
As noted above in the “Response to Applicant’s Arguments” section, claim 17 has been previously amended to recite a particular use for the kit. This is considered intended use, and thus, this preamble is not limiting. This is because this preamble does not impart particular structural limitations on the claim that would be required in addition to the listed components. See MPEP 2111.02.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 46 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
As noted above in the “Response to Applicant’s Arguments” section, claim 46 does not further limit the kit of claim 17, from which the claim depends, as it does not recite an additional component for the kit or require a new/change in structure for the components of the kit established in claim 17.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 17-18, 25, 32, 34-35, 38, and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Ai et al. (Oncotarget, 2017), in view of Bullman et al. (Science, 2017), in view of GenBank (Accession #s ADGQ01000060.1, CR626927.1, AE015928.1, and LS483440.1), in view of Ye et al. (BMC Bioinformatics, 2012), and in view of Godfrey et al. (US 2006/0068433 A1).
Ai teaches methods for screening for colorectal cancer based on fecal microbiota and fecal occult blood tests (Abstract). Samples were taken from two populations of subjects with colorectal abnormalities, as well as controls (page 9552-9553, “Sample collection for study population A” and “Acquisition of published fecal microbiome data”). Genomic DNA was extracted, amplified based on 16S rRNA sequences, and sequenced and put into operational taxonomic units (OTUs; page 9553, “DNA extraction and 16S rRNA gene sequencing”). This sequencing data was then placed into various models to determine their predictive power (e.g. Figure 1). This data was then combined with FOBT data (page 9549, “Fecal microbiome combined with FOBT moderately improved the prediction ability”). This combination increased the prediction ability of several models. In Figure 3C and D, using the combined bacterial markers and FOBT data resulted in higher true positive rates and lower false positive rates in most instances (note the two combined datasets in Figure 3C where the TPR dot is further to the left on the x-axis than for FOBT alone, indicating a lower false positive rate. A similar pattern is shown for the black line in Figure 3D). Figure 4 and pages 9549-9550 (“Interpretation of gut microbial species in the prediction model”) also detail some of the particular bacterial species associated with colorectal cancer and examined in the invention of Ai. Peptostreptococcus stomati is specifically noted to be one of them. It is also noted that the reverse primer used in Ai, 5′-TTACCGCGGCTGCTGGCAC-3′, is contained within instant SEQ ID NO: 6 (page 9553, column 1, para. 2). This primer and the forward primer used in Ai are within the 15 to 25 nucleotide length limitation established by instant claim 17.
However, Ai does not teach the specific oligonucleotides of instant claim 17, nor the use of the bacteria Bacteroides fragilis and Bacteroides thetaiotaomicron, or the specific use of a kit containing the FOBT and oligonucleotides.
Bullman teaches bacterial species that are prevalent in colorectal cancer tissues (Abstract). Specifically, the reference teaches that Bacteroides fragilis and Bacteroides thetaiotaomicron are present in primary tumor and metastatic tumor tissue (page 1, column 3, para. 4 and Figure 1C and 3B), as well as Gemella morbillorum (Table S3 in the Supplementary Methods).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to use the teachings of Bullman to inform the method of Ai. Specifically, though Ai is not specific on all the bacterial species used in their OTUs, Bullman teaches many bacterial species, such as Bacteroides fragilis, Bacteroides thetaiotaomicron, and Gemella morbillorum, that are correlated with colorectal cancer, and so would be useful in predictive models. By including these bacterial species, this could lead to enhanced predictive power and accuracy, which may further increase true positive rates and decrease false positive rates in the models of Ai, leading to better diagnostic and patient outcomes, thus motivating the ordinary artisan. There would be a reasonable expectation of success, as Bullman teaches performing sequencing and analysis of sequencing data to obtain the Bacteroides and Gemella morbillorum data, indicating that methods of sequencing and identifying these bacterial species are known (page 1, column 2, paras. 3-4 and page 3, column 3, para. 4).
GenBank teaches Accession #s ADGQ01000060. 1, CR626927.1, and AE015928.1, which comprise instant SEQ ID NOs: 2-4, respectively. It is noted that instant SEQ ID NOs: 24-25 align to instant SEQ ID NO: 2, instant SEQ ID NO: 26 has an alignment to instant SEQ ID NO: 3, and instant SEQ ID NOs: 30-31 align to instant SEQ ID NO: 4. Instant SEQ ID NO: 27 also mostly aligns to instant SEQ ID NO: 3, though there is a single nucleotide mismatch. A sequence with the exact match for SEQ ID NO: 3 in the same location as the alignment for SEQ ID NO: 27 would meet the “at least 80% identity” requirement presented in instant claim 18, as this sequence would have 95% identity to SEQ IDNO: 27. See alignments below:
SEQ ID NO: 2 with SEQ ID NO: 24
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63
326
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Greyscale
SEQ ID NO: 2 with SEQ ID NO: 25
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57
325
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SEQ ID NO: 3 with SEQ ID NO: 26
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61
305
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SEQ ID NO: 4 with SEQ ID NO: 30
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56
309
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SEQ ID NO: 4 with SEQ ID NO: 31
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56
289
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SEQ ID NO: 3 with SEQ ID NO: 27
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70
366
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Greyscale
GenBank also teaches Accession # LS483440.1, which is the Gemella morbillorum genome. This genome contains instant SEQ ID NO: 1 in region 82710-827892 (alignment not shown due to sequence length, but this information is also shown in the instant Sequence Listing).
Ye teaches designing primers from known genomic sequences using the publicly available software Primer-BLAST (Abstract, page 2, column 2, para. 2), including creating primers from Accession #s (page 3, column 1, para. 1). Ye also gives examples of primers with lengths of around 20 bases (Figures 3 and 4 and page 8, column 2, para. 1).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious to create the oligonucleotides of instant SEQ ID NOs: 24-26 and 30-31, as well as a sequence with 95% similarity to SEQ ID NO: 27, to bind to instant SEQ ID NOs: 2-4 using the teachings of Ai, Bullman, and GenBank, as these oligonucleotides could function as primers in the detection of Peptostreptococcus stomatis, Bacteroides fragilis, and Bacteroides thetaiotaomicron, respectively. Additionally, it would be obvious to develop a primer sequence to detect Gemella morbillorum using a sequence complementary a portion of SEQ ID NO: 1. Ai teaches the importance of accurately predicting and diagnosing colorectal cancer, as it is the third most common malignancy and causes 600,000 deaths worldwide, but can be prevented with screenings (page 9546, column 1, para. 1). Also, the teachings of Ye indicate that software for PCR primer design is available and can be used by the ordinary artisan to obtain probes suitable for amplifying a known sequence (Abstract). In view of the above, the ordinary artisan would have been motivated to use the publicly available software disclosed in Ye and the known bacterial sequences disclosed by GenBank to design primers for use in the method of Ai in view of Bullman, and in the absence of unexpected results, the claimed oligonucleotides (instant SEQ ID NOs: 24-26 and 30-31 and a sequence with 95% similarity to SEQ IDNO: 27), and oligonucleotides for detecting additional bacteria of interest (Gemella morbillorum) simply represent the result of an obvious series of steps. Additionally, the ordinary artisan would be motivated to make primers of similar lengths to those already known in the art, such as the lengths discussed by Ai and Ye, as these lengths have been shown to be successful for amplifying target sequences. Therefore, the ordinary artisan would be motivated to make primers with the length requirements stated in instant claim 17.
Neither Ai, nor Bullman, nor GenBank, nor Ye specifically teach that the reagents and components for their methods may be present in a kit. However, doing so would have been obvious to the ordinary artisan at the time of the invention in view of the teachings of Godfrey. In particular, since Godfrey teaches that kits can be “particularly useful’ for commercializing nucleic acid detection methods that make use of reagents that include oligonucleotides such as nucleic acid primers (para. 112), the ordinary artisan would have recognized that the methods disclosed by Ai could also be commercialized by providing the reagents used to practice the methods (e.g., DNA polymerases, dNTPs) in a packaged kit, along with the provided FOBT, which is already a packaged item. Accordingly, the ordinary artisan would have been motivated to so provide kits containing the FOBT and primers disclosed by Ai, in view of Bullman, in view of GenBank, and in view of Ye to obtain the ability to commercialize the disclosed PCR amplification and sequencing methods. Godfrey also teaches that these kits contain packaging and labels indicating use, and specifically mentions that instructions can be included in this packaging (para. 112, and see claim 19 of Godfrey for an example of a kit with such instructions). The ordinary artisan would have had a reasonable expectation of success in view of the guidance provided by Godfrey in paras. 112-115.
Thus, claims 17-18, 38, and 46 are prima facie obvious over Ai, in view of Bullman, in view of GenBank, in view of Ye, and in view of Godfrey.
Regarding claim 25, Bullman teaches that Escherichia coli is also implicated in primary colorectal tumors and metastasis tissues (Figures 1C and F). Thus, it would be prima facie obvious to add this bacteria to the kit of Ai, in view of Bullman, in view of GenBank, in view of Ye, and in view of Godfrey for much the same reasons as described for adding Bacteroides fragilis, Bacteroides thetaiotaomicron, and Gemella morbillorum above – namely, adding additional bacteria to the modeling methods of Ai would allow for more predictors, which could improve model accuracy, and therefore produce better diagnostic and patient related outcomes. There would be a reasonable expectation of success, as Bullman teaches performing sequencing and analysis of sequencing data to obtain the E. coli data, indicating that methods of sequencing and identifying these bacterial species are known (page 1, column 2, para. 4).
Thus, claim 25 is prima facie obvious over Ai, in view of Bullman, in view of GenBank, in view of Ye, and in view of Godfrey.
Regarding claims 32 and 34-35, Ai teaches the detection of many bacterial species, and thus teaches the detection of additional Eubacteria (see Figure 4 for example, which lists additional Eubacteria examined, such as Eubacterium cylindroides). As noted above, Ai teaches that their 16S rRNA primers include a sequence that contains 19 of the 22 nucleotides of instant SEQ ID NO: 6 (page 9553, column 1, para. 2, the 533R sequence). As this 533R primer has more than 80% sequence identity to instant SEQ ID NO: 6, it meets the requirements of instant claim 35, and as it is used for detecting Eubacteria species, also meets the requirements of instant claims 32 and 34.
Thus, claims 32 and 34-35 are prima facie obvious over Ai, in view of Bullman, in view of GenBank, in view of Ye, and in view of Godfrey.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Ai et al. (Oncotarget, 2017), in view of Bullman et al. (Science, 2017), in view of GenBank (Accession #s ADGQ01000060.1, CR626927.1, AE015928.1, and LS483440.1), in view of Ye et al. (BMC Bioinformatics, 2012), in view of Godfrey et al. (US 2006/0068433 A1), and further in view of Zhang et al. (Cancer Medicine, 2019).
Ai, in view of Bullman, in view of GenBank, in view of Ye, and in view of Godfrey teach the kit of claims 17-18, 25, 32, 34-35, 38, and 46. However, the FOBT used is not a fecal immunochemical test (FIT).
Zhang teaches the use of FIT and bacterial marker screening strategies in detecting colorectal cancer (Abstract and Introduction). Regarding FIT, Zhang teaches that this test has several limitations, but that these limitations can be ameliorated by combining the test results with those of bacterial markers to enhance the detection ability and potential lower false-positive results (page 487, column 2, para. 1).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to use the teachings of Zhang to substitute the FOBT test of Ai, in view of Bullman, in view of GenBank, in view of Ye, and in view of Godfrey with the FIT taught by Zhang. MPEP 2143 I (B) states, “The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art.” This substitution would change the fecal occult blood test used in the method and kit of Ai, in view of Bullman, in view of GenBank, in view of Ye, and in view of Godfrey, but the analysis of the FIT and bacterial data would remain the same, and would therefore be predictable. Moreover, Zhang teaches that FIT is a typical screening strategy for colorectal cancer, and would therefore be relatively easy for the ordinary artisan to obtain and utilize (pages 480-481, joining para.).
Thus, claim 24 is prima facie obvious over Ai, in view of Bullman, in view of GenBank, in view of Ye, in view of Godfrey, and further in view of Zhang.
Conclusion
No claims are currently allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRANCESCA F GIAMMONA whose telephone number is (571)270-0595. The examiner can normally be reached M-Th, 7-5pm.
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/F.F.G./Examiner, Art Unit 1681
/ANGELA M. BERTAGNA/Primary Examiner, Art Unit 1681
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