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 .
Election/Restrictions
Applicant’s election of Group 1 and the species (i) food for sample type and (ii) Salmonella spp. for pathogen in the response filed April 10, 2026 is acknowledged. In the election, the Applicant responded that both the election of Group 1 and the election of species were ‘without traverse,’ but provided argument against restriction on the grounds that there is no serious examiner burden. This argument is noted; however, the election is treated as ‘without traverse’ as recited by the Applicant.
Claims 1-19, 23, and 24 are currently pending.
Claims 6, 7, 19, 23, and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 10, 2026.
Claims 1-5 and 8-18 are examined herein on their merits.
Claim 2 has been examined to the extent that it reads on the elected sample type. The additionally recited sample types have been withdrawn from consideration as being directed to non-elected subject matter. Prior to allowance of the claim, any non-elected subject matter that is not rejoined with any allowed elected subject matter may be required to be removed from the claims.
Claim 9 has been examined to the extent that it reads on the elected pathogen. The additionally recited pathogens have been withdrawn from consideration as being directed to non-elected subject matter. Prior to allowance of the claim, any non-elected subject matter that is not rejoined with any allowed elected subject matter may be required to be removed from the claims.
Priority
It is acknowledged that the instant application is a 371 of international PCT Application No. PCT/US2022/032188, filed June 3, 2022, and that it claims benefit of provisional 63/208,609, filed June 9, 2021. Please note that while a certified copy of the priority document was received on December 8, 2023, no copy of the international publication itself has been provided. The effective filing date of amended claim set filed on 12/08/2023 is considered to be June 9, 2021.
Claim Objections
Claim 1 is objected to because of the following informalities: improper punctuation. The claim includes periods in the beginning of each step (e.g. “a.”), and should only have a period at the end of the claim. Appropriate correction is required.
Claim 17 is objected to because of the following informalities: sentence fragment. If the claim was meant to read “…to a detectable level, while the other…” the claim must be amended. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-5 and 8-18 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 1-5 and 8-18 are rejected for the recitation of “each sample” in step (c) claim 1, as lacking antecedent basis. The claim requires the provision of “a sample,” which is divided in step (b), but does not recite multiple samples. It is therefore unclear whether ‘each sample’ refers to the divided portions of the single sample or whether multiple samples are present. As a result, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter so as to avoid infringement.
Claims 1-5 and 8-18 are rejected for the recitation of “the others” in line 5 of step c in claim 1, as being indefinite. It is not clear what ‘the others’ refers to in this context. For example, is ‘at least one primer in each primer set’ required to have varying specificity to the other primers in the same set or to primers in any primer set, or is some other variance is required by the claim? If what is meant is that at least one primer in a given primer set has varying specificity for the target compared to primers in the other set(s), the claims must be amended to reflect that meaning.
Claims 1-5 and 8-18 are rejected for the recitation of “the amplification product” in step (d) of claim 1, as being indefinite. Claim 1 requires the presence of at least a first set of primers in a first container and a second set of primers in a second container which amplify a target nucleic acid, resulting in multiple amplification products. It is unclear if ‘the amplification product’ of step (d) refers to both the first and second container amplification products and whether the amplification products are required to be the same. Furthermore, each container may additionally amplify several targets in multiplex. It is unclear whether every amplification product (including the multiplex products of several gene targets) must be targeted by the same probe. As a result, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter so as to avoid infringement.
Claims 8 and 9 are rejected for the recitation of “target nucleic acid comprises…pathogens” in claim 8 as being unclear. Generally, pathogens are comprised of nucleic acids but nucleic acids are not themselves pathogens. It is therefore unclear what is being required by the claim. For example, does the claim require the presence of entire pathogenic organisms in the sample or merely any nucleic acids originating from a pathogen, or is some other meaning intended by the claim? If what is meant is that the target nucleic acid originates from a foodborne or human pathogenic organism, the claim must be amended to reflect that meaning.
Claim 9 is rejected for the recitation of “pathogen is…Salmonella spp.” as being unclear. Pathogen is recited in the singular, but ‘spp.’ is the plural abbreviation for species. It is therefore unclear whether the claim requires that the target nucleic acid be from any one Salmonella spp. present in the sample, or if nucleic acid from multiple species is allowed or is required to be amplified (e.g. using primers targeting sequences conserved in more than one species). If what is meant is that ‘the pathogen is…a Salmonella spp.,’ the claim must be amended to reflect that meaning.
Claim 13 is rejected for the recitation of “a different set of primers” / the other set of primers” as being indefinite. Claim 1, on which it depends, already recites “a different set of primers” and “the others.” It is therefore unclear whether the ‘different set of primers’ in claim 13 is the same ‘different set of primers’ as claim 1 or if it’s another ‘different set of primers.’ It is also unclear whether ‘the others’ from claim 1 and ‘the other set of primers’ from claim 13 are referring to the same entity. As a result, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter so as to avoid infringement.
Claims 13-16 are rejected for the recitation of “amplification efficiency” in claims 13 and 14, as being indefinite. Neither the claims nor the specification provides a clear limiting definition for ‘amplification efficiency.’ Furthermore, art definitions of the term are at odds with the use of the term in the claims. For example, claim 13 implies that amplification efficiency is a characteristic of a set of primers, while claim 14 indicates that amplification efficiency can be measured for a single primer. Kelly (Kelly et al. Sci Rep. 2019 Aug 20;9(1):12133) demonstrates that amplification efficiency can be considered a property of a pair of primers (pg. 3: “DNA Amplification during PCR”). Therefore, it is unclear whether the amplification efficiency recited in the claims is meant to apply to a single primer or to a primer pair and it is not clear how amplification efficiency should be measured. Clarification is requested.
Claims 14-16 are rejected for the recitation of “two-three primer sets” in claim 14, as being indefinite. Neither the claims nor the specification provides a definition of ‘two-three primer sets.’ The colloquial meaning of ‘two-three’ is ‘approximately between 2 and 3,’ but it is not clear that the colloquial meaning is the claim’s intended meaning. An alternative interpretation is that the claim requires two primers sets, each composed of three primers. However, the specification gives no support for this definition. In Example 3, the specification gives support for a multiplex reaction using three primer pairs (or three two-primer sets), but this embodiment is not a reasonable interpretation of the specific language ‘two-three primer sets.’ Clarification is requested. For the purposes of compact prosecution, the claim is interpreted to mean three sets of primer pairs.
Claim 16 is rejected for the recitation of “the at least one primer with less than 100% homology” as lacking antecedent basis. The claims on which it depends, claims 1 and 14, do not recite ‘at least one primer with less than 100% homology.’ Claim 15 recites at least one primer which is less than 100% complementary to the target nucleic acid but: a) claim 16 does not depend from claim 15, and b) sequence homology and complementarity are distinct concepts. If claim 16 is meant to depend from claim 15, and also meant to refer to sequence complementarity (instead of homology), the claim must be amended to reflect the proper dependencies and meanings.
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 pre-AIA 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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1, 8, 11, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu et al. (Liu et al. J Virol Methods. 2010 Jan;163(1):109-15, Epub 2009 Sep 15.; NPL #2 in the IDS filed by Applicants on 04/30/2025).
Regarding claim 1, Liu recites a method for quantifying an amount of target nucleic acid in a sample (Abstract), the method comprising: providing a sample comprising at least one target nucleic acid (pg. 110, col. 1, 4th par.) and dividing the sample into two containers (pg. 110, col. 2: “qPCR experimental procedure”).
Liu recites amplifying the target nucleic acid in each container by exposing each sample to a different set of primers in uniplex under conditions suitable for nucleic acid amplification, thereby creating an amplification product, and exposing the amplification product to a probe which is specific for the target nucleic acid (pg. 110, col. 2: “qPCR experimental procedure”; Table 1). Liu recites that each set of primers comprises a forward and reverse primer, and further that at least one primer in each primer set has varying specificity for the target nucleic acid compared to the others (Table 1; pg. 112, col. 2: “Design of FluASMA primers and probes”).
In Liu, a sample is divided into at least two reaction vessels (pg. 110, col. 2: “qPCR experimental procedure”). As shown in Table 1, each portion of sample is exposed to a different set of primers; for example, one portion of sample in the V27A assay is exposed to the ‘shared forward primer’ and ‘WT reverse primer’ while the other is exposed to the ‘shared forward primer’ and ‘mutant reverse primer.’ The ‘shared forward primer’ is designed to have 100% complementarity to the target, while each of the reverse primers incorporates a mismatch (Table 1, legend).
Liu recites determining which of the containers showed a detectable level of amplification using the probe, thereby quantifying the amount of target nucleic acid in the sample (Figure 2; Table 1). In Liu, this quantification is a percentage of the mutant present in the sample (Figure 2, legend).
Regarding claim 8, Liu recites a target nucleic acid from a human pathogen (Abstract).
Regarding claim 11, Liu recites a method which does not explicitly require the use of any external standard curve. Liu is silent regarding an explicitly ‘external’ standard curve and recites methods ‘independent of an in-run standard curve” (pg. 114, col. 2, 1st par.). Barring evidence to the contrary, the limitation of claim 11 is considered to have been met.
Regarding claim 18, Liu recites the same probe is used in each container (Table 1).
Claim 10 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu et al. (Liu et al. J Virol Methods. 2010 Jan;163(1):109-15, Epub 2009 Sep 15.; NPL #2 in the IDS filed by Applicants on 04/30/2025), as evidenced by Wangh et al. (published March 18, 2004; Patent Application Publication US 20040053254).
The teachings of Liu et al. have been documented above.
Regarding claim 10, Liu recites TaqMan probes (pg. 110, col. 2: “qPCR experimental procedure”). As evidenced by Wangh, TaqMan probes are dual-ended probes (Wangh: par. 6). Therefore, the limitation is considered to have been anticipated.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 2-5 and 9 are rejected under 35 U.S.C. 103 as unpatentable over Liu et al. (published September 15, 2009; Liu et al. J Virol Methods. 2010 Jan;163(1):109-15) in view of Peters et al. (published Aug. 4, 2016; Patent Application Publication US 20160222440).
The teachings of Liu et al. have been documented in the 102(a)(1) rejection above.
Regarding claims 2-5 and 9, Liu does not disclose that samples are any kind of food samples or that target nucleic acids are from pathogenic Salmonella spp.
Regarding claims 2-4, Peters teaches samples comprising food (Abstract) and meat including poultry, fish, and beef (par. 13).
Regarding claim 5, Peters teaches samples comprising produce (par. 13).
Regarding claim 9, Peters teaches amplifying target nucleic acids from pathogenic Salmonella spp. (par. 13).
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to combine the teachings of Liu with the teachings of Peters with reasonable expectation of success. One would have been motivated to do so in order to prevent contaminated food products from entering the food chain (par. 3).
Claim 12 is rejected under 35 U.S.C. 103 as unpatentable over Liu et al. (published September 15, 2009; Liu et al. J Virol Methods. 2010 Jan;163(1):109-15).
The teachings of Liu et al. have been documented in the 102(a)(1) rejection above. Regarding claim 12, Liu recites the same sample divided into two vessels and the assay includes reactions occurring in more than two containers – two for each of the SNPs tested (Table 1; pg. 110, col. 2: “qPCR experimental procedure”).
Liu does not explicitly recite that the same sample is divided into more than two containers. The samples in Liu are distinct for each SNP tested, due to the fact that Liu’s disclosure pertains to the design and validation of an assay meant for antiviral resistance surveillance (Introduction). Because of validation efforts, each ‘sample’ is therefore only divided into two containers for analysis (one for mutant and one for wildtype reactions: see Methods). However, it would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to use the same sample for analysis of multiple SNPs – resulting in a single sample subdivided into more than 2 containers and exposed to at least three sets of primer pairs with reasonable expectation of success. One would have been motivated to do so for monitoring of antiviral resistance associated with several common viral SNPs (Abstract; Introduction).
Claims 13-17 are rejected under 35 U.S.C. 103 as unpatentable over Liu et al. (published September 15, 2009; Liu et al. J Virol Methods. 2010 Jan;163(1):109-15) in view of Solomon et al. (published Jan 12, 1999; US Patent No. 5,858,732).
Liu discloses the limitations of claim 1, as discussed above.
Regarding claim 13, Liu discloses amplifying a target nucleic acid from a sample divided into multiple containers by exposing each sample to a different set of primers, as discussed for claim 1 above.
Regarding claim 14, Liu discloses three sets of primer pairs (Table 1).
Regarding claims 15 and 16, Liu discloses that at least one of the primers in the primer sets is 100% complementary to the target nucleic acid (Table 1: shared primers containing no mismatches), and at least one of the primers in another primer set is less than 100% complementary comprising 1 mismatch to the target nucleic acid sequence (Table 1: WT/mutant primers containing a mismatch indicated by underlining).
Regarding claims 13 and 17, Liu does not disclose any varying amplification efficiency for primers, nor that one set of primers is capable of amplifying the target nucleic acid in a particular range of DNA concentration to a detectable level while the other set of primers amplify the target at a different levels of DNA concentration.
Regarding claim 13 and 17, Solomon teaches the use of different sets of primers with varying sensitivity for the target nucleic acid when compared to the other set of primers (col. 5-6) and teaches that one set of primers is capable of amplifying the target nucleic acid in a particular range of DNA concentration to a detectable level while another set of primer amplifies the target at a different levels of DNA concentration (col. 5, 1st par.). Although Solomon does not explicitly recite the use of the term ‘amplification efficiency,’ Solomon’s definition of primer sensitivity (Solomon, col. 5, 1st par) aligns with the usage of the term in the instant application (Instant Patent Application Publication: par. 80). Therefore, the limitation is considered to have been met.
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to combine the teachings of Liu and Solomon with reasonable expectation of success. One would have been motivated to do so in order to avoid laborious steps of sample preparation including sample dilution series (Solomon, col. 3, ln. 32-43).
Regarding claim 14, Liu does not recite that three sets of primer pairs are used on the same sample. However, as discussed for claim 12 above, it would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to expose the same divided sample to at least three sets of primer pairs. One would have been motivated to do so to monitor antiviral resistance associated with several common viral SNPs (Abstract; Introduction).
Conclusion
No claims are allowed.
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/C.M.J./Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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