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 without traverse of Group I, claims 1-16 in the reply filed on 12/16/25 is acknowledged.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/307513, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Claims 1, 2, 3, 4, 6, 7, 9, 10 11, 12, 13, 14, 15, and 16 are sufficiently broad so as to encompass method of amplification that do not rely on LAMP isothermal amplification, whereas the provisional application only teaches LAMP isothermal amplification using primers comprising SEQ ID NO: 2-7. The broader scope in the instant claims is not disclosed in the provisional and so the effective filing date for these claims is the actual filing date of this application, namely 2/6/2023.
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.
Claim 16 is 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.
Claim 6, from which claim 16 depends recites contacting a biological sample with “LAMP” primers, but it does not require a complete set of LAMP primers, nor does it require that the “amplification conditions” are isothermal. As some “LAMP” primers are the same structure as regular PCR primers, for example, providing “LAMP” primers is sufficiently broad enough to encompass providing a primer pair that is identical to a PCR primer. Calling the primers “LAMP” primers goes to intended use of the primers, but the claim does not require carrying out a LAMP amplification. Following this, claim 16 is indefinite because it sets forth a comparison to “conventional PCR” but it is unclear what this means, since claim 6 itself could be carried out using PCR. It is unclear what makes PCR conventional. Furthermore, as neither the conditions of the claimed amplification nor those of the “conventional PCR” are set forth it impossible to know the metes and bounds of the claim since the sensitivity of a method can vary with regard to how the sample is prepared, the primers selected and the rection conditions.
Claim Rejections - 35 USC § 102
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-4, 6-8, 10-16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Matthew et al. (Microorganisms 2022, 10, 594. https://doi.org/10.3390/microorganisms10030594. 11 pages).
This reference is available because the rejected claims are not entitled to benefit of the claim to priority to the provisional application.
The reference teaches a method that includes carrying out a LAMP reaction using primers consisting of SEQ ID NO: 2-7 as instantly claimed to determine if T. Tenax is present in a biological sample, see section 2.2 and Table 1. These primers hybridize to the ITS and 5.8S rRNA gene, inherently, see section 2.2. The reference teaches testing canine saliva samples and oral swabs (see section 2.5-2.6). The optimized reaction temperature was 60 degrees C, the optimized MgSO4 concentration was 6mm, and the optimized reaction time was 60 minutes (section 3.1). The LAMP assay was demonstrated to be 1000X more sensitive than conventional PCR (section 3.2). Thus, the reference anticipates the claims.
Claim(s) 1, 2, 3, 4, 6, 7, 9, 10, and 15 are is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mallat (JOURNAL OF CLINICAL MICROBIOLOGY, Aug. 2004, p. 3886–3887).
The reference teaches contacting nucleic acid obtained form a biological sample with at least two polynucleotide primer pairs under amplification conditions, thereby generating an amplified nucleic acid mixture and analyzing the products, wherein one or more of the primer pairs hybridizes to SEQ ID NO: 1. The reference teaches adding primers sufficient for PCR amplification to a mixture, this amplification reaction inherently had many copies of both primers, and this “at least two polynucleotide primer pairs” were added. Furthermore, the forward primer was identical to 1-20 of SEQ ID NO: 1, and the reverse primer was the complement of nucleotide 349-368 of SEQ ID NO: 1. The amplicon amplified a portion of T. tenax when the T. tenax was in the sample, and this was confirmed by sequencing the amplicon (p. 3886, Col. 2). With regard to the limitation that the set of primers “comprises” LAMP primers, it is noted that the claim does not require that a complete set of LAMP primers or any required number of LAMP primer pairs is present, and so since any primer pair could be used as a LAMP primer when combined with appropriate FIP and BIP primers, the primer pair taught in the reference is construed as a LAMP primer pair. Regarding claim 15, the primers do not share identity with E. coli and if E. coli were present, it would not be expected to be amplified.
Claim(s) 1, 3, 4, 6, 7, 9, 10, and 15 are is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Duboucher et al. (JOURNAL OF CLINICAL MICROBIOLOGY, Mar 2006, p. 1165-1168).
The reference teaches contacting nucleic acid obtained from a biological sample with at least two polynucleotide primer pairs under amplification conditions, thereby generating an amplified nucleic acid mixture and analyzing the products, wherein one or more of the primer pairs hybridizes to SEQ ID NO: 1.
The reference teaches a nested PCR amplification wherein two different primer sets which hybridize to instant SEQ ID NO: 1 were utilized to amplify a target from the sample, which was then sequenced. The outer forward primer was identical to 1-20 of SEQ ID NO: 1, and the outer reverse primer was the complement of nucleotide 349-368 of SEQ ID NO: 1. See p. 1166 and Figure 2. The sample was a bronchoalveolar lavage specimen from a human (p. 1165, Col. 2).
With regard to the limitation that the set of primers “comprises” LAMP primers, it is noted that the claim does not require that a complete set of LAMP primers or any required number of LAMP primer pairs is present, and so since any primer pair could be used as a LAMP primer when combined with appropriate FIP and BIP primers, the primer pair taught in the reference is construed as a LAMP primer pair.
Regarding claim 15, the primers do not share identity with E. coli and if E. coli were present, it would not be expected to be amplified.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1-10, 15 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mallat (JOURNAL OF CLINICAL MICROBIOLOGY, Aug. 2004, p. 3886–3887) in view of Reyes et al. (Diagnostic Microbiology and Infectious Disease 79 (2014) 337–341) and Duboucher (JOURNAL OF CLINICAL MICROBIOLOGY, Mar. 2006, p. 1165–1168).
Mallet teaches that Trichomonas tenax caused a pulmonary infection in a 58-year old man (title). The reference teaches that amplification of the 5.8S rRNA sequence followed by sequence is a way to identify species of Trichomonas in a sample (p. 5886, 2nd column). The 5.8S rRNA sequences present the advantages of being present in multiple copies in the genome and of being conserved in certain regions and variable in others, even between very closely related species (p. 3887). The additional teachings Mallet are given previously in this Office action and are fully incorporated here.
Mallet does not teach detection T. tenax using LAMP isothermal amplification, or a complete set of LAMP primers.
Reyes teaches using LAMP for the detection of Trichomonas vaginalis. The reference teaches that LAMP primers were designed using commercially available software, namely LAMP Designer version 1.02 (section 2.4). The reference teaches that the LAMP method demonstrated advantages over conventional PCR, including high efficiency, use of simple equipment, and its fast, ideal for rapid point-of-care tests. The DNA polymerase can tolerate PCR inhibitors found in many samples, and thus, only simple sample preparation is needed for amplification. The method is a rapid and cost-effective tool for detecting targets (section 4). Furthermore, Reyes teaches that the LAMP assay was 10-1000 times more sensitive than the conventional PCR performed.
Furthermore, the complete sequence of the target amplified by Mallet was known, and had been aligned with closely related species. See Duboucher et al., Figure 2, noting that the outer primers taught by the reference are identical to the primers taught by Mallet, and that the sequence given for T. tenax in Figure 2 is identical to instant SEQ ID NO: 1.
It would have been prima facie obvious to have modified the method for detection taught by Mallet so as to have selected LAMP primers and carried out a LAMP amplification for the detection of T tenax from the sequence disclosed by Duboucher. One would have been motivated to do so (1) because Mallet teaches that the region is good for detection of T. tenax since it is 5.8S rRNA sequences present the advantages of being present in multiple copies in the genome and of being conserved in certain regions and variable in others, even between very closely related species, (2) Reyes teaches multiple advantages of using LAMP, including a much higher sensitivity than conventional PCR, (3) Duboucher provided the full length sequence of the 5.8S rRNA sequence for T. tenax and (4) Reyes teaches that there were commercially available primer selection tools for designing LAMP primers. Therefore, it would have been obvious to have selected primers from within the known 5.8S rRNA gene for the specific detection of T. tenax.
Furthermore, regarding claims 5 and 8, which require SEQ ID NO: 2-7, each of these primers are identical to portions of or the complement of to the very short sequence taught in Figure 2 of Duboucher. The combined teachings of the cited references would have suggested a finite number of possible PCR primer pairs that could be designed from the known amplicon taught by Mallet to the ordinary artisan, and, based on the teachings of Reyes, the ordinary artisan would have expected predictable results in obtaining and using these oligonucleotides in a LAMP amplification reaction for the sensitive and specific detection of T. tenax. Thus, absent any evidence of unexpected results with respect to particular primers the method of claims 5 and 8 would have been prima facie obvious before the instant filing date in view of the combined teachings of the cited references.
Claim(s) 11 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mallet in view of Reyes and Duboucher, as applied to claims 1, 4, and 6 above, and further in view of Jiang et al. International Journal of Infectious Diseases 107 (2021) 145–152.
The teachings of Mallet in view of Reyes and Duboucher as they relate to claims 1, 4, and 6 are given previously in this Office action and are fully incorporated here.
Reyes teaches the LAMP reaction was incubated at 60°C for 30-45minutes, with a MgSO4 concentration of 8mmol/L.
Mallet in view of Reyes and Duboucher does not teach the conditions recited in claims 11 and 12.
However, these were well known to be optimizable variables of a LAMP reaction. For example, Jiang taught optimization of a LAMP assay by testing performance at different reagent concentrations, including MgSO4, reaction times, and incubation temperatures (p. 148). The optimized LAMP assay taught by Jiang ran at 6mM MgSO4, at 65°C for 60 minutes.
Generally, differences in concentration or temperature will not support the patentabilty of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Here the prior art recognized time, temperature and reagent concentrations as variables which achieve a result of supporting LAMP amplification, and thus, it would have been obvious to determine optimum or workable ranges for a LAMP assay for the detection of T. tenax. One of ordinary skill in the art would have had a reasonable expectation of success to formulate the claimed combination of variables because the prior art demonstrates that these values are with ranges routinely tested for the development of LAMP assays.
Claim(s) 13 and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mallet, as applied to claims 1 and 6 above, and further in view of Dybicz et al. (Cited in IDS 9/19/23).
The teachings of Mallet in view of Reyes and Duboucher as they relate to claims 1, 4, and 6 are given previously in this Office action and are fully incorporated here.
Mallet in view of Reyes and Duboucher does not teach detecting T. tenax in one of the samples listed in claims 13 and 14.
Dybicz teaches that T. tenax is present in the human oral cavity and teaches obtaining oral washes (which include saliva) for the detection of T. tenax in samples by PCR.
It would have been prima facie obvious to have modified the method taught by Mallet so as to have detected T. tenax in oral washing samples in order to provide an alternative method for detecting T. tenax in patients, particularly as a way to survey the oral health of patients.
Conclusion
Applicant is advised that should claims 4 and 5 be found allowable, claims 6 and 8 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Juliet Switzer whose telephone number is (571)272-0753. The examiner can normally be reached Monday to Thursday, 8:00 AM-3:30 PM.
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Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/Primary Examiner, Art Unit 1682