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 without traverse of Group I, claims 1-26 in the reply filed on 2/13/2026 is acknowledged.
Claims 27-35 are withdrawn from consideration as being directed to a non-elected invention.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located in figure 2B.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
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.
Claims 1-26 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The claims are generally narrative and contain grammatical errors.
For example, the recitation in the claimed steps use both the present participle (“pre-annealing”) and the past participle (the … primer being “conjugated”) in the passive voice. It is suggested that the claims be amended to recite active steps (for example: “pre-annealing a first primer which is conjugated to a fluorophore at the 5’ end with a first reverse complementary oligonucleotide sequence which is conjugated with a fluorescence quencher at the 3’ end to form a first primer-first reverse complementary oligonucleotide complex, wherein the first primer hybridizes to the SARS-CoV-2 N gene and wherein the first primer is selected from FIP, BIP, F3, B3, Loop F, and Loop P”).
It is suggested that the claimed steps be demarcated by particular indicators such as a), b), c), etc, so that reference can be made to previous steps by the step indicator rather than incorporating the entire step each time it is referred to in the method (for example: “a) collecting a sample of raw saliva; b) adding a chemical stabilizer to the raw saliva thereby forming stabilized saliva; c) heating the stabilized saliva for a chosen time…”.
It is suggested that the claims be amended to refer to a particular step or structure formed, once it has been recited, with a shortened construct. For example, claim 1 continually recites “the annealed first primer with a first reverse complementary oligonucleotide from said pre-annealing step for said first primer”, making each step confusing. The claim would be clearer if it referred to this pre-annealed construct as “a first primer-first reverse complementary oligonucleotide complex”.
These examples are not exhaustive, appropriate correction is required for all claims.
The claims also repeat certain phrases, so that it is confusing if the recitation is to be performed twice. For example, claim 1 recites “providing an ultraviolet light, wherein the cooled amplification solution is illuminated using the ultraviolet light, wherein the cooled amplification solution is illuminated using the ultraviolet light…”. Is the solution illuminated two times? It is also noted, in keeping with the issues and suggestions for amendment made above, that it would be clearer to recite incite instead “illuminating the cooled amplification solution with ultraviolet light that has a chosen wavelength so that the first primers incorporated into products formed in said RT-LAMP amplification reaction emit fluorescent radiation…”. This example is not exhaustive, appropriate correction is required for all claims.
The claims contain numerous spelling errors. For example, claim 17 recites the confusing phrase “the annealed first FIP rimer with he first reverse…”. This example is not exhaustive, the claims should be reviewed and appropriate correction is required for all claims.
The claims contain trademark/trade name (eg: BHQ2, BHQ1, IowaBlack-FQ, BlackBerry Quencher 650). Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademarks should be deleted or the claims amended to refer to the chemical name if it is supported by the specification. Appropriate correction is required for all claims.
The designation of SEQ ID NO: 7 in the claims is confusing because the sequence in the sequence listing does not match the sequence attributed to it in the specification/drawing. At para 0008, the specification states that figure 2B illustrates the hybridization of the reverse complementary oligonucleotide having SEQ ID NO: 14 with the FIP primer having SEQ ID NO: 7. However, the sequence of what appears to be noted as SEQ ID NO: 7 in figure 2B does not match the sequence in the sequence listing. Accordingly, the metes and bounds of the claims are unclear.
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.
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.
Rabe, Ball, and Baek
Claims 1, 2, 4, and 10-16 are rejected under 35 U.S.C. 103 as being unpatentable over Rabe (Rabe et al. PNAS, vol 117, pages 24450-24458, September 29, 2020) in view of Ball (Ball et al. Analytical Chemistry, 2016, vol 88, pages 3562-3568) and Baek (Baek et al., Emerging Microbes & Infections; vol 9, pages 1-10, published online May 2020).
Rabe teaches a method using RT-LAMP amplification for detecting nucleic acid from SARS-CoV-2 (see abstract, whole document). Rabe teaches obtaining samples of raw saliva (pg 24452, col 1), providing a chemical stabilizer and heating to 95°C to denature proteins and inactivate RNase activity (pages 24451-24452; 24456-24457). Rabe teaches the resulting inactivated sample is fully compatible with direct addition to an RT-LAMP reaction. Rabe teaches oligonucleotides for detection of SARS-CoV-2 Orf1a gene including primers FIP, BIP, F3, B3, Loop F, and Loop B (pg 24456-7). Rabe teaches that using a strand displacing polymerase and loops formed during the reaction, a fast amplification reaction occurs upon proper oligo binding to the desired target and a reverse transcriptase can be included to improve sensitivity within the reaction when detecting an RNA target (RT-LAMP), such as the SARS-CoV-2 RNA (pg 24456-7). Rabe teaches that amplification was carried out at 65°C. Rabe teaches detection of fluorescence for detection of target nucleic acid.
Rabe does not teach pre-annealing a LAMP primer fluorescently labeled at the 5’ end with a revere complementary oligonucleotide labeled at the 3’ end with a quencher, however Ball teaches a method of conducting RT-LAMP comprising pre-annealing a LAMP primer fluorescently labeled at the 5’ end with a revere complementary oligonucleotide labeled at the 3’ end with a quencher to detect viral nucleic acid (see abstract; whole document). Ball teaches the technique uses a LAMP primer (eg FIP, BIP, Loop F or Loop B) labeled with a fluorophore at the 5' end. Ball teaches as amplification proceeds, the fluorophore labeled primers are incorporated into the amplicon. Ball teaches including a short reverse complementary quencher probe, typically with 7-13 bases complementary to the 5' end of the labeled primer, including probes with a single mismatch (see page 3566, supplemental tables). Ball teaches optimizing the Tm of the quencher probe (see supplemental information, whole document). Ball teaches the quencher probe is modified at the 3' end with a dark quencher and the melting temperature of the quenching probe annealed to the labeled primer (typically <55 C) must be well below the temperature of the LAMP amplification (typically 60-65 C), such that during the amplification the quenching probe is dissociated and does not participate in or inhibit the reaction. Ball teaches after amplification the reaction is stopped and cooled down, followed by excitation to detect fluorescence by visual inspection. Ball teaches this allows for better discrimination of target nucleic acids. Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have included a pre-annealing step as taught by Ball in the method of Rabe for increased discrimination of SARS-CoV-2.
Rabe and Ball do not teach targeting the N gene of SARS-CoV2, however Baek teaches detecting SARS-CoV-2 N gene with RT-LAMP (see abstract). Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have substituted the target gene taught by Rabe and Ball with N gene of SARS-CoV-2 with a reasonable expectation of success because it is considered the substitution of one known element for another with predictable results.
With regard to components of the amplification solution and fluorescent and quenching dyes set forth in the claims, these limitation are considered routine optimization as evidenced by the different solutions and conditions used in the cited prior art for RT-LAMP assays. Additionally, although the cited art does not teach illumination with UV for fluorescence detection, the use of UV in LAMP assays is routine and obvious. As set forth in the MPEP 2144.05 II A:
Generally, differences in concentration or temperature will not support the patentability of
subject matter encompassed by the prior art unless there is evidence indicating such
concentration or temperature is critical. “[W]here the general conditions of a claim are
disclosed in the prior art, it is not inventive to discover the optimum or workable ranges
by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235
(CCPA 1955) (Claimed process which was performed at a temperature between 40°C
and 80°C and an acid concentration between 25% and 70% was held to be prima facie
obvious over a reference process which differed from the claims only in that the reference
process was performed at a temperature of 100°C and an acid concentration of 10%.)…
Therefore, absent secondary consideration, these limitation are considered obvious in view of the cited art.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Rabe in view of Ball and Baek, as applied to claims 1, 2, 4, and 10-16 above, and further in view of Broughton (Broughton et al; WO 2020/257356-December 24, 2020; note the sequence cited is disclosed in the 62/985,850 priority document dated March 2020)).
The teachings of Rabe in view of Ball and Baek are set forth above. Rabe, Ball, and Baek do not teach a first primer with SEQ ID NO: 1 or a reverse complementary probe with the sequence of SEQ ID NO: 13, however Broughton teaches RT-LAMP primers for detection of SARS-CoV-2 N gene wherein a primer has the sequence of SEQ ID NO: 1 (see SEQ ID NO: 350; table 23, page 328). Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have included use of the primer sequences taught by Broughton in the method of Rabe, Ball, and Baek with a reasonable expectation of success as it represents substitution of one known element for another with predictable results. It would have additionally been prima facie obvious to arrive at a quencher of SEQ ID NO: 13 given the teachings of Ball. Absent secondary considerations, these primer and probe sequences are considered obvious in view of the teachings of the cited prior art.
Claims 5-9 and 17-26 are rejected under 35 U.S.C. 103 as being unpatentable over Rabe in view of Ball, Baek, and Broughton, as applied to claims 1-4, and 10-16 above, and further in view Curtis (Curtis et al; Journal of Virological Methods, 2018; vol 255, pages 91-97).
The teachings of Rabe, Ball, Baek, and Broughton are set forth above. Rabe, Ball, Baek, and Broughton do not teach conducting the method with a second LAMP primer set and quenching probe directed to the RNase P POP7 gene, however Curtis teaches performing RT-LAMP for detecting viral nucleic acid and including a positive control set of LAMP primers and quencher directed to the RNase P POP7 gene (see whole documents). Curtis teaches (Table 2) LAMP primer that comprises the sequence of SEQ ID NO: 7 as taught in figure 2B of the instant specification. Therefor it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have used positive amplification controls as taught by Curtis in the method of Rabe, Ball, Baek, and Broughton as well as arriving at LAMP primers including SEQ ID NO: 7 as taught by Curtis and a quencher probe given the parameters taught by Ball. Absent secondary considerations, these sequences are considered obvious in view of the teachings of the prior art.
Sawyer and Ball
Claims 1-2, 4-7, and 9-16 are rejected under 35 U.S.C. 103 as being unpatentable over Sawyer (Sawyer et al; WO 2021/236696) in view of Ball.
Sawyer teaches a method using RT-LAMP amplification for detecting nucleic acid from saliva for SARS-CoV-2 (see abstract, whole document). Sawyer teaches saliva samples were stabilized with a chemical stabilizer (EDTA, NaOH, Proteinase K) followed by heating (pages 9-12, 21-26, 28-30). Sawyer teaches preparing an aqueous solution comprising LAMP primers FIP, BIP, F3, B3, Loop F, and Loop B, dNTPs, polymerase, and reverse transcriptase. Sawyer teaches amplification followed by visualization of fluorescence emission to detect target nucleic acid. Sawyer teaches using RNase P gene as positive control.
Sawyer does not teach pre-annealing a LAMP primer fluorescently labeled at the 5’ end with a revere complementary oligonucleotide labeled at the 3’ end with a quencher, however Ball teaches a method of conducting RT-LAMP comprising pre-annealing a LAMP primer fluorescently labeled at the 5’ end with a revere complementary oligonucleotide labeled at the 3’ end with a quencher to detect viral nucleic acid (see abstract; whole document). Ball teaches the technique uses a LAMP primer (eg FIP, BIP, Loop F or Loop B) labeled with a fluorophore at the 5' end. Ball teaches as amplification proceeds, the fluorophore labeled primers are incorporated into the amplicon. Ball teaches including a short reverse complementary quencher probe, typically with 7-13 bases complementary to the 5' end of the labeled primer, including probes with a single mismatch (see page 3566, supplemental tables). Ball teaches optimizing the Tm of the quencher probe (see supplemental information, whole document). Ball teaches the quencher probe is modified at the 3' end with a dark quencher and the melting temperature of the quenching probe annealed to the labeled primer (typically <55 C) must be well below the temperature of the LAMP amplification (typically 60-65 C), such that during the amplification the quenching probe is dissociated and does not participate in or inhibit the reaction. Ball teaches after amplification the reaction is stopped and cooled down, followed by excitation to detect fluorescence by visual inspection. Ball teaches this allows for better discrimination of target nucleic acids. Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have included a pre-annealing step as taught by Ball in the method of Sawyer for increased discrimination of SARS-CoV-2.
Although Sawyer does not teach LAMP primers for the N gene of SARS-CoV-2, Sawyer does teach amplification of this gene for SARS-CoV-2 detection using real time PCR, therefore it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have included the use of LAMP primers to the N gene, with a reasonable expectation of success.
With regard to components of the amplification solution and fluorescent and quenching dyes set forth in the claims, these limitation are considered routine optimization as evidenced by the different solutions and conditions used in the cited prior art for RT-LAMP assays. Additionally, although the cited art does not teach illumination with UV for fluorescence detection, the use of UV in LAMP assays is routine and obvious. As set forth in the MPEP 2144.05 II A:
Generally, differences in concentration or temperature will not support the patentability of
subject matter encompassed by the prior art unless there is evidence indicating such
concentration or temperature is critical. “[W]here the general conditions of a claim are
disclosed in the prior art, it is not inventive to discover the optimum or workable ranges
by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235
(CCPA 1955) (Claimed process which was performed at a temperature between 40°C
and 80°C and an acid concentration between 25% and 70% was held to be prima facie
obvious over a reference process which differed from the claims only in that the reference
process was performed at a temperature of 100°C and an acid concentration of 10%.)…
Therefore, absent secondary consideration, these limitation are considered obvious in view of the cited art.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Sawyer in view of Ball as applied to claims 1, 2, 4-7, and 9-16 above, and further in view of Broughton (Broughton et al; WO 2020/257356-December 24, 2020; note the sequence cited is disclosed in the 62/985,850 priority document dated March 2020)).
The teachings of Sawyer in view of Ball are set forth above. Sawyer and Ball do not teach a first primer with SEQ ID NO: 1 or a reverse complementary probe with the sequence of SEQ ID NO: 13, however Broughton teaches RT-LAMP primers for detection of SARS-CoV-2 N gene wherein a primer has the sequence of SEQ ID NO: 1 (see SEQ ID NO: 350; table 23, page 328). Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have included use of the primer sequences taught by Broughton in the method of Sawyer and Ball with a reasonable expectation of success as it represents substitution of one known element for another with predictable results. It would have additionally been prima facie obvious to arrive at a quencher of SEQ ID NO: 13 given the teachings of Ball. Absent secondary considerations, these primer and probe sequences are considered obvious in view of the teachings of the cited prior art.
Claims 8 and 17-26 are rejected under 35 U.S.C. 103 as being unpatentable over Sawyer in view of Ball, as applied to claims 1-7 and 9-16 above, and further in view Curtis (Curtis et al; Journal of Virological Methods, 2018; vol 255, pages 91-97).
The teachings of Sawyer, Ball and Broughton are set forth above. Sawyer, Ball, and Broughton do not teach conducting the method with a second LAMP primer set and quenching probe directed to the RNase P POP7 gene with SEQ ID NO: 7, however Curtis teaches performing RT-LAMP for detecting viral nucleic acid and including a positive control set of LAMP primers and quencher directed to the RNase P POP7 gene (see whole documents). Curtis teaches (Table 2) LAMP primer that comprises the sequence of SEQ ID NO: 7 as taught in figure 2B of the instant specification. Therefor it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have used positive amplification controls as taught by Curtis in the method of Sawyer Ball, and Broughton as well as arriving at LAMP primers including SEQ ID NO: 7 as taught by Curtis and a quencher probe given the parameters taught by Ball. Absent secondary considerations, these sequences are considered obvious in view of the teachings of the prior art.
Yang I/II and Ball
Claims 1-2, 4-7, and 9-16 are rejected under 35 U.S.C. 103 as being unpatentable over Yang I (Yang et al; medRxiv preprint doi.org/10.1101/2020.07.16.20150250; November 23, 2020; pages 1-36) or, in the alternative, Yang II (Yang et al; eLife; 2021, doi.org/10.7554/eLife.65113; pages 1-28), each in view of Ball.
Yang I and Yang II each teach a method using RT-LAMP amplification for detecting nucleic acid from saliva for SARS-CoV-2 (see abstract, whole document). Yang I and Yang II each teaches saliva samples were stabilized with a chemical stabilizer (EDTA, NaOH, Proteinase K) followed by heating (pages 9-12, 21-26, 28-30). Yang I and Yang II each teaches preparing an aqueous solution comprising LAMP primers FIP, BIP, F3, B3, Loop F, and Loop B, dNTPs, polymerase, and reverse transcriptase. Yang I and Yang II each teaches amplification followed by visualization of fluorescence emission to detect target nucleic acid. Yang I and Yang II each teaches using RNase P gene as positive control.
Yang I and Yang II each does not teach pre-annealing a LAMP primer fluorescently labeled at the 5’ end with a revere complementary oligonucleotide labeled at the 3’ end with a quencher, however Ball teaches a method of conducting RT-LAMP comprising pre-annealing a LAMP primer fluorescently labeled at the 5’ end with a revere complementary oligonucleotide labeled at the 3’ end with a quencher to detect viral nucleic acid (see abstract; whole document). Ball teaches the technique uses a LAMP primer (eg FIP, BIP, Loop F or Loop B) labeled with a fluorophore at the 5' end. Ball teaches as amplification proceeds, the fluorophore labeled primers are incorporated into the amplicon. Ball teaches including a short reverse complementary quencher probe, typically with 7-13 bases complementary to the 5' end of the labeled primer, including probes with a single mismatch (see page 3566, supplemental tables). Ball teaches optimizing the Tm of the quencher probe (see supplemental information, whole document). Ball teaches the quencher probe is modified at the 3' end with a dark quencher and the melting temperature of the quenching probe annealed to the labeled primer (typically <55 C) must be well below the temperature of the LAMP amplification (typically 60-65 C), such that during the amplification the quenching probe is dissociated and does not participate in or inhibit the reaction. Ball teaches after amplification the reaction is stopped and cooled down, followed by excitation to detect fluorescence by visual inspection. Ball teaches this allows for better discrimination of target nucleic acids. Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have included a pre-annealing step as taught by Ball in the method of Yang I and Yang II each for increased discrimination of SARS-CoV-2.
Although Yang I and Yang II each does not teach LAMP primers for the N gene of SARS-CoV-2, Yang I and Yang II each does teach amplification of this gene for SARS-CoV-2 detection using real time PCR, therefore it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have included the use of LAMP primers to the N gene, with a reasonable expectation of success.
With regard to components of the amplification solution and fluorescent and quenching dyes set forth in the claims, these limitation are considered routine optimization as evidenced by the different solutions and conditions used in the cited prior art for RT-LAMP assays. Additionally, although the cited art does not teach illumination with UV for fluorescence detection, the use of UV in LAMP assays is routine and obvious. As set forth in the MPEP 2144.05 II A:
Generally, differences in concentration or temperature will not support the patentability of
subject matter encompassed by the prior art unless there is evidence indicating such
concentration or temperature is critical. “[W]here the general conditions of a claim are
disclosed in the prior art, it is not inventive to discover the optimum or workable ranges
by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235
(CCPA 1955) (Claimed process which was performed at a temperature between 40°C
and 80°C and an acid concentration between 25% and 70% was held to be prima facie
obvious over a reference process which differed from the claims only in that the reference
process was performed at a temperature of 100°C and an acid concentration of 10%.)…
Therefore, absent secondary consideration, these limitation are considered obvious in view of the cited art.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Yang I, or in the alternative, Yang II each in view of Ball as applied to claims 1, 2, 4-7, and 9-16 above, and further in view of Broughton (Broughton et al; WO 2020/257356-December 24, 2020; note the sequence cited is disclosed in the 62/985,850 priority document dated March 2020)).
The teachings of Yang I and Yang II each in view of Ball are set forth above. Yang I, Yang II, and Ball do not teach a first primer with SEQ ID NO: 1 or a reverse complementary probe with the sequence of SEQ ID NO: 13, however Broughton teaches RT-LAMP primers for detection of SARS-CoV-2 N gene wherein a primer has the sequence of SEQ ID NO: 1 (see SEQ ID NO: 350; table 23, page 328). Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have included use of the primer sequences taught by Broughton in the method of Yang I or Yang II each in view of Ball with a reasonable expectation of success as it represents substitution of one known element for another with predictable results. It would have additionally been prima facie obvious to arrive at a quencher of SEQ ID NO: 13 given the teachings of Ball. Absent secondary considerations, these primer and probe sequences are considered obvious in view of the teachings of the cited prior art.
Claims 8 and 17-26 are rejected under 35 U.S.C. 103 as being unpatentable over Yang I, or in the alternative, Yang II each in view of Ball, as applied to claims 1-7 and 9-16 above, and further in view Curtis (Curtis et al; Journal of Virological Methods, 2018; vol 255, pages 91-97).
The teachings of Yang I or Yang II each, in view of Ball and Broughton are set forth above. Yang I or Yang II each in view of Ball, and Broughton do not teach conducting the method with a second LAMP primer set and quenching probe directed to the RNase P POP7 gene with SEQ ID NO: 7, however Curtis teaches performing RT-LAMP for detecting viral nucleic acid and including a positive control set of LAMP primers and quencher directed to the RNase P POP7 gene (see whole documents). Curtis teaches (Table 2) LAMP primer that comprises the sequence of SEQ ID NO: 7 as taught in figure 2B of the instant specification. Therefor it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have used positive amplification controls as taught by Curtis in the method of Yang I or Yang II each in view of Ball, and Broughton as well as arriving at LAMP primers including SEQ ID NO: 7 as taught by Curtis and a quencher probe given the parameters taught by Ball. Absent secondary considerations, these sequences are considered obvious in view of the teachings of the prior art.
Conclusion
No claims are allowed.
The prior art made of record is considered pertinent to applicant's disclosure: Lamb (Lamb et al; PLOS ONE 15(6):e0234682; June 12, 2020, pages 1-15) exemplifies further the state of the prior art regarding the use of RT-LAMP for rapid detection of target nucleic acids. Lamb teaches methods of using RT-LAMP for detecting SARS-CoV-2. Lamb teaches samples included saliva. Lamb exemplifies the method with LAMP primers FIP, BIP, F3, B3, Loop B, and Loop F; amplification solution comprising polymerase and reverse transcriptase, dNTPs, UDG to reduce crossover contamination, and visualization using UV excitation to visualize fluorescence.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner can normally be reached Mondays-Fridays from 8:00 AM to 2:00 PM Eastern Time Zone.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Winston Shen, can be reached at (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
