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 .
Claims 1-20 are pending. Claims 1-6, 13-15 and 17-20 are being examined on the merits. Claims 7-12 and 16 are withdrawn.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-6, 13-15 and 17-20) and the species of SEQ ID NO: 7 (T7 mFIP) in the reply filed on October 27, 2025 is acknowledged.
Claims 7-12 and 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 27, 2025.
The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
The Information Disclosure Statement submitted June 7, 2023 has been considered.
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 - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is incomplete. See item 1) a) or 1) b) above. Specifically, as noted above, the size of the ASCII text file must be listed in bytes, not kilobytes.
Required response – Applicant must 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.
Specification
The use of the terms for various reporter molecules, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Specifically, the following trademarks appear in the specification on pp. 43-44: “IRIS”, “Texas Red”, “Oregon Green”, “Pacific [Blue/Green/Orange]”; and on p. 16: “FAM”, HEX”.
Claim Objections
Claims 4-5 and 19 are objected to because of the following informalities:
In claim 4, the limitation “the sequence is interior” in ll. 1-2 should be “the sequence tag is interior”.
In claim 5, the limitation “flop” in l. 2 should be “floop”.
In claim 19, a period should be added at the end of the claim.
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.
Claim 6 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 refers to the primers listed in “Table 2 or Table 5”. Where possible, claims are to
be complete in themselves. Reference to a specific table is permitted only in exceptional circumstances when there is no other practical way to define the invention in words. MPEP 2173.05(s). Here, clearly the primers listed in Tables 2 and 5 can be recited in the claims (perhaps by their SEQ ID NOs), and thus it is not a necessity for Applicant to refer to the tables.
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.
Claims 1-3, 13, 15 and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Calvert (WO 2018/204175 A1).
Regarding independent claim 1, Calvert teaches …
A system for amplifying at least one target nucleic acid sequence, the system
comprising: (a) at least one target DNA sequence obtained from a sample, optionally wherein the target DNA sequence is transcribed from RNA obtained from the sample (Example 1; p. 2, ll. 28-34 through p. 3, ll. 1-2);
(b) at least four primers including: (i) a forward inner primer (FIP) that binds to the target DNA sequence; (ii) a backward inner primer (BIP) that binds to the target DNA sequence; (iii) a forward outer primer (F3), wherein the forward outer primer binds to the target DNA sequence 5' to the FIP; (iv) a backward outer primer (B3), wherein the backward outer primer binds to the target DNA sequence 3' to the BIP (Example 1; Table 1; p. 7, ll. 12-24; p. 23, ll. 25-34 through p. 24, ll. 1-2);
optionally further comprising (v) a forward loop primer (floop); and (vi) a backward loop primer (bloop) (Example 1; Table 1; p. 7, ll. 19-20; p. 23, ll. 25-34 through p. 24, ll. 1-2);
wherein at least one of the primers comprises a sequence tag, optionally wherein the sequence tag is an RNA polymerase promoter sequence such as a T7 polymerase promoter, such that in the presence of a DNA polymerase, the target DNA sequence is amplified to generate amplicons comprising the sequence tag, optionally wherein the amplicons comprise a detectable label (Example 1; p. 28, ll. 3-8; p. 23, ll. 1-4).
Regarding dependent claims 2-3, Calvert additionally teaches that (c) RNA substrate amplicons transcribed from the amplicons comprising the RNA polymerase promoter sequence (Example 1), as recited in claim 2, and that the sequence tag is 5’ of the primer (Example 1), as recited in claim 3.
Regarding dependent claims 13, 15 and 19, Calvert additionally teaches that the at least one target nucleic acid sequence is obtained from a virus (Example 2: ZIKV), as recited in claim 13, that the sample is a biological sample, optionally serum and urine (Example 2), as recited in claims 15 and 19.
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.
Claims 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Calvert (WO 2018/204175 A1) as applied to claim 1 above, and further in view of Chen (WO 2020/028729 A1).
Regarding dependent claims 4-5, Chen teaches that the sequence tag (T7 promoter) is
interior in the primer, and that it is included in the FIP or BIP primer (para. 124; Fig. 47B)
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious to modify the Calvert system with the Chen promoter locations. Calvert teaches modifying a LAMP primer set so that one of the primers comprises a T7 promoter. Chen teaches LAMP primers that comprise T7 promoters, and teaches the T7 promoter can be placed in various primers and positions in the primers. One of ordinary skill in the art would have been motivated to optimize the choice of the primer and the location of the T7 promoter sequence in the primer in order to customize the system as needed to perform a desired assay, perhaps to ensure the proper orientation of the T7 promoter in the primer. Further, there are a limited number of primers and locations where the T7 promoter can be placed, and the art recognizes the suitability of placing the T7 promoter in various primers/locations for use in LAMP assays. MPEP 2144.07. The ordinary artisan would have had an expectation of success since optimizing primer sequences is well-known in the art, and because Chen does not limit where the T7 promoter can be placed.
Claims 14 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Calvert (WO 2018/204175 A1) as applied to claims 1 and 13 above, and further in view of Ecker (US Patent App. Pub. No. 2009/0004643 A1).
Regarding dependent claim 14, Ecker teaches that the virus is a SARS coronavirus (para.
51; Example 1).
Regarding dependent claim 17, Ecker teaches assembling the various reagents into a kit with instructions for use (paras. 62, 65).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious to modify the Calvert LAMP system so that the target nucleic acid is a SARS coronavirus. Calvert teaches that the system is useful for detecting a virus, that it is highly sensitive and specific, and that it is an “easy to use, convenient and cost-effective alternative to laboratory-based testing” in point-of-care settings (p. 38, ll. 10-18). Calvert does not specifically teach detecting a SARS coronavirus. Ecker teaches the need for systems that are capable of detecting SARS coronavirus in various samples, and specifically teaches PCR systems for doing so. The ordinary artisan would have been motivated to try the SARS coronavirus target nucleic acid in the Calvert system, with the expectation that doing so would result in the advantage of an improved system that is easier to use, more convenient and more cost-effective than the Ecker system. The ordinary artisan would have had an expectation of success as optimizing amplification techniques is well-known in the art.
In addition, it would have been further obvious to modify the Calvert system to arrange the various components into a kit with instructions for use. The ordinary artisan would have been motivated to do so with the expectation that the resulting kit would provide the advantage of a useful, efficient method of shipping, storing and using the system, as reagent kits are understood in the art to have these properties. Ecker also suggests that kits have these properties (para. 65). The ordinary artisan would have had an expectation of success as arranging various related reagents into kits is well-known in the art.
Claims 15, 18 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Calvert (WO 2018/204175 A1) in view of Ecker (US Patent App. Pub. No. 2009/0004643 A1) as applied to claims 1 and 14 above, and further in view of Mallapaty1 (How sewage could reveal true scale of coronavirus outbreak, Nature, 580(7802): 176-177; April 9, 2020).
Regarding dependent claims 15 and 20, Mallapaty teaches that the sample is an environmental sample, optionally from a sewage system or a waste water treatment facility (p. 176, middle col., paras. 1-2).
Regarding dependent claim 18, Mallapaty teaches that the coronavirus is SARS-CoV-2 (p. 176, middle col., para. 2).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious to further modify the modified Calvert LAMP system, discussed above, so that the target nucleic acid is specifically SARS-CoV-2. Calvert teaches that the system is useful for detecting a virus, that it is highly sensitive and specific, and that it is an “easy to use, convenient and cost-effective alternative to laboratory-based testing” in point-of-care settings (p. 38, ll. 10-18). Calvert does not specifically teach detecting a SARS coronavirus. Ecker teaches the need for systems that are capable of detecting SARS coronavirus in various samples, and specifically teaches PCR systems for doing so. The ordinary artisan would have been motivated to try the SARS-CoV-2 target nucleic acid in the modified Calvert system, with the expectation that doing so would result in the advantage of a system for detecting SARS-CoV-2 that is easy to use, convenient and cost-effective. It would have been additionally obvious to try using environmental samples, such as from wastewater or sewage, as the art teaches that surveillance of such sources can be useful for detecting the spread of various human pathogens (Mallapatty, p. 177, left col., para. 2). The ordinary artisan would have had an expectation of success as optimizing known systems to detect different targets from different samples is well-known in the art.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Calvert (WO 2018/204175 A1) as applied to claim 1 above, in view of Chen (WO 2020/028729 A1), Ecker (US Patent App. Pub. No. 2009/0004643 A1), Mallapaty2 (How sewage could reveal true scale of coronavirus outbreak, Nature, 580(7802): 176-177; April 9, 2020), GenBank Accession No. MT246667.1 (Severe acute respiratory syndrome coronavirus 2 strain FDAARGGOS_983 isolate SARS-CoV-2/human/USA/USA-Wa1/2020, complete genome, July 2020) and Eichen Chemical (A Guide to LAMP primer designing, PrimerExplorerV4, 2005), as evidenced by New England Biolabs (FAQ: What is the promoter sequence of T7 RNA Polymerase, 2025).
Regarding dependent claim 6, as noted above, Calvert teaches a system comprising
LAMP primers for detecting a virus, where one of the primers comprises a T7 promoter sequence at the 5’ end of the primer (Example 1; p. 28, ll. 3-8; p. 23, ll. 1-4; Table 1; p. 7, ll. 12-24; p. 23, ll. 25-34 through p. 24, ll. 1-2). In addition, Chen teaches LAMP primers with internal T7 promoter sequences, and more specifically that the T7 sequence is between the F1c and F2 sequences in the FIP primer (para. 124; Fig. 47B), while the combination of Calvert, Ecker and Mallapaty teaches or suggests detecting SARS-CoV-2 using nucleic acid amplification techniques, including LAMP (Calvert: Example 2; Ecker: para. 51; Example 1; Mallapaty: p. 176, middle col., para. 2). Finally, The T7 promoter sequence is known in the art, as evidenced by New England Biolabs. However, this combination of references does not teach SEQ ID NO: 7, specifically.
GenBank Accession No. MT246667.1 teaches the nucleic acid sequence of SARS-CoV-2, with the nucleotides in instant SEQ ID NO: 7 that are 5’ to the T7 sequence having 100% homology to GenBank Accession No. MT246667.1 nucleotides 29224-29243, and the nucleotides in instant SEQ ID NO: 7 that are 3’ to the T7 sequence having 100% homology to the reverse complement of GenBank Accession No. MT246667.1 nucleotides 29265-29283. Further,
Eichen Chemical teaches that LAMP primer design is well-known in the art and can be completed by computer software, e.g., PrimerExplorer V4.
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious to modify the Calvert system with the Chen promoter locations. Calvert teaches modifying a LAMP primer set so that one of the primers comprises a T7 promoter. Chen teaches LAMP primers that comprise T7 promoters, and teaches the T7 promoter can be placed in various primers and positions in the primers. One of ordinary skill in the art would have been motivated to optimize the choice of the primer and the location of the T7 promoter sequence in the primer in order to customize the system as needed to perform a desired assay, perhaps to ensure the proper orientation of the T7 promoter in the primer. Further, there are a limited number of primers and locations where the T7 promoter can be placed, and the art recognizes the suitability of placing the T7 promoter in various primers/locations for use in LAMP assays. MPEP 2144.07. The ordinary artisan would have had an expectation of success since optimizing primer sequences is well-known in the art, and because Chen does not limit where the T7 promoter can be placed.
It would have been further obvious to modify the Calvert LAMP system so that the target nucleic acid is a SARS coronavirus. Calvert teaches that the system is useful for detecting a virus, that it is highly sensitive and specific, and that it is an “easy to use, convenient and cost-effective alternative to laboratory-based testing” in point-of-care settings (p. 38, ll. 10-18). Calvert does not specifically teach detecting a SARS coronavirus. Ecker teaches the need for systems that are capable of detecting SARS coronavirus in various samples, and specifically teaches PCR systems for doing so. The ordinary artisan would have been motivated to try the SARS coronavirus target nucleic acid in the Calvert system, with the expectation that doing so would result in the advantage of an improved system that is easier to use, more convenient and more cost-effective than the Ecker system. The ordinary artisan would have had an expectation of success as optimizing amplification techniques is well-known in the art.
It would have been additionally obvious to further modify the modified Calvert LAMP system, discussed above, so that the target nucleic acid is specifically SARS-CoV-2. Calvert teaches that the system is useful for detecting a virus, that it is highly sensitive and specific, and that it is an “easy to use, convenient and cost-effective alternative to laboratory-based testing” in point-of-care settings (p. 38, ll. 10-18). Calvert does not specifically teach detecting a SARS coronavirus. Ecker teaches the need for systems that are capable of detecting SARS coronavirus in various samples, and specifically teaches PCR systems for doing so. The ordinary artisan would have been motivated to try the Mallapatty SARS-CoV-2 target nucleic acid in the modified Calvert system, with the expectation that doing so would result in the advantage of a system for detecting SARS-CoV-2 that is easy to use, convenient and cost-effective. The ordinary artisan would have had an expectation of success as optimizing known systems to detect different targets from different samples is well-known in the art.
Finally, it would have been obvious to the ordinary artisan to design the SEQ ID NO: 7 primer based on the combination of the teachings above, and using the GenBank Accession No. MT246667.1 sequence and Eiken Chemical. The ordinary artisan would have been motivated to do so with expectation of achieving the advantages discussed above. The ordinary artisan would have had an expectation of success as primer design is well-known in the art.
Conclusion
Claims 1-6, 13-15 and 17-20 are being examined and are rejected. Claims 4-5 and 19 are objected to. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CAROLYN L GREENE/Examiner, Art Unit 1681
1 Mallapaty was cited in the Information Disclosure Statement submitted June 7, 2023.
2 Mallapaty was cited in the Information Disclosure Statement submitted June 7, 2023.