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 .
DETAILED ACTION
1. The Applicant’s response to the office action filed on January 15, 2026 is acknowledged.
Status of the Application
2. Claims 1-2, 4-6, 8-12, 15, 18-19, 21-23, 26, 28-29, 31-33, 37-38, 40-43 are pending under examination. New claims 123-125 are added. The Applicant’s arguments have been fully considered and found persuasive for the following reasons.
Objection to the Specification-Withdrawn
3. The objection to the specification has been withdrawn in view of the amendment.
Claim Rejections - 35 USC § 102-Withdrawn
4. The rejection of claims under 35 USC 102(a)(1) as being anticipated by Yang et al. has been withdrawn in view of the amendment.
New Rejections Necessitated by the Amendment
Claim Rejections - 35 USC § 102
5.. 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.
A. Claims 1-2, 4-6, 8-9, 12, 15, 18-19, 21-23, 28-29 and 123-124 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cui et al. (Chem. Commun., Vol. 50, p. 1576-1578, 2014).
Cui et al. teach a method of claim 1-2, 123, for detecting an amplicon from amplification of a target nucleic acid in a sample, the method comprising:
hybridizing a nucleic acid probe to an amplicon produced from amplification of a target nucleic acid, wherein the nucleic acid with a first enzyme comprising polymerase, wherein probe comprises a nucleotide sequence substantially complementary or identical to a nucleotide sequence of the target nucleic acid or a primer used in the amplification of the target nucleic acid, wherein the nucleic acid probe comprises a reporter molecule capable of producing a detectable signal, and wherein the detectable signal from the reporter molecule is partially quenched when the nucleic acid probe is hybridized to the amplicon; cleaving the hybridized nucleic acid probe with a second enzyme double-strand specific exonuclease having 5’ to 3’ exonuclease activity; and detecting the reporter molecule from the cleaved nucleic acid probe or detecting any remaining uncleaved nucleic acid probe or detecting any remaining uncleaved nucleic acid probe (page 1576, paragraph 2 on the right-hand side column, line 1-12 and paragraph 1-2 on left-hand side column on page 1577, Fig. 1, page 1578, paragraph 1 on right-hand side column).
With reference to claim 4-6, 8-9, Cui et al. teach that the reporter molecule is a fluorescent molecule comprising a quencher wherein the quencher molecule quenches the detectable signal from the reporter molecule when the nucleic acid probe is not hybridized to the amplicon or when the nucleic acid probe is hybridized to the amplicon, the nucleic acid probe further comprises at least one additional quencher (fluorophore) molecule or the nucleic acid probe comprises a plurality of reporter molecules (page 1577, line 1-5).
With reference to claim 12, Cui et al. teach that the nucleic acid probe comprises at least one nucleic acid modification capable of inhibiting extension by a polymerase (page 1577, line 1-5).
With reference to claim 15, 124, Cui et al. teach that the exonuclease lacks polymerase activity (phi29 DNA polymerase); the exonuclease has polymerase activity; or the exonuclease is T7 Exonuclease (page 1576, paragraph 2 on the right-hand side column, line 1-12 and paragraph 1-2 on left-hand side column on page 1577, Fig. 1, page 1578, paragraph 1 on right-hand side column).
With reference to claim 18-19, Cui et al. teach that said amplification is isothermal amplification wherein said amplification is a rolling circle amplification (RCA) or strand displacement amplification (page 1576, paragraph 2 on the right-hand side column, line 1-12 and paragraph 1-2 on left-hand side column on page 1577, Fig. 1, page 1578, paragraph 1 on right-hand side column).
With reference to claim 21-22, Cui et al. teach that the amplicon is single-stranded and wherein the method further comprises a step of preparing the single-stranded amplicon from the target nucleic acid prior to hybridizing the nucleic acid probe with the amplicon (page 1576, paragraph 2 on the right-hand side column, line 1-12 and paragraph 1-2 on left-hand side column on page 1577, Fig. 1, page 1578, paragraph 1 on right-hand side column).
With reference to claim 23, Cui et al. teach that said detecting the reporter molecule comprises: detecting a detectable signal produced by the reporter molecule; fluorescence detection, page 1576, paragraph 2 on the right-hand side column, line 1-12 and paragraph 1-2 on left-hand side column on page 1577, Fig. 1, page 1578, paragraph 1 on right-hand side column, Fig. 3).
With reference to claim 28-29, Cui et al. teach that said detecting the uncleaved nucleic acid probe comprises sequence-specific detection, gel electrophoresis, and fluorophore- quencher (page 1576, paragraph 2 on the right-hand side column, line 1-12 and paragraph 1-2 on left-hand side column on page 1577, Fig. 1, page 1578, paragraph 1 on right-hand side column, Fig. 2). For all the above, the claims are anticipated.
B. Claims 1-2, 4-6, 8-9, 11-12, 15, 18-19, 21-23, 28-29, 33, 37-38 and 123-124 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hoser et al. (US 2008/0286835).
Hoser et al. teach a method of claim 1-2, 123, for detecting an amplicon from amplification of a target nucleic acid in a sample, the method comprising:
hybridizing a nucleic acid probe to an amplicon produced from amplification of a target nucleic acid, wherein the nucleic acid with a first enzyme comprising polymerase, wherein probe comprises a nucleotide sequence substantially complementary or identical to a nucleotide sequence of the target nucleic acid or a primer used in the amplification of the target nucleic acid, wherein the nucleic acid probe comprises a reporter molecule capable of producing a detectable signal, and wherein the detectable signal from the reporter molecule is partially quenched when the nucleic acid probe is hybridized to the amplicon; cleaving the hybridized nucleic acid probe with a second enzyme double-strand specific exonuclease having 5’ to 3’ exonuclease activity; and detecting the reporter molecule from the cleaved nucleic acid probe or detecting any remaining uncleaved nucleic acid probe or detecting any remaining uncleaved nucleic acid probe (para 0200-0225, Table 1).
With reference to claim 4-6, 8-9, Hoser et al. teach that the reporter molecule is a fluorescent molecule comprising a quencher wherein the quencher molecule quenches the detectable signal from the reporter molecule when the nucleic acid probe is not hybridized to the amplicon or when the nucleic acid probe is hybridized to the amplicon, the nucleic acid probe further comprises at least one additional quencher (fluorophore) molecule or the nucleic acid probe comprises a plurality of reporter molecules (para 0220-0225, Table 1).
With reference to claim 11, Hoser et al. teach that at least one primer used in the amplification comprises a nucleic acid modification capable of inhibiting the 5’-3’ exonuclease activity of the exonuclease (para 0221-0222, table 1).
With reference to claim 12, Hoser et al. teach that the nucleic acid probe comprises: at least one nucleic acid modification, at least one nucleic acid modification capable of inhibiting extension by a polymerase (para 0220-0225, table 1).
With reference to claim 15, 124, Hoser et al. teach that the exonuclease lacks polymerase activity; and the exonuclease having exonuclease is T7 Exonuclease (para 0220-0222).
With reference to claim 18-19, Hoser et al. teach that said amplification is isothermal amplification strand displacement amplification (SDA) (para 0220-0225, 0218).
With reference to claim 21-22, Hoser et al. teach that the amplicon is single-stranded and wherein the method further comprises a step of preparing the single-stranded amplicon from the target nucleic acid prior to hybridizing the nucleic acid probe with the amplicon (para 0220-0225).
With reference to claim 23, Hoser et al. teach that said detecting the reporter molecule comprises: detecting a detectable signal produced by the reporter molecule and fluorescence detection (para 0222-0225).
With reference to claim 28-29, Hoser et al. teach that said detecting the uncleaved nucleic acid probe comprises sequence-specific detection, gel electrophoresis, and fluorophore- quencher (para 0220-0225, table 1).
With reference to claim 33, 37-38, Hoser et al. teach that the nucleic acid probe comprises: a nucleotide sequence substantially complementary to a nucleotide sequence at an internal position of the amplicon; a first nucleic acid strand and a second nucleic acid strand, wherein the first strand comprises a region that is substantially complementary to a region in the second strand; or a single-stranded region when hybridized to the amplicon wherein the first and second strands are linked to each other, wherein the nucleic acid probe forms a hairpin structure when hybridized to the amplicon (para 0220-0225, table 1, 0054, 0214). For all the above the claims are anticipated.
Claim Rejections - 35 USC § 103
6. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 4-6, 8-12, 15, 18-19, 21-23, 26, 28-29, 31-33, 37-38, 40-43 and 123-125 are rejected under 35 U.S.C. 103 as being unpatentable over Hoser et al. (US 2008/0286835) in view of Ellington et al. (US 2016/0076083).
Hoser et al. teach a method for detecting an amplicon from amplification of a target nucleic acid in a sample as discussed above in 5B.
However, Hoser et al. did not specifically teach multiplex detection using at least two reporters and target nucleic acids, performing amplification in a lateral flow device comprising two or more chambers, using a probe or primer immobilized on a support via a ligand, signal detection and loop-mediated amplification, probe hybridizing to the loop of the amplicon.
Ellington et al. teach a multiplex loop mediated isothermal amplification method using a lateral flow device, wherein the device comprises two or more reaction chambers for amplifying two or more target nucleic acids using two or more reporter oligonucleotides, wherein the primer or probe is immobilized on a support through a ligand binding (para 0108-0111, 0116-0120, 0122, 0128, 0128-0149, 0013-0014, 0144, 0148-0149, 0020-0023).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the invention, to modify the method of Hoser et al. with multiplex LAMP in a lateral flow device as taught by Ellington et al. to develop an improved method. The ordinary person skilled in the art would have motivated to combine the references and have a reasonable expectation of success that the combination would result in improving the sensitivity of the method because Ellington et al. explicitly taught point-of-care method for detecting multiple target nucleic acids in a LAMP reaction (para 0023, 0102) and such a modification of the method is considered to be obvious over the cited prior art.
Conclusion
No claims are allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681