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.A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on July 16, 2026 has been entered.
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 and 123-124 are pending under examination. Claims 3, 7, 13-14, 16-17, 20, 24-25, 27, 30, 34-36, 39, 44-122 and 125 are canceled. The Applicant’s arguments and the amendment have been fully considered and found persuasive for the following reasons.
Response to Arguments:
3. The rejection of claims under 35 USC 102(a)(1) as being anticipated by Cui et al. has been withdrawn in view of the amendment.
4. The rejection of claims under 35 USC 102(a)(1) as being anticipated by Hoser et al. has been withdrawn in view of the amendment.
5. The rejection of claims under 35 USC 103 as being obvious over Hoser in view of Ellington et al. has been withdrawn in view of the amendment.
Claim Rejections - 35 USC § 112
6. 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 19 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 19 recites amplification selected from the group consisting of, LAMP, RPA, HAD….CPA’. The limitations in claim 19 are unclear and indefinite because the claim 1 upon which claim 19 depends requires LAMP amplification and it is not clear how LAMP amplification encompasses different amplifications as recited in claim 19.
Claim Rejections - 35 USC § 103
7. 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 123-124 are rejected under 35 U.S.C. 103 as being unpatentable over Ellington et al. (US 2016/0076083) in view of Duan et al. (Nature Protocols, Vol. 9(3), p.597-607, (2014)).
Ellington 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 (para 0005-0008, 0109); and
detecting the reporter molecule (para 0005-0008, 0109), wherein the first enzyme is a DNA polymerase having strand displacement activity and said amplification comprises amplifying the target nucleic acid with the first enzyme and a set of Loop-Mediated Isothermal Amplification (LAMP) primers comprising a forward outer primer (F3), a reverse outer primer (R3), a forward inner primer (FIP), and a reverse inner primer (RIP), and optionally a forward loop primer (LF), and a reverse loop primer (LR), and wherein the nucleic acid probe hybridizes to a single-stranded loop region of the amplicon (para 0109-0111, 0116-0120, 0231-0235, 0010, 0245-0252).
With reference to claim 4-6, 8-10, Ellington 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 different reporter molecules (0116-0120, 0213).
With reference to claim 11-12, Ellington 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 wherein at least one nucleic acid modification, at least one nucleic acid modification capable of inhibiting extension by a polymerase (para 0218, 0080,0132, 0118).
With reference to claim 15, 124, Ellington et al. teach that the exonuclease lacks polymerase activity; and the exonuclease having exonuclease is Bst polymerase (para 0245).
With reference to claim 18-19, Ellington et al. teach that said amplification is isothermal amplification strand displacement amplification (LAMP) (0116-0120, 0231-0235, 0010, 0245-0252).
With reference to claim 21-22, Ellington 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 0005, 0008, 0272).
With reference to claim 23, Ellington et al. teach that said detecting the reporter molecule comprises: detecting a detectable signal produced by the reporter molecule and fluorescence detection (0272).
With reference to claim 28-29, Ellington et al. teach that said detecting the nucleic acid probe comprises toe-hold mediated strand displacement, gel electrophoresis, and fluorophore- quencher (0272, 0116-0120, 0231-0235, 0010, 0246-0252).
With reference to claim 31-33, 37-38, Ellington et al. teach that the nucleic acid probe or a primer is immobilized to a surface, wherein 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 0148-0152, 0005).
With reference to claim 40, Ellington et al. teach that the detection is multiplexed detection of at least two target nuclei acids (para 0013, 0246-0252).
With reference to claims 41-43, Ellington et al. teach that the method is performed in a device comprising two or more chambers, means for irreversibly moving a fluid form chambers by built-in spring and the device comprises means for detecting the detectable signal (para 0128, 0152-0164).
However, Ellington et al. did not specifically teach cleaving by double-strand specific exonuclease.
Duan et al. teach a method comprising a hairpin or molecular beacon-mediated enzymatic amplification and detection of a target nucleic acid, wherein the amplification comprises isothermal amplification using a molecular beacon, a polymerase, a nicking endonuclease, an exonuclease and phosphothioate labeled modified primers and molecular beacon, wherein exonuclease cleaves the probe (molecular beacon), separating the labeled phophothioates, wherein nicking enzyme and lambda exonuclease cleave reporter and recycle target nucleic acid and produce multiple copies of single-stranded target nucleic acid and detection of said target nucleic acid (page 597-598, paragraphs under subheading ‘hairpin-mediated quadratic enzymatic amplification).
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 Ellington et al. with exonuclease mediated cleaving of molecular beacon probe as taught by Duan 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 Duan et al. explicitly taught ultrasensitive detection of target nucleic acids through quadratic amplification of target oligonucleotide by using a Bst DNA polymerase-induced strand displacement reaction and lambda exonuclease-aided cleaving and recycling reaction in the presence of a molecular beacon probe (abstract on page 597) and such a modification of the method is considered to be obvious over the cited prior art.
Conclusion
No claims are allowed.
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/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681
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