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 .
Applicant’s amendment filed on July 14, 2025 is acknowledged and has been entered. Claims 1-16 have been canceled. Claims 17-21 and have been amended. Claim 25-29 has been added. Claims 21 and 23-24 have been withdrawn. Claims 17-20, 22 and 25-29 are pending.
Claims 17-20, 22 and 25-29 are discussed in this Office action.
All of the amendments and arguments have been thoroughly reviewed and considered but are not found persuasive for the reasons discussed below. Any rejection not reiterated in this action has been withdrawn as being obviated by the amendment of the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is made FINAL.
Claim Interpretation
Regarding the probe immobilized substrate and reagent as mentioned in claim 17 and 22, as “immobilized substrate provided in combination with the reagent configured to perform amplification of the plurality of long-chain nucleic acids” will be interpreted as reading on a probe immobilized substrate and a reagent, such as a polymerase and primer capable of primer extension or amplification.
Regarding claim 19, where the kit recites “wherein amplification conditions are reaction conditions of LAMP”, the claims are drawn to a composition or combinatorial analysis kit. While the kit, as claimed, is useful within methods of amplification, the interpretation of a kit or composition is focused on the physical components of the kit or composition. Unless the reaction conditions impart a physical transformation or other change to the components, the amplification conditions will be interpreted as reading on the components of the kit alone.
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 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, line 16 has an amendment to strike out the word “contains” and replace with “wherein”. The phrase now reads “on the first sub-chain-elongation nucleic acid, between a base adjacent to the F1 binding region and a region overlapping with the F2 binding region to avoid overlapping with the F1 binding region, and “wherein” a region without overlapping the F2 binding region”. The interpretation of the final part of the quoted phrase with the word wherein inserted is unclear. It appears the wherein in line 16 should read comprises, instead. Clarification is required and requested.
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) 17-20, 22, 25 and 27 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fang et al. (Anal Chem, 2011, 83:690-695 with supplemental information) as evidenced by Notomi et al. (Nucleic Acids Research, 2000, 28(12):e63, i-vii).
With regard to claim 17, Fang teaches a kit for detecting a plurality of target nucleic acids of short chain that are 18 to 30 nucleotides in length, wherein the kit comprises
(1) reagents that elongate each target nucleic acid within the plurality of target nucleic acids to form long-chain nucleic acids (p 694, “LAMP establishment” heading, where the amplification reagents and the process are described);
reagents that amplifv each of the long-chain nucleic acids (p 694, “LAMP establishment” heading, where the amplification reagents and the process are described): and,
(2) at least one probe immobilized substrate that detects one or more of the amplification products of said long-chain nucleic acids (Figure 1 and figure legend, where the microchamber “were coated with seasonal H1N1-probes, flu A-probes, and pandemic H1N1-probes, respectively; The fourth microchamber set (4 and 40) loaded with human β actin-probes was applied as a positive control while the chamber 5/50 with no probes patterned worked as the negative control; see also p 691, col. 1 describes “LAMP probe sets using the flow patterning technique”; see also Table S1 and Table S2, where Table S1 provides the gene region of different influenze subtypes and Table S2 provides the LAMP probe sets for each sequence)
wherein each of the plurality of target nucleic acids of short chain comprises
a first sub-target sequence at a 5'-terminal and a second sub-target sequence at a 3'-terminal,
wherein the reagents (I) comprise:
(a) a plurality of chain-elongation nucleic acid groups comprising a first sub-chain- elongation nucleic acid and a second sub-chain-elongation nucleic acid corresponding to each of the plurality of target nucleic acids,
wherein the first sub-chain-elongation nucleic acid comprises a first target binding region comprises the first sub-target sequence or a first complementary sequence complementary thereto at one terminal and a first amplification region at another terminal and
wherein the second sub-chain-elongation nucleic acid comprises a second target binding region comprising the second sub-target sequence or a second complementary sequence complementary thereto at the 3'-terminal and a second amplification region at the 5'-terminal, and
wherein, at least one of the first sub-chain-elongation nucleic acids and at least one of the second sub-chain-elongation nucleic acid is further associated with each of the plurality of target sequences in advance and comprises one corresponding detection region among a plurality of detection regions having different sequences from each other (Figure 1 and figure legend, where the microchamber “were coated with seasonal H1N1-probes, flu A-probes, and pandemic H1N1-probes, respectively; The fourth microchamber set (4 and 40) loaded with human β actin-probes was applied as a positive control while the chamber 5/50 with no probes patterned worked as the negative control; see also p 691, col. 1 describes “LAMP probe sets using the flow patterning technique”; see also Table S1 and Table S2, where Table S1 provides the gene region of different influenze subtypes and Table S2 provides the LAMP probe sets for each sequence; where it is noted that each probe includes a distinct sequence which includes detection sequence inherently),
wherein when the first sub-chain-elongation nucleic acid comprises a first detection region, the first detection region is present between the first target binding region and the first amplification region without overlapping the first target binding region and (Figure 1 and figure legend, where the microchamber “were coated with seasonal H1N1-probes, flu A-probes, and pandemic H1N1-probes, respectively; The fourth microchamber set (4 and 40) loaded with human β actin-probes was applied as a positive control while the chamber 5/50 with no probes patterned worked as the negative control; see also p 691, col. 1 describes “LAMP probe sets using the flow patterning technique”; see also Table S1 and Table S2, where Table S1 provides the gene region of different influenze subtypes and Table S2 provides the LAMP probe sets for each sequence; where it is noted that each probe includes a distinct sequence which includes detection sequence inherently),
wherein when the second sub-chain-elongation nucleic acid comprises a second detection region, the second detection region being present between the second target binding region and the second amplification region without overlapping the second target binding region, and (Figure 1 and figure legend, where the microchamber “were coated with seasonal H1N1-probes, flu A-probes, and pandemic H1N1-probes, respectively; The fourth microchamber set (4 and 40) loaded with human β actin-probes was applied as a positive control while the chamber 5/50 with no probes patterned worked as the negative control; see also p 691, col. 1 describes “LAMP probe sets using the flow patterning technique”; see also Table S1 and Table S2, where Table S1 provides the gene region of different influenze subtypes and Table S2 provides the LAMP probe sets for each sequence; where it is noted that each probe includes a distinct sequence which includes detection sequence inherently)
(b) a universal primer set comprising at least a first primer comprising a sequence common among the plurality of target nucleic acids and bound to the first amplification region, and a second primer comprising a sequence common among the plurality of target nucleic acids and bound to the second amplification region, and (p 694, “LAMP establishment” heading, where the amplification reagents and the process are described)
wherein the probe immobilized substrate comprises
a substrate (Figure 1 and figure legend, where the microchamber “were coated with seasonal H1N1-probes, flu A-probes, and pandemic H1N1-probes, respectively; The fourth microchamber set (4 and 40) loaded with human β actin-probes was applied as a positive control while the chamber 5/50 with no probes patterned worked as the negative control; see also p 691, col. 1 describes “LAMP probe sets using the flow patterning technique”; see also Table S1 and Table S2, where Table S1 provides the gene region of different influenze subtypes and Table S2 provides the LAMP probe sets for each sequence; where it is noted that each probe includes a distinct sequence) and
a plurality of probes immobilized to a surface in contact with a first reaction field provided by the substrate (Figure 1 and figure legend, where the microchamber “were coated with seasonal H1N1-probes, flu A-probes, and pandemic H1N1-probes, respectively; The fourth microchamber set (4 and 40) loaded with human β actin-probes was applied as a positive control while the chamber 5/50 with no probes patterned worked as the negative control; see also p 691, col. 1 describes “LAMP probe sets using the flow patterning technique”; see also Table S1 and Table S2, where Table S1 provides the gene region of different influenze subtypes and Table S2 provides the LAMP probe sets for each sequence; where it is noted that each probe includes a distinct sequence),
wherein each of the plurality of probes,
(1) comprises a same sequence as that of a respective one of the plurality of sequences of the first detection region,
(2) comprises a complementary sequence to a respective one of the plurality of sequences of the first detection region (p 694, “LAMP establishment” heading, where the amplification reagents and the process are described),
(3) comprises a same sequence as that of a respective one of the plurality of sequences of the second detection region, and/or
(4) comprises a complementary sequence to a respective one of the plurality of sequences of the second detection region (p 694, “LAMP establishment” heading, where the amplification reagents and the process are described).
With regard to claim 18, Fang teaches the kit of claim 17, wherein the universal primer set is suitable for PCR,
wherein a combination of the first primer and the second primer is a combination of a forward primer and a reverse primer,
wherein the plurality of target nucleic acids are first to m-th target nucleic acids, where m is an integer equal to 2 or greater (Figure 1 and figure legend, where the microchamber “were coated with seasonal H1N1-probes, flu A-probes, and pandemic H1N1-probes, respectively and where the target nucleic acids include the unknown samples and the reference samples, as depicted in Table 1 and Fig 2),
wherein the plurality of target sequences are first to m-th target sequences corresponding respectively to the target nucleic acids, the first sub-target sequences are 11 to lm-th sub- target sequences corresponding respectively to the plurality of target sequences, the second sub-target sequences are 21 to 2m-th sub-target sequences corresponding to respectively the plurality of target sequences (Figure 1 and figure legend, where the microchamber “were coated with seasonal H1N1-probes, flu A-probes, and pandemic H1N1-probes, respectively and where the target nucleic acids include the unknown samples and the reference samples, as depicted in Table 1 and Fig 2),
wherein the sequence of the first amplification region is common among 11 to lm-th sub- chain-elongation nucleic acids, the first amplification region comprises a sequence that binds to the sequence of the first primer (p 694, “LAMP establishment” heading, where the amplification reagents and the process are described), and
wherein the sequence of the second amplification region is common among 21 to 2m-th sub- chain-elongation nucleic acids, and the second amplification region comprises a sequence that binds to the sequence of the second primer (p 694, “LAMP establishment” heading, where the amplification reagents and the process are described).
With regard to claim 19, Fang teaches the kit of claim 17, wherein amplification conditions are reaction conditions of LAMP, the target nucleic acids are first to m-th target nucleic acids, where m is an integer equal to 2 or greater (Figure 1 and figure legend, where the microchamber “were coated with seasonal H1N1-probes, flu A-probes, and pandemic H1N1-probes, respectively and where the target nucleic acids include the unknown samples and the reference samples, as depicted in Table 1 and Fig 2),
the plurality of target sequences are first to m-th target sequences corresponding to each of the plurality of target nucleic acids, the first sub-target sequences are 11 to lm-th sub- target sequences corresponding to each of the plurality of target sequences (Figure 1 and figure legend, where the microchamber “were coated with seasonal H1N1-probes, flu A-probes, and pandemic H1N1-probes, respectively and where the target nucleic acids include the unknown samples and the reference samples, as depicted in Table 1 and Fig 2),
the second sub-target sequences are 21 to 2m-th sub-target sequences corresponding to each of the target sequences, the first amplification region is an F2 binding region, and the first sub-chain- elongation nucleic acid comprises an F1 binding region, the F1 binding region being present between the F2 binding region and a first sub-target binding region,
when the first detection region is comprised in the first sub-chain-elongation nucleic acid, the first detection region is present, on the first sub-chain-elongation nucleic acid, between a base adjacent to the F1 binding region and a region overlapping with the F2 binding region to avoid overlapping with the F1 binding region, and contains a region without overlapping the F2 binding region,
the sequence of the second amplification region is a B2 binding region, and the second sub-chain-elongation nucleic acid comprises a B1 binding region, the B1 binding region being present between the B2 binding region and a second sub-target binding region,
when the second detection region is comprised in the second sub-chain-elongation nucleic acid, the second detection region is present, on the second sub-chain-elongation nucleic acid, in a range on the 3'-terminal side from the 5'-terminal of the B2 binding region from a 5'-terminal side bases at the 5'-terminal of the B1 binding region,
the first primer is an FIP primer comprising an Flc sequence at the 5'-terminal and an F2 sequence at the 3'-terminal,
the second primer is a BIP primer comprising a Bic sequence at the 5'-terminal and a B2 sequence at the 3'-terminal (p 694, “LAMP establishment” heading, where the amplification reagents and the process are described),
the first detection regions are 11 to l m-th detection regions corresponding respectively to the target sequences, the second detection regions are 21 to 2m-th detection regions corresponding respectively to the target sequences, and the probes are 11 to l m-th probes and/or 21 to 2m-th probes corresponding respectively to the first detection region and/or the second detection region (p 694, “LAMP establishment” heading, where the amplification reagents and the process are described).
With regard to claim 20, Fang teaches a kit of claim 17, wherein the reagent:
(1) is a first reagent associated with a first series and the plurality of target sequences for the first reagent is a target nucleic acid group associated with the first series and the kit further comprises:
(3) at least one of second to n-th reagents associated with second to n-th series respectively provided in combination with the first reagent in the above (1),
wherein each of the second to n-th reagents is associated with each of the second to n-th series and is a reagent that elongates each of the plurality of target nucleic acids comprising the plurality of target sequences mutually different in the series respectively,
forms the plurality of long-chain nucleic acids, and obtains amplification products of the long-chain nucleic acids;
and/or (4) the probe immobilized substrate provided in combination with at least one of the above
(1) and/or the second to n-th reagents in the above (3), wherein
first to n-th small item sets comprising m1 to mn small items preset for each of the first to n-th series are set respectively, numbers of the small items comprised in the first to n- th small item sets are mi to mn respectively, m to mn are identical to each other or different from each other, a maximum number in the first to n-th small item sets is mmax, m and n are independent of each other and integers equal to 2 or greater, and types the small items comprised in each of the first to n-th series are at least partially between the series,
any x-th series of the first to n-th series is analyzed using a corresponding x-th small item set and a x-th small item set comprises lx-th to mx-th small items and I<mx<mmax applies,
the lx-th to mx-th small items are intended to obtain presence or an amount of presence of each of lx-th to mx-th target nucleic acids having lx-th to mx-th target sequences having different sequences from each other, respectively and the lx-th to mx-th target sequences comprised in the x-th small item set are a target nucleic acid group related to a theme common throughout the x-th series,
and the 1x-th to mx-th target sequences comprise 1ix-th to 1mx-th sub-target sequences at the 5'-terminal and 2ix-th to 2mx-th sub-target sequences at the 3'-terminal respectively (p 694, “LAMP establishment” heading, where the amplification reagents and the process are described).
With regard to claim 22, Fang teaches the combinatorial analysis kit of Claim 17, wherein the kit comprises
at least one of the probe immobilized substrate configured to perform an amplification reaction of a plurality of types of elongated products and detection of amplification products obtained by the amplification reaction in a same reaction field in a same period (Figure 1 and figure legend, where the microchamber “were coated with seasonal H1N1-probes, flu A-probes, and pandemic H1N1-probes, respectively; The fourth microchamber set (4 and 40) loaded with human β actin-probes was applied as a positive control while the chamber 5/50 with no probes patterned worked as the negative control; see also p 691, col. 1 describes “LAMP probe sets using the flow patterning technique”; see also Table S1 and Table S2, where Table S1 provides the gene region of different influenze subtypes and Table S2 provides the LAMP probe sets for each sequence; where it is noted that each probe includes a distinct sequence).
With regard to claim 25, Fang teaches a kit of claim 17 in a form suitable for conducting combinatorial analysis (Abstract, Fig 1, where the teachings of Fang are focused on analysis).
With regard to claim 27, Fang teaches a kit of claim 17, wherein the at least one probe immobilized substrate comprises a DNA chip, a nucleic acid chip, a micro array, or a DNA array (Figure 1 and figure legend, where the microchamber “were coated with seasonal H1N1-probes, flu A-probes, and pandemic H1N1-probes, respectively; The fourth microchamber set (4 and 40) loaded with human β actin-probes was applied as a positive control while the chamber 5/50 with no probes patterned worked as the negative control; see also p 691, col. 1 describes “LAMP probe sets using the flow patterning technique”; see also Table S1 and Table S2, where Table S1 provides the gene region of different influenze subtypes and Table S2 provides the LAMP probe sets for each sequence; where it is noted that each probe includes a distinct sequence).
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.
Claim(s) 26 and 28-29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fang et al. (Anal Chem, 2011, 83:690-695 with supplemental information) as evidenced by Notomi et al. (Nucleic Acids Research, 2000, 28(12):e63, i-vii) as applied over claims 17-20, 22, 25 and 27 above and further in view of Li et al. (Chem Commun 2011, 47:2595-2597).
Regarding claims 26 and 28-29, while Fang teaches a probe immobilized support and includes analysis of short nucleic acids, Fang does not specifically teach loop mediated amplification of miRNA targets.
With regard to claim 26, Li teaches a kit of claim 17, wherein the target nucleic acids of short chain that are 21 to 23 nucleotides in length (Fig 3b, where the microRNA sequences are provided and within the range of 21-22 bp in length).
With regard to claim 28, Li teaches a kit of claim 17, wherein the plurality of target nucleic acids are detected as one series, wherein said series comprises a plurality of miRNAs related by a specific disease (p 2595, col. 1, where the applicability of detection of miRNA for specific disease is discussed; see also Fig 3, figure legend and Fig 3b).
With regard to claim 29, Li teaches a kit of claim 17, wherein the plurality of target nucleic acids are detected as one series, wherein said series comprises a plurality of miRNAs related by a specific health condition (p 2595, col. 1, where the applicability of detection of miRNA for specific health condition is discussed; see also Fig 3, figure legend and Fig 3b).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Fang to include amplification of miRNA targets via loop mediated amplification as guided by Li to arrive at the claimed invention with a reasonable expectation for success. Li teaches “we have demonstrated that the LAMP reaction can be applied to ultrasensitive detection of miRNAs. By using target miRNA to initiate the LAMP reaction, as low as 1.0 amol miRNA can be accurately determined. The determination can be accomplished with one-step operation under isothermal conditions within 90 min (p. 2597, col. 1). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Fang to include amplification of miRNA targets via loop mediated amplification as guided by Li to arrive at the claimed invention with a reasonable expectation for success.
Response to Arguments
Applicant’s arguments with respect to claim(s) 17-20, 22 and 25-29 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claims are allowed. All claims stand rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHANIE KANE MUMMERT whose telephone number is (571)272-8503. The examiner can normally be reached M-F 9:00-5:30.
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/STEPHANIE K MUMMERT/Primary Examiner, Art Unit 1681
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