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 .
Response
Applicant’s response and claims amendment filed on May 18, 2026 are acknowledged.
Claims 1-4 and 19-21 were canceled.
Claims 5-13 were amended.
Claims 5-18 are pending.
Claims 13-18 are considered.
Claims 5-12 are still withdrawn from consideration.
Examiner’s Nots: The following concepts related to the claimed subject matters are explained based on the state of art:
(A) LAMP: Loop‐mediated isothermal amplification (LAMP) is an assay used for amplifies nuclear acid molecules of both DNA. In particular, Loop‐mediated isothermal amplification (LAMP) amplifies DNA with high specificity, efficiency and rapidity under isothermal conditions by using a DNA polymerase with high displacement strand activity and a set of specifically designed primers to amplify targeted DNA strands. LAMP was further developed over the years which involved the combination of this technique with other molecular approaches, such as reverse transcription and multiplex amplification for the detection of infectious diseases caused by micro‐organisms in humans, livestock and plants summarized herein as evidenced by Wong et al. (J. Appl. Microbiol. 2018, Vol. 124 (3)., pp. 626-643. doi: 10.1111/jam.13647):
1) Conventional LAMP, A loop‐mediated isothermal amplification is used for detection of DNA, so it is then called a Conventional LAMP.
2). RT-LAMP. the amplification assay is used for detecting an RNA molecule, so it is called Reverse transcription RT-LAMP.
3).Furthermore, If the LAMP is used simultaneously for detecting multiple target genes . it may produce an enhance the specificity and reliability of a diagnosis This was named multiplex LAMP (mLAMP). It has also been developed as RT‐LAMP in a single tube coupled with mLAMP approach for detection of other viruses such as different serotypes of dengue viruess, which can also is a simplest mLAMP for RNA detection. The sensitivity of this RT‐mLAMP system was 10 RNA copies for all serotypes, and there was no cross‐reactivity with three closely related arboviruses observed.
On the Other hand, LAMP primer sets were specifically designed for each serotype of the dengue virus: DENV‐1, DENV‐2, DENV‐3 and DENV‐4 targeting on the 3′‐noncoding region (NCR). Interestingly, all the primer sets were added together into a single tube of LAMP reaction for detecting a presence of one or more serotypes of dengue viruses within 60 min of a LAMP reaction. The samples used in this reaction was the serum of dengue infected patients and healthy donors. Colorimetric detection was performed by using hydroxynaphthol blue (HNB), in which it allows the naked eye observationof final LAMP products.
4). LFA: A combination of lateral flow assay (LFA) for end‐point detection of LAMP product is called as LFA‐LAMP or IR-LAMP in certain condition when the antibody /antigen immunoaffinity binding/migration involved. Most generally, lateral flow test was established using fluorescein in isothiocyanate (FITC) labelled DNA probes (which will recognize the specific region in the LAMP amplicon) hybridized with biotinylated LAMP amplicons . This complex or complexed sometime would be captured by streptavidin on the biotin, forming another complexes with variety of anti‐FITC antibodies coated on the gold nanoparticles or adsorption pads, each of different LAMP amplification products hybridized with one or more different pathogenic or any antigenic gene products will be identified or captured at different detection zones that are coated with different antibody labeled coulometric zones respectively as evinced by Park et al. (Biosensors and Bioelectronics , 2017, Vol. 91, pp. 334-340). This would give a visible result on the test line.
(2) The lateral flow test, is also known as the lateral flow immunochromatography test (ICT), is designed to detect the presence of a particular target within a complex mixture. Some of them are called IC-LAMP assay others are named as IC-RT-LAMP assay as evidenced by Selvara et al. ( PLOS ONE | https://doi.org/10.1371/journal.pone.0222170 September 5, 2019, pages 1-13).
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 13-15 and 17-18 are still rejected under 35 U.S.C. 102 (a) (1) by June et al. (Analytica Chimica Acta, Volume 853, 1 January 2015, Pages 541-547).
In the response, Applicants traverse the rejection by amendment of claim 13 and further argue that claim 13 is amended with more limitations of using two different antibodies binding to two different hapten tags and the plurality of primers are conjugated at the 5'-end thereof with said two different hapten tags that comprised a forward inner primer (FIP) or a reverse inner primer (BIP), and a loop backward (LB) primer.", which features were not taught by June et al., hence, the rejection should be removed.
Applicants’ argument has been respectfully considered, however, it is not found persuasive to overcome the rejection because June et al. teach all limitations explicitly, implicitly and/or inherently for interpretations summarized below :
1). June et al. is also a combination method using Multiplex RT-LAMP for HA and M genes was developed for subtyping influenza A virus. For instance, they teach that Six primers including outer primers (F3/B3), inner primers (FIP/BIP), and loop primers (LF/LB) for targeting HA genes, and five primers including F3/B3, FIP/BIP, and LF for targeting conserved M gene were designed as shown in Fig. 2,
2). Each of the primers is respectively labeled with different hapten tags including at least digoxigenin, biotin as well as Texas Red to process multiplex RT-LAMP for detecting the RNA molecules of different serotypes of different HA and conserved M genes of influenza viruses, such as H1N1, H3N2, H5N1 etc. The multiplex RT-LAMP amplicons were simply analyzed by the colorimetric ICS detection, such as the Multiplex RT-LAMP (40 min) and ICS detection (15 min) could be complete in 55 min.(See Abstract, Content high lights, and Graphic Abstract and Experimental procedure 2.1 to 2.6, Figs; 1-3). The Figure 2 also indicates that plurality of primers are conjugated at the 5'-end thereof with said two different hapten tags that comprised a forward inner primer (FIP) or a reverse inner primer (BIP), and a loop backward (LB) primer."
3). They also teach at section of 2.2. regarding the Design of the ICS, they also teaches that at least two antibodies to different tags are used in the ICS assays, which include the monoclonal antibody to biotin, monoclonal antibody to digoxigenin and monoclonal antibody to Texas Red.
In particular, the packaged ICS in a polystyrene case and the structure of an ICS are illustrated in Fig. 1. The ICS consists of four parts: a buffer loading pad, a conjugate pad, a detection region with test and control lines, and an absorbent pad. Streptavidin and mouse IgG coated gold nanoparticles (AuNPs) were concentrated in the conjugate pad to capture the biotin labeled RT-LAMP products. In the detection region, two test lines and one control line were patterned. The test line 1 and line 2 were coated with Digoxigenin monoclonal antibodies (Medisensor Inc., Korea), and Texas Red monoclonal antibodies (Medisensor Inc., Korea) respectively, and the control line was immobilized with goat anti-mouse IgG. The Fig. 1 also shows Digital image of the packaged ICS and its structure, wherein the Streptavidin and IgG coated gold nanoparticles are immobilized in the conjugate pad. In the detection region, anti-Digoxigenin, anti-Texas Red and anti-IgG are immobilized on the test line 1, test line 2, and control line, respectively. The Fig ! also shows that Digital image of the packaged ICS and its structure. Streptavidin and IgG coated gold nanoparticles are immobilized in the conjugate pad. In the detection region, anti-Digoxigenin, anti-Texas Red and anti-IgG are immobilized on the test line 1, test line 2, and control line, respectively.
Therefore, the cited reference still teaches all limitations required by the rejected claims explicitly or implicitly or inherently. The rejection is maintained.
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.
Claims 13-18 are still rejected under 35 U.S.C. 103 (a) (1) by DE 202021100985U1. (985U1) and further evidenced by June (Analytica Chimica Acta, Volume 853, 1 January 2015, Pages 541-547). (It is noted that the rejection made by the non-final contained a typographic error, now it is corrected )
In the response, Applicants argue that Responsive to the instant rejection, the above underlined feature in the currently amended claim 13 is neither taught nor suggested in DE202021100985U1, and therefore DE202021100985U1 does not remedy the deficiency of the combination of Jung and He as above mentioned. The above underlined feature is also not arrived at by a reasonable expectation of success based on the teaching of DE202021100985U1. The "unexpected" result, i.e., the two lowest Cq (or the most efficient amplification) by tagging the hapten specifically to the 5'-end of FIP (or BIP) and LB primers provided in the original specification of the present application (see tables 20-21 and paragraphs [0153]-[0157]; FIG. 26). By virtue of the foregoing Remarks and present amendments, claim 13 is non-obvious further in view over Jung et al. or He et al. Hence, it is respectfully submitted that the instant rejection is overcome and should be withdrawn.
Applicants argument has been respectfully considered, however, it is not found persuasive because there is no solid evidence to support the claimed method with same combination method using a multiple RT-LAMP and ICS to produce any unexpected result as Applicants asserted with quick and efficient result.
Because both DE 202021100985U1 and June et al. wall teach the same method as it is claimed comprising the same combination of using Multiplex RT-LAMP and ICS with multiple primers, wherein the primers are conjugated with the same hapten tags and the product of the target RNA amplified with the different tags are immediately load onto a ICS which is immobilized with a monoclonal antibody specifically binding to the hapten tags linked to the amplified target RNA molecules. The time reported by June et al. is less then 1 hour or about 55 minutes, which meet the limitation as applicants asserted as short and/or efficient without any specified short or efficient time neither defined by the claims nor by the disclosed specification. For instant, both June et al. describe The multiplex RT-LAMP amplicons were simply analyzed by the colorimetric ICS detection, such as the Multiplex RT-LAMP (40 min) and ICS detection (15 min) could be complete in 55 min.(See Abstract, Content high lights, and Graphic Abstract and Experimental procedure 2.1 to 2.6, Figs; 1-3). The Figure 2 also indicates that plurality of primers are conjugated at the 5'-end thereof with said two different hapten tags that comprised a forward inner primer (FIP) or a reverse inner primer (BIP), and a loop backward (LB) primer."
Moreover, DE 202021100985U1 teach multiple primers used for detecting Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-Cov2) using RT-LAMP system followed by a suitable ICS, particularly immunochromatographic lateral flow assay (LFA), wherein June et al. teach the multiple primers to do Multiplex RT-LAMP (40 min) in combination with ICS detection.
Still further, regarding the limitation of using either colorimetric assay or a florescent assay, both DE 202021100985U1 and June et al. teach to use either colorimetric assay and/or a florescent assay. Furthermore, both DE 202021100985U1 and June et al. teach to use a florescent dye such as FITC from the family of metallochromic dyes, or just a Texas Red as regular florescent dye, that is not belong to to either metallochromic dye nor halochromic dye. In addition, DE 202021100985U1 teaches using a phenol red as a halochromic dye.
Therefore, the argument is not persuasive to overcome the rejection.
As there are no unexpected results have been provided, the claimed invention as a whole is prima facie obvious absence unexpected results, the rejection is maintained.
Upon further consideration of rejection of Claims 13-18 under 35 U.S.C. 103(a) by June (Analytica Chimica Acta, Volume 853, 1 January 2015, Pages 541-547) further in view of He et al. (Biosene Bioelectron 2012, May 13, 187:113330. doi: 10.1016/j.bios.2021.113330), the rejection has been removed as the argument has been persuasive. No motivation to combine the He et al. with June et al.
The examiner’s notes:
While claims 5-12 are not belong to the group of examination, it is still worth to reminder for following issue:
Regarding the series of singular dependent claims, MPEP 6.18 cites:
A series of singular dependent claims is permissible in which a dependent claim refers to a preceding claim which, in turn, refers to another preceding claim.
A claim which depends from a dependent claim should not be separated by any claim which does not also depend from said dependent claim. It should be kept in mind that a dependent claim may refer to any preceding independent claim. In general, applicant's sequence will not be changed. See MPEP § 608.01(n).
Appropriate correction would be required if a response is going to file.
Conclusion
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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BAO Q. LI
Examiner
Art Unit 1671
/BAO Q LI/Primary Examiner, Art Unit 1671
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