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
Application status
In response to the previous Office action, a non-final rejection (mailed on 11/25/2025), Applicants filed a response and amendment received on 05/12/2026. Said amendment canceled Claims 9-10, 28-61 and 67, and amended Claims 1, 65-66 and 68. Thus, Claims 1-8, 11-27, 62-66 and 68 are at issue and present for examination.
Claim Rejections - 35 U.S.C. § 103 - MAINTAINED
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 previous rejection of Claim 1-8, 11-27, 62-66 and 68 under 35 U.S.C. 103 as being unpatentable over Vries et al. (A Sensitive Assay for Virus Discovery in Respiratory Clinical Samples, Plos One, January 2011, Volume 6, Issue 1, e16118, pages 1-9) in view of Shum et al. (WO2018/144240, publication date 08/09/2018, see IDS), Krjutskov et al. (Globin mRNA reduction for whole-blood transcriptome sequencing, Sci Rep, 2016 Aug 12:6:31584), QIAGEN OneStep RT-PCR handbook (retrieved from the internet: << https://www.qiagen.com/be/resources/download.aspx?id=57743726-84e1-423a-9d8f-a3fa89bbe7eb&lang=en>>, retrieved on 09/11/2024, which was published on October 2012), Becker et al. (US Patent No. 7713697) and Chim et al. (US Patent No. 10683557), is maintained. The Examiner notes that the previous rejection has been modified as it was necessitated by Applicants’ new amendment to claims.
The instant claims are drawn to a method for inhibiting cDNA synthesis of one or more unwanted RNA species in an RNA sample during reverse transcription, comprising: (a) providing an RNA sample that comprises one or more desired RNA species and one or more unwanted RNA species, (b) annealing one or more blocking oligonucleotides to one or more regions of the one or more unwanted RNA species in the RNA sample to generate a template mixture, wherein the one or more blocking oligonucleotides are complementary, and stably bind, to the one or more regions of the one or more unwanted RNA species, and comprise 3' modifications that prevent the one or more blocking oligonucleotides from being extended, wherein the number of the one or more blocking oligonucleotides is at least 10, and wherein 10 or more of the blocking oligonucleotides anneal to different regions of one of the one or more unwanted RNA species, and (c) incubating the template mixture with a reaction mixture that comprises: (i) at least one reverse transcriptase,(ii) one or more reverse transcription primers and (iii) a reaction buffer, under conditions sufficient to synthesize cDNA molecules using the one or more desired RNA species as template(s), wherein cDNA synthesis using the one or more unwanted RNA species is inhibited.
Vries et al. teach a method for inhibiting cDNA synthesis of one or more unwanted RNA species in an RNA sample during reverse transcription, comprising: (a) providing an RNA sample that comprises one or more desired RNA species and one or more unwanted RNA species, (b) annealing one or more blocking oligonucleotides (BO) to one or more regions of the one or more unwanted RNA species in the RNA sample to generate a template mixture, wherein the one or more blocking oligonucleotides are complementary, and stably bind, to the one or more regions of the one or more unwanted RNA species, and comprise 3' modifications that prevent the one or more blocking oligonucleotides from being extended, wherein the number of the blocking oligonucleotides is 5, and wherein two or more of the blocking oligonucleotides anneal to different regions of at least one of the one or more unwanted RNA species, and (c) incubating the template mixture with a reaction mixture that comprises: (i) at least one reverse transcriptase, (ii) one or more reverse transcription primers and (iii) a reaction buffer, under conditions sufficient to synthesize cDNA molecules using the one or more desired RNA species as template(s), wherein cDNA synthesis using the one or more unwanted RNA species is inhibited (see section under “3) rRNA-blocking oligos in the reverse transcription reaction” on page 3, and VIDISCA on page 7).
Vries et al. specifically teach said method comprising the use of 10 µM rRNA-blocking oligonucleotides comprising 18S rRNA and 28S rRNA, which contained a 3’ dideoxy C6 amino modification as an LNA, which were:
(1) 1-Morrna 59 CTTTCGCTCTGGTCCGT 39 –C6 [18S, nt. 977–1071];
(2) 2-Morrna 59 CACTAATTAGATGACGAGG 39–C6 [28S, nt. 3767–3785];
(3) 3-Morrna 59 TGACATTCAGAGCACTGG 39–C6 [28S, nt. 3679–3696];
(4) 4-Morrna 59 GTTACTGAGGGAATCCTG 39 –C6 [28S, nt. 72–89]; and
(5) 5-Morrna 59 CACCAGTTCTAAGTCGG 39–C6 [28S, nt. 3580–3596],
wherein the distance between two neighboring regions is between 0-100, i.e., 3679 (3) – 3596 (5) = 83 nucleotides, thereby reading on claims 1-6, 8, 12-16, 21-22, 24-27 and 62-68 (see section under “3) rRNA-blocking oligos in the reverse transcription reaction” on page 3; and under VIDISCA on page 7).
Since the Office does not have the facilities for examining and comparing the number/amount of blocking oligonucleotides used by applicants', i.e., 10 or more, or about 0.1 to 50 pmol per blocking oligonucleotide, with that of Vries et al., i.e., 10 µM rRNA-blocking oligonucleotides, the burden is on the applicant to show a novel or unobvious difference between the claimed amount and the number/amount used in the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Vries et al. do not teach [1] the use of 10 or more BO, [2] the use of specific temperatures, i.e., at least 65, 70, or 75 degrees Celsius, subsequently reducing the temperature to lower than 40 degrees Celsius (claims 7 and 20); [3] the different regions are evenly distributed (claim 11); [4] the use of salt of KCl and its concentrations (claims 17-18); and [4] the RNA sample is from whole blood, serum or plasma.
Shum et al. teach a method of selective amplification, comprising: providing a sample comprising a plurality of nucleic acid target molecules and one or more undesirable nucleic acid species; providing a plurality of oligonucleotide probes, wherein each of the plurality of oligonucleotide probes comprises a molecular label sequence and a binding region; contacting the plurality of oligonucleotide probes with the plurality of nucleic acid target molecules for hybridization; extending oligonucleotide probes that are hybridized to the plurality of nucleic acid target molecules to generate a plurality of extension products using a reverse transcriptase and/or a polymerase (see claim 72); providing a blocking oligonucleotide that specifically binds to at least one of the one or more undesirable nucleic acid species; and amplifying the plurality of extension products to generate a plurality of amplicons,
whereby the amplification or the extension of the undesirable nucleic acid species is reduced by the blocking oligonucleotide (claim 1),
wherein the blocking oligonucleotide is a locked nucleic acid (LNA), a peptide nucleic acid (PNA), a DNA, an LNA/PNA chimera, an LNAIDNA chimera, or a PNA1DNA chimera (see claim 3),
wherein the blocking oligonucleotide is unable to function as a primer for a reverse transcriptase or a polymerase (see claim 10),
wherein the blocking oligonucleotide is 10 nt, 15 nt, 20 nt, 25 nt, 30 nt, 35 nt, 40 nt, 45 nt, 50 nt, 60 nt, 70 nt, 80 nt, 90 nt, 100 nt, 200 nt long or any range thereof including being fully complementary (see para [0053] and claim 16),
wherein the blocking oligonucleotide has a Tm of at least 50°C, 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C (see para [0051] and claim 9),
wherein said method comprising providing blocking oligonucleotides that specifically binds to at least 100 undesirable nucleic acid species in the sample (see claim 6), which meets the newly added limitation of “wherein the number of the one or more blocking oligonucleotides is at least 10” in Applicants’ claim 1, wherein the undesirable nucleic acid species comprises rRNA, mtRNA, genomic DNA, intronic sequence, high abundance sequence, and any combination thereof (see claim 23), wherein the plurality of nucleic acid target molecules comprises mRNA target molecules (see claim 51), wherein the plurality of amplicons comprises a cDNA library thereby constructing a sequencing library (see para [0072]).
Shum et al. teach that the plurality of blocking oligonucleotides can specifically bind to at least 1, at least 2, at least 5, at least 10, at least 100, at least 1,000 or more of the one or more undesirable nucleic acid species, and that in some embodiments, the blocking oligonucleotide can specifically bind to within 10 nt, 20 nt, 30 nt, 40 nt, 50 nt, 100 nt, 200 nt, 300 nt, 400 nt, 500 nt, or 1,000 nt of the 5' end of at least one of the one or more undesirable nucleic acid species…, blocking oligonucleotide can specifically binds to a sequence close to the 3' end of the undesirable nucleic acid species, for example, the blocking oligonucleotide can specifically bind to within 10 nt, 20 nt, 30 nt, 40 nt, 50 nt, l 00 nt, 200 nt, 300 nt, 400 nt, 500 nt, 1,000 nt of the 3' end of at least one of the one or more undesirable nucleic acid species…i.e., blocking oligonucleotide can specifically binds to a sequence in the middle portion of the undesirable nucleic acid species…the blocking oligonucleotide can specifically bind to within 10 nt, 20 nt, 30 nt, 40 nt, 50 nt, 100 nt, 200 nt, 300 nt, 400 nt, 500 nt, 1,000 nt from the middle point of at least one of the one or more undesirable nucleic acid species, which encompasses annealing to at least two or more different regions that are evenly or unevenly distributed regions (see para [0049]-[0056]) , thereby meeting the limitations of Applicants’ claims 11-12.
Shum et al. teach that an "undesirable nucleic acid species'' refers to a nucleic acid species that is present, e.g., in high amount, in a sample, for example the nucleic acid species representing 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20'%, 30%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, or more, or a range between any two of these values of the nucleic acid content in the sample (see para[0047]), and the specifically binding between the blocking oligonucleotide and the undesirable nucleic acid species can reduce the amplification and/or extension of the undesirable nucleic acid species by at least l 0%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, at least 99%, or more (see para [0050]), therefore, it is inherent that about 0.1 pmol to about 50 pmol per blocking oligonucleotide is used, thereby meeting the limitations of Applicants’ claim 19.
Shum et al. further teach that the oligonucleotide probes (i.e., primer) can comprise stochastic barcodes (see para [0088]), which can comprise a non-specific target nucleic acid sequence (i.e., random), which can be a random dimer, trimer, quatramer, pentamer, hexamer, septamer, octamer, nonamer, decamer (see para [0102]), which is also interpreted to encompass a fragmented RNA molecule, thereby meeting the limitations of Applicants’ claims 21 and 22.
Shum et al. also teach that “sample” includes, tissues, organs or organisms, which comprise whole blood, serum or plasma (see para [0033]), thereby meeting the limitations of Applicants’ claim 23.
Shum et al. further teach a method to correct for such a bias in PCR product is Molecular Indexing; however, high expressers such as ribosomal protein mRNAs, mitochondrial mRNAs, or housekeeping genes often dominate the sequencing run with little contribution to the experimental interpretation.
Krjutskov et al. teach a method for inhibiting cDNA synthesis of one or more unwanted globin mRNA (gmRNA hereafter) species in a whole-blood human, mouse, rat RNA samples during reverse transcription, comprising:
(a) providing the whole-blood RNA sample that comprises one or more desired RNA species and one or more unwanted gmRNA species,
(b) annealing 5 to 6 differently designed GlobinLock blocking oligonucleotides (GL hereafter) comprising LNA or ZNA at 3’ ends (see Figure 1a and Figure 2d) with linear GLs comprising up to 30bp (see “GlobinLock design” on page 5) to one or more regions of the one or more unwanted gmRNA species in the whole-blood RNA sample to generate a template mixture, wherein the one or more GLs are complementary, and stably bind, to the one or more regions of the one or more unwanted gmRNA species, and comprise 3' modifications such as LNA or ZNA (see Figure 1) that prevent the one or more blocking oligonucleotides from being extended, and (c) incubating the template mixture with a reaction mixture that comprises: (i) at least one reverse transcriptase, (ii) one or more reverse transcription primers, and (iii) a reaction buffer comprising Tris-HCl (salt) and KCl (see under “GlobinLock efficiency by quantitative PCR (qPCR)” on page 5), under conditions sufficient to synthesize cDNA molecules using the one or more desired RNA species as template(s), wherein cDNA synthesis using the one or more unwanted gmRNA species is inhibited (see sections “Methods”, especially under headings “GlobinLock design”, “GlobinLock efficiency by quantitative PCR (qPCR)”), thereby meeting the limitations of Applicants’ claims 2, 4-6, 8, 15-17, 23 and 27.
Krjutskov et al. teach GL used as a control didn’t have any modified nucleotides, thereby meeting the limitations of Applicants’ claim 3.
Krjutskov et al. further teach that the number of unwanted RNA species is 2, one being alpha globin mRNA and the other being beta globin mRNA (see Figure 2b), thereby meeting the limitations of Applicants’ claim 13.
Krjutskov et al. further teach the salt concentration of 0.05 μl of 1M Trix-HCL in 4 μl reaction volume is 12.5 mM, thereby meeting the limitations of Applicants’ claim 18.
Krjutskov et al. further teach that 5 μM GL was used to 30 ng/μl of human wbRNA sample (see under “GlobinLock effect by RNA-seq” on page 5 which is encompassed by about 50 pmol (italicized for added emphasis), thereby meeting the limitations of Applicants’ claim 19.
Krjutskov et al. teach synthesizing double stranded cDNA from complementary strands of the cDNA molecules, amplifying the double stranded cDNA molecules to construct a sequencing library, and sequencing the one or more desired RNA species using the sequencing library constructed (see under “GlobinLock effect by RNA-seq”, “RNA-seq data analysis” and “GlobinLock design for other species and Sanger re-sequencing” on pages 5-6), thereby meeting the limitations of Applicants’ claims 24-26.
Krjutskov et al. further teach that the RNA sample was incubated with GL for 10 min at 60 degrees Celsius and it was cooled to 42 degrees Celsius for 60 min (see last line on page 5).
QIAGEN OneStep RT-PCR handbook teaches a RT-PCR protocol wherein one performs an annealing step between 50-68 degrees Celsius for 0.5-1 min (see page 13, Table 3 and “Note”).
Becker et al. teach a method of performing RT-PCR using at least two blocking primers that anneal to different regions (see Figures 2-A to 2-D) which reduces the amplification of side products.
Chim et al. teach a method of performing RT-PCR wherein bacterial 16S rRNA is an unwanted species (see column 31, line 49; column 26, line 46)
It would have been obvious to a person of ordinary skill in the art (POSITA) prior to the effective filing date of the claimed invention to practice the RT-PCR methods taught by Vries et al., and [1] use 10 or more BOs while modifying the annealing temperature to 50-68 degrees Celsius for 0.5-1 min then cooling to ~40 degrees Celsius prior to adding a reverse transcriptase as taught by Qiagen, in order allow sufficient time for blocking oligonucleotides to anneal and stabilize; [2] use BOs so that the entire regions of the unwanted rRNAs are evenly covered; [3] the use of salt of KCl and its concentrations during RT-PCR; and [4] obtain the RNA sample is from whole blood, serum or plasma, as taught by Shum et al., and Krjutskov et al. A POSITA would have been motivated to practice such methods [A] in order to gain higher efficiency by using 10 or more blocking oligos to anneal to different parts of unwanted RNA depending on the length of such unwanted RNA, i.e., longer the unwanted RNA, more BOs would be used to cover the longer size as inhibition of longer unwanted RNAs would be more efficient if more blocking RNAs anneal to it; [B] in order to optimize the reduction in cDNA synthesis of unwanted RNA species; [C] optimize the temperature range for maximum annealing of the blocking oligonucleotides prior to reverse transcription reaction so that amplification of the unwanted RNA species is minimized; [D] optimize the reaction buffer for RT-PCR with a salt or KCl for improving catalysis, [E] design BOs in order to cover the entire rRNAs evenly so as to prevent the unwanted RNA species from any and all rRNA; and [F] obtain samples from whole blood of a subject so that one can determine if the subject has been infected with any virus. One would have had a reasonable expectation of success to practice such methods because all of the biochemical reagents and techniques for performing these types of RT-PCR using at least 5 or more BOs were rampantly used prior to the filing of the instant application, as evidenced by Vries et al., Shum et al., Krjutskov et al., QIAGEN OneStep RT-PCR handbook, Becker et al. and Chim et al.. For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Applicants’ Arguments:
First, none of the cited references teaches or suggests the feature of annealing ten or more blocking oligonucleotides to different regions of an unwanted RNA species as recited in claim 1.
Specifically, D6 relates to an assay for virus discovery in respiratory clinical samples. The largest number of blocking oligonucleotides used to block different regions of an unwanted RNA species is 4 (see the section titled "VIDISCA" on page 7). Accordingly, D6 fails to disclose that ten or more blocking oligonucleotides anneal to different regions of an unwanted RNA species.
Regarding D1, although this reference discloses that "[t]he plurality of blocking
oligonucleotides can specifically bind to at least 1, at least 2, at least 5, at least 10, at least 100, at least 1,000 or more of the one or more undesirable nucleic acid species" (see last paragraph on page 18), it fails to disclose that multiple blocking oligonucleotides anneal to different regions of an unwanted RNA species.
Similar to D1, D2 also fails to disclose annealing ten or more blocking oligonucleotides to different regions of an unwanted RNA species.
D3 also fails to teach or suggest annealing ten or more blocking oligonucleotides to different regions of an unwanted RNA species. D3 is cited in the Office Action as teaching "a RT-PCR protocol wherein one performs an annealing step between 50-68 degrees Celsius for 0.5-1 min (see page 13, Table 3 and "Note")" (see last paragraph on page 11 of the Office Action).
D4 fails to teach or suggest annealing ten or more blocking oligonucleotides to different regions of an unwanted RNA species. Applicant respectfully disagrees with the assertion in the Office Action that "Becker et al. teach a method of performing RT-PCR using at least two blocking primers that anneal to different regions (see Figures 2-A to 2-D) which reduces the amplification of side products" (see 1st paragraph on page 12 of the Office Action). Figs. 2A-2D of D4 depict the general methods of Figs. 1A-1D with the further inclusion of an extender oligonucleotide hybridized to an extension product or target sequence 3' to the blocked promoter oligonucleotide (see column 21, line 66 to column 22, line 2 of D4). Figs. lA-1D in turn depict four general methods of the present invention (see column 21, lines 64-65 of D4), which is an autocatalytic amplification method for synthesizing large numbers of RNA copies of an RNA or DNA target sequence (see column 35, lines 35-38 of D4). Thus, in D4, the nucleic acid to which the two primers anneal is a target nucleic acid, not an unwanted RNA species. In addition, the use of the two primers in D4 is not for reducing side-products. For reducing side-products, D4 discloses using promoter oligonucleotides modified to prevent primer extension by a DNA polymerase or using a cap that hybridizes to a region at the 3'-end of a priming oligonucleotide to prevent oligonucleotide dimer formation, instead (see column 46, lines 50-61 of D4). Applicant notes that while the same assertion was made in the previous Office Action dated May 19, 2025 (see 2nd last full paragraph on page 11), no response has been provided in the instant Office Action to the argument same as above made in Applicant's submission of November 12, 2025. Should D4 be relied on in maintaining this rejection in the next Office Action, a response to Applicant's above argument is respectfully requested.
Lastly, D5 fails to teach or suggest annealing ten or more blocking oligonucleotides to different regions of an unwanted RNA species. D5 relates to a method for predicting the risk of an adverse pregnancy or neonatal outcome for a pregnant subject by detecting the elevated level of bacteria from one or more selected bacterial taxa (e.g., genera or species) (see Abstract). This reference is cited as disclosing a method of performing RT-PCR wherein bacterial 16S rRNA is an unwanted species (see 3rd full paragraph on page 11 of the Office Action.
Second, Applicant submits that the methods claimed in the present application is
unexpectedly superior to prior art methods in effectively inhibiting cDNA synthesis of one or more unwanted RNA species in an RNA sample during reverse transcription and improving subsequent analysis. Specifically, as shown in the Declaration submitted on November 12, 2025, a statistically significant increase in Reads Per Kilobase per Million mapped reads (PRKM) value of target nucleic acids was observed when 10 blocking oligonucleotides were used during RT-PCR but not when 5 blocking oligonucleotides were used. Such superior properties have not been taught or suggested by any of the cited references and thus were unexpected.
Examiner’s Explanations:
Applicants’ arguments have been fully considered but are not deemed persuasive for the following reasons. In response to applicant's arguments against the references individually, i.e., each reference fails to teach the use of 10 or more BOs, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Even assuming arguendo that the cited references do not teach annealing of 10 or more of the blocking oligonucleotides (BO) to different regions on the same unwanted RNA species, stemming from the use of 5 BOs as taught by Vries et al., it would have been obvious for a POSITA to increase that number to 10 or more BOs because a POSITA would have been motivated to use more BOs [A] in order to gain higher efficiency by using 10 or more blocking oligos to anneal to different parts of unwanted RNA depending on the length of such unwanted RNA, i.e., longer the unwanted RNA, more BOs would be used to cover the longer size as inhibition of longer unwanted RNAs would be more efficient if more blocking RNAs anneal to it; and [B] simply the use of more BOs falls under ‘routine optimization’ in order to optimize the reduction in cDNA synthesis of unwanted RNA species.
Furthermore, Applicants’ affidavit showing that using 5 BOs versus 10 BOs showed statistically significant increase in reducing unwanted RNA species is moot because the combined teachings of Vries et al., and Shum et al. point to the use of more than 10 BOs, i.e., Vries et al. specifically use 10 μM concentration of the BOs while Shum et al. teach the use of at least 1, at least 2, at least 5, at least 10, at least 100, at least 1,000 or more of the BOs that bind to one or more undesirable nucleic acid species, and therefore, it would have been obvious to a POSITA that increasing the number of BOs would improve the reduction in cDNA synthesis of unwanted RNA species.
See MPEP 2144.05(II)(A) regarding ‘ROUTINE OPTIMIZATION’:
A. Optimization Within Prior Art Conditions or Through Routine Experimentation
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.");
Lastly, Applicants have not pointed out any criticality of using 10 or more BOs.
For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Conclusion
Claims 1-8, 11-27, 62-66 and 68 are rejected for the reasons as stated above. Applicants must respond to the objections/rejections in this Office action to be fully responsive in prosecution.
THIS ACTION IS MADE FINAL. 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 extension fee 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 JAE W LEE whose telephone number is (571)272-9949. The examiner can normally be reached on M-F between 9:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571)272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAE W LEE/
Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656