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 September 08, 2026 is acknowledged.
Status of the Application
2. Claims 1, 3, 6, 8, 10-12, 14-16, 18-19, 22-23, 26-27, 29, 34-35 are pending under examination. Claim 41 is withdrawn from further consideration as being drawn to nonelected group. Claims 2, 4-5, 7, 9, 13, 17, 20-21, 24-25, 28, 30-33, 36-40 are canceled. The Applicant’s arguments have been fully considered and found persuasive in-part for the following reasons.
Objection to the Specification-Withdrawn
3. The objection to the specification has been withdrawn in view of the amendment and persuasive arguments.
Objection to informalities-Withdrawn
4. The objection to the informalities has been withdrawn in view of the amendment.
Claim Rejections - 35 USC § 103-Maintained
5. 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, 3, 6, 8, 10-12, 14-16, 18-19, 22-23, 26-27, 29 and 34-35 are rejected under 35 U.S.C. 103 as being unpatentable over Vigneault et al. (US 2016/0032282) in view of Davis (WO 2018/069484).
Vigneault et al. teach a method of claim 1, for quantifying a first species of RNA within a sample, the method comprising: a) receiving a sample comprising RNA and substantially devoid of DNA polymers (para 0874);
b) contacting said sample with a first primer that hybridizes to said first species of RNA under conditions sufficient for reverse transcription (RT) of said first species of RNA to cDNA, thereby producing a first cDNA strand complementary to at least a portion of said species of RNA and comprising said first primer (para 0881, 0874);
c) treating said sample with an RNAse enzyme thereby producing a sample comprising said first cDNA strand and substantially devoid of RNA polymers (para 0881, 0874);
d) contacting said sample with a second primer that hybridizes to said first cDNA strand and performing 1-5 cycles of amplification to produce amplification products with a first termini that is identical to a sequence of said first primer and a second termini that is a reverse complement to a sequence of said second primer or with a first termini that is a reverse complement of a sequence of said first primer and a second termini that is identical to a sequence of said second primer (para 0881, 0874, 0566);
e) treating said sample with a proteinase enzyme to produce a solution substantially devoid of polypeptides other than said proteinase (para 0882); and f) quantifying a species of RNA within a sample (para 0883-0885).
With reference to claim 3, Vigneault et al. that said receiving comprises receiving a sample of isolated RNA or receiving a cell lysate contacted with a DNAse enzyme (para 0266, 0403, 0753).
With reference to claim 6, Vigneault et al. that (b) comprises contacting said sample with a reverse transcriptase and DNA nucleotides (para 0881, 0874, 0575).
With reference to claim 8, Vigneault et al. that said step (c) a. occurs before said step (d); and said RNAse treatment produces a sample comprising said first cDNA strand and said amplification products are substantially devoid of RNA (para 0881, 0874).
With reference to claim 11-12, Vigneault et al. that said proteinase is proteinase K, wherein said treating with a proteinase is under conditions sufficient for degradation of polypeptides to single amino acids, conditions sufficient for protection of said proteinase from autolysis or both (para 0882).
With reference to claim 14, 23-24, Vigneault et al. that wherein said amplification product is a) at least 20 nucleotides shorter than said first cDNA strand; b) not larger than 10,000 nucleotides (para 0454).
With reference to claim 15, Vigneault et al. that said first primer, said second primer or both are DNA primers, is are specific to said RNA species, are 100% complementary to said RNA species or both a combination thereof (para 0627, 0347, 0566).
With reference to claim 16, Vigneault et al. that the method comprising a single cycle of amplification thereby producing on average a single amplification product for each molecule of said species of RNA (para 0507, 0702).
With reference to claim 18, Vigneault et al. that said amplification does not comprises integrating a detectable moiety into said amplification products, said method is devoid of a washing or isolation step after step (a) or both (para 0874-0885).
With reference to claim 22, Vigneault et al. that further comprising in step (b) contacting said sample with a third primer that hybridizes to a second species of RNA, thereby producing a first cDNA strand complementary to at least a portion of said second species of RNA and comprising said second primer; and further comprising in step (d) contacting said sample with a fourth primer that hybridizes to said first cDNA strand complementary to at least a portion of said second species of RNA to produce
amplification products with a first termini that is identical to a sequence of said third
primer and a second termini that is a reverse complement to a sequence of said fourth
primer or with a first termini that is a reverse complement of a sequence of said third
primer and a second termini that is identical to a sequence of said fourth primer (para
0275, claim 302).
With reference to claims 29, 34-35, Vigneault et al. a method of diagnosing a disease
in a subject in need thereof, performing the method of claim 1, wherein said sample is
from said subject, said first RNA species is an mRNA of a gene associated with said
disease, and detection of said first RNA species in said sample indicates said subject
suffers from said disease (para 0581-0588, 0740-0744). However, Vigneault et al. did not teach nanopore apparatus to quantify amplification product.
Davis teaches a method for quantifying a target polynucleotide using a nanopore
apparatus, wherein the method comprising amplifying a target nucleic acid, passing the
nucleic acid through a nanopore apparatus, applying a potential difference across the
nanopore, measuring a change in current across the nanopore that produces one or
more electrical signals by translocation of the polynucleotide through the pore and
quantifying target polynucleotide (para 0048-0062, 0075, 0080-0092, 0115, 0008).
Davis also teaches providing an oligonucleotide (probe) set, hybridizing to the target
polynucleotide and ligating the oligonucleotides to form ligated products to quantitate
the polynucleotide (para 0048-0062, 0075, 0080-0092, 0115, 0008).
It would have been prima facie obvious to an ordinary person skilled in the art
before the effective filling date of the invention to combine the method of Vigneault et al.
with nanopore method as taught by Davis to improve the method for quantifying target
nucleic acid. 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
improve the sensitivity of the method because Davis explicitly taught use of a nanopore
device to accurately quantitate a polynucleotide, which allows precise and accurate
measurement of the polynucleotides in a sample (para 0075) and such a modification of
the method to derive at the claimed method is considered obvious over the cited prior
art.
Response to Arguments:
With reference to the rejection of claims under 35 USC 103 as being obvious over Vigneault et al. in view of Davis et al., the Applicant’s arguments have been fully considered and found unpersuasive. With reference to the Applicant’s arguments drawn to no teaching of substantially devoid of RNA polymers, the arguments have been found unpersuasive because substantially devoid of RNA polymers does not indicate a sample completely devoid of RNA. Further, as required by the claim 1, Vigneault et al. teach treating the sample with RNase enzyme which removes RNA from the sample and said activity of RNase enzyme is inherent property of said enzyme. In addition, as discussed in the rejection Vigneault et al. teach use of RNase inhibitor, which inherently removes nucleic acid polymers, including RNA polymers. As discussed above, the claims do not require complete removal of RNA polymers with said treatment of the sample, instead claims as presented only require substantial removal of RNA polymers. With reference to the Applicant’s arguments drawn to Davis and nonobviousness of the claims, the arguments have been found unpersuasive. As discussed above, Vigneault et al. teach substantially devoid of RNA polymers and as discussed in the rejection it would be obvious to modify the method as taught by Vigneault et al. with a nanopore quantitation as taught by Davis. With reference to the Applicant’s arguments and amendment drawn to claim 18, the arguments and the amendment have been found unpersuasive because Vigneault et al. teach no washing or isolation step which is within the scope of claim 18. For all the above the rejection has been maintained and restated.
Claim Rejections - 35 USC § 101-Maintained
6. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 29, 34-35 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims 29, 34-35 in combination with claim 1 recite a method of diagnosing a disease in a subject, a process, statutory category. Claims 29, 34-35 in combination with claim 1 recite a judicial exception (law of nature, natural phenomenon) because claims recite a correlation of RNA species with a disease in a subject, which is a law of nature or natural phenomenon that exists in nature. Claims 29, 34-35 in combination with claim 1 do not include any additional elements that are sufficient to amount to significantly more than the judicial exception because the additional steps (amplifying, quantitating) which do not add significantly more to the claimed method. The additional steps are not themselves natural laws, but neither are they sufficient to transform the nature of the claims because they consist of well-understood, routine, conventional activity already
engaged in by the scientific community. The additional steps consist of well-understood, routine, conventional activity already engaged in by the scientific community (Vigneault et al. (US 2016/0032282); Davis (WO 2018/069484); Gliddon et al. Immunology, Vol. 153(2), page 171-178, (2018); Squires et al. Scientific Reports, Vol. 5, 11643, page 1-11, (2015)). The additional steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately. The Court has made clear that to transform an unpatentable law of nature into a patent-eligible application of such a law, one must do more than simply state the law of nature while adding the words "apply it." Essentially, appending conventional steps specified at a high level of generality, to laws of nature, natural phenomena, and abstract ideas cannot make those laws, phenomena, and ideas patent-eligible. This judicial exception is not integrated into a practical application because the judicial exception is not markedly different from the natural phenomenon because the claims recite the abstract idea of determining by a computer processing. It is noted that a judicial exception itself, such as an abstract idea, cannot be considered to meet the criteria of "significantly more" than a judicial exception. The
Courts decision rested upon an examination of the particular claims in light of the Court's precedents, specifically Bilski, Flook and Diehr. The Court repeated the longstanding exceptions (laws of nature, natural phenomena, and abstract ideas) to categories of patent eligibility defined in 35 U.S.C. § 101. In conducting the analysis, the Court addressed the "machine-or-transformation" test explained in Bilski with a reminder that the test is an "important and useful clue" to patentability but that it does
not trump the "law of nature" exclusion. A claim that recites a law of nature or natural correlation, with additional steps that involve well-understood, routine, conventional activity previously engaged in by researchers in the field is not patent-eligible, regardless of whether the steps result in a transformation. On the other hand, reaching back to Neilson, the Court pointed to an eligible process that included not only a law of nature (hot air promotes ignition) but also several unconventional steps involving a blast
furnace) that confined the claims to a particular, useful application of the principle. For all the above, the claims are rejected under 35 USC 101.
Response to Arguments:
With reference to the rejection of claims 1, 29, 34-35 under 35 USC 101, the Applicant’s arguments have been fully considered and found unpersuasive. The claims 29, 34-35 recite a correlation of target RNA with a disease in a subject, said correlation is considered a judicial exception, nature phenomenon, that exists in nature. For all the above the rejection has been maintained and restated.
Conclusion
No claims are allowed.
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 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 SURYAPRABHA CHUNDURU whose telephone number is (571)272-0783. The examiner can normally be reached 8.00am-4.30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681
