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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-15) in the reply filed on 04/07/2026 is acknowledged.
Notice to Comply with Requirements for Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosure.
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a) (1) and (a) (2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 regarding instant application containing nucleotide Sequence disclosures.
Specifically, the application fails to comply with CFR 1.821(c)-(f), which states:
(c) Patent applications which contain disclosures of nucleotide and/or amino acid sequences must contain, as a separate part of the disclosure, a paper or compact disc copy (see § 1.52(e)) disclosing the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of §§ 1.822 and 1.823. This paper or compact disc copy is referred to elsewhere in this subpart as the "Sequence Listing." Each sequence disclosed must appear separately in the "Sequence Listing." Each sequence set forth in the "Sequence Listing" must be assigned a separate sequence identifier. The sequence identifiers must begin with 1 and increase sequentially by integers. If no sequence is present for a sequence identifier, the code "000" must be used in place of the sequence. The response for the numeric identifier <160> must include the total number of SEQ ID NOs, whether followed by a sequence or by the code "000."
d) Where the description or claims of a patent application discuss a sequence that is set forth in the "Sequence Listing" in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by "SEQ ID NO:" in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application.
(e) A copy of the "Sequence Listing" referred to in paragraph (c) of this section must also be submitted in computer readable form (CRF) in accordance with the requirements of § 1.824. The computer readable form must be a copy of the "Sequence Listing" and may not be retained as a part of the patent application file. If the computer readable form of a new application is to be identical with the computer readable form of another application of the applicant on file in the Office, reference may be made to the other application and computer readable form in lieu of filing a duplicate computer readable form in the new application if the computer readable form in the other application was compliant with all of the requirements of this subpart. The new application must be accompanied by a letter making such reference to the other application and computer readable form, both of which shall be completely identified. In the new application, applicant must also request the use of the compliant computer readable "Sequence Listing" that is already on file for the other application and must state that the paper or compact disc copy of the "Sequence Listing" in the new application is identical to the computer readable copy filed for the other application.
(f) In addition to the paper or compact disc copy required by paragraph (c) of this section and the computer readable form required by paragraph (e) of this section, a statement that the "Sequence Listing" content of the paper or compact disc copy and the computer readable copy are the same must be submitted with the computer readable form, e.g., a statement that "the sequence listing information recorded in computer readable form is identical to the written (on paper or compact disc) sequence listing."
The instant specification discloses nucleic acid sequences in pages 45-46 which are not identified by "SEQ ID NOS" to comply with CFR 1.821(c)-(f).
For compliance with sequence rules, it is necessary to include the sequence in the "Sequence Listing" and identify them with SEQ ID NOS for both nucleic acid sequences and amino acids sequences of more than three amino acids. In general, any nucleotide sequence that is disclosed that otherwise meets the criteria of CFR 1.821(a), must be set forth in the "Sequence Listing" (See MPEP 2422.03 for further guidance). The nucleic acid sequences present in pages 45-46 need to be identified by SEQ ID NOS.
While the Examiner has made every attempt to check the instant specification for sequence compliance, Applicant is required to carefully check the entire specification for any and all issues regarding sequence compliance.
For the response to this office action to be complete, Applicant is required to comply with the requirements for patent Applications containing nucleotide sequence disclosures. Failure to comply with the requirements will be considered nonresponsive.
Specification -Objected
The disclosure is objected to because of the following informalities:
The specification is objected because as discussed above in section 5, the specification is not in compliance with the nucleic acid sequences present in the instant specification. Applicant is suggested to amend the specification to identify nucleic acid sequences with their SEQ ID NOS.
Appropriate corrections are required.
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) 1-15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Clark et al. US 20190352709.
With regards to claim 1, Clark et al. discloses a method of characterizing a polynucleotide. The polynucleotide may comprise DNA or RNA (this is viewed to be inclusive of claim 2). The method comprising:
(i) combining in a solution: (a) a construct comprising a double-stranded polynucleotide, having a template strand and a complement strand (this is viewed to be inclusive of claim 3), wherein the template strand and the complement strand are not covalently linked, with (b) a nanopore, wherein one or more tags that bind to a portion of the construct is conjugated to the nanopore, wherein the construct and the nanopore are combined under conditions in which the construct binds to the nanopore;
(ii) providing a condition so as to permit the template strand of the construct to enter the nanopore, so as to permit separation of the template strand and translocation of at least a portion of the template strand through the nanopore;
(iii) measuring a change in a property indicative of translocation of the template strand through the nanopore; and
(iv) characterizing the polynucleotide based on the measured change in the property as the template strand translocates through the nanopore [0022-0030].
Clark et al. discloses the concentration of the tether is at least 100nm ([0415] A priming buffer was flowed through the nanopore system. To prepare a sequencing mix, 400 nM Tether (SEQ ID NO: 9), the recovered bead purified Library and library loading beads were mixed in a buffer following the manufacturer's instructions. The sequencing mix was then added to the nanopore system. The experiment was run at −180 mV and helicase-controlled DNA movement monitored) (this is viewed to be inclusive of claim 1, step (i) and claim 13).
Clark et al. discloses “In some embodiments, an adaptor is attached to one or both of the two ends of the double-stranded polynucleotide, each adaptor comprising a duplex stem and a first single strand extending from the duplex stem, wherein the first single strand of one adaptor is contiguous with the template strand and the first single strand of the other adaptor is contiguous with the complement strand” [0031] ; “The nanopores for use in the methods described herein are modified to comprise one or more binding sites for binding to one or more analytes. In some embodiments, the nanopores may be modified to comprise one or more binding sites for binding to an adaptor attached to the analytes. For example, in some embodiments, the nanopores may bind to a leader sequence of the adaptor attached to the analytes. In some embodiments, the nanopores may bind to a single stranded sequence in the adaptor attached to the analytes. In some embodiments, the nanopores may bind to a capture sequence within a duplex stem of the adaptor attached to the analytes, wherein the capture sequence is revealed only upon unwinding of the duplex stem [0175] ; (this is viewed to be inclusive of claim 1, step (ii)). ([0048]; [0101] FIG. 32A-B and Fig 34A-B show embodiments of Y adapter designs [0101-0103]).
Clark et al. discloses “In some embodiments, step (ii) comprises: applying a potential difference across the membrane so as to permit the first single strand contiguous with the template strand of the construct to enter the nanopore, maintaining the potential difference across the nanopore for a sufficient period of time so as to permit separation of the template strand and translocation of at least a portion of the template strand through the nanopore [0032] (this is viewed to be inclusive of claim 1, step (iii)).
With regards to claim 4, Clark et al. discloses “In some embodiments, an adaptor is attached to one or both of the two ends of the double-stranded polynucleotide, each adaptor comprising a duplex stem and a first single strand extending from the duplex stem, wherein the first single strand of one adaptor is contiguous with the template strand and the first single strand of the other adaptor is contiguous with the complement strand” [0031]; In some embodiments, a double stranded polynucleotide can have an adaptor to its 3′ end or 5′ end [0137] (see also Fig. 3B).
With regards to claims 5-8, Clark et al. discloses “The leader sequence typically comprises a polymer. The polymer is preferably negatively charged. The polymer is preferably a polynucleotide, such as DNA or RNA, a modified polynucleotide (such as a basic DNA), PNA, LNA, polyethylene glycol (PEG) or a polypeptide. The leader preferably comprises a polynucleotide and more preferably comprises a single stranded polynucleotide. The single stranded leader sequence most preferably comprises a single strand of DNA, such as a poly dT section. The leader sequence preferably comprises the one or more spacers” (see [0185]; e.g., sp18s [0422]; [0432]).
With regards to claim 9, Clark et al. discloses “The nucleotides in the adaptor are preferably selected from AMP, TMP, GMP, UMP, dAMP, dTMP, dGMP or dCMP. The nucleotides may be abasic (i.e., lack a nucleobase). The nucleotides may contain additional modifications. In particular, suitable modified nucleotides include, but are not limited to, 2′amino pyrimidines (such as 2′-amino cytidine and 2′-amino uridine), 2′-hyrdroxyl purines (such as, 2′-fluoro pyrimidines (such as 2′-fluorocytidine and 2′fluoro uridine), hydroxyl pyrimidines (such as 5′-a-P-borano uridine), 2′-O-methyl nucleotides (such as 2′-O-methyl adenosine, 2′-O-methyl guanosine, 2′-O-methyl cytidine and 2′-O-methyl uridine), 4′-thio pyrimidines (such as 4′-thio uridine and 4′-thio cytidine) and nucleotides have modifications of the nucleobase (such as 5-pentynyl-2′-deoxy uridine, 5-(3-aminopropyl)-uridine and 1,6-diaminohexyl-N-5-carbamoylmethyl uridine)” [0239].
With regards to claim 10, Clark et al. discloses FIG. 27A shows a SYPRO Ruby Protein Gel showing monomers and oligomeric nanopores of CsgG modified with or without morpholino pore tags. FIG. 27B shows a schematic representation of a nanopore modified with a pyridyl-dithio morpholino [0096].
With regards to claim 11, Clark et al. discloses “For example, one or more tags or tethers can be attached to the nanopore via one or more cysteines (cysteine linkage), one or more primary amines such as lysines, one or more non-natural amino acids, one or more histidines (His tags), one or more biotin or streptavidin, one or more antibody-based tags, one or more enzyme modification of an epitope (including, e.g., acetyl transferase), and any combinations thereof” [0189].
With regards to claim 12, Clark et al. discloses “If the membrane is an amphiphilic layer, such as a triblock copolymer membrane, the one or more anchors preferably comprise a polypeptide anchor and/or a hydrophobic anchor that can be inserted into the membrane. The hydrophobic anchor is preferably a lipid, fatty acid, sterol, carbon nanotube, polypeptide, protein or amino acid, for example cholesterol, palmitate or tocopherol” [0247].
With regards to claim 14, Clark et al. discloses “In some embodiments of various aspects described herein, the method can further comprise measuring a change in a property indicative of translocation of the complement strand through the nanopore. The property may be ionic current flow through the nanopore as the complement strand translocates through the nanopore. In some embodiments, the method can further comprise characterizing the polynucleotide based further on the change in a measured property indicative of translocation of the complement strand through the nanopore. In some embodiments, data indicative of the measured properties indicative of translocation of both the complement and template strands through the nanopore can be obtained and used to characterize the polynucleotide. The template strand data may be compared or combined with the complement strand data to characterize the polynucleotide” [0043].
With regards to claim 15, Clark et al. discloses ”Accordingly, one aspect of the present invention provides a method of sequencing a target polynucleotide, comprising: (a) contacting a transmembrane pore with: (i) a double stranded polynucleotide comprising the target polynucleotide and a polynucleotide complementary to the target polynucleotide, wherein the target polynucleotide and the polynucleotide complementary to the target polynucleotide each comprise a single stranded leader sequence; and (ii) a polynucleotide binding protein capable of separating the strands of a double stranded polynucleotide and controlling the movement of a polynucleotide through a transmembrane pore; (b) detecting a signal corresponding to ion flow through the pore to detect polynucleotides translocating through the pore; (c) identifying a signal corresponding to translocation of the target polynucleotide and a sequential signal corresponding to the separate translocation of the polynucleotide complementary to the target polynucleotide; (d) analyzing the signals identified in (c), thereby sequencing the target polynucleotide. [0009]-[0016]
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEZIA RILEY whose telephone number is (571)272-0786. The examiner can normally be reached 7:30-6:00pm.
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/JEZIA RILEY/Primary Examiner, Art Unit 1681 4 June 2026
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