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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/22/2023 has been considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group II, Claims 14-18 in the reply filed on 11/21/2025 is acknowledged. In response to restriction, Applicant has canceled claims 15-18 and added claims 21-46, which are drawn to Group II. Therefore, Claims 14 and 21-46 are currently examined herein.
Claim Objections
Claims 14, 33, and 37 are objected to because of the following informalities:
Claim 14, please amend “a nanopore disposed in a membrane” to “[[a]] the nanopore disposed in a membrane”.
Claim 33, please amend “in a cis orientation” to “in [[a]] the cis orientation”.
Claim 37, please amend “modified ribonucleic acid (RNA) or native” to “modified ribonucleic acid (RNA), or native”.
appropriate correction is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 14 is rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Roorda (US 2020/0096493 A1, provided in IDS dated 06/22/2023).
Regarding Claim 14, Roorda teaches a method for translocating a polymer through a nanopore (methods of controlling the movement of molecules through a nanopore [abstract]), comprising:
(a) contacting a polymer-magnetic particle conjugate (magnetic bead 620 and DNA 600 [para. 0065]; illustrated in Figure 3) with a system comprising a chip (system illustrated in Fig. 3 comprises a nanopore chip 501 [para. 0064]), wherein:
the polymer of the conjugate (DNA 600 [para. 0065]) comprises a proximal end and a distal end (as illustrated in Fig. 3, DNA 600 has a proximal in on the cis side and a distal end on the trans side);
the proximal end of the polymer is attached to the magnetic particle (DNA 600 is attached to magnetic bead 620 [para. 0065]; as illustrated in Fig. 3, magnetic bead 620 is attached on the proximal end);
the system comprises a magnet (controllable magnet 520 [para. 0066]) disposed in a cis orientation relative to the nanopore (as illustrated in Figure 3, controllable magnet 520 is disposed in a cis orientation relative to nanopore 500]); and
the system comprises a chamber (nanopore well 509 in Figure 16) disposed in a trans orientation relative to the nanopore (as illustrated in Fig. 16, isolated nanopore well 509 is disposed in the trans direction in relation to nanopore 500);
(b) exerting an electrophoretic and/or electroosmotic force on the conjugate (electric potential or voltage bias 530 is provided [para. 0064] that provides a voltage bias and electroosmotic flow [para. 0054]), in a cis to trans direction (as illustrated in Fig. 3, voltage bias is provided in a cis to trans direction to draw the molecule in [para. 0133],), sufficient to dispose a portion of the polymer in the nanopore and a portion of the polymer in the chamber (DNA assembly is partially pulled into the nanopore [para. 0065]); and
(c) after (b), exerting a magnetic force on the conjugate in a trans to cis direction (controllable magnet 520 is used to alter the field strength and move the DNA [paras. 0066-0067]; magnetic field is increased so that the magnetic force is stronger than the electromotive force to sequence the DNA [para. 0137]), and
translocating the polymer of the conjugate in the trans to cis direction by a net force between (i) the electrophoretic and/or electroosmotic force and (ii) the magnetic force (as described above, a bias voltage and magnetic force are both applied [paras. 0054, 0067]; and DNA is translocated using a combination of electromotive force and magnetic force [para. 0137]).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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.
Claims 21-25, 27-28, 37-38, 40-41, and 43-46 are rejected under 35 U.S.C. 103 as being unpatentable over Roorda, as applied to claim 14, in view of Huff (US 2018/0188230 A1).
Claim 21, Roorda teaches the method of claim 14.
Roorda is silent on after (c), (d) iteratively modulating the net force on the conjugate and thereby iteratively translocating the polymer of the conjugate in opposing directions through the nanopore, wherein in an iteration, the polymer of the conjugate translocates through the nanopore in a direction different than the direction in a preceding iteration.
Huff teaches methods and devices for analyte analysis using nanopores (abstract), and teaches iteratively modulating the net force on the conjugate (polarity of electrodes may be reversed on the nanopore [para. 0327]) and thereby iteratively translocating the polymer of the conjugate in opposing directions through the nanopore (tags/aptamers translocate to the other side of the nanopore layer 402 [para. 0327]), wherein in an iteration, the polymer of the conjugate translocates through the nanopore in a direction different than the direction in a preceding iteration (reversing polarity translocates tags/aptamers to a different side, thus a different direction [para. 0327]).
Roorda and Huff are considered analogous art to the claimed invention because they are in the same field of methods to translocate a polymer through a nanopore. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Roorda by providing (d) iteratively modulating the net force on the conjugate and thereby iteratively translocating the polymer of the conjugate in opposing directions through the nanopore, wherein in an iteration, the polymer of the conjugate translocates through the nanopore in a direction different than the direction in a preceding iteration after a portion of the polymer is in the nanopore, as taught by Huff, as reversing the direction allows for multiple readings on the same polymer (Huff, [para. 0328]).
Regarding Claim 22, modified Roorda teaches the method of claim 21.
Roorda teaches wherein the polymer translocates through the nanopore without modifying the magnetic field applied by the magnet (magnetic field can be superimposed onto a scan plate, and as the scan plate is moved away from magnetic field, the magnetic field is not modified [claim 28]).
Regarding Claim 23, modified Roorda teaches the method of claim 21.
Roorda teaches wherein the polymer translocates through the nanopore without altering the position of the magnet (magnetic field can be superimposed onto a scan plate, as the scan plate is moved away from magnetic field, the magnet is not moved [claim 28]).
Regarding Claim 24, modified Roorda teaches the method of claim 21.
Roorda teaches wherein the polymer translocates through the nanopore without the conjugate contacting the magnet (as illustrated in Fig. 3 DNA 600 is attached to magnetic particle 620 [para. 0065], which is separated from controllable magnet 520, so that the DNA 600 does not contact the magnetic particle during translocation; illustrated in Fig. 3).
Regarding Claim 25, modified Roorda teaches the method of claim 21.
Roorda teaches wherein in (c) and (d) the polymer is elongated (DNA is stretched through nanopore [para. 0006]; Fig. 3 also illustrates elongated DNA).
Regarding Claim 27, modified Roorda teaches the method of claim 25.
Roorda teaches a tensile force is exerted on the polymer in (c) and (d) (tensile force is provided via the nanopore bias voltage [para. 0054] and magnetic bead force [para. 0055]), and the tensile force is about 18 to 108 picoNewtons (pN) (as the nanopore bias voltage commonly ranges between 10 to 100 pN [para. 0054], and the magnetic bead can exert a force of approximately 8 pN [para. 0055], the range of tensile force applied is 10+8 pN to 100+8 pN, or 18 to 108 pN).
Regarding Claim 28, modified Roorda teaches the method of claim 27.
Roorda is silent wherein the tensile force is about 2 pN to about 60 pN.
However, Roorda teaches wherein the tensile force is about 18 to 108 picoNewtons (pN) (as the nanopore bias voltage commonly ranges between 10 to 100 pN [para. 0054], and the magnetic bead can exert a force of approximately 8 pN [para. 0055], the range of tensile force applied is 10+8 pN to 100+8 pN, or 18 to 108 pN).
Given the teachings of Roorda regarding a tensile force ranging from 18 to 108 pN, it would have been obvious to have selected and utilized a tensile force within the disclosed range, including those amounts that overlap within the claimed range. It has been held that obviousness exists where the claimed ranges overlap or lie inside ranges disclosed by the prior art. See MPEP 2144.05 (I).
Regarding Claim 37, modified Roorda teaches the method of claim 21.
Roorda teaches wherein the polymer comprises native or modified deoxyribonucleic acid (DNA) or native or modified ribonucleic acid (RNA) (polymer can be a charged molecule that is ssDNA, dsDNA, ssRNA, oligonucleotide, or a sequence comprising a modified nucleotide [claim 17]).
Regarding Claim 38, modified Roorda teaches the method of claim 21.
Roorda teaches wherein the polymer in (a) is single stranded or partially double stranded (polymer can be a charged molecule that is ssDNA, dsDNA [claim 17]).
Regarding Claim 40, modified Roorda teaches the method of claim 21.
Roorda teaches wherein the chip comprises an electrode disposed in a trans potion relative to the nanopore for application of a voltage bias across the nanopore (as illustrated in Fig. 3, a voltage bias is applied across the nanopore using electrical bias source 530 located in the trans position).
Regarding Claim 41, modified Roorda teaches the method of claim 21.
Roorda teaches wherein the nanopore is chosen from a DNA nanopore reader (nanopore system is used to sequence DNA [para. 0137]).
Regarding Claim 43, modified Roorda teaches the method of claim 14.
Roorda is silent on wherein the net force is controlled by modulating the electrophoretic and/or electroosmotic force, or modulating the magnetic force, or modulating the electrophoretic and/or electroosmotic force and the magnetic force.
Huff teaches wherein the net force is controlled by modulating the electrophoretic force (sample droplets in the nanopore device may be moved via programmable fluid manipulation, such as electric-field mediation [para. 0336]).
It would be obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify and net force of the method of modified Roorda by modulating the electrophoretic force, as taught by Huff, as modifying the electrophoretic force allows for controlled movement of liquid sample in the nanopore device (Huff, [para. 0336]).
Regarding Claim 44, modified Roorda teaches the method of claim 21.
Roorda is silent on wherein the net force is controlled by modulating the electrophoretic and/or electroosmotic force, or modulating the magnetic force, or modulating the electrophoretic and/or electroosmotic force and the magnetic force.
Huff teaches wherein the net force is controlled by modulating the electrophoretic force (sample droplets in the nanopore device may be moved via programmable fluid manipulation, such as electric-field mediation [para. 0336]).
It would be obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify and net force of the method of modified Roorda by modulating the electrophoretic force, as taught by Huff, as modifying the electrophoretic force allows for controlled movement of liquid sample in the nanopore device (Huff, [para. 0336]).
Regarding Claim 45, modified Roorda teaches the method of claim 21.
Roorda is silent on wherein the magnetic particle has a diameter of about 200 nm to about 10 micrometers.
However, Roorda teaches wherein the magnetic particle has a diameter from about 100 nanometers to 20 microns [claim 14].
Given the teachings of Roorda regarding the magnetic particle has a diameter from about 100 nanometers to 20 microns, it would have been obvious to have selected and utilized a magnetic particle diameter within the disclosed range, including those amounts that overlap within the claimed range. It has been held that obviousness exists where the claimed ranges overlap or lie inside ranges disclosed by the prior art. See MPEP 2144.05 (I).
Regarding Claim 46, modified Roorda teaches the method of claim 21.
Roorda teaches wherein the system comprises: a permanent magnet (controllable magnet may be a permanent magnet [para. 0067]), a magnet containing a ferromagnetic material (ferromagnetic [claim 16]).
Claims 26, 39, and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Roorda and Huff, as applied to claim 25 above, and in view of Xi (Nanopore-Based Single-Molecule Investigation of DNA Sequences with Potential to Form i-Motif Structures ACS Sensors 2021, 6, 2691-2699). Supporting Information for Xi also provided to clarify DNA lengths used in study for claim 39.
Regarding Claim 26, modified Roorda teaches the method of claim 25.
Roorda is silent on wherein the polymer in (a) contains secondary structure and/or tertiary structure, and the net force on the conjugate in (c) exceeds a force required to disrupt the secondary structure and/or the tertiary structure.
Xi teaches nanopore-based single-molecule investigation of DNA sequences with the potential to form i-motifs (abstract), and teaches wherein the polymer in (a) contains secondary structure (DNA to be sequences is a minimal human telomere i-motif [third para. col. 1, page 2692]), and the net force on the conjugate in (c) exceeds a force required to disrupt the secondary structure (force applied to DNA unfolds the DNA structure as it transports through nanopore [third and fourth paras. col. 2, page 2692; also illustrated in Scheme 1, page 2692]).
Modifed Roorda and Xi are considered analogous art to the claimed invention because they are in the same field of methods to translocate a polymer through a nanopore. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the polymer in (a) of the method of modified Roorda to contain a secondary structure and/or tertiary structure, and the net force on the conjugate in (c) exceeds a force required to disrupt the secondary structure and/or the tertiary structure, as taught by Xi, as sequencing secondary structures including i-motifs facilitates studies in both the human genome and for biosensor development (Xi, [second para. col. 1, page 2692]).
Regarding Claim 39, modified Roorda teaches the method of claim 21.
Roorda is silent on the length of the polymer is about 5 to about 10,000 monomer units.
Xi teaches the length of the polymer is between 40-67 monomers (10 DNA sequences that form i-motifs were used [third para. col. 1, page 2692], which are between 40-67 monomers further listed in Table S1 on page 6 of Xi Supporting Information).
It would be obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the polymer in the method of modified Roorda to be 40-67 monomers, as taught by Xi, as DNA of these lengths are successful in translocating across a nanopore (Xi, [Figure 1]).
Regarding Claim 42, modified Roorda teaches the method of claim 21.
Roorda is silent on wherein the nanopore is chosen from alpha-hemolysin (αHL), mycobacterium smegmatis porin A (MspA), Escherichia coli CsgG, Cytolysin A (ClyA), and outer membrane protein F (OmpF), NetB protein toxin, modified or mutant forms of secretin, and Fragaceatoxin C (FraC).
Xi teaches wherein the nanopore is chosen from alpha-hemolysin (αHL) (nanopore is α-HL [third para. col. 1, page 2692]).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the nanopore in the method of modified Roorda to be alpha-hemolysin, as taught by Xi, as alpha-hemolysin is successful at successfully identifying the characteristics of DNA secondary structure (Xi, [para. 1 col. 1, page 2692]).
Claim 29 and 31-32 are rejected under 35 U.S.C. 103 as being unpatentable over Roorda and Huff, as applied to claim 21 above, and in view of Turner (US 2014/0061048 A1).
Regarding Claim 29 modified Roorda teaches the method of claim 21.
Roorda is silent on wherein: the magnetic particle is, or the membrane is, or the magnetic particle and the membrane are, passivated, and non-specific adsorption of the magnetic particle to the membrane is reduced compared to a system in which the magnetic particle and membrane are not passivated.
Turner teaches an invention relating to nanopore sequencing [abstract], and teaches the membrane is passivated (nanopores may be PEGylated to allow for passivation of pores [para. 0108]).
Modifed Roorda and Turner are considered analogous art to the claimed invention because they are in the same field of methods to translocate a polymer through a nanopore. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify nanopore membrane in the method of modified Roorda to be passivated, as taught by Turner, as passivating the nanopore allows for ease of transportation (Turner, [para. 0108]); the limitation “non-specific adsorption of the magnetic particle to the membrane is reduced compared to a system in which the magnetic particle and membrane are not passivated” is an intended result of a positively recited step. The court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
Regarding Claim 31, modified Roorda teaches the method of claim 29, and teaches wherein the membrane is passivated by a covalently attached passivating agent (as outlined in the claim 29 rejection above, Turner teaches the nanopore membrane is PEGylated [para. 0108]).
Regarding Claim 32, modified Roorda teaches the method of claim 29, and teaches wherein the membrane is passivated with a passivating agent comprising polyethylene glycol (PEG) (as outlined in the claim 29 rejection above, Turner teaches the nanopore membrane is PEGylated [para. 0108]).
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Roorda Huff, and Turner, as applied to claim 29 above, and in view of Eppendorf (NGS library preparation, 2021).
Regarding Claim 30, modified Roorda teaches the method of claim 29, and teaches wherein the membrane is passivated (as outlined in the claim 29 rejection above, Turner teaches the membrane can be passivated with PEG [para. 0108]).
Roorda is silent on wherein the magnetic particle is passivated.
Eppendorf teaches a NGS library preparation (title), and teaches magnetic particle is passivated (magnetic beads are mixed with PEG-solution [first para. page 3]).
Modifed Roorda and Eppendorf are considered analogous art to the claimed invention because they are in the same field of method of sequencing a polymer. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the magnetic particle in the method of modified Roorda to be passivated, as taught by Eppendorf, as passivating the magnetic particle allows for easier handling of DNA (Eppendorf, [last para. page 2 to first para. page 3]).
Claims 33-34 are rejected under 35 U.S.C. 103 as being unpatentable over Roorda and Huff, as applied to claim 21 above, and in view of Ghadiri (Single DNA Rotaxanes of a Transmembrane Pore Protein Angew Chem Int Ed 2004; 43(23), 3063-3067).
Regarding Claim 33, modified Roorda teaches the method of claim 21.
Roorda teaches in part (b) the magnetic particle disposed in a cis orientation relative to the nanopore (as illustrated in Fig. 3, magnetic bead 620 is disposed in a cis orientation relative to nanopore), a portion of the polymer disposed in the nanopore (as illustrated in Fig. 3, a portion of the DNA to be analyzed is disposed in the nanopore).
Roorda is silent on wherein: part (b) comprises forming a rotaxane; the rotaxane comprising the magnetic particle disposed in a cis orientation relative to the nanopore, a portion of the polymer disposed in the nanopore, and a hard stop structure formed at a distal portion or distal terminus of the polymer in the chamber, and a hydrodynamic diameter of the hard stop structure is larger than a constriction region diameter of the nanopore.
Ghadiri teaches a α-hemolysin transmembrane pore with functional DNA-PEG hybrid strands to yield functional rotaxanes (abstract), and teaches forming a rotaxane (threaded ss-DNA-PEG copolymer form a rotaxane [second para. page 2], which is a DNA hairpin as illustrated in Figure 1(b) on page 7), a portion of the polymer disposed in the nanopore (as illustrated in Figure 1(a) and 1(b) on page 7, a portion of the DNA is located in the nanopore), and a hard stop structure formed at a distal portion or distal terminus of the polymer in the chamber (DNA in chamber forms a duplex formation [last para. page 2, illustrated in Figure 1(a) and 1(b) on page 7]), and a hydrodynamic diameter of the hard stop structure is larger than a constriction region diameter of the nanopore (DNA duplex sterically blocks end from entering nanopore [last para. page 2]).
Modifed Roorda and Ghadiri are considered analogous art to the claimed invention because they are in the same field of method of sequencing a polymer. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the DNA polymer in the method of modified Roorda comprises forming a rotaxane; the rotaxane comprising a portion of the polymer disposed in the nanopore, and a hard stop structure formed at a distal portion or distal terminus of the polymer in the chamber, and a hydrodynamic diameter of the hard stop structure is larger than a constriction region diameter of the nanopore, as taught by Ghadiri, as using a rotaxane allows for multiple pass single-molecule DNA sequencing that leads to lower sequencing errors (Ghadiri, [first para., page 4]). Note that the magnetic particle of modified Roorda remains in the cis position relative to the nanopore.
In addition, as the apparatus of modified Roorda already has the magnetic particle disposed in the cis orientation relative to the nanopore, and a portion of the polymer disposed in the nanopore, the rotaxane of modified Roorda after modification with the teaching of Ghadiri results in the claimed limitation of the rotaxane comprising the magnetic particle disposed in a cis orientation relative to the nanopore, a portion of the polymer disposed in the nanopore, and a hard stop structure formed at a distal portion or distal terminus of the polymer in the chamber, and a hydrodynamic diameter of the hard stop structure is larger than a constriction region diameter of the nanopore.
Regarding Claim 34, modified Roorda teaches the method of claim 33, and teaches wherein the hard stop structure is a folded DNA structure (as outlined in the claim 33 rejection above, Ghadiri teaches the rotaxane is formed using a DNA hairpin as illustrated in Figure 1(b) on page 7).
Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Roorda Huff, and Ghadiri, as applied to claim 34 above, and in view of Megalathan (Single-molecule analysis of i-motif within self-assembled DNA duplexes and nanocircles Nucleic Acids Research 2019; 47(14), 7199-7212).
Regarding Claim 35, modified Roorda teaches the method of claim 34.
Roorda is silent on wherein the folded DNA structure is chosen from an i-motif and a G-quadruplex.
Megalathan teaches single-molecule analysis of i-motif within a nanopore (abstract), and teaches wherein the folded DNA structure is chosen from an i-motif (DNA nanoassemblies were made with the hTel i-motif [caption of Figure 1, page 7201]; as illustrated in Fig. 1C on page 7201, the DNA, when folded as an i-motif, does not translocate through the nanopore).
Modifed Roorda and Megalathan are considered analogous art to the claimed invention because they are in the same field of method of sequencing a polymer. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the hard stop structure in the method of modified Roorda by selecting the folded DNA structure is chosen from an i-motif, as taught by Megalathan, as using an i-motif DNA structure has been shown to prevent DNA translocation through the nanopore (Megalathan, [Figure 1C caption, page 7201]).
Claim 36 is rejected under 35 U.S.C. 103 as being unpatentable over Roorda and Huff, as applied to claim 21 above, and in view of Schmidt (Membrane platforms for biological nanopore sensing and sequencing Current Opinion in Biotechnology, 2016; 39, pages 17-27).
Regarding Claim 36, modified Roorda teaches the method of claim 21.
Roorda is silent on wherein the membrane is a crosslinked membrane.
Schmidt teaches membrane platforms for biological nanopore sensing and sequencing (abstract), and teaches the membrane is a crosslinked membrane (polymerizable lipids can include photoactivated crosslinking [second para. col. 1, page 23]).
Modifed Roorda and Schmidt are considered analogous art to the claimed invention because they are in the same field of method of sequencing a polymer. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the membrane in the method of modified Roorda by crosslinking the membrane, as taught by Schmidt, as crosslinking the membrane can improve lifetime, mechanical stability, and voltage tolerance of the membrane (Schmidt, [second para. col. 1, page 23]).
Conclusion
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/R.L.G./Examiner, Art Unit 1795
/SHIZHI QIAN/Examiner, Art Unit 1795