CTFR 17/745,399 CTFR 94755 DETAILED ACTION Applicant’s response, filed 18 May 2026, has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Notice of Pre-AIA or AIA Status 07-03-fti AIA The present application is being examined under the pre-AIA first to invent provisions. 12-151 AIA 26-51 12-51 Status of Claims Claims 1-30 and 35 are canceled. Claim 51 is newly added. Claims 31-34 and 36-51 are pending. Claims 31-34 and 36-51 are rejected. Priority The effective filing date of the claimed invention is 16 Feb. 2012. Drawings The objection to the drawings filed 16 May 2022 in the Office action mailed 19 Nov. 2025 has been withdrawn in view of the replacement drawings received 18 May 2026. The drawings received 18 May 2026 are accepted. 07-30-03-h AIA Claim Interpretation Claims 31 and 46 recite a “translocase”. Applicant’s specification at para. [0055] (as published), defines the term “protein translocase” to mean a protein-binding peptide, such as a polypeptide which is able to control movement of a protein substrate, for example a an enzyme, enzyme complex, or part of an enzyme complex that operates on a protein and moves it relative to the enzyme in a processive manner. Therefore, the term will be interpreted accordingly. Claim 43 recites “wherein the protein comprises an exogenous sequence”, which further limits the source of a sequence to have been “exogenous”, which further limits the sequence of the protein to have been developed from external factors (e.g. by a mutagen). This is interpreted as a product by process limitation defining the process in which the protein was previously generated. See MPEP 2113 I, stating "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.". Claim 46 recites “A device for determining one or more characteristics of a protein, the device comprising:….instructions….cause the device to: monitor ionic current changes during translocation of a protein through the nanopore by the ring-shaped NTP driven unfoldase present on the first side of the fluidic chamber…”. The device of claim 46 is interpreted to merely be programmed and able to monitor ionic current changes across a membrane, but the process in which the ionic current change was generated is not part of the claimed device (i.e. the device does not include an actively translocation protein). For example, Applicant’s specification at pg. 4, lines 11-13 discloses a computer attached to a patch amplifier for rapidly recording changes in ionic current through the nanopore. That is, the method in which the device is intended to be operated (i.e. by monitoring currents generated by translocation of a protein ) is not part of the device. See MPEP 2114 I. "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). Accordingly, any device with a processor that causes the device to monitor ionic current changes across a membrane reads on the claim. Claim 51 also recites “wherein the instructions…cause the device to monitor…during translocation of a protein…”, which is interpreted similarly to claim 46 above. That is, the method in which the device is intended to be operated (i.e. by monitoring currents generated by translocation of a protein from the second to the first side ) is not part of the device. See MPEP 2114 I. "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). Claim Rejections - 35 USC § 112 (pre-AIA), second paragraph The rejection of claims 46-50 under 35 U.S.C. 112 (pre-AIA), second paragraph in the Office action mailed 19 Nov. 2025 has been withdrawn in view of claim amendments received 18 May 2026. 07-30-02 The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. Claim 39 is rejected under 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the applicant regards as the invention. This rejection is newly recited and necessitated by claim amendment. Claim 39 recites “wherein the protein is in a non-denatured states”. Amended claim 31, from which claim 39 depends, recites “adding to the first side…a ring-shape NTP driven unfoldase ; (c) monitoring ionic current changes during translocation of a protein by the ring-shaped NTP driven unfoldase through the nanopore…”. Given claim 31 requires an unfoldase acts on the protein to perform translocation, one of ordinary skill in the art understands the unfoldase unfolds, or denatures , the protein as also discussed in Applicant’s specification (pg. 6, lines 28-30; pg. 14, lines 5-8; pg. 17, lines 15-17). As a result, it is not clear when Applicant intends for the protein to be in a non-denatured state given the claim requires applying an unfoldase to unfold (denature) and translocate the protein. For example, it is not clear if Applicant intends for the protein to be added to the fluid chamber in a non-denatured state, but it is later denatured/unfolded, if Applicant intends for the protein to remain in a non-denatured state even through translocation, or if the protein is in a non-denatured state during some other time. Clarification is requested via claim amendment. Response to Arguments 07-37 AIA Applicant's arguments filed 18 May 2026 regarding 35 U.S.C. 112(pre-AIA), second paragraph have been fully considered but they are not persuasive because they do not pertain to the new grounds of rejection set forth above . Claim Rejections - 35 USC § 112 (pre-AIA), fourth paragraph The following is a quotation of 35 U.S.C. 112(d): 07-36 The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claim 51 is rejected under pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. This rejection is newly recited and necessitated by claim amendment. Claim 51 recites “wherein the instructions…cause the device to monitor ionic current changes during translocation of a protein through the nanopore from the second side…to the first side”. As discussed above in claim interpretation, the limitation “during translocation of a protein through the nanopore from the second side…to the first side…”. That is, the method in which the device is intended to be operated (i.e. by monitoring currents during translocation of a protein from a second to first side ) is not part of the device. See MPEP 2114 I. "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). Claim 46 already requires “a non-transitory computer-readable medium comprising instructions that, when executed by a processor, cause the device to: monitor ionic current changes during translocation of a protein through the nanopore…”. Claim 51 only serves to further specify the manner on which the device is intended to be operated (i.e. during translocation of a protein), which does not further limit the claimed device. Because claim 46 already requires the instructions cause the device to monitor ionic current changes, claim 51 fails to further limit the device of claim 46. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Claim Rejections - 35 USC § 102 The rejection of claims 31-34, 38-43, and 45-50 under pre-AIA 35 U.S.C. 102(a) as being anticipated by Gundlach (2011), as evidenced by Akeson (2007) in the Office action mailed 19 Nov. 2025 has been withdrawn in view of claim amendments received 18 May 2026. Claim Rejections - 35 USC § 103 The rejection of claim 35 under pre-AIA 35 U.S.C. 103(a) a in the Office action mailed 19 Nov. 2025 has been withdrawn in view of the cancellation of this claim received 18 May 2026. The rejection of claims 36-37 and 44 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Gundlach (2011) in view of Kravats (2010) and Howorka (2009) in the Office action mailed 19 Nov. 2025 has been withdrawn in view of claim amendments received 18 May 2026 and further consideration of the claims. 07-06 AIA 15-10-15 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. 07-20-fti The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action: (a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made. 07-20-02-fti This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a). 07-21-fti Claim s 46-51 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Gundlach (2011) in view of Kravats (2010) and Howorka (2009). This rejection is newly recited and necessitated by claim amendment . Cited references: Gundlach et al. WO2011106459 A2; Pub. Date: 01 Sept. 2011 (previously cited); Kravats et al., Unfolding and translocation pathway of substrate protein controlled by structure in repetitive allosteric cycles of the ClpY ATPase, 2011, PNAS , 108(6), pg. 2234-2239; cited in IDS filed 25 Aug. 2022 (previously cited); and Howorka et al., Nanopore analytics: sensing of single molecules, 2009, Chem. Soc. Rev. , 38, pg. 2360-2384 (previously cited). Regarding claim 46 , Gundlach discloses a device for analyte sequencing, including protein sequencing, with nanopores (Abstract; pg. 7, lines 17-26; claims 1-2; Figure 2) comprising the following: Gundlach discloses a nanopore that forms a tunnel upon insertion into a membrane, wherein the nanopore is positioned between a cis side (i.e. a first side) comprising a first liquid medium and a trans side (i.e a second side) comprising a second liquid medium (pg. 1, lines 28-32; pg. 7, lines 17-24). Gundlach discloses (b) adding a “molecular motor”, defined as a molecule or enzyme that physically interacts with an analyte, which includes a protein (pg. 7, lines 17-26) and is capable of physically moving the analyte through an opening of a nanopore in a sequential manner, to the cis side (i.e. the first side) of a membrane (pg. 23, line 23 to pg. 24, lines 11). Therefore, the molecular motor of Gundlach is considered a translocase, consistent with Applicant’s definition of a “protein translocase” discussed above in claim interpretation. Gundlach discloses a patch clamp amplifier, or circuit, providing a voltage between the cis and trans side (pg. 59, lines 13-24; FIG. 2A-C; pg. 5, lines 29-32, e.g. voltage applied) for monitoring ionic current through the nanopore (FIG. 2D, e.g. see monitored current). Gundlach discloses the device is configured to monitor ion current levels across the membrane during translocation of the analyte protein from the cis side to the trans side (i.e. in a direction toward the first side of the fluid chamber) (pg. 59, lines 19-24; FIG. 2D; claims 1-2). Gundlach does discloses the translocation is by a protein translocase capable of physically moving the analyte through an opening of a nanopore in a sequential manner, to the trans side (i.e. the second side) of a membrane (pg. 23, line 23 to pg. 24, lines 11). Gundlach discloses the device analyzes the ionic current levels to sequence two or more units of the analyte protein (i.e. determine characteristics of the protein) (claims 1-2; FIG. 5 and 7, e.g. nanopore perform sequencing). Further regarding the dependent claims: Regarding claims 47-48 , Gundlach discloses the characteristics of the analyte protein include determining the identity of units of a protein to determine the analyte sequence (pg. 6, lines 28-30; pg. 8, lines 4-11), and discloses the sequence of the analyte corresponds to an identify of the analyte (pg. 43, line 19 through pg. 44, line 22). Regarding claim 49 , Gundlach discloses the nanopore is a α-hemolysin pore protein (claim 45; pg. 18, lines 18-21; pg. 42, lines 7-9). Regarding claim 50 , Gundlach discloses the nanopore can be a solid-state pore (pg. 8, lines 17-20; pg. 12, lines 2-4). Regarding claim 51 , Gundlach discloses the device is configured to monitor ion current levels across the membrane during translocation of the analyte protein (pg. 59, lines 19-24; FIG. 2D; claims 1-2). It is noted that the protein is not part of the claimed device, and thus the translocation of the protein to the first side is not considered part of the claimed system, as discussed above in claim interpretation. See MPEP 2114 II, which states "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc. , 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a "recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus" if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987). Gundlach does not disclose the following limitations: Regarding claim 46, while Grundlach discloses a molecular motor (i.e. protein translocase) may be used to physically move the protein analyte through an opening of a nanopore in a sequential manner, to the trans side (i.e. the first side) of a membrane (pg. 23, line 23 to pg. 24, lines 11), and further discloses the methods in which the molecular motor (i.e. protein translocase) may be immobilized on the trans side of the membrane (pg. 24, lines 1-4), Grundlach does not disclose the protein translocase is an AAA+ enzyme of ClpX. However, these limitations were known to one of ordinary skill in the art, as shown by Howorka and Kravats. First, Howorka overviews nanopore analytics involving passing individual molecules such as peptides through a single nanopore to give rise to detectable temporary blockades in ionic pore current (Abstract). Howorka discloses that peptides and proteins larger than the pore lumen must unfold to pass through the narrow opening and unfolded proteins can be obtained using a denaturing agent (pg. 2375, col. 2, para. 4; Table 1). Furthermore, Kravats discloses ClpX is an ATpase motor protein that translocates proteins through nanopores, and includes a domain which stabilizes unfolded conformations of the protein and makes them competent for translocation through narrow pores (Abstract; pg. 2234, col. 2, para. 3). Kravats further discloses loops of the Clpx involve recognizing peptide specific tags fused to target proteins (pg. 2234, col. 1, para. 2). Kravats further discloses this allosteric pore mechanism has been selected for its ability to effect unfolding and translocation without assistance from cofactors or environmental variations such as an electrostatic gradient (pg. 2238, col. 1, para. 1). It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the molecular motor and protein of Gundlach to have utilized the ClpX unfoldase and a protein with a fused peptide tag recognized by ClpX, shown by Kravats, discussed above. One of ordinary skill in the art would have been motivated to combine the methods of Gundlach and Kravats in order to allow for the unfolding and translocation of proteins through narrow nanopores without assistance from cofactors or environmental variations such as electrostatic gradients, as shown by Kravats (pg. 2238, col. 1, para. 1) or without using denaturing agents (see Howorka pg. 2375, col. 2, para. 4) , given Howorka explains that large proteins must be unfolded to be able to pass through narrow openings (pg. 2375, col. 2, para. 4). This modification would have had a reasonable expectation of success given Gundlach provides methods in which molecular motors can be immobilized on the cis side of nanopores to facilitate translocation, as discussed above, such that the motor protein of Kravats is applicable to the method of Gundlach. Therefore, the invention is prima facie obvious . Response to Arguments 07-37 AIA Applicant's arguments filed 18 May 2026 regarding 35 U.S.C. 103 have been fully considered but they are not persuasive with respect to claims 46-51 . Applicant remarks that Gundlach fails to teach or suggest a membrane comprising a nanopore and a protein translocase on the first side of the membrane (Applicant’s remarks at pg. 8, para. 3-6). Applicant remarks that while Gundlach mentions that the analyte may be a “modified peptide” or a “modified protein”, the disclosure therein only mentions molecular motors in the context of nucleic acid analysis, and where Gundlach states the molecular motor may be disposed on the cis side or the trans side of the membrane, the disclosure is in the context of DNA/nucleic acid analysis and not protein analysis (Applicant’s remarks at pg. 8, para. 6). This argument is not persuasive. A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc . 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). Furthermore, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi , 440 F.2d 442, 169 USPQ 423 (CCPA 1971). See MPEP 2123. First it is noted that the “first side” of the membrane in claim 46 can be referring to either the cis or trans side of the membrane, and is not required to be the trans side (i.e. the side toward which the protein is translocated) as in independent claim 31. Gundlach explicitly defines “Molecular motors” to refer to a molecule that physically interacts with an analyte, such as a polymer , and is capable of physically moving the analyte with respect to the opening of a nanopore, and that a molecular motor may be disposed on the cis side or the trans side of a membrane (pg. 23, line 23 to pg. 24, line 11. Gundlach discloses the analyte may be a protein (pg. 13, lines 13-28), as discussed in the above rejection. Therefore, Gundlach does not only mention molecular motors for nucleic acid, but instead broadly discloses molecular motors interact with any analyte, while then providing examples of motors that interact with nucleic acids. However, simply because Gundlach discloses various embodiments that utilize nucleotides as the analyte, this does not teach away from the broader disclosure in which an analyte such as a protein may be moved by a molecular motor that physically interacts with a protein analyte. Applicant remarks Howorka does not teach or suggest adding a ring-shaped NTP driven unfoldase to the first side of a membrane (Applicant’s remarks at pg. 8, para. 8). This argument is not persuasive because Howorka is not relied upon to teach this limitation. Applicant remarks that while Kravats may disclose a ring-shaped NTP driven unfoldase, Kravats does not disclose the instantly claimed step of adding to the first side of the fluidic chamber a ring-shaped NTP drive unfoldase and monitoring ionic current changes during translocation of a protein by the ring-shaped NTP drive unfoldase, and that is because in Kravats, any pore or nanopore is formed by the translocase itself (Applicant’s remarks at pg. 8, para. 9 to pg. 9, para. 1). Applicant remarks that Kravats states that Clp ATPases are ring-shaped AAA+ motors that unfold and translocate substrate proteins through narrow pores, which is achieved by loops in the central channel of the Clp ATPase hexaminer, and further describes this in FIG. 1, and thus in Kravats the translocase is the nanopore, and the nanopore is not separate from the translocase as recited in the claims (Applicant’s remarks at pg. 9, para. 3). This argument is not persuasive. It is acknowledged that the ClpX ATPase contains a pore. However, Kravats does not disclose or suggest the use of ClpX as a nanopore sensor for sequence analysis. Kravats describes the pore of Clp ATPase serves to unfold the protein, and the protein is translocated by ClpY through repetitive allosteric motions of ClpY channel loops (Figure 1; pg. 2234, col. 1, para. 1), and further discloses loops of the ClpX involve recognizing peptide specific tags fused to target proteins (pg. 2234, col. 1, para. 2). These features are contrary to a nanopore typically used for nanopore sensing, as disclosed by Howorka. Howorka discloses that most importantly, nanopores are usually “blank” and lack any intrinsic ability to bind molecules with specificity (pg. 2361, col. 2, para. 4), and further explains advantages of a widely used sensing nanopore, α-hemolysin, including that its robust structure lacks any moving parts , which results in unitary conductance that facilitates the detection of analyte-induced blockages (pg. 2362, col. 1, para. 2-3). While Applicant suggests that the Clp ATPase of Kravats would serve as the nanopore itself, rather than being a translocase separate from the nanopore, one of ordinary skill in the art would not consider the Clp ATPase a candidate sensing nanopore for sequence analysis due to its moving parts and intrinsic ability to bind specific molecules, in view of the teachings of Howorka. Instead, Gundlack clearly teaches the use of a molecular motor that physically interacts with an analyte and moves the analyte with respect to the opening of a nanopore (pg. 23, line 23 to pg. 24, line 11), while Howorka discloses that peptides and proteins larger than the pore lumen must unfold to pass through the narrow opening and unfolded proteins can be obtained using a denaturing agent (pg. 2375, col. 2, para. 4; Table 1). Kravats discloses that Clp ATPases are ring-shaped AAA+ molecular motors that have the ability to effect unfolding and translocating a protein without assistant from cofactors or environmental variations (Abstract; pg. 2238, col. 1, para. 1), thus providing a direct motivation to utilize ClpX as the molecular motor on the cis side in Gundlach in order to facilitate the passing of unfolded proteins through a nanopore without the use of a denaturing agent. Applicant remarks that Gundlach and Howorka are cited for a membrane comprising a nanopore, a protein, and a protein translocase, while in contrast, in Kravats there is no translocase separate from the nanopore to allow monitoring of ionic current changes, let alone to permit determining characteristics of a protein (Applicant’s remarks at pg. 9, para. 4-5). Applicant remarks that therefore, one of ordinary skill in the art would not have been motivated to use the protein translocase of Kravats in the methods of Gundlach and Howorka (Applicant’s remarks at pg. 9, para. 6-8) . 07-37-13 AIA This argument is not persuasive. In response to applicant's arguments against the references individually, 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). Kravats is not relied upon to disclose structure including a membrane comprising a nanopore separate from a protein translocase that allows for monitoring of ionic current changes. Instead, Gundlach is relied upon to teach these limitations as discussed in the above rejection. Kravats is relied upon to disclose a type of motor protein that unfolds proteins, as required for large proteins prior to passing through a sensor nanopore as shown by Howorka, without assistant from cofactors or environmental variations as discussed above. Double Patenting The rejection of claim 35 on the grounds of non-statutory double patenting in the Office action mailed 19 Nov. 2025 has been withdrawn in view of the cancellation of this claim received 18 May 2026. 08-33 AIA The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. Claims 31-34 and 36-51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. US 11,339,365 B2. Any newly recited portion is necessitated by claim amendment. Although the claims at issue are not identical, they are not patentably distinct from each other because: The reference claims disclose a narrower embodiment of the instant claims. Reference claim 1 discloses the limitations of instant claims 31, 46, and 51 . Reference claim 1 discloses the ring-shaped NTP driven unfoldase is added to the fluidic chamber, which includes a cis side and a trans side, such that the ring-shaped NTP driven unfoldase can be added to either side. Reference claims 5-6 disclose the limitations of instant claims 32-33 and 49 . Reference claims 1 and 12 disclose the limitation of instant claims 36-37. Reference claim 9 discloses the limitation of instant claim 38. Reference claims 10-11 disclose the limitation of instant claim 39 . Reference claim 13 discloses the limitation of instant claim 40 . Reference claims 14-15 disclose the limitation of instant claims 41-42 and 47-48 . Reference claims 1 and 16 disclose the limitation of instant claims 43-44 . Reference claim 17 disclose the limitation of instant claims 45 and 50 . Response to Arguments 07-37 AIA Applicant's arguments filed 18 May 2026 regarding the double patenting rejection have been fully considered but they are not persuasive. Applicant remarks the claims are patentably distinct from claims 1-17 of ‘365 because the instant claims require a ring-shaped NTP driven unfoldase on a first side of a chamber and monitoring ionic current changes during translocation of the protein in a direction toward the first side of the fluidic chamber (Applicant’s remarks at pg. 10, para. 1-2). This argument is not persuasive. Instant claim 1 of ‘365 adds a ring-shaped NTP driven unfoldase added to the fluidic chamber including a cis and trans side, and then allowing the protein to be translocated by the ring-shaped NTP driven unfoldase through the nanopore to the trans side (i.e. translocation of the protein in a direction toward the first side of the fluidic chamber). Given the unfoldase is added to the fluidic chamber, this shows adding the unfoldase to either the cis or trans side, which shows the instant claim. Conclusion No claims are allowed. Claims 31-34 and 36-45 are free of the prior art . Claim 31, and claims dependent therefrom, recite “(b) adding to the first side of the fluidic chamber a ring-shaped NTP driven unfoldase; (c) monitoring ionic current changes during translocation of a protein by the ring-shaped NTP driven unfoldase through the nanopore in a direction toward the first side of the fluid chamber ”. Accordingly, claim 31 requires the unfoldase is added to the trans side of the membrane, which is the side the protein is pulled toward, through the nanopore. The closest prior art of record, Gundlach discloses a method for analyte sequencing, including protein sequencing, with nanopores (Abstract; pg. 7, lines 17-26; claims 1-2; Figure 2), which includes adding a “molecular motor”, defined as a molecule or enzyme that physically interacts with an analyte, which includes a protein (pg. 7, lines 17-26; pg. 13, lines 13-28) and is capable of physically moving the analyte through an opening of the nanopore in a sequential manner, to the trans side (i.e. the first side) of a membrane (pg. 23, line 23 to pg. 24, lines 11). Gundlach further discloses monitoring ion current levels across the membrane during translocation of the analyte protein from the cis side to the trans side (i.e. in a direction toward the first side of the fluid chamber) (pg. 59, lines 19-24; FIG. 2D; claims 1-2). However, Gundlach does not disclose the motor protein is a ring-shaped NTP driven unfoldase. Howorka discloses that peptides and proteins larger than the pore lumen must unfold to pass through the narrow opening and unfolded proteins can be obtained using a denaturing agent (pg. 2375, col. 2, para. 4; Table 1), while Kravats discloses that ClpX is an ATPase motor protein that translocates proteins, and has been selected for its ability to effect unfolding and translocation without assistance from cofactors or environmental variations such as an electrostatic gradient (pg. 2238, col. 1, para. 1). Based on the teachings of Howorka and Kravats, one of ordinary skill in the art would be motivated to add a ClpX motor protein to the second (cis) side of the fluidic chamber in order to unfold the protein before passing the protein through the narrow nanopore opening (Howorka at pg. 2375, col. 2, para. 4; Table 1). However, it would not have been obvious to have placed ClpX on the first (trans) side of the fluid chamber, as claimed, which would require part of the protein pass through the nanopore prior to binding with ClpX (thus prior to unfolding). As a result, there further would not have been a reasonable expectation of success in using ClpX specifically on the trans side of the fluid chamber, given Kravats does not explain how ClpX could be used as a molecular motor in a nanopore device on the trans side of the nanopore. 07-40 AIA 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. Inquiries Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAITLYN L MINCHELLA whose telephone number is (571)272-6485. The examiner can normally be reached 7:00 - 4:00 M-Th. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685 Application/Control Number: 17/745,399 Page 2 Art Unit: 1685 Application/Control Number: 17/745,399 Page 3 Art Unit: 1685 Application/Control Number: 17/745,399 Page 4 Art Unit: 1685 Application/Control Number: 17/745,399 Page 5 Art Unit: 1685 Application/Control Number: 17/745,399 Page 6 Art Unit: 1685 Application/Control Number: 17/745,399 Page 7 Art Unit: 1685 Application/Control Number: 17/745,399 Page 8 Art Unit: 1685 Application/Control Number: 17/745,399 Page 9 Art Unit: 1685 Application/Control Number: 17/745,399 Page 10 Art Unit: 1685 Application/Control Number: 17/745,399 Page 11 Art Unit: 1685 Application/Control Number: 17/745,399 Page 12 Art Unit: 1685 Application/Control Number: 17/745,399 Page 13 Art Unit: 1685 Application/Control Number: 17/745,399 Page 14 Art Unit: 1685 Application/Control Number: 17/745,399 Page 15 Art Unit: 1685 Application/Control Number: 17/745,399 Page 16 Art Unit: 1685 Application/Control Number: 17/745,399 Page 17 Art Unit: 1685 Application/Control Number: 17/745,399 Page 18 Art Unit: 1685 Application/Control Number: 17/745,399 Page 19 Art Unit: 1685
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