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 statements (IDS) submitted on 07/20/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of Claims
This office action is in response to Applicant's Response to Election / Restriction filed on July 20, 2026. No claims amendment are made in the response filed on July 20, 2026.
Claims 24-30 and 32-44 are currently pending, with claims 42-44 withdrawn.
Claims 24-30 and 32-41 are under examination. This is the first action on the merits.
Election/Restrictions
Applicant’s election without traverse of the following species in the reply filed on July 20, 2026 is acknowledged:
Species of analyte and a concomitant specific tertiary structure:
Analyte: IgG anti-SARS-CoV-2 antibody
Tertiary Structure: a triangular regular-polygon nanopore geometry (Tri-20 type pore)
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 42-44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Examination on the merits commences on claims 24-30 and 32-41.
Priority
For the instant claims 24-30 and 32-41 in this U.S. Application, the applicant claims priority of Foreign Application UNITED KINGDOM 2108820.8, which has a filling date on June 18, 2021.
Claim Objections
Claim 29 is objected to because of the following informalities:
· In claim 29, lines 1, "wherrein" should read "wherein."
Claim Interpretation
In evaluating the patentability of the claims presented in this application, claim terms have been given their broadest reasonable interpretation (BRI) consistent with the specification, as understood by one of ordinary skill in the art, as outlined in MPEP§ 2111.
For the purpose of applying prior art, claim 24 recites:
"wherein the nanopore has a tertiary structure and the tertiary structure of the nanopore is configured to conform to a three-dimensional shape of at least a portion of an analyte molecule."
However, the three-dimensional shape or structure of the analyte molecule is not defined, and the analyte molecule is not identified as any specific molecule. Therefore, the analyte molecule encompasses any molecule.
Accordingly, because the analyte molecule encompasses any molecule, under BRI, the tertiary structure of the nanopore is interpreted as encompassing any configuration.
For the purpose of applying prior art, claim 37 recites:
"wherein the tertiary structure of the nanopore is configured to conform to a three-dimensional shape of at least a portion of the analyte molecule to facilitate a mating engagement between the analyte molecule and the nanopore. "
The application's disclosure does not define the term "mating engagement." The relevant description in the specification appears to describe a nanopore having a configuration that allows an analyte or part of the analyte to fit within the pore:
"By way of non-limiting example, a nanopore that is geometrically optimised to accommodate an IgG analyte may be configured to have a lumen that is generally triangular or even Y-shaped. Geometrical optimization may include configuring the nanostructure to receive all or a part of an analyte in a mating engagement, such as a lock and key type arrangement. " (spec. p. 24, lines 13-17)
Accordingly, in light of the specification and under BRI, this wherein clause is interpreted as the nanopore structure allows at least a portion of the analyte to fit within the lumen of nanopore.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 32-41 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A) Regarding claim 32, it recites "the sterols," "the alkylated phenols," "the flavones," "the saturated and unsaturated fatty acids," and "the synthetic lipid molecule," which are terms that lack antecedent basis. The claim contains no earlier recitations of these terms, it is therefore unclear to what element the limitation is making reference.
Claims 33-41 are rejected for depending from claim 32 and not remedying the indefiniteness.
B) Regarding claim 38, it recites "wherein the tertiary structure of the nanopore is configured to facilitate a stereo- or regio-specific interaction between a binding moiety and the analyte molecule."
This claim language is indefinite. The issue is two-fold:
.1. The metes and bounds of the terms "stereo- specific interaction" and "regio-specific interaction" is unclear.
.2. The disclosure does not clearly disclose any specific structural feature that directly support the recited function.
First, the specification does not define or explain what "stereo- or regio-specific interaction" means in the context of a binding interaction. The terms "Stereo-specificity" and "Regio-selectivity" are typically applied to describe chemical reactions1, not for describing binding interactions. There is no commonly understood meaning for "stereo- or regio-specific interaction" in the context of a binding interaction.
Accordingly, the phrase "a stereo- or regio-specific interaction between a binding moiety and the analyte molecule" renders the scope of the claim unclear. For example, it is unclear whether an antibody-antigen interaction, such as that disclosed in Figure 4, qualifies as a stereo-specific interaction, a regio-specific interaction, or neither.
Second, it is unclear what nanopore structure is required by the claim language of "configured to facilitate a stereo- or regio-specific interaction between a binding moiety and the analyte molecule."
The only relevant description in the specification regarding these interactions states that:
"the configuration of the tertiary nanostructure in terms of dimensions, geometry and binding moiety placement (i.e. within or proximate to the lumen) may even influence factors such as the stereo- or regioselectivity of analyte binding. " (specification, p. 22, lines 31-33)
However, this merely lists factors that "may" influence stereo- or regio-selectivity. It does not specify whether the influence is positive or negative, nor does it identify any structural feature that directly relates to or supports the recited function to "facilitate a stereo- or regio-specific interaction between a binding moiety and the analyte molecule."
Therefore, the scope of the claim is indefinite. Claims 39-41 are rejected for depending from claim 38 and not remedying the indefiniteness.
For the purpose of compact prosecution and applying prior art under 35 USC§ 102 and 103, because the specification does not identify any specific feature that distinguishes a "stereo- or regio-specific interaction" from other interactions known in the art between a binding moiety and an analyte molecule, the phrase "stereo- or regio-specific interaction" is interpreted as encompassing any interaction between a binding moiety and an analyte molecule. Therefore, the recited tertiary structure configured to facilitate such an interaction is interpreted as encompassing structures that allow a binding interaction between a binding moiety and an analyte molecule.
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.
Claims 24-30 and 32-34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Howorka (WO2020025974A1 - Membrane bound nucleic acid nanopores; Published 2020-02-06; cited as Foreign Patent Doc#4 in IDS filed 07/20/2026).
Regarding claim 24, Howorka teaches a sensing nucleic acid nanopore comprising:
a nucleic acid nanopore (Figure 1; p.8, lines 18-28),
wherein the nanopore defines a central lumen passing therethrough (Figure 1; p.8, lines 18-28, “ nucleic acid nanopore structure… that defines a lumen of internal width of 10 nm”), and
wherein the central lumen has a cis-facing first open end that defines a first aperture and a trans-facing second open end that defines a second aperture (Figure 1(d), as indicated by the arrow, the analyte first enters the pore from the cis-side via first aperture then exits via the second aperture to the trans side; see also p.8, lines 18-28); and
an analyte binding moiety (Figure 1(b), a linker group comprising biotin; p.8, lines 21-23),
wherein the analyte binding moiety comprises an affinity binding molecule (Figure 1(b), biotin), and
wherein the analyte binding moiety is located within the central lumen between the first and second apertures (Figure 1(b); p.8, lines 21-23, “analyte binding agent (biotin) tethered within the channel defined by the pore” );
wherein the nanopore has a tertiary structure (Figure 1(b), the nanopore is configure to allow the streptavidin to fit within the pore and bind to biotin).
Regarding claim 25, Howorka teaches the nanopore is configured to be located within a membrane(Figure 1(d)).
Regarding claim 26, Howorka teaches nanopore further comprises at least one hydrophobic anchor that facilitates insertion of the nanopore into the membrane (Figure 1(c); p. 17, lines 17-21; claim 2).
Regarding claim 27, Howorka teaches the at least one hydrophobic anchor is comprised of a polynucleotide strand and at least one hydrophobic anchor molecule (claim 2; claim 11; p. 4, lines 22-30).
Regarding claim 28, Howorka teaches the at least one hydrophobic anchor molecules are: attached to and spaced substantially equidistantly about the periphery of the nanopore, and wherein the at least one hydrophobic anchor molecules are orientated radially outwardly from the longitudinal axis of the central lumen of the nanopore (p. 4, lines 32-34).
Regarding claim 29, Howorka teaches the nanopore comprises at least four hydrophobic anchor molecules (p. 5, lines 1-3; Figure 1(c)).
Regarding claim 30, Howorka teaches hydrophobic anchor molecule is a lipid (p. 5, lines 5--6).
Regarding claim 32, it recites:
wherein:
- the sterols are selected from the group consisting of: cholesterol; derivatives of cholesterol; phytosterol; ergosterol; and bile acid;
- the alkylated phenols are selected from the group consisting of: methylated phenols; dolichols and tocopherols;
- the flavones are selected from the group consisting of: flavanone containing compounds; and 6-hydroxyflavone;
- the saturated and unsaturated fatty acids are selected from the group consisting of: derivatives of lauric acid; oleic acid; linoleic acid; and palmitic acids; and/or
- the synthetic lipid molecule is dodecyl-beta-D-glucoside.
This claim merely describes elements (e.g., "the sterols," "the alkylated phenols," "the flavones," "the saturated and unsaturated fatty acids ," "the synthetic lipid molecule") that are not required as being comprised by the nanopore. Therefore, claim 32 is anticipated by Howorka because it does not further limit the claimed nanopore.
Regarding claim 33, Howorka teaches the analyte binding moiety is located proximate to or within the first aperture (Figure 1(b); p. 5, lines 34-38).
Regarding claim 34, Howorka teaches the affinity binding molecule comprises an antibody (p. 6, lines 1-2; p. 24, lines 17-20).
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.
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 35-41 are rejected under 35 U.S.C. 103 as being unpatentable over
Howorka (WO2020025974A1 - Membrane bound nucleic acid nanopores; Published 2020-02-06 ; cited as Foreign Patent Doc#4 in IDS filed 07/20/2026), in view of Premkumar (Premkumar et al.,The receptor-binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients.Sci. Immunol.5,eabc8413 (2020).DOI:10.1126/sciimmunol.abc8413).
A) Regarding claim 35, Howorka teaches a nucleic acid nanopore sensing device comprising an affinity binding molecule for binding to an detecting a target analyte (Figure 1(b); p. 25, lines 7-14 ;p. 7, lines 11-18)
Howorka teaches that its nanopore device is useful for sensing and detecting a variety of analytes, including biomolecules (p. 25, lines 7-14).
“The nanopore structures of the present invention may be incorporated within a plurality of improved devices and sensors. Such devices and sensors are useful in applications requiring to sensing and characterization of a variety of materials and analytes. By way of non-limiting example, particularly useful applications, including genome sequencing, protein sequencing, other biomolecular sequencing, and detection of ions, molecules, chemicals, small molecules, biomolecules, metal atoms, contaminants, polymers, nanoparticles etc. Such detecting and characterizing can, in turn, be used to diagnose diseases, in drug development, to identify contamination or adulteration or food or water supplies, and in quality control and standardization.” (p. 25, lines 7-14)
Although Howorka does not explicitly teach that the affinity binding molecule comprises a SARS-CoV-2 Spike receptor binding domain (RBD), this feature would have been an obvious result of applying a known analyte-sensing device (i.e., nanopore device in Howorka) to detect a known analyte (i.e., RBD-binding antibodies, disclosed in Premkumar) using a known analyte-binding molecule (i.e., receptor-binding domain (RBD) portion of the SARS-CoV-2 spike protein, , disclosed in Premkumar).
Premkumar teaches detecting RBD-binding antibodies in serum using RBD, which specifically captures RBD antibodies in an immunoassay for serology testing (Abstract; p. 7, right-hand col, “In-house RBD Ig and IgM ELISA”).
Premkumar further highlights the importance of serology testing for RBD-binding antibodies, including for disease control measures and vaccine development (p. 6, left-hand col., para. 1).
Accordingly, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to detect RBD-binding antibodies for serological testing using the nanopore device disclosed in Howorka, with RBD as the affinity binding molecule for binding to and detecting RBD-binding antibodies, as taught by Premkumar.
A skilled artisan would have been motivated make this modification because doing so would adapt Howorka’s general analyte-detection device to a known clinically relevant analyte target, thereby providing utility to infectious disease control and vaccine development.
This combination would have been obvious as it represents the KSR principle of predictable use of prior art elements (i.e., affinity binding pair of RBD and RBD-binding antibody in Premkumar) according to a known method (i.e., analyte detection using Nanopore device based on affinity binding in Howorka) to yield predictable results. (See MPEP §2143).
There would have been a reasonable expectation of success because the references provide technically compatible teachings. Howorka already teaches that its nanopore device is suitable for detecting an analyte by using specific binding between the analyte and an affinity molecule (Figure 1(b); see also pp. 23-24, “Binding of the analyte will serve to fully or partially occlude the channel of the nanopore such that a detectable electrical readout can be obtained.”). Premkumar teaches that RBD and RBD-binding antibody are such a specific binding pair.
B) Regarding claim 36, Howorka teaches the analyte binding moiety comprises the affinity binding molecule that is tethered to the nanopore (p. 24, lines 7-8).
Regarding claim 37, Howorka teaches the tertiary structure of the nanopore is configured to conform to a three-dimensional shape of at least a portion of the analyte molecule to facilitate a mating engagement between the analyte molecule and the nanopore (Figure 1(b); p. 21, lines 29-30, "The specificity of the translocation to certain folded proteins may be controlled through variation of the size of the channel in the nanopore."; p.2, lines 11-12, "the pore dimensions should be easily tunable to adapt them to different biomolecule sizes"; p.14, lines 32-33, "minimum interior width of a channel defines the maximum size of an object, such as an analyte, that may pass through the channel" ) .
Regarding claim 38, Howorka teaches tertiary structure of the nanopore is configured to facilitate specific interaction between a binding moiety and the analyte molecule (Figure 1 (b), nanopore facilitates specific interaction between biotin and streptavidin).
Regarding claim 39, as discussed above for claim 24, Premkumar teaches analyte being RBD-binding antibody (Abstract; p. 7, right-hand col, “In-house RBD Ig and IgM ELISA”).
Regarding claim 40, Howorka teaches central lumen has a regular polygonal shape (p. 18, lines 14-15 “the lumens defined by the channel may be a regular or irregular circle or polygon, such as a triangle” ; Figure 8).
Regarding claim 41 , Howorka teaches the regular polygonal shape is a triangle (p. 18, lines 14-15 “the lumens defined by the channel may be a regular or irregular circle or polygon, such as a triangle” ; Figure 8).
Prior Art
Below are relevant prior art not used in rejection but pertinent to the claims or disclosure.
Other prior art references also teach Nucleic acid Nanopores comprising a binding moiety specific to binding an analyte:
Langecker (EP2695949B1 - Nucleic acid based nanopores or transmembrane channels and their uses; Published 2014-02-12);
Guo (US20190093157A1 - Rna nanotubes for single molecule sensing and dna/rna/protein sequencing; Published 2019-03-28)
Other prior art references also teach Nucleic acid Nanopores having different shape and pore size to allow specific molecules to pass through:
US20190309350A1- Membrane-spanning nanopores; Published on 2019-10-10;
Bell NA, Keyser UF. Nanopores formed by DNA origami: a review. FEBS Lett. 2014 Oct 1;588(19):3564-70. doi: 10.1016/j.febslet.2014.06.013. Epub 2014 Jun 10. PMID: 24928438.
Conclusion
Claim 29 is objected to; claims 24-30 and 32-41 are rejected. No claims are allowed.
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/TIAN NMN YU/Examiner , Art Unit 1681
1 See Regioselectivity - Wikipedia; Archived Feb 04, 2021 on WaybackMachine;
Stereospecificity - Wikipedia; Archived Nov 12, 2020 on WaybackMachine
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