Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of Application, Amendments, and/or Claims
Applicant's amendment filed on 01/08/2026 has been entered. Claims 44-45, 53-54, 56-61, and 63-72 are pending and currently under consideration. The declaration of Dr. William Dawson under 37 C.F.R. §1.132 filed on 01/08/2026 has been received and considered.
Information Disclosure Statement
The information disclosure statement filed on 01/08/2025 has been considered by the Examiner and an initialed copy of the form PTO-1449 is attached to this communication.
Claim Rejections under 35 USC § 112 (a)
(i). The following is a quotation of the first paragraph of 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
(ii). Claims 44-45, 53-54, 56-61, and 63-72 are rejected under 35 U.S.C. 112(a), as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention. The basis for the rejection is set forth in the office action mailed on 07/09/2025.
(iii). Response to Applicant’s argument
In the declaration, Dr. Dawson states that protein nanopores having the number of monomer subunits and diameters recited in the claims ·were known at the time of filing (#7). Dr. Dawson states that protein adaptors of the enzyme classes and suitable sizes recited in the claims were known at the time of filing (#11). Dr. Dawson states that pairs of protein nanopores and protein adaptors suitable for use in the claimed nanopore sensors can be identified by the size of a protein adaptor relative to the cis and trans diameters of the protein nanopore (#16).
Referring to the declaration of Dr. Dawson, Applicant argues that one ordinary skill in the art would have understood that the recited structural features of protein nanopores (e.g., number of monomer subunits, cis- and trans-diameters) and protein adaptors are relevant identifying characteristics that define genera of protein nanopores and protein adaptors suitable for nanopore sensors. Applicant argues that one of ordinary skill in the art at the time of filing would have recognized that the number of monomer subunits and relative opening diameters recited in the claims are relevant identifying characteristics of protein nanopores suitable for use in the claimed nanopore sensors. Applicant argues that based on the Application as filed and general knowledge at the time of filing, one of ordinary skill in the art would recognize that the enzyme class and relative sizes recited in the claims are relevant identifying characteristics of protein adaptors suitable for use in the claimed nanopore sensors. Therefore, one of ordinary skill in the art would recognize that the inventors were in possession of protein adaptors having the features recited in the instant claims. Applicant argues that one of ordinary skill in the art would have recognized that nanopore sensors could be made from pairs of protein nanopores and protein adaptors having the structural features of claim 44. As described by Dr. Dawson, the Application teaches that a protein adaptor can be selected based on the size of the protein adaptor relative to the cis and trans diameters of the protein nanopore and this selection allows the protein adaptor to be internalized in a protein
The declaration of Dr. Dawson has been fully considered but is insufficient to overcome the rejection. Applicant’s argument has been fully considered but is not deemed to be persuasive for the following reasons.
For each claim drawn to a genus, MPEP §2163 II.A.3(a) ii) (page 2100-189) states, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406”.
Claim 44 is drawn to a nanopore sensor comprising (i) a protein nanopore comprising a cis side and a trans side connected by a lumen having a cis-diameter and a trans-diameter, the cis-diameter of the protein nanopore ranging from 4.5 nm to 7 nm, and the trans-diameter of the protein nanopore ranging from 1.5 nm to 4.0 nm, wherein the nanopore comprises 7 to 13 monomer subunits; (ii) a protein adaptor that is an enzyme selected from the group consisting of an oxidoreductase, a transferase, an hydrolase, a lyase, an isomerase, or a ligase, wherein the protein adaptor is not thrombin, wherein the protein adaptor is smaller than the cis-diameter of the protein nanopore but larger than the trans-diameter of the protein nanopore, wherein the protein adaptor is internalized in the lumen of the nanopore such that the protein adaptor is not covalently bound to the nanopore, wherein the protein adaptor binds a small molecule ligand while the protein adaptor is internalized; and (iii) the small molecule ligand. Claims 45, 53-54, 56-61, and 63-72 depend from claim 44. The claims recite an enormous genus of nanopores without a defined structural feature.
In the instant case, the claimed nanopore sensor comprises three components, a protein nanopore, an enzyme adaptor, and a small molecule ligand. With respect to the protein nanopore, claim 44 recites a protein nanopore comprising a cis side and a trans side connected by a lumen having a cis-diameter and a trans-diameter, the cis-diameter of the nanopore ranging from 4.5 nm to 7 nm, and the trans-diameter of the nanopore ranging from 1.5 nm to 4.0 nm, wherein the nanopore comprises 7 to 13 monomer subunits. The size of cis-diameter and a trans-diameter alone does not represent identifying characteristics about the protein nanopore because it says nothing about amino acid sequence of the protein nanopore. The specification discloses a nanopore, ClyA and its mutants (page 4; Table on pages 37-40). However, the instant disclosure is insufficient to support the broad genus of nanopores.
With respect to the enzyme adaptor, claim 44 recites an oxidoreductase, a transferase, a hydrolase, a lyase, an isomerase, or a ligase. Thus, claim 44 encompasses eight general class of enzymes. Other than E. coli AlκB demethylase (see, e.g., Example 2) and E. coli dihydrofolate reductase (DHFR; see, e.g., Example 3), the specification does not disclose any other globular enzymes that meet the requirement to be internalized into the ClyA nanopore or any other nanopores that can accommodate E. coli AlB demethylase and E. coli dihydrofolate reductase.
Furthermore, the pairing of a particular nanopore with a particular globular enzyme protein adaptor of a suitable shape and size in the nanopore is required so that the single globular enzyme adaptor can be functionally and reversibly trapped inside the confined space of a nanopore and the binding of analytes to the internalized globular enzyme protein is mirrored by specific changes to the nanopore conductance (Soskine et al., J. Am. Chem. Soc.137 (17): 5793–5797, 2015 May 6; see, e.g., Abstract). It is not known if the environment of the nanopore lumen is compatible with enzymatic functions, as experiments with solid-state nanopores revealed that proteins might be stretched by the electrical field and unfolded under applied potentials greater than +200 mV (Soskine et al., J. Am. Chem. Soc.137 (17): 5793–5797, 2015 May 6; see, e.g., Introduction).
Finally, 35 U.S.C. 112(a) require that Applicant was in possession of the claimed invention at the time of the application was filed. The declaration of Dr. Dawson does not provide sufficient evidence showing that Applicant was in possession of the claimed invention at the time of the application was filed. If Applicant disagrees with Examiner’s opinion, Applicant is requested to list the art-known protein nanopore, cis-diameter, trans-diameter, number of monomer subunits, and corresponding enzyme adaptor (the size and small molecule ligand of an oxidoreductase, a transferase, a hydrolase, a lyase, an isomerase, or a ligase), as well as the reference.
Due to the breadth of the genus of nanopores and enzyme protein adaptors, and lack of the definitive structural features of the genus, one skilled in the art would not recognize from the disclosure that Applicant was in possession of the genus of instantly claimed genus of nanopore sensors.
Conclusion
No claims are allowed.
Advisory Information
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ruixiang Li whose telephone number is (571) 272-0875. The examiner can normally be reached on Monday through Friday from 8:30 am to 5:00 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached on (571) 272-0857. The fax number for the organization where this application or proceeding is assigned is (571) 273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, please contact the Electronic Business Center (EBC) at the toll-free phone number 866-217-9197.
/RUIXIANG LI/Primary Examiner, Art Unit 1674 February 13, 2026