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
1. Claims 1-20 are pending and currently under consideration.
Information Disclosure Statement
2. The information disclosure statements filed on 10/24/2023 has been considered and an initialed copy is attached to the office action.
Drawings
3. The drawings filed on 08/02/2023 are accepted by the examiner.
Claim Rejections[Symbol font/0xBE] Nonstatutory Obviousness-Type Double Patenting
4. Basis for nonstatutory double patenting:
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. See 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);and, 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
5. Claims 1-20 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-22 of US Patent No. 10,006,905 B2, claims 1-16 of US Patent No. 10,514,378 B2, claims 1-18 of US Patent No.10,976,311 B2, or claims 1-20 of US Patent No. 11,761,956 B2. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 1-20 of the instant application are drawn to a modified ClyA pore comprising a plurality of subunits, wherein each subunit comprises a polypeptide represented by an amino acid sequence at least 80% identical to SEQ ID NO:1, wherein one or more amino acids of the modified ClyA pore is substituted, deleted, and/or added relative to SEQ ID NO: 1; a method for detecting a target protein or a target analyte in a sample using the modified ClyA pore; or a sensor system comprising the modified ClyA pore.
On the other hand, claims 1-22 of US Patent No. 10,006,905 B2 are drawn to a modified ClyA pore comprising a plurality of subunits, wherein each subunit comprising a polypeptide represented by an amino acid sequence of at least 80% identical to SEQ ID NO: 1, a method for translocating DNA through a modified GlyA pore that is capable of translocating DNA, and a device for translocating DNA, comprising a fluid-filled compartment separated by a membrane into a first chamber and a second chamber, electrodes capable of applying potential across the membrane, one or more nanopores inserted in the membrane, a solution of high ionic strength in one chamber of the membrane, wherein DNA translocates through the nanopore from the first chamber to the second chamber.
Claims 1-16 of US Patent No. 10,514,378 B2 are drawn to a nanopore sensor comprising a modified ClyA pore, wherein the modified ClyA pore comprises at least 12 subunits, each subunit comprising a polypeptide represented by an amino acid sequence with at least 80% identity to SEQ ID NO:1, wherein the amino acid at position 103 (D) is substituted with a cysteine residue and wherein the position of the amino acid substitution is numbered with reference to an amino acid sequence as set forth in SEQ ID NO: 1, starting from the second amino acid residue.
Claims 1-18 of US Patent No.10,976,311 B2 are drawn to a nanopore sensor system comprising: i) a fluid-filled compartment separated by a membrane into a first chamber and a second chamber, wherein the fluid is an ionic solution; ii) a ClyA pore inserted in the membrane, wherein the ClyA pore comprises 14 subunits, wherein each subunit of the ClyA pore comprises a polypeptide represented by an amino acid sequence with at least 80% identity to SEQ ID NO: 1; and iii) electrodes configured for generating an electrical potential difference across the membrane to facilitate ionic flow through the ClyA pore from the first chamber to the second chamber.
Claims 1-20 of US Patent No. 11,761,956 B2 are drawn to a sensor system comprising i) a fluid-filled compartment separated by a membrane into a first cis chamber and a second trans chamber, wherein the fluid is an ionic solution; ii) a ClyA pore inserted in the membrane, wherein the ClyA pore comprises 12 or more ClyA subunits and has a pore lumen of at least 3 nm in diameter, wherein the cis diameter of the pore lumen is at least 5.5 nm and the trans exit of the pore lumen is at least 3.3 nm, wherein each subunit of the ClyA pore comprises a polypeptide represented by an amino acid sequence with at least 80% identity to SEQ ID NO: 1; iii) electrodes configured for generating an electrical potential difference across the membrane to facilitate ionic flow through the ClyA pore from the first chamber to the second chamber, and iv) a double stranded DNA that translocates through the ClyA pore from the first chamber to the second chamber.
Thus, claims 1-20 of the instant application and claims 1-22 of US Patent No. 10,006,905 B2, claims 1-16 of US Patent No. 10,514,378 B2, claims 1-18 of US Patent No.10,976,311 B2, or claims 1-20 of US Patent No. 11,761,956 B2 vary in scopes and are obvious over each other.
6. Claims 1-20 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-17 of US Patent No. 10,802,015 B2. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 1-20 of the instant application are drawn to a modified ClyA pore comprising a plurality of subunits, wherein each subunit comprises a polypeptide represented by an amino acid sequence at least 80% identical to SEQ ID NO:1, wherein one or more amino acids of the modified ClyA pore is substituted, deleted, and/or added relative to SEQ ID NO: 1; a method for detecting a target protein or a target analyte in a sample using the modified ClyA pore; or a sensor system comprising the modified ClyA pore.
On the other hand, claims 1-17 of US Patent No. 10,802,015 B2 are drawn to a nanopore sensor system comprising i) a fluid-filled compartment separated by a membrane into a first cis chamber and a second trans chamber, wherein the fluid is an ionic solution; ii) a ClyA pore inserted in the membrane, wherein the ClyA pore comprises 12 or more ClyA subunits and has a pore lumen of at least 3nm in diameter, wherein the cis diameter of the pore lumen is at least 5.5 nm and the trans exit of the pore lumen is at least 3.3nm, wherein each subunit of the ClyA pore comprises a polypeptide represented by an amino acid sequence with at least 80% identity to SEQ ID NO: 1; and iii) electrodes configured for generating an electrical potential difference across the membrane to facilitate ionic flow through the ClyA pore from the first chamber to the second chamber.
Thus, claims 1-20 of the instant application and claims 1-17 of US Patent No. 10,802,015 B2 vary in scopes and are obvious over each other.
Claim Rejections[Symbol font/0xBE]35 USC § 112 (b)
7. The following is a quotation of the second paragraph of 35 U.S.C. 112:
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.
8. Claims 1-20 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 regards as the invention.
Claims 1-20 recite the acronym, “ClyA”. First, such a term is determined arbitrarily without a definitive structure. Others in the field may isolate the same protein and give an entirely different name. Thus, claiming biochemical molecules by a particular name given to the protein by various workers in the field fails to distinctly claim what the protein is. Applicants should particularly point out the “ClyA” by reciting characteristics associated with the molecule and provide its full name.
Claim Rejections[Symbol font/0xBE]35 USC § 102 (a)(1)
9. 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.
10. Claims 1-2, 8-9, 11, and 13-16 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Soskine et al. (Nano Letters 12 (9):4895–4900, August 1, 2012).
Soskine et al. teach an engineered (modified) Escherichia coli cytolysin A (ClyA) nanopore with two native cysteine residues at positions 87 and 285 being replaced by serine (page 4895, right column, the 2nd paragraph), which would share at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1. The modified ClyA pore comprises 12 subunits (page 4895, right column, the 2nd paragraph). The modified ClyA pore has a cis diameter of 7.0 nm (Figure 1 A) and comprises a lumen and a protein analyte binds within the lumen of the modified ClyA pore (Figure 5). Thus, the teachings of Soskine et al. meet the limitations of claims 1-2, 8-9, 11, and 13-16.
11. Claims 1-2 and 8-16 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Atkins et al. (J. Biol. Chem. 275:41150-41155, 2000), as evidenced by Wallace et al. (Cell 100:265-276, 2000).
Atkins et al. teach a pore-forming toxin hemolysin E, which comprises amino acid residues 3 to 305 of the amino acid sequence of SEQ ID NO: 1 as evidenced by Wallace et al. (see the amino acid sequence of Salmonella typhi shown in Fig. 1). The publication of Wallace et al. is referred as No.1 reference in the publication of Atkins et al. The sequence alignment with SEQ ID NO: 1 of the present application is shown below.
Atkins et al. teach the specific mutagenesis of the Cystein residue at position 87 or 285 and its substitution with a Serine (Table III). The properties recited in claims 8-16 are inherent to the structure of the mutant pore-forming toxin hemolysin E. Thus, the teachings of Atkins et al. meet the limitations of claims 1-2 and 8-16.
PNG
media_image1.png
552
733
media_image1.png
Greyscale
Claim Rejections under 35 USC § 103(a)
12. The following is a quotation of 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 of this title, 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 negatived by the manner in which the invention was made.
13. Claims 18-20 are rejected under 35 U.S.C. 103(a) as being unpatentable over Atkins et al. (J. Biol. Chem. 275:41150-41155, 2000), Wallace et al. (Cell 100:265-276, 2000) as applied to claims 1-2 and 8-16 above, and further in view of US Patent No. US 8,105,846 B2 (Date of patent: Jan. 31, 2012), US 2002/0094526 A1 (Pub. Date: Jul. 18, 2002), and US 2015/0177237 (Pub. Date: Jun. 25, 2015; earliest filing date: Feb. 15, 2012).
Atkins et al. and Wallace et al. teach a modified ClyA pore as applied to claims 1-2 and 8-16 above.
Atkins et al. and Wallace et al. do not teach (i). a sensor system comprising a modified ClyA pore as recited in claim 20; (ii). a method for detecting at least one target protein or analyte in a sample comprising a modified ClyA pore as recited in claims 18-19.
US 8,105,846 B2 teaches a sensor system comprising a transmembrane pore inserted in a membrane (column 4, lines 33-35), which permits ions to flow from one side of the membrane to the other along an electrochemical gradient (column 5, the 1st paragraph), a fluid-filled compartment separated by a membrane into a first chamber and a second chamber, wherein the fluid is an ionic solution, and configured electrodes (column 9, the 6th an 7th paragraphs). US 8,105,846 B2 teaches the pore may be attached to a solid support in order to insert the pore into the membrane (column 7, lines 31-35).
The transmembrane pores include α-hemolysin (column 5, the 4th and 5th paragraphs). US 8,105,846 B2 also teaches a method of identifying a nucleotide using a transmembrane pore and an adaptor (see, e.g., abstract; claim 1). The method comprises contacting nucleotide with a transmembrane protein pore so that the nucleotide interacts with the pore, wherein the pore comprises a molecular adaptor, cyclodextrin, which facilitates the interaction between the pore and the nucleotide and measuring a current passing through the pore during the interaction (claim 1; last paragraph of column 9 to 1st paragraph of column 10). The adaptor may reversibly interact with the pore and may be covalently attached to the barrel or channel of the pore (column 10, the 2nd paragraph).
US 2002/0094526 A1 teaches a modified pore-subunit polypeptide comprising a pore subunit polypeptide covalently linked to a sensing moiety, which is a ligand-binding functional group (claims 1-3), such as an analyte-binding peptide (claims 11 and 12) or an analyte-binding protein (page 3, paragraph [0029])). The sensing moiety binds an enzyme, a peptide, a protein or an oligonucleotide (claim 13). US 2002/0094526 A1 also teaches a nanopore sensor comprising at least 10 or more pore–forming subunits (page 4, paragraph [0036]). US 2002/0094526 A1 teaches a method for detecting an analyte in a sample comprising contacting the sample with a nanopore biosensor comprising the pore and detecting a signal or electrical current (Fig. 1; claims 39 and 40; page 5, right column, paragraph [0053]).
US 2015/0177237 teaches a method of determining in a sample the presence of one or more analytes using aptamers and transmembrane pores or nanopore (see, e.g., Abstract; Examples). The aptamers include a peptide aptamer and an oligonucleotide aptamer that selectively binds to an analyte (page 12, paragraphs [0141]-[0146]). Such a peptide aptamer would inherently bind to a protein analyte with a molecular weight in the range of 15-70 kDa.
Therefore, in view of the teachings in the prior art, it would have been obvious for one skilled in the art to make a sensor system comprising a modified ClyA pore as taught by Atkins et al. and Wallace et al. and to apply the sensor system to detect a target protein or a target analyte in a sample with a reasonable expectation of success. One would have been motivated to do so because such a sensor system would have provided an approach to selectively detect an analyte in a sample.
Conclusion
14. No claims are allowed.
Advisory Information
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 1646
February 4, 2026