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 .
Response to Arguments
Applicant's arguments filed December 16, 2025 have been fully considered but they are not persuasive.
With respect to the rejections under 35 U.S.C. 112(b), Applicant has amended the claims in a manner that has overcome the rejections detailed in the previous Office Action. As such, the rejections under 35 U.S.C. 112(b) have been removed.
With respect to the prior art rejections, Applicant has amended the claims to recite an engineered pore forming protein wherein the engineered pore forming protein is a part and not an entirety of a β-barrel or an α-helix, and argued that reference to Nivala et al., do not teach an engineered pore forming protein. The Examiner points to paragraph 0080 of Nivala et al., (Pre-Grant Publication) which teaches an engineered alpha-hemolysin/ClpP fusion protein pore. Nivala et al., also teach the pore proteins comprising a transmembrane sequence of a β-barrel or an α-helix (paragraphs 0046, 0047). Additionally, Nivala et al., teach that α-hemolysin pores consists of both beta-sheets and alpha helices (paragraph 0047) thereby meeting the limitation of the pore forming protein being a part and not an entirety of a β-barrel or an α-helical pore forming protein. As such, the Examiner contends that the amendments to independent claim 1 does not overcome the prior art. Therefore, in light of the teachings of the prior art, the Examiner contends that the limitations of the instant claims are taught by the references cited below, thus the rejection is maintained.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1-6, 8-11, 13-22, 26, 27, 29, and 30 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nivala et al., (US 2016/0032236).
For claim 1, Nivala et al., teach a nanopore sensor for protein translocation comprising a transmembrane sequence of an engineered β-barrel or α-helical pore forming protein (paragraphs 0046, 0047), fused to a subunit of a ring forming protein capable of translocating macromolecules (paragraphs 0052, 0080). Nivala et al., teach the pore forming protein consisting of β-barrels and α-helices thereby meeting the limitation of the pore forming proteins being a part and not an entirety of β-barrel pore forming proteins and α-helical pore forming proteins (paragraph 0047).
For claims 2 and 3, Nivala et al., teach the transmembrane sequence being an α-helix, or a β-barrel (paragraphs 0046, 0047).
For claim 4, Nivala et al., teach a pore forming protein identical to that of the instant claims (α-hemolysin, paragraph 0047), thus the transmembrane sequence would be identical.
For claims 5 and 6, Nivala et al., teach the ring forming protein fused to the N-terminal of the transmembrane sequence (paragraph 0080).
For claim 8, Nivala et al., teach a heptameric protein as the ring forming protein (paragraph 0080).
For claims 9 and 11, Nivala et al., teach the heptameric protein controlling translocation (paragraph 0080).
For claim 10, Nivala et al., teach an ATPase as the heptameric protein (paragraph 0052).
For claims 13 and 14, Nivala et al., teach a transmembrane sequence fused to the N terminus of a proteasome a-subunit and the C-terminus of a Clp protease subunit (paragraph 0080).
For claims 15 and 17, Nivala et al., teach AAA+ ATPases which comprise α-subunits and β-subunits (paragraph 0052).
For claim 16, Nivala et al., teach utilizing a truncated ClpX variant (ClpXΔN) which lacks at least 5 N-terminal amino acids (paragraph 0115).
For claims 18 and 19, Nivala et al., teach a nanopore system comprising a protein translocase and/or an NTP driven unfoldase (paragraphs 0014, 0016).
For claim 20, Nivala et al., teach a nanopore sensor comprising a membrane having cis and trans sides (Abstract, 0013, 0014, 0048) and an artificial nanopore (paragraph 0045).
For claims 21 and 22, Nivala et al., teach a method of sequencing a biopolymer by translocating the biopolymer through a nanopore sensor (paragraph 0061).
For claim 26, Nivala et al., teach ClyA as the α-helical pore (paragraph 0046).
For claim 27, Nivala et al., teach α-hemolysin as β-barrel pore forming protein(paragraph 0047).
For claim 29, Nivala et al., teach AAA+ATPases (paragraph 0052) which are A. aeolicus ATPases.
For claim 30, Nivala et al., ClpX as the NTP-driven unfoldase (Abstract, 0016, 0022, 0051, 0052).
Claim Rejections - 35 USC § 103
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.
Claim(s) 7 and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nivala et al.,(US 2016/0032236) in view of Nivala et al., (US 2022/0396758).
Regarding claims 7 and 28, Nivala et al., '236 do not teach the transmembrane sequence having a linker on the N and/or C termini.
Nivala et al., '758 teach a nanopore sensor for protein translocation wherein the transmembrane sequence having a flexible 5-15 glycine-serine sequence (paragraph 0086). Nivala et al., '758 also teach that α-hemolysin (transmembrane sequence) is tolerant to fusion at both the N and C termini (paragraph 0086). Nivala et al., '758 teach that it is advantageous to utilize a flexible linker as a means of allowing each protein monomer to fold properly (paragraph 0086).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify Nivala et al., '236 wherein the transmembrane sequence comprises a flexible linker having 5-15 glycine-serine sequence in order to allow proper protein folding as taught by Nivala et al., '758.
Claim(s) 23-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nivala et al., (US 2016/0032236) in view of Maglia et al., (US 2018/0364214).
Regarding claims 23-25, Nivala et al., do not teach a nucleic acid molecule encoding an artificial nanopore, an expression vector comprising the nucleic acid molecule, and a host cell comprising the expression vector.
Maglia et al., teach modified nanopores comprising a nucleic acid molecule encoding the nanopore, an expression vector comprising the nucleic acid molecule, and a host cell comprising an expression vector comprising the nanopore (paragraph 0079). With respect to claim 25, the Examiner notes that the optional limitations are not given patentable weight as they are not required by the claim. Maglia et al., teach that it is advantageous utilize an expression vector and host cell as a means of controlling expression of the nanopore (paragraph 0079).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of Nivala et al., wherein a nucleic acid molecule encoding the nanopore is inserted into an expression vector and a host cell in order to control expression of the nanopore as taught by Maglia et al.
Allowable Subject Matter
Claim 12 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: the prior art of record does not teach or suggest an artificial nanopore comprising a transmembrane sequence of a β-barrel or an α-helical pore forming protein and a subunit of a ring forming protein wherein the ring-forming protein is a proteosome activator PA28, PA26, a homolog of PA28, a homolog of PA26, a functional equivalent of PA28, or a functional equivalent of PA26.
Conclusion
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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DWAN A GERIDO whose telephone number is (571)270-3714. The examiner can normally be reached Mon-Fri 10-6.
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/DWAN A GERIDO/Examiner, Art Unit 1797 /LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797