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 .
Inventorship
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 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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-7, 12-15, 24-25 and 27-29 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Graige et al (WO 2024/015875, submitted in the IDS filed on May 28, 2026).
It is noted that Graige et al qualifies as prior art under 35 USC 102(a)(2) since it has a priority filing date of July 12, 2022, which is prior to the earliest effective filing date of the instant application of August 2, 2022.
With regards to claims 1-3, Graige et al teach of a method of identifying a modified amino acid, wherein the modified amino acid comprises a polymerizable molecule which is a cycle nucleic acid. The method comprises providing the modified amino acid by coupling a peptide to a solid support so that the N-terminal amino acid of the peptide is not directly coupled to the solid support and is exposed to reaction conditions, providing a chemically-reactive conjugate that comprises a cycle nucleic acid associated with a cycle number, a reactive moiety that binds to the N-terminal amino acid of the peptide coupled to the solid support, and an immobilizing moiety for immobilization to the solid support, contacting the peptide with the chemically-reactive conjugate thereby coupling the conjugate to the N-terminal amino acid of the peptide to form a conjugate complex comprising the N-terminal amino acid bound to the reactive moiety and the cycle nucleic acid of the conjugate, wherein the cycle nucleic acid comprises a polymerizable molecule, immobilizing the conjugate complex to the solid support via the immobilizing moiety of the chemically-reactive conjugate, cleaving and thereby separating the N-terminal amino acid from the peptide to form an immobilized amino acid complex on the solid support, wherein the immobilized amino acid complex comprises the cleaved and separated N-terminal amino acid bound to the reactive moiety and the cycle nucleic acid, contacting the immobilized amino acid complex with a binding agent that comprises a binding moiety for binding to the immobilized amino acid complex and a recode tag comprising a recode nucleic acid, bringing the cycle nucleic acid on the immobilized amnio acid complex into proximity to the recode nucleic acid to transfer information of the recode nucleic acid to the cycle nucleic acid of the immobilized amino acid complex, obtaining sequence information of the amino acid comprising the polymerizable cycle nucleic acid in the immobilized amino acid complex by releasing the immobilized amino acid complex from the solid support and translocating the complex through a nanopore in a nanopore sequencing process, measuring a signal as the complex passes through the nanopore, and using the measured signal to determine an identity and positional information of the amino acid in the peptide. See paragraphs 008 and 00191 in Graige et al.
With regards to claims 4-5, Graige et al teach that the amino acid modified with the polymerizable cycle nucleic acid is cleaved from an N-terminal amino acid of the peptide. See paragraph 008 in Graige et al.
With regards to claim 6, Graige et al teach that the modified amino acid comprises a linker that is coupled to the polymerizable cycle nucleic acid, wherein the linker comprises the reactive moiety in the chemically-reactive conjugate that binds to the N-terminal amino acid of the peptide. See paragraph 008 in Graige et al.
With regards to claim 7, Graige et al teach that the linker can be covalently coupled to the polymerizable cycle nucleic acid. See paragraphs 008 and 0364 in Graige et al.
With regards to claims 12-13, Graige et al teach that the polymerizable molecule comprises a nucleic acid molecule such as DNA or RNA. See paragraph 008 in Graige et al.
With regards to claims 14-15, Graige et al teach that the nucleic acid molecule comprises a barcode sequence that comprises temporal information, wherein the barcode sequence comprises the specific sequence of the cycle nucleic acid associated with a cycle number.
With regards to claim 24, Graige et al teach that the modified amino acid can comprise a post-translational modification, and the sequencing method can identify the post-translation modification. See paragraphs 008 and 0377 in Graige et al.
With regards to claim 25, Graige et al teach that the modified amino acid can comprise a derivatized amino acid. See paragraph 008 in Graige et al.
With regards to claims 27-28, since the polymerizable molecule in the modified amino acid taught by Graige et al (a nucleic acid) is the same as one of the types of polymerizable molecules used to modify an amino acid of a protein in the instant invention, it would be expected that the nucleic acid polymerizable molecule taught by Graige et al would cause a change in a translocation velocity through a nanopore and cause an increase in a signal-to-noise ratio of the measured signal as the modified amino acid translocates through a nanopore as compared to that of an amino acid without the polymerizable molecule.
With regards to claim 29, Graige et al teach that the peptide is derived from a biological sample. See paragraph 0352 in Graige et al.
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.
Claim(s) 11, 21-23 and 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Graige et al (WO 2024/015875, submitted in the IDS filed on May 28, 2026) in view of Gundlach et al (US 2017/0199149). For a teaching of Graige et al, see previous paragraphs in this Office action.
With regards to claims 11, 21-23 and 30, Graige et al fail to teach that the nanopore sequencing of the modified amino acid comprises measuring a current signal as the modified amino acid passes through the nanopore, that the nanopore comprises a naturally-occurring or an engineered variant, that the nanopore comprises a solid state nanopore, that the nanopore sequencing occurs at or below ambient temperature, and that the modified amino acid is repeatedly passed through the nanopore.
Gundlach et al teach of a method for nanopore-based protein analysis comprising repeatedly passing amino acids in a protein through a nanopore while applying an electrical potential to the nanopore, and measuring a resulting current pattern that represents the structure and sequence of amino acids in the protein. Gundlach et al teach that the nanopore used in the sequencing method can be a solid state nanopore or a naturally-occurring biologically adapted nanopore. See the abstract and paragraphs 0007-0010, 0012, 0014 and 0016-0022 in Gundlach et al.
With regards to claim 11 and based on the combination of Graige et al and Gundlach et al, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to measure a current signal as the modified amino acid taught by Graige et al passes through a nanopore during the nanopore sequencing because Gundlach et al teach that a current signal or pattern is measured during nanopore sequencing of amino acids in a protein.
With regards to claims 21-22, and based on the combination of Graige et al and Gundlach et al, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use either a naturally occurring nanopore or a solid state nanopore in the nanopore sequencing taught by Graige et al to analyze the modified amino acid because Gundlach et al teach that both of these types of nanopores are routinely used during nanopore sequencing of amino acids in proteins.
With regards to claim 23, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the nanopore sequencing taught by Graige et al at or below ambient temperature because this would allow the sequencing to occur very quickly without having to change the temperature of the environment in which the testing takes place.
With regards to claim 30, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to repeatedly pass the modified amino acid through the nanopore in the method taught by Graige et al because doing so would produce multiple measurement signals that define a statistical error of measurement.
Claim Objections
Claims 8-10, 16-20 and 26 are 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 since the combination of the references to Graige et al and Gundlach et al fail to teach or fairly suggest each of the limitations recited in these claims in combination with the steps recited in independent claim 1.
Response to Arguments
Applicant's arguments filed May 26, 2026 have been fully considered but they are not persuasive.
The previous objections to the specification and the abstract in the last Office action mailed on March 30, 2026 have been withdrawn in view of the amendments made to the abstract and specification. The previous rejections of the claims under 35 USC 112(b) in the last Office action have also been withdrawn in view of the amendments made to the claims. The previous rejection of the claims under 35 USC 102(a)(2) as being anticipated by Estandian et al has been withdrawn in view of Applicant’s statement pursuant to 35 USC 102(b)(2)(C) that not later than the effective filing date of the claimed invention, the subject matter disclosed in Estandian et al and in the present application were owned by the same assignee, Glyphic Biotechnologies, Inc., and therefore, were owned by the same person or subject to an obligation of assignment to the same person. The previous rejections of the claims on the ground of nonstatutory double patenting have also been withdrawn in view of the proper terminal disclaimer filed on May 26, 2026.
Some of the claims are newly rejected under 35 USC 102(a)(2) as being anticipated by Graige et al (WO 2024/015875, submitted in the IDS filed on May 28, 2026), or under 35 USC 103 as being obvious over Graige et al in view of Gundlach et al (US 2017/0199149) for the reasons set forth above. This Office action is being made final since according to MPEP 706.07(a), Where information is submitted in an information disclosure statement during the period set forth in 37 CFR 1.97(c) with a fee, the examiner may use the information submitted, e.g., a printed publication or evidence of public use, and make the next Office action final whether or not the claims have been amended, provided that no other new ground of rejection which was not necessitated by amendment to the claims is introduced by the examiner. See MPEP § 609.04(b).
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 MAUREEN M WALLENHORST whose telephone number is (571)272-1266. The examiner can normally be reached on Monday-Thursday from 6:30 AM to 4:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander, can be reached at telephone number 571-272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MAUREEN WALLENHORST/Primary Examiner, Art Unit 1797 June 4, 2026
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