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 .
Election/Restrictions
Applicant’s election without traverse of Group II in the reply filed on February 24, 2026 is acknowledged.
Claims 7, 8, 12, 43, and 62 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 24, 2026.
Information Disclosure Statement
The IDS received on February 8, 2024 is proper and is being considered by the Examiner.
Drawings
The drawings received on November 28, 2023 are acceptable.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
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.
Claims 15, 16, 18, 19, 21, 22, 27, 30, 31, 35, 37, 39, and 41 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, 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.
Claim 14 is indefinite because the claim sets forth various elements of a method without reciting their structural relations, rendering the claimed steps being incoherent. For example, the claim recites that a polymerase with a first polynucleotide, a second polynucleotide and a fluid comprising a first nucleotide coupled to a first fluorophore. The actual method, however, must be performed in a chamber comprising a fluid (or buffer/reagent), wherein the polymerase, the first, the second, and the first fluorophore are comprised therein. As well, the method recites the step of inhibiting a current flow across a barrier. However, the claim does not set how the barrier is structurally configured so as to inhibit a current flow.
As well, a polymerase is simply recited as being utilized in the method. However, the polymerase must at least be located proximate to the barrier in order for the ionophores to allow a current across the barrier. None of such configurations are recited in the claim. While minor elements are not required, some elements and their structural relationships should be recited in order for the recited steps to be coherent in achieving the outcome of the preamble.
MPEP 2106(II)(C) states that while it is appropriate to use the specification to determine what applicant intends a term to mean, a positive limitation from the specification cannot be read into a claim that does not impose that limitation.
For the same reason, claims 37 and 39 that recite the use of electrode(s) (without reciting how the electrodes are structurally related) renders the claim vague and indefinite and incoherent.
Claims 15, 16, 18, 19, 21, 22, 27, 30, 31, 35, 37, 39, and 41 are indefinite by way of their dependency on claim 14.
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.
Claims 14-16, 18, 19, 21, 22, 27, 30, 31, 35, 37, 39, and 41 are rejected under 35 U.S.C. 103 as being obvious over Moon et al. (WO 2022/212038 A1, published October 6, 2022, priority March 2021).
The applied reference has a common inventor (Boyanov) and assignee (Illumina) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
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With regard to claim 14, Moon et al. teach the below configuration for producing a sequence of a target molecule (from Fig. 3):
As shown, Moon et al. teach providing a barrier (or membrane), the step of contacting a polymerase (element 3010, also “single polymerase 3010 may be anchored into the membrane 3020”, section [0083]) with a first polynucleotide (element 3002), with a second polynucleotide (element 3001), and a fluid comprising a first nucleotide coupled to a first ionophore (element 3031 and 3003, respectively).
The artisans teach that when the primer (or the second polynucleotide) is extended with the nucleotide (3003) along the template sequence (or first polynucleotide), the ionophore (3031) aligns with another ionophore within the membrane (3030), allowing the current to flow (see 3040, also “polymerase may interact with a template polynucleotide 3002 and a primer 3001, which may not pass through the pore …Gamma phosphate labeled nucleotide 3003 may be attached to the other half of the gramicidin dimer (gA) 3031 … When the nucleotide sits in the polymerase active site, a dimer 3040 may be formed from the two halves of the gramicin opening up a nanopre or ion channel permitting current 3050 to flow”, section [0083]); and
Identifying the first nucleotide using an electrical characteristic of the first ionophore (“[t]o read out the identity of the labeled nucleotide, the disclosed method can apply an AC voltage … determine the unique identity of the labeled nucleotide”, section [0083]).
With regard to claim 15, the artisans teach that gramicidin peptide sequences can be modified to affect the current flow as well as the voltage (see above, also “[s]imple modifications to the gramicidin peptide sequence may affect the current flow, so four different modifications can permit four different signals”, section [0083]).
With regard to claim, the artisans teach decoupling the polymerase, the first ionophore from the first nucleotide and diffusing the decoupled first ionophore away from the barrier (“after the gammaphosphate linkage is cleaved, gA will diffuse away into the bulk”, section [0083]).
With regard to claim 19, the barrier comprises second ionophore to which the first ionophore becomes coupled to provide the first current flow across the barrier (element 3030 is the second ionophore that is embedded within the membrane, and element 3031 is from the ionophore coupled to the nucleotide “T”, the two bind together to form a channel through which current (element 3050) flows.
With regard to claim 21, when polymerase cleaves the bond that coupled the nucleotide and the ionophore (i.e., 3031), the ionophore diffuses away (“after the gammaphosphate linkage is cleaved, gA will diffuse away into the bulk”, section [0083]), which results in closing of the channel that formed in the barrier (or membrane) and blockage of the current.
With regard to claim 22, the ionophore is gA (or gramicidin A, see above, also “gramicidin A”, section [0176]).
With regard to claims 27 and 30, the barrier comprises an electrical insulator (which is lipid membrane itself, “membrane 3020 … may be a lipid monolayer or a lipid bilayer”, section [0083]), and the first ionophore inserts into a layer of the lipid bilayer membrane (see 3031 inserting into the membrane 3020 above).
While the artisans explicitly teach that the coupling of the ionophores (elements 3031 and 3030) results in the formation of a channel through which current is rendered to flow, the artisans do not explicitly teach that the membrane inhibits current flow.
While artisans explicitly teach that various characteristics that pertain to the current generated is determinant of a nucleotide incorporation, the artisans do not explicitly teach that a temporal duration of the first current flow is examined (claim 16).
While artisans explicitly teach the use of four different nucleotides can be used in conjunction with modifications to gramicidin sequence to produce distinguishable signals of each nucleotide, the artisans do not explicitly teach the step of performing the reaction by utilizing additional nucleotides, their incorporation and the examination of the current characteristics produced therefrom (claim 31 and 35).
While artisan explicitly teach that a current flows from one portion to the next portion through the barrier, the artisans do not explicitly teach that electrodes are utilized (claims 37 and 39) via an external circuit (claims 39 and 41).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to take the teachings of Moon et al. and arrive at the invention as claimed based on common sense of the artisan in the field of molecular diagnostics involving sequencers/sensors for the following reasons.
Preliminarily, while the artisans did not explicitly teach that the membrane inhibits current flow, such would have been an obvious implication based on the artisans stating the current is allowed to flow when the ionophores couple to provide a channel through which a current is made to “flow”.
With regard to providing an external circuit that control the electrodes that operates with a membrane intervening two different chambers, Moon et al. evidence that such is a well-known configuration (see Fig. 6):
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As seen, a membrane 6003 that intervenes two chambers 6002 and 6006 is configured with an external circuit control (6001) and two electrodes (top portion and bottom portion connected to the chamber), one of ordinary skill in the art would have been well-aware that for the current to be generated between the two chambers of the embodiment discussed by Moon et al. above would have required an external circuit and means (i.e., electrodes) by which the current could be generated.
As to repeating the sequencing reaction with the different sets of nucleotides that are tagged with different ionophores and examining their respective electrical current characteristics, such as temporal duration of the current, amplitude, etc., such would also have been an obvious step. This is because the sequencing reaction disclosed by Moon et al. was a sequencing-by-synthesis reaction, wherein the nucleotide being incorporated is tied to a unique electrical current characteristic that can be distinguished from that of different nucleotides. Therefore, ordinary skill in the art would have been motivated to employ different gramicidin peptides with different nucleotide, so as to produce a unique electrical current property that relate to each nucleotide, allowing for the sequence of the template polynucleotide to be deduced, yielding no more than a predictable outcome.
In KSR, the Supreme Court particularly emphasized “the need for caution in granting a patent based on the combination of elements found in the prior art,” Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.”
Conclusion
No claims are allowed.
Moon et al. is the closest prior art. Applicants are encouraged to overcome the 112b rejection and the prior art rejection based the 102(b)(2)(A)/(C) exception.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 March 23, 2026
/YJK/