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 .
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on November 1st, 2022 and August 13th, 2024 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-12, in the reply filed on September 8th, 2025 is acknowledged.
Claims 13-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 September 8th, 2025.
Claim Summary
Claim 1 has been amended. Claims 1-21 are pending. Claims 13-21 are withdrawn from consideration as being drawn to a non-elected invention/species. Claims 1-12 are under examination and discussed in this Office action.
Drawings
The drawings are objected to because Figures 15A and 15B appear to have legend boxes that have been cut off. The legends are not fully legible because of this. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112(b)
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 1-12 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 1 recites the limitation “flowing a solution comprising a membrane forming material and an organic solvent through a flow channel over a well of a sequencing chip to displace a first aqueous solution from the flow channel such that the first aqueous solution remains in the well”. It is unclear from this recitation what mechanistic function is involved with the phrase “such that” as it relates to the first aqueous solution remaining in the well. As claimed, a membrane solution is flowed over a well that already contains an aqueous solution. The membrane solution would reasonably be capable of displacing the aqueous solution without further indication of what is preventing this displacement. This also brings into question how the aqueous solution was capable of getting into the well in the first place. If the membrane solution is flowed such that it does not get into the well, how does an earlier aqueous solution flow through the same flow channel such that it does get into the well. For the purpose of compact prosecution, it is interpreted that some mechanistic function of the flow channel helps with the membrane solution’s displacement of the first aqueous solution from the flow channel but not the well.
Claim 1 also recites the limitation “applying a first voltage between the working electrode and the counter electrode during the step of flowing the solution comprising the membrane forming material in order to trap a charge in the first aqueous solution in the well.” It is unclear from this recitation what exactly the charge is that is being trapped. Sources for charge can include ions and free electrons, and distribution of these sources can affect what kind of charge would be trapped. For instance, a trapped charge could be positive if more positive ions are in the well, neutral if an equal number of ions are in the well, or negative if more negative ions are in the well. This can be further influenced by the voltage applied, but ultimately any charge could reasonably be a trapped charge without further clarification. For the purpose of compact prosecution, the charge that is claimed is interpreted as charge from the ions in the aqueous solution trapped in the well.
Claims 2-12 depend from claim 1 and do not further clarify the issues noted above. Therefore, they are also rejected here. Claim 8 has further clarity issues as addressed below:
Claim 8 recites the limitation “wherein the trapped charge that is sealed in the well is configured to increase the likelihood of nanopore insertion into the membrane.” It is unclear from this recitation how a trapped charge can be configured. The ability to configure something in this context presumably means being able to change it in some way. However, it is unclear from simply saying “configured” what is being changed about the trapped charge. It is further unclear how an aspect of the trapped charge that is changed can then increase the likelihood of nanopore insertion. Without a specific “configuration”, it is unclear how there would be any effect on nanopore insertion into the membrane. Claims 9 and 10 depend from claim 8 and do not further clarify the issues noted above. Therefore, they are also rejected here.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—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 or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 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.
Claims 1-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In making a determination of whether the application complies with the written description requirement under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is claiming and what Applicant has possession of. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was “ready for patenting” such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991). See MPEP § 2163.
Claim 1 recites “[a] method, the method comprising: flowing a solution comprising a membrane forming material and an organic solvent through a flow channel over a well of a sequencing chip to displace a first aqueous solution from the flow channel such that the first aqueous solution remains in the well, the well comprising a working electrode in electrical communication with a counter electrode; applying a first voltage between the working electrode and the counter electrode during the step of flowing the solution comprising the membrane forming material in order to trap a charge in the first aqueous solution in the well; displacing the solution comprising the membrane forming material from the flow channel by flowing a second aqueous solution through the flow channel, thereby leaving a layer of membrane forming material covering the well and sealing the first aqueous solution with the trapped charge in the well; and thinning the layer of membrane forming material into a membrane capable of receiving a nanopore for a sequencing application.” The claim as written appears to embrace a method wherein charge is intentionally trapped in the first aqueous solution in a well. However, this intentional entrapment is not further defined or described in the claims.
Regarding claim 1, the specification does not clearly describe or define intentional entrapment of a charge in a well. When turning to the specification, there are many mentions of what appears to be incidental trapping of a charge during the claimed process. For instance, at paragraph [000128], it is described that “…leakage current can cause a buildup of voltage in one or more cells in the array once a membrane is placed over the cells. This trapped charge can vary in magnitude over time and between cells, making it difficult to apply a uniform voltage across all the membranes of the cells when inducing poration. For example, applying a uniform voltage (Vapp) to all the cells when varying amounts of trapped charge are present in the cells in the array…” At paragraph [000134], it is described that “[t]his effect may be mediated by voltage which may persist with a relatively long time constant due to the high resistance of the lipid and solvent, which may effectively trap charge within the wells as they are covered.” At paragraph [000138], it is described that “[a]pplying a voltage between the electrodes during the lipid dispense step may trap charge in the well so that the voltage across the bilayer or membrane that is eventually formed will not be zero even when no voltage is actively being applied by the electrodes.” Finally, at paragraph [000139], it is described that “[i]n some embodiments, if charge has been trapped in the wells, the polarity of the thinning voltage stimulus can be chosen to further increase the voltage across the membrane as the thinning voltage is applied”. This is a non-exhaustive list of examples from the specification. These cited descriptions indicate some amount of ambiguity regarding if a charge is trapped in a well or not, indicating that trapping a charge is coincidental to applying a voltage during the flowing of the membrane solution step. Therefore, it cannot be said that there is a definitive description of intentional trapping of a charge in a well as claimed. It is also noted that claims 2-12 suffer from the same issue of not providing adequate description of intentional charge trapping and are also rejected here. Based on the specification, the Applicant does not have possession of the method as claimed. Claims 1-12 do not present possession of the method as claimed and do not have support based on the specification.
Claim 8 is noted for further issues. Claim 8 recites “[t]he method of claim 1, further comprising: flowing a nanopore solution over the membrane; and inserting a nanopore into the membrane, wherein the trapped charge that is sealed in the well is configured to increase the likelihood of nanopore insertion into the membrane.” The claim as written appears to embrace a method wherein a trapped charge in a well increases the likelihood of nanopore insertion into the membrane. However, this increase likelihood is not further defined or described in the claims.
Regarding claim 8, the specification does not clearly describe or define the increased likelihood of nanopore insertion given a trapped charge. When turning to the specification, this ability is described in general terms without clear indication of a configuration related to an increased likelihood. At paragraph [000136], it is described that “[i]n some embodiments, by combining voltages and flows it is possible to obtain sufficient trapped charge and voltage to yield spontaneously thinning bilayers or membranes, and passive insertion of pores.” At paragraph [000138], it is described that “[a]s stated above, trapping charge in the well may enhance the rate of passive insertion of a pore into a bilayer or membrane (i.e., when the bilayer or membrane is formed, the likelihood of pore insertion may be increased if charged in trapped in the well during the lipid or triblock copolymer dispense step).” At paragraph [000141], it is described that “[i]n some embodiments, the trapped charge in the wells can induce nanopore insertion into the membrane in the absence of an active applied voltage between the working electrode and the counter electrode.” These cited descriptions do not give a clear description of how exactly a trapped charge is acting on nanopore insertion, nor is it described that trapped charge definitively has an effect on the likelihood of nanopore insertion. Therefore, it cannot be said that a trapped charge is truly configured to increase the likelihood of nanopore insertion in a membrane as claimed. It is also noted that claims 9 and 10 suffer from the same issue of not providing adequate description of increased likelihood of nanopore insertion as it relates to trapped charge and are also rejected here. Based on the specification, the Applicant does not have possession of the method as claimed. Claims 8-10 do not present possession of the method as
claimed and do not have support based on the specification.
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.
Claims 1-7 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Wahba (US20170283866A1), as evidenced by Semat (Physics, Chapter 28: Electrical Conduction in Liquids and Solids, Robert Katz Publications, 1958, 524-538; available at: digitalcommons.unl.edu/physicskatz/154).
Regarding instant claim 1, Wahba teaches a method, the method comprising: flowing a solution comprising a membrane forming material and an organic solvent through a flow channel over a well of a sequencing chip to displace a first aqueous solution from the flow channel such that the first aqueous solution remains in the well (Page 6, paragraph [0078]; Pages 6-7, paragraph [0083]-[0084]), the well comprising a working electrode in electrical communication with a counter electrode (Figure 5); applying a first voltage between the working electrode and the counter electrode during the step of flowing the solution comprising the membrane forming material (Page 7, paragraph [0086]); displacing the solution comprising the membrane forming material from the flow channel by flowing a second aqueous solution through the flow channel (Page 7, paragraph [0090]), thereby leaving a layer of membrane forming material covering the well and sealing the first aqueous solution in the well (Page 7, paragraph [0090]); and thinning the layer of membrane forming material into a membrane capable of receiving a nanopore for a sequencing application (Page 7, paragraph [0086]; Page 7, paragraph [0090]).
Wahba teaches that the step of flowing a second solution happens after applying a voltage for thinning the layer of membrane. However, with respect to the order of steps, it is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. Thus, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Wahba does not directly teach that a charge is trapped in the first aqueous solution in the well. However, Wahba does teach that the lipid membrane is ion-impermeable (Page 2, paragraph [0027]). Wahba also teaches that a voltage is applied for thinning of the lipid bilayer while the lipid solution is still flowing to establish the lipid bilayer (Page 7, paragraph [0086]). Wahba further teaches that the first aqueous solution contains salts (Page 6, paragraph [0082]). As evidenced by Semat, salts break down into their respective ionic components when dissolved in water (Page 525, last paragraph to Page 526, second paragraph; Figure 28-1). Furthermore, as evidenced by Semat, ions have a charge (Page 525, last paragraph to Page 526, second paragraph; Figure 28-1). Given that Wahba has a salt solution, it can reasonably be said that a charge will be present in the wells of Wahba. Once the lipid bilayer forms, which is ion-impermeable as cited earlier, the charge will be trapped in the well. Therefore, it would be obvious to one of ordinary skill in the art that Wahba inherently teaches trapping a charge in a well in their method (also see 112(b) interpretation).
Regarding instant claim 2, Wahba, as evidenced by Semat, teaches the method of claim 1. Wahba further teaches wherein the first voltage applied between the working electrode and the counter electrode has a magnitude between about 10 to 2000 mV (Page 7, paragraph [0086]).
Regarding instant claim 3, Wahba, as evidenced by Semat, teaches the method of claim 1. Wahba further teaches wherein the first voltage applied between the working electrode and the counter electrode has a magnitude between about 10 to 2000 mV (Page 7, paragraph [0086]). Wahba does not directly teach wherein the first voltage applied between the working electrode and the counter electrode has a magnitude at least about 10 mV. However, it is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. The general conditions of establishing a trapped charge, along with the other claimed method steps, are disclosed in Wahba, as analyzed above. From there, determining a suitable voltage would amount to routine optimization. Thus, the claimed voltage merely represents routine optimization of the values of the cited prior art.
Regarding instant claim 4, Wahba, as evidenced by Semat, teaches the method of claim 1. Wahba further teaches wherein the first voltage applied between the working electrode and the counter electrode has a magnitude between about 10 to 2000 mV (Page 7, paragraph [0086]). Wahba does not directly teach wherein the first voltage applied between the working electrode and the counter electrode has a magnitude at least about 100 mV. However, it is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. The general conditions of establishing a trapped charge, along with the other claimed method steps, are disclosed in Wahba, as analyzed above. From there, determining a suitable voltage would amount to routine optimization. Thus, the claimed voltage merely represents routine optimization of the values of the cited prior art.
Regarding instant claim 5, Wahba, as evidenced by Semat, teaches the method of claim 1. Wahba further teaches wherein the first voltage applied between the working electrode and the counter electrode has a magnitude between about 10 to 2000 mV (Page 7, paragraph [0086]). Wahba does not directly teach wherein the first voltage applied between the working electrode and the counter electrode has a magnitude at least about 200 mV. However, it is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. The general conditions of establishing a trapped charge, along with the other claimed method steps, are disclosed in Wahba, as analyzed above. From there, determining a suitable voltage would amount to routine optimization. Thus, the claimed voltage merely represents routine optimization of the values of the cited prior art.
Regarding instant claim 6, Wahba, as evidenced by Semat, teaches the method of claim 1. Wahba further teaches wherein the first voltage applied between the working electrode and the counter electrode has a magnitude at least about 500 mV (Page 7, paragraph [0086]).
Regarding instant claim 7, Wahba, as evidenced by Semat, teaches the method of claim 1. Wahba further teaches wherein the step of thinning the layer of membrane forming material comprises flowing a fluid over the layer of membrane forming material (Page 7, paragraph [0090]).
Regarding instant claim 11, Wahba, as evidenced by Semat, teaches the method of claim 1. Wahba further teaches wherein the sequencing chip comprises an array of wells (Pages 1-2, paragraph [0025]: array of cells; Pages 2-3, paragraph [0035]: cells contain wells).
Regarding instant claim 12, Wahba teaches the method of claim 1. Wahba does not directly teach that the first voltage is applied as a first waveform having a frequency of at least 10 to 1000 Hz. However, Wahba does teach that a voltage source, which is used to establish the voltage as cited in claim 1 (Page 4, paragraph [0046]: Voltage source Vliq…is a square wave with… a frequency between 25 and 100 Hz; Page 7, paragraph [0086]: the absolute magnitude Vliq for lipid thinning may be between 250 mV to 500 mV), can be a square wave with a frequency between 25 and 100 Hz. Therefore, it would be obvious that the voltage source as earlier cited could be applied as a first waveform having a frequency of at least 10 to 1000 Hz.
Conclusion
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allison E Schloop whose telephone number is (703)756-4597. The examiner can normally be reached Monday-Friday 8:30-5 ET.
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/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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