DETAILED ACTION
Claims 1-12, 16, and 17 are pending in the instant application.
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 .
Priority
The instant application claims priority to 371 of PCT/EP2022/057225 filed 03/18/2022 which claims priority to EPO 21305411.7 filed 03/31/2021.
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 05/29/2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
The information disclosure statement (IDS) submitted are in compliance with the provisions of 37 CFR 1.97, except where noted. Accordingly, the information disclosure statement was considered by the examiner. Please see attached initialed Forms 1449.
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 Interpretation
“A compacted emulsion” is an emulsion wherein the inverted micelles are compacted against each other so as to increase the surface of lipid bilayers. Any and all emulsions containing inverted micelles contacting one another meet this limitation.
Claims 11, 12 and 17 include the wording “for its use”. The intended use of the claimed composition does not further limit the claimed subject matter. It is well established that a statement of intended use generally does not distinguish a claim from the prior art where the prior art discloses the same or substantially the same structure or composition (MPEP 2111.02).
Claims 1-12 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Holden et al. (Functional Bionetworks from Nanoliter Water Droplets, JACS, 2007), Kohler et al. (Functional nanostructure of NhaA protein in tethered lipid bilayer membranes, European Biophysics Journal, 2019), Cinquin et al. (US 2010/0178592 A1), and Dibrov (Calcium transport mediated by NhaA, a Na+/H+ antiporter from E.coli, FEBS, 1993)
Holden discloses networks formed from aqueous droplets. Various protein channels and pores can be incorporated into the droplet-interface bilayer (DIB), and the application of a potential with electrodes embedded within the droplets allows ionic currents to be driven across the interface. Networks of droplets can be powered with internal “biobatteries” that use ion gradients or the light-driven proton pump bacteriorhodopsin (Abstract). Herein, we describe the creation of droplet-interface bilayer (DIB) networks as model systems (nanostructured biomimetic neuromorphic system) for the study of membrane based biological phenomena. Each droplet is a self-contained unit of a larger overall system. The interfaces between droplets are robust bilayers which enable electrical recording through incorporated membrane channels and pores for several days. The DIB networks are studied by measuring ionic currents using electrodes, which are inserted into the droplets. By rearranging the droplets in a network, the overall functional properties of the network can be changed. We used the DIB system to build functional linear and branched networks that act as wires, batteries, or light sensors. In addition, we demonstrate the utility of DIBs for high-throughput membrane protein screening (pg 8651, left col, 1st paragraph). Holden discloses the biobattery in Figure 3.
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Droplets contain alpha-hemolysin heptamer (which allows two-directional transport of ions through the pore). Holden shows micelles compacted against one another (Figure 2e below).
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Furthermore, one of ordinary skill in the art would have been motivated to use a compacted emulsion to increase the surface of lipid bilayers because Holden discloses that when droplet 2 was removed (scan, arrow 2), the current further decreased. When droplet 3 was removed, the current was abolished. Because the pores were randomly distributed in the DIBs, the magnitude of the current drop with each droplet removed varied from experiment to experiment (Figure 3, description, last 2 sentences)
Holden does not explicitly mention transmembrane protein NhaA from E. coli.
Kohler discloses a study of active membrane proteins; Kohler discloses tethered lipid bilayers (tBLMs) for biological membranes that offers a high level of control. The tBLMs were used to incorporate the NhaA protein, which is the main sodium proton antiporter of E. coli. NhaA serves to maintain sodium homeostasis and for pH control. This study provides the information to optimize the membrane/protein system regarding protein activity to enable further optimization for biomimetic fuel cells, which take advantage of NhaAs electrogenic properties (pg 2, left col, 2nd study).
Cinquin discloses a devise comprising a casing and a biomimetic artificial membrane arranged to form two distinct chambers, wherein each chamber is provided for enclosing a liquid, and wherein the biomimetic artificial membrane comprises a semi-permeable membrane for supporting a lipid membrane, the lipid membrane comprising a plurality of lipid molecules arranged in a layer and including at least a transport protein, the transport protein being adapted for transport of ions and/or molecules of the liquids between the two chambers. Cinquin discloses a first tank and a second tank with ion transporting membrane protein that exchanges at least one ion (Fig 1). Combined with Holden, one of ordinary skill in the art would immediately envisage that this system would also be possible with inverted micelles.
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Dibrov discloses that membranes of E. coli possess two Na+/H+ antiporters. NhaA is electrogenic, exchanging two protons per each sodium ion (pg 530, left col). Dibrov discloses that Rosen and co-workers identified two distinct systems exchanging protons for Na+ (or Li+) and for Ca2+ in E. coli. Data reveal a new type of NhaA activity, namely, its ability to catalyze Ca2+/H+ antiport.
Therefore, it would have been obvious to one of ordinary person in the art before the effective filing date of the claimed invention to have combined teachings of above to create a nanostructured biomimetic neuromorphic system that includes a solution comprising inverted micelles with an electrogenic antiporter such as transmembrane protein NhaA. This is taking some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Regarding claim 2, inverted micelles forming a line is taught above.
Regarding claim 3, electrogenic antiporter is taught above.
Regarding claims 4-5, NhaA protein is taught above.
Regarding claim 6, a fuel-cell with a first and second tank are taught above.
Regarding claim 7, Cinquin discloses that electrodes across the membrane detect the change in voltage or current caused by the transport of ions ([0149]). One of ordinary skill in the art would routinely insert an electrode such as a cathode or an anode for this purpose.
Regrading claims 8-10, NhaA is capable of transporting many ions including calcium ions, protons, sodium and lithium ions as taught above.
Regarding claims 11-12 and 17, the nanostructured biomimetic neuromorphic system with inverted micelles and NhaA membrane proteins could be used as voltage source for a device as Holden teaches that the system produced an electrical current as taught above. the nanostructured biomimetic neuromorphic system would sense any ionic and chemical responses of cells and tissues or provide an ionic signal to influence the biological responses of cells and tissues. Holden discloses that DIB networks containing engineered pores that mimic the channels and gap junctions found in cardiac tissue might be arranged in a three-dimensional array to simulate and study the mechanism of electrical impulse propagation. These systems could be divided into regions dedicated to specific functions that are autonomously powered by using one or several “biobatteries (pg 8654, right col, last paragraph).
Regarding claim 16, fuel-cell or biobattery is taught above.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN SEUNGJAI KWON whose telephone number is (571)272-7737. The examiner can normally be reached Mon - Fri 8:00 - 5:00.
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/JOHN SEUNGJAI KWON/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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