DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments
Status of Claims
The amendment, filed on 9 December 2025, is acknowledged.
Claims 1-5, 9, 11-18, and 20 have been amended.
Claims 10 and 19 have been cancelled.
New claims 21-25 have been added.
Claims 6-7 and 14-15 were previously withdrawn from consideration in the non-final Office Action mailed on 10 June 2025.
Claim 16 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. The election was made without traverse in the reply filed on 5 May 2025, and confirmed in the Remarks filed on 9 December 2025.
Claims 1-5, 8-9, 11-13, 17-18, and 20-25 are pending and under consideration in the instant Office Action, to the extent of the following previously elected species:
single stranded DNA (ssDNA) is the moiety delivered by the nanotube;
the specific polynucleotide attached to the nanotube is single stranded DNA; and
the specific composition of the lipid coating is dioleoylphosphatidylcholine (DOPC).
Objections Withdrawn
Objections to Specification
Applicant’s amendment to para. [0078] of the instant specification, submitted on 9 December 2025, has overcome the objection to the specification set forth in the Office Action mailed on 10 June 2025. Accordingly, the relevant objection is withdrawn.
Objections to Claims
Applicant’s amendments to claims 4 and 20, submitted on 9 December 2025, have overcome the objections to the claims set forth in the Office Action mailed on 10 June 2025. Accordingly, the relevant objections are withdrawn. Applicant’s cancellation of claim 19 has rendered the relevant objection moot.
Rejections Withdrawn
Rejections pursuant to 35 U.S.C. § 112
The rejection of claim 12 under 35 U.S.C. § 112 is withdrawn in view of Applicant’s amendment to claims 1 and 12. The rejection of claim 16 under 35 U.S.C. § 112 is rendered moot in view of the withdrawal of the claim from consideration.
Rejections pursuant to 35 U.S.C. § 103
The rejections of claims 1-5, 8-13, and 16-20 under 35 U.S.C. § 103 are withdrawn in view of Applicant’s amendments to the claims and in favor of the grounds of rejection made anew below.
Maintained Objections
Claims
Claim 18 remains objected to because of the following informalities:
Claim 18 recites “the nanotube has a length greater than a thickness of the lipid membrane” (bold added for emphasis). The Examiner believes the article “a” should be “the”, so the claim instead recites “the nanotube has a length greater than the thickness of the lipid membrane”, mirroring the amendment to claim 4 (bold added for emphasis). If the claim is intended to recite “a thickness”, the thickness to which the claim is referring would be overly broad.
Appropriate correction is required.
Response to Remarks
The Applicant’s remarks, filed on 9 December 2025, regarding the withdrawal of claim 16 are acknowledged. Instant claim 18 was amended to add the word “inserted”, but does not address the objection presented in the non-final Office Action, mailed on 10 June 2025.
New Grounds of Objection
Claim Objections
Claims 3-5 are objected to because of the following informalities:
Claims 3-5 recite “non-aggregated lipid-coated nanotube” in the second line of each claim. The word “nanotube” should be pluralized to mirror claim 1, upon which all of claims 3-5 depend, and read “non-aggregated lipid-coated nanotubes” (bold added for emphasis).
Appropriate correction is required.
New Grounds of Rejection
Claim Rejections - 35 USC § 112
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 1-5, 8-9, 11-13, 17-18, and 20 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.
Claims 1-2, 17, and 20 were amended in the response filed on 9 December 2025, to recite a “bare” nanotube. The remarks state in the Status of Claims section on pg. 7 that support may be found in para. [0062] and [0075] for the amendments. However, the referenced paragraphs disclose techniques used to characterize the nanotubes and the stability of lipid-coated nanotubes, respectively. Neither paragraph, nor any paragraph in the instant specification, disclose a “bare” nanotube, and therefore claims 1-2, 17, and 20 have been amended to introduce new matter. Claims 3-5, 8-9, 11-13, and 18 depend from claim 1 and therefore are also rejected for introducing new matter.
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 1-5, 8-9, 11-13, 17-18, and 20 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.
Claims 1-5, 8-9, 11-13, 17-18 and 20 are indefinite in reciting “bare nanotube” in claims 1, 2, 17 and 20. Neither the claims nor, the specification define the phrase “bare nanotube”, and the meaning cannot be readily ascertained by one skilled in the art. It is unclear if the phrase “bare nanotube” refers to the nanotube directly after synthesis such as its purity, or means that the structure of the nanotube is a hollow, cylindrical structure, or does the phrase mean the outer walls of the nanotube are unmodified, or the phrase is defining properties of the nanotube due to lack of functional groups, or if the phrase has some other meaning. As written, one skilled in the art would not be reasonable apprised of the metes and bounds of the claims.
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 1-5, 8, 10-13 and 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Bangera et al. (U.S. Patent Application Publication No. US 2010/0069606 A1, published on 18 March 2010, provided by Applicant in IDS filed on 17 August 2022, hereafter referred to as Bangera) in view of Noy et al. (U.S. Patent Application Publication No. US 2006/0169975 A1, published on 3 August 2006, hereafter referred to as Noy) and Konduru et al. (PLoS ONE, 2009, 4(2), e4398., hereafter referred to as Konduru).
Bangera teaches tubular nanostructures, targeted to a lipid bilayer, which can pass through the lipid bilayer to form a pore across which one or more compounds may transition, and methods of producing said tubular nanostructures (Abstract). The tubular nanostructure is described as being a carbon nanotube, boron nitride nanotube, or polymer/carbon nanotube mixture (para. [0007] and claims 13 and 17). The nanostructure is further taught to have “a length of about 1 nm to about 1500 nm, or a length of about 20 Å to about 40 Å. The nanostructure may have a diameter of about 0.5 nm to about 5 nm or a diameter of about 5 Å to about 20 Å” (para. [0007] and claims 24-27). Further, the tubular nanostructures can be inserted into the lipid bilayer singularly or in groups of 2 or more (para. [0027-0029]).
Bangera teaches that “carbon nanotubes, for example, have a tendency to form large, insoluble aggregates due to substantial van der Waals interactions. As such, solubilization techniques may be used to break up these aggregates into smaller bundles and/or individual nanotubes” (para. [0123]). Bangera follows this teaching with methods of separating nanotubes and monitoring aggregation (para. [0123]) and exemplifies these principles in Example 8, wherein an aqueous suspension of nanotubes is either sonicated or oxidized via acid to prevent aggregation, with monitoring performed via Raman spectroscopy (para. [0192]). The aqueous suspension taught by Bangera is determined to read on a suspension comprising a solvent – in this case, the solvent being water.
The method of inserting the nanostructure into the lipid bilayer of a cellular organelle is taught to involve contacting the cell with at least one tubular nanostructure, which is configured to pass through the lipid bilayer, assisted by one or more ligands bound to the nanostructure which in turn bind to one or more cognates on the lipid bilayer (para. [0012]). The one or more ligand are taught to be portions of an antibody, polynucleotide, polypeptide, protein, lipid, and other molecules (para. [0020] and claim 28).The one or more ligands are taught in Figure 1A to be bound to the end of the nanotube (130 in Fig. 1A), connected to the regions of the tube described as the hydrophilic surface regions (120 in Fig. 1A, para. [0031]). Bangera further teaches that the “[p]olynucleotide biomolecules that might be added to a tubular nanostructure include, but are not limited to, aptamers, antisense RNA, RNAi, DNA, or combinations thereof” (para. [0055]). In an alternative embodiment, the biomolecule bound to the surface of the nanostructure is taught to be a single stranded DNA (ssDNA) (para. [0055]). The instant specification does not define a “bare” nanotube with one or more lipids on an outer surface, therefore the carbon, boron nitride, or polymer/carbon mixture nanotube with lipids attached to the hydrophilic region(s) are interpreted as being equivalent the nanotubes recited in instant claim 1.
To form a pore spanning the lipid membrane, the nanostructure must pass through the two sides of the lipid membrane and is necessarily greater in length than the width of the lipid bilayer membrane (claim 10, Figure 1C). Bangera teaches that the pore “permits transit or translocation of at least one compound across the membrane of the cellular organelle” (claim 48). In Example 5, one example of a compound delivered is an aptamer, which is determined to be equivalent to the artificial ssDNA of instant claim 8, and may be “administered subsequent to administration of the tubular nanostructures…flows through the pore and through the associated lipid bilayer (para. [0171]). Finally, the pore formed by the nanostructure is taught to be capable of opening and closing in response to stimuli such as pH, temperature, or electric field change (para. [0131]).
Bangera does not teach incubating the nanostructure with the lipid bilayer to form a channel spanning the lipid bilayer nor the lipids on the exterior of the nanotubes to comprise DOPC. These deficiencies are offset by the teachings of Noy and Konduru.
Noy teaches a “lipid bilayer on a nano-template comprising a nanotube or nanowire and a lipid bilayer around the nanotube or nanowire” (Abstract). Carbon nanotubes and nanowires are taught to be important to discoveries in the fields of physics, chemistry, and materials science, but difficulties have been encountered in biological research due to the lack of biocompatibility in carbon nanotubes and nanowires (para. [0021]). To overcome these difficulties, the invention of Noy employs a phospholipid bilayer on the surface of nanotubes or nanowires, which is a “main component of biological membranes” (para. [0021]). The formation of a lipid bilayer around a carbon nanotube is taught to be difficult, in part, due to the hydrophobic nature of the nanotube surface (para. [0028]). To overcome this difficulty and obtain carbon nanotubes coated with a phospholipid bilayer, Noy teaches carbon nanotubes with a hydrophilic polymer “cushion” layer, which aid lipid bilayer stability around the nanotubes, which are subsequently surrounded by a lipid bilayer using “vesicle fusion” (para. [0028-0032] and Fig. 2). To produce the desired lipid bilayer-encapsulated carbon nanotubes, the nanotubes were incubated with lipid vesicles (para. [0032] and Fig. 2).
Konduru teaches a method of improving cell uptake of single-walled carbon nanotubes (SWCNT) by different phagocytic cells via coating the nanotubes with various phospholipids (Abstract). Carbon nanotubes that are not-functionalized are described as having poor uptake in intended cells and modifying the surface of the nanotubes is taught as a strategy to overcome this issue, including with “glycopolymers - that mimic cell surface mucin glycoproteins and facilitate carbohydrate receptor interactions – [which] have been developed to stimulate target engulfment of SWCNT by specific types of cells” (pg. 1, Introduction, para. 1). The specific method taught by Konduru involves coating carbon nanotubes with the phospholipids DOPC and 1,2-Dioleoyl-sn-Glycero-3-[Phosphor-L-Serine] (DOPS) (pg. 1, final para. – pg. 2, para. 1 and Materials and Methods, Reagents and Coating of SWCNT with phospholipids and other cargoes).
Konduru teaches that carbon nanotubes were coated with DOPC or a mixture of DOPC and DOPS by incubating the nanotubes in the presence of liposomes containing the lipids, producing similarly dispersed coatings on all nanotubes with similar physical characteristics (pg. 5, Results, Physico-chemical characterization of functionalized SWCNT). Neither of the phospholipid coated nanotubes were found to be cytotoxic (pg. 5, Results, Cytotoxicity of SWCNT). However, uptake into the interior of cells was notably higher for nanotubes coated with a mixture of DOPC and DOPS than for nanotubes coated with only DOPC (pg. 8, para. 1).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the teachings of Bangera with the teaching of Noy and Konduru to arrive at the method of claims 1-5, 8, 10-13, and 17-19 because the combination of known techniques to improve a known method produces predictable results. The teachings of Bangera provide an artisan with a method of delivering compounds across a lipid bilayer, including ssDNA, by utilizing one or more carbon nanotubes to form pores that span the thickness of said lipid bilayer. The carbon nanotube(s) of Bangera is additionally taught to comprise hydrophilic and hydrophobic regions on the exterior of the nanotube, one or more ligands bound to the end(s) of the nanotube(s), which may be a ssDNA sequence, and the preferable dimensions of said nanotube(s). However, the method of inserting the nanotube(s) into the lipid bilayer taught by Bangera involves “contacting the cell” with at least one tubular nanostructure, which is configured to pass through the lipid bilayer, assisted by one or more ligands bound to the nanostructure which in turn bind to one or more cognates on the lipid bilayer. The method of “contacting” lacks details for an artisan to create the nanotube pores across a lipid bilayer and they would subsequently be motivated to modify the method of Bangera with a method that is further detailed. The method of integrating a lipid bilayer with carbon nanotubes via incubation taught by Noy would be obvious to an artisan to try in the invention of Bangera, as Noy teaches it to be a successful method of nanotube insertion into a lipid bilayer and the nanotubes of Bangera contain hydrophilic regions, which Noy teaches to provide a “cushion” that aids lipid bilayer stability. While Noy teaches the use of polymers to achieve the hydrophilic “cushion”, a person of ordinary skill in the art would recognize that the hydrophilic regions of the nanotubes taught by Bangera would achieve the same result, even if the hydrophilicity originates from a source other than polymers.
Bangera also teaches compounds attached to the exterior of nanotubes to aid insertion into a lipid bilayer, including phospholipids, but all example phospholipids contain large polyethylene glycol chains (Bangera para. [0046]). An artisan would be motivated to try attaching DOPC phospholipids or a mixture of DOPC and DOPS phospholipids to the exterior of the carbon nanotubes because Konduru teaches that they impact the uptake of said nanotubes into cells. An artisan would have a reasonable expectation of success in modifying the insertion of carbon nanotubes into a lipid bilayer by attaching DOPC or DOPC and DOPS to the exterior of the nanotube. As a result, there is a reasonable expectation of success in arriving at the method of claims 1-5, 8, 10-13, and 17-19 in view of the teachings of Bangera, Noy, and Konduru.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Bangera (U.S. Patent Application Publication No. US 2010/0069606 A1, published on 18 March 2010, provided by Applicant in IDS filed on 17 August 2022) in view of Noy (U.S. Patent Application Publication No. US 2006/0169975 A1, published on 3 August 2006) and Konduru (PLoS ONE, 2009, 4(2), e4398.) as applied to claims 1-5, 8, 10-13, and 17-19 above, and further in view of Majumder et al. (Langmuir 2007, 23, 8624., provided by Applicant in IDS filed on 17 August 2022, hereafter referred to as Majumder).
Bangera, Noy, and Konduru teach the above and particularly relevant to claim 9, the pore formed by the nanostructure is taught to be capable of opening and closing in response to stimuli such as pH, temperature, or electric field change (Bangera, para. [0131]).
Bangera, Noy, and Konduru do not teach the delivery of ssDNA via potential difference across the nanotube. This deficiency is offset by the teachings of Majumder.
Majumder teaches “membranes composed of an array of aligned carbon nanotubes, functionalized with charged molecular tethers, [which] show voltage gated control of ionic transport through the cores of carbon nanotubes” (Abstract). Controlled and selective transport of molecules across cell walls, via biological channels, is taught to be of fundamental importance to biological processes, for example in voltage gated potassium ion channels which are vital to neural transmissions (1. Introduction, para. 1). One approach to synthetically mimicking these natural phenomena is a synthetic macromolecule channel, which spans a micelle, and responds to changes in voltage, light, and/or pH to sense chemicals or delivery drugs (1. Introduction, para. 2).
To this end, Majumder teaches carbon nanotubes with charged “gatekeeper” molecules at each end (pg. 8629, 3.2. Voltage Gated Chemical Transport, para. 4). By applying a bias, an electric field can be concentrated at the nanotube entrance, which can improve separation of molecules, as exemplified with the charged molecules methyl viologen and ruthenium (II) tris-bipyridine (Ru(bpy)3) (pg. 8629, 3.2. Voltage Gated Chemical Transport, para. 4). Majumder concludes by stating that voltage gating can be used with nanotubes for chemical separations and active drug delivery, teaching that ongoing research is investigating the use of “electrostatic gatekeeping to control the diffusion flux of addictive substances such as fentanyl or nicotine” (pg. 8630, 4. Conclusions).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the filing date of the instant application, to modify the method rendered obvious by Bangera, Noy, and Konduru with the teachings of Majumder to arrive at the method of claim 9 because the use of a technique known in the art to improve a similar method in the same way yields predictable results. Bangera taught a method of delivering molecules, including ssDNA, across a lipid bilayer via a pore formed by carbon nanotubes and further taught the pores to be capable of opening and closing in response to stimuli such as pH, temperature, or electric field change. However, Bangera did not explicitly teach applying a voltage bias across the nanotube to deliver molecules. An artisan would be motivated to apply a bias across the nanotube in view of the teachings of Majumder because the latter demonstrates that the applied voltage has utility in molecule delivery and can introduce selectivity of molecules delivered through the nanotube pore. As a result, there is a reasonable expectation of success in arriving at the method of claim 9 in view of the teachings of Bangera, Noy, and Konduru and further in view of the teachings of Majumder.
Claims 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Bangera (U.S. Patent Application Publication No. US 2010/0069606 A1, published on 18 March 2010, provided by Applicant in IDS filed on 17 August 2022) in view of Noy (U.S. Patent Application Publication No. US 2006/0169975 A1, published on 3 August 2006) and Konduru (PLoS ONE, 2009, 4(2), e4398.) as applied to claims 1-5, 8, 10-13, and 17-19 above, and further in view of Maud de Saint-Jean et al. (J. Cell Bio. 2011, 195 (6), 965., hereafter referred to as MS-J).
Bangera, Noy, and Konduru teach the above and particularly relevant to claim 16, the pore formed by the nanostructure is taught to span a lipid bilayer.
Bangera, Noy, and Konduru do not teach the composition of the lipid bilayer. This deficiency is offset by the teachings of MS-J.
MS-J teaches that sterols, biomolecules that are vital to eukaryotic cell survival, are often not synthesized in the cell compartments in which they are needed, therefore requiring transport vesicles or soluble carriers (pg. 965, Introduction, para. 1). One identified potential transport protein is the oxysterol-binding homology protein (Osh) Osh4p, which must be able to interact with and pass through two lipid bilayers (pg. 965, Introduction, para. 2 - pg. 966, Introduction, para. 1). One of the lipids with which Osh4p is taught to interact is phosphatidylinositol (PI) 4,5 bisphosphate (PI(4,5)P2), a lipid taught to be found in eukaryotic cell plasma membrane (pg. 966, Introduction, para. 2). To test the ability of Osh4p to act as a sterol exchanger, MS-J teach a number of assays involving liposome vesicles comprising a variety of lipids (pg. 966, Introduction, para. 2). The liposomes tested were made of DOPC doped with other biomolecules, including dehydroergosterol (DHE), PI 4-phosphate (PI(4)P), PI(4,5)P2, and dioleoyl phosphatidylserine (DOPS) (pg. 966-967, Results, Osh4p quickly extracts and solubilizes the fluorescent ergosterol dehydroergosterol (DHE) from neutral liposomes and Fig. 2). The lipids DOPC, DOPS, and PI(4,5)P2 were found to not inhibit DHE extraction from the liposomes by Osh4p and DOPS was found to “retain the protein [Osh4p] on the liposome surface” (pg. 967-968, Results, Effect of anionic lipids on DHE solubilization by Osh4p).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to combine the teachings of MS-J with the method rendered obvious by the teachings of Bangera, Noy, and Konduru to arrive at the method of claims 12, 16, and 21-23 because combining prior art elements according to known methods yields predictable results. An artisan would be motivated to combine the teachings of MS-J with those of Bangera, Noy, and Konduru because the latter references did not teach specific lipids in the bilayer spanned by the carbon nanotubes nor the bilayer being formed from a liposome vesicle. MS-J teaches several lipids that can form a lipid bilayer, the formation of a liposome vesicle from the lipids, and that DOPS, DOPC, and PI(4,5)P2 do not interfere with vital eukaryotic cell processes such as sterol transport. An artisan would reasonably expect that the three lipids could be used to form a biocompatible lipid bilayer across which a carbon nanotube could form a pore as a method of delivering molecules. As a result, there is a reasonable expectation of success in arriving at the method of claims 21-23 in view of the teachings of Bangera, Noy, and Konduru, and further in view of the teachings of MS-J.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Bangera (U.S. Patent Application Publication No. US 2010/0069606 A1, published on 18 March 2010, provided by Applicant in IDS filed on 17 August 2022) in view of Noy (U.S. Patent Application Publication No. US 2006/0169975 A1, published on 3 August 2006) and Konduru (PLoS ONE, 2009, 4(2), e4398.) as applied to claims 1-5, 8, 10-13, and 17-19 above, and further in view of Bakajin et al. (WIPO International Publication No. WO 2009/148959 A2, published on 10 December 2009, provided by Applicant in IDS filed on 17 August 2022, hereafter referred to as Bakajin).
Bangera, Noy, and Konduru teach the above.
Bangera, Noy, and Konduru do not teach the angle of the nanotubes with respect to a plane of the lipid bilayer membrane. This deficiency is offset by the teachings of Bakajin.
Bakajin teaches methods for embedding carbon nanotubes in a membrane for use in the fields of liquid and gas separations, chemical sensing, and fabric formation (Abstract). Utilizing aligned carbon nanotubes with chemical modifications at the openings, a membrane embedded with the nanotubes is taught to provide selective transport of desired compounds through the pores of the nanotubes (pg. 5, lines 8-12). The aligned nanotubes are defined as being “substantially parallel to each other as ‘substantially vertically aligned’ and [can] be generally or substantially perpendicular to a substrate” (pg. 11, lines 28-32). The nanotubes are also taught in some embodiments to be “substantially aligned and span the whole membrane thickness” (pg. 27, lines 7-8). Bakajin further teaches that the alignment of nanotubes “improves permeability by reducing the path length a permeable molecule has to follow to cross the entire membrane thickness” (pg. 27, lines 25-27). Substantially all of the nanotubes are taught to be vertically-aligned, in some embodiments taught to be “more than about 50%” and in other embodiments taught to be “about 100% of the carbon nanotubes” (pg. 13, lines 25-30).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the method rendered obvious by the teachings of Bangera, Noy, and Konduru with the teachings of Bakajin because combining prior art elements according to known methods yields predictable results. Bangera depicts the nanotubes of their invention to be perpendicular to the surface of the lipid bilayer they span in Fig. 1C-1D and 2B, but the angle and portion of total nanotubes aligned in such a manner are not explicitly taught. An artisan would be motivated to align the nanotubes in the method rendered obvious by Bangera, Noy, and Konduru in the manner taught by Bakajin because the latter reference teaches that such an alignment improves permeability through a membrane by reducing the path length the permeating molecule must travel. Bakajin further teaches that >50% of all nanotubes should be aligned vertically, i.e., perpendicular to the surface of the substrate, which in the instant case would be perpendicular to the surface of the lipid bilayer membrane. As a result, there is a reasonable expectation of success in arriving at the method of claim 20 in view of the teachings of Bangera, Noy, and Konduru, and further in view of the teachings of Bakajin.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Bangera (U.S. Patent Application Publication No. US 2010/0069606 A1, published on 18 March 2010, provided by Applicant in IDS filed on 17 August 2022) in view of Noy (U.S. Patent Application Publication No. US 2006/0169975 A1, published on 3 August 2006), Konduru (PLoS ONE, 2009, 4(2), e4398.), and MS-J (J. Cell Bio. 2011, 195 (6), 965.) as applied to claims 21-23 above, and further in view of Majumder (Langmuir 2007, 23, 8624., provided by Applicant in IDS filed on 17 August 2022).
Bangera, Noy, Konduru, and MS-J have been described above.
Bangera, Noy, Konduru, and MS-J do not teach the delivery of ssDNA via potential difference across the nanotube. This deficiency is offset by the teachings of Majumder.
Majumder has been described above.
It would have been prima facie obvious to a person of ordinary skill in the art, to one of ordinary skill in the art, prior to the filing date of the instant application, to modify the method rendered obvious by Bangera, Noy, Konduru, and MS-J with the teachings of Majumder to arrive at the method of claim 24 because the use of a technique known in the art to improve a similar method in the same way yields predictable results. Bangera taught a method of delivering molecules, including ssDNA, across a lipid bilayer via a pore formed by carbon nanotubes and further taught the pores to be capable of opening and closing in response to stimuli such as pH, temperature, or electric field change. However, Bangera did not explicitly teach applying a voltage bias across the nanotube to deliver molecules. An artisan would be motivated to apply a bias across the nanotube in view of the teachings of Majumder because the latter demonstrates that the applied voltage has utility in molecule delivery and can introduce selectivity of molecules delivered through the nanotube pore. As a result, there is a reasonable expectation of success in arriving at the method of claim 9 in view of the teachings of Bangera, Noy, Konduru, and MS-J, and further in view of the teachings of Majumder.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Bangera (U.S. Patent Application Publication No. US 2010/0069606 A1, published on 18 March 2010, provided by Applicant in IDS filed on 17 August 2022) in view of Noy (U.S. Patent Application Publication No. US 2006/0169975 A1, published on 3 August 2006), Konduru (PLoS ONE, 2009, 4(2), e4398.), and MS-J (J. Cell Bio. 2011, 195 (6), 965.) as applied to claims 21-23 above, and further in view of Bakajin (WIPO International Publication No. WO 2009/148959 A2, published on 10 December 2009, provided by Applicant in IDS filed on 17 August 2022).
Bangera, Noy, Konduru, and MS-J have been described above.
Bangera, Noy, Konduru, and MS-J do not teach the angle of the nanotubes with respect to a plane of the lipid bilayer membrane. This deficiency is offset by the teachings of Bakajin.
Bakajin has been described above.
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the method rendered obvious by the teachings of Bangera, Noy, Konduru, and MS-J with the teachings of Bakajin because combining prior art elements according to known methods yields predictable results. Bangera depicts the nanotubes of their invention to be perpendicular to the surface of the lipid bilayer they span in Fig. 1C-1D and 2B, but the angle and portion of total nanotubes aligned in such a manner are not explicitly taught. An artisan would be motivated to align the nanotubes in the method rendered obvious by Bangera, Noy, Konduru, and MS-J in the manner taught by Bakajin because the latter reference teaches that such an alignment improves permeability through a membrane by reducing the path length the permeating molecule must travel. Bakajin further teaches that >50% of all nanotubes should be aligned vertically, i.e., perpendicular to the surface of the substrate, which in the instant case would be perpendicular to the surface of the lipid bilayer membrane. As a result, there is a reasonable expectation of success in arriving at the method of claim 25 in view of the teachings of Bangera, Noy, Konduru, and MS-J, and further in view of the teachings of Bakajin.
Response to Arguments
The Applicant’s arguments, filed on 9 December 2025, have been fully considered but are not persuasive.
The Affidavit, filed on 9 December 2025, by Aleksandr Noy, Ph.D. (Inventor), is acknowledged. Beginning in the final para. of pg. 8 of the Remarks, the Affidavit is reproduced, therefore both will be addressed with references made to the Remarks filed on 9 December 2025.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
From para. 2 of pg. 9 to para. 1 of pg. 10, Applicant argues that the Bangera reference does not teach a lipid-coated nanotube because the nanotube of Bangera’s invention “does not have any lipids on it”. The Examiner respectfully disagrees and directs the Applicant to para. [0020] and [0031], Fig. 1A, and claim 28 of the reference, which teach that lipids may be bound to the nanotube in the regions described as hydrophilic.
Further, Applicant states that the Inventor would expect that “Bangera’s targeted tubular nanostructures would likely aggregate when put in a suspension comprising a solvent”. Bangera addresses the issue of aggregation in para. [0123], teaching that “carbon nanotubes, for example, have a tendency to form large, insoluble aggregates due to substantial van der Waals interactions. As such, solubilization techniques may be used to break up these aggregates into smaller bundles and/or individual nanotubes”, and follows with methods of separating nanotubes and monitoring aggregation. Bangera additionally exemplifies these principles in Example 8. As a result, Applicant’s argument is found to be unpersuasive.
In para. 2 of pg. 11, Applicant argues that, because the nanotube taught by the Noy reference requires a polymer “cushion” layer and is mounted on a nanotemplate device, the Noy reference does not teach the suspension recited in instant claim 1. This is not found persuasive because the rejection under 35 U.S.C. 103 did not rely upon the Noy reference to teach a suspension – the Noy reference was used for its teachings regarding incubation of nanostructures with lipid bilayers. In addition, the polymer “cushion” layer taught by Noy is a solution to the difficulty experienced in forming a lipid bilayer around a carbon nanotube due to the hydrophobic nature of the nanotube surface (Noy, para. [0028]). Noy teaches their carbon nanotubes to possess a hydrophilic polymer “cushion” layer to aid lipid bilayer stability around the nanotubes. Bangera teaches their carbon nanotubes to have hydrophilic regions and whether the hydrophilic regions arise from polymer “cushion” layers or other origins, an ordinary artisan would recognize that the presence of hydrophilic regions on the nanotubes of Bangera would address the difficulties taught by the Noy reference. Applicant is reminded that "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418, 82 USPQ2d at 1396.
Applicant argues that Majumder reference (final para. of pg. 11), Konduru reference (para. 1 of pg. 12), MS-J reference (para. 2 of pg. 12), and Bakajin reference (penultimate para. of pg. 12) do not teach a lipid-coated nanotube and/or a suspension as recited in instant claim 1. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). These references were used for their teachings regarding delivery of ssDNA via potential difference, DOPC, composition of a lipid bilayer, and angles of nanotubes with respect to the lipid bilayer, respectively. The rejection under 35 U.S.C. 103 regarding suspensions and lipid-coated nanotubes cited the Bangera and Noy references (vide supra), therefore the argument is found to be unpersuasive.
In the final para. of pg. 12, Applicant argues that the instant application is distinct from the references cited in the non-final Office Action, mailed on 10 June 2025, because only the instant invention can deliver a moiety across a lipid membrane via a channel formed via a lipid-coated nanotube. While the instant application does teach this invention in one embodiment, the combination of the references cited above render the invention prima facie obvious at the time of filing (vide supra) and the argument is not found to be persuasive.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/S.J.S./
Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619