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 .
Claim Status
Claims 1-17 and 24-26 were previously pending.
A non-final rejection office action was mailed 11 March 2026.
In response to that 11 March 2026 office action, Applicant filed an amendment/request for reconsideration received 01 June 2026, whereby claims 1, 4, 6, 7, 13-15, and 17 were amended, claims 25 and 26 cancelled, and claims 32 and 33 were added.
Therefore, claims 1-17, 24, and 32-33 are now pending. Claim 24 remains withdrawn from further consideration pursuant to the 28 October 2025 restriction/election requirement. Therefore, claims 1-17 and 32-33 are currently under examination.
Withdrawn Claim Objections/Rejections
I. Claims 4, 6-7, 13-15, and 17 were previously objected to. Applicant’s claim amendments were sufficient to overcome the aforementioned claim objections and they are hereby withdrawn.
II. Claims 1-17 were previously rejected under 35 USC 112(b). Applicant’s claim amendments were sufficient to overcome the aforementioned claim rejections and they are hereby withdrawn.
Maintained Claim Rejections
The following rejections have been maintained, only modified to
incorporate Applicant’s claim amendments, newly added claims, and claim
cancellations.
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 1-6 and 13-17 are rejected under 35 U.S.C. 103 as being unpatentable over Bangera (previously cited as: cited by Applicant on 26 April 2023 IDS as: US 2017/0173177; published: 22 June 2017).
Bangera discloses devices, compositions, and methods which provide a tubular nanostructure targeted to a lipid bilayer membrane (abstract). As it pertains to the instant application, Bangera is directed to functionalized nucleic acid nanostructures, including DNA nanotubes, that are modified with targeting ligands (e.g., antibodies), polyethylene glycol (PEG), fluorescent labels, and streptavidin/biotin systems for attachment to cells and delivery of payloads. See, e.g., [0025]-[0035], [0058]-[0065], [0088]-[0096].
Regarding instant claim 1, Bangera discloses several embodiments of devices, compositions, and methods comprising a tubular nanostructure that may include at least one ligand configured to bind to one or more cognates on the lipid bilayer membrane of a target cell as shown below:
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(Fig. 1B and abstract).
These embodiments disclosed by Bangera meet the limitations of instant claim 1:
(1) A cell: Bangera teaches contacting nucleic acid nanostructures with cells, including mammalian cells, for targeting and delivery applications (Fig. 1B, [0068]-[0072]).
(2) A nucleic acid nanotube: Bangera expressly discloses nucleic acid nanostructures, including DNA nanotubes (Fig. 3, [0031], [0239] – claim 2).
(3) The proximal end of the nanotube attached to a linker: Bangera teaches functionalization of nucleic acid nanostructures at defined locations, including termini, via chemical modifications ([0056]-[0064]). Bangera further teaches attaching targeting ligands to the nanostructure via electrostatic forces ([0065]) or streptavidin-biotin interactions ([0068], [0078]).
Terminal functionalization of DNA nanostructures for oriented attachment is a conventional design in the art and is expressly contemplated by Bangera’s disclosure of site-specific modifications. Accordingly, Bangera teaches attachment of a linker at a defined region of the nanotube, which reasonably encompasses attachment at the proximal end.
(4) A linker configured to bind a moiety located on the surface of the cell: Bangera teaches targeting cell-surface proteins using antibodies and other binding ligands conjugated to nucleic acid nanostructures ([0034], [0068]-[0071]). Bangera further teaches such ligands bind cell surface receptors ([0073]) and other surface proteins ([0071]).
Therefore, Bangera discloses embodiments of a nucleic acid nanotube proximally linked to an antibody or antibodies configured to bind to a moiety located on the surface of a cell.
Regarding instant claim 2, Bangera discloses embodiments of the DNA nanotube linked to one or more ligands wherein the ligands are configured to bind to one or more cognates associated with the lipid bilayer membrane of a target cell ([0071]). The target cell, Bangera discloses, may be a tumor cell and/or other diseased cell type in a mammalian subject ([0071]), thereby meeting the limitations set forth in instant claim 2.
Regarding instant claim 3 and as previously discussed, Bangera discloses embodiments of the nanotube that explicitly include a DNA nanotube ([0007]).
Regarding instant claim 4, Bangera discloses the hydrophilic surface region of the tubular nanotube includes polyethylene glycol (PEG) ([0033]). Bangera further discloses the PEG comprises repeating units represented by the structure (-CH2CH2O)n ([0033]), thereby meeting the limitations set forth in instant claim 4.
Regarding instant claim 5, Bangera discloses the PEG on the surface of the nanotube should have a molecular weight less than 200 kDa ([0033]). The claimed range (“approximately 20 kDa”) falls within the range disclosed by Bangera (see MPEP 2144.05(I)), which would have been a matter of routine optimization of a known variable, absent a showing of criticality. “[W]here 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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.).
Regarding instant claim 6, Bangera discloses the nanotube may be functionalized with a fluorescent marker ([0009]), which can include fluorescent dyes ([0034]) or fluorescent markers that may be used to facilitate imaging of the tubular nanostructure in association with target cells or organelles ([0103]).
Regarding instant claims 13 and 14, Bangera discloses the moiety includes one or more cell surface receptors or cells surface markers in the lipid bilayer membrane that can be a protein ([0010]). For example, the nanotube disclosed by Bangera includes ligands which bind to cognates associated with tumor cells such as: TNF receptor (a membrane receptor protein) ([0073]).
Regarding instant claims 15 and 16, Bangera discloses functionalizing the tubular nanotube with small chemical compound drugs ([0069]) linked via cross linking agents ([0070]).
Regarding instant claim 17, Bangera discloses the tubular nanostructures embodiments include devices ([0005]).
Bangera discloses embodiments of tubular nanotube attached to a moiety located on the surface of the cell. The nanotube, as disclosed by Bangera, can be selected from a DNA nanotube and further comprise each of the limitations required by instant claims 1-6 and 13-17. The difference between the applied reference and the claimed invention is that the applied references may not teach the instantly claimed method with particularity so as to amount to anticipation. See MPEP “[t]he identical invention must be shown in as complete detail as is contained in the ... claim.” Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is
not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990). Bangera discloses various embodiments of the tubular nanotube requiring the skilled artisan to choose from those embodiments to arrive at the currently claimed invention.
With that said, the applied reference discloses the elements of the claimed composition with sufficient guidance, particularity, and with a reasonable expectation of success for the skilled artisan, that the invention would have been prima facie obvious to one of ordinary skill in the art, prior to the instant effective filing date. Bangera discloses all the claim limitations with a reasonable expectation of success –it would have been obvious to pick and choose from the disclosed components, together forming embodiments of tubular nanotube compositions, because Bangera discloses successful creation of compositions from those disclosed components. Therefore, Bangera makes obvious the invention claimed in instant claims 1-6 and 13-17.
Response to Applicant Arguments
Applicant’s arguments have been considered but are not found to be persuasive.
Applicant argues that Bangera concerns insertion of a nanotube into a cell membrane, whereas the present application allegedly employs a substantially different architecture in which a nucleic acid nanotube is anchored to and extends outwardly from the cell surface. However, this argument is not commensurate in scope with claim 1.
Claim 1 does not require the nanotube remain entirely extracellular, does not exclude insertion of a portion of the nanotube into the cell membrane, and does not require the particular seeded nanotube or antibody-mediated attachment architecture as disclosed in the present specification. Claim 1 only requires that:
The composition contains a cell and a nucleic acid nanotube;
The proximal end of the nanotube be closer to the cell surface;
The proximal end of the nanotube be attached to a linker bound to a cell-surface moiety, thereby anchoring the nanotube; and
The distal end of the nanotube extends away from the cell.
Thus, the fact that Bangera permits or describes membrane insertion, does not, by itself, distinguish the claimed composition nor does it preclude a showing that Bangera’s embodiment meets the limitations of instant claim 1 regardless if that configuration occurs during the insertion process. A nanotube may interact with, or partially penetrate the membrane while still having a proximal end anchored through a linker to a cell-surface moiety and a distal portion extending away from the attachment site. Claim 1 does not recite “without penetrating the cell membrane,” “remaining entirely extracellular,” or comparable language.
Bangera teaches a DNA nanotube having an end-associated linker and a ligand that binds to a moiety on the cell surface. Once the ligand binds its cell surface cognate, the ligand/linker anchors the associated end of the nanotube to the cell surface and the remainder of the elongated nanotube projects from the attachment site and extends away from the cell surface. Bangera’s additional teaching that the nanotube may subsequently penetrate the plasma membrane, undergo endocytosis, or interact with an intracellular membrane does not negate the cell surface bound composition that exists upon ligand-cognate binding. Bangera’s membrane insertion is a potential subsequent interaction or use of the surface-targeted nanotube; it does not eliminate Bangera’s express disclosure of an embodiment meeting the limitations of instant claim 1.
If applicant intends to exclude Bangera’s membrane-interacting architecture, the claim must affirmatively recite the structural distinction, rather than relying upon unclaimed features described in the specification.
Claims 7-10 are rejected under 35 U.S.C. 103 as being unpatentable over Bangera (previously cited) as applied to claims 1-6 and 13-17 above, and further in view of Dai (previously cited as: cited by Applicant on 26 April 2023 IDS as: US 2009/0166560; published: 02 July 2009).
As discussed above, Bangera discloses a DNA nanotube attached to a linker configured to bind a moiety located on the surface of the cell via a ligand. Bangera further discloses embodiments comprised of the following:
The ligand may include at least a portion of an antibody ([0028]); the nanostructure may further include at least one second ligand configured to bind to one or more cognates on the lipid bilayer membrane ([[0010]); one or more elements further includes at least one second ligand configured to reversibly bind a cognate of interest ([0008]); and the at least one second ligand includes a monospecific antibody or bispecific antibody ([0008]).
Additionally, Bangera teaches:
A single chain antibody attached to the tubular nanostructure whereby the antibody may also incorporate streptavidin as part of the fusion protein to facilitate attachment of the antibody to the tubular nanostructure via a biotin-streptavidin linkage ([0080]);
Use of secondary antibodies and conjugation systems ([0105]-[0106]);
A bifunctional antibody that may be two or more intact antibodies that are linked to one another by chemical conjugation, crosslinking, and/or linker moieties ([0192]).
However, Bangera does not explicitly disclose the sandwiched antibody configuration with the particularity required by instant claims 7-10.
Dai discloses methods and materials including carbon nanotubes which have a strong Raman and/or fluorescent signal which have been modified with an amphiphilic molecule having available functional linking groups for linking to a biological compound (abstract).
Regarding the instantly claimed invention, Dai teaches PEG-functionalized single walled nanotubes (SWNTs), specifically analogous to the architecture of antibodies as recited in instant claim 7 as shown below:
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Dai teaches this configuration includes a goat anti-mouse antibody labeled with an SWNT ([0090]). Additionally, this formulation comprises a fluorescently-tagged cy3-conjugated donkey anti-goat antibody attached to the goat anti-mouse secondary antibody ([0025] and [0089]-[0092]). Finally, Dai teaches the disclosed nanoparticle conjugates can be used as specific probes for cell surface receptors, using specific biological labeling molecules such as antibodies ([0073]).
Regarding instant claim 8, Bangera discloses use of streptavidin protein modification to facilitate antibody attachment to the tubular nanostructure ([0065], [0080]).
Regarding instant claim 9, Bangera discloses an alternative conjugation where the nanotube may be functionalized with streptavidin by non-covalent interactions and a biotinylated antibody attaches to the nanotube via a streptavidin-biotin linkage ([0210]).
Regarding instant claim 10, Bangera discloses DNA or RNA aptamers may be linked to the nanotube via a streptavidin-biotin linkage whereby the biotin is introduced into the DNA or RNA aptamer during synthesis of the aptamer and then bound to streptavidin associated with the nanotube ([0068]).
While Bangera discloses many antibody configurations involving two antibodies attached to a tubular nanotube, Bangera does not disclose the structural configuration with specificity as required by instant claim 7. However, this structure is made obvious in view of Dai, which discloses a particular antibody configuration whereby one antibody is attached to a nanotube and another antibody, with specificity for a cell-surface receptor, is attached to that antibody. Dai’s disclosure makes obvious the particular configuration as required by instant claim 7. Bangera then discloses useful attachment and linking strategies for these two antibodies and, in addition, conjugation strategies for polynucleotide attachment to the tubular nanotube.
Therefore, regarding instant claims 7-10, it would have been obvious to one of ordinary skill in the art, prior to the instant effective filing date, to modify the attachment of two antibodies to a nanotube, as disclosed by Bangera, to mimic the attachment strategy disclosed by Dai. One would have been motivated to do so because Dai discloses use of this configuration as a fluorescent detection strategy to confirm ligand selectivity. Additionally, one of ordinary skill could easily pick and choose from the conjugation strategies disclosed by Bangera to achieve the antibody-antibody-tubular nanotube configuration disclosed by Dai to arrive at what is claimed in instant claims 8-10. This would involve one of ordinary skill using a known technique (Dai) to improve upon similar compositions (Bangera) in the same way and combining prior art elements according to known methods to yield predictable results. Therefore, instant claims 7-10 are obvious over Bangera in view of Dai.
Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Bangera (previously cited) and Dai (previously cited) as applied to claims 7-10 above, and further in view of Lu (previously cited as: “Self-assembled branched nanostructures of single-walled carbon nanotubes with DNA as linkers,” published online: 27 December 2005).
Bangera in further view of Dai renders obvious the limitations of instant claims 7-10.
While Bangera contemplates self-assembly of the nanoparticles ([0054]-[0055] and Dai contemplates SWNTs ([0018]), neither reference discloses that which is required by instant claims 11-12.
Lu discloses self-assembly of DNA functionalized single-walled carbon nanotubes (SWNTs) which form highly branched structures (abstract). The formation of the branched structures was explained by the hybridization of DNA attached to the ends and sides of SWNTs based on the DNA complementary sequence-specific pairing interactions (abstract). Lu discloses the branched structure formation was attributed to the hybridization of two complementary single-strand DNA (ssDNA) attached on SWNTs (p. 390, right column). Furthermore, Lu discloses that the interconnected degree of self-assembled SWNTs via DNA hybridization is seven times more than that of single strand DNA functionalized SWNTs (p. 390, right column).
While Bangera and Dai contemplate antibodies and polynucleotides attached to a tubular nanotube, neither reference disclosed he structural configuration of polynucleotide attachment with specificity as required by instant claims 11 and 12. However, this structure is made obvious in view of Lu, which discloses hybridization of DNA attached to the ends of SWNTs leads to self-assembly and a significantly higher interconnected degree compared to that of ssDNA functionalized SWNTs. Lu teaches this is attributed to DNA complementary sequence-specific pairing interactions.
Therefore, regarding instant claims 11-12, it would have been obvious to one of ordinary skill in the art, prior to the instant effective filing date, to modify the attachment of polynucleotide to a nanotube, as disclosed by a combination of Bangera and Dai, to mimic the attachment strategy disclosed by Lu. One would have been motivated to do so because Lu discloses this strategy produces self-assembled and highly branched SWNTs with a higher interconnected degree. Therefore, one of ordinary skill could use the strategy taught by Lu to modify the tubular nanotubes disclosed by Bangera and Dai to arrive at that which is claimed in instant claims 11 and 12 with an expectation of success. This would involve one of ordinary skill using a known technique (Lu) to improve upon similar compositions (Bangera and Dai) in the same way and combining prior art elements according to known methods to yield predictable results. Therefore, instant claims 11-12 are obvious over Bangera and Dai in view of Lu.
New rejection
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Bangera (previously cited) as applied to claims 1-6 and 13-17 above, and further in view of Mohammed (cited by Applicant on 26 April 2023 IDS as: “Directing self-assembly of DNA nanotubes using programmable seeds,” 2013).
As discussed above, Bangera teaches the composition of claim 1, including a cell-associated nanotube attached through a linker to a moiety located on the cell surface. Bangera does not expressly teach the limitations of instant claim 32, however, this is made obvious in view of Mohammed.
Mohammed teaches DNA nanotubes extending from DNA origami nanotube seeds (abstract). In particular, Mohammed teaches constructing a DNA-origami seed that functions as a nucleation template from which DNA nanotubes grow (abstract). Mohammed explains that seeds greatly accelerate nanotube nucleation and growth because they serve as nanotube nucleation templates (abstract). Mohammed further teaches that the seed may control where and when the nanotube grows (p. 4006-4008 including Figs. 1(e)-(f) and 2(c), (f), and (i). The figures and accompanying description show the seed positioned at an end of the resulting nanotube, with the nanotube extending from that seed.
It would have been obvious to a person of ordinary skill, before the effective filing date of the claimed invention, to modify Bangera’s cell-associated nucleic acid nanotube to include DNA origami nanotubes seeds taught by Mohammed at the end attached to the cell surface linker. A person of ordinary skill would be motivated to do so because Mohammed teaches that such seeds:
Provide a defined site from which nanotube growth is initiated;
Substantially increase nucleation and growth;
Permit spatial and temporal control of nanotube formation; and
Control the circumference and resulting structure of the nanotube.
When Mohammed’s seed is placed at the proximal end of the nanotube disclosed by Bangera, the seed would be attached to the linker so that the nanotube remains anchored to the cell surface moiety. This constitutes predictable use of Mohammed’s known nanotube see according to its established function of nucleating and positioning a DNA nanotube.
Therefore, the combination of Bangera and Mohammed teaches or suggests a nanotube extending from a nanotube seed located at the proximal end, with the nanotube see attached to the linker as required by instant claim 32.
New rejection
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Bangera (previously cited) as applied to claims 1-6 and 13-17 above, and further in view of Mohammed (cited by Applicant on 26 April 2023 IDS as: “Directing self-assembly of DNA nanotubes using programmable seeds,” 2013), and optionally further in view of Mohammed 2017 (cited by Applicant on 26 April 2023 IDS as: “Self-assembling nanotubes to connect molecular landmarks,” 2017).
As discussed above, Bangera teaches the composition of claim 1, including a cell-associated nanotube attached through a linker to a moiety located on the cell surface. Bangera does not expressly teach the limitations of instant claim 33, however, this is made obvious in view of Mohammed, and optionally further in view of Mohammed 2017.
Mohammed teaches micron-scale DNA nanotubes grown from DNA origami seeds as discussed in the rejection above. Figure 3(e) depicts the mean nanotube length from unseeded, 0.004 nm seeds, or 0.04 nm seeds over a period of 60 hours (p. 4009). The unseeded and seeded nanotubes reached lengths over 2 µm as depicted in Figure 3, thereby falling within the range of claim 33. See MPEP 2144.
Mohammed 2017 further teaches DNA nanotubes nucleate at fixed molecular landmarks and grow outwardly while their free ends diffuse (abstract). Mohammed 2017 teaches connecting landmark pairs separated by approximately 1-10 µm and reports DNA nanotubes capable of reaching approximately 10 µm (p. 312, 314). Thus, Mohammed 2017 expressly establishes that nucleic acid nanotubes extending at least 2 µm were known before applicant’s effective filing date.
It would have been obvious to form Bangera’s cell-associated nucleic acid nanotube with a length of at least 2 µm because Mohammed and Mohammed 2017 teach DNA nanotubes are routinely formed at micron scale lengths exceeding 2 µm. A person of ordinary skill would have selected a nanotube length sufficient to project away from the cell surface and provide the desired filament, connection, structural, or functional distance. Selecting a length of at least 2 µm from the known micron scale range as disclosed by Mohammed and Mohammed 2017 would have involved nothing more than selecting a suitable nanotube length according to the intended spatial application, with a reasonable expectation of success based on the teaches of Mohammed and Mohammed 2017.
Accordingly, the combination teaches or suggests a distance from the proximal end to the distal end of at least 2 µm as required by claim 33.
Conclusion
Claims 1-17 and 32-33 are rejected. Claim 24 remains withdrawn from consideration.
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.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Julia A. Rossi whose telephone number is (571)272-0138. The examiner can normally be reached M-Th 7:30-5:30 (MST).
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/JULIA A. ROSSI/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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