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 .
Status of the Claims
This action is in response to the communication of 12/23/2025
Claims 1-20 are pending.
Claims 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/23/2025
Claim Objections
Claim 14 is objected to because of the following informalities: typo. Claim should probably read “…nanostructures comprise from two to ten rods…” Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5, 14, and 7 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.
Regarding claim 5 and 14, the phrase "e.g." and “such as” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 7 recites the limitation "…via the hydrophobic moiety". There is insufficient antecedent basis for this limitation in the claim. This was interpreted to instead read as “….via a hydrophobic moiety.”
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Dietz
Claims 1, 11-12, and 16 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by:
Dietz US20230019867A1 reads on claim 1 for encapsulating a virus particle.
Regarding claim 1, Dietz teaches a macromolecule-based nanostructure, such as a DNA-based nanostructure, for encapsulating a virus or viral particle (Dietz, abstract). Dietz teaches that their particle may be a DNA-based nanostructure comprising a plurality of DNA-based building blocks (first and second nucleic acids) (Dietz, claim 1). Dietz teaches that these crosslinked by a plurality of nucleic acid staples. (Dietz [0184]). Dietz teaches that their structure is anchored to the viral particle to set anchor points on certain subunits (Dietz, [0169]). Dietz anticipates claims 1.
Regarding claim 11 and 12, Dietz teaches that their composition may encapsulate HBV, which naturally comprises a lipid-bilayer vesicle, i.e., Dietz teaches that their composition may encapsulate “a vesicle”. (Dietz, [0148]).
Regarding claim 16, Dietz teaches that their DNA nano shells may be labeled with a FRET-pair. (Dietz, [0018]). Dietz anticipates claims 16.
Shi
Claims 1-3, 7-8, 10, and 13-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Shi, Peng, et al. "DNA-templated synthesis of biomimetic cell wall for nanoencapsulation and protection of mammalian cells." Nature communications 10.1 (2019): 2223. (Provided in IDS of 1/3/2024)
Regarding claim interpretation of “nucleic acid analog” the specification provides a non-limiting definition: ‘“nucleic acid analog” can be a composition comprising a sequence of nucleobases arranged on a substrate, such as a polymeric backbone, and can bind DNA and/or RNA by hybridization by Watson-Crick, or Watson-Crick-like hydrogen bond base pairing. Non-limiting examples of common nucleic acid analogs include peptide nucleic acids (PNAs), such as γPNA, nucleic acids with modified backbones, for example as described above, morpholino nucleic acids, phosphorothioates, locked nucleic acid (2′-O-4′-C-methylene bridge, including, but not limited to, oxy, thio or amino versions thereof), unlocked nucleic acid (the C2′-C3′ bond is cleaved), 2′-O-methyl-substituted RNA, threose nucleic acid, glycol nucleic acid, etc.’ (Spec. [0107]). “
For purposes of examination, this appears to read on any polymer that comprises nucleobases, such as the DM2-alginate taught by Shi as described below.
Regarding claim 1 and 3 , Shi teaches a first plurality of nucleic acid structures anchored to a cell membrane via a Cholesterol-conjugated DNA initiator (DI anchor). (Shi, Fig 1). This first plurality of framing template is a supramolecular DNA structure comprising a DM1 hairpin DNA which functions to direct molecular assembly and crosslinking of other components, notably an alginate conjugated with a second DNA hairpin to form a DM2-alginate. (Shi, intro, last paragraph). Shi’s DNA framing template comprises DM1 hairpin DNA which hybridizes with DM2 hairpin DNA of the DM2-alginate macromer. (Shi, Results, DNA template-directed polymer assembly and crosslinking, Fig 1 attached).
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The Cholesterol-DI anchored supramolecular DNA framing template comprising DM1 DNA hairpins reads on a first plurality of nucleic acid nanostructures anchored to the cell membrane. The associated alginate-DM2 reads on a plurality of second nucleic acid analog nanostructures. These two pluralities are crosslinked to each other by DM1-DM2 hybridization, which reads on the two compositions being crosslinked by a plurality of nucleic acid staples.
Regarding claim 2, Shi teaches that their composition encapsulates a live cell. (Shi, Results, “Synthesis of BCW on mammalian cells, first paragraph).
Regarding claim 7 and 8, Shi teaches that the membrane anchored framing template is comprised of a dsDNA strand anchored to the cell membrane with a cholesterol-conjugated DNA initiator, (i.e., the DNA is a hydrophilic moiety, and the cholesterol is a hydrophobic moiety) was inserted into the lipid bilayer. Shi goes on to teach that this insertion would be sufficient for the immobilization of DNA initiators and the initiation of HCR since membrane lipids are the major components in the plasma membrane. (Shi, Results, “Synthesis of BCW on mammalian cells, first paragraph).
Regarding claim 10, Shi uses a CCRF-CEM cell line, which are human T lymphoblasts. (Shi, Results, “Synthesis of BCW on mammalian cells, first paragraph).
Regarding claim 13, the specification does not recite a limiting definition for a “nanostructure beam”. The specification does recite that “The structures, such as beams, …described herein, comprise ordered nucleic acid or nucleic acid analogs, and are referred to herein as nucleic acid and/or nucleic acid analog nanostructure (e.g., DNA nanostructure), produced from nucleic acids (including modified nucleic acids) and/or nucleic acid analogs. Nucleic acid and/or nucleic acid analog nanostructures may be nucleic acid and/or nucleic acid analog origami (e.g., DNA origami) structures or tiled structures.” (Spec. [0146]). Or in other words, a nanostructure beam may be comprised of any nucleic acid.
In paragraph [0150] The specification recites that “A beam may be a single rod nucleic acid nanostructure, or may be a larger bundle of rods, e.g. a tube, formed from a bundle of single rods, such as from 2-20 rods.” “Rod” is also not defined in the spec. Paragraph [0151] recites examples that the second nucleic acid and/or nucleic acid analog nanostructure may be a beam comprising from two to ten rods (e.g., helical nucleic acid and/or nucleic acid analog bundles). It appears that in many instances where a “rod” is mentioned, a helix is given for sake of example. (Spec [159-160]). But again, this does not appear to be a limiting example.
However, these are not phrased as limiting examples. Nonlimiting examples of diameters for the rods are given in paragraph [0152], but again, in non-limiting language “The beams may comprise a diameter of…”.
For purposes of examination, any nucleic acid sequence, or nucleic acid analog, and especially but not necessarily if it is composed in a helix shape, must be considered to be a “rod”. For example, a ssDNA strand is considered to be a “beam” consisting of one “rod” of ssDNA. A double strand of DNA is considered to be a “beam” of two “rods” of ssDNA. Shi’s DNA-templated crosslinked alginate also qualifies as a “nanostructure beam” as it is a nucleic acid analog. Shi’s alginate forms a complex with polylysine which Shi appears to represent as the alginate possessing a helical structure (Fig 1, red) and then the alginate and polylysine also possesses a helical structure and they appear to be depicted as winding around each other (Fig 1, red and blue) . (Shi, Fig. 1, zoomed in figures below ). This reads on the claimed “nanostructure beam.”
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Shi’s BCW reads on claim 13.
Regarding claim 14, Shi’s supramolecular dsDNA template strands are considered to be “beams” composed of two “rods” of ssDNA.
Regarding claim 15, Shi’s supramolecular dsDNA template strands are anchored at an end to the cell via the cholesterol-DI.
Gao
Claims 1-7 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Gao, Tao, et al. "Design and fabrication of flexible DNA polymer cocoons to encapsulate live cells." Nature Communications 10.1 (2019): 2946.
As evidenced by Rothemund (Rothemund, Paul WK. "Folding DNA to create nanoscale shapes and patterns." Nature 440.7082 (2006): 297-302)
As evidenced by Gao 2017 (Gao, Tao, et al. "Ultrasensitive quantitation of plasma membrane proteins via is RTA." Analytical chemistry 89.20 (2017): 10776-10782.)
Regarding claim 1, Gao teaches what they describe as a flexible DNA polymer cocoon to encapsulate live cells. (Gao, Title, Abstract). Gao teaches that their DNA polymer is composed of a first plurality of nucleic acid nanostructures called longitudinal DNA or LonDNA. These re generated from initiating primers (IP) which are anchored to the cell membrane, thus the LonDNA is also anchored to the cell membrane. Gao then introduces a second plurality of single-stranded DNA nanostructures called the latitude DNA or LatDNA. Gao’s LonDNA and LatDNA are automatically cross-assembled during the replication processes, and the DNA cocoon is thus fabricated in situ at the cell surface. (Gao, Fig 1 attached, Results, “Principles of isDOP”, second para).
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Regarding the nucleic acid staple limitation, Gao does not specifically use the word “nucleic acid staple” to describe the crosslinked DNA nanostructures. The specification does not give a specific definition of a nucleic acid staple, so the prior art is relied on to define the term. It appears that the broadest reasonable interpretation of a staple strand is a shorter DNA strand or strands designed to bind to specific sequences on a scaffold strand, dictating its folding. (Rothemund, Paul WK. "Folding DNA to create nanoscale shapes and patterns." Nature 440.7082 (2006): 297-302.).
In this case, the LatDNA appears to serve as a nucleic acid staple as well as forming the second nucleic acid nanostructure. The LatDNA branches and connects the adjoining LonDNA, binding specific sequences, and apparently dictates the polymer structure.
Gao anticipates a ruggedized cell comprising a live cell, a shell comprising a plurality of first nucleic acid nanostructures anchored to the cell, and a plurality of second nucleic acid nanostructures cross-linking (crossed linked to) the first nucleic acid nanostructures by a plurality of nucleic acid staples. That is, the “staple” part of the LatDNA is considered to be the portion of the LatDNA that binds the LonDNA, and the part of the LonDNA that binds the Lat DNA. (circled area below with red arrow appears to qualify as the “staple”).
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Regarding claim 2, Gao teaches the coating of bacteria, yeast, and mammalian cells (Gao, abstract).
Regarding claim 3, Gao’s nanostructures are a combination of two different pluralities of crosslinked ssDNA (LatDNA and LonDNA), thus Gao reads on the “beam” limitations of claim 3.
Gao teaches a live cell, a plurality of first nucleic acid nanostructure beams anchored to the cell, the beams comprising one or more single stranded scaffold nucleic acids (LonDNA). Gao teaches nucleic acid staples attached to the plurality of first nucleic acid nanostructure beams and nucleic acid staples attached to the plurality of second nucleic acid nanostructures (LatDNA crosslinked to LonDNA). Gao teaches the nucleic acid staples attached to the plurality of second nucleic acid analog structures are complementary to regions on the first plurality of nucleic acids. (LatDNA / LonDNA staple region) (Gao, Results, Fig 1). Gao teaches that the plurality of second nucleic acid nanostructures (LatDNA) are linked to the first plurality of nucleic acid nanostructure beams (LonDNA) by staples and which cross-link two or more of the first nanostructures to the second nanostructure (where the LatDNA and LonDNA bind).
Regarding claim 4 and 5, Gao teaches that to enable DNA polymerization directly on the cells, the IP has been attached to the cell surface by employing the cell walls and membrane compounds as the anchor sites. Gao doesn’t go into great detail about precisely what their DNA structure is anchored to in the cell membrane, but when Gao does discuss how this anchorage takes place, they refer to another article (Gao 2017). “To assemble the DNA network at cell surface, we have performed in situ DNA-orientated polymerization (isDOP) (Fig. 1b). Here, the initiating primer (IP) is attached to cell membrane (Gao here refers to Gao 2017 and a second article) , so isDOP is started at the site of IP” (Gao, Results, second paragraph).
Gao 2017 teaches the use of a primer/aptamer nucleic acid, where the aptamer end binds selectively to a target protein embedded in the cell membrane (i.e., a protein that is part of the glycocalyx) in order to label the target protein. (Gao 2017, Scheme 1, Figure 1)
Regarding claim 6, “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted)I)).
The end product of claim 2 is anticipated by Gao, and does not appear to be materially different from the end product arrived at via click chemistry or other reaction method. Thus, the product taught by Gao also anticipates claim 6.
Regarding claim 7, Gao, referring to Gao 2017 teaches anchoring their first plurality of nucleic acid nanostructures to proteins located at the plasma membrane. Gao 2017 lists a few example membrane proteins (MUC1, EpCAM, and HER2) to demonstrate the effectiveness of aptamer-primer probes. So, Gao’s first nucleic acid nanostructure is linked to a hydrophilic primer end of the aptamer-primer. Then the aptamer is bound to the membrane proteins, which possess hydrophobic moieties to remain within the cell membrane.
So, Gao teaches that the plurality of first nucleic acid nanostructures is linked to a hydrophilic moiety, and are anchored to the lipid bilayer membrane of the cell via a hydrophobic moiety.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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.
Gao
Gao (Gao, Tao, et al. "Design and fabrication of flexible DNA polymer cocoons to encapsulate live cells." Nature Communications 10.1 (2019): 2946).
As evidenced by Gao 2017 (Gao, Tao, et al. "Ultrasensitive quantitation of plasma membrane proteins via is RTA." Analytical chemistry 89.20 (2017): 10776-10782.)
As evidenced by Brown (Brown, Dennis, and Gerald L. Waneck. "Glycosyl-phosphatidylinositol-anchored membrane proteins." Journal of the American Society of Nephrology 3.4 (1992): 895-906)
Claims 1-7 are rejected as being anticipated by Gao.
Regarding claim 9, Gao teaches that the plurality of first nucleic acid nanostructures may be linked to plasma membrane proteins, and refers to Gao 2017 as the method for anchoring those nucleic acid nanostructures. Gao lists some proof-of-concept proteins (MUC1, EpCAM, and HER2), but none of them possess a fatty acid or cholesterol moiety or more specifically a GPI moiety. (Gao 2017, pg. 10777 left column, second paragraph). Gao 2017 seems more interested in just demonstrating that their aptamer-primer marker can bind a membrane protein and quantify their expression in living cells, instead of being concerned with the specific hydrophobic regions of those target membrane proteins. In other words, Gao 2017 suggests that they have developed a robust method for quantitating/labeling/ virtually any PMP (Gao 2017, Conclusion), whether the target PMP possess a GPI/ cholesterol/fatty acid moiety or otherwise.
Glycosylphosphatidylinositol (GPI)-anchored proteins are a class of eukaryotic membrane proteins covalently attached to the cell surface via a glycolipid, rather than a traditional transmembrane domain. GPI is a common anchor for naturally-occuring membrane proteins. (Brown, Dennis, and Gerald L. Waneck. "Glycosyl-phosphatidylinositol-anchored membrane proteins." Journal of the American Society of Nephrology 3.4 (1992): 895-906.)
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to elect to anchor Gao’s composition to a membrane protein anchored with a GPI. One of ordinary skill in the art would have been motivated to do so, since such a combination would be combining prior art elements according to known methods to yield predictable results. (MPEP 2143(I)(A)). An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)
Gao teaches the known method of anchoring/labeling essentially any membrane protein. GPI-anchored proteins are known in the art to be a commonly-occuring motif in membrane-bound proteins. Electing to anchor Gao’s composition to a GPI-anchored with Gao 2017’s aptamer-primer would have the predictable result of anchoring the composition to such a protein, regardless of how it may be anchored to the membrane.
One of ordinary skill in the art would have had a reasonable expectation of success, since Gao/Gao 2017 appears to suggest that virtually any membrane protein would suffice as an anchor for their composition.
Conclusion
Claim 14 is objected to.
Claims 1-16 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THOMAS RUSSE AMICK whose telephone number is (571)272-5474. The examiner can normally be reached 7:30-5 M-F.
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/THOMAS R. AMICK/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638