DETAILED ACTION
Applicant’s response filed 1/22/2026 has been received and entered into the application file. Applicant’s arguments and amendments to the claims have been fully considered.
Claims 1, 3-5, 7-8, 10, 12-13, 15-16, 18-19, 21, 23-27, 29-37, 39-45, and 47-51 from the claim set filed 1/22/2026 are pending. Examiner acknowledges claims 2, 6, 9, 11, 14, 17, 20, 22, 28, 38, and 46 were previously canceled. Claims 1 and 18-19 have been amended. Claims 4-5, 7-8, 10, 12, 33, 35-36, 40, 44-45, and 47 are withdrawn. Thus, claims 1, 3, 13, 15-16, 18-19, 21, 23-27, 29-32, 34, 37, 39, 41-43, and 48-51 are being examined on the merits herein.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/6/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
REJECTION(S) MAINTAINED/UPDATED FOR AMENDMENT
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RESPONSE TO APPLICANT REMARKS
Claim Rejections - 35 USC § 102
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.
RE: Claims 1, 3, 13, and 15 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Guo (US 2019 / 0127739 A1, published May 2, 2019, EFD Aug 26, 2016; PTO 892).
Applicant amended claim 1 to now require “wherein the cargo comprises one or more guide molecules, and wherein the one or more guide molecules are part of the structure of the nucleic acid assembly.”
Applicant remarks (p11) state Guo does not teach or suggest a composition comprising a nucleic acid assembly with guide molecules as the cargo and further, amended claim 1 is distinguished from Gou in that Guo fails to teach or suggest a composition wherein guide molecules that serve as cargo are also part of the nucleic acid assembly structure. Applicant remarks state Guo’s teachings are limited to conventional encapsulation approaches where cargo remains separate and distinct from the structural components of the nanocage. Amended claim 1 requires guide molecules that function dually as both cargo and integral structural components of the nucleic acid assembly.
Examiner respectfully notes Guo teaches the RNA nanocages can contain one or more cargo compounds and the cargo compounds can be DNA, RNA, amino acids, antibodies, aptamers, ribozymes, guide sequences for ribozymes, etc [0110]. Thus, Guo teaches wherein the cargo comprises guide sequences, as required by the current language of claim 1.
In addition, Guo teaches the RNA nanocage can include one or more functional moieties and said moieties can facilitate targeting the RNA nanocage (i.e., said moieties are targeting moieties) to a specific cell-type, tissue-type, organ or locale [0103]. Guo teaches said targeting moieties may be an aptamer, a ribozyme, an antibody, an RNA molecule, a DNA molecule, etc [0103].
Thus, the functional targeting moiety of Guo and the cargo molecule of Guo may be one and the same, i.e., a ribozyme with a guide sequence, i.e., a guide sequence.
Moreover, Examiner respectfully notes Guo teaches said functional moieties may be integrated into an RNA strand that form the RNA nanocage [0103]. This reads on “are part of the structure of the nucleic acid assembly”. Further, Guo teaches the cargo compounds can be linked to the RNA nanocage [0109]. This reads on “are part of the structure of the nucleic acid assembly”.
Therefore, Guo teaches “wherein the cargo comprises one or more guide molecules, and wherein the one or more guide molecules are part of the structure of the nucleic acid assembly.”
Thus, Guo teaches the newly added limitation of claim 1.
Therefore, the previously filed rejections are maintained and updated below for amendment. As solely claim 1 has been amended, Examiner has not included the previously filed rejections of claims13 and 15. Please see the previously filed OA (9/6/2025) for the rejections of said claims. As claim 3 is included in the rejection of claim 1, the claim 3 rejection is thus included below. In addition, Applicant amendment added new claim 51 which is included below.
Claims 1, 3, 13, 15, and 51 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Guo.
In regards to claims 1 and 3, Guo teaches of 3D cage molecules, wherein the cage molecule is composed of RNA (i.e., said 3D cage is a nucleic acid assembly comprising RNA). Guo further teaches of compositions including said 3D cages (Abstract). Guo teaches the RNA cages are RNA tetrahedrons [0012]. Guo further teaches the RNA nanocage can be any desired 3D shape and specifically contemplated herein are prisms as well as tetrahedrons, cubes, and dodecahedrons. One of ordinary skill in the art will appreciate other 3D structures in view of this disclosure [0095].
Per the instant specification (p24, line30-32), platonic polyhedrons include polyhedrons with multiple faces, for example, 4 faces (tetrahedron), 6 faces (cube or hexahedron), 8 faces (octahedron), and 12 faces (dodecahedron). Therefore, Guo teaches of platonic polyhedrons.
Thus, Guo teaches of claim 1(a).
Guo teaches of RNA nanocages that are able to encapsulate a cargo molecule (i.e., said cargo molecule is enclosed and/or protected by said nanocage) [0094]. Guo further teaches of RNA 3D nanocages for loading and protection of small RNAs and model drugs (Example 2). Guo teaches of placing, for example, RNA MGA (i.e., cargo) within a container (i.e., 3D cage) that will protect the RNA from a degrading environment and further teaches that the need for protection is a common problem among many small RNAs and small molecule drugs with therapeutic utility [0273]. Guo teaches that due to the programmable nature of the RNA prism, the size of the nanocontainer can be adjusted by simply increasing or decreasing the sides of the prism by complete helical turns. This is advantageous as the capacity of the RNA nanocontainer can be controlled enabling encapsulation of diverse size biomolecules or inorganic nanoparticles, as well as increase the payload of a single nanocontainer for increased detection sensitivity and increased efficacy in the treatment of disease. Moreover, from a medical point of view, size alteration of the nanocage imparts differences in toxicity, cellular binding and internalization, renal clearance, physicochemical features, as well as pharmacokinetics and pharmacodynamics profiles. As such, the prismoidal nanocontainer provides
a unique system to further exploit these factors [0282].
Per the instant specification (p7), in some forms, the defined stoichiometric ratio of the cargo molecules is based on a desired relative effect of the cargo molecules. Further, per the instant specification (p16), the sequence-specific functionalization of nucleic acid assemblies provides stoichiometric and spatial control over delivered cargo, targeting ligands and other modalities. Additionally, the instant specification teaches (p73) that “Such systems and components are benefited by protection and delivery in defined stoichiometric ratios. Cargo that includes more than one cargo molecule, whether part of a
multicomponent cargo or not, can be attached to a nucleic acid assembly in a defined stoichiometric ratio. A defined stoichiometric ratio can be any stoichiometric ratio of
interest. Preferred forms of stoichiometric ratios include functional stoichiometric ratios and relative effect stoichiometric ratios. As used here, a functional stoichiometric ratio is a stoichiometric ratio at which the components function together. For example, CRISPR-Cas effector proteins, guides (such as sgRNAs), and HDR templates typically function at a 1:1:1 ratio and so a 1:1:1 ratio of a CRISPR-Cas effector protein, a guide for a target, and an HDR template for that target is a functional stoichiometric ratio for these components.”
Thus, it is inherent that the cargo of Guo is enclosed and/or protected by the nucleic acid assembly in a defined stoichiometric ratio as Guo teaches of RNA 3D nanocages for loading and protection of small RNAs and model drugs (Example 2) and Guo further teaches of placing, for example, RNA MGA (i.e., cargo) within a container (i.e., 3D cage) that will protect the RNA from a degrading environment and additionally teaches that the need for protection is a common problem among many small RNAs and small molecule drugs with therapeutic utility [0273].
Thus, Gou teaches of claim 1(b).
In regards to the newly added limitation “wherein the cargo comprises one or more guide molecules, and wherein the one or more guide molecules are part of the structure of the nucleic acid assembly”, Examiner respectfully notes Guo teaches the RNA nanocages can contain one or more cargo compounds and the cargo compounds can be DNA, RNA, amino acids, antibodies, aptamers, ribozymes, guide sequences for ribozymes, etc [0110]. Thus, Guo teaches wherein the cargo comprises guide sequences, as required by the current language of claim 1.
In addition, Guo teaches the RNA nanocage can include one or more functional moieties and said moieties can facilitate targeting the RNA nanocage (i.e., said moieties are targeting moieties) to a specific cell-type, tissue-type, organ or locale [0103]. Guo teaches said targeting moieties may be an aptamer, a ribozyme, an antibody, an RNA molecule, a DNA molecule, etc [0103].
Thus, the functional targeting moiety of Guo and the cargo molecule of Guo may be the same molecule, i.e., a ribozyme with a guide sequence, i.e., a guide sequence.
Moreover, Examiner respectfully notes Guo teaches said functional moieties may be integrated into an RNA strand that form the RNA nanocage [0103]. This reads on “are part of the structure of the nucleic acid assembly”. Further, Guo teaches the cargo compounds can be linked to the RNA nanocage [0109]. This reads on “are part of the structure of the nucleic acid assembly”.
Therefore, Guo teaches “wherein the cargo comprises one or more guide molecules, and wherein the one or more guide molecules are part of the structure of the nucleic acid assembly.”
Thus, Guo teaches the newly added limitation of claim 1.
Therefore, claims 1 and 3 are anticipated and are properly rejected.
In regards to newly added claim 51, Guo teaches the composition of claim 1. Further, Guo teaches wherein the guide molecules are part of one or more staples of the nucleic acid assembly. As discussed supra in regards to claim 1, Guo teaches of guide molecule, i.e., guide sequences for ribozymes. Further, Guo teaches said functional moieties (i.e., guide sequences for ribozymes) may be integrated into an RNA strand that form the RNA nanocage [0103]. This reads on “wherein the guide molecules are part of one or more staples of the nucleic acid assembly”. Further, Guo teaches the cargo compounds (i.e., guide sequences for ribozymes) can be linked to the RNA nanocage [0109]. This reads on “wherein the guide molecules are part of one or more staples of the nucleic acid assembly”.
Thus, the claim is anticipated and is properly rejected.
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.
RE: Claims 16, 18-19, 21, 23, 24, 32, 34, 37, 39, 41-43, and 48-50 are rejected under 103 as being obvious over Guo in view of Sun.
RE: Claims 25, 26, and 30 are rejected under 35 U.S.C. 103 as being obvious over Guo, in view of Sun, and further in view of Shen.
RE: Claim 29 is rejected under 35 U.S.C. 103 as being obvious over Guo, in view of Sun, and in further view of Jacobi, as evidenced by IDT.
RE: Claim 31 is rejected under 35 U.S.C. 103 as being obvious over Guo in view of Sun, and in further view of Zhang.
Applicant remarks (p12) address two main points:
There is no motivation to combine Guo and Sun and Examiner relies on impermissible hindsight.
Applicant further notes Guo and Sun address fundamentally different technologies: Guo teaches RNA nanocages for encapsulating conventional therapeutics and does not teach of CRISP-Cas systems where as Sun teaches DNA nanoclews for surface delivery of Cas9/sgRNA complexes. Applicant notes the references operate through incompatible mechanisms (encapsulation vs surface attachment), use different materials (RNA polyhedran vs DNA yarn-like structures), and deliver different cargo types (small molecules vs large protein-RNA complexes). Applicant state these incompatible approaches serve different purposes and cannot be meaningfully combined.
In response to point (1), Examiner respectfully notes, as discussed in the previously filed rejection of claim 16 (p10), that Guo does not per se teach of the cargo comprising one or more components of the CRISPR/Cas system but rather teaches of delivering RNA or DNA molecules for replacement gene/transcript therapy, delivering RNAi to specifically inhibit RNA transcripts to reduce gene expression, and further teaches the cargo can be such molecules as guide sequences for ribozymes that inhibit transcription. As a POSITA will appreciate, the cargo of Guo (i.e., guide sequences for ribozymes, RNAi, transcription therapy molecules, etc.) thus reads on molecules involved in nucleic acid manipulation. As a POSITA will further appreciate, the CRISPR/Cas system is also involved in nucleic acid manipulation. Further, both the cargo molecules of Guo and CRISPR/Cas are known to be used for treatment/prevention of various diseases and disorders.
Sun teaches of nucleic acid assemblies (i.e., DNA nanoclews) and further teaches said assemblies can be loaded with and deliver Cas9 protein together with a sgRNA for genome editing (i.e., nucleic acid manipulation). Thus, Sun teaches of wherein the cargo comprises one or more components of one or more CRISPR-Cas systems.
Thus, it would have been obvious to a POSITA before the effective filing date of the claimed invention, to do a simple substitution of one known element for another to obtain predictable results. It would have been obvious to substitute the cargo molecules involved in nucleic acid manipulation taught by Guo (i.e., ribozymes, RNAi, transcription therapy molecules, etc.) for the cargo molecules involved in nucleic acid manipulation as taught by Sun (i.e., CRISPR-Cas9) in order to provide protection to said molecules as Guo teaches.
The skilled artisan would have had a reasonable expectation of successfully substituting said molecules for treating disorders and diseases requiring nucleic acid manipulation. Substitution of one element for another known in the field is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
Thus, Examiner respectfully notes a POSITA would have been motivated to perform said substitution due to both Guo and Sun teaching of molecules for treating disorders and diseases requiring nucleic acid manipulation.
In addition, Examiner respectfully notes MPEP 2144(I-IV) noting that “the rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992).”
Applicant is respectfully reminded that “[a] person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 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. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id., 82 USPQ2d at 1396 (see MPEP § 2141.03).
In the instant case, Guo and Sun teach of nucleic acid assemblies for treating disorders and diseases requiring nucleic acid manipulation. Therefore, it would have been prima facie obvious to substitute one element known for another known in the field. As noted in KSR International Co. v Teleflex, Inc., 82 USPQ2d 1385, 1397 (U.S. 2007), “When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In this case, the rejection of record clearly takes into account the disclosures of Guo and Sun, disclosed at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure. The previously filed rejection of record points to specific disclosures in the cited prior art that describe the limitations of Applicant’s claimed method.
It is noted that the test for obviousness is what the combined teachings of references would have suggested to one of ordinary skill in the art. See In re Keller, 642 F.2d 413, 425 (CCPA 1981) (citing cases). Applicant is reminded that “[a] person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 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. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id., 82 USPQ2d at 1396 (see MPEP § 2141.03).
In regards to point (2), Applicants remarks have been carefully considered but have not been found persuasive. When looking to the prior art in regards to nucleic acid assemblies, one encounters multiple reviews discussing both RNA and DNA nucleic acid assemblies/nanocages/nanoclews/origami and Examiner notes said reviews commonly refer to RNA and DNA nucleic acid assemblies as DNA/RNA nanotechnology. Thus, Examiner respectfully disagrees that Guo and Sun address fundamentally different technologies. The prior art directed to DNA nucleic acid assemblies/nanocages/nanoclews/origami may be applied to RNA nucleic acid assemblies/nanocages/nanoclews/origami. As RNA is made from DNA, thus it is obvious that the insights gleaned from DNA technology would be applied to RNA technology.
Further, in regards to surface attachment versus encapsulation of the cargo molecules, it would have been obvious to a POSITA, upon encountering the teachings of Guo, to encapsulate the cargo molecules to better protect said molecules. In regards to Sun teaching of Cas9/sgRNA complexes and Guo teaching of conventional therapeutics, Examiner respectfully notes both Guo and Sun teaching of molecules for treating disorders and diseases requiring nucleic acid manipulation.
Thus, Examiner respectfully notes Guo and Sun do not address fundamentally different technologies. Thus, Applicant’s remarks have been carefully considered but have not been found persuasive.
Therefore, the previously filed rejections are maintained.
Examiner notes claims 18 and 19 have been amended via Applicant amendment. Said claims are thus included below. As no other claims have been amended, please see the previously filed OA for said rejections.
In regards to claim 18 and 19, Guo and Sun teach claim 16. Claim 18 has been amended to state: “wherein the cargo further comprises one or more template oligonucleotides” and claim 19 has been amended to state: “wherein one or more of the template oligonucleotides is part of the nucleic acid assembly.”
Examiner respectfully notes Sun teaches future implementation of the delivery vehicles (i.e., nucleic acid assemblies) may focus on employing packaged DNA sequences as templates for homology directed repair (p12032, 1st column, 1st paragraph). This reads on “wherein the cargo further comprises one or more template oligonucleotides” (i.e., claim 18). Further, Sun teaches the cargo (i.e., sgRNA, Cas9, and in the future template oligonucleotides) is integrated into the nucleic acid assembly (Figure 1) and as discussed supra, Guo teaches cargo molecules may be integrated into the nucleic acid assembly. This reads on “wherein one or more of the template oligonucleotides is part of the nucleic acid assembly” i.e., claim 19.
Thus, the claims are obvious and are properly rejected.
Conclusion
No claims are allowable. No claims are free of the prior art.
Applicant's amendment necessitated the updated 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE R SMALL whose telephone number is (703)756-4783. The examiner can normally be reached Monday - Friday 8:30am-4pm.
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/KATHERINE R SMALL/Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633