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 .
Election/Restrictions
1. Applicant’s election of tumor-associated antigen and dodecyl-beta-D-glucoside in the reply filed on 11/06/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Upon further considerations the election requirement between the different species of gene products and between the different species of membrane binding moieties set forth in the Office action mailed on 09/9/2025 is withdrawn.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 11, 13, 24, 25, 29-35, and 37-43 have been cancelled.
Claims 1-10, 12, 14-23, 26-28, 36, and 44 are pending and under examination.
Claim Objections
2. Claims 9 and 22 should recite “of the group” in line 2.
3. Claim 26 should recite “the nanostructure” in line 1.
4. Claim 44 should recite “the RDH nanostructure” in line 1.
Claim Rejections - 35 USC § 112(b)
5. 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.
6. Claims 10, 14, 23, and 27 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 claims 10 and 23, the phrase "such as" in line 5 renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 14 and 27 recite “alkylated phenols (including methylated phenols and tocopherols); flavones (including flavanone containing compounds such as 6-hydroxyflavone); saturated and unsaturated fatty acids (including derivatives such as lauric, oleic, linoleic and palmitic acids); and synthetic lipid molecules (including dodecyl-beta-D-glucoside)”.
The recitations within parenthesis render the claims indefinite because it is unclear whether the limitations within the parenthesis are part of the claimed invention, The recitations within parenthesis comprise the phrase "such as" makes it unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 103
7. 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.
8. Claims 1-4, 9, 12, 14, 16, 17, 22, 26-28, 36, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Chem. Commun., 2013, 49: 5462-5464), in view of both Kim et al. (Scientific Reports, 2015, 5: 1-9) and Zhang et al. (Drug Delivery, 2019, 26: 328-342; online 03/24/2019).
Wang et al. teach an RNA-DNA hybrid origami scaffold having a maximum dimension of less than 100 nm; the hybrid origami is obtained by using short DNA staples to fold a long RNA (scaffold sequence) into predefined higher order structures (ribbons, rectangles, and triangles). Wang et al. teach that, as opposed to attaching, programmed RNA self-assembly could integrate multiple functions into the nanostructure such that the nanostructure could perform complex activities (claims 1 and 4) (see p. 5462; p. 5463, column 1 and Fig. 3; p. 5464, Fig. 4, column 1, first full paragraph, and paragraph bridging columns 1 and 2; Supplementary Material, Table S1 and Fig. S5).
Wang et al. do not teach that the single-stranded RNA is an mRNA (claims 1 and 3). Kim et al. teach that nanoparticles made entirely of mRNA (mRNA NPs) exhibit enhanced resistance to nucleases and could be used for effective gene delivery; the mRNA NPs slowly undergo translation into cells to provide continuous and prolonged gene expression (see Abstract; p. 4; p. 5, fifth paragraph). Based on these teachings, one of skill in the art would have found obvious to modify Wang et al. by using an mRNA in the RNA-DNA hybrid origami, to achieve the predictable result of obtaining nanoparticles capable of mediating effective gene delivery, when gene delivery was needed.
With respect to claims 9, Kim et al. teach that the mRNA NPs could be used for vaccination (see p. 5, sixth paragraph). Thus, using an antigen-encoding mRNA would have been obvious to one of skill in the art, to achieve the predictable result of obtaining a composition suitable for inducing immune responses. With respect to claims 28 and 36, one of skill in the art would have found obvious to further formulate the composition with a pharmaceutically acceptable excipient and administer the resultant pharmaceutical composition to a subject in need of immunization, with the reasonable expectation that doing so would induce immune responses in the subject.
Wang et al. and Kim et al. do not teach a membrane binding moiety (claims 2, 12, 14, 16, 17, 22, 26, 27, and 44). Zhang et al. teach that cellular uptake is enhanced by decorating the nanoparticles with hydrophobic moieties (such as cholesterol and alkyl chains) which promote interaction with the phospholipid bilayer (see p. 329, paragraph bridging columns 1 and 2; p. 330, paragraph bridging columns 1 and 2; p. 331, column 1, first paragraph). Based on these teachings, one of skill in the art would have found obvious to decorate the mRNA-DNA hybrid origami with cholesterol or alkyl, to achieve the predictable result of enhancing its cellular uptake.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
9. Claims 1-4, 9, 12, 14, 16, 17, 22, 26-28, 36, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. taken with both Kim et al. and Zhang et al., in further view of Howorka et al. (WO 18/011603).
The teachings of Wang et al., Kim et al. and Zhang et al. are applied as above for claims 1-4, 9, 12, 14, 16, 17, 22, 26-28, 36, and 44. Wang et al., Kim et al. and Zhang et al. do not teach the elected species dodecyl-beta-D-glucoside (claims 14 and 27).
Howorka et al. teach that decorating nucleic acid nanostructures with dodecyl-beta-D-glucoside promotes interaction with the phospholipid bilayer (see p. 3, lines 18-20; p. 4, lines 38-40; p. 14, lines 27-36). Replacing cholesterol/alkyl with dodecyl-beta-D-glucoside would have been obvious to one of skill in the art to achieve the predictable result of enhancing the cellular uptake of the mRNA-DNA hybrid origami.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
10. Claims 1-4, 9, 10, 12, 14, 16, 17, 22, 23, 26-28, 36, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. taken with both Kim et al. and Zhang et al., in further view of Fiedler et al. (Recent Results in Cancer Research, 2016, 209: 61-85; Abstract).
The teachings of Wang et al., Kim et al. and Zhang et al. are applied as above for claims 1-4, 9, 12, 14, 16, 17, 22, 26-28, 36, and 44. Wang et al., Kim et al. and Zhang et al. do not teach that the antigen is a tumor-associated antigen (TAA) (claims 10 and 23). Fiedler et al. teach treating cancer by immunizing with mRNAs encoding TAAs (see Abstract). Thus, specifically using a TAA-encoding mRNA would have been obvious to one of skill in the art, to achieve the predictable result of obtaining a composition suitable for treating cancer.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
11. Claims 1-4, 9, 12, 14, 16, 17, 22, 26-28, 36, and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. taken with both Kim et al. and Zhang et al., in further view of both Andersen et al. (Nature, 2009, 459: 73-76) and Veneziano et al. (Science, 2016, 352: 1-8).
The teachings of Wang et al., Kim et al. and Zhang et al. are applied as above for claims 1-4, 9, 12, 14, 16, 17, 22, 26-28, 36, and 44. Wang et al., Kim et al. and Zhang et al. do not teach second and third scaffolds (claims 5-8 and 18-21). However, Wang et al. teach that RNA-DNA hybrid origami provide the potential for integration of diverse RNAs and functions into a single nanomachine (see p. 5464, column 2, last paragraph). Andersen et al. teach obtaining a DNA cubic higher-order structure (nanobox having a lid functionalized with a DNA dual lock-key) for the controlled release of cargoes of interest; the nanobox is obtained by using edge staples to assemble six DNA origami sheets into a cuboid structure (see Abstract; p. 73, Fig.1b-c; paragraph bridging p. 73 and 74; paragraph bridging p. 74 and 75; p. 75, Fig. 4a-b and paragraph bridging columns 1 and 2; p. 76, column 1, first paragraph). While Anderson et al. do not specifically teach vertex staples, Veneziano et al. teach using both edge and vertex staples to obtain 3-D higher-order structures (see p. 2, column 1, last paragraph and Fig. 1; Supplemental Materials, p. 3, Fig. S1 and p. 6, last paragraph). Based on these teachings, one of skill in the art would have found obvious to use the teachings of Wang et al., Kim et al. and Zhang et al. to fold an mRNA (scaffold sequence) encoding a protein of interest into six origami sheets and further assembling the sheets into the nanobox structure taught by Andersen et al. by using edge and vertex staples, with the reasonable expectation that doing so would result in a nanobox suitable to be used for continuous and prolonged expression of the protein of interest and also as a device for controlled release of agents of interest, when the delivery of the combination between proteins and agents of interest was needed. By doing so, one of skill in the art would have obtained a cuboid comprising vortex staples, each holding three facets together, i.e., a plurality of staples hybridizing with a region of a first, second, and third scaffold sequences, as recited in claims 5, 7, 18, and 20.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
12. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633