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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/21/2026 has been entered.
Claims 1, 3-6, 10-25, 28-31, 33-35 are pending. Claims 15-25, 28-31, 33 and 34 are withdrawn. Claims 1, 3-6, 10-14 and 35 are currently under examination.
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.
Claim(s) 1, 3-6, 10-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Malone (cited previously), in view of Rieder (US20180326038) and Lin et al (Biomed Microdevices, 2016, Vol.18, no. 41, pages 1-11) and Fanning (cited previously).
Malone discloses a capsid comprising recombinant engineered Arc polypeptide and endogenous Gag (endo-gag) polypeptides that can form capsids, and may be loaded with heterologous molecules for delivery to a target of interest (paragraph [0003]). Malone discloses the cargos may be a therapeutic agent (paragraph [0118], [0127]). Malone discloses Arc or endo-gag comprises a capsid assembly/forming domain (paragraph [0054]), and each of recombinant or engineered Arc or endo-gag polypeptide forms a capsid subunit (paragraph [0106], page 14, line 4-5). Malone discloses various vector and expression system for expressing Arch and endo-Gag polypeptides, including pFLAG, pTRCHis2 series, and pFLAG-Myc-CMV, which comprises epitope tags FLAG, Myc and His (paragraph [0189], [0193]). Malone gives an example of the 6xHis tagged recombinant Arc and endo-Gag (paragraph 0273, line 13-14). Malone discloses endo-gag based capsid including proteins PEG10, RTL3, RTL6, RTL8A and RTL8B (paragraph [0014], [0107], lines 10-13), all of which belong to Sushi-class protein as evidenced by Figure 2 of the present application. The endo-gag polypeptides thus meets the limitation of Gag-homology proteins because they encompasses same protein as recited in claim 1, Sushi-class proteins.
The teaching from Malone is silent on whether the epitope tag is expressed on the surface of the capsid, and wherein the epitope tag is the glycoprotein of vesicular stomatitis virus (VSVG) as a fusogenic membrane glycoprotein.
Rieder teaches a method of genetically engineer FMD viruses by insertion of protein tags into the selected regions of the capsid of the FMD, and said tagged FMD viruses are suitable to be used in various diagnostic and therapeutic applications as well as in applications wherein production of the FMD virus and/or its components are desired (paragraph [0006]). Rieder teaches the tags are strategically inserted into viral capsid proteins in targeted regions predicated to be exposed on the surface of the viral capsid (paragraph [0050]). Rieder teaches the epitope tags that may be used include 6xHis, Flag, V5, Myc, HA and NE (paragraph [0065]), and gives examples of using 6xHis to decorate FMDV capsid surface (paragraph [0096]).
Fanning et al. teach a method of isolation and functional characterization of ZO-1, using C-terminally VSVG tagged constructs (Figure 1 and legend, page 3, Material and Methods section, paragraph 1).
Lin et al. teach overexpression of the spike glycoprotein of vesicular stomatitis virus (VSVG) has been shown to induce the release of fusogenic vesicles which are capable of direct transport of cytoplasmic, nuclear and surface proteins to target cells, and proteins of interest can be encapsidated in the particle of a fusion protein Gag and efficiently delivered to recipient cells (page 1, 1st col., 2nd paragraph). Lin et al. demonstrated that fusogenic plasma membrane vesicles (fPMVs) containing bioactive macromolecules and mitochondria by a simple mechanical extrusion of VSVG expression Ad293 cells, wherein cytoplasmic proteins and mitochondria entrapped in fPMVs can efficiently be transferred to target cells (page 2, 1st col., last paragraph).
It would have been obvious to an ordinary skilled in the art that epitope tags may be strategically inserted into the endo-gag peptide to be assembled into capsid displaying on the outer surface of the capsid based on the combined teaching from Malone and Rieder. The ordinary skilled in the art would recognize that the epitope tag such as His taught in the Malone reference may be used to purify the endo-gag polypeptide or in a different position to be expressed on the outer surface of the capsid as demonstrated by Rieder. An ordinary skilled in the art reading Fanning would recognize that VSVG are routinely used as a protein tag for isolation and characterization of the protein of interest as demonstrated by Fanning et al., and Malone teaches using VSV envelope protein to target cells of interest for delivery (paragraph [0250] and [0254]). The ordinary skilled in the art would recognize VSVG tagging, would have additional advantage of fusogenic delivery of encapsulated contents as taught by Lin et al. The ordinary skilled in the art would have reasonable expectation of success to insert the epitope tag VSVG to be displayed on the capsid surface following combined teaching from Malone, Rieder, Fanning and Lin. Therefore, the claimed invention of claim 1 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claim 4, Malone discloses the heterologous cargo comprises nucleic acid (paragraph [0127]).
Regarding claim 5-6, Malone disclose that endo-gag polypeptide is a human Endo-Gag polypeptide, and its RNA binding domain is modified to bind to a RNA cargo that is not native to human endo-Gag (paragraph [0042]), which meets the claim limitation of “reprogram binding specificity.”
Regarding claim 10, Malone discloses endo-gag based capsid including a protein RTL3, PEG10, RTL6, RTL8A and RTL8B (paragraph [0014], [0107], lines 10-13).
Regarding claim 11, Malone teaches making modification to Arc with its RNA binding domain to bind to a cargo that is not native to human Arc (paragraph [0041]), which meets the limitation of carrier tag as defined by the present specification.
Regarding claim 12, Malone further teaches delivery component further comprises liposome, micelle, microvesicle (paragraph [0237]).
Regarding claims 3 and 13, Malone further teaches the delivery component further comprises a viral envelope protein for specifically targeting the capsid to a target cell (paragraph [0250]), which meets the limitation of engineered capsid to provide cell specific uptake (claim 3) and a targeting molecules (claim 13).
Regarding claim 14, Malone teaches the targeting molecule is viral proteins comprises cell specific binding protein, that binds to cell surface molecule (paragraph [0250], [0255]), which meets the limitation of ligands for receptors on a surface of a target cell of interest.
Claim(s) 35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Malone, Reider, Fanning and Lin, as applied to claims 1, 3-6, 10-14 above, and further in view of Barile (Pharmacology & Therapeutics 2017, Vol. 174, pages 63-78).
The teaching from Malone, Reider, Fanning and Lin has been discussed above.
However, none of the reference teaches the capsid is contained in an exosomes.
Barile teaches virtually all cells in the organism secrete extracellular vesicles, a heterogeneous population of lipid bilayer membrane-enclosed vesicles that transport and deliver payloads of protein and nucleic acids to recipient cells (abstract). Barile teaches exosomes may be loaded with therapeutic cargo molecules, including a variety of molecules, such as siRNA, miRNA mimic, synthetic drugs, proteins and viral vectors (page 70, 1st and 2nd col., under section 13). Barile teaches exosome offers appealing feature for therapeutic delivery, including biocompatibility, stability in the circulation, biological barrier permeability, low immunogenicity, and low toxicity (page 70, 1st col., 2nd paragraph).
It would have been obvious to an ordinary skilled in the art that exosomes may be used to deliver the capsid having a cargo rendered obvious by combined teaching from Malone, Reider, Fanning and Lin, based on the teaching from Malone and Barile. Malone teaches the delivery system further comprises liposome, micelle, microvesicle (paragraph [0237]), although not specifically teach exosome, an ordinary skilled in the art reading Barile would recognize that exosome may also be used in the delivery system due to their “appealing feature for therapeutic delivery, including biocompatibility, stability in the circulation, biological barrier permeability, low immunogenicity, and low toxicity (page 70, 1st col., 2nd paragraph). The ordinary skilled in the art would have reasonable expectation of success to include exosomes in the delivery system following combined teaching from Malone, Reider, Fanning, Lin and Barile. Therefore, the claimed invention of claim 35 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Response to Arguments
Applicant's arguments filed 1/21/2026 have been fully considered but they are not persuasive. Applicant argues that the combined teaching from Malone, Reider and Fanning does not teach the limitation that VSVG is a fusogenic membrane protein. This argument is addressed in the rewritten rejection as discussed above.
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/CELINE X QIAN/ Primary Examiner, Art Unit 1637