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
Applicant’s election without traverse of Group I, claims 1-2, 4, 7-9, 11-12 in the reply filed on 04/20/2026 is acknowledged.
Claims 15-18, 20-22, 25, 28-29, 32-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim.
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.
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) 1-2, 4, 7-8, 11-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kao et al. (Science Advances, 2018, cited in IDS) in view of GHO et al., (US 2018/0036240, cited in IDS).
Kao et al. teaches “a nonviral system based on megakaryocytic microparticles (MPs) for targeting delivery of plasmid DNA (pDNA) and small RNAs to HSPC [hematopoietic stem and progenitor cells]” (Abstract; clms. 1, 4, 7, 8, 11). Further, “we demonstrate pDNA, siRNA, and MiRNA delivery to HSPCs using megakaryocyte-derived MPs (MkMps)” (p. 1, last paragraph).
The megakaryocytic microparticles (cellular membrane vesicle; clm. 4) are taught to have a particle size range of “0.1- to 1-µm”, which is also 100nm to 1000nm (clm. 2); “have promising characteristics for RNA, DNA, and protein and other cargo delivery; “stable biological activity under -80ºC long term storage” (p. 1, Introduction, 1st paragraph).
The Kao et al. technique uses “electroporation” to load pDNA (active agent; nucleic acid;clm. 8) into megakaryoacitic MPs (p. 2, 1st full paragraph). The reference teaches suspending MkMps “in hypotonic buffer (Eppendorf)”, mixing with “CY5-labeld pGFPns”, where the pGFPns were loaded into the cells by electroporation” (p. 8, last paragraph, through p. 9, 1st paragraph). Electroporation is the process by which an electric pulse in used to create temporary pores in cell membranes through which substances like nucleic acids can pass. In a fluid environment, as discussed in Kao et al., electroporation would have caused fluid, in addition to nucleic acids, to enter the cell via the temporary pores created by the process, thereby providing liquid medium comprising an active agent for the MkMps, as claimed.
In regard to claim 11, Kao et al. teaches, “Beyond pDNA delivery, small RNAs (miRNAs or siRNAs) constitute an important cargo for a broad variety of therapeutic applications, especially so for delivery to HSPCs” (p. 6, left column, 1st full paragraph). Accordingly, it would have been obvious for the cells to further comprise a therapeutic.
Kao et al. further teaches “using cationic polymers such as polyethylenimine, which has been shown to enhance endosomal escape” (p. 6, left column, 1st paragraph), which suffices as a part of the liquid medium encapsulated by the biological membrane, as per claim 12.
Kao et al. does not teach that the cells do not comprise a native cytoplasmic component.
GHO et al. teaches “cell membrane-derived nanovisicles”, used for delivering therapeutic substances, “may prevent the occurrence of potential side effects because intracellular materials (e.g., genetic materials and cytosolic proteins) unnecessary for delivery of therapeutic or diagnostic substances are removed from the nanovesicles” (Abstract).
GHO et al. further teaches, “when the cell membrane-derived nanovesicles are applied to disease treatment, the side effects of therapeutic substances such as drugs may be reduced, so that suffering and inconvenience of patients may be alleviated during the course of treating diseases, and therapeutic efficacy may be improved” (Id.).
It would have been obvious to a person having ordinary skill in the art at the time of applicant’s filing to remove native cytoplasmic components from the cells of Kao et al. for the advantage of preventing the occurrence of potential side effects and improving therapeutic efficacy, as taught by GHO et al. With the native cytoplasmic components removed, it would have been obvious for the vesicles to consist of the biological membrane and the liquid medium, as per claim 2.
2) Claim(s) 9 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kao et al. (Science Advances, 2018, cited in IDS) in view of GHO et al., (US 2018/0036240, cited in IDS) as applied to claim 1 above, and further in view of Ryu et al., (Nanomedicine: Nanotechnology, Biology, and Medicine, 2018).
The combination of Kao et al. and GHO et al., which is taught above differs from claim 9 insofar as it does not teach where the target cell expresses a guide RNA with Cas9.
Ryu et al. teaches an effective PEI-mediated delivery of CRISPR-Cas9 complex for targeted gene therapy (Ti).
Ryu et al. further teaches, “This CRISPR/Cas9 system has been used in various applications, such as elucidating gene function by manipulating genes at the nucleotide level. By providing a single guide RNA (sgRNA) designed to target specific loci, it is possible to edit the genome by mediating cleavage of DNA strands, allowing endogenous repair either by error-prone non-homologous end joining (NHEJ), inducing unpredictable insertions or deletions (indels), or by homology-directed repair (HDR), which precisely repairing damaged sites in the presence of monologous templates” (p. 2095, 1st paragraph after abstract).
It would have been obvious to a person having ordinary skill in the art at the time of applicant’s filing to add Cas9 with guide RNA to the cells of Kao et al. since the cells of Kao et al. are used for gene therapy applications. The artisan would have reasonably expected success with the combination insofar as PEI is used in both references to enhance delivery of the therapeutic agents.
Technological Background
The prior art made of record and considered pertinent to applicant's disclosure DeVry et al., (Progress in Neurobiology, 2010). DeVry et al. is pertinent for teaching, “Electroporation is based on the application of electric pulses to disrupt cell membranes and to drive DNA through these temporary pores inside the cell” (p. 228, right column, 3rd paragraph). DeVry et al. further teaches that other mechanisms play a role in electroporation beside electropermeabilization, such as “passive diffusion, convection, and endocytosis” (Id. last paragraph). With convective mechanisms, constituents carried along with a fluid are involved in the uptake by the cell (Id.)
Conclusion
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER E WEBB whose telephone number is (571)270-3287 and fax number is (571) 270-4287. The examiner can normally be reached from Mon-Fri 7-3:30.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Walter E. Webb
/WALTER E WEBB/Primary Examiner, Art Unit 1612
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