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 .
Claims 1-3, 8-9, 11-18, 20-23, 25 and 27-28 are pending.
Claims 9, 12-18, 20-23, 25 and 27-28 are withdrawn.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/18/2025 has been entered.
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.
Claims 1-3 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by KIM (Therapeutic Efficacy-potentiated and Diseased Organ-targeting Nanovesicles Derived from Mesenchymal Stem Cells for Spinal Cord Injury Treatment. Nanoletters. July 11, 2018).
Regarding 1, KIM teaches a method to produce exosome mimetics for use in therapeutics (abstract). The method comprises incubating human mesenchymal stem cells (hMSC) and iron oxide nanoparticles (IONP) to internalize the IONPs with the hMSCs (Supporting information, IONP Uptake by hMSC), which reads on (i) incubating a cell with a magnetic nanoparticle such that the magnetic nanoparticle enters an endosome in the cell. The iron oxide stem cells were then scaped off and centrifuged to lyse the cell and a cell pellet was collected, resuspended, extruded and centrifuged again to achieve a cell lysate (Supporting information, IONP Uptake by hMSC), which reads on (ii) lysing the cell to produce a cell lysate containing the endosome. After centrifugation, the resulting pellet was resuspended to isolate the iron oxide nanoparticle incorporated exosome-mimetic nanovesicles (NV-IONP) (Supporting information, Pg. 4, first partial paragraph), which reads on (iii) isolating the endosome encapsulating the magnetic nanoparticle from the cell lysate in step (ii). The NV-IONP were prepared by serial extrusion (Pg. 7, Lns. 37-38) The synthesized NV-IONP were then filtered through 0.22 μm syringe-filter, which reads on nanoporous membrane (Supporting Information, Pg. 4, first partial paragraph), which reads on (iv) extruding the isolated endosome obtained in step (iii) through a nanoporous membrane to produce the exosome mimetic.
Regarding claim 2, KIM teaches the method uses human mesenchymal stem cells (hMSC ) (Supporting information, IONP Uptake by hMSC).
Regarding claim 3, KIM teaches the iron oxide nanoparticles were internalized within the hMSCs, which reads on the magnetic nanoparticle enters the endosome in the cell via endocytosis (Supporting information, IONP Uptake by hMSC and figure 1).
Regarding claim 8, KIM teaches magnetic sorting was used to isolate the NV-IONP from the exosome-mimetic nanovesicles that were not encapsulated, which reads on removing unencapsulated magnetic nanoparticles (Page 4970, paragraph 2).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1-3, 8 and 11 are rejected under 35 U.S.C. 103 as being anticipated by KIM (Therapeutic Efficacy-potentiated and Diseased Organ-targeting Nanovesicles Derived from Mesenchymal Stem Cells for Spinal Cord Injury Treatment. Nanoletters. July 11, 2018) in view of MANRIQUE (Therapeutic biomaterials based on extracellular vesicles: classification of bio-engineering and mimetic preparation routes. Journal of Extracellular Vesicles. 2018.).
KIM teaches Applicant’s invention as discussed above.
KIM does not teach conjugating a targeting moiety to the magnetic nanoparticle.
Regarding claim 11, MANRIQUE teaches mimetic exosomes for targeted delivery using a conjugated monoclonal antibody (Page 13, paragraph 3), which reads on conjugating a targeting moiety.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate conjugating a targeting moiety. The person of ordinary skill in the art would have been motivated to make those modifications, because it allows for the nanoparticle to reach the desired area for therapeutic purposes, and reasonably would have expected success because attaching a targeting moiety is common in the art and both references are in the same field of endeavor, such as exosome mimetics for therapeutic purposes.
Response to Arguments
Applicant argues, Kim teaches a method of producing exosome mimetics in which whole cells comprising endosomes are serially extruded to produce iron oxide nanoparticle- incorporated exosome-mimetic nanovesicles (NV-IONPs) prior to two rounds of ultracentrifugation followed by magnet sorting to isolate NV-IONPs (see FIG. 1 of Kim). In contrast, in the claimed methods, whole cells comprising endosomes are lysed and the endosomes comprising magnetic nanoparticles are isolated directly from the cell lysate. The isolated endosomes comprising endosomes comprising magnetic particles are then
subjected to an extrusion step to produce the exosome mimetics. That is, Kim does not teach at least a step of extruding isolated endosomes to produce exosome mimetics. It follows that Kim does not teach every element of the claimed invention as required for anticipation under § 102(a)(1).
Examiner does not find the argument persuasive because as discussed above KIM teaches a method to produce exosome mimetics for use in therapeutics (abstract). The method comprises incubating human mesenchymal stem cells (hMSC) and iron oxide nanoparticles (IONP) to internalize the IONPs with the hMSCs (Supporting information, IONP Uptake by hMSC), which reads on (i) incubating a cell with a magnetic nanoparticle such that the magnetic nanoparticle enters an endosome in the cell. The iron oxide stem cells were then scaped off and centrifuged to lyse the cell and a cell pellet was collected, resuspended, extruded and centrifuged again to achieve a cell lysate (Supporting information, IONP Uptake by hMSC), which reads on (ii) lysing the cell to produce a cell lysate containing the endosome. After centrifugation, the resulting pellet was resuspended to isolate the iron oxide nanoparticle incorporated exosome-mimetic nanovesicles (NV-IONP) (Supporting information, Pg. 4, first partial paragraph), which reads on (iii) isolating the endosome encapsulating the magnetic nanoparticle from the cell lysate in step (ii). The NV-IONP were prepared by serial extrusion (Pg. 7, Lns. 37-38) The synthesized NV-IONP were then filtered through 0.22 μm syringe-filter, which reads on nanoporous membrane (Supporting Information, Pg. 4, first partial paragraph), which reads on (iv) extruding the isolated endosome obtained in step (iii) through a nanoporous membrane to produce the exosome mimetic.
Conclusion
No claims are allowable.
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/S.L.M./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618