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Claims 9, 12-18, 20-23, 25 and 27-28 are withdrawn.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn.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.
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.).
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).
KIM does not teach a version without using ultracentrifugation or teach conjugating a targeting moiety to the magnetic nanoparticle.
Regarding claim 1, MANRIQUE teaches mimetic exosomes for targeted delivery using a conjugated monoclonal antibody (Page 13, paragraph 3). MANRIQUE teaches that different methods can be used for isolation, such as ultracentrifugation, filtration, immunoaffinity isolation, polymeric precipitation and microfluidics techniques (page 4, paragraph 7). Ultracentrifugation can limit the sample volume, while size exclusion chromatography can be used instead and can allow for larger volume to be isolated (page 4, paragraph 10).
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 size exclusion chromatography. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because ultracentrifugation and size exclusion chromatography are functional equivalents of isolation methods commonly used in the pharmaceutical industry for exosome mimetics. Furthermore, size exclusion chromatography can be used to allow for larger volume to be isolated at once therefor saving time.
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 for preparing IONP-harboring nanovesicles derived from human mesenchymal stem cells (hMSCs) comprising a step of density gradient ultra-centrifugation (see, FIG. lA of Kim). Therefore, Kim does not anticipate the amended claims. This deficiency is not remedied by the disclosure of Manrique, which teaches mimetic exosomes for targeting delivery using a
conjugated monoclonal antibody. Therefore, the combination of Kim and Manrique does not render
obvious the amended claims.
The argument is not persuasive because as discussed above, MANRIQUE teaches that different methods can be used for isolation, such as ultracentrifugation, filtration, immunoaffinity isolation, polymeric precipitation and microfluidics techniques (page 4, paragraph 7). Ultracentrifugation can limit the sample volume, while size exclusion chromatography can be used instead and can allow for larger volume to be isolated (page 4, paragraph 10).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate size exclusion chromatography. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because ultracentrifugation and size exclusion chromatography are functional equivalents of isolation methods commonly used in the pharmaceutical industry for exosome mimetics. Furthermore, size exclusion chromatography can be used to allow for larger volume to be isolated at once therefor saving time.
Applicant argues, The amended claims are directed to methods of producing an exosome mimetic, wherein the method does not comprise ultracentrifugation. The instant application demonstrates that the claimed methods produce over 30-fold higher yield of exosomes as compared to methods comprising ultracentrifugation (see, para. [0160]).
The argument is not persuasive because in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., magnetic separator which is what allowed the higher yield to be obtained according to the specification) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Instant claim 1 only states that ultracentrifugation cannot be used, however it does not state what should be used in its place. This leaves the claim very broad and is not commensurate in scope with the unexpected results claimed.
Conclusion
No claims are allowable.
Applicant's amendment necessitated the new 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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/S.L.M./ Examiner, Art Unit 1618 /JAKE M VU/Primary Examiner, Art Unit 1618
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