DETAILED ACTION
Formal Matters
Claims 3, 12 and 13 are cancelled. Claims 1-2, and 4-11 are pending and under examination.
Priority
This application is a national stage entry of PCT/KR2022/006429 filed on 5/4/2022, which claims priority from KR10-2021-0058171 filed on 5/4/2021.
Information Disclosure Statements
The information disclosure statement (IDS) filed on 12/18/2025 has been considered by the examiner.
Objections and Rejections Withdrawn
The objection over claims 1 and 11 is withdrawn per applicant’s amendments.
The rejection under USC 112(a) for scope for enablement of preventing is withdrawn as applicant has deleted preventing from the claims.
The rejections under USC 112(b) over claims 4, 8 and 9 are withdrawn per applicant’s amendments and arguments.
The rejections under non-statutory type double patenting over claim 12 are withdrawn per the cancellation of claim 12 rendering the rejections moot.
As these rejections are withdrawn, applicant’s arguments toward the rejections are now moot.
Maintained Rejections – Modified As Necessitated by Amendment to Claims 1 and 11
Claim Rejections – 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 1-2, 4, 6-8 and 10-11 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Bang US 20200129433 (published 4-30-2020) and Azarin et al (Biotechnol Appl Biochem, 2013, volume 59, pages 88-96).
Bang teaches treating of stroke with cell derived microvesicles that have enhanced expression of microRNAs and high levels of materials (abstract and paragraphs 41-42). Stroke is a neurological disorder or damage (damages brain). Bang teaches 3D culturing of stem cells (abstract). Bang teaches neurogenesis using 3D-microvesicles (paragraph 36 and paragraph 49). Bang teaches mesenchymal stem cells that formed spheroids when cultured in microwells and spherical cell aggregates (paragraph 45, also paragraph 30). Bang teaches statically culturing the cells (paragraph 46). Bang teaches static 3D cultures (paragraphs 61 and 67). Bang teaches microwells with 200 micron diameter for 3D culturing (paragraph 57). Bang teaches 400 cells/microwell (paragraph 57). Bang teaches isolating and obtaining MSC derived microvesicles (paragraphs 5 and 31-32). Bang also teaches embryonic stem cell, iPSC or adult stem cell (paragraph 17 and claim 17 of Bang). Bang teaches FGF, VEGF and other factors that are enhanced in the microvesicles (paragraphs 24-25). Bang teaches a pharmaceutical composition for treating stroke (paragraph 7).
Bang does not teach the depth of the microwell for the cultures.
Azarin teaches the effects of 3D microwell culture on growth kinetics and metabolism of human embryonic stem cells (title and abstract). Azarin teaches a microwell lateral size of 100, 300 or 500 microns laterally and a depth of 120 microns (section 3.1).
One of ordinary skill in the art before the time of filing would have utilized depths of Azarin for the microwells as they were seen as effective for 3D microwell cell culturing as provided by Bang. Thus, there was a reasonable expectation of success in using such microwell depths of Azarin to obtain a method for 3D stem cells culturing and the subsequent collection of extracellular vesicles with Bang also teaching microwells for culturing.
Claim 5 in addition to Claims 1-2, 4, 6-8 and 10-11 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Bang US 20200129433 (published 4-30-2020), Azarin et al (Biotechnol Appl Biochem, 2013, volume 59, pages 88-96) and Feng et al (Frontiers in Cell and Developmental Biology, March 2021, volume 8, pages 1-16).
Bang and Azarin teach the claims as discussed above.
Bang and Azarin do not teach the miRNAs of claim 5.
Feng teaches that extracellular vesicles encapsulating miR-132 released from mesenchymal stem cells attenuated ischemic neuronal injury (title and abstract).
One of ordinary skill in the art before the time of filing would have obtained extracellular vesicles with miR-132 or other microRNAs effective for neurogenesis and treating stroke (neuronal injury) by the combined teachings of Bang, Azarin and Feng as Bang recognizes an increase in microRNAs that leads to benefits for neurogenesis and treating stroke while Feng recognizes that miR-132 is effective for treating ischemic neuronal injury which makes it a recognized miRNA for such treatments that comes from mesenchymal stem cells. There was a reasonable expectation of in combining the teachings of the prior art to arrive at methods of applicant’s claims to obtain better treatment for a neurological disease or damage.
Claim 9 in addition to Claims 1-2, 4, 6-8 and 10-11 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Bang US 20200129433 (published 4-30-2020), Azarin et al (Biotechnol Appl Biochem, 2013, volume 59, pages 88-96) and Moura et al (Frontiers in Neurology, 2019, volume 10, https://doi.org/10.3389/fneur.2019.00445).
Bang and Azarin teach the claims as discussed above.
Bang and Azarin do not teach the miRNAs of claim 5.
Moura teaches using DTI, diffusion MRI to predict stroke motor recovery (abstract and Concepts of Diffusion MRI).
One of ordinary skill in the art before the time of filing would have utilized techniques such as MRI DTI to monitor stroke recovery in patients. There would be a reasonable expectation of success in monitoring patients being treated for stroke by teachings of Bang and Azarin with techniques taught by Moura in order to better monitor response to treatment.
Claims 1-2, 4, 6-8 and 10-11 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Bang US 20200129433 (published 4-30-2020), Azarin et al (Biotechnol Appl Biochem, 2013, volume 59, pages 88-96) and KR101991038B1 (in applicant’s IDS, Google English translation provided).
Bang and Azarin teach the claims as discussed above.
Bang and Azarin do not teach other neurological conditions than stroke.
KR ‘038 teaches extracellular vesicles derived from stem cells using 3D cell culture (abstract). KR ‘038 teaches “The pharmaceutical composition may be used for the treatment of diseases for which conventional stem cell injection / grafting therapy is applied, such as central nervous system diseases (e.g., stroke, dementia, spinal cord injury, Parkinson’s disease, etc.)” (English translation of KR ‘038).
There was a reasonable expectation of success in treating other central nervous system diseases including strokes, Parkinson’s, dementia and spinal cord injury by teachings of KR ‘038 and having successful treatment of such diseases and damage with stem cell extracellular vesicle treatment. The prior art is combined as it teaches isolated stem cell extracellular vesicles for treatments of diseases/disorders.
Response to Applicant’s Arguments over the Rejections under USC 103
Applicant argues claim limitations toward the process of making stem cell extracellular vesicles. In regards to the claims, these are method of using claims (treating (applicant claim 1) or in vitro method of promoting neurogenesis (applicant claim 11)) by administering extracellular vesicles derived from stem cells where the claim also contains product-by-process limitations toward how the extracellular vesicles are produced. The prior art (Bang) recognizes using isolated extracellular vesicles collected from stem cells that are useful for treating neurological diseases and that have the ability to promote/stimulate neurogenesis. Therefore, the methods are taught by the teachings of Bang where effective treatment and neurogenesis is provided. It is notable that Bang’s stem cells being in spherical aggregates are similar to those used by applicant regardless of culturing method.
Applicant argues that the static culturing process is important to obtaining more vesicles and increasing amounts of miRNAs in the vesicles. Bang’s formulations are also derived from mesenchymal stem cells with Bang providing for different ways of culturing that involve spheroidal aggregates along with effective therapeutic treatment of a neurological condition, and thus, its extracellular vesicles are effective and presumed to be in effective amounts. KR101991038B1 also recognizes the ability of stem cell extracellular vesicles to treat central nervous system disorders. Applicant has evidenced that extracellular vesicles and miRNAs are still present in extracellular vesicles where stem cells were cultured as in methods of teachings of Bang. One of ordinary skill in the art is capable of adjusting doses/amounts of an item in order to treat a condition recognized for that item in the prior art, and so, can increase such amounts of extracellular vesicles to treat stroke (a neurological disease) with an expectation of higher efficacy. Additionally, the Feng reference combined to teach claim 5, which first introduces miRNAs, provides for miRNA-132 in extracellular vesicles that is effective to treat neuronal injury allowing one of ordinary skill in the art to use these miRNAs in their effective amounts with an expectation of treatment. Thus, the methods of treatment and promoting neurogenesis by administering stem cell extracellular vesicles of applicant’s claims would reasonably be expected by teachings of Bang in view of Azarin, Bang, Azarin and Feng, and Bang, Azarin and KR ‘038 with a reasonable expectation of success and one of ordinary skill in the art would be able to adjust/optimize the amounts of extracellular vesicles and miRNAs that such vesicles contain like miRNA-132 that are seen to provide the beneficial effects for treating neuronal injury. A claim toward “a process of producing extracellular vesicles” would be considered differently, but again, the claims are toward methods of using the resulting stem cell extracellular vesicles (via product-by-process steps found in the methods of using) where the only noted differences regarding extracellular vesicles relate to number/concentration of vesicles and amounts of miRNAs found with them. The stem cell extracellular vesicles and the contained miRNA are already recognized by the prior art teachings to be useful for the claimed methods of use/treatment and could be provided in efficacious amounts as the references recognize the efficacies.
Applicant argues that the steps to producing the extracellular vesicles produce more efficacious extracellular vesicles due to miRNAs contained therein. Again, this is an argument toward the process of producing the vesicles rather than the applicant claimed methods of using although it was mentioned by the examiner that “Bang teaches statically culturing the cells (paragraph 46)”. Static 3D cultures are provided in Bang paragraph 67. It is noted that only claim 5 provides for a limitation to miRNAs in the extracellular vesicles. The prior art already does recognize miRNAs contained in stem cell extracellular vesicles is effective for treating neuronal injuries (teachings of Feng), and thus, such miRNA is available to be adjusted in the vesicles for its recognized benefit (see MPEP 2144.05). The miRNA of the extracellular vesicles is expected to have such efficacy based on prior art teachings.
For these reasons, the rejections under USC 103 are maintained.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached on M-F 9:00 am to 6:00 pm EST.
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/MARK V STEVENS/
Examiner, Art Unit 1613