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 in the reply filed on 08/24/2025 is acknowledged.
Claims 7-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/24/2025.
Claims 1-6 are being examined on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for extracellular vesicles…from adipose-derived stem cells does not reasonably provide enablement for an extracellular vesicle. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The issue with the claims is that the applicant is claiming a composition which at least comprises an extracellular vesicle. The applicant is thus, at least in one interpretation, claiming a single extracellular vesicle for treating Alzheimer’s diseases.
The applicant shows evidence that delivering compositions comprising 109 particles a high dose was effective in regulating extracellular Aβ1-40 and Aβ1-42 decreased (see page 12). However claiming that a composition which can comprise of a single extracellular vesicle would not be expected to have any meaningful treatment on Alzheimer’s disease. Although the specifications may recite specific embodiments that would lead to an enabled composition the claims as currently written are not enabled.
Examiner’s comments: It is advised to amend the claims in such a manner that would not merely be directed to a single EV but more particularly to a composition with an effective amount needed for treatment.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-6 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is also indefinite for the same reasons as being unenabled for the scope of a single EV being used as a treatment for Alzheimer’s disease. It is unclear how a composition comprising of a single EV can be used to treat Alzheimer’s disease. Therefore the claims are indefinite.
Examiner’s comments: It is advised to amend the claims in such a manner that would not merely be directed to a single EV but more particularly to a composition with an effective amount needed for treatment.
Claims 4 and 5 are indefinite for the phrase “highly expresses” as this is a relative term and it is not defined in the specifications thus it can be interpreted in more than one way, making the claims unclear.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1 and 6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claims recite an extracellular vesicle. The first step of the eligibility analysis evaluates whether the claim falls within a statutory category (see MPEP 2106.03). Since the claim is directed to a composition comprising an extracellular vesicle the markedly different characteristics is performed by comparing the nature-based product limitation to its natural counterpart.
The claim recites the naturally occurring components found within or outside of living cells. These extracellular vesicles are derived from living cells and are lipid encased membranes containing signaling molecules such as amino acids, proteins, and different cellular components that originate from the cells that they are excreted from. The closest naturally occurring counterparts of extracellular vesicles are the same vesicles found excreted from the cells they came from, which would be identical to the extracellular vesicles being claimed. All of these are naturally occurring in nature and are not markedly different from its naturally occurring counterpart in its natural state. The properties of the nature-based product as claimed are not markedly different than the properties of these naturally occurring counterparts found in nature as these activities would inherently be found within the vesicles they come from. The components which would give the activities claimed in the instant invention would inherently do the same in nature as there has been nothing done in the instant invention that would make them act in any different way.
Step 2A prong two evaluates whether the claim as a whole integrates the recited judicial exception into a practical application (see MPEP 2106.04(d)). This evaluation is performed by (a) identifying whether there are any additional recited elements in the claim beyond the judicial exception and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. This judicial exception is not integrated into a practical application because the applicant is merely claiming them with an intended use, such as a pharmaceutical composition for treating Alzheimer’s disease. Doing so would be implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b).
The claims do not integrate the judicial exceptions into a practical application because in this context, such integration for a claimed product would be a physical form of the specific practical application instead of a more general composition that is not so limited.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because these components and their activity are already found naturally occurring in nature and the addition of an intended use does not impart any added benefit to the compounds or integrate the composition into a practical application.
Step 2 B evaluates whether the claim as a whole, amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim (see MPEP § 2106.05(b)).
The applicant claims different culturing steps however has not shown that these culturing steps attribute anything more to the extracellular vesicles. The culturing steps appear to be only a mechanism to assist with amplification of the cells in which the vesicles come from. Keeping cells alive and allowing them nutrients and the required components needed to proliferate is does not add significantly more to the vesicles themselves. Also claiming how the natural product is administered is merely an intended use.
Please also note, the mere modifying the concentration and proportions of the product/composition is not sufficient to remove the claimed composition from a judicial exception.
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 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao Lu et. al. (CN112402456A) and Ra Jeong Chan et. al. (KR2016-0050412A).
Zhao teaches of extracellular vesicles for treating Alzheimer’s disease and teaches wherein the extracellular vesicles can be from mesenchymal stem cells derived from adipose (see page 3, top).
Zhao does not teach the culturing step.
Chan teaches “the present invention relates to a composition of a culture medium for stem cells, and more specifically, to a composition of a culture medium for mesenchymal stem cells, wherein the composition comprises a basal medium in which DMEM and defined keratinocyte-SFM are mixed, L-ascorbic acid 2phosphate, fetal bovine serum, basic fibroblast growth factors (b-FGF), insulin, N-acetyl-L-cysteine, calcium chloride, and hydrocortisone. The present invention can improve the differentiation and proliferation capacities of mesenchymal stem cells, and culture the mesenchymal stem cells at a lower cost than conventional methods, thereby making it possible to economically produce cell therapeutics using the mesenchymal stem cells” (see abstract). Chan teaches this process for adipose-derived stem cells and teaches subculturing to prepare four differentiated multipotent mesenchymal stem cells (see page 5 at bottom).
Therefore it would have been obvious to persons having ordinary skill in the art before the effective filing date to use the growing conditions taught by Chan for growing adipose-derived stem cells and to first grow at a cell density as instantly claimed until the cells are above 90% of that before the culture and to have a second culture at a higher density as claimed because one would want to expand the cells to being nearly confluent in order to obtain a larger amount of extracellular vesicles for the composition as taught by Zhao. Chan teaches using the same culturing components as instantly claimed for reasons of improving the proliferation capacity of the stem cells. Additionally, the this is a product-by-process case which means that the product is what is being examined including the implied structure therein, not the process and not in the administering of the resultant product, and patentability is not limited to the recited method of production steps (see MPEP 2113). Furthermore, the limitation wherein the composition is administered transnasally is an intended use for the product and does not change the composition in any structural or functional way.
Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao Lu et. al. (CN112402456A) and Ra Jeong Chan et. al. (KR2016-0050412A) as applied to claims 1 and 6, above, and further in view of Ly James Lee et. al. (US11674130B2).
Zhao and Chan teach a pharmaceutical composition for treating Alzheimer's disease, which at least comprises an extracellular vesicle and teach the culturing method however are silent on the gene transfection as described in claim 2.
Lee’s general disclosure teaches a method for producing therapeutic exosomes from nanoelectroporation (see abstract).
Lee teaches that “therapeutic extracellular vesicles (EVs) containing high copies of functional nucleic acids and other biomolecules are produced in large quantities by laying donor cells on a surface of a chip, adding various plasmids, other transfection vectors and their combinations to a buffer on the chip, applying a pulsulatic electric field across the cells laid on top of the chip surface and plasmids/vectors buffer solution below the chip surface, and collecting the EVs secreted by the transfected cells. The chip surface has a three-dimensional (3D) nanochannel electroporation (NEP) biochip formed on it, capable of handling large quantities of the donor cells. The buffer is adapted for receiving plasmids and other transfection vectors” (see abstract).
Therefore it would have been obvious to persons having ordinary skill in the art before the effective filing date to use the gene transfection process from Lee to transfect the EV’s with a plasmid which can be used to treat genes/proteins targeting Alzheimer’s disease. It would have also been obvious to optimize the plasmids concentration in the PBS to that be within the instantly claimed range because one would want to make sure the concentration was at a maximal point for transfection. This is an optimization well within the purview of any skilled artisan.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Zhao Lu et. al. (CN112402456A) and Ra Jeong Chan et. al. (KR2016-0050412A) as applied to claims 1 and 6 above, and further in view of Louis Hersh (US20030165481A1).
Zhao and Chan teach a pharmaceutical composition for treating Alzheimer's disease, which at least comprises an extracellular vesicle and teach the culturing method however are silent on the EV’s expressing neprilysin.
Hersh’s general composition is to amyloid peptide inactivating enzymes for treating Alzheimer’s disease (see abstract).
Hersh teaches that A method for preventing formation or growth of amyloid plaque without causing neurotoxicity, comprising: a) generating a recombinant viral or plasmid vector comprising a DNA sequence encoding at least one amyloid peptide inactivating enzyme operatively linked to a promoter; (see claim 1) and wherein the inactivating enzyme is neprilysin (see claim 4), because neprilysin is known to cleave Aβ 1-40 and Aβ1-42 into what appears to be innocuous products (see 0007).
Therefore it would have been obvious to persons having ordinary skill in the art before the effective filing date to have the EV’s highly express neprilysin because this enzyme can cleave Aβ 1-40 and Aβ1-42 into what appears to be innocuous products. These peptides are a known complication in Alzheimer’s disease and so including it in a composition for such a treatment is prima facie obvious.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Zhao Lu et. al. (CN112402456A) and Ra Jeong Chan et. al. (KR2016-0050412A) and Ly James Lee et. al. (US11674130B2) as applied to claims 1-3 and 6 above, and further in view of Patricia A. Pereira et. al. (Recombinant pre-miR-29b for Alzheimer’s disease therapeutics, Nature: Scientific Reports, 6:19946, 28-Jan-2016).
Zhao and Chan teach a pharmaceutical composition for treating Alzheimer's disease, which at least comprises an extracellular vesicle and teach the culturing method along with a gene transfection plasmid however are silent on the EV’s highly expressing either miR-29a or miR-29b.
Pereira’s general disclosure is to miR-29b being used as a therapeutic for Alzheimer’s disease (See abstract).
Pereira teaches “Recently, several studies have been published concerning the expression of miR-29 in patients with Alzheimer’s disease, suggesting that this biomolecule can play an important role in the regulation of this neurodegenerative disease. The generation and subsequent accumulation of amyloid-β peptides (Aβ) is a histological characteristic that is strongly implicated in the pathogenesis of AD. One of the mechanisms that contribute to the accumulation of Aβ is sequential proteolytic cleavages of full-length amyloid precursor protein (APP) by β -site amyloid precursor protein cleaving enzyme 1 (BACE1), being considered as a prime drug target for therapeutic inhibition of Aβ production in AD. Hence, the regulation of the protein’s expression levels involved in the Aβ generation process has demonstrated to be important in AD. Several research groups showed that the miR-29 is potentially involved in the regulation of APP and BACE1 expression because in vitro studies revealed that in sporadic AD patients, displaying abnormally high BACE1 protein levels, the miR-29 cluster was significantly decreased. These findings provided support for a causal relationship between miR-29 and AD, since the miR-29b suppresses the expression levels of BACE1 and, consequently, Aβ peptides levels in neuronal cells16. Thus, miR-29 can be used as a potential therapeutic weapon for pharmacological intervention of AD” (see page 1-2).
Therefore it would have been obvious to persons having ordinary skill in the art before the effective filing date to have the EV’s highly express miR-29b because this micro-RNA’s expression helps to suppress levels of BACE1 and consequently Aβ peptide levels.
Conclusion
Currently no claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACOB ANDREW BOECKELMAN whose telephone number is (571)272-0043. The examiner can normally be reached Monday-Friday 8am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Terry McKelvey can be reached at 571-272-0775.The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
JACOB A BOECKELMAN Examiner, Art Unit 1655
/TERRY A MCKELVEY/ Supervisory Patent Examiner, Art Unit 1655