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 1-9) in the reply filed on 10/8/2025 is acknowledged.
Claims 10-25 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-9 have been considered on the merits.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
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 7-8 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.
Claims 7-8 disclose the ratio of exosomes and MVs in the EV composition. There is no disclosure what the claimed ratio is based on. Thus, it is not clear if the ratio is based on the quantity of the vesicles or any other unit, e.g. weight, volume, or any contents, e.g. protein, nucleic acid, etc. Without the ratio being limited with a specific unit, it is considered indefinite.
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 1-6 and 8-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product, a judicial exception, without significantly more. The claim(s) recite(s) an extracellular vesicle (EV) composition derived from mesenchymal stem cells (MSCs) and the composition comprising a mixture of microvesicles and exosomes. The claimed extracellular vesicle composition is considered to be naturally occurring as it is known in the art that many cells if not all are capable of producing and secreting extracellular vesicles including microvesicles and exosomes according to Akuma et al. (2019, Frontiers in Sustainable Food Systems) and Raposo et al. (2013, JCB). The MSCs including Wharton’s jelly derived MSCs would naturally secrete EVs (McLaughlin et al. 2022, Cells; Chen et al., 2022, Int. J. Pharm.). Thus, the extracellular vesicle composition comprising MVs and exosomes are naturally occurring as cells including MSCs derived from Wharton’s Jelly would secrete the mixture of microvesicles and exosomes in nature. Thus, the claims recite a product of nature, a judicial exception.
Claims 2-6 disclose the limitations directed to the source of the extracellular vesicles and structural properties of these naturally occurring product, and thus, these additional elements do not add significantly more to the judicial exception, and thus, these limitations do not render the claimed product markedly different from the naturally occurring microvesicles and exosomes.
Regarding claims 8-9 directed to the ratio of exosomes and MVs in the EV composition being about 0.5 to 1.5 or 1:1, in the absence of any evidence that the claimed ratio of MVs and exosomes in the EV composition markedly change the characteristics of the EV composition or MVs and exosomes therein, it is considered that the ratio of the components in the naturally occurring product is not significantly different from the judicial exception. (STEP 2A Prong One: YES).
This judicial exception is not integrated into a practical application because there is no additional element that would integrate the judicial product into any improvement in their function or the use of a particular treatment or applying or using the judicial exception in some other meaningful way. Thus, the judicial exception is not integrated into a practical application (STEP 2A Prong Two: NO).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because as discussed in the analysis of STEP 2A, Prong One, the additional elements directed to the source, structure of the MVs and exosomes in the composition do not add significantly more to the judicial exception. For the same rationale, the ratio as claimed in claims 8-9 do not amount significantly more than the judicial exception.
Based on the above discussion, it is the Examiner’s position that the claims are not directed to eligible subject matter under 35 U.S.C. 101.
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.
Claim(s) 1-6 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Joerger-Messerli et al. (2018, Cell Transplantation) as evidenced by Kowal et al (.
Joerger-Messerli et al. teach extracellular vesicles derived from human Wharton’s Jelly mesenchymal stem cells (Abstract).
Regarding the wherein clause of claim 1, it is considered that the wherein clause is directed to the result of the composition when it is used, i.e. intended use of the product. As the wherein clause does not provide any structural limitation to the claimed product, the wherein clause does not limit the claimed product.
Regarding claim 2 directed to the MSCs are derived from an infant, it is considered that the Wharton’s jelly is from an umbilical cord, i.e. a tissue from the newborn infant.
Regarding claims 3-4 directed to the exosomes having a diameter less than 100 nm or MVs having a diameter from about 100 nm to 1000 nm, Joerger-Messerli et al. teach that EVs can be classified including microvesicles (MVs) and exosomes, and the diameter of MVs is 50 to 1000 nm, and that of exosomes is 30 to 120 nm (p.169, 1st col.). Thus, the EVs of hWJ-MSCs taught by Joerger-Messerli et al. would inherently contain exosomes having a diameter less than 100 nm and MVs having a diameter about 100 to 1000 nm.
Regarding claim 5 directed to the exosomes and microvesicles expressing CD63, Joerger-Messerli et al. teach that CD63 is a marker for exosomes (p.170, 1st col.). However, Joerger-Messerli et al. is silent with regard to the MVs expressing CD63. However, it is inherent that MVs also express CD63 as CD63 is a marker for EVs according to Kowal et al. Kowal et al. teach that CD63 is detected not only in exosome containing fraction (100k pellet) but also in the fraction having other EVs with larger size (2k and 10k pellets) (p.E696, 1st col.), indicating that EVs larger than exosome would also express CD63, and the larger EVs than exosomes would encompass MVs. Furthermore, the instant specification discloses that EVs derived from Wharton’s jelly MSCs would contain MVs and exosomes expressing CD63, and thus, the EVs of Joerger-Messerli et al. would inherently contain MVs expressing CD63 in addition to exosomes.
Thus, the reference anticipates the claimed invention.
Claim(s) 1, 4-6 and 7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al. (2016, J. Thor. Cardio. Sur.) as evidenced by Nguyen et al. (2018, J. Ext. Ves.)
Zhang et al. teach that bone marrow mesenchymal stem cells (BMSCs) were exposed to edaravone in the culture medium for 30 min., 2 hr or 6 hr, and the supernatant from edaravone pretreated or treated BMSCs was incubated with cardiac stem cells (CSCs) (p.571, 2nd col.). The supernatant or conditioned medium of culturing BMSCs in the presence of edaravone taught by Zhang et al. would inherently contain EVs secreted from the BMSCs into the culture medium, and thus, meet the EV composition derived from MSCs treated with Edaravone.
As the supernatant of Zhang et al. would inherently contain EVs, and EVs inherently contain MVs and exosomes according to Nguyen et al. Nguyen et al. teach that the EVs from bone marrow MSCs are purified from tissue culture medium, i.e. conditioned medium or secretome (p.10, 2nd col.). The EVs of Zhang et al. would inherently contain MVs and exosomes, and the diameter of these vesicles would be inherently met by the EVs present in the supernatant of BMSCs taught by Zhang et al.
Thus, the reference anticipates the claimed invention.
Claim(s) 1-7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zeng et al. (2015, Scientific Reports) as evidenced by Zhou et al. (2014, PLOS One), Joerger-Messerli et al. (supra) and Kowal et al. (supra)
Regarding claim 1 and 7, Zeng et al. teach human umbilical cord mesenchymal stem cells (hUCMSCs) in a culture were incubated with Edaravone (p.2, Methods), and conditioned medium (p.4, In vitro and in vivo secretion of HGF by hUCMSCs). This process of pre-treating the hUCMSCs in culture medium with Edaravone would inherently produce secretome released from the cells, i.e. conditioned medium.
Regarding claims 2-3, while the source of the hUCMSCs is not particularly disclosed Zeng et al., however, Zeng et al. teach that the hUCMSCs are obtained by the method of Zhou et al. (p.2, Methods). According to Zhou et al., the hUCMSCs are isolated from Wharton’s jelly of the umbilical cord (p.2, 1st col., Isolation and expansion of hUCMSCs). As the Wharton’s jelly is isolated from umbilical cord, this teaching would inherently meet the limitation of claim 2 directed to the MSCs being from an infant.
Regarding the limitations of claims 4-6, it is considered that the conditioned medium of Zeng et al. would inherently meet the limitation based on the teaching of Joerger-Messerli et al. and Kowal et al. Joerger-Messerli et al. teach that EVs can be classified including microvesicles (MVs) and exosomes, and the diameter of MVs is 50 to 1000 nm, and that of exosomes is 30 to 120 nm (p.169, 1st col.). Kowal et al. teach that CD63 is detected not only in exosome containing fraction (100k pellet) but also in the fraction having other EVs with larger size (2k and 10k pellets) (p.E696, 1st col.), indicating that EVs larger than exosome would also express CD63, and the larger EVs than exosomes would encompass MVs.
Thus, the reference anticipates the claimed invention.
Claim(s) 1 and 4-6 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Collino et al. (2017, Stem Cell Rev. and Rep)
Collino et al. teach fractions enriched with exosomes and microvesicles isolated from bone marrow mesenchymal stem cells (Abstract). Collino et al. characterized EVs isolated from the conditioned medium of MSCs and collect fractions 1-4 (CF1), fractions 5-8 (CF2) and fractions 9-12 (CF3) after separating the EVs on density gradient separation (p.227, Materials and Methods). According to Figure 1 of Collino et al., CF1 represents EV population having the size of 10-150 nm; and CF2 represents EV population having the size of 170 nm to 310 nm. These CF1 and CF2 would meet exosome and MVs of the instant claims 4-5.
Collino et al. teach that CD63 expression in all of the fractions (Fig. 2), and thus, meet the limitation of claim 6.
Thus, the reference anticipates the claimed invention.
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.
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.
Claim(s) 1, 4-6 and 8-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Collino et al. (supra)
Collino et al. teach the subject matter of claims 1 and 4-6 and thus, render them obvious (see above).
Regarding claims 8-9, Collino et al. do not particularly teach the limitation. However, Collino et al. teach that these fractions have different biological effect as for cell proliferation and apoptosis, only CF1 and CF2 would have significant effect (p.230-231, Fig. 3e) whereas for ischemia reperfusion injury, only CF2 not CF1 or CF3 produced significant effect (p.231, 1st col.), and thus, this teaching indicates that these fractions would have different biological effects. Based on this teaching, it would have been obvious to a person skilled in the art to use a single fraction or combine multiple fractions for the desired outcome in their therapeutic use. For example, as for the cell proliferation and apoptosis, one would combine CF1 and CF2 as they both have significant biological effect.
Furthermore, when these combined fractions are combined, it would have been obvious to a person skilled in the art to use any ratio as desired including the equal amount of vesicle quantity or RNA and/or protein quantity measured with a reasonable expectation of success in the absence of any evidence to the contrary.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAEYOON KIM whose telephone number is (571)272-9041. The examiner can normally be reached 9-5 EST Monday-Friday.
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, JAMES SCHULTZ can be reached at 571-272-0763. 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.
/TAEYOON KIM/ Primary Examiner, Art Unit 1631