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 1-3, 8, 14-19 and 22-24 in the reply filed on Nov. 6, 2025 is acknowledged. Claims 27 and 39-44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The most recent claim set, dated Jan. 1, 2023, is being considered. Claims 27, and 39-44 are withdrawn. Claims 1-3, 8, 14-19, and 22-24 are examined on their merits below.
Priority
The application is a continuation-in-part of application 17/085,695, filed Oct. 30, 2020; as such the earliest possible priority date is Oct. 30, 2020.
Information Disclosure Statement
The information disclosure statements filed Jan. 31, 2023; Feb. 13, 2024; July 5, 2024; and Dec. 26, 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs have been considered by the examiner.
The information disclosure statement filed April 1, 2025* fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits. *Please note that IDSs filed after Jan. 19, 2025 must be filed with an IDS size fee assertion form and the appropriate fee, if applicable.
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 8, and 14-19 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 8, 14, 16, and 18 recite that the concentration of the ECM component is higher or x times higher “than a concentration of the ECM component in a comparable exosome preparation.” The term “comparable exosome preparation” is a relative term which renders the claim indefinite. The term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. While para. [0016] of the specification appears to give a definition “…the comparable exosome preparation is an exosome preparation prepared via ultracentrifugation;” in paras. [0073]-[0077] and [0079], multiple times, an exosome preparation prepared by ultracentrifugation is referred to as only an example (“e.g. prepared via ultracentrifugation”) of a “comparable exosome preparation,” not the singular definition of it. As such, unless and until applicants provide clarification that resolves this contradiction in the specification, there is no other evidence (within the claims or known by those of ordinary skill in the art) that enables resolution.
Additionally, the claims are directed to a product (“exosome composition”) and there is nothing in the claims themselves that indicates how the claimed “exosome composition” is prepared (save that the exosomes are from MSCs). As such, how is one to determine the difference between the claimed products and comparable exosome preparation, as the difference appears to be imparted by the preparation.
Claims 15, 17 and 19 depend from claims that recite the indefinite term and fail to resolve the indefiniteness. They are rejected on this basis.
It is noted that claim 22 recites a definition for the term, making that claim definite.
It is not possible to interpret these rejected claims. As explained above, there is no way to determine what a comparable exosome preparation is. Furthermore, in light of the fact that dependent claims serve to further differentiate the claim from both its independent claim and other dependent claims, it is inappropriate to apply the narrow definition established in claim 22, as clearly, this was not the intended scope of dependent claims as this interpretation would render dependent claim 8 and 22 as duplicate claims.
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 1-3, 8, 14-19, and 22-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring composition without significantly more. The claim(s) recite(s) an exosome composition including at least one exosome produced by a mesenchymal stem cell or fibroblast cell and at least one component isolated from an extracellular matrix. This judicial exception is not integrated into a practical application because as shown in Fig. 1 of the application, the claimed cell product (exosomes and an extracellular matrix component) is naturally occurring and the process that is applied to collect this naturally occurring product does not alter the claimed product enough to distinguish it from its naturally occurring counterpart. In fact, for the exosomes and extracellular matrix product to be therapeutically useful, it must maintain a similarity to the naturally occurring product. (See para. [0003] of the published application). Para. [0098] of the specification indicates that the exosome composition is isolated from conditioned media produced by human mesenchymal stem cells. See also Han et al. (Stem Cells Internl, 2016), Fig 1, showing the exosomes. Note that the extracellular matrix is in and around the space between the cells and the exosomes, so adjacent to the exosomes in its naturally-occurring environment.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because each of the dependent claims further defines what is in the claimed cell product (or how it differs by using an isolation process that keeps the product more intact, e.g. closer to its naturally occurring product than counterparts that are isolated in a less intact manner). Claim 24 recites that the exosome composition further includes a carrier or excipient. This additional element is not enough to amount to sufficiently more. Since no specific carrier or excipient is recited, a naturally occurring one, such as saline, would meet this limitation. Neither the exosome composition on it own, a saline carrier on its own or the combination of the cells and saline would amount to significantly more than the naturally occurring product, as the media is intended to maintain the EVs, replicating the surrounding fluid that they encounter while in the human body. Additionally, neither the limitation that the ECM component is isolated (independent claim 1) nor the recitation of a carrier or excipient (claim 24) renders the claims markedly different from what exists in nature. Myriad clarified that not every change to a product will result in a marked difference, and that the mere recitation of particular words (e.g., “isolated” or “excipient or carrier”) in the claims does not automatically confer eligibility. Id. at 2119. See also Mayo, 132 S. Ct. at 1294 (eligibility does not “depend simply on the draftsman’s art”). There is no indication in the specification, nor have applicants provided any evidence that the claimed exosome composition including an exosome and a component isolated from an ECM in a carrier/excipient (e.g. saline or water) is markedly different from its naturally occurring counterpart.
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) 1-3 and 22-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wong et al. (Arthroscopy, Aug., 2020).
The claims are directed to an exosome composition comprising (a) at least one exosome produced by a mesenchymal stem cell (MSC) or fibroblast cell and (b) at least one component isolated from an extracellular matrix (ECM component).
With respect to independent claim 1, Wong et al. teach a composition that contains exosomes produced by MSCs and an isolated ECM component (hyaluronan) (Abstract, pg. 2217, 1st col, 1st full para. “…Intra-articular 1-mL injections of exosomes + HA (exosome + HA) or HA alone were administered…”).
With respect to claims 2 and 3, Wong et al. teach that hyaluronic acid and exosomes are present in the administered composition (“a glycoaminoglycan” and “hyluronan”). (Abstract, pg. 2217, 1st col, 1st full para.).
With respect to claim 22, Wong et al. teach that the exosomes are derived from conditioned media that is not centrifuged. (pg. 2216, “Preparation and Characterization of MSC Exosomes”).
With respect to claim 24, Wong et al. teach that the 1-mL injections of exosomes + HA contained 200 µg of exosomes, suspended in 1 mL of 3% (w/v) HA. (pg. 2217, 1st col, 1st full para.) While Wong et al. do not explicitly teach what the excipient or carrier the 3% HA is in, it would be understood by one of ordinary skill in the art that the HA and exosomes were suspended in a carrier.
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.
Claims 23 is rejected under 35 U.S.C. 103(a) as obvious over Wong et al. (Arthroscopy, Aug., 2020) as applied to claims 1-3, 22 and 24 above and further in view of Haraszti et al. (Molecular Therapy, 2018, cited in IDS filed on Jan. 31, 2023.
Wong et al. do not teach the number of exosomes in their exosome + HA preparation. Wong et al. indicate that exosomes were isolated from MSC conditioned media, size fractionated and concentrated 50x by tangential flow filatration. (pg. 2216, “Preparation and Characterization of MSC Exosomes”). 200 µg of exosomes are then suspended in 1 mL of 3% (w/v) HA. pg. 2217, 1st col, 1st full para.)
Haraszti et al. teach that the range of administration of exosomes per animal (mouse) in preclinical small animal studies is 109 – 1011, or from about 100 million to 10 billion. (pg. 2842, 1st col., 1st full para.).
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the exosome + HA preparation taught by Wong et al. to incorporate including at least a billion exosomes because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Making this modification would have led to predictable results with a reasonable expectation of success because both Wong et al. and Haraszti are directed to use of therapeutic exosomes isolated using tangential flow filtration and Haraszti et al. teach that administering at least a billion exosomes is in an appropriate range for small animals. As such, a person of ordinary skill in the art would be motivated to form a composition that contained at least a billion exosomes for use in larger animals (such as the rabbits used by Wong et al (pg. 2216, “Animal Study Design and Surgical Procedure”) or for use in pre-clinical trials in humans.
Conclusion
No claims are allowed.
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/TERESA E KNIGHT/Primary Examiner, Art Unit 1634