DETAILED ACTION
Status of the Claims
Claims 1, 5–7, and 14 are pending and remain under examination. In the Applicant’s December 18, 2025 Response, independent claim 1 and dependent claims 6, 7, and 14 were amended, and claims 2, 8, and 10–13 were canceled without prejudice and withdrawn from consideration.
35 U.S.C. § 112(b) Rejection — Indefiniteness – Withdrawal
The rejection of claims 1, 5–7 under 35 U.S.C. § 112(b) as indefinite is hereby withdrawn. Applicant’s December 18, 2025 amendment removed “PEP” from claim 14 and all pending claims now consistently recite “exosomes” (with claim 1 defining exosomes prepared by a specified process). Because the antecedent‑basis deficiency has been removed and the amended claims now particularly point out and distinctly claim the subject matter, the indefiniteness rejection under 35 U.S.C. § 112(b) is withdrawn.
35 U.S.C. § 102(a)(1) Rejections – Withdrawal
The rejections of claims 1, 5–7, and 14 under 35 U.S.C. § 102(a)(1) as anticipated by the cited references are hereby withdrawn. Independent claim 1 was amended to contain explicit process limitations requiring exosomes “prepared by a process that comprises: freezing material comprising cells comprising the exosomes under conditions effective to disrupt the cells but maintain the structure of the exosomes; and thawing the frozen material at a controlled rate of from 0.1 °C to 5 °C per minute.” The cited references disclose exosome compositions prepared by other methods (e.g., ultracentrifugation, PEG precipitation, affinity capture) and do not expressly disclose the claimed freeze–thaw process or the claimed controlled thaw‑rate numeric range. On the present record, there is insufficient evidence that the exosomes produced by the cited references necessarily possess the structural or process‑derived features recited in the amended claims (i.e., those features, referenced in Applicant’s response with supporting evidence, attributable to the claimed freeze–thaw with controlled thawing). Accordingly, the § 102(a)(1) anticipation rejections based on the cited references cannot be sustained and are withdrawn. (See MPEP §§ 2112, 2113 for the standards governing inherency and product‑by‑process considerations.)
Double Patenting Rejection – Withdrawal
Because the “freeze-thaw process” limitations and subsequent structural requirements are not disclosed in the identified claims of U.S. Patent No. 10,596,123, the obviousness‑type double patenting rejection over U.S. Patent No. 10,596,123 is hereby withdrawn as to claims 1, 5, 6, and 14.
Claim Rejections - 35 USC § 112 – Indefiniteness – Maintained
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.
Claim 14 remains 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 14 still refer to exosomes as “PEP” exosomes. Claim 1 also now lacks antecedent basis for the term “PEP exosomes.”
The term “PEP” (or purified exosome product) renders the claimed invention indefinite because a skilled artisan would not be reasonably apprised of the structural characteristics required by such term.
First, the disclosure does not provide a clear structural definition for the term. While the specification mentions that a PEP is a “modified exosome product having unique physical structure compared to standard exosomes” (see pg. 6), the disclosure fails to clearly identify the unique physical structures required by the term. Further, the specification exemplifies a PEP preparation method from PCT/2018/065627 (WO 2019/118817) but does not clearly limit the term PEP to structures within such disclosure, nor does it identify any physical characteristics required for a PEP. PCT/2018/065627 appears to disclose related work of Applicant (see also U.S. 12,036,325).
Next, a review of the relevant art revealed no common, art-accepted plain meaning of the term PEP. Such term appeared only in reference to what appears to be additional related work of Applicant (see e.g., Qi et al. “Characterization of a purified exosome product and its effects on canine flexor tenocyte biology.” J Orthop Res. 2020; 38: 1845–1855; reference to
PEPs according to US Patent 20160324A1, presumably US Pat Pub 2016/0324794 A1). The art did not reveal any clear structural requirements for PEPs.
Lastly, Applicant clearly intends to delineate the term PEP from the plain meaning of the term “exosome” as accepted in the art. In addition to the specification sections noted above, Applicant argued that exosomes produced by common, established purification methods are different than PEPs (see pg. 10 remarks dated 5/21/2025). However, without a clear standard for ascertaining the requisite structural characteristics of a PEP, a skilled artisan would not be reasonably apprised of the scope of the invention.
Defective Incorporation by Reference — 37 C.F.R. § 1.57
New Matter — 35 U.S.C. § 132 – New Grounds
In the December 18, 2025 Response, Applicant amended independent Claim 1 and dependent Claims 6, 7, and 14 to add limitations including: (i) a freeze–thaw preparative process with thawing at a controlled rate of 0.1 °C to 5 °C per minute; (ii) performing the freezing “under conditions effective to disrupt the cells but maintain the structure of the exosomes”; and (iii) specifying antioxidant proteins and particle size parameters. Applicant’s remarks state that support for these limitations is found in International Publication WO 2019/118817, which is clearly identified in the specification and properly incorporated by reference. Applicant further states that several U.S. patent publications are expressly cited and incorporated by reference in the specification.
While the WO publication is clearly identified, a review of the U.S. patent publications expressly cited and incorporated by reference in the specification did not reveal disclosure of the newly‑added limitations. Essential subject matter may only be incorporated by reference into a U.S. patent application through U.S. patent documents (i.e., U.S. patents or U.S. published patent applications) in compliance with 37 C.F.R. § 1.57 and applicable USPTO guidance. Incorporation by reference of non-U.S. documents, such as foreign patents or international publications (e.g., WO documents), cannot alone supply essential disclosure for claim support or written description purposes. Therefore, any essential subject matter relied upon to support claims must be explicitly disclosed within the application as filed or properly incorporated U.S. patent documents.
On the present record, the incorporated U.S. documents lack explicit disclosure of the freeze–thaw process, controlled thaw‑rate range, structural preservation conditions, or antioxidant protein cargo as recited in the amended claims. Reliance solely on the incorporated WO publication for these limitations, without corresponding disclosure in the incorporated U.S. documents, is insufficient to supply written‑description support under USPTO incorporation rules.
Accordingly, Claims 1, 5–7, and 14 are rejected under 35 U.S.C. § 132 as containing new matter.
Written Description / Enablement — 35 U.S.C. § 112(a) – New Grounds
Because the incorporated U.S. documents lack disclosure of the freeze–thaw preparation steps, the claimed controlled thaw-rate range, structural preservation conditions, and specified antioxidant cargo, the amended claims are not adequately supported or enabled by the application as filed or by the incorporated U.S. material. Reliance solely on the incorporated WO publication does not satisfy USPTO incorporation-by-reference requirements for essential subject matter in U.S. documents. Therefore, claims 1, 5–7, and 14 are rejected under 35 U.S.C. § 112(a) for lack of adequate written description and enablement.
Double Patenting Rejection – Maintained
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined
application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 5, 6, and 14 remain rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 1, 18, 35, and 36 of U.S. Patent No. 12,036,325 (‘325), in further view of Batrakova et al. (WO 2017173034 A1; ISR of record 01/24/2022).
The ‘325 patent discloses and claims methods of preparing exosome-containing compositions from biological source material and administering such compositions for therapeutic purposes, including exosomes prepared by freezing and thawing biological material.
The presently amended claim 1 recites a method of treating tissue damage caused by oxidative stress by administering a composition comprising exosomes containing at least one antioxidant protein, wherein the exosomes are prepared by freezing material comprising cells under conditions effective to disrupt the cells but maintain the structure of the exosomes, and thawing the frozen material at a controlled rate of 0.1 °C to 5 °C per minute. Claims 1 and 18 of ‘325 specifically recite such freeze thaw method, including the controlled rate.
The reference claims do not teach use of the PEPs to treat tissue damaged by oxidative stress as recited in application Claims 1, 5, 6, and 14.
As outlined in previous prosecution, Batrakova et al. exemplifies successful treatment of tissue damage caused by oxidative stress using exosomes to deliver antioxidant proteins, i.e. Batrakova discloses a method of treating tissue damage in a subject comprising the attenuation of astrocytosis by exoCAT. Batrakova discloses a decrease of neuroinflammation in animals treated with exoCAT (page 7, paragraph 0035).
It would have been prima facie obvious to a skilled artisan at the effective filing date of the application to utilize the exosomes disclosed by the reference claims in the treatment methods of Batrakova et al. with predictable success because Batrakova et al. demonstrates that exosomes were useful in such a capacity.
Prior Art Status
The claims, as amended, appear to be free from the prior art. However, the claims remain rejected for other reasons as set forth herein, including the rejections under 35 U.S.C. §§ 112(a) and 132 relating to written description, enablement, and new matter, as well as the incorporation‑by‑reference deficiencies.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTOPHER M BABIC whose telephone number is (571)272-8507. The examiner can normally be reached Mon - Fri, 8:30 AM - 5 PM.
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, Yvonne Eyeler can be reached at 571-272-8507. 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.
/CHRISTOPHER M BABIC/ Supervisory Patent Examiner, Art Unit 1633