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 .
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This Action is in response to the papers filed on 08/07/2026. Claims 1-2, 5, 7-11, 15-16, 18 and 21-30 are currently pending. Claims 5, 7, 9, 16, 18 and 21 have been amended by Applicant’s amendment filed on 08/07/2026.
Election/Restrictions
Applicants’ election of Group I, which include claims 1-2, 5, 7-11, 15-16, 18, 21-27 and election of species for Group I, plasma as a single biological material in claim 2, a small molecule as a single biomolecule in claim 22, and kidney disease as a single specific pathology relevant to claim 25 and 26 in the reply filed on 02/26/2026 was previously acknowledged. The requirement for election of species in claim 22 for a specific biomolecule was withdrawn.
Because applicants did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 28-30 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected subject matter, there being no allowable generic or linking claim. Claim 27 was previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected species, there being no allowable generic or linking claim.
The requirement for restriction was previously made final.
Therefore, claims 1-2, 5, 7-11, 15-16, 18, 21-26 are currently under examination to which the following grounds of rejection are applicable.
Priority
The instant application a 371 of PCT/US2021/015488 filed 01/28/2021, which claims priority to PRO 62/966,730 filed 01/28/2020.
Thus, the earliest possible priority for the instant application is 01/28/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/07/2026 were filed before the mailing date of the non-final office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections/Rejections in response to Applicants’ arguments or amendments
Claim Objections
The objection of claims 9 is withdrawn in view of the amendments in the response filed on 08/07/2026.
Maintained and modified rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 112 (b)
Claims 1-2, 5, 7-11, 15-16, 18, 21-26 remain 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 applicant regards as the invention.
Claim 1 recites “extracorporeal transfusion” in line 7. The term " extracorporeal transfusion " is not defined by the claim, the specification does not provide a definition of the term, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Moreover, a Google® search of this term does not give any hit which demonstrates that this is not commonly used term. As such the metes and bounds of the claim are indefinite.
Claims 2, 5, 7-11, 15-16, 18, 21-26 are indefinite insofar as they depend from claim 1.
Response to Applicants’ Arguments as they apply to the maintained rejection of claims 1-2, 5, 7-11, 15-16, 18, 21-26 under 35 U.S.C. 112(b)
PNG
media_image1.png
521
850
media_image1.png
Greyscale
At Pg. 7 of applicants’ remarks filed 08/07/2026, applicants argue the following:
Applicants’ arguments have been considered but have not been found persuasive.
The manner in which “extracorporeal” is intended to modify “transfusion” is claim 1 remains unclear. With respect to applicants’ argument, claim 1 does not recite an extracorporeal circuit, extracorporeal device, or a continuous withdrawal and return arrangement. Although the specification does describe embodiments of such devices and treatment setups, those disclosed embodiments do not establish that such features are required by the broader recited phrase in claim 1 of “extracorporeal transfusion”.
The applicants’ assertion that the transfusion is carried out via an extracorporeal circuit or device” introduces limitations not recited in the instant claim 1. Moreover, claim 10 separately requires the transfusing step be performed by a recipient adjusted extracorporeal device and claim 15 separately requires a closed-loop system. It therefore remains unclear whether claim 1 encompasses any administration of biological material that has previously been processed outside the body or instead requires the return/transfusion itself to occur as part of an extracorporeal apparatus or circuit. The cited portions of the specification identify examples of extracorporeal equipment and treatment arrangements, but do not provide an objective boundary resolving that distinction. Accordingly, a person of ordinary skill in the art would not be reasonably comprised of the metes and bounds of the phrase “extracorporeal transfusion” and the rejection is maintained.
Claim Rejections - 35 USC § 102
Claim(s) 1-2, 5, 7-9, 16 and 21-22 remain rejected under 35 U.S.C. 102 as being unpatentable over Cheng et al. (WO 2018/195393 Al; hereafter “Cheng”).
Regarding claim 1, Cheng teaches a process for acellular therapy, including the collection and use of exosomes (Abstract). Cheng teaches obtaining a biological material (Pg. 2, Lines 1-9 and Lines 18-21), providing a sample of essentially purified extracellular vesicles (Pg. 2, Line 2), fusing the extracellular vesicle with the biological material (Pg. 2, Lines 5-7) and transfusing the fused vesicle and biological material (Pg. 4, Lines 3-11; Figure 10; Pg. 27, Lines 3-4). Cheng further teaches that the biological material and platelet-derived membrane vesicles may be obtained from the same human subject, including the recipient subject (Pg. 2, Lines 24-37). Cheng teaches an autologous embodiment wherein cardiac stem cells are derived from a cardiac tissue sample excised from the patient to be treated, cultured, engineered by fusion with platelet membrane vesicles, and thereafter administered to the same patient (Pg. 18, Lines 24-31). Cheng further teaches that engineered cells or engineered extracellular vesicles may be administered back to the individual from which the cells were derived (Pg. 26, Lines 12-14), including by infusion (Pg. 27, Lines 3-4). Thus, Cheng teaches obtaining the subject’s biological material, extracorporeally engineering the biological material by vesicle fusion, and returning the resulting engineered biological material to the same subject.
Regarding Claim 2, Cheng teaches plasma (elected species) as a biological source (Pg. 13, Line 20).
Regarding Claim 5, Cheng teaches the extracellular vesicles may consist of those from several groups, including platelet membrane derived vesicle, or its fragments, and exosomes (Pg. 2, Lines 2-10)
Regarding Claims 7-8, the particles sizes of the vesicles taught by Cheng can be between 100 and 1000, which anticipates the ranges recited in the instant claims (Pg. 12, Line 36).
Regarding Claim 9, Cheng teaches samples containing exosomes can be purified using centrifugation, ultracentrifugation, filtration or ultrafiltration (Pg. 13, Lines 34-35).
Regarding Claim 16, Claim 16 recites “The process of claim 1, wherein the sample of therapeutic extracellular vesicles is prepared immediately prior to the transfusion step, or in advance of the transfusion step. The teachings of Cheng that anticipate claim 1 as discussed above would necessarily require the sample the be prepared “in advance of the transfusion step”. Therefore, Cheng inherently would anticipate claim 16.
Regarding Claim 21-22, Cheng teaches the that the exosomes of their invention “may contain, or have present in their membrane, nucleic acid, protein, or other biomolecules and may serve as carriers of this cargo between diverse locations in a body or biological (Pg. 13, Line 11-15). Cheng teaches the term "exosomes" as used herein advantageously refers to extracellular vesicles that can have therapeutic properties…” (Pg. 13, Lines 11-15). Cheng further teaches that their exosomes can be externally decorated or encapsulated with platelet derived membrane vesicles and that such decoration of exosomes augments targeting for enhanced therapeutic outcomes (Pg. 20, Lines 5-18).
Response to Applicants’ Arguments as they apply to the maintained rejection of claims 1-2, 5, 7-9, 16 and 21-22 under 35 U.S.C. 102
At pages 9-11 of the remarks, Applicants essentially argue that Cheng does not anticipate the method of claim 1 and thus claims 2, 5, 7-9, 16 and 21-22 are novel by virtue of their dependance upon claim 1.
These arguments have been considered but have not been found persuasive.
At Pg. 10, applicants assert that “Cheng's fusion is not the claimed fusion.” and further assert that “Cheng does not disclose obtaining biological material from the subject, fusing a separately provided therapeutic-EV sample into that obtained biological material, and then transfusing the fused material back to the subject. Accordingly, Cheng does not disclose every element of claim 1 arranged as claimed.”
Applicant argues at Pg. 10 that Cheng merely describes an in vitro manufacturing process in which platelet-derive membrane vesicles are fused with cultured cells or encapsulate extracellular vesicles, rather than a process in which therapeutic extracellular vesicles are fused with biological material obtained from the recipient subject and the resulting material is returned to that subject.
These arguments have been considered but have not been found persuasive.
Applicants’ argument does not account for Cheng’s express disclosure of autologous embodiments. Cheng teaches that the cells or vesicles and the platelet-derived membrane vesicles may be derived from the same animal or human subject, including the recipient of the resulting therapeutic composition (Pg. 18, Lines 24-31). Cheng further teaches “The engineered cells, such as cardiac stem cells, or engineered extracellular vesicles such as an exosomes, of the disclosure can be administered back to the individual from which the cells were derived…” (Pg. 26, Lines 12-14). Thus, Cheng expressly describes obtaining biological material from the recipient, engineering the material via vesicle fusion outside the body, and returning the engineered material to the same recipient.
Applicant further argues at Pgs. 10-11 that Cheng does not disclose an “extracorporeal transfusion” because Cheng’s intracoronary injection or infusion constitutes direct in vivo administration.
Considered in isolation, the final injection or infusion occurs within the body. However, Cheng’s disclosed autologous process expressly requires removal of the patient’s biological material, culture and vesicle-fusion engineering of said material outside of the patient’s body, followed by administration of the resulting material back to the same patient (Pg. 18, Lines 24-31). Cheng further teaches that administration may be performed by infusion (Pg. 27, Lines 3-5). Accordingly, the claimed extracorporeal transfusion does not distinguish the process from Cheng. In fact, the applicant is on record as stating that the ordinary artisan would readily understand the term "extracorporeal" is a well-understood term in the art meaning "occurring or situated outside the body." (Applicant’s remarks pg 7), thus Cheng’s disclosed autologous vesicle-fusion engineering of said material outside of the patient’s body, followed by administration of the resulting material back to the same patient via infusion reads on the claimed term "extracorporeal".
With respect to applicants’ argument that inherency requires the allegedly missing limitations to necessarily be present is therefore not persuasive because the maintained rejection is supported by Cheng’s express disclosure of the above autologous process (removal, engineering, and return of engineered material), rather than merely by an inference that intracoronary administration itself is extracorporeal. Accordingly, the rejection of claims 1-2, 5, 7-9, 16 and 21-22 is maintained.
Claim Rejections - 35 USC § 103
Claims 10-11, 15, and 23 remain rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al. (WO 2018/195393 Al; hereafter “Cheng”) as applied to claim 1 above and in view of Briggs et al. (US 2004/0127841 Al; hereafter “Briggs”).
Cheng anticipates the method of claim 1 above, the contents of which is incorporated herein in its entirety.
Regarding Claims 10-11, 15, and 23, Cheng does not expressly teach transfusion using a recipient adjusted extracorporeal device as recited in claim 10 or a specific species of the device as recited in instant claim 11. Cheng does not teach the use of a closed-loop system as recited in instant claim 15 or storage of the vesicles to be administered prior to the transfusion as recited in instant claim 23.
Briggs cures the deficiencies of Cheng as Briggs teaches an extracorporeal blood-component collection and treatment system in which whole blood is withdrawn from a source and pumped into a separator. Plasma and or/blood cells are collected and processed extracorporeally prior to returning the processed biological component to the patient (Abstract). Briggs also teaches apheresis systems used with respect to their invention (Pg. 1, Paragraph [0004]). The method taught by Briggs may be performed in a closed-loop process (Pg. 2, Paragraph [0014]). Briggs expressly teaches storage arrangements of the patients biological material prior to administration ( Pg. 2, Paragraph [0014]; Pg. 6, Paragraph [0113]; Claims 7 and 17). It would have been prima facie obvious to a person of ordinary skill in the art at the time of the instant application to have combined the teachings of Cheng who demonstrates collection and engineering of biological material, such as extracellular vesicles for therapeutic usage with the teachings of Briggs which demonstrates the use of multiple systems for collection and administration of biological products such as apheresis type/closed loop systems. Combining these teachings would allow for the vesicle-fusion step taught by Cheng to be performed within the treatment bag of the closed-loop system of Briggs, thereby carrying out both the fusion step and the transfusion step withing a closed loop system. One would have been motivated to combine these teachings to permit controlled extracorporeal introduction and interaction of the therapeutic extracellular vesicle with the subject derived biological material while maintaining the material in a closed, sterile treatment pathway for return to the subject. These systems have been well documented for therapeutic usage and would predictably allow for controlled extracorporeal handing and return of Cheng’s therapeutic biological material.
There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the same field to give predictable results. Furthermore, Briggs successful demonstrates within their teachings the introduction of externally supplied treatment material into a patient-derived biological material within the treatment bag, followed by further extracorporeal processing and returning of the treated material to the original subject/patient.
Response to Applicants’ Arguments as they apply to the maintained rejection of claims 10-11, 15, and 23 under 35 U.S.C. 103
At pages 10-14 of the remarks, Applicants essentially argue that Cheng does not anticipate the method of claim 1 and the addition of the teachings of Briggs does not remedy the deficiencies of Cheng and thus claims 10-11, 15, and 23 are not obvious over the teachings of Cheng in view of Briggs.
These arguments have been considered but have not been found persuasive.
As discussed above in 102 rejection and the response to applicants’ arguments with respect to the 102 rejection, Cheng anticipates the method of the instant claim 1.
Therefore, the rejection of claims 10-11, 15, and 23 as being unpatentable over Cheng in view of Briggs is maintained as described in the maintained 103 rejection above.
Claim 24 remains rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al. (WO 2018/195393 Al; hereafter “Cheng”) in view of Briggs et al. (US 2004/0127841 Al; hereafter “Briggs”) as applied to claim 1 and 23 above and in view of Kusuma et al. (Kusuma GD et al., 2018; hereafter “Kusuma”).
The combined teachings of Cheng and Briggs render obvious the method of claims 1 and 23, as iterated above in the 103 rejection the content of which is incorporated herein, in its entirety.
Regarding Claim 24, The combined teachings of Cheng and Briggs do not expressly teach the cryopreservation of extracellular vesicles.
However, Kusuma teaches that enhancing long term stability of EVs intended for clinical use was well known in the art prior to the instant application (Introduction) and that “…the commercial and clinical applications of EVs require standard criteria for long-term storage.” (Pg. 5, Section: Conventional Methods for EVs Preservation). Kusuma also teaches strategies related to EV cryopreservation (Pg. 5, Section: Cryopreservation).
It would have been prima facie obvious to a person of ordinary skill in the art at the time of the instant application to have modified the teachings of Cheng and Briggs demonstrating collection and engineering of biological material, such as extracellular vesicles for targeted therapeutic usage and storage of the patient’s biological material prior to administration by further incorporating a method of cryopreserving these therapeutics for their clinical use as taught by Kusuma. One would be motivated to include a cryopreservation step as Kusuma demonstrates the importance (deeming it a required criteria) of having therapeutic EVs cryopreserved for clinical use.
There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the prior art to give predictable results.
Response to Applicants’ Arguments as they apply to the maintained rejection of claims 24 under 35 U.S.C. 103
At page 14 of the remarks, Applicants essentially argue that Cheng does not anticipate the method of claim 1 and the addition of the teachings of Briggs and Kusuma do not remedy the deficiencies of Cheng and thus claim 24 is not obvious over Cheng in view of Briggs and in further view of Kusuma under 35 U.S.C. 103.
These arguments have been considered but have not been found persuasive.
As discussed above in 102 rejection and the response to applicants’ arguments with respect to the 102 rejection, Cheng anticipates the method of the instant claim 1. Moreover, the rejection of claim 23 (from which 24 depends) as being unpatentable over Cheng in view of Briggs is maintained as described in the maintained 103 rejection above.
Therefore, the rejection of claim 24 as being unpatentable over Cheng in view of Briggs and in view of Kusuma is maintained as described in 103 rejection of claim 24 above.
Claims 25-26 remains rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al. (WO 2018/195393 Al; hereafter “Cheng”) as applied to claim 1 above and in view of Aghajani et al. (Aghajani Nargesi A et al., Stem Cell Res Ther., 2017; hereafter “Aghajani”).
Cheng et al. anticipates the method of claim 1, as iterated above in the 102 rejection the content of which is incorporated herein, in its entirety.
Regarding Claims 25-26, Cheng et al. does not teach the subject in need of their invention is afflicted with kidney disease or end stage renal disease.
Aghajani cures the deficiencies of Cheng as Aghajani teaches extracellular vesicles as potential therapeutics for kidney disease have been studied in the art prior to the filing of the instant application (Pg. 6, Table 3; Pg. 6, Section: MSC-derived EVs in experimental CKD), specifically consider ESRD when discussing the renal repair capabilities of EVs (Discussion).
It would have been prima facie obvious to a person of ordinary skill in the art at the time of the instant application to have modified the teachings of Cheng who demonstrates collection and engineering of biological material, such as extracellular vesicles for targeted therapeutic usage by further incorporating the teachings of Aghajani which demonstrates the potential capacity of EVs as a therapy for renal disease, including end stage renal disease, and arrive at a method allowing for use of engineered EVs to combat renal pathologies.
There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the prior art to give predictable results.
Response to Applicants’ Arguments as they apply to the maintained rejection of claims 25-26 under 35 U.S.C. 103
At page 14-15 of the remarks, Applicants essentially argue that Cheng does not anticipate the method of claim 1 and the addition of the teachings of Aghajani do not remedy the deficiencies of Cheng and thus claims 25-26 are not obvious over Cheng in view of Aghajani under 35 U.S.C. 103.
These arguments have been considered but have not been found persuasive.
As discussed above in 102 rejection and the response to applicants’ arguments with respect to the 102 rejection, Cheng anticipates the method of the instant claim 1.
Therefore, the rejection of claims 25-26 as being unpatentable over Cheng in view of Aghajani is maintained as described in the maintained 103 rejection above.
Conclusion
Claim 1-2, 5, 7-11, 15-16, 18 and 21-26 remain rejected.
Applicants’ 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 KODYE LEE ABBOTT whose telephone number is (703)756-1111. The examiner can normally be reached M-F 8-5.
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, Maria G. Leavitt can be reached on (571) 272-1085. 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
/KODYE LEE ABBOTT/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
