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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 22 September 2025 has been entered.
Priority
The application was filed on 04 September 2020 and is the national stage entry of PCT/US19/20971 filed on 06 March 2019. The Applicant claims domestic benefit to provisional application 62/639,300 filed on 06 March 2018. Therefore, the effective filing date of the application is 06 March 2018.
Examiner’s Note
Applicant's amendments and arguments filed 22 September 2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections
and/or objections not reiterated from previous office actions are hereby withdrawn. The
following rejections and/or objections are either reiterated or newly applied. They constitute the
complete set presently being applied to the instant application. In the Applicant’s response, filed
22 September 2025, it is noted that claim 1 has been amended for clarity. Support can be found in pgs. 1-3 of the specification. No new matter has been added.
Claim Objections
Claim 1 is objected to because of the following informalities: “an effective amount of i) an effective amount of a therapeutic agent” and “ii) an effective amount of an autologous exosome.” Applicant should correct the redundancy of “an effective amount.” Appropriate correction is required.
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.
Claim 5 is 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 5 recites the limitation "the cancer." There is insufficient antecedent basis for this limitation in the claim.
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.
Claim(s) 1, 3, 5, 7, 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (US 20140093557 A1) and Ha et al. (Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges, Acta Pharmaceutica Sinica B, 2016), as evidenced by Badi et al. (Lung Metastasis in Cutaneous Malignant Melanoma: It Is Never Too Late, Chest, 2018), Yi (Current understanding of plant-derived exosome-like nanoparticles in regulating the inflammatory response and immune system microenvironment, Pharmacological Research, 2023), and Liu (Exosomes in cancer nanomedicine: biotechnological advancements and innovations, Molecular Cancer, 2025).
Zhang teaches compositions and methods for treating cancer (abs; entire teaching) using a therapeutic agent. The agent may be a chemotherapeutic agent (abs) or plant-derived phytochemical agent and is encapsulated by an exosome (abs). The exosomes may be derived from various sources, such as fruit cells or cancer cells (para. 11) and may be delivered in multiple doses (para. 67), where exosomes derived from different types of cells offer various advantages (para. 65). In Zhang’s teaching, the nanovesicles derived from plants are interpreted as plant-derived exosome-like nanoparticles (Yi, pg. 1) and nanovesicles derived from a patient’s tissues or cells are interpreted as autologous exosomes, addressing claims 1 and 3, where the art seemingly uses terms such as exosomes, nanovesicles, nanoparticles, etc. interchangeably. Plant-derived exosome-like nanoparticles are interpreted as nanoparticles and not exosomes, addressing claim 18 and step (i) of claim 1. Furthermore, it is also demonstrated in the art that exosomes are interpreted as naturally-occurring from subjects, whereas nanoparticles are interpreted as synthetic (evidenced by Liu, abs). The methods may be used to treat melanoma (para. 91), lung cancer (para. 16), breast cancer (para. 16), or various carcinomas such as bronchioalveolar carcinoma, which give rise to metastatic cancers (para. 93), addressing claims 5 and 7. Malignant melanoma often leads to metastatic lesions in the lung (pg. 1), as evidenced by Badi et al.
Zhang et al. do not teach an exact method of delivering a plant-derived nanoparticle comprising a chemotherapeutic agent and an autologous exosome.
Ha teaches that there are advantages to using certain drug delivery vehicles and that nanoparticles are preferred over other vehicles (pg. 290). Nanoparticles are helpful in entrapment, encapsulation, or attachment of drug molecules (pg. 290), as well as better stability (pg. 291). Exosomes may provide better biocompatibility, less toxicity issues, and long-term safety (pg. 291).
In regards to selecting a combination of exosomes, phytochemical agent, chemotherapeutic agent, “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G.Pro, 425 U.S. 273, 282 (1976)). “When the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been obvious to have selected various
combination of various disclosed ingredients from within a prior art disclosure, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
Zhang teaches compositions and methods for treating cancer using a chemotherapeutic agent or plant-derived phytochemical agent that is encapsulated by an autologous exosome, whereas the claimed invention is directed towards methods for treating cancer and compositions comprising a nanoparticle derived from an edible plant and an autologous exosome. Since Zhang teaches the individual components of the claimed invention and also provides a reasoning for using nanovesicles derived from different sources, it is obvious for one of ordinary skill in the art to select the different combinations of ingredients and steps to arrive at the claimed invention with a reasonable expectation of success.
In regards to delivering the nanoparticle and exosome in separate steps in claim 1, Zhang teaches exosomes derived from various sources, such as plants or human cells, where using a variety of sources for the exosomes offers some advantages. Additionally, Zhang teaches delivering the composition in multiple doses. Therefore, one of ordinary skill in the art would have been led to use a method of treating cancer by delivering a plant-derived exosome-like nanoparticle (step i) and autologous exosome (step ii) to a patient, or vice versa given the general broadness of the teaching. Ha teaches that there are advantages to using certain drug delivery vehicles, such as in regards to biocompatibility, stability, and drug encapsulation. Therefore, one of ordinary skill in the art would have been motivated to use Ha’s teaching to modify and improve Zhang’s teaching to arrive at a method of delivering a nanoparticle and exosome.
Claim(s) 1, 3-5, 7, 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (US 20140093557 A1), Ha et al. (Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges, Acta Pharmaceutica Sinica B, 2016), and Williams et al. (WO 2018039119 A1), as evidenced by Badi et al. (Lung Metastasis in Cutaneous Malignant Melanoma: It Is Never Too Late, Chest, 2018), Yi (Current understanding of plant-derived exosome-like nanoparticles in regulating the inflammatory response and immune system microenvironment, Pharmacological Research, 2023), and Liu (Exosomes in cancer nanomedicine: biotechnological advancements and innovations, Molecular Cancer, 2025).
In regards to claim(s) 1, 3, 5, 7, 18, Zhang and Ha, as applied supra, is herein applied in its entirety for its teachings of compositions and methods for treating lung and breast cancer using exosomes and phytochemical and chemotherapeutic agents.
Zhang does not specifically teach administering the exosome 30 minutes prior to administering the nanoparticle.
Williams et al. teach methods for treating lung cancer (para. 291) using autologous exosomes (para. 214). The method includes administering a therapeutic second dose 15 minutes to 3 hours after the first dose (para. 5). This type of administration is designed to partially block the uptake of therapeutic exosomes in the liver and/or spleen to improve systemic delivery to other organs and tissues (para. 2). Williams teaches that their exosomes may be derived from various cell sources, such as eukaryotes, prokaryotes, archae, fungi and protists (para. 213).
Since Zhang does not teach a method of administering the exosome 30 minutes prior to the nanoparticle in claim 4, one skilled in the art would have been motivated to use the method of administering the therapeutic second dose 15 minutes to 3 hours after the first dose from Williams et al. to address the deficiencies in Zhang’s teachings to increase systemic delivery of the therapeutic agent to other organs and tissues to treat cancer. A skilled artisan would be able to use Zhang’s broad and general teaching considering the sources of the nanoparticles and exosomes and number of doses. Since Zhang teaches that different sources for the nanoparticles provide various advantages, a skilled artisan would have been able to adjust and modify the composition itself, as well as the order of administration to arrive at the claimed invention with a reasonable expectation of success. Additionally, Williams teaches that their cells may be derived from various sources, which include humans and non-humans, which, consistent with the other cited art, may be interpreted as a nanoparticle instead. Williams’ teaching is to demonstrate the administration method of using vehicles derived from different sources to deliver therapeutic agents.
Response to Arguments
Applicant's arguments filed 22 September 2025 have been fully considered but they are not persuasive.
The Applicant argues that Zhang uses exosomes and nanoparticles interchangeably, whereas the claimed invention distinctly uses nanoparticles and exosomes as separate items (Remarks, pg. 5).
Applicant’s argument is not found persuasive. As stated in the previous Office Action, Zhang seemingly uses many of the terms (nanoparticles, nanovesicles, exosomes, etc.) interchangeably. However, the nanovesicles derived from plants are interpreted as plant-derived exosome-like nanoparticles (Yi, pg. 1) and nanovesicles derived from a patient’s tissues or cells are interpreted as autologous exosomes. Additionally, it is also demonstrated in the art that exosomes are interpreted as naturally-occurring from subjects, whereas nanoparticles are interpreted as synthetic (evidenced by Liu, abs).
The Applicant argues that Zhang does not teach autologous exosomes (Remarks, pg. 6).
Applicant’s argument is not found persuasive. Zhang teaches that the vehicle may be derived from cancer cells (para. 11). A person of ordinary skill in the art would recognize that it is obvious that the cells come from a subject or patient.
The Applicant argues that Yi never references Zhang and does not expand the understanding of Zhang nor provide any description of autologous exosomes (Remarks, pg. 6).
Applicant’s argument is not found persuasive. Yi’s teaching is to demonstrate that the nanovesicles derived from plants are interpreted as plant-derived exosome-like nanoparticles and highlight the overlapping nature over the vehicle terminology.
The Applicant argues that the nanoparticle and exosome are delivered separately and the distinction is reflected in the amendment (Remarks, pgs. 6-7).
Applicant’s argument is not found persuasive. In regards to delivering the nanoparticle and exosome in separate steps in claim 1, Zhang teaches exosomes derived from various sources, such as plants or human cells, where using a variety of sources for the exosomes offers some advantages. Additionally, Zhang teaches delivering the composition in multiple doses. Therefore, one of ordinary skill in the art would have been led to use a method of treating cancer by delivering a plant-derived exosome-like nanoparticle (step i) and autologous exosome (step ii) to a patient, or vice versa given the general broadness of the teaching. Ha teaches that there are advantages to using certain drug delivery vehicles, such as in regards to biocompatibility, stability, and drug encapsulation. Therefore, one of ordinary skill in the art would have been motivated to use Ha’s teaching to modify and improve Zhang’s teaching to arrive at a method of delivering a nanoparticle and exosome.
The Applicant argues that the nanoparticle is derived from an edible plant and the exosome is autologous to the subject (Remarks, pg. 7).
Applicant’s argument is not found persuasive. The nanovesicles derived from plants are interpreted as plant-derived exosome-like nanoparticles and nanovesicles derived from a patient’s tissues or cells are interpreted as autologous exosomes.
The Applicant argues that Badi does not cure the deficiencies of Zhang (Remarks, pg. 7).
Applicant’s argument is not found persuasive. Badi is used as evidentiary support that shows that malignant melanoma often leads to metastatic lesions in the lung (pg. 1). In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The Applicant argues a synergistic effect on the survival of treated mice (Remarks, pgs. 7-8).
Applicant’s argument is not found persuasive. Figures 7C, 7D, and 7F show the survival of mice with just Dox or PTX, the anticancer agent in the nanovesicle, and the anticancer agent with the exosome and nanovesicle. Any evidence of a synergistic effect does not have a causal relationship with the merits and scope of the claimed invention, which is, broadly, a method for treating metastasis in the lungs using a nanoparticle derived from any edible plant with any therapeutic agent and an effective amount of any autologous exosome. As such, the data are not commensurate in scope with the claims. Furthermore, to show synergy, the applicant must prove that their invention exhibits more than mere additive effects. The effectiveness of the combination should be shown versus the individual components, and the effectiveness also should be shown over what the closest cited prior art suggests.
“For objective evidence of secondary considerations to be accorded substantial weight, its proponent must establish a nexus between the evidence and the merits of the claimed invention.” Wyers v. Master Lock Co., 616 F.3d 1231, 1246 [95 USPQ2d 1525] (Fed. Cir. 2010) (quotation omitted). Where the offered secondary consideration actually results from something other than what is both claimed and novel in the claim, there is no nexus to the merits of the claimed invention. Tokai Corp. v. Easton Enters., Inc., 632 F.3d 1358, 1369 [97 USPQ2d 1673] (Fed. Cir. 2011) (“If commercial success is due to an element in the prior art, no nexus exists.”); Ormco Corp., 463 F.3d at 1312 (“[I]f the feature that creates the commercial success was known in the prior art, the success is not pertinent.”); In re Woodruff, 919 F.2d 1575, 1578 [16 USPQ2d 1934] (Fed. Cir. 1990).
The Applicant argues that the cited prior art teachings (Zhang and Williams) do not account for all of the limitations recited in the claims (Remarks, pgs. 8-9).
Applicant’s argument is not found persuasive. Since Zhang does not teach a method of administering the exosome 30 minutes prior to the nanoparticle in claim 4, one skilled in the art would have been motivated to use the method of administering the therapeutic second dose 15 minutes to 3 hours after the first dose from Williams et al. to address the deficiencies in Zhang’s teachings to increase systemic delivery of the therapeutic agent to other organs and tissues to treat cancer. A skilled artisan would be able to use Zhang’s broad and general teaching considering the sources of the nanoparticles and exosomes and number of doses. Since Zhang teaches that different sources for the nanoparticles provide various advantages, a skilled artisan would have been able to adjust and modify the composition itself, as well as the order of administration to arrive at the claimed invention with a reasonable expectation of success.
The Applicant argues that the exosome and nanoparticle were conflated and the issue of separate administration was not addressed (Remarks, pg. 9).
Applicant’s argument is not found persuasive and has already been addressed above.
The Applicant argues that Williams teaches administration of a first dose of an autologous exosome followed by a second dose of the same autologous exosome comprising a therapeutic (Remarks, pg. 9).
Applicant’s argument is not found persuasive. Williams teaches methods for treating lung cancer (para. 291) using autologous exosomes (para. 214), which may be derived from various cell sources, such as eukaryotes, prokaryotes, archae, fungi and protists (para. 213). The method includes administering a therapeutic second dose 15 minutes to 3 hours after the first dose (para. 5). This type of administration is designed to partially block the uptake of therapeutic exosomes in the liver and/or spleen to improve systemic delivery to other organs and tissues (para. 2). Therefore, it is interpreted that the vehicles taught in Williams may be derived from humans through autologous exosomes, as well as non-human sources, which, consistent with the other cited art, may be interpreted as a nanoparticle instead. Williams’ teaching is to demonstrate the administration method of using vehicles derived from different sources to deliver therapeutic agents.
The Applicant argues a synergistic effect on the survival of treated mice (Remarks, pgs. 9-10).
Applicant’s argument is not found persuasive and has already been addressed above.
Conclusion
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/D.A.K./Examiner, Art Unit 1613
/BRIAN-YONG S KWON/Supervisory Patent Examiner, Art Unit 1613