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 .
In view of the amendment, previous 112(b) rejections on claims 2, 6 and 27 are hereby withdrawn.
THIS ACTION IS MADE FINAL. 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.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 2 recites that CPEVs are formulated for intranasal administration. However, instant claim 1 already recites a step of intranasally administering to the subject a therapeutically effective amount of CPEVs. Thus, claim 2 fails to further limit the subject matter of claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1, 2, 6 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Sawyer et al (US 2016/0271100 A1) in view of Rome (“Biological properties of plant-derived extracellular vesicles”, Food & Function, vol.10(2) (Feb 20, 2019), pg.529-538), Akuma et al (“Naturally Occurring Exosome Vesicles as Potential Delivery Vehicle for Bioactive Compounds”, Frontiers in Sustainable Food Systems, vol.3, Article 23 (April 16, 2019), pg.1-8, provided in the IDS), and Chukly et al (US 2021/0260201 A1).
Sawyer teaches (claims 1 and 11) a method for treating a tumor, such as a brain tumor, the method comprising identifying a subject having a tumor and administering to the subject a chemotherapy agent and/or radiation (instant co-administration of an adjunct cancer therapy protocol), and topically administering a composition containing a cannabinoid.
Sawyer does not teach instant cannabinoid-containing plant extracellular vesicles (CPEVs). As taught by Rome (see pg.534, left-hand column, last paragraph), Akuma et al (See pg.4, right-hand column, 1st paragraph) and Chukly et al (see [0065]), plant-derived extracellular vesicles are excellent candidates for the delivery of therapeutic agents, including cannabinoids, as they are able to cross mammalian barriers without inducing inflammatory response or necrosis, unlike conventional liposomal delivery vehicles. They are more biocompatible and safer than synthetic liposomes. Furthermore, Rome teaches (pg.534, right-hand column, 2nd paragraph) that plant derived extracellular vesicles (“plant-EVs” as called by Rome) are able to bind hydrophobic agents (cannabinoids are hydrophobic) increasing the bioavailability of the hydrophobic agents and their cellular uptake. Also, as taught by Rome (pg.534, left-hand column, 2nd paragraph) and Akuma (pg.4, left-hand column, 1st paragraph), plant-derived extracellular vesicles are known to be enriched in bioactive compounds from their plant source, which implies that cannabis plant-derived extracellular vesicles would naturally be enriched in cannabinoids. Since Sawyer teaches topically administering cannabinoid (in its method of treating brain tumors), it would have been obvious to one skilled in the art to use cannabis plant-derived extracellular vesicles (instant CPEVs) as Sawyer’s cannabinoid with a reasonable expectation of success because CPEVs are already enriched with cannabinoids, they can cross mammalian barriers without inducing inflammatory response or necrosis, they are more biocompatible and safter than synthetic liposomes and they increase the bioavailability and cellular uptake of the cannabinoids (hydrophobic agents). As to instant step of intranasally administering the CPEVs, Sawyer teaches ([0026]) that the cannabinoid-containing composition can be applied intranasally to the mucous membrane inside of the nose. Furthermore, Rome teaches (pg.534, right-hand column, 1st paragraph) that when plant-derived EVs (grapefruit-derived EVs) were administered intranasally, a majority of the fluorescence-labelled GF-EVs were found in the brain and lungs and GF-EVs remained in the brain for at least five days post-treatment. Thus, it would be obvious to one skilled in the art to administer the CPEVs (as Sawyer’s cannabinoid as discussed above) intranasally with a reasonable expectation that the CPEVs will remain in the brain at least for several days post-administration and thus will be more bioavailable to treat the brain tumor. Thus, Sawyer in view of Rome, Akuma and Chukly renders obvious instant 1 and 2.
With respect to instant claim 6, as discussed above, Sawyer’s method for treating a tumor (such as a brain tumor) comprises administering to the subject a chemotherapy agent and/or radiation (instant co-administration of an adjunct cancer therapy protocol), and topically administering a composition containing a cannabinoid. Sawyer further teaches ([0038]) that the chemotherapy agent and/or radiation treatment can be administered (to the subject having a tumor) together with topically administering its cannabinoid composition. Sawyer also teaches (claims 20 and 6) that the cannabinoid, such as dronabinol, can be administered subsequent to or together with administering chemotherapy agents, such as taxanes, platinum compounds, vinca alkaloids, thalidomide, bortezomib, corticosteroids and bevacizumab. Thus, Sawyer in view of Rome, Akuma and Chukly renders obvious instant claim 6.
With respect to instant claim 27, Sawyer in view of Rome, Akuma and Chukly does not explicitly teach instant composition of the CPEVs. However, Akuma teaches (pg.2, right-hand column, 2nd paragraph) that the gold standard procedure for isolating and purifying exosomes and exosome-like particles is through differential ultracentrifugation. In such process, the exosome source (for example, cannabis plant juice in this case) is subjected to a series of centrifugation processes with increasing speeds and duration to eliminate the larger and higher density components, and the pellets derived from such steps are discarded. The final round of centrifugation of the supernatant is done at higher speeds of about 100,000 x g to recover the pellet containing the exosome, which is then re-suspended and washed in a buffer. It would have been obvious to one skilled in the art to apply the process as described in Akuma to isolate the CPEVs from cannabis plant juice (hemp juice) with a reasonable expectation of success. Since Akuma’s process is almost identical to the process used by applicant to obtain their CPEVs (see pg.20, lines 10-26 of present specification), it is the Examiner’s position that the CPEVs from cannabis plant juice (hemp juice), which is isolated using Akuma’s process would inherently or naturally contain the same composition as that of instant claim 27. Thus, Sawyer in view of Rome, Akuma and Chukly renders obvious instant claim 27.
Claim(s) 4 is rejected under 35 U.S.C. 103 as being unpatentable over Sawyer et al (US 2016/0271100 A1) in view of Rome (“Biological properties of plant-derived extracellular vesicles”, Food & Function, vol.10(2) (Feb 20, 2019), pg.529-538), Akuma et al (“Naturally Occurring Exosome Vesicles as Potential Delivery Vehicle for Bioactive Compounds”, Frontiers in Sustainable Food Systems, vol.3, Article 23 (April 16, 2019), pg.1-8, provided in the IDS), and Chukly et al (US 2021/0260201 A1), as applied to claim 1 above, and further in view of Kaufman (US 2018/0296493 A1).
As discussed above, Sawyer in view of Rome, Akuma and Chukly renders it obvious to administer the CPEVs (as Sawyer’s cannabinoid) intranasally to the mucous membrane inside of the nose. Although Sawyer in view of Rome, Akuma and Chukly does not explicitly teach a specific device that can be used for the intranasal administration, as evidenced by Kaufman ([0262]), it is well known in the art that phospholipid nanoparticle formulations of cannabinoids can be delivered intranasally by using a precision liquid pump device bottle (instant pump). It would have been obvious to one skilled in the art to use a precision liquid pump device bottle to administer the CPEVs intranasally with a reasonable expectation of success. Thus, Sawyer in view of Rome, Akuma and Chukly, and further in view of Kaufman renders obvious instant claim 4.
Response to Arguments
First of all, applicant argue that amended claim 1 is directed to a specific therapeutic method involving intranasal administration of naturally occurring CPEVs for treatment of brain cancer. However, “CPEVs” as defined by applicant (see the last paragraph on pg.3 of present specification) just mean PEVs containing one or more cannabinoids. Naturally occurring CPEVs – PEVs obtained from plant material of a Cannabis spp plant - are referred to as “csPEV” (see pg.12, lines 15-16 of present specification).
Applicant then argue the following: (a) Sawyer does not contain a discussion of CPEVs, plant-derived EVs, or intranasal administration of such EVs in the context of brain cancer, and even if Sawyer contained such a discussion, Sawyer provides no suggestion that would lead one skilled in the art to predict that administration of CPEVs would produce therapeutically meaningful cannabinoid accumulation in brain tissue; (b) Rome does not mention cannabinoids, cannabis-derived material, brain cancer treatment and does not establish that EVs from different plant species share predictable cargo, surface properties, or bio-distribution or therapeutic behavior; (c) Chukly is directed to engineered EV delivery systems, where phytocannabinoids are loaded into EVs after vesicle isolation, rather than naturally occurring CPEVs. At most, Chukly suggests that EVs may broadly function as delivery vehicles for certain therapeutic agents, and such generalization does not provide the reasonable expectation that intranasally administered CPEVs would accumulate cannabinoids in brain tissue at meaningful levels comparable to those demonstrated in the presently claimed methods; (d) Akuma does not establish predictability because Akuma confirms that in-vivo behavior, tissue interactions and contents of plant-derived vesicles including CPEVs remain uncertain. Applicant’s such arguments are found to be unpersuasive. First of all, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Where a rejection of a claim is based on two or more references, a reply that is limited to what a subset of the applied references teaches or fails to teach, or that fails to address the combined teaching of the applied references may be considered to be an argument that attacks the reference(s) individually. The Examiner already explained in detail in Paragraph 7 above how the combined teachings of Sawyer, Rome, Akuma and Chukly render obvious instant claims.
Applicant next argue that the specific cannabinoid profile recited in claim 27 would not inherently result from Akuma’s broadly similar vesicle isolation method because the cannabinoid composition of CPEVs is not dictated by ultracentrifugation alone. Applicant argue that such composition may depend on a variety of factors such as cannabis or hemp cultivar, plant chemotype, plant tissue use, growth condition, harvest timing, processing condition, EV population isolated, endogenous vesicle cargo and analytical quantification method. Applicant argue that instant rejection of claim 27 relies on possibilities instead of inherency. However, as already discussed above, it is still the Examiner’s position that when one skilled in the art applies Akuma’s process (which is very similar to applicant’s process) to isolate the CPEVs from hemp juice (which is also used by applicant), the CPEVs from the hemp juice would naturally yield the same composition as that of instant claim 27 (or a composition close to it), in the absence of applicant’s showing otherwise. Applicant only showed a single composition obtained from the CPEVs of juice from floral parts of fresh hemp plant and did not show any other comparative results. The Examiner is also unsure whether this specific composition (i.e., specific profile) claimed in claim 27 is critical or not (i.e., how it affects the cancer treatment when compared to other compositions).
Applicant lastly argue that cited references do not show that one skilled in the art would have reasonably expected intranasally administered CPEVs to accumulate cannabinoids in the brain tissue at a meaningful level to treat brain cancer. Applicant then cite the results shown in Fig.9 (describing a 5-fold increase in cannabinoid accumulation in brain tissue) and Fig.6 (demonstrating that hemp EV treatments increase median survival in glioma-bearing animals from 31 days in control animals to 47.5 days in treated animals) to argue the non-predictable nature of the claimed method as the cited references provide no basis for expecting the magnitude of cannabinoid accumulation and therapeutic efficacy observed in present application. However, first of all, the accumulation of cannabinoid in the brain tissue through intranasal administration of CPEVs is not unexpected because Rome already teaches that when plant-derived EVs were administered intranasally, a majority of the fluorescence-labelled GF-EVs were found in the brain and lungs and GF-EVs remained in the brain for at least five days post-treatment. It is also already known in the art, as evidenced by Solinas et al (“Cannabidiol inhibits angiogenesis by multiple mechanisms”, British Journal of Pharmacology, vol.167(6) (Nov 2012), pg.1218-31, as obtained from the website: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2012.02050.x ) (see abstract), that the non-psychoactive cannabinoid CBD effectively inhibits the growth of tumors in-vitro and in-vivo and down-regulates some pro-angiogenic signals produced by glioma cells.
For the reasons stated above, instant 103 rejections over Sawyer in view of Rome, Akuma and Chukly still stand.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SIN J. LEE whose telephone number is (571)272-1333. The examiner can normally be reached on M-F 9 am-5:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Kwon can be reached on 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov . Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
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 .
/SIN J LEE/
Primary Examiner, Art Unit 1613
September 19, 2026
