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 .
DETAILED ACTION
2. This Office Action is responsive to Applicant’s Amendment and Remarks, filed April 14, 2026. The amendment, filed April 14, 2026, is entered, wherein claims 1, 4 – 5, 7 – 11, 19, and 25 – 26 are amended and claims 3, 12 – 18, 24, and 27 are canceled.
Claims 1 – 2, 4 – 11, 19 – 23, and 25 – 26 are pending in this application and are currently examined.
Priority
3. This application is a national stage application of PCT/US2021/055383, filed October 18, 2021, which claims benefit of domestic application, filed October 16, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/15/2026 was filed after the mailing date of the previous Office Action on October 14, 2025. 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Withdrawn Objections
5. The objection of the disclosure in the previous Office Action, mailed October 14, 2025, is withdrawn in view of the amended specification.
Withdrawn Rejections
6. The rejection of claims 1 – 23 and 25 in the previous Office Action, mailed October 14, 2025, under 35 U.S.C. 102(a)(1) as being anticipated by Chen has been considered and is withdrawn in view of the amended claim 1.
The rejection of claims 1 – 27 in the previous Office Action, mailed October 14, 2025, under 35 U.S.C. 103 as being unpatentable over Chen in view of Peralta et al. and Najjar et al. has been considered and is withdrawn upon further consideration.
The rejection of claims 1 – 23 and 25 in the previous Office Action, mailed October 14, 2025, under 35 U.S.C. 101 as claiming the same invention as that of claims 1 – 23 of copending Application No. 16/967,549 has been considered and is withdrawn in view of the amended claim 1.
The rejection of claims 1, 3 – 11, 15, 19 – 23, and 25 in the previous Office Action, mailed October 14, 2025, under 35 U.S.C. 101 as claiming the same invention as that of claims 1 – 10 and 12 – 17 of copending Application No. 18/190,643 has been considered and is withdrawn because the application was abandoned.
The rejection of claims 1 – 3, 5 – 11, 16 – 18, and 20 – 23 in the previous Office Action, mailed October 14, 2025, under 35 U.S.C. 101 as claiming the same invention as that of claims 1 – 13 of copending Application No. 18/984,062 has been considered and is withdrawn in view of the amended claim 1.
The rejection of claims 1 – 3, 5 – 11, 16 – 18, and 20 – 23 in the previous Office Action, mailed October 14, 2025, under 35 U.S.C. 101 as claiming the same invention as that of claims 1 – 13 of prior U.S. Patent No. 12208066B2 has been considered and is withdrawn in view of the amended claim 1.
The rejection of claims 1, 10 – 11, 19, and 25 in the previous Office Action, mailed October 14, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 7 and 9 of copending Application No. 18/557,650 has been considered and is withdrawn in view of the amended claim 1.
The rejection of claims 1 – 2, 9 – 12, 19 – 23, and 25 in the previous Office Action, mailed October 14, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3 – 6, and 8 – 17 of copending Application No. 15/997,300 has been considered and is withdrawn in view of the amended claim 1.
The rejection of claims 1 – 2, 10 – 15, 19 – 23, and 25 in the previous Office Action, mailed October 14, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3 – 6, and 8 – 17 of U.S. Patent No. 9700524B2 has been considered and is withdrawn in view of the amended claim 1.
The rejection of claims 1 – 2, 10 – 14, 19, and 25 in the previous Office Action, mailed October 14, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 30 and 32 of copending Application No. 18/461,562 has been considered and is withdrawn in view of the amended claim 1.
The rejection of claims 1 – 2, 9, 12 – 15, and 20 – 21 in the previous Office Action, mailed October 14, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 3 and 6 of U.S. Patent No. 11970436B2 has been considered and is withdrawn in view of the amended claim 1.
The following are modified / new grounds of rejection necessitated by Applicant’s Amendment and Remarks, filed April 14, 2026, wherein claims 1, 4 – 5, 7 – 11, 19, and 25 – 26 are amended and claims 3, 12 – 18, 24, and 27 are canceled. Previously and newly cited references have been used to establish the modified / new grounds of rejection.
New 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:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. Considering objective evidence present in the application indicating obviousness or
nonobviousness.
Claims 1 – 2, 4 – 11, 19, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) in view of Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025).
a. Richardson et al. teach that coronaviruses are able to enter CNS and cause neurological deficits (page 1880, Left Col., para. 1). About 36.4% of hospitalized patients with COVID-19 show neurologic symptoms, such as headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular disease, and epilepsy. There are more severely ill patients exhibiting cerebrovascular disease and epilepsy (page 1880, Left Col., para. 2). In addition, it is likely that virus-induced neurological damage could have consequences for surviving patients, with a dysexecutive syndrome being observed in up to one third of discharged patients (page 1880, Right Col., para. 1). Six most common drugs for COVID-19 have been assessed for their potential CNS penetration:
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The data show that remdesivir has a predictable low brain penetrance (page 1880, Right Col., para. 2). Thus, Richardson et al. teach that there is a need for enhancing the CNS penetration of remdesivir because coronaviruses are able to enter CNS and cause neurological deficits and these neurologic symptoms are found in 36.4% of hospitalized patients with COVID-19, which read on the limitations “administering remdesivir to a central nervous system of a mammal” of claim 1, “brain” of claim 2, and “human” of claim 6.
However, Richardson et al. do not teach administering perillyl alcohol before or concurrently with remdesivir to the mammal. Richardson et al. do not teach that perillyl alcohol is administered intraarterially. Richardson et al. do not teach that the perillyl alcohol is administered at a dose ranging from about 0.05 mg/kg to about 500 mg/kg of body weight. Richardson et al. do not teach that the perillyl alcohol is administered from about 0.2 minutes to about 60 minutes before the remdesivir is administered. Richardson et al. do not teach that the perillyl alcohol and the remdesivir are administered separately. Richardson et al. do not teach that the perillyl alcohol and the remdesivir are administered together in a pharmaceutical composition. Richardson et al. do not teach that the perillyl alcohol is administered by inhalation, intranasally, orally, intravenously, subcutaneously, or intramuscularly.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. POH may be administered into a vascular system of the mammal intraarterially, via inhalation, or intranasally. Thus, Chen teaches that monoterpene, such as POH, is administered before, after, or concurrently with the therapeutic agent to a human intraarterially, via inhalation, or intranasally, which corresponds to the limitations “before or concurrently” of claim 1, “intraarterially” of claim 4, “human” or claim 6, “administered separately” of claim 9, “administered concurrently” of claim 10, and “inhalation” and “intranasally” of claims 19 and 25.
Chen teaches that POH may be administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of body weight. The administration is about 0.2 minutes to about 60 minutes or about 1 minute to about 15 minute before the therapeutic agent is administered. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition. The disclosure read on the limitations of claims 5 and 7 – 11.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine remdesivir as taught by Richardson et al. with perillyl alcohol in view of Chen because Richardson et al. identify that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that perillyl alcohol may be used in combination with antiviral agents and it helps to permeabilize the blood brain barrier. One would have been motivated to combine remdesivir as taught by Richardson et al. with perillyl alcohol in view of Chen because it is known in the art that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that perillyl alcohol helps to permeabilize the blood brain barrier. One of ordinary skill in the art would have had a reasonable expectation of success to combine remdesivir as taught by Richardson et al. with perillyl alcohol in view of Chen because it is known in the art that perillyl alcohol helps to permeabilize the blood brain barrier.
Regarding claim 6, Richardson et al. do not explicitly teach administering remdesivir to human, but the study conducted is intended for treating neurologic symptoms induced from COVID-19 in human because Richardson et al. disclose that the patients with COVID-19 having neurologic symptoms are all human subjects. Chen also teaches that the therapeutic agent and perillyl alcohol are administered to mammal, wherein the mammal is human. Therefore, the combination of Richardson et al. and Chen teach a method for a human. Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) in view of Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025) as applied to claims 1 – 2, 4 – 11, 19, and 25 above, and further in view of Park (Time, 2020, See PTO-892).
b. Richardson et al. and Chen teach the limitations discussed above.
However, Richardson et al. and Chen do not teach that remdesivir is administered by inhalation or intranasally.
Park teaches that remdesivir has been made into inhaled form by a pharmaceutical company rather than IV infusion (page 1, para. 1).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park explicitly teaches that remdesivir has been made into an inhalation formulation. One would have been motivated to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because it is known in the art that the ease of administration will improve patient convenience by avoiding invasion infusion procedures, permit self-administration, and reduce complications associated with intravenous access. One of ordinary skill in the art would have had a reasonable expectation of success to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park teaches that remdesivir is already formulated for inhalation.
Claims 1 and 20 – 23 are rejected under 35 U.S.C. 103 as being unpatentable over Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025) in view of Ivy Center (Ivy Brain Tumor Center, 2020, See PTO-892) and Jonas (HICCC, 2020, See PTO-892).
c. Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition.
Chen further teaches that perillyl alcohol (POH), a naturally occurring monoterpene, has been suggested to be an effective agent against a variety of cancers, including CNS cancer, breast cancer, pancreatic cancer, lung cancer, melanoma, and colon cancer (page 3, lines 23 – 25). Chen teaches a method of administering a therapeutic agent to a CNS of a mammal, wherein the mammal may have cancer, such as a tumor of the nervous system that is a glioblastoma (page 5, lines 1 – 2; lines 29 – 30). Thus, Chen teaches that POH is known to be an effective agent against CNS cancer, such as glioblastoma, which encompasses the limitations of administering POH to a mammal, “wherein the mammal has cancer”, “wherein the cancer is a tumor of the nervous system”, “wherein the tumor is glioblastoma” of claims 20 – 22. Chen teaches that the method further comprises the step of treating the mammal with radiation (page 5, lines 1 – 31). Moreover, Chen discloses that monoterpene can be used to deliver at least one therapeutic agent across the BBB (page 8, lines 4 – 5) and the monoterpene may be used in combination with antiviral agents (page 8, lines 23 – 24). The disclosure correspond to the limitation of claim 23.
However, Chen does not teach administering remdesivir to mammal having glioblastoma.
Ivy Center teaches that coronavirus infection posed a risk to brain tumor patients because brain tumor patients are immune-suppressed and are at particular risk from infection (page 1, para. 2). Ivy Center further teaches that coronavirus is extremely dangerous for brain tumor patients because their bodies have limited ability to fight the infection (page 1, para. 7).
Jonas teaches that there was a particular need to find ways to treat COVID-19 in cancer patients because COVID-19 could have particularly severe consequences in cancer patients (page 1, para. 1). Jonas further teaches that the CCC19 study evaluates COVID-19 treatments in cancer patients, including remdesivir, and that remdesivir was the only treatment showing any benefit, with reduced death rate compared with untreated controls (page 1, para. 4 – 5).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to administer POH as taught by Chen to a mammal having cancer that is further suffering from COVID-19, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches that POH permeabilizes the blood-brain-barrier and may be used to deliver therapeutic agents, including antiviral agents, to the CNS and further teaches use in CNS cancer, including glioblastoma, with radiation treatment, Ivy Center teaches that brain tumor patients are particularly susceptible to coronavirus infection because they are immunosuppressed, and Jonas teaches that remdesivir is evaluated as a COVID-19 therapeutic in cancer patients. One would have been motivated to administer remdesivir to a glioblastoma patient when antiviral therapy is indicated because Chen teaches that antiviral agents may be used along with POH and both Ivy Center and Jonas teach that brain tumor patients are immunosuppressed and remdesivir is shown to be effective to treat COVID-19 in cancer patients. One of ordinary skill in the art would have had a reasonable expectation of success to administer POH as taught by Chen to a mammal having cancer, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches POH as a BBB-permeabilizing monoterpene for delivery of therapeutic agents, including antiviral agents, to the CNS. Chen further teaches that POH is used to treat mammals having CNS cancer, including glioblastoma, and may be used with radiation treatment and Ivy Center and Jonas show that brain tumor/cancer patients are recognized as COVID-19 susceptible patient populations for whom COVID-19 treatment, including remdesivir, is clinical relevant.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed April 14, 2026, have been fully considered but are moot because the new ground of rejection does not rely on the same primary reference in the prior rejection of record. However, upon further consideration, a new ground(s) of rejection is made in view of newly found primary reference.
Applicant argues that Peralta et al. teach that the nanoemulsion of remdesivir is applied to nasal mucosa, ocular sites, and the mouth area, which teaches away from the claimed invention where the remdesivir is delivered to the central nervous system. Applicant further argues that remdesivir disclosed by Peralta et al. is intended to act locally and does not have to cross the blood brain barrier because the treatment site where the remdesivir does its work in the nasal mucosa, ocular sites, and the mouth area.
Applicant argues that Najjar et al. does not teach or suggest using remdesivir, POH-remdesivir, or any similar treatment for subjects with COVID-19. Applicant argues that Najjar et al. merely teach an observational study explaining complications that can come with COVID-19.
Applicant submits that there would be no reasonable expectation of success at arriving at the claimed invention based on the combination of references cited because the success of CNS delivery of drugs is highly unpredictable and drug specific. Applicant argues that the cited art provide no basis to conclude that remdesivir would perform predictably in the monoterpene-based CNS delivery system of Chen. Applicant also argues that the combination of references is based on impermissible hindsight.
Applicant’s arguments have been considered but are not persuasive with respect to the present rejection. Applicant’s arguments are directed primarily to the prior rejection based on Chen in view of Peralta et al. and Najjar et al., which has been withdrawn. The present rejection relies on Richardson et al. as the primary reference for teaching the need for enhancing the blood brain barrier penetration of remdesivir and relies on Chen to teach that POH helps drugs to permeabilize the blood brain barrier. Accordingly, Applicant’s arguments do not address the present rejection.
Modified / New Double Patenting
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 – 2, 4 – 11, 19, and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 3 and 7 – 8 of U.S. Patent No. 9700524B2 in view of Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) and Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025).
a. ‘524B2 claims a method for treating a tumor of the nervous system comprising the step of delivering to a subject in need thereof a therapeutically effective amount of (S)-perillyl alcohol (claim 1), wherein the tumor is a glioblastoma (claim 2). ‘524B2 claims that the method further comprising the step of treating the subject in need thereof with radiation (claim 3). ‘524B2 claims that the (S)-perillyl alcohol is delivered by inhalation, intranasally, orally, intravenously, subcutaneously, or intramuscularly (claim 7). The (S)-perillyl alcohol is admixed or coformulated with a therapeutic agent (claim 8).
However, ‘524B2 does not claim administering remdesivir to a central nervous system of a mammal. ‘524B2 does not claim that the central nervous system is the brain. ‘524B2 does not claim the POH is administered intraarterially. ‘524B2 does not claim the POH is administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of body weight. ‘524B2 does not claim the mammal is a human. ‘524B2 does not claim the POH is administered from about 0.2 minutes to about 60 minutes before the remdesivir is administered. ‘524B2 does not claim that the POH and the remdesivir are administered separately. ‘524B2 does not claim that the POH and the remdesivir are administered concurrently. ‘524B2 does not claim that the POH and the remdesivir are administered together in a pharmaceutical composition. ‘524B2 does not claim that the POH is administered by inhalation, intranasally, orally, intravenously, subcutaneously, or intramuscularly.
Richardson et al. teach that coronaviruses are able to enter CNS and cause neurological deficits (page 1880, Left Col., para. 1). About 36.4% of hospitalized patients with COVID-19 show neurologic symptoms, such as headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular disease, and epilepsy. There are more severely ill patients exhibiting cerebrovascular disease and epilepsy (page 1880, Left Col., para. 2). In addition, it is likely that virus-induced neurological damage could have consequences for surviving patients, with a dysexecutive syndrome being observed in up to one third of discharged patients (page 1880, Right Col., para. 1). Six most common drugs for COVID-19 have been assessed for their potential CNS penetration:
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The data show that remdesivir has a predictable low brain penetrance (page 1880, Right Col., para. 2). Thus, Richardson et al. teach that there is a need for enhancing the CNS penetration of remdesivir because coronaviruses are able to enter CNS and cause neurological deficits and these neurologic symptoms are found in 36.4% of hospitalized patients with COVID-19, which read on the limitations “administering remdesivir to a central nervous system of a mammal” of claim 1, “brain” of claim 2, and “human” of claim 6.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. POH may be administered into a vascular system of the mammal intraarterially, via inhalation, or intranasally. Thus, Chen teaches that monoterpene, such as POH, is administered before, after, or concurrently with the therapeutic agent to a human intraarterially, via inhalation, or intranasally, which corresponds to the limitations “before or concurrently” of claim 1, “intraarterially” of claim 4, “human” or claim 6, “administered separately” of claim 9, “administered concurrently” of claim 10, and “inhalation” and “intranasally” of claims 19 and 25.
Chen teaches that POH may be administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of body weight. The administration is about 0.2 minutes to about 60 minutes or about 1 minute to about 15 minute before the therapeutic agent is administered. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition. The disclosure read on the limitations of claims 5 and 7 – 11.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine POH as taught by ‘524B2 with remdesivir in view of Richardson et al. and Chen because Richardson et al. identify that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that perillyl alcohol may be used in combination with antiviral agents and it helps to permeabilize the blood brain barrier. One would have been motivated to combine POH as taught by ‘524B2 with remdesivir in view of Richardson et al. and Chen because it is known in the art that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that perillyl alcohol helps to permeabilize the blood brain barrier. One of ordinary skill in the art would have had a reasonable expectation of success to combine POH as taught by ‘524B2 with remdesivir in view of Richardson et al. and Chen because it is known in the art that perillyl alcohol helps to permeabilize the blood brain barrier.Claim 26 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 3 and 7 – 8 of U.S. Patent No. 9700524B2 in view of Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) and Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025) as applied to claims 1 – 2, 4 – 11, 19, and 25 above, and further in view of Park (Time, 2020, See PTO-892).
b. ‘524B2, Richardson et al., and Chen teach the limitations discussed above.
However, ‘524B2, Richardson et al., and Chen do not teach that remdesivir is administered by inhalation or intranasally.
Park teaches that remdesivir has been made into inhaled form by a pharmaceutical company rather than IV infusion (page 1, para. 1).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park explicitly teaches that remdesivir has been made into an inhalation formulation. One would have been motivated to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because it is known in the art that the ease of administration will improve patient convenience by avoiding invasion infusion procedures, permit self-administration, and reduce complications associated with intravenous access. One of ordinary skill in the art would have had a reasonable expectation of success to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park teaches that remdesivir is already formulated for inhalation.
Claims 1 and 20 – 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 3 and 7 – 8 of U.S. Patent No. 9700524B2 in view of Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025), Ivy Center (Ivy Brain Tumor Center, 2020, See PTO-892), and Jonas (HICCC, 2020, See PTO-892).
c. ‘524B2 claims a method for treating a tumor of the nervous system comprising the step of delivering to a subject in need thereof a therapeutically effective amount of (S)-perillyl alcohol (claim 1), wherein the tumor is a glioblastoma (claim 2). ‘524B2 claims that the method further comprising the step of treating the subject in need thereof with radiation (claim 3). ‘524B2 claims that the (S)-perillyl alcohol is delivered by inhalation, intranasally, orally, intravenously, subcutaneously, or intramuscularly (claim 7). The (S)-perillyl alcohol is admixed or coformulated with a therapeutic agent (claim 8).
However, ‘524B2 does not teach administering remdesivir to mammal having glioblastoma.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition.
Chen further teaches that perillyl alcohol (POH), a naturally occurring monoterpene, has been suggested to be an effective agent against a variety of cancers, including CNS cancer, breast cancer, pancreatic cancer, lung cancer, melanoma, and colon cancer (page 3, lines 23 – 25). Chen teaches a method of administering a therapeutic agent to a CNS of a mammal, wherein the mammal may have cancer, such as a tumor of the nervous system that is a glioblastoma (page 5, lines 1 – 2; lines 29 – 30). Thus, Chen teaches that POH is known to be an effective agent against CNS cancer, such as glioblastoma, which encompasses the limitations of administering POH to a mammal, “wherein the mammal has cancer”, “wherein the cancer is a tumor of the nervous system”, “wherein the tumor is glioblastoma” of claims 20 – 22. Chen teaches that the method further comprises the step of treating the mammal with radiation (page 5, lines 1 – 31). Moreover, Chen discloses that monoterpene can be used to deliver at least one therapeutic agent across the BBB (page 8, lines 4 – 5) and the monoterpene may be used in combination with antiviral agents (page 8, lines 23 – 24). The disclosure correspond to the limitation of claim 23.
Ivy Center teaches that coronavirus infection posed a risk to brain tumor patients because brain tumor patients are immune-suppressed and are at particular risk from infection (page 1, para. 2). Ivy Center further teaches that coronavirus is extremely dangerous for brain tumor patients because their bodies have limited ability to fight the infection (page 1, para. 7).
Jonas teaches that there was a particular need to find ways to treat COVID-19 in cancer patients because COVID-19 could have particularly severe consequences in cancer patients (page 1, para. 1). Jonas further teaches that the CCC19 study evaluates COVID-19 treatments in cancer patients, including remdesivir, and that remdesivir was the only treatment showing any benefit, with reduced death rate compared with untreated controls (page 1, para. 4 – 5).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to administer POH as taught by ‘524B2 and Chen to a mammal having cancer that is further suffering from COVID-19, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches that POH permeabilizes the blood-brain-barrier and may be used to deliver therapeutic agents, including antiviral agents, to the CNS and further teaches use in CNS cancer, including glioblastoma, with radiation treatment, Ivy Center teaches that brain tumor patients are particularly susceptible to coronavirus infection because they are immunosuppressed, and Jonas teaches that remdesivir is evaluated as a COVID-19 therapeutic in cancer patients. One would have been motivated to administer remdesivir to a glioblastoma patient when antiviral therapy is indicated because Chen teaches that antiviral agents may be used along with POH and both Ivy Center and Jonas teach that brain tumor patients are immunosuppressed and remdesivir is shown to be effective to treat COVID-19 in cancer patients. One of ordinary skill in the art would have had a reasonable expectation of success to administer POH as taught by ‘524B2 and Chen to a mammal having cancer, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches POH as a BBB-permeabilizing monoterpene for delivery of therapeutic agents, including antiviral agents, to the CNS. Chen further teaches that POH is used to treat mammals having CNS cancer, including glioblastoma, and may be used with radiation treatment and Ivy Center and Jonas show that brain tumor/cancer patients are recognized as COVID-19 susceptible patient populations for whom COVID-19 treatment, including remdesivir, is clinical relevant.
Claims 1 – 2, 4 – 11, 19, and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 12 of U.S. Patent No. 12514828B2 in view of Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) and Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025).
d. ‘828B2 claims a method for treating a central nervous system (CNS) cancer, the method comprising administering to a mammal POH before or concurrently with a therapeutic agent, wherein the POH may be administered by intraarterial injection, wherein the CNS cancer is a malignant glioma (claim 1). ‘828B2 claims that the POH is administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of a body weight of the mammal (claim 2). ‘828B2 claims that the mammal is a human (claim 3). ‘828B2 claims that the POH is administered from about 0.2 minutes to about 60 minutes or 1 minute to about 15 minutes before the CAR-T cell is administered (claim 4 – 5). ‘828B2 claims that the POH and the CAR-T cell are administered separately or concurrently (claims 6 – 7). ‘828B2 claims that the POH and the CAR-T cell are administered together in a pharmaceutical composition (claim 8). ‘828B2 claims that the CNS cancer is malignant glioma, wherein the malignant glioma is a glioblastoma (claims 9 – 11). ‘828B2 claims that the method further comprising treating the mammal with radiation (claim 12).
However, ‘828B2 does not claim administering remdesivir to a central nervous system of a mammal. ‘828B2 does not claim that the central nervous system is the brain. ‘828B2 does not claim that the POH is administered by inhalation, intranasally, orally, intravenously, subcutaneously, or intramuscularly.
Richardson et al. teach that coronaviruses are able to enter CNS and cause neurological deficits (page 1880, Left Col., para. 1). About 36.4% of hospitalized patients with COVID-19 show neurologic symptoms, such as headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular disease, and epilepsy. There are more severely ill patients exhibiting cerebrovascular disease and epilepsy (page 1880, Left Col., para. 2). In addition, it is likely that virus-induced neurological damage could have consequences for surviving patients, with a dysexecutive syndrome being observed in up to one third of discharged patients (page 1880, Right Col., para. 1). Six most common drugs for COVID-19 have been assessed for their potential CNS penetration:
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The data show that remdesivir has a predictable low brain penetrance (page 1880, Right Col., para. 2). Thus, Richardson et al. teach that there is a need for enhancing the CNS penetration of remdesivir because coronaviruses are able to enter CNS and cause neurological deficits and these neurologic symptoms are found in 36.4% of hospitalized patients with COVID-19, which read on the limitations “administering remdesivir to a central nervous system of a mammal” of claim 1, “brain” of claim 2, and “human” of claim 6.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. POH may be administered into a vascular system of the mammal intraarterially, via inhalation, or intranasally. Thus, Chen teaches that monoterpene, such as POH, is administered before, after, or concurrently with the therapeutic agent to a human intraarterially, via inhalation, or intranasally, which corresponds to the limitations “before or concurrently” of claim 1, “intraarterially” of claim 4, “human” or claim 6, “administered separately” of claim 9, “administered concurrently” of claim 10, and “inhalation” and “intranasally” of claims 19 and 25.
Chen teaches that POH may be administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of body weight. The administration is about 0.2 minutes to about 60 minutes or about 1 minute to about 15 minute before the therapeutic agent is administered. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition. The disclosure read on the limitations of claims 5 and 7 – 11.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine POH as taught by ‘062 with remdesivir in view of Richardson et al. and Chen because Richardson et al. identify that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that POH may be used in combination with antiviral agents and it helps to permeabilize the blood brain barrier. One would have been motivated to combine POH as taught by ‘062 with remdesivir in view of Richardson et al. and Chen because it is known in the art that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that POH helps to permeabilize the blood brain barrier. One of ordinary skill in the art would have had a reasonable expectation of success to combine POH as taught by ‘062 with remdesivir in view of Richardson et al. and Chen because it is known in the art that POH helps to permeabilize the blood brain barrier.Claim 26 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 12 of U.S. Patent No. 12514828B2 in view of Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) and Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025) as applied to claims 1 – 2, 4 – 11, 19, and 25 above, and further in view of Park (Time, 2020, See PTO-892).
e. ‘828B2, Richardson et al., and Chen teach the limitations discussed above.
However, ‘828B2, Richardson et al., and Chen do not teach that remdesivir is administered by inhalation or intranasally.
Park teaches that remdesivir has been made into inhaled form by a pharmaceutical company rather than IV infusion (page 1, para. 1).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park explicitly teaches that remdesivir has been made into an inhalation formulation. One would have been motivated to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because it is known in the art that the ease of administration will improve patient convenience by avoiding invasion infusion procedures, permit self-administration, and reduce complications associated with intravenous access. One of ordinary skill in the art would have had a reasonable expectation of success to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park teaches that remdesivir is already formulated for inhalation.
Claims 1 and 20 – 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 12 of U.S. Patent No. 12514828B2 in view of Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025), Ivy Center (Ivy Brain Tumor Center, 2020, See PTO-892) and Jonas (HICCC, 2020, See PTO-892).
f. ‘828B2 claims a method for treating a central nervous system (CNS) cancer, the method comprising administering to a mammal POH before or concurrently with a therapeutic agent, wherein the POH may be administered by intraarterial injection, wherein the CNS cancer is a malignant glioma (claim 1). ‘828B2 claims that the POH is administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of a body weight of the mammal (claim 2). ‘828B2 claims that the mammal is a human (claim 3). ‘828B2 claims that the POH is administered from about 0.2 minutes to about 60 minutes or 1 minute to about 15 minutes before the CAR-T cell is administered (claim 4 – 5). ‘828B2 claims that the POH and the CAR-T cell are administered separately or concurrently (claims 6 – 7). ‘828B2 claims that the POH and the CAR-T cell are administered together in a pharmaceutical composition (claim 8). ‘828B2 claims that the CNS cancer is malignant glioma, wherein the malignant glioma is a glioblastoma (claims 9 – 11). ‘828B2 claims that the method further comprising treating the mammal with radiation (claim 12).
However, ‘828B2 does not teach administering remdesivir to mammal having glioblastoma.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition.
Chen further teaches that perillyl alcohol (POH), a naturally occurring monoterpene, has been suggested to be an effective agent against a variety of cancers, including CNS cancer, breast cancer, pancreatic cancer, lung cancer, melanoma, and colon cancer (page 3, lines 23 – 25). Chen teaches a method of administering a therapeutic agent to a CNS of a mammal, wherein the mammal may have cancer, such as a tumor of the nervous system that is a glioblastoma (page 5, lines 1 – 2; lines 29 – 30). Thus, Chen teaches that POH is known to be an effective agent against CNS cancer, such as glioblastoma, which encompasses the limitations of administering POH to a mammal, “wherein the mammal has cancer”, “wherein the cancer is a tumor of the nervous system”, “wherein the tumor is glioblastoma” of claims 20 – 22. Chen teaches that the method further comprises the step of treating the mammal with radiation (page 5, lines 1 – 31). Moreover, Chen discloses that monoterpene can be used to deliver at least one therapeutic agent across the BBB (page 8, lines 4 – 5) and the monoterpene may be used in combination with antiviral agents (page 8, lines 23 – 24). The disclosure correspond to the limitation of claim 23.
Ivy Center teaches that coronavirus infection posed a risk to brain tumor patients because brain tumor patients are immune-suppressed and are at particular risk from infection (page 1, para. 2). Ivy Center further teaches that coronavirus is extremely dangerous for brain tumor patients because their bodies have limited ability to fight the infection (page 1, para. 7).
Jonas teaches that there was a particular need to find ways to treat COVID-19 in cancer patients because COVID-19 could have particularly severe consequences in cancer patients (page 1, para. 1). Jonas further teaches that the CCC19 study evaluates COVID-19 treatments in cancer patients, including remdesivir, and that remdesivir was the only treatment showing any benefit, with reduced death rate compared with untreated controls (page 1, para. 4 – 5).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to administer POH as taught by ‘828B2 and Chen to a mammal having cancer that is further suffering from COVID-19, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches that POH permeabilizes the blood-brain-barrier and may be used to deliver therapeutic agents, including antiviral agents, to the CNS and further teaches use in CNS cancer, including glioblastoma, with radiation treatment, Ivy Center teaches that brain tumor patients are particularly susceptible to coronavirus infection because they are immunosuppressed, and Jonas teaches that remdesivir is evaluated as a COVID-19 therapeutic in cancer patients. One would have been motivated to administer remdesivir to a glioblastoma patient when antiviral therapy is indicated because Chen teaches that antiviral agents may be used along with POH and both Ivy Center and Jonas teach that brain tumor patients are immunosuppressed and remdesivir is shown to be effective to treat COVID-19 in cancer patients. One of ordinary skill in the art would have had a reasonable expectation of success to administer POH as taught by ‘828B2 and Chen to a mammal having cancer, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches POH as a BBB-permeabilizing monoterpene for delivery of therapeutic agents, including antiviral agents, to the CNS. Chen further teaches that POH is used to treat mammals having CNS cancer, including glioblastoma, and may be used with radiation treatment and Ivy Center and Jonas show that brain tumor/cancer patients are recognized as COVID-19 susceptible patient populations for whom COVID-19 treatment, including remdesivir, is clinical relevant.
Claims 1 – 2, 4 – 11, 19, and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6 and 9 of copending Application No. 18/557,650 in view of Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) and Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025).
g. ‘650 claims a method of treating one or more symptoms in a patient that has Parkinson’s Disease, the method comprising administering a pharmaceutical composition comprising POH and L-Dopa to a patient (claim 6). ‘650 claims that the pharmaceutical composition is administered intranasally (claim 9).
However, ‘650 does not claim administering remdesivir to a central nervous system of a mammal. ‘650 does not claim that the central nervous system is the brain. ‘650 does not claim the POH is administered intraarterially. ‘650 does not claim the POH is administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of body weight. ‘650 does not claim the mammal is a human. ‘650 does not claim the POH is administered from about 0.2 minutes to about 60 minutes before the remdesivir is administered. ‘650 does not claim that the POH and the remdesivir are administered separately. ‘650 does not claim that the POH and the remdesivir are administered concurrently. ‘650 does not claim that the POH and the remdesivir are administered together in a pharmaceutical composition.
Richardson et al. teach that coronaviruses are able to enter CNS and cause neurological deficits (page 1880, Left Col., para. 1). About 36.4% of hospitalized patients with COVID-19 show neurologic symptoms, such as headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular disease, and epilepsy. There are more severely ill patients exhibiting cerebrovascular disease and epilepsy (page 1880, Left Col., para. 2). In addition, it is likely that virus-induced neurological damage could have consequences for surviving patients, with a dysexecutive syndrome being observed in up to one third of discharged patients (page 1880, Right Col., para. 1). Six most common drugs for COVID-19 have been assessed for their potential CNS penetration:
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The data show that remdesivir has a predictable low brain penetrance (page 1880, Right Col., para. 2). Thus, Richardson et al. teach that there is a need for enhancing the CNS penetration of remdesivir because coronaviruses are able to enter CNS and cause neurological deficits and these neurologic symptoms are found in 36.4% of hospitalized patients with COVID-19, which read on the limitations “administering remdesivir to a central nervous system of a mammal” of claim 1, “brain” of claim 2, and “human” of claim 6.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. POH may be administered into a vascular system of the mammal intraarterially, via inhalation, or intranasally. Thus, Chen teaches that monoterpene, such as POH, is administered before, after, or concurrently with the therapeutic agent to a human intraarterially, via inhalation, or intranasally, which corresponds to the limitations “before or concurrently” of claim 1, “intraarterially” of claim 4, “human” or claim 6, “administered separately” of claim 9, “administered concurrently” of claim 10, and “inhalation” and “intranasally” of claims 19 and 25.
Chen teaches that POH may be administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of body weight. The administration is about 0.2 minutes to about 60 minutes or about 1 minute to about 15 minute before the therapeutic agent is administered. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition. The disclosure read on the limitations of claims 5 and 7 – 11.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine POH as taught by ‘650 with remdesivir in view of Richardson et al. and Chen because Richardson et al. identify that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that POH may be used in combination with antiviral agents and it helps to permeabilize the blood brain barrier. One would have been motivated to combine POH as taught by ‘650 with remdesivir in view of Richardson et al. and Chen because it is known in the art that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that POH helps to permeabilize the blood brain barrier. One of ordinary skill in the art would have had a reasonable expectation of success to combine POH as taught by ‘650 with remdesivir in view of Richardson et al. and Chen because it is known in the art that POH helps to permeabilize the blood brain barrier.
This is a provisional nonstatutory double patenting rejection.Claim 26 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6 and 9 of copending Application No. 18/557,650 in view of Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) and Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025) as applied to claims 1 – 2, 4 – 11, 19, and 25 above, and further in view of Park (Time, 2020, See PTO-892).
h. ‘650, Richardson et al., and Chen teach the limitations discussed above.
However, ‘650, Richardson et al., and Chen do not teach that remdesivir is administered by inhalation or intranasally.
Park teaches that remdesivir has been made into inhaled form by a pharmaceutical company rather than IV infusion (page 1, para. 1).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park explicitly teaches that remdesivir has been made into an inhalation formulation. One would have been motivated to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because it is known in the art that the ease of administration will improve patient convenience by avoiding invasion infusion procedures, permit self-administration, and reduce complications associated with intravenous access. One of ordinary skill in the art would have had a reasonable expectation of success to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park teaches that remdesivir is already formulated for inhalation.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 20 – 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6 and 9 of copending Application No. 18/557,650 in view of Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025), Ivy Center (Ivy Brain Tumor Center, 2020, See PTO-892), and Jonas (HICCC, 2020, See PTO-892).
i. ‘650 claims a method of treating one or more symptoms in a patient that has Parkinson’s Disease, the method comprising administering a pharmaceutical composition comprising POH and L-Dopa to a patient (claim 6). ‘650 claims that the pharmaceutical composition is administered intranasally (claim 9).
However, ‘650 does not teach administering remdesivir to mammal having glioblastoma. ‘650 does not teach that the method further comprises treating the mammal with radiation.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition.
Chen further teaches that perillyl alcohol (POH), a naturally occurring monoterpene, has been suggested to be an effective agent against a variety of cancers, including CNS cancer, breast cancer, pancreatic cancer, lung cancer, melanoma, and colon cancer (page 3, lines 23 – 25). Chen teaches a method of administering a therapeutic agent to a CNS of a mammal, wherein the mammal may have cancer, such as a tumor of the nervous system that is a glioblastoma (page 5, lines 1 – 2; lines 29 – 30). Thus, Chen teaches that POH is known to be an effective agent against CNS cancer, such as glioblastoma, which encompasses the limitations of administering POH to a mammal, “wherein the mammal has cancer”, “wherein the cancer is a tumor of the nervous system”, “wherein the tumor is glioblastoma” of claims 20 – 22. Chen teaches that the method further comprises the step of treating the mammal with radiation (page 5, lines 1 – 31). Moreover, Chen discloses that monoterpene can be used to deliver at least one therapeutic agent across the BBB (page 8, lines 4 – 5) and the monoterpene may be used in combination with antiviral agents (page 8, lines 23 – 24). The disclosure correspond to the limitation of claim 23.
Ivy Center teaches that coronavirus infection posed a risk to brain tumor patients because brain tumor patients are immune-suppressed and are at particular risk from infection (page 1, para. 2). Ivy Center further teaches that coronavirus is extremely dangerous for brain tumor patients because their bodies have limited ability to fight the infection (page 1, para. 7).
Jonas teaches that there was a particular need to find ways to treat COVID-19 in cancer patients because COVID-19 could have particularly severe consequences in cancer patients (page 1, para. 1). Jonas further teaches that the CCC19 study evaluates COVID-19 treatments in cancer patients, including remdesivir, and that remdesivir was the only treatment showing any benefit, with reduced death rate compared with untreated controls (page 1, para. 4 – 5).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to administer POH as taught by ‘650 and Chen to a mammal having cancer that is further suffering from COVID-19, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches that POH permeabilizes the blood-brain-barrier and may be used to deliver therapeutic agents, including antiviral agents, to the CNS and further teaches use in CNS cancer, including glioblastoma, with radiation treatment, Ivy Center teaches that brain tumor patients are particularly susceptible to coronavirus infection because they are immunosuppressed, and Jonas teaches that remdesivir is evaluated as a COVID-19 therapeutic in cancer patients. One would have been motivated to administer remdesivir to a glioblastoma patient when antiviral therapy is indicated because Chen teaches that antiviral agents may be used along with POH and both Ivy Center and Jonas teach that brain tumor patients are immunosuppressed and remdesivir is shown to be effective to treat COVID-19 in cancer patients. One of ordinary skill in the art would have had a reasonable expectation of success to administer POH as taught by ‘650 and Chen to a mammal having cancer, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches POH as a BBB-permeabilizing monoterpene for delivery of therapeutic agents, including antiviral agents, to the CNS. Chen further teaches that POH is used to treat mammals having CNS cancer, including glioblastoma, and may be used with radiation treatment and Ivy Center and Jonas show that brain tumor/cancer patients are recognized as COVID-19 susceptible patient populations for whom COVID-19 treatment, including remdesivir, is clinical relevant.
This is a provisional nonstatutory double patenting rejection.
Claims 1 – 2, 4 – 11, 19, and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16 of copending Application No. 18/001,082 in view of Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) and Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025).
j. ‘082 claims a method of delivering a polynucleotide to a subject, wherein the method comprising administering the polynucleotide and POH to the subject (claim 16).
However, ‘082 does not claim administering remdesivir to a central nervous system of a mammal. ‘082 does not claim that the central nervous system is the brain. ‘082 does not claim the POH is administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of body weight. ‘082 does not claim the mammal is a human. ‘082 does not claim the POH is administered from about 0.2 minutes to about 60 minutes before the remdesivir is administered. ‘082 does not claim that the POH and the remdesivir are administered separately. ‘082 does not claim that the POH and the remdesivir are administered concurrently. ‘082 does not claim that the POH and the remdesivir are administered together in a pharmaceutical composition. ‘082 does not claim that the method further comprising treating the mammal with radiation. ‘082 does not claim that the administration is intranasal, intratumoral, intracranial, intraventricular, intrathecal, epidural, intradural, intravascular, intravenous, intraarterial, intramuscular, subcutaneous, intraperitoneal, or oral.
Richardson et al. teach that coronaviruses are able to enter CNS and cause neurological deficits (page 1880, Left Col., para. 1). About 36.4% of hospitalized patients with COVID-19 show neurologic symptoms, such as headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular disease, and epilepsy. There are more severely ill patients exhibiting cerebrovascular disease and epilepsy (page 1880, Left Col., para. 2). In addition, it is likely that virus-induced neurological damage could have consequences for surviving patients, with a dysexecutive syndrome being observed in up to one third of discharged patients (page 1880, Right Col., para. 1). Six most common drugs for COVID-19 have been assessed for their potential CNS penetration:
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The data show that remdesivir has a predictable low brain penetrance (page 1880, Right Col., para. 2). Thus, Richardson et al. teach that there is a need for enhancing the CNS penetration of remdesivir because coronaviruses are able to enter CNS and cause neurological deficits and these neurologic symptoms are found in 36.4% of hospitalized patients with COVID-19, which read on the limitations “administering remdesivir to a central nervous system of a mammal” of claim 1, “brain” of claim 2, and “human” of claim 6.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. POH may be administered into a vascular system of the mammal intraarterially, via inhalation, or intranasally. Thus, Chen teaches that monoterpene, such as POH, is administered before, after, or concurrently with the therapeutic agent to a human intraarterially, via inhalation, or intranasally, which corresponds to the limitations “before or concurrently” of claim 1, “intraarterially” of claim 4, “human” or claim 6, “administered separately” of claim 9, “administered concurrently” of claim 10, and “inhalation” and “intranasally” of claims 19 and 25.
Chen teaches that POH may be administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of body weight. The administration is about 0.2 minutes to about 60 minutes or about 1 minute to about 15 minute before the therapeutic agent is administered. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition. The disclosure read on the limitations of claims 5 and 7 – 11.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine POH as taught by ‘082 with remdesivir in view of Richardson et al. and Chen because Richardson et al. identify that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that POH may be used in combination with antiviral agents and it helps to permeabilize the blood brain barrier. One would have been motivated to combine POH as taught by ‘082 with remdesivir in view of Richardson et al. and Chen because it is known in the art that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that POH helps to permeabilize the blood brain barrier. One of ordinary skill in the art would have had a reasonable expectation of success to combine POH as taught by ‘082 with remdesivir in view of Richardson et al. and Chen because it is known in the art that POH helps to permeabilize the blood brain barrier.
This is a provisional nonstatutory double patenting rejection.Claim 26 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16 of copending Application No. 18/001,082 in view of Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) and Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025) as applied to claims 1 – 2, 4 – 11, 19, and 25 above, and further in view of Park (Time, 2020, See PTO-892).
k. ‘082, Richardson et al., and Chen teach the limitations discussed above.
However, ‘082, Richardson et al., and Chen do not teach that remdesivir is administered by inhalation or intranasally.
Park teaches that remdesivir has been made into inhaled form by a pharmaceutical company rather than IV infusion (page 1, para. 1).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park explicitly teaches that remdesivir has been made into an inhalation formulation. One would have been motivated to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because it is known in the art that the ease of administration will improve patient convenience by avoiding invasion infusion procedures, permit self-administration, and reduce complications associated with intravenous access. One of ordinary skill in the art would have had a reasonable expectation of success to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park teaches that remdesivir is already formulated for inhalation.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 20 – 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16 of copending Application No. 18/001,082 in view of Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025), Ivy Center (Ivy Brain Tumor Center, 2020, See PTO-892), and Jonas (HICCC, 2020, See PTO-892).
l. ‘082 claims a method of delivering a polynucleotide to a subject, wherein the method comprising administering the polynucleotide and POH to the subject (claim 16).
However, ‘082 does not teach administering remdesivir to mammal having glioblastoma. ‘082 does not teach that the method further comprises treating the mammal with radiation.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition.
Chen further teaches that perillyl alcohol (POH), a naturally occurring monoterpene, has been suggested to be an effective agent against a variety of cancers, including CNS cancer, breast cancer, pancreatic cancer, lung cancer, melanoma, and colon cancer (page 3, lines 23 – 25). Chen teaches a method of administering a therapeutic agent to a CNS of a mammal, wherein the mammal may have cancer, such as a tumor of the nervous system that is a glioblastoma (page 5, lines 1 – 2; lines 29 – 30). Thus, Chen teaches that POH is known to be an effective agent against CNS cancer, such as glioblastoma, which encompasses the limitations of administering POH to a mammal, “wherein the mammal has cancer”, “wherein the cancer is a tumor of the nervous system”, “wherein the tumor is glioblastoma” of claims 20 – 22. Chen teaches that the method further comprises the step of treating the mammal with radiation (page 5, lines 1 – 31). Moreover, Chen discloses that monoterpene can be used to deliver at least one therapeutic agent across the BBB (page 8, lines 4 – 5) and the monoterpene may be used in combination with antiviral agents (page 8, lines 23 – 24). The disclosure correspond to the limitation of claim 23.
Ivy Center teaches that coronavirus infection posed a risk to brain tumor patients because brain tumor patients are immune-suppressed and are at particular risk from infection (page 1, para. 2). Ivy Center further teaches that coronavirus is extremely dangerous for brain tumor patients because their bodies have limited ability to fight the infection (page 1, para. 7).
Jonas teaches that there was a particular need to find ways to treat COVID-19 in cancer patients because COVID-19 could have particularly severe consequences in cancer patients (page 1, para. 1). Jonas further teaches that the CCC19 study evaluates COVID-19 treatments in cancer patients, including remdesivir, and that remdesivir was the only treatment showing any benefit, with reduced death rate compared with untreated controls (page 1, para. 4 – 5).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to administer POH as taught by ‘082 and Chen to a mammal having cancer that is further suffering from COVID-19, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches that POH permeabilizes the blood-brain-barrier and may be used to deliver therapeutic agents, including antiviral agents, to the CNS and further teaches use in CNS cancer, including glioblastoma, with radiation treatment, Ivy Center teaches that brain tumor patients are particularly susceptible to coronavirus infection because they are immunosuppressed, and Jonas teaches that remdesivir is evaluated as a COVID-19 therapeutic in cancer patients. One would have been motivated to administer remdesivir to a glioblastoma patient when antiviral therapy is indicated because Chen teaches that antiviral agents may be used along with POH and both Ivy Center and Jonas teach that brain tumor patients are immunosuppressed and remdesivir is shown to be effective to treat COVID-19 in cancer patients. One of ordinary skill in the art would have had a reasonable expectation of success to administer POH as taught by ‘082 and Chen to a mammal having cancer, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches POH as a BBB-permeabilizing monoterpene for delivery of therapeutic agents, including antiviral agents, to the CNS. Chen further teaches that POH is used to treat mammals having CNS cancer, including glioblastoma, and may be used with radiation treatment and Ivy Center and Jonas show that brain tumor/cancer patients are recognized as COVID-19 susceptible patient populations for whom COVID-19 treatment, including remdesivir, is clinical relevant.
This is a provisional nonstatutory double patenting rejection.
Claims 1 – 2, 4 – 11, 19, and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 12 of U.S. Patent No. 12208066B2 in view of Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) and Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025).
m. ‘066B2 claims a method of treating a CNS cancer, the method comprising administering to a mammal POH before or concurrently with a therapeutic agent that is a CAR-T cell, wherein the CNS cancer is malignant glioma (claim 1). ‘066B2 claims the method, wherein the POH is administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of a body weight of the mammal (claim 2). ‘066B2 claims that the mammal is a human (claim 3). ‘066B2 claims that the POH is administered from about 0.2 minutes to about 60 minutes before the CAR-T cell is administered (claim 4). ‘066B2 claims that the POH is administered from about 1 minutes to about 15 minutes before the CAR-T cell is administered (claim 5). ‘066B2 claims that the POH and the CAR-T cell are administered separately (claim 6). ‘066B2 claims that the POH and the CAR-T cell are administered concurrently (claim 7). ‘066B2 claims that the POH and the CAR-T cell are administered together in a pharmaceutical composition (claim 8). ‘066B2 teaches that the CNS cancer is malignant glioma (claim 9), wherein the malignant glioma is glioblastoma (claims 10 – 11). ‘066B2 claims that the method further comprises treating the mammal with radiation (claim 12).
However, ‘066B2 does not claim administering remdesivir to a central nervous system of a mammal. ‘066B2 does not claim that the CNS is the brain. ‘066B2 does not claim that the POH is administered intraarterially or by inhalation, intranasally, orally, intravenously, subcutaneously, or intramuscularly.
Richardson et al. teach that coronaviruses are able to enter CNS and cause neurological deficits (page 1880, Left Col., para. 1). About 36.4% of hospitalized patients with COVID-19 show neurologic symptoms, such as headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular disease, and epilepsy. There are more severely ill patients exhibiting cerebrovascular disease and epilepsy (page 1880, Left Col., para. 2). In addition, it is likely that virus-induced neurological damage could have consequences for surviving patients, with a dysexecutive syndrome being observed in up to one third of discharged patients (page 1880, Right Col., para. 1). Six most common drugs for COVID-19 have been assessed for their potential CNS penetration:
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The data show that remdesivir has a predictable low brain penetrance (page 1880, Right Col., para. 2). Thus, Richardson et al. teach that there is a need for enhancing the CNS penetration of remdesivir because coronaviruses are able to enter CNS and cause neurological deficits and these neurologic symptoms are found in 36.4% of hospitalized patients with COVID-19, which read on the limitations “administering remdesivir to a central nervous system of a mammal” of claim 1, “brain” of claim 2, and “human” of claim 6.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. POH may be administered into a vascular system of the mammal intraarterially, via inhalation, or intranasally. Thus, Chen teaches that monoterpene, such as POH, is administered before, after, or concurrently with the therapeutic agent to a human intraarterially, via inhalation, or intranasally, which corresponds to the limitations “before or concurrently” of claim 1, “intraarterially” of claim 4, “human” or claim 6, “administered separately” of claim 9, “administered concurrently” of claim 10, and “inhalation” and “intranasally” of claims 19 and 25.
Chen teaches that POH may be administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of body weight. The administration is about 0.2 minutes to about 60 minutes or about 1 minute to about 15 minute before the therapeutic agent is administered. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition. The disclosure read on the limitations of claims 5 and 7 – 11.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine POH as taught by ‘066B2 with remdesivir in view of Richardson et al. and Chen because Richardson et al. identify that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that POH may be used in combination with antiviral agents and it helps to permeabilize the blood brain barrier. One would have been motivated to combine POH as taught by ‘066B2 with remdesivir in view of Richardson et al. and Chen because it is known in the art that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that POH helps to permeabilize the blood brain barrier. One of ordinary skill in the art would have had a reasonable expectation of success to combine POH as taught by ‘066B2 with remdesivir in view of Richardson et al. and Chen because it is known in the art that POH helps to permeabilize the blood brain barrier.Claim 26 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 12 of U.S. Patent No. 12208066B2 in view of Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) and Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025) as applied to claims 1 – 2, 4 – 11, 19, and 25 above, and further in view of Park (Time, 2020, See PTO-892).
n. ‘066B2, Richardson et al., and Chen teach the limitations discussed above.
However, ‘066B2, Richardson et al., and Chen do not teach that remdesivir is administered by inhalation or intranasally.
Park teaches that remdesivir has been made into inhaled form by a pharmaceutical company rather than IV infusion (page 1, para. 1).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park explicitly teaches that remdesivir has been made into an inhalation formulation. One would have been motivated to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because it is known in the art that the ease of administration will improve patient convenience by avoiding invasion infusion procedures, permit self-administration, and reduce complications associated with intravenous access. One of ordinary skill in the art would have had a reasonable expectation of success to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park teaches that remdesivir is already formulated for inhalation.
Claims 1 and 20 – 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 12 of U.S. Patent No. 12208066B2 in view of Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025), Ivy Center (Ivy Brain Tumor Center, 2020, See PTO-892), and Jonas (HICCC, 2020, See PTO-892).
o. ‘066B2 claims a method of treating a CNS cancer, the method comprising administering to a mammal POH before or concurrently with a therapeutic agent that is a CAR-T cell, wherein the CNS cancer is malignant glioma (claim 1). ‘066B2 claims the method, wherein the POH is administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of a body weight of the mammal (claim 2). ‘066B2 claims that the mammal is a human (claim 3). ‘066B2 claims that the POH is administered from about 0.2 minutes to about 60 minutes before the CAR-T cell is administered (claim 4). ‘066B2 claims that the POH is administered from about 1 minutes to about 15 minutes before the CAR-T cell is administered (claim 5). ‘066B2 claims that the POH and the CAR-T cell are administered separately (claim 6). ‘066B2 claims that the POH and the CAR-T cell are administered concurrently (claim 7). ‘066B2 claims that the POH and the CAR-T cell are administered together in a pharmaceutical composition (claim 8). ‘066B2 teaches that the CNS cancer is malignant glioma (claim 9), wherein the malignant glioma is glioblastoma (claims 10 – 11). ‘066B2 claims that the method further comprises treating the mammal with radiation (claim 12).
However, ‘066B2 does not teach administering remdesivir to mammal having glioblastoma.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition.
Chen further teaches that perillyl alcohol (POH), a naturally occurring monoterpene, has been suggested to be an effective agent against a variety of cancers, including CNS cancer, breast cancer, pancreatic cancer, lung cancer, melanoma, and colon cancer (page 3, lines 23 – 25). Chen teaches a method of administering a therapeutic agent to a CNS of a mammal, wherein the mammal may have cancer, such as a tumor of the nervous system that is a glioblastoma (page 5, lines 1 – 2; lines 29 – 30). Thus, Chen teaches that POH is known to be an effective agent against CNS cancer, such as glioblastoma, which encompasses the limitations of administering POH to a mammal, “wherein the mammal has cancer”, “wherein the cancer is a tumor of the nervous system”, “wherein the tumor is glioblastoma” of claims 20 – 22. Chen teaches that the method further comprises the step of treating the mammal with radiation (page 5, lines 1 – 31). Moreover, Chen discloses that monoterpene can be used to deliver at least one therapeutic agent across the BBB (page 8, lines 4 – 5) and the monoterpene may be used in combination with antiviral agents (page 8, lines 23 – 24). The disclosure correspond to the limitation of claim 23.
Ivy Center teaches that coronavirus infection posed a risk to brain tumor patients because brain tumor patients are immune-suppressed and are at particular risk from infection (page 1, para. 2). Ivy Center further teaches that coronavirus is extremely dangerous for brain tumor patients because their bodies have limited ability to fight the infection (page 1, para. 7).
Jonas teaches that there was a particular need to find ways to treat COVID-19 in cancer patients because COVID-19 could have particularly severe consequences in cancer patients (page 1, para. 1). Jonas further teaches that the CCC19 study evaluates COVID-19 treatments in cancer patients, including remdesivir, and that remdesivir was the only treatment showing any benefit, with reduced death rate compared with untreated controls (page 1, para. 4 – 5).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to administer POH as taught by ‘066B2 and Chen to a mammal having cancer that is further suffering from COVID-19, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches that POH permeabilizes the blood-brain-barrier and may be used to deliver therapeutic agents, including antiviral agents, to the CNS and further teaches use in CNS cancer, including glioblastoma, with radiation treatment, Ivy Center teaches that brain tumor patients are particularly susceptible to coronavirus infection because they are immunosuppressed, and Jonas teaches that remdesivir is evaluated as a COVID-19 therapeutic in cancer patients. One would have been motivated to administer remdesivir to a glioblastoma patient when antiviral therapy is indicated because Chen teaches that antiviral agents may be used along with POH and both Ivy Center and Jonas teach that brain tumor patients are immunosuppressed and remdesivir is shown to be effective to treat COVID-19 in cancer patients. One of ordinary skill in the art would have had a reasonable expectation of success to administer POH as taught by ‘066B2 and Chen to a mammal having cancer, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches POH as a BBB-permeabilizing monoterpene for delivery of therapeutic agents, including antiviral agents, to the CNS. Chen further teaches that POH is used to treat mammals having CNS cancer, including glioblastoma, and may be used with radiation treatment and Ivy Center and Jonas show that brain tumor/cancer patients are recognized as COVID-19 susceptible patient populations for whom COVID-19 treatment, including remdesivir, is clinical relevant.Claims 1 – 2, 4 – 11, 19, and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11970436B2 in view of Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) and Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025).
p. ‘436B2 claims a method of treating a CNS cancer, the method comprising administering intraarterially to a patient a therapeutically effective amount of (S)-perillyl alcohol (claim 1).
However, ‘436B2 does not claim administering remdesivir to a central nervous system of a mammal. ‘436B2 does not claim that the central nervous system is the brain. ‘436B2 does not claim the POH is administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of body weight. ‘436B2 does not claim the mammal is a human. ‘436B2 does not claim the POH is administered from about 0.2 minutes to about 60 minutes before the remdesivir is administered. ‘436B2 does not claim that the POH and the remdesivir are administered separately. ‘436B2 does not claim that the POH and the remdesivir are administered concurrently. ‘436B2 does not claim that the POH and the remdesivir are administered together in a pharmaceutical composition. 436B2 does not claim the POH is administered by inhalation, intranasally, orally, intravenously, subcutaneously, or intramuscularly.
Richardson et al. teach that coronaviruses are able to enter CNS and cause neurological deficits (page 1880, Left Col., para. 1). About 36.4% of hospitalized patients with COVID-19 show neurologic symptoms, such as headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular disease, and epilepsy. There are more severely ill patients exhibiting cerebrovascular disease and epilepsy (page 1880, Left Col., para. 2). In addition, it is likely that virus-induced neurological damage could have consequences for surviving patients, with a dysexecutive syndrome being observed in up to one third of discharged patients (page 1880, Right Col., para. 1). Six most common drugs for COVID-19 have been assessed for their potential CNS penetration:
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The data show that remdesivir has a predictable low brain penetrance (page 1880, Right Col., para. 2). Thus, Richardson et al. teach that there is a need for enhancing the CNS penetration of remdesivir because coronaviruses are able to enter CNS and cause neurological deficits and these neurologic symptoms are found in 36.4% of hospitalized patients with COVID-19, which read on the limitations “administering remdesivir to a central nervous system of a mammal” of claim 1, “brain” of claim 2, and “human” of claim 6.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. POH may be administered into a vascular system of the mammal intraarterially, via inhalation, or intranasally. Thus, Chen teaches that monoterpene, such as POH, is administered before, after, or concurrently with the therapeutic agent to a human intraarterially, via inhalation, or intranasally, which corresponds to the limitations “before or concurrently” of claim 1, “intraarterially” of claim 4, “human” or claim 6, “administered separately” of claim 9, “administered concurrently” of claim 10, and “inhalation” and “intranasally” of claims 19 and 25.
Chen teaches that POH may be administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of body weight. The administration is about 0.2 minutes to about 60 minutes or about 1 minute to about 15 minute before the therapeutic agent is administered. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition. The disclosure read on the limitations of claims 5 and 7 – 11.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine POH as taught by ‘436B2 with remdesivir in view of Richardson et al. and Chen because Richardson et al. identify that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that POH may be used in combination with antiviral agents and it helps to permeabilize the blood brain barrier. One would have been motivated to combine POH as taught by ‘436B2 with remdesivir in view of Richardson et al. and Chen because it is known in the art that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that POH helps to permeabilize the blood brain barrier. One of ordinary skill in the art would have had a reasonable expectation of success to combine POH as taught by ‘436B2 with remdesivir in view of Richardson et al. and Chen because it is known in the art that POH helps to permeabilize the blood brain barrier.Claim 26 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11970436B2 in view of Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) and Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025) as applied to claims 1 – 2, 4 – 11, 19, and 25 above, and further in view of Park (Time, 2020, See PTO-892).
q. ‘436B2, Richardson et al., and Chen teach the limitations discussed above.
However, ‘436B2, Richardson et al., and Chen do not teach that remdesivir is administered by inhalation or intranasally.
Park teaches that remdesivir has been made into inhaled form by a pharmaceutical company rather than IV infusion (page 1, para. 1).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park explicitly teaches that remdesivir has been made into an inhalation formulation. One would have been motivated to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because it is known in the art that the ease of administration will improve patient convenience by avoiding invasion infusion procedures, permit self-administration, and reduce complications associated with intravenous access. One of ordinary skill in the art would have had a reasonable expectation of success to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park teaches that remdesivir is already formulated for inhalation.
Claims 1 and 20 – 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11970436B2 in view of Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025), Ivy Center (Ivy Brain Tumor Center, 2020, See PTO-892), and Jonas (HICCC, 2020, See PTO-892).
r. ‘436B2 claims a method of treating a CNS cancer, the method comprising administering intraarterially to a patient a therapeutically effective amount of (S)-perillyl alcohol (claim 1).
However, ‘436B2 does not teach administering remdesivir to mammal having glioblastoma. ‘436B2 does not teach that the method further comprises treating the mammal with radiation.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition.
Chen further teaches that perillyl alcohol (POH), a naturally occurring monoterpene, has been suggested to be an effective agent against a variety of cancers, including CNS cancer, breast cancer, pancreatic cancer, lung cancer, melanoma, and colon cancer (page 3, lines 23 – 25). Chen teaches a method of administering a therapeutic agent to a CNS of a mammal, wherein the mammal may have cancer, such as a tumor of the nervous system that is a glioblastoma (page 5, lines 1 – 2; lines 29 – 30). Thus, Chen teaches that POH is known to be an effective agent against CNS cancer, such as glioblastoma, which encompasses the limitations of administering POH to a mammal, “wherein the mammal has cancer”, “wherein the cancer is a tumor of the nervous system”, “wherein the tumor is glioblastoma” of claims 20 – 22. Chen teaches that the method further comprises the step of treating the mammal with radiation (page 5, lines 1 – 31). Moreover, Chen discloses that monoterpene can be used to deliver at least one therapeutic agent across the BBB (page 8, lines 4 – 5) and the monoterpene may be used in combination with antiviral agents (page 8, lines 23 – 24). The disclosure correspond to the limitation of claim 23.
Ivy Center teaches that coronavirus infection posed a risk to brain tumor patients because brain tumor patients are immune-suppressed and are at particular risk from infection (page 1, para. 2). Ivy Center further teaches that coronavirus is extremely dangerous for brain tumor patients because their bodies have limited ability to fight the infection (page 1, para. 7).
Jonas teaches that there was a particular need to find ways to treat COVID-19 in cancer patients because COVID-19 could have particularly severe consequences in cancer patients (page 1, para. 1). Jonas further teaches that the CCC19 study evaluates COVID-19 treatments in cancer patients, including remdesivir, and that remdesivir was the only treatment showing any benefit, with reduced death rate compared with untreated controls (page 1, para. 4 – 5).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to administer POH as taught by ‘436B2 and Chen to a mammal having cancer that is further suffering from COVID-19, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches that POH permeabilizes the blood-brain-barrier and may be used to deliver therapeutic agents, including antiviral agents, to the CNS and further teaches use in CNS cancer, including glioblastoma, with radiation treatment, Ivy Center teaches that brain tumor patients are particularly susceptible to coronavirus infection because they are immunosuppressed, and Jonas teaches that remdesivir is evaluated as a COVID-19 therapeutic in cancer patients. One would have been motivated to administer remdesivir to a glioblastoma patient when antiviral therapy is indicated because Chen teaches that antiviral agents may be used along with POH and both Ivy Center and Jonas teach that brain tumor patients are immunosuppressed and remdesivir is shown to be effective to treat COVID-19 in cancer patients. One of ordinary skill in the art would have had a reasonable expectation of success to administer POH as taught by ‘436B2 and Chen to a mammal having cancer, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches POH as a BBB-permeabilizing monoterpene for delivery of therapeutic agents, including antiviral agents, to the CNS. Chen further teaches that POH is used to treat mammals having CNS cancer, including glioblastoma, and may be used with radiation treatment and Ivy Center and Jonas show that brain tumor/cancer patients are recognized as COVID-19 susceptible patient populations for whom COVID-19 treatment, including remdesivir, is clinical relevant.
Claims 1 – 2, 4 – 11, 19, and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17 – 28 of copending Application No. 19/410,039 in view of Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) and Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025).
s. ‘039 claims a method of treating a CNS cancer, wherein the method comprising administering to a mammal POH before or concurrently with a therapeutic agent that is CAR-T cell, wherein the POH and CAR-T cells are administered intranasal injection, and wherein the CNS cancer is malignant glioma (claim 17). ‘039 claims the method, wherein the POH is administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of a body weight of the mammal (claim 18). ‘039 claims that the mammal is a human (claim 19). ‘039 claims that the POH is administered from about 0.2 minutes to about 60 minutes before the CAR-T cell is administered (claim 20). ‘039 claims that the POH is administered from about 1 minutes to about 15 minutes before the CAR-T cell is administered (claim 21). ‘039 claims that the POH and the CAR-T cell are administered separately (claim 22). ‘039 claims that the POH and the CAR-T cell are administered concurrently (claim 23). ‘039 claims that the POH and the CAR-T cell are administered together in a pharmaceutical composition (claim 24). ‘039 claims that the CNS cancer is a malignant glioma, wherein the malignant glioma is glioblastoma (claims 25 – 27). ‘039 claims that the method further comprises treating the mammal with radiation (claim 28).
However, ‘039 does not claim administering remdesivir to a central nervous system of a mammal. ‘039 does not claim that the CNS is the brain. ‘039 does not claim that the POH is administered intraarterially or by inhalation, intranasally, orally, intravenously, subcutaneously, or intramuscularly.
Richardson et al. teach that coronaviruses are able to enter CNS and cause neurological deficits (page 1880, Left Col., para. 1). About 36.4% of hospitalized patients with COVID-19 show neurologic symptoms, such as headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular disease, and epilepsy. There are more severely ill patients exhibiting cerebrovascular disease and epilepsy (page 1880, Left Col., para. 2). In addition, it is likely that virus-induced neurological damage could have consequences for surviving patients, with a dysexecutive syndrome being observed in up to one third of discharged patients (page 1880, Right Col., para. 1). Six most common drugs for COVID-19 have been assessed for their potential CNS penetration:
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The data show that remdesivir has a predictable low brain penetrance (page 1880, Right Col., para. 2). Thus, Richardson et al. teach that there is a need for enhancing the CNS penetration of remdesivir because coronaviruses are able to enter CNS and cause neurological deficits and these neurologic symptoms are found in 36.4% of hospitalized patients with COVID-19, which read on the limitations “administering remdesivir to a central nervous system of a mammal” of claim 1, “brain” of claim 2, and “human” of claim 6.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. POH may be administered into a vascular system of the mammal intraarterially, via inhalation, or intranasally. Thus, Chen teaches that monoterpene, such as POH, is administered before, after, or concurrently with the therapeutic agent to a human intraarterially, via inhalation, or intranasally, which corresponds to the limitations “before or concurrently” of claim 1, “intraarterially” of claim 4, “human” or claim 6, “administered separately” of claim 9, “administered concurrently” of claim 10, and “inhalation” and “intranasally” of claims 19 and 25.
Chen teaches that POH may be administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of body weight. The administration is about 0.2 minutes to about 60 minutes or about 1 minute to about 15 minute before the therapeutic agent is administered. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition. The disclosure read on the limitations of claims 5 and 7 – 11.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine POH as taught by ‘039 with remdesivir in view of Richardson et al. and Chen because Richardson et al. identify that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that POH may be used in combination with antiviral agents and it helps to permeabilize the blood brain barrier. One would have been motivated to combine POH as taught by ‘039 with remdesivir in view of Richardson et al. and Chen because it is known in the art that remdesivir is in need of enhancing the CNS penetrance and Chen teaches that POH helps to permeabilize the blood brain barrier. One of ordinary skill in the art would have had a reasonable expectation of success to combine POH as taught by ‘039 with remdesivir in view of Richardson et al. and Chen because it is known in the art that POH helps to permeabilize the blood brain barrier.
This is a provisional nonstatutory double patenting rejection.Claim 26 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17 – 28 of copending Application No. 19/410,039 in view of Richardson et al. (Journal of Neurology, May 2020, Vol. 267, Issue 7, page 1880 – 1882, See PTO-892) and Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025) as applied to claims 1 – 2, 4 – 11, 19, and 25 above, and further in view of Park (Time, 2020, See PTO-892).
t. ‘039, Richardson et al., and Chen teach the limitations discussed above.
However, ‘039, Richardson et al., and Chen do not teach that remdesivir is administered by inhalation or intranasally.
Park teaches that remdesivir has been made into inhaled form by a pharmaceutical company rather than IV infusion (page 1, para. 1).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park explicitly teaches that remdesivir has been made into an inhalation formulation. One would have been motivated to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because it is known in the art that the ease of administration will improve patient convenience by avoiding invasion infusion procedures, permit self-administration, and reduce complications associated with intravenous access. One of ordinary skill in the art would have had a reasonable expectation of success to formulate remdesivir as taught by Richardson et al. into an inhaled form in view of Park because Park teaches that remdesivir is already formulated for inhalation.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 20 – 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17 – 28 of copending Application No. 19/410,039 in view of Chen (WO2019/157195A1, cited in the PTO-892 on October 14, 2025), Ivy Center (Ivy Brain Tumor Center, 2020, See PTO-892), and Jonas (HICCC, 2020, See PTO-892).
u. ‘039 claims a method of treating a CNS cancer, wherein the method comprising administering to a mammal POH before or concurrently with a therapeutic agent that is CAR-T cell, wherein the POH and CAR-T cells are administered intranasal injection, and wherein the CNS cancer is malignant glioma (claim 17). ‘039 claims the method, wherein the POH is administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of a body weight of the mammal (claim 18). ‘039 claims that the mammal is a human (claim 19). ‘039 claims that the POH is administered from about 0.2 minutes to about 60 minutes before the CAR-T cell is administered (claim 20). ‘039 claims that the POH is administered from about 1 minutes to about 15 minutes before the CAR-T cell is administered (claim 21). ‘039 claims that the POH and the CAR-T cell are administered separately (claim 22). ‘039 claims that the POH and the CAR-T cell are administered concurrently (claim 23). ‘039 claims that the POH and the CAR-T cell are administered together in a pharmaceutical composition (claim 24). ‘039 claims that the CNS cancer is a malignant glioma, wherein the malignant glioma is glioblastoma (claims 25 – 27). ‘039 claims that the method further comprises treating the mammal with radiation (claim 28). However, ‘039 does not teach administering remdesivir to mammal having glioblastoma.
Chen teaches an invention relates to using monoterpene to permeabilize the blood brain barrier (BBB) (Abstract). Chen teaches a method of administering a therapeutic agent to a central nervous system of a mammal, such as human, wherein the method comprising administering a monoterpene before, after or concurrently with the therapeutic agent. The central nervous system may be the brain and the monoterpene may be POH. The POH and the therapeutic agent may be administered separately or concurrently. In one embodiment, the POH and the therapeutic agent are administered together in a pharmaceutical composition.
Chen further teaches that perillyl alcohol (POH), a naturally occurring monoterpene, has been suggested to be an effective agent against a variety of cancers, including CNS cancer, breast cancer, pancreatic cancer, lung cancer, melanoma, and colon cancer (page 3, lines 23 – 25). Chen teaches a method of administering a therapeutic agent to a CNS of a mammal, wherein the mammal may have cancer, such as a tumor of the nervous system that is a glioblastoma (page 5, lines 1 – 2; lines 29 – 30). Thus, Chen teaches that POH is known to be an effective agent against CNS cancer, such as glioblastoma, which encompasses the limitations of administering POH to a mammal, “wherein the mammal has cancer”, “wherein the cancer is a tumor of the nervous system”, “wherein the tumor is glioblastoma” of claims 20 – 22. Chen teaches that the method further comprises the step of treating the mammal with radiation (page 5, lines 1 – 31). Moreover, Chen discloses that monoterpene can be used to deliver at least one therapeutic agent across the BBB (page 8, lines 4 – 5) and the monoterpene may be used in combination with antiviral agents (page 8, lines 23 – 24). The disclosure correspond to the limitation of claim 23.
Ivy Center teaches that coronavirus infection posed a risk to brain tumor patients because brain tumor patients are immune-suppressed and are at particular risk from infection (page 1, para. 2). Ivy Center further teaches that coronavirus is extremely dangerous for brain tumor patients because their bodies have limited ability to fight the infection (page 1, para. 7).
Jonas teaches that there was a particular need to find ways to treat COVID-19 in cancer patients because COVID-19 could have particularly severe consequences in cancer patients (page 1, para. 1). Jonas further teaches that the CCC19 study evaluates COVID-19 treatments in cancer patients, including remdesivir, and that remdesivir was the only treatment showing any benefit, with reduced death rate compared with untreated controls (page 1, para. 4 – 5).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to administer POH as taught by ‘039 and Chen to a mammal having cancer that is further suffering from COVID-19, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches that POH permeabilizes the blood-brain-barrier and may be used to deliver therapeutic agents, including antiviral agents, to the CNS and further teaches use in CNS cancer, including glioblastoma, with radiation treatment, Ivy Center teaches that brain tumor patients are particularly susceptible to coronavirus infection because they are immunosuppressed, and Jonas teaches that remdesivir is evaluated as a COVID-19 therapeutic in cancer patients. One would have been motivated to administer remdesivir to a glioblastoma patient when antiviral therapy is indicated because Chen teaches that antiviral agents may be used along with POH and both Ivy Center and Jonas teach that brain tumor patients are immunosuppressed and remdesivir is shown to be effective to treat COVID-19 in cancer patients. One of ordinary skill in the art would have had a reasonable expectation of success to administer POH as taught by ‘039 and Chen to a mammal having cancer, wherein the cancer is a tumor of the nervous system and the tumor is glioblastoma, with remdesivir in view of Ivy Center and Jonas because Chen teaches POH as a BBB-permeabilizing monoterpene for delivery of therapeutic agents, including antiviral agents, to the CNS. Chen further teaches that POH is used to treat mammals having CNS cancer, including glioblastoma, and may be used with radiation treatment and Ivy Center and Jonas show that brain tumor/cancer patients are recognized as COVID-19 susceptible patient populations for whom COVID-19 treatment, including remdesivir, is clinical relevant.
This is a provisional nonstatutory double patenting rejection.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed April 14, 2026, have been fully considered and are not found to be persuasive.
Regarding the rejections, Applicant requests that the rejections be held in abeyance until at least one claim is otherwise found allowable. As no allowable subject matter has been identified, the double patenting rejections are maintained.
Conclusion
No claim is found to be allowable.
THIS ACTION IS MADE NON-FINAL.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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