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
The office acknowledges Applicants filing of the claim amendments and arguments on 12/3/2025 in response to the office action dated 6/3/2025. The IDS filed on 7/3/2025 has not been considered as the fees has not been paid. Claims 1, 3, 6- 8, 15, 21 have been amended and claims 26-29 have been added new. Claims 2, 9-14, 20, 22-25 are cancelled. Applicants arguments have been fully considered. Rejections not reiterated from previous office actions are hereby withdrawn. Arguments, which are directed to withdrawn rejections, are thus rendered moot. The arguments in regards to the reiterated rejections/references from the previous office action are addressed below. In view of Applicant's claim amendments, the following rejections are either reiterated or newly applied. The action is made final. Claims 1, 3-8, 15-19, 21, 26-29 are pending and are examined based on the merits herein.
Response to Applicants Arguments
Byrareddy:
Applicants argue that the reference is simply a review paper and provides no new data. Even if Ribeiro and Byrareddy could be combined to meet the elements of the amended claims, there is not a reasonable expectation of success in using a cannabinoid such cannabidiol to treat inflammation associated with virus-induced ARDS, as-claimed. Byrareddy does not provide any new data showing that the claimed compositions can treat virus-induced.
In response, Byrareddy as correctly stated by the Applicants, is a review article that explicitly teaches (i) SARS-Cov-2 is caused by ARDS (ii) acute infection is associated with cytokine superstorm (iii) it is imperative to explore alternate therapies in treating COVID-19, potential effects of cannabinoids, in particular, the non-psychotropic cannabidiol (CBD), that has shown beneficial anti-inflammatory effects in pre-clinical models of various chronic inflammatory diseases cannabinoid, in particular cannabidiol can be considered because of its anti-inflammatory effects (iv) CBD can inhibit the production of proinflammatory cytokines like interleukin (IL)-2, IL-6, IL-1α and β, interferon gamma, inducible protein-10, monocyte chemo attractant protein-1, macrophage inflammatory protein-1α, and tumor necrosis factor-α that have been associated with SARS-CoV2 induced multi-organ pathology and mortality. CBD has a high margin of safety and is well tolerated pharmacologically even after treatments of up to 1500 mg/day for two weeks in both animals and humans (v) the findings of the remdesivir treatment support the investigation of cannabinoids as a plausible option to be added as an adjunct to remdesivir or any new antivirals on SARS-CoV2 induced lung inflammation. In summary, Byrareddy provides a rationale, suggestion and a strong motivation to use CBD in patients with SARS-Cov-2 to treat symptoms including lung inflammation.
(2) Novak: Applicants argue that the claims have been amended to recite that the subject has inflammation caused by virus-induced Acute Respiratory Distress Syndrome (ARDS). Nowak focuses on developing cannabinoid formulations with increased bioavailability upon oral administration. Nowak is directed to preventing cytokine release syndrome (CRS). ARDS is mentioned as a symptom of severe COVID-19. Nowak teaches that "[t]he treatment is initiated during the non-severe symptomatic period of COVID-19." Thus, at most Nowak indicates that early treatment of COVID-19 with cannabidiol may prevent or reduce the later manifestation of CRS and/or ARDS. Nowak does not teach or suggest that a subject with viral-induced ARDS can be treated directly for the ARDS as currently claimed. Furthermore, Nowak provides no actual reduction to practice of any treatment whatsoever. The only Examples are prophetic formulations. Thus, Nowak fails to teach the claimed invention, and further, given the lack of actual reduction to practice, there is not a reasonable expectation of success that the claimed treatment.
In response, Novak is explicit in teaching the use of cannabinoids in particular cannabidiol in treating a patient suffering from an infection with SARS- CoV-2. Further the reference explicitly teach in reducing the ARDS and the cytokine storm, both associated with COVID-19 with the cannabinoid treatment; the pro-inflammatory cytokine IL-6 has a central role in the cytokine release syndrome (CRS) in patients with severe COVID-19 and IL-6 signaling is among the main canonical pathways affected by cannabinoids and in particular CBD. It is noted that from Novak a skilled artisan would have found it obvious to treat all COVID-19 subjects including the ones with ARDS to treat the infection and the associated cytokine storm. In fact the instant application teach and claims that pulmonary inflammation comprises cytokine storm. Novak explicitly describes and teaches that the cannabinoid treatment ameliorates cytokine release syndrome and reduces serum IL-6 level. From the teachings of the prior art an ordinary artisan would have had a reasonable expectation of success in achieving the desirable clinical outcome in using the compositions of Novak in treating the inflammatory symptoms or pulmonary inflammation in a subject with ARDS or COVID-19 because (i) Novak and Byrareddy teach that cannabinoids, in particular cannabidiol provide anti-inflammatory effects, inhibit the production of proinflammatory cytokines like interleukin (IL)-2, IL-6, IL-1α and β, interferon gamma, inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and tumor necrosis factor-α that have been associated with SARS-CoV-2 and (ii) ARDS is associated with SARS-CoV-2. Novak has described the technical details and description to make and use the cannabinoid composition. A skilled artisan would have been motivated to arrive at the claimed method to treat symptoms associated with COVID-19 or SARS-Cov-2 and provide therapeutic effects. Thus the instantly claimed method(s) would have been obvious over the prior teachings.
Claim Rejections - 35 USC § 103
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:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3-8, 15-19, 21, 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Nowak et al. (WO 2021/228365, effective filing date: May 11 2020) and ByraReddy (Brain, Behavior, and Immunity, Vol 87, pp. 120-121, publication date: 27 Apr 2020).
Nowak teach a cannabinoid, e.g. cannabidiol for treatment of a patient suffering from an infection with SARS- CoV-2, wherein the treatment is for ameliorating the cytokine release syndrome (CRS); wherein the treatment reduces the serum IL-6 level; wherein the treatment is ameliorating the acute respiratory distress syndrome (ARDS) (See claims 1-5). The cannabinoid is administered at a dose between 250 mg-5000 mg/day (see p 2, last two lines). Nowak teach CRS is a form of systemic inflammatory response syndrome (p 4, lines 6-7). In COVID-19, systemic hyperinflammation results in inflammatory lymphocytic and monocytic infiltration of the lung and the heart, causing ARDS and cardiac failure (p 4, lines 14-15). A high level of IL-6 is a hallmark and important driving force of the CRS (p 4, para 6). In patients progressing to the severe stage III, lung inflammation is the main cause of acute respiratory distress syndrome (ARDS). The rapid onset of widespread inflammation in the lungs leads to respiratory failure. ARDS is a major cause of death from COVID-19 (p 4, last para). Further taught is that cannabinoids include, for example, tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD) (p 7, last para). Cannabinoids, in particular cannabidiol, are in particular suitable for preventing CRS in COVID-19 patients or at least halting or significantly slowing down progression of CRS to severe stages in COVID-19 patients (p 10, para 10).
Nowak teach that many studies demonstrate that cannabinoids and in particular CBD exert their immune suppressive and anti-inflammatory effects by the suppression of pro-inflammatory cytokines such as TNF-a, IFN-g, IL-6, I L- 1 b , IL-2, IL-17A, and of chemokines, such as CCL-2. The pro-inflammatory cytokine IL-6 has a central role in the cytokine release syndrome (CRS) in patients with severe COVID-19 and IL-6 signaling is among the main canonical pathways affected by cannabinoids and in particular CBD. Since cannabinoids and in particular CBD suppress circulating IL-6 in various inflammation animal models including a model of acute lung injury, suppression of IL-6 thereby preventing the CRS is considered the most relevant mode of action of cannabinoids and in particular CBD in patients with COVID-19 (p 13, para 2). Nowak teach that cannabinoid in combination an antiviral agent is used to treat idiopathic pulmonary fibrosis (See claim 18). Nowak teach compositions comprising cannabinoids (See p 18, para 2) and composition comprising cannabidiol (See example 3). Further taught is the amount of the cannabinoid composition, is administered at a dose between 250 mg and 5000 mg one to four times per day (p 14, lines 16-17).
Byrareddy suggests that cannabidiol can act as a co-therapeutic agent for reducing symptoms of inflammation of COVID-19 (page 120, left column, paragraph 2 through right column, paragraph 1, page 121, Fig. 1). Byrareddy teach that coronavirus disease-2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome coronoavirus-2 (SARS-CoV2) (col. 1, page 120, lines 1-2). It is taught that recent reports have suggested that acute infection is associated with a cytokine superstorm, which contributes to the symptoms of fever, cough, muscle pain and in severe cases bilateral interstitial pneumonia (see p 120, col. 1, para 1, lines 3-6). The reference teaches that non-psychotropic cannabidiol (CBD), has shown beneficial anti-inflammatory effects in pre-clinical models of various chronic inflammatory diseases (p 120, para 1). It is taught that like Δ9 -tetrahydrocannabinol (Δ9 -THC), the most well-studied cannabinoid, CBD decreased lung inflammation in a murine model of acute lung injury potentially through the inhibition of proinflammatory cytokine production by immune cells and suppressing exuberant immune responses; CBD can inhibit the production of proinflammatory cytokines like interleukin (IL)-2, IL-6, IL-1α and β, interferon gamma, inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and tumor necrosis factor-α that have been associated with SARS-CoV2 induced multi-organ pathology and mortality. In a murine model of chronic asthma, CBD reduced proinflammatory cytokine production, airway inflammation and fibrosis; moreover, CBD can effectively inhibit the JAK-STAT pathway including the production and action of type I interferons without leading to addiction, alterations in heart rate or blood pressure and adverse effects on the gastrointestinal tract and cognition (see para 2, p 120). CBD has a high margin of safety and is well tolerated pharmacologically even after treatments of up to 1500 mg/day for two weeks in both animals and humans (Nichols and Kaplan, 2020), which suggests its feasibility to reduce SARS-CoV2 induced lung inflammation/pathology and disease severity (p 120, col. 2, para 1). Being a negative allosteric modulator of the cannabinoid receptor-1, CBD can counter the psychotropic effects of THC when co-administered with THC (p 120, col. 2, last para). Although Remdesivir reduced the mortality rate of seriously ill COVID-19 patients needing invasive ventilation, similar studies in rhesus macaques revealed minimal subpleural inflammatory cellular infiltrates in the lungs of clinically recovered remdesivir treated RMs at necropsy. This suggests persistence of inflammation and may partly explain the 20–30% reduction in lung function in COVID-19 patients after recovery, which if left unresolved may lead to pulmonary fibrosis. Collectively, these findings support the investigation of cannabinoids as a plausible option to be added as an adjunct to remdesivir or any new antivirals on SARS-CoV2 induced lung inflammation (see p 120-121, col. 1, lines 1-9).
From the teachings of Nowak and Byrareddy a person skilled in the art before the effective filing date of the invention would have found it obvious to use an effective amount of cannabinoid, e.g. cannabidiol by itself or in combination with other cannabinoids to reduce the inflammatory symptoms associated with COVID-19 in subjects in need thereof including a subject with SARS-Cov-2 induced ARDS. Nowak teach Severe Acute Respiratory Syndrome as Coronavirus-2 (SARS-CoV2). Hence the subjects of COVID-19 include acute respiratory distress syndrome subjects. A person skilled in the art would have been motivated to use cannabidiol in treating inflammatory symptoms of COVID-19 in the subjects as claimed with a reasonable amount of success and to provide therapeutic benefits as CBD is available commercially, CBD has been shown to have anti-inflammatory effects, it decreases lung inflammation and can inhibit the production of proinflammatory cytokines (e.g. IL-6). Thus claim 1 would have been obvious over the prior art teachings.
As to claims 3-7 cannabidiol when administered to the same set of subjects (COVID-19), will necessarily result in the recited limitations which are the functions/properties of the agent, e.g. reducing the level of inflammatory cytokines in the subject, reduces inflammatory damage, improves the functional capacity of the lungs. Nowak teach inflammatory cytokines associated with COVID-19 include IL-6, TNF-α and are in the lung. As to claim 8, the reference teach that acute respiratory distress is associated with COVID-19.
As to claims 15-16, from Nowak a person of ordinary skill in the art would have found it obvious to use an effective amount of CBD in reducing pulmonary inflammation associated with COVID-19 in subjects including as claimed because Novak teach systemic hyperinflammation results in inflammatory lymphocytic and monocytic infiltration of the lung and the heart, causing ARDS and cardiac failure. As to the subject having ARDS from Nowak it is obvious that ARDS is associated with Coronavirus infection. A person of ordinary skill in the art would have been motivated to arrive at the claimed method with a reasonable amount of success and provide therapeutic benefits.
As to claims 17-19, Nowak teach cannabinoid, THC can be used to treat infection with SARS-CoV-2. Hence a skilled artisan would have found it obvious to use THC in treating the pulmonary or lung inflammation associated with SARS-CoV-2.
As to claim 21, it is noted that from Novak and Byrareddy it is obvious that cytokine storm is associated with pulmonary inflammation in SARS-Cov-2. As to claims 28-29, the instant specification teach administration of 5 mg/kg (examples). Nowak teach administration of a dose between 250 mg and 5000 mg one to four times per day. Adjusting dose or dosage regimen depending on the condition to be treated and the route of administration is within the skill of an artisan and it is routine. A skilled artisan would have found it obvious to administer an effective amount of the cannabinoid in the treatment of inflammation as claimed. Administration of the same agent in an effective amount of cannabidiol to the subject as claimed to treat inflammation would result in raise the level of apelin in the subject’s lung tissue.
Claim(s) 1, 3-8, 15-19, 21, 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over ByraReddy (Brain, Behavior, and Immunity, Vol 87, pp. 120-121, publication date: 27 Apr 2020).
Byrareddy suggests that cannabidiol can act as a co-therapeutic agent for reducing symptoms of inflammation of COVID-19 (page 120, left column, paragraph 2 through right column, paragraph 1, page 121, Fig. 1). Byrareddy teach that coronavirus disease-2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome coronoavirus-2 (SARS-CoV2) (col. 1, page 120, lines 1-2). It is taught that recent reports have suggested that acute infection is associated with a cytokine superstorm, which contributes to the symptoms of fever, cough, muscle pain and in severe cases bilateral interstitial pneumonia (see p 120, col. 1, para 1, lines 3-6). The reference teaches that non-psychotropic cannabidiol (CBD), has shown beneficial anti-inflammatory effects in pre-clinical models of various chronic inflammatory diseases (p 120, para 1). It is taught that like Δ9 -tetrahydrocannabinol (Δ9 -THC), the most well-studied cannabinoid, CBD decreased lung inflammation in a murine model of acute lung injury potentially through the inhibition of proinflammatory cytokine production by immune cells and suppressing exuberant immune responses; CBD can inhibit the production of proinflammatory cytokines like interleukin (IL)-2, IL-6, IL-1α and β, interferon gamma, inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and tumor necrosis factor-α that have been associated with SARS-CoV2 induced multi-organ pathology and mortality. In a murine model of chronic asthma, CBD reduced proinflammatory cytokine production, airway inflammation and fibrosis; moreover, CBD can effectively inhibit the JAK-STAT pathway including the production and action of type I interferons without leading to addiction, alterations in heart rate or blood pressure and adverse effects on the gastrointestinal tract and cognition (see para 2, p 120). CBD has a high margin of safety and is well tolerated pharmacologically even after treatments of up to 1500 mg/day for two weeks in both animals and humans (Nichols and Kaplan, 2020), which suggests its feasibility to reduce SARS-CoV2 induced lung inflammation/pathology and disease severity (p 120, col. 2, para 1). Being a negative allosteric modulator of the cannabinoid receptor-1, CBD can counter the psychotropic effects of THC when co-administered with THC (p 120, col. 2, last para). Although Remdesivir reduced the mortality rate of seriously ill COVID-19 patients needing invasive ventilation, similar studies in rhesus macaques revealed minimal subpleural inflammatory cellular infiltrates in the lungs of clinically recovered remdesivir treated RMs at necropsy. This suggests persistence of inflammation and may partly explain the 20–30% reduction in lung function in COVID-19 patients after recovery, which if left unresolved may lead to pulmonary fibrosis. Collectively, these findings support the investigation of cannabinoids as a plausible option to be added as an adjunct to remdesivir or any new antivirals on SARS-CoV2 induced lung inflammation (see p 120-121, col. 1, lines 1-9).
From the teachings of Byrareddy a person skilled in the art before the effective filing date of the invention would have found it obvious that inflammation is associated with COVID-19 (SARS-CoV-2) and with respiratory distress. Hence a skilled artisan would have found it obvious to try administering an effective amount of CBD in subjects with coronavirus (SARS-CoV-2) or ARDS to treat inflammation. A person skilled in the art would have been motivated to do so because CBD is available commercially, CBD has been shown to have anti-inflammatory effects, it decreases lung inflammation and can inhibit the production of proinflammatory cytokines (e.g. IL-6). The reference teach ARDS is associated with coronavirus infection. Thus administration of cannabidiol to a subject in need thereof (e.g. Covid-19 subject or ARDS) will result in reduction of inflammatory symptoms as in claim 1, reduction of inflammatory cytokines reduction of inflammatory damage to the lungs, improvement of the functional capacity of the lungs thus addressing claims 1, 3, 6-7. As to claim 4-5, Byrareddy teach the inflammatory cytokines associated with COVID-19 include IL-6 and the lung inflammation associated with coronavirus infection. As to claim 8, the reference teach that acute respiratory distress is associated with COVID-19. It is noted that ARDS is a critical condition that affects the lungs' ability to exchange gases, leading to severe respiratory distress. In fact the instant specification defines, “The lung is a primary site of entry for SARS-CoV-2, as evidenced by massive pulmonary inflammation and development of acute respiratory distress syndrome (ARDS). ARDS is a serious inflammatory lung condition responsible for the highest rate of medical complications and mortality among critically ill patients” (see p 1). Hence as to claims 15-16, a person skilled in the art from Byrareddy would have found it obvious to administer cannabidiol in a subject with pulmonary inflammation and relieve symptoms of inflammation in subjects with ARDS. As to claim 17, Byrareddy suggests combining THC with CBD to negate the psychotropic effects of CBD and provide additive or synergistic benefits in treating inflammation in a subject in need thereof. As to claims 18-20, Byrareddy teachings suggest administration of cannabidiol to a subject infected with coronavirus infection (e.g. SARS-CoV-2) or ARDS. As to claim 21, from Byrareddy it is obvious that inflammation and cytokine storm is associated with SARS-Cov-2. It is noted that SARS-Cov-2 and ARDS are respiratory conditions and hence pulmonary inflammation is associated with such conditions.
Claim(s) 26-29 are rejected under 35 U.S.C. 103 as being unpatentable over ByraReddy (Brain, Behavior, and Immunity, Vol 87, pp. 120-121, publication date: 27 Apr 2020) as applied to claims 1, 3-8, 15-19, 21 above and in view of Bryson (US 20170348276 A).
ByraReddy teachings as discussed above. The rejection above is incorporated herein.
The reference do not teach that the cannabinoid is administered pulmonary, nasal or rectal.
Bryson teach cannabinoid compositions, for e.g. comprising cannabidiol for nasal administration and the composition can be used for treating inflammation (See claims 1, 9, 49). Bryson teach that the novel methods involve depositing the nasal cannabinoid pharmaceutical compositions topically into the nasal cavity of each nostril to deliver a therapeutically effective amount of cannabinoid, e.g., from about 0.5 mg/nostril to about 37.5 mg/nostril per application [0042].
A person skilled in the art would have found it obvious to administer cannabinoid, e.g. cannabidiols in the instant methods for treating inflammation or pulmonary inflammation associated with SARS-Cov-2 in ARDS subject because Bryson teach cannabidiol composition, e.g. 0.5-37.5 mg for nasal administration for treating inflammation in general. A person skilled in the art would have been motivated to use Bryson’s cannabidiol composition in the method of ByraReddy to treat inflammation or pulmonary inflammation as claimed and derive therapeutic response. Thus claims 26-27 would have been obvious over the prior art teachings. As to claims 28-29, the instant specification teach administration of 5 mg/kg (examples). Bryson teach dosage amount of from about 0.5 mg/nostril to about 37.5 mg/nostril per application. Adjusting dose or dosage regimen depending on the condition to be treated and the route of administration is within the skill of an artisan and it is routine. A skilled artisan would have found it obvious to administer an effective amount of the cannabinoid in the treatment of inflammation as claimed. Administration of the same agent in an effective amount of cannabidiol to the subject as claimed to treat inflammation would result in raise the level of apelin in the subject’s lung tissue.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/Umamaheswari Ramachandran/ Primary Examiner, Art Unit 1627