DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Application Status
The Amendment filed on 2/06/2026 in response to the Non-Final Office action of 08/06/2023 is acknowledged and has been entered. Claims 1-22 are currently pending and under consideration.
Claim Interpretation
Claim 21 has been added and recites “The composition of claim 1, wherein the synergistic effect is determined accordingly to the Colby method, such that the observed results of the two-active agent combination on ALS or an ALS-related symptom exceeds the effect predicted by the Colby calculation from the individual agents”. As such, while the composition claims now contain a limitation of how the synergistic effect is determined, said limitation does not appear to be an active step positively recited. For prior purposes, such limitation will be not be considered as further limiting as it does not appear to be limiting the composition.
Rejections Maintained but many be modified in view applicants amendments
Claim Rejections - 35 USC § 101
Claims 1-15 and 17-18 remain and new claim 21 is rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter for the reasons of record and incorporated herein.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
In response to this rejection Applicants contend that the claims are not directed to a product of nature (Step 2A). Specifically, Applicants contend that independent claim 1 affirmatively limits the compositions to one “wherein the two active agents have a synergistic effect on the treatment of ALS”, wherein this limitation is not a mere result-statement, but defines the compositions scope. Moreover, Applicants contend that the Office Action’s Step 2A analysis overlooks this required property and treats the compositions as though it were just an aggregation of natural constituents, but the law and the USPTO’s own guidance recognizes that functional, combination-dependent properties, especially synergy, constitute “markedly different characteristics”. Accordingly, Applicants contend that the asserted synergy is, by definition, not inherent in the individual components, it emerges from the intentional human selection and formulation of specific combinations.
In response to these arguments, the Examiner acknowledges that the USPTO’s own guidelines recognize that functional, combination-dependent properties constitute “markedly different characteristics”. However, the examiner recognizes that the courts have emphasized that to show a marked difference, a characteristic must be changed as compared to nature, and cannot be an inherent or innate characteristic of the naturally occurring counterpart or an incidental change in a characteristic of the naturally occurring counterpart. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. Thus, in order to be markedly different, the inventor must have caused the claimed product to possess at least one characteristic that is different from that of the counterpart. In the instant case, the specification provides a number of examples. For example, Example 1 is entitled Demonstration of Synergy and involves experiments done to demonstrate synergy of the components of the composition, wherein each putative synergistic agent is administered to cells in an in vitro model and/or to animals in an animal model of the disease process, and the quantitative response is recorded … Synergistic combinations in terms of ratios of the two components and in terms of dose response are further optimized in subsequent tests based upon the first series of test. However, while the specification discusses recording these responses, no data is provided. Example 2 provides a specific formulation with specific amounts. However, there is no mention of whether this formulation is specifically synergistic. Example 4 discusses a transmucosal formulation including THC and CBD that was found to have synergistic effects, wherein the formulation was found to provide antioxidant neuroprotection and to allay disease progression. Thus, while Applicants assert synergy (see for example, Examples 1-8), there is no data provided by Applicants to show that the result of the combination is more than the individual combined, nor is there any data to show which ratio’s produce this effect. Moreover, the specification teaches that synergistic ingredients can range from 10:1 to 1:5000 or less, such as a ratio of 10:1, 1:1, 1:10, 1:500, 1:1000, 1:1500, … 1:4500 or 1:5000 (paragraph 0105). As such, the CBN/THC ratio from commercial hemp seeds is 0.11:1 to 62.56:1 and 3.21:1 to 22.50 in hemp see oil appears to fall within the scope of the instant invention (see Jang et al. (Forensic Science International 2020; 306: 110064).
Applicants further contend that the claim requires transmucosal pharmaceutical forms with a carrier, thereby imparting structural and pharmacokinetic different that nature does not supply. For example, Applicants assert that dependent claims further limit the claims to different types of sprays as well as solid transmucosal forms which impose manufactured structural characteristics (e.g. solvent systems, viscosity/particle characteristics, permeation enhancers, disintegration profiles) and functional characteristics (mucosal uptake, first-pass avoidance, faster onset) that categorically differ from Cannabis plant tissues or compounds “as found in nature”. contain limitations which impose manufactured structural characteristics.
In response to Applicants arguments, the examiner recognizes that at least claim 1 is drawn to composition comprising a combination of at least two active agents extracted from Cannabis and a pharmaceutically acceptable carrier, wherein the composition is provided in a form suitable for transmucosal administration, the claims do not require a transmucosal pharmaceutical form as asserted by Applicants, only one that is suitable. As such, the claims only require the two active agents and an additional ingredient of a pharmaceutical acceptable carrier. Moreover, the additional ingredients appear to be additional elements of the claim which were discussed in step 2B of the prior office action and further herein. As noted by Riva et al., nabiximols is an oral mucosal spray containing 2.7 mg of THC and 2.5mg cannabidiol in a 50:50: solution of ethanol and propylene glycol (page 157, 2nd column, Procedure). As such, the additional elements or “form” appear to be well-understood, routine and conventional. Note: The examiner has not rejected claim 16, which limits the dosage for to specific structural forms.
Lastly, Applicants assert that the claims integrate any such exception into practical application:
They recite a particular manufacture: a pharmaceutical composition in transmucosal form with a pharmaceutically acceptable carrier, not a generic admixture.
They confine the scope to combination that achieve synergy in the treatment of ALS, a specific therapeutic improvement beyond the activity of individual components.
These arguments have been carefully considered, but are not found persuasive.
Applicants arguments regarding the transmucosal form have been addressed above and incorporated herein. Regarding the synergy, as noted above, the specification is devoid of any examples showing the improvements of the combination compared to the individual components. Lastly, it is noted that the “achieve synergy in the treatment of ALS” language appears to be an intended use limitation. If the limitation does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration. For example, a step of "prescribing a topical steroid to a patient with eczema" is not a positive limitation because it does not require that the steroid actually be used by or on the patient, and a recitation that a claimed product is a "pharmaceutical composition" or that a "feed dispenser is operable to dispense a mineral supplement" are not affirmative limitations because they are merely indicating how the claimed invention might be used. See MPEP 2106.04(d)(2)
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-3, 5, 11-14, 17 and 19-20 remain and new claim 21 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Riva et al. (Lancet Neurol 2019; 18: 155-164, IDS) as evidenced by Package leaflet: Information for the patient Sativex ® Oromucosal Spray (2025).
Riva teaches the safety and efficacy of nabiximols on spasticity symptoms in patients with motor neuron disease (CANALS) (Tittle). With regards to the patients, the reference teaches that eligible patients include, but are not limited to, that that had patients that have amyotrophic lateral sclerosis (abstract). With regards to the nabiximols, the reference teaches that nabiximols is an oral mucosal spray containing 2.7 mg of THC and 2.5mg cannabidiol in a 50:50: solution of ethanol and propylene glycol (page 157, 2nd column, Procedure). Moreover, the reference also teaches that nabiximols is also referred to as Sativex (see citation 29). Thus, while the prior art does not specifically teach nabiximols further includes a flavoring agent, as evidenced by the Package leaflet, Sativex contains other ingredients such as peppermint oil (page 8). As such, the claimed limitation appears to be met by the prior art reference. Regarding new claim 21, new claim 21, depends from the composition of claim 1, and recites “…wherein the synergistic effect is determined accordingly to the Colby method”. In the instant case, claim 1 is a composition claim and it is unclear how claim 21 further limits claim 1 since it is attempting to put a determining step within a composition claim.
In response to this rejection, Applicants contend that the rejection fails to account for a required limitation of claim 1: “wherein the two active agents have a synergistic effect on the treatment of ALS or a related condition and/or symptom”. In particular, Applicants assert that the Riva article reports a combination of THC and CBD administered oromucosally to ALS/MND patents and compares the combination vs. placebo, but does not disclose that the combination is synergistic relative to the components individually, nor does it provide any synergy analysis. Thus, Applicants contend that the office has not shown that synergy in ALS is inevitable for the cited combination under the condition of administration.
These arguments have been carefully considered, but are not found persuasive.
In the instant case, the Examiner acknowledged and does not dispute Applicants contention that Riva does not specifically teach synergy. However, the examiner recognizes that both the claims and prior art teach a composition suitable for transmucosal administration, the same two active agents, CBD and THC, and the same patient population. While the claims do recite that the two active agents have a synergistic effect on the treatment of ALS or a related condition and/or symptom, the claims imply that the synergy is associated with the two active agents and do not require a specific synergistic amount of the two active agents. Applicants are reminded that
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01
Moreover, a review of the specification as originally filed discusses “synergy” at various portions within the specification including the Examples. For example, paragraph 0099 teaches that “synergistic” and/or “synergistic effect” are used in the present invention to mean a biological effect created from the application of two or more agents to produce a biological effect that is greater than the sum of the biological effects produced by the application of the individual agents. Moreover, paragraph 00101 discusses “synergistic ingredients”, as well as paragraph 00102. It is important to note here that the specification refers to these as synergistic ingredients vs. a synergistic amount. Moreover, Example 1 is entitled Demonstration of Synergy and involves experiments done to demonstrate synergy of the components of the composition, wherein each putative synergistic agent is administered to cells in an in vitro model and/or to animals in an animal model of the disease process, and the quantitative response is recorded … Synergistic combinations in terms of ratios of the two components and in terms of dose response are further optimized in subsequent tests based upon the first series of test. However, while the specification discusses recording these responses, no data is provided. Example 2 provides a specific formulation with specific amounts. However, there is no mention of whether this formulation is specifically synergistic. Example 4 discusses a transmucosal formulation including THC and CBD that was found to have synergistic effects, wherein the formulation was found to provide antioxidant neuroprotection and to allay disease progression. However, it is unclear what the formulation actually contains, the amounts of the two agents or whether the assertion of the synergistic effects are generic or directly related to the antioxidant neuroprotection and to allay disease progression. Moreover, similar to Applicants arguments regarding Riva, Example 4 of the instant specification does not disclose that the combination is synergistic relative to the components individually, nor does it provide any synergy analysis. Note: It is not readily apparent that the formulation of Example 2 is the same as the formulation of Example 4.
Claim(s) 1-3, 5-8 and 11-20 remain and new claim 21 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Eyal, Aharon (US 2018/0169035 A1, 2018-06-21, IDS) referred to herein as Eyal.
Eyal teach a cannabinoid composition comprising (i) at least one cannabinoid, (ii) a primary terpen and (iii) a carrier (paragraph 0004). For example, the PG PUB teaches that the compositions comprises CBD and/or THC and/or THCa and said primary terpene is selected from the group consisting of beta-caryophyllene, caryophyllene oxide, beta-myrcene, terpineol, linalool, humulene, eucalyptol, and limonene, resulting in a terpene-enriched cannabinoid composition with enhanced therapeutic effect for treating Amyotrophic lateral sclerosis (ALS) (paragraph 0028). With regards to the increased therapeutic effect, the PG Pub teaches that said therapeutic effect is generated while administering said composition sublingually (paragraph 0079). Moreover, the PG Pub teaches that the composition further comprises a sweetener (0071) and is in the form of cannabis tablets, gel capsules, patches, vaporizer liquids, candies, drinks and baked product (0072). Specifically, the PG Pub teaches a number of formulations such as THC plus CBD and beta caryophyllene or CBD and linalool (paragraph 0118).
In response to this rejection, Applicants contend that Eyal is similar to Riva in that Eyal does not disclose synergy in ALS. Moreover, Applicants contend that Eyal’s “enhanced therapeutic effect” is expressly defined by comparison to a composition “comprising the same cannabinoids amounts and one half the amount of the primary terpene” which is not a demonstration of synergy (i.e. more than additive efficacy relative to the individual active agents) in ALS and contains no monotherapy arms and no synergy analysis.
These arguments have been carefully considered, but are not found persuasive.
Similar to the response to Riva, the Examiner acknowledged and does not dispute Applicants contention that Riva does not specifically teach synergy. However, the examiner recognizes that both the claims and prior art teach a composition suitable for transmucosal administration, the same active agents, CBD, THC and beta caryophyllene or CBD and linalool, and the same patient population. While the claims do recite that the two active agents have a synergistic effect on the treatment of ALS or a related condition and/or symptom, the claims imply that the synergy is associated with the two active agents and do not require a specific synergistic amount of the two active agents. Applicants are reminded that
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01
Moreover, a review of the specification as originally filed discusses “synergy” at various portions within the specification including the Examples. For example, paragraph 0099 teaches that “synergistic” and/or “synergistic effect” are used in the present invention to mean a biological effect created from the application of two or more agents to produce a biological effect that is greater than the sum of the biological effects produced by the application of the individual agents. Moreover, paragraph 00101 discusses “synergistic ingredients”, as well as paragraph 00102. It is important to note here that the specification refers to these as synergistic ingredients vs. a synergistic amount. Moreover, Example 1 is entitled Demonstration of Synergy and involves experiments done to demonstrate synergy of the components of the composition, wherein each putative synergistic agent is administered to cells in an in vitro model and/or to animals in an animal model of the disease process, and the quantitative response is recorded … Synergistic combinations in terms of ratios of the two components and in terms of dose response are further optimized in subsequent tests based upon the first series of test. However, while the specification discusses recording these responses, no data is provided. Example 2 provides a specific formulation with specific amounts. However, there is no mention of whether this formulation is specifically synergistic. Example 4 discusses a transmucosal formulation including THC and CBD that was found to have synergistic effects, wherein the formulation was found to provide antioxidant neuroprotection and to allay disease progression. Example 5 discusses a transmucosal formation including THC and beta-caryophyllene that was found to have synergistic effects, wherein the formulation was found to provide analgesia. Example 6 discusses a transmucosal formation including CBD and beta-caryophyllene that was found to have synergistic effects, wherein the formulation was found to provide anti-inflammatory effect. Example 7 discusses a transmucosal formation including CBD and linalool that was found to have synergistic effects, wherein the formulation was found to provide anti-anxiety effects. However, it is unclear what the formulations of Examples 4-7 actually contain, the amounts of the two agents or whether the assertion of the synergistic effects are generic or directly related to the “effects”. Moreover, similar to Applicants arguments regarding Riva, Example 4-7 of the instant specification do not disclose that the combination is synergistic relative to the components individually, nor does it provide any synergy analysis. Note: It is not readily apparent that the formulation of Example 2 is the same as the formulation of Examples 4-7.
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:
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.
Claim(s) 9 remain rejected under 35 U.S.C. 103 as being unpatentable over Eyal, Aharon (US 2018/0169035 A1, 2018-06-21, IDS) referred to herein as Eyal, as applied to claims 1-3, 5-8 and 11-21 above, in view of Russo et al. (British Journal of Pharmacology (2011) 163, 1344-1364, IDS).
The teachings of Eyal above are incorporated herein. In short, Eyal teach a cannabinoid composition comprising (i) at least one cannabinoid, (ii) a primary terpen and (iii) a carrier (paragraph 0004). Moreover, Eyal teach specific formulations such as THC and pinene (Paragraph 0118).
Eyal does not specifically teach that pinene is in the alpha form.
Russo et al. reviews the cannabis terpenoids (Page 1349, 1st column, Cannabis terpenoids: neglected encourage compounds?). Specifically, Russo et al. teach that alpha pinene has anti-inflammatory activity, is a bronchodilator and acetylcholinesterase inhibitor which aids in memory and is synergistic with CBD and THC (page 1351, Table 2).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select alpha pinene as the pinene in the formulation taught by Eyal in view of the teachings of Russo et al.. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Russo et al. teach that alpha pinene has anti-inflammatory activity, is a bronchodilator and acetylcholinesterase inhibitor which aids in memory and is synergistic with CBD, THC.
In response to this rejection, Applicants contend that Russo does not overcome the deficiencies of Eyal and should be withdrawn.
These arguments are not found persuasive for the reasons of set forth above relating to Eyal. As such, the rejection is maintained.
Claim(s) 10 remain rejected under 35 U.S.C. 103 as being unpatentable over Eyal, Aharon (US 2018/0169035 A1, 2018-06-21, IDS) referred to herein as Eyal, as applied to claims 1-8 and 11-21 above, in view of Pellati et al. (Molecules 2018, 23, 2639, 1-21).
The teachings of Eyal above are incorporated herein. In short, Eyal teach a cannabinoid composition comprising (i) at least one cannabinoid, (ii) a primary terpen and (iii) a carrier , wherein the composition is useful for treating a variety of disorders (see for example page 13, starting at claim 8).
Eyal does not specifically teach that the composition further comprises cannflavin A.
Pellati et al. teach that the main phytochemicals that are found in Cannabis sativa L are represented by cannabinoids, flavones and terpenes, wherein some biological activities of cannabinoids are known to be enhanced by the presence of terpenes and flavonoids in the extracts, due to synergistic action (Abstract). With regards to the flavonoids, Pellati et al. teach that cannflavin A was observed to be the main flavonoid in almost all the samples (abstract). With regards to cannflavin A, the reference teaches that cannflavin A is known to possess anti-inflammatory action and microsomal prostaglandin E2 synthase and 5-lipoxygenase have been identified as their molecular targets (page 2, last full paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to add cannflavin A to the formulation taught by Eyal in view of the teachings of Pellati et al.. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
- Pellati et al. teach some biological activities of cannabinoids are known to be enhanced by the presence of terpenes and flavonoids in the extracts, due to synergistic action,
- cannflavin A was observed to be the main flavonoid in almost all the samples and,
- cannflavin A is known to possess anti-inflammatory action.
In response to this rejection, Applicants contend that Pellati does not overcome the deficiencies of Eyal and should be withdrawn.
These arguments are not found persuasive for the reasons of set forth above relating to Eyal. As such, the rejection is maintained.
Claim(s) 1-9 and 11-18 remain and new claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over the Farokhi et al. (US2020/0398184 A1, 2020-12-24, priority to 2018-08-08) in view of Russo, Ethan (Frontiers in Plant Science, (2019), 9, Article 1969, 1-8) referred to herein as Russo 2.
Farokhi et al. teach a composition comprising a cannabis extract and a pharmaceutically acceptable carrier, diluent or excipient, wherein the composition is formulated for oral administration and/or transmucosal administration (Claims 23 and 24 of the PG Pub). With regards to the oral administration, Farokhi et al. teach that the compositions is a liquid, gel, tablet, gum, lozenge or a drop (Claim 25 of the PG Pub). With regards to transmucosal administration, Farakhi et al. teach that transmucosal administration encompasses oral formulations for buccal administration or aerosol sprays for nasal administration (paragraph 0148). With regards to the cannabis extract, Farakhi et al. teach that the extract is derived from Cannabis plant material including, but not limited to, Cannabis sativa or a hybrid thereof and includes at least one bioactive molecule comprising a cannabinoid, a flavonoid or a terpene (claim s 16 and 18 of the PG PUB). the administration comprises buccal administration or intra-nasal administration (claim 27 of the PG Pub). The PG Pub further teaches a number of cannabinoids such as THC, CBD, CBG, THCA, CBDA, as well as, a number of terpenes such as beta caryophyllene, alpha-pinene, D-limonene and linalool (beginning at paragraph 0048 to 0056). With regards to the terpenes, the PG Pub teaches that it is thought that interplay between the effects of cannabinoids and other compounds derived from Cannabis such as terpenes and/or flavonoids can enhance the efficacy of Cannabis extractions for the treatment of a variety of disorders or disease (0055). For example, Farakhi et al. teach that it is thought that the terpene myrcene can enhance penetration across the blood brain barrier, pinene can counteract memory or cognition problems, while the combination of pinene, myrcene and caryophyllene can help treat anxiety (0055). Lastly, Farakhi et al. teach that a person of ordinary skill will be able to select a Cannabis strain producing the desired terpenes for use with this extraction method (paragraph 0056).
Farakhi et al. does not specifically teach an extract comprising at least THC, CBD, CBG, THCA, CBDA, beta-caryophyllene, alpha-pinene, D-limonene, and linalool.
Russo 2 teaches that in 1998, Professors Raphael Mechoulam and Shimon Ben-Shabat posited that the endocannabinoid system demonstrated an “entourage effect” in which a variety of “inactive” metabolites and closely related molecules markedly increased the activity of the primary endogenous cannabinoids, anandamide and 2-arachidonoylglycerol, wherein this helped explain how botanical drugs were often more efficacious than their isolated components (page 4, 1st column, last full paragraph). Moreover, Russo 2 teach that recent data supports the possibility that cannabis preparation or single molecule may be too pure leading to reduced synergistic potential. For example, Russo teach that clinicians utilizing high -CBD Cannabis extracts to treat severe epilepsy demonstrated notable improvement in seizure frequency with doses far lower than those reported in formal clinical trials with Epidiolex, a 97% pure CBD preparation (Page 4, 2nd column last paragraph). In view of this, Russo 2 teach that such observations support the hypothesis of greater efficacy for Cannabis extracts, combining multiple anticonvulsant components, such as CBD, THC, THCA, THCV, CBDV, linalool and even caryophyllene (page 6, 1st column, 1st paragraph). Lastly, Russo 2 teaches an example of selective breading is illustrated in the form of a Cannabis chemovar named Caryodiol for its enhanced caryophyllene content and highly favorable THC:CBD ratio which portends to be applicable to treatment of numerous clinical conditions including pain, inflammation, fibrotic disorders, addiction, anxiety, depression, autoimmune diseases, dermatological conditions and cancer (page 6, 1st column, 1st full paraph). It is important to note that Caryodiol comprises THC, CBD, CBG, THCA, CBDA, beta-caryophyllene, alpha-pinene, D-limonene and linalool (page 5, figure 2)
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to utilize an extract of the Cannabis strain referred to as Caryodiol in the composition taught by Farakhi et al. in view of the teachings of Russo 2. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
- Russo 2 teaches that a Cannabis chemovar named Caryodiol has enhanced caryophyllene content and highly favorable THC:CBD ratio which portends to be applicable to treatment of numerous clinical conditions including pain, inflammation, fibrotic disorders, addiction, anxiety, depression, autoimmune diseases, dermatological conditions and cancer.
In response to this rejection, Applicants contend that Farokhi is an extraction/processing disclosure explaining low-temperature solvent extraction and downstream purification, but does not disclose synergy in ALS, nor any comparative data showing more than additive efficacy of a pair of Cannabis actives for ALS. Moreover, Applicants contend that Farokki actually teaches away from the claimed muti-component, synergy-oriented composition, wherein Farokhi’s thrust is to maximize cannabinoid purity and minimizes co-constituents such as waxes, chlorophyll and practically, terpenes are also reduced by such process. Regarding Russo 2, Applicants assert that Russo 2 does not bridge the gap in that it is a review article arguing for a general “entourage effect” and cites anecdotal/heterogenous data largely in epilepsy and other conditions. It does not provide an enabling teaching of synergy in ALS, nor a reasoned expectation of success that any particular pair of actives will behave synergistically in ALS when delivered transmucosally.
These arguments have been carefully considered, but are not found persuasive.
In response to Applicants arguments regarding Farokhi, the Examiner acknowledges and does not dispute Applicants contention that Farokhi explains a low-temperature solvent extraction and downstream purification process. However, the Examiner does not agree that practically terpenes are also reduced by such processing. For example, Farakhi teaches that the extraction process of the invention maximizes extraction efficiency and minimizes contaminants and impurities such as waxes and chlorophyl (paragraph 044), but there is no mention of removal of the terpenes. In contrast, Farakhi appears to recognize the importance of the terpenes which enhance the Cannabis extracts for the treatment of a variety of disorders or disease (0055). Regarding Applicants arguments about Russo 2, the examiner recognizes that Applicants arguments appear to pertain to ALS and ALS alone. In the instant case, the claims do not appear to be limited solely to ALS but encompass a related condition and/or symptoms of ALS or related condition are ameliorated. Thus, Russo 2 teaches an example of selective breading is illustrated in the form of a Cannabis chemovar named Caryodiol for its enhanced caryophyllene content and highly favorable THC:CBD ratio which portends to be applicable to treatment of numerous clinical conditions including pain, inflammation, fibrotic disorders, addiction, anxiety, depression, autoimmune diseases, dermatological conditions and cancer which appears to encompass a related condition and/or symptoms of ALS or related condition.
Claim(s) 10 remain rejected under 35 U.S.C. 103 as being unpatentable over the combination of Farokhi et al. (US2020/0398184 A1, 2020-12-24, priority to 2018-08-08) in view of Russo, Ethan (Frontiers in Plant Science, (2019), 9, Article 1969, 1-8) referred to herein as Russo 2, as applied to claims 1-9, 11-18 and 21, in view of Pellati et al. (Molecules 2018, 23, 2639, 1-21).
The combination of Farokhi et al. and Russo 2 has been described above and incorporated herein. In short, the combination teach a composition comprising a Cannabis extract, wherein the Cannabis extract comprises THC, CBD, CBG, THCA, CBDA, beta-caryophyllene, alpha-pinene, D-limonene and linalool. Moreover, Russo 2 teaches that the extract would be useful for treatment of numerous clinical conditions including pain, inflammation, fibrotic disorders, addiction, anxiety, depression, autoimmune diseases, dermatological conditions and cancer.
The combination of Farokhi et al. and Russo 2 does not specifically teach that the composition further comprises cannflavin A.
Pellati et al. teach that the main phytochemicals that are found in Cannabis sativa L are represented by cannabinoids, flavones and terpenes, wherein some biological activities of cannabinoids are known to be enhanced by the presence of terpenes and flavonoids in the extracts, due to synergistic action (Abstract). With regards to the flavonoids, Pellati et al. teach that cannflavin A was observed to be the main flavonoid in almost all the samples (abstract). With regards to cannflavin A, the reference teaches that cannflavin A is known to possess anti-inflammatory action and microsomal prostaglandin E2 synthase and 5-lipoxygenase have been identified as their molecular targets (page 2, last full paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to add cannflavin A to the composition taught by the combination of Farokhi et al. and Russo 2 in view of the teachings of Pellati et al.. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
- Pellati et al. teach some biological activities of cannabinoids are known to be enhanced by the presence of terpenes and flavonoids in the extracts, due to synergistic action,
- cannflavin A was observed to be the main flavonoid in almost all the samples and,
- cannflavin A is known to possess anti-inflammatory action.
In response to this rejection, Applicants contend that Pellati does not overcome the deficiencies of Farokhi and Russo 2 should be withdrawn.
These arguments are not found persuasive for the reasons of set forth above relating to Farokhi and Russo 2. As such, the rejection is maintained.
Claim(s) 19-20 remain rejected under 35 U.S.C. 103 as being unpatentable over the combination of Farokhi et al. (US2020/0398184 A1, 2020-12-24, priority to 2018-08-08) in view of Russo, Ethan (Frontiers in Plant Science, (2019), 9, Article 1969, 1-8) referred to herein as Russo 2, as applied to claims 1-9, 11-18 and 21, in view by Riva et al. (Lancet Neurol 2019; 18: 155-164, IDS).
The combination of Farokhi et al. and Russo 2 has been described above and incorporated herein. In short, the combination teach a composition comprising a Cannabis extract, wherein the Cannabis extract comprises THC, CBD, CBG, THCA, CBDA, beta-caryophyllene, alpha-pinene, D-limonene and linalool. Moreover, Russo 2 teaches that the extract would be useful for treatment of numerous clinical conditions including pain, inflammation, fibrotic disorders, addiction, anxiety, depression, autoimmune diseases, dermatological conditions and cancer. Russo 2 further teach that recent data supports the possibility that cannabis preparation or single molecule may be too pure leading to reduced synergistic potential. For example, Russo teach that clinicians utilizing high -CBD Cannabis extracts to treat severe epilepsy demonstrated notable improvement in seizure frequency with doses far lower than those reported in formal clinical trials with Epidiolex, a 97% pure CBD preparation (Page 4, 2nd column last paragraph). In view of this, Russo 2 teach that such observations support the hypothesis of greater efficacy for Cannabis extracts, combining multiple anticonvulsant components, such as CBD, THC, THCA, THCV, CBDV, linalool and even caryophyllene (page 6, 1st column, 1st paragraph).
The combination of Farokhi et al. and Russo 2 does not specifically teach a method of treating ALS comprising administering a formulation comprising the extract.
Riva teaches the safety and efficacy of nabiximols on spasticity symptoms in patients with motor neuron disease (CANALS) (Tittle). With regards to the patients, the reference teaches that eligible patients include, but are not limited to, that that had patients that have amyotrophic lateral sclerosis (abstract). With regards to the nabiximols, the reference teaches that nabiximols is an oral mucosal spray containing 2.7 mg of THC and 2.5mg cannabidiol in a 50:50: solution of ethanol and propylene glycol (page 157, 2nd column, Procedure).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to treat ALS using the composition comprising the Cannabis extract taught by the combination of Farokhi et al. and Russo 2 in view of the teachings of Riva. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
- Riva teach that the combination of THC and CBD are useful for treating spasticity in ALS patients and,
-Russo 2 teaches that Cannabis extracts offer benefits above Cannabis preparations.
In response to this rejection, Applicants contend that Riva does not overcome the deficiencies of Farokhi and Russo 2 should be withdrawn.
These arguments are not found persuasive for the reasons of set forth above relating to Farokhi and Russo 2. As such, the rejection is maintained.
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 1-3, 7, 11-16 remain and new claim 21 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 11 and 12 of U.S. Patent No. 11,154,515 B2 to Biro and Russo (2021-10-26) in view of Russo and Guy (Medical Hypotheses (2006) 66, 324-246).
US Patent No 11,154,515 B2 claims a pharmaceutical composition comprising CBD and €-beta caryophyllene, wherein the composition is a transdermal patch or an oral mucosal absorption spray.
The US Patent does not specifically claim that the pharmaceutical composition comprises a carrier.
Russo and Guy teach that Sativex is a highly standardized medicinal product comprising of THC and CBD (page 239, , 1st column, last paragraph). Specifically, Russo and Guy teach that Sativex is formulated into a spray for oromucosal administration and further comprises ethanol:propylene glycol (page 239, 2nd column, bridging paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to add a carrier such as ethanol:propylene glycol to the composition claimed by the US Patent in view of the teachings of Russo and Guy. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Russo and Guy teach a similar formulation for oromucosal spray administration which comprises ethanol and propylene glycol in addition to the THC and CBD.
Applicant request that these rejections be held in abeyance until allowable subject matter is found. As such, the rection is maintained.
Claims 1-3 and 11 remain and new claim 21 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3 of copending Application No. 18/000,586 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application and the reference application overlap in scope. For example, the reference application claims a formulation comprising a combination of at least two active substances extracted from Cannabis and a carrier oil. The reference application further claims that the active substance is a cannabinoid, a terpene or a flavonoid, wherein the active substances include, but are not limited to, CBDA, THCA, linalool, limonene, pinene. It is noted that the references differ in the intended use or “activity” of the combination. However, the two compositions overlap in scope and as such would be capable to performing each of these functions.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant request that these rejections be held in abeyance until allowable subject matter is found. As such, the rection is maintained.
New Rejections Necessitated by the Amendment
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:
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.
Claim(s) 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Eyal, Aharon (US 2018/0169035 A1, 2018-06-21, IDS) referred to herein as Eyal, as applied to claims 1-3, 5-8 and 11-21 above.
Eyal teach a cannabinoid composition comprising (i) at least one cannabinoid, (ii) a primary terpen and (iii) a carrier (paragraph 0004). For example, the PG PUB teaches that the compositions comprises CBD and/or THC and/or THCa and said primary terpene is selected from the group consisting of beta-caryophyllene, caryophyllene oxide, beta-myrcene, terpineol, linalool, humulene, eucalyptol, and limonene, resulting in a terpene-enriched cannabinoid composition with enhanced therapeutic effect for treating Amyotrophic lateral sclerosis (ALS) (paragraph 0028). With regards to the increased therapeutic effect, the PG Pub teaches that said therapeutic effect is generated while administering said composition sublingually (paragraph 0079). Moreover, the PG Pub teaches that the composition further comprises a sweetener (0071) and is in the form of cannabis tablets, gel capsules, patches, vaporizer liquids, candies, drinks and baked product (0072). Specifically, the PG Pub teaches a number of formulations such as THC plus CBD and beta caryophyllene or CBD and linalool, wherein the % by weight of THC plus CBD and beta caryophyllene is 5-25% (THC) plus 5-25% (CBD and 1-10%( beta caryophyllene) (paragraph 0118).
The prior art does not specifically teach that the weight ratio of CBD:beta-caryophyllene is selected from 3:1, 2:1, 1:2 and 1:3.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to optimize the weight ratio of CBD:beta-caryophyllene in the formulation taught by Eyal. One of ordinary skill in the art would have been motivated to make such an optimization, with a reasonable expectation of success, because:
-Eyal teaches weight ratios of CBD:beta-caryophyllene which overlap the instantly claimed ratio’s.
"[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05.
Note: A review of the specification, including the examples, does not appear to show any criticality of the instantly claimed range. Applicants can rebut a prima facie case of obviousness by showing the criticality of the range. "The law is replete with cases in which the difference between the claimed invention and the prior art is some range or other variable within the claims. . . . In such a situation, the applicant must show that the particular range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range." In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Conclusion
Therefore, NO claim is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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/BRANDON J FETTEROLF/ Primary Examiner, Art Unit 1626