DETAILED ACTION
This office action is in response to applicant’s filing dated November 13, 2025.
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 .
Status of Claims
Claims 49, 54-57, 60-64, 66, 81, and 83-88 are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed November 11, 2024. Acknowledgement is made of Applicant's amendment of claims 49, 57, 60, 62, and 83; cancelation of claims 1-48, 50-53, 58, 59, 65, 67-80, and 82; and addition of new claim 86-88.
Applicants elected without traverse dronabinol as the elected synthetic cannabinoid species and N-palmitoylethanolamine (PEA) as the N-acylethanolamine species in the reply filed on December 14, 2021. The requirement is still deemed proper. New claims 83-85 are directed to a composition comprising at least one synthetic cannabinoid, THC. Dronabinol is a known alternative name for synthetic THC. Thus, new claims 83-85 are directed to the elected species and thus are presently under examination.
Claims 49, 54-57, 60-64, 66, and 81-88 are presently under examination as they relate to the elected species: dronabinol and palmitoylethanolamine (PEA).
Priority
The present application is a continuation of US Application No. 15/570,118 filed on October 27, 2017, which is a 371 of PCT/IL2016/050414 filed on April 19, 2016, which claims benefit of US Provisional Application No. 62/154,144 filed on April 29, 2015.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application, Provisional Application No. 62/154,144, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre- AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
In a review of the Provisional Application No. 62/154,144, disclosure of a molar ratio between the cannabinoid and the N-acylethanolamine between about 1:10 to about 1:500; 1:25 to about 1:450; about 1:50 to about 1:100; between about 1:10 and about 1:100; or about 1:10 to about 1:500 of claims 49, 54, 55, 81, and 83 was not identified. Moreover, disclosure of the amounts claimed in instant claims 56 and 57 was not identified. Thus, the disclosure of the provisional application does not provide written description support for the limitations of instant claims 49, 54-57, 81, and 83 and the claims dependent therefrom.
The effective filing date of the instant application is April 19, 2016.
Objections and/or Rejections and Response to Arguments
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
Modified Objections and/or Rejections
Modifications Necessitated by Claim 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 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.
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.
Claims 49, 54-57, 60-64, 66, 81, and 83-87 are rejected under 35 U.S.C. 103 as being unpatentable over Eaton et al (WO 2014/057067 A1, cited in a previous Office Action); Unimed Pharmaceuticals (MARINOL®, NDA 18-651/S-025 and S-026; July 2006); and Impellizzeri et al (Journal of Neuroinflammation 2014, 11:136, pp. 1-9).
Regarding claims 49 and 83, Eaton teaches a pharmaceutical composition comprising one or more endocannabinoids, cannabinoids and/or modified versions thereof complexed with one or more lipoproteins, wherein said endocannabinoids include N-acylethanolamides and cannabinoids include tetrahydrocannabinols (claim 1). Eaton teaches N-acylethanolamides (16:0) is a preferred N-acylethanolamide (page 5, lines 27-28). N-acylethanolamides (16:0) is also known as N-palmitoylethanolamide. Eaton teaches tetrahydrocannabinol have the structure:
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R is preferably C5-alkyl and the first ring is in Δ9 position (page 9, lines 1-10). This reads on dronabinol.
Eaton teaches the term “complexed” in the context of lipoproteins and endocannabinoids means that the endocannabinoids become incorporated into the outer polar lipid monolayer of the lipoprotein; this is accomplished by adding a solution of one or more endocannabinoids described herein to an aqueous solution containing lipoproteins; the endocannabinoid(s) partition into the outer polar lipid monolayer of the lipoprotein because they have similar hydrophobicities (page 10, lines 30-34). Moreover, Eaton teaches endocannabinoids, cannabinoids and/or modified versions thereof recited herein above are complexed with one or more lipoproteins, said complex dictates the form of the pharmaceutical composition and the mode of administration, preferably, said complex is in liquid form such as a solution (page 3, lines 14-19). Thus, the lipoprotein and endocannabinoids complex taught by Eaton reads on a liquid pharmaceutically acceptable excipient. Therefore, Eaton teaches a composition consisting of the endocannabinoids (N-palmitoylethanolamide and dronabinol) and an aqueous pharmaceutically acceptable excipient, wherein the excipients are a lipoprotein complex in an aqueous solution.
Regarding the limitation wherein the at least one synthetic cannabinoid is emulsified or suspended in the aqueous liquid pharmaceutically acceptable carrier, Eaton teaches the term “complexed” in the context of lipoproteins and endocannabinoids means that the endocannabinoids become incorporated into the outer polar lipid monolayer of the lipoprotein; this is accomplished by adding a solution of one or more endocannabinoids described herein to an aqueous solution containing lipoproteins; the endocannabinoid(s) partition into the outer polar lipid monolayer of the lipoprotein because they have similar hydrophobicities (page 10, lines 30-34). Eaton teaches the term “lipoprotein” is used herein according to its well-known meaning in the art; briefly, a lipoprotein is a biochemical assembly of proteins and lipids bound to the proteins; they are generally organized as a polar lipid monolayer surrounding a neutral lipid core assembled onto an apolipoprotein scaffold (page 10, lines 6-9). Eaton teaches suitable pharmaceutical carriers are well known in the art and include phosphate buffered saline solutions, water, emulsions, such as oil/water emulsions (page 3, lines 21-23). Moreover, it is well known in the art that lipoproteins are utilized as excipients in pharmaceutical formulations as emulsifiers as evidenced by van Hoogevest (Eur J Lipid Sci Technol, 2014; 116:1088-1107). Van Hoogevest teaches phospholipids are pharmaceutical excipients (title); and phospholipids are surface‐active, amphiphilic molecules, which comprise a polar head group and a lipophilic tail; because of this amphiphilic character they are used as emulsifier (page 1089, left, 2nd paragraph). Thus, the complexed endocannabinoids in an aqueous solution reads on wherein the at least one synthetic cannabinoid is emulsified in the aqueous liquid pharmaceutically acceptable carrier.
Eaton does not explicitly teach wherein the at least one cannabinoid and at least one N-acylethanolamine is in the molar ratios of instant claims 49, 54, 55, 81 and 83 or that the at least one cannabinoid and at least one N-acylethanolamine are in the claimed amounts of instant claims 56, 57, and 60-62.
However, Eaton does teach the pharmaceutical composition should be in the range of 1 µg to 5 g units per day, a more preferred dosage might be in the range of 0.01 mg to 100 mg, even more preferably 0.01 mg to 50 mg and most preferably 0.01 mg to 10 mg per day (page 3, lines 37-40) and that the compositions are useful in the treatment of tumor (page 25, lines 14-15).
Moreover, Unimed Pharmaceuticals teaches dronabinol is commercially available in capsules in doses of 2.5 mg, 5 mg, and 10 mg (page 3, 4th paragraph).
Impellizzeri teaches PeaVera is a commercially available palmitoylethanolamide product comprising 400 mg of palmitoylethanolamide (Table 3) and PeaVera are capsules (page 3, left, last paragraph).
It would have been prima facie obvious to one of ordinary skill in the art to utilize the amounts taught by Eaton, Unimed Pharmaceuticals, and Impellizzeri as a starting point for optimizing the amounts of palmitoylethanolamide and dronabinol to formulate the combination for use in treating a tumor. Similarly, with regard to instant claims 49, 54, 55, 81, 83, 86, and 87, it would have been prima facie obvious to one of ordinary skill in the art to utilize amounts of palmitoylethanolamide and dronabinol known to be safe and effective for use in humans (2.5 mg - 10 mg dronabinol and 400 mg palmitoylethanolamide as a starting point for optimizing the ratio of palmitoylethanolamide and dronabinol within the amounts taught to formulate a composition for use in treating a tumor. Given that the molecular weight of dronabinol is 314.46 g/mol, as evidenced SciFinder (CAS Registry #1972-08-3, cited in a previous Office Action), and the molecular weight of palmitoylethanolamide is 299.49 g/mol, as evidenced SciFinder (CAS Registry #544-31-0, cited in a previous Office Action), a composition comprising a 10 mg of dronabinol and 400 mg of palmitoylethanolamide would give a composition that wherein the molar ratio is about 1:42, which falls within the ranges of claims. Moreover, dosage and ratio are result-effective variables, i.e., a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages and ratios would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Regarding claims 63 and 64, Eaton teaches routes of administration include oral (page 4, lines 4-6).
Regarding claim 66, the wherein limitations of these claims, are considered to simply express the intended result of a process step positively recited, which is not given patentable weight (See MPEP 2111.04: [T]he court noted (quoting Minton v. Nat'lAss'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQgd 1614, 1690 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.'" Hoffer v. Microsoft Corp., 405 F.3d 1396, 1399, 74 USPQgd 1481, 1483 (Fed. Cir. 2005).).
Regarding claim 83, Eaton teaches the composition may be in solid form (page 12, line 19).
Taken together, all this would result in the composition of claims 49, 54-57, 60-64, 66, 81, 83, 86, and 87 with a reasonable expectation of success.
Regarding claims 84 and 85, Eaton teaches the routes of administration include oral but does not explicitly teach the composition is a soft, sealed capsule made of gelatin.
However, Unimed Pharmaceuticals teaches dronabinol is commercially available in soft gelatin capsules (page 13, 4th paragraph).
Impellizzeri teaches PeaVera is a commercially available palmitoylethanolamide product comprising 400 mg of palmitoylethanolamide (Table 3) and PeaVera are capsules (page 3, left, last paragraph).
It would have been prima facie obvious to one of ordinary skill in the art to formulate the composition comprising dronabinol, palmitoylethanolamide, and an aqueous solution in a soft capsule made of gelatin with a reasonable expectation of success since the prior art teaches gel capsules are a suitable formulations for both dronabinol and palmitoylethanolamide.
Taken together, all this would result in the composition of claims 84 and 85 with a reasonable expectation of success.
Regarding claim 88, Eaton does not explicitly teach dronabinol is formulated in oil. However, Eaton teaches the pharmaceutical composition of the present invention may, optionally and additionally, comprise a pharmaceutically acceptable carrier; examples of suitable pharmaceutical carriers are well known in the art and include phosphate buffered saline solutions, water, emulsions, such as oil/water emulsions (page 3, lines 20-23).
Moreover, Unimed Pharmaceuticals teaches the capsules contain cannabinoid and sesame oil. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the composition of Eaton to formulate the dronabinol in sesame oil with a reasonable expectation of success, since the prior art teaches sesame oil is a suitable excipient for formulating compositions comprising dronabinol.
Taken together, all this would result in the practice of the method of claim 88 with a reasonable expectation of success.
Response to Arguments
35 U.S.C. § 103 in view of Eaton
Applicant argues:
The Office alleges that Eaton purportedly teaches a formulation comprising "one or more endocannabinoids, cannabinoids, and/or modified versions thereof complexed with one or more lipoproteins." Contrary to the Examiner's contention that Eaton provides formulations without a lipoprotein complex, Eaton in fact requires a lipoprotein-PEA complex when PEA is used. Unimed and Impellizzeri are each silent on combining synthetic THC and PEA, let alone dissolved in an aqueous carrier as in amended claim 49. Thus, a skilled artisan reading the cited art would not have any reason to disregard Eaton's teaching of a lipoprotein-PEA complex and instead dissolve PEA directly in an aqueous liquid pharmaceutically acceptable carrier as recited in claim 49. Furthermore, the cited art is silent regarding a composition formulated in a solid dosage form and containing a solid pharmaceutically acceptable carrier as recited in Applicant's amended claim 83. Eaton requires a lipoprotein-PEA complex when PEA is formulated in a pharmaceutical composition and excludes PEA when a lipoprotein is absent. Indeed, Eaton teaches that PEA should not be formulated in a pharmaceutical composition unless a lipoprotein complex is present, which is contrary to the instant claims.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As set forth above, Eaton teaches endocannabinoids, cannabinoids and/or modified versions thereof recited herein above are complexed with one or more lipoproteins, said complex dictates the form of the pharmaceutical composition and the mode of administration, preferably, said complex is in liquid form such as a solution (page 3, lines 14-19). Thus, the lipoprotein and endocannabinoids complex taught by Eaton reads on a liquid pharmaceutically acceptable excipient. Therefore, Eaton teaches a composition consisting of the endocannabinoids (N-palmitoylethanolamide and dronabinol) and a liquid pharmaceutically acceptable excipient, wherein the excipients are a lipoprotein complex in liquid form.
Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). In the instant case, although Eaton teaches an embodiment wherein the composition comprises one or more endocannabinoids and cannabinoids wherein N-palmitoylethanolamide is excluded. The Examiner notes that the cited embodiment would also exclude a modified version (i.e., complexed) of N-palmitoylethanolamide. As set forth above, Eaton teaches use of one or more endocannabinoids comprising N-acylethanolamides and/or modified versions thereof and (b) cannabinoids and/or modified versions thereof (claim 1) and preferably the N-acylethanolamide includes N-acylethanolamide (16:0) (page 5, lines 27-28).
Applicant argues:
Eaton's lipoprotein-PEA complex is not equivalent to dissolving PEA in an aqueous liquid pharmaceutically acceptable carrier.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As set forth above, Eaton teaches endocannabinoids, cannabinoids and/or modified versions thereof recited herein above are complexed with one or more lipoproteins, said complex dictates the form of the pharmaceutical composition and the mode of administration, preferably, said complex is in liquid form such as a solution (page 3, lines 14-19). Thus, one of ordinary skill in the art would readily envisage a composition comprising a non-modified endocannabinoid and a modified-cannabinoid modified with the lipoprotein emulsifier from the teachings of Eaton.
Applicant argues:
Eaton teaches away from a pharmaceutical composition in a solid dosage form.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As set forth above, Eaton teaches the composition may be in solid form (page 12, line 19).
Applicant argues:
Unimed and Impellizzeri cannot be combined with Eaton to arrive at the claimed combination. The cited secondary references do not cure these deficiencies in Eaton. Unimed teaches a pharmaceutical composition containing a single active pharmaceutical ingredient: synthetic THC (dronabinol). Impellizzeri teaches a pharmaceutical composition containing a single active pharmaceutical ingredient: PEA (i.e., noncomplexed PEA). Neither Unimed nor Impellizzeri teach the combination of multiple actives in a single pharmaceutical composition or a single dosage form. Furthermore, neither reference provides information such as a combined formulation or dosage, the process for combining both actives, or evidence regarding the preserved stability, solubility, bioavailability, and efficacy of the actives in a combination treatment.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
Applicant has not independently argued the merits of this rejection. Arguments regarding Eaton have been addressed above. Therefore, the rejection is maintained for the reasons set forth on the record and for those set forth in the response to the arguments above.
Conclusion
Claims 49, 54-57, 60-64, 66, 81 and 83-88 are rejected.
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 RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Rayna Rodriguez/ Primary Examiner, Art Unit 1628
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