NON-FINAL REJECTION
This application is a 35 U.S.C. 371 (national stage) application of PCT/EP2021/069881, filed Jul. 15, 2021, which claims benefit of foreign priority to GB 2011166.2, filed Jul. 20, 2020.
Claims 1-14, as amended, are pending.
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 .
Priority
Acknowledgment is made of applicant's claim to foreign priority under 35 U.S.C. 119(a)-(d).
Information Disclosure Statement
The information disclosure statements (IDS) submitted on Mar. 21, 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Claim Objections
Claim 7 is objected to because of the following informalities: claim 7 refers to the cannabidiol (CBD) preparation of claim 1, "wherein the CBD is present is isolated from" cannabis plant material, which is not grammatically correct.
Appropriate correction is required.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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.
Claims 1-14 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Shimell et al. (Cell Reports 29, 2422–2437 (2019)), in view of Silvestro et al. (Molecules 24, 1459 (2019)), Neubauer et al. (Epilepsy & Behavior 81, 79-85 (2018)) (all cited on the IDS dated 3/21/2024) and Guy et al. (WO 2015/193667, cited on PTO-892).
Shimell et al. disclose that Zdhhc9 knockout mice exhibit seizure-like activity (abstract), and teach that mutations in Zdhhc9 have been linked to rolandic epilepsy, an epileptic syndrome most commonly observed in children (p. 2431, right col.). Shimell et al. propose that abnormal dendritic and synaptic phenotypes resulting from disrupted palmitoylation by Zdhhc9 contribute to the pathogenesis of intellectual disability and epilepsy observed in humans (p. 2433, left col.).
Guy et al. disclose methods of administering cannabidiol (CBD) for the reduction of total convulsive seizure frequency in the treatment of treatment-resistant epilepsy (TRE) (abstract), including childhood epilepsies, which refers to many different syndromes and genetic mutations that can occur to cause epilepsy in childhood, such as benign rolandic epilepsy (para. [0049]).
Silvestro et al. review dozens of clinical trials which evaluated the use of cannabidiol (CBD) to treat severe treatment-resistant epilepsy (abstract). Most of the trials enrolled pediatric patients with genetically-based types of epilepsy which are resistant to common epileptic treatments (p. 5, Sec. 5.1; Table 1). On the basis of these studies, Silvestro et al. conclude that CBD is effective as an adjunctive treatment to common anti-epileptic drugs (AEDs), e.g., levetiracetam, which yields clinically significant reductions in the frequency of convulsive and total seizures in different etiologies of treatment-resistant epilepsy (p. 20).
Further, Neubauer et al. report that CBD was an effective add-on therapy for refractory childhood epilepsies in 66 pediatric patients, mainly by reducing seizure burden (abstract).
Among the patients in the Neubauer et al. study, the etiologies of epilepsies included: a known chromosomal/genetic abnormality in 14 patients, morphological brain abnormality in 10 patients, hypoxic-ischemic brain injury in 6 patients, metabolic/mitochondrial disorder in 5 patients, known epileptic syndrome in 4 patients, postinfectious brain injury in 2 patients, and an undefined etiology for a refractory epilepsy in 25 patients (p. 80, right col.).
Therefore, it would have been predictable to one of ordinary skill in the art as of the filing date to administer cannabidiol (CBD) to treat seizures associated with a ZDHHC9 mutation, as recited by claim 1, with a reasonable expectation of success, because Shimell et al. teach that ZDHHC9 knockout mice exhibit seizure-like activity, and ZDHHC9 mutations are linked to childhood rolandic epilepsy; and Guy et al. teach methods of administering CBD to treat childhood rolandic epilepsy. Further, Silvestro et al. and Neubauer et al. teach that adjunctive administration of cannabidiol to pediatric patients with various forms of genetically-based, treatment-resistant epilepsy (CBD) reduces seizure frequency, regardless of etiology.
As evidenced by, e.g., the instant specification, seizures associated with ZDHHC9 inherently include atonic and tonic-clonic seizures (paras. [0074]-[0075]), as recited by claim 2.
Guy et al. disclose methods of administering cannabidiol (CBD) for the reduction of total convulsive seizure frequency in the treatment of treatment-resistant epilepsy (TRE) (abstract). In particular, Guy et al. exemplify a CBD preparation comprising greater than 95% (w/w) CBD and not more than 0.15% (w/w) tetrahydrocannabinol (THC) (para. [0002]), as recited by claim 3.
Guy et al. further exemplify the preparation of a highly-purified CBD extract comprising greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) other cannabinoids (tetrahydrocannabinol (THC); cannabidiol-C1 (CBD-C1); cannabidivarin (CBDV); and cannabidiol-C4 (CBD-C4)) (paras. [0050]-[0056]; Table 1), as recited by claim 4.
The CBD and at least a portion of at least one of the cannabinoids are isolated from cannabis plant material (paras. [0050]-[0056]), as recited by claims 7-8.
The CBD and/or at least a portion of at least one of the cannabinoids may also be prepared synthetically (paras. [0002], [0043], [0044], [0046]), as recited by claims 9-10.
Silvestro et al. and Guy et al. disclose methods of treating various forms of epilepsy by administering a CBD preparation in combination with one or more anti-epileptic drugs (AED): e.g., levetiracetam, valproic acid, or clobazam (Silvestro et al., Table 1; Guy et al., paras. [0018]-[0019]), as recited by claims 5-6.
Guy et al. disclose that the dose of CBD is greater than 5 mg/kg/day, such as greater than 10/mg/kg/day, greater than 15 mg/kg/day, greater than 20mg/kg/day, and greater than 25 mg/kg/day, which are also envisaged to be effective (para. [0038]), as recited by claims 11-14.
While Guy et al. do not explicitly identify a dose of 50 mg/kg/day, as recited by claim 14, this is clearly contemplated and within the range of greater than 25 mg/kg/day disclosed by Guy et al. As recognized by MPEP § 2144.05,
Generally, differences in concentration or tempera-ture will not support the patentability of subject mat-ter 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 dis-cover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Therefore, it would have been predictable to an ordinarily skilled clinician as of the filing date to modify the cannabidiol (CBD) amounts and dosages disclosed by Guy et al. and Silvestro et al. with a reasonable expectation of success, because optimizing drug dosage based on patient-specific variables is a routine aspect of therapeutic drug monitoring. Further, "the normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382.
Citation of Additional Prior Art
Additional references made of record are considered pertinent to applicant's disclosure:
US Pub. 20190091177 (cited on PTO-892).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 9:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARA ELIZABETH TOWNSLEY/Examiner, Art Unit 1629