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 .
Claim Objections
Claim 6 is objected to because of the following informalities: the word “effect” is a misspelling of what appears to be the word “effective”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 6 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. In the instant case, claim 6 depends from claim 1, and does not further limit its claim scope. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 6, 9, 10 and 13-15 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by US 2019/0091178 A1 to Abu-Izza et al. (“Abu-Izza”).
Regarding claim 1, Abu-Izza teaches a method for the treatment of a subtype of epilepsy ("A method of treating patient with a subtype of epilepsy (e.g., Dravet syndrome, Lennox-Gastaut syndrome, Doose syndrome)”, Abstract, para [0001])) in a subject in need thereof, the method comprising: administering an effective amount of a composition comprising a compound capable of elevating ketone body concentrations in the body of a subject in need thereof (Abstract "by administering to the patient an effective dose of a fenfluramine formulation in combination with a ketogenic diet over a period of time sufficient to reduce or completely eliminate seizures in the patient", para [0072] "An example of a traditional 1500 calorie/day ketogenic diet recommended by the Marriott Corp. Health Care Services, Pediatric Diet Manual, Revised August 1987 as suitable for a 4-6 year old epileptic child contained from 3:1 to 4:1 g of fat for each g of combined carbohydrate and protein. . . In practice this means that at each meal the child must eat the equivalent of 32 g of margarine per day (about 1/4 stick) and drink 92 g of heavy cream (about 100 ml), comprised mainly as medium chain length triglycerides", para [0071] "Either oral or parenteral administration of free fatty acids or triglycerides can increase blood ketones").
Abu-Izza further teaches the subtype of epilepsy can include Infantile Spasms. To that end, Abu-Izza explicitly provides that “seizures in addition to and other than those that are photosensitive or induced, can be suppressed by treatment in accordance with a method of the present invention. Thus, in context of the present invention, the term “seizure” is used to not only encompass photosensitive or induced seizures, but some or all of the other types of seizures experienced by patients with epilepsy.” (para [0048]). It further goes on to provide that: (para [0050] "There are a large number of subtypes of epilepsy that have been characterised. For example, the following list of conditions is set out in Meritt's Neurology (12th Edition)", “Il. Symptomatic epilepsy syndromes (focal or generalised), A. West syndrome (infantile spasms)").
Abu-Izza further specifically underscores the importance of a ketogenic diet for patients with infantile spasms (West syndrome). (para [0070] “According to another aspect of the present invention, the subject may be on, or may be starting on, a ketogenic diet. By “on a ketogenic diet” is meant that the patient consumes nutrition in the form of ketogenic meals, such as ketogenic breakfasts, lunches and dinners. The ketogenic diet, comprised mainly of lipid, has been used for the treatment of epilepsy in children, particularly myoclonic and akinetic seizures (Wilder, R. M. Effect of ketonuria on the course of epilepsy. Mayo Clin. Bull., 1921, 2:307-ff), and has proven effective in cases refractory to usual pharmacological means (Freeman, J. M., E. P. G. Vining. Intractable epilepsy. Epilepsia, 1992, 33:1132-1136). Since the early 1990's, when research studies and clinical trials in children demonstrated efficacy of a ketogenic diet in drug-resistant patients and particular pediatric epilepsy syndromes, worldwide interest in the use of ketogenic diets to manage drug-resistant epilepsy in adults has been increasing. Approximately 19.5 million people with epilepsy have seizures uncontrolled by medications. There is also general agreement that patients with infantile spasms (West syndrome), Lennox-Gaustat syndrome, Dravet syndrome, Angelman syndrome (particularly with the LGIT) and myoclonic-astatic epilepsy benefit from a trial of diet therapy once their epilepsy has become refractory to medication (Nangia et al., 2012, Thibert et al., 2012). Williams, et al., op. cit.).”).
Regarding claim 2, Abu-Izza teaches the method of claim 1, wherein the compound capable of elevating ketone body concentrations is a medium chain triglyceride (MCT) (para(0072] "In practice this means that at each meal the child must eat the equivalent of 32 g of margarine per day (about 1/4 stick) and drink 92 g of heavy cream (about 100 ml), comprised mainly as medium chain length triglycerides", para[0071] "Either oral or parenteral administration of free fatty acids or triglycerides can increase blood ketones").
Regarding claim 3, Abu-Izza teaches the method of claim 2, wherein the composition is an emulsion (para[0084] "Liquid dosage forms are available orally as solutions, suspensions, or emulsions") comprising at least one MCT (para[0072] "In practice this means that at each meal the child must eat the equivalent of 32 g of margarine per day (about 1/4 stick) and drink 92 g of heavy cream (about 100 ml), comprised mainly as medium chain length triglycerides", para[0071] "Either oral or parenteral administration of free fatty acids or triglycerides can increase blood ketones").
Regarding claim 6, Abu-Izza teaches the method of claim 1, wherein the composition is administered in an amount effect to treat Infantile Spasms in a subject in need thereof (Abstract “by administering to the patient an effective dose of a fenfluramine formulation in combination with a ketogenic diet over a period of time sufficient to reduce or completely eliminate seizures in the patient").
Regarding claim 9, Abu-Izza teaches the method of claim 1, wherein the composition is administered orally (para[ 0072] “In practice this means that at each meal the child must eat the equivalent of 32 g of margarine per day (about 1/4 stick) and drink 92 g of heavy cream (about 100 ml), comprised mainly as medium chain length triglycerides”).
Regarding claim 10, Abu-Izza teaches the method of claim 1, wherein the composition is administered orally as a nutritional supplement (para [0072] "In practice this means that at each meal the child must eat the equivalent of 32 g of margarine per day (about 1/4 stick) and drink 92 g of heavy cream (about 100 ml), comprised mainly as medium chain length triglycerides").
Regarding claims 13 and 14, Abu-Izza teaches the method of claim, wherein the composition is administered in multiple doses, or three times daily. (para [0072] "An example of a traditional 1500 calorie/day ketogenic diet recommended by the Marriott Corp. Health Care Services, Pediatric Diet Manual, Revised August 1987 as suitable for a 4-6 year old epileptic child contained from 3:1 to 4:1 g of fat for each g of combined carbohydrate and protein. . . In practice this means that at each meal the child must eat the equivalent of 32 g of margarine per day (about 1/4 stick) and drink 92 g of heavy cream (about 100 ml), comprised mainly as medium chain length triglycerides", para [0071] "Either oral or parenteral administration of free fatty acids or triglycerides can increase blood ketones").
Regarding claim 15, Abu-Izza teaches the method of claim 1, wherein the subject is a human (para [0072] “In practice this means that at each meal the child must eat the equivalent of 32 g of margarine per day (about 1/4 stick) and drink 92 g of heavy cream (about 100 ml), comprised mainly as medium chain length trigiycerides").
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.
Claims 7, 8, 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0091178 A1 to Abu-Izza et al. (“Abu-Izza”), as applied to claims 1-3, 6, 9, 10 and 13-15 in the 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) rejection above.
Abu-Izza is discussed in the 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) rejection above.
Regarding claim 7, Abu-Izza teaches the method of claim 1, but does not teach wherein the composition is administered in an amount effective to reduce spasms of Infantile Spasm in a subject in need thereof by at least 50%, when compared to no treatment. Regarding claim 8, Abu-Izza teaches the method of claim 1, but does not teach wherein the composition is administered in an amount effective to reduce spasms of Infantile Spasm in a subject in need thereof by at least 75%, when compared to no treatment.
However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to quantify the outcome of treatment or prevention efficacy. The skilled artisan would have been motivated to quantify the reduction of Infantite Spasm by routine experimentation in order to elucidate the efficacy of the composition.
Regarding claim 11, Abu-Izza teaches the method of claim 1, but does not teach wherein the composition is administered in an amount ranging from about 0.01 g/kg/day to about 30 g/kg/day of compound in the composition. Regarding claim 12, Abu-Izza teaches the method of claim 1, but does not teach wherein the composition is administered in an amount ranging from about 0.05 g/kg/day to about 20 g/kg/day of compound in the composition. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the dose of compound, which is effective for practicing the claimed method. The skilled artisan would have been be motivated to adjust the dosing amount by routine experimentation because Abu-Izza teaches the amount to a result-effective variable, and further in order to find the most effective method for treatment or prevention, which is also free of side effects and/or toxicity. "When 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).
Claims 4 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0091178 A1 to Abu-Izza et al. (“Abu-Izza”), as applied to claims 1-3, 6, 9, 10 and 13-15 in the 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) rejection above, and further in view of Vandenberghe et al., "Tricaprylin Alone Increases Plasma Ketone Response More Than Coconut Oil or Other Medium-Chain Triglycerides: An Acute Crossover Study in Healthy Adults," Curr Dev Nutr 2017;1:1-5 (“Vandenberghe”, of record).
Abu-Izza is discussed in the 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) rejection above.
Regarding claim 4, Abu-Izza teaches the method of claim 2, but does not teach wherein the MCT is tricaprilin. Regarding claim 5, Abu-Izza further does not teach the method of claim 4, wherein greater than 95% of the fatty acids of the MCT are octanoic acid comprised of 8 carbons (C8).
Vandenberghe discloses as a way of background that ketones are the brain's main alternative fuel to glucose, and that dietary medium-chain triglyceride (MCT) supplements increase plasma ketones. The stated objective of the study is to compare the acute ketogenic effects of the following test oils in healthy adults: coconut oil [CO; 3% tricaprylin (C8), 5% tricaprin (C10)], classical MCT oil (C8-C10; 55% C8, 35% C10), C8 (>95% C8), C10 (>95% C10), or CO mixed 50:50 with C8-C10 or C8. In a crossover design, 9 participants received two 20-mL doses of the test oils. The results showed that C8 was the most ketogenic test oil. (Abstract).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Abu-Izza by specifically determining particular medium-chain fatty acid triglycerides with a therapeutic effect, such as in view of Vandenberghe, and to further determine its therapeutic amount. The skilled artisan would have been motivated to apply tricaprilin to the method disclosed by Abu-Izza by routine experimentation in order to find the most effective MCT for treating Infantile Spasm, to characterize it by determining its carbon numbers (C8) and needed amount for an optimal therapeutic effect, and to particularly test tricparylin (C8), in view of the test results in Vandenberghe that C8 was the most ketogenic MCT of all tested. "When 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).
Other relevant art
The Examiner also notes for the record the following cumulative prior art over which no rejections were made solely in view of its cumulative nature:
- Hanifiha et al., "The efficacy of the ketogenic diet in improving seizures and eeg findings in patients with refractory infantile spasms,” Iranian Journal of Child Neurology, 2022, 16(4), 45-54 (of record)
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- Dressler et al., "Efficacy and tolerability of the ketogenic diet versus high-dose adrenocorticotropic hormone for infantile spasms: a single-center parallel-cohort randomized controlled trial," Epilepsia, 2019, 60(3), 441-451 (of record)
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- Su et al., "SCN2A mutation in an infant presenting with migrating focal seizures and infantile spasm responsive to a ketogenic diet," Brain & Development 40 (2018) 724- 727 (of record)
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- Liu et al., "Medium-chain triglyceride ketogenic diet, an effective treatment for drug-resistant epilepsy and a comparison with other ketogenic diets," Biomedical Journal 2013, 36(1), 9-15 (of record)
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- 2005/0228188 A1 to Sumida et al. (“Sumida”)
However, Sumida teaches that tricaprilin is a medium-chain fatty acid triglyceride, and that tricaprilin comprises 8 carbons (C8). (para [0132] "A mixture of two types of medium-chain fatty acid triglycerides (C8:0:tricaprilin and C10:0: tricaprin) is commercially available, and it can be used as a reaction material").
- US 20200147025
1. A method for use in treating epilepsy or controlling epileptic seizures comprising administering a composition comprising a decanoic acid to octanoic acid ratio of 70:30 to 90:10 wt/wt to an individual in need of same.
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/SVETLANA M IVANOVA/ Primary Examiner, Art Unit 1627