DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
Election/Restrictions
Applicant’s election of Group I, claims 1-10, in the response dated 9 April 2025, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
Claims 11-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Status
Claims 27-38 are cancelled.
Claims 1-26 are pending.
Claims 11-26 are withdrawn.
Claims 1-10 are examined on the merits in this prosecution.
CLAIM REJECTIONS
Obviousness Rejection
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
1) Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Amatangelo (WO 2017/146794 A1), in view of Dokou (US 2013/0224293 A1).
Amatangelo teaches a tablet or capsule comprising compound 1, known as enasidenib or 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl ]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol (structure below). See Abstract
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enasidenib
Amatangelo teaches the compound is useful in treating the hematologic malignancy acute myelogenous leukemia (AML) characterized by the presence of a mutant allele of IDH2 (pg 6, [0024]). Amatangelo teaches the compound is useful in treating AML regardless of the patients age (pg 56, [00188]).
Amatangelo teaches the formulation comprises 10 mg to 5000 mg of compound I (pgs 27-28, [0099]). Amatangelo teaches the following (pg 24, [081] to [087]):
In one embodiment, the diluent is a microcrystalline cellulose.
[082] In one embodiment, the binder is a hydroxypropyl cellulose.
[083] In one embodiment, the disintegrant is sodium starch glycolate.
[084] In one embodiment, the wetting agent is sodium lauryl sulfate.
[085] In one embodiment, the stabilizer is hypromellose acetate succinate.
[086] In one embodiment, the glidant is colloidal silicon dioxide.
[087] In one embodiment, the lubricant is magnesium stearate.
For the percentage of Compound 1A in the claimed minitablet, routine optimization of would have led to the claimed range based on the amount of drug effective in the subject. The person of ordinary skill in the art would have found it obvious to optimize within the claimed range because Amatangelo teaches a range that treats the disease in a subject of at least 10 years of age ([00188]) and methods of determining a safe range for subjects younger than this age are well-known to practitioners of the pharmaceutical arts.
Amatangelo teaches microcrystalline cellulose as a binder in an amount of 42 or 44% (pg 32, [00107]); mannitol as a diluent in an amount of 26 or 28% ([00108]); the binder in an amount of 2% (pg 32, [00107]); the disintegrant in an amount of about 6%, about 8%, or about 10% (pg 34, [00110]); the sodium lauryl sulfate in an amount of about 2% (pgs 33-34, [00109]); the stabilizer in an amount of about 1% (pg 35, [00111]); the glidant in an amount of about 1%, about 2%, or about 3% (pg 36, [00112]); and a lubricant in an amount of about 1.4% or 1.6% (pg 34, [00109]).
For claims 1, 2, and 7 (for the amount of Compound 1A), Amatangelo teaches an amount that overlaps the claimed range of each component taught by Amatangelo as discussed above. Because the claimed range overlaps with the range disclosed by the prior art, a prima facie case of obviousness exists.
Amatangelo does not teach the presence of 3.5% to 5% sucralose in the dosage form. Amatangelo also does not teach a minitablet formulation or the dimensions of the minitablet.
Dokou teaches the missing elements of Amatangelo.
Dokou teaches pharmaceutical compositions, including mini-tablets, that may comprise sucralose in an amount of 10% or less (Abstract; pg 4, [0049]), overlapping the claimed range. Dokou teaches the mini-tablets may also contain microcrystalline cellulose or mannitol as a filler (pg 9, [0100]); hydroxypropyl methylcellulose (pg 4, [0045]); sodium starch glycolate as a disintegrant (pg 4, [0049]); sodium lauryl sulfate as a wetting agent (pg 4, [0047]); colloidal silicon dioxide as a glidant (pg 4, [0049]); hypromellose acetate succinate (pg 84, [1693]); and magnesium stearate as a lubricant ([0049]). Dokou exemplifies the composition in a drug for pediatric cystic fibrosis (pg 2, [0014]).
Dokou teaches the compositions are useful in pediatric patients since the minitablet formulation is readily added to foods or liquids such as pudding or applesauce for ingestion (pg 5, [0056]; pg 48, [1246]; pg 49, [1259]).
For claim 3, routine optimization of Dokou’s minitablet would have led to the claimed range of a weight of about 1.67 mg because Dokou teaches that the minitablet in any dimension is from about 1 mm to 5 mm (pg 6, [0054]). For example, a cubic minitablet having dimensions of 1.17 mm on a side and a density of 1 gm/cm3 would have a mass of 1.6 gm, reading on the limitation of “about 1.67 mg”.
For claims 4, 5 and 8, Dokou teaches minitablet that can be formulated into capsules. The minitablets range in size from about 1 mm to about 5 mm in any dimension (pg 6, [0054]), overlapping the ranges recited in claims 4 and 5.
For claim 6, Dokou teaches an average tensile strength of between about 0.5 MPa and about 4 MPa (pg 5, [0054]), overlapping the claimed range. For the limitation of the mini-tablet having a solid fraction of about 0.9 to 0.95, it is known in the pharmaceutical arts that one of ordinary skill can optimize the solid fraction by manipulating tableting parameters such as compaction pressure, powder properties such as particle size, and use of an appropriate tableting machine
For claims 9 and 10, Dokou teaches the composition comprises over 60 minitablets, including 65, 78, 91, 104, 117, 130, or 336 mini-tablets. (pgs 4-5, [0053]), overlapping the claimed range.
It is further noted that the tablet components taught by Amatangelo are likewise taught by Dokou as the components useful in preparing minitablets also comprising sucrose.
The skilled artisan would have expected success in adding the claimed amount of sucralose to the composition Amatangelo, and formulating the capsules taught by Amatangelo in the dosage form of minitablets or minitablets comprised within a capsule, since Amatangelo teaches dosage forms for children wherein the addition of sucralose would make the medication more palatable, and Amatangelo further teaches minitablets of the claimed size, weight, and tensile strength are useful for pediatric dosing since the minitablets are readily dispersed in foods such as applesauce or pudding that may increase the compliance of children.
CONCLUSION
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL P COHEN whose telephone number is (571)270-7402. The examiner can normally be reached on M-Th 8:30-5:30; F 9-4.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Frederick Krass can be reached on (571)272-0580. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL P COHEN/Primary Examiner, Art Unit 1612