Granted Patent
B2
US 12,433,868 · App. 18/545,961 · Granted Oct 7, 2025
Polymorphic forms of ST-246 and methods of preparation
Inventors:
Shanthakumar R. Tyavanagimatt (Sammamish, WA); Melialani A. C. L. S. Anderson (Corvallis, OR); William C. Weimers (Corvallis, OR); Dylan Nelson (Corvallis, OR); Tove′ C. Bolken (Keizer, OR); Dennis E. Hruby (Albany, OR); Michael H. O'Neill (Painesville, OH); Gary Sweetapple (Madison, OH); Kelley A. McCloughan (South Haven, MI)
Assignee:
Siga Technologies, Inc.
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Abstract
Polymorph forms of 4-trifluoromethyl-N-(3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-ethenocycloprop[f]isoindo1-2(1H)-yl)-benzamide are disclosed as well as their methods of synthesis and pharmaceutical compositions.
Claims (21)
1. A unit dosage form comprising a pharmaceutical composition formulated for oral administration, wherein:
(a) said pharmaceutical composition comprises a polymorph Form I of 4-trifluoromethyl-N-(3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-ethenocycloprop [f] isoindol-2 (1H)-benzamide which shows an X-ray powder diffraction pattern having characteristic peaks at a reflection angle 2θ of about
7.63, 10.04, 11.47, 14.73, 15.21, 15.47, 16.06, 16.67, 16.98, 18.93, 19.96, 20.52, 20.79, 22.80, 25.16, 26.53, 27.20, 27.60, 29.60, 30.23, 30.49, 30.68, 31.14, 33.65, 34.33, 35.29, 35.56, 36.30, 37.36, 38.42, 38.66
degrees and further comprises one or more pharmaceutically acceptable ingredients selected from the group consisting of carriers, excipients, diluents, additives, fillers, lubricants and binders; and
(b) said polymorph Form I has a D90% particle size diameter of up to about 300 microns.
2. The unit dosage form according to claim 1 , wherein said polymorph Form I has a D90% particle size diameter of about 5 microns.
3. The unit dosage form according to claim 1 , wherein said polymorph Form I has a D90% particle size diameter of about 16.6 microns.
4. The unit dosage form according to claim 1 , wherein said polymorph Form I has a D90% particle size diameter of about 26.6 microns.
5. The unit dosage form according to claim 1 , wherein said polymorph Form I has D90% particle size diameter of about 75 microns.
6. The unit dosage form according to claim 1 , present in the form of a capsule or a tablet.
7. The unit dosage form according to claim 1 , comprising 200 mg of polymorph Form I wherein a D90% particle size is less than about 10 microns.
8. A unit dosage form for oral administration comprising:
(a) about 200 mg of ST-246, wherein ST-246 is polymorph Form I of 4-trifluoromethyl-N-(3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-ethenocycloprop [f] isoindol-2 (1H)-yl)-benzamide which shows an X-ray powder diffraction pattern having characteristic peaks at a reflection angle 2θ of about
7.63, 10.04, 11.47, 14.73, 15.21, 15.47, 16.06, 16.67, 16.98, 18.93, 19.96, 20.52, 20.79, 22.80, 25.16, 26.53, 27.20, 27.60, 29.60, 30.23, 30.49, 30.68, 31.14, 33.65, 34.33, 35.29, 35.56, 36.30, 37.36, 38.42, 38.66 degrees;
(b) about 33.15 mg of lactose monohydrate;
(c) about 42.90 mg of croscarmellose sodium;
(d) about 1.95 mg of colloidal silicon dioxide;
(e) about 13.65 mg of hydroxypropoyl methylcellulose;
(f) about 7.8 mg of sodium lauryl sulfate;
(g) about 1.95 mg of magnesium stearate; and
(h) a quantity of microcrystalline cellulose up to about 88.60 mg such that the total weight of the dosage form is about 390 mg.
Assignments (2)
CHANGE OF ADDRESS
Recorded Mar 25, 2026
From: SIGA TECHNOLOGIES, INC.
To: SIGA TECHNOLOGIES, INC.
Reel/Frame 075242/0438 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 19, 2023
From: TYAVANAGIMATT, SHANTHAKUMAR R.; ANDERSON, MELIALANI A.C.L.S.; WEIMERS, WILLIAM C.; NELSON, DYLAN; BOLKEN, TOVE' C.; HRUBY, DENNIS E.; O'NEILL, MICHAEL H.; SWEETAPPLE, GARY; MCCLOUGHAN, KELLEY A.
To: SIGA TECHNOLOGIES, INC.
Reel/Frame 065916/0155 →
Continuity (9)
Provisional Application
61316747
· Mar 23, 2010
Provisional Application
61373031
· Aug 12, 2010
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