Claims for Patent: 10,745,343

Summary for Patent: 10,745,343

Title:	Polymorphic forms of RAD1901-2HCl
Abstract:	Various polymorphic forms of RAD1901-2HCl, including three crystalline and amorphous forms, are prepared and characterized. Uses of the various polymorphic forms of RAD1901-2HCl for cancer treatment are also disclosed.
Inventor(s):	Cruskie, Jr. Michael Paul, Bolger Joshua Kyle, McKenzie Jonathan Blake, Sheth Pratik, Edwards Richard, Eberlin Alex, Markey Michael
Assignee:	RADIUS PHARMACEUTICALS, INC.
Application Number:	US16456314
Patent Claims:	2. The method of claim 1 , wherein the solid form has an X-ray powder diffraction pattern comprising peaks claim 1 , in terms of 2-theta claim 1 , at 7.1 degrees 2θ±0.2 degree 2θ and 14.3 degrees 2θ±0.2 degree 2θ at about relative humidity 0%.3. The method of claim 1 , wherein the solid form has an X-ray powder diffraction pattern further comprising at least one peak claim 1 , in terms of 2-theta claim 1 , selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ and 18.3 degrees 2θ±0.2 degree 2θ at about relative humidity 0%.4. The method of claim 1 , wherein the solid form has an X-ray powder diffraction pattern further comprising at least two peaks claim 1 , in terms of 2-theta claim 1 , selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ claim 1 , 18.3 degrees 2θ±0.2 degree 2θ claim 1 , 13.8 degrees 2θ±0.2 degree 2θ and 12.0 degrees 2θ±0.2 degree 2θ claim 1 , at about relative humidity 0%.5. The method of claim 1 , wherein the solid form has an X-ray powder diffraction pattern further comprising at least three peaks claim 1 , in terms of 2-theta claim 1 , selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ claim 1 , 18.3 degrees 2θ±0.2 degree 2θ claim 1 , 13.8 degrees 2θ±0.2 degree 2θ claim 1 , 12.0 degrees 2θ±0.2 degree 2θ claim 1 , 25.1 degrees 2θ±0.2 degree 2θ and 18.9 degrees 2θ±0.2 degree 2θ claim 1 , at about relative humidity 0%.6. The method of claim 1 , wherein the solid form has an X-ray powder diffraction pattern further comprising at least four peaks claim 1 , in terms of 2-theta claim 1 , selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ claim 1 , 18.3 degrees 2θ±0.2 degree 2θ claim 1 , 13.8 degrees 2θ±0.2 degree 2θ claim 1 , 12.0 degrees 2θ±0.2 degree 2θ claim 1 , 25.1 degrees 2θ±0.2 degree 2θ claim 1 , 18.9 degrees 2θ±0.2 degree 2θ claim 1 , 27.2 degrees 2θ±0.2 degree 2θ and 11.0 degrees 2θ±0.2 degree 2θ claim 1 , at about relative humidity 0%.7. The method of claim 1 , wherein the solid form has an X-ray powder diffraction pattern further comprising at least four peaks claim 1 , in terms of 2-theta claim 1 , selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ claim 1 , 18.3 degrees 2θ±0.2 degree 2θ claim 1 , 13.8 degrees 2θ±0.2 degree 2θ claim 1 , 12.0 degrees 2θ±0.2 degree 2θ claim 1 , 25.1 degrees 2θ±0.2 degree 2θ claim 1 , 18.9 degrees 2θ±0.2 degree 2θ claim 1 , 27.2 degrees 2θ±0.2 degree 2θ claim 1 , 11.0 degrees 2θ±0.2 degree 2θ and 16.2 degrees 2θ±0.2 degree 2θ claim 1 , at about relative humidity 0%.8. The method of claim 1 , wherein the solid form has an X-ray powder diffraction pattern further comprising at least six peaks claim 1 , in terms of 2-theta claim 1 , selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ claim 1 , 18.3 degrees 2θ±0.2 degree 2θ claim 1 , 13.8 degrees 2θ±0.2 degree 2θ claim 1 , 12.0 degrees 2θ±0.2 degree 2θ claim 1 , 25.1 degrees 2θ±0.2 degree 2θ claim 1 , 18.9 degrees 2θ±0.2 degree 2θ claim 1 , 27.2 degrees 2θ±0.2 degree 2θ claim 1 , 11.0 degrees 2θ±0.2 degree 2θ and 16.2 degrees 2θ±0.2 degree 2θ claim 1 , at about relative humidity 0%.9. The method of claim 1 , wherein the solid form has an X-ray powder diffraction pattern further comprising at least seven peaks claim 1 , in terms of 2-theta claim 1 , selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ claim 1 , 18.3 degrees 2θ±0.2 degree 2θ claim 1 , 13.8 degrees 2θ±0.2 degree 2θ claim 1 , 12.0 degrees 2θ±0.2 degree 2θ claim 1 , 25.1 degrees 2θ±0.2 degree 2θ claim 1 , 18.9 degrees 2θ±0.2 degree 2θ claim 1 , 27.2 degrees 2θ±0.2 degree 2θ claim 1 , 11.0 degrees 2θ±0.2 degree 2θ and 16.2 degrees 2θ±0.2 degree 2θ claim 1 , at about relative humidity 0%.10. The method of claim 1 , wherein the solid form has an X-ray powder diffraction pattern further comprising at least eight peaks claim 1 , in terms of 2-theta claim 1 , selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ claim 1 , 18.3 degrees 2θ±0.2 degree 2θ claim 1 , 13.8 degrees 2θ±0.2 degree 2θ claim 1 , 12.0 degrees 2θ±0.2 degree 2θ claim 1 , 25.1 degrees 2θ±0.2 degree 2θ claim 1 , 18.9 degrees 2θ±0.2 degree 2θ claim 1 , 27.2 degrees 2θ±0.2 degree 2θ claim 1 , 11.0 degrees 2θ±0.2 degree 2θ and 16.2 degrees 2θ±0.2 degree 2θ claim 1 , at about relative humidity 0%.11. The method of claim 1 , wherein the solid form has an X-ray powder diffraction pattern comprising the peaks claim 1 , in terms of 2-theta claim 1 , of 7.1 degrees 2θ±0.2 degree 2θ claim 1 , 14.3 degrees 2θ±0.2 degree 2θ claim 1 , 18.3 degrees 2θ±0.2 degree 2θ claim 1 , 13.8 degrees 2θ±0.2 degree 2θ claim 1 , 12.0 degrees 2θ±0.2 degree 2θ claim 1 , 25.1 degrees 2θ±0.2 degree 2θ claim 1 , 18.9 degrees 2θ±0.2 degree 2θ claim 1 , 27.2 degrees 2θ±0.2 degree 2θ claim 1 , 11.0 degrees 2θ±0.2 degree 2θ and 16.2 degrees 2θ±0.2 degree 2θ claim 1 , at about relative humidity 0%.12. The method of claim 1 , wherein the solid form has an X-ray powder diffraction pattern as shown in at about relative humidity 0%.13. The method of claim 1 , wherein the solid form has a differential scanning calorimetry (DSC) thermogram comprising a melting onset at 218.2° C. and an endothermic peak at 232.1° C.14. The method of claim 13 , wherein the solid form has a differential scanning calorimetry (DSC) thermogram as shown in the bottom figure of .15. The method of claim 1 , wherein the solid form has a thermogravimetric analysis (TGA) as shown in the top graph of .16. The method of claim 1 , wherein said breast cancer is ER+.17. The method of claim 16 , wherein the breast cancer is a resistant ER-driven cancer that progressed after endocrinological treatment claim 16 , wherein the endocrinological treatment comprises administration of a drug selected from a Selective Estrogen Receptor Degrader (SERD) claim 16 , an aromatase inhibitor claim 16 , a selective estrogen receptor modulator (SERM) claim 16 , a Human Epidermal Growth Factor Receptor 2 (Her2) inhibitor claim 16 , a chemo therapeutic agent claim 16 , a cdk4/6 inhibitor claim 16 , an m-TOR inhibitor claim 16 , or rituximab.18. The method of claim 17 , whereinthe SERD is selected from fulvestrant, 17β-[2-[4-[(diethylamino)methyl]-2-methoxyphenoxy]ethyl]-7α-methylestra-1,3,5(10)-trien-3-ol (TAS-108BU or SR16234), 11β-Fluoro-7a-(14,14,15,15-pentafluoro-6-methyl-10-thia-6-azapentadecyl)estra-1,3,5(10)-triene-3,17β-diol (ZK191703), (11β,17β)-11-[4-[[5-[(4,4,5,5,5-Pentafluoropentyl)sulfonyl]-pentyl]oxy]phenylestra-1,3,5,(10)-triene-3,17-diol (RU58668), Brilanestrant (GDC-0810 or ARN-810), Etacstil (GW5638 or -DPC974), (S)-2-(4-(2-(3-(fluoromethyl)-azetidin-1-yl)ethoxy)phenyl)-3-(3-hydroxyphenyl)-4-methyl-2H-chromen-6-ol (SRN-927), and (E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid (AZD9496);the aromatase inhibitor is selected from anastrozole, exemestane, and letrozole;the selective estrogen receptor modulator is selected from tamoxifen, raloxifene, lasofoxifene, and toremifene;the Her2 inhibitor is selected from trastuzumab, lapatinib, ado-trastuzumab emtansine, and pertuzumab;the chemo therapeutic agent is selected from abraxane, adriamycin, carboplatin, cytoxan, daunorubicin, doxil, ellence, fluorouracil, gemzar, helaven, Ixempra, methotrexate, mitomycin, micoxantrone, navelbine, taxol, taxotere, thiotepa, vincristine, and xeloda; andthe angiogenesis inhibitor is bevacizumab.19. The method of claim 17 , wherein the subject is further administered a cdk4/6 inhibitor and/or an m-TOR inhibitor.20. The method of claim 19 , wherein the cdk4/6 inhibitor and/or m-TOR inhibitor is selected from palbociclib claim 19 , ribociclib claim 19 , abemaciclib claim 19 , or everolimus claim 19 , or a combination thereof.21. The method of claim 16 , wherein the breast cancer is a resistant ER-driven cancer that progress after endocrinological treatment claim 16 , wherein the breast cancer has one or more mutant ER binding domains comprising one or more mutations selected from the group consisting of Y537Xwherein Xis S claim 16 , N claim 16 , or C claim 16 , D538G claim 16 , L536Xwherein Xis R or Q claim 16 , P535H claim 16 , V534E claim 16 , S463P claim 16 , V392I claim 16 , and E380Q claim 16 , or a combination thereof.