TH-302 solid forms and methods related thereto
Inventors
Duan, Jian-Xin • Matteucci, Mark • Davar, Nipun • Andersen, Denise
Assignees
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Publication Number
US-10131683-B2
Publication Date
2018-11-20
Expiration Date
Abstract
The present invention provides a new method for making TH-302 and solid forms thereof. The compound in its solid form is an effective anti-cancer agent and may be used in various pharmaceutical compositions, and are particularly effective for the treatment of cancer. The invention also provides a method for preparing such compounds and forms and for treating cancer in a mammal comprising the step of administering a therapeutically effective amount of a solid form of TH-302 thereof.
Core Innovation
The invention concerns the anti-cancer compound TH-302 (N,N′-Bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester) and pharmaceutically acceptable salts provided as an anhydrous crystalline solid form. A key aspect is solid-form control through analytical characterization, including DSC, XRPD, and Raman/IR spectra, to identify and distinguish the crystalline form.
A specific anhydrous crystalline solid form of TH-302, identified as Form A, is discovered and characterized by DSC, XRPD, and Raman/IR spectral properties. The Form A is characterized by a DSC onset/peak around 98.06°C/100.06°C, XRPD peaks around 19.3° and 26.2° (2θ), and Raman/IR absorption peaks, including Raman absorption peaks and IR absorption peaks as reported.
The disclosure also addresses stability for the crystalline solid form. TH-302 Form A is described as stable to about 15% RH at 25°C, and the document further places the compound in an anti-cancer use framework by describing administration of a therapeutically effective amount for treating cancer in mammals, including alone or in combination with other anti-cancer agents.
Claims Coverage
The independent claim defines a compound of Formula V in a crystalline solid form characterized by matching at least one analytical criterion among X-ray powder diffraction, DSC, and Raman spectrum, as substantially in accordance with specified figures. The claim set also includes pharmaceutical composition and cancer treatment contexts.
Crystalline form defined by XRD, DSC, and/or Raman match
A compound of Formula V provided in a crystalline solid form characterized by at least one of: an X-ray powder diffraction pattern substantially in accordance with FIG. 3, a DSC scan substantially in accordance with FIG. 1, and a Raman spectrum substantially in accordance with FIG. 5.
Crystalline form with defined XRD peaks
The compound of Formula V in a crystalline solid form characterized by an X-ray powder diffraction pattern having peaks at about 19.3° and 26.2° (2θ).
Crystalline form with defined DSC endotherm
The compound of Formula V in a crystalline solid form characterized by a DSC scan showing an endotherm at about 100°C.
Crystalline form with Raman absorption peak set
The compound of Formula V in a crystalline solid form characterized by a Raman spectrum having specified absorption peaks including the listed wavenumbers, along with additional specified Raman absorption peak wavenumbers.
Therapeutically effective composition for cancer in a human
A pharmaceutical composition comprising a therapeutically effective amount intended to treat cancer in a human subject, specifically pancreatic cancer or ovarian cancer.
Overall claim coverage centers on TH-302/Formula V in a crystalline solid form defined by spectral matching criteria, with dependent claim features specifying particular XRD peak positions, a DSC endotherm temperature, and a defined Raman absorption peak set. Additional coverage extends to pharmaceutical compositions using a therapeutically effective amount to treat pancreatic or ovarian cancer in a human.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating cancer in a mammal by administering a therapeutically effective amount of TH-302, alone or in combination with other anti-cancer agents.
Treating cancer in a human subject, specifically pancreatic cancer or ovarian cancer, using a pharmaceutical composition comprising a therapeutically effective amount.
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