Amorphous and crystalline forms of IDO inhibitors
Inventors
Powers, Jay Patrick • BECK, Hilary Plake • Osipov, Maksim • Reilly, Maureen Kay • Shunatona, Hunter Paul • Walker, James Ross • Zibinsky, Mikhail • Rosenbaum, Tamar • YOUNG, Ian Scott • Nelson, Jennifer • Vlahova, Petinka
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11236049-B2
Publication Date
2022-02-01
Expiration Date
Abstract
The present disclosure relates to amorphous and crystalline forms of (R)-N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoro-quinolin-4-yl) cyclohexyl)propanamide and its salts and hydrates, processes for their production, pharmaceutical compositions comprising them, and methods of treatment using them.
Core Innovation
The patent relates to solid forms of an IDO inhibitor, (R)-N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide (Compound 1). The document characterizes multiple amorphous and crystalline forms of Compound 1, including a free base crystalline form (Form 4), a free base monohydrate (Form 2), a methanesulfonic acid (MSA) salt (Form 1), and an MSA salt monohydrate (Form 2).
Form identification is supported by powder X-ray diffraction using selected PXRD peak criteria with 2θ values and an allowed tolerance of ±0.2° for the presence of specific peaks. The patent includes characterization of these solid forms using XRPD/PXRD, ssNMR, FT-IR, DSC, TGA, and single-crystal X-ray data, together with stability and purity statements.
The solid forms are described in the context of therapeutic use of the IDO inhibitor in IDO-mediated disease, notably cancer, including combination approaches with immune checkpoint inhibitors. The document frames the solid-state characterization and stability/purity testing as enabling pharmaceutical compositions comprising the crystalline solid forms for treating disease involving IDO activity.
Claims Coverage
The independent claim defines crystalline Form 4 of Compound 1 using a PXRD-based peak presence criterion with specified 2θ values selected from a defined set and an angular tolerance of ±0.2°. Dependent claims further restrict the Form 4 identification by requiring an increasing number of those selected peaks to be present (two, three, or four).
Crystalline form 4 characterized by selected pxrd peaks within a ±0.2° tolerance
A crystalline (R)-N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl) cyclohexyl)propanamide Form 4 characterized by a powder X-ray diffraction pattern comprising at least one peak selected from 7.6, 12.0, 13.5, 14.4, 17.6, 20.1, 20.7, and 22.0 degrees 2θ, wherein the peak match uses an angular tolerance of ±0.2° 2θ.
Form 4 pxrd signature with exactly two selected peaks within a ±0.2° tolerance
A crystalline Form 4 characterized by a powder X-ray diffraction pattern containing two peaks at specified 2θ values within ±0.2° 2θ.
Form 4 pxrd signature with exactly three selected peaks within a ±0.2° tolerance
A crystalline Form 4 characterized by a powder X-ray diffraction pattern with three selected peaks occurring at 7.6, 12.0, 13.5, 14.4, 17.6, 20.1, 20.7, and 22.0 degrees 2θ with ±0.2° 2θ tolerance.
Form 4 pxrd signature with exactly four selected peaks within a ±0.2° tolerance
A specified crystalline Form 4 characterized by a powder X-ray diffraction (PXRD) pattern with four selected 2θ peaks at specified positions within ±0.2° 2θ.
Overall claim coverage focuses on identifying crystalline Form 4 of Compound 1 by PXRD peak presence and multiplicity using a defined set of 2θ values and a ±0.2° 2θ tolerance, with dependent claims tightening the requirement to two, three, or four selected peaks.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Therapeutic use in IDO-mediated disease, notably cancer, including combination approaches with immune checkpoint inhibitors (e.g., ipilimumab, nivolumab, pembrolizumab).
Pharmaceutical compositions comprising the crystalline solid forms described for treating disease involving IDO activity.
Interested in licensing this patent?