Claims for Patent: 9,303,051

Summary for Patent: 9,303,051

Title:	Phosphonate ester derivatives and methods of synthesis thereof
Abstract:	The disclosure describes methods of synthesis of phosphonate ester derivatives. Preferred methods according to the disclosure allow for large-scale preparation of phosphonate ester compounds having high purity. In some embodiments, preferred methods according to the disclosure also allow for the preparation of phosphonate ester derivatives without the use of chromatographic purification methods and in better yield than previously used methods for preparing such compounds. Also disclosed are morphic forms of phosphonate ester derivatives.
Inventor(s):	Ware; Roy W. (Raleigh, NC), Almond; Merrick R. (Apex, NC), Lampert; Bernhard M. (Rougemont, NC)
Assignee:	Chimerix Inc. (Durham, NC)
Application Number:	14/808,388
Patent Claims:	1. Morphic Form B of phosphonic acid, [[(S)-2-(4-amino-2-oxo-1(2H)-pyrimidinyl)-1-(hydroxymethyl)ethoxy]methyl]- mono[3-(hexadecyloxy)propyl]ester characterized by an X-ray diffraction pattern including peaks at about 5.8, 12.5, and 24.0 degrees 2.theta.. 2. The Morphic Form of claim 1, characterized by an X-ray diffraction pattern further including a peak at 11.6 degrees 2.theta.. 3. The Morphic Form of claim 1, characterized by an X-ray diffraction pattern further including peaks at 11.6 and 17.4 degrees 2.theta.. 4. The Morphic Form of claim 1, characterized by an X-ray diffraction pattern further including peaks at 11.6, 17.4, 20.8 and 21.6 degrees 2.theta.. 5. The Morphic Form of claim 1 characterized by an X-ray diffraction pattern substantially similar to that set forth in FIG. 6. 6. The Morphic Form of claim 1 characterized by an X-ray diffraction pattern substantially similar to that set forth in FIG. 7, lot 6. 7. A pharmaceutical composition comprising a Morphic Form B of phosphonic acid, [[(S)-2-(4-amino-2-oxo-1(2H)-pyrimidinyl)-1-(hydroxymethyl)ethoxy]m- ethyl]mono[3-(hexadecyloxy)propyl]ester and a pharmaceutically acceptable carrier. 8. A method of treating a viral infection in a subject, comprising administering to a subject in need thereof an effective amount of a Morphic Form B of phosphonic acid, [[(S)-2-(4-amino-2-oxo-1(2H)-pyrimidinyl)-1-(hydroxymethyl)ethoxy]methyl]- mono[3-(hexadecyloxy)propyl]ester. 9. The method of claim 8, wherein the viral infection is selected from the group consisting of: human immunodeficiency virus (HIV), influenza, herpes simplex virus (HSV), human herpes virus 6 (HHV-6), cytomegalovirus (CMV), hepatitis B and C virus, Epstein-Barr virus (EBV), varicella zoster virus, variola major and minor, vaccinia, smallpox, cowpox, camelpox, monkeypox, ebola virus, papilloma virus, adenovirus or polyoma viruses including John Cunningham virus (JCV), BK virus and Simian vacuolating virus 40 or Simian virus 40 (SV40).