PTAB denied Inter Partes Review against Bayer’s STIVARGA (Regorafenib) patent

PTAB denied Fustibal LLC IPR  2016-01490 against the Bayer’s patent US 8,637,553 B2 which claims Regorafenib as a product. The structure of  Regorafenib is shown below:

untitled

product approval history:

Bayer Healthcare received US FDA approval on September 27, 2012 to market Regorafenib for the treatment of metastatic colorectal cancer (CRC) which is marketed under the brand name STIVARGA.

Regorafenib is patented generically in US 7,351,834, this patent is listed in OB for STIVARGA. US ‘834 is set to expire in January 2020. The closest analogs to Regorafenib were specifically enabled in this patent.

Regorafenib is specifically claimed in US 8,637,553 B2 which is set to expire in February 2031 and it claim the priority as 23 Jul 2003.

IPR  2016-01490 decision summary:

The petition includes the unpatentability of claims 1 to 16 of US ‘553; the following prior art was considered by the petitioner for the invalidity of US ‘553

  1. Riedl et al., WO 00/42012 A1 (PCT equivalent of US 7,351,834), published July 20, 2000- this application discloses structurally closest analogs of Regorafenib including Sorafenib.
  2. Aherne et al.,Finding the needle in the haystack: why high-throughput screening is good for your health, 4(4) BREAST CANCER RES. 148–154, © 2002- this paper states that high-throughput screening is an essential component of the toolbox of modern technologies that improve speed and efficiency in contemporary cancer drug development and presents examples of successful drug discovery programmes based on high-throughput screening . . . which offer potential in the treatment of breast cancer and other malignancies.
  3. Park et al., Metabolism of Fluorine-Containing Drugs, 41 ANN. REV. PHARMACOL. TOXICOL, 443–70,© 2001 Annual Reviews-this paper discussed the potential benefits of fluorination.

Riedl teaches that the oncogene is a major contributor to the development and progression of human solid cancers and is mutated in 30% of all human cancers. Riedl specifically discloses the following compounds of Formulae

 untitledThe above structure depicts the structure of Sorafenib and its analog. Riedl also discloses the synthesis of the said compounds.

The following table discloses the structural differences between Regorafenib and the prior art compounds:

untitled3

The difference between the Regorafenib and the prior art compounds is a single halogen substitution which derives Regorafenib.

The petitioner considered Riedl as the closest prior art and argued that Riedl inherently discloses single substitutions of chlorine at both the 3 and 2 positions of Sorafenib.

The board commented that the Examiner repeatedly considered Riedl during prosecution, determined that Riedl was the closest prior art to the invention claimed, and expressly allowed the challenged claims over the Riedl reference and the board decline to institute trial with respect to Riedl as the Ground I.

The board further stated that “to anticipate a later-claimed species, a pattern of preferences or other related teaching or suggestion must lead to a genus small enough that a person of ordinary skill in the art would at once envisage the claimed species”

The board further stated that the genus relied on by Petitioner, having “‘eight individual chemical compounds possible when substituting a halogen”—F, Cl, Br, or I—at position 2/2’ or 3/3’ of the central ring of Sorafenib, does not exist in Riedl, and only results from Petitioner’s improper picking and choosing disparate aspects of the disclosure.

The board further stated that the petitioner “merely assumes—without explanation—that the POSA would select Sorafenib for modification.” Neither Petitioner nor Petitioner’s expert address why a skilled artisan reading Riedl would select that compound for further development.

The petitioner also argued that the claims 1-16 are rendered obvious by the combination of Riedl with the other prior art cited. However, the board has declined the arguments and ordered to deny the IPR.