Page: 52
[139] According to Dr. Zusman, only the information included in paragraphs 44-104 and 124-
125 of his report formed part of the CGK. Dr. Zusman does not mention many of the prior art
references in those paragraphs.
[140] Turning to the patent references in particular, Dr. Zusman only considers these references
in the section of his report that describes the state of the art. He does not opine that any of the
patent references formed part of the CGK. Certain patent references are said to be relevant
because they would have led the skilled person to test the combination of ERAs and PDE5-Is, or
they would have led the skilled person to combine macitentan with a PDE5-I. The following are
patent references from Dr. Zusman’s report:
a. US 2004/0063731 (US 731) published April 1, 2004, describes the use of PDE5-
Is in combination with at least one ERA;
b. US 5,250,534, published October 5, 1993, describes a class of PDE5-Is, including
sildenafil, for treating conditions that include angina, hypertension, and heart
failure;
c. US 5,859,006, published January 12, 1999, describes a class of PDE5-Is,
including tadalafil, for treating conditions that include hypertension, PH, angina,
and congestive heart failure;
d. WO 99/64004 (WO 004), published December 16, 1999, describes a class of
PDE5-Is said to be useful for the treatment of a wide range of “cGMP-associated”
conditions including hypertension, angina, heart failure, and erectile dysfunction;
the disclosure refers to classes of therapeutic agents that can be administered with
the PDE5-Is including, for endothelin antagonists, “bosentan, ABT-627, and those
described in U.S. Patent No. 5,612,359 and U.S. Patent Application Serial No.
601035,832”;
e. WO 00/27848, published May 18, 2000, describes PDE5-Is, including udenafil,
for treating erectile dysfunction;