In view of Hospira’s <http://biopharmapatent.blogspot.com/2016/12/hospira-has-filed-petition-for-inter.html>
and Mylan’s http://biopharmapatent.blogspot.com/2016/11/mylans-herceptin-ipr-biosimilar-inter.html
recent IPR (Inter Partes Review) petitions
of patents covering the drug HERCEPTIN®, we look back at a
previously decided IPR (IPR2014-00676) proceeding relating to a patent that covers immunoconjugates
of the drug HERCEPTIN®.
On October 27, 2015, the PTAB (Patent Trial and
Appeal Board) found the claims of U.S. Patent No. 8,337,856, relating to
immunoconjugates of an anti-ErbB antibody to be patentable. The ‘856 Patent covers immunoconjugates of
the humanized anti-ErbB2 antibody known as HERCEPTIN®, linked to a
maytansinoid toxin. The Patent covers
the drug KADCYLA® (ado-trastuzumab emtansine).
The Petitioner (Phigenix Inc.) argued that an
ordinary artisan would have had reason to substitute the mouse monoclonal antibody
in the immunoconjugate of the prior art (Chari 1992) with huMAB4D5-8 (HERCEPTIN®)
in particular because it was known that (1) humanized antibodies were preferred
over mouse counterparts for clinical applications, (2) huMAB4D5-8 had been FDA
approved for use to treat breast tumors in humans, and (3) clinical studies
indicated that huMAB4D5-8 worked well in combination with microtubule-directed
chemotherapy agents for the treatment of breast cancer.
Patent Owner (Genentech, Inc. and ImmunoGen, Inc.) argued
that the prior art indicated that HERCEPTIN® -maytansinoid
immunoconjugates would have been expected to exhibit unacceptable levels of toxicity
in normal human liver tissue in patients. The Patent Owner pointed to Pai-Scherf 1999, which
describes a Phase I clinical study of human patients receiving an
immunoconjugate (erb-38) comprising a portion of the anti-HER2 monoclonal
antibody e23 fused to a truncated form of Pseudomonas exotoxin A. Although the
Pai-Scherf group “initiated the study in humans based on ‘excellent antitumor
activity and acceptable animal toxicities,’” it nonetheless observed
unacceptable hepatotoxicity in all patients in the treatment group. Pai-Scherf 1999 indicates that, in a clinical
study, human patients experienced “hepatic injury” when exposed to erb-38. Pai-Scherf 1999 discloses that the “toxicity
of erb-38 is most likely due to the presence of erbB2 on hepatocytes, not
detected by immunohistochemical staining in earlier publications.”
In response, Petitioner contended that Pai-Scherf
1999 was not relevant because it described the use of a “fusion protein,” not
an antibody-drug conjugate. The PTAB
disagreed, stating that although the reference disclosed clinical studies using
a single-chain immunoconjugate comprising a portion of an antiHER2/erbB2
antibody and a truncated form of a toxin, Pai-Scherf 1999 discusses generally
the “targeting of tumors with antibodies to erbB2 armed with radioisotopes or
other toxic agents.”
The PTAB held that the ordinary artisans would
not have had a reasonable expectation that any immunoconjugate, much less the
claimed Herceptin®- maytansinoid immunoconjugate in particular,
would be useful to treat solid tumors in humans.
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