Something for Everyone, but the Injunction Stands
By Kevin E. Noonan --
Amgen has several times successfully defended its
erythropoietin (EPO) franchise, the company's first commercial success and in
many ways the crown jewel of its (or anyone's) biologics drug pipeline. That string of successes continued
today with a decision by the Federal Circuit against its latest challenger,
Hoffman-La Roche. But the decision
also put several of the patents protecting Amgen's EPO at risk, making this a
mixed victory at best for the biotechnology company.
The case involved the most recent challenge, Roche's
Mircera® product, a pegylated derivative of human
EPO. Amgen sued Roche in a
declaratory judgment action in Massachusetts asserting six patents: U.S.
Patent Nos. 5,547,933
(the '933 patent), 5,441,868
(the '868 patent), and 5,618,698
(the '698 patent), U.S. Patent Nos. 5,955,422
(the '422 patent, claim 1) and 5,756,349
(the '349 patent, claim 7) and U.S. Patent No. 5,621,080
(the '080 patent). On October 23,
2007, a jury found that Mircera® infringed the '933
patent, the '868 patent and the '698 patent, and that these patents as well as
the '422 patent and the '349 patent were not invalid. (The jury reached neither
infringement nor validity of the '080 patent). Specifically, the jury found that Roche's Mircera® infringed
claims 3, 7, and 8 of the '933 patent (claim 12 was found not to be literally infringed but infringed under the
Doctrine of Equivalents); claims 1 and 2 of the '868 patent;
and claims 6 through 9 of the '698 patent. On October 1, 2008, Massachusetts District Court Judge William Young ruled (in
Amgen's favor for each) on several post-trial motions, including: 1)
affirming the jury's infringement decision by denying Roche's motion for
judgment as a matter of law (JMOL); 2) reaffirming its pretrial decision to
grant summary judgment regarding infringement of claim 1 of the '422 patent; 3)
"explaining" its reasoning for ruling, also pretrial, that the claims
of Amgen's patents-in-suit are not invalid for obviousness-type double patenting
(despite the intervening Federal Circuit decision in Pfizer, Inc. v. Teva Pharmaceuticals USA,
Inc.); 4) denying Roche's motion for JMOL that claim 1 of the '422
patent and claims 3, 7, and 9 of the '933 patent are not invalid for
indefiniteness for reciting the term "human erythropoietin"; and 5)
granting Amgen a permanent injunction barring "Roche, its agents,
servants, employees, counsel, and all persons and entities acting in concert
therewith" from infringing the claims of the patents-in-suit for the
remaining life of those patents.
The Federal Circuit's decision, written by Judge Schall and joined by Judges Mayer and Clevenger, affirmed most of the determinations by the District Court and the jury. These will be discussed more extensively in future posts, but can be summarized simply here: the panel vacated Judge Young's decision on whether the '933 (claims 3, 7, and 8), '349 (claim 7) and '422 (claim 1) patents are not invalid under obviousness-type double patenting and remanded this issue to the trial court; vacated the judgment that claim 7 of the '349 patent was not infringed and remanded for a new trial on that issue; affirmed the judgments that the asserted claims of the '868 patent (claims 1 and 2) and the '698 patent (claims 6-9) are not invalid and were infringed, and that claims 3, 7, and 8 of the '933 patent and claim 1 of the '422 patent were infringed; and finally that claims 9, 11, 12, and 14 of the '933 patent are not infringed by Mircera®.
Because of the number claims asserted and the status of these various claims under the CAFC's opinion, a scorecard seems in order:
The following claims of the '933 patent are infringed but may be invalidated by the trial court for obviousness-type double patenting:
3. A non-naturally occurring glycoprotein product of the expression in a mammalian host cell of an exogenous DNA sequence comprising a DNA sequence encoding human erythropoietin said product possessing the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells.
7. The glycoprotein product according to claim 3 . . . wherein the host cell is a non-human mammalian cell.
8. The glycoprotein product according to claim 7 wherein the non-human mammalian cell is a CHO cell.
The following claim is infringed by Mircera® under the doctrine of equivalents, but its status with regard to the obviousness-type double patenting question is uncertain (it does not fall within the CAFC's remand):
12. A pharmaceutical composition comprising an effective amount of a glycoprotein product effective for erythropoietin therapy according to claim 7 and a pharmaceutically acceptable diluent, adjuvant or carrier. [Infringed under the doctrine of equivalents.]
The following claims of the '868 patent are both not invalid and are infringed:
1. A process for the production of a glycosylated erythropoietin polypeptide having the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells comprising the steps of:
(a) growing, under suitable nutrient conditions, mammalian host cells transformed or transfected with an isolated DNA sequence encoding human erythropoietin; and
(b) isolating said glycosylated erythropoietin polypeptide therefrom.
2. The process according to claim 1 wherein said host cells are CHO cells.
The following claims of the '698 patent are not
invalid and are infringed:
6. A process for the production of a glycosylated erythropoietin polypeptide having the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells comprising the steps of:
a) growing, under suitable nutrient conditions, vertebrate cells comprising amplified DNA encoding the mature erythropoietin amino acid sequence of FIG. 6; and
b) isolating said glycosylated erythropoietin polypeptide expressed by said cells.
7. The process of claim 6 wherein said vertebrate cells further comprise amplified marker gene DNA.
8. The process of claim 7 wherein said amplified marker gene DNA is Dihydrofolate reductase (DHFR) gene DNA.
9. The process according to claims 2, 4 and 6 wherein said cells are mammalian cells.
Claim 1 of the '422 patent is infringed but
may be invalidated for obviousness-type double patenting:
1. A pharmaceutical composition comprising a therapeutically effective amount of human erythropoietin and a pharmaceutically acceptable diluent, adjuvant or carrier, wherein said erythropoietin is purified from mammalian cells grown in culture
Finally, infringement of claim 7 of the '349
patent will be decided in a new trial, but may be invalid under
obviousness-type double patenting:
7. A process for producing erythropoietin comprising the step of culturing, under suitable nutrient conditions, vertebrate cells according to claim 1, 2, 3, 4, 5 or 6.
Wherein claims 1 through 6 of the '349 patent
related to vertebrate cells encoding recombinant EPO:
1. Vertebrate cells which can be propagated in vitro and which are capable upon growth in culture of producing erythropoietin in the medium of their growth in excess of 100 U of erythropoietin per 106 cells in 48 hours as determined by radioimmunoassay, said cells comprising non-human DNA sequences which control transcription of DNA encoding human erythropoietin.
The significance of the Federal Circuit's decision, and the consequences of an adverse decision on remand for the '933, '349 and '422 patents are illustrated by the respective expiration dates of the five patents at issue in the litigation:
*term shortened by terminal disclaimer
Thus, invalidation of the '933, '349 and '422
patents would reduce Amgen's patent protection on its various EPO products
(including Aranesp® and Epogen®)
from May 2015 to August 2012 (more than 3 years), which would have a
significant (negative) effect on the corporate bottom line. Accordingly, Amgen can be expected to
continue this litigation.
The CAFC's opinion did not disturb the permanent
injunction imposed by Judge Young, preventing Roche from marketing Mircera®
in the U.S. despite obtaining FDA approval in November, 2007, giving Roche more
than sufficient incentive to continue as well.
The substance of the Federal Circuit's opinion, including its reasoning on the standards for obviousness type double patenting, will be the subject of later posts.
Amgen Inc. v. F. Hoffman-La Roche Ltd. (Fed. Cir. 2009)
Panel: Circuit Judges Mayer, Clevenger, and Schall
Opinion by Circuit Judge Schall