On
March 24, 2017, Celltrion filed two separate IPR petitions against Genentech’s
patents covering "a method for treatment a human patient diagnosed with cancer
characterized by overexpression of ErbB2 receptor.” The patents cover the drug Herceptin (trastuzumab),
and claim administering an initial dose of Herceptin, followed by subsequent
doses that are “same or less than the initial dose.”
Patent/IPR
|
Claim
1
|
6,627,196
IPR2017-01139
|
1. A method for the treatment of a human
patient diagnosed with cancer characterized by overexpression of ErbB2
receptor, comprising administering an effective amount of an anti-ErbB2
antibody to the human patient, the method comprising: administering to the
patient an initial dose of at least approximately 5 mg/kg of the anti-ErbB2
antibody; and administering to the patient a plurality of subsequent doses of
the antibody in an amount that is approximately the same or less than the
initial dose, wherein the subsequent doses are separated in time from each
other by at least two weeks.
|
7,371,379
IPR2017-01140
|
1. A method for the treatment of a human
patient diagnosed with cancer characterized by overexpression of ErbB2
receptor, comprising administering an effective amount of an anti-ErbB2
antibody to the human patient, the method comprising: administering to the
patient an initial dose of at least approximately 5 mg/kg of the anti-ErbB2
antibody; and administering to the patient a plurality of subsequent doses of
the antibody in an amount that is approximately the same or less than the
initial dose, wherein the subsequent doses are separated in time from each
other by at least two weeks; and
further comprising administering an effective amount of a chemotherapeutic
agent to the patient.
|
The patents admit that
the prior art trastuzumab dosing regimen consisted of a 4 mg/kg loading dose,
followed by a weekly 2 mg/kg maintenance doses. The patents claim a higher initial dose (at least
5mg/kg versus 4mg/kg) followed by a less frequent tri-weekly dose (“separated by
at least two weeks”) than the admitted prior art’s more frequent weekly dose.
Celltrion’s position is
that the claims of these two patents are obvious over Slamon[1]
and Watanabe[2],
in View of Baselga[3]
and Pegram[4]. Celltrion does not have an anticipatory
position.
Celltrion mainly relies on Slamon, which discloses administration of trastuzumab “of
8 mg/kg over the first three week period, followed by 6 mg/kg every three weeks
thereafter:”
Week
|
1
|
2
|
3
|
4
|
5
|
6
|
7
|
8
|
9
|
10
|
11
|
12
|
||||
Weekly dose
(mg/kg)
|
4
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
||||
Q 3 week dose (mg/kg)
|
8
|
6
|
6
|
6
|
||||||||||||
Claims of the Patents
|
5 or more
|
0
|
0
|
Same or less as initial
|
0
|
0
|
Same or less as initial |
0
|
0
|
Same or less as initial |
0
|
0
|
||||
According to Celltrion,
“to account for an every-three-week schedule, a POSA would have administered an
8 mg/kg loading dose, followed by 6 mg/kg maintenance doses, each administered
three weeks apart.”
Celltrion relies on Baselga
and Pegram for disclosing pharmacokinetic data that allow POSA to calculate
serum concentration since “the prior art repeatedly disclosed a target
efficacious serum concentration of 10 μg/ml. . .Starting with an initial serum
concentration of 169 μg/ml, and applying the conservative one week half-life
discussed above, a POSA would have calculated that the serum concentration
would still remain well above the 10 μg/ml target efficacious serum
concentration three weeks after the 6 mg/kg dose is administered (i.e., 50% would remain after one week,
25 % after two weeks, and 12.5%, or approximately 21.1 μg/ml would remain after
three weeks).”
Celltrion relies on Watanabe
for disclosing “that administration of weekly doses as high as 8 mg/kg were
safe and relatively well-tolerated.”
Celltrion’s petition
also addresses statements by Genentech during prosecution that the prior art
taught away from the claimed invention:
The applicants responded that the prior art taught
away from the claimed invention because (1) a POSA would not have wanted to
increase the interval between doses beyond trastuzumab’s known half-life (i.e.,
either 5.8, 8.3, or 9.1 days) “for fear that insufficient levels of drug would
remain in the patient to treat cancer;” and (2) Watanabe recommended further
studies with a 2 mg/kg or 4 mg/kg weekly dose, not a higher, less frequent
dose.
Regarding Genentech’s first point on not increasing
the interval between doses beyond the half-life, Celltrion argues that “half-life
is only one piece of the relevant information. . . Rather, when determining
whether a less frequent regimen was likely to be effective, a POSA would have
considered half-life together with initial serum concentration and target
trough serum concentration.” Regarding the second point of Watanabe
recommending lower doses than the claimed dose, Celltrion argues that “Watanabe
was published in the same proceedings as Slamon, and there is no reason to
believe that Watanabe was aware of Slamon’s results prior to its publication. Thus, because Watanabe’s suggestion to pursue
a weekly regimen was made without the benefit of Slamon’s disclosure, it is not
reflective of all of the prior art available to a POSA at the time of the
alleged invention.”
The Board has not yet
made a decision on the petitions. Genentech's related patent in Europe has been found to be invalid. <http://www.kwm.com/en/uk/knowledge/insights/court-of-appeal-upholds-invalidity-of-herceptin-dosing-regime-patent-20150211>.
[1] Trial, 17 J. CLIN. ONCOLOGY,
*377, 98a (May 1998).
[2] 17 J. CLIN. ONCOLOGY, *702, 182a
(May 1998)
[3] 14 J. CLIN. ONCOLOGY, No. 3
737-744 (Mar. 1996)
[4] 16 J. CLIN. ONCOLOGY, No. 8
2659-2671 (Aug. 1998)
No comments:
Post a Comment