Thursday, October 01, 2015

PTAB zaps claims on on Novartis' multiple sclerosis blockbuster Gilenya in IPR

In IPR2014-00784 on US Patent 8,324,283, PTAB found claims 1–32 of US '283 unpatentable.
MS drugs are a big deal economically; the current market for MS drugs is worth an estimated $20 billion a year.

This oral drug for treating MS comprises a sphingosine-1
phosphate (S1P) receptor agonist and a sugar alcohol. Ex. 1001, 1:11–14,
1:33–35. “The sugar alcohol may act as a diluent, carrier, filler or bulking
agent, and may suitably be mannitol.”

PTAB noted

We disagree, however, with Patent Owners’ argument that the
inventors’ mere discovery of a new reason to combine fingolimod and
mannitol renders nonobvious an invention that was known in the prior art.
Where the prior art teaches the claimed invention, a claim is not rendered
patentable by virtue of being motivated in the inventors’ minds by a newlydiscovered
advantage of the prior-art combination; allowing such a claim to
stand “would remove from the public that which is in the public domain.” In
re Wiseman, 596 F.2d 1019, 1022 (CCPA 1979); see also Cross Med.
Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323 (Fed.
Cir. 2005) (“One of ordinary skill in the art need not see the identical
problem addressed in a prior art reference to be motivated to apply its

As explained
above, though, it does not matter that the prior art failed to recognize this
advantage of a fingolimod-mannitol combination. “[T]he motivation in the
prior art to combine the references does not have to be identical to that of the
[patentee] to establish obviousness.” In re Kemps, 97 F.3d 1427, 1430 (Fed.
Cir. 1996)

Of long-felt need:

Next, Patent Owners argue that the invention claimed in claim 19
satisfied the long-felt but previously unmet need “for a solid oral [multiple
sclerosis] treatment.” PO Resp. 55 (citing Ex. 2044 ¶¶ 25–27). The
supporting evidence is a declaration stating that “some patients are resistant,
afraid, or even unwilling to use needles,” which caused some patients to
“drop[] the [multiple sclerosis] treatment”; that “parenteral medications were
universally inconvenient,” making patients less likely to take their
medication; and that “there were a number of side effects commonly
associated with parenteral [multiple sclerosis] treatments” that “discouraged
patients from continuing with their prescribed course[s] of treatment.”
Ex. 2044 ¶¶ 25–27. Although no other evidence is cited in Patent Owners’
briefing,21 additional record evidence shows that patients asked about the
availability of an oral medication as early as 1993, id. ¶ 34, and that the
introduction of the first oral medication in 2010 caused a “‘major shift in the
treatment landscape,’” with “‘many patients . . . switching to oral therapy,’”
id. ¶ 37 (quoting Ex. 2012, 1).
Petitioners argue, Reply 18–19, that there is no evidence that the longfelt
need was for claim 19’s combination of fingolimod and mannitol;
instead, as Patent Owners acknowledge, PO Resp. 55, the need was merely
“for a solid oral [multiple sclerosis] treatment.” According to Petitioners,
any need for a solid oral dosage form of a multiple sclerosis treatment was
satisfied by treatments that were known in the prior art but did not receive
FDA approval until after Patent Owners’ Gilenya product did. Reply 18–19.
Therefore, argue Petitioners, there was no longer any long-felt need by the
time of the invention claimed in the ’283 patent. Id


In 1999, Chiba itself suggested treating multiple
sclerosis using a solid oral form of fingolimod. Ex. 1006, 6:26–49, 8:19–26.
In addition, teriflunomide, marketed in solid tablet form as Aubagio®, was
known in the prior art at least by April 1, 2002, when it was disclosed to be
useful for treating multiple sclerosis when administered in tablets or
capsules. Ex. 1037, at [22], 1:19–30, 2:60–3:2, 5:1–21; Ex. 2045 ¶ 63.22
Similarly, a capsule form of dimethyl fumarate for the treatment of multiple
sclerosis, marketed as Tecfidera™, Ex. 1070, 2, was disclosed in U.S. Patent
No. 6,509,376 B1, issued January 21, 2003. Ex. 1097, at [45], 2:64–67,
4:25–27, 4:31–33.


Industry praise must be linked to the patented invention. Power-One,
Inc. v. Artesyn Techs., Inc., 599 F.3d 1343, 1352 (Fed. Cir. 2010). Again, if
objective indicia of nonobviousness are “due to an element in the prior art,
no nexus exists.” Tokai Corp., 632 F.3d at 1369. Here, the evidence shows
that what was praised about Gilenya was not the specific formulation recited
in claim 19, but rather the general fact that Gilenya was a solid oral multiple
sclerosis medication. As discussed above, however, a solid oral multiple
sclerosis formulation was known in the prior art, so there is no nexus
between the claimed invention and the industry praise.

Tysabri (natalizumab ) is mentioned

In either case, Dr. Blackburn excluded
from his analysis any data regarding sales of Tysabri, id. ¶ 20 n.24,24
multiple sclerosis drug that generates more than $1 billion in annual sales,
Ex. 1041 ¶ 38; Ex. 1057, 5–6; Ex. 1058, 37. Dr. Blackburn’s evidence of
Gilenya’s market share is biased towards more significant sales of Gilenya
by this exclusion and, thus, is unreliable as evidence that Gilenya’s sales are
significant in relation to the relevant market as a whole.

As to amendment:

Because we find each of claims 1–32 unpatentable, we next address
Patent Owners’ motion to amend, in which claims 33–64 are proposed.
Motions to amend are permitted by 35 U.S.C. § 316(d) and 37 C.F.R.
§ 42.121. In moving to amend their claims, as the moving the party, Patent
Owners have the burden to show entitlement to the relief requested. 37
C.F.R. § 42.20(c). “The burden is not on the petitioner to show [the]
unpatentability [of the proposed claims], but on the patent owner to show
patentable distinction over the prior art of record and also [the] prior art
known to the patent owner.” Idle Free Sys., Inc. v. Bergstrom, Inc., Case
IPR2012-00027, slip op. at 7 (PTAB June 11, 2013) (Paper 26)
(representative). The “prior art of record” includes “any material in the
prosecution history of the patent,” “any material art of record in the current
proceeding, including art asserted in grounds on which the Board did not
institute review,” and “any material art of record in any other proceeding
before the Office involving the patent.” MasterImage 3D, Inc. v. RealD
Inc., Case IPR2015-00040, slip op. at 2 (PTAB July 15, 2015) (Paper 42)

***Gilyena is for relapsing remitting MS ["RRMS"]. Forbes noted a possible
game changer as to primary progressive MS, with new results on ocrelizumab [by Roche / Biogen], which
is a humanized anti-CD20 monoclonal antibody, which targets mature B lymphocytes:

On Monday [28 Sept 2015], the company disclosed that its experimental multiple sclerosis treatment ocrelizumab has become the first therapy to hit the main endpoint in a large Phase III study for primary progressive MS. This form of the disease accounts for between 10% and 15% of all MS patients, but is devoid of effective therapies.

As such, ocrelizumab is looking like an increasingly significant future sales growth driver for Roche, capable of generating multi-billion dollar sales on a global basis. In June, the company announced that two Phase III studies in the more common form of relapsing remitting MS had hit their primary and key secondary endpoints. Full data from each of the late-stage trials will be presented at next month’s annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

CD-20 immune cells are thought to be a key contributor to myelin and axonal damage in MS.

Forbes noted that ocrelizumab might compete against Tysabri in the RRMS market :

In the larger RRMS market, there is a growing consensus that ocrelizumab will gain an initial foothold in second-line patients and compete primarily with Biogen’s Tysabri. Roche’s drug offers comparable efficacy, but what appears to be a notably superior safety profile. Furthermore, while Tysabri is dosed once a month, ocrelizumab is administered twice a year.

Another monoclonal antibody for MS is alemtuzumab (Lemtrada) which binds to CD52, a protein present on the surface of mature lymphocytes,

See the story from 14 Nov. 2014 Sanofi’s Lemtrada Wins U.S. Approval to Treat MS which includes the text:

There are about 10 treatments for relapsing-remitting MS, in a market estimated at $16 billion, including Avonex made by Biogen Idec Inc. and Copaxone from Teva Pharmaceutical Industries Ltd. Multiple sclerosis, a neurological disease that can cause severe disability, affects as many as 350,000 people in the U.S. and is twice as likely to occur in women, according to the National Institute of Neurological Disorders and Stroke.
Patients receive five infusions of Lemtrada in the first year, followed by three more a year later. Data presented at a meeting in September showed that 70 percent of those involved in the key clinical trials of the drug didn’t require any additional treatment after the first two years. The drug will cost $158,000 over the two years, compared with about $135,000 for Merck KGaA’s Rebif, Sibold said.

“We could see that this would become the most cost-effective, least-expensive, highest-value product over time,” he said.


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