Post-Grant for Practitioners: Significant PTAB Decisions in BioPharma 1 November 9, 2016 Dorothy Whelan Principal and Post-Grant Practice Co-Chair Tasha Francis Associate
Post-Grant for Practitioners: Significant PTAB Decisions in BioPharma
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November 9, 2016
Dorothy Whelan
Principal and Post-Grant
Practice Co-Chair
Tasha Francis
Associate
Overview
• How often? … bi-monthly
• When? … 2nd Wednesday
• Topics? …
• Important decisions
• Developments
• Practice tips
• Housekeeping
• CLE
• Questions
• Materials
• http://fishpostgrant.com/webinars/
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Agenda
• Overview of Webinar Series
• USPTO Statistics on Adversarial Post-Grant
Proceedings
• Kyle Bass Update
• Noteworthy PTAB Decisions in Bio-Pharma
• Upcoming Post-Grant Webinar
• Post-Grant Resources
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USPTO Statistics on Adversarial Post-Grant Proceedings
PTAB – Most Active Forum
In 2014, the PTAB was the most active forum for US patent validity
challenges, and in 2015 the PTAB had a record year for filings.
*11/8/2016. Source: DocketNavigator Analytics
Most active
courts by
number of
cases
2011 2012 2013 2014 2015 2016
PTAB - 112 792 1,677 1,800 1,474
TXED 580 1,252 1,498 1,428 2,548 1,385
DED 486 1,001 1,335 942 544 382
CACD 329 506 411 320 277 268
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AIA Petitions Have Exceeded Expectations . .
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91%
8%
1%
IPR CBM PGR
5,744 AIA
Petitions Filed
Since 2013
Source: LexMachina, data current as of 11/7/2016
. . . But They May Be Leveling Off Slightly
Source: LexMachina, data current as of 10/31/2016
0
200
400
600
800
1,000
1,200
1,400
1,600
1,800
2013 2014 2015 2016 (Projected)
IPR CBM PGR
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BioPharma IPR Filings Steadily Increase
8
44
125
186
161
0
20
40
60
80
100
120
140
160
180
200
2013 2014 2015 2016 YTD
IPRs Filed in TC1600
Source: LexMachina, data current as of 11/7/2016; projecting
187 IPRs in TC1600 at year end
Technology Breakdown by USPTO Tech Center (2013-Present)
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Source: LexMachina, data current as of 11/7/2016; Design
Patents make up <1% of remaining petitions
Electrical/Computer59%
Mechanical/Business Method
25%
Bio/Pharma9%
Chemical7%
BioPharma by the Numbers
• 2016 YTD, the institution win rate for biopharma is 57.7%*
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89.3%
60.8%
40.0%
53.6%
92.0%
63.2%
55.0%57.7%
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
80.0%
90.0%
100.0%
2013 2014 2015 2016 YTD
Institution Win Rate "Pure" Institution Win Rate
Source: LegalMetric, data current as of 11/4/2016;
*“Institution win rate” includes pre-institution settlements, “pure institution win rate” does not
BioPharma by the Numbers
• 2016 YTD, the percentage of claims for which trial is instituted is
44.7%
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Source: LegalMetric, data current as of 11/4/2016
0
500
1,000
1,500
2,000
2,500
3,000
2013 2014 2015 2016
Number of Claims Challenged Number of Claims Instituted
FWD Win Rates – BioPharma IPRs (2014-2016)
• 73 biopharma petitions have reached a Final Written Decision
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Source: LegalMetric, data current as of 11/4/2016; “Petitioner Win on At Least 1
Claim includes all cases where petition resulted in at least one instituted claim
being cancelled and also includes those cases where all claims were invalidated.
63.2%
57.7% 46.4%
73.7%
61.5%53.6%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2014 2015 2016
Complete Petitioner Win Petitioner Win on At Least 1 Claim
Kyle Bass Update
Kyle Bass IPRs
• 37 IPR Petitions Filed between February 2015 and March 2016
• 21 trials instituted (56.8%)
• 9 FWD
• 8 victories for Bass
• Shire/NPS patent covering Gattex® was invalidated
• 2 Celgene patents covering Pomalyst® and Revlimid® were invalidated
• Alpex Pharma declined to file a Response to Bass’s petition and a FWD
was entered against it, canceling claims covering Suprenza®
• Nissan Chemical abandoned contest and FWD was entered against patent
covering Bravecto®
• Shire’s challenged patent covering Lialda® was upheld
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Other IPR Activity Related to Biologics
• Avastin (bevacizumab)
• Patent Owner Response pending
• Herceptin (trastuzumab)
• Patent Owner Response pending
• Neulasta (pegfilgrastim)
• Patent Owner Response pending
• Rituxan (rituximab)
• Patent Owner Response pending
• Humira (adalimumab)
• Trial instituted, no FWD
• Orencia (abatacept)
• FWD due by 1/15/2017
• Tysabri (natalizumab)
• Denied institution
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Noteworthy PTAB Decisions in Bio-Pharma
PTAB Decisions—Objective Evidence
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Innopharma Licensing, Inc., et al., Mylan Pharmaceuticals, Inc. and Mylan, Inc. v. Senju Pharm. Co.,
Ltd., Bausch & Lomb, Inc., and Bausch & Lomb Pharma Holdings, IPR2015-00902, Paper No. 90
(PTAB July 28, 2016)
• Claims covered an aqueous liquid preparation for ophthalmic use comprising two components: (1) bromfenac (type of NSAID) and (2) tyloxapol in an amount “sufficient to stabilize” bromfenac
• Petitioner challenged claims as obvious over the combination of two references (Ogawa and Sallman)
• Ogawa disclosed ophthalmic compositions containing bromfenac and polysorbate 80. Both tyloxapol and polysorbate 80 were non-ionic surfactants.
• Sallman disclosed the use of tyloxapol as a solubilizer for a different NSAID in an ophthalmic composition.
• Final written decision: Petitioner failed to prove that any of the claims were unpatentable
• Objective evidence of nonobviousness key to decision!
PTAB Decisions—Objective Evidence
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Innopharma Licensing, Inc., et al., Mylan Pharmaceuticals, Inc. and Mylan, Inc. v. Senju Pharm. Co.,
Ltd., Bausch & Lomb, Inc., and Bausch & Lomb Pharma Holdings, IPR2015-00902, Paper No. 90
(PTAB July 28, 2016)
• Issue was the interchangeability of tyloxapol and polysorbate 80
• Patent Owner put in objective evidence of non-obviousness and the
PTAB analyzed it:
“We put Patent Owner on notice that, ‘absent evidence to the contrary,
it would have been well within the level of ordinary skill in the art to
replace one non-ionic surfactant (polysorbate 80) with another non-
ionic surfactant (tyloxapol) in Ogawa’s Example 5=6, because both
were known to be useful as surfactants in ophthalmic preparations ….’
In that regard, we take account of objective considerations of non-
obviousness raised by Patent Owner in the Response ….” Paper 90,
p. 13
PTAB Decisions—Objective Evidence
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Innopharma Licensing, Inc., et al., Mylan Pharmaceuticals, Inc. and Mylan, Inc. v. Senju Pharm. Co.,
Ltd., Bausch & Lomb, Inc., and Bausch & Lomb Pharma Holdings, IPR2015-00902, Paper No. 90
(PTAB July 28, 2016)
• PTAB cited recent Federal Circuit decision rejecting proposition that
objective evidence of nonobviousness could never overcome strong
prima facie case of obviousness. WBIP, LL, v. Kohler Co.., Nos.
2015-1038, 2015-1044, 2016 WL 3902668 at *5 (Fed. Cir. July 19,
2016).
• Patent owner presented evidence of unexpected results, commercial
success, and industry acclaim.
PTAB Decisions—Objective Evidence
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Innopharma Licensing, Inc., et al., Mylan Pharmaceuticals, Inc. and Mylan, Inc. v. Senju Pharm. Co.,
Ltd., Bausch & Lomb, Inc., and Bausch & Lomb Pharma Holdings, IPR2015-00902, Paper No. 90
(PTAB July 28, 2016)
• Unexpected results evidence: experimental results showing
tyloxapol increased bromfenac stability significantly better than
polysorbate 80. Expert witness explained test results and
significance.
• Commercial success evidence: showed that success of commercial
product (Prolensa) falling within claims was due to stabilizing effect
of tyloxapol and ability to eliminate burning and stinging associated
with other eye drops. PTAB: “The fact that Prolensa replaced such
prescriptions suggests commercial success.” Paper 90, p. 20.
• Industry acclaim evidence: Expert testimony “supported by objective
evidence” describing benefits of Prolensa, praise by leading doctors,
and praise in peer-reviewed medical journals.
PTAB Decisions—Objective Evidence
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Innopharma Licensing, Inc., et al., Mylan Pharmaceuticals, Inc. and Mylan, Inc. v. Senju Pharm. Co.,
Ltd., Bausch & Lomb, Inc., and Bausch & Lomb Pharma Holdings, IPR2015-00902, Paper No. 90
(PTAB July 28, 2016)
• PTAB credited objective evidence of nonobviousness in concluding that claims would not have been obvious:
“Taking account of the objective indicia of non-obviousness, including Patent Owner’s significant evidence of unexpected results, we are not persuaded that Petitioner demonstrates sufficiently that the combined disclosures of Ogawa and Sallmann, when considered in light of the asserted background prior art references, establish the obviousness of the claimed invention. Petitioner’s proposed substitution of tyloxapol for polysorbate 80 produced a surprising and unexpected stabilizing effect on bromfenac. The other objective indicia of non-obviousness flow from that surprising results.” Paper 90, p. 72 (emphasis added).
PTAB Decisions—Objective Evidence
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Innopharma Licensing, Inc., et al., Mylan Pharmaceuticals, Inc. and Mylan, Inc. v. Senju Pharm. Co.,
Ltd., Bausch & Lomb, Inc., and Bausch & Lomb Pharma Holdings, IPR2015-00902, Paper No. 90
(PTAB July 28, 2016)
• Note that PTAB placed most emphasis on evidence of unexpected
results based upon experimental data
• Unexpected results evidence is still the most persuade objective
evidence of non-obviousness.
PTAB Decisions—Objective Evidence
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Coalition for Affordable Drugs II LLC v. NPS Pharmaceuticals, Inc., IPR2015-01093, Paper No. 67 (PTAB October 21, 2016)
• Kyle Bass hedge fund filing.
• Claims covered L-histidine stabilized drug formulations of glucagon-
like peptide-2 (“GLP-2”) and GLP-2 analogs (sold by Shire as
GATTEX®).
• Claims set forth several combinations of GLP-2 peptides and
peptide concentrations, pH levels, L-histidine concentrations, and
different bulking agents and concentrations.
• Claims challenged as obvious on 4 related grounds. Issue was
whether it would have been obvious to formulate GLP-2 analogs
with histidine and mannitol (bulking agent/excipient).
• PTAB found all claims unpatentable under § 103.
PTAB Decisions—Objective Evidence
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Coalition for Affordable Drugs II LLC v. NPS Pharmaceuticals, Inc., IPR2015-01093, Paper No. 67 (PTAB October 21, 2016)
• Patent owner presented objective evidence of nonobviousness:
unexpected results, commercial success, and satisfaction of long-felt
need.
• PTAB was not persuaded.
PTAB Decisions—Objective Evidence
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Coalition for Affordable Drugs II LLC v. NPS Pharmaceuticals, Inc., IPR2015-01093, Paper No. 67 (PTAB October 21, 2016)
• Unexpected results: Patent Owner presented bar graphs illustrating
heat stress stability studies. PTAB concluded that results were NOT
unexpected:
“[W]e determine that a preponderance of the evidence demonstrates
that an ordinary artisan would have expected the addition of histidine
to improve the stability of a protein formulation, at least to some
degree, based on the disclosures [of the prior art].” Paper 67, p. 29.
• PTAB further held that even if results were unexpected, they were
not probative of nonobviousness because any differences in stability
improvement were “a difference in degree, not kind.” Id., p. 30.
PTAB Decisions—Objective Evidence
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Coalition for Affordable Drugs II LLC v. NPS Pharmaceuticals, Inc., IPR2015-01093, Paper No. 67 (PTAB October 21, 2016)
• Commercial success: Patent Owner presented evidence of large
market share, high price, sales and sale growth, and large economic
returns for GATTEX®.
• PTAB held that Patent Owner failed to establish a nexus between
GATTEX® sales and patent claims:
“[I]t is unclear if the sales are due to the stability of the product, or to
the active agent, which is disclosed [by the prior art].” Paper 67, p. 32.
PTAB Decisions—Objective Evidence
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Coalition for Affordable Drugs II LLC v. NPS Pharmaceuticals, Inc., IPR2015-01093, Paper No. 67 (PTAB October 21, 2016)
• Long-felt need: Patent Owner presented evidence that GATTEX®
was the first approved GLP-2 product for short bowel syndrome.
• PTAB held that Patent Owner failed to establish a nexus between
the alleged long-felt need and the patent claims:
“Patent Owner does not provide evidence sufficient to permit a
determination as to whether the long-felt need was met by the
discovery of GLP-2 analogs having the necessary activity (disclosed in
the prior art), or the use of L-histidine and mannitol or sucrose in a
stabilized GLP-2 analog formulation.” Paper 67, p. 33.
PTAB Decisions—Objective Evidence
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Take-Aways
• Experimental evidence to support unexpected results is the most
persuasive evidence but it will be scrutinized.
• Commercial success and long-felt need are given lesser weight. For
formulations and dosing, need to ask whether success/need is
attributable to the drug or to the subsequent formulation/dosing
regimen?
PTAB Decisions—Lead Compound Analysis
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Mylan Laboratories Ltd. v. Aventis Pharma S.A., IPR2016-00627, Paper No. 10 (PTAB Aug. 23, 2016)
• Claim directed towards a specific compound (cabataxel)
with methoxy group at C-7 position.
• Petitioner raised two grounds of unpatentability based on
§ 103: Kant and Kant + Klein. Arguments were based
on a “lead compound” analysis.
• PTAB declined to grant the petition.
• Patent owner did not file an expert declaration with its
preliminary response (option not available).
PTAB Decisions—Lead Compound Analysis
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Mylan Laboratories Ltd. v. Aventis Pharma S.A., IPR2016-00627, Paper No. 10 (PTAB Aug. 23, 2016)
• Petitioner proposed Kant’s compound 20 as the lead compound and
proposed modifying compound 20 (docetaxel) to include a C-7
methoxy group.
• PTAB: Kant taught modifying a precursor of docetaxel (“10-DAB”)
only at the C-10 position to prepare docetaxel. Kant did not suggest
additionally modifying docetaxel, let alone at the C-7 position.
PTAB Decisions—Lead Compound Analysis
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Mylan Laboratories Ltd. v. Aventis Pharma S.A., IPR2016-00627, Paper No. 10 (PTAB Aug. 23, 2016)
• Petitioner argued a POSITA would modify both the C-10 and C-7
positions to increase potency and lipophilicity. PTAB disagreed.
“Petitioner recognizes that alkylating the C-7 and C-10 functional
groups would optimize lipophilicity (Pet. 22) but does not address the
well-known problems with lipophilicity and limited aqueous solubility of
intravenously administered paclitaxel and docetaxel. Therefore, we
are not persuaded by Petitioner’s argument that a POSA would have
been motivated to optimize lipophilicity in a paclitaxel or docetaxel
analogue via simultaneous substitution of the C-7 and C-10 positions.”
Paper 10, p. 14
PTAB Decisions—Lead Compound Analysis
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Mylan Laboratories Ltd. v. Aventis Pharma S.A., IPR2016-00627, Paper No. 10 (PTAB Aug. 23, 2016)
• PTAB also rejected Petitioner’s proposed ground combining Kant
with Klein. Petitioner used Kant’s compound 20 as the lead
compound and argued a POSA would have substituted compound
20’s C-7 hydroxyl group with the methoxy groups shown in Klein’s
compounds. Unlike Kant’s compound 20 and the claimed
compound, Klein’s compounds had an acetyl group at C-10 and a
hydroxyl group at C-9.
“[W]e are not persuaded a POSA would have disregarded the
improved aqueous solubility and stability provided by a C-9 hydroxyl, a
key teaching in Klein, when considering possible modifications to Kant
Compound 20 …. We reach the same conclusion with respect to
Klein’s C-10 acetyl.” Paper 10, p. 16.
PTAB Decisions—Lead Compound Analysis
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Take-Aways• Patent owner does not necessarily need an expert declaration to
defeat a petition based on the lead compound analysis, even when
the analysis is highly factual
• In Mylan, Patent owner successfully convinced the PTAB that
Petitioner was using a hindsight-based analysis by drilling down into
the details and rationales behind the proposed modifications.
• Petitioners must present more than superficial reasoning to support
selection of a proposed lead compound and proposed modifications.
PTAB Decisions—Printed Publications
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Teva Pharm. USA, Inc. v. Indivior UK Ltd., IPR2016-00280, Paper No. 23 (PTAB June 10, 2016)
• Claims directed towards an orally dissolvable film that included
buprenorphine, naloxone, a buffer, and a polymer carrier matrix.
Film had a bioequivalent release profile and drug absorption as a
Suboxone® tablet.
• Petitioner raised four grounds of unpatentability based on § 103.
Each included the “Suboxone® 2002 label” and the “Suboxone®
Table Summary Basis of Approval” (“SBOA”) as secondary
references.
• PTAB declined to grant the petition.
• PTAB held that Petitioner failed to establish that either the
Suboxone® 2002 label or the SBOA was a printed publication.
PTAB Decisions—Printed Publications
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Teva Pharm. USA, Inc. v. Indivior UK Ltd., IPR2016-00280, Paper No. 23 (PTAB June 10, 2016)
• Petitioner argued that in co-pending litigation, Patent Owner stipulated
that both the Suboxone® 2002 label and the SBOA were prior art to the
patent at issue. Petitioner offered no further evidence that either was a
printed publication.
• PTAB held Petitioner failed to meet its threshold burden of
demonstrating that either was a printed publication:
(a) Petitioner filed no exhibits, such as a court document, from the district
court case relating to the stipulation;
(b) The stipulation alone is insufficient to meet the threshold requirement
because parties may have had others reason to stipulate to the issue;
(c) The petition lacked any information “directly related” to whether either
the label or the SBOA were actually publicly accessible in the relevant
timeframe. Paper 23, p. 10.
PTAB Decisions—Printed Publications
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Take-Aways
• Do not simply rely on stipulations or statements made in briefs from
related proceedings to prove that a document qualifies as a printed
publication!
• Need to produce independent evidence
Post-Grant Resources
Resources
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• Fish websites:
• Post-Grant for Practitioners: http://fishpostgrant.com/webinars/
• General: http://fishpostgrant.com/
• IPR: http://fishpostgrant.com/inter-partes-review/
• PGR: http://fishpostgrant.com/post-grant-review/
• Rules governing post-grant: http://fishpostgrant.com/
• Post-Grant App: http://fishpostgrant.com/app/
• Post-Grant Radio: http://fishpostgrant.com/podcasts/
• USPTO sites:
• AIA Main: http://www.uspto.gov/aia_implementation/index.jsp
• Inter Partes: http://www.uspto.gov/aia_implementation/bpai.jsp
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Post-Grant Webinar Series
Mark Your Calendar!
Our next Post-Grant for Practitioners webinar will be on Wednesday, January 11, 2017 (1:00-2:00PM ET)
Post-Grant Year in Review with Dorothy Whelan and Karl Renner – Fish’s Post-Grant Practice Chairs
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Thank You!
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Tasha Francis
Associate
Twin Cities
612-766-2015
Dorothy Whelan
Principal
Twin Cities
612-337-2509
Please send your NY CLE forms or questions about the webinar
to Lauren McGovern at [email protected]
A replay of the webinar will be available for viewing at
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