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571.272.7822 Entered: February 15, 2019
Case IPR2018-01494
Patent 8,921,348 B2
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DECISION
Granting Institution of Inter Partes Review
35 U.S.C. § 314(a)
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Patent 8,921,348 B2
INTRODUCTION
Neptune Generics, LLC (“Petitioner” or “Neptune”) filed a Petition
requesting an inter partes review of claims 1–7 of U.S. Patent No. 8,921,348
B2 (Ex. 1001, “the ’358 patent”).1 Paper 1 (“Pet.”). Corcept Therapeutics,
Inc. (“Patent Owner” or “Corcept”) filed a Preliminary Response to the
Petition. Paper 9 (Prelim. Resp.). 2
Institution of an inter partes review is authorized by statute only when
“the information presented in the petition . . . and any response . . . shows
that there is a reasonable likelihood that the petitioner would prevail with
respect to at least 1 of the claims challenged in the petition.” 35 U.S.C.
§ 314; see 37 C.F.R. §§ 42.4, 42.108. Upon considering the Petition, the
Preliminary Response, and the cited evidence, we conclude that Petitioner
has satisfied the burden under 35 U.S.C. § 314(a) to show that there is a
reasonable likelihood that it would prevail with respect to at least one of the
challenged claims.
A. Related Proceedings
Petitioner represents that it is unaware of any other matters related to
the ’348 patent. Patent Owner identifies Corcept Therapeutics, Inc. v. Teva
Pharmaceuticals USA, Inc., No. 18-cv-03632-SDW (D.N.J. Mar. 15, 2018)
as relating to the ’348 patent. Paper 4, 1.
B. The ’348 Patent (Ex. 1001)
The ’348 patent issued December 30, 2014, identifying Joseph K.
Belanoff as the inventor. Ex. 1001. The patent discloses “a method for
1
Petitioner identifies Neptune Generics, LLC as the real party in interest.
Pet. 1.
2
Patent Owner identifies Corcept Therapeutics, Inc. as the real party in
interest. Paper 4, 1.
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3
Belanoff, US Patent No. 9,964,953, issued Nov. 15, 2005 (Ex. 1010,
“Belanoff ’953”).
4
Claim 1 of the ’144 application, as originally filed, reads as follows:
1. A method for optimizing levels of mifepristone in a patient
suffering from a mental disorder amenable to treatment by
mifepristone, the method comprising:
treating the patient with seven or more daily doses of
mifepristone over a period of seven or more days;
testing the serum levels of the patient to determine whether
the blood levels of mifepristone are greater than 1300 ng/mL;
and
adjusting the daily dose of the patient to achieve
mifepristone blood levels greater than 1300 ng/mL.
Ex. 1003, 233 (emphasis added to reflect differences as compared to claim 1
of the ’348 patent).
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In a May 24, 2013 Office Action, the Examiner indicated that Patent
Owner’s arguments were persuasive. The Examiner stated:
The method of using the mifepristone level for adjusting the
treatment of mental disorder is not taught or fairly suggested by
the prior art. Although the effective dosages of mifepristone for
treating mental disorders are known, the correlation of the level
of mifepristone to the therapeutic effectiveness of mifepristone
is not known.
Id. at 52; see also id. at 34 (Notice of Allowability).
D. The Asserted Ground of Unpatentability
Petitioner challenges the patentability of claims 1‒7 of the ’348 patent
on the following grounds: 7
Ground References Basis Claims
Challenged
1 Belanoff ’848 8 § 103(a) 1, 2, 4, 6, and 7
2 Belanoff 2002, Sitruk-Ware, 9 § 103(a) 1, 2, 4, 6, and 7
and Chu and Belanoff 10
3 Belanoff 2002, Sitruk-Ware, § 103(a) 3
Chu and Belanoff, and Belanoff
’953
7
Petitioner numbers the grounds differently in different parts of the Petition.
Compare Pet. 25 with Pet. 42, 43, 45, and 46. We have numbered the
grounds in a manner consistent with the headings used in the Petition. See,
Pet. 42, 43, 45, and 46. For convenience and consistency, the parties are
encouraged to use this numbering going forward when referencing the
grounds.
8
Belanoff, US Patent Publication No. 2004/0029848 A1, published
Feb. 12, 2004 (Ex. 1024, “Belanoff ’848”).
9
Sitruk-Ware et al., Pharmacological Properties of Mifepristone:
Toxicology and Safety in Animal and Human Studies, 68 Contraception 409–
420 (2003) (Ex. 1008, “Sitruk-Ware”).
10
Chu et al., Successful Long-Term Treatment of Refractory Cushing’s
Disease with High-Dose Mifepristone (RU 486), 86(8) Journal of Clinical
Endocrinology & Metabolism 3568–3573 (2001) (Ex. 1023, “Chu and
Belanoff”).
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ANALYSIS
A. Person of Ordinary Skill in the Art
Factual indicators of the level of ordinary skill in the art include “the
various prior art approaches employed, the types of problems encountered in
the art, the rapidity with which innovations are made, the sophistication of
the technology involved, and the educational background of those actively
working in the field.” Jacobson Bros., Inc. v. U.S., 512 F.2d 1065, 1071 (Ct.
Cl. 1975); see also Orthopedic Equip. Co., v. U.S., 702 F.2d 1005, 1011
(Fed. Cir. 1983) (quoting with approval Jacobson Bros.).
Petitioner contends that the person of ordinary skill would have
“either a Pharm. D. or a Ph.D. in organic chemistry, pharmacy,
pharmacology, or a related discipline; or a Bachelor’s or Master’s degree in
organic chemistry or a related field with at least four years of experience
relating to the study of pharmacokinetics or dosing of drugs, their detection
and quantification, or their metabolism.” Pet. 12.
11
Murphy et al., Possible Use of Glucocorticoid Receptor Agonists in the
Treatment of Major Depression: Preliminary Results Using RU 486, 18(5)
J. Psychiatr. Neurosci. 209–213 (1993) (Ex. 1006, “Murphy”).
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The broadest reasonable interpretation (“BRI”) construction standard
applies to inter partes reviews filed before November 13, 2018. 77 Fed.
Reg. 48727 (Aug. 14, 2012) (codified at 37 C.F.R. § 42.100(b)), as amended
at 81 Fed. Reg. 18766 (Apr. 1, 2016); see also 83 Fed. Reg. 51340 (Oct. 11,
2018) (changing the standard for interpreting claims in inter partes reviews
filed on or after November 13, 2018). Because the Petition was filed prior to
this date, on August 2, 2018, the BRI construction standard applies.
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ii. Analysis
Claim 1
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since it was known that such dosages were efficacious in the treatment of
stress disorders.” Id. at 36–37, citing Ex. 1004, ¶ 19.
Patent Owner argues that “none of the references teach or disclose the
efficacious 1300 ng/mL serum level.” Prelim. Resp. 33. We are not
persuaded. Patent Owner cannot demonstrate the non-obviousness of the
claimed method by attacking the prior art references individually. See, In re
Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986) (“Non-obviousness
cannot be established by attacking references individually where the
rejection is based upon the teachings of a combination of references.”).
Here, the doses that Belanoff 2002 teaches are efficacious for treating
patients with PMD (600 and 1200 mg/day) are described in Sitruk-Ware as
producing a mean serum concentration of “greater than 1300 ng/mL.”
Ex. 1007, 4–5 (“In the higher dose groups (600 mg and 1200 mg), nearly
two thirds of the subjects showed significant reductions in their psychosis in
a week or less”); Ex. 1008, 6 (“Following single-dose administration of
mifepristone (600 mg), to healthy female volunteers, mean maximum
plasma concentrations were about 2.0 mg/L at 1.35 h (tmax).”). We find that,
for purposes of institution, the current record tends to support Petitioner’s
contention that the combination of Belanoff 2002 and Sitruk-Ware discloses
1300 ng/mL as an efficacious serum level.
Patent Owner argues that Petitioner fails to provide a reasoned
explanation “why a POSA would understand a dosage range of 600–1200
mg or any of the various dosages within that range to correlate with a
specific serum level, particularly in view of the nonlinear relationship
between dose and serum level, and the unpredictability in the art as further
discussed in Section IX.” Prelim. Resp. 37–38. With respect to the alleged
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to further support obviousness because the skilled artisan would have had all
the more reason to measure the serum levels to ensure proper dosage for
each patient. See, e.g., Ex. 2007, 8 (“([t]he similar serum levels of RU 486
[mifepristone] measured following various doses seems to explain the
observation that there is no correlation between the regimen of RU 486 and
the clinical outcome[.]”)
4. “adjusting the daily dose of the patient to achieve
mifepristone blood levels greater than 1300 ng/ml”
The third step of claim 1 requires “adjusting the daily dose of the
patient to achieve mifepristone blood levels greater than 1300 ng/ml.”
Petitioner contends that Chu and Belanoff teaches “adjusting the daily dose
of the patient to achieve effective or functional mifepristone dosing.” Pet.
37. In view of this teaching, Petitioner, asserts that it would have been
obvious to adjust the patient dose meet the claimed threshold. Petitioner
explains:
Knowing 600 mg was efficacious in treating a patient in need of
mifepristone treatment as described by Belanoff 2002 and
knowing that 600 mg daily should be reasonably expected to
give blood serum levels higher than 1300 ng/mL as disclosed
by Sitruk-Ware, it would have been readily obvious to one of
ordinary skill in the art to adjust the daily dosing of the patient
as described by Chu and Belanoff for treating psychotic major
depression with dosages in the range of those described by both
Belanoff 2002 and Sitruk-Ware in order to achieve mifepristone
blood levels greater than 1300 ng/mL so that efficacy could be
maintained.
Id. at 38 (citing Ex. 1004, Heikinheimo Decl. ¶ 19).
Patent Owner’s arguments with respect to the “testing” limitation
discussed above also apply to this limitation. We are not persuaded by these
arguments for the reasons already discussed.
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Based on our review of the current record, we find that evidence tends
to support the obviousness of the “adjusting” limitation for the reasons
provided by the Petitioner. We note that Chu and Belanoff discloses
adjusting dose based on how the patient responds to treatment rather than
based on the detected serum level of mifepristone. Based on the current
record, we do not find this to be fatal to Petitioner’s case because Chu and
Belanoff provides support for the general proposition to adjust mifepristone
dosage during treatment. Ex. 1023, 4. At this point in the proceeding, we
find that the evidence tends to support Petitioner’s position that it would
have been obvious to adjust the dosage of mifepristone during a course of
treatment if serum levels were found to fall below the level that the
combination of Belanoff 2002 and Sitruk-Ware suggests is efficacious. See,
e.g., Ex. 1004, ¶ 19.
Having determined that Petitioner has demonstrated a reasonable
likelihood of success in proving that at least one claim of the ’368 patent is
unpatentable, we institute a review as to all of challenged claims and all
grounds contained in the Petition. See SAS Inst., Inc. v. Iancu, 138 S. Ct.
1348, 1359–60 (2018); USPTO, Guidance on the Impact of SAS on AIA
Trial Proceedings (April 26, 2018).
We offer the following views on the remaining claims and grounds for
the parties’ consideration, to the extent they wish to address them in any
further briefing.
Claim 2
Claim 2 depends from claim 1 and further requires that “the disorder
is a member selected from the group consisting of a stress disorder, delirium,
mild cognitive impairment (MCI), dementia, psychosis and psychotic major
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Claim 7
Claim 7 depends from claim 1 and further requires that “the adjusting
step comprises increasing the daily dose of the patient to achieve
mifepristone blood levels greater than 1300 ng/mL.” Petitioner contends
that this limitation would have been obvious for essentially the same reasons
that the limitation in claim 1, “adjusting the daily dose of the patient to
achieve mifepristone blood levels greater than 1300 ng/ml,” would have
been obvious. Pet. 40–42. Patent Owner’s Preliminary Response does not
separately contest this limitation. We find that the current record tends to
support Petitioner’s position.
D. Ground 3: Obviousness of claim 3 over Belanoff 2002, Chu and
Belanoff, Sitruk-Ware and Belanoff ’953
Petitioner asserts that claim 3 would have been obvious over the
combination of Belanoff 2002, Chu and Belanoff, Sitruk-Ware, and
Belanoff ’953. We offer the following views on for the parties’
consideration, to the extent they wish to address them in any further briefing.
i. Disclosures of the Asserted Prior Art
Belanoff ’953
Belanoff ’953 discloses a “method of ameliorating the symptoms of a
stress disorder in a patient who has normal or decreased cortisol levels” by
administering “a therapeutically effective amount of a glucocorticoid
receptor antagonist to the patient.” Ex. 1010, 2:52–59. The stress disorders
identified include “Post-Traumatic Stress Disorder, Acute Stress Disorder,
or Brief Psychotic Disorder with Marked Stressor(s).” Id.
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ii. Analysis
Claim 3 depends from claim 1 and further requires that the stress
disorder is “a member selected from the group consisting of Acute Stress
Disorder, Post-Traumatic Stress Disorder and Brief Psychotic Disorder with
Marked Stressor(s).” Petitioner contends that it would have been obvious to
treat one of the stress disorders recited in claim 4 because “Belanoff ‘953
uses the same compound (mifepristone) to treat similar stress disorders as
does Belanoff 2002.” Pet. 43. Patent Owner’s Preliminary Response does
not separately contest this limitation. At this stage in the proceeding, and
absent evidence differentiating considerations for treating the stress
disorders recited in claim 4 from psychotic major depression, we find that
the current record tends to support Petitioner’s position.
Murphy
Murphy discloses a study in which four patients with chronic severe
depression were treated with 200 mg/day of mifepristone for “periods up to
eight weeks.” Ex. 1006, Abstract. The results of the study “suggest that
glucocorticoid antagonists may be of use for treatment-resistant depression.”
Id. at 4.
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ii. Analysis
Claim 5 depends from claim 1 and further requires that “the patient is
treated with 28 or more daily doses over a period of 28 or more days.”
Petitioner contends that it would have been obvious to have treated patients
for a period of at least 28 days with 28 or more daily doses because Murphy
teaches “the usefulness and efficacy of dosing for periods up to 56 days.”
Pet 44. Patent Owner’s Preliminary Response does not separately contest
this limitation. At this stage in the proceeding, and absent evidence to the
contrary, we find that the current record tends to support Petitioner’s
position. See, Ex. 1006, 4 (“While the results are not dramatic, they suggest
that glucocorticoid antagonists may be of use for treatment-resistant
depression.”).
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ii. Analysis
Claim 1
Petitioner contends that Belanoff ’848 discloses all of the elements of
claim 1 with the exception that it does not disclose the serum level of 1300
ng/ml. Pet. 29. With respect to this limitation, Petitioner asserts:
[A]dministration of mifepristone at the dosage levels taught by
Belanoff ‘848 would necessarily and inevitably result in a range
of blood serum concentrations that achieve mifepristone blood
levels greater than 1300 ng/mL as claimed. (Ex. 1004 at ¶20).
It would have been readily obvious to one of ordinary skill in
the art with a very high expectation of success that the daily
dosing of the patient could be adjusted to optimize mifepristone
blood level, whatever level that might be. (Id.)
Id. at 30.
Patent Owner argues that Petitioner’s position is “unsupported by any
reasoned rationale and is based purely on hindsight.” Prelim. Resp. 37.
Patent Owner contends that Petitioner and Dr. Heikinheimo failed to
explain, inter alia, “why a POSA would understand, and how they would
determine, that the 1300 ng/mL serum level was the minimum required for
efficacy.” Id. at 38.
As an initial matter, Petitioner repeatedly invokes the language of
inherency in connection with this ground. Pet. 29–30 (“These dosage levels
inherently translate directly into mifepristone serum levels.”). However, the
current record does not tend to show that, in every case, administration of
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this limitation. Pet. 31–32. Patent Owner’s Preliminary Response does not
contest that Belanoff ’848 discloses this limitation. We find that the current
record tends to support Petitioner’s contention that Belanoff ’848 discloses
this limitation. See Ex. 1024, ¶ 44.
Claim 7
Claim 7 depends from claim 1 and further requires that “the adjusting
step comprises increasing the daily dose of the patient to achieve
mifepristone blood levels greater than 1300 ng/mL.” Petitioner contends
that this limitation would have been obvious for essentially the same reasons
that the limitation in claim 1, “adjusting the daily dose of the patient to
achieve mifepristone blood levels greater than 1300 ng/ml,” would have
been obvious. Pet. 32. Patent Owner’s Preliminary Response does not
separately contest this limitation. We find that the current record tends to
support Petitioner’s position.
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over a period of 28 or more days.” Pet. 46. Our views with respect to
Murphy’s application to this limitation are discussed in connection with
Ground 4.
I. 35 U.S.C. 325(d)
We have discretion to deny review when “the same or substantially
the same prior art or arguments previously were presented to the Office.”
35 C.F.R. § 325(d). When evaluating whether the same or substantially the
same prior art or arguments were previously presented to the Office under
§ 325(d), the Board has considered a number of non-exclusive factors,
including, for example: (1) the similarity of the asserted art and the prior art
involved during the examination; (2) the extent to which the asserted art was
considered during examination, including whether the prior art was the basis
for rejection; (3) the cumulative nature of the asserted art and the prior art
considered during examination; (4) whether Petitioner has pointed out
sufficiently how the Examiner erred in its consideration of the asserted prior
art; (5) the extent of the overlap between the arguments made during
examination, and the manner in which Petitioner relies on the prior art or the
applicant’s arguments during examination; and (6) the extent to which
additional evidence and facts presented in the Petition warrant
reconsideration of the asserted prior art. Becton, Dickinson & Co. v. B.
Braun Melsungen AG, Case IPR2017-01586, slip op. at 17–28 (PTAB
Dec. 15, 2017) (Paper 8) (informative).
Patent Owner invites us to enter a discretionary denial under
35 C.F.R. § 325(d) because “Grounds 1-6 present substantially the same art
and arguments that were overcome during prosecution, and Petitioner fails to
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CONCLUSION
For the foregoing reasons, we conclude that the information presented
in the Petition establishes a reasonable likelihood that Petitioner will prevail
in showing that at least claim 1 of the ’348 patent is unpatentable.
Accordingly, we institute an inter partes review of all challenged claims and
all ground presented in the Peition. SAS Inst., Inc. v. Iancu, 2018 WL
1914661, at *10 (U.S. Apr. 24, 2018).
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ORDER
In consideration of the foregoing, it is hereby:
ORDERED that pursuant to 35 U.S.C. § 314(a), an inter partes
review is instituted as to claims 1, 2, 4, 6, and 7 of the ‘348 Patent under
35 U.S.C. § 103 as obvious over Belanoff ‘848.
ORDERED that pursuant to 35 U.S.C. § 314(a), an inter partes
review is instituted as to claims 1, 2, 4, 6, and 7 of the ‘348 Patent
under 35 U.S.C. § 103 as obvious over the combination of Belanoff 2002,
Sitruk-Ware, and Chu and Belanoff.
ORDERED that pursuant to 35 U.S.C. § 314(a), an inter partes
review is instituted as to claims claim 3 of the ‘348 Patent under 35
U.S.C. § 103 as obvious over the combination of Belanoff 2002, Sitruk-
Ware, Chu and Belanoff, and Belanoff ‘953.
ORDERED that pursuant to 35 U.S.C. § 314(a), an inter partes
review is instituted as to claim 5 of the ‘348 Patent under 35 U.S.C. § 103 as
obvious over the combination of Belanoff 2002, Sitruk-Ware, Chu and
Belanoff, and Murphy.
ORDERED that pursuant to 35 U.S.C. § 314(a), an inter partes
review is instituted as to claim 3 of the ‘348 Patent under 35 U.S.C. § 103 as
obvious over the combination of Belanoff ‘848 and Belanoff ‘953.
ORDERED that pursuant to 35 U.S.C. § 314(a), an inter partes
review is instituted as to claim 5 of the ‘348 Patent under 35 U.S.C. § 103 as
obvious over the combination of Belanoff ’848 and Murphy.
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For PETITIONER:
Kenneth Goldman
MASSEY & GAIL LLP
Ken.Goldman98@gmail.com
Bob Steinberg
David Frazier
LATHAM & WATKINS LLP
Bob.Steinberg@lw.com
David.Frazier@lw.com
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