Btg International Limited v. Amneal Pharmaceuticals LLC
Opinion
*1066
Appellants BTG International Limited et al. ("Appellants") sued Appellees Amneal Pharmaceuticals LLC et al. ("Appellees") in the U.S. District Court for the District of New Jersey ("District Court"), asserting that Appellees' Abbreviated New Drug Applications ("ANDA") for the generic version of Appellants' abiraterone product ZYTIGA® infringes claims 1-20 ("Asserted Claims") of
In all three IPRs, the USPTO's Patent Trial and Appeal Board ("PTAB") issued claim construction orders adverse to Appellants, as well as final written decisions finding the Asserted Claims obvious.
Amerigen Pharm. Ltd. v. Janssen Oncology, Inc
., No. IPR2016-00286,
Appellants appeal the PTAB's Final Written Decisions and the District Court's Final Judgment. We consolidated the appeals. We have jurisdiction pursuant to
BACKGROUND
I. The '438 Patent
Entitled "Methods and Compositions for Treating Cancer," the '438 patent teaches
*1067
a method "compris[ing] administering a 17a-hydroxylase/C
17,20
-lyase [ ('CYP17')
3
] inhibitor, such as abiraterone acetate [ ('abiraterone') ] (i.e., 3ß-acetoxy-17-(3-pyridyl)androsta-5,16-diene), in combination with at least one additional therapeutic agent such as an anti-cancer agent or a steroid." '438 patent col. 1 ll. 8-12. Specifically, the '438 patent discloses the administration of a therapeutically effective amount of a CYP17 inhibitor, such as abiraterone, with a therapeutically effective amount of at least one additional therapeutic anti-cancer agent.
Independent claim 1 is representative and recites: "[a] method for the
treatment
of a prostate cancer in a human comprising administering to said human a therapeutically effective amount of abiraterone acetate or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of prednisone."
II. The Relevant Prior Art
A. Gerber
Gerber, G.S. & Chodak, G.W., Prostate Specific Antigen for Assessing Response to Ketoconazole and Prednisone in Patients with Hormone Refractory Metastatic Prostate Cancer , 144 J. Urology 1177-79 (1990) ("Gerber") (J.A. 23053-55) is a study that evaluates prostate specific antigen ("PSA") level changes, which Gerber identifies as a "good indicator of disease activity," with "increasing PSA levels" being associated with "evidence of progressive disease." J.A. 23053. This study evaluated PSA level changes in "[a] total of [fifteen] patients with hormone refractory metastatic prostate cancer [that were] treated with [a combination of] ketoconazole [ 5 ] and prednisone." J.A. 23053. It defined "[u]nresponsiveness to the initial hormone therapy ... as an increasing PSA level on [two] consecutive determinations that were at least [one] month apart." J.A. 23053. Gerber explains that patients exhibiting "progressively increasing PSA levels had a decrease in PSA in response to treatment with ketoconazole and prednisone." J.A. 23055. More specifically, Gerber explains that "PSA levels may be useful to define the small subgroup of men *1068 failing standard hormonal therapy who will benefit from the combination of ketoconazole and prednisone." J.A. 23055. Therefore, Gerber concludes that "there appears to be a small subgroup of patients with progressive prostate cancer despite hormonal therapy who will derive significant benefit from the combination of ketoconazole and glucocorticoid [such as prednisone ] replacement therapy." J.A. 23055.
B. O'Donnell
O'Donnell, A., et al., Hormonal Impact of the 17a-hydroxylase/C 17,20 -lyase Inhibitor Abiraterone Acetate (CB7630) in Patients with Prostate Cancer , 90 Brit. J. of Cancer 2317-25 (2004) ("O'Donnell") (J.A. 23171-79) is an article publishing the results of three clinical studies, see J.A. 23171-79, and discloses the treatment of prostate cancer with abiraterone at dosages between 500-800 milligrams ("mg"), J.A. 23171. A daily dose of abiraterone between 500-800 mg resulted in suppression of testosterone levels to the castrate range in non-castrate males. J.A. 23171. O'Donnell explains that "abiraterone acetate ... was developed ... [to be] selectiv[e and it is] ... a potent inhibitor of the [CYP17] enzyme." J.A. 23172. O'Donnell states that "it is common practice to administer supplementary hydrocortisone [ 6 ] and this may prove necessary with ... abiraterone acetate." J.A. 23177. Finally, O'Donnell shows that abiraterone was safe; as such, O'Donnell explains that "[i]n addition to ketoconazole... and abiraterone, other compounds designed to inhibit general androgen production have been developed and show promise." J.A. 23178. On the basis of the clinical evidence, O'Donnell reports that "further studies with abiraterone acetate will be required to ascertain if concomitant therapy with glucocorticoid is required on a continuous basis." J.A. 23177.
C. Sartor
Sartor, O., et al., Effect of Prednisone on Prostate-Specific Antigen in Patients with Hormone-Refractory Prostate Cancer , 52 Urology 252-56 (1998) ("Sartor") (J.A. 23087-91) evaluates the effects of prednisone on PSA levels in patients with hormone-refractory prostate cancer. J.A. 23087. Sartor discloses a trial in which "[twenty-nine] consecutive patients with hormone-refractory progressive prostate cancer," J.A. 23087, who were not receiving any concomitant anti-cancer therapies, "or any other known confounding variables such as ketoconazole, suramin, aminoglutethimide, or chemotherapy," J.A. 23088, "were treated with 10 mg of oral prednisone prescribed two times a day," J.A. 23087. Sartor also discloses that administration of prednisone alone led to "the average PSA decline compared with [the] baseline [of] 33%" in PSA responses after initiating prednisone treatment; a majority of patients had PSA progression-free survival for a matter of months following treatment. J.A. 23089. Sartor concludes that "[p]rednisone (10 mg orally two times a day) can decrease PSA by more than 50% in approximately one third of patients" and hypothesizes that "a dose-respons[ive] relationship between glucocorticoid dose and PSA decline" exists. J.A. 23087.
III. Procedural History
From July 2015 to August 2017, Appellants filed multiple complaints in the District Court alleging infringement of the '438 patent based on various ANDAs filed by Appellees, which sought approval to market generic abiraterone in 250 mg *1069 tablets. See J.A. 432, 437, 461-62. Appellants later amended their complaints to add additional claims against two new parties, Amerigen in May 2016 and Appellee Teva Pharmaceuticals, USA, Inc. ("Teva") in August 2017, after those parties filed their respective ANDAs. See J.A. 5. In January 2018, the District Court consolidated the cases involving Amerigen and Teva. See J.A. 475. Prior to trial, Amerigen, Mylan, and Wockhardt timely petitioned the USPTO for IPRs of the '438 patent. See J.A. 29276-348 (Amerigen Petition), 35051-126 (Mylan Petition), 41321-400 (Wockhardt Petition).
Amerigen and Mylan's Petitions seeking IPR argued that the Asserted Claims would have been obvious over a combination of three prior art references: (1) O'Donnell; (2) Gerber; and (3)
Similarly, Wockhardt's Petition asserted that the Asserted Claims would have been obvious over a combination of Gerber, O'Donnell, and Sartor.
Wockhardt
,
The District Court denied Appellants' motion to stay the litigation pending the result of the IPRs.
Id
. at 374 n.13. Following a bench trial, and after the IPR proceedings concluded, the District Court issued its opinion finding all Asserted Claims invalid as obvious.
BTG filed separate requests for rehearing against Amerigen, Mylan, and Wockhardt on all three Final Written Decisions, asserting that the PTAB misconstrued the term "treatment" in claim 1 of the '438 patent and improperly determined that the Asserted Claims were obvious. J.A. 29448, 30135, 35725 (Requests for Rehearing).
8
In December 2018, ten months after the filing, the PTAB denied the Requests for Rehearing and explained that the Requests for Rehearing were used "as an opportunity to argue positions with which we disagreed in our Final Written Decision. Merely disagreeing with our analysis or conclusions does not serve as a proper basis for a request for rehearing."
Amerigen Pharm. Ltd. v. Janssen Oncology, Inc.
, No. IPR2016-00286,
DISCUSSION
Appellants assert that the PTAB erred by (1) improperly construing the term "treatment" by not requiring prednisone to have an anti-cancer effect, see Appellants' Br. 29, and (2) relying on that incorrect construction to find that the Asserted Claims would have been obvious over a combination of Gerber, O'Donnell, and Sartor, see id. at 35. After discussing the applicable standards, we address each of Appellants' arguments.
I. Claim Construction
A. Standard of Review and Legal Standard
At the time the Final Written Decisions issued, the PTAB gave "[a] claim ... its broadest reasonable construction in light of the specification of the patent in which it appears."
B. The PTAB Properly Construed the Treatment Limitation of the Asserted Claims
The PTAB construed the Asserted Claims' use of "treatment" as "includ[ing] the eradication, removal, modification, management or control of a tumor or primary, regional, or metastatic cancer cells or tissue and the minimization or delay of the spread of cancer."
Wockhardt
,
The '438 patent 's claims, specification, and prosecution history teach that "treatment" includes both anti-cancer effects and palliation or reduction in side effects of a different anti-cancer drug. We begin our analysis with the claim language and the specification.
In re Power Integrations, Inc.,
The specification states that a "therapeutic agent" may be
either
"an anti-cancer agent
or
a steroid."
If the patentee intended to limit "treating" and "therapeutic agents" to anti-cancer agents, the patentee neither would have identified steroids separately as an agent for reducing adverse side effects of CYP17 inhibitors, nor described prednisone repeatedly in the specification as a steroid without mentioning any anti-cancer
*1072
effect.
See, e.g.,
The prosecution history does not detract from, and if anything, supports the PTAB's construction.
See
Knowles Elecs., LLC v. Iancu
,
Appellants did not distinguish Tannock from the application that led to the '438 patent, but rather just stated that neither Tannock nor O'Donnell "teach or suggest combining prednisone and abiraterone to treat prostate cancer." J.A. 26006. Instead, the Examiner allowed the claims based on Appellants' assertion that their FDA approved abiraterone product was commercially successful, J.A. 26505-07, and the Examiner's finding that "the unexpected commercial success of the launch of the drug [combining abiraterone and prednisone] obviates the" § 103 rejection, J.A. 26113; see J.A. 26047 (explaining, by the Examiner, that "the present invention possesses unexpected results and is non-obvious over the cited art" because, inter alia, a PHOSITA "reading Tannock[ ] would expect there to be no difference in survival between one cancer agent alone, and that same cancer agent in combination with prednisone"). As such, the prosecution history is consistent with the understanding that the claimed "treatment" requires the use of abiraterone coincidingly with prednisone because the claims were not allowable otherwise. We conclude that the PTAB, in light of intrinsic evidence and under the BRI standard, correctly construed "treatment" to mean "the eradication, removal, modification, management or control of a tumor or primary, regional, or metastatic cancer cells or tissue and the *1073 minimization or delay of the spread of cancer."
Appellants' primary counterargument is unavailing. Appellants suggest that, under the "[PTAB's] erroneous construction," of "treatment," a PHOSITA could practice the invention "without having any effect on the cancer itself." Appellants' Br. 36. Appellants assert that based on this construction, the PTAB concluded that the claims would cover "a therapy in which only abiraterone treats cancer," which is "the wrong invention."
II. Obviousness
A. Standard of Review and Legal Standard
"We review the PTAB's factual findings for substantial evidence and its legal conclusions de novo."
Redline Detection, LLC v. Star Envirotech, Inc.
,
A patent claim is invalid "if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a [PHOSITA]."
B. Substantial Evidence Supports the PTAB's Findings Regarding *1074 Obviousness 11
In
Wockhardt
, the PTAB held that the Asserted Claims would have been obvious over a combination of Gerber, O'Donnell, and Sartor.
Substantial evidence supports the PTAB's finding that a PHOSITA would have a reasonable expectation of success in combining Gerber, O'Donnell, and Sartor to arrive at the invention of the Asserted Claims. First, under our claim construction, there is no requirement that prednisone must have an anti-cancer effect. See supra Section I.B. Appellants make no reasonable expectation of success arguments under this construction. Appellants' Br. 38 (arguing only that "[u]nder a [claim construction where prednisone must have an anti-cancer effect], the [PTAB] could not have found the required expectation of success").
Second, even under Appellants' construction, the record shows that a PHOSITA would have a reasonable expectation of success in combining abiraterone and prednisone because they were both together and individually considered promising prostate cancer treatments at the time.
See
J.A. 45665-69. The PTAB found as much when it stated that in the
Wockhardt
IPR, "in which [Wockhardt] relies on Sartor to demonstrate that prednisone has its own anti-cancer effect, ... prednisone would 'treat' prostate cancer" even under Appellants' preferred construction.
Appellants' counterarguments are unavailing. First, Appellants' assertion that the PTAB "did not even consider whether a [PHOSITA] would have had a reasonable expectation of success in achieving the inventions of the '438 patent
as claimed
because the [PTAB] did not have the right claimed invention in mind" lacks merit. Appellants' Br. 22. More specifically, Appellants assert that "[i]n each case, the [PTAB]'s findings on expectation of success concerned something other than the claimed invention because of its erroneous claim construction,"
id.
at 37, and that "[u]nder a proper claim construction, the [PTAB] could not have found the required expectation of success,"
id.
at 38. Appellants argue that because, by 2006, Sartor had "acknowledged that glucocorticoids such as prednisone had not 'demonstrated a survival advantage,' " there was no reasonable expectation of success.
Id.
(citation omitted). The Asserted Claims, however, do not require a survival advantage,
see
'438 patent col. 16 ll. 16-20, and Sartor states that "because no study with [secondary hormonal manipulations] has demonstrated a survival advantage, their potential role is not agreed upon by all," J.A. 44462. While prednisone's effect in combination may have been uncertain at the time, the law only requires a reasonable expectation of success.
See
Pfizer, Inc. v. Apotex, Inc.
,
Second, Appellants assert that the "[PTAB's] erroneous [claim] construction also infected its analysis of objective indicia of non-obviousness." Appellants' Br. 39. Specifically, Appellants assert that "[t]hese [objective] indicia cannot be assessed without
*1076
a clear and correct understanding of the scope of the claims," which it lacked due to an allegedly improper claim construction.
Id.
at 40. Here, however, the PTAB properly construed the claim terms and, therefore, properly understood the scope of the claims.
See
Polaris Indus., Inc. v. Arctic Cat, Inc.
,
Because we conclude that the Asserted Claims are unpatentable as obvious, as the PTAB found in
Wockhardt
, we need not reach the remaining issues on appeal. Appellants challenge to the PTAB's decision in
Amerigen
and
Mylan
, as well as their challenge to the District Court's Final Judgment relating to
BTG
, all pertain to the same Asserted Claims in
Wockhardt
that we have affirmed as unpatentable.
Compare
Wockhardt
,
CONCLUSION 12
We have considered Appellants' remaining arguments and find them unpersuasive. We dismiss as moot the appeals relating to Amerigen , Mylan , and BTG . Accordingly, the Wockhardt Final Written Decision of the U.S. Patent and Trademark Office's Patent Trial and Appeal Board is
AFFIRMED; APPEAL NOS. 2019-1147, 2019-1148, 2019-1323, 2019-1324 DISMISSED
Congress amended § 103 when it enacted the Leahy-Smith America Invents Act ("AIA"). Pub. L. No. 112-29, § 3(c),
When a party challenging the actions taken by an agency in separate appeals and "the decision [in one case] resolves the substantive issues appealed" in the other cases, the other cases are moot.
See
Dep't of Commerce v. U.S. House of Representatives
,
CYP17 is involved in testosterone synthesis and is a key enzyme for both testicular and adrenal synthesis of androgens. '438 patent col. 3. l. 66-col. 4 l. 1; see J.A. 27911 (explaining, in the British Journal of Urology International, that "[t]he two sites thought to produce most of the androgenic steroids in humans are the testis and the adrenal cortex").
Prednisone is a glucocorticoid. '438 patent col. 13 ll. 20-21. "Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic[.]" J.A. 28072 (Predni-SONE® Prescribing Information).
"Ketoconazole was originally developed as an anti-fungal agent effective against a wide variety of pathogenic fungi." J.A. 23053. It was also discovered, however, that "this drug is a potent inhibitor of gonadal and adrenocortical steroid synthesis." J.A. 23053.
The '438 patent explains that hydrocortisone, like prednisone, is a glucocorticoid,
see
'438 patent col. 3 ll. 9-10, and a steroid,
see
Amerigen and Mylan raised the same obviousness challenges and the PTAB ultimately made identical or substantially similar obviousness determinations in both IPRs.
See
Amerigen
,
Appellants first raised the claim construction dispute in their Requests for Rehearing.
See, e.g.,
J.A. 30135-51;
see also
A patent's prosecution history "consists of the complete record of the proceedings before the [US]PTO," which provides "evidence of how the [US]PTO and the inventor understood the patent."
Phillips v. AWH Corp.
,
The PTAB recognized, and Appellants do not contest, that a "therapeutically effective" amount is an amount that is "effective for treating prostate cancer."
See
Wockhardt
,
Because Appellants predicate their obviousness arguments upon their assertion that the "PTAB's erroneous construction infected its analysis of obviousness," Appellants' Br. 35, we need not separately address Appellants' conditional invalidity arguments,
see
Knowles
,
Even if we considered the Appellants' assertion that the District Court erred by considering an obviousness challenge that was barred by
Reference
- Full Case Name
- BTG INTERNATIONAL LIMITED, Janssen Biotech, Inc., Janssen Oncology, Inc., Janssen Research & Development, LLC, Plaintiffs-Appellants v. AMNEAL PHARMACEUTICALS LLC, Amneal Pharmaceuticals of New York, LLC, Dr. Reddy's Laboratories, Inc., Dr. Reddy's Laboratories, Ltd., Wockhardt Bio AG, Wockhardt USA LLC, Wockhardt Ltd., Mylan Pharmaceuticals Inc., Mylan Inc., West-Ward Pharmaceuticals Corp., Nka Hikma Pharmaceuticals USA Inc., Hikma Pharmaceuticals LLC, Teva Pharmaceuticals USA, Inc., Defendants-Appellees Par Pharmaceutical, Inc., Par Pharmaceutical Companies, Inc., Rising Pharmaceuticals, Inc., Defendants BTG International Limited, Janssen Biotech, Inc., Janssen Oncology, Inc., Janssen Research & Development, LLC, Plaintiffs-Appellants v. Amerigen Pharmaceuticals, Inc., Amerigen Pharmaceuticals Limited, Defendants-Appellees Janssen Oncology, Inc., Appellant v. Amerigen Pharmaceuticals Limited, Argentum Pharmaceuticals LLC, Appellees Janssen Oncology, Inc., Appellant v. Mylan Pharmaceuticals Inc., Amneal Pharmaceuticals LLC, Amneal Pharmaceuticals of New York, LLC, Dr. Reddy's Laboratories, Inc., Dr. Reddy's Laboratories, Ltd., Teva Pharmaceuticals USA, Inc., West-Ward Pharmaceutical Corporation, Hikma Pharmaceuticals LLC, Appellees Janssen Oncology, Inc., Appellant v. Wockhardt Bio AG, Appellee
- Cited By
- 16 cases
- Status
- Published