`Tel: 571-272-7822
`Paper 88
`Entered: October 3, 2018
`Celltrion, Inc.
`Patent Owner.
`Case IPR2017-01122
`Patent 7,892,549 B2
`ROBERT A. POLLOCK, Administrative Patent Judges.
`POLLOCK, Administrative Patent Judge.
`Claims 1–11 and 14–17 Shown to Be Unpatentable
`35 U.S.C. § 318(a); 37 C.F.R. § 42.73
`Denying Patent Owner’s Motion to Amend
`35 U.S.C. § 316(d); 37 C.F.R. § 42.121
`Denying Patent Owner’s Motion to Exclude Evidence
`Denying Petitioner’s First and Second Motions to Exclude Evidence
`37 C.F.R. § 42.64
`Granting-In-Part Parties’ Motions to Seal
`37 C.F.R. § 42.55


`Patent 7,892,549 B2
`This is a Final Written Decision in an inter partes review challenging the
`patentability of claims 1–11 and 14–17 of U.S. Patent No. 7,892,549 B2 (Ex. 1001,
`“the ’549 patent”). We have jurisdiction under 35 U.S.C. § 6.
`Having reviewed the arguments of the parties and the supporting evidence,
`we find that Petitioner has demonstrated by a preponderance of the evidence that
`each of the challenged claims is unpatentable.
`Procedural History
`Petitioner Celltrion, Inc. (“Celltrion”)1 filed a Petition requesting inter partes
`review of claims 1–11 and 14–17 of the ’549 patent. Paper 2 (“Pet.”). Patent
`Owner, Genentech, Inc., filed a Preliminary Response to the Petition. Paper 6
`(“Prelim. Resp.”). Based on the record then before us, we instituted trial with
`respect to all challenged claims. Paper 9, 27–28 (“Dec.”).
`After institution of trial, Patent Owner filed a Patent Owner Response (Paper
`28, “PO Resp.”) and Petitioner filed a Reply to the Patent Owner Response (Paper
`45, “Pet. Reply”).
`Patent Owner also filed a Contingent Motion to Amend. Paper 26.
`Petitioner opposed. Paper 42. Patent Owner responded with a Reply in support of
`its motion (Paper 53); Petitioner further submitted an authorized Sur-Reply (Paper
`With respect to technical experts, Petitioner relies on the declarations of
`Robert Earhart, MD., Ph.D. (Exs. 1002, 1054, 1105); Patent Owner relies on the
`1 Petitioner further identifies Celltrion Healthcare Co., Ltd. and Teva
`Pharmaceuticals International GmbH as real parties-in-interest. Paper 10, 2.


`Patent 7,892,549 B2
`declarations of Robert S. Kerbel, Ph.D. (Exs. 2061, 2143), Dr. Susan Tannenbaum
`(Exs. 2062, 2144).
`Patent Owner filed motions for observations on the depositions of
`Dr. Earhart (Papers 69, 72), to which Petitioner provides responses (Papers 76, 80).
`We heard oral argument on May 18, 2018. A transcript of that proceeding is
`entered as Paper 85 (“Tr.”).
`The parties filed the following motions to exclude evidence. Patent Owner
`filed one motion to exclude evidence. Paper 59. Petitioner opposed (Paper 72)
`and Patent Owner submitted a reply in support of its motion (Paper 75). Petitioner
`filed a first motion to exclude evidence. Paper 61. Patent Owner opposed (Paper
`71) and Petitioner submitted a reply in support of its first motion (Paper 80).
`Petitioner filed a second motion to exclude evidence. Paper 81. Patent Owner
`opposed (Paper 83) and Petitioner submitted a reply in support of its second
`motion (Paper 84). Also before us are five unopposed motions to seal pursuant to
`the Modified Default Standing Protective Order governing this case: Papers 27 and
`52 (by Patent Owner) and Papers 44, 47, and 62 (by Petitioner); see also Paper 24
`(entering Modified Default Standing Protective Order (Exhibit 2036) and granting
`Patent Owner’s motion to seal Exhibits 2001–2005, 2007, and 2008).
`Related Applications and Proceedings
`The ’549 Patent issued from Application No. 10/356,824, filed February 3,
`2003, which is a continuation of Application No. 09/208,649, filed Dec. 10, 1998
`(the “649 Application”). U.S. Patent No. 7,846,441 B2 (“the ’441 Patent) issued
`from the ’649 Application on December 7, 2010. The ’549 and ’441 Patents claim
`benefit of priority to Provisional Application No. 60/069,346, filed Dec. 12, 1997
`(“the ’346 application”). See e.g., Ex. 1001, (21), (63) (60), 1:4–9.


`Patent 7,892,549 B2
`In addition to this proceeding, Petitioner has challenged claims 1–14 of the
`related ’441 Patent in copending IPR2017-01121. Petitioner has also filed
`IPR2017-01139 and IPR2017-01140 involving claims of U.S. Patent Nos.
`6,627,196 and 7,371,379, respectively. These two patents are not in the chain of
`priority of the ’549 and ’441 Patents but involve subject matter similar to that at
`issue here.
`The ’549, ’441, ’196, and ’379 Patents are also the subject of pending inter
`partes reviews, IPR2017-00737, IPR2017-00731, IPR2017-00804, and
`IPR2017-00805, respectively, brought by Hospira, Inc. (“Hospira”).2 With respect
`to the ’549 Patent, we refer herein to our Decision to institute trial in
`IPR2017-00737 as the “Hospira Decision.” See Hospira, Inc. v. Genentech, Inc.,
`Case IPR2017-00737 (PTAB July 27, 2017) (Paper 19).
`We issue concurrently our Decisions in IPR2017-00731, IPR2017-00737,
`IPR2017-01139, IPR2017-01140, IPR2017-01121, IPR2017-00804, and IPR2017-
`Patent Owner identifies the following District Court actions, “that relate or
`may relate to U.S. Patent Application No. 10/356,824, which issued as U.S. Patent
`No. 7,892,549:” Celltrion, Inc. v. Genentech, Inc., No. 18-cv-00274 (N.D. Cal.)
`and Celltrion, Inc. v. Genentech, Inc., No. 18-cv-00095 (D. Del.). Paper 33, 2.
`The ’549 Patent and Relevant Background
`According to the Specification, 25% to 30% of human breast cancers
`overexpress a 185-kD transmembrane glycoprotein receptor (p185HER2), also
`known as HER2 (human epidermal growth factor receptor-2) or ErbB2. Ex. 1001,
`2 Hospira also challenged claims of the ’549 and ’441 Patents in IPR2017-00739
`and IPR2018-00016, respectively, which we denied. See IPR2017-00739, Paper
`16; IPR2018-00016, Paper 25.


`Patent 7,892,549 B2
`1:21–32, 5:16–21. These HER2-positive cancers are associated with poor
`prognoses and resistance to many chemotherapeutic regimens including
`anthracyclines (e.g., doxorubicin or epirubicin). Id. at 3:43–52; 4:11–12, and
`11:41–45. Conversely, patients with HER2-positive cancers are three times more
`likely to respond to treatment with taxanes than those with HER2 negative tumors.
`Id. at 3:52–56 (citing Baselga ’97 (Ex. 1007)).
`Although “ErbB2 overexpression is commonly regarded as a predictor of
`poor prognosis,” “a humanized version of the murine anti-ErbB2 antibody 4D5,
`referred to as rhuMAb HER2 or HERCEPTIN®3 has been clinically active in
`patients with ErbB2-overexpressing metastatic breast cancers that had received
`extensive prior anti-cancer therapy.” Ex. 1001, 3:35–61 (citing Baselga ’96
`(Ex. 1020)).4 Anti-ErbB2 4D5 antibodies also “enhance the activity of paclitaxel
`(TAXOL®) and doxorubicin against breast cancer xenographs in nude mice
`injected with BT-474 human breast adenocarcinoma cells, which express high
`levels of HER2.” Id. at 3:56–61 (citing Baselga Abstract 53 (Ex. 1019)). 5
`According to the Specification,
`treatment of disorders
`The present
`invention concerns
`characterized by overexpression of ErbB2, and is based on the
`recognition that while treatment with anti-ErbB2 antibodies markedly
`enhances the clinical benefit of the use of chemotherapeutic agents in
`3 As Patent Owner notes, “HERCEPTIN® is the tradename for the commercial
`product of the humanized antibody, trastuzumab.” Paper 26, 3 fn.2.
`4 Baselga et al., Phase II Study of Weekly Intravenous Recombinant Humantized
`Anti-p195HER2 Monoclonal Antibody in Patients with HER2/neu-Overexpressing
`Metastatic Breast, Cancer, 14(3) J. Clin. Oncol. 737–44 (1996). Ex. 1020.
`5 Baselga et al., Anti Her2 Humanized Monoclonal Antibody (Mab) Alone And In
`Combination With Chemotherapy Against Human Breastcarcinoma Xenografts, 15
`PROC. AM. SOC’Y. CLIN. ONCOL. 63, Abstract 53 (1994) (designated “Baslega ’94”
`in IPR2017-00737). Ex. 1019.


`Patent 7,892,549 B2
`general, a syndrome of myocardial dysfunction that has been observed
`as a side-effect of anthracycline derivatives is increased by the
`administration of anti-ErbB2 antibodies.
`Id. at 3:65–4:5.
`The ’549 Patent, thus, relates to the treatment of breast cancers that
`overexpress HER2/ErbB2 “comprising administering a therapeutically effective
`amount[6] of a combination of an anti-ErbB2 antibody and a chemotherapeutic
`agent other than an anthracycline derivative, e.g. doxorubicin or epirubicin, in the
`absence of an anthracycline derivative to the human patient.” Id. at 4:6–13. In
`some embodiments, the anti-ErbB2 antibody of the combination is Herceptin® and
`the chemotherapeutic agent “is a taxoid, such as TAXOL® (paclitaxel) or a
`TAXOL® derivative.” Id. at 4:23–25. The combination may further include one
`or more additional anti-ErbB2 antibodies, “antibodies which bind to the EGFR . . .
`ErbB3, ErbB4, or vascular endothelial factor (VEGF),” “one or more cytokines,”
`or “a growth inhibitory agent.” Id. at 11:4–40 (defining “chemotherapeutic agent”
`and “growth inhibitory agent”), 23:60–24:5, and 25:20–34.
`The ’549 Patent also provides an Example disclosing the conduct and results
`of a clinical trial involving 469 women with metastatic HER2-positive breast
`cancer. Id. at 26:34–30:25. All patients were treated with one of two
`chemotherapy regimens (CRx) designated either “AC” for anthracycline
`(doxorubicin or epirubicin) and cyclophosphamide, or “T” for Taxol (paclitaxel).
`See id. at 28:5–47; 29:13–30:12. Half of the patients were also treated with the
`anti-ERbB2 antibody Herceptin, designated “H.” Id. The Specification discloses
`6 The Specification defines a “therapeutically effective amount” of the combination
`as “an amount having an antiproliferative effect,” which can be “measured by
`assessing the time to disease progression (TTP) or determining the response rates
`(RR).” Id. at 10:41–50.


`Patent 7,892,549 B2
`that “[a]t a median follow-up of 10.5 months, assessments of time to disease
`progression (TTP in months) and response rates (RR) showed a significant
`augmentation of the chemotherapeutic effect by HERCEPTIN®, without increase
`in overall severe adverse events (AE).” Id. at 29:13–18. In addition, “[a]
`syndrome of myocardial dysfunction similar to that observed with anthracyclines
`was reported more commonly with a combined treatment of AC-H (18% Grade ¾)
`than with AC alone (3%), T (0%), or T+H (2%).” Id. at 30:13–16. According to
`the inventors:
`These data indicate that the combination of anti-ErbB2 antibody
`treatment with chemotherapy markedly increases the clinical benefit,
`as assessed by response rates and the evaluation of disease progression.
`However, due to the increased cardiac side-effects of doxorubicin or
`epirubicin, the combined use of anthracyclines with anti-ErbB2
`antibody therapy is contraindicated. The results, taking into account
`risk and benefit, favor the combined treatment with HERCEPTIN® and
`paclitaxel (TAXOL®).
`Id. at 30:17–25.
`D. Challenged Claims and Reviewed Ground of Unpatentability
`We instituted trial on the sole Ground set forth in the Petition, that claims
`1–11 and 14–17 are unpatentable under 35 U.S.C. § 103 based on the combination
`of Baselga 1996, Seidman 1996,7 Pegram, 8 1995 TAXOL PDR,9 and the
`7 Seidman et al., Her-2/neu Over-Expression and Clinical Taxane Sensitivity: A
`Multivariate Analysis in Patients with Metastatic Breast Cancer (MBC), 15 PROC.
`AM. SOC’Y. CLIN. ONCOL. 104, Abstract 80 (1996). Ex. 1011.
`8 Pegram et al., Phase II Study of Intravenous Recombinant Humanized Anti-p185
`HER-2 Monoclonal Antibody (rhuMAB HER-2) Plus Cisplatin in Patients with
`HER-2/NEU Overexpressing Metastatic Breast Cancer, 14 PROC. AM. SOC’Y.
`CLIN. ONCOL 106, Abstract 124. Ex. 1022.
`9 TAXOL (paclitaxel) for Injection Concentrate, in PHYSICIAN’S DESK REFERENCE,
`682–85 (49th ed. 1995). Ex. 1012.


`Patent 7,892,549 B2
`knowledge of one of ordinary skill in the art. Dec. 27–28; see Pet. 24.
`Claims 1, 5, and 16 are independent. Claim 1, reproduced below, requires
`“administering a combination” of three agents—an anti-ErbB2 antibody, a taxoid,
`and “a further growth inhibitory agent”—“in an amount effective to extend the
`time to disease progression:”
`1. A method for the treatment of a human patient with breast cancer that
`overexpresses ErbB2
`combination of an antibody that binds ErbB2, a taxoid, and a further
`growth inhibitory agent to the human patient in an amount effective to
`extend the time to disease progression in the human patient, wherein
`the antibody binds to epitope 4D5 within the ErbB2 extracellular
`domain sequence.
`Independent claim 16 is similar to claim 1, but further includes a negative
`limitation requiring the administration of an anti-ErbB2 antibody, a taxoid, and a
`further growth inhibitory agent “in the absence of an anthracycline derivative.”
`Independent claim 5 recites “administering an effective amount of a combination”
`of three agents similar to those of claims 1 and 16, wherein the antibody binds to
`the 4D5 epitope of ErbB2, the taxoid is paclitaxel, and the third element is broadly
`described as a “therapeutic agent.”
`Patent Owner does not separately argue the patentability of claims 2–4,
`6–11, 14, 15, or 17.
`Principles of Law
`A claim is unpatentable under 35 U.S.C. § 103(a) 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


`Patent 7,892,549 B2
`person having ordinary skill in the art to which that subject matter pertains.10 KSR
`Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007). The question of obviousness is
`resolved based on underlying factual determinations including: (1) the scope and
`content of the prior art; (2) any differences between the claimed subject matter and
`the prior art; (3) the level of ordinary skill in the art; and (4) objective evidence of
`nonobviousness, if present. Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
`“[T]he [obviousness] analysis need not seek out precise teachings directed to
`the specific subject matter of the challenged claim, for a court can take account of
`the inferences and creative steps that a person of ordinary skill in the art would
`employ.” KSR, 550 U.S. at 418. Moreover, “any need or problem known in the
`field of endeavor at the time of invention and addressed by the patent can provide a
`reason for combining the elements in the manner claimed.” Id. at 420.
`Accordingly, a party that petitions the Board for a determination of unpatentability
`based on obviousness must show that “a skilled artisan would have been motivated
`to combine the teachings of the prior art references to achieve the claimed
`invention, and that the skilled artisan would have had a reasonable expectation of
`success in doing so.” In re Magnum Oil Tools Int’l, Ltd., 829 F.3d 1364, 1381
`(Fed. Cir. 2016) (citations omitted).
`We analyze the instituted ground of unpatentability in accordance with these
`10 The Leahy-Smith America Invents Act, Pub. L. No. 112-29, 125 Stat. 284
`(2011) (“AIA”), amended 35 U.S.C. §§ 102 and 103. Because the challenged
`claims of the ’405 patent have an effective filing date before the effective date of
`the applicable AIA amendments, throughout this Final Written Decision we refer
`to the pre-AIA versions of 35 U.S.C. §§ 102 and 103.


`Patent 7,892,549 B2
`Person of Ordinary Skill in the Art
`Patent Owner argues that we should apply the same definition of a person of
`ordinary skill as set forth in the Hospira Petition, which also involves the ’549
`Patent. Prelim. Resp. 37; PO Resp. 33. In that case, we adopted Petitioner
`Hospira’s definition of one of ordinary skill as “a clinical or medical oncologist
`specializing in breast cancer with several years of experience with breast cancer
`research or clinical trials.” Hospira Decision at 8–9 (quoting IPR2017-00737 Pet.
`6). In the present Petition, however, Celltrion argues that a person of ordinary skill
`in the art as of the effective filing date of the ’549 patent “would have been an
`M.D. with subspecialty training in oncology and substantial experience treating
`breast cancer patients and/or a Ph.D. with substantial experience in researching and
`developing oncologic therapies.” Pet. 43 (citing Ex. 1002, ¶ 29). According to
`Petitioner, “[s]uch an individual would also have had substantial experience in the
`design and/or implementation of clinical trials for breast cancer treatments, and/or
`an active research role relating to breast cancer treatments.” Id.
`For the reasons set forth in our institution Decision, we agree with Patent
`Owner. Dec. 8–9. Petitioner has not explained why its proposed definition better
`defines the level of ordinary skill in the art, nor why its alternative definition would
`have any bearing on the outcome of the present case. We do not discern an
`appreciable difference in the parties’ respective definitions of the level of ordinary
`skill in the art. Indeed, both parties contend that a person of ordinary skill in the
`art would have had experience with breast-cancer research and treatment.
`Accordingly, we adopt Patent Owner’s definition of the level of ordinary skill in
`the art as “a clinical or medical oncologist specializing in breast cancer with
`several years of experience with breast cancer research or clinical trials.” See also
`Hospira Decision, 8–9 (defining the skill level the same way); Ex. 2020 ¶ 78


`Patent 7,892,549 B2
`(implicitly adopting same definition). In any event, as Petitioner does not explain
`why its alternative definition would have any bearing on the outcome of the
`present case, and as we discern no appreciable difference in the parties’ definitions,
`we note our findings and conclusions would be the same regardless of which
`definition were adopted. See PO Resp. 33 (arguing that the challenged claims
`would not have been obvious under either parties proposed definition).
`We further note that the prior art itself demonstrates the level of skill in the
`art at the time of the invention. See Okajima v. Bourdeau, 261 F.3d 1350, 1355
`(Fed. Cir. 2001) (explaining that specific findings regarding ordinary skill level are
`not required “where the prior art itself reflects an appropriate level and a need for
`testimony is not shown”) (quoting Litton Indus. Prods., Inc. v. Solid State Sys.
`Corp., 755 F.2d 158, 163 (Fed. Cir. 1985)).
`Claim Construction
`In an inter partes review, claim terms in an unexpired patent are interpreted
`according to their broadest reasonable construction in light of the specification of
`the patent in which they appear. 37 C.F.R. § 42.100(b); Cuozzo Speed Techs., LLC
`v. Lee, 136 S. Ct. 2131, 2144–46 (2016) (upholding the use of the broadest
`reasonable interpretation standard). “Under a broadest reasonable interpretation,
`words of the claim must be given their plain meaning, unless such meaning is
`inconsistent with the specification and prosecution history.” Trivascular, Inc. v.
`Samuels, 812 F.3d 1056, 1062 (Fed. Cir. 2016). Any special definitions for claim
`terms must be set forth with reasonable clarity, deliberateness, and precision. In re
`Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994).
`“administering a combination”
`In IPR2017-00737 (involving claims 1–17 of the same patent), we initially
`adopted Patent Owner’s unopposed definition of “administering a combination” as


`Patent 7,892,549 B2
`requiring “a single treatment regimen in which the patient receives all drugs that
`are part of the claimed combination.” Hospira Decision, 10. Patent Owner
`subsequently recast its proposed definition “to mean that the drugs are
`administered as part of the same treatment regimen,” which we adopted.
`IPR2017-00737, PO Resp. 37, IPR2017-00737 Final Decision, 11–12. Also in that
`proceeding, we noted that Patent Owner’s two definitions were interchangeable, as
`they would be here. See IPR2017-00737 Final Decision, 12. In the interests of
`clarity and consistency, we again define “administering a combination” to mean
`that the drugs are administered as part of the same treatment regimen.
` “an amount effective to extend the time of disease progression” and
`“an effective amount”
`Independent claims 1 and 16 require administering a combination of an
`anti-ErbB2 antibody, a taxoid, and a further agent, “in an amount effective to
`extend the time to disease progression [TTP] in the human patient.” Claim 5, the
`remaining independent claim before us, similarly recites administering the three-
`part combination to a human patient in “an effective amount.” To the extent that
`these terms may differ in scope, neither party contends that any difference affects
`the patentability analysis and we consider them together.
`In our Decision to Institute, we construed “an amount effective to extend the
`time to disease progression in the human patient” in independent claims 1 and 16
`as an amount sufficient to extend the time to disease progression in a human
`patient having breast cancer that overexpresses ErbB2 receptor as compared to one
`receiving no treatment. Dec. 11–13. We also construed the language “an effective
`amount” of independent claim 5 as encompassing “an amount effective to extend
`the time to disease progression in the human patient” and, thus, similarly indicating
`a comparison to an untreated patient. See id.


`Patent 7,892,549 B2
`Patent Owner disagrees with our construction, contending that the proper
`comparator in both claim terms is not an untreated patient, but to a patient treated
`with taxoid alone. PO Resp. 34–37. In particular, Patent Owner argues that
`comparison to an untreated patient “is not consistent with the specification as
`understood by a POSA,” and “makes no sense in the context of a disease like
`breast cancer.” Id. at 34–35. Yet this is precisely the comparison Applicants made
`to obtain allowance of the challenged claims.
`“A patent’s specification, together with its prosecution history, constitutes
`intrinsic evidence to which the [the Board] gives priority when it construes
`claims.” Knowles Elecs. LLC v. Cirrus Logic, Inc., 883 F.3d 1358, 1361 (Fed. Cir.
`2018). “The purpose of consulting the prosecution history in construing a claim is
`to exclude any interpretation that was disclaimed during prosecution.” Chimie v.
`PPG Indus., Inc., 402 F.3d 1371, 1384 (Fed. Cir. 2005) (internal quotation marks
`omitted). Prosecution disclaimer
`requires that the alleged disavowing actions or statements made during
`prosecution be both clear and unmistakable. Thus, when the patentee
`unequivocally and unambiguously disavows a certain meaning to
`obtain a patent, the doctrine of prosecution history disclaimer narrows
`the meaning of the claim consistent with the scope of the claim
`surrendered. Such disclaimer can occur
`through amendment or
`argument. . . . [and] includes all express representations made by or on
`behalf of the applicant to the examiner to induce a patent grant . . .
`includ[ing] amendments to the claims and arguments made to convince
`the examiner.
`Aylus Networks, Inc. v. Apple Inc., 856 F.3d 1353, 1359 (Fed. Cir. 2017) (internal
`citations and quotations omitted); see Arendi S.A.R.L. v. Google LLC, 882 F.3d
`1132, 1135–36 (Fed. Cir. 2018). Those conditions are satisfied here.
`The claim language “an amount effective to extend the time to disease
`progression” implies that time to disease progression is extended in relation to


`Patent 7,892,549 B2
`some metric, but none of the challenged claims expressly identifies the intended
`comparator. The Examiner addressed this facial ambiguity during the prosecution
`leading to the issuance of the ’549 Patent. In particular, during the prosecution of
`the ’649 Application (the direct predecessor to the ’842 Application, from which
`the ’549 Patent issued), the Examiner rejected then-pending claims under
`35 U.S.C. § 112, second paragraph because:
`The phrase “extend the time to disease progression” . . . is a relative
`term which renders the claim[s] indefinite. The term “extend time to
`disease progression” is not defined by the claim, the specification does
`not provide a standard for ascertaining the requisite degree, and one of
`ordinary skill in the art would not be reasonably apprised of the scope
`of the invention. Specifically, it is never set forth what the extension
`of time to disease progress is relative to, for example, is the extension
`of time to disease progress relative to untreated patients? Patients who
`received antibody or taxoid alone? Patients who received antibody and
`an anthracycline?
`Ex. 3001, 400-402 (OA dated 7/17/01).11 In response, Applicants asserted that:
`the expression[] “extend the time to disease progression”. . . [is] clear
`from the specification (see, in particular, page 15, lines 15-17; and
`pages 42-43) and would be readily understood by the skilled oncologist.
`Clearly, the combination of anti-ErbB2 antibody and taxoid is
`administered in an amount effective to extend the time to disease
`progression relative to an untreated patient.
`Id. at 416 (Response dated 1/17/2001); see also Ex. 3001-1, 19, (15:12–17), 46–47
`(42–43). The Examiner withdrew the rejection in the next office action, stating
`that “[a]ll claims are allowable.” Id. at 624 (OA dated 3/27/2002) (suspending
`prosecution due to potential interference); see also id. at 634–39 (OA dated
`11 Excerpts of prosecution history of US Application No. 09/208,649. Citations
`refer to pages of the exhibit overall rather than to the native pagination.


`Patent 7,892,549 B2
`8/12/2003) (new grounds of rejection not relating to the phrase “extend the time to
`disease progression”).
`Accordingly, Applicants overcame the § 112 rejection by providing an
`express definition of the term “extend the time to disease progression” as meaning
`“relative to an untreated patient.” Our construction reflects Applicants’ choice.
`See In re Paulsen, 30 F.3d at 1480 (holding an applicant may choose to be his own
`Patent Owner contends that “the clinical trial results reported in the ’441
`specification measure efficacy of the combination of an anti-ErbB2 antibody
`(rhuMAb HER2) with a taxoid (paclitaxel) against a control arm of paclitaxel
`alone,” whereas “[t]here is no data in the patent comparing the TTP of patients
`treated with an anti-ErbB2 antibody and a taxoid against an untreated patient.” PO
`Resp. 34–35. That may well be the case; yet, it does not render our construction
`inconsistent with the Specification of the ’441 patent. As Dr. Tannenbaum, an
`expert for Patent Owner, explains, “cancer generally continues to progress without
`treatment.” Ex. 2062 ¶ 133. As a result, an ordinary artisan would have
`understood that, even without any explicit disclosure in the ’549 Patent,
`administering the claimed combinations would extend the TTP as compared to
`untreated patients. See e.g., Ex. 1002 ¶ 111 (Dr. Earhart indicating that the choice
`of claim construction does not impact the obviousness analysis); Ex. 1054 (Dr.
`Earhart testifying that “a person of ordinary skill would have had a reasonable
`expectation that a combination treatment with paclitaxel and trastuzumab would
`extend the time to disease progression relative to treatment with paclitaxel and
`relative to no treatment”); id. ¶ 24 (same analysis with respect to proposed
`amended claims).


`Patent 7,892,549 B2
`With respect to the prosecution history, Dr. Tannenbaum testifies that, “in
`context,” Applicants used the term “untreated patient” to refer to “a patient that
`had not received the combination therapy, but instead received paclitaxel alone.”
`Ex. 2062 ¶ 138. We do not find Dr. Tannenbaum’s argument persuasive.
`The Examiner asked Applicants to choose from various potential meanings
`for the claim language: “is the extension of time to disease progress[ion] relative
`to untreated patients? Patients who received antibody or taxoid alone? Patients
`who received antibody and an anthracycline?” Ex. 3001, 401–402. Despite being
`presented with the option of selecting “taxoid alone” as the comparator, Applicant
`did not do choose that option. Applicant instead specifically excluded that
`possibility. Id. at 416 (stating “[c]learly, the combination of anti-ErbB2 antibody
`and taxoid is administered in an amount effective to extend the time to disease
`progression relative to an untreated patient”) (emphases added). Indeed,
`Dr. Tannenbaum admitted that much at her deposition in the related Hospira case,
`agreeing that “there can be no confusion” that Applicants were “choosing the
`comparator untreated patients rather than taxoid alone.” See IPR20117-00737
`Ex. 1087, 225:15–226:13.
`For the reasons set forth above, we maintain that the proper analysis of the
`claim language “in an amount effective to extend the time to disease progression
`[TTP] in the human patient” and administering the three-part combination to a
`human patient in “an effective amount” involves comparing the claimed
`combination treatments to no treatment. To the extent Patent Owner is correct that
`our construction “makes no sense in the context of a disease like breast cancer”
`(PO Resp, 35), Applicants chose this definition “with reasonable clarity,
`deliberateness, and precision,” and obtained the ’549 Patent only after doing so.
`See In re Paulsen, 30 F.3d at 1480. Under such circumstances, we must give the


`Patent 7,892,549 B2
`term the construction the applicant set out, even if such construction would lead to
`a “nonsensical result.” Source Vagabond Sys. Ltd. v. Hydrapak, Inc., 753 F.3d
`1291, 1301 (Fed. Cir. 2014).
`D. Asserted Ground of Unpatentability
`Petitioner challenges claims 1–11 and 14–17 as unpatentable under
`35 U.S.C. § 103 based on the combination of Baselga 1996, Seidman 1996,
`Pegram, 1995 TAXOL PDR, and the knowledge of one of ordinary skill in the art,
`evidenced, in part, by Baselga Abstract 53, Baselga Abstract 2262,12 and Seidman
`1995.13 See Pet. 43–53; Pet Reply 4–22. Patent Owner opposes.14 PO Resp. 37–
`We begin with an overview of the above-recited references.
`Overview of Baselga 1996 (Ex. 1020)
`Baselga 1996 teaches that “[i]n preclinical studies . . . rhuMAb HER2
`markedly potentiated the antitumor effects of several chemotherapeutic agents,
`including cisplatin, doxorubicin, and paclitaxel, without increasing their toxicity.”
`Ex. 1020 at 9 (citing Baselga Abstract 53). As a result, “[l]aboratory studies of the
`12 Baselga et al., Antitumor Activity of Paclitaxel in Combination with Anti-growth
`Factor Receptor Monoclonal Antibodies in Breast Cancer Xenografts, 35 PROC.
`AM. ASS’N FOR CANCER RES. 380, Abstract 2262. Ex. 1021.
`13 Seidman et al., Memorial Sloan-Kettering Cancer Center Experience with
`Paclitaxel in the Treatment of Breast Cancer, 22(5) Suppl. 12 SEMINARS
`ONCOLOGY 108–16. Ex. 1010.
`14 Although Patent Owner objects to Petitioner’s reliance of references other than
`Baselga 1996, Seidman 1996, Pegram, 1995 TAXOL PDR (PO Resp. 37, n.12.) to
`establish the knowledge of one of ordinary skill in the art, “it is permissible, and
`sometimes even necessary, to establish such background knowledge by pointing to
`other prior art.” Rovalma, S.A.

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