or _a solvate thereof, wherein the compound is administered in one or more cycles, each of which comprises administering the compound for a period of time followed by a period of rest.
1, “A method of treating multiple myeloma”? Celgene Defendants* The Court “A method of treating multiple myeloma” is “A method of treating “A method of treating limiting, such that the term multiple myeloma” is not multiple myeloma” is not requires efficacy in treating limiting. limiting. multiple myeloma.
The parties dispute whether the preamble of the method of treatment patents should be construed as limiting. Celgene argues that the phrase “treating multiple myeloma” in the preamble limits the claim by requiring efficacy in patients who received pomalidomide. (Celgene Open. Br. at 5). Defendants argue to the contrary. (Def. Open. Br. at 4). Before discussing the merits of the parties’ arguments, the Court first addresses Defendants’ argument regarding the proper test to apply to construe the preamble. At oral argument, Defendants argued for the first time that, in Boehringer Ingelheim v. Schering-Plough, 320 F. 3d 1339 (Fed. Cir. 2003), the Federal Circuit
3 This disputed term appears in asserted claims 1—2, 4-16, 18-27, and 29 of the ’262 Patent; claims 1-14 and 16-35 of the ?3,939 Patent; and all claims of the ’428 Patent. (Am. Joint Stmt. at 4). 4 Apotex and Hetero initially proposed that the preamble is not limiting; but to the extent that the Court holds that the preamble is limiting, Apotex and Hetero proposed that the term should be construed as “[a] method of administering pomalidomide, or a pharmaceutically acceptable salt, solvate, stereoisomer thereof, after the onset of symptoms of multiple myeloma.” (D.E. No. 251 (“Celgene Open. Br.) at 5). Apotex and Hetero have since withdrawn their alternative construction and joined the other defendants in their proposed claim construction. (D.E. No. 250 (“Def. Open. Br.”) at 4 n.4).
laid out a two-step process where, first and foremost, the Court must apply the Federal Circuit’s guidance and principles to decide whether a preamble is a limitation. (See D.E. No. 649 (“Markman Tr.”) at 30:15–23 & 32:2–12). Counsel further argued that “if, and only if” the Court finds that the preamble is a limitation, the Court then construes what the preamble means. (Id. at
32:13–33:11). The Court agrees that, in Boehringer, the Federal Circuit first affirmed that the disputed term in the preamble imposed a limitation on the claim, then concluded that the district court also “gave the term its proper construction.” 320 F. 3d at 1345. But nothing in Boehringer suggests that the Federal Circuit established an analytic framework under which courts must construe a preamble. See generally id. It certainly makes sense to use the two-step analysis, when, for example, finding that a disputed term imposes a limitation does not resolve the parties’ dispute. See, e.g., Boehringer, 320 F.3d at 1345–56; Computer Docking Station Corp. v. Dell, Inc., 519 F.3d 1366 (Fed. Cir. 2008). However, where, as here, the analyses of whether the preamble is limiting and what the preamble means are necessarily intertwined, neither the Federal Circuit nor the district courts have construed the disputed terms using such a rigid multi-step test. See, e.g.,
Symantec Corp. v. Computer Assocs. Int’l, Inc., 522 F.3d 1279, 1289–90 (Fed. Cir. 2008) (construing the terms in the preamble before holding that the preamble does not impose a separate claim limitation); Sanofi-Aventis U.S. LLC v. Fresenius Kabi USA, LLC, No. 14-7869, 2016 WL 5898627 (D.N.J. Oct. 7, 2016) (spontaneously construing the preamble language and analyzing whether it is limiting). The Court will thus analyze the disputed preamble language based on “the facts of [the] case in light of the overall form of the claim, and the invention as described in the specification and illuminated in the prosecution history.” Applied Materials, 98 F.3d at 1573. Defendants argue that courts around the country have found that the plain and ordinary meaning of the word “treating” means “to seek cure or relief of” a disease. (See Markman Tr. at 24:10–26:17). According to Defendants, “treating” is “a broader concept than just efficacious treatment,” and includes ineffective treatment and palliative care where the treatment targets the symptoms and not the underlying condition. (Id. at 25:17–21). Defendants point out that the specification supports this broader concept and states that “[a]s used herein, unless otherwise
specified, the term ‘treating’ refers to the administration of a compound of the invention or other additional active agent after the onset of symptoms of the particular disease or disorder.” (Def. Open. Br. at 8 (quoting ’262 Patent at 16:11–15)5). Celgene does not appear to dispute that the plain and ordinary meaning of the word “treating” includes more than efficacious treatment but argues that the specification’s definition of “treating” does not define the disputed phrase “a method of treating multiple myeloma.” (D.E No. 384 (“Celgene Resp. Br.”) at 6–7). Celgene contends that “treating” and “multiple myeloma” cannot be construed separately. (See Celgene Resp. Br. at 7). Rather, the full phrase, “treating multiple myeloma,” was used throughout the prosecution history to require efficacy, without which “the invention would lose its entire purpose.” (See id. & Celgene Open. Br. at 7).
While the Court agrees that the disputed term, “treating multiple myeloma,” must be construed in its entirety, nothing in the claim language, the specification, or the prosecution history warrants reading into the claim an efficacy limitation based on the preamble. The Court begins its claim construction with the language of the claim. See Innova/Pure Water, Inc. v. Safari Water filtration Sys., Inc., 381 F.3d 1111, 1116 (Fed. Cir. 2004) (“Claim construction analysis must begin and remain centered on the claim language itself, for that is the language the patentee has chosen to particularly point out and distinctly claim the subject matter which the patentee regards as his
5 The parties agree that the ’262 Patent, the ’3,939 Patent, and the ’428 Patent share a common specification. (Celgene Open. Br. at 7 n. 9; Defs. Open. Br. at 5 n.7). For the sake of brevity, the Court’s citations to the specification of the ’262 Patent include the corresponding citations to the ’3,939 Patent and the ’428 Patent. invention.”) (internal quotation marks and alterations omitted). It is important to note that the parties do not dispute that the preamble does not provide any antecedent basis for terms in the body of the claim. (Def. Open. Br. at 5–8; Markman Tr. at 10:17–21). While Celgene argues that the patentability of the MOT claims “hinge[s] upon” the presence of the preamble in the claim
language, Celgene’s argument is not grounded in the language of the claim itself. (See Celgene Open. Br. at 11–12). For example, this is not a case where the preamble “sets forth the objective of the method, and the body of the claim directs that the method be performed on someone ‘in need.’” Jansen, 342 F.3d at 1333; see also Rapport v. Dement, 254 F.3d 1053, 1059 (Fed. Cir. 2001). Nor does Celgene argue that a term used in the preamble provides antecedent basis because the same term is used in the body of the claim. See Pacing Techs., LLC v. Garmin Int’l, Inc., 778 F.3d 1021, 1024 (Fed. Cir. 2015). Indeed, Celgene advances no argument based on the language of the claims. The Court thus agrees with Defendants that the claim language strongly suggests that the preamble is independent from, and not limiting to, the body of the claim, and the steps of the claimed method at issue are “performed in the same way regardless whether or not the patient
experiences [any efficacy].” See Bristol-Myers Squibb Co. v. Ben Venue Labs, Inc., 246 F.3d 1368, 1375 (Fed. Cir. 2001). The Court is also not persuaded that statements in the specification identified by Celgene compel a finding that that the preamble at issue here sets forth “the essence or a fundamental characteristic[s] of the claimed invention[s].” (See Celgene Open. Br. at 10). Celgene points to the “Background” section of the specification, which identifies “a significant need for safe and effective methods of treating, preventing and managing cancer . . . , particularly for diseases that are refractory to standard treatments . . . .” (Id. at 7 (quoting ’262 Patent at 3:8–11) (emphasis Celgene’s)). The specification then states, under “Summary of the Invention,” that “[t]he methods comprise administering to a patient in need of such treatment or prevention a therapeutically or prophylactically effective amount of an immunomodulatory compound, or a pharmaceutically acceptable [alternative] thereof.” (Id. at 8 (quoting ’262 Patent at 3:41–47) (emphasis Celgene’s)). Celgene further points to various places in the specification where the patentee discusses
combination therapies, dosing cycles, and examples in terms of efficacy. (Id. at 8–9). In response, Defendants essentially argue that, if efficacy is a “fundamental or essential feature” of the invention, the patentee could have drafted the claims to require efficacy or included clinical data to substantiate it. (D.E. No. 385 (“Def. Resp. Br.”) at 11–12). The cases Defendants rely on do not support the proposition that efficacy, as a fundamental or essential feature, must be supported by clinical data. See Hoffman-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2004). However, the Court agrees that the statements in the specification merely stated that the intended use or purpose of the claimed invention is to achieve “safe and effective” treatment. None of the cited portions of the specification suggests that efficacious treatment is a limitation of the claims. See Sanofi-Aventis, 2016 WL 5898627 at *5
(finding that the preamble “a method of increasing the survival” is not limiting and that the specification’s statement that “an aspect of the invention comprises increasing the survival of a patient [at issue] . . . merely appears to describe the purpose of the invention”); Novartis Pharmaceuticals Corp. v. Accord Healthcare Inc., 387 F. Supp. 3d 429, 437–38 (D. Del. 2019) (holding that the efficacy is not a limitation despite the patentee’s argument that efficacy is “the core of the invention” and where the specification stated that “there is a need for agents which are effective in the inhibition or treatment of . . . multiple sclerosis”). Moreover, nothing in the specification supports Celgene’s argument that “treating” and “multiple myeloma” are so “inextricably intertwined” such that it is inappropriate to construe the entire phrase by construing “treating” separately. (See Celgene Resp. Br. at 7). Other than in the claims, “treating multiple myeloma” appears only in the patent’s title. (’262 Patent at 1:1–2). Where the specification discusses “multiple myeloma” or “patients with multiple myeloma,” the words “treat,” “treating,” or “treatment” are either not used, or are used without an efficacy
requirement. See, e.g., ’262 Patent at 18:24–27 (“In a specific embodiment, [Actimid™] may be administered in an amount of about 1, 2, or 5 mg per day to patients with relapsed multiple myeloma.”) (emphasis added); id. at 19:34–37 (“In a specific embodiment, Revimid™ is administered to patients with relapsed or refractory multiple myeloma in an amount of about 15 mg/d twice a day or about 30 mg/d four times a day in a combination with dexamethasone.”) (emphasis added); id. at 33:44–46 (“Once the [maximum tolerance dose] has been identified, four additional patients are enrolled at that dose level so that a total of 10 patients is treated at the MTD.”); id. at 35:53–54 (“In this study, the first cohort of 3 patients was treated for 28 days at 5 mg/day without any dose limiting toxicity . . . .”). The Court thus finds that nothing in the specification compels a finding that the patentee intended “treating multiple myeloma” to deviate
from the plain and ordinary meaning of the term “treating,” such that the claims require efficacy. Celgene also argues that the preamble is limiting because “it is the basis upon which the Patent Office allowed the claims.” (Celgene Open. Br. at 11). During the prosecution of the ’3,939 Patent and the ’428 Patent, the patentee submitted evidence of “unexpected results” to overcome an obviousness rejection and argued that “one skilled in the art would not have expected that pomalidomide would be able to treat multiple myeloma that is relapsed after or refractory to prior treatment.” (D.E. No. 251-3, Ex. 10 (“Celgene Ex. 10”) at CELPOM00001074 (emphasis Celgene’s); id., Ex. 11 at CELPOM000001375) (emphasis Celgene’s)). In a subsequent Applicant-Initiated Interview Summary, the Examiner essentially agreed with the patentee and stated that “the claims, as is, are patentable because pomalidomide (POM) alone was shown to unexpectedly treat multiple myeloma that is or has become resistant to lenalidomide (LEN), a structurally close analog of POM that is known to be effective for treating multiple myeloma.” (Id., Ex. 12 at CELPOM00001113). Celgene thus argues that the prosecution history shows that
“the claims issued only because the inventors demonstrated to the Examiner that their invention was efficacious against” multiple myeloma. (Celgene Open. Br. at 12). Celgene further argues that, when the patentee and the Examiner referred to “‘treat[ing] multiple myeloma’ in the prosecution history, they meant that pomalidomide was providing efficacy against” multiple myeloma. (Id.). Defendants argue that the “unexpected results” cannot define the scope of the claims because: (i) the data was generated after the priority date; (ii) the “unexpected results” were not commensurate in scope with the claimed invention; (iii) the unexpected results were never submitted in the ’262 Patent, which is the first patent issued in the family; and (iv) Celgene did not present the “unexpected results” as a necessary feature of the invention, but merely as a result of
carrying out the claimed methods. (Def. Resp. Br. at 4–5 & 8–11). The Court finds merit in Defendants’ argument that reliance on unexpected results to show nonobviousness does not limit or otherwise define the scope of the claim. See Takeda Pharm. Co. v. Actavis Labs. FL, Inc., No. 15-451, 2016 WL 3193188, at * (D. Del. June 6, 2016) (stating that unexpected results “do not define the claimed invention in any real respect—they merely state one of the intended results or purposes of the claimed invention”); Viiv Healthcare UK Ltd. v. Lupin Ltd,, 904 F. Supp. 2d 379, 386–87 (D. Del. 2012) (holding that, unlike arguments made to overcome rejection of anticipation, unexpected results submitted and argued to prove nonobvious did not “require the claims to be narrowed, distinguished, or amended”); McNeil-PPC, Inc. v. Perrigo Co., 443 F. Supp. 2d 492, 505 (S.D.N.Y. 2006) (stating that the courts cannot “mechanically import limitations from the [unexpected] test results into the claims”). The argument is particularly strong here because the unexpected results were generated after the priority date. (See Def. Resp. Br. at 4). But more importantly, the Federal Circuit’s en banc
opinion in Purdue Pharma L.P. v. Endo Pharm. Inc. is directly on point. 438 F.3d 1123 (Fed. Cir. 2006). There, in response to an obviousness rejection, the patentee told the PTO that its claimed oxycodone formulation was distinguishable from the prior art because the patentee had “surprisingly discovered” that the four-fold range of dosages achieves the same clinical results as the prior art formulation using an eight-fold range. See id. at 1130. Based on this “discovery,” which overcame the obviousness rejection, the trial court construed the claims to be “limited to a four-fold dosage range that controls pain for 90% of patients.” Id. at 1135. The Federal Circuit disagreed and held that the four-fold range was not a “necessary feature of the claimed oxycodone formulations.” Id. at 1136. Rather, the court explained that the four-fold range was “a property of, or a result of administering, the oxycodone formulation characterized” by the limitations set
forth in the body of the claims. Id. Similarly here, the unexpected efficacious treatment of relapsed or refractory multiple myeloma with pomalidomide was merely a “result of administering” the claimed invention. Celgene thus fails to distinguish Purdue and establish that the prosecution history demonstrates that the patentee intended efficacy to be a “necessary feature” of the claimed methods. See id.; Sanofi-Aventis, 2016 WL 5898627, at *6 (holding that “[w]hile the Examiner noted the unexpected result in allowing the patent, [p]laintiffs have failed to show that the claims require the unexpected results”). Moreover, the Court is not persuaded that the inventors consistently used “treat[ing] multiple myeloma” in the prosecution history to mean efficacious treatment. (Celgene Open. Br. at 12). As evidence to support the “unexpected results,” Celgene submitted to the Patent Office a declaration by Dr. Anjan Thakurta during the prosecution of the ’3,939 Patent. (D.E. No. 250-11 at 75 (ECF Pagination)6). Dr. Thakurta explained the results of Phase I and Phase II clinical studies where patients with relapsed or refractory multiple myeloma were treated with single-agent
pomalidomide in a cyclic regimen as recited in the claims of the ’3,939 Patent. (Id. at 76). Dr. Thakurta further stated that, based on these clinical data, the FDA “has approved the use of pomalidomide alone for treating patients with multiple myeloma,” where such condition was relapsed or refractory. (Id. at 76–77) (emphasis added). Thus, as used in the very declaration Celgene relied on to prove unexpected efficacy, the phrase “treating patients with multiple myeloma” clearly did not require efficacy—it is insensible to understand the statement to mean that the FDA only approved the use of pomalidomide when it efficaciously treated patients. Therefore, contrary to Celgene’s argument, the applicant does not consistently use “treating [patients with] multiple myeloma” to mean efficacious treatment, and it is thus improper to import an efficacious limitation from the prosecution history into the claims. See Metabolite Labs., Inc.
v. Lab. Corp. of Am. Holdings, 370 F.3d 1354, 1360 (Fed. Cir. 2004) (“the patent applicant’s consistent usage of a term in prosecuting the patent may enlighten the meaning of that term.”); Purdue, 428 F. 3d at 1136–37. Finally, as the other example that applicant clearly relied on the preamble to distinguish prior art during prosecution, Celgene refers to arguments made during the prosecution of the ’262 Patent. (Celgene Resp. Br. at 9). Specifically, Celgene explains that the Examiner rejected all pending claims for obviousness over the combination of three prior art references: United States Patent No. 5,635,517 (the “’517 Patent”), an article dubbed “Davies,” and United States Patent
6 Unless stated otherwise, the Court’s citations to the prosecution history refer to the pagination generated by the Court’s ECF system. No. 6,555,554. (D.E. No. 250-3 at 27). To overcome the obviousness rejection, the applicant argued that, inter alia, the Examiner’s reliance on Davies is misplaced because Davies would not motivate a POSA to choose more potent TNF-α inhibitors, such as pomalidomide, to treat multiple myeloma. (Id.). The applicant submitted publications to show that “potent known TNF-α
inhibitors failed in treating multiple myeloma.” (Id.) (emphasis added). The applicant further stated that, for example, Enbrel®, which is a well-known TNF-α inhibitor, “did not have anti- myeloma activity. Thus, not all TNF-α inhibitors treat multiple myeloma.” (Id.). Based on these statements, Celgene argues that the applicant “relied on the express language of the preamble in disclaiming ineffective treatments from the scope of the claimed inventions.” (Celgene Resp. Br. at 9). In response, Defendants urge that the Federal Circuit has established a high standard for “clear reliance” on preamble, where, after the applicant disparaged the prior art, the applicant must “put their hands on the preamble” and argue that, “by contrast,” the claimed invention is distinct. (Markman Tr. at 82:3–20 & 84:8–85:25). Defendants argue that, because the applicant only used
the preamble language to characterize the prior art, without relating back to the claimed invention, it was insufficient to find “clear reliance” on the preamble such that the preamble imports an efficacy limitation. The Court is not persuaded that the law requires such a formalistic approach. The cases Defendants rely on only show that “clear reliance on the preamble” was found where the applicant explicitly distinguished the claimed invention after disparaging the cited reference. See, e.g., Roundtable Techs. LLC v. Motorola Mobility LLC, 567 Fed. Appx. 941, 943 (Fed. Cir. 2014). The Court agrees, however, that Celgene fails to establish clear reliance on the preamble because the applicant’s arguments made to distinguish the prior art were insignificant to patentability. Indeed, when the Examiner withdrew the obviousness objection, he stated that “[a]pplicant’s arguments, see page 7, 2nd full paragraph, filed 12/23/2010, with respect to the rejections of the claims under 35 U.S.C. 103(a) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn.” (D.E. No. 250-4 at 28). In the paragraph the
Examiner referenced, the applicant argued that another prior art reference, the ’517 Patent, was also misplaced because it does not disclose “the treatment of multiple myeloma with thalidomide and dexamethasone, much less the cyclical treatment.” (Id. at 54). In other words, the applicant overcame the obviousness rejection based on arguments that were irrelevant to Davies, to efficacious treatment, or to arguments made based on the preamble to distinguish Davies. Because the applicant’s argument invoking the preamble had no bearing on the Examiner’s decision to withdraw the obviousness rejection, the efficacy requirement that purportedly distinguished Davies and other TNF-α inhibitors was insignificant for patentability. Thus, the applicant’s reliance on the preamble to distinguish prior art does not amount to clear reliance, nor does it compel reading an efficacy limitation into the claim. See Catalina, 289 F. 3d at 810 (holding that,
where the Examiner considered the feature recited in the preamble insignificant for patentability, the applicant’s statements distinguishing the prior art based on such feature “do not indicate a clear reliance on the preamble”). For the foregoing reasons, the Court adopts Defendants’ proposed construction and holds that the preamble of the claims in the MOT patents, “a method of treating multiple myeloma,” is not limiting. 2. “about 1 mg to about 5 mg per day of a compound having the formula [of pomalidomide] or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof” and “about 1 mg to about 5 mg of a compound having the formula [of pomalidomide] or a solvate thereof”7 Celgene Defendants The Court “about 1 mg to about 5 mg “about 1 mg to 5 mg ... of a “about 1 mg to about 5 mg per day of a compound compound having the per day of a compound having the formula [of formula [of pomalidomide] having the formula [of pomalidomide] or a or about 1 mg to 5 mg of a pomalidomide] or a pharmaceutically acceptable pharmaceutically acceptable pharmaceutically acceptable salt, solvate, or stereoisomer salt or solvate of salt, solvate, or stereoisomer containing about 1 mg to [pomalidomide] or about 1 containing about 1 mg to about 5 mg per day of a mg to 5 mg of any single about 5 mg per day of a compound having the stereoisomer of compound having the formula [of pomalidomide]” [pomalidomide]” formula [of pomalidomide]” and and and “about 1 mg to about 5 mg “about 1 mg to 5 mg ... of a “about 1 mg to about 5 mg per day of a compound compound having the per day of a compound having the formula [of formula [of pomalidomide] having the formula [of pomalidomide] or a solvate or about 1 mg to 5 mg of a pomalidomide] or a solvate containing about 1 mg to solvate of [pomalidomide]” containing about 1 mg to about 5 mg per day of a about 5 mg per day of a compound having the compound having the formula [of pomalidomide]” formula [of pomalidomide]”
The MOT patents claim methods of treatment using pomalidomide compound in its free base form, as well as pomalidomide in the form of “a pharmaceutically acceptable salt, [ ] solvate, [or] stereoisomer.” See, e.g., ’262 Patent, Claim 1. When the drug is a pharmaceutically acceptable salt or solvate of pomalidomide, the active moiety of the drug, which is the portion that is responsible for the physiological or pharmacological action, remains the same. However, depending on the weight of the additional molecules that are added to the active moiety, the overall weight of pomalidomide salt and pomalidomide solvate varies. The parties thus dispute whether the weight requirement in the disputed terms, “about 1 mg to 5 mg,” applies to the active moiety
7 These disputed terms appear in asserted claims 1–2, 4–16, 18–27, and 29 of the ’262 Patent; claims 1–14 and 16–35 of the ’3,939 Patent; and all claims of the ’428 Patent. (Am. Joint Stmt. at 4). only (as Celgene proposes), or to the entire pomalidomide salt and pomalidomide solvate (as Defendants propose). (See, e.g., Def. Open. Br. at 12; Celgene Open. Br. at 14). Celgene argues that the word “thereof” in the disputed terms refers back to everything that precedes the word ‘or’, which includes the specifically claimed amounts of pomalidomide.
(Celgene Open. Br. at 14; Celgene Resp. Br. at 13). Accordingly, Celgene contends that the claims are directed to the use of “salt, solvate, or stereoisomer of pomalidomide that is equivalent to the about 1 mg to about 5 mg of pomalidomide free base.” (Celgene Resp. Br. at 13). Defendants, on the other hand, rely on the word “or” in the disputed terms, and argue that it “identif[ies] different, alternative forms for the active ingredient.” (Def. Open. Br. at 13). According to Defendants, “about 1 mg to about 5 mg refers to the amount of each of the claimed forms of pomalidomide, including pomalidomide free base, pomalidomide salt, pomalidomide solvate, and a single pomalidomide stereoisomer.” (Def. Resp. Br. at 18). Essentially, under Celgene’s proposed construction, the claims are directed to treatment using the same dose of active moiety, regardless of the form of the drug (i.e., free base, salt, solvate, or isomers). To the contrary, under Defendants’
proposed construction, the claims are directed to treatment using varying amounts of active moiety, because the total weight of the drug remains the same regardless of the drug form. The Court agrees with Celgene. Defendants essentially argue that a plain reading of the claims support their construction, because the word “or” identifies “different, alternative forms of the active ingredient,” to which “about 1 mg to 5 mg” must be applied equally. (Def. Open. Br. at 12–13 (“Defendants’ proposed constructions merely follow the language of the claims by stating that the ‘about 1 mg to about 5 mg’ weight limitation applies to the alternative forms of the administered drug . . . .”); Def. Resp. Br. at 18 (“Defendants’ proposed construction is based on a plain reading of the unambiguous language of the claims.”)). But an “ordinary meaning” of a claim term is merely a “short-hand for the appropriate connotation under the law: the meaning, to a person of ordinary skill in the art.” See Combined Sys., Inc. v. Def. Tech. Corp. of Am., 350 F.3d 1207, 1216 n.6 (Fed. Cir. 2003) (citing Teleflex, Inc. v. Ficosa N. Am. Corp., 299 F.3d 1313, 1325 (Fed. Cir 2002)). Absent certain established exceptions, and Defendants have argued none, “a
plain and simple reading” of the claim terms cannot deviate from the “objective base line from which to begin claim interpretation;” that is, “how a person of ordinary skill in the art understands a claim term.” See Phillips, 415 F.3d at 1313. Here, Defendants’ own expert, Dr. Kinam Park, agreed during a deposition that a person of ordinary skill in the art (“POSA”) would understand that “in pharmacotherapeutics, it is the pharmacologically active moiety of a drug compound that is responsible for the therapeutic response.” (D.E. No. 384-1, Ex. 26 (“Park Depo. Tr.”) at 108:11–20). Here, that pharmacologically active moiety is the pomalidomide, and “specifically, the free base of pomalidomide.” (Id. at 109:12–19). Dr. Park further agrees that a POSA would understand that when “a different form of a drug is used to satisfy formulation requirements[,] the quantity of the
pharmacologically active drug moiety is maintained at the desired therapeutic dose or concentration.” (Id. at 110:14–111:7). Dr. Park further opined, and the Court agrees, that “nothing in the specifications of the MOT patents indicates that the calculations should be performed contrary to accepted practice in the field.” (D.E. No. 250-32 (“Park Decl.”) ¶ 61). Thus, based on Dr. Park’s own opinion, the standard practice in the field is that the same amount of pharmacologically active moiety must be administered to a patient, regardless of whether the drug is in the form of a salt, solvate, or stereoisomer. This construction is supported by other extrinsic evidence, including evidence Dr. Park references to demonstrate what a POSA would consider as “relevant and reflective of the state of prior art at the time” of the invention. (Park Decl. ¶ 59 & D.E. No. 250-39). For example, based on the 2010 Ansel textbook titled “Pharmaceutical Calculations” (“2010 Ansel”), among others, Dr. Park stated that “it is the standard practice to take into account the weight of the entire compound, including the weight of the proton and counterion or solvent molecules, when the
active moiety is described as taking the form of a salt or solvate.” (Park Decl. ¶ 59). Similarly, to support that the weight requirement of the claims applies to the entire molecule, Defendants emphasized that pharmaceutical calculations must “account for the active ingredient, or active moiety, and water content of drug substances.” (Def. Open. Br. at 14–15). However, 2010 Ansel itself states that, as “objectives” of calculation of active drug moiety, [a] pharmacist must be able to calculate the pharmacologically active drug (chemical) moiety when present in salt, ester, hydrated, or complex chemical form. Such calculations are essential when quantitatively comparing products of the same drug moiety but differing in chemical form. The calculations are applied in compounding procedures in which a different form of a drug is used to satisfy formulation requirements while the quantity of the pharmacologically active drug moiety is maintained at the desired therapeutic dose or concentration. (D.E. No. 250-39 (“Park Decl. Ex. 7”) at 325) (emphasis added). In other words, Defendants’ own extrinsic evidence shows that, by “taking into account” the molecular weight of the entire molecule of different drug products, the objective of pharmaceutical calculation is, indeed, to maintain the same therapeutic dose or concentration. That is, to maintain the same amount of active drug moiety. Finally, Defendants argue that “stereoisomer” should be construed to mean “any single stereoisomer.” (Def. Open. Br. at 15). According to Defendants, the chemical structure of pomalidomide free base as depicted in the disputed terms already includes combinations of stereoisomers; a POSA thus would have understood the portion of the claim that involves “stereoisomer” to mean “about 1 mg or 5 mg of any single stereoisomer.” (Id.). Celgene proposes no construction for this term and provides no support for its position, except for referencing “stereoisomer” along with “salt” and “solvate” and arguing that “the claims call for treatment with about 1 [mg] to about 5 mg of pomalidomide itself, regardless of whether the pomalidomide is in the form of a salt, solvate, or stereoisomer.” (Celgene Open. Br. at 13–15; see also Celgene Resp.
Br. at 13–14). Nevertheless, the Court is not persuaded by Defendants’ argument. The parties do not appear to dispute that stereoisomers are molecules with the same molecular formula and sequence of bonded atoms but differ in the three-dimensional orientations of their atoms in space. (See Celgene Open. Br. at 49; Park Decl. ¶¶ 36–39). It is also seemingly undisputed that the chemical structure depicted in the disputed terms encompasses combinations of stereoisomers of pomalidomide. See, e.g., ’262 Patent at 11:43–46 (“if the stereochemistry of a structure or a portion of a structure is not indicated with, for example, bold or dashed lines, the structure or portion of the structure is to be interpreted as encompassing all stereoisomers of it.”). The Court thus finds that there does not appear to be a dispute among the parties and that the meaning of
“stereoisomer” is clear and needs no construction. Vivid Techs., Inc. v. Am. Science & Eng’g, Inc., 200 F. 3d 795, 803 (Fed. Cir. 1999) (stating that “only those terms need be construed that are in controversy, and only to the extent necessary to resolve the controversy”). For the foregoing reasons, the Court adopts Celgene’s proposed construction, which is supported by the claim language and is consistent with the standard industry practice. B. Formulation Patents 1. “Lubricant” Celgene Teva and Aurobindo Apotex The Court “a substance capable “an excipient, in addition “a substance capable of reducing friction to the binder or filler, Requires no of reducing friction and/or reducing having the primary construction and/or reducing adhesion” function of reducing adhesion” friction and/or reducing adhesion beyond the level achieved by other excipients (i.e. carrier, diluent, binder or filler)”
The ’427 Patent, the ’467 Patent, and the ’5,939 Patent claim pharmaceutical formulations containing pomalidomide. The disputed term “lubricant” appears in Claims 6 to 8 of the ’467 Patent, as well as Claims 6 to 8 of the ’5,939 Patent. Claims in the ’467 Patent are representative, where Claim 1, the only independent claim, recites the following: 1. An oral dosage form in the form of a capsule which comprises: 1) pomalidomide at an amount of 0.1 to 3 weight percent of the total weight of the composition; 2) a binder or filler at an amount of 90 to 99 weight percent of total weight of the composition, wherein the binder or filler is a mixture of starch and mannitol; and wherein the ratio of mannitol:starch in the dosage form is from about 1:1 to about 1:1.5. Claims 6 to 8 then claim “[the] oral dosage form of claim 1 further comprising a lubricant at an amount of” varying weight percent of total weight of the composition. ’467 Patent, Claims 1 & 6–8. The dispute with regard to the construction of “lubricant” is mainly between Teva and Aurobindo, on the one hand, and Celgene, on the other; while Apotex believes that no construction is necessary, and Breckenridge, Hetero, and Mylan take no position as to the construction of this term. (See D.E. No. 349 (“Celgene Supp. Open. Br.”) at 8–11; D.E. No. 350 at 2; D.E. No. 351 (“Teva Supp. Open. Br.”) at 10–18; D.E. No. 354 at 7). Teva and Aurobindo argue that the “further comprising” language in Claims 6 to 8 indicates that “‘lubricant’ must . . . be a distinct and additional component” relative to the “binder or filler.” (Teva Supp. Open. Br. at 12). For support, Teva and Aurobindo cite to the specification and prosecution history of the ’467 Patent and argue that the patentee “consistently characterizes the invention as dosage forms containing pomalidomide and ‘excipients [which] comprise a carrier, diluent, binder, or filler and a lubricant.’” (Id. at 14) (emphasis Teva and Aurobindo’s). In other words, Teva and Aurobindo argue that, by referring to excipients as either a “binder or filler” or a “lubricant,” an excipient cannot function both as a “binder or filler” and a “lubricant”. (Id. at 12–13). A “lubricant,”
according to Teva and Aurobindo, is “a separate and distinct excipient, the primary function of which is to lubricate.” (Id. at 15–16). Celgene, on the other hand, does not dispute that Claims 6 to 8 of the ’467 Parent require a lubricant in addition to a binder or filler. (See, e.g., Markman Tr. at 145:19–23 (counsel for Celgene stating that “Claim 6 adds a further limitation that requires the presence of an additional functional ingredient. So it does add that there has to be a lubricant in the formulation.”)). Yet Celgene contends that the phrase “further comprising” only requires “additional recited elements,” as opposed to “a distinct and additional component.” (Celgene Resp. Br. at 25–26). According to Celgene, the “additional recited elements” added in Claims 6 to 8 are the “specific weight percentage of the lubricant.” (Id. at 26). Celgene states that “as long as the required weight
percentage of one structural inactive ingredient is functioning as a binder/filler, and the other claimed weight percentage of that same structural inactive ingredient is functioning as a lubricant, the claims are met.” (Id.). The Court agrees with Celgene. This is a situation where “the claims themselves provides substantial guidance” as to the meaning of the term “lubricant.” See Philips, 415 F.3d at 1314. The “further comprising” language in Claims 6 to 8 requires that the “lubricant” must be an additional component relative to “binder or filler.” As Teva and Aurobindo correctly point out,
the Federal Circuit and this Court have recognized that the phrase “further comprising” indicates that the elements following the phrase “further comprising” are not part of the limitations preceding that phrase. See David Netzer Consulting Eng’r LLC v. Shell Oil Co., 824 F.3d 989, 996 (Fed. Cir. 2016); Purdue Pharm. Prod. L.P. v. Actavis Elizabeth LLC, 12-5311, 2015 WL 5032650, at *13 (D.N.J. Aug. 25, 2015). This is especially true where, as here, the patentee uses the word “wherein” in other dependent claims to indicate that patentee’s intention to narrow the
meaning of the “binder/filler.” For example, Claim 3 of the ’467 patent reads: “The oral dosage form of claim 1, wherein the binder or filler is present at an amount of 95 to 99 weight percent of total weight of the composition.” Claim construction principles thus dictate that, for example, Claim 6 must include all limitations of Claim 1 and “a lubricant at an amount of 0.01 to 1 weight percent of the total composition.” Teva and Aurobindo are thus correct in that Claims 6 to 8 “add an additional element required to be present in an infringing product: a lubricant.” (See Teva Supp. Br. at 13). However, nothing in the specification or the prosecution history supports Teva and Aurobindo’s proposition that the “lubricant” has to be a substance that is “distinct from” a binder or filler. The specifications Teva and Aurobindo cite to are merely examples where the lubricant
used is a different substance from the binder or filler. (See, e.g., ’467 Patent at 7:52–62, 8:21–31, 8:57–67, 9:26–36, 9:62–10:5 & 10:30–40). Similarly, language from prosecution history only shows that the patentee intended the claimed formulations to comprise excipient or excipients of different functions. (See, e.g., D.E. No. 355-4 at CELPOM12428172–74). None of the evidence supports that the patentee intended that these different functions necessarily be served by different substances. Therefore, “it is improper to read limitations from a preferred embodiment described in the specification—even if it is the only embodiment—into the claims absent a clear indication in the intrinsic record that the patentee intended the claims to be so limited.” Dealertrack, Inc. v. Huber, 674 F.3d 1315, 1327 (Fed. Cir. 2012) Because Teva and Aurobindo do not argue, nor could they, that the intrinsic evidence reveals “an intentional disclaimer, or disavowal, of claim scope by the inventor,” the Court thus agrees with Celgene that a single excipient, as disclosed in the ’467 Patent and the ‘5,399 Patent, can serve different functions. Accordingly, the Court also rejects Teva and Aurobindo’s position
that a lubricant must have a primary function of lubricating. For the foregoing reasons, the Court adopts Celgene’s proposed construction of “lubricant”. IV. Conclusion The Court will construe the disputed terms as explained above. An appropriate Order accompanies this Opinion.