NOT FOR PUBLICATION
`UNITED STATES DISTRICT COURT
`DISTRICT OF NEW JERSEY
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`::
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`Defendants.
` :
`
`Cooper, District Judge
`
`PRELIMINARY STATEMENT
`
`OUTLINE
`
`I.
`
`II.
`
`BACKGROUND
`A.
`Legal standard
`B.
`The ‘219 patent and related patents
`C.
`Prosecution history
`
`DISCUSSION
`A.
`Phrase One: “for intravenous administration to a human”
`B.
`Phrase Two: “to reduce the likelihood of CINV”
`
`III.
`
`CONCLUSION
`
`PRELIMINARY STATEMENT
`
`This is a consolidated action involving four patents listed as covering plaintiffs’
`
`marketed pharmaceutical product Aloxi®. Defendants have filed Abbreviated New Drug
`
`Applications (“ANDAs”) with the Federal Food and Drug Administration (“FDA”),
`Dr. Reddy’s Laboratories, Ltd., et al.
`v.
`Helsinn Healthcare S.A., et al.
`U.S. Patent No. 9,(cid:20)(cid:26)(cid:22),(cid:28)(cid:23)(cid:21)
`Reddy Exhibit 1058
`
`HELSINN HEALTHCARE S.A., et al.,
`
`CIVIL ACTION NO. 11-3962 (MLC)
`
` MEMORANDUM OPINION
`
`::
`
`Plaintiffs,
`
`v.
`
`DR. REDDY’S LABORATORIES,
`LTD., et al.,
`
`Exh. 1058
`
`

`
`seeking to market generic versions of the product and challenging those patents as invalid
`
`or unenforceable, pursuant to Section 505(j) of the Federal Food, Drug and Cosmetic Act,
`
`21 U.S.C. § 355(j). This Court has jurisdiction under the Hatch-Waxman Act, 35 U.S.C.
`
`§ 271(e)(2)(A), and 28 U.S.C. §§ 1331 and 1338(a). (See, e.g., dkt. 1.) 1
`
`Aloxi® contains the active pharmaceutical ingredient palonosetron hydrochloride,
`
`and is FDA-approved to treat chemotherapy-induced nausea and vomiting and
`
`postoperative nausea and vomiting. (Dkt. 178-2 at 3.) The four related patents-in-suit are
`
`United States Patents No. 7,947,724 (“‘724 patent”), No. 7,947,725 (“‘725 patent”), No.
`
`7,960,424 (“‘424 patent”), and No. 8,598,219 (“‘219 patent”). (Dkt. 174 at 2.) Those are
`
`all composition patents. There are other patents in the same patent family history,
`
`including method patents. Only the four composition patents listed above, however, are
`2
`
` The Court will cite to the documents filed in the Electronic Case Filing System (“ECF”)
`1
`by referring only to their docket entry numbers by the designation of “dkt.” All of those
`references are to the consolidated docket in the lead case, Civil Action No. 11-3962, unless
`another docket is specified. The two later-filed actions that have been consolidated into this lead
`case are Civil Actions No. 11-5579 and No. 13-5815. Copies of the four patents-in-suit are
`attached as exhibits to those respective complaints, and also to various Markman filings
`throughout the docket. We will simply cite to the patents by page or column and line number.
`The plaintiffs in this consolidated action are Helsinn Healthcare S.A. and Roche Palo Alto LLC.
`The originally-named defendants are Dr. Reddy’s Laboratories, Ltd., Dr. Reddy’s Laboratories,
`Inc., Sandoz Inc., Teva Pharmaceuticals USA, Inc., and Teva Pharmaceutical Industries, Ltd. For
`purposes of this claim construction opinion, we will refer to each side collectively as “plaintiffs”
`and “defendants.”
`
` The parties supplied, upon request by the Court, a Diagram of the Patent Family History
`2
`of the Patents-in-Suit, which we have had filed on the docket in this action. (Dkt. 289.) It is very
`helpful in showing all applications, and approved patents, stemming from an original Provisional
`Application No. 60/444,351, filed on January 30, 2003. That date is the critical date for all of the
`ensuing patents, and the patents-in-suit are subject to terminal disclaimers tied to the first-issued
`of those patents, the ‘724 patent.
`
`2
`
`Exh. 1058
`
`

`
`asserted in this particular consolidated action.
`3
`
`This opinion addresses certain language that appears in the preamble portion of the
`
`two independent claims of the ‘219 patent, including asserted claim 1. The entire
`
`preamble of claim 1 reads: “A pharmaceutical single-use, unit-dose formulation for
`
`intravenous administration to a human to reduce the likelihood of cancer chemotherapy-
`
`induced nausea and vomiting, [comprising....].” See n.7, infra (quoting ‘219 patent).
`
`Language in the body of claim 1 refers to “said formulation.” Id.
`
`The parties agree that all of the words of that preamble up to and including
`
`“formulation” constitute claim limitations, because those words provide antecedent basis
`
`for the “said formulation” language that follows in the claim body. However, the parties
`
`dispute whether the balance of the preamble text, consisting of the phrases “for
`
`intravenous administration to a human to reduce the likelihood of cancer chemotherapy-
`
`induced nausea and vomiting,” should be read as claim limitations. Plaintiffs argue that
`
` The parties have filed a Stipulation, narrowing and specifying the patents and claims at
`3
`issue in this consolidated action. Those are as follows: ‘724 patent, claims 2 and 9; ‘725 patent,
`claim 2; ‘424 patent, claim 6; and ‘219 patent, claims 1, 2, 6, and 7. (Dkt. 174 at 2.) Here in the
`District of New Jersey, other patent cases involving this family of patents (those asserted here
`and a later-issued patent) are docketed as Civil Actions No. 12-2867, No. 14-4274, No. 14-6341,
`No. 15-1228, No. 15-2077, and No. 15-2078. Some of those are consolidated with each other,
`and others are not currently consolidated. There is also pending litigation in the District of
`Delaware involving the same patent family. See, e.g., Helsinn Healthcare S.A., et al. v. Cipla
`Ltd., et al., D. Del. Civil Action No. 13-688 (consol.).
`
`3
`
`Exh. 1058
`
`

`
`the language is limiting, and defendants argue to the contrary. (Dkt. 175 at 6–9 (joint
`
`claim construction chart).) 4
`
`The Court has considered the written submissions of the parties and conducted oral
`
`argument on this issue. The evidence presented by the parties as relevant to this claim
`
`construction was all intrinsic evidence. That evidence included the claims, specification,
`
`and prosecution history of the ‘219 patent and related patents in the same family history,
`
`as well as some of the prior art references cited in those United States Patent and
`
`Trademark Office (“USPTO”) filings. Based on the intrinsic evidence and the arguments
`
`of the parties presented in these claim construction proceedings, this Court concludes that
`
`the disputed preamble language in claim 1 of the ‘219 patent does constitute claim
`
`limitations of the patent.5
`
` In addition to the Joint Claim Construction & Prehearing Statement (dkt. 175), the
`4
`submissions on this claim construction issue are as follows: dkt. 176, Defs.’ Opening Br.; dkt.
`176-1 to 176-4, Barker I Decl.; dkt. 177, Pls.’ Opening Br.; dkt. 178 to 178-4, Ni I Decl.; dkt.
`182, Defs.’ Responsive Br.; dkt. 182-1 to 182-17, Barker II Decl.; dkt. 181, Pls.’ Responsive Br.;
`dkt. 181-1, Ni II Decl.; and dkt. 220, Markman Oral Arg. Tr. The attorney declarations contain
`numerous exhibits, which we will cite simply by reference to ECF page numbers. Following oral
`argument, the Court requested and received from the parties the complete ‘219 patent
`prosecution history file from the United States Patent and Trademark Office (three volumes,
`not docketed).
`
` Defendants have provided discovery and contentions relating to their invalidity
`5
`arguments in alternative form, depending on whether the Court would find the disputed preamble
`language to be limiting. Those arguments include written description contentions. (Dkt. 182 at
`17 n.12.)
`
`4
`
`Exh. 1058
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`

`
`I.
`
`BACKGROUND
`
`A.
`
`Legal standard
`
`Courts define the meaning and scope of patent claims by the process of claim
`
`construction. Markman v. Westview Instruments, 52 F.3d 967, 976, 978, 1026 (Fed.Cir.
`
`1995) (en banc), aff’d, 517 U.S. 370 (1996). A court first looks to the intrinsic evidence
`
`to construe claims. See Interactive Gift Express v. Compuserve, 256 F.3d 1323, 1331
`
`(Fed.Cir. 2001) (en banc reh’g denied). Here, the parties have argued their positions
`
`primarily with reference to the intrinsic evidence and did not request an evidentiary
`
`hearing. (See dkt. 175.) Although some extrinsic evidence was identified in the parties
`
`Joint Claim Construction Statement (id.), the Court finds the briefing and the oral
`
`argument to be sufficient to resolve this issue without resort to extrinsic evidence.
`
`The intrinsic record, which includes the claims, specification, and complete
`
`prosecution history, is the most significant source for the legally operative meaning of
`
`disputed claim language. Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582
`
`(Fed.Cir. 1996). A patent’s prosecution history consists of the record of proceedings
`
`before the USPTO and the prior art cited during the patent’s examination. Phillips v.
`
`AWH Corp., 415 F.3d 1303, 1317 (Fed.Cir. 2005) (en banc).
`
`It is well settled that “[t]he determination of whether a preamble limits a claim is
`
`made on a case-by-case basis in light of the facts in each case; there is no litmus test
`
`defining when a preamble limits the scope of a claim.” Manual of Patent Examining
`
`5
`
`Exh. 1058
`
`

`
`Procedure § 2111.02 (Rev. Aug. 2012) (citing Catalina Mktg. Int’l v. Coolsavings.com,
`
`289 F.3d 801, 808 (Fed.Cir. 2002)). (Dkt. 182-8 at 2.)
`
`“Whether a preamble stating the purpose and context of the invention constitutes a
`
`limitation of the claim[s] ... is determined on the facts of each case in light of the overall
`
`form of the claim, and the invention as described in the specification and illuminated in the
`
`prosecution history.” Catalina Mktg., 289 F.3d at 808 (quoting Applied Materials, Inc. v.
`
`Advanced Semiconductor Materials Am., Inc., 98 F.3d 1563, 1572–73 (Fed.Cir. 1996)).
`
`The Federal Circuit in Catalina Mktg. set forth certain “guideposts that have
`
`emerged from various decisions exploring the preamble’s effect on claim scope.” (Dkt.
`
`182-8 at 2.) Here is a summary of those principles insofar as relevant to this case, as
`
`expressed in Catalina Mktg.:
`
`In general, a preamble limits the invention if it recites essential structure or
`steps, or if it is “necessary to give life, meaning, and vitality” to the claim....
`Conversely, a preamble is not limiting “where a patentee defines a structurally
`complete invention in the claim body and uses the preamble only to state a
`purpose or intended use for the invention.”
`
`289 F.3d at 808 (internal citations omitted).
`
`Additionally, dependence on a particular disputed preamble phrase for
`antecedent basis may limit claim scope because it indicates a reliance on both
`the preamble and claim body to define the claimed invention.... Likewise,
`when the preamble is essential to understand limitations or terms in the claim
`body, the preamble limits claim scope....
`
`Further, when reciting additional structure or steps underscored as important
`by the specification, the preamble may operate as a claim limitation.....
`
`6
`
`Exh. 1058
`
`

`
`Moreover, clear reliance on the preamble during prosecution to distinguish the
`claimed invention from prior art transforms the preamble into a claim limitation
`because such reliance indicates use of the preamble to define, in part, the
`claimed invention..... Without such reliance, however, a preamble generally is
`not limiting when the claim body describes a structurally complete invention
`such that deletion of the preamble phrase does not affect the structure or steps
`of the claimed invention.... Thus, preamble language merely extolling benefits
`or features of the claimed invention does not limit the claim scope without
`clear reliance on those benefits or features as patentably significant....
`Moreover, preambles describing the use of an invention generally do not limit
`the claims because the patentability of apparatus or composition claims
`depends on the claimed structure, not on the use or purpose of that structure....
`More specifically, this means that a patent grants the right to exclude others
`from making, selling, ... the claimed apparatus or composition for any use of
`that apparatus or composition, whether or not the patentee envisioned such
`use.... Likewise, this principle does not mean that apparatus claims necessarily
`prevent a subsequent inventor from obtaining a patent on a new method of
`using the apparatus where that new method is useful and nonobvious.
`
`Id. at 808–09 (internal citations omitted).
`
`Those are the general guiding principles in this discrete area of patent law. Cf.
`
`Am. Med. Sys., Inc. v. Biolitec, Inc., 618 F.3d 1354, 1363–64 (Fed.Cir. 2010) (Dyk, J.,
`
`dissenting). Additional precedents cited by the parties are discussed in Sections II.A and
`
`II.B, infra.
`
`B.
`
`The ‘219 patent and related patents
`
`The ‘219 patent shares essentially the same specification with the related patents-
`
`in-suit. (See dkt. 220 at 6.) To summarize this group of patents, as relevant to the claim
`
`construction issues here, we will describe the precise claims of the four patents-in-suit,
`
`and the specification language common to them all.
`
`7
`
`Exh. 1058
`
`

`
`Clearly, the primary focus of all four of these patents is shelf stability of the
`
`claimed palonosetron formulations. See, e.g., Civil Action No. 12-2867, dkt. 92 at 25–33
`
`(‘724 patent claim construction opinion (sealed)). The question raised in this claim
`
`construction proceeding, however, is whether certain other aspects of the ‘219 claim
`
`language (and, perhaps, corresponding parts of the claim preambles of the other three
`
`patents-in-suit) are claim limitations rather than merely non-limiting preamble language.
`
`The aspects of the ‘219 patent that are placed in issue in this Markman proceeding
`
`derive from the two distinct prepositional phrases in the disputed portion of the preamble
`
`language in claim 1 of the ‘219 patent. Those read, in their entirety: “for intravenous
`
`administration to a human to reduce the likelihood of cancer chemotherapy-induced
`
`nausea and vomiting.” See n.7, infra.6
`
`The parties make arguments addressed to each phrase separately, and to both
`
`phrases jointly. See Sections II.A & II.B, infra. However, for discussion purposes we
`
`will often refer to them separately as follows: (1) “for intravenous administration to a
`
`human” (“Phrase One”); and (2) “to reduce the likelihood of cancer chemotherapy-
`
`induced nausea and vomiting” (“Phrase Two”). Portions of the ‘219 patent specification
`
` There are two independent claims in the ‘219 patent, claims 1 and 8. See n.7, infra
`6
`(quoting ‘219 claims). Only claim 1 of the ‘219 patent, and its dependent claims 2, 6, and 7, are
`asserted in this litigation. (See dkt. 174 at 2.) Of course, all claims of the patents-in-suit and
`related patents may be relevant to claim construction. Nevertheless, because independent claims
`1 and 8 of the ‘219 patent have identical preambles, and because claim 8 is not asserted, we will
`refer to the preambles of both claims 1 and 8 as “the preamble” of the ‘219 patent claims.
`
`8
`
`Exh. 1058
`
`

`
`and various relevant prosecution history files pertain to those separate phrases, as
`
`described below.
`
`The ‘219 patent, like all of its related patents in the same patent family, is entitled
`
`“Liquid Pharmaceutical Formulations of Palonosetron.” It contains eight claims, of
`
`which independent claim 1 and dependent claims 2, 6, and 7 are asserted in this case. See
`
`n.3, supra. The full text of the ‘219 claim language is quoted here in the margin. 7
`
` The complete claims of the ‘219 patent are as follows:
`
`hat is claimed is:
` 1. A pharmaceutical single-use, unit-dose formulation for intravenous
`administration to a human to reduce the likelihood of cancer chemotherapy-
`induced nausea and vomiting, comprising a 5 mL sterile aqueous isotonic
`solution, said solution comprising:
`palonosetron hydrochloride in an amount of 0.25 mg based on the weight
`of its free base;
`from 0.005 mg/mL to 1.0 mg/mL EDTA; and
`from 10 mg/mL to 80 mg/mL mannitol,
`wherein said formulation is stable at 24 months when stored at room
`temperature.
` 2. The pharmaceutical formulation of claim 1, wherein said EDTA is in an
`amount of 0.5 mg/mL.
` 3. The pharmaceutical formulation of claim 1, wherein said mannitol is in an
`amount of 41.5 mg/mL.
` 4. The pharmaceutical formulation of claim 1, wherein said solution further
`comprises a citrate buffer.
` 5. The pharmaceutical formulation of claim 4, wherein said citrate buffer is at
`a concentration of 20 millimolar.
` 6. The pharmaceutical formulation of claim 1, wherein said solution is
`buffered at a pH of 5.0 ±0.5.
` 7. The pharmaceutical formulation of claim 1, wherein said EDTA is in an
`amount of 0.5 mg/mL, wherein said mannitol is in an amount of 41.5 mg/mL,
`wherein said solution further comprises a citrate buffer at a concentration of 20
`millimolar, and wherein said solution is buffered at a pH of 5.0 ±0.5.
`
`7 W
`
`9
`
`Exh. 1058
`
`

`
`There is preamble language in each of the other three patents-in-suit that is similar
`
`but not identical to the disputed preamble phrases in the ‘219 patent. Here, also in the
`
`margin, we quote the corresponding portions of the other patents-in-suit, the ‘724 patent, 8
`
` 8. A pharmaceutical single-use, unit-dose formulation for intravenous
`administration to a human to reduce the likelihood of cancer chemotherapy-
`induced nausea and vomiting, comprising a 5 mL sterile aqueous isotonic
`solution, said solution comprising:
`palonosetron hydrochloride in an amount of 0.25 mg based on the weight
`of its free base;
`from 0.005 mg/mL to 1.0 mg/mL EDTA; and
`from 10 mg/mL to 80 mg/mL mannitol,
`wherein said formulation is stable at 18 months when stored at room
`temperature.
`
`(‘219 patent, col. 10, lines 1–38 (emphasis added).)
`
` The ‘724 patent provides, in pertinent part:
`
`8 W
`
`hat is claimed is:
` 1. A pharmaceutically stable intravenous solution for reducing emesis or
`reducing the likelihood of emesis comprising:
`....
` 2. The solution of claim 1 wherein ....
` ....
` 8. A pharmaceutically stable isotonic intravenous solution for reducing
`emesis or reducing the likelihood of emesis comprising:
`....
` 9. The solution of claim 8 wherein ....
` ....
` 14. The solution of claim 8 adapted for intravenous administration.
`
`(‘724 patent, col. 9, lines 27–35, col. 10, lines 1–33 (emphasis added).)
`
`10
`
`Exh. 1058
`
`

`
`the ‘725 patent, and the ‘424 patent.
`9
`
`
`10
`
`As can be seen, all three of those patents contain preamble language directed to
`
`“reducing ... the likelihood of emesis,” similar to the ‘219 preamble directed to “reducing
`
`the likelihood of cancer chemotherapy-induced nausea and vomiting.” Also, the ‘724 and
`
`‘424 patents contain preamble language specifying an “intravenous solution”, or an
`
`“isotonic intravenous solution.” See nn. 8 & 10, supra. Similarly, the ‘725 patent in the
`
`body of the claims refers to “sterile injectable” and “a tonicifying amount of mannitol”
`
`(features associated with injectable solutions, as explained infra). See n.9, supra.
`
` The ‘725 patent provides, in pertinent part:
`
`9 W
`
`hat is claimed is:
` 1. A pharmaceutically stable solution for reducing emesis or reducing the
`likelihood of emesis comprising:
`....
` 2. A pharmaceutically stable solution for reducing emesis or reducing the
`likelihood of emesis comprising:
`....
`
`(‘725 patent, col. 10, lines 3–19 (emphasis added).) Text in the body of the claims refers to
`“sterile injectable” and “a tonicifying effective amount of mannitol.” (Id., lines 8–9; see also id.,
`lines 14–19.)
`
`10
`
` The ‘424 patent provides, in pertinent part:
`
`What is claimed is:
` 1. A pharmaceutically stable isotonic intravenous solution of palonosetron
`hydrochloride for reducing emesis or reducing the likelihood of emesis
`comprising
`....
` 2. The solution of claim 1 wherein ....
`
`(‘424 patent, col. 10, lines 5–15 (emphasis added).)
`
`11
`
`Exh. 1058
`
`

`
`An earlier claim construction proceeding in this consolidated case pertained to the
`
`term “pharmaceutically stable” in the preambles of the ‘724, ‘725, and ‘424 patents.
`
` In
`11
`
`joining issue on that claim construction dispute, the parties agreed that the preamble
`
`language in those patents, up to and including the word “solution,” was limiting. Thus,
`
`the words “pharmaceutically stable intravenous solution,” in the ‘724 preamble, and the
`
`words “pharmaceutically stable isotonic intravenous solution,” in the ‘424 preamble, were
`
`agreed by the parties to be limiting. Defendants, however, did not stipulate with respect
`
`to those three patents that the “reducing ... the likelihood of emesis” language of their
`
`preambles should be construed to be claim limitations. (Dkt. 182 at 5–6, 20.)
`
`Defendants maintain their opposition here to interpreting the “reducing ... the
`
`likelihood of emesis” in the ‘724, ‘725 and ‘424 preambles, and the “reducing the
`
`likelihood of cancer chemotherapy-induced nausea and vomiting,” in disputed Phrase
`
`Two of the ‘219 preamble, as claim limitations. They also contend that the disputed
`
`Phrase One language — “for intravenous administration to a human” in the ‘219
`
`preamble — is not to be equated with the “intravenous solution” form that they
`
`acknowledged as limiting in the ‘724 and ‘424 preambles. (Id.) The parties’ competing
`
`arguments on those points are discussed in Sections II.A and II.B, infra.
`
` That claim construction dispute was considered by the Court during the earlier
`11
`Markman proceedings here, but we declined to rule on briefs alone, deferring the issue for
`extrinsic evidence to be provided at the non-jury ANDA trial. (Dkt. 103 at 77–78.) See also
`Helsinn Healthcare S.A., et al. v. Cipla Ltd., et al., D. Del. Civil No. 13-688, dkt. 169 at 3
`(same).
`
`12
`
`Exh. 1058
`
`

`
`As previously noted, the four patents-in-suit share essentially the same
`
`specification, as do the other patents stemming from the same original provisional
`
`application. For purposes of the following summary of their specifications, we will quote
`
`the ‘219 specification, recognizing that the corresponding sections of the three other
`
`patents-in-suit are the same.
`
`Most of the text of the ‘219 patent specification addresses the prior art stability
`
`problems with palonosetron in liquid formulations, and the new formulations claimed in
`
`this patent family to overcome those stability problems. See, e.g., Civil Action No. 12-
`
`2867, dkt. 92 at 25–33 (reviewing corresponding portions of ‘724 specification (sealed)).
`
`Furthermore, the specification gives examples of both intravenous and oral formulations,
`
`and all of the test results provided in the specification measure shelf life stability, rather
`
`than the therapeutic effects of the drug itself. Id. (See ‘219 patent, col. 2, line 42 to col.
`
`9, line 35.)
`
`There are, however, significant references to the anti-emetic properties of
`
`palonosetron in the ‘219 and related patent specifications. There are also discussions of
`
`intravenous and other types of formulations in those same specifications. Here we quote
`
`some of those portions of the ‘219 specification.
`
`The references to intravenous medicaments and the use of palonosetron to reduce
`
`emesis are found throughout the specification. As those are somewhat entwined in the
`
`text, we will quote them together where they appear together, highlighting those two
`
`topics in bold type.
`
`13
`
`Exh. 1058
`
`

`
`The Abstract states:
`
`The present invention relates to shelf-stable liquid formulations of
`palonosetron for reducing chemotherapy and radiotherapy induced
`emesis with palonosetron. The formulations are particularly useful in the
`preparation of intravenous and oral liquid medicaments.
`
`(‘219 patent, p.1.)
`
`The Background of the Invention states:
`
`Emesis is a devastating consequence of cytotoxic therapy, radiotherapy,
`and post-operative environments that drastically affects the quality of life
`of people undergoing such treatments. In recent years a class of drugs
`referred to as 5-HT3 ... receptor antagonists has been developed that treat
`such emesis by antagonizing cerebral functions associated with the 5-HT3
`receptor.... These 5-HT3 antagonists are often administered intravenously
`shortly before chemotherapy or radiotherapy is initiated, and can be
`administered more than once during a cycle of chemotherapy or
`radiotherapy. In addition, they are often supplied as tablets for oral elixirs to
`either supplement intravenous administration, or to ease home usage of the
`drug if the patient is self-administering the chemotherapeutic regimen.
`....
`Recently, clinical investigations have been made concerning palonosetron,
`a new 5-HT3 receptor antagonist reported in [a prior art patent]. These
`investigations have shown that the drug is an order of magnitude more
`potent than most existing 5-HT3 receptor antagonists, ... and is effective to
`reduce delayed-onset nausea induced by chemotherapeutic agents.
`However, formulating palonosetron in liquid formulations has not proven an
`easy task.
`....
`Therefore, there exists a need for a palonosetron formulation with increased
`stability and thereby increased shelf life....
`It is an object of the present invention to provide a formulation of
`Palonosetron hydrochloride with increased pharmaceutical stability for
`preventing and/or reducing emesis.
`....
`
`(Id., col. 1, line 12 to col. 2, line 51.)
`
`14
`
`Exh. 1058
`
`

`
`The Summary of the Invention states:
`
`The inventors have made a series of discoveries that support a surprisingly
`effective and versatile formulation for the treatment and prevention of
`emesis using palonosetron. These formulations are shelf stable for periods
`greater than 24 months at room temperature....
`
`In one aspect, the inventors have discovered that formulations which
`include the active ingredient palonosetron require in some instances only
`1/10th the amount of other previously known compounds for treating
`emesis, which surprisingly allows the use of concentrations of
`palonosetron far below those that would ordinarily be expected. Thus, in
`one embodiment the invention provides a pharmaceutically stable solution
`for preventing or reducing emesis comprising....
`
`The inventors have further discovered that by adjusting the formulation’s pH
`and/or excipient concentrations it is possible to increase the stability of
`palonosetron formulations. Therefore, in another embodiment, the
`invention provides a pharmaceutically stable solution for preventing or
`reducing emesis comprising.... In another embodiment the invention
`provides a pharmaceutically stable solution for preventing or reducing
`emesis comprising....
`
`(Id., col. 2, line 53 to col. 3, line 14.)
`
`The Discussion section repeats some of the above-quoted text. It also states:
`
`A particular advantage associated with the lower dosages of intravenous
`palonosetron is the ability to administer the drug in a single intravenous
`bolus over a short, discrete time period.... In one particular embodiment the
`palonosetron is supplied in vials that comprise 5 ml. of solution, which equates
`to about 0.25 mg of palonosetron at a concentration of about 0.05 mg/ml.[ ]12
`
` It is perhaps noteworthy that the structural formulation described in this paragraph of
`12
`the specification appears to correspond precisely with the claim language of the ‘219 patent
`itself. As stated in claim 1: “A pharmaceutical single-use, unit-dose formulation for
`intravenous administration to a human ... comprising a 5 mL sterile aqueous isotonic solution,
`said solution comprising: palonosetron hydrochloride in an amount of 0.25 mg....” (‘219 patent,
`col. 10, lines 2–7 (emphasis added).)
`
`15
`
`Exh. 1058
`
`

`
`....
`The formulations of the present invention are particularly suited for use
`in injectable and oral liquid formulations, but it will be understood that the
`solutions may have alternative uses. For example, they may be used as
`intermediaries in the preparation of other pharmaceutical dosage forms.
`Similarly, they may have other routes of administration including intranasal or
`inhalation. Injectable formulations may take any route including
`intramuscular, intravenous or subcutaneous.
`
`(Id., col. 4, line 59 to col. 6, line 24.)
`
`We will refer to this summary of the ‘219 claim language and specification, and
`
`the corresponding text in the ‘724, ‘725, and ‘424 patents, in Sections II.A and II.B, infra,
`
`when we discuss the parties’ contentions drawn from that intrinsic evidence.
`
`C.
`
`Prosecution history
`
`The entire prosecution history of the ‘219 patent, and the relevant portions of its
`
`rather complicated patent family history, have been supplied to the Court in the parties’
`
`Markman submissions. See n.4, infra.
`
`Any patent file history includes both procedural and substantive aspects. First, we
`
`briefly summarize the pertinent procedural chronology relevant to the ‘219 file. The
`
`substantive aspects of these events are next described here, and discussed in Sections II.A
`
`and II.B, infra.
`
`The ‘219 patent is recent, having been issued on December 3, 2013. (‘219 patent,
`
`p.1.) The actual prosecution file for the ‘219 patent is fairly simple, but the patent comes
`
`from a long and complicated family tree. The original provisional application, No.
`
`16
`
`Exh. 1058
`
`

`
`60/444,351, was filed on January 30, 2003. (Id.) The first generation of patents to be
`
`issued subsequent to that provisional application were the ‘724 and ‘725 patents-in-suit,
`
`dated May 24, 2011. (Dkt. 289.) Thus, the basic prosecution for this patent family took
`
`approximately eight-and-a-half years. The next patent-in-suit, the ‘424 patent, was issued
`
`on June 14, 2011. (Id.) Each of those three patents had their own application number,
`
`and their own prosecution file.
`
`As stated on the cover page of the ‘219 patent, its application number was
`
`Application No. 13/901,437. The preceding United States application data for the ‘219
`
`patent, following the original ‘351 provisional application in January, 2003, is quoted in
`
`the margin.
`
` The other patents issued to date in this family tree, and abandoned
`13
`
`applications, are listed in the chart supplied by the parties. (Dkt. 289.)
`
`This procedural history establishes that the ‘724 patent is a parent patent to the
`
`‘219 patent, and the two other patents-in-suit, the ‘725 and ‘424 patents, came from
`
`continuation-in-part applications derived from the application for the ‘724 patent. Thus,
`
`all four prosecution histories are relevant to the claim construction issues here, while it is
`
`recognized that the specific claims of the individual patents do contain differences.
`
`13
`
` The intermediate application history of the ‘219 patent is stated to be as follows:
`
`Continuation-in-part of application No. 13/087,012, filed on Apr. 14, 2011, now Pat.
`No. 8,518,981, which is a continuation of application No. 11/186,311, filed on Jul.
`21, 2005, now Pat. No. 7,947,724, which is a continuation of application No.
`PCT/EP2004/000888, filed on Jan. 30, 2004.
`
`(‘219 patent, p.1 (emphasis added).)
`
`17
`
`Exh. 1058
`
`

`
`Masco Corp. v. United States, 303 F.3d 1316, 1324 (Fed.Cir. 2002) (“The prosecution
`
`history of a parent application may be considered in construing claim terms.”).
`
` 14
`
`The ‘724, ‘725, and ‘424 patents, all stemming from the same original ‘351
`
`provisional application and all issued prior to the ‘219 patent, had extensive prosecution
`
`histories. The patents were approved only after appeals in all three cases to the
`
`Commissioner for Patents. Much file history was accumulated in those prosecution files.
`
`Some of that file history is discussed by the parties as relevant here. The application file
`
`for the ‘219 patent itself, albeit not as extensive as those of its predecessor patents, also
`
`includes its share of dialogue with the USPTO. That too is referred to by the parties,
`
`insofar as now pertaining to this claim construction. Here we summarize those portions
`
`of the substantive file history relating to the disputed ‘219 patent preamble phrases.
`
`There are several features in the substantive prosecution history that plaintiffs refer
`
`to in support of their position that the two disputed preamble phrases in the ‘219 patent
`
`are limiting. Those may be summarized as follows, with details provided in the margin:
`
`1.
`
`The preambles of both independent claims of the ‘724 patent were
`amended during prosecution to add the adjective “intravenous,” while
`deleting from a dependent claim [as-issued claim 7] the phrase “adapted
`for oral administration.” This amendment was made to overcome an
`obviousness rejection based on certain oral formulations disclosed in
`prior art. [There were also intravenous formulations in prior art, but the
`applicants narrowed the field of prior art by eliminating all oral
`
` Plaintiffs’ briefing also cites at least one a