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IN THE UNITED STATES DISTRICT COURT

FOR THE NORTHERN DISTRICT OF CALIFORNIA

CHIRON CORPORATION,

Plaintiff,

 v.

SOURCECF INC., SOURCECF CLINICAL

RESEARCH & DEVELOPMENT, L.L.C.,

MAXOR NATIONAL PHARMACY

SERVICES CORPORATION d/b/a IV

SOLUTIONS, FOUNDATION CARE L.L.C.,

and PHARMACEUTICAL SPECIALTIES,

INC.,

Defendants. /

No. C 05-01938 WHA

FINDINGS OF FACT AND

CONCLUSIONS OF LAW 

AFTER BENCH TRIAL

INTRODUCTION

The issue presented is the extent to which cystic fibrosis victims, their parents and their

doctors are barred by a medical-method patent asserted by Chiron Corporation from using

inhaled tobramycin to treat lung infections. Cystic fibrosis victims, their parents and their

physicians have long used inhaled antibiotics to treat lung infections. Tobramycin and

nebulizers were known well before the invention in question. Neither was invented by Chiron. 

A drug-device combination using tobramycin with a particular nebulizer came on the market in

1997. Chiron later acquired it and has successfully marketed the combination as TOBI. It is

prior art for purposes of Chiron’s later patent asserted herein.

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More efficient and more portable nebulizers have been invented by others. Being more

efficient, the new nebulizers can cut the treatment duration at least in half. The shorter

treatment duration encourages children to comply with their treatment regimens. The new

nebulizers are also small and portable, unlike the heavy TOBI machine. It seems undisputed

between the parties that the new generation of nebulizers represents an improvement.

Despite this development, Chiron has not come out with a new drug-device combination

using a new nebulizer. Instead, it has continued to promote TOBI, which still enjoys a

dominant market position. Chiron has, however, successfully sought and obtained a recent

medical-method patent to prevent CF victims, their parents and their physicians from using the

new generation of nebulizers with tobramycin, or at least from using those treatment methods

within the limits of the claims.

Chiron does not claim to have invented tobramycin or a nebulizer of any type. Rather,

Chiron claims to have discovered safe and efficacious concentrations of tobramycin for use in

the new nebulizers. Chiron based its patent application on three clinical studies. The clinical

studies vetted reduced volumes of Chiron’s standard TOBI solution with more efficient

nebulizers. These studies were eventually published as the disclosure in the patent in suit. 

Significantly, all of the studies involved tobramycin concentrations of 60 mg/ml or 120 mg/ml. 

All of the claims called out concentrations of “about 60 mg/ml” or higher. No study in the

patent vetted weaker concentrations. No claim called out weaker concentrations.

Through the patent in suit, Chiron asserts that CF victims, their parents and their

physicians are barred from using any treatment method administering tobramycin via the new

and efficient nebulizers when the total dose to be nebulized is four milliliters or less and the

concentration of tobramycin to solution is within the range of “about 60 mg/ml to about 200

mg/ml.” The accused methods of treatment at issue herein, however, all involve concentrations

below 60 mg/ml. In one, CF victims, their parents and doctors use a concentration of 50 mg/ml. 

In the other, the concentration is 40 mg/ml. The issue for decision is whether Chiron’s patent

covers and therefore bars use of these methods involving weaker concentrations.

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1

 Although voluminous proposed findings were submitted and considered, this order finds its own way

and makes its own findings rather than picking and choosing between the competing versions. That a proposed

finding has not been expressly incorporated does not necessarily mean it has been rejected; rather it means that

this order has found it unnecessary to adopt or reject it per se. To the extent, however, that any proposed

finding was expressly admitted by the responding party in the most recent round of proposals and responses,

this order hereby adopts the proposal (to the extent expressly admitted). It is unnecessary for this order to cite

the record and it will not do so except to particulars that may assist the court of appeals.

3

The issue is important to Chiron because its sole entry in the relevant market is TOBI. 

Although, as stated, Chiron does not sell products for use with the patented method, the

emergence of the new class of better nebulizers poses a threat to TOBI’s dominant market

share.

After a bench trial, this order holds that Chiron’s patent does not cover the weaker

concentrations at issue in this suit. It is true that the lower concentrations seem safe and

efficacious. But the patent is limited by the concentrations actually claimed. The patent does

not go so far as to claim all safe and effective doses regardless of concentration. The injunction

sought by Chiron must be denied.

FINDINGS OF FACT AND PROCEDURAL HISTORY1

The patent in suit is United States Patent No. 6,890,907 (“the ’907 patent”), owned by

Chiron Corporation. The ’907 patent purportedly discloses a method of treating lung infections,

namely using certain concentrations of liquid tobramycin with high-efficiency nebulizers, for

patients suffering from cystic fibrosis.

Cystic fibrosis strikes children. The symptoms manifest in early childhood. The

average life expectancy of CF patients is thirty-five years. Approximately 30,000 children and

adults in the United States currently suffer from CF.

CF causes mucus in the airways to become thick, dry, and sticky. The mucus builds up

rather than continually refreshing itself as would be normal. The buildup is unhealthy,

especially in the lungs. The lungs become breeding grounds for harmful bacteria. The most

significant of these pathogens is Pseudomonas aeruginosa.

Well before the alleged invention, physicians administered and pharmacists dispensed

antibiotics to CF patients to treat pulmonary infections including Pseudomonas aeruginosa. 

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The most successful of such antibiotics was (and remains) tobramcyin. Tobramycin, however,

is poorly absorbed across mucosal surfaces.

In the early 1990’s, therefore, physicians began administering tobramycin to CF patients

via inhalation therapy. The total doses of tobramycin used at that time ranged from 80 mg to

400 mg. The tobramycin was dissolved in a solution. The doctor would prescribe a

concentration, for example, “100 mg/ml” or state “200 mg in 2 ml of saline solution” (which

would translate to a concentration of 100 mg/ml). Pharmacists would dispense concentrations

pursuant to physicians’ orders. A brand-name version of tobramcyin for inhalation in the early

1990’s was NEBCIN, which came in either a 40 mg/ml concentration in 2 ml volume or in a

powder form to allow pharmacists to dispense the medication pursuant to a physician’s

specifications. NEBCIN was part of the prior art. It was not Chiron’s product.

The primary inhalation device available for tobramycin in the early 1990’s was the jet

nebulizer. A nebulizer is an apparatus that converts a liquid (such as a medication) into aerosol

droplets. A jet nebulizer uses gas flow through an aperture to pick up and atomize a solution. 

Pari Respirator Equipment, Inc. manufactured one such jet nebulizer known as the Pari LC Plus.

Prior to any application for the ’907 patent, an earlier patent issued on April 16, 1996,

relating to an antibiotic solution for aerosolization for CF patients. This was United States

Patent No. 5,508,269 (“the ’269 patent”). That patent was obtained by PathoGenesis, later

acquired by plaintiff Chiron. The ’269 is prior art for our purposes. The ’269 described an

antibiotic solution for inhalation, limited by amount of antibiotic, total volume, nebulization

method and particle size.

On December 22, 1997, the Food and Drug Administration approved TOBI as a drugdevice combination. TOBI was essentially the drug-device combination described in the ’269

patent. TOBI is a particular concentration of tobramcyin solution for inhalation in the Pari LC

Plus. The marketed version of TOBI contained 300 mg/ml of tobramcyin in 5 ml of quarter

saline solution, i.e., a concentration of 60 mg/ml. The FDA’s approval allowed marketing of

TOBI, without deviation. In other words, PathoGenesis (and later Chiron) could not advertise

or make representations about the safety and efficacy of any concentration of tobramycin other

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 Defendant SourceCF Clinical Research & Development, L.L.C. is merely a holding company that has

no employees. This order’s use of “SourceCF” thus refers to SourceCF, Inc.

5

than 60 mg/ml, nor could it make any representations about the use of TOBI in any nebulizer

other than the Pari LC Plus. As with the ’269 patent, TOBI is prior art for our purposes.

TOBI became the leading treatment on the market for pulmonary infections in CF

patients. One drawback was (and is) that it takes the Pari LC Plus over fifteen minutes to

nebulize the 5 ml volume of TOBI. This has led to compliance problems, particularly in

children uncomfortable sitting through long treatment sessions. Furthermore, the compressor

attached to the Pari LC Plus was (and is) bulky and heavy, rendering the device unportable. It

was (and remains) hard for children to immobolize themselves for the required TOBI duration.

In the late 1990’s, several companies (other than Chiron) began developing higher

efficiency nebulizers. These nebulizers were known as ultrasonic nebulizers, which used

vibration of a piezoelectric crystal to create aerosolization. Two such nebulizers are of

particular note in this litigation.

First, Aerogen, Inc. came out with the high-efficiency nebulizer known as the

AeroDose. The AeroDose is a breath-actuated nebulizer meaning that the nebulizer only

produces the atomized liquid during the patient’s inhalation phase. (The AeroDose has never

been cleared by the FDA.)

Second, at about the same time, Pari Respirator Equipment, Inc. introduced to the

market its own high-efficiency nebulizer known as the eFlow. (Pari, it will be recalled, also

makes the older model used with TOBI; Pari is not an affiliate of Chiron.) Defendant

SourceCF, Inc. serves as the exclusive distributor of the eFlow device, the device at the heart of

this controversy.2

 In 2004, the FDA ultimately cleared the eFlow as a device for inhalation of

medication (with no limitation as to the particular medication). In contrast to the AeroDose, the

eFlow produces a steady stream of aerosolized medication; it is not breath actuated. The eFlow

inhaler weighs about as much as an orange and has the diameter of a saucer. The eFlow can

operate by battery power. It is more user friendly than the TOBI device and it is more efficient.

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On August 14, 2000, plaintiff Chiron acquired PathoGenesis. Chiron thus acquired the

rights to TOBI, which it continues to market today. TOBI can be sold, under FDA regulations,

only with the older Pari LC Plus nebulizer.

To take advantage of the new generation of nebulizers, defendants herein began

promoting the use of the eFlow as a more convenient and more user-friendly way to administer

tobramycin solutions to CF victims. The defendants include, as stated, the SourceCF entities,

which distribute the eFlow. There are also three pharmacy defendants that dispense

concentrations of tobramycin for use in the eFlow: Maxor National Pharmacy Services

Corporation (IV Solutions), Foundation Care L.L.C., and Pharmaceutical Specialities, Inc. 

These latter defendants are licensed pharmacies specializing in what is known as

“compounding.” Compounding is the manipulation of a medication from its commercial form

pursuant to a physician’s orders. Such compounding is regulated by the various state boards of

pharmacy rather than the FDA. Preparing a tobramycin solution at a specified concentration

constitutes compounding. Putting aside patent issues, it is lawful for a physician to prescribe an

antibiotic like tobramycin for inhalation with a nebulizer like the eFlow and for pharmacists to

fill these prescriptions with vials of the prescribed solutions and sale or rental of the prescribed

nebulizer. There is no legal or medical requirement that only FDA-approved drug-device

combinations be used.

As more efficient nebulizers were being invented by others, Chiron sought a patent that

covered methods of treatment utilizing the new and more efficient nebulizers. This became the

’907 patent. Before diving into its history, it is worthwhile to identify two paramount themes: 

over the entire history of the ’907 patent, no ’907 study has ever tested a concentration below

60 mg/ml, i.e., all ’907 studies tested concentrations at 60 mg/ml (with one exception even more

concentrated at 120 mg/ml), and no final or interim claim in the ’907 patent ever covered any

concentrations below “about 60 mg/ml,” i.e., all claims called out “about 60 mg/ml” or higher. 

As will be seen, the ’907 disclosure taught away from using weaker concentrations.

On May 18, 2001, a provisional application was filed, docketed as Application

No. 60/292,234 (TX 96 at 388). All of the claims in the provisional application indicated

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antibiotic concentrations in the range of about 60 mg/ml to about 200 mg/ml. The disclosure

was a set of two studies, one involving CF patients and one involving healthy adult patients,

comparing the efficiency and efficacy of 60 mg/ml concentrations of tobramycin in the highefficiency AeroDose, with the commercial concentration of TOBI nebulized in the Pari LC

Plus. These two studies were ultimately included in the specification of the final patent. The

provisional application’s specification also provided (id. at 400):

Formulations according to the invention typically contain from

about 60 to about 200 mg, more preferably from about 80 to about

180, and most preferably from about 90 to about 120 mg of

aminoglycoside per ml of solution.

On May 12, 2002, a non-provisional application was filed by Chiron with the PTO,

docketed as Application No. 10/151,701 (TX 96 at 206). Again, all of the claims were thus

limited to concentrations of 60 mg/ml or greater. The specification also contained the two

studies from the provisional application plus a third similar study testing different compressors

for the Pari LC Plus with a different concentration of tobramycin (at 120 mg/ml). This latter

study was also ultimately part of the final ’907 disclosure. All of the studies, in other words,

involved concentrations at 60 mg/ml or 120 mg/ml.

On October 22, 2002, the patent examiner indicated that Chiron had improperly

attempted to merge a patent application for a method of administration with a patent describing

a formulation of an antibiotic for inhalation delivery (TX 96 at 359). Apparently during an

ex parte interview with Chiron’s counsel, Chiron indicated a preference to seek a patent of the

formulation, thus the remainder of the claims were to be cancelled (id. at 361–62). The claims

describing the formulation, however, were rejected by the examiner as obvious under 35 U.S.C.

103 in light of the ’269 patent (id. at 363). On April 22, 2003, Chiron amended its claims

(TX 96 at 341). On July 2, 2003, the patent examiner again rejected the claims (TX 96 at 325). 

The examiner determined that even the amended claims were obvious in light of the ’269 patent

(id. at 329–31).

On December 22, 2003, plaintiff filed a continuation of the earlier application, docketed

as Application No. 10/743,529 (TX 96 at 4), which finally survived the critique of anticipation. 

Once more, none of the claims identified concentrations weaker than 60 mg/ml.

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While Chiron’s patent application was pending, SourceCF filed an abbreviated new drug

application (“ANDA”) for approval of a “generic” competitor to TOBI named TOFIN. TOFIN

involved a concentration of tobramycin of 100 mg/ml for administration in the high-efficiency

nebulizer, the eFlow. TOFIN involved a lower total volume than TOBI and was capable of

faster nebulization than TOBI.

On April 20, 2004, Chiron submitted two letters to the FDA regarding SourceCF’s

ANDA to the FDA (TX 215, TX 216). Among Chiron’s criticisms, Chiron contended that

TOFIN needed to be tested more, that TOFIN was potentially unsafe, that SourceCF was

improperly filing an ANDA when it need to file a new application for approval of a drug-device

combination product, that TOFIN was less effective than TOBI, and that SourceCF had

misappropriated and misused certain of Chiron’s studies (which were ultimately part of the

’907 patent). Most notably, according to Chiron, “[t]he petition requests a change in product

concentration, volume, total drug content and formulation, and also proposes administration of

the new drug product via a delivery system that is unapproved or uncleared as well as different

from the delivery system in the approved labeling of the reference listed drug [TOBI]”

(TX 216). Chiron also commented “the Petition should be denied because the proposed

changes in drug concentration, volume and formulation clearly raise serious questions of safety

and effectiveness.” Moreover, “small changes in formulation parameters such as osmolality,

pH, and inactive ingredients are likely to produce changes in the delivery pattern and therefore

have the potential to impact the safety and efficacy of inhaled drug products.” The ANDA was

ultimately put on hold.

In June 2004, Chiron submitted an amendment to the pending patent application. In this

amendment, Chiron sought to add a claim that would have provided a total-dose limitation. 

Proposed claim 27 would have introduced the limitation of “[a] method of claim 1 wherein at

least 20 mg of trobramycin is administered to the patient” (id. at 154). On August 11, 2004, an

examiner’s amendment issued that cancelled claim 27. Chiron thus withdrew that claim.

On May 10, 2005, the ’907 patent issued. The primary claim of the ’907 patent

indicated (col. 63, lines 23–31) (emphasis added):

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1. A method of treatment of a patient having an endobronchial infection comprising administering to the patient for

inhalation a nebulized unit dose of 4.0 ml or less of an aqueous

solution comprising from about 60 to about 200 mg/ml of

tobramycin in a physiologically acceptable carrier for a duration

of nebulization less than about 10 minutes, using an inhalation

device having a rate of aerosol output of not less than about

4:l/sec, that releases at least about 75% of the loaded dose, and

that produces aerosol particles having particle sizes between

about 1 :m to about 5:m.

No claim in the ’907 patent identified a limitation to a particular “total dose” or “respirable

dose” of tobramycin. All claims called out concentrations of “about 60 mg/ml”or higher.

* * *

Litigation between these parties began even before the ’907 patent issued. An earlier

complaint, filed on October 5, 2004, accused defendants of unfair competition under California

Business and Professions Code § 17200 (Compl. ¶ 2). After one ruling, that lawsuit was

dismissed via settlement (id. ¶¶ 3–4).

In this action, commenced on the day that the patent issued, May 10, 2005, defendants

are alleged to infringe, induce infringement of and/or contributorily infringe one or more claims

of the ’907 patent by (1) selling a product called the eFlow inhaler and (2) instructing doctors

and CF victims how to use it. As noted, the defendants in this action are the SourceCF entities,

Maxor National Pharmacy Services Corporation (IV Solutions), Foundation Care L.L.C., and

Pharmaceutical Specialities, Inc.

At the time of the issuance of the ’907 patent, it was uncontested that the compounding

pharmacists were dispensing concentrations of tobramycin of 100 mg/ml (the concentration

contained in TOFIN) for use in the eFlow device. The parties entered into settlement

negotiations almost immediately after the filing of this lawsuit, with defendants essentially

conceding that such a concentration of tobramycin fell within the claims of the ’907 patent. 

Shortly after these negotiations, the pharmacy defendants stopped filling prescriptions for

concentrations of 100 mg/ml.

On December 1, 2005, upon the stipulated motion of the parties, this Court granted

plaintiff the following permanent injunction (at page 6):

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Defendants are preliminarily and permanently enjoined from

making, using, offering for sale, selling, promoting or importing

into the United States any tobramycin formulation in an aqueous

solution comprising from 60 to 200 mg/ml of tobramycin in a

physiologically acceptable carrier in a nebulized unit dose volume

of 4.0 ml or less for use in the eFlow® Electronic Inhaler by

PARI or a similar inhalation device having a rate of aerosol

output of not less than about 4:l/sec, releases at least about 75%

of the loaded dose, and produces aerosol particles having particle

sizes between about 1 :m to about 5:m, for a duration of

nebulization of less than about 10 minutes. Defendants are

further enjoined from instructing doctors or patients in such use.

By this point, however, the pharmacy defendants had shifted to dispensing concentrations of

40 mg/ml and 50 mg/ml tobramycin for use in the eFlow device pursuant to physicians’ orders. 

Some physicians, however, preferred the higher TOBI concentration and reverted back to

TOBI, prescriptions that the pharmacist defendants honored.

Chiron then contended that even concentrations of 50 mg/ml or less violated the patent. 

An issue remaining after the injunction order, therefore, was whether concentrations of

50 mg/ml or less infringed the ’907 patent. Given the narrow scope of the dispute, the Court

agreed to advance the trial date. To make this workable for the Court’s calendar, no issue of

patent invalidity was to be included in the trial. Defense counsel so agreed. An amended case

management order set a trial date of April 17, 2006. Defendants then moved for leave to file an

amended answer to add for the first time the affirmative defenses of non-infringement,

prosecution-history estoppel, patent invalidity for indefiniteness and patent misuse and to assert

a counterclaim for declaratory judgment with respect to non-infringement and patent invalidity. 

When this move threatened to undo the early trial date, the motion was withdrawn by

defendants’ counsel. Plaintiff dropped its claims for money damages. A bench trial thus

commenced on April 17, 2006, limited to the infringement issue. After two sets of closing

arguments, this order now follows.

CONCLUSIONS OF LAW

Applying the above factual findings to the law, this order holds that the accused 40 and

50 mg/ml concentrations at issue do not infringe the ’907 patent.

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1. LITERAL INFRINGEMENT—“ABOUT” AND “APPROXIMATELY” SHOULD BE APPLIED WITH CAUTION.

Chiron did not invent tobramycin. It did not invent any nebulizer, much less the class of

newer nebulizers. TOBI was, of course, already known by the time of the ’907 application. 

NEBCIN was likewise already known. Rather, as Chiron explains it, the ’907 patent disclosed

a concentration range and volume that would be safe and effective with the new generation of

nebulizers so as to provide treatment times of less than ten minutes. To have simply used the

existing TOBI vials in the newer equipment, Chiron says, would have led to overdoses, given

the ability of the newer equipment to atomize the liquid in a more absorbable mist.

The formulation claimed in the ’907 patent entailed a “unit dose of 4.0 ml or less of an

aqueous solution comprising from about 60 to about 200 mg/ml of tobramycin in

physiologically acceptable carrier.” A primary question at issue in this litigation is whether

concentrations of tobramycin of 50 mg/ml and 40 mg/ml infringe the patent. This requires a

determination of how far the term “about” stretches. The Court’s December 1 permanent

injunction construed “about” to mean “approximately.”

Regarding the term “about,” the Federal Circuit has noted:

Such broadening usages as “about” must be given reasonable

scope; they must be viewed by the decisionmaker as they would

be understood by persons experienced in the field of the

invention. Although it is rarely feasible to attach a precise limit

to “about,” the usage can usually be understood in light of the

technology embodied in the invention. When the claims are

applied to an accused device, it is a question of technologic fact

whether the accused device meets a reasonable meaning of

“about” in the particular circumstances.

Modine Mfg. Co. v. U.S. Int’l Trade Com’n, 75 F.3d 1545, 1554 (Fed. Cir. 1996), cert. denied,

518 U.S. 1005 (1996) (internal citation omitted); see also Eiselstein v. Frank, 52 F.3d 1035,

1040 (Fed. Cir. 1995) (“The meaning of the word ‘about’ is dependent on the facts of a case, the

nature of the invention, and the knowledge imparted by the totality of the earlier disclosure to

those skilled in the art”). In other words, setting the parameters of “about” in a patent is a

difficult and fact-specific task. With the benefit of the trial evidence, this order undertakes this

task now.

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 There are numerous other examples where the ’907 patent emphasized and showed preference for

specific concentrations: col. 6, line 25; col. 7, line 51 (“high concentrations”); col. 8, lines 21, 37, 42; col. 15,

lines 55–58; col. 23, line 14 (“TOBI 90 mg treatment”); col. 26, line 45 (“TOBI 90 mg dose using the Aeroose

inhaler were not as high as results achieved by the TOBI 300 mg”); col. 35, line 36 (“at least one of the three

TOBI doses (TOBI 90 mg) delivered by the experimental Aerodose inhaler achieved similar actual sputum

tobramycin concentrations”); col. 36, line 13 (“present serum tobramycin results demonstrated that TOBI 90 mg

delivered by the Aerodose inhaler were similar”).

12

Viewing the ’907 specification and the trial evidence, the terms “about” and

“approximately” must be read with caution. However far a concentration might deviate and still

be “about” or “approximately” 60 mg/ml, this order finds that the term does not extend to

concentrations as low as 50 mg/ml.

First, we must remember that the ’907 disclosure consisted solely of three clinical

studies. The ’907 clinical studies all involved concentrations of 60 mg/ml or higher. None

involved lower concentrations. The specification — despite its length — never addressed

concentrations of tobramycin of less than 60 mg/ml. On the contrary, the specification

repeatedly referred to the concentration involved as 60 mg/ml or above. For instance (col. 5,

line 62–col. 6, line 3) (emphasis added):

The aerosol formulations administered in the practice of the

invention may comprise from about 60 to about 200 mg/ml of

aminoglycoside antibiotic. In other aspects of the invention, the

aerosol formulations administered in the practice of the invention

may comprise from about 80 to about 180 mg/ml of

aminoglycoside antibiotic. In yet other aspects of the invention,

the aerosol formulations administered in the practice of the

invention may comprise from about 90 to about 150 mg/ml of

aminglycoside antibiotic.

Note well that in the above quotation the specified concentrations start at 60 mg/ml and then go

higher in concentration, not lower. The specification favored even higher concentrations as the

preferred embodiment (col. 7, lines 30–34) (emphasis added):

Formulations according to the invention typically contain from

about 60 to about 200 mg, more preferably from about 80 to

about 180, and most preferably from about 90 to about 120 mg of

aminoglycoside per ml of solution.

Again, the patent indicated (col. 7, lines 45–48):

Typically, about 90 to about 120 mg of aminoglycoside antibiotic

is dissolved in 1 ml solution of a diluted, typically quarter normal

saline containing about 0.225% NaCl.3

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All of the ’907 studies in the specification tested concentrations of 60 mg/ml or higher

(120 mg/ml), as will now be summarized.

The first example compared Chiron’s TOBI to a new nebulizer called AeroDose (made

by an independent company). That in vivo study involved individuals suffering from CF (col. 8,

line 55). The study used only 60 mg/ml concentrations of tobramycin: 30 mg in 0.5 ml

solution, 60 mg in 1.0 ml solution, and 90 mg in 1.5 ml solution. Those amounts were used

with the new AeroDose nebulizer in some patients. This concentration of 60 mg/ml

corresponded exactly to the TOBI concentration of 60 mg/ml. Other patients used Chiron’s

TOBI combination. The study analyzed the results on several parameters, including

nebulization time, efficiency, amount of tobramycin absorbed, and adverse side effects. The

study concluded that the AeroDose nebulized the three solution amounts faster and more

efficiently than the Pari LC Plus nebulized its total amount of solution.

The second example in the ’907 patent was a “Scintagraphy Study” (col. 37, line 15). 

Once again, it considered only a concentration of 60 mg/ml. The study compared doses of

60 mg of tobramycin in 1 ml solution inhaled in the AeroDose versus doses of 300 mg of

tobramycin in 5 ml of solution. Again, the conclusion was that the AeroDose was more

efficient. The second example did not suggest that concentrations of less than 60 mg/ml of

tobramycin could or should be used.

The last example tested two concentrations: 60 mg/ml and 120 mg/ml. This in vivo

study compared the Pari LC Plus equipped with a DeVilbiss PulmoAide compressor versus the

Pari LC Plus equipped with a Mobiliare compressor (col. 50, lines 48–56). The doses

administered to patients with CF were 420 mg of tobramycin in 3.5 ml of solution in the

Mobiliare unit and 300 mg of tobramycin in 5 ml of solution in the PulmoAide unit. The study

determined that the Mobiliare was faster, more efficient and equally effective as compared to

the PulmoAide. As with the first two examples, the third example tested no concentrations of

tobramycin below 60 mg/ml.

If it is true, as Chiron asserts, that the ’907 clinical studies were needed to show that

concentrations in the indicated range could be effectively and safely used with a more efficient

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 In light of Chiron’s argument, one must wonder about the upper end of the claimed concentration

range. A concentration of 200 mg/ml in a volume of four milliliters is within the claim. This would result in

800 milligrams of tobramycin, a large amount, being inhaled by children in a brief period; compare this to the

300 milligrams inhaled using TOBI and less efficient absorption equipment over more time. None of the ’907

studies vetted such methods.

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nebulizer for treatment times less than ten minutes, then the same physical and physiological

complexities necessitating the studies in the first place would require one of ordinary skill in the

art to use caution in attempting to extrapolate the conclusions in those studies to weaker

concentrations. Put differently, small changes in the parameters, Chiron maintains, can lead to

dangerous or ineffective results. Under Chiron’s own rationale for the invention, it would be

imprudent to view the ’907 tests as teaching broad conclusions about the interchangeability of

the various concentrations and volumes outside the specified range.4

Second, the specification of the ’907 patent expressly incorporated by reference the

’269 patent which, in turn, stated that concentrations below 60 mg/ml were normally

ineffective. Recall that the ’269 patent was obtained to cover TOBI and was owned by Chiron

by the time of the ’907 application. The ’907 patent expressly incorporated the ’269 in full (col.

3, lines 18–33) (emphasis added):

A preservative-free, stable and convenient formulation of

tobramycin (TOBI® tobramycin solution for inhalation; 60

mg/mL tobramycin in 5 mL of 1/4 normal saline) for administration via jet nebulizer was developed by PathoGenesis

Corporation, Seattle, Wash. (now Chiron Corporation,

Emeryville, Calif.). The combination of a 5 mL BID TOBI dose

(300 mg tobamycin) and the PARI LC PLUS/PalmoAide

compressor delivery system was approved under NDA 50-753,

December 1997, for the management of P. aeruginosa in CF

patients, and remains the industry standard for this purpose. The

aerosol administration of a 5ml dose of a formulation containing

300 mg of tobramycin in quarter normal saline for the suppression

of P. aeruginosa in the endobronchial space of a patient is

disclosed in U.S. Pat. No. 5,508,269, the disclosure of which is

incorporated herein in its entirety by this reference.

In turn, the ’269 specification included the following language about preferred

concentrations of tobramycin in the treatment of CF (col. 6, lines 38–47) (emphasis added):

Typically, two to four, preferably 300 mg of tobramycin is

dissolved in 5 ml solution of a diluted quarter normal saline,

preferably containing 0.225% NaCl.

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The most preferred aerosol tobramycin formulation

according to the invention contains 300 mg of tobramycin sulfate

per 5 ml of the quarter normal saline. This corresponds to 60

mg/ml of tobramycin which is minimal yet efficacious amount of

tobramycin to suppress the Pseudomonas aeruginosa infection in

endobronchial space.

The ’269 patent provided (col. 8, lines 3–41) (emphasis added):

The formulated dose of 60 mg/ml of one quarter diluted

saline has been found to be optimal for the most efficacious

delivery. Although in some instances both lower or higher doses,

typically from 40–80 mg/ml may be advantageously used, the 60

mg/ml dose of tobramycin is preferred. A more concentrated

tobramycin solution has three disadvantages. First, if the solution

approaches the solubility of tobramycin, 160 mg/ml, precipitation

on storage is expected. Second, a higher concentration of

tobramycin than is clinically needed is economically

disadvantageous. Thirdly, a more concentrated solution will

increase the osmorality of the solution, thus decreasing the output

of the formulation with both jet and ultrasonic nebulizers. The

alternative of a more concentrated solution in a smaller total

volume is also disadvantageous. Most nebulizers have a dead

space volume of 1 ml, i.e., that of the last 1 ml of solution is

wasted because the nebulizer is not performing. Therefore, while

for example, a 2 ml solution would have 50% wastage, the 5 ml

solution (the capacity of the nebulizer) has only 20% wastage. 

Additionally, since there is no sufficient aerosolization of the drug

into the small particles, the drug in large particles or as a solution

is deposited in the upper airways and induces cough and may also

cause bronchospasm. Large aerosol particles also limit the drug

delivery.

The dose lower than 60 mg of tobramycin of diluted saline

is not sufficient to suppress the bacterium and to treat the

infection. Lower concentrations of tobramycin will not be

sufficiently effective in at least 90% of patients. This is due to

variability of sputum tobramycin levels caused by anatomical

variability among patients as observed in Examples 4 and 5, and

also because the minimum inhibitory concentration of

Pseudomonas aeruginosa also varies. As seen in Table 4, a dose

of 300 mg total has been found to be optimal. Previously studied

doses 80 mg, Pedia Pulmonol., 6:91–8 (1989) were reported

effective, however, the dose would be predicted to be efficacious

in approximately sixty to seventy percent of patients initially. If

any degree of drug resistance developed, only a small percentage

of patients would be effectively treated.

One issue raised by this language is an estoppel to invoke the doctrine of equivalents to

reach concentrations weaker than 60 mg/ml. That issue will be considered below. For the

immediate purpose of literal infringement, the quoted language further supports a cautious

reading of the term “about.”

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In brief, although the earlier patent noted that “in some instances both lower or higher

doses, typically from 40–80 mg/ml may be advantageously used” (’269 patent, col. 8,

lines 3–4), the remainder of the language was an unequivocal critique of concentrations below

60 mg/ml. The ’269 patent described the 60mg/ml concentration as the concentration “which is

minimal yet efficacious,” “optimal,” and “preferred.” Lower concentrations were deemed “not

sufficient to suppress the bacterium and to treat the infection” and “will not be sufficiently

effective in at least 90% of patients.” In light of this critique, the limits of about 60 to about

200 mg/ml set forth in the ’907 patent must be read narrowly.

Third, the trial evidence was persuasive that the phrase “about 60 mg/ml” would

ordinarily be understood by those practicing such methods to refer to the limits of the

pharmacy’s professional measuring capabilities. Pharmacists typically provide actual

concentrations within two to five percent of the prescribed concentrations. Put differently,

doctors prescribe with precision, e.g., “60 mg/ml. They do not prescribe “about 60 mg/ml.” 

The pharmacists then dispense at concentrations, subject only to the industry-acceptable limits

of their equipment and professional capabilities, which, as stated, the trial evidence established

are two to five percent. Pharmacists cannot substitute a different concentration. The word

“about” refers to the range of tolerances prevailing in the subject field.

In short, the specification of the ’907 patent, the three examples in the ’907 patent, the

incorporated ’269 patent, and the measuring capabilities of the profession all lend a narrow and

cautious meaning to the word “about.” This rules 50 mg/ml as outside the literal scope of the

patent.

2. DOCTRINE OF EQUIVALENTS.

Chiron next asserts infringement under the doctrine of equivalents. “The scope of a

patent is not limited to its literal terms but instead embraces all equivalents to the claims

described.” Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., Ltd., 535 U.S. 722, 732

(2002). “[A] patentee may invoke this doctrine to proceed against the producer of a device ‘if it

performs substantially the same function in substantially the same way to obtain the same

result.’” Graver Tank & Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605, 608 (1950) (internal

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citations omitted). “The doctrine of equivalents allows the patentee to claim those insubstantial

alterations that were not captured in drafting the original patent claim but which could be

created through trivial changes.” Honeywell Int’l, Inc. v. Hamilton Sundstrand Corp., 370 F.3d

1131, 1139 (Fed. Cir. 2004) (citing Festo, 535 U.S. at 733).

“The doctrine of equivalents must be applied on an element by element basis.” Phillips

Petroleum Co. v. Huntsman Polymers Corp., 157 F.3d 866, 877 (Fed. Cir. 1998) (citing

Warner-Jenkinson Co. v. Hilton Davis Chem. Co., 520 U.S. 17 (1997)). Moreover, under the

“all limitations” rule, “an accused product or process is not infringing unless it contains each

limitation of the claim, either literally or by an equivalent.” Freedman Seating Co. v. Am.

Seating Co. 420 F.3d 1350, 1358 (Fed. Cir. 2005).

A. ESTOPPEL.

Under certain circumstances a patent owner is barred from relying on the doctrine of

equivalents. See, e.g., Honeywell, 370 F.3d 1131, 1140–41. “A particular structure can be

deemed outside the reach of the doctrine of equivalents because that structure is clearly

excluded from the claims whether the exclusion is express or implied.” SciMed Life Sys., Inc. v.

Advanced Cardiovascular Sys., Inc., 242 F.3d 1337, 1345 (Fed. Cir. 2001); see also Gaus v.

Conair Corp., 363 F.3d 1284, 1291 (Fed. Cir. 2004) (“[T]he patentee cannot reclaim that

surrendered claim coverage by invoking the doctrine of equivalents”); Astrazeneca AB,

Aktiebolaget Hassle, KBI-E, Inc. v. Mutual Pharm. Co., Inc., 384 F.3d 1333, 1342 (Fed. Cir.

2004) (“The specification’s clear disavowal of nonsurfactant solubilizers precludes the

application of the doctrine of equivalents to recapture the disavowed solubilizers”). The test for

such “specification disclaimer estoppel” thus is whether the patentee clearly disclaimed the

contested scope.

Application of such estoppel is a legal question, not a question of fact. “A patent

applicant may limit the scope of any equivalents of the invention by statements in the

specification that disclaim coverage of subject matter. Such limitations on the scope of

equivalents are legal determinations.” Frank’s Casing Crew & Rental Tools, Inc. v.

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 “Whether and to what extent material has been incorporated by reference into a host document is a

question of law.” Advanced Display, 212 F.3d at 1283. Any incorporated material must be considered in

interpreting the host document. “When a document is ‘incorporated by reference’ into a host document, such as

a patent, the referenced document becomes effectively part of the host document as if it were explicitly

contained therein.” Telemac Cellular Corp. v. Topp Telecom, Inc., 247 F.3d 1316, 1329 (Fed. Cir. 2001). 

Indeed, the whole point of incorporation by reference is to make the material part of the patent:

Instead of repeating some information contained in another document, an

application may attempt to incorporate the content of another document or

part thereof by reference to the document in the text of the specification. 

The information incorporated is as much a part of the application as filed

as if the text was repeated in the application, and should be treated as part

of the text of the application as filed.

Manual of Patent Examining Procedure, § 2163.07(b) (8th ed. 2006) (emphasis added).

It does not matter that the ’269 patent is a different patent with different inventors. A patentee may, in

fact, incorporate by reference any source “which is available to the public.” In re Howarth, 654 F.2d 103, 106

(C.C.P.A. 1981).

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Weatherford Int’l, Inc., 389 F.3d 1370, 1376 (Fed. Cir. 2004) (citing J & M Corp. v.

Harley-Davidson, Inc., 269 F.3d 1360, 1366 (Fed. Cir. 2001)).

As noted above, the ’907 patent expressly incorporated the ’269 patent by reference “in

its entirety.” “To incorporate material by reference, the host document must identify with

detailed particularity what specific material it incorporates and clearly indicate where that

material is found in the various documents.” Advanced Display Sys., Inc. v. Kent State Univ.,

212 F.3d 1272, 1282 (Fed. Cir. 2000); see also Manual of Patent Examining Procedure,

§ 2163.07(b) (8th ed. 2006). This order holds that the ’269 specification must be deemed in its

entirety to be part and parcel of the ’907 specification.5

As stated, the ’907 patent plainly and explicitly incorporated the entirety of the ’269

patent. We must now consider whether this disclaimed concentrations of less than 60 mg/ml.

To reiterate the key portions cited above, the ’269 patent stated that (col. 6, lines 42–47):

The most preferred aerosol tobramycin formulation

according to the invention contains 300 mg of tobramycin sulfate

per 5 ml of the quarter normal saline. This corresponds to 60

mg/ml of tobramycin which is minimal yet efficacious amount of

tobramycin to suppress the Pseudomonas aeruginosa infection in

endobronchial space.

Again, the ’269 patent stated (col. 8, lines 3–7, 28–31):

The formulated dose of 60 mg/ml of one quarter diluted

saline has been found to be optimal for the most efficacious

delivery. Although in some instances both lower or higher doses,

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 It is also worth noting that the disclaimer need not be in response to an action by the United States

Patent Office. See Festo, 535 U.S. at 736. While defendants have not pointed to any aspect of the prosecution

history of the ’269 patent suggesting office action, neither was such a fact suggested in SciMed.

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typically from 40–80 mg/ml may be advantageously used, the 60

mg/ml dose of tobramycin is preferred.

* * *

The dose lower than 60 mg of tobramycin of diluted saline

is not sufficient to suppress the bacterium and to treat the

infection. Lower concentrations of tobramycin will not be

sufficiently effective in at least 90% of patients.

The overt critique of concentrations less than 60 mg/ml places our case within the four

corners of Federal Circuit precedent limiting the reach of the doctrine of equivalents. In

SciMed, supra, the Federal Circuit explained:

As noted above, the common specification of SciMed’s patents

referred to prior art catheters, identified them as using the dual 

lumen configuration, and criticized them as suffering from the

disadvantages of having “larger than necessary shaft sizes” and

being “stiffer in their distal regions than would be desired.” That

criticism of the dual lumen configuration was consistent with the

evidence from SciMed witnesses and documents, which noted the

advantages of the coaxial lumen configuration in increasing the

flexibility of catheters and their ability to track through the

coronary arterial system. The disclaimer of dual lumens was

made even more explicit in the portion of the written description

in which the patentee identified coaxial lumens as the

configuration used in “all embodiments of the present invention.”

SciMed, 242 F.3d at 1345 (internal citations omitted). In SciMed, just as in the instant case, the

patentee did not state that the dual lumen configuration was completely useless, but did describe

in detail the disadvantages of that alternative configuration. Accordingly, the opinion ruled that

“[h]aving specifically identified, criticized, and disclaimed the dual lumen configuration, the

patentee cannot now invoke the doctrine of equivalents to ‘embrace a structure that was

specifically excluded from the claims.’” Ibid. (quoting Dolly, Inc. v. Spalding & Evenflo Cos.,

16 F.3d 394, 400 (Fed. Cir.1994)).6

Likewise, a similar result was reached in Dawn Equip. Co. v. Kentucky Farms Inc.,

140 F.3d 1009, 1016 (Fed. Cir. 1998). The Federal Circuit there overturned a jury verdict

finding infringement under the doctrine of equivalents. The opinion explained that:

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The patent teaches that such mechanisms are time-consuming to

adjust and are prone to misadjustment by inserting the pin in the

wrong holes, and furthermore the loose pins in such mechanisms

are easily lost. Kentucky Farms’ multiple-hole, pinned

height-adjustment mechanism is such a mechanism and shares

these same problems.

Ibid. (internal citations omitted). Accordingly, “[t]hese statements in the patent alone strongly

suggest, if not mandate, judgment in Kentucky Farms’ favor.”

Plaintiff relies on Micro Chemical v. Great Plains Chemical Company, 194 F.3d 1250,

1260 (Fed. Cir. 1999), for its argument that simply critiquing prior art in a later patent is not

sufficient to clearly disavow those claims in the later patent. In Micro Chemical, the

Federal Circuit ruled that inclusion of a prior art reference that contained certain limitations

could not be translated as a disclaimer for purposes of the later patent. The decision stated:

In restricting the scope of the apparatus and method claims

to cover only a cumulative weigh system, the district court read

the patentee’s statements about the Brewster prior art as a clear

disavowal of the weigh dump method. To the contrary, although

the applicant noted certain inefficiencies in the Brewster system,

the patent never clearly disavows the weigh dump method as

being incapable of performing the claimed functions. The

statements relied on by the district court in both the background

section and the prosecution history were directed to a particular

prior art device, the Brewster machine, not to the weigh dump

method in general.

The background section notes that the Brewster machine

“weighed and then dispensed each additive separately and

sequentially.” The background section further explains that this

machine “was unsuccessful because it was too slow and too

inaccurate for handling additive concentrates in a feedlot

environment.” Nothing, however, directly attributes the failures

of the Brewster machine to anything other than its particular

design. The patentee did not at any time assert that the weigh

dump method itself is the reason for the inaccuracies or slowness

of the Brewster system.

Ibid.

But the inventors’ critique of the prior art patent here is different from the critique in

Micro Chemical. It is true that there is a difference in the two patents — the ’269 patent

involved a low-efficiency nebulizer, not the high-efficiency nebulizer used in the ’907 patent. 

The ’907 inventors, however, did not rely on the earlier patent just to criticize the slow

nebulization time involved. Rather, they explicitly relied on the earlier patent as guiding the

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way for the proper concentration of tobramycin to put in the new high-efficiency nebulizer. 

Indeed, it is unpersuasive for Chiron to contend that the ’269 patent’s teachings on

concentration were criticized in the later ’907 patent when the later patent contained very

similar language about the efficacy of tobramycin concentrations below 60 mg/ml. As stated,

the ’907 patent, just like the ’269 patent, provided (col. 7, lines 30–34):

Formulations according to the invention typically contain from

about 60 to about 200 mg, more preferably from about 80 to about

180, and most preferably from about 90 to about 120 mg of

aminoglycoside per ml of solution.

Given that the ’907 patent not only incorporated the earlier patent but perpetuated its expression

of the preferred tobramycin concentrations, this order finds that plaintiff is estopped from

proving infringement by equivalence.

B. 50 MG/ML NOT EQUIVALENT TO ABOUT 60 TO 200 MG/ML.

Even if plaintiff were not estopped from relying on the doctrine of equivalents,

defendants’ formulations of tobramycin of 50 mg/ml and 40 mg/ml would not infringe the

’907 patent via the doctrine of equivalents.

An expansive view of equivalency is inappropriate where, as here, the patent involves,

at most, a modest improvement over the prior art. As the Federal Circuit has explained:

. . . while a pioneer invention is entitled to a broad range

application of the doctrine of equivalents, an invention

representing only a modest advance over the prior art is given a

more restricted (narrower range) application of the doctrine.

When a patentee claims an improvement over an earlier invention,

other parties are entitled to practice variations of that prior

invention, so long as they are not the same as, or an equivalent of,

the improvement claimed by the patentee.

Thomas & Betts Corp. v. Litton Systems, Inc., 720 F.2d 1572, 1580 (Fed. Cir. 1983); see also

GMI Holdings, Inc. v. Stanley Door Sys., Inc., 943 F. Supp. 1420, 1427 (N.D. Ohio 1996) (“a

pioneer invention, one which represents a major advance over the prior art, is entitled to a broad

and liberal application of the doctrine of equivalents, while one that adds little to the state of the

art is not”). The Supreme Court has also expressed general skepticism about broad readings of

the doctrine of equivalents. Warner-Jenkinson Co., Inc. v. Hilton Davis Chem. Co., 520 U.S.

17, 29 (1997) (“There can be no denying that the doctrine of equivalents, when applied broadly,

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conflicts with the definitional and public-notice functions of the statutory claiming

requirement”).

Here, as indicated above, the ’907 patent represented at most a modest improvement. 

Chiron did not invent tobramycin. Chiron did not invent high-efficiency nebulizers. Chiron did

not invent even low-efficiency nebulizers. Chiron did not invent inhalation therapy. As stated,

the ’907 patent disclosed nothing about concentrations lower than 60 mg/ml and called out

concentrations higher than 60 mg/ml (90 mg/ml to be precise) as the preferred embodiment. 

Via the ’269 incorporation, the patent itself taught away from weaker concentrations as

effective.

Chiron asserts that its ’907 studies established the medically-appropriate concentration

and volumes suitable for use with the new generation of nebulizers. In its most favorable light

to Chiron, the ’907 studies proved that the standard 60 mg/ml TOBI dose of 5 ml could be

reduced to 1.5, 1.0 and 0.5 ml and still remain effective when used with the new generation of

nebulizers. Chiron has emphasized the inherent complexities and tradeoffs with small

variations portending large possible variations as justifying the patent in the first place. If so,

the teaching of the ’907 studies must be viewed with caution, as stated above. Accordingly, a

wide swath of equivalents would be unreasonable. Chiron has not proven that one of ordinary

skill in the art would regard the accused methods as an insubstantial change from the methods

taught or claimed in the patent in suit or would regard the accused methods to use substantially

the same concentrations as the disclosed or claimed methods.

Contrary to Chiron, a “hypothetical claim analysis” does not supersede all other

requirements of the doctrine of equivalents. A “hypothetical claim analysis” is used to test the

validity of supposed equivalents against the prior art. It asks whether a hypothetical claim

covering the range of asserted equivalents “could have been allowed by the PTO over the prior

art.” Wilson Sporting Goods Co. v. David Geoffrey & Assoc., 904 F.2d 677, 684 (Fed. Cir.

1990). If the answer is yes, then Chiron asserts the doctrine of equivalents inquiry is

over — equivalence has been shown. This is wrong.

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Before any “hypothetical claim analysis” comes into play, the doctrine of equivalents

must otherwise be satisfied and the equivalence issue must have devolved to whether the prior

art would have anticipated or rendered obvious the proposed scope of equivalents, thus

preventing application of the doctrine of equivalents. In analyzing the latter, it may be useful to

pose the question of whether a hypothetical claim — drawn to cover the asserted

equivalents — could have been allowed by the PTO over the prior art.

Here, however, the immediate problem is not the prior art. It is the fact that the

’907 tests taught little (if anything) about concentrations below 60 mg/ml. That is not a prior art

problem. It is a specification/disclosure problem. The problem is also that the ’907 disclosure

expressly taught away from concentrations below 60 mg/ml. That also is not a prior art

problem. It is a specification/disclosure problem. Put differently, one of ordinary skill in the

art would not view the accused method as an insubstantial change from the teaching of the

patent. The fundamentals of the doctrine have not been met in the first place. Chiron is wrong

in asserting, therefore, that Abbott Laboratories v. Dey, L.P., 287 F.3d 1097, 1105–07 (Fed. Cir.

2002), somehow collapsed the entire doctrine of equivalents into a “hypothetical claim

analysis.”

The thrust of Chiron’s case is that total dose — not concentration — is the essential

consideration. This would read the concentration limitation out of the claim. According to

Chiron, the total dose used in the accused methods falls within the total dose reachable via

concentrations covered by the claim. For example, if 100 mg in 1 ml is within the claim,

Chiron argues that 100 mg in 2 ml should also be deemed within the claim since the total dose

is still 100 mg.

The doctrine of equivalents cannot be used to vitiate an entire claim limitation. As the

Federal Circuit instructed:

. . . courts must consider the totality of the circumstances of each

case and determine whether the alleged equivalent can be fairly

characterized as an insubstantial change from the claimed subject

matter without rendering the pertinent limitation meaningless.

Freedman, 420 F.3d at 1359. When Chiron filed this action, it argued vociferously that

defendants were infringing the patent by dispensing concentrations of 100 mg/ml. When

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defendants ceased using any concentration within the range, Chiron reversed field and advanced

its current argument that the concentration limitation should, in effect, be ignored.

Under Chiron’s view, concentration would become meaningless. This became glaringly

obvious during the testimony of Chiron’s expert witnesses. For example, plaintiff presented

testimony from Dr. Warren Finlay, an expert in aerosol science and aerosol delivery systems of

medications (Tr. 165–66). According to this expert’s math, the potential concentration and the

accused concentration result in similar amounts of tobramycin being captured in the lungs

(Tr. 189). But his methodology wound up proving too much. When he was asked to run the

numbers for even weaker concentrations, i.e., concentrations at 30 mg/ml or less, the difference

in lung-captured amounts was yet again small. His methodology tended to prove that almost

any weak concentration would still infringe.

Similarly, Dr. Gerald Smaldone, plaintiff’s expert in aerosol science and aerosol

delivery systems of medication, used a methodology that proved too much. He testified (Tr.

119):

Q: In your opinion, Doctor, does it — does a change in

concentration from 60 to 50 to 40 in the context of the

’907 patent, and in comparing that to the defendants’

formulations, is that kind of change meaningful in any

way with regard to what these formulations are designed

to do?

A. In my opinion, there’s no difference between any of these

formulations that are described in the patent, because what

they’re all designed to do is to provide the same nebulizer

dose, and I’ve tried to illustrate in my calculations that

they’re all covered by the claims in that patent.

Later, he testified “I mean, there’s no way to distinguish the formulations at 50 milligrams

per ml from the 60 milligrams per ml solution. They provide the same nebulized dose”

(Tr. 123). So, too, concentrations of 40 and 60 mg/ml are “completely interchangeable,”

according to Dr. Smaldone (Tr. 124). The Court then asked Dr. Smaldone to consider

concentrations of 30 mg/ml in a 3.4 ml total dose (Tr. 144). In response, Dr. Smaldone testified

that the example given by the Court would infringe under his methodology and, indeed, resulted

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 Given that Chiron places such emphasis on the Abbott opinion, supra, it is worth noting that Chiron’s

expert testimony provides another distinction from Abbott. In Abbott, the Federal Circuit found that the district

court erred in its hypothetical claim analysis by concluding that Abbott’s experts would have completely

eviscerated all boundaries to the claimed range at issue. The Federal Circuit concluded that Abbott would not

be precluded from relying on the doctrine of equivalents because the application “does not eliminate the upper

limit of phospholipid from the claim.” 287 F.3d at 1107. Here, as Chiron’s experts made clear, on their view,

there would be no lower boundary. It was evident from the expert that there would be almost no concentration

too weak to fall outside of Chiron’s proposed range of equivalents.

8

 This is further substantiated by the fact that Chiron withdrew proposed claim 27, which would have

described a claim in terms of total dose, not concentration (TX 96 at 154). The Federal Circuit has deemed that

such an amendment can limit a patent holder’s ability to reclaim the withdrawn limitation via the doctrine of

equivalents. See, e.g., Honeywell, 370 F.3d at 1141.

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in a total dose (about 100) greater than a lower total dose (80) he had already testified was an

infringing equivalent.7

Chiron also points to the PTO examiner’s reasons for allowance as further support that

the ’907 patent was not concerned with concentration. The examiner noted that the novel

features of the ’907 invention, as compared to the ’269 patent, “reside in requiring 10 minutes

or less for duration of nebulization, with an inhalation device having a rate of aerosol output of

not less than 4μl/sec that releases at least 75% of the loaded dose and that produces particle

sizes of between about 1μ to about 5μ” (TX 96 at 141). More than suggesting that the

concentration limitation contained in the ’907 was trivial, it appears the examiner simply did

not think the concentration described was different from the ’269 patent. After all, the ’907

patent, the ’269 patent and TOBI all described concentrations of at least 60 mg/ml and the ’907

patent incorporated the ’269 patent’s teachings (and disavowals) regarding concentration. The

concentration in the ’907 did not expand the boundaries of tobramycin concentrations for

inhalation (such as by demonstrating that weaker concentrations could be used). Instead, the

method of this patent reiterated that the concentration was to be kept at 60 mg/ml or higher. 

The patent must be limited by that reasoning.8

Chiron extolled the importance of concentration in its letters to the FDA in response to

SourceCF’s ANDA for TOFIN in 2004 (TX 215, TX 216). As noted above, Chiron informed

the FDA that the change in concentration from TOBI to TOFIN (60 mg/ml to 100 mg/ml) could

have significant consequences on the safety and efficacy of the medication. It is true, as Chiron

argues, “that the quantum of proof necessary for FDA approval is significantly higher than that

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 The exceptions occurred after the patent issued. Instead of drawing a parallel to TOBI, they drew a

parallel to the pre-patent eFlow therapy using 100 mg/ml (TX 30; TX 45; TX 72A; Sledge Depo. 208). For the

reasons stated in the text, however, the decisive factor is that the result was not achieved in the same way as the

patented method.

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required by the PTO.” Purdue Pharma L.P. v. Endo Pharmaceuticals Inc., 438 F.3d 1123,

1134 (Fed. Cir. 2006). This order, therefore, does not view Chiron’s letters as conclusive

admissions of non-equivalence. Chiron’s representations to the FDA at the least, however,

indicate that Chiron has long agreed that small changes in concentration are non-trivial.

Finally, Chiron also argues “[d]efendants’ own witnesses testified, and their own

documents reflect, that their 50 mg/ml and 40 mg/ml formulations are deliberately designed to

deliver an equivalent respirable dose as compared to the enjoined 100 mg/ml formulations”

(Br. 4) (emphasis in original). There is some truth to this charge but it does not carry the day,

for the following reasons.

Before the patent issued, defendants promoted their eFlow therapy as delivering an

“equivalent respirable dose” to TOBI (TX 6). “Respirable dose” means the amount of

tobramycin absorbed into the lungs (Tr. 120). Due to its efficiency, the eFlow nebulizer could,

it was claimed, deliver as much absorption as TOBI while using less solution than TOBI and

taking less time. Before the patent issued, the eFlow promotion was based, as Chiron points

out, on a concentration of 100 mg/ml.

After the patent issued, defendants eventually began promoting the two weaker

concentrations at issue. This was done to respect Chiron’s patent rights (TX 30). The

promotion, however, still portrayed the eFlow therapy as delivering a respirable dose

“equivalent” to that delivered by TOBI. This time, of course, the promotion featured weaker

concentrations than those called out by the ’907 patent (TX 72A).

With some exceptions, defendants are correct that the equivalence was drawn to TOBI

and that TOBI is prior art for our purposes.9

 But this is not a satisfactory answer, for the point

was to achieve TOBI’s effectiveness but in less time with the newer equipment, like the

inventors.

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10 It must be noted that the ’907 contains no claim limitation for a certain “respirable dose.” Indeed,

nowhere in the specification does “respirable dose” appear. So too for the ’269 patent. The only use of the

word respirable at all in the ’907 specification is in relation to “respirable” particles (col. 49, lines 37–40).

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The convincing point of distinction lies elsewhere. Although defendants have used the

word “equivalent,” nowhere have they stated that the method promoted was equivalent to the

method patented. Rather, they have said that the respirable dose delivered by each method is

equivalent. At most, this admitted that the result achieved is the same.10 But the key is that the

result is not achieved in the same way. The basics of inhalation therapy and even TOBI were

already known. The supposed invention was the discovery that concentrations at about

60 mg/ml or higher could be safely and effectively administered via the more efficient

nebulizers. That lower concentrations could also be safely and effectively used was discovered

by defendants. For the reasons stated earlier, the ’907 patent did not teach use of the lower

concentration. It taught away from using lower concentrations as ineffective. Based on what

was the supposed discovery of the ’907 patent, one of ordinary skill in the art would not have

understood that the weaker concentrations at issue would have been safe and effective or merely

an insubstantial change from the patented method. The use of the specified concentration range

was an integral step in the patented method. The accused methods may well achieve the same

result but it gets there via a different way.

3. ISSUES NOT REACHED.

This order does not address the potential invalidity of the ’907 patent. The patent in suit

is in the category of “medical-method patents.” The validity of such patents is controversial. 

See Donald S. Chisum, Chisum on Patents, § 1.03[2][d][3] (2005). The Federal Circuit,

however, has approved the validity of some medical-method patents and this Court need not

determine the issue here. As noted, the Court agreed to advance the trial date. The parties in

turn agreed to narrow scope of the dispute to make this schedule workable, including agreeing

not to argue patent invalidity at trial.

This order also does not address whether the claims in the ’907 patent constitute “stepplus-function” or “means-plus-function” limitations under 35 U.S.C. 112 ¶ 6. Of course, if

Paragraph 6 were to apply, “a claim term will cover nothing more than the corresponding

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structure or step disclosed in the specification, as well as equivalents thereto.” CCS Fitness,

Inc. v. Brunswick Corp., 288 F.3d 1359, 1367 (Fed. Cir. 2002). A recent legal issue that has

arisen is the interplay between Paragraph 6 limitations and method patents. See Chisum,

§ 18.03[5][e][iii]. This order, however, finds that defendants did not infringe the patent in suit

on other grounds and thus need not reach this issue.

CONCLUSION

For the foregoing reasons, this order finds that the 40 mg/ml and 50 mg/ml

concentrations in dispute do not infringe the ’907 patent under any theory. Judgment for

defendants will be entered accordingly.

IT IS SO ORDERED.

Dated: May 16, 2006. WILLIAM ALSUP

UNITED STATES DISTRICT JUDGE

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