  United States Court of Appeals
      for the Federal Circuit
                ______________________

        CUBIST PHARMACEUTICALS, INC.,
             Plaintiff-Cross-Appellant

                           v.

                   HOSPIRA, INC.,
                 Defendant-Appellant
                ______________________

            2015-1197, 2015-1204, 2015-1259
                ______________________

    Appeals from the United States District Court for the
District of Delaware in No. 1:12-cv-00367-GMS, Judge
Gregory M. Sleet.
                 ______________________

              Decided: November 12, 2015
                ______________________

   WILLIAM F. LEE, Wilmer Cutler Pickering Hale and
Dorr LLP, Boston, MA, argued for plaintiff-cross-
appellant. Also represented by MARK CHRISTOPHER
FLEMING, LISA JON PIROZZOLO; WILLIAM G. MCELWAIN,
Washington, DC.

   JAMES F. HURST, Kirkland & Ellis LLP, Chicago, IL,
argued for defendant-appellant. Also represented by JOHN
C. O'QUINN, Washington, DC; LESLIE M. SCHMIDT, New
York, NY; STEFFEN NATHANAEL JOHNSON, JOVIAL WONG,
Winston & Strawn LLP, Washington, DC; JAMES
MATTHEW HILMERT, TYLER JOHANNES, GEORGE C.
2              CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.



LOMBARDI, Chicago, IL; STEPHEN R. SMEREK, Los Angeles,
CA.
               ______________________

    Before WALLACH, BRYSON, and HUGHES, Circuit Judges.
BRYSON, Circuit Judge.
    This case arises under the Hatch-Waxman Act, which
governs certain patent disputes between pharmaceutical
companies. 1 The plaintiff, Cubist Pharmaceuticals, Inc.,
owns five patents that relate to the antibiotic daptomycin.
The defendant, Hospira, Inc., sought authorization to sell
a generic version of Cubist’s daptomycin product, which
led Cubist to file this action charging Hospira with patent
infringement.
    Daptomycin was developed by Eli Lilly & Co. (“Lilly”).
The original patent to daptomycin expired in 2002. The
five patents at issue in this case are all follow-on patents
owned by Cubist. The first is U.S. Patent No. RE39,071
(“the ’071 patent”), which is a reissue of U.S. Patent No.
5,912,226 (“the ’226 patent”) and is directed to antibiotic
compounds, compositions, formulations, and methods of
treating bacterial infections. The next two are U.S.
Patent Nos. 6,852,689 and 6,468,967 (“the ’689 and ’967
patents”), which are entitled “Methods for Administration
of Antibiotics” and are directed to dosage regimens for
administering daptomycin. The final two are U.S. Patent
Nos. 8,058,238 and 8,129,342 (“the ’238 and ’342 pa-
tents”), which are entitled “High Purity Lipopeptides” and




      1 The Hatch-Waxman Act is the name commonly
used to refer to the Drug Price Competition and Patent
Term Restoration Act of 1984, Pub. L. No. 98-417, 98 Stat.
1585, the principal provisions of which are codified at 21
U.S.C. § 355 and 35 U.S.C. §§ 156 and 271(e)(2).
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.            3



are directed to the purification of daptomycin composi-
tions.
    Cubist sells its daptomycin formulation under the
trade name Cubicin. In 2011, Hospira filed an Abbreviat-
ed New Drug Application with the Food and Drug Admin-
istration seeking approval to manufacture and sell an
equivalent daptomycin product prior to the expiration of
Cubist’s patents. Pursuant to procedures set forth in the
Hatch-Waxman Act, Cubist then filed an action in the
United States District Court for the District of Delaware,
alleging that Hospira had infringed all five of Cubist’s
patents. Hospira responded by challenging the validity of
the asserted claims of each of those patents. Two other
related actions brought by Cubist were subsequently
consolidated with the initial lawsuit.
     Following a bench trial, the district court held some of
the asserted claims of four of Cubist’s patents invalid for
anticipation and all the asserted claims of those patents
invalid for obviousness. As for the fifth patent, the court
held the two asserted claims not invalid and ruled that
Hospira’s proposed products infringed those claims. Both
parties appeal from the portions of the judgment adverse
to them. We affirm the judgment of the district court,
relying heavily on the factual findings made by the court
following the trial.
                              I
    Hospira appeals from the district court’s ruling that
Hospira infringed claims 18 and 26 of the ’071 patent and
that those claims are not invalid. Hospira’s appeal focus-
es on a certificate of correction granted to Cubist with
regard to the ’071 patent. The certificate corrected a
diagram of the chemical structure of a compound de-
scribed in the specification and recited in four of the
claims of the ’071 patent, including claims 18 and 26.
4             CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.



                            A
                            1
     The asserted claims of the ’071 patent recite an anti-
biotic composition and a pharmaceutical formulation,
each comprising a combination of three compounds. The
first and second compounds in each claim are daptomycin-
related substances. The first is known as anhydro-
daptomycin and the second is known as the beta isomer of
daptomycin. The third compound, referred to as Formula
3, is the compound known in the art as daptomycin. 2
    The specification of the ’071 patent describes the
Formula 3 compound in three ways. First, it refers to the
compound as “an A-21978C cyclic peptide.” According to
the specification, A-21978C cyclic peptides “are prepared
from the A-21978C antibiotics,” which are “a group of
closely related, acidic peptide antibiotics” that are de-
scribed in U.S. Patent No. 4,208,403 (“the ’403 patent”).
’071 patent, col. 6, ll. 59-61; col. 7, ll. 41-42. The ’403
patent in turn describes the A-21978C antibiotics as being
produced by a process involving the fermentation of the
bacterium Streptomyces roseosporus.
    Second, the specification of the ’071 patent refers to
the Formula 3 compound by the code name LY146032.
That code name was assigned to the compound by Lilly
and was known in the art to refer to daptomycin.
    Third, the specification states that the Formula 3
compound has the following structure, where RN is n-
decanoyl:




    2  For clarity, we refer to “daptomycin” as the com-
pound that is found in Cubicin and was the subject of
Hospira’s Abbreviated New Drug Application.
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.         5




    It turns out that the structural diagram of the com-
pound identified as Formula 3 and depicting daptomycin
was inaccurate in one respect. The structure in the
diagram contained 13 amino acids, including asparagine
(abbreviated “Asn”). While the diagram accurately identi-
fied the amino acids and their location in the daptomycin
molecule, it mistakenly identified the stereoisomer of the
asparagine amino acid as the “L” stereoisomer of aspara-
gine, rather than the “D” stereoisomer.
     At the time the application for the ’226 patent was
filed, and until well after that patent was issued, it was
universally believed that the asparagine amino acid in
daptomycin was the L-isomer of asparagine, as set forth
in the structural diagram. Years after the issuance of the
’226 patent and after the reissue application for the ’071
patent was filed, Lilly researchers discovered that dap-
tomycin actually contains the D-isomer of asparagine, not
the L-isomer.
6              CUBIST PHARMACEUTICALS, INC.    v. HOSPIRA, INC.



    In 2007, Cubist sought to correct the error by request-
ing a certificate of correction from the Patent and Trade-
mark Office (“PTO”) pursuant to 35 U.S.C. § 255. Cubist
explained that the mistake in the patent as to the identity
of the stereoisomer of asparagine was “the result of the
mischaracterization of one of the A-21978C factors de-
scribed by Formula 3.” Specifically, Cubist explained,
“the patentees erred in describing one amino acid’s stere-
ochemistry as ‘L-Asn’ in the tail of the compound illus-
trated in Formula 3, when the correct stereochemistry of
the disclosed and claimed amino acid is ‘D-Asn.’” Cubist
further explained that the true nature of the stereochem-
istry of daptomycin was disclosed in a 2005 journal article
by Vivian Miao et al. The Miao article, Cubist stated,
“demonstrates that the A-21978C factors of Formula 3
inherently contain the ‘D-Asn’ in the tail portion illustrat-
ed in Formula 3 when isolated from their native source,
not an ‘L-Asn.’”
    The examiner concluded that it was appropriate to
use a certificate of correction to correct the error identified
by Cubist. Accordingly, the examiner issued the certifi-
cate, correcting the diagram of Formula 3 in the specifica-
tion and four of the claims of the ’071 patent by
substituting “D-Asn” for “L-Asn” in the diagram.
                              2
     Before the district court, Hospira argued that the PTO
had erred by issuing the certificate of correction because
the change in the structural diagram of Formula 3 altered
the substance of the claims, broadening their reach.
Accordingly, Hospira argued, the ’071 patent should be
construed to be limited to the variant of the daptomycin
compound containing the L-isomer of asparagine. The
compound with the L-isomer of asparagine is an antibi-
otic, but a much less potent one than daptomycin.
    Hospira’s expert testified that Formula 3 with the L-
isomer of asparagine was an entirely different compound
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.            7



from Formula 3 with the D-isomer of asparagine. He
therefore concluded that the asserted claims did not read
on daptomycin. The expert admitted, however, that he
had not considered the specification of the ’071 patent in
reaching his determination that the certificate of correc-
tion had the effect of broadening the claims of the patent
to read on daptomycin for the first time.
     Cubist’s expert testified that the specification made it
clear that the claims of the ’071 patent were directed to
daptomycin, not to the variant containing the L-isomer of
asparagine. Because it was plain that the claims were
directed to daptomycin, Cubist argued, it was appropriate
for the PTO to correct the error in the structural diagram
of Formula 3.
    The district court acknowledged that the chemical
structure of Formula 3 in the corrected version of the ’071
patent is different from that of the pre-correction version
of the patent. However, the court characterized the PTO’s
action as simply correcting an error in the diagram of
Formula 3 without changing the scope of the patent. The
court agreed with Cubist that the specification made clear
that the patent claimed the daptomycin compound all
along; the pre-correction version merely misidentified the
stereoisomer of the asparagine amino acid found in that
compound.
    Based on the evidence summarized above, the district
court concluded that Hospira had not satisfied its burden
to show that the certificate of correction was invalid. In
particular, the court ruled that the specification as a
whole “confirms that the Formula 3 compound identified
in the claims is truly D-asparagine daptomycin, the by-
product of the fermentation process” described in the
specification. Accordingly, the court held, substituting L-
asparagine for D-asparagine in the Formula 3 chemical
structure was “a correction of minor character because it
did not result in ‘the new version cover[ing] territory the
8             CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.



old one did not.’” Contrary to Hospira’s contention, the
court explained, “D-asparagine was covered both before
and after correction.”
                            3
    On appeal, Hospira argues that the change in the ’071
patent made by way of the certificate of correction was not
a change “of minor character,” as provided for in section
255, because the change broadened the scope of the as-
serted claims. See Superior Fireplace Co. v. Majestic
Prods. Co., 270 F.3d 1358, 1375 (Fed. Cir. 2001) (“A
mistake that, if corrected, would broaden the scope of a
claim must thus be viewed as highly important and thus
cannot be a mistake of ‘minor character.’”). In Hospira’s
view, because the change from L-Asn to D-Asn in the
structural diagram broadened the scope of the claims to
read on daptomycin rather than the L-Asn variant of
daptomycin, the certificate of correction was invalid.
     Once the PTO has issued a certificate of correction, a
court may invalidate the certificate only upon a showing
of clear and convincing evidence that it was improperly
issued. Superior Fireplace Co., 270 F.3d at 1367. In this
case, no such showing has been made.
    The problem with Hospira’s argument is that the
district court did not view the change in the diagram as
changing the scope of the claims at all. Instead, the court
regarded the change as simply conforming the structural
diagram of Formula 3 to the compound described in the
specification and covered by the claims.
    Contrary to Hospira’s argument, the original struc-
tural diagram in the ’071 patent did not establish that the
patent was directed to a compound other than daptomy-
cin. As this court has noted, a chemical structure is
“simply a means of describing a compound; it is not the
invention itself.” Regents of Univ. of N.M. v. Knight, 321
F.3d 1111, 1122 (Fed. Cir. 2003). In determining what
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.           9



compound the patent claims were directed to, the proper
focus is not limited to the chemical structure depicted in
the diagram. Instead, the specification as a whole must
be considered. As the district court explained, the Formu-
la 3 compound is defined not only by the structural dia-
gram, but also by other portions of the specification.
    The specification of the ’071 patent does not rely ex-
clusively on the structural diagram of Formula 3 to de-
scribe the subject compound. By reference to a co-pending
application (later issued as U.S. Patent No. 4,885,243),
the specification teaches that daptomycin is obtained
through fermentation of Streptomyces roseosporus. That
fermentation process necessarily results in daptomycin,
not the variant with the L-isomer of asparagine. The
evidence at trial established that the L-isomer variant
cannot be produced by fermentation and can only be
produced synthetically.
    In addition, the specification describes the claimed
compound by the code name given to it by Lilly—the
designation LY146032. Evidence introduced by Cubist at
trial showed that the code name LY146032 refers to
daptomycin, not the variant of daptomycin with the L-
isomer of asparagine.
    Finally, at the time of the original application that
matured into the ’226 patent, it was universally believed
that the asparagine amino acid in daptomycin was the L-
isomer of asparagine, not the D-isomer. It was not until
well after the filing of the original ’226 patent (in 1991),
the issuance of that patent (in 1999), and the filing of the
reissue application (in 2000) that Lilly researchers deter-
mined that the previous understanding of the structure of
daptomycin was mistaken, and that the asparagine amino
acid in daptomycin is the D-isomer of asparagine, not the
L-isomer, as previously thought. Even though research-
ers had previously been mistaken about the precise
chemical structure of daptomycin, it was nonetheless
10            CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.



clear from the specification that the patentees possessed
daptomycin (with the D-isomer of asparagine) and that
the references to Formula 3 in the claims of the ’071
patent were directed to daptomycin.
                             4
    Hospira relies heavily on this court’s decision in Bayer
v. Dow Agrosciences LLC, 728 F.3d 1324 (Fed. Cir. 2013).
That case, however, is different in important ways from
this one. The patentee in Bayer claimed, in pertinent
part, a recombinant gene comprising a DNA sequence
encoding for a polypeptide “having the biological activity
of 2,4-D monooxygenase.” Id. at 1326. Although it was
determined long before Bayer’s patent issued that the
gene Bayer had sequenced encoded for an enzyme that
was a dioxygenase, not a monooxygenase, Bayer did not
seek to change the claim language to reflect the error.
Instead, Bayer argued that the claim language should be
interpreted to cover any DNA sequence that codes for an
enzyme that alters a common herbicide known as 2,4-D by
cleaving its side chain, regardless of whether the cleaving
enzyme is a monooxygenase or a dioxygenase. Id. at
1327.
     This court rejected that argument as a matter of claim
construction. We explained that Bayer’s proposed con-
struction would be inconsistent with the “strong accepted
scientific meaning” of the claim language by “strip[ping]
the monooxygenase half of the claim phrase of its accept-
ed descriptive meaning” and “assert[ing] a specification
‘definition’ of the biological-activity half.” 728 F.3d at
1330. Beyond that, Bayer’s proposed claim construction
would have raised serious doubts about the validity of
Bayer’s claim by broadening the claim to cover the enzy-
matic function of causing the cleavage of the side chain of
2,4-D, but not “providing even an indirect structural
identification of all that would be within the claim’s
scope.” Id. at 1331.
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.           11



     In this case, unlike in Bayer, the applicants sought a
certificate of correction to correct the structural diagram,
which was based on a previous misunderstanding of the
chemical structure of the claimed compound. Given the
other descriptions of the claimed compound in the specifi-
cation, the PTO and the district court concluded that the
reference to the L-isomer of asparagine was an error and
that the claimed compound was the compound with the D-
isomer of asparagine. In Bayer, by contrast, the patentee
sought a broad, functional claim construction based on the
original claim language. We found that claim construc-
tion to be seriously flawed and rejected it. Given the very
different approaches employed by the patentees in the
two cases, as well as the strong indications in the specifi-
cation of the ’071 patent that Formula 3 was in fact
daptomycin (despite the error in the structural diagram),
the outcome of this case is not controlled by Bayer.
    In light of the heavy burden on a party seeking to in-
validate a certificate of correction, we uphold the district
court’s conclusion that the certificate of correction did not
alter the scope of the patent, but merely corrected an
error as to the chemical structure of daptomycin. We
therefore reject Hospira’s argument that the asserted
claims of the ’071 patent should be limited to the variant
of daptomycin containing the L-isomer of asparagine.
                             B
    Hospira next argues that if the validity of the certifi-
cate of correction is sustained, the asserted claims of the
’071 patent should be held invalid for violating the writ-
ten description requirement of 35 U.S.C. § 112. Like the
district court, we reject that argument, and for the same
reasons.
    Hospira contends that the written description re-
quirement was not satisfied because the specification did
not disclose the features or structure of daptomycin
(containing the D-isomer of asparagine), and thus the
12            CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.



specification provided no indication that the inventors
knew they were working with daptomycin having that
structure.
    The district court found as a matter of fact that the
disclosure of the specification reasonably conveyed to
those skilled in the art that the inventors had possession
of the claimed subject matter as of the filing date, i.e.,
that the specification described “an invention under-
standable to [a] skilled artisan and show[ed] that the
inventor actually invented the invention claimed.” Ariad
Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed.
Cir. 2010) (en banc). Notwithstanding the error in the
structural diagram of Formula 3, the court concluded that
one skilled in the art would have understood that the
inventors possessed and were working with the naturally
occurring fermentation product, i.e., the daptomycin
molecule containing D-asparagine. For that reason, the
court held that Hospira had failed to show, by clear and
convincing evidence, that the ’071 patent was invalid for
lack of an adequate written description.
    Hospira has not shown that the district court commit-
ted clear error in finding that the written description
requirement was satisfied. The references in the specifi-
cation to the “A21978C cyclic peptide,” and to LY146032,
Lilly’s codename for daptomycin, would have demonstrat-
ed to a person of skill in the art that the inventors were in
possession of daptomycin, the product of the fermentation
of Streptomyces roseosporus, in spite of the error in the
structural diagram.
    The fact that the inventors were mistaken as to one
aspect of the structure of daptomycin at the time the
application for the original ’226 patent was filed does not
render the specification inadequate to satisfy the written
description requirement. It was enough that the specifi-
cation disclosed relevant identifying characteristics that
distinguished daptomycin from other compounds and thus
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.         13



showed that the inventors had possession of daptomycin,
even though they may not have had an accurate picture of
the entire chemical structure of that compound. See
Invitrogen Corp. v. Clontech Labs., Inc., 429 F.3d 1052,
1072 (Fed. Cir. 2005).
    Hospira relies on In re Wallach, 378 F.3d 1330 (Fed.
Cir. 2004), in support of its written description argument,
but that case has little in common with this one. In
Wallach, the applicants were in possession of only about
5% of the amino acids of the nucleic acid encoding a
particular protein, but they sought to claim all DNA
molecules that would code for the protein. That is, they
claimed the entire nucleotide sequence of any DNA mole-
cule that would code for the protein, even though they
were in possession of only a small portion of one such
nucleotide sequence. This court upheld the PTO’s deci-
sion rejecting the applicants’ claims.
    The applicants in Wallach argued that they were enti-
tled to patent protection for the claimed DNA molecules
because they had shown that they were in possession of
the protein. This court noted, however, that whether the
applicants “were in possession of the protein says nothing
about whether they were in possession of the protein’s
amino acid sequence.” 378 F.3d at 1334.
    Because the applicants had not “provided any evi-
dence that the full amino acid sequence of a protein can
be deduced from a partial sequence and the limited addi-
tional physical characteristics that they have identified,”
the court concluded that the applicants had not shown
that they were in possession of the claimed nucleic acid
sequences. Id. at 1335. The court summed up its ruling
by stating that the applicants had not shown “that there
is any known or disclosed correlation between the combi-
nation of a partial structure of a protein, the protein’s
biological activity, and the protein’s molecular weight, on
14            CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.



the one hand, and the structure of the DNA encoding the
protein on the other.” Id.
    In this case, the applicants claimed only what they
had produced—the daptomycin molecule—which they
identified in several ways. The district court found that
the identification of the molecule in the specification was
sufficient to inform a person skilled in the art that the
inventors were in possession of the daptomycin molecule,
even though the structure that they ascribed to it was
inaccurate in one respect. The description of the molecule
provided in the specification in this case was far greater
than the very limited description of the DNA sequence in
the Wallach case, and the claims in this case, unlike those
at issue in Wallach, were limited to the compound itself.
We therefore uphold the district court’s finding that the
specification of the ’071 patent contained the written
description required by 35 U.S.C. § 112 and that the
asserted claims are not invalid for lack of adequate writ-
ten description.
                             C
    Finally, Hospira argues that the asserted claims of
the ’071 patent are invalid because they violate the “re-
capture rule” applicable to reissued patents. Relying on
the proposition that a patentee may not “regain[] through
reissue the subject matter that he surrendered in an
effort to obtain allowance of the original claims,” Pannu v.
Storz Instruments, Inc., 258 F.3d 1366, 1370-71 (Fed. Cir.
2001), Hospira argues that the claims of the reissued ’071
patent are impermissibly broader than the corresponding
original claims of the ’226 patent.
    The recapture rule applies if (1) the reissue claims are
broader than the original patent claims; and (2) the
broader aspects of the reissued claims relate to subject
matter that was surrendered in the prosecution of the
original patent. In re Youman, 679 F.3d 1335, 1345 (Fed.
Cir. 2012); In re Mostafazadeh, 643 F.3d 1353, 1358 (Fed.
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.            15



Cir. 2011); In re Clement, 131 F.3d 1464, 1469 (Fed. Cir.
1997). The recapture rule does not apply if the reissue
claims were materially narrowed compared to the original
claims “such that full or substantial recapture of the
subject matter surrendered during prosecution is avoid-
ed.” In re Mostafazadeh, 643 F.3d at 1358. Moreover, the
recapture rule applies only if the patentee surrendered
subject matter in the original prosecution in order to
overcome a prior art rejection. In re Clement, 131 F.3d at
1469.
    The reissue claims here did not violate the recapture
rule. Besides the fact that reissue claims 18 and 26 are
narrower than original claim 24 by requiring the presence
of the Formula 1 and Formula 2 compounds, which are
not required by original claim 24, the evidence shows that
the applicants did not surrender subject matter in the
prosecution of the ’226 patent to avoid prior art.
    In the course of the prosecution of the application that
matured into the ’226 patent, the examiner rejected claim
24 on three occasions, each time on indefiniteness
grounds. In response to the third rejection, the applicants
cancelled claim 24. Although the applicants stated that
claim 24 was nonobvious, that statement was made in the
context of an argument that a large number of the claims
of the application, including claim 24, were nonobvious.
The applicants did not cancel the other claims, but they
cancelled claim 24, which was the only claim rejected on
indefiniteness grounds. The applicants ultimately suc-
ceeded in overcoming the obviousness objection to the
other claims.
   The prosecution history thus makes it clear that the
applicants withdrew claim 24 from the application be-
cause of the indefiniteness rejection, not to avoid prior art.
Accordingly, the recapture rule does not render claims 18
and 26 of the ’071 patent invalid.
16             CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.



    For the foregoing reasons, we hold that the asserted
claims of the ’071 patent are not invalid. Because Hospira
does not contest the district court’s ruling that its prod-
ucts infringe the ’071 claims if the certificate of correction
was properly issued and the patent is otherwise valid, we
sustain the district court’s judgment of infringement as to
the ’071 patent.
                              II
    Cubist has cross-appealed from the portions of the
district court’s judgment invalidating the other four
patents at issue in this case: the two patents that the
district court referred to as the “dosing patents” (the ’967
patent and the ’689 patent) and the two patents that the
district court referred to as the “purity patents” (the ’238
patent and the ’342 patent). We affirm the district court’s
decision that all four of those patents are invalid for
obviousness.
                              A
                              1
    In the 1980s, Lilly researchers who were looking for
an antibiotic effective against Staphylococcus aureus (“S.
aureus”) infections discovered daptomycin. At the time,
Lilly’s drug vancomycin was the only available treatment
for infections caused by methicillin-resistant S. aureus
bacteria. While sufficiently high doses of daptomycin
proved effective against such infections, the researchers
discovered that high doses of daptomycin administered
every twelve hours resulted in skeletal muscle toxicity in
some patients. When the Lilly researchers encountered
the toxicity problem, they suspended further testing of
daptomycin.
    Cubist subsequently licensed the daptomycin com-
pound from Lilly and conducted studies designed to
overcome the problem of skeletal muscle toxicity that
Lilly had encountered. Cubist researchers discovered
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.           17



that the toxic side effects of daptomycin could be reduced
by administering the drug less frequently than twice
daily. They subsequently sought patent protection for
treatment methods involving large doses of daptomycin
and large intervals between doses.
                             2
    Asserted claims 16, 17, 34, and 35 of the ’967 patent
and asserted claims 51 and 52 of the ’689 patent recite
dosage regimens. The claims of the ’967 patent recite a
method of administering daptomycin at a dosage interval
that minimizes skeletal muscle toxicity; the recited dos-
age is 4 or 6 milligrams per kilogram of patient weight
(abbreviated as “mg/kg”) and the recited dosage interval is
once every 24 hours. The claims of the ’689 patent recite
administering daptomycin in doses of 4 or 6 mg/kg once
every 48 hours.
    At trial, Hospira sought to prove that the asserted
claims of the ’967 patent are anticipated by a 1991 journal
article by James Woodworth et al. The Woodworth article
stated that, based on the pharmacokinetics and antibac-
terial activity of daptomycin, “doses of 4 to 6 mg/kg/day,
possibly in divided doses, are predicted to be effective.”
The article added that the reported data “suggest that
good antibacterial activity would be produced from single
doses of 4 to 6 mg/kg,” and that the drug’s long half-life in
the body would “allow[] once- or twice-daily administra-
tion with the proper doses.”
    Although the Woodworth article did not mention the
objective of minimizing skeletal muscle toxicity, the
district court found that the effect of minimizing skeletal
toxicity was inherently disclosed by Woodworth’s sugges-
tion to administer 4 or 6 mg/kg of daptomycin once a day.
That is, the court found that minimizing skeletal toxicity
was “a necessary accompaniment to the other disclosed
claimed limitations and therefore was inherently dis-
closed by the Woodworth article.”
18            CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.



    In response to Cubist’s argument that the Woodworth
article was not enabling, the court found that Woodworth
“identified the exact dosage amounts and interval claimed
by the ’967 patent: 4 mg/kg/day and 6 mg/kg/day.” The
dosage level and timing, the court found, “were two major
variables that required no additional experimentation.”
Accordingly, the court found that Cubist had failed to
rebut the presumption that the Woodworth article ena-
bled the disclosed invention. 3
    The court also found the asserted claims of the ’967
patent to be invalid for obviousness based on the Wood-
worth article and the ’226 patent, in view of the known
properties of daptomycin. The court explained that the
Woodworth article and the ’226 patent contained disclo-
sures “indicating that the claimed dosage levels would be
effective.” Beyond that, the known properties of dap-
tomycin provided “additional support for why one skilled
in the art would find daily dosing to be preferable and
obvious.” In particular, the court found, it was known
that daptomycin’s effectiveness is concentration-
dependent, which suggests that less frequent and more
concentrated treatments would be more effective than
smaller doses of the drug administered at more frequent
intervals.
    The court reached the same conclusion with respect to
the ’689 patent, which provides for doses of daptomycin to
be administered every 48 hours. The court explained that
a person of skill in the art would know that in treating
patients with impaired renal function, either the doses
would have to be reduced or the dosage intervals in-
creased. In light of the concentration-dependent killing
capacity of daptomycin, the court concluded, it would have


     3   Hospira argued that the ’226 patent also antici-
pated the asserted claims of the dosing patents, but the
district court rejected that argument.
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.         19



been obvious to consider doubling the dosage interval for
a patient with impaired kidney function, such as 50% of
normal.
    Finally, the district court analyzed the secondary
considerations invoked by Cubist, but found them insuffi-
cient to overcome the showing of obviousness based on the
cited prior art references.
                            3
     Focusing largely on the Woodworth reference, Cubist
challenges the district court’s ruling that the asserted
claims of the dosing patents would have been obvious. We
hold that the district court did not commit legal error and
that the findings underlying the court’s obviousness
ruling were not clearly erroneous. Because we uphold the
district court’s obviousness ruling with respect to the
dosing patents, it is not necessary for us to address Cub-
ist’s challenge to the court’s ruling on anticipation.
    In challenging the district court’s finding of obvious-
ness, Cubist places great weight on the fact that the
Woodworth reference does not mention skeletal muscle
toxicity. In addition, Cubist argues that the court’s
reliance on the once-daily administration of other similar
antibiotics to reduce toxic side-effects is too remote to
support the court’s obviousness finding as to the once-
daily administration of daptomycin.        Finally, Cubist
complains that the district court ignored secondary evi-
dence of non-obviousness, including evidence of long-felt
but unmet need, failure of others, commercial success,
and unexpected results.
                            4
    Cubist did not discover daptomycin, nor did it invent
the use of daptomycin for treating bacterial infections.
Beginning in the 1980s, Lilly tested daptomycin treat-
ment protocols including once-daily doses of 2mg/kg, and
twice-daily doses of 3 mg/kg. Both of those protocols were
20            CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.



determined to be effective against some infections, al-
though they were not as effective as conventional thera-
pies in treating the most serious targeted infection, S.
aureus endocarditis (“SAE”). Lilly researchers concluded
that the dosages used in those studies did not result in
enough free daptomycin in the bloodstream to kill the
targeted bacteria. Lilly conducted a follow-up study in
which subjects were given up to 4 mg/kg of daptomycin
every 12 hours. At that dosage level, however, several
subjects developed symptoms of skeletal muscle toxicity,
and the study was abandoned.
    The dosing patents proposed the administration of
doses of either 4mg/kg or 6mg/kg, similar to the dosage in
the Lilly follow-up study, but given only once per day or
once every 48 hours. Given what was previously known
about daptomycin and related compounds, the district
court reasonably concluded that the treatment protocols
claimed in the dosing patents would have been obvious in
light of the prior art.
     As the district court observed, the Woodworth article
clearly pointed to the use of once daily administration of
daptomycin in doses of 4 to 6 mg/kg per day. It did so in
the abstract of the article, where the authors predicted
that doses of 4 to 6 mg/kg per day would be expected to be
effective either in single doses or “possibly in divided
doses.” It also did so in the body of the article, where the
authors specifically noted that the long half-life of dap-
tomycin would allow the administration of daptomycin
once or twice a day, and that anti-bacterial effects could
be achieved from single daily doses of 4mg/kg to 6 mg/kg,
exactly the doses set forth in the dosing patents. Similar-
ly, the ’226 patent discloses that a “typical daily dose for
an adult human” of about 1.4 mg/kg to 14 mg/kg “can be
administered as a single daily dose or in multiple doses
per day.” ’226 patent, col. 10, ll. 56-61. The district court
found that the ’226 patent, like the Woodworth article,
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.             21



disclosed that the claimed dosage levels would be effec-
tive, “either through daily or divided administrations.”
     Cubist takes issue with the Woodworth reference on
two grounds: first, that it is based on laboratory studies,
not clinical trials, and is thus predictive in nature with
respect to the likely effects of the drug in patients; and
second, that it does not advert to minimizing skeletal
muscle toxicity, which is an objective expressly set forth
in the asserted claims.
    While it is true that the Woodworth reference is
predictive in nature, it is based on extensive laboratory
research, and its predictions of the efficacy of a dosage
regimen of 4 mg/kg to 6 mg/kg at daily intervals give rise
to a reasonable expectation that dosages in that amount
would be effective in patients. Moreover, published
accounts of Lilly’s clinical trials indicated a dosage level of
2 mg/kg administered once daily produced no reported
side effects and a dosage level of 3 mg/kg administered
twice daily produced no symptoms of skeletal muscle
toxicity, but were not highly effective against SAE. Those
results would have given rise to a reasonable expectation
that somewhat higher doses administered less frequently
than twice daily could be expected to be both safe and
effective.
    The district court’s obviousness finding is also sup-
ported by evidence of the known properties of daptomycin,
from which persons of skill in the art could reasonably
conclude not only that doses given once per day or even
less frequently would be effective, but also that increased
dosage intervals would result in less risk of skeletal
muscle toxicity.
     That evidence included four characteristics of dap-
tomycin that suggested the use of high dosages of dap-
tomycin with long intervals between doses.             First,
daptomycin is especially effective at killing bacteria when
it is found in high concentrations in the patient’s body.
22             CUBIST PHARMACEUTICALS, INC.     v. HOSPIRA, INC.



Second, daptomycin has a long half-life, which allows it to
act in the body over an extended period of time before
being cleared by the kidneys. Third, daptomycin has a
long post-antibiotic effect, i.e., it continues to suppress
bacteria after leaving the body. Those three characteris-
tics suggest that it is not necessary to administer dap-
tomycin frequently. Fourth, muscle toxicity resulting
from daptomycin was known to be reversible in most
cases. That characteristic suggests that administering
doses at greater intervals would allow the muscles more
time to repair between doses, thus reducing the cumula-
tive toxic effect of the drug.
    The district court’s finding is also supported by evi-
dence pertaining to aminoglycosides, a group of antibiotic
compounds similar to daptomycin. The court found
aminoglycosides to be “within the relevant prior art” that
“would have been considered by one skilled in the art,”
and it found that aminoglycosides share many properties
with daptomycin.       Like daptomycin, aminoglycosides
exhibit concentration-dependent killing, long-lasting post-
antibiotic effects, and reversible toxicity. And the evi-
dence showed that less frequent dosing resulted in the
avoidance of toxicity problems with aminoglycosides.
Those characteristics, the district court found, would have
led one of skill in the art to believe that increasing the
dosage intervals for daptomycin would give rise to a
reasonable expectation of increased efficacy while mini-
mizing the toxic side effects of the drug.
     Cubist does not separately argue the validity of the
asserted claims of the ’689 patent; in any event, however,
we agree with the district court that those claims, which
recite dosage intervals of 48 hours, would have been
obvious based on the same analysis that applies to the
claims of the ’967 patent. The ’689 patent notes that
longer dosage intervals are appropriate for patients with
impaired renal function or requiring dialysis. ’689 patent,
col. 5, line 63, to col. 6, line 5. The district court explained
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.          23



that it is known that patients with compromised renal
function do not clear drugs such as daptomycin from their
systems as quickly as persons with healthy kidneys.
Accordingly, it was reasonable for the court to conclude
that a person of skill in the art would expect that for such
a patient a longer dosage interval would be equally effec-
tive against bacteria and would be necessary to avoid
building up concentrations of daptomycin in the patient’s
body that could lead to skeletal muscle toxicity.
                             5
    Cubist relies heavily on secondary consideration evi-
dence to support its argument that the asserted claims of
the dosing patents would not have been obvious. The
district court acknowledged that secondary consideration
evidence must be weighed in the obviousness analysis,
but the court concluded that “any weight certain factors
may have does not overcome Hospira’s prima facie show-
ing of obviousness.”
    Cubist argues that, prior to the invention claimed in
the dosing patents, there was a long-felt but unmet need
for such a treatment regimen and that the success of
Cubist’s invention was unexpected. As the district court
pointed out, however, daptomycin treatment regimens
that were only slightly different from Cubist’s had previ-
ously been shown to be effective against a variety of
bacterial infections. Although the prior art daptomycin
treatment methods had not proved effective for SAE, the
court noted that SAE is the target infection in only about
5% of the cases in which daptomycin is administered.
Accordingly, the court concluded that any “long-felt need”
or “unexpected results” applied only to the small percent-
age of cases in which daptomycin was used to treat SAE.
    The court made the same observation with regard to
Cubist’s argument regarding the commercial success of
Cubist’s daptomycin product, Cubicin. Although Cubist
attributes the success of Cubicin to the invention of the
24            CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.



’967 and ’689 patents, the district court concluded that
Cubicin’s commercial success is mainly attributable to
daptomycin itself; it is attributable only in small measure
to the dosage and interval protocols disclosed in the
dosing patents. For Cubicin’s use in treating other infec-
tions that make up the bulk of the market, the court
found, “Cubist was unable to establish that the claimed
features drove market success.” The court likewise found
that any “unexpected results” obtained from the dosing
patents were limited to the treatment of serious infections
such as SAE.
    Cubist sought to show the failure of others by pointing
to Lilly’s failure to develop the dosing regimens set forth
in the dosing patents. The court, however, found that
Cubist’s showing was undercut by the fact that Lilly
owned and marketed vancomycin, which was regarded as
the “gold standard” for treating many serious infections
such as infections caused by methicillin-resistant S.
aureus bacteria. Referring to vancomycin, Hospira’s
expert on secondary considerations testified that Lilly
“had a drug that was generating four to five hundred
million dollars a year in the late eighties and early 1990s.
They would have very little incentive to cannibalize those
sales by the introduction of a substitutable drug.” There-
fore, the court concluded, “economic considerations, and
not merely difficulties in the lab, weighed on Eli Lilly’s
decision to ‘shelve’ daptomycin development.”
    We are not persuaded that the district court commit-
ted legal error in its analysis of the secondary considera-
tion evidence.       The court weighed the secondary
consideration evidence against the other evidence of
obviousness and concluded that the secondary considera-
tion evidence was not sufficiently strong to overcome the
showing of obviousness arising from an analysis of the
prior art. That conclusion was not clearly erroneous. We
therefore sustain the district court’s judgment that the
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.           25



asserted claims of the dosing patents are invalid for
obviousness.
                             B
    The second portion of Cubist’s cross-appeal is its chal-
lenge to the district court’s ruling that the asserted claims
of the purity patents (the ’238 and ’342 patents) are
invalid. The district court held that claim 98 of the ’238
patent is anticipated by Lilly’s U.S. Patent No. 4,874,843
(“the ’843 patent”), and that all of the asserted claims of
the two purity patents are invalid for obviousness. Be-
cause we sustain the district court’s ruling that all of the
asserted claims of the purity patents are invalid on
grounds of obviousness, we do not need to address the
issue of anticipation.
                             1
     Of the three asserted claims of the ’238 patent, claim
91 recites a method of preparing a pharmaceutical dap-
tomycin composition that is essentially free of each of 14
identified impurities, i.e., in which the composition has
less than 0.5% of each impurity and is obtained by a
process comprising the step of forming an aggregate
containing daptomycin. Claim 98 recites a daptomycin
composition that is at least 93% pure, in which the com-
position is obtained by the steps of forming a daptomycin
aggregate, separating the aggregate from low molecular
weight contaminants, causing the aggregate to dissociate
into monomers, and separating the daptomycin monomers
from high molecular weight contaminants by a size selec-
tion technique of either ultrafiltration or size exclusion
chromatography. Claim 187 recites a daptomycin compo-
sition that is at least 97% pure relative to certain dap-
tomycin-related impurities, in which the composition is
obtained from a lipopeptide aggregate containing dap-
tomycin.
26            CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.



     Of the two asserted claims of the ’342 patent, claim 23
recites a pharmaceutical daptomycin composition that is
at least 93% pure with respect to certain daptomycin-
related impurities and has less than 4% each of anhydro-
daptomycin and the beta isomer of daptomycin, in which
the composition is prepared by a process comprising the
steps of subjecting the daptomycin to anion exchange
chromatography, forming a daptomycin aggregate, and
obtaining the daptomycin from the daptomycin aggregate
by a method comprising the steps of filtering the dap-
tomycin aggregate so that the aggregate is retained on the
filter and collecting the aggregate. Claim 53 recites a
daptomycin lyophilized powder pharmaceutical composi-
tion that is 94 to 96% pure relative to certain daptomycin-
related impurities and has less than 1% of the lactone
hydrolysis product of daptomycin and less than 4% each of
anhydro-daptomycin and the beta isomer of daptomycin,
in which the composition is prepared by a process com-
prising the steps of forming a daptomycin aggregate,
converting the aggregate to monomers by a process in-
cluding either anion exchange chromatography or hydro-
phobic interaction chromatography.
                             2
    In its obviousness analysis, the court focused on the
two primary purification steps recited in the asserted
claims: (1) micelle or aggregation filtration and (2) anion
exchange chromatography. Those steps, the court ex-
plained, enable the daptomycin to be separated from
impurities such as saponins and endotoxins. Saponins
are found in the soy commonly used in daptomycin fer-
mentation, and endotoxins are segments of the cell walls
of certain bacteria that are left over after the fermenta-
tion process that is used to produce daptomycin.
    With respect to micelle filtration, the district court
explained that in an acidic solution, daptomycin forms
micelles, or aggregates, of daptomycin molecules. The
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.          27



formation of the micelles effectively increases the size of
the particles of daptomycin, so that the daptomycin will
not pass through the pores of certain filters. Because
smaller impurities such as saponins can pass through the
filters and be discarded, the process of forming micelles
enables the filters to separate the saponins from the
daptomycin.
    After that filtration step is completed and the sapo-
nins are discarded, the solution is neutralized. That step
causes the daptomycin aggregates to break apart into
individual daptomycin molecules, which are small enough
to pass through the filters’ pores. Larger molecules, such
as endotoxins, cannot pass through the filters, resulting
in the separation of the daptomycin from the endotoxins.
As a result of the two-step filtering process, the daptomy-
cin solution is free of both saponins and endotoxins.
    The district court held that the use of micelle filtra-
tion would have been obvious to a person of skill in the art
based on two references: a 1997 publication by Sung-Chyr
Lin et al. that showed that it was possible to employ
micelle filtration for the recovery and purification of most
surfactants; and a 1988 reference by Jeremy H. Lakey et
al. teaching one skilled in the art that daptomycin dis-
plays the properties of a surfactant.
    With respect to anion exchange chromatography, the
district court found that the technique was a familiar one,
and that it was well understood in the industry that it
could be used to filter out impurities similar to daptomy-
cin in size but differing in chemical structure. The court
found that anion exchange chromatography would have
been an obvious method of purification to one of skill in
the art after solving the problem of removing saponins.
    As in the case of the dosing patents, the court re-
viewed Cubist’s secondary consideration evidence in
detail and concluded that the secondary consideration
evidence did not undermine Hospira’s showing that the
28             CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.



purity patents would have been obvious to a person of
skill in the art. Accordingly, the court held the asserted
claims of the purity patents invalid for obviousness.
                              3
    In its brief, Cubist does not directly address the
district court’s analysis of the micelle filtration and anion
exchange chromatography limitations of the asserted
claims. Instead, Cubist argues that the court failed to
analyze obviousness on a claim-by-claim basis and failed
to conduct an analysis of each of the limitations of the
asserted claims. In doing so, Cubist asserts, the court
“did not address a number of limitations that were mate-
rial to the obviousness analysis.” Focusing on claim 187
of the ’238 patent and claims 23 and 53 of the ’342 patent,
Cubist argues that the court ignored the claim limitations
requiring greater than 93% purity with respect to dap-
tomycin-related substances. Cubist also contends that
the district court ignored the requirement of claim 91 of
the ’238 patent that the daptomycin be “essentially free”
of 14 daptomycin-related impurities, which has the effect
of requiring that the claimed daptomycin composition
contain no more than 0.5% of each of the impurities
referred to in the patent. See ’238 patent, col. 7, ll. 52-56.
     Although the district court focused on the two limita-
tions relating to the mechanics of the purification process,
the court’s focus on those limitations does not undermine
its obviousness analysis. The use of the two techniques
set forth in those limitations—micelle filtration and anion
exchange chromatography—are the keys to the purifica-
tion process described in the specifications of the purity
patents and recited in each of the asserted claims. The
purity patents do not point to any additional techniques
that are necessary to obtain the recited purity levels in
each of the claims. Once the saponins and endotoxins are
eliminated from the daptomycin composition by micelle
filtration, the desired purification levels can be obtained
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.          29



by what the district court referred to as “the simple
concept” of ion exchange purification.
     Cubist contrasts its purification process with the
process used by Lilly, which is described in Lilly’s ’843
patent. That process produced daptomycin that was
approximately 93% pure relative to daptomycin-related
impurities. Cubist argues that its claimed process of
micelle filtration followed by anion exchange chromatog-
raphy constituted a breakthrough for the purification of
daptomycin compositions, providing a means both for
filtering out endotoxins and saponins, and for obtaining
levels of purity relative to daptomycin-related substances
that were significantly higher than the 93% achieved by
Lilly’s process.
     Although Cubist argues that the techniques for ob-
taining purity levels of up to 97% with respect to dap-
tomycin-related substances (as in claim 187 of the ’238
patent) and levels of less than 0.5% for each of 14 dap-
tomycin-related impurities (as in claim 91 of the ’238
patent) would not have been obvious, the district court
found that it would have been obvious to use both micelle
filtration and anion exchange chromatography and that
by using those steps the desired purity levels could easily
be achieved.
    The court’s obviousness finding as to micelle filtration
was soundly based on its reliance on the Lin and Lakey
prior art references. Given the similarities between
daptomycin and surfactants, and the known utility of
micelle filtration of surfactants, the court permissibly
found that a person of skill in the art would have looked
to micelle filtration to remove saponins and endotoxins
from the daptomycin composition.
   The court’s findings as to the obviousness of anion ex-
change chromatography were also well supported. Based
on evidence that ion exchange chromatography “was
known to be one of the most common purification tech-
30            CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.



niques in the field,” the court found that ion exchange
techniques, and in particular anion exchange chromatog-
raphy, “would have been an obvious method of purifica-
tion to one skilled in the art, after solving the problem of
removing saponins.” That technique, the court found,
could produce the high purity levels recited in each of the
asserted claims. 4 The court rejected Cubist’s argument
that those skilled in the art believed there was an upper
limit on the obtainable purity level of daptomycin, a belief
that that would have “discouraged one skilled in the art
from applying a common purification technique after the
saponin problem was resolved.” The court’s findings as to
anion exchange chromatography and the purity results
obtainable from its use were not clearly erroneous.
                             4
     Finally, Cubist argues that the district court erred by
failing to give sufficient weight to the secondary consider-
ations of nonobviousness, in particular the long-felt need
for a commercial-scale purification process for daptomycin
and the unexpected result that daptomycin would form


     4   Cubist complains that by referring to the observa-
tion in the purity patents that “running samples obtained
via the ’843 Patent process through an anion exchange
column yielded a very high purity,” the district court
improperly relied on disclosures in the patent in suit to
buttress the case of obviousness. To the contrary, the
court made the observation about the high purity levels
obtained by anion exchange chromatography to show that
once the saponins had been removed by micelle filtration,
that well-known technique was sufficient by itself to
achieve the purity levels claimed in the purity patents,
and that the purity patents added nothing to what was
known in the art. As the court explained, the purity
patents “do not claim anything other than this simple
concept.”
CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.          31



reversible micelles under conditions compatible with
purification.
    The district court considered the evidence of second-
ary considerations but did not find that evidence suffi-
ciently strong to overcome the proof of obviousness based
on the prior art. As for Cubist’s claim that there was a
long-felt need for a commercial-scale purification process
for daptomycin, the court noted that the asserted claims
did not refer to production-scale purification, but were
simply directed to purification “whether produced in an
economical or wasteful manner.” The court added that it
was not persuaded by Cubist’s argument that there was a
long-felt need for an efficient method of purifying dap-
tomycin, particularly in light of the evidence that many
believed daptomycin was a “dead drug.”
    As for Cubist’s assertion that the propensity to form
micelles was an unexpected property of daptomycin, the
district court acknowledged that “Cubist’s being the first
to observe daptomycin’s micelle-forming properties offers
some objective evidence of non-obviousness.” However, in
light of the evidence that it was known that daptomycin
behaves like surfactants, which in turn were known to
form micelles, the court concluded that the unexpected
results argument was not “entitled to serious weight.”
Ultimately, the court found that the secondary considera-
tions relied on by Cubist were not sufficiently strong to
“upset Hospira’s prima facie showing that the asserted
claims of the purity patents are obvious.”
    We sustain the district court’s determination that the
secondary consideration evidence did not overcome the
showing of obviousness based on the prior art. With
respect to Cubist’s claim of a long-felt need, the evidence
showed that Lilly’s decision not to pursue its research into
daptomycin was based on economic considerations, not on
the absence of methods of obtaining sufficiently high
purity levels. With respect to Cubist’s claim that it was
32             CUBIST PHARMACEUTICALS, INC.   v. HOSPIRA, INC.



unexpected that daptomycin would form “reversible
micelles,” the district court did not clearly err in rejecting
that argument in light of the Lakey reference that taught
that daptomycin behaves like a surfactant and the Lin
reference that taught that surfactants form micelles
under the proper conditions. We therefore uphold the
district court’s ruling that the asserted claims of Cubist’s
purity patents are invalid for obviousness.
     Each party shall bear its own costs for these appeals.
                        AFFIRMED
