United States Court of Appeals
for the Federal Circuit
__________________________
GENETICS INSTITUTE, LLC,
Plaintiff-Appellant,
v.
NOVARTIS VACCINES AND DIAGNOSTICS, INC.,
Defendant-Appellee.
__________________________
2010-1264
__________________________
Appeal from the United States District Court for the
District of Delaware in Case No. 08-CV-0290, Judge Sue
L. Robinson.
__________________________
Decided: August 23, 2011
__________________________
BRADFORD J. BADKE, Ropes & Gray LLP, of New York,
New York, argued for plaintiff-appellant. With him on
the brief were JEANNE C. CURTIS and MATTHEW A.
TRAUPMAN. Of counsel was CHRISTOPHER J. HARNETT.
GEORGE A. RILEY, O’Melveny & Myers LLP, of San
Francisco, California, argued for defendant-appellee.
With him on the brief was GEORGE C. YU. Of counsel on
the brief was JOHN C. KAPPOS, of Newport Beach, Califor-
nia. Also of counsel were POLAPHAT VERAVANICH,
O’Melveny & Myers LLP, of Newport Beach, California,
GENETICS INST v. NOVARTIS VACCINES 2
and MARK S. DAVIES, Orrick, Herrington & Sutcliffe LLP,
of Washington, DC.
__________________________
Before LOURIE, PLAGER, and DYK, Circuit Judges.
Opinion for the court filed by Circuit Judge LOURIE.
Opinion concurring-in-part and dissenting-in-part filed by
Circuit Judge DYK.
LOURIE, Circuit Judge.
Genetics Institute, LLC, (“Genetics”) appeals from the
decision of the United States District Court for the Dis-
trict of Delaware dismissing its action under 35 U.S.C.
§ 291 for lack of an interference in fact between certain
claims of its U.S. Patent 4,868,112 (the “’112 patent”) and
certain claims of U.S. Patents 6,228,620 and 6,060,447
(the “’620 patent” and the “’447 patent”; collectively, the
“Novartis patents”). Novartis asserts that the expiration
of the ’112 patent following the district court’s entry of
judgment renders us without jurisdiction over Genetics’
appeal. Novartis also asserts that the district court
lacked jurisdiction over certain claims of the ’112 patent
because its term extension under 35 U.S.C. § 156 applied
only on a claim-by-claim basis. Because the district court
did not err in dismissing Genetics’ § 291 action for lack of
an interference in fact, and because we disagree with
Novartis’s jurisdictional arguments, we affirm.
BACKGROUND
I
The district court’s opinion summarizes the science
underlying the patented technology in this case, which
relates to truncated forms of a protein called Factor VIII.
Genetics Inst., LLC v. Novartis Vaccines & Diagnostics,
Inc., 687 F. Supp. 2d 486, 490-92 (D. Del. 2010). Factor
3 GENETICS INST v. NOVARTIS VACCINES
VIII is an essential blood-clotting protein that circulates
freely in the blood in an inactive state. Factor VIII be-
comes activated as part of a chain of reactions called the
“blood-clotting cascade,” which causes the formation of a
blood clot to stop bleeding from damaged blood vessels.
Defects in the gene encoding Factor VIII result in hemo-
philia A, a genetic disorder associated with prolonged
bleeding.
The human Factor VIII protein is stabilized in the
bloodstream by binding to von Willebrand factor (“vWF”),
a large blood protein that prevents the degradation of
Factor VIII. Id. at 491. If Factor VIII is not able to form
a complex with vWF, the half-life of Factor VIII in plasma
is reduced about five-fold. Thus, while Factor VIII retains
its procoagulant activity even without vWF binding, the
association of Factor VIII with vWF is critical for the
optimal regulation of blood coagulation. In addition, a
Factor VIII protein that cannot bind vWF may cause
unwanted clots in areas such as heart vessels because
unbound Factor VIII can bind blood platelets even when
no injury has been detected.
The full-length Factor VIII protein consists of 2,332
amino acid residues—the chemical building blocks of
proteins. Id. The protein contains several regions, or
“domains,” each of which folds into a three-dimensional
structure independent of the others. Factor VIII contains
the following domains: A1, A2, B, A3, C1, and C2. The
Figure below depicts the locations of these domains in the
full-length Factor VIII protein. See Br. of Pl.-Appellant at
9; see also Def.-Appellee Br. at 10-11. The “heavy chain”
or “A domain” portion of the protein consists of amino
acids 1 to 740 and contains the A1 and A2 domains as
GENETICS INST v. NOVARTIS VACCINES 4
well as two acidic regions known as a1 and a2. 1 The B
domain contains amino acids 741 to 1648. The “light
chain” or “C domain” portion of the protein consists of
amino acids 1649 to 2332. It contains a third acidic
region, a3, as well as the A3, C1, and C2 domains. The a3
acidic region, of particular importance to the dispute in
this case, contains amino acids 1649 to 1689. It is directly
adjacent to the B domain.
Figure
Treating patients with hemophilia A traditionally in-
volved administering partially purified Factor VIII de-
rived from porcine or human plasma. In the 1980s,
however, human plasma sources had become contami-
nated with viruses, such as HIV and hepatitis, making
treatment with plasma-derived Factor VIII dangerous.
Recombinant Factor VIII, produced from DNA cloning,
offered a safer and more abundant new source of thera-
peutic material. Scientists raced to clone Factor VIII
successfully for the first time. Yet cloning Factor VIII
proved to be an enormous technical undertaking, because
the Factor VIII protein was nearly ten times larger than
1 The amino acid numbering system used through-
out this opinion, unless otherwise specified, is the system
referred to as “ala-1,” in which the 20-amino-acid region
known as the “signal peptide” at the beginning of the N
terminal of the protein is omitted for numbering purposes.
The ’620 and ’447 patents use ala-1 numbering. The ’112
patent follows the met-1 system; its amino acid numbers
can be converted to the ala-1 system by subtracting 19
amino acids.
5 GENETICS INST v. NOVARTIS VACCINES
any protein previously cloned. The large size of the DNA
sequence encoding the full-length Factor VIII protein also
complicated the cloning process. Id. at 491-92.
Once the feat of cloning the full-length Factor VIII
protein was achieved, researchers focused their efforts on
finding a smaller, more easily cloned recombinant protein
that mimicked the biological activity of Factor VIII in
humans. Id. at 492. Those efforts formed the basis of the
patents at issue in this appeal. As described below,
scientists discovered that portions of the full-length
Factor VIII protein were unnecessary for procoagulant
activity, and they designed truncated Factor VIII proteins
lacking these portions. Scientists further found that the
a3 acidic region of Factor VIII is responsible for binding to
vWF and is therefore critical to Factor VIII’s performance.
II
The ’112 patent is assigned to Genetics, a wholly
owned subsidiary of Wyeth (which itself was recently
acquired by Pfizer Inc.). Genetics, 687 F. Supp. 2d at 489-
90. The ’112 patent, which issued on September 19, 1989,
claims priority from an application filed April 12, 1985,
and names John J. Toole, Jr., as the sole inventor. The
’112 patent was set to expire on September 19, 2006, at
the end of its seventeen-year term. In 2000, however,
Genetics obtained a patent term extension under 35
U.S.C. § 156 based on the time consumed by testing and
regulatory review of its commercial recombinant Factor
VIII protein, ReFacto®. The United States Patent and
Trademark Office (“PTO”) extended the term of the ’112
patent to February 28, 2010.
At issue in this appeal are claims 1, 5, 9, and 10 of the
’112 patent. These claim, respectively, a recombinant
DNA whose expression results in a truncated Factor VIII
protein; a host cell containing the recombinant DNA; a
GENETICS INST v. NOVARTIS VACCINES 6
method of producing the truncated Factor VIII protein by
culturing the host cells; and a truncated human Factor
VIII protein.
The truncated Factor VIII protein of claims 1, 5, and 9
has the amino acid sequence for human Factor VIII
protein except that, in the region between amino acid 740
and amino acid 1690, a number of amino acids are de-
leted; the size of the deletion ranges from at least 581 to
all 949 amino acids in this region. 2 The region eligible for
deletion encompasses the inactive B domain (amino acids
741 to 1648) and the a3 acidic region in the light chain
(amino acids 1649 to 1689). Claim 10 claims a truncated
Factor VIII protein having one of three specific deletions:
between amino acids 981 to 1563; 759 to 1640; or 759 to
1675. 3
2 Using the met-1 numbering system, claim 1 of the
’112 patent reads:
1. A recombinant DNA which upon expression
results in a truncated Factor VIII protein which is
an active procoagulant wherein the recombinant
DNA encodes for a protein having the amino acid
sequence of a human Factor VIII:C except for hav-
ing a deletion corresponding to at least 581 amino
acids within the region between Arg-759 and Ser.-
1709, wherein the amino acid numbering is with
reference to Met-1 of the human Factor VIII:C
leader sequence.
See also Genetics Inst., LLC v. Novartis Vaccines & Diag-
nostics, Inc., No. 08-290-SLR, 2010 WL 677745, at *1 (D.
Del. Feb. 24, 2010) (construing a “truncated Factor VIII
protein which is an active procoagulant” as a “Factor VIII
protein that promotes blood coagulation and lacks a
portion of the amino acid sequence of the human Factor
VIII protein”).
3 Using the met-1 numbering system, claim 10 of
the ’112 patent reads:
10. A truncated human Factor VIII:C protein
which is an active procoagulant protein having a
7 GENETICS INST v. NOVARTIS VACCINES
Novartis Vaccines and Diagnostics, Inc., (“Novartis”)
is the assignee of the ’620 and ’447 patents. Both of the
Novartis patents claim priority from an application filed
January 27, 1986.
At issue in the ’620 patent are claims 68, 74, and 83.
Claim 68 claims a nucleic acid expressing a truncated
recombinant Factor VIII protein in which all or part of the
B domain is deleted. The claimed recombinant protein
retains the amino acids in the heavy chain (amino acids 1
to 740) and the light chain (amino acids 1649 to 2332,
including the a3 acidic region) with the requirement that
these retained portions have at least 90% sequence iden-
tity to the native human Factor VIII protein. The protein
also optionally retains certain amino acids in the B do-
main: up to 10 amino acids contiguous to amino acid 740,
and up to 10 amino acids contiguous to amino acid 1649. 4
peptide sequence of human Factor VIII:C but
lacking a peptide region selected from the group
consisting of:
(a) the region between Pro-1000 and Asp-1582;
(b) the region between Thr-778 and Pro-1659; and,
(c) the region between Thr-778 and Glu-1694.
See also Genetics, 2010 WL 677745, at *1 (construing
“having a peptide sequence of human factor VIII:C but
lacking a peptide region selected from the group consist-
ing of” as “[h]aving the amino acid sequence of the human
Factor VIII protein lacking only the particular segment of
the human Factor VIII protein in one of the specified
alternatives (a), (b) or (c)”).
4 Claim 68 of the ’620 patent reads:
68. A nucleic acid composition for introducing
nucleic acid into a eukaryotic host cell to obtain
expression of a recombinant protein lacking all or
a portion of the B domain of human Factor VIII,
wherein said recombinant protein consists of:
a first amino acid sequence which consists of
an amino acid sequence having at least 90% se-
quence identity with the contiguous amino acid
GENETICS INST v. NOVARTIS VACCINES 8
Claim 74 claims a host cell containing nucleic acid capa-
ble of expressing the truncated recombinant Factor VIII
protein, and claim 83 claims a method of producing the
truncated recombinant Factor VIII protein by culturing
the host cell.
The only claim at issue in the ’447 patent is claim 1,
which claims a composition comprising Factor VIII pro-
teins consisting essentially of two polypeptides: a first
comprising an amino acid sequence of the heavy chain (A
domain), and a second comprising an amino acid sequence
of the light chain (C domain). At least 90% sequence
identity with each region is required.5
sequence of amino acids 1 to 740 of the native,
mature A domain of human Factor VIII and op-
tionally up to 10 amino acids of the human Factor
VIII B domain sequence contiguous to amino acid
740 as encoded by the polynucleotide present in
plasmid pSVF8-200 (ATCC No. 40190); and
a second amino acid sequence which consists
of an amino acid sequence having at least 90% se-
quence identity with the contiguous amino acid
sequence of amino acids 1649 to 2332 of the na-
tive, mature C domain of human Factor VIII and
optionally up to 10 amino acids of the human Fac-
tor VIII B domain sequence contiguous to amino
acid 1649 as encoded by the polynucleotide pre-
sent in plasmid pSVF8-200 (ATCC No. 40190);
wherein said nucleic acid encodes said first
and second amino acid sequences, and further
wherein said recombinant protein is capable of co-
agulation activity in a coagulation activity assay.
5 Claim 1 of the ’447 patent reads:
1. A composition comprising Factor VIII:C
proteins, wherein the Factor VIII:C proteins con-
sist essentially of a first polypeptide comprising
an amino acid sequence of the A domain of human
Factor VIII:C as encoded by the polynucleotide
present in plasmid pSVF8-200 (ATCC No. 40190)
9 GENETICS INST v. NOVARTIS VACCINES
III
On May 16, 2008, Genetics sued Novartis in the
United States District Court for the District of Delaware
to determine priority of invention under 35 U.S.C. § 291.
Genetics alleged that an interference in fact existed
between the following claims: (1) claim 1 of the ’112
patent and claim 68 of the ’620 patent; (2) claim 5 of the
’112 patent and claim 74 of the ’620 patent; (3) claim 9 of
the ’112 patent and claim 83 of the ’620 patent; and
(4) claims 9 and 10 of the ’112 patent and claim 1 of the
’447 patent. Genetics asserted that all three patents are
directed to the same subject matter, viz., truncated Factor
VIII proteins lacking all or part of the B domain while
retaining procoagulant activity.
Novartis moved to dismiss, arguing that the court
lacked subject matter jurisdiction because the extension
of the ’112 patent under 35 U.S.C. § 156 applied to fewer
than all of that patent’s claims. Novartis further argued
that there was no interference in fact between the as-
serted claims because the Novartis patents—unlike the
’112 patent—are directed to truncated Factor VIII pro-
teins that preserve the functional a3 acidic region.
In a memorandum order dated February 24, 2010, the
district court construed the disputed claim language of
the ’112 patent. Genetics Inst., LLC v. Novartis Vaccines
& Diagnostics, Inc., No. 08-290-SLR, 2010 WL 677745 (D.
or an amino acid sequence that differs therefrom
in having not more than 10 number % amino acid
substitutions, and a second polypeptide compris-
ing an amino acid sequence of the C domain of
human Factor VIII:C as encoded by the polynu-
cleotide present in plasmid pSVF8-200 (ATCC No.
40190) or an amino acid sequence that differs
therefrom in having not more than 10 number %
amino acid substitutions.
GENETICS INST v. NOVARTIS VACCINES 10
Del. Feb. 24, 2010). In a memorandum opinion of the
same date, the district court held that the patent term
extension under § 156 applied to all claims of the ’112
patent. Genetics, 687 F. Supp. 2d at 497. The court also
granted Novartis’s motion to dismiss, holding that there
was no interference in fact as to any of the allegedly
interfering claims. Id. at 502. The court entered its final
judgment on February 25, 2010. On March 12, 2010,
Genetics filed a timely notice of appeal.
Under 28 U.S.C. § 1295(a)(1), we have jurisdiction
over final judgments arising under the patent laws.
DISCUSSION
I. Appellate Jurisdiction
As noted, the district court entered final judgment on
February 25, 2010, and the extended term of the ’112
patent expired three days later, on February 28, 2010.
On April 12, 2010, Novartis filed a motion in this court to
dismiss Genetics’ appeal for lack of subject matter juris-
diction in light of the expiration of the ’112 patent. In an
order dated December 1, 2010, we denied the motion to
dismiss Genetics’ appeal, dismissed Novartis’s related
cross-appeal, and directed the parties to present argu-
ments in their briefs on the issue of jurisdiction. Genetics
Inst., LLC v. Novartis Vaccines & Diagnostics, Inc., No.
2010-1264, -1301, slip. op. at 3-4 (Fed. Cir. Dec. 1, 2010).
Novartis disputes our jurisdiction over Genetics’ ap-
peal. Novartis contends that we should dismiss Genetics’
appeal because the expiration of the extended term of the
’112 patent following the district court’s entry of final
judgment divested this court of jurisdiction. Relying on
Albert v. Kevex Corp., 729 F.2d 757 (Fed. Cir. 1984),
Novartis argues that “invocation of Section 291 requires
the rather unusual step of the court dismissing the action
11 GENETICS INST v. NOVARTIS VACCINES
for lack of jurisdiction after the filing of a well-pleaded
complaint whenever it becomes apparent that there is no
interference.” Def.-Appellee Br. at 29.
Genetics argues in response that we have jurisdiction
over its appeal despite the expiration of the ’112 patent.
Genetics contends that an interference action under § 291
may apply to any patent, including an expired patent.
Genetics contrasts § 291 with an interference action
under § 135, which by its terms is limited to unexpired
patents. Genetics further contends that the holding in
Albert is limited to disclaimed patents and does not
extend to expired patents.
We have an independent obligation to determine
whether subject matter jurisdiction exists over an appeal.
Litecubes, LLC v. N. Light Prods., Inc., 523 F.3d 1353,
1362 (Fed. Cir. 2008); see also Arbaugh v. Y & H Corp.,
546 U.S. 500, 514 (2006). As we explain below, we con-
clude that we possess jurisdiction over the present appeal.
The dispute over appellate jurisdiction in this case
boils down to the parties’ divergent interpretations of
Albert, 729 F.2d 757. That case, like this one, involved an
interfering patents action under 35 U.S.C § 291. Section
291 reads:
The owner of an interfering patent may have re-
lief against the owner of another by civil action,
and the court may adjudge the question of the va-
lidity of any of the interfering patents, in whole or
in part. The provisions of the second paragraph of
section 146 of this title shall apply to actions
brought under this section.
Albert asserted, among other causes of action, that claims
in his patent interfered with claims of a patent owned by
Kevex Corporation. Albert, 729 F.2d at 759. Albert also
GENETICS INST v. NOVARTIS VACCINES 12
asserted that the claims of the Kevex patent were invalid
under 35 U.S.C. § 102(b). Subsequently, Kevex filed in
the PTO a disclaimer of the claims in its patent that
allegedly interfered with Albert’s claims. The trial court
held that the filing of the disclaimer mooted the interfer-
ing patents action. Id. at 760. Yet the trial court pro-
ceeded to evaluate Albert’s invalidity contentions,
ultimately granting Albert’s motion for summary judg-
ment of invalidity. Id.
Kevex argued on appeal that the existence of an inter-
ference in a § 291 action is jurisdictional, such that the
district court was required to determine that the patents
interfered before determining the validity of either. Id.
We agreed and held that after the entry of Kevex’s dis-
claimer there were no interfering patents to support
jurisdiction for an action under § 291. Id. at 760-61. We
therefore vacated and remanded to the district court with
instructions to dismiss for lack of jurisdiction. Id. at 762.
Novartis seeks to enlarge our holding in Albert to
reach patent expirations. We reject this expansive read-
ing, and we decline to extend Albert’s holding beyond the
effect of a patent disclaimer in a § 291 action. Disclaim-
ers of patent claims are provided for under 35 U.S.C.
§ 253, which provides in part that:
A patentee, whether of the whole or any sectional
interest therein, may, on payment of the fee re-
quired by law, make disclaimer of any complete
claim, stating therein the extent of his interest in
such patent. Such disclaimer shall be in writing,
and recorded in the Patent and Trademark Office;
and it shall thereafter be considered as part of the
original patent to the extent of the interest pos-
sessed by the disclaimant and by those claiming
under him.
13 GENETICS INST v. NOVARTIS VACCINES
Id. (emphasis added). Disclaiming particular claims
under § 253 “effectively eliminate[s] those claims from the
original patent.” Vectra Fitness, Inc. v. TNWK Corp., 162
F.3d 1379, 1383 (Fed. Cir. 1998). In other words, upon
entry of a disclaimer under § 253, we treat the patent as
though the disclaimed claim(s) had “never existed.” Id.
(“This court has interpreted the term ‘considered as part
of the original patent’ in section 253 to mean that the
patent is treated as though the disclaimed claims never
existed.”).
We held in Albert that “the court has no jurisdiction
under § 291 unless interference is established.” 729 F.2d
at 760-61 (“[I]nterference between patents is a sine qua
non of an action under § 291.”). Jurisdiction under § 291
thus requires the existence of an interference, and a claim
that “never existed,” Vectra, 162 F.3d at 1383, cannot
form the basis for an interference. Because the disclaimer
in Albert precluded any basis for an interference between
the patents in suit, we held that it also eliminated juris-
diction under § 291.
Unlike a disclaimed claim, however, an expired patent
is not viewed as having “never existed.” Much to the
contrary, “a patent does have value beyond its expiration
date.” In re Morgan, 990 F.2d 1230, 1232 (Fed. Cir. 1992).
For example, an expired patent may form the basis of an
action for past damages subject to the six-year limitation
under 35 U.S.C. § 286. See, e.g., id. (recognizing that an
action for patent infringement may be filed up to six years
after the patent’s expiration). There is no comparable
statute providing any such rights in a disclaimed claim.
Furthermore, the expiration of the ’112 patent does
not deprive this § 291 action of meaning. In Kimberly-
Clark Corp. v. Procter & Gamble Distributing Co., 973
F.2d 911, 914 (Fed. Cir. 1992), in determining that juris-
GENETICS INST v. NOVARTIS VACCINES 14
diction in a § 291 action existed following the parties’
settlement of infringement liability issues, we noted in
support of our holding that “a declaration of priority and
the subsequent elimination of an invalid patent that
claims the same subject matter as claimed in one’s patent
are ‘relief’ under [§ 291].” Similar reasoning applies here.
Genetics points out that the outcome of this § 291 action
“will have real-world consequences,” because Genetics’
corporate parent, Wyeth, has been sued for allegedly
infringing the Novartis patents in a related case in the
United States District Court for the Eastern District of
Texas. Pl.-Appellant’s Reply Br. at 10; see also Compl. at
1, Novartis Vaccines & Diagnostics, Inc. v. Wyeth, No.
2:08-cv-067 (E.D. Tex. Feb. 15, 2008), ECF No. 1. A
determination that the ’112 patent interferes with and
has priority over the Novartis patents would directly
affect the outcome of that infringement suit.
We also note an important distinction between § 291
and the statute governing interferences before the PTO,
35 U.S.C. § 135. Whereas an interfering patents action
under § 291 involves two “interfering patents” without
qualification, a § 135 action, in contrast, is declared
between one pending application and “any pending appli-
cation, or . . . any unexpired patent.” 35 U.S.C. § 135
(emphasis added). This meaningful difference in statu-
tory language indicates that § 291, unlike § 135, is not
limited to “unexpired” patents. That is but one essential
difference between these two statutes. Compare Guinn v.
Kopf, 96 F.3d 1419, 1421-22 (Fed. Cir. 1996) (holding that
the disclaimer of an allegedly interfering claim did not
divest the PTO of jurisdiction over the § 135 interference),
with Albert, 729 F.2d at 760-61 (holding that the dis-
claimer of the allegedly interfering claims divested the
district court of jurisdiction over the § 291 interfering
patents action).
15 GENETICS INST v. NOVARTIS VACCINES
In view of the substantial differences between a dis-
claimer and an expiration, we decline to extend the hold-
ing in Albert to patent expiration situations. Accordingly,
we hold that the expiration of the ’112 patent following
the district court’s final decision does not strip our court
of jurisdiction over the present appeal.
II. District Court Jurisdiction
Novartis alleges that the district court lacked jurisdic-
tion to decide whether certain claims of the ’112 patent
and the Novartis patents interfered. Novartis argues that
claims 1 and 5 of the ’112 patent are not entitled to an
extended term because Genetics, in its patent term exten-
sion application under § 156(d)(1), identified only claims 9
and 10 of the ’112 patent as relating to its commercial
product ReFacto®. Because patent term extensions apply
only on a claim-by-claim basis, Novartis argues, claims 1
and 5 expired on September 19, 2006, following the origi-
nal seventeen-year patent term. Novartis also maintains
that because claim 10, as construed by the district court,
does not cover ReFacto®, it too is ineligible for patent
term extension under § 156. Citing Albert, 729 F.2d 757,
Novartis argues that because expired claims cannot
support an interfering patents action under § 291, claims
1, 5, and 10 of the ’112 patent were not properly before
the district court.
Genetics argues in response that the district court
correctly held that a patent term extension under § 156
applies to the term of the patent as a whole, i.e., to all
claims in the patent. Genetics asserts that the plain
language of § 156 compels this statutory interpretation.
Genetics further maintains that each of claims 1, 5, and 9
covers ReFacto®. Specifically, Genetics argues that
because claim 9 of the ’112 patent covers ReFacto® (a
point conceded by Novartis), claims 1 and 5 must also
GENETICS INST v. NOVARTIS VACCINES 16
cover this commercial product, since claim 9 depends from
claim 5, which in turn depends from claim 1.
We, like the district court, Genetics, 687 F. Supp. 2d
at 497, reject Novartis’s assertion that a patent term
extension under § 156 applies on a claim-by-claim basis.
The plain language of § 156 refutes Novartis’s argument.
The title of this section is “Extension of patent term.” 35
U.S.C. § 156 (emphasis added). Subsection (a) dictates
that the term of the patent, as opposed to specific claim(s),
shall be extended:
The term of a patent which claims a product, a
method of using a product, or a method of manu-
facturing a product shall be extended in accor-
dance with this section from the original
expiration date of the patent . . . .”
§ 156(a) (emphases added).
The text of subsection (b), which sets forth “the rights
derived from any patent the term of which is extended
under this section,” id. § 156(b) (emphasis added), is
equally clear that § 156 applies to the term of the patent,
not individual claim(s). The restrictions on the “rights
derived” set forth in subsection (b) do not suggest other-
wise. Subsection (b) was intended not to restrict the
extension to particular claims, but rather to limit the
effect of the extension. Id. (stating, for example, that for
patents that claim a product, the rights in the extended
term are “limited to any use approved for the product”).
As the accompanying 1982 House Report explained: “[I]f
a chemical is subjected to regulatory review for new drug
uses, but is also marketed for other commercial uses, the
patent term extension would apply only to the new drug
uses for which regulatory review was required.” H.R.
Rep. No. 97-696, at 10 (1982).
17 GENETICS INST v. NOVARTIS VACCINES
Thus, neither § 156(a) nor § 156(b) supports Novar-
tis’s position that § 156 applies only to particular claims.
A patent as a whole is extended even though its effect
may be limited to certain of its claims. Novartis nonethe-
less contends that the extension must apply on a claim-
by-claim basis because § 156(d)(1) requires an application
for a patent term extension to identify each claim that
claims the approved product or method of using or manu-
facturing the approved product. 35 U.S.C. § 156(d)(1)(B).
Yet subsection (d)(1) merely lists the required contents of
an application for a patent term extension. Subsections
(a) and (b), on the other hand, set forth the legal effect of
the patent term extension itself. 6
In sum, in light of the plain language of § 156, and
absent any indication that Congress intended that the
extension should apply only to particular claims, we
decline to adopt Novartis’s arguments.
To the extent Novartis contends that the restrictions
under § 156(b) on the rights derived from the extension of
the ’112 patent prevented Genetics from asserting claims
1, 5, and 10 in this § 291 action, we also disagree. Novar-
tis concedes that claim 9 covers Refacto®, the approved
product for which Genetics received the patent term
extension. Because claim 9 depends from claims 1 and 5,
those claims must also cover Refacto®. See 35 U.S.C.
§ 112 ¶ 4. Regarding claim 10, Novartis incorrectly
asserts that “the district court construed claim 10 as not
covering the active ingredient of ReFacto®.” Def.-
Appellee’s Br. at 63. In fact, the district court noted that,
6 In Boehringer Ingelheim International GMBH v.
Barr Laboratories, Inc., 592 F.3d 1340, 1349 (Fed. Cir.
2010), a case involving obviousness-type double patenting,
we suggested in passing that a patent term extension
might apply only to specific claims. That dictum was not
cited in support of either party’s position in this case.
GENETICS INST v. NOVARTIS VACCINES 18
under its claim construction, “ReFacto® may not be
encompassed by claim 10.” Genetics, 687 F. Supp. 2d at
497 n.14 (emphasis added). The court thus did not make
a factual finding on the issue of whether claim 10 of the
’112 patent covers ReFacto®, and we decline to do so for
the first time on appeal. See Sage Prods., Inc. v. Devon
Indus., Inc., 126 F.3d 1420, 1426 (Fed. Cir. 1997).
Finally, we also reject Novartis’s related argument
that no patent extended under § 156 can form the basis of
a § 291 interfering patents action. The statutory text does
not suggest that rights afforded by § 156 are so limited.
And, as the district court correctly noted, Genetics, 687 F.
Supp. 2d at 497, the legislative history advises against
Novartis’s interpretation: the 1984 House Report discuss-
ing the Hatch-Waxman Act provides that “all provisions
of the patent law apply to the patent during the period of
extension.” H.R. Rep. No. 98-857, pt. 1, at 39 (emphasis
added).
III. Interference In Fact
The patent laws recognize two types of actions involv-
ing interfering claims. An “interference” action under 35
U.S.C. § 135 can be declared by the PTO “[w]henever an
application is made for a patent which . . . would interfere
with any pending application, or with any unexpired
patent.” An “interfering patents” action under 35 U.S.C.
§ 291 permits “[t]he owner of an interfering patent [to
seek] relief against the owner of another by civil action.”
This case is an appeal from an interfering patents suit
under § 291 to determine the priority of invention be-
tween certain issued patents. See Slip Track Sys., Inc. v.
Metal Lite, Inc., 159 F.3d 1337, 1341 (Fed. Cir. 1998).
The first step in a § 291 interfering patents action is
the determination whether an interference in fact exists
between claims of the two patents. Medichem, S.A. v.
19 GENETICS INST v. NOVARTIS VACCINES
Rolabo, S.L., 353 F.3d 928, 934 (Fed. Cir. 2003). This
requires application of a “two-way test,” which, as dis-
cussed below, involves underlying questions of anticipa-
tion and obviousness under 35 U.S.C. §§ 102, 103. Id. at
932. Accordingly, the standards of review for an interfer-
ence in fact mirror those of anticipation and obviousness
inquiries. Id.
Anticipation and obviousness require the court to
compare the properly construed claims to the available
prior art. Oakley, Inc. v. Sunglass Hut Int’l, 316 F.3d
1331, 1339 (Fed. Cir. 2003). If “each and every limitation
is found either expressly or inherently in a single prior art
reference,” then the claim is invalid under § 102 for
anticipation. Sanofi-Synthelabo v. Apotex, Inc., 470 F.3d
1368, 1375 (Fed. Cir. 2006) (internal quotation marks
omitted). We review a finding of anticipation for clear
error. Zenon Envtl., Inc. v. U.S. Filter Corp., 506 F.3d
1370, 1377 (Fed. Cir. 2007). Obviousness under § 103 is a
question of law based on underlying factual determina-
tions. Oakley, 316 F.3d at 1339. We review the legal
conclusion of obviousness de novo and the underlying
findings of fact for clear error. Id.
An interference in fact under § 291 requires that the
two patents claim “the same or substantially the same
subject matter.” Slip Track, 304 F.3d at 1263. Interfer-
ing subject matter is defined by courts in the same man-
ner as in the PTO—by using the “two-way test.”
Medichem, 353 F.3d at 934. Under the PTO’s regulations,
“[a]n interference exists if the subject matter of a claim of
one party would, if prior art, have anticipated or rendered
obvious the subject matter of a claim of the opposing
party and vice versa.” 37 C.F.R. § 41.203(a). In other
words, for two claims to interfere, each claim must antici-
pate or render obvious the other; failure of either claim to
anticipate or render obvious the other defeats the test for
GENETICS INST v. NOVARTIS VACCINES 20
interfering patents. Medichem, 353 F.3d at 935 (“[T]here
can be no interference-in-fact without satisfaction of each
leg of the two-way test.”).
A. There is no interference in fact between the asserted
claims of the ’112 patent and the ’620 patent
Genetics argues that the district court erred by failing
to find that an interference in fact existed between the
allegedly interfering claims. According to Genetics, the
court erroneously determined that all of the allegedly
interfering claims of the Novartis patents require binding
to vWF, when in fact that is not an explicit claim limita-
tion. Moreover, Genetics asserts, the court incorrectly
applied the two-way test in finding no interference in fact.
Regarding the allegedly interfering claims in the ’112
and ’620 patents in particular, Genetics maintains that
the amino acid deletion claimed by the ’620 patent is
subsumed entirely by the deletion claimed by the ’112
patent; thus, the ’620 patent’s claims would have been
prima facie obvious over the allegedly interfering claims
of the ’112 patent. Genetics further contends that the
district court misunderstood the testimony of its expert,
Dr. Phillip Fay, who stated that with knowledge of the
deletion points claimed in the ’112 patent (i.e., amino
acids 740 and 1690) it would have been obvious to select
the deletion points claimed in the ’620 patent (i.e., amino
acids 740 and 1649) because the latter points were known
in vivo cleavage points of the full- length Factor VIII
protein. Genetics does not allege error in the district
court’s determination that the ’112 patent’s claims would
not have anticipated the ’620 patent’s claims. As for the
second leg of the two-way test, Genetics contends that the
district court erred by failing to find that the ’620 patent’s
claims anticipate the ’112 patent’s claims.
21 GENETICS INST v. NOVARTIS VACCINES
Novartis responds that there is no interference in fact
between the allegedly interfering claims of the ’112 patent
and the Novartis patents. Novartis contends that the
two-way test is not satisfied because the broader range of
deletions permitted by the claims of the ’112 patent does
not anticipate or render obvious the narrower range
claimed in the Novartis patents. Novartis asserts that
only the claimed Novartis proteins retain the a3 region
and possess the increased stability associated with vWF
binding, and even if this increased stability was not
known as of the priority dates of the Novartis patents,
that property may nonetheless support the claimed pro-
teins’ nonobviousness. Novartis then proceeds on a claim-
by-claim basis to demonstrate why, in its view, the dis-
trict court correctly concluded that the claims of the ’112
patent do not interfere with the claims of the Novartis
patents.
As we shall explain, we agree with the district court’s
determinations that (1) claim 1 of the ’112 patent would
not have rendered obvious claim 68 of the ’620 patent;
(2) claim 5 of the ’112 patent would not have rendered
obvious claim 74 of the ’620 patent; and (3) claim 9 of the
’112 patent would not have rendered obvious claim 83 of
the ’620 patent. We therefore affirm the district court’s
conclusion that the two-way test is not satisfied and that
there is no interference in fact between these claims.
The district court started (and ultimately ended) by
examining the first leg of the two-way test, i.e., whether
the claims of the ’112 patent, if prior art, would invalidate
the claims of the ’620 patent. Genetics, 687 F. Supp. 2d at
497-500. The court noted that these claims differ in terms
of the nature of the truncated Factor VIII proteins en-
coded by the nucleic acids. Id. at 498. The court then
proceeded to analyze the differences between the groups
of proteins claimed in the two patents.
GENETICS INST v. NOVARTIS VACCINES 22
To summarize the district court’s analysis, the
claimed truncated Factor VIII proteins in the ’112 and
’620 patents differ in terms of the size of the permitted
amino acid deletions, the location of the permitted amino
acid deletions, and the degree of allowable amino acid
substitutions. In particular, the deletion in claim 1 of the
’112 patent (and, by extension, claims 5 and 9) ranges in
size from 581 to 949 amino acids and is located between
amino acids 740 and 1690, 7 whereas the deletion in
claims 68, 74, and 83 of the ’620 patent ranges in size
from 889 to 909 amino acids and is located between amino
acids 740 and 1649. The ’620 patent’s claims permit
substitution of up to 10% of the amino acids, whereas the
’112 patent’s claims do not. Importantly, it is undisputed
that the ’112 patent permits deletion of amino acids in the
1649-1689 region, whereas the ’620 patent does not.
In view of these structural differences between the
proteins claimed in the ’112 and ’620 patents, the district
court correctly required as part of the prima facie obvi-
ousness inquiry the identification of some reason that
would have prompted a researcher to modify the prior art
compounds in a particular manner to arrive at the
claimed compounds. Id. at 500; see also Takeda Chem.
Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350,
1357 (Fed. Cir. 2007); In re Dillon, 919 F.2d 688, 692
(Fed. Cir. 1990) (en banc) (“[S]tructural similarity be-
tween claimed and prior art subject matter, proved by
combining references or otherwise, where the prior art
gives reason or motivation to make the claimed composi-
tions, creates a prima facie case of obviousness.” (empha-
sis added)); In re Grabiak, 769 F.2d 729, 731-32 (Fed. Cir.
1985) (To establish prima facie obviousness, “there must
7 As the district court found, this deletion range
forms a group of protein variants numbering about
68,000. Genetics, 687 F. Supp. 2d at 498.
23 GENETICS INST v. NOVARTIS VACCINES
be adequate support in the prior art for the . . . change in
structure.”); In re Lalu, 747 F.2d 703, 705 (Fed. Cir. 1984)
(“In determining whether a case of prima facie obvious-
ness exists, it is necessary to ascertain whether the prior
art teachings would appear to be sufficient to one of
ordinary skill in the art to suggest making the claimed
substitution or other modification.”). This principle was
reaffirmed by the Supreme Court’s opinion in KSR Inter-
national Co. v. Teleflex Inc., which acknowledged the
importance of identifying “a reason that would have
prompted a person of ordinary skill in the relevant field to
combine the elements in the way the claimed new inven-
tion does.” 550 U.S. 398, 418 (2007).
The district court correctly found that Genetics failed
to establish any such reason for modifying the group of
proteins claimed in the ’112 patent to produce the group
claimed in the ’620 patent. Genetics, 687 F. Supp. 2d at
500. As of the 1986 priority date of the ’620 patent, those
of skill in the art understood the inactive B domain of the
Factor VIII protein to be “essentially delimited by resi-
dues 740 and 1689”—i.e., to include the amino acids in the
a3 region. Id. (quoting J.A. 6117, John J. Toole et al., A
Large Region (≈95 kDa) of Human Factor VIII Is Dispen-
sable for In Vitro Procoagulant Activity, 83 Proc. Nat’l
Acad. Sci. 5939, 5939 (1986)). Indeed, as the district court
noted, Dr. Randal Kaufman, a former Genetics scientist,
confirmed this fact. During his deposition, he stated that,
in 1986, the 1649-1689 amino acid region was understood
to be part of the B domain. Id.
Genetics argues that amino acid 1649 was one of the
known in vivo cleavage sites on the Factor VIII protein,
and, on account of this fact, it “would be readily apparent”
to make a truncated Factor VIII protein that retained
amino acids in the 1649-1689 region, contrary to the
teachings of the ’112 patent. Br. of Pl.-Appellant at 35.
GENETICS INST v. NOVARTIS VACCINES 24
In support of its position, Genetics cites two articles
published in 1984 that disclosed a number of in vivo
cleavage cites on the Factor VIII protein. J.A. 5181-86,
5195-200; see also J.A. 3781-83. Yet Genetics concedes
that it was not known prior to the filing of the ’620 patent
that amino acids 1649-1689 were critical to maintain vWF
binding. Br. of Pl.-Appellant at 35. And Genetics offers
no basis for its assertion that the mere existence of in vivo
cleavage points between particular amino acid residues
would have provided one of ordinary skill with a reason or
motivation to make the particular truncated proteins
claimed in the ’620 patent. Genetics, 687 F. Supp. 2d at
500.
Indeed, those same in vivo cleavage sites were known
as of the 1985 priority date of the ’112 patent, but the
proteins claimed in the ’112 patent do not require reten-
tion of amino acids 1649-1689. That indicates the weak-
ness of Genetics’ position and supports the district court’s
conclusion that mere knowledge of in vivo cleavage sites
on Factor VIII would not have provided a sufficient reason
for making the proteins claimed in the ’620 patent. Id.
Genetics’ arguments also run contrary to the research
objectives of those in the field of truncated Factor VIII
proteins. The district court found that research in the
Factor VIII field focused on “finding a smaller recombi-
nant protein that mimicked the biological activity of
Factor VIII in humans.” Id. at 492 (emphasis added).
That is consistent with the disclosure of the ’112 patent,
which is focused on making “proteins which have proco-
agulant activity similar to that of factor VIII:C and also
have substantially lower molecular weight.” ’112 patent
col.2 ll.10-13; see also id. col.20 ll.9-14 (“I contemplate
that my compounds may be produced by recombinant
DNA techniques at a much lower cost than is possible for
production of human factor VIII. The host organisms
25 GENETICS INST v. NOVARTIS VACCINES
should more efficiently process and express the substan-
tially simpler molecules of this invention.” (emphasis
added)). Genetics fails to explain why, with knowledge of
the claimed range of proteins in the ’112 patent, one of
ordinary skill would have sought out a range encompass-
ing larger recombinant proteins (i.e., proteins having
smaller amino acid deletions), such as the range of pro-
teins claimed in the ’620 patent. Thus, contrary to Genet-
ics’ arguments, the mere existence of an in vivo cleavage
point, without more, would not have provided the requi-
site “reason or motivation,” Dillon, 919 F.2d at 692, to
manipulate the claimed proteins of the ’112 patent at that
cleavage point to make those claimed in the ’620 patent.
The dissent, in arguing for obviousness, relies on
those claimed proteins of the ’112 patent that retain the
a3 region. Dissent Op. at 8-9. But the dissent selectively
parses the prior art disclosure with impermissible hind-
sight. Each disputed claim of the ’112 patent teaches
deletion of the a3 region in some variants, thus leading
away from a requirement that that region be retained.
Viewed as a whole, the prior art would not have prompted
one of ordinary skill to require retention of the a3 region.
See Panduit Corp. v. Dennison Mfg. Co., 810 F.2d 1561,
1568 (Fed. Cir. 1987) (“[A] prior patent must be consid-
ered in its entirety, i.e., as a whole, including portions
that would lead away from the invention in suit[.]”).
Further, the dissent challenges well-established law
requiring the identification of some reason that would
have prompted a researcher to substantially modify a
prior art compound to produce the claimed compound.
Dissent Op. at 3-5. While the dissent accepts that the
prior art here provided “no suggestion or stated need for
further experimentation” and “no motivation to optimize
for some value within the range” of proteins disclosed by
the ’112 patent, id. at 8, the dissent nonetheless contends
GENETICS INST v. NOVARTIS VACCINES 26
that, because of “structural similarity” in the patented
proteins, no reason for chemical modification need be
shown. The dissent vastly oversimplifies the differences
in the claimed proteins, however. One of ordinary skill
would appreciate that the claimed truncated proteins
vary enormously in structure: for example, the a3 region
alone contains 40 amino acid residues and has a relative
molecular mass of about 4,500. J.A. 5199. In contrast,
the homologs, analogs, and isomers referenced by the
dissent typically differ, at most, by only a few atoms—and
even in cases involving such ostensibly minor chemical
differences, prima facie obviousness is by no means inevi-
table. See, e.g., Grabiak, 769 F.2d at 730 (reversing the
PTO’s finding of prima facie obviousness even though the
prior art compound differed from the claimed compound
“only by the presence . . . of a sulfur atom instead of a
particular oxygen atom”). The dissent’s oversimplification
violates our longstanding admonition that “generalization
is to be avoided insofar as specific structures are alleged
to be prima facie obvious one from the other.” In re Jones,
958 F.2d 347, 350 (Fed. Cir. 1992) (citing Grabiak, 769
F.2d at 731). On the facts of this case, the nontrivial
differences in the proteins at issue compel the require-
ment of identifying a reason for the chemical modification.
Genetics asserts that the district court’s conclusion of
nonobviousness is contrary to In re Peterson, 315 F.3d
1325 (Fed. Cir. 2003). According to Genetics, Peterson
holds that a broad range necessarily renders obvious a
narrower range falling within that broader range. That is
incorrect. In Peterson, we stated that “[a] prima facie case
of obviousness typically exists when the ranges of a
claimed composition overlap the ranges disclosed in the
prior art.” Id. at 1329 (emphasis added). The facts here
do not present the “typical[]” case contemplated in Peter-
son, however.
27 GENETICS INST v. NOVARTIS VACCINES
First, we noted in Peterson that “we do not have here
any assertion that the disclosed range is so broad as to
encompass a very large number of possible distinct com-
positions,” and that our reasoning did not necessarily
extend to “a disclosed range of such breadth.” Id. at 1330
n.1. In this case, in contrast, about 68,000 protein vari-
ants are encompassed by the claims of the ’112 patent.
Genetics, 687 F. Supp. 2d at 498. Genetics fails to ac-
knowledge this important distinction.
Moreover, in Peterson our holding was based on the
recognition that “[t]he normal desire of scientists or
artisans to improve upon what is already generally known
provides the motivation to determine where in a disclosed
set of percentage ranges is the optimum combination of
percentages.” 315 F.3d at 1330. As noted above, however,
the only evidence of motivation in the present record is
that of researchers to make smaller, truncated proteins to
solve the cloning difficulties associated with the large size
of Factor VIII. That motivation would not have supplied
researchers with a reason to make the group of proteins
claimed in the ’620 patent encompassing larger truncated
proteins than those claimed in the ’112 patent. Simply
put, the typical desire of scientists to find an optimum
value within a narrow disclosed range, id., does not apply
to the facts of this case.
The dissent also attempts to shoehorn the facts of this
case into our holding in Peterson. But the Novartis inven-
tors did not simply “[s]elect[] a narrow range from within
a somewhat broader range,” as did the Peterson inventors
when selecting the range of “about 1–3%” rhenium from
the prior art range of “0–7%” rhenium. Peterson, 315 F.3d
at 1329-30. As noted, the ’112 patent contains 68,000
truncated variants of a protein made up of 2,332 amino
acids, and the allegedly interfering inventions differ in
terms of the size of the permitted amino acid deletions,
GENETICS INST v. NOVARTIS VACCINES 28
the location of those deletions, and the degree of allowable
amino acid substitutions. The facts here present a case
where the “disclosed range is so broad as to encompass a
very large number of possible distinct compositions” thus
“requir[ing] nonobvious invention,” not a case, as in
Peterson, where prior art “ranges that are not especially
broad invite routine experimentation to discover optimum
values.” Id. at 1330 n.1. On this point the dissent ap-
pears to agree, conceding not only that the prior art ’112
patent claims a “large breadth of possible protein vari-
ants,” but also that “there was no motivation to optimize
for some value within the range” disclosed by prior art.
Dissent Op. at 8. Viewed in context, our holding in Peter-
son does not extend to the facts of this case.
We therefore hold that the district court did not err in
concluding that the ’620 patent’s claims would not have
been prima facie obvious over the ’112 patent’s claims.
We also reject Genetics’ contention that the district
court erred by crediting the unexpected results of the
claimed invention in the ’620 patent as part of its obvi-
ousness analysis. Genetics maintains that, because the
importance of the a3 region to vWF binding was not
known as of the filing date of the ’620 patent, the reten-
tion of the a3 region in the claimed proteins of the ’620
patent and their corresponding ability to bind vWF may
not be relied upon to demonstrate the unexpected results
of those proteins. We disagree. Our case law is clear that
the structure of a claimed compound and its properties
are inseparable for purposes of § 103. Sanofi-Synthelabo
v. Apotex, Inc., 550 F.3d 1075, 1086 (Fed. Cir. 2008) (“For
chemical compounds, the structure of the compound and
its properties are inseparable considerations in the obvi-
ousness determination.”); In re Papesch, 315 F.2d 381,
391 (CCPA 1963) (“From the standpoint of patent law, a
29 GENETICS INST v. NOVARTIS VACCINES
compound and all of its properties are inseparable; they
are one and the same thing.”).
Our law is equally clear that every property of a
claimed compound need not be fully recognized as of the
filing date of the patent application to be relevant to
nonobviousness. Knoll Pharm. Co. v. Teva Pharms. USA,
Inc., 367 F.3d 1381, 1385 (Fed. Cir. 2004) (“There is no
requirement that an invention’s properties and advan-
tages were fully known before the patent application was
filed, or that the patent application contains all of the
work done in studying the invention, in order for that
work to be introduced into evidence in response to litiga-
tion attack.”). For those reasons, we have held that
evidence of unexpected results may be used to rebut a
case of prima facie obviousness even if that evidence was
obtained after the patent’s filing or issue date. Id. (“Evi-
dence [of unexpected results] developed after the patent
grant is not excluded from consideration, for understand-
ing of the full range of an invention is not always achieved
at the time of filing the patent application.”); In re Khel-
ghatian, 364 F.2d 870, 876 (CCPA 1966) (holding the
claimed invention nonobvious in view of post-filing evi-
dence of an unexpected property not disclosed in the
specification, while noting that the evidence “[wa]s di-
rected to that which ‘would inherently flow’ from what
was originally disclosed” (quoting In re Zenitz, 333 F.2d
924, 927 (CCPA 1964)); see also Eli Lilly & Co. v. Zenith
Goldline Pharms., Inc., 471 F.3d 1369, 1378 (Fed. Cir.
2006) (“This court will not ignore a relevant property of a
compound in the obviousness calculus.” (citing Lalu, 747
F.2d at 707)).
The dissent, like Genetics, misstates our precedent
regarding secondary considerations of nonobviousness.
Dissent Op. at 10-17. Although the § 103 analysis re-
mains properly focused “at the time the invention was
GENETICS INST v. NOVARTIS VACCINES 30
made,” it would be error to prohibit a patent applicant or
patentee from presenting relevant indicia of nonobvious-
ness, whether or not this evidence was available or ex-
pressly contemplated at the filing of the patent
application. See Graham v. John Deere Co., 383 U.S. 1,
17-18 (1966). Relevant secondary considerations often are
not manifest even until well after the issuance of a pat-
ent. The dissent would require either an express predic-
tion of unexpected properties in the patent specification or
a showing of the inventors’ contemporaneous knowledge
of such properties before the PTO or any court could
consider such probative evidence. Our precedent contains
no such requirement. See, e.g., In re Chu, 66 F.3d 292,
298-99 (Fed. Cir. 1995) (noting that evidence supporting
nonobviousness need not be contained within the specifi-
cation, and holding that the PTO erred by failing to
consider unexpected results even though the specification
was “virtually silent on the matter”); see also KSR, 550
U.S. at 406 (“The analysis is objective[.]”). Even so, the
dissent’s supposed requirement is an incorrect basis for
rejecting the evidence in this case, where the patents
expressly disclose the claimed proteins’ high stability and
ability to bind vWF, e.g., ’447 patent col.2 ll.29-31, col.8
ll.19-22; ’620 patent col.2 ll.30-32, col.8 ll.25-29, and
where the parties do not dispute that the Novartis inven-
tors’ development of the claimed proteins used a tech-
nique that excluded any protein that did not bind vWF,
J.A. 3707-08.
Consequently, the district court did not err in its
nonobviousness analysis by considering, as evidence of
unexpected results, the ability of the claimed proteins to
bind vWF, even if, as Genetics contends, the role of the a3
region was not appreciated as of the ’620 patent’s priority
date. Genetics, 687 F. Supp. 2d at 500.
31 GENETICS INST v. NOVARTIS VACCINES
Genetics alleges yet another error in the district
court’s nonobviousness determination. Genetics contends
that Novartis’s proffered unexpected results are not
commensurate with the full scope of its claims because
the Novartis patents permit amino acid substitution that
may reduce or eliminate vWF binding. Again, we dis-
agree. Whether an invention has produced unexpected
results is a question of fact, In re Harris, 409 F.3d 1339,
1341 (Fed. Cir. 2005), and we do not perceive clear error
in the district court’s decision to credit Novartis’s evidence
of vWF binding. The district court explicitly recognized
that the claims of the Novartis patents permit substitu-
tion (i.e., replacement of one amino acid with another) in
up to 10% of the protein’s amino acids. Genetics, 687 F.
Supp. 2d at 499, 501. Notwithstanding that finding,
Genetics points to an article published by Leyte in 1991
demonstrating that the substitution of the amino acid
phenylalanine for tyrosine at position 1680 in the a3
region eliminated vWF binding but retained procoagulant
activity in the resulting B-domain deleted protein. See
Anja Leyte et al., Sulfation of Tyr1680 of Human Blood
Coagulation Factor VIII Is Essential for the Interaction of
Factor VIII with von Willebrand Factor, 266 J. Biological
Chem. 740, 744 (1991); J.A. 6084-90. Based on this
information, Genetics asserts that the unexpected result
of improved stability through vWF binding is not com-
mensurate in scope with the claims of the ’620 patent, and
therefore must be ignored.
The district court’s opinion did not explicitly address
the Leyte article. Even taking Genetics’ assertions as
true, however, the Leyte article demonstrates at most
that one particular amino acid substitution at one par-
ticular position eliminates vWF binding—in a claimed
truncated protein of between 1,424 and 1,444 total amino
acids. This solitary fact does not undermine the district
GENETICS INST v. NOVARTIS VACCINES 32
court’s decision to credit the vWF binding properties of
the proteins claimed in the Novartis patents—properties
that Genetics itself concedes are possessed by truncated
Factor VIII proteins retaining the a3 region.
While we have held that unexpected results must be
commensurate in scope with the claims, we have not
required absolute identity of scope; rather, we have re-
jected unexpected results where the evidence was plainly
disproportionate to the scope of the claim. See, e.g.,
Peterson, 315 F.3d at 1331 (affirming obviousness where
the applicant claimed an alloy with 1–3% rhenium, yet
presented unexpected results only for 2% rhenium, and
evidence suggested that 3% rhenium possessed inferior
properties); In re Grasselli, 713 F.2d 731, 743 (Fed. Cir.
1983) (concluding that unexpected results “limited to
sodium only” were not commensurate in scope with claims
to a catalyst having “an alkali metal”); In re Greenfield,
571 F.2d 1185, 1189 (CCPA 1978) (affirming the obvious-
ness of a genus containing “several hundred compounds,”
where unexpected results were proved for “only one” such
compound); cf. In re Glatt Air Techniques, Inc., 630 F.3d
1026, 1030 (Fed. Cir. 2011) (stating that objective evi-
dence of commercial success relating “only to a single
embodiment” should be considered even if claim covers
“multiple embodiments”). Indeed, a rigid requirement of
absolute identity that ignores relevant properties of
claimed compounds would defy the mandate of § 103
requiring consideration of the claimed “subject matter as
a whole.” On the facts of this case, it was not improper for
the district court, in its nonobviousness analysis, to weigh
Novartis’s proffered evidence of unexpected results.
Because on appeal Genetics challenges only the dis-
trict court’s conclusion of nonobviousness, we need not
review the court’s determination that the ’112 patent’s
claims would not, if prior art, anticipate the ’620 patent’s
33 GENETICS INST v. NOVARTIS VACCINES
claims, Genetics, 687 F. Supp. 2d at 499. In view of our
conclusion that the claims of the ’112 patent would not
invalidate the claimed subject matter of the ’620 patent,
we also need not consider whether the reverse is true.
Because the two-way test was not met, we conclude that
the district court did not err in holding that there was no
interference in fact between claims 68, 74, and 83 of the
’620 patent and claims 1, 5, and 9 of the ’112 patent,
respectively.
B. There is no interference in fact between the asserted
claims of the ’112 patent and the ’447 patent
Genetics maintains that the district court erred by
finding no interference in fact between the allegedly
interfering claims of the ’112 and ’447 patents. Genetics
argues in general that the court committed the same
errors as with the allegedly interfering claims of the ’112
and ’620 patents. As explained above, we reject those
arguments.
Regarding claim 9 of the ’112 patent and claim 1 of
the ’447 patent, Genetics additionally asserts that it
would have been obvious to use the method of claim 9 to
make the composition of claim 1, because there is no
patentable distinction between a method of making a
protein and the protein itself. We need not address this
argument, however, because it is premised on Genetics’
flawed assertion (the basis for which we rejected above)
that the court erred by finding a patentable distinction
between the proteins of claim 9 of the ’112 patent and
those of claim 1 of the ’447 patent. Genetics does not
contend on appeal that claim 9 of the ’112 patent would
anticipate claim 1 of the ’447 patent. Accordingly, at least
the first leg of the two-way test fails for the alleged inter-
ference in fact between claim 9 of the ’112 patent and
GENETICS INST v. NOVARTIS VACCINES 34
claim 1 of the ’447 patent. Genetics, 687 F. Supp. 2d at
501.
Regarding claim 10 of the ’112 patent and claim 1 of
the ’447 patent, Genetics contends that the district court
erred because each claim, as prior art, would render the
other obvious. We disagree. Taking claim 1 of the ’447
patent as prior art to claim 10 of the ’112 patent, Genetics
again asserts that “it would be readily apparent” to one of
ordinary skill in the art to modify the protein of claim 1 of
the ’447 patent to make the three proteins of claim 10 of
the ’112 patent. Br. of Pl.-Appellant at 43. As an initial
matter, Genetics, which describes the necessary modifica-
tions as “smaller deletions,” id., misconstrues the scope of
claim 10. As the district court correctly determined,
whereas claim 1 of the ’447 patent deletes the complete B
domain (909 amino acids), claim 10 of the ’112 patent
claims three specific proteins, two of which have smaller
deletions (581 and 880 amino acids) and one of which has
a larger deletion (915 amino acids) than the B domain.
Genetics, 687 F. Supp. 2d at 501. The larger deletion
ranges from amino acid 759 to 1675, which includes part
of the a3 acidic region.
As the district court noted, Genetics failed to present
evidence showing why one of ordinary skill would modify
the protein of claim 1 of the ’447 patent to make the three
different proteins of claim 10 of the ’112 patent. Id. at
502. Genetics alleges that obviousness of a chemical
compound does not require evidence of some reason for
modification. As we explained above, however, this
reflects a misunderstanding of the law. Moreover, Genet-
ics’ position is belied by the testimony of Debra Pittman, a
Genetics scientist who worked with Toole on Factor VIII
proteins. As explained by Pittman, a researcher intent on
designing a new truncated Factor VIII protein would first
identify the amino acid regions he or she wished to delete,
35 GENETICS INST v. NOVARTIS VACCINES
and only then would consider particular protein design
strategies:
Q. What steps were involved in going about mak-
ing the deletion variants of Factor VIII that Dr.
Toole had in mind?
A. Well, first, was to identify the regions that he
wanted to delete, and then devising a scheme to
make those deletions, using either restriction sites
or oligonucleotides.
J.A. 3612 (emphases added). Common sense dictates that
“want[ing] to delete” a particular amino acid region
implies that a reason must exist for that deletion.
Pittman’s testimony thus corroborates what our case law
requires for proving that a claimed compound would have
been obvious: the identification of some reason why one
of ordinary skill would make the necessary chemical
modifications to arrive at the claimed compound. Takeda,
492 F.3d at 1357; Dillon, 919 F.2d at 692.
We therefore affirm the district court’s conclusion that
claim 1 of the ’447 patent would not have rendered obvi-
ous claim 10 of the ’112 patent. Moreover, Genetics does
not contend that claim 1 would have anticipated claim 10.
Because one leg of the two-way test fails, we need not
consider the second leg. Medichem, 353 F.3d at 935.
Accordingly, we agree with the district court’s deter-
minations that there is no interference in fact between
claims 9 and 10 of the ’112 patent and claim 1 of the ’447
patent.
CONCLUSION
For the foregoing reasons, we affirm the district
court’s order granting Novartis’s motion to dismiss due to
the absence of an interference in fact between the alleg-
GENETICS INST v. NOVARTIS VACCINES 36
edly interfering claims. In particular, we conclude that
the expiration of the ’112 patent following the district
court’s entry of final judgment did not divest our court of
appellate jurisdiction; that the patent term extension of
the ’112 patent applied to all of the allegedly interfering
claims; and that there is no interference in fact between
(1) claim 1 of the ’112 patent and claim 68 of the ’620
patent, (2) claim 5 of the ’112 patent and claim 74 of the
’620 patent, (3) claim 9 of the ’112 patent and claim 83 of
the ’620 patent, and (4) claims 9 and 10 of the ’112 patent
and claim 1 of the ’447 patent.
AFFIRMED.
United States Court of Appeals
for the Federal Circuit
__________________________
GENETICS INSTITUTE, LLC,
Plaintiff-Appellant,
v.
NOVARTIS VACCINES AND DIAGNOSTICS, INC.,
Defendant-Appellee.
__________________________
2010-1264
__________________________
Appeal from the United States District Court for the
District of Delaware in Case No. 08-CV-0290, Judge Sue
L. Robinson.
__________________________
DYK, Circuit Judge, concurring-in-part and dissenting-in-
part.
I join Parts I and II of the majority's opinion, but I re-
spectfully dissent from Part III. In my view, the majority
erred in holding that the asserted claims of the ’112
patent would not render obvious the asserted claims of
the ’620 and ’447 patents (collectively the “Novartis
patents”) and in holding that there was, accordingly, no
interference-in-fact.
In the mid-1980s, the ’112 patent and the Novartis
patents were co-pending before the Patent and Trade-
mark Office (“PTO”). At the time, there was concern that
pathogens, like the HIV and hepatitis virus, were con-
GENETICS INST v. NOVARTIS VACCINES 2
taminating the supply of hemophilia treatments made
from human Factor VIII proteins. Genetics and Novartis
thus competed to clone safer, synthetic forms of Factor
VIII. Because of the large size of Factor VIII, however,
yields from the host cells expressing the gene were very
low. The patents-in-suit were directed to solving this
problem by producing truncated forms of Factor VIII that
would nonetheless maintain the same procoagulant (i.e.
blood-clotting) activity of the full-length protein.
By comparing human Factor VIII to porcine Factor
VIII, Genetics discovered that, while significant regions of
human and porcine Factor VIII were homologous, the
large B domain of human Factor VIII diverged greatly
from the B domain of porcine Factor VIII. Because por-
cine Factor VIII was nonetheless effective in treating
human hemophilia patients, Genetics deduced that the B
domain was superfluous and could be excised without
compromising Factor VIII’s procoagulant activity. This
discovery led to the innovations of the ’112 patent. The
truncated Factor VIII proteins of the ’112 patent have a
“substantially lower molecular weight,” ’112 patent col.2
ll.10–12, but have “similar procoagulant activity” to the
full-length version of human Factor VIII, id. col.1 ll.8–9.
These “simpler molecules” were advantageous because
they could “be produced . . . at a much lower cost.” Id.
col.20 ll.9–14. Around the same time, Novartis scientists
were researching a more efficient way to clone Factor
VIII. The objective of the Novartis patents was, similarly,
to design a truncated protein with “activity equal to that
of cloned full-length Factor VIII[ ].” ’447 patent col.2
ll.18–19; ’620 patent col.2 ll.18–19.
All of the patents-in-suit are directed to truncated
Factor VIII proteins in which the B domain is either
partially or completely deleted. These proteins differ
mainly in one respect: while the Novartis proteins retain
3 GENETICS INST v. NOVARTIS VACCINES
the a3 region, the proteins of the ’112 patent permit (but
do not require) deletions in that region. As it turned out,
years later, independent researchers discovered that the
a3 region had the previously unforeseen benefit of being
able to bind to von Willebrand Factor (“vWF”). Though it
had been known since the late 1970s that vWF had a
stabilizing effect on Factor VIII, the location of vWF
binding in the a3 region was not known until at least
1988, years after the Novartis patents were filed, as the
Novartis witnesses themselves described. One Novartis
expert admitted that there was “nothing in the scientific
literature by April 1986 suggesting the importance of [the
a3 region] to interactions between Factor VIII and vWF.”
J.A. 2683. And one of the inventors testified that the
Novartis patents “do[ ] not specifically tell you [the loca-
tion of the vWF binding sites within the Factor VIII
protein], [because] that was not the intention of the
patent, to specify the binding to von Willebrand Factor.”
J.A. 3732. The majority does not dispute this, stating
that “Genetics concedes that it was not known prior to the
filing of the ’620 patent that [the a3 region] was critical to
maintain vWF binding.” Maj. Op. at 24.
In my view, there are four fundamental flaws with the
majority’s conclusion of non-obviousness. First, the
majority holds that the Novartis patents could not be
obvious over the ’112 patent unless Genetics could iden-
tify “some reason that would have prompted a researcher
to modify” the ’112 patent to retain the a3 region. Id. at
21. However, a requirement for a motivation to retain the
a3 region should not be the test where, from an objective
standpoint, no inventor—including the Novartis inventors
themselves—could have been aware of the benefits of
retaining the a3 region at the time of the invention.
Rather, we should look to whether there was enough
structural similarity between the patents-in-suit to make
GENETICS INST v. NOVARTIS VACCINES 4
a prima facie case of obviousness, given what was known
to the inventors at the time of the invention.
Our precedent has established that “[s]tructural rela-
tionships may provide the requisite motivation or sugges-
tion to modify known compounds to obtain new
compounds.” In re Deuel, 51 F.3d 1552, 1558 (Fed. Cir.
1995). Moreover, such structural similarity (i.e., an
established structural relationship between a prior art
compound and the claimed compound) can give rise to a
case of prima facie obviousness. Id. Thus, “a known
compound may suggest its [homologs,] analogs, or iso-
mers” because such compounds “often have similar prop-
erties and therefore chemists of ordinary skill would
ordinarily contemplate making them to try to obtain
compounds with improved properties.” Id. In In re Jones,
958 F.2d 347, 349 (Fed. Cir. 1992), we acknowledged that
“particular types or categories of structural similarity[,]
without more[,] have, in past cases, given rise to prima
facie obviousness.” (citing In re Dillon, 919 F.2d 688, 692–
94 (Fed. Cir. 1990) (tri-orthoesters and tetra-orthoesters),
cert. denied, 500 U.S. 904 (1991)); In re May, 574 F.2d
1082 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d
457 (CCPA 1977) (adjacent homologs and structural
isomers); In re Hoch, 428 F.2d 1341 (CCPA 1970) (acid
and ethyl ester)). 1 In this case, the truncated Factor VIII
1 See also In re Mayne, 104 F.3d 1339, 1343 (Fed.
Cir. 1997) (finding a claimed enterokinase recognition
sequence containing the amino acid sequence Phe-Pro-
Leu was merely “an obvious functional equivalent” to
prior art sequences that included arrangements of Phe-
Pro-Ile and Leu-Pro-Leu); In re Dillon, 919 F.2d 688, 693
(Fed. Cir. 1990) (finding a prima facie case of obviousness
where the prior art tri-orthoester compound was found to
be equivalent to the claimed tetra-orthoester compound
and the use of the tri-orthoester as a fuel additive was
expected to produce essentially the same result as the use
5 GENETICS INST v. NOVARTIS VACCINES
proteins of the ’112 patent and the truncated Factor VIII
proteins of the Novartis patents are not merely homologs,
analogs, or isomers—they are all variants of the exact
same protein, exhibiting the exact same procoagulant
functions. Here, the majority found that the patents-in-
suit differed in terms of the size of the permitted amino
acid deletions, the location of the deletions, and the de-
gree of allowable amino acid substitutions. However,
these differences are of no consequence to the core proco-
agulation function of the proteins. This is so because the
main innovation of the patents-in-suit is the discovery
that the B domain is completely unnecessary to procoagu-
lation. Consequently, it does not matter whether the
deletions are large or small or whether the deletions begin
at one amino acid or another. Any deletion in the B
domain, ipso facto, would retain the procoagulation func-
tion of Factor VIII. The similarities in structure and
function would provide the requisite motivation to modify
the proteins of the ’112 patent to obtain the proteins of
the Novartis proteins. See In re Dillon, 919 F.2d 688, 696
(“[T]he fact that the claimed and the prior art compounds
possessed the same activity were added factors in the
establishment of a prima facie case.”).
Second, under our prior authority, a prima facie case
of obviousness can also exist if the range of an earlier
patent incorporates the range of later patents. 2 That is
of the tetra-orthoester); In re Payne, 606 F.2d 303, 313–15
(CCPA 1979) (discussing the presumption of obviousness
based on close structural similarity).
2 Though the majority does not appear to dispute
that the broader range of deletions in the ’112 patent
subsumed the narrower range of deletions in the Novartis
patents, I think the proper focus should be on the range of
retentions, not the range of deletions. This is so because
we are concerned with whether the Novartis patents can
be differentiated based on what they retain rather than
GENETICS INST v. NOVARTIS VACCINES 6
the case here where it is clear that the range of retentions
in the ’112 patent fall within the range of retentions of the
Novartis patents, as discussed above. Our case law has
held that “[a] prima facie case of obviousness typically
exists when the ranges of a claimed composition overlap
the ranges disclosed in the prior art.” In re Peterson, 315
F.3d 1325, 1329–30 (Fed. Cir. 2003). “[E]ven a slight
overlap in range establishes a prima facie case of obvi-
ousness.” Id. at 1329; see also In re Geisler, 116 F.3d
1465, 1469 (Fed. Cir. 1997) (finding prima facie obvious-
ness where range of prior art reference (100–600 Ang-
stroms) overlapped the claimed range (50–100
Angstroms)); In re Woodruff, 919 F.2d 1575, 1578 (CCPA
1990) (holding a claimed invention obvious because
claimed range (“more than 5% to about 25%” carbon
monoxide) abutted range of prior art (“about 1–5%” car-
bon monoxide)); In re Malagari, 499 F.2d 1297, 1303
(CCPA 1974) (finding prima facie obviousness where the
claimed range of the prior art reference (0.020–0.035%
carbon) overlapped the claimed range (0.030–0.070%
carbon)). Significantly, when “the claimed ranges are
completely encompassed by the prior art, the conclusion
[of obviousness] is even more compelling than in cases of
mere overlap.” Peterson, 315 F.3d at 1330. 3 Here, as in
what they delete. Nonetheless, whether the focus is on
deletions or retentions, there is still an overlap.
3 We have also held that a prima facie case of obvi-
ousness exists when the claimed range and the prior art
range do not overlap but are close enough such that one
skilled in the art would have expected them to have the
same properties.” Peterson, 315 F.3d at 1329; see Tita-
nium Metals Corp. v. Banner, 778 F.2d 775, 776, 783 (Fed.
Cir. 1985) (concluding that a claim directed to an alloy
containing “0.8% nickel, 0.3% molybdenum, up to 0.1%
maximum iron, balance titanium” would have been prima
facie obvious in view of a reference disclosing alloys
containing 0.75% nickel, 0.25% molybdenum, balance
7 GENETICS INST v. NOVARTIS VACCINES
Peterson, the range of retentions or deletions in the No-
vartis patents overlap significantly with the range of the
’112 patent, and are, in my view, prima facie obvious.
The majority, nevertheless, concludes that the com-
pound here was not the “‘typical[ ]’ case” contemplated in
Peterson, Maj. Op. at 26 (quoting 315 F.3d at 1329),
pointing to a footnote in Peterson that opined:
Although ranges that are not especially broad
invite routine experimentation to discover opti-
mum values, rather than require nonobvious in-
vention, we do not have here any assertion that the
disclosed range is so broad as to encompass a very
large number of possible distinct compositions.
We thus do not need to decide whether a disclosed
range of such breadth might present a situation
analogous to our cases involving the failure of a
very broad disclosed genus of substances to render
prima facie obvious specific substances within its
scope.
315 F.3d at 1330 n.1 (emphases added). Because the
majority found that the ’112 patent claims encompassed a
very large number of possible distinct compositions—
nearly “68,000 truncated variants”—it declined to extend
the reasoning in Peterson to a “disclosed range of such
breadth.” Maj. Op. at 27.
However, as the court in Peterson made clear, it is the
facts of a particular case that will render it “typical” or
not. 315 F.3d at 1329. An expansive range of variants
should not per se defeat a prima facie case of obviousness.
Moreover, the court’s concern in Peterson was less the
breadth of the claims, than the ability to conduct “routine
titanium and 0.94% nickel, 0.31% molybdenum, balance
titanium).
GENETICS INST v. NOVARTIS VACCINES 8
experimentation to discover optimum values.” Id. at 1330
n.1. Narrower ranges would presumably invite more
routine experimentation and “motivate[ ] [scientists] to
determine where in a disclosed set of . . . ranges is the
optimum combination,” see id. at 1330, while broader
ranges would presumably discourage such experimenta-
tion. Here, there is no suggestion or stated need for
further experimentation to discover some “optimum
range.” As the majority acknowledges, the “typical desire
of scientists to find an optimum value within a narrow
disclosed range, does not apply to the facts of this case”
because “the only evidence of motivation in the present
record is that of researchers [trying] to make smaller,
truncated proteins to solve the cloning difficulties associ-
ated with the large size of Factor VIII.” Maj. Op. at 27
(emphasis added; internal citations omitted). Because
there was no motivation to optimize for some value within
the range of possible retentions, the large breadth of
possible protein variants is of no consequence. In sum, I
would find that the claims of the Novartis patents are
prima facie obvious in view of the overlapping ranges of
the ’112 patent. The burden of proving nonobviousness
should thus have shifted to the holder of the later-
developed patent, in this case, Novartis. Peterson, 315
F.3d at 1330.
Third, the majority appears to suggest that the
“ret[ention] of amino acids in the [a3] region” was “con-
trary to the teachings of the ’112 patent.” Maj. Op. at 23.
This is wrong on the facts. The majority ignores that
some variants of the ’112 patent actually retain the a3
region and therefore have the ability to bind to vWF. For
instance, claim 10 of the ’112 patent claims a truncated
Factor VIII protein having one of three specific deletions,
two of which are the deletions of amino acids 981–1563
and 759–1640. See col.26 ll.28–34. These two deletions
9 GENETICS INST v. NOVARTIS VACCINES
clearly retain the a3 region (amino acids 1649–1689).
Retention of the a3 region is also within the scope of
retentions allowed by claim 1 of the ’112 patent. 4 There-
fore, many of the variants claimed in the ’112 patent
actually conserve the a3 region necessary for vWF bind-
ing. If, as the majority concludes, “the structure of a
claimed compound and its properties are inseparable for
purposes of § 103,” it seems inconsistent to credit the a3
region in the Novartis compounds for giving rise to vWF
binding while not doing the same for the compounds of
the ’112 patent. Maj. Op. at 28 (citing Sanofi-Synthelabo
v. Apotex, Inc., 550 F.3d 1075, 1086 (Fed. Cir. 2008) (“For
chemical compounds, the structure of the compound and
its properties are inseparable considerations in the obvi-
ousness determination.”); In re Papesch, 315 F.2d 381,
391 (CCPA 1963) (“From the standpoint of patent law, a
compound and all of its properties are inseparable; they
are one and the same thing.”)).
The majority also urges that some variants of the ’112
patent teach away from retaining the a3 region. The
majority, however, ignores the fact that certain variants
of the Novartis patents also teach away from keeping the
a3 region intact, with the result that vWF binding is not
achieved. In particular, the Novartis patents allow up to
10 percent of the amino acids in the Factor VIII protein to
be substituted, including substitutions in the a3 region:
[U]sually not more than 10, more usually not
more than 5[%], preferably not more than about
1[%] of the amino acids in the chains will differ
from the amino acids naturally present in the
4 For example, claim 1 of the ’112 patent teaches
deletions that range from 581 to 949 amino acids. A more
conservative deletion in this range could still leave intact
the a3 region critical to vWF binding.
GENETICS INST v. NOVARTIS VACCINES 10
Factor VIII[ ] . . . C domain[ ] . . . . Conservative
substitutions include: . . . Phe[nylalanine]
Tr[yptophan] Tyr[osine].
’620 patent col.4 ll.39–53. With the substitution of
phenylalanine for tyrosine in the a3 region—that is, a
“conservative substitution” expressly taught in the Novar-
tis patents—vWF binding would be “completely abol-
ished.” See Anja Leyte et al., Sulfation of Tyr-1680 of
Human Blood Coagulation Factor VIII Is Essential for the
Interaction of Factor VIII with von Willebrand Factor, 266
J. Biological Chem. 740, 744 (1991), available at J.A.
6084–90 (“vWF binding was completely abolished” when
“Tyr[osine]-1680 [in the a3 region] . . . was replaced by
phenylalanine.”). In this respect, the ’112 patent and the
Novartis patents all teach some variants that retain the
a3 region and some variants that teach away from retain-
ing the a3 region necessary for vWF binding.
Finally, the majority found that the later-discovered,
undisclosed benefits of retaining the a3 region qualified as
unexpected results to help defeat the prima facie case of
obviousness, even though the role of the a3 region was not
appreciated as of the Novartis patents’ priority date. I
disagree. The majority’s finding of nonobviousness is
based entirely on hindsight and happenstance, and not on
what the inventors knew at the time the Novartis patents
were filed. See 35 U.S.C. § 103(a) (stating that an inven-
tion cannot be patented if “the subject matter as a whole
would have been obvious at the time the invention was
made”) (emphasis added). The Supreme Court has never
suggested that it is permissible to look beyond the inven-
tor’s knowledge at the time of patent filing in determining
unexpected results. To the contrary, the Supreme Court
has characterized such after-acquired knowledge as an
“afterthought,” Ball & Socket Fastener Co. v. Kraetzer,
150 U.S. 111, 117, 116–17 (1893), and has declined to give
11 GENETICS INST v. NOVARTIS VACCINES
it weight in determining patent validity. For example, in
Graham v. John Deere Co., 383 U.S. 1, 25 (1966), the
Supreme Court rejected the patentee’s argument that his
patented plow had the unexpected result of additional
“flex” over the prior art, noting that “[n]o ‘flexing’ argu-
ment was raised in the Patent Office.” See also Lincoln
Eng’g Co. v. Stewart-Warner Corp., 303 U.S. 545, 550
(1938) (“If this [new feature] were so vital an element . . .
it is strange that all mention of it was omitted [in the
specification].”).
Similarly, our court and our predecessor court have
rejected later-acquired knowledge as supporting unex-
pected results. Early cases from the Court of Customs
and Patent Appeals (“CCPA”) have gone so far as to hold
that unexpected results must be described in the specifi-
cation itself. 5 Contrary to the majority’s suggestion, Maj.
Op. at 30, I do not propose such a stringent requirement.
5 See In re Herr, 304 F.2d 907, 909 (CCPA 1962)
(“[If] an [unexpected advantage] is not disclosed in appel-
lant’s application, he is not in a favorable position to urge
it as a basis for the allowance of claims.”) (internal quota-
tion marks omitted) (citing In re Lundberg, 253 F.2d 244,
247 (CCPA 1958)); In re Crawford, 250 F.2d 370, 373
(CCPA 1957) (“[T]here is no disclosure in appellant’s
application that the glass of which the casing is made has
the property recited in [the claim] of ‘substantially com-
plete disintegration at a vibration frequency correspond-
ing to that of the shock wave generated by detonation of
the explosive body’ and accordingly patentability cannot
be predicated on that feature.”); In re Stewart, 222 F.2d
747, 754 (CCPA 1955) (“[U]nexpected results sufficient to
spell out patentability must be disclosed, not in briefs or
affidavits filed in support of such patentability, but in-
stead in the specification itself. In adjudging, in the first
instance, a patent applicant’s right to a patent, we are
guided in our determination by that which is taught in
the application and not by some subsequent undisclosed
discovery.”).
GENETICS INST v. NOVARTIS VACCINES 12
But I do think that unexpected properties must either be
set forth in the specification or contemporaneously known
to the inventors, rather than being discovered long after
the fact.
In more recent CCPA cases, the court has suggested
that a new, undisclosed feature must “inherently flow
from the indicated use” of the invention. In re Zenitz, 333
F.2d 924, 927 (CCPA 1964) (emphasis added); see also In
re Khelghatian, 364 F.2d 870, 876 (CCPA 1966) (allowing
an unexpected result to overcome an obviousness rejection
where the improved result “‘inherently flow[ed]’ from
what was originally disclosed [in the patent application]”)
(emphasis added). Here, the sole “indicated use” of the
truncated Factor VIII proteins was the ability to proco-
agulate blood—not the ability to bind to vWF. In fact, the
parties do not dispute that the protein’s ability to proco-
agulate blood was completely independent of its ability to
bind to vWF. Thus, the ability to bind to vWF was a
wholly new and undisclosed function that did not “inher-
ently flow from the indicated use” of the invention—the
procoagulation of blood. See Zenitz, 333 F.2d at 927. This
later-discovered advantage should not have been allowed
to defeat a finding of obviousness.
Nonetheless, the majority concludes that Sanofi, 550
F.3d at 1086, Knoll Pharmaceutical Co. v. Teva Pharma-
ceuticals USA, Inc., 367 F.3d 1381, 1385 (Fed. Cir. 2004),
and Papesch, 315 F.2d at 391, support its decision to
ignore that the inventors here knew nothing about the
benefits of retaining the a3 region at the time its patents
were filed. However, Sanofi, Knoll, and Papesch are quite
different. In contrast to the present case, in each of these
cases, it was shown that, as of the time of the invention,
the inventor had contemplated that a particular claimed
structure would confer a special and unanticipated advan-
tage, even if the full scope of that advantage was un-
13 GENETICS INST v. NOVARTIS VACCINES
known. While it may have been known at the time of the
Novartis patent that binding to vWF helped increase the
stability of Factor VIII, there was no indication that the
structure proposed in the Novartis patent (i.e., the reten-
tion of the a3 region) was any more effective in doing this
than the structure of the ’112 patent. Nor were the
differences in the Novartis patents designed to achieve
any such objective.
In Sanofi, we affirmed the district court’s holding that
the unpredictable and unusual properties of a claimed
structure and the therapeutic advantages provided by
that structure weighed in favor of nonobviousness. 550
F.3d at 1090. Unlike the prior art, the claimed compound
“provide[d] all of the antiplatelet activity and none of the
adverse neurotoxicity” of the prior art. Id. at 1087. At
the time of the invention, it was known that scientists
were “seeking optimum anti-platelet aggregation proper-
ties with minimal undesirable effects.” Id. at 1079. Thus,
it was clear that the evidence of unexpected results was
based on the knowledge of what the inventor wanted to
achieve at the time of the invention.
In Knoll, the district court refused to consider evi-
dence showing the greater analgesic effect of a combina-
tion of drugs over the prior art, concluding that “the
unexpected benefits or results were discovered after the
. . . patent had been issued.” 367 F.3d at 1384 (internal
quotation marks omitted). We reversed, finding that,
“[c]ontrary to the district court’s perception, the specifica-
tion expressly acknowledge[d] that the efficacy of the
combination [was] ‘surprising’” and stated that the com-
bination of the drugs obtained “an analgesic effect greater
than that obtained by increasing the dose of either [anal-
gesic] alone.” Id. To demonstrate the unexpected activity
of the claimed combination, the patentee submitted
additional data from experiments conducted after the
GENETICS INST v. NOVARTIS VACCINES 14
patent had been filed. Id. at 1385. In concluding that the
district court erred in rejecting this after-acquired data,
we simply held that it was “not improper to obtain addi-
tional support consistent with the patented invention”
because “understanding of the full range of an invention
[was] not always achieved at the time of filing the patent
application.” Id. at 1385 (emphases added). Thus, where
there was already support showing that the inventor
contemplated the unexpected result at the time the patent
was filed, it was not improper to supplement this evidence
of unexpected results with evidence obtained at a later
time. Knoll is therefore consistent with a requirement
that unexpected results be tied to what the inventor knew
at the time of the invention.
In Papesch, the Board of Patent Appeals and Interfer-
ences (“Board”) had rejected the claims for a chemical
compound containing three ethyl groups as obvious over
prior art homologs that contained three methyl groups.
315 F.2d at 383. The applicant responded with an affida-
vit showing that the claimed compound was an active
anti-inflammatory agent while the prior art was inactive
in that respect, but the Board rejected the affidavit. Id.
Our predecessor court reversed, finding that, in addition
to comparing the structural similarities and differences
between a claimed compound and the prior art, a court
should also “tak[e] into consideration their biological and
pharmacological properties.” Id. at 391. The court there-
fore accepted the affidavit and reversed the decision of the
Board. Id. at 392. The specification in Papesch clearly
underscored the advantageous property of the drugs,
expressly stating that the “compounds of this invention
have been found to possess unexpectedly potent anti-
inflammatory activity in contrast to the related trimethyl
compound.” Id. at 382. This unexpected result was a
15 GENETICS INST v. NOVARTIS VACCINES
property contemplated by the inventor at the time of the
invention.
Thus, the cases cited by the majority actually support
a requirement that an unexpected result be either con-
tained in the specification or contemporaneously known to
the inventors. This rule is consistent with the written
description requirement, which demands that the inven-
tion be in possession of the inventor as of the time the
patent was filed. Ariad Pharms., Inc. v. Eli Lilly & Co.,
598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc) (holding
that our written description requirement requires that a
specification “reasonably convey[ ] to those skilled in the
art” that the inventor “actually invented” and “had pos-
session of the claimed subject matter as of the filing date
[of the invention]”) (citing Vas-Cath Inc. v. Mahurkar, 935
F.2d 1555, 1562–63 (Fed. Cir. 1991)); see also Ralston
Purina Co. v. Far-Mar-Co, Inc., 772 F.2d 1570, 1575 (Fed.
Cir. 1985). While, as the majority points out, certain
secondary considerations, such as evidence of commercial
success, can depend on after-acquired knowledge, such
evidence must be directed to the significance of the inven-
tion and its scope. Those factors can not expand the scope
of the invention beyond what was known to the inventors
at the time of the patent filing.
The majority rule—dispensing with any requirement
that an inventor possess knowledge of the unexpected
results at the time the patent was filed—is not only
unsupported by the cases it cites, it is also contrary to
common sense. An applicant should not be able to avoid
an obviousness determination merely by claiming addi-
tional, undifferentiated structure, like the a3 region,
without any showing that this structure conferred any
known benefit over the prior art at the time the invention
was made. Just as a challenger to a patent must rely on a
known motivation to combine existing prior art to achieve
GENETICS INST v. NOVARTIS VACCINES 16
what the invention was designed achieved, 6 so too the
patent holder must prove that he actually contemplated
the unexpected results at the time the patent was filed
and not at some later time.
It is significant that if Genetics had brought this ac-
tion at an earlier time—before it was discovered that vWF
binding resided in the a3 region—the Novartis patents
would likely have been found obvious. Instead, by hap-
penstance and on hindsight, Novartis can now claim an
advantage over the ’112 patent based on information it
did not know at the time of filing and based on research
that was conducted by other parties.
My fear is that the majority’s rule could ultimately
stifle the important incentives for innovation that drive
our patent system. Even though Novartis did not foresee
the significance of the a3 region to vWF binding at the
6 As we discussed in Eisai Co. Ltd v. Dr. Reddy’s
Labs, Ltd., 533 F.3d 1353, 1359 (Fed. Cir. 2008), obvious-
ness must be judged from the knowledge of one skilled in
the art at the time of invention:
First, KSR assumes a starting reference point or
points in the art, prior to the time of invention,
from which a skilled artisan might identify a prob-
lem and pursue potential solutions. Second, KSR
presupposes that the record up to the time of in-
vention would give some reasons, available within
the knowledge of one of skill in the art, to make
particular modifications to achieve the claimed
compound. . . . Third, . . . KSR presumes that the
record before the time of invention would supply
some reasons for narrowing the prior art universe
to a finite number of identified, predictable solu-
tions.
(internal citations and quotation marks omitted) (empha-
ses added).
17 GENETICS INST v. NOVARTIS VACCINES
time its patent was filed, the majority has effectively
allowed Novartis to broaden the scope of its claims to
usurp the fruits of research by the subsequent, independ-
ent inventors who actually discovered the location of vWF
binding in the a3 region. By ruling that a patentee can
have a monopoly on the later-discovered properties of a
structure merely by claiming the structure itself, the
majority’s decision would discourage others from invest-
ing in future research into that very structure.
I would therefore hold that the asserted claims of the
’112 patent would render the asserted claims of the No-
vartis patents prima facie obvious, satisfying the first
prong of the two-way interference test. I would not reach
the question of whether the second prong would be satis-
fied, that is, whether the asserted claims of the Novartis
patents would render obvious or anticipated the asserted
claims of the ’112 patent. It seems to me likely that they
would, but that is an inquiry I would leave to the district
court on remand.