*1 ” Principi 318 v. Cook error.’ dural INC., Plaintiff- AMGEN holding, (Fed.Cir.2002). In so 1334, 1339 Appellant, Cross that “a concluded expressly the veteran duty to assist v. breach deci- of an RO finality not vitiate does ROUSSEL, INC. MARION HOECHST principle The same Id. at 1341. sion.” (now Pharmaceuti- as known Aventis decision, have we a Board to applies Inc.) Transkaryotic Thera- cals, here. Defendants-Appellants. Inc., pies, case, Tetro does Mr.
In this 01-1191, 01-1218. Nos. to statutory exceptions of the either assert Appeals, Court United States Instead, to he seeks finality rule. Circuit. Federal 1990 decision March reopen 6, 2003. Jan. Decided: a he suffered theory that on the Board Banc Rehearing En Hayre. Rehearing under error” procedural “grave 3, 2003. Denied: March committed that the YA argues Mr. Tetro obtaining by not error procedural grave records associated
the medical decision.
SSA proven Hayre, even
Having overruled error” procedural “grave
allegation duty to assist breach of the on a VA
based rule of circumventing the
is insufficient arguendo, Assuming,
finality. the SSA records procure failure
Board’s duty to assist of the breach
constitutes a error, that error procedural a grave
and is exception judicial longer
no invokes reconsideration enabling finality rule Mr. decision. 1990 Board March statutory two available the still
Tetro has ease his war- finality, should
exceptions appeal instant but his reopening,
rant fail. solely Hayre must
based
CONCLUSION duty to violation of
The Board’s finality
assist, not vitiate any, if did 1990 decision.
the Board’s March
COSTS costs. own shall bear its party
Each
AFFIRMED. *6 Casebeer, Hocker, Day, E. Matthew
and LLP, Batchelder, Cupertino, & Madrid Duane, CA; Wong, M. Morris and Richard Boston, Heckscher, LLP, of MA. & Neave, Schwartz, Fish & Herbert F. York, NY, argued for defendants- New him on brief were With appellants. Jr., Herman, Haley, B. F. James Kenneth Gilbert, Loring, Douglas L. J. Denise Flattmann, Lynch, M. Gerald J. Frances Jr., counsel on B. Of and Robert Wilson. Frank, S. Jr. the brief were Robert Choate, Marandett, &Hall Stew- Eric J. Boston, art, MA. Also of counsel on Mary S. were Michael J. Astrue brief Inc., Consalvi, Transkaryotic Therapies, Cambridge, MA. CLEVENGER, MICHEL,
Before SCHALL, Judges. Circuit MICHEL, Judge. Circuit Inc. Amgen Appellant Plaintiff-Cross pat- of numerous is the owner (“Amgen”) erythro- to the production directed ents (“EPO”), hor- naturally occurring poietin of red formation that controls the mone mar- cells in bone marrow. blood EPOGEN®, highly suc- and sells kets *7 pat- of the embodiment commercial cessful Seeking impede erythropoietin. ented Hoechst Marion defendants-appellants Roussel, Transkaryotic Therapies, Inc. and Casebeer, Jr., Ma- Day, Day, Lloyd R. “TKT”) from commercial- (collectively Inc. CA, Batchelder, LLP, Cupertino, &drid Amgen product, competitive izing Of appellant. argued plaintiff-cross in the action declaratory judgment filed a Edward M. were on the brief counsel Dis- for the District Court States United White, Simon, O’Toole, Arnold & Howrey, 1997, alleg- April of Massachusetts trict Watt, IL; Amgen L. Chicago, Stuart Drug New Investigational TKT’s ing that Oaks, CA; and D. Den- Inc., of Thousand (“INDA”) infringed United Application Heckscher, Duane, & Allegretti, Morris (“the nis '933 5,547,933 Nos. Patent States Boston, were LLP, Of counsel MA. (“the 5,618,698 patent”); '698 patent”); Odre, Whiteford, Mo- (“the M. Wendy A. Steven patent”). 5,621,080 '080 and Cook, Amgen R. Cordray, L. nique Robert October amended complaint was 5,756,- Oaks, Inc., Of counsel Nos. CA. Patent of Thousand States include United (“the Galvin, 5,955,422 (“the Madrid, M. and patent”) Robert '349 David M. were was after suit Grewal, which issued patent”), Richard C. '422 Paul S. Terry Tang, L. Nakamura, Loeb, filed. Lin, N. Jackie Jonathan three-day
After a hearing, Markman suit is inequitable unenforceable for con- (ii) duct; the tried days case was to the court for 23 contingent its determination that ¶ over 1; the course of four months. In the '933 is patent Janu- invalid under (iii) ary grant its of summary the district court judgment issued ex- (iv) (i) infringement 1; of '422 patent 244-page opinion haustive in which it: (ii) '080, '933, its claims; '349, determination that the disputed construed the held and '698 enforceable; (iii) patents anticipated by not patents each of the the held (v) reference; Sugimoto and '080, its determina- claims), (product the '349 and '422 tion that patent 3^4, '349 (iv) and 6 patents valid and infringed; held the are infringed. Because the district court (v) patent not infringed; '698 and held the law, misapplied however, (i) the we vacate: or, patent '933 not infringed in the alterna- its determination that patent the '933 tive, invalid for satisfy failure to 35 U.S.C. (ii) infringed; not determination § 112. Amgen, Inc. v. Hoechst Marion patent '080 is infringed under the doc- Roussel, Inc., 126 F.Supp.2d (iii) equivalents; trine of its determination (D.Mass.2001). USPQ2d 1449 appeal, On '080, '349, that the and '422 patents are urges reversal grounds on the (iv) invalid; its determination that patents unenforceable, in suit are all the asserted method claims of '698 that the district court’s claim construction patent and '349 patent claim 7 are not erroneous, and alternatively, if that infringed. Accordingly, we remand for the correct, claim construction was (i) district court to reconsider: whether validity court’s determinations were erro- '080, '349, and '422 patents are obvious asserts, neous. appeal, its cross in light Sugimoto prior art or antici- (i) that the district court committed error: pated or in light obvious of the Goldwasser by comparing the accused process (ii) art; prior whether '422 patent examples in specification rather than anticipated by (and Sugimoto reference limitations the method claims of the whether Amgen can prove its nonenable- (ii) '349 and '698 patents; and by holding (iii) ment); whether the asserted claims of patent '933 invalid for failure to com- and '349 claim 7 are §with ply 112. We heard argument oral infringed by method; (iii) the accused 7,May whether the '080 patent is infringed under We commend the district court for its sum, doctrine of equivalents. careful, thorough, precise work on explained below, further in detail af-we what is indubitably a legally difficult and firm part, vacate in part, and remand technologically complex case. There is no for proceedings further consistent here- doubt that the court marshaled tremen- with. *8 dous time and resources in its effort to reach correct Nevertheless, results. be- BACKGROUND we cause must conclude that the court As the district court in painstak- set out committed certain errors of in law certain ing detail the basics of the underlying validity its infringement and determina- we will technology, provide only a brief
tions, we cannot affirm judgment in its summary here. The familiarity reader’s entirety. with the fundamentals of molecular biolo-
We affirm in toto the district court’s gy, genetics, and recombinant DNA tech- (i) claim construction. We also affirm: its nology necessary to appeal is pre- determination that none of patents in sumed.1 reading For further subjects, ed., generally these see Meyers, Robert A. Molecular naturally protein occurring production
EPO is successful method of of a thera- erythropoiesis, initiates and controls peutically effective erythro- amount of in production of red blood cells bone (“rEPO”) poietin used recombinant EPO Red blood cells are critical marrow. be- techniques; Amgen recognized is as the they hemoglobin, protein cause contain See, pioneer. e.g., Biology Molecular and responsible transporting oxygen for from Biotechnology at 108. lungs peripheral tissues. Because Amgen scientist Dr. Fu-Kuen Lin is the in produced kidney, patients EPO is named inventor on all five patents suit. (renal) kidney with chronic failure lack Instead of attempting purify EPO from and, result, normal as a levels of EPO have sources, natural Lin isolated and charac- a sub-optimal number of red blood cells—a monkey terized and human genes, EPO therapeutic condition called anemia. The then used conventional recombinant DNA goal treating patients anemic is to in- technology to produce large amounts of level,” crease the “hematocrit which repre- 13, patent, rEPO. '933 col. lines 50-53. sents ratio red blood cells to total Lin was able to determine entire DNA volume, blood to normal or near-normal sequence that, of human EPO from levels. This accomplished through predicted Id., amino sequence. acid Fig. introduction of additional EPO into the 6; 10, 11, col. lines 65—col. line 2. Using patient’s system. the isolated human gene, EPO Lin de- implementation seemingly The of this scribed several producing methods for solution, simple exogenous introduction of therapeutically effective amounts of human EPO, proved to difficult. be Because hu- using expression Id., EPO vector.2 col. man produced very EPO is small line 42—col. line 27. (even healthy amounts from the EPOGEN®, the commercial embodi- kidney), it is difficult to obtain conven- Amgen’s ment of patented product, EPO
tional Early attempts methods. to recover produced by the method in pat- disclosed plasma from EPO or from human urine ent specification Example 10. That exam- “uEPO”) (“urinary EPO” or were unsuc- ple production describes the of human recovery cessful because such employed (introduction) through EPO transfection techniques that were complicated, yet still exogenous DNA into host Chinese hamster low-yield, resulted in a high-impurity, or (“CHO”) ovary cell, cells. The CHO host unstable end product. patent, using its own transcription machinery, col. line 60—col. line 42. Similar abundance, then expresses human rEPO attempts using antibody techniques failed which then accumulates the host cell difficulty because of in providing for the Id., cytoplasm or the culture large-scale media. quantities isolation of of EPO col. lines 43-49. The mammalian sources rEPO so recov- sufficient for fur- analysis, ther clinical ered has testing, therapeu- the same or similar amino acid Id., tic use. col. lines 2-8. sequences biological The first properties as nat- Biology Biotechnology: Comprehensive expression A gene vector carries the encod- *9 Reference, (1995); (in ing Desk VCH protein Publishers Ben- for of interest this case Lewin, VII, jamin EPO), Genes Oxford Univ. Press human a marker that assures that the (2000); al., James D. et Watson Recombinant properly vector is introduced into the host (2d ed.1992). cell, DNA promoter and a site that the host will recognize to transcribe the vector's DNA. See ed., 2. "expression An piece generally vector” is a circular Crieghton, Ency- of Thomas E. (or “plasmid”) DNA clopedia Biology, that is inserted into a Molecular vol. John of (or Sons, produce "express”) protein. (1999) host cell to Wiley a & Inc. at 883-86. of biological property in having the vivo EPO, in but differs human occurring
urally i.e., increase patterns of marrow cells to causing in the bone “glycosylation,” that attach chains carbohydrate reticulocytes red blood and branched of production col. lines patent, '933 protein. to the steps: comprising cells 34-41. a) nutrient suitable growing, under suit, pri conditions, which all comprising in cells patents
The vertebrate long application December 1983 ority DNA, to a er- other than human promoter of abandoned, continuations a are since DNA, opera- ythropoietin promoter Patent States ancestor —United common encoding tively linked 4,703,008 was at issue this No. —which se- amino acid erythropoietin mature Inc. decision landmark court’s 6; FIG. quence of Co., 927 F.2d Pharm. Chugai v. b) erythro- glycosylated isolating said (Fed.Cir.1991).3 The '933 USPQ2d 1016 by said expressed polypeptide poietin contain August on patent issued cells to a non- primarily 14 claims drawn ing claim 4 wherein said of process 5. The product with naturally occurring EPO promoter viral DNA. promoter DNA At issue characteristics. certain a production of process A for 6. (with 1, 2, and 9 claims lawsuit polypeptide erythropoietin glycosylated un below here and claim terms disputed of biological property having the vivo derscored): cells to increase causing bone marrow occurring erythro- non-naturally A1. reticulocytes and red blood production having the glycoprotein product poietin steps of: comprising cells causing activity of bone biological in vivo production a) marrow cells increase suitable nutrient growing, under cells and blood reticulocytes red conditions, comprising cells vertebrate glycosylation which having encoding differs from the mature amplified DNA urinary erythropoietin. human that of sequence amino acid erythropoietin occurring EPO non-naturally 2. The 6; and FIG. according to claim product glycoprotein b) glycosylated erythro- isolating said higher has a product 1 wherein said by said expressed poietin polypeptide urinary weight molecular than cells. measured SDS-PAGE. EPO as claim 6 wherein said process The 7. com- composition A pharmaceutical 9. ampli- comprise further vertebrate cells glyco- amount of a an effective prising DNA. gene fied marker erythro- for product effective protein claim 7 wherein said process The 8. 1, 2, to claim therapy according poietin Dihydro- gene DNA is amplified marker 4, 5, pharmaceutically a or 6 and (DHFR) gene DNA. folate reductase diluent, carrier. adjuvant or acceptable 2, 4 according to claims process 9. The 8, 1997, April on issued mammalian cells are and 6 wherein said process to a nine drawn containing claims cells. erythropoiet- producing glycosylated patent, which issued seven At are claims 4-9: The '080 polypeptide. issue claims April both production 4. A for the process glycoprotein erythropoietin polypeptide isolated erythropoietin glycosylated noted. specification unless otherwise patents an identi- in suit share 3. Because disclosure, all will be to the '933 cal citations *10 method therapeutically administering for in culture are capable of producing in pharmaceutical composition Only thereof. the medium of their growth in excess of product 2-4 claims are issue: erythropoietin U of per 106 cells in
2. An isolated erythropoietin glycopro- hours as by determined radioimmu- having tein the in vivo biological activity noassay causing
of bone marrow cells to increase 6. Vertebrate cells according to claim 4 production reticulocytes and red blood capable of producing excess of 1000 U cells, erythropoietin wherein said glyco- erythropoietin per 106 cells in 48 hours. protein comprises erythro- the mature 7. A process for producing erythro- poietin sequence amino acid FIG. 6 poietin comprising the step of culturing, and is not isolated from human urine. under conditions, suitable nutrient verte- 3. A non-naturally occurring erythro- 1, 2, 3, brate cells according 4, 5, to claim poietin glycoprotein having vivo or 6. biological activity of causing bone mar- Last, '422 patent, containing two row production cells to increase of reti- claims directed to therapeutically effective culocytes cells, and red blood wherein pharmaceutical EPO, compositions of said erythropoietin glycoprotein com- granted September 1999. Only prises the erythropoietin mature amino claim 1 is in dispute: sequence acid FIG. 6. A pharmaceutical 1. composition com- pharmaceutical A composition com- prising therapeutically effective prising therapeutically effective amount of human erythropoietin and a amount of an erythropoietin glycopro- pharmaceutically diluent, acceptable ad- tein product according or 3. juvant carrier, wherein erythro- said patent, The '349 May which issued on poietin purified mammalian 1998, contains one method claim and six grown cells in culture. product claims that are drawn generally to The district court conducted the Mark types of grown vertebrate cells in culture. man hearing late March early April 1, 3-4, At issue are claims and 6-7: Amgen’s advance of motion for 1. Vertebrate cells which can propa- be summary judgment of infringement. The gated in vitro and which capable argument, entertained oral aided upon growth in producing culture of er- exhibits, demonstrative but heard no wit ythropoietin in the medium of their testimony ness and received no evidence. growth in excess of 100 U of erythro- F.Supp.2d poietin per 106 cells in 48 hours as at 1455. At the close of the hearing, the determined radioimmunoassay, said court announced its claim constructions comprising cells non-human DNA se- bench; from the these oral rulings were quences that control transcription expounded included and upon in the writ DNA encoding erythropoietin. opinion ten ruling on following the merits 3. Vertebrate according cells to claim 1 84-94, trial. Id. at at 1457-64. capable producing in excess of 1000 U
erythropoietin per Immediately 106 cells in 48 following hours. the Markman hearing, the court Amgen’s turned to 4. Vertebrate cells can propa- which be pending gated summary motion for judgment vitro which comprise transcrip- infringement tion control DNA of '422 sequences, patent claim 1 other than human erythropoietin 3-4, '349 transcription con- and 6. As to the sequences, (1) trol production patent, of human the district court found: erythropoietin, and which upon growth that it was uncontradicted that the accused
1324
v.
infringed. Markman
West
allegedly
HMR4396,
pharmaceutical
was a
product,
967, 976,
Instr.,
Inc.,
34
F.3d
con-
52
(2)
necessarily
it
view
composition;
(Fed.Cir.1995),
1321,
aff'd,
amount
1326
effective
therapeutically
tained a
(otherwise,
1384,
134 L.Ed.2d
116 S.Ct.
erythropoietin
517 U.S.
of human
(1996).
properly
and
pointless);
577, USPQ2d
be
To
an INDA would
1461
filing of
38
(3)
claims,
demonstrated
record evidence
must examine
that the
court
construe the
pharmaceuti-
contained
claims,
specification,
that HMR4396
the rest
diluent, adjuvant, or carri-
cally acceptable
evidence,
history.
and,
prosecution
if in
94-95,
at
57
Inc.,
in claim Id.
claimed
er as
Conceptronic,
Corp. v.
Vitronics
remaining
USPQ2d at 1455-56. The sole
1576, 1582, USPQ2d
1576-77
F.3d
erythro-
the accused
whether
question
Thereafter,
(Fed.Cir.1996).
properly
had been “purified
poietin product
ac
to the
compared
are
construed claims
in
grown
cells
culture.”
mammalian
to
process
or
determine
product
cused
found,
construc-
light
of its claim
court
of the claim limitations
each
whether
comprises
term “mammalian”
that the
tion
met,
literally
equivalently.
CCS
either
cells,
had
the last limitation
Fitness,
Corp.,
v. Brunswick
Inc.
95-96,
USPQ2d at
Id. at
met.
been
(Fed.
1359, 1365, USPQ2d
sum-
court therefore granted
1466. The
Cir.2002).
infringement
mary judgment
dispute
general
two
areas
There are
claim 1.
district court’s
regarding the
TKT raises
15, 2000.
May
commenced
Trial
First, TKT
urges
claim construction.
its
at
close of
Amgen rested
When
failing to limit the
by
erred
the court
case,
granted
infringement
DNA, de
exogenous
to
asserted claims
judgment of non-in-
TKT’s motions
that none of the claims
the fact
spite
and literal
of the '698
fringement
limita
“exogenous DNA”
an
suit contain
patent.
Id.
of the '080
non-infringement
Second, TKT
that the court
tion.
asserts
99-104,
At
USPQ2d at 1469-73.
“ver
refusing to limit the terms
by
erred
case, the court
of TKT’s rebuttal
close
“mammalian,”
tebrate,”
“non-naturally
judgment of
Amgen’s motion for
granted
vary
appear
which
occurring”
—each
not carried
finding that
validity,
had
within the asserted claims—
ing degrees
convincingly
clearly and
burden of
cells
they exclude host human
such that
Id.
anticipation or obviousness.
proving
which,
course,
are used
the accused
104-17,
USPQ2d at 1473-82. The
the trial court’s
infringers. We consider
under advise-
remaining issues were taken
matter of law—
claim construction —a
opinion
court’s
on Janu-
ment. The
issued
Cybor
review. See
appellate
afresh on
timely cross-ap-
and these
ary
Techs., Inc.,
v.
Corp.
FAS
jurisdiction
peals followed. Vested
(Fed.Cir.
1295(a)(1),
we address
under 28 U.S.C.
1998) (en banc).
myriad issues
us.
before
below
A
DISCUSSION
a thresh
turn first to address
We
I
carries with it
dispute that
old definitional
infringe
consequences for
important
known. Be-
now well
The rules
by the district court
decided
ment issues
scope,
language
cause claim
defines
wit,
is the
appeal,
us on
what
facing
infringement analysis
step
first
exogenous,
opposed
claims, i.e.,
between
distinction
determine
to construe
endogenous, DNA recombinant
which is
scope
meaning
of that
*12
TKT,
parlance? According to
it practices
ticular
or phrases
words
in the claim.”
(citation
process using
omitted)).
an innovative
homologous
The danger of improp
it
ordinarily
recombination:
takes
the
erly importing a limitation
greater
is even
(or “native”)
unexpressed
endogenous
purported
when the
limitation is based
gene
EPO
in human cells and
“a
transfects
upon a term
appearing
in the claim.
promoter
viral
certain
other DNA”
“If we
begin
once
to include elements not
that does not encode EPO. That “other” mentioned in the claim in order to limit
DNA is inserted into the chromosome at a
...,
such claim
we should never know
pre-determined,
targeted
location up-
stop.”
where to
Johnson Worldwide As
from
endogenous
stream
the
gene
to
socs.,
Inc. v. Zebco Corp., 175 F.3d
produce what TKT has termed “Gene-
990, USPQ2d 1607,
(Fed.Cir.1999)
EPO,”
Activated
or “GA-EPO.” TKT (quoting McCarty
R.R.,
Lehigh
v.
Val.
contrasts this method with that Amgen,
110, 116,
U.S.
16 S.Ct.
“It is the claims that measure the foreign organism. the host See id. col. invention.” SRI Int’l v. Matsushita Elec. (“[T]he 2, lines 41-47 Cohen et al. Corp., USPQ first (Fed.Cir.1985) (en banc). involve[s] of a transfor- manufacture Because mation vector enzymatically cleaving the claims are best understood light viral or circular plasmid DNA specification to form they of which a part, are however, linear DNA foreign strands. Selected courts must take extreme care (‘exogenous’ or ‘heterologous’) ascertaining proper when DNA scope claims, usually including strands they sequences coding lest simultaneously import for product prepared into desired limitations that were unin linear See, by the form patentee. through enzymes.”). tended use of similar e.g., Hoga Indus., Inc., AB v. 948, During prosecution nas Dresser Serial No. (Fed.Cir.1993) USPQ2d 1936, 08/468,369, which patent, became (“It improper for a court to add the examiner applica- extrane commented that the claim, ous limitations to a that is limita tion only “teaches enables that cells added wholly apart any tions have need been transformed exogenous interpret what the patentee par- (EPO) meant by DNA erythropoietin that encodes 4. That is not to say there are no claims sion in exoge- a mammalian host cell of an that have such a limitation. Unasserted sequence nous comprising DNA a DNA se- patent, example, claim 3 of the '933 does quence encoding erythropoietin contain such a non-naturally "A limitation: col. lines 26-29. occurring glycoprotein product expres- the invention is The statement production re- high EPO have the expression characterized” “uniquely asserts, as a the claims.”
quired by im- does not sequences exogenous pro- result, product GA-EPO when the position TKT’s pel accept us to the asserted scope of cess fall outside *13 contain such claims do not asserted has repeatedly Amgen because fact, position TKT’s express limitation. products claimed its characterized of claim by the doctrine is undermined exoge- the use of requiring as processes differentiation, to other claims as reference DNA, the claims and hence nous EPO in- did not clearly indicates limited thereto. should be the use of limit the invention to tend to of claim con- principles our Guided claim 3 of the DNA. Unasserted exogenous court struction, with the district agree virtually we identi- example, patent, import limita- 1, express seeks improperly that TKT claim save for cal to claims. “exogenous limitation into the the use of regarding tion “exogenous” (underlined indicating dif- portioned claims controls DNA” plain meaning ferences). limited. here, are not so they plainly presumption There is a rebuttable ry.”). clear that court has made Our not contain scope. claim “does claims are of different when that different does, Co., another claim Foods, certain limitation and Trading Inc. v. Int’l See Kraft cannot be read into the limitation 1814, 1366-67, 1362, 203 F.3d validity determining either former claim (Fed.Cir.2000); Desic Multiform Int’l, 775 F.2d at SRI infringement.” Medzam, Ltd., cants, Inc. v. 133 F.3d 586; USPQ Corp. see also O.I. (Fed.Cir. 1479-80, USPQ2d Co., Inc., v. Tekmar 1998). (ex (Fed.Cir.1997) prose- The examiner’s statement practical that there are pressing the notion pause, no history gives cution us of claim differentia limits to the doctrine rejection was not because for his basis cannot alter a definition tion: “the doctrine DNA was exogenous transformation claim lan clear from the is otherwise high “the EPO taught, but because histo- guage, description, prosecution ” production required by the claims” was encoding erythropoietin.... By (“The not. See J.A. at 1302 appli- terms, then, instant this claim would cover the guide cation does not one ordinary skill expression of human DNA in a cat host in the art in discovery of non-trans- cell, for example, because a cat is a mam- formed vertebrate cells that capable of mal. The thus concluded that the high production EPO recited phrase “non-naturally occurring” would be claims, instant [as demonstrated redundant in claim 3 if the phrase had the reference,] of which each discloses levels of meaning TKT sought to ascribe to it. production by cells in cul- vertebrate Further, because specification ture are far below levels re- those compares biological activity synthet- *14 claims.”). in quired the instant po- TKT’s products ic to “EPO isolates from natural sition is further undermined because the isolates,” sources” “natural EPO the asserted claims issued. presume We must court concluded that non-naturally occur- job, the examiner did his if truly he and ring simply means “not in occurring na- thought specification that the taught or ture.” F.Supp.2d 90-91, 126 at 57 only enabled DNA, the use of exogenous USPQ2d at 1462-63. the asserted claims would not have issued. Similarly, finding that the term verte- end, In the TKT has not directed our is widely brate known and understood to attention to in anything the intrinsic rec- anything cover segmented with “a bony or ord that presumption rebuts the that the cartilaginous spinal cord obviously [which plain meaning the terms controls. Ac- humans],” 85, includes USPQ2d id. at 57 cordingly, we conclude that scope the of 1457-58, the court adopted Amgen’s pro- the asserted claims should be limited not posed construction. court also expression to the exogenous DNA. adopted Amgen’s proposed construction of the term “mammalian cells” in appearing B '422 patent claim and '698 claim 9 asserts, TKT addition the ex 84-86, under a similar rationale. Id. at ogenous/endogenous distinction discussed USPQ2d at 1458. above, that the district court misconstrued the “non-naturally indulge terms We occurring,” heavy presumption “ver cells,” tebrate and “mammalian a claim cells”— that term carries ordinary appear which in many of asserted customary Fitness, the meaning. CCS claims—to include human 1366, cells. Reviving 1662; F.3d at see also the same argument the district court re Inc., Logitech, 1334, v. 1341, Gart below, jected TKT Amgen contends ex USPQ2d 1290, (Fed.Cir.2001). Al pressly disavowed the use of human cells though TKT is correct that the prosecution to make human EPO. history is always relevant to claim con struction, it is also true that piosecu the
The district court found the defini- that history tion not may be used infer the tion of the “non-naturally term occurring” intentional narrowing of a claim absent can through be discerned the doctrine of applicant’s clear claim disavowal of claim cover Specifically, differentiation. age, such as an amendment to overcome proffered concluded TKT’s con- rejection. Prods., struction fail See light must York Inc. v. of '933 Central Ctr., Tractor Farm previously, which & Fam. discussed claims (Fed.Cir. a “non-naturally occurring glycoprotein 1996). product of expression in a No mammalian such clear disavowal occurred host cell of exogenous an sequence here. scope narrow the by Amgen to specifica- agree
We experi- light of certain a sub- asserted describes humans expressly tion turn, mammals, particular, advances mammals, as mental data. set of Amgen intentionally re- theory whereby patent, See '933 of vertebrates. a subset ap- 47-48; subsequent language line 21. More- col. moved lines col. to, because test results over, fairly (allegedly) be read specification plications can human later good, not disclose use cells were expressly, using if not opposition proceeding human host cells culture: (during DNA in admitted patent) counterpart European ex- against comprehended Conspicuously not of ho- omission was inadvertent. involving vectors systems pression variety benign applied to a contains a origins But the record more mogeneous bacterial, cells yeast, happened. and mammalian Accord- explanation as to what sys- Lin, well as to expression testimony in culture as of Dr. he was ing to In this involving vectors.... of, not did autho- tems and therefore unaware ex- be regard, it will understood Further, rize, prosecuting change. origin DNA in of, e.g., monkey pression that to attorney deposition in his testified and human monkey host cells in culture *15 the error was knowledge of his the best culture, actually constitute cells in host error. typographical expres- DNA ‘exogenous’ instances of that the error assuming even But DNA whose the EPO inasmuch as sion intentional, the district court’s would sought high expression level not our construction would be foreclosed: origins genome in the the have its per that claims are not precedent is clear host. to the embodiments disclosed force limited (emphasis lines 33-43 ’933 col. patent, E.g., Corp. Rexnord specification. in the added). astute reader will observe The 1336, 1344, 60 Corp., 274 F.3d v. Laitram in the to be a breakdown appears what (“[A]n (Fed.Cir.2001) in emphasized of the sentence parallelism in to the applicant required is not describe above. the quote Specifically, the block every possi conceivable and specification “monkey expression to the reference invention.”). of his ble embodiment future monkey in host in culture origin DNA cells Here, the use patent plainly discloses in host cells culture” seems and human culture, cells in and our of human host expression bit because nonsensical “clear the record indicates no review of DNA in human host cells is monkey origin to undercut the ex disavowal” sufficient expression exogenous perforce the specification. in the press disclosure from application original DNA. The result, are satisfied that As a we in priority, all the suit claim patents which occurring,” “verte- “non-naturally terms contrast, up- that by language contained brate,” be con- “mammalian” should of the parallelism holds the sentence court, read, they by were the district perti- in strued as makes sense. It logically plain that in a manner consistent with their part: will be understood “[I]t nent of, monkey origin reject DNA in we TKT’s expression e.g., meaning. Accordingly, monkey cells in culture and human scope host limit the of the asserted attempt to in consti- DNA in human host cells culture unduly constricted read- claims under expres- ‘exogenous’ tute instances ing specification. added). (emphasis
sion.” J.A. at 2862 C that boldly asserts the variance TKT issue final claim construction and the original application between aimed at the district court’s act TKT raises is bespeaks in suit some volitional patents alleged pro- patent, failure to discern “source and the '080 “non-naturally occur '080, '349, limitations in claims of the cess” ring” limitation claims 4 merely 3 and TKT, '422 patents. According prevents Amgen claiming the human by concluding trial court erred that produced the natural By course. claims, i.e., product asserted claims are limiting its way Amgen claims this sim they are directed to a structural enti- ply claiming specific subject avoids matter ty that is not defined or limited how it that would be unpatentable under summarily is made. states this This has endorsed approach, because, holding must be erroneous it as- recognizing patentees can nega use serts, patentability of the claims de- tive limitations such as “non-human” and tried, pended process “Amgen on the since “non-natural” rejection to avoid under failed, but distinguish prior rEPO from § 101. See Animal Legal Fund v. Def. art physical EPOs based on differences.” 920, 923, 18 Quigg, 932 USPQ2d 1677, agree. do not We (Fed.Cir.1991). The district court ar It telling that neither in the conclusion, at rived a similar Amgen, 126 briefing argument nor at oral did TKT F.Supp.2d 1462-63, any specific direct us to statement and TKT has not any demonstrated error prosecution history support the conten in that conclusion. Similarly, the “not iso tion that patentability of the product lated from human urine” limitation in depended upon process claims suit claims and 4 of the '080 simply products which those are obtained. requires EPO, the claimed however fact, original of at least one of made, be obtained from a source other *16 (the the patents patent) '080 were drafted than human urine. Each of these limita claims, as product-by-process which claims only tions excludes EPO from spe replaced “pure” were cancelled and cific sources and does not restrict product This strong claims. is evidence produced that claimed EPO to that patentee any both the and the examiner from viewed the that ultimately claims issued as particular by any particular source lacking process component. See Van sum, 2, 3, method. In 4 and of the guard Corp. Prods. v. Parker broadly remain drawn to the Hannifin 1370, 1372, Corp., 234 USPQ2d F.3d 57 “erythropoietin described glycoprotein” or (Fed.Cir.2000) (“Parker 1087, 1089 Hanni “pharmaceutical composition” produced by fin argues prosecution that history method, any source, any or obtained from Vanguard shows that the inventors viewed specifically other than those excluded. co-extrusion as ‘fundamental’ to manufac '422 patent, As to the ture limitation gasket, of the claimed thereby impos ing process upon “purified of manufacture from mammalian grown cells However, product claims.... review of the clearly culture” in claim 1 limits the source prosecution history that during shows ex of the “pharma EPO used the claimed amination the examiner as well as the ap composition.” ceutical The only limitation plicant product treated the claims as di speaks to the source of the EPO and does itself, rected to the product and examined process not limit which the EPO is application accordingly.”). Rather, expressed. broadly the claim is drawn to a “pharmaceutical composition” event, any we are not con elements, having being certain one of those vinced the source limitations in the “purified from mammalian cells in asserted claims convert the claims into anything than product other claims. As reading culture.” This is in line with the
1330 and, reproduction quately and enable again, construction court’s district Mahurkar, v. 935 Vas-Cath Inc. us to no error.5 use. See TKT directs 1563, 1111, 1555, USPQ2d 1117 19 F.2d II (Fed.Cir.1991). Third, though not in issue here, con that claims are he must disclose what he considers It axiomatic is invalidity way for both practicing the same mode of his invention. strued the best Assoc., & W.L. Gore infringement. A Garlock, Inc., 6 842 Inc. v. (Fed.Cir.1988). 1277, But USPQ2d 1280 de purpose of the written prod of the accused the features because ap scription requirement prevent is to undisputed, this are often process uct or asserting later that he invent plicant in the approach a common axiom invites not; applicant ed that which he did infringers: by accused appellate arguments required therefore to “recount is challenges the cor principal argument future his invention such detail his trial broad con rectness of a court’s claims can be determined to be encom struction; argument, as contingent passed original within his creation.” Id. claim construction suming the trial court’s 1561, 1555, USPQ2d 1115 935 F.2d affirmed, validity under 35 challenges omitted). (citation of this re Satisfaction ¶ patents asserted of the U.S.C. quirement is measured the understand See, e.g., light of that broad construction. ing ordinarily skilled artisan. Lock Medtronic, Sys. v. Adv. Cardiovascular Airlines, Inc., wood v. Am. 107 F.3d (Fed. Inc., USPQ2d 1161 265 F.3d (Fed.Cir. Cir.2001); Indus. v. Guardian Indus. PPG 1997) (“The description clearly must allow Corp., 75 F.3d ordinary skill in the art persons (Fed.Cir.1996); Kimberly- v. Kalman what recognize inventor] invented [the USPQ Corp., Clark claimed.”). “Compliance with the writ (Fed.Cir.1983). ap employs essentially description requirement is ten it appro We therefore think proach here. ‘necessarily inquiry fact-based that will § 112 the relevant issues priate address vary depending on the nature of the inven *17 infringe of turning before to the issue ” tion claimed.’ Enzo Biochem v. Gen- ment. Probe, Inc., 1316, 1324, 296 F.3d 63 patent 112 of the statute Section (Fed.Cir.2002) (cita 1609, USPQ2d 1613 must be contained in the describes what omitted). tion Because of its fact intensive specification. Among things, other nature, deci we review district court’s description “a it must contain written adequacy description sion on the of written invention, pro and of the manner and the for clear error. Purdue Pharma L.P. v. it ... making using [such] cess of and as Inc., Faulding 230 F.3d 56 any ordinary person to enable skill (Fed.Cir.2000) (cita 1481, USPQ2d 1483 pertains art which it ... to make the to omitted). tions the 35 112 and use same....” U.S.C. addressing description ¶ In TKT’s written Thus, statutory language this man arguments, carefully the district court ex- inde separate dates satisfaction of two and Amgen’s specification amined ade- whether applicant must pendent requirements: the full breadth of the quately both describe the claimed invention ade- described obtained, lack which the EPO is the 5. We do not hold that these limitations only they just they meaning, mean what produced. method which it is Accordingly, they only say. the source limit end, invention, In polypeptides claims. the the district court re of the Amgen iden jected description challenge, TKT’s written tified exogenous EPO DNA as an essential only that TKT had finding proven its ease element of the invention. As a result of preponderance of the evidence—not TKT, these shortcomings, argues it has clear and standard convincing required clearly and convincingly proven invalidity as a matter of law. Acknowledging the under Regents the University Cali presence genuine of “a dispute between Co., Lilly 1559, v. Eli & 119 F.3d fornia witnesses,” expert weighed the court USPQ2d (Fed.Cir.1997), Gentry testimony and found that the evidence Gallery, Inc. Corp., v. Berkline 134 F.3d descriptions showed that adequately 1473, USPQ2d (Fed.Cir.1998), ordinary described to those of skill Biochem, Gen-Probe, Inc., Enzo Inc. v. art in 1984 the of the use broad class of 1316, (Fed.Cir. USPQ2d 296 F.3d available mammalian and vertebrate cells 2002). persuaded We are not that these produce high the claimed levels of hu precedents mandate reversal of the trial man culture. findings court’s factual clearly errone 149, F.Supp.2d at 1507. In regarding ous descriptions. written doing, so the court credited in particular First, in addressing adequacy testimony Amgen’s expert, Dr. Har description written '422 patent Lodish, testified, vey among who other respect exogenous TKT’s things, might that there be “minor differ arguments, the district court noted: in applying ences” the method of the dis When the claim is to a composition rath examples (utilizing closed CHO and COS-1 er process, than a descrip the written cells) (monkey) any vertebrate or mam tion requirement does not demand that cells, malian but that those of ordinary specification technological describe “easily” figure skill could out those differ developments in way in which the Id., methodology. ences in 126 F.Supp.2d claimed composition may is made that 69, USPQ2d at 1507. arise after the application is filed. Much of argument appeal TKT’s See United Corp. Phillips States Steel v. challenging finding dovetails with its Co., Petroleum 865 F.2d 1251 [9 arguments claim construction we have al- (Fed.Cir.1989); 1465] ready found lacking. example, For Roller, re 613 F.2d [204 824-25 asserts that Amgen patents do not USPQ (C.C.P.A.1980); see 707] also satisfy the description requirement written Hogan, In re 606 [194 (1) Amgen because: sufficiently failed to (C.C.P.A.1977). USPQ In 538] describe the use of all vertebrate *18 stead, only section 112 requires the (2) cells; mammalian Amgen deleted use Court to determine specifi whether the exogenous of human EPO DNA in human conveys cation to ordinary one of skill in (3) applications;6 cells from its Amgen the art as of 1984 that Dr. Lin invented expressly endogenous excluded the use of (4) DNA; subject the matter in pat claimed the Amgen EPO emphasized that Reiffin, 214 advantage the of ents-in-suit. F.3d at 1346 its invention was “free- dom from v. 214 Corp., association with human pro- [Reiffin Microsoft (5) teins”; (Fed. 1342, 1346, using USPQ2d the “uniquely 54 1917 Cir.2000) language characterized” to describe the The written in- description ]. point 6. We scope addressed this in our claim con- human cells from the of the claims. ante, analysis pages finding struction 1328 analysis That suffices here as well. description that the written did not exclude necessarily fail as a mat- therefore, material compari- genetic on a focuses quiry, and the specification description the the written between ter of law to meet son of the by the terms invention referenced rather, requirement may requirement; between how comparison claim—not if of the art knowledge in the be satisfied disclosed was made as product sufficiently corre- the disclosed function is developments of this and future structure. particular, lated to a known improve might alter or even process that Biochem, 296 F.3d at See Enzo made. product is how the same Lilly Eli USPQ2d at 1613. Both 150, USPQ2d at Amgen, F.Supp.2d inapposite to this case Enzo Biochem 1508; USPQ2d at id. at at see also at here are because the terms issue patent), at 154 n. (discussing materials biological not new or unknown 51, USPQ2d (discussing the '349 at 1510 easily ordinarily skilled artisans would con- court therefore patent). The district Instead, of the claims miscomprehend.7 exogenous arguments DNA sidered TKT’s Amgen’s patents types refer to of cells above, and, rejected stated for the reasons recombinant produce that can be used to argued TKT appeal them. has On Thus, only human EPO. can chal- analysis erroneous. Because legal its of lenge adequacy disclosure any case law we have not been directed or mammalian host cell—not vertebrate contrary, we conclude the district to the DNA itself. This difference the human Phillips based on legal court’s conclusion distinguishes Lilly, Eli sufficiently alone and that it was not erroneous Petroleum here, used, merely as because when exogenous DNA is- handled the properly (instead identify types of cells of unde- sue. scribed, previously unknown DNA se- argu move now to TKT’s We quences), the words “vertebrate” sufficiently failed to de ment that readily “eonvey[ “mammalian” distin- ] and mammalian cells scribe all vertebrate guishing concerning information [their] engineered in the claimed invention. ordinary identity” such that one of skill Lilly adequate in Eli We held recognize art or could “visualize requires DNA description of claimed identity genus.” of the members of precise sequence definition of the Lilly, Eli func merely a recitation itself—not Indeed, at 1406.8 the district potential tion or a reference to a method speci- court’s reasoned conclusion 1566-67, it. 119 F.3d at isolating description producing fication’s (holding at 1406 the disclosure species claimed EPO two vertebrate gene of the insulin sequence the cDNA adequately supports mammalian cells adequately a rat did not describe the covering using ge- made ev gene cDNA of the insulin sequence cells, or mammalian ren- vertebrate). nus vertebrate recently, in ery More Enzo Lilly Eli Biochem, ders listless this ease. Lilly that Eli did we clarified 149, USPQ2d descriptions F.Supp.2d functional of 126 at 1507. not hold that all Indeed, Amgen’s patents appear satisfy 8. in haec There is no issue here as to verba because, description body *19 as stated in the requirement Lilly sequence in Eli insofar opinion, in contrast to “cDNA”—that Figure patents expressly of the discloses as 6 clearly sequence does not describe the actual (albeit incorrect) complete slightly se- of the cDNA—the words "mammalian cells” genomic quence EPO DNA and the of human convey exactly and "vertebrate cells” what encoded DNA. Thus, they aspect holding are. of the in Lilly inapplicable Eli is also here.
1333 remaining arguments rely TKT’s sofa to independent have two reclining However, Gentry Gallery. we see Gen seats face in the same direction (solving a Gallery similarly inapt. TKT try would art). problem present in prior 134 case, Gentry us have view as watershed at USPQ2d F.3d 45 at 1499. The in on an prob reliance isolated undisclosed element leading to the Gentry statement — ably only dicta—that of ordinary one skill holding court’s of invalidity for lack of an clearly in the art would understand that adequate description was a location for the location reclining of the controls on the controls other than on the console—lead- claimed only impor sectional sofa “was not ing to a different and product. undescribed tant, but essential to invention.” [the] 134 See id. at 45 at 1502-03. 1480, USPQ2d F.3d at 45 at 1503. But as Amgen’s invention is not the location of recently Cooper we indicated in Cameron sequences the control and EPO in Prods., Inc., Corp. v. Kvaerner 291 Oilfield cell, relation to the produc- but rather the 1317, 1323, USPQ2d 1846, 62 1850-51 tion of human using those sequences. (Fed.Cir.2002), “we did not [in announce Thus, the undisclosed element TKT urges Gentry a new ] ‘essential element’ test Amgen’s invalidates product claims is a mandating inquiry an into an what inven activation) different (endogenous method tor considers to be essential to his inven of making But, the claimed compositions. tion and requiring incorpo that the claims noted, as the district court under our pre- Vas-Cath, rate those elements.” See also cedent the patentee only need describe the 1565, USPQ2d 1114; F.2d at 935 19 at cf. claimed, invention as and need not de Mfg. Aro v. Top Replace Co. Convertible an scribe unclaimed method making Co., ment U.S. 81 S.Ct. product. Amgen, claimed 126 F.Supp.2d (1961) (“[T]here L.Ed.2d 592 legally is no 150, USPQ2d at (citing at 1507 Phillips recognizable or protected ‘essential ele Petroleum, 1251, USPQ2d 865 F.2d at at ment,’ ‘gist’ or ‘heart’ of the invention in a 1465; Koller, 824-25, In re 613 F.2d at patent.”). combination in this Understood 707); USPQ Vas-Cath, at see also light, one holding Gentry sees the 1563-64, 19 USPQ2d F.2d at at 1117. This really what it application was: an of the factual difference alone is sufficient to dis principle settled that a broadly drafted tinguish Gentry. this case from fully claim must supported be the writ Second, the statements patentee description drawings. ten See Cooper Cameron, the written description this case fall 291 F.3d at short of what Gentry prohibits. 1850-51. After considering extensive tes timony Gentry parties, both the district court concluded that the inventor had held this principle clearly expressed met and TKT failed to descrip- the written analysis clearly demonstrate that this tion that he considered his invention to be factually erroneous based on error of limited to specific location of the con- 149-50, F.Supp.2d (“the law. only trols on the console on the sofa USPQ2d at 1507-08. location”) possible any and that variation purpose was “outside the stated
To the extent particular facts of Gentry invention.” Gallery, 134 F.3d at relevant, Gentry are we also find it distin- 1479, USPQ2d Indeed, at 1503. in Gen- First, guishable. there is fundamental try only the inventor testified that he con- Amgen’s difference between in- patented locating sidered the controls outside of the vention in Gentry. and the invention only applica- console'—and broadened his Gentry the invention placement was the reclining tion accordingly' seeing controls on a central console on a Gen- —-after unit of a try’s sectional sofa so as to competitors products allow introduce *20 Here, specifica The description requirement. Id. off the console. located
controls sure, statements that in the Amgen explicitly made tion need not teach those to be by invention; characterized” “uniquely its invention make and the the art use of DNA. '933 expression exogenous if, they requirement given is satisfied what considered col. 15-20. When lines know, teaches already specification context, however, do not these statements they art that can make enough those Gentry. conclusion as lead to the same without “undue ex and use the invention clearly not simply do Amgen’s statements Genentech, Inc. v. Novo perimentation.” exogenous expression is indicate that Nordisk, A/S, 1361, 1365, 42 108 F.3d or that mode of the invention only possible (Fed.Cir.1997); USPQ2d In re were outside the stated methods other Vaeck, 488, 495, USPQ2d 1438, 947 F.2d Instead, Amgen the invention. purpose of (Fed.Cir.1991). Before district of its writ- background section begins the court, clearly TKT the burden of bore stating present by “[t]he description ten convincingly proving showing facts generally manipu- relates to the invention E.g., the claims were not enabled. Enzo and, par- more genetic lation of materials Biochem, Inc., Calgene, Inc. v. 188 F.3d ticularly, procedures to recombinant mak- (Fed. 1362, 1375, USPQ2d polypeptides ing possible production Cir.1999). question Enablement is a possessing part primary or all of struc- law; we therefore review the trial court’s one or more of tural conformation and/or novo, deferring to its as determination de naturally occur- biological properties underlying of subsidiary sessment facts Patent, col. ring erythropoietin.” clearly legal question unless erroneous. this lack of clear lines 18-23. Because of Hirose, Bruning v. limiting the patentee statements (Fed.Cir.1998). 1934, 1939 (and light of the case claimed invention discussed, ante), cannot invalidate law we TKT contends that the asserted failure a method of patent for to describe claims are invalid for lack of enablement. producing compositions the claimed that is Taking position virtually mirrors the patentee not claimed. Nor could the itself (and claim description written construc method, the other as it was have described tion) rejected, TKT arguments previously developed years until 10 later. We see posits specifications do not enable in this re- Gentry Gallery inapplicable ordinarily practice skilled artisan to gard. light evidentiary record full scope of the asserted claims without inability persuade us that TKT’s experimentation they undue because fail to result, precedent requires contrary we production using describe the hu finding hold that district court’s endogenous man cells or human EPO Amgen description the written re- satisfied bottom, complains DNA. At that the quirement clearly erroneous. is not failing findings court erred to follow its logical to their conclusion.9
B But the district court made requirement enablement indulgent thorough complete findings than the factual is often more written light state- it 9. TKT refers here to the district court's stand of how close the court viewed reflection, appears ment that "it that Dr. Lin claimed far the issue: "After much the court he delivered." more than finds that survives [the enablement F.Supp.2d at at 1514. Al- challenge], barely.” albeit Id. at though this statement does seem out of kilter USPQ2d at 1513. holding, we with the court’s ultimate under-
1335
holding
the claims
supporting
the district court’s conclusions in this
enabled,
not
not
.proven
expressly
were
regard were erroneous.
incorporating many of its factual deter-
Focusing specifically on the '422
respect
minations made with
to written
patent, the
inquiry
enablement
is whether
description.
endoge-
As
to TKT’s
Amgen has
pharmaceutical
enabled all
nous/exogenous
arguments,
court
compositions comprising “a therapeutically
arguments
inapplica-
concluded the
were
effective amount of human erythropoietin,”
ble as a matter of law for two reasons.
diluent,
“a pharmaceutically acceptable
ad
First, “where the method is immaterial
juvant
carrier,”
erythro
and human
claim,
to the
the enablement
inquiry
poietin “purified from mammalian cells
simply
require
specification
does not
grown in culture.” The court found that
technological
to describe
developments
specification
described and enabled
concerning
the method
which a paU
various possible diluents and carriers and
composition
may
ented
is made that
provided specific information on effective
arise
after
the patent
application is
dosages and therapeutic effect in mice.
160,
Amgen,
F.Supp.2d
filed.”
at
126
57
148, USPQ2d
Id. at
57
at
Amgen
USPQ2d
(citing Phillips
at 1515
Petrole
also described and enabled at least one
um,
1251,
USPQ2d
1998); produc- enabled the Engel Indus. Inc. v. Lockformer tion of all Co., glycoproteins having “the USPQ2d F.2d in vivo (Fed.Cir.1991)); biological activity causing bone see also Du production marrow cells to increase Corp. Inc., rel of reti- Sylvania v. Osram cells,” culocytes and red blood “the mature (Fed.Cir.2001). erythropoietin sequence amino acid This again conclusion 6,” FIG. hu- specification’s “[are] makes the isolated from failure to dis endogenous “non-naturally close TKT’s man urine” or occurring.” activation tech nology legally irrelevant. noted that disclosed F.Supp.2d biological in vivo upon at 1515. effect of EPO he- We reach the ap same conclusion on matocrit levels in adequately mice and dis- peal, as TKT persuaded has not us that sequence closed the of the amino acid resi- *22 that were USPQ2d types of cells specific at ed to Id. at 57 figure in 6.
dues and en- that other vertebrate example, described used in this Amgen also 1508-09. producing cells, cells, one method of have at least mammalian could been abled “non-naturally occur- Biochem, that was both used”); EPO F.3d at Enzo 188 cf. urine”: from human and “not isolated ring” 1367-68, 1372, USPQ2d 1136- 52 at and manipulation of CHO genetic nonenablement of claims (affirming 37 partic- noted with The court cells. COS-1 technology to all applied anti-sense witness, King- Dr. ularity that even TKT’s eukaryotic prokaryotic organisms and be- ston, ordinary that if one of skill agreed “highly unpredict- a cause anti-sense was teachings Example art followed “high quantity a technology” able and successfully a could person then such prac- would be needed to experimentation” invention. Id. at the claimed practice the disclosed tice invention outside of USPQ2d 1516. 57 at Vaeck, 495-96, F.2d at 20 example); product claims of address We USPQ2d (holding 1444-45 the examiner at detail, they in more differ rejecting as nonenabled did not err we patents from the discussed slightly all genetically-engineered claims drawn to genetically above. The '349 cyanobacteria expressing given protein a compo- “vertebrate cells”—a manipulated genera cyano- claimed 150 because the certain characteristics and having sition— vast, diverse, a and represent bacteria ability produce including properties, heterologous poorly group; understood of human EPO.10 The the claimed levels “un- expression cyanobacteria gene posed thus is this: question enablement predictable”; patent’s and the disclosure way one to make the having disclosed only genus). a The district referred to cell, Amgen en- EPO-producing claimed court found that a skilled artisan could “can claim all such cells that be titled to cultured verte- readily have used various vitro,” comprise “non-hu- propagated hu- produce brate and mammalian cells to tran- sequences man DNA control EPO, fact was man and this buttressed encoding hu- scription,” transcribe “DNA post-filing publications numerous erythropoietin,” produce man enabling demonstrated the extent of the prece- our claimed amount of EPO? While F.Supp.2d at disclosure. hold that disclosure of one or dent does Quigg, v. (citing at 1517 Gould genus, species may two not enable broad (Fed.Cir. 1074, USPQ2d Vaeck, 495-96, e.g., In re 1987) expert for the that an proposition 1444-45, USPQ2d at the district court publications to may rely post-filing on fact-findings indicating that made several enablement). The court also found show the disclosures and the any gaps between in the art it was a that for those skilled easily bridged. claim breadth could be relatively simple matter to determine See, e.g., Amgen, F.Supp.2d would work promoter whether certain (crediting Amgen’s expert at 1514 cell, within a vertebrate whether specific that “one of ordi- Dr. Lodish’s statement produce art, me, students, particular vertebrate cell would nary my skill in the culture, and whether a have understood this not to be limit- human EPO would gene Following EPO is inserted or activated— the dissent’s "machine” analo- man through genetically it be transformation with gy, the "machine” is a altered whether transcription exogenous through of an containing con- DNA or activation vertebrate cell endogenous gene not make this a dif- sequences used to transcribe a human trol —does built; rather, only it gene express claimed levels ferent "machine” once altering way changes way "constructed.” Simply the hu- it was human EPO. ty and relied on our case 'law operatively interpreting could be promoter particular transcription applying largely control the 112. We are limit- linked to summary, DNA. Id. deciding human EPO ed review to whether those Amgen’s to credit again court once chose findings testimony based on that are clear- Wall, witnesses, on the Drs. Lodish ly erroneous and we cannot so conclude. *23 issue of enablement: course, may, We review de novo the testimony interpretation of these wit-
Throughout precedent. the court’s of our nesses, apparent: any a theme becomes dissent, however, directly The does not ordinary challenge which one of skill challenge findings, court’s factual nor in at- might have encountered by does it mention the decisions relied tempting to make and use the claimed Instead, the district court. it finds fault in cultured mammali- using invention other prece- absence of discussion of other by experimen- an cells could be resolved dents, namely Lilly, Gentry Gallery, Eli falling tation short of undue. Vaeck, Mayhew, In re and In re 159, USPQ2d at 1515. Id. at arguments makes broader seemingly us, findings these factual before
With
upon policy
based
considerations.
by
prevail simply
reasserting
TKT cannot
The dissent would vacate and remand
conclusory
Amgen’s
manner
dis-
description
the written
issue because the
not enable the transformation
closure does
district court
precedents
did not cite our
of all mammalian or
cells or the
vertebrate
Lilly
Gentry Gallery.
Eli
According
The district
production of
EPO.
dissent,
to the
the district court “did not
issues,
carefully
considered these
applied”
focus on the correct law to be
in the
finding
end that
had not met
and,
reason,
for that
its “factual findings
convincing
proof.
its clear and
burden of
merit no deference.” It is difficult to see
clear
factual
Finding no
error
these
analysis
how the district court’s
must be
determinations,
having
been directed
rejected because it did not include discus-
by
no
committed
the trial
legal
error
or, per
sions of these two decisions
court,
holding
we will not disturb its
dissent,
principles they espouse.”
“the
patents
the asserted
are not invalid for
First, it is far from clear that the defen-
require-
failure to meet
the enablement
description
dant based its written
chal-
¶
§
ment of 112 1.
lenge
primarily on these two cases.
below
above,
Second,
these cases are
as we hold
C
simply inapplicable here. Given these con-
by
Certain concerns
raised
dis-
siderations, we decline to hold that
My
sent.
brother
dissent sees the dis-
cite
failure of the district court to
these
having
fully
trict court as
“abstained from
constitutes reversible error.
precedents
with the writ-
inquiring”
compliance
about
inquiry
addressing
In
the enablement
description
require-
ten
and enablement
the dissent looks to two other cases
¶
§
light
strong
ments of
1. In
of this
It cites In
by
discussed
the district court.
statement,
highlight
we write here to
what
Mayhew,
re
the district court did and did not do in
(C.C.P.A.1976),
USPQ
deciding the case below. The district
proposition
failing
to recite a
“claims
deciding
court should be seen as
the chal-
fail for
necessary element of the invention
lenges
validity
requirement
under each
There,
enabling
lack
disclosure.”
presented
infringer.
it
the accused
however,
so,
step
claims omitted a
the method
doing
fully
the court
found the facts
invention as claimed was
under-girded
its conclusions on validi- without which the
fundamentally, we think the
simply
it
But more
(meaning
wholly inoperative
produce
unfairly
and could not
characterizes
district
not work
dissent
would
Here,
of a
Id.
the lack
handling
and reasoned
product).
claimed
court’s careful
ex-
exogenous
to the
limitation directed
repeatedly
112 issues. The dissent
product
claims is not
pression vector
“simply
suggests that
the district court
the structure
a failure to describe
whether, having dis-
refused” to consider
necessary element of the claimed
cell or
only
pro-
one means to make EPO
closed
cell,
transcrip-
Once inside
EPO.
cells,
or mammalian
duced
vertebrate
the human EPO
sequence and
tion control
for all such
Amgen was entitled to claims
randomly into the host cell
integrate
the dissent
Specifically,
cells and EPO.
required descrip-
only
chromosomes.
asserts that the district court “abstained”
*24
tion,
then,
of the EPO
and
a
considering
whether the absence of
because it
sequences
control
transcription
expression
claim limitation on the means of
sequences in the
of these
presence
is the
§
raises
112 issues.11 We find this hard to
produce
the cell to
cell that causes
explicitly
understand. The district court
Thus,
the lack of
de-
EPO as claimed.
addressing
analyzed
requirements
these
to)
(or a limitation directed
scription of
challenges
validity.
specific
defendant’s
(as separate from
vector itself
expression
they
proven
It decided
were not
sufficient-
transcription
DNA and
control
the EPO
supported
by
decision is
both
ly and its
the invention
does not render
sequences)
fac-
precedent
citations to our
and its own
therefore does not run
inoperable and
Thus,
findings.
refusing
tual
rather than
Mayhew,
re
527 F.2d at
afoul of In
§ 112
it
questions,
to answer the
seems
USPQ
(affirming
at
examiner’s
188
358
answer them affirma-
district
did
rejection
having
claims not limited
tively.
strip
the exit of a steel
cooling zone at
issue,
addressing
In
specific
dis-
specification
from a zinc bath because the
principally
trict court relied
on two of our
cooling
that without that
bath
indicated
Petroleum,
precedents: Phillips
and Cell-
work).
process would not
the invented
pro. The court construed the former as
The dissent’s reliance on
re Vaeck is
requiring
description
not
the written
cited for the
misplaced.
also
Vaeck is
mak-
later-developed
include
methods for
that the disclosure of one or
proposition
ing
product.
a claimed
126
(here
species
monkey and hamster
two
USPQ2d
at
at
F.Supp.2d
cells)
genus
a broad
un-
“may not enable
1515. The court construed the latter as
the circumstances.” 947 F.2d at
der
holding
product
supported
that a
claim is
But then
it
again,
at 1444-45.
en-
adequate
description
written
may;
inquiry
fact-specific.
Here the
abling
only
disclosure even if it describes
did en-
district court held
disclosure
making
prod-
one method of
the claimed
be-
genus
able the
because
differences
uct.
Id. at
at 1515.
using the
mammalian
tween
two described
These cases have not been shown to be
(and vertebrate) cells and other such cells
incorrectly applied by the district court.
easily
were small and
accommodated
we,
court,
obligat-
And
like the district
Thus, in assessing
the artisan.
the evi-
both,
dence,
they explicitly
to follow them
as
ed
the court found that the defendant’s
convincing.
support
rulings. Phillips
clear and
Pe-
evidence fell short of
court’s
vein,
§
suggests
requirements
product
claims.
11. In this same
the dissent
of 112
our court here has somehow "waived” the
troleum,
1251, USPQ2d
heavy
at
at
challenger.
burden falls on the
(holding
patentee
that the
was enti-
district court found that the challenger had
filing
because the
prior
tled to a
date
carried
burden.
It admitted that
polypropylene
disclosure of
earlier
questions
indeed,
were
it found
close—
known at that time described and enabled
invalidity proven,
only by
but
a preponder-
“[n]ormally
polypro-
a later claim to
solid
Hence,
ance.
rather than refusing to de-
new,
pylene”
though
higher
even
molecu-
questions
validity
§
cide
under
it
weight
polypropylene
lar
form of
had been
did decide them under
proper
standard
discovered),
subsequently
Cellpro,
proof.
no
We see
reversible error.
(affirm-
1361, USPQ2d
ing summary judgment of enablement of a
Ill
product
challenge
claim over a
two
Having addressed the claim in
alternative embodiments disclosed
issues,
terpretation and
we move to
patent were not enabled because “the en-
step
infringement analy
the second
of the
if
requirement
ablement
is met
the de-
comparison
properly
sis:
construed
scription
any
making
enables
mode of
invention”).
claims to the
product
process.
accused
using the
*25
See,
Fitness,
1365,
e.g., CCS
A. The Patent limit differs” “glycosylation failed to which three following asserted the ruled, The court there- to those methods. patent against TKT: the '933 claims of fore, “Glycosyla- phrase that the means: erythro- non-naturally occurring A1. tion as to which there is a detectable dif- poietin glycoprotein product having upon based what was known ference activity causing bone biological vivo urinary human er- 1983-1984 from that of production to increase marrow cells pat- in mind that the ythropoietin, having reticulocytes and red blood cells and holder, the use of this Amgen, taught ent which having glycosylation differs blot, SDS-PAGE and monosac- Western urinary erythropoietin. that of F.Supp.2d charide test.” non-naturally occurring 2. 91-92, USPQ2d at 1463. product according to claim glycoprotein product higher has a wherein said undisputed It that in there were is urinary weight molecular than human analytical techniques at least two available measured EPO as SDS-PAGE. glycosylation detecting differences composition A com- pharmaceutical 9. two glycoproteins. between SDS-PAGE glyco- an effective amount of a prising type gel electrophoresis in which erythro- effective for protein product glycoprotein of interest is bound to a 1, 2, poietin therapy according to claim charged compound gly- that denatures the pharmaceutically 6 and a coprotein, subjected which in turn to an diluent, adjuvant or carrier. acceptable field; glycoproteins electric of different purposes for our is the final Critical weight (reflecting molecular their different limitation of claim which states that the glycosylations) migrate through will *26 “glycosylation has glycoprotein claimed speeds. electric field at different Id. at urinary which differs from that of human 124, USPQ2d Isoelectric fo- erythropoietin.” Glycosylation is the addi- (“IEF”), cusing technique a second known carbohydrate tion of side chains to amino to artisans is similar to SDS protein sequences acid form residues except pH that it determines the PAGE glycoproteins. Encyclopedia Molecular of protein electrically which a is neutral be- Biology at 1047. At the Markman hear- charge placed gel cause the the the ing, Amgen that the phrase asserted pH gradient, form of a than on the rather carbohydrate meant “the attached groups 125, USPQ2d glycoprotein itself. Id. at analyzed by prior differ when standard art by The data at 1488. obtained both these techniques known as of 1983-84.” TKT blot, by methods can be visualized Western contrast, argued, by that it meant “the allowing approximation an of the molecular carbohydrate groups attached to side weight. erythropoietin chains of the polypeptide by analysis backbone differ Western blot any There was little dispute of carbohydrate compo- SDS/PAGE these could be used to determine tests the analysis sition from those of human uri- Indeed, a glycosylation glycoprotein. nary erythropoietin degree to at least the testimony the district court noted that the patents-in-suit.” described in the witness, Amgen Dr. Cummings, discharge duty Amgen’s showing “would Thus, primary difference concerned by a of the evidence that preponderance which, any, techniques acceptable if were glycosylation HMR4396 has which differs determine glycosylation whether urinary from that of human Id. at was different. The EPO.” district court found However, examples specification in the teach at 1490. product.” that indicated uEPO and the accused But it also credited evidence from the preparations produced Amgen to us that two uEPO seems has failed to nev- starting materials could question same batch address the trenchant on this is- glyeosylation pat- i.e., have different sue, ertheless whether is necessarily gly- uEPO Id. at at 1492 terns. cosylated way. in the same deals (“[A] artisan in 1984 would have skilled cavalierly question rather in both urinary erythropoietin understood brief, reply principal stating sum- using purifica- different samples obtained marily that the district court erred and glyeosy- could have different tion methods suggesting question unimpor- result, glyeosylation a lation. As tant. urinary was in erythropoietin human definition, By one must know what be, a moving target.”). and continues to glyeosylation certainty of uEPO is with Consequently, because the district court one can determine before whether patent identify that the failed to concluded claimed has a glycoprotein glyeosylation single a standard which the “difference” different from that of uEPO. its discus- measured, be it held that TKT did could characterizing sion glycopro- recombinant infringe and the '938 was inval- products, specification tein of the '933 satisfy id for failure to 112: U.S.C. ordinary does not direct those of language patent, '933 art a skill standard which the however, glyeosy- that the presupposes appropriate comparison can be made. See urinary erythropoietin lation of is a patent, col. line 33—col. line 7. fixed, against identifiable marker which The district court evidence that considered glyeosylation of recombinant EPOs by Amgen in experiments conducted Yet, can be measured. how can one urinary prepa- showed that different EPO gly- that a has prove recombinant EPO glyeosylation. rations had different For cosylation which that of uri- differs from purified from the urine example, EPO nary glyeosylation when the of uri- (“Lot 82”) single patient using modified nary varies? The need EPO itself Court shown to Miyake procedure was have not answer this conundrum. All that glyeosylation different from other Amgen’s showing need be is that said Goldwasser). (taken uEPO glyeosylation that GA-EPO has which *27 129, USPQ2d at 1491- F.Supp.2d 126 at 57 many differs from but one of the hetero- so, assuming Amgen is 92. And even geneous urinary EPOs is insufficient to ordinary in art correct that one of skill carry proving infringement its burden the benchmark test would have understood a by preponderance evidence glyeosylation Miyake, for to be its conten- infringes the claim limitation. noted, fails. the district court tion still As 129, USPQ2d at 1492. Id. at 57 a method of Miyake provides article Amgen argues appeal that an ordi- hardly uniformi- purification, suggests but have narily skilled artisan 1984 would the human-uEPO ty glyeosylation understood, disclo- upon patent based studied: sure, principal pro- there were two for Miyake publication, The 1977 et al. uEPO, with the tech- purifying cesses purification example, describes (SDS-PAGE) by Miyake nique taught starting the same material of two homo- recognized as the standard. It asserts geneous urinary preparations it in- proving carried its burden of IIIA) (Fraction II Fraction that had fringement empirical because its evidence potency same terms of bio- about the “unequivocally glyeosy- demonstrated the II and IIIA logical activity. Fractions Miyake-purified lation difference between 1342 Indus., Inc., 1336, 1349, carbohydrate composi-
... had different tell 299 F.3d 63 (Fed.Cir.2002) (“It and, therefore, 1769, USPQ2d differed from each tions 1776 Thus, these two glycosylation. other not our function to rewrite [indefinite] though produced by preparations, uEPO preserve validity.”). Apply claims to their (*Miyake) and de- procedure the same ing legal these maxims to the facts of this of starting rived from the same batch case, agree we with the district court that material, gly- nonetheless had different requiring “glycosylation the claims which cosylation. differs” are invalid for indefiniteness. 1491; USPQ2d Id. at 57 at see also erroneous, however, We find Miyake, Erythro Human Purification invalidity conclusion that for indefiniteness (1977) poietin, J. Bio. Chem. 5562 only should be in the A found alternative. (“In spite finding potency of our of similar if, fight claim is indefinite when read in size, preparations and molecular these two specification, reasonably it does not II and must be consid [Fractions IIIA] apprise scope those skilled the art of the ered different. The chemical basis for this of the invention. See Solomon v. Kimber studied.”). being Amgen difference is now 1372, 1378, ly-Clark Corp., 216 F.3d fails to controvert or otherwise address (Fed.Cir.2000) USPQ2d 1279, 1282 (citing in its cross-appeal. this evidence Comm., ITC, Personalized Media LLC v. ¶2, § 112 Under 35 U.S.C. 696, 705, USPQ2d 161 F.3d patent applicant required, the close of (Fed.Cir.1998)). So it is here. Recogniz specification, “particularly point[ his ] ing that it was faced with a “conundrum” distinctly subject out and mat elaim[ ] construction, regarding claim the court applicant regards ter the as his invention.” infringed held that was not requirement of claim definiteness set because could not meet its burden ¶ §in 112 2 out assures that claims simply showing gly “that GA-EPO has “sufficiently precise permit cosylation which differs from but one of potential competitor to determine whether many heterogeneous urinary EPOs.” Int’l, infringing.” or not he is Morton Inc. F.Supp.2d Co., v. Cardinal Chem. 5 F.3d at 1492. That the court recognized that (Fed.Cir.1993). ordinary one of skill in the art would have The standard of indefiniteness is somewhat been faced with this “conundrum” should high; a claim merely is not indefinite be inquiry, ambiguity have ended the for such scope cause its is not ascertainable from in claim scope is at the heart of the defi Cf., e.g., the face of the LNP claims. requirement niteness of 35 U.S.C. Plastics, Eng’g Mills, Inc. v. Miller Waste ¶ 2. cannot logically One determine wheth Inc., 1347, 1359-60, USPQ2d er an product accused comes within the (Fed.Cir.2001) (affirming dis *28 bounds of a claim scope. of unascertainable trict finding patent that was not Accordingly, the that TKT finding does not indefinite, despite testimony from a co- infringe patent the '933 is vacated and the inventor that he did understand what finding that the patent '933 is invalid un “substantially the claim limitation com §der 112 is affirmed. meant). Rather, pletely wetted” a claim is ¶ indefinite 112 2 if “insolubly under it is B. The '080 Patent ambiguous, and no narrowing construction 2-4 patent Claims of the '080 properly can be adopted.” Exxon Re issue: States, Eng’g & search Co. v. United 265 1371, 1375, USPQ2d 1272, 2. An erythropoietin isolated glycopro-
(Fed.Cir.2001); Eng’g Corp. having Allen v. Bar tein the in biological activity vivo relying on what it adopted proposal, increase TKT’s marrow cells to causing bone of specifica- in key language considered the reticulocytes and red blood of production that supporting “Fig. tion construction: cells, erythropoietin glyco- wherein said identify erythro- primary thus serves to struc- the mature comprises protein acid) (amino sequence 6 tural conformation sequence of FIG. amino acid poietin including of mature human EPO as human urine. not isolated from and is ” amino acid residues .... '080 specified erythro- non-naturally occurring A3. Amgen, 126 patent, col. lines 3-5. having the vivo glycoprotein poietin 86-87, USPQ2d at F.Supp.2d at 1459. mar- causing bone activity of biological of reti- production to increase row cells total, of Figure sepa- 6 consists five cells, and red blood wherein culocytes through figures Figs. rate denominated 6A com- glycoprotein erythropoietin said 6E, collectively which disclose the se- amino erythropoietin prises the mature genomic of human EPO quence 6. sequence acid FIG. description encoded EPO. The detailed com- composition A pharmaceutical patent speci- '080 indicates that the effective therapeutically a prising ficity Figure lightly 6 is not to be disre- erythropoietin glycopro- amount of garded: according to claim or 3. product
tein identify pri- to Fig. 6 thus serves (amino mary structural conformation The critical limitation asse^ed sequences) acid of mature require- is the claims the '080 acid including specified amino glycoprotein erythropoietin that the ment (estimate M.W.=18,399). residues Also erythropoietin the mature “comprise[ ] the DNA Figure revealed in the is se- Fig. 6.” The court sequence amino acid leader quence coding for a residue erythro- “mature term construed along with and 3' DNA sequence 5' Figure 6” sequence amino acid poietin may significant which to sequences be 4 and 6 of the '698 appears that hu- functions of the promoter/operator 2 and 4 of the '080 and claims potential gene operon. man Sites here arises out of patent. dispute human EPO glycosylation of the mature At time specification. in the mistake designated Figure in the polypeptide are drafted, it patent was was believed worthy It is of note asterisks. sequence included 166 amino Fig. specific sequence amino acid acids, Figure is depicted and this belief naturally likely constitutes that of fact, 6. In later research demonstrated erythro- occurring allelic form of human actually 165 sequence the full Support position for this poietin. acids; actually (arginine) the last amino in the results of continued efforts found protein’s secretion prior cleaved off of hu- sequencing urinary isolates Amgen argued that from the cell. erythropoietin provided which man irrelevant, Figure 6 was even reference to number of er- finding significant acids, many had amino figure if the too have a ythropoietin molecules therein [i.e., “mature it still showed the because opposed methionine at residue 126 as sequence.” amino erythropoietin acid 165] Figure. in the a serine as shown Figure argued that the reference patent, col. fines 29-40. de- the term to be construed as required *29 6, ami- district court revisited and thus with 166 When the picted Figure issue, trial,12 it concluded “Figure the court 6” Following no acids. 12. The court declined to See 126 the matter under advisement. rule this issue at take on USPQ2d F.Supp.2d 57 at 1459. hearing, choosing to at instead Markman claims, conclusion, conjunction read in
language rejected of the argu TKT’s Amgen ment that any was not entitled to portion specification with the of the ex range equivalents Corp. under Festo v. above, clearly identified the ma cerpted Kabushiki, Kogyo Shoketsu Kinzoku erythropoietin sequence ture amino acid as (Fed. USPQ2d exactly depicted Figure doing, 6. In so Cir.2000), during because prosecution it rejected expressly Amgen’s the court con had narrowed the scope of the claim for tention that the claim should be read as to patentability. par reasons related covering sequence, the mature amino acid have cross-appealed ties on this patent, erythropoietin, whatever its number of Amgen asserting that the district amino F.Supp.2d acids. court erred finding infringe no literal (“Had Amgen at 1470 ment and TKT continuing press its es- only erythropoietin claimed ‘the mature toppel theory denying any as a basis for sequence’ amino acid without associating range of equivalents. linking sequence that amino acid Naturally, Amgen continues to focus on Figure .argument 6 its that its claims cover the “mature” portion of the relevant claim (whether sequence whatever it contained support limitations to argument its acids) ultimately or 166 amino se the trial court by finding erred no literal creted the cell might have more mo infringement. According to Amgen, the mentum.”). The district court therefore practical result of the trial court’s conclu- Amgen’s found at the close of case that sion is to read out from the claims the literally HMR4396 does not infringe the preferred embodiment of the invention be- patent. asserted claims of the '080 cause specification makes clear that “mature” human The issue EPO is that form which infringement under the doc- blood, ie., circulates in the the 165 closer, amino trine of was much equivalents acid form that has already been secreted. “Figure likewise centered on the 6” limita- argument This strains reason to its break- tion.13 The district court concluded that ing point; reading patent, our like proven by preponderance had court’s, the district support will no such the evidence that the 165 amino acid se- interpretation. quence satisfied function-way-result test, crediting particular testimony Amgen’s argument is based upon of Dr. Lodish that TKT’s missing arginine a misconstruction of the “including” term (the residue 166th amino acid appearing in that evinces a misunderstanding of the 6) Figure does not affect the in vivo bio- plain term, meaning of that as well as the logical activity of product. its EPO Id. at “comprise,” term appears which in the '080 133, USPQ2d In reaching 1495. its “Comprising claims.14 is a term of every The district court held that 'including' other 13. 'limited to’— —not limitation of the asserted claims in the construed, sequence. Properly the 1-166 literally by were met prod- the accused sequence Lin's claimed mature se- —the uct/process. Amgen, F.Supp.2d at 132- quence fully processed form of —includes Thus, at 1493. whether any glycoprotein having Figure 6 se- equivalent infringement occurred turned quence. That includes both the 1-165 and "Figure whether the 6” equiva- limitation was sequences Figure the 1-166 amino acid 6. lently met. Only this construction affords 'mature' proper meaning, preferred and includes Lin's Amgen argues: specification "The de- embodiment.” sequence scribes the mature amino acid *30 patentability. to an amendment related which means language in claim art used essential, agree. but elements We named that the and still may be added elements other correctly found The district court of the scope within
form a construct
amendment, although voluntary,
Genentech,
Corp.,
v.
Inc.
Chiron
claim.”
a “same invention”
made to avoid
was
1608,
495, 501, USPQ2d
112 F.3d
rejection, Amgen, 126
patenting
double
means
(Fed.Cir.1997).
“include”
The word
135, USPQ2d
1496,
at
F.Supp.2d at
Co.
thing.
Hewlett-Packard
the same
See
reversed our
although
Supreme
Court
Inc.,
Corp.,
Mfg.
Stencil
Repeat-O-Type
v.
rejected the notion of
in Festo and
decision
123 F.3d
equiva
to the doctrine of
an absolute bar
(“The
(Fed.Cir.1997)
‘in-
claim term
lents,
holding “that a
agreed
it
with our
‘comprising,’
synonymous
cluding’ is
satisfy any re
narrowing
to
amendment
un-
of
the inclusion
thereby permitting
may give
Act
rise
quirement
Patent
also Webster’s
components.”); see
named
Corp. v. Shoketsu
estoppel.”
an
Festo
to
University Dictionary
II New Riverside
Kabushiki,
535 U.S.
Kogyo
Kinzoku
(1984) (“include:
have or take
1. To
1831, 1839,
shown of a production process 4. A polypeptide erythropoietin glycosylated finding infringe Turning to the biological property in vivo having the equivalents, the doctrine under ment cells to increase marrow causing bone be es- should TKT asserts red blood reticulocytes and production un coverage obtaining such topped steps: comprising cells alleges that Specifically, der Festo. a) suitable nutrient growing, under Figure sequence of amino acid the “mature comprising conditions, cells vertebrate pat in the '080 appears 6” limitation DNA, than er- other promoter double-pat ent added overcome DNA, opera- promoter ythropoietin rejection, and therefore constitutes enting *31 tively linked to DNA encoding the DNA immediately adjacent to the DNA erythropoietin mature amino acid se- EPO, encoding the term “operatively 6; quence of FIG. ought linked” be limited by location. The b) isolating glycosylated erythro- said district court held that “opera- the term poietin polypeptide by said expressed tively promoter linked” means “the DNA cells is linked to the EPO DNA such a way process 6. A for production of a that maintains the capability of pro- glycosylated erythropoietin polypeptide moter DNA to transcription initiate having biological vivo property of EPO DNA.” Amgen, 126 F.Supp.2d at causing marrow bone cells to increase USPQ2d at 1462. production reticulocytes of and red blood The district granted TKT sum- cells comprising steps of: mary judgment of non-infringement of in- a) growing, under suitable nutrient (and dependent claims 4 and 6 hence de- conditions, vertebrate cells comprising pendent 7-9) claims 5 and of the '698 amplified encoding DNA the mature patent because it found Amgen had erythropoietin amino sequence acid 52(c) failed carry to its Rule burden. Id. 6; FIG. at Amgen 1471. as- b) isolating said glycosylated erythro- sails this conclusion as not accordance poietin polypeptide expressed by said law, with inasmuch as the differences con- cells. sidered dispositive by the district court are Infringement dependent claims 5 and not claimed and thus have no bearing on a 7-9 rises falls with analysis proper infringement analysis. fact, ac- applies independent to claims and 6.15 cording Amgen, the district court ne- phrase “operatively appears linked” in glected to identify any limitation of the claim 4 of the patent, '698 and is related that the process accused fails by dependency to claims 5 9. and Accord- meet, literally and also explain failed to
ing court, to the district phrase relates why, in the absence of infringement, literal to the relationship between promoter DNA those limitations were not equiv- otherwise and the DNA that is transcribed down- alently met. agree We stream from promoter DNA. Amgen therefore conclude vacatur appropriate. contended that the phrase “posi- means The district court properly tioned such rec that it provides for initiation ognized that the infringement transcription gene.” analysis of a argued process the term claims is positioned means adjacent necessarily different “to product encoding claims. way id. at that main- See (“The tains the capability to initiate transcription process patent words, gives EPO DNA.” In competitors other notice to that the steps argued that the words “operatively described linked” therein not to repeated be imposed restriction, no spatial achieve Thus, whereas the same result. whereas in TKT contended that the patent product because patent context, differences in allegedly taught placing promoter process here, are meaningless, pro- process Claim 5 claims "[t]he amplified of claim 4 gene Dihydrofolate marker DNA is promoter wherein said promoter DNA is viral (DHFR) gene reductase DNA.” And claim 9 DNA.” Claim claims process ”[th]e of claim process according ”[t]he to claims 6 wherein said vertebrate cells further com- and 6 wherein said cells are mammalian prise amplified gene marker DNA.” Claim 8 cells.” process claims "[t]he claim wherein said *32 initiating ATG 5' to the pairs 44 base context, these differences patent cess approxi- and pre-peptide coding for the a correct But after everything”). mean the in- 3' to the Hindlll pairs in 680 base mately the differences discussion has process eschewed the court site’.... TKT’s analysis, restriction fringement accused de- upstream that the sequence the principle cardinal within the claims rath- to the compared poly- the express be EPO vice must codons that the em- commercial preferred to a er than The court ATG sites.... several peptide (“Based many ... the on Id. bodiment. sufficiently process a that such finds TKT’s Amgen’s and between Am- by encompassed from different differences infringe- proof ... Amgen’s processes non- judgment invention gen’s insufficient [is] the '698 ment follow. infringement should added). ....”) (emphasis Id. that a court concluded example, the For the legal insofar as error Again, re- the distinction between fundamental the analysis is not tied to infringement employs was that TKT spective processes and vacate We therefore asserted claims. heterologous re- than rather homologous a may conduct the court remand so to make combination, order “[i]n whereas in the first inquiry infringement proper EPOGEN®, [CHO] transfects Amgen instance, the device comparing accused both viral that contains a vector cells with lim- without claims the construed properly EPO the human DNA and promoter the examples the in scope to iting their to the This clear reference Id. gene.” are limitations that or other specification Example embodiment preferred 4-9. part a of claims properly not “the court considered district the which by Am- upon heavily relied most process Patent D. The %22 103, USPQ2d id. patent,” in gen its patent, '422 of the Claim 1 none of the point that misses the pharmaceu dispute, “[a] in only one a limitation. contain such issue claims at therapeuti comprising composition tical as- of the limitations from the apart And erythro of human cally effective amount the two claims, the differences serted acceptable pharmaceutically in- poietin to the wholly irrelevant processes carrier, said wherein diluent, adjuvant or analysis. fringement mammalian from purified erythropoietin is found materi- likewise The district Markman In culture.” grown cells promoter places TKT al fact “pu phrase contended hearing, than upstream does enhancer farther cul grown in cells from mammalian rified court’s con- light of Amgen. in vitro from “purified ture” meant however, seem TKT struction, it would have cells the mammalian in which culture limitation, linked” “operatively satisfies it argued that whereas grown,” been promot- that TKT’s question nois as there substantially homo in a “obtained meant effect. In functional its intended er causes cells the mammalian state from geneous again com- event, court once the trial any not from produced it was which by reference process accused pared the Concluding that media.” cell culture pro- claimed than the example rather pat exclude would construction TKT’s cess: 10), (Example embodiment preferred ent’s illustrat- 7 and Example explained As “mammalian phrase read the court the vec- 4, Amgen created Figure ined en a whole to culture” grown cells restriction BstEII cleaving, with tor techniques purification compass which position ... ‘at a endonucelases or the cell cells culture medium. Id. at specification ent defines pharmaceutical 88-89, USPQ2d at 1460-61. As indicat- compositions “as comprising ‘polypeptides earlier, ed court immediately district invention’,” of the and HRM4396 is granted turned to and Amgen’s motion for “polypeptide of the invention” inasmuch as summary judgment infringement the invention is “uniquely characterized” at the close of the Markman (and to) hence exogenous limited hearing. *33 DNA. Finally, TKT challenges the finding infringement because, asserts, it According court, the the district it was clear intrinsic evidence phrase from the limits the beginning “puri- that the accused fied met from product most limitations mammalian grown of claim 1. cells in cul- That pharmaceutical purification HMR4396 was a ture” to place com- takes inside position cells, that contained a the therapeutically and not—like TKT —from the effective amount of human erythropoietin culture media.16 infringement As plain, was view of the Investigational patent '422 granted was summary judg- (“INDA”) Drug Application New that TKT ment, we review the district court’s conclu- filed with the and Drug Food Administra- novo, sion de applying the same standard 94-95, tion. Id. at 57 at 1465. applied by the trial Sehering court. Corp. The district court further concluded Inc., v. Amgen, 222 HRM4396 contained “a pharmaceutically USPQ2d 1650, (Fed.Cir.2000). Un- diluent, acceptable adjuvant or carrier” standard, der agree we with the trial view of the testimony of TKT’s Rule court that a grant of summary judgment of 30(b)(6) designee, who testified that the infringement of the '422 was war- HRM4396 recovered in bulk from the cul- ranted. turing of human cells was diluted with a We cannot accept, for the reasons al- phosphate buffer to control the pH stated, ready TKT’s proposed reading of provide product of desired strength. See the claim term “mammalian” and its at- 95, USPQ2d id. at at 1466. The sole tempt import the exogenous term into issue, then, remaining was whether the claims; the we reject therefore out of hand product accused “purified from mam- the contention expressly ex- malian grown cells in culture.” Rather the use cluded of human cells to express than taking utterly the position untenable EPO and the use of endogenous DNA mammals, that humans are not TKT con- from scope Thus, of its invention. ceded infringement under the court’s claim issue resolves to a narrow one: the ac- construction. Id. at product, cused HRM4396, infringes '422 1466. patent claim 1 unless TKT is correct that TKT tries different three ap- tactics on the claim limitation “purified from mam- peal to escape this concession of infringe- malian cells grown in culture” means that First, ment. argues TKT that “mammali- product must be recovered di- cells,” an as the phrase is used in rectly cell, from the and not from the patent, do not include its cells because culture medium. Amgen excluded the use of human cells to produce human EPO from its At invention. hearing, Markman Amgen con- Second, TKT asserts that the finding phrase tended the “purified means from infringement was in error because pat- vitro culture in which the mammali- The argument 16. basis for this Therefore, growth.” TKT, that claim asserts “Amgen of the '698 recites recombinant EPO seeks, also knew how to what it now “isolated from the host cell or the medium of but failed to do so.” chal- Accordingly, TKT’s Example argued grown”; have been cells we read substantially fail unless ultimately must lenge in a “obtained means that it mammalian out of from the embodiment preferred state homogeneous produced where we claims, it was the case in which but rare is cells trial media. cell culture interpreta- A claim do so. or will should encompass purifi- phrase to read the embodi- preferred that reads out tion cell or the the cells techniques from cation ever, if correct and would rarely, ment “i§ otherwise, it to do because medium culture sup- evidentiary persuasive require highly pre- patent’s found, exclude would Conceptronic, v. Corp. Vitronics port.” in Exam- as disclosed embodiment ferred 1583, USPQ2d Inc., 88-89, F.Supp.2d at ple 10. (Fed.Cir.1996). so We have done USPQ2d at 1461. an instance where one time—in only *34 sys- expression scope the full of 10 “describes Example applicant limited ovary hamster preferred employing Chinese to omit language tems claim (CHO) disclosed) and the selectable DHFR cells (and in order only embodiment 25, lines marker, patent, col. DHFR.” rejection. See an examiner’s to overcome description, of the part As a 38-40. O.U.R. Instr. S.A. v. Elekta Scientific gene amplification example discloses 1308, USPQ2d Int’l, Inc., to increase possible media is in cell culture (Fed.Cir.2000). present The targeted recombinant productivity evidentiary sup- “persuasive lacks the case exam- describing an After product. the claims necessary for to read us port” system, amplification gene of such ple embodiment preferred to exclude the so as “The on to state: goes specification 10; de- Example we therefore in disclosed CHO producing of the EPO productivity cline to do so. improved can be lines described above cell techniques. culture appropriate cell by Patent E. The '319 in cells of mammalian propagation one method The '349 contains of presence requires generally culture are product claims and six A method growth media. in the serum of vertebrate types generally drawn CHO erythropoietin production from of At are claims culture. issue grown in cells serum that does not contain in media cells 3-4, and 6-7: er- purification greatly of facilitates propa can be which 1. cells Vertebrate Id., media.” ythropoietin culture from capable which in vitro and gated added). We (emphasis lines 8-14 col. er- producing in culture upon growth this dis- court that the district agree with of their in medium ythropoietin embodi- preferred undisputed closure—the erythro- 100 U in excess of growth puri- contemplates ment of invention — hours as in 48 per 106 cells poietin the culture erythropoietin fication radioimmunoassay, said determined 28, lines col. patent, also '933 See media. DNA se comprising cells non-human (“Mammalian prod- expression cell 28-32 transcription that control quences in substan- readily may be recovered ucts erythropoietin. encoding DNA human media culture tially purified form from (C4) according to claim an ethanol employing cells 3. Vertebrate using HPLC of 1000 U pH7.” (emphasis in excess producing preferably capable of gradient, added)). in 48 hours. per cells erythropoietin propa can be cells which 4. Vertebrate challenge the district
TKT does
transcrip
comprise
in vitro which
gated
the disclosure
regarding
court’s conclusion
tion
DNA sequences,
control
other than
originate
did not
in the
genome,
human erythropoietin transcription con which initiate and regulate
synthesis
RNA
sequences,
trol
for production of human
adjacent DNA,
replace
which
erythropoietin,
upon growth
and which
human EPO transcription control
se-
capable
culture are
of producing in quences.” By including
“adja-
the term
growth
medium their
in excess of
construction,
cent DNA” in its
TKT sought
of erythropoietin per
U
cells
require
sequences
the DNA
that control
hours
determined
radioimmu-
transcription to be
position
located
noassay.
adjacent to the gene segment intended to
6. Vertebrate
according
cells
to claim 4
expressed. Furthermore,
be
TKT con-
capable of
producing
excess of 1000 U tended that in
order
“control” transcrip-
erythropoietin per
106 cells
48 hours.
tion, the DNA sequences must both initi-
process
A
for producing erythro-
ate
regulate
the transcription of a
poietin comprising the step of culturing,
gene. Amgen objected to the use of
under suitable nutrient conditions, verte-
“and,” preferring a construction that re-
brate
1, 2, 3, 4,
cells according to claim
quired
sequences
either to initiate or
5, or 6.
regulate transcription. Finally,
par-
Each of the claims contain the limitation
disagreed
ties
as to the meaning of “non-
“non-human DNA sequences that control
human.”
argued that “non-hu-
*35
transcription” that appears in claim 1 of man”
part
means “not
of the
ge-
human
patent
the '349
or the limitation “tran-
nome,” whereas TKT contended it meant
scriptional control DNA sequences, other
“not originating in the human genome.”17
than human erythropoietin transcription
First, the
rejected
court
position
TKT’s
control sequences”
appears
that
claim
and concluded that “non-human” DNA se-
of the '349 patent. Transcription is the
quences are DNA sequences that are “not
process whereby
polymerase
RNA
copies
part of the
genome.”
court
The
genetic information contained in a DNA
similarly rejected
“adjacent”
TKT’s
lan-
sequence
nucleotide
into an RNA se-
guage because “no claim term could rea-
quence.
It
ais
step
expres-
critical
the
sonably be construed to be limiting the
sion of proteins
erythropoietin
like
and is
transcription control DNA sequences by
itself
controlled
specific DNA se-
their location.” Finally,
the court held
quences. According
patent,
to the
“tran-
that
sequences
DNA
that control
tran-
scription
sequences”
control
is the collec-
scription are
sequences
DNA
that initiate
tive
for
term
DNA
that
sequences
only
regulate
the processes of transcrip-
“provide a site for initiation of transcrip-
tion.
F.Supp.2d
at
mRNA,”
tion into
but also are capable of
USPQ2d at 1459-60.
binding proteins that determine “the fre-
(or rate)
quency
of transcriptional
initi-
The district court
judg
entered
ation.”
'349 patent, col.
lines 3-12.
ment of noninfringement
for TKT on
Amgen
method claim 7 of
patent
contended
the '349
that
under
phrase
means “non-human
identical
sequences
DNA
rationale to that
used
grant
are able to initiate
regulate
judgment
or
syn-
of noninfringement
RNA
for the meth
thesis from EPO DNA.” TKT argued
od
claims of the
patent.
'698
Id. at
phrase
means “DNA sequences
which
at 1486. As we have found the
importance
that,
of this distinction
promoter
viral
DNA that
employs
TKT
thus
scientifically
it is
arguable
because
that viral
might not fall
meaning
within the
of the
originates
genome,
the human
claim.
1991),
infringer proves
the accused
when
'698
respect
to the
with
analysis
court’s
literally
that,
claims
su-
asserted
despite
see
unsupportable,
legally
to be
patent
device,
has
1340-41,
vacate
the accused
“it
been
reading
we likewise
on
pra
respect
the same
longer
that it is no
judgment
changed
so
court’s
district
Avionics,
and remand
Inc. v.
'349
Mar
7 of the
Del
invention.”
product
Co.,
1320, 1325,
As to
Quinton
further consideration.
Instr.
court held
(Fed.Cir.1987)
patent,
(citing
'349
of the
claims
were
and 6
608-09,
each of
Tank,
70 S.Ct.
U.S.
Graver
(alter-
held
infringed, and further
literally
854).
equiva-
and 6 were
claims 3
natively) that
TKT
persuaded
are not
We
lently infringed.18
equity
case where
commands
that this is a
already reject-
challenge,
Aside
de
non-infringement
a determination
construction
ed,
court’s
to the trial
falling
literally
within
product
its
spite
cells,”
mounts
TKT
term “vertebrate
TKT relies
claims.
of the asserted
scope
in-
findings
challenge to these
weak
regarding
of the district
findings
the reverse
under
apparently
fringement
way the
device
in the
accused
differences
equivalents.19
doctrine of
patent.
in the
transcription
controls
doctrine
the reverse
Under
admits,
true,
candidly
It is
process
or
product
an accused
equivalents,
tran
TKT controls
by which
the method
a claim
the literal words
that falls within
Whereas
not identical.
scription is
prod
if
infringe
may not
nevertheless
promoter
placing
describes
princi
changed
far
“is so
process
uct or
adjacent,
even
proximity,
DNA in close
performs
it
article that
patented
from a
ple
places
peptide,
leader
in a sub
function
similar
the same or
it
again,
But
upstream.
further
promoter
Tank &
way.” Graver
*36
stantially different
analyses
infringement
conduct
is error to
Co., 339 U.S.
Prod.
v. Linde Air
Mfg. Co.
the
vacuum,
reference
in a
without
1097,
854,
85
605, 608-09,
94 L.Ed.
70 S.Ct.
claims at issue.
(1950);
Don
328,
generally
see
USPQ
330
patent,
the '349
cells of
The vertebrate
Chisum,
5A Chisum
ald S.
on Patents
claimed,
of non-human
comprised
are
as
(1999).
equitably
is
doctrine
§
This
18.04
transcription
that control
sequences
DNA
of
underlying questions
upon
applied based
erythropoietin.
encoding
DNA
of
Foun
fact,
&
Scripps Clinic Research
see
transcription
“controlling]
1565, And
Inc.,
Genentech,
927
dation v.
simply
(Fed.Cir.
erythropoietin”
encoding human
1001,
USPQ2d
1013
18
conclusion, we affirm
trial court’s
granted
ror in the
court
also that the trial
We note
18.
infringement.
finding of
the
the
infringement of
judgment of
summary
patent.
It modi-
'349
product claims
challenge
to the
of TKT's
The sum total
19.
(but
finding
judgment
summary
fied
"verte-
finding,
from the
aside
infringement
result)
respect
the
with
same
reached the
issue,
do[es]
also
“[TKT]
is
follows:
brate”
as
light
transcription”
limitation
"controlling
sequences’
'transcription control
use the
not
Amgen,
testimony.
126
trial
of extensive
found,
patent. As
court
the '349
USPQ2d
Ac-
at 1485.
57
F.Supp.2d at
are
[TKTj’s transcription
sequences
control
in the
cordingly,
the other limitations
unlike
Amgen’s
structurally different from
only
not
conclusion
patent, we review
court's
a different
also function
sequences but
transcription”
"controlling
for
struc-
respect to
those differences
way. Because of
function,
infringe
error,
though
do[es]
to us from
not
[TKT]
it comes
even
ture and
clear
sequences'
limita-
infringement.
’transcription control
summary judgment
grant of
claims.”
the '349
tion in
clear er-
has not demonstrated
Because TKT
means initiating and regulating
pro-
an
in erythroid cells,
increase
plasma iron
cess of
transcription.
rate,
clearance
and red cell mass in at
88, USPQ2d
at
F.Supp.2d
at 1460. This
least one patient, Goldwasser admitted
literally
limitation is met
cyto-
because the
“[tjhere
significant
was no
change in
megalovirus in TKT’s R223 cells performs
any
hematocrit in
patient.”
111-12,
Id. at
function,
this
id. at
USPQ2d
at
at 1478. And because there
1484, notwithstanding TKT’s reliance on
hematocrit,
was no
increase
Goldwasser
analysis
court’s erroneous
of the '698 testified in his deposition that he consid
patent method claims.
study
ered the
a failure. The district
concluded,
court
result,
as a
study
IV
could not be invalidating anticipatory prior
Our affirmance of the district court’s
art:
“[AJnother’s experiment,
imperfect
findings
certain of the asserted claims
perfected
and never
will not serve either
infringed
yet
is not
the coup
grace
de
as
anticipation
or
part
prior
TKT;
non-frivolous validity issues re-
art, for it has not served to enrich it.” Id.
main.
statutory
One of the
requirements
at 1479 (quoting From
for patentability
that the
invention for
son
Plate, Inc.,
v. Advance
Offset
which a
sought
known
or
(Fed.Cir.
USPQ 26,
used
country,
others
patented
or
1985)).
or
in printed publication
described
in this
The district court similarly concluded
or
foreign
country, before the invention
that Goldwasser did not render
patents
applicant.
102(a).
§
See 35 U.S.C.
obvious.
paramount
Of
Similarly,
importance
one is not entitled to a
to the
patent if
subject
was the
fact
prior
matter
that the
invention as a
art refer-
ences,
whole would have
Goldwasser,
including
been obvious at the time
lacked Am-
the invention was made to a person
gen’s
having
genetic
disclosure of the
sequence of
ordinary skill in the art to which the inven- EPO and failed to describe any transcrip-
tion is directed.
§
id.
See
103. TKT re-
tion
sequences.
control
Id. at
lies particularly on two
prior
items of
art USPQ2d
The court also consid-
that allegedly render certain of the assert-
ered
secondary
particularly
factors—
ed
102(a)
claims anticipated
§
under
long-felt need and commercial success—to
under
obvious
103. We discuss each in be
high
importance.
Id. at
*37
turn.
(“Before
at 1482
the
of
advent
Amgen’s product, whether EPO could ac-
A
tually produce a sustainable increase in a
TKT contends the asserted claims are
patient’s hematocrit
not
was
known. Fur-
anticipated by the work of
Eugene
Dr.
thermore, Amgen’s
product,
which
(“Goldwasser”).
Goldwasser
Beginning in was the first EPO-containing pharmaceuti-
1979-80, Goldwasser
conducted
clinical cal composition to obtain FDA approval,
study at the University of Chicago at Illi- has greatly improved
quality
the
of life of
nois in which he obtained a preparation of
chronic renal failure patients throughout
highly purified erythropoietin derived from
the
result,
world. As a
Dr. Lin received
human urine and
approxi-
administered
widespread public
work.”).
acclaim for his
10,000
mately
units of human urinary EPO
to
assigns
three anemic
patients. Amgen,
error to the
district
at
F.Supp.2d
57 USPQ2d
alleged
court’s
at
blind acceptance
of Gold
Although this study showed an
in
increase
wasser’s assertion that the test
a fail
reticulocyte count in all
patients,
three
and ure without considering the contemporane-
dispute.
in
are
terms that
of the
collaborator,
discussion
testimony of Goldwasser’s
ous
Worth, Inc.,
v.
See,
Sports
e.g., DeMarini
and
the Food
to
reported
Baron, who
Dr.
F.3d
that evidence 239
in 1984
Administration
Drug
here,
Cir.2001).
the
(Fed.
But
was de-
stimulation
1893-94
marrow
erythroid
of
TKT,
in dis
is
to
effective”
according
“therapeutically
term
particular,
tected.
Gold-
“look[ ]
whether
failing to
it is
to
by
central
because
pute
court erred
speci-
in
art.
prior
effect
considered
therapeutic
properly
of
is
definition
wasser
“therapeutically
Donohue,
that
agree
We
In re
fication.”
See
in accordance
(Fed.Cir.1985)
defined
that
(holding
must be
effective”
USPQ 619
Instruments
v. Westview
as
Markman
not suffice
will
with
disclosure
non-enabled
resolved,
properly
be
issue can
this
art).
before
prior
§ 102
for
and remand
vacate
we therefore
in
treatment
endgame
Although
to Gold-
respect
proceedings
further
in-
to
is
patients
chronically anemic
of
wasser.
hematocrit,
recognized
as
crease
case,
in
hearing
the Markman
For
“thera-
court,
term
district
upon
based
“pre-selected”
were
terms
ten
be understood
must
effective”
peutically
then-pending
Amgen’s
relationship to
their
it
which
is
of
specification
light
infringe-
of
summary judgment
motion
to
appears
specification
that
And
part.
USPQ2d at 1455.
81, 57
Id.
ment.
simply an
addition
that results
teach
were
terms
“pre-selected”
those
Whether
effec-
provide
can
in hematocrit
increase
is un-
parties
or the
by the court
chosen
33, lines
col.
patent,
See
therapy.
tive
is
record,
clear
what is
but
clear
prod-
(“[The
polypeptide
claimed
19-31
was not
effective”
“therapeutically
for use
suitable
conspicuously
ucts]
court,
district
so the
And
them.
among
...
therapy procedures
erythropoietin
effec-
“therapeutically
viewing
assumedly
heretofore
the effects
all
any or
of
develop
init
construed
dispute,
as not
tive”
EPO, e.g., stimulation
in vivo to
attributed
reference:
of the Goldwasser
discussion
...,
erythrocyte
response
reticulocyte
eryth-
[of,
increased
e.g.,
evidence
Such
and,
...,
indicated
changes
mass
out-
be
should
stimulation]
roid marrow
levels
10, increasing hematocrit
Example
pro-
the achial
the fact
weighed
added)).
(emphasis
in mammals.”
cells was
red blood
mature
duction
district
asserts
result,
and,
hematocrit
aas
achieved
not
ef
“therapeutically
construction
court’s
an in-
Because
unchanged.
were
levels
by admissions
supported
is
fective”
hemoglobin
in hematocrit
crease
“in
means
the term
experts
TKT’s
therapeutic
mark
true
levels
he
patient’s
maintaining the
creasing
study,
Goldwasser’s
Dr.
effectiveness,
levels.”
normal
or near
normal
matocrit
indicators
only inchoate
revealed
which
whether
question
relevant
But
falls far
production,
cell
red blood
*38
so understand
would
ordinary skill
a
requiring
one
claims
anticipating
short
be
term should
term,
that
whether
but
EPO.
therapeutic amount
disclosure
express
upon
based
limited
(second
USPQ2d at 1479
112, 57
at
Id.
Fitness, 288
CCS
specification.
in
ef-
ours).
“therapeutically
Had
emphasis
(“[A]
USPQ2d at 1662-63
1367, 62
at
F.3d
error
no
dispute,
been
not
fective”
ordinary
carry its
not
will
term
may
court
A district
arise.
would
—in-
shows
evidence
the intrinsic
meaning if
a
define
interpret
deed, often must —
term
that
distinguished
patentee
in that
dispute
not
that is
in the
term
particular
aof
basis
on the
art
prior
for the
context
proper
to provide
order
embodiment, expressly
subject
disclaimed
cation procedures to release human eryth-
matter, or
a particular
described
embodi-
ropoietin.” Sugimoto,
col.
lines 30-38.
important
invention.”)-
ment as
to the
If Given the similarity of Sugimoto’s disclo-
the claim term “therapeutically effective”
sure
patents
to the
by
asserted
Amgen,
encompasses
patient
responses de- TKT naturally raised Sugimoto
poten-
specification,
scribed
itas
appears to
tially
art,
invalidating prior
though
even
does,
us it
then the Goldwasser study may Sugimoto had been before the examiner.
constitute invalidating prior art under
The district court concluded
Sugi-
that
102(a)
§
or § 103
if
even
he did not
moto was not prior art under 35 U.S.C.
achieve his intended
We
result.
therefore
102(a)
§
because it was
proven
not
to be
vacate the trial court’s determination that
enabled.
126 F.Supp.2d at
Goldwasser cannot
prior
constitute
art be-
(“In
light
of the intense
cause the study was a failure. Resolution
competition that grew
out
the race to
of the issue turns on the construction of
make human EPO
for
suitable
treatment
meaning
“therapeutically effective,”
anemia,
chronic
one would imagine
which the trial
have
should
an oppor-
if Sugimoto’s
tunity to
invention
construe in
were truly
en-
first
instance
abling,
under
then he
principles.
Markman
would have won
Bayer
See
that lucra-
race.”).
AG. v.
tive
Corp.,
Biovail
1340, 1349,
F.3d
On appeal,
argues
61 USPQ2d 1675,
(Fed.Cir.2002).
trial court erred in placing on it the
Accordingly,
remand,
the court should burden of proving
Sugimo-
enablement of
construe
and,
this term
in light
to,
of that
because United
patents
States
—even
construction, should determine whether
those only asserted as
art
prior
Goldwasser
any
invalidates
of the asserted
invalidity defense—are presumed enabled
patents
102(a)
under
§§
35 U.S.C.
or 103.20 under
35 U.S.C.
282.
agree
We
prior
patents
art
are presumed enabled,
B
but under authority going beyond § 282.
A second
prior
item of
germane
art
A claimed invention cannot be an
this appeal is United States Patent No.
ticipated by a prior art reference if the
4,377,513 (“Sugimoto”), issued in March
allegedly anticipatory disclosures cited as
1983. Sugimoto
process
discloses a
prior art are not enabled. Long
our
ago
producing human erythropoietin “charac-
predecessor court recognized that
non-
by
terized multiplying human lymphoblas-
enabled disclosure cannot be anticipatory
toid
capable
cells
of producing human er-
(because it is
truly
art)
prior
if
ythropoietin
by transplanting said cells
disclosure fails to
into a
“enable one of skill
non-human
warm-blooded animal
the art to
body, or
reduce the
alternatively
disclosed
multiplying
invention to
said cells
practice.”
allowing
Borst,
In re
said cells to
multiply with
C.C.P.A.
device by
which the
nutrient body
USPQ
fluid of
554, 557
a non-human
(C.C.P.A.1962);
warm-blooded
sup-
animal is
Donohue,
accord In re
plied to
cells,
said
and allowing
F.2d at
cells
USPQ
Thus,
multiplied by either of the above multipli-
critical issue here is not whether Sugimoto
20. We note also that on remand when
consid-
the addition
process
of source or
limita-
ering obviousness
anticipation
issues re-
tions. General Electric Co. v. Wabash Corp.,
*39
lating to the '080
patents
and '422
364, 373,
the district
899,
U.S.
58 S.Ct.
82 L.Ed.
court
cognizant
should be
the
of
(1938);
rule that a
Cochrane v. Badische Anilin &
product
claimed
present
shown to
Fabrik,
be
the
Soda
111 U.S.
4 S.Ct.
prior art
be
patentable
cannot
rendered
solely
(1884).
Here, the district court determined that No costs. there was no evidence of intent to de- ceive, and TKT has directed us to none CLEVENGER, Circuit Judge, on appeal. Thus, to conclude the Amgen dissenting part. patents are unenforceable —as TKT re- quests (1) must join my conclude I colleagues’ thorough —we opinion in district court clearly by erred all respects failing one, save albeit significant, find the minimal requisite intent exception. to de- Because the claims lack mean- ceive, (2) that it abused its ingful discretion limitations on the structure of the in weighing the degree of materiality cells, erythropoietin-producing I cannot vulner claims the asserted tions rendered have should district that the agree challenge mounted to the enablement able fully whether inquiring abstained According to 112. TKT under section the enablement under suspect were claims court, the asserted because of 35 the district description provisions and written than ¶ rather “compositions” were U.S.C. need teach “the specification “processes,” specifications described As *43 using making and of only one mode and suit, in 1984 cloned Amgen in patents Inc. v. composition.” claimed er- encoding human DNA sequenced Roussel, Inc., Marion Hoechst (EPO). showed Amgen then ythropoietin 69, 160, USPQ2d F.Supp.2d DNA EPO the cloned introducing that n. (D.Mass.2001). at also id. See mam- into (linked sequence) to a promoter Like 1518 n. 57. at engi- be cells, cells could those malian inquire to wise, court refused the district functional of high levels express to neered on the limitations absence of whether the to refer parties The protein. human EPO questions raised expression of EPO means of expression DNA” “exogenous this as description the written with compliance of that patents several obtained EPO. inquiry such holding that requirement, cloned manipulation of the use and cover Id. composition claims. was irrelevant DNA, patents, battle-test- these and EPO 150-51, USPQ2d 1508. foun- have been litigation, through ed of business Amgen’s successful pat- of dation '080 and '422 to the respect With recombinant selling manufacturing and “non-naturally occur- ents, which claim in suit are not patents these EPO. But from “purified and EPO ring” EPO producing here, for culture,” TKT’s method and grown cells mammalian of manipulation rely upon court, EPO does essen- the district majority, like DNA” “exogenous DNA or EPO cloned wheth- of question tially passes over technology. expression are essential limitations —which er these is- claims—raise of the patentability for signif- no here contain in suit The claims with enablement compliance of sues recombi- how the as to icant limitations requirements description written and struc- or as expressed, nant EPO is that majority holds The section cells, long so EPO-producing of the ture com- their free decorate are patentees occurring” or “non-naturally the EPO as process and with source claims position cen- cells.” in “vertebrate produced for any concern without limitations therefore case is question tral limita- those scope full whether means of one Amgen’s disclosure whether described, that is enabled tions in mammalian synthetic EPO producing section 112 requirements these expression, cells, exogenous namely patentee succeeds long as waived so produced it to claim all entitles “product” characterizing its claims culture, cultured or all cells mammalian attorneys Competent claims. I think produce EPO. cells vertebrate advantage of to take quick be should importance. some question this is the dis- exemption majority’s broad court district question that it is a Yet appropriate by the requirements closure Athough to consider. refused simply endorse than Rather phraseology. dis- Amgen’s admitted district court over of form elevation court’s district DNA ex- exogenous limited to closure was its decision substance, I would vacate clearly quite the district pression, the '080 and regarding these issues whether to decide explicitly refused further consid- remand patents, limita- exogenous DNA any the absence in light eration of the scope vast EPO, defined amount of only single suit for which appears there to limitation on their structure: they be insufficient enabling disclosure or “comprisfe] non-human DNA sequences description. written which control transcription of DNA encod- ing human erythropoietin,” or that they particular With reference to the '349 “comprise transcription control DNA se- patent, which claims not EPO polypeptides quences, other than human erythropoietin but the produce them, cells that I think transcription control sequences, for pro- the district court’s abstention from scruti- duction of human erythropoietin.” ny This is section 112 under is even more little precise more than a error. recitation of “A The majority focuses on the dis- machine that X, makes polymer trict findings court’s wherein the invention the machine comprises readily could means practiced be for control- in mammalian or *44 ling how much polymer vertebrate X is cells made.” other than the hamster specification only and teaches monkey a taught by single cells means specifica- by which tion. I the use agree of a transcription that TKT has control not shown sequence error in can coax But, these findings. a it vertebrate cell to did for claims, the EPO secrete EPO: the district transforming court that simply cell with an exogenous to refused consider expression whether the vector absence of on any exogenous which DNA the transcription control sequence limitations raised en- is “[bjecause issues, ablement linked to cloned EPO DNA. only is Yet the claims required to enable leave this skilled essential artisans to of aspect make the invention product claimed by only undefined. It one is meth- black-letter law that od. ...” 57, Id. at n. 164 failing 57 to at recite a necessary element 1518 n. 57. For the of cells, EPO-secreting invention fail for lack of an enabling the absence of an exogenous disclosure, DNA limita- In re Mayhew, 1229, 527 F.2d tion is not 1233, to limit USPQ (CCPA failure how prod- 1976), made, uct is but a failure and that to limit the disclosure of one or species two structure of the product may claimed itself. A enable a genus broad under these cell, as employed in the patents suit, Vaeck, circumstances. In re 947 F.2d more nothing than a biological 20 USPQ2d 1438, (Fed.Cir. machine for 1444-45 1991). making EPO. Even more predictable least, the very At the absence of arts, one who is first make a structural machine is limitations in the '349 not entitled as a questions matter of law raises to claim any enablement, of its and I or all machines so long as cannot they perform agree that the district court chose the same function. I correctly by would think it un- ignoring questions those alto controversial that gether. even one who is first to We should vacate the district make polymer X alloy Y court’s judgment cannot obtain a that claim as broad as “A passes muster, machine that makes enablement and require the X,” polymer or “A process that yields alloy apply the correct law to plain Y,” without reciting additional facts. limitations that define the structure of the claimed I must disagree also with the majority machine or the steps necessary to carry that the district approach court’s out the claimed process. faithful to this court’s articulation of the ' Yet that exactly what the district written description requirement of section court and the majority allow the '349 pat- as expressed in Regents the Uni- ent to achieve. It claims any or all cul- versity Co., v. Eli Lilly & of California tured vertebrate cells that can secrete a F.3d (Fed.Cir.1997) limitations on they included no Corp., because v. Berkline Gallery, Inc. Gentry (Fed.Cir. Like- arranged. were elements 1473, USPQ2d 1498 how those wise, I think it 1998). principles two claims'—for which articulated the '349 Lilly Eli requirement: of the description that structure written be conceded must broadly description of question— haec verba is a relevant EPO-secreting that in cell may not subject matter generic in the found particular described elements recite matter subject (cells, suffice describe se- non-human control specification claim, particular DNA), that do not EPO-coding but quences, 1404-05, that disclosure USPQ2d at the arrangement limitations on include to describe suffice may not species elements, the non-human e.g. those USPQ2d at 1405- 1568-69, 43 id. genus, DNA are coding sequences control neither court followed 06. The district expression vector exogenous an on present here, majority, and the principles these a matter of I that as agree the cell. grounds Lilly on dismissing Eli justifica- there is no interpretation appears molecule undisclosed no DNA” “exogenous importing tion Lilly to Eli case, confining verges But absence claims. into the limitation its facts. heavily in weigh must limitations such the district I convinced Nor am else we hold inquiry, section *45 Gentry faithful approach court’s written resistant become more claims claims Gentry, only those Gallery. broadly challenges more description as “wherein such included limitations they are. drafted the console” located on means are control colleagues’ admiration my I share While description require- the written satisfied of the district efforts the considerable for failed specification ment. Because case, I cannot complicated in this court other for controls any location disclose the district faith that their share console, claims that those than on Eli conscientiously applied properly under were invalid limitations such lacked the dis- Gallery, when Gentry Lilly and 1479-80, ¶1. devoid of completely opinion is court’s trict here is question The 1503-04. or to the those cases either to reference writ- fail the the claims whether similar: district If the they espouse. principles lack of for requirement description ten law to be on the correct not focus limitations, court did because “exogenous DNA” no findings merit factual then only exogenous applied, its discloses specification remedy for this deference, the art and the correct that was state technology DNA court’s the district is to vacate omission in 1984. point remand this judgment patents’ statement ignore if Even we has precedent Our consideration. further are molecules the claimed may over- district courts if little value by being prod- “uniquely characterized plain if pertinence, its certain look exogenous ... of expression ... uct of applicability. (which we can- of course sequences” between not), parallels I think inescapable. Gallery Gentry
case and recited ele- Gentry invalid found in the readily be
ments could controls, (a couch, of the specification
text nonetheless console), those claims but requirement description
failed written