# Amgen, Inc. v. Hoechst Marion Roussel, Inc.

> District Court, D. Massachusetts · October 15, 2004 · 339 F. Supp. 2d 202

URL: https://www.frixlaw.com/law-library/cases/2463968

## Case

- **Full name:** AMGEN, INC., Plaintiff, v. HOECHST MARION ROUSSEL, INC. and Transkaryotic Therapies, Inc., Defendants
- **Court:** District Court, D. Massachusetts
- **Decided:** October 15, 2004
- **Citations:** 339 F. Supp. 2d 202; 2004 U.S. Dist. LEXIS 22943; 2004 WL 2381550
- **Precedential status:** Published
- **Opinion:** Opinion by Young
- **Judges:** Young
- **Cited by:** 7 later opinions in the Frix Law Library

## Citator (automated)

- No negative treatment found by the automated citator. That is not the same as a confirmation that the case is good law; read the citing cases.
- Full citator and citing cases: https://www.frixlaw.com/law-library/cases/2463968

## How later opinions describe it (automated extraction)

- describing the “conundrum” our claim construction jurisprudence has created by “discouraging resort to extrinsic evidence while at the same time urging courts to begin claim construction by considering the plain and customary meaning of a term as understood by one skilled in t…
- finding that "two crucial witnesses for the defense conceded” points which support the district court's claim construction
- explaining that the prior art disclosed to the patent examiner also supports the district court's interpretation
- noting that expert testimony "is extrinsic evidence to which resort ought to be had only ‘if necessary' ”
- noting that extrinsic evidence was not being used "to define the term"

## Opinion text

MEMORANDUM AND ORDER
YOUNG, Chief Judge.
I. INTRODUCTION
This patent infringement action concerns patents held by Amgen, Inc. (“Am-gen”), relating to the manufacture of a recombinant (genetically engineered) DNA
1
product, known as epoietin alfa,
2
that is similar to natural erythropoietin (“EPO”), a hormone that stimulates production of red blood cells, and is useful in, among other things, treating patients who need blood transfusions and suffer from blood composition disorders such as hemophilia, anemia, and sickle cell disease. This product and this case are not new to the public or to this Court. The ease began brewing in 1997, when Amgen filed a declaratory judgment in the United States District Court for the District of Massachusetts against Defendants Hoechst Marion Roussel, Inc.
3
and Tran-skaryotic Therapies, Inc. (collectively “HMR/TKT”) claiming that three of its patents were infringed by HMR/TKT’s human EPO product, “HMR 4396,” produced from the R223 cell line grown in culture.
See Amgen, Inc. v. Hoechst Marion Rous-sel, Inc.,
3 F.Supp.2d 104, 106 (D.Mass.1998). In 1999, Amgen amended the complaint to include two other patents.
Amgen, Inc. v. Hoechst Marion Roussel, Inc.,
126 F.Supp.2d 69, 96-98 (D.Mass.2001)
(“Amgen I
”). A lengthy jury-waived trial ensued. It commenced in May 2000 and lasted twenty-three days over the course of four months. Id. at 78 . Not surprisingly, HMR/TKT appealed this Court’s decision, Amgen
I,
126 F.Supp.2d 69 . In
Amgen Inc. v. Hoechst Marion Roussel, Inc.,
314 F.3d 1313 (Fed.Cir.2003)
(“Amgen II”),
the Federal Circuit affirmed a majority of this Court’s findings and rulings but vacated and remanded a few issues to this Court.
Id.
at 1358 . This memorandum and order addresses those issues on remand, some of which have already been decided by the Court and announced to the parties, thus requiring only a brief review.
II. BACKGROUND: PROCEDURAL AND SUBSTANTIVE HISTORY
A. The Patents, at Issue
There were originally five patents at issue in this case. Only four, however, remain on remand. The patents and claims now at issue are: Claim 1 of U.S. Patent No. 5,955,422 (issued Sept. 21, 1999) (“ ’422 patent”); Claims 2-4 of U.S. Patent No. 5,621,080 (issued Apr. 15, 1997) (“ ’080 patent”); Claims 4-9 of U.S. Patent No. 5,618,698 (issued Apr. 8, 1997) (“ ’698 patent”); and Claims 1, 3, 4, 6, and 7 of U.S. Patent No. 5,756,349 (issued May 26, 1998) (“ ’349 patent”).
Amgen I,
126 F.Supp.2d at 79 ;
Amgen II,
314 F.3d at 1320 .
4
*214
Although the patents vary, they all share a common disclosure and identical specifications.
Amgen I,
126 F.Supp.2d at 79 . For ease of reference, the Court cites to the specification found in the ’933 patent, which is identical to the specification of the patents in dispute on remand. ’933 Patent, Ex. I.
5
B. The Technology
As
Amgen I
set out the basics of the underlying technology in detail, only a brief summary is provided here. EPO is a naturally occurring hormone that controls erythropoiesis, the production of red blood cells in bone marrow. ’933 Patent, Ex. 1, col. 5: 39-67. Erythropoiesis occurs continuously to offset cell destruction.
Id.
It enables a sufficient (but not excessive) amount of red blood cells to be available in the blood to provide tissue oxygenation.
Id.
Hemoglobin is the protein in the red blood cells that actually transports the oxygen.
Amgen I,
126 F.Supp.2d at 98 . The amount of hemoglobin correlates to the amount of oxygen.
Id.
Hematocrit, which indicates the relative proportion of red blood cells to the total volume of blood, measures the ability of the blood to supply oxygen to the body.
Id.
Thus, generally an increase or decrease in hematocrit equates with an increase or decrease in the ability to supply oxygen to the body.
Id.
Under normal conditions, a person has a hematocrit of about forty-five to fifty, which means forty-five to fifty percent of the blood is made up of red blood cells.
Id.
EPO is produced in the kidney and liver. Therefore, patients with chronic renal failure lack normal levels of EPO and suffer from anemia.
Amgen II,
314 F.3d at 1321 . Introduction of additional EPO into the patient’s body can increase a patient’s he-matocrit level and sustain it at or near normal levels.
Id.
In other words, the blood is able to provide a steady supply of sufficient oxygen to the tissues.
Id.; Amgen I,
126 F.Supp.2d at 99 .
Early attempts to obtain EPO from plasma or urine proved unsuccessful 'because the body only produces human EPO in very small amounts, ’933 Patent, Ex. 1, col. 5: 54-58, and the techniques were very complicated and resulted in the collection of very small amounts of impure and unstable amounts of EPO,
id.
at col. 6: 60-65. Amgen is recognized as the pioneer in the production of a therapeutically effective amount of EPO via recombinant EPO (“rEPO”) techniques.
See, e.g., Molecular Biology and Biotechnology: A Comprehensive Desk Reference
108 (Robert A. Meyers ed., VCH Publishers 1995).
Dr. Fu-Kuen Lin (“Lin”), the named inventor of all the patents in issue, isolated and characterized DNA sequences encoding EPO from humans and monkeys. ’933 Patent, Ex. 1, col. 13: 50-53. Lin determined the DNA sequence of human EPO and its predicted amino acid sequence. ’933 Patent, Ex. 1, col. 10: 65-11: 2. Lin then produced large amounts of EPO by using recombinant DNA technology.
Id.
at col. 14: 23-29. In the patent specification, many methods of producing EPO are described. EPOGEN® is pro
*215
duced by the method described in Example 10, wherein human EPO is produced by introducing exogenous DNA into host Chinese hamster ovary (“CHO”) cells.
Id.
at col. 25: 30-29: 7.
6
The rEPO that is produced has the same or similar amino acid sequences or primary structural conformation as that of naturally-occurring EPO.
Id.
at col. 29: 1-7. As a result, it possesses one or more the biological properties of naturally-occurring EPO but differs from natural EPO in its “glycosylation,” that is, it has a different average carbohydrate composition.
Id.
at col. 10: 35-41.
HMR/TKT, in producing its human er-ythropoietin, HMR 4396 (also called Gene-Activated EPO “GA-EPO”), also uses recombinant technology. HMR/TKT, however, does not use a host cell from a nonhuman species but manipulates the ordinarily unexpressed human EPO gene where it naturally resides.
Amgen I,
126 F.Supp.2d at 102 . In that way, the human EPO DNA material is endogenous to the human cell.
Id.
After introducing a promoter sequence, human EPO is expressed in a human rather than a hamster cell.
Id.
C. The Federal Circuit’s Decision
A brief review of the key rulings and findings that were affirmed and remanded on appeal follows:
1. Claim Construction
a. Affirmed
The Federal Circuit upheld all of the Court’s claim constructions.
Amgen II,
314 F.3d at 1320 . Specifically, the Federal Circuit upheld this Court’s construction that Amgen’s claims do not limit the invention to using only exogenous DNA (as opposed to endogenous DNA).
Id.
at 1327 . It also upheld this Court’s determinations that (1) non-naturally occurring means “ ‘not occurring in nature” ’; (2) vertebrates are anything with “ ‘a segmented bony or cartilaginous spinal cord’ which obviously includes humans”; and (3) humans are a subset of mammals and mammals are a subset of vertebrates.
Id.
at 1327-28 (quoting
Amgen I,
126 F.Supp.2d at 85, 90-91 ). To that end, the Federal Circuit agreed that the specification indicates that the invention uses human DNA in human host cells in culture.
Id.
The Federal Circuit also upheld the Court’s determination that claim 1 of the ’422 patent, claims 2, 3, and 4 of the ’080 patent, and claims 1, 3, 4, and 6 of the ’349 patent are product claims (not process claims) and thus are not restricted or defined by any method of production or any particular source, other than what is specifically excluded.
Amgen II,
314 F.3d at 1329-30 .
b. Remanded
Although all the terms that this Court construed in
Amgen I
under the principles of
Markman v. Westview Instruments, Inc.,
517 U.S. 370 , 116 S.Ct. 1384 , 134 L.Ed.2d 577 (1996), were upheld, the Federal Circuit remanded to this Court the construction of the term “therapeutically effective.”
7
Amgen II,
314 F.3d at 1354 .
*216
This phrase was not considered by the Court to be in dispute during the first trial. In its written analysis, however, this Court interpreted the term.
Amgen I,
126 F.Supp.2d at 112 ;
see also id.
at 99. While interpreting a term to provide context for the discussion is proper when the term is not in dispute, the Federal Circuit determined that the term “therapeutically effective” actually was in dispute “because it is central to whether Goldwasser is properly considered prior art.”
Amgen II,
314 F.3d at 1353 . Therefore, it remanded so this Court could construe “therapeutically effective” pursuant to
Markman. Id.
at 1358. Since claim construction is matter of law,
Markman,
517 U.S. at 386 , 116 S.Ct. 1384 ;
but see
Arthur R. Miller,
The Pretrial Rush to Judgment: Are the “Litigation Explosion,
”
“Liability Crisis,
”
and Efficiency Cliches Eroding Our Day in Court and Jury Trial Commitments?,
78 N.Y.U. L.Rev. 982, 1087 (2003). (criticizing the decision in
Markman),
the Federal Circuit could have proceeded to construe the phrase itself. Where a word or phrase has not been first construed in the district court, the Federal Circuit follows the courteous and prudential path of first seeking claim construction below. Hon. Pauline Newman, Remarks at the American Law Inst. — Am. Bar Assoc. Panel on the Trial of a Patent Case (Sept. 18, 2003).
2. Infringement
a. Affirmed
The Federal Circuit affirmed this Court’s ruling on summary judgment that claim 1 of the ’422 patent is literally infringed.
Amgen II,
314 F.3d at 1348 . It also affirmed this Court’s ruling that the ’080 patent is not literally infringed by HMR/TKT’s HMR 4396,
id.
at 1344-45 , but that claims 1, 3, 4, and 6 of the ’349 patent are literally infringed by it,
id.
at 1351-52 .
b. Remanded
(1) The ’080 Patent
After finding that HMR 4396 did not literally infringe claims 2, 3, and 4 of the ’080 patent because HMR 4396 comprised only 165 amino acids,
Amgen I,
126 F.Supp.2d at 99-101 , this Court held that HMR 4396 performed substantially the same function in substantially the same way to obtain substantially the same result as the EPO glycoprotein of claims 2 and 3 of the ’080 patent,
id.
at 133 . Therefore, it ruled that Amgen’s ’080 patent was infringed by HMR/TKT’s product under the doctrine of equivalents.
Id.
In response to HMR/TKT’s argument that Amgen should be estopped from arguing equivalent infringement, this Court ruled that prosecution history estoppel did not apply because Amgen did not add the “mature amino acid sequence of Figure 6” limitation “in an attempt to overcome a rejection [or] to avoid prior art,” but, instead, to “demonstrate that ‘same invention’ type double patenting did not apply,” — that is, to distinguish the ’080 patent from the ’933 patent.
Id.
at 134-35 .
The Federal Circuit agreed that the amendment was made for this purpose but made clear that under
Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki,
535 U.S. 722, 731 , 122 S.Ct. 1831 , 152 L.Ed.2d 944 (2002)
(“Festo II
”), “ ‘a narrowing amendment to satisfy
any
requirement of the Patent Act may give rise to an estoppel.’ ”
Amgen II,
314 F.3d at 1345 (quoting
Festo II,
535 U.S. at 736 ), 122 S.Ct. 1831 (emphasis added). Therefore, it held that the presumption of prosecution history estop-pel applied.
Id.
at 1345. The Federal Circuit then vacated this Court’s finding of equivalent infringement and remanded for an analysis based on the “narrow ways of
*217
rebutting the Supreme Court’s presumption of estoppel” outlined in
Festo II. Id.
at 1345.
(2) The ’698 Patent
On appeal, the Federal Circuit vacated and remanded this Court’s ruling regarding infringement of the ’698 patent because this Court had compared the accused device to the preferred or commercial embodiments of the patent instead of to the properly construed claims themselves.
Amgen II,
314 F.3d at 1347 . Therefore, it remanded to this Court the question whether claims 4-9 of the ’698 patent are infringed.
Id.
(3) The ’349 patent
Although this Court found that claims 1, 3, 4, and 6 of the ’349 patent are literally infringed by HMR/TKT’s 4396, it held that HMR/TKT did not literally or equivalently infringe claim 7, the process claim, of the ’349 patent.
Amgen I,
126 F.Supp.2d at 122 . The Court compared the accused process to the preferred embodiment in the claim and concluded that HMR/TKT’s “process for producing erythropoietin differs markedly from that disclosed by Am-gen’s specification.”
Id.
The Federal Circuit, as it did with the Court’s holding of infringement of the ’698 patent, vacated this ruling and remanded so that the Court could analyze infringement by comparing the accused process to the properly construed claims themselves.
Amgen II,
314 F.3d at 1350-51 .
3.Inequitable Conduct
The Court’s determination that HMR/ TKT had not proven by clear and convincing evidence that the ’933, ’080, ’349 and ’422 patents were unenforceable due to inequitable conduct was affirmed on appeal.
Amgen II,
314 F.3d at 1357-58 .
4. Written Description, Definiteness, and Enablement
a. Affirmed
The Federal Circuit affirmed this Court’s rulings that the ’422, ’080, and ’349 patents are adequately described and enabled.
Id.
at 1337 . In so ruling, the Federal Circuit explained that this Court “carefully considered these issues, finding in the end that HMR/TKT had not met its clear and convincing burden of proof.”
Id.
Because the Federal Circuit found “no clear error in these factual determinations,” and the parties did not allege any legal error, it reasoned that it would “not disturb [this Court’s] holding that the asserted patents are not invalid for failure to meet the enablement requirement of § 112 ¶ 1.”
Id.
As mentioned in an earlier footnote,
see
note 3,
supra,
this Court held and the Federal Circuit affirmed that the ’933 patent (specifically the claims requiring “gly-cosylation which differs”) was invalid for indefiniteness under section 112.
Amgen I,
126 F.Supp.2d at 156-57 . Therefore, the ’933 patent is not at issue on remand.
5. Anticipation and Obviousness
a. Affirmed
The Court’s ruling that the asserted claims of the ’080, ’349, and ’933 patents are not anticipated under 35 U.S.C. § 102 by the Sugimoto reference was affirmed by the Federal Circuit.
Id.
at 1320, 1356 .
8
*218
In affirming, however, the Federal Circuit made clear that the Court’s determination that Sugimoto was not enabled was an error, though harmless, because the Court put the burden of proving enablement of Sugimoto on HMR/TKT when the burden of proving non-enablement should have been put on Amgen.
Id.
at 1356 .
9
b. Remanded
The Federal Circuit remanded, however, the Court’s findings that Sugimoto does not anticipate claim 1 of the ’422 patent stating that the “district court should consider whether claim 1 of the ’422 patent is novel over Sugimoto in light of the court’s new definition of ‘therapeutically effective’ ” and be “mindful of the principle that source limitations cannot impart novelty to old compositions.”
Id.
at 1356 .
10
Additionally, the Federal Circuit remanded this Court’s finding that the ’422, ’080, and ’349 patents were not obvious in light of Sugi-moto because this Court based its decision, in part, on the fact that it concluded that Sugimoto was not enabled.
Id.
at 1357 . The Federal Circuit explained that under section 103, a reference need not be enabled to qualify as prior art.
Id.
In
Amgen I ,
this Court found that the asserted claims of the ’080, ’422 and ’349 patents were not anticipated or rendered obvious by the Goldwasser reference.
Amgen I,
126 F.Supp.2d at 112-17 . The Federal Circuit remanded these findings for further proceedings given that “therapeutically effective” was not construed in accordance with
Markman. Amgen II,
314 F.3d at 1354 . As mentioned above, it directed the Court to construe the term and determine whether Goldwasser invalidates any of the asserted patents under 35 U.S.C. § 102 (a) or § 103. in light of the Court’s construction.
Id.
at 1354.
D. Procedural and Substantive History Since
Amgen II
The Federal Circuit’s decision issued on January 6, 2003. This Court received the action on remand on March 13, 2003 [Doc. No. 653], and it held a status conference on April 16, 2003 [Doc. No. 657]. On May 16, 2003, Amgen moved for: (1) judgment under Federal Rule of Civil Procedure 52(c) that claims 2-4 of the ’080 patent were infringed under the doctrine of equivalents [Doc. No. 659]; (2) summary judgment of infringement of claims 4-9 of the ’698 patent [Doc. No. 663]; (3) judgment pursuant to Rule 52(c) that claim 1 of the ’422 patent and claim 4 of the ’080 patent are valid [Doc. No. 670]; and (4) judgment pursuant to Rule 52(c) that claims 1, 3, 4, 6, and 7 of the ’349 patent are valid and that claim 7 of the ’349 patent is infringed [Doc. No. 674]. HMR/TKT simultaneously moved for: (1) judgment that Amgen is estopped from asserting infringement of the ’080 patent pursuant to the doctrine of equivalents [Doc. No. 678]; (2) judgment that claim 1 of the ’422 patent is invalid as
*219
anticipated [Doc. No. 682]; (3) judgment pursuant to Rule 52(c) that the asserted process claims of the ’698 patent and ’349 patents are not infringed [Doc. No. 686]; and (4) judgment that the ’422, ’080, and ’349 claims are invalid for obviousness [Doc. No. 690],
The memoranda in support of and in opposition to these motions raised additional issues that are reviewed in this opinion. They are described briefly below.
In its opposition to Amgen’s renewed motion for summary judgment of infringement of the ’698 patent,
11
HMR/TKT argued, among other things, that Amgen’s proposed construction of the words “DNA encoding” found in claims 4 and 6 of the ’698 patent is incorrect. HMR/TKT’s Mem. in Opp’n re ’698 [Doc. No. 700] at 7-8. Second, HMR/TKT argued that in claims 4 and 6 of the ’698 patent, Amgen set forth a step-plus-function claim in referring to the “steps of ... growing, under suitable nutrient conditions” and that an assessment of whether HMR/TKT infringed this aspect of the claim must focus on a comparison between HMR/TKT’s process for growing and the process for growing described by Amgen in the specification.
Id.
at 9. Finally, HMR/TKT argued that even if there is literal infringement here, it can justifiably invoke the defense of the reverse doctrine of equivalents.
Id.
at 13.
12
With regard to claim 7 of the ’349 patent, HMR/TKT made four “new” arguments, two of which are very similar to those made in conjunction with the ’698 patent. First, HMR/TKT contended that its process does not infringe claim 7 of the ’349 patent when considered in light of its proposed claim construction of “DNA encoding.” HMR/TKT’s Mem. in Support re ’698/’349 [Doc. No. 687] at 8-9. Second, HMR/TKT argued that its process does not infringe claim 7 of the ’349 patent because claim 7 is a step-plus-function limitation; and, as such, HMR/TKT’s process does not literally infringe the “step of culturing” found in claim 7 because it does not involve the culturing procedures set forth in Amgen’s specification.
Id.
at 12-15. Third, HMR/TKT claimed that its process does not infringe the process claim under the reverse doctrine of equivalents.
Id.
at 15-18. Fourth and lastly, HMR/ TKT argued that if the Court construes the term “DNA encoding” as Amgen urges, then the validity of the asserted claim of the ’349 patent is called into question.
Id.
at 12.
Amgen, in response, did not dispute that “DNA encoding” needs to be construed by the Court.
See, e.g.,
Amgen’s Reply re ’698 [Doc. No. 731] at 6-10. It did, however, assert that HMR/TKT should not be allowed to make its “new” arguments relating to step-plus-function and the reverse doctrine of equivalents given the procedural posture of the case.
13
See, e.g., id.
at 10-15.
*220
On July 29, 2003, this Court held a
Markman
hearing regarding those terms in dispute and in need of construction and considered other pending motions, including motions for summary judgment. At the end of the
Markman
portion of the hearing, the Court tentatively construed the terms “DNA encoding” and “therapeutically effective,” providing two constructions for the latter, one being an alternate. 7/29/03 Hr’g Tr. at 55: 1-56: 23. It then continued to hear argument. At the end of the day, the Court noted that it would determine whether the asserted claims of the ’698 and ’349 patents were step-plus-function claims at a later date.
Id.
at 176: 1-10. It then continued the motion hearing to July 31, 2003.
Id.
at 176: 11-15.
During a hearing two days later, the Court retracted the alternative construction and reiterated its primary “working construction,” retaining its right to revise it after a more careful review of the claims, specification, and prosecution history. 7/31/03 Hr’g Tr. at 87: 5-88: 7. Additionally, it ruled that claims 4 and 6 of the ’698 patent and claim 7 of the ’349 patent were not step-plus-function claims pursuant to 35 U.S.C. § 112 .
Id.
at 88: 8-89: 9. It then denied Amgen’s motion for summary judgment of infringement of the ’698 patent, citing Arthur Miller’s recent article,
The Pretrial Rush to Judgment. Id.
at 89: 23-90: 25;
see
Miller,
supra.
The Court took everything else under advisement and set the final pretrial conference for September 18, 2003.
Id.
at 91: 25-92: 2.
On August 5, 2003, the Court entered an order regarding the pending motions. [Doc. No. 740], It denied HMR/TKT’s motions for summary judgment with respect to the validity of the asserted claims of the ’422, ’080 and ’349 patents. Order of 8/5/03 at 1. It denied in part and allowed in part Amgen’s motions, under Rule 52(c), for judgment that claim 1 of the ’422 patent and claim 4 of the ’080 patent are valid and that claims 1, 3, 4, 6, and 7 of the ’349 patent are valid.
Id.
Because HMR/TKT did not dispute that the ’080 and ’349 patents are not anticipated by Goldwasser and that the ’349 patent is not rendered obvious by Goldwasser, the Court allowed Amgen’s motions with respect to these matters.
Id.
at 1-2. Specifically, the Court held that claim 4 of the ’080 patent is not anticipated by Goldwasser and that claims 1, 3, 4, 6, and 7 of the ’349 patent are not anticipated or rendered obvious by Goldwasser.
Id.
at 2. Because Amgen did not have the opportunity to rebut HMR/ TKT’s remaining validity arguments concerning the ’422, ’080, and ’349 patents during trial in 2000, the Court stated that Amgen would have that opportunity at the October trial.
Id.
On September 18, 2003, the Court held a final pretrial conference. After explaining that this case will not “turn into a patent version of Penelope’s robe,” in other words, that the Court and the parties were “not going to unravel anything [that the Court has] woven thus far which has not been unraveled by a higher court,” the Court made the following findings and rulings. First, it ruled that it would hear and take evidence on the reverse doctrine of equivalents as it related to the ’698 patent and that HMR/TKT could address other patent defenses. 9/18/03 Final Pretrial Conf. Tr. at 6: 4-16. Second, it ruled that Amgen had met its burden (outlined in
Festo II)
of proving that the prosecution history does not estop it from arguing equivalent infringement with regard to the ’080 patent and it affirmed its earlier
*221
finding that HMR/TKT infringes claims 2-4 of the ’080 patent.
Id.
at 7: 17-8: 5. It explained that it would issue a full opinion at a later date but that it might have to revisit the
Festo
issue due to the rapidly-developing law in that area.
Id.
at 7: 19-25. The Court then turned to the ’349 patent and explained that it would allow Amgen to put on rebuttal evidence as to the matter of obviousness and Sugimoto only and it made clear that the Court would not accept other evidence from HMR/TKT regarding the ’349 patent.
Id.
at 8: 12-19, 16: 5-6 (“As far as evidence goes, ’349 is in the can and I’m done with it.”). The Court then issued a revised claim construction of “therapeutically effective” based on a more thorough analysis of the claims, specification, and prosecution history.
Id.
at 9: 3-10: 25. The Court mentioned, however, that this revision may have made the third sentence of the construction unnecessary and, therefore, reserved its right to further consider the proper construction.
Id.
at 10: 21-25. It directed the parties to try the case based on the construction it had just issued along with a construction that eliminated the third sentence.
Id.
at 11: 1-5. The pretrial conference was continued until September 24, 2003.
Id.
at 30: 22-23.
During the further pretrial conference, the Court reviewed the issues to be tried and outlined the procedure for trial and the parameters for the introduction of evidence and expert testimony.
See
9/24/03 Final Pretrial Conf. Tr. After the Court provided both parties with an opportunity to be heard on the subject, pursuant to Federal Rule of Civil Procedure 53(b)(1), the Court appointed Michele D. Beardslee as Special Master, beginning January 1, 2004, to assist the Court in research, analysis, and drafting of the forthcoming opinion. Order re Special Master [Doc. No. 801];
see also
11/07/03 Beardslee Aff. [Doc. No. 799].
14
The trial on remand was set to commence on October 7, 2003. 9/24/03 Final Pretrial Conf. Tr. at 40: 23.
On October 30, 2003, the Court issued an opinion supporting its ruling that Am-gen had successfully rebutted the presumption of prosecution history estoppel as outlined in
Festo II
and, therefore, was not estopped from asserting equivalent infringement of the ’080 patent.
Amgen, Inc. v. Hoechst Manon Roussel, Inc.,
287 F.Supp.2d 126 (D.Mass.2003)
(“Amgen III”).
15
The remanded trial lasted nine days over the course of four and a half weeks.
16
*222
All the remaining issues — those remanded to the Court from the Federal Circuit and those raised by the parties in the course of this remanded trial — are addressed herein.
17
III. CLAIM CONSTRUCTION
As expounded in great detail in
Amgen I ,
this Court strongly believes in the importance of construing patent claims without regard to the alleged infringement issues.
Amgen I,
126 F.Supp.2d at 80-81 ;
MediaCom Corp. v. Rates Tech., Inc.,
4 F.Supp.2d 17, 21-24 (D.Mass.1998);
see also
Anthony R. Zeuli & Rachel Clark Hughey,
Avoiding Patent Claim Construction Errors: Determining the Ordinary and Customary Meaning Before Reading the Written Description,
Fed. Law., June 2004, at 29. One way to avoid conflating issues of fact and law and to ensure division between the fact finding and law explaining roles in a patent case is to hold the
Markman
hearing prior to and separate from the summary judgment motion hearing. Although (as mentioned above) this Court held the
Markman
hearing for the trial on remand on the same day as the summary judgment motions hearing, it kept the hearings independent of one another by separating the hearing into two parts. The first part dealt with claim construction. Then the Court held a recess, issued its preliminary constructions, and moved on to the summary judgment motions hearing.
The Court followed its usual procedure in conducting the
Markman
hearing. The Court entertained oral argument from counsel for each party. Counsel referred the Court to the relevant portions of the patent, specification, and prosecution history. Demonstrative exhibits were presented and references were made to certain expert testimony, but extrinsic evidence was not admitted.
At the conclusion of the
Markman
portion of the hearing the Court interpreted “therapeutically effective” and “DNA encoding”' — cautioning that they were “working constructions” — and held off deciding whether the asserted claims of the ’349 and ’698 patent were step-plus-function claims. The Court then announced during the July 31, 2003 hearing that it did not construe the asserted claims of the ’349 and ’698 patents as step-plus-function claims. During the pretrial conference on September 18, 2003, after the Court had engaged in a more careful review of the patents, specification, and prosecution history, the Court issued a revised claim construction for “therapeutically effective.” The final claim constructions are reproduced and explained below.
18
A. “Therapeutically Effective”
1. Background
The term “therapeutically effective” is contained in claim 1 of the ’422 patent and claim 4 of the ’080 patent.
19
As
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mentioned above, although this phrase was not construed during the first trial, in determining whether prior art anticipated the ’422 and ’080 patents, the Court interpreted the term to mean an increase in hematocrit:
Such evidence [of e.g., increased eryth-roid marrow stimulation] should be outweighed by the fact that the
actual
production of mature red blood cells was not achieved and, as a result, hematocrit levels were unchanged. Because an increase in hematocrit and hemoglobin levels is the true mark of therapeutic effectiveness, Dr. Goldwasser’s study, which revealed only inchoate indicators of red blood cell production, falls far short of anticipating claims requiring a therapeutic amount of human EPO.
Amgen I,
126 F.Supp.2d at 112 ;
see also id.
at 99 (“The therapeutic effectiveness or benefit of an erythropoietin preparation is shown by demonstrating a correction in anemia by increasing and maintaining the hematocrit of a patient to normal or near normal levels.”).
The Federal Circuit, in addition to remanding so that the Court could construe the term pursuant to
Markman ,
provided some guidance. It agreed that the “endgame in the treatment of chronically anemic patients is to increase the hematocrit,” but pointed out that the term should be construed in light of the specification.
Amgen II,
314 F.3d at 1353 . It stated, however, that the “specification appears to teach that results in addition to simply an increase in hematocrit can provide effective therapy.”
Id.
(citing ’933 Patent, col. 33: 19-31). It pointed out that Amgen was arguing that one skilled in the art would construe “therapeutically effective” as “increasing and maintaining the patient’s hematocrit to normal or near normal levels,” but that “the relevant question is not whether one of ordinary skill would so understand the term, but whether that term should be limited based upon the express disclosure in the specification.”
Id.
at 1353-54 (citing
CCS Fitness v. Brunswick Corp.,
288 F.3d 1359, 1367 (Fed.Cir.2002) (“[A] claim term will not carry its ordinary meaning if the intrinsic evidence shows that the patentee distinguished that term from prior art on the basis of a particular embodiment, expressly disclaimed subject matter, or described a particular embodiment as important to the invention.”)). The Federal Circuit stated that it appeared that the term “therapeutically effective” encompassed the list of effects described in the specification and noted that if the Court also held this to be true, then the Goldwasser study may indeed invalidate some of the claims at issue in this case under 35 U.S.C. § 102 (a) or § 103.
Id.
at 1354 (“If the claim term ‘therapeutically effective’ encompasses the patient responses described in the specification,
as it appears to us it does,
then the Goldwasser study may constitute invalidating prior art under § 102(a) or § 103 even if he did not achieve his intended result.”) (emphasis added). Therefore, it vacated this Court’s determination that Goldwasser did not constitute prior art
20
and ordered this Court to construe the term and thereafter determine whether Goldwasser invalidates any of the asserted patents.
Id.
2. The Claims at Issue
The actual words of the claims are as follows:
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’422 Claim 1:
A pharmaceutical composition comprising a
therapeutically effective
amount of human erythropoietin and a pharmaceutically acceptable diluent, adjuvant or carrier, where insaid erythropoietin is purified from mammalian cells grown in culture.
’422 Patent, Ex. 1, col. 88: 36-41 (emphasis added).
21
’080 Claim 4:
A pharmaceutical composition comprising a
therapeutically effective
amount of an erythropoietin gly-coprotein product according to Claim 1, 2, or 3.
’080 Patent, Ex. 1, col. 38: 51-53 (emphasis added).
3. Summary of the Parties’ Arguments
Amgen urges adoption of the ordinary meaning of “therapeutically effective” given by those skilled in the art. Amgen’s Mem. in Support re ’422/’080 [Doc. No. 671] at 7. Specifically, it argues that (1) expert testimony shows that the ordinary meaning of “therapeutically effective” is “sufficient to produce a sustained increase in hematocrit,” and that the term requires a therapeutic — not merely biological — effect; (2) the other effects listed in the specification, to which the Federal Circuit referred, are known biological effects of EPO, not the intended therapeutic effects; (3) the specification taken as a whole supports the plain meaning of “therapeutically effective,” and that no special meaning was given to the term; (4) the prosecution history shows that Amgen specifically noted that its invention shares the same in vivo biological activity as naturally occurring human EPO, but differentiated its invention from prior art by pointing out that human recombinant EPO (unlike naturally-occurring human EPO) is not a viable, effective human therapeutic product; and (5) the doctrine of claim differentiation requires that this term have a different meaning than the recitation of EPO’s biological activities.
Id.
at 8-17. In its reply memorandum, Amgen also argues that the dictionary definition of the term supports its asserted meaning. Amgen’s Reply re ’422/’080 [Doc. No. 730] at 5-6.
HMR/TKT, on the other hand, argues that the Federal Circuit made clear that it believed that the term “therapeutically effective” encompasses all of the effects set forth in the specification described. HMR/ TKT’s Mem. in Opp’n re ’422/’080 [Doc. No. 702] at 5. Thus, it argues, the term encompasses those effects observed in the Goldwasser study.
Id.
at 6. Moreover, it asserts that Amgen is trying to import limitations from the specification to make the claims require an increase in the he-matocrit levels when the claims contain no language indicating such a requirement and the specification language itself is actually inconsistent with such a requirement. HMR/TKT points to the same section of the specification as did the Federal Circuit did to make its point:
[T]o the extent that polypeptide products of the invention share the in vivo activity of natural EPO isolates
they are conspicuously suitable for use in erythropoietin therapy procedures
practiced on mammals, including humans,
to develop any or all of the effects herefore attributed in vivo to EPO,
e.g., stimulation of reticulocyte response, development of ferrokinetic effects ... erythrocyte mass changes, stimulation of hemoglobin C syntheses ... and, as in
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dicated in Example 10, increasing he-matocrit levels in mammals.
Id.
at 13 (quoting ’933 Patent, Ex. 1, col. 33: 19-31). This, HMR/TKT asserts, makes clear that “erythropoietin therapy procedures” include procedures that “develop any or all of the effects heretofore attributed in vivo to EPO,” and, therefore, “therapeutically effective amount” includes any or all of the effects listed in this portion of the specification — which, HMR/ TKT argues, are defined in terms of biological effects.
Id.
at 14. HMR/TKT further argues that Amgen is trying to rely on isolated references of the specification to restrict the term meaning when these restrictions are not apparent in the plain language, and when the intrinsic record, as a whole, supports a broader interpretation.
Id.
at 16.
4. Discussion
While the Federal Circuit indeed mentioned that the term “therapeutically effective” appeared to encompass the biological effects listed within lines 19-31 of column 33, the Court notes that the Federal Circuit did not, in
Amgen II,
actually construe the term “therapeutically effective.”
See Amgen II,
314 F.3d at 1324 (noting that the Federal Circuit considers claim construction “afresh” on appellate review);
Bayer AG. v. Biovail Corp.,
279 F.3d 1340, 1349 (Fed.Cir.2002) (noting that, notwithstanding its
de novo
review, “it would be premature for this court to engage in its own claim construction without ... evidence of the meaning of the terms to one of skill in the art at the time of the invention”). On the contrary, the Federal Circuit remanded that task to this Court. To perform it properly, however, the Court must consider the prosecution history in addition to the claims and the specification — something that the Federal Circuit did not do.
See Amgen II,
314 F.3d at 1324 (“To properly construe the claims, a court must examine the claims, the rest of the specification, and if in evidence, the prosecution history.”);
Vitronics Corp. v. Conceptronic, Inc.,
90 F.3d 1576, 1582 (Fed.Cir.1996) (“[I]t is well-settled that, in interpreting an asserted claim, the court should look first to the intrinsic evidence of record, i.e., the patent itself, including the claims, the specification and, if in evidence, the prosecution history.”);
SRI Int’l v. Matsushita Elec. Corp. of Am.,
775 F.2d 1107, 1118 (Fed.Cir.1985) (noting that a claim is construed in light of its language, the specification, and the prosecution history). Moreover, the Court must begin by determining what the plain and ordinary meaning of “therapeutically effective” is in order to determine whether Amgen has become its own lexicographer.
Intellectual Prop. Dev., Inc. v. UA-Columbia Cablevision of Westchester, Inc.,
336 F.3d 1308, 1315 (Fed.Cir.2003) (“Consulting the written description and prosecution history as a threshold step in the claim construction process, before any effort is made to discern the ordinary and customary meanings attributed to the words themselves, invites a violation of our precedent counseling against importing limitations into the claims.” (quoting
Texas Digital Systems, Inc. v. Telegenix, Inc.,
308 F.3d 1193, 1204 (Fed.Cir.2002)) (internal quotation marks omitted)).
a. The Plain and Ordinary Meaning
Generally, it is the plain and ordinary meaning of the words — as defined by one skilled in the relevant art — that governs.
Vitronics,
90 F.3d at 1582 ; Erik Paul Belt,
Federal Circuit Stresses Ordinary Meaning,
Nat’l L.J., Sept. 22, 2003, at SI. Amgen argues that the plain and ordinary meaning of the term “therapeutically effective” is “sufficient to produce a sustained increase in hematocrit.” HMR/ TKT argues, on the other hand, that the
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plain and ordinary meaning of “therapeutically effective” is not so restricted.
22
Interestingly, HMR/TKT never states what it believes the plain and ordinary meaning of the term to be — it only discusses the meaning of the term with reference to how it believes Amgen has so defined it in the specification and prosecution history.
Amgen, on the other hand, grounds its assertion of the plain and customary meaning of the disputed term upon expert testimony. This, however, is extrinsic evidence to which resort ought be had only
“if necessary.” Vitronics,
90 F.3d at 1583 (quoting
Hormone Research Foundation, Inc. v. Genentech, Inc.,
904 F.2d 1558, 1562 (Fed.Cir.1990)). Therefore, the Court does not begin by considering this evidence. Instead, it turns first to the dictionary and to technical treatises to decipher the plain and ordinary meaning of “therapeutically effective.”
See id.
at 1584 & n. 6 (noting that judges are free to consult technical treatises and dictionaries in order to gain a better understanding of the claims and to interpret them, “so long as the dictionary definition does not contradict any definition found in or ascertained by a reading of the patent documents.”).
23
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The dictionary definition of “therapeutic” is “[h]aving healing or curative powers,” or “[o]f or relating to the treatment of disease or disorders by remedial agents or methods.”
The American Heritage Dictionary
1260 (2d college ed.1985);
Webster’s Ninth New Collegiate Dictionary
1223 (1984), attached as Tab X to Supp.App. [Doc. No. 735] to Amgen’s Reply re ’422/’080;
see also Chamber’s Technical Dictionary
844 (3d ed.1961), attached as Tab W to Supp.App. to Amgen’s Reply re ’422/’080 (“Of, or pertaining to, the medical treatment of disease: remedial: curative”). The definition of therapeutics is “[t]he medical treatment of disease.”
The American Heritage Dictionary, supra,
at 1260. The dictionary definition of “effective” is “[h]aving an intended or expected effect” or “[pjroducing or designed to produce the desired impression or response.”
Id.
at 439.
Based on these definitions alone, one would surmise that a “therapeutically effective” amount is one that produces healing or curing as it relates to medical treatment of disease.
24
This is, in essence, consistent with the definition that Amgen proposes.
See
Amgen’s Mem. in Support re ’422/’080 [Doc. No. 671] at 14 (arguing that the ordinary meaning is an amount sufficient to “cure or relieve a disease state” and “require[s] a meaningful benefit to the health of patients”). Amgen, however, goes further, asserting that the plain and ordinary meaning of “therapeutically effective amount,” to one skilled in the art, taken in the context of this patent, is an amount that provides more than the biological effects of EPO and “produce[s] a
*229
sustained increase in hematocrit,” because only this result provides a meaningful benefit to the health of patients suffering from anemia.
25
Id.
at 7-8, 14. Neither the claims, the specification, nor the prosecution history, however, demonstrate clearly that the plain and ordinary meaning of the term to one skilled in the art involves an increase in hematocrit. Therefore, the Court begins with the assumption that the plain and ordinary meaning of “therapeutically effective amount” is one in line with that found in the dictionaries and treatises noted above — i.e., one that heals or cures as it relates to medical treatment of disease.
The next step is to look to the claims, specification, and prosecution history to see if Amgen redefined the term in the file wrapper. In addition, the Court will look to these sources to determine whether the file wrapper indicates clearly the types of patients for which this product is “therapeutically effective” and thus infuses the term with real meaning. Indeed, this is the elephant in the room. Without tackling this question, the term “therapeutically effective” or “therapeutically effective amount” is vague and meaningless. The public must know upon reading the patent what disease state is cured or healed by the product.
26
As the Federal Circuit pointed out, “indiscriminate reliance on definitions found in dictionaries can often produce absurd results.... One need not arbitrarily pick and choose from the various accepted definitions of a word to decide which meaning was intended .... The subject matter, the context, etc., will more often than not lead to the correct conclusion.”
Renishaw PLC v. Marposs Societa’ per Azioni,
158 F.3d 1243, 1250 (Fed.Cir.1998) (quoting
Liebscher v. Boothroyd,
258 F.2d 948 , 46 C.C.P.A. 701 (1958)) (first alteration in original). Thus, the Court, in addition to determining whether Amgen has expanded or confined the meaning of the disputed term, will look to the file wrapper to clarify this ambiguity.
b. The Claims
“The name of the game is the claim.”
Amgen I,
126 F.Supp.2d at 80 (quoting Giles S. Rich,
Extent of Protection and Interpretation of Claims
— Amer
ican Perspectives,
21 Int’l Rev. Indus. Prop. & Copyright L. 497, 499 (1990)) (internal quotation marks omitted). Thus, the first step in claim construction is to look to the plain and ordinary meaning of the words of the patent claim to determine the meaning of a term.
Vitronics,
90 F.3d at 1582 ;
Bell Communications Research, Inc. v. Vitalink Communications Corp.,
55 F.3d 615, 619-20 (Fed.Cir.1995);
Renishaw,
158 F.3d at 1248 (“[T]he claim construction inquiry, therefore, begins and ends in all cases with the actual words of the claim_[T]he resulting claim interpretation must, in the end, accord with the words chosen by the patentee to stake out the boundary of the claimed property.”).
Do the claims redefine the plain and ordinary meaning of the terms used? Am-gen asserts that the claims do not support HMR/TKT’s argument that it has redefined the term to include the biological effects of EPO. Amgen asserts that be
*230
cause claim terms are construed to give each term meaning,
Lantech, Inc. v. Keip Mack Co.,
32 F.3d 542, 546 (Fed.Cir.1994), the patent claims themselves distinguish between biological and therapeutic effects. Amgen’s Reply re ’422/’080 at 10. To make its point, it refers to claims 4 and 2 of the ’080 patent.
’080 Claim, 4:
A pharmaceutical composition comprising a therapeutically effective amount of an erythropoietin gly-coprotein product according to claim 1, 2, or 3.
’080 Claim 2:
An isolated erythro-poietin glycoprotein having the in vivo biological activity of causing bone marrow cells to increase production of reti-culocytes and red blood cells, wherein said erythropoietin glycoprotein comprises the mature erythropoietin amino acid sequence of FIG. 6 and is not isolated from human urine.
Amgen asserts that under the doctrine of claim differentiation, claim 4 of the ’080 patent must not include any or all of the effects listed in the specification because otherwise claim 4 would be identical to that of claim 2. Specifically, it points out that claim 4 of the ’080 patent requires “[a] pharmaceutical composition comprising a therapeutically effective amount” of EPO according to claim 1, 2, or 3. Amgen’s Mem. re ’422/’080 at 15-16. It then asserts that the claim 2 requires the “in vivo biological activity of causing bone marrow cells to increase production of reticulocytes and red blood cells.” Therefore, if “therapeutically effective” included the effects listed in the specification to which the Federal Circuit pointed, Amgen argues, it would include the in vivo biological activity cited by claims 1, 2, or 3 of the ’080 patent and render claim 4 of the ’080 patent superfluous.
Id.
at 16.
As HMR/TKT urges, however, this argument is flawed because claim 4 concerns a
pharmaceutical composition
comprising a “therapeutically effective amount” of an
EPO
that happens to have the qualities described in claim 2. HMR/TKT’s Opp’s re ’422/’080 at 22. HMR/TKT correctly points out that claim 2 recites an isolated EPO glycoprotein and therefore refers to biological effects whereas claim 4 recites a pharmaceutical composition and involves therapeutic effects.
Id.
at 21-22. Hence, claim 2 would not be rendered superfluous if this Court construed “therapeutically effective” to include the biological effects listed in the specification.
Id.
at 22.
Another equally flawed argument is that claim 4, by encompassing claim 2 (in referring to a “therapeutically effective” amount of the product claimed in claim 2), indicates that a
“therapeutically effective
amount” is one that does more than cause the in vivo biological activities described in claim 2. After a careful review of the technology and its history, it is clear that this is not a correct reading of the claims. This review relied on extrinsic evidence, as is permissible under Federal Circuit precedent.
Vitronics,
90 F.3d at 1584 (noting that a court may resort to extrinsic evidence and expert testimony to help it understand the technology);
Altiris, Inc. v. Symantec Corp.,
318 F.3d 1363, 1371 (Fed.Cir.2003) (“In this regard, the expert testimony serves the permissible purposes of aiding our understanding of the technology and in helping us view the patent through the eyes of the skilled artisan.”).
27
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Before Amgen’s invention, human EPO was known to elicit certain biological effects, but it was impossible to extract an efficient amount of it for use in treatment of patients with anemias and other low red blood cell disorders. Amgen invented a product, recombinant EPO, that had the same in vivo biological effects as natural EPO but differed in its carbohydrate composition and was capable of manufacture in quantities large enough to provide effective treatment.
With this understanding of the technology, it is clear that claims 2 and 4 of the ’080 patent, by themselves, do not define “therapeutically effective” beyond its plain and ordinary meaning, nor do they indicate that a “therapeutically effective amount” of EPO is one that does more than elicit the biological effects noted in claim 2. Instead, claim 2 stakes out Am-gen’s novel recombinant EPO that has the same in vivo biological activities of natural EPO (causing bone marrow cells to increase production of reticulocytes and red blood cells). Claim 4 sets out a pharmaceutical composition that has a novel amount of the EPO — an amount that can actually treat or cure patients. Notably, these claims do not indicate whether biological effects are themselves sufficient to treat or cure patients.
Similarly, the claims of the ’422 patent do not define a “therapeutically effective amount” as one that does something above and beyond eliciting the biological effects of EPO listed in the specification.
The next question is whether the claims themselves indicate for what types of patients this product is “therapeutically effective.” Amgen contends that its EPO is specifically designed for those suffering from anemias and thus only an increase in hematocrit is “therapeutically effective.” Indeed, the record shows that Amgen’s product
can
be used to increase levels of hematocrit, in other words, it
can
be used to “cure” or “relieve” the diseased state brought on by anemia.
Amgen I,
126 F.Supp.2d at 99 (“The therapeutic effectiveness or benefit of an erythropoietin preparation is shown by demonstrating a correction in anemia by increasing and maintaining the hematocrit of a patient to normal or near normal levels.”).
28
Dr. Er-slev testified at the first trial that a sustained increase in hematocrit and hemoglobin is required to determine whether or not anemia has been corrected. Erslev Test., Trial Tr. at 1688: 14-1689: 4; Means Test., Trial Tr. at 1905: 17-20; 1910: 9-13. Dr. Erslev also testified that the other effects listed in the specification such as an increase in reticulocyte count or an increase in iron uptake cannot — each standing alone — correct anemia. Erslev Test., Trial Tr. at 1688: 14-1689: 4.
The problem with Amgen’s argument, however, is that the claims that contain the disputed term do not themselves include a limitation directed to the specific clinical benefit of correcting
anemia.
Therefore, the plain and ordinary meaning of “therapeutically effective” cannot be limited to curing
anemia,
i.e., producing an increase in hematocrit levels based on the claims
*232
alone. The claim language simply does not allow for such a specific interpretation. This conclusion is further supported by the fact that claim 6 of the ’080 patent (unlike claim 4) does indeed specify the type of treatment (kidney dialysis) for which the EPO should be used and calls out, in that context, that an effective amount is one that increases hematocrit:
’080 Claim 6:
A method for treating a kidney dialysis patient which comprises administering a pharmaceutical composition of claim 4 in an amount effective to increase the hematocrit level of said patient.
’080 Patent, Ex. 1, col. 38: 57-60. Had Amgen used similar claim language in claim 4 — that is, had it referred specifically to anemia — then its argument would have merit. Based on the non-specific language of claim 4, however, this argument fails.
In sum, the claim language supports only the plain and ordinary definition of “therapeutically effective” — an amount that produces a result that, in and of itself, helps to heal or cure. The language of the claims at issue does not delineate the type of disease for which the EPO is “therapeutically effective.” Therefore, the Court must now turn to the specification and the prosecution history to determine whether Amgen has limited or altered the plain meaning of the term either by defining the term or specifying the disease states for which the product is intended.
c. The Specification
The second step in claim construction is to review the specification to determine whether the patentee has used terms in a manner inconsistent with the ordinary meaning or has become his own lexicographer.
Vitronics,
90 F.3d at 1582 . In essence, “[t]he specification acts as a dictionary when it expressly defines terms used in the claims or when it defines terms by implication.”
Id.
(noting that the specification is “the single best guide to the meaning of a disputed term”). The Federal Circuit has stated that “a claim must be read in view of the specification of which it is part,” and therefore, a court can use the written description to define a term that is already in a claim limitation.
Renishaw,
158 F.3d at 1248 ;
SciMed Life Sys. v. Advanced Cardiovascular Sys.,
242 F.3d 1337, 1341 (Fed.Cir.2001) (noting that claims can be given a narrow construction in light of the written description and explaining that one reason to look to the specification is “to determine if the paten-tee has limited the scope of the claims” (quoting
Watts v. XL Systems, Inc.,
232 F.3d 877, 882 (Fed.Cir.2000))).
The part of the specification to which the Federal Circuit in
Amgen II
pointed is as follows:
Similarly,
to the extent
that polypeptide products of the invention share the in vivo activity of natural EPO isolates they are conspicuously suitable for use in erythropoietin therapy procedures practiced on mammals, including humans, to develop any or all of the effects
herefore
attributed in vivo to EPO, e.g., stimulation of reticulocyte response, development of ferrokinetie effects (such as plasma iron turnover effects and marrow transit time effects), erythrocyte mass changes, stimulation of hemoglobin C synthesis (see, Eschbach, et al., supra)
and,
as indicated in Example 10, increasing hematocrit levels in mammals.
’933 Patent, Ex. 1, col. 33: 19-31 (emphases added).
The Court begins by analyzing whether this section defines therapeutically effective to include the effects listed above. It is undisputed that this section declares that Amgen’s recombinant EPO is similar to natural EPO in that it shares some of the same in vivo activity.
Id.
at col. 33:
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19-22.
“[T]o the extent
” that it does so— to the extent that it is similar to natural EPO — Amgen’s EPO are “conspicuously suitable for use in erythropoeitin therapy procedures” to develop any or all of the effects that were “herefore” (before) attributed in vivo to EPO, such as the stimulation of reticulocyte response, development of ferrokinectic effects, erythrocyte mass changes, and stimulation of hemoglobin C synthesis. What is unclear and disputed, however, is whether the section that begins with “and, as indicated in Example 10, increasing hematocrit levels in mammals” is part of the laundry list of effects previously attributed in vivo to EPO or a separate suitable use for the product. In other words, this portion of the specification can be interpreted one of the following two ways:
1) Amgen’s EPO is “conspicuously suitable for use in erythropoietin therapy procedures practiced on mammals, including humans, to develop any or all of the effects herefore attributed in vivo to EPO, e.g., stimulation of reticulocyte response, ... and, as indicated in Example 10, increasing hematocrit levels in mammals.”
2) Amgen’s EPO is “conspicuously suitable for” (a) “use in erythropoietin therapy procedures practiced on mammals, including humans, to develop any or all of the effects herefore attributed in vivo to EPO, e.g., stimulation of reticulocyte response, ...”
and,
(b) “as indicated in Example 10, increasing hematocrit levels in mammals.”
The former interpretation — a direct quote of the specification — suggests that an increase in hematocrit level was an effect previously attributed to natural EPO and that it, along with the biological effects, are a type of effective therapy. In other words, it includes “increasing the hematocrit levels” as
one of the many effects
of EPO that were previously identified and that are now produced by this product and useful in “erythropoietin
therapy
procedures.” The problem with this reading is that the intrinsic evidence (the claims, the specification, and the prosecution history) and extrinsic evidence suggest that an increase in hematocrit levels was
not
previously attributed to natural EPO.
29
In remarks following an amendment made during prosecution of the ’080 patent, Amgen explained to the Patent, and Trademark Office (“PTO”) that Example 10 is novel in that it is the first therapeutic procedure ever practiced with EPO to demonstrate that EPO has the capacity to generate an increase in hematocrit in vivo. Amgen’s ’422/’080 App., Tab G (Ex. 2), at Tab 6, at 179. The extrinsic record also suggests that an increase in hematocrit was not previously attributed to natural EPO.
Vitronics,
90 F.3d at 1583 (“Included within an analysis of the file history may be an examination of the prior art cited therein.”). Therefore, the first reading implies a factually incorrect conclusion.
The latter interpretation — and the one that the Court adopts — suggests that an increase in hematocrit is independent or different from the in vivo effects previously attributed to natural EPO. In other words, in this section, Amgen calls out that its recombinant EPO can elicit “any or all” of the effects that natural EPO does — and more. Admittedly, the use of the words “therapy procedures” supports the interpretation that a “therapeutically effective amount” encompasses an amount that would result in the biological effects because it implies that the effects are a part
*234
of therapy. That being said, however, the way in which the increase in hematocrit is set off from the rest of the language suggests that this product elicits something in addition to what the prior art elicited, something more than the biological effects. Moreover, it makes clear that “any or all” only modifies those effects previously attributed to natural EPO — not the increase in hematocrit. Indeed, if the phrase “as indicated in Example 10, increasing hemat-ocrit levels in mammals” were merely an item in the list of “any or all of the effects herefore attributed in vivo to EPO,” then the words “in mammals” would be redundant. The list of items refers to “effects herefore attributed in vivo to EPO” for “use in erythropoietin therapy procedures practiced
on mammals
”,
so
“increasing hematocrit levels
in mammals
” must be a second end for which Amgen’s EPO is “conspicuously suitable.”
This interpretation comports with the Court’s understanding — developed over the course of two intensive trials — of what hematocrit actually measures. Hematocrit measures the ability of the blood to supply oxygen to the body. It indicates the relative proportion of red blood cells to the total volume of blood. By introducing additional EPO into the patient’s body, a patient’s hematocrit level can be increased to and sustained at or near normal levels. In other words, the blood is able to provide a steady supply of sufficient oxygen to the tissues. It is the Court’s understanding that, in
most
cases, an increase in hemato-crit is accompanied, if not preceded, by “any or all” of the biological effects listed in the specification.
30
In other words, this portion of the specification explains what happens when a “therapeutically effective amount” of EPO is used — that is, it produces an increase in hematocrit — along with any or all of the biological affects previously attributed to natural EPO. As will be discussed below, this reading is further supported by other parts of the specification and the prosecution history.
Therefore, while this Court agrees with the Federal Circuit that therapeutic effectiveness “encompasses the patient responses described in the specification,” this part of the specification does not indicate that these biological responses are sufficient or that Amgen “broadened” the plain meaning of the term “therapeutically effective” to encompass the elicitation of biological effects alone regardless of whether they heal or cure. Indeed, the term “therapeutically effective” is never even mentioned in this section of the specification. While guidance as to a claim term’s meaning or a claim’s scope need not be provided in explicit definitional format,
SciMed Life Systems,
242 F.3d at 1344 , to alter the plain and customary meaning of a term that is not ambiguous on its face, a patentee must do so clearly and deliberately.
Renishaw,
158 F.3d at 1249 (noting that when a patent applicant “has elected to be a lexicographer by providing an explicit definition in the specification for a claim term[,] ... the definition selected by the patent applicant controls” as long as the patentee’s lexicography is made “ ‘with reasonable clarity, deliberateness, and precision’ ” (quoting
In re Paulsen,
30 F.3d
*235
1475, 1480 (Fed.Cir.1994)));
Vitronics,
90 F.3d at 1582 ;
Altiris,
318 F.3d at 1370 .
31
Here, there is no “manifest exclusion or restriction, representing a clear disavowal of claim scope.”
Teleflex, Inc. v. Ficosa N. Am. Corp.,
299 F.3d 1313, 1325 (Fed.Cir.2002). Thus, this portion of the specification does not redefine the plain and ordinary meaning of the term to include the biological effects regardless of whether they heal or cure. Likewise, this portion of the specification does not limit the term to an increase in hematocrit. While it makes clear that its product is useful because it can increase hematocrit, it does not redefine the term in question to equate only with an increase in hematocrit (or relate only to curing anemia).
Amgen points to a few other portions of the specification in support of its argument that while it did not alter the meaning of “therapeutically effective” to include the biological effects, it did limit the claimed therapy to patients suffering from anemia and anemia-like disorders and likewise limited the claim to an increase in hemato-crit.
32
The first such passage is the one immediately following the portion of the specification cited by the Federal Circuit:
Included within
the class of humans treatable with products of the invention are patients generally requiring blood transfusion and including trauma victims, surgical patients, renal disease patients including dialysis patients, and patients with a variety of blood composition affecting disorders, such as hemophilia, sickle cell disease, physiologic anemias, and the like.
’933 Patent, Ex. 1, col. 83: 31-36 (emphasis added).
33
As HMR/TKT correctly points out, this list of patients is obviously incomplete as it begins with the words “included within,” which suggests that there are other types of patients for which the product is intended. HMR/TKT’s Posb-Hr’g Mem. [Doc. No. 747] at 4. While this is true, it still provides insight into the type of patients who may receive a therapeutic benefit from the pharmaceutical compositions of the invention. Therefore, while the specification does not actively limit the term to this class of patients, it provides guidance to the Court in defining the term.
Vitronics,
90 F.3d at 1582 ;
Teleflex, Inc.,
299 F.3d at 1325 (“The specification may assist in resolving ambiguity where the ordinary and customary meaning of the words used in the claims lack sufficient clarity to permit the scope of the claim to be ascertained from the words alone.”). By listing the types of patients responding to treatment by the product, the specification implies that the term “therapeutically effective” amount was written with respect
*236
to these types or classes of patients. “The specification acts as a dictionary when it expressly defines terms used in the claims or when it defines terms by
implication.” Vitronics,
90 F.3d at 1582 (emphasis added).
34
It does not, however, indicate that this invention is only for the treatment of anemia but instead for all the ailments listed. While this may not be an exhaustive list and patients with similar or like disorders might also benefit from the product, this list begins to infuse “therapeutically effective amount” with real meaning.
Other portions of the specification support interpreting the claims with reference to the class of patients listed in the specification. For example, the specification states: “The minimization of the need for transfusion therapy through use of EPO therapy can be expected to result in reduced transmission of infectious agents.” ’933 Patent, Ex. 1., col. 33: 37-39. While this is only one example of how the product is useful or advantageous, it falls within the class of patients listed in the specification.
35
Other pertinent sections are as follows:
It has recently been estimated that the availability of erythropoietin in quantity would allow for treatment each year of anemias of 1,600,000 persons in the United States alone.
Id.
at col. 6: 35-39.
... clinical testing and potential wide-ranging
therapeutic use
of [Lin’s recombinant EPO] in treatment of e.g., chronic kidney disease wherein diseased tissues fail to sustain production of er-ythropoietin.
Id.
at col. 9: 6-9 (emphasis added).
Also
comprehended by the invention are pharmaceutical compositions comprising effective amounts of polypeptide products of the invention together with suitable diluents, adjuvants and/or carriers which allow for provision of erythro-poietin therapy,
especially in
the treatment of anemic disease states and most especially such anemic states as attend chronic renal failure.
Id.
at col. 12: 1-7 (emphasis added).
Because erythropoietin is essential in the process of red blood cell formation, the hormone has potential useful application in both the diagnosis and the
treatment
of blood disorders characterized by low or defective red blood cell production.
*237
Id.
at col. 6: 20-24 (emphasis added).
36
Amgen also points to column 6, lines 28-33 of the ’933 patent, which cites a study-done by Eschbaeh:
See, generally, ... Eschbaeh, et al[.] ... describing a therapeutic regimen for uremic sheep based on in vivo response to erythropoietin-rich plasma infusions and proposing a dosage of 10 U EPO/kg per day for 15-40 days as corrective of anemia of the type associated with chronic renal failure.
That Amgen intended its invention to treat anemic patients is clear from these sections (along with the prosecution history, as will be discussed below) and is pertinent to the analysis.
Renishaw,
158 F.3d at 1250 (noting that what the “inventors actually invented and intended to envelop with the claim” is relevant in claim construction);
CVI/Beta Ventures v. Tura LP,
112 F.3d 1146 , 1160 (Fed.Cir.1997) (“In construing claims, the problem the inventor was attempting to solve, as discerned from the specification and the prosecution history, is a relevant consideration.”). None of these sections, however, shows that Amgen intentionally re-defined the plain meaning of the term “therapeutically effective” to refer exclusively to anemia or to an increase in hematocrit.
While these sections do not suggest that the product is solely intended for anemic patients and to increase hematocrit, they do imply, in combination, that it is designed for the class of patients listed in column 33 and noted above.
37
That being said, it seems to stretch the doctrine of claim construction too far to incorporate into the plain and ordinary meaning a reference to a class of patients that at best is only implied in the specification.
Northern Telecom Ltd. v. Samsung Elees. Co.,
215 F.3d 1281, 1294 (Fed.Cir.2000);
EX Indus., L.P. & Koslow Technologies Corp.,
18 Fed. Appx. 871, 876 (Fed.Cir. Aug.10, 2001) (unpublished opinion)
38
(“[W]hat is determinative is whether the patentee has defined a claim term as excluding a broader interpretation with reasonable clarity and deliberateness.”). On the other hand, it seems foolish to construe a term such as “therapeutically effective,” without reference to a class of patients for which the product is intended to be “therapeutically effective.” This quandary, however, is put to rest by the prosecution history. When the specification is considered along with the prosecution history, it becomes apparent that a class-of-patients limitation is appropriate.
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d. The Prosecution History
The third step in claim construction is to consider the prosecution history to determine whether the applicant has made any express representations regarding the claim’s scope.
Vitronics,
90 F.3d at 1582-83 ;
Standard Oil Co. v. American Cyanamid Co.,
774 F.2d 448, 452 (Fed.Cir.1985) (“[A]ll express representations made by or on behalf of the applicant to the examiner to induce a patent grant ... [can] limit[ ] the interpretation of claims.”);
Alpex Computer Corp. v. Nintendo Co. Ltd.,
102 F.3d 1214, 1220 (Fed.Cir.1996) (noting that prosecution history is “relevant ... for construing the meaning and scope of the claims”).
The amendments made early on in pursuance of the patents support HMR/TKT’s contention that Amgen defined a “therapeutically effective amount” of EPO to encompass an amount sufficient to elicit any or all of the biological effects that were attributed to natural EPO.
On December 5, 1988, in response to a rejection under 35 U.S.C. §§ 112 , 102(b) and 103 of what eventually became the ’080 patent, Amgen submitted independent claim 41 and dependent claims 55-57 and 61-66. The pertinent amendments are claim 41 (which relates to claim 2 of the ’080 patent), claim 55 (which relates to claim 4 of the ’080 patent), claim 57 (which relates to claim 6 of the ’080 patent), and claim 56 (because it is referenced in claim 57).
Claim 41: A
glycoprotein product having a primary structural conformation and glycosylation sufficiently duplicative of that of a naturally occurring human erythropoietin to allow possession of the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells and having an average carbohydrate composition which differs from that of naturally occurring human erythropoiet-in.
Claim 55:
A pharmaceutical composition comprising an effective amount of a glycoprotein product according to claim 41 and a pharmaceutically acceptable diluent, adjuvant or carrier.
Claim 56:
A method for providing er-ythropoietin therapy to a mammal comprising administering an effective amount of a glycoprotein product according to claim 41.
Claim 57:
A method according to claim 56 wherein the therapy comprises enhancing hematocrit levels.
Amgen’s ’422/’080 App., Tab G (Ex. 2), at Tab 6, at 174-75.
These claims make clear that Amgen’s product purposefully duplicates natural EPO in that it elicits the in vivo biological activity of causing bone marrow cells to increase production of reticulocytes and red blood cells, but that it differs from natural EPO in its carbohydrate composition. These claims also make clear that claim 55 (similar to claim 4 in the ’080 patent) is not limited to increasing hemato-crit because that is precisely what claim 57 does (and what claim 6 in the ’080 patent how does). In the remarks accompanying the amendment, Amgen twice explained that its product produces the same in vivo biological activity as that of natural EPO:
Applicant’s novel glycoprotein preparations ... hav[e] the glycosylation-requir-ing
in vivo
biological activity (promoting reticulocyte and red blood cell production) characteristics of naturally occurring human erythropoietin.
Amgen’s ’422/’080 App., Tab G (Ex. 2), at Tab 6, at 175.
[T]he glycoprotein products herein claimed ... possess the essential
in vivo
biological activity of naturally occurring erythropoietin.
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Amgen’s ’422/’080 App., Tab G (Ex. 2), at Tab 6, at 181. It then explained, with reference to claim 56, that Amgen “first developed knowledge of the full amino acid sequence of erythropoietin and first generated the presently claimed glycoprotien products which allowed for full scale clinical application to provide
therapeutic effects
consistent with the
in vivo
activity of naturally occurring erythropoietin.”
Id.
at 177 (first emphasis added). With reference to claim 41, it stated that Amgen “was the first to provide a glycoprotein which is
both
different from previously isolated urinary erythropoietin in its glycoys-lation and yet sufficiently like the natural product ... in terms of its glycosylation to allow it to fill the long-felt need (unsatisfiable by urinary isolates) for life-sustaining human therapeutic agents for, e.g., the anemia associated with dialysis in renal failure patients.”
Id.
at 178 . It then explained that the product is “sufficiently like” natural EPO in glycosylation because it “allow[s] for
in vivo
biological activity.”
Id.
at 179 . Later, it explained that Example 10 is novel in that it is the first therapeutic procedure ever practiced with EPO to demonstrate that EPO has the capacity to generate in vivo an increase in hemato-crit.
Id.
Taken in combination, the amendments and these remarks support the interpretation that Amgen intended “therapeutically effective amounts” of EPO to encompass an amount that elicited in patients any or all of the biological effects previously attributed to natural EPO and that it did not limit the term to an increase in hemato-crit.
39
Such an effect is separately claimed in claim 6 (here claim 57).
Were this the entire prosecution history, the Court would agree with HMR/TKT and the Federal Circuit that Amgen broadened the term to mean one that elicits any or all of the in vivo effects before attributed to natural EPO regardless of whether they actually heal or cure the patient. In the course of overcoming two additional rejections later on in the process, however, Amgen differentiated its product from natural EPO (i.e., it overcame rejection) by asserting that natural EPO — which elicits the biological effects— was not therapeutically viable, whereas its product was clinically effective and designed specifically for a class of patients for which the product was intended. In doing so, Amgen avowed that its invention produced enough quantity of EPO to elicit responses that actually healed or cured the patient.
Renishaw,
158 F.3d at 1249 n. 3 (“[A]ny interpretation that is provided or disavowed in the prosecution history also shapes the claim scope.”);
Standard Oil Co.,
774 F.2d at 452 (“[T]he prosecution history (or file wrapper) limits the interpretation of claims so as to exclude any interpretation that may have been disclaimed or disavowed during prosecution in order to obtain claim allowance.”).
For example, in a June 5, 1989 amendment, in response to a PTO rejection under 35 U.S.C. § 103 for obviousness, Am-gen distinguished its recombinant EPO product from natural EPO by claiming natural EPO was “not a viable therapeutic product” whereas its recombinant EPO was “clinically effective” and the “first
*240
therapeutic product” successfully to treat anemia and other disorders involving low red blood cell counts:
All of the references cited by the Examiner in this rejection relate to naturally occurring erythropoietin. The claims of the subject invention relate to erythro-poeitin which is produced through recombinant DNA techniques. Recombinant erythropoietin is different from naturally occurring erythropoietin... Moreover, naturally occurring human erythropoietin is not a viable human therapeutic product; human recombinant erythropoietin, on the other hand, has been proven to be clinically effective,
and
is the first therapeutic product which can be used to effectively treat the hundreds of thousands of patients who suffer from anemia and other disorders involving low red blood cell counts.
Amgen’s ’422/’080 App., Tab G (Ex. 2), at Tab 11, at 227 (emphasis omitted). Amgen further explained that “[i]n contrast to recombinant erythropoietin, naturally occurring human erythropoietin is not used to treat patients. In the past, efforts were made to obtain purified erythropoietin from natural sources .... The results of these efforts however yielded only a small amount of material which was far too little for clinical research.”
Id.
at 229 . As the FDA stated in its approval of recombinant EPO “there is not enough naturally occurring enthropoetin produced to collect it from healthy persons for use in treatment,” but “gene splicing techniques have permitted its production.”
Id.
Thus, in response to this rejection, Amgen differentiated its EPO from natural EPO in two respects. First, Amgen claimed its invention allowed for a sufficient amount of EPO actually to treat patients — as opposed to natural EPO which was not available in large enough quantities. Second, it claimed its EPO, as opposed to prior art, effectively treated patients suffering from anemia or other disorders involving low red blood cell count.
40
This was a clear and definitive statement about what the invention “envelopes.”
Renishaw,
158 F.3d at 1250 (noting that a term can only be properly interpreted “with a full understanding of what the inventors actually invented and intended to envelop with the claim” and that the correct construction is that which “stays true to the claim language and most naturally aligns with the patent’s description of the invention”). Here, the prosecution history makes clear that Amgen intended its invention to be clinically effective at least for the class of patients suffering from anemia and low red blood cell disorders.
See Standard Oil Co.,
774 F.2d at 452 (“[A]ll express representations made by or on behalf of the applicant to the examiner to induce a patent grant or ... to reissue a patent ... [can] limit[ ] the interpretation of claims.”);
Spectrum Int’l Inc. v. Sterilite Corp.,
164 F.3d 1372, 1378 (Fed.Cir.1998) (“[Explicit statements made by a patent applicant during prosecution to distinguish a claimed invention over prior art may serve to narrow the scope of the claim.”). Amgen was trying to cure anemia and other diseases associated with low red blood cell count— not simply to duplicate the effects of natural EPO regardless of whether those effects cured or healed.
CVI/Beta Ventures,
112 F.3d at 1160 (“In construing claims, the problem the inventor was attempting to solve, as discerned from the specification and the prosecution history, is a relevant consideration.”).
*241
That Amgen intended its invention to provide a meaningful health benefit to the list of patients expressly mentioned in the specification is supported by another portion of the prosecution history. On November 6, 1990, Amgen claimed the following in an application that eventually resulted in the ’422 patent:
Claim 61: An erythropoietin-containing, pharmaceutically-acceptable composition wherein human serum albumin is mixed with erythropoietin.
Claim 62: A composition according to claim 61 containing a therapeutically effective amount of erythropoietin.
Claim 63: A composition according to claim 61 containing a therapeutically effective amount of recombinant erythro-poietin.
41
HMR/TKT’s App. to Opp’n [Doc. No. 705], Tab 2 (Ex.2003, 11/6/90 Preliminary Amendment) at 9. The examiner rejected claims 62 and 63 as “being indefinite for failing to particularly point out and distinctly claim the subject matter which [the] applicant regard[ed] as the invention.”
Id.
(Ex.2003, 6/1/94 Examiner’s Action) at 2. Claim 62 was rejected for being “vague and indefinite because it is unclear what the claimed composition is required to be ‘effective’ for,” and claim 63 was rejected as “vague and indefinite because it is unclear as to how the recitation that the claimed erythropoietin is ‘recombinant’ modifies the physical erythropoietin composition[;] ... while the claimed erythro-poietin may be prepared using recombinant techniques, the product would not necessarily distinguish over that found in nature.”
Id.
In essence, then, the examiner rejected Amgen’s patent because it did not specify for what type of patients the product was intended to be “therapeutieally effective”
and
it did not distinguish how the recombinant EPO was different than natural EPO besides its preparation. In other words, it did not differentiate what recombinant EPO provided to patients that natural EPO did not.
Amgen requested reconsideration, stating that the terms “effective” and “recombinant” are, “in view of the extensive disclosure of the specification,” well-defined and understood by a person of skilled in the art.
Id.
(Ex.2003, 12/1/94 Request for Reconsideration) at 1. Amgen argued that “the specification indicates
several potential therapeutic uses
for the claimed invention.”
Id.
at 2 (emphasis added). It then quoted the exact portion of the specification to which the Federal Circuit had pointed, where the in vivo effects along with the effect of an increase in hematocrit levels are mentioned.
Id.
Importantly, however, Amgen also quoted the following sections regarding the class of humans treatable with products:
Similarly, to the extent that polypeptide products of the invention share the in vivo activity of natural EPO isolates they are conspicuously suitable for use in erythropoietin therapy procedures practiced on mammals, including humans, to develop any or all of the effects heretofore attributed in vivo to EPO e.g., stimulation of reticulocyte response, development of ferrokinetie effects (such as plasma iron turnover effects and marrow transit time effects), erythrocyte mass changes, stimulation of hemoglobin C synthesis (see, Eschbach, et al[.], supra) and[,] as indicated in Example 10, increasing hematocrit levels in mammals. Included within the class of humans treatable with products of the invention are patients generally requiring
*242
blood transfusions and including trauma victims, surgical patients, renal disease patients including dialysis patients, and patients with a variety of blood composition affecting disorders, such as hemophilia, sickle cell disease, physiologic anemias[,] and the like.
Id.
(Ex.2003, 12/1/94 Request for Reconsideration) at 2 (emphasis omitted) (quoting ’933 Patent, Ex. 1, col. 33: 19-36). According to Amgen,
these sentences from the specification and others provide a clear and definite description of the
uses for which the claimed erythropoietin compositions would be therapeutically effective.
A person of skill in the art would understand that the amount of erythropoeitin necessary to achieve these defined therapeutic results would vary for each use. However,
clinicians can readily determine the “therapeutically effective” amounts for each condition, and indeed for each patient.
Id.
(emphasis added).
The question then is what are the “uses” to which Amgen refers. At first blush, it may appear that the “therapeutic uses” are the effects listed in the specification. A close reading of the remarks, however, makes clear that the words “uses” and “use” refer to treatment of the conditions listed in the specification — not to eliciting the effects. If this were not the case, the following sentence would not make sense: “A person of skill in the art would understand that the amount of erythropoeitin necessary to achieve these defined therapeutic results would vary for each
use.” Id.
(emphasis added). Amgen overcame a rejection of indefiniteness, in part by claiming that its product was specifically designed to treat patients suffering from the types of disease listed in the specification. Such a clear avowal — when considered alone or along with the other parts of the prosecution history and specification— would estop Amgen now were it to try to claim that its product was “therapeutically effective” in treating patients with
high
red blood cell counts.
Alpex Computer Corp.,
102 F.3d at 1221 (“Just as prosecution history estoppel may act to estop an equivalence argument under the doctrine of equivalents, positions taken before the PTO may bar an inconsistent position on claim construction.”);
Ekchian v. Home Depot, Inc.,
104 F.3d 1299, 1304 (Fed.Cir.1997) (“[B]y distinguishing the claimed invention over the prior art, an applicant is indicating what the claims do not cover, [and] he is by implication surrendering such protection.”). Here we have prosecution history estoppel in reverse — that is, Amgen wants this Court to constrain the meaning of the term to this class of patients. This does not change the effect the Court must give Amgen’s clear and definite statements. Thus, the Court holds that Amgen limited the term in dispute to refer to the class of patients listed in the specification and quoted to the examiner.
Teleflex,
299 F.3d at 1327 (noting that a term can be limited or extended by the specification or prosecution history as long as the patentee
clearly
intended to do so);
Altiris,
318 F.3d at 1370 (same).
42
The trickier question, however, is whether these remarks define the disputed term to include the in vivo effects of EPO
regardless
of whether they heal or cure this
*243
class of patients.
43
While it is a close call, the Court does not so read these remarks. Admittedly, all of the effects — the in vivo effects and an increase in hematocrit — are labeled together as “therapeutic results.” What is not made clear, however, is whether “therapeutic results” equates with “therapeutically effective.” While there is support for reading the terms as coextensive, there is also support for viewing them differently. Amgen specifically differentiates between an amount that achieves therapeutic
results
and a “therapeutically effective amount:”
A person of skill in the art would understand that the
amount
of erythropoeitin necessary to achieve these defined therapeutic results would vary for each use. However, clinicians can readily determine the
“therapeutically effective”
amounts for each condition, and indeed for each patient.
HMR/TKT’s App. to Opp’n, Tab 2 (Ex. 2003, 12/1/94 Request for Reconsideration), at 2 (emphasis added). These two sentences indicate that a different amount of EPO is used to achieve each of the effects listed in the specification — including the in vivo effects — depending on the condition and needs of the patient,
but
that a clinician can determine the amount that would be “therapeutically effective.” Thus, when read together, these sentences indicate that (1) the biological effects listed in the specification are part- of the “therapy” but not necessarily “therapeutically effective,” i.e., they do not necessarily heal or cure the patient, and (2) the amount necessary for therapeutic effectiveness — an amount that heals or cures — depends on the types of patients to which the recombinant EPO is being administered.
Because these remarks do not clearly disavow the ordinary and customary meaning of the disputed term and can actually be interpreted to support the ordinary and customary meaning of the disputed term,
44
the Court does not construe “therapeutically effective” to encompass any or all of the biological effects regardless of whether they work to heal or cure.
Amgen II,
314 F.3d at 1327 (“We indulge a heavy presumption that a claim term carries its ordinary and customary meaning ... [Prosecution history may not be used to infer the intentional narrowing of a claim absent the applicant’s clear disavowal of claim coverage.”);
see KX Industries, L.P. & Koslow Technologies Corp.,
18 Fed. Appx. 871, 876 (Fed.Cir.2001) (unpublished opinion);
see also Northern Telecom Ltd. v. Samsung Elec. Co., Ltd.,
215 F.3d 1281, 1294-95 (Fed.Cir.2000) (analyzing whether the pat-entee in the prosecution history “with reasonable clarity and deliberateness” excluded a broader interpretation of the claims).
45
In further support of this con-
*244
elusion is the fact that the examiner allowed the claims to stand. As the Federal Circuit pointed out in a slightly different context in
Amgen II,
“[w]e must presume the examiner did his job, and if he truly thought that” Amgen’s EPO was the same as natural EPO in that it merely elicited the biological effects, “the asserted claims would not have issued.” 314 F.3d at 1327 .
46
5. Conclusion and Claim Construction of “Therapeutically Effective”
The Federal Circuit has stated that “any interpretation [of a patent claim term] that is provided or disavowed in the prosecution history shapes the claim scope.”
Renishaw,
158 F.3d at 1243 n. 3;
see Digital Biometrics, Inc. v. Identix, Inc.,
149 F.3d 1335, 1347 (Fed.Cir.1998) (“The public has a right to rely on such definitive statements made during prosecution.”);
Ekchian,
104 F.3d at 1303-04 (noting that the courts and the public may rely on an information disclosure statement to interpret a claim). Here, to overcome a patent rejection for indefiniteness, Amgen avowed that its invention was “therapeutically effective” for the class of patients listed in column 33 of the specification. Therefore, the Court rules that “therapeutically effective” must be read with reference to this class of patients despite the fact that the specification uses the words “included within.” Amgen did not, however, go so far as to limit the list of patients to those suffering from anemia only or refine the term to mean an increase in hematocrit.
47
Nor did Amgen
*245
clearly redefine the term “therapeutically effective amount” to mean an amount that induces the effects heretofore attributed to natural EPO regardless of whether they work to heal or cure the patient. To the contrary, Amgen repeatedly states in the prosecution history and in the specification that recombinant EPO’s novelty is that it can actually effectively treat, that is heal or cure, patients. While “the inventor’s subjective intent as to claim scope,
when unexpressed in the patent documents,
[should not] have any effect,”
Vitronics,
90 F.3d at 1584 (emphasis added), the correct construction is that which “stays true to the claim language and most naturally aligns with the patent’s description of the invention,”
Renishaw,
158 F.3d at 1243 . Throughout the prosecution history, Am-gen repeatedly describes the invention as one that
heals
patients suffering from low red blood cell counts — something that could not be done before. While the prosecution history and specification indicate a clear intent to define “therapeutically effective amount” as one that elicits “one or more” of the in vivo effects of natural EPO, they do not define the in vivo effects as
necessarily
being “therapeutically effective.” In other words, they do not define these effects as being “therapeutically effective” regardless of whether they heal or cure. Instead, the plain and ordinary meaning of the term “therapeutically effective amount” was refined to (1)
reqidre
(in addition to healing or curing) an elicitation of one or more of the in vivo effects that was attributed to natural EPO and (2) be read in the context of a certain class of patients. Thus, the Court’s claim construction is as follows:
A therapeutically effective amount is a quantity that produces a result that in and of itself helps to heal or cure. A therapeutically effective amount is one that elicits in vivo biological activity of natural EPO such as those listed in the specification, column 33, lines 24 through 28: stimulation of reticulocyte response, development of ferrokinetic effects (such as plasma iron turnover effects and marrow transit time effects), erythrocyte mass changes, stimulation of hemoglobin C synthesis (see, Eschbach, et al., supra) and, as indicated in Example 10, increasing hematocrit levels in mammals.
Therapeutically effective is to be interpreted as being therapeutically effective with respect to the class of patients listed in the specification, column 33 lines 31 through 36: patients generally requiring blood transfusions and including trauma victims, surgical patients, renal disease patients including dialysis patients, and patients with a variety of
*246
blood composition affecting disorders, such as hemophilia, sickle cell disease, physiologic anemias, and the like.
See
9/18/03 Pretrial Conference Tr. at 9-11.
As will be discussed further below, in deciding whether the Goldwasser reference anticipates Amgen’s patents, this construction leaves the Court with a very fact-intensive task: determining which, if any, of the effects listed in the specification actually heal or cure the class of patients referred to therein.
B. “DNA Encoding”
1. Background
At the close of Amgen’s case-in-chief during the first trial, this Court granted HMR/TKT’s Fed.R.Civ.P. 52(c) motions for judgment of non-infringement of claims 4-9 of Amgen’s ’698 process patent.
Amgen I,
126 F.Supp.2d at 99-101 . On appeal, the Federal Circuit vacated and remanded this Court’s rulings regarding infringement of the ’698 patent because the Court had compared the accused device to the preferred or commercial embodiments of the patent instead of to the properly construed claims themselves.
Amgen II,
314 F.3d at 1347 .
In the memoranda in support and in opposition to each party’s motions regarding infringement of the ’698 patent, the parties argued different interpretations of the term “DNA encoding” found in claims 4 and 6 of the ’698 patent. Thus, the Court concluded that the term is in dispute and needed to be construed in order properly to determine the issue of literal infringement.
48
2. The Claims at Issue
Claim 4 of the ’698 Patent:
A process for the production of a glyco-sylated erythropoietin polypeptide having the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells comprising the steps of: (a) growing, under suitable nutrient conditions, vertebrate cells comprising promoter DNA, other than human erythropoietin promoter DNA, operatively linked to
DNA encoding
the mature erythropoiet-in amino acid sequence of FIG. 6; and (b) isolating said glycosylated erythro-poietin polypeptide expressed by said cells.
’698 Patent, Ex. 1, col. 38: 37-47 (emphasis added) (paragraph structure altered).
Claim 6 of the ’698 Patent:
A process for the production of a glyco-sylated erythropoietin polypeptide having the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells comprising the steps of: (a) growing under suitable nutrient conditions, vertebrate cells comprising amplified
DNA encoding
the mature erythropoiet-in amino acid sequence of FIG. 6; and (b) isolating said glycoslated erythro-poietin polypeptide expressed by said cells.
Id.
at col. 38: 50-59 (emphasis added) (paragraph structure altered).
3.Summary of the Parties’ Arguments
HMR/TKT’s proposed claim construction rests on the argument that the word “encoding” means “producing.” HMR/ TKT’s Mem. in Opp’n re ’698 [Doc. No. 700] at 8. HMR/TKT argues that the phrase at issue in Amgen’s ’698 patent means that the DNA actually produces a
*247
glycosylated erythropoietin polypeptide having a 166 amino acid sequence.
Id.
In other words, HMR/TKT argues that section (a) of claims 4 and 6 of the ’698 patent should be construed to require the production of an EPO protein with 166 amino acids.
Id.
at 1; HMR/TKT’s Reply re ’698 [Doc. No. 725] at 3.
Amgen agrees that the term “mature erythropoietin amino acid sequence of FIG 6” refers to a fully processed EPO glyco-protein having a 166 amino acid sequence. Amgen argues, however, that section (a) of the disputed claims refers to the
DNA
that encodes the fully processed EPO glycopro-tein — not to the EPO glycoprotein itself. In other words, Amgen argues that the disputed claims refer to the type of DNA that is involved and describe that DNA as one that has a certain sequence, the genetic code, for the amino acid sequence spanning +1 through +166 of Figure 6. Am-gen’s Reply re ’698 [Doc. No. 731] at 6. Amgen asserts that the proper construction of the claim language is “a DNA sequence that contains the genetic code for the amino acid sequence spanning from position +1 through position +166 of Figure 6.” Amgen’s Reply re ’698 at 6. Amgen contends that a process can contain DNA that encodes the full 166 amino acids but result in an end-product that does not have the full 166 amino acid sequence. Thus, according to Amgen, this portion of the disputed claims refers to a
type
of DNA and to what that DNA
encodes
— not the end-protein that is ultimately
produced.
4. Discussion
It is true that the Court construed the “mature erythropoietin amino acid sequence of FIG. 6,” as stated in both the ’080 and ’698 patent, to mean a mature (fully realized) erythropoietin having 166 amino acids.
Amgen I,
126 F.Supp.2d at 100 . HMR/TKT’s argument that “DNA encoding ... [the] amino acid sequence of FIG. 6” means that the DNA actually must produce an EPO with a 166 amino acid sequence, however, stretches this construction too far.
The Court notes that HMR/TKT supports its definition of “encoding” primarily with extrinsic evidence — evidence to which resort ought be had only “if necessary.”
Vitronics,
90 F.3d at 1583 . As will be discussed below, use of extrinsic evidence here is not appropriate in construing these terms because “the patent documents, taken as a whole,” are sufficient “to enable the court to construe [the] disputed claim terms.”
Id.
Moreover, even if it were necessary, and thus appropriate, for this Court to consider extrinsic evidence as to the meaning of the word “encoding,” HMR/TKT’s arguments would still fail. HMR/TKT misinterprets the extrinsic evidence to which it points from the first trial. Dr. Kingston did indeed state that “the protein that is encoded is the protein that is actually produced,” Kingston Test., Trial Tr. at 1390-91, but this does not define “DNA encoding” as referring directly and exclusively to the specific product that is actually produced. Instead, what this language requires is DNA that is
capable
of encoding the final product — not DNA that produces the final product. HMR/TKT’s interpretation of Dr. Lodish’s testimony is also faulty. In the trial transcript pages to which HMR/ TKT referred, Dr. Lodish never states that “encoding” means “producing,” nor does Dr. Lodish define the fragment in question. He does indeed explain the end of the process as one that produces the same EPO glycoprotein. Lodish Test., Trial Tr. at 156-60. But this is the same point. Amgen’s argument, and it is a sound one, is that this part of the claim is not describing the last step of the process, but an interim step — -one that requires a
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DNA with a certain type of sequence or encoding capability.
Furthermore, the extrinsic evidence adduced during the second trial shows that “DNA encoding” in these claims does not mean that the end product must be produced. Dr. Lodish testified that those of skill in the art at the time would understand the plain meaning of the disputed term to mean “a DNA which when copied into RNA, and if necessary spliced, specifies the order of amino acids that are the mature erythropoietin amino-acid sequence depicted in Figure 6 of the patent.”
49
Lodish Test., R. Trial Tr. at 1054: 17-22, 1058: 10, 1059: 1-3 (explaining that genes have two parts, one of which involves the “coding sequence, the piece of DNA that actually specifies the amino acids in the encoded product” and stating that it is this part that is the subject of the claim, “that is, it is an issue of DNA encoding specifying an amino-acid sequence as determined by the genetic code”);
id.
at 1059: 16-21 (stating that “DNA encoding the mature erythropoietin amino acid sequence of FIG. 6” refers to “the DNA sequences that encode all of the amino acids from +1 to +166 of the EPO sequence”);
id.
at 1063: 17-19 (explaining that “DNA encoding” refers to DNA in the cell, not to “the polypeptide that is ultimately secreted by the cell. It’s a statement of the coding capacity of the DNA in the cell”);
id.
at 1055: 13-18 (“It simply refers to a sequence of DNA which has the capability of encoding, which encodes, a particular protein. It is not a statement about a protein that the cell actually makes or secretes.”). Indeed, even Dr. Kingston, HMR/TKT’s expert, admitted that one way the word “encoding” “could be used very precisely is to describe a very, very precise small bit of the gene, and that is the codons.” Kingston Test., R. Trial Tr. at 163: 2-16.
50
Further, consistent with Dr. Lodish’s testimony, Dr. Kingston stated that the phrase “DNA encoding the mature erythropoietin amino acid sequence of FIG. 6” means “DNA that provides the instruction to make th[e] protein which would be the sequences” found in Figure 6 and depicted as the codons encoding amino acids +1 through +166. Kingston Test., R. Trial Tr. at 135: 2-142: 7 (circling the entire sequence of Figure 6); Lodish Test., R. Trial Tr. at 1059: 22-1060: 25 (same).
Again, however, none of this evidence is necessary to the Court’s construction because an examination of the plain and ordinary meaning of the words, the claims themselves, and the specification demonstrates that HMR/TKT’s asserted construction is off base.
Vitronics,
90 F.3d at 1582 ;
SRI Int’l,
775 F.2d at 1118 ;
Autogiro,
384 F.2d at 397.
51
a. The Plain and Ordinary Meaning
The plain and ordinary meaning of “encode” is to “convert from one system of communication to another” and “to convert (a message) into code.”
Webster’s Ninth New Collegiate Dictionary
1990. This implies that “DNA encoding” is DNA that converts one type of message or text into
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another type of message and that it provides information to the cell.
b. The Claims
The claim language supports the plain and ordinary meaning of the term. The claim language establishes that “DNA encoding” refers to DNA that contains a certain sequence in the cells. Both claims 4 and 6 describe processes for producing a glycosylated erythropoietin polypeptide. The sentences in section (a) of the disputed claims do not, as HMR/TKT argues, require the production of the end-product of the claimed processes — an EPO polypeptide with 166 amino acids. To the contrary, the claims clearly distinguish between the cells grown in step (a) (which comprise “DNA encoding the mature er-ythropoietin amino acid sequence of Figure 6”) and the EPO glycoprotein itself that is isolated in step (b). Here, the “mature erythropoietin amino acid sequence of FIG. 6” modifies “DNA encoding” in the cells grown in step (a) — not the “glycosylated erythropoietin polypeptide” isolated in step (b). Therefore, based on the claim language and the ordinary meaning of the words, it appears that the sentences containing the disputed phrase mean, in conjunction, that the DNA must provide or contain the code or instructions for the “mature erythropoietin amino acid sequence of FIG. 6.”
The claims do not, however, imply that a protein with the “mature erythropoietin amino acid sequence of FIG. 6” must at the end of the process be produced. This point becomes clear when comparing these claims to that of the ’080 patent. The ’698 claims recite a “DNA
encoding
the mature erythropoietin amino acid sequence of FIG. 6.” as opposed to the claims of the ’080 patent that specifically recite an
EPO glycoprotein
that “comprises the mature erythropoietin amino acid sequence of FIG. 6.” ’080 Patent, Ex. 1, col. 38: 42-43.
In a nutshell, HMR/TKT’s construction conflates the concept of DNA that encodes for a protein with requiring the production of a specific protein and in so doing ignores how proteins are actually produced. The DNA encodes the protein. It provides the instruction set used by the
cell
to synthesize a polypeptide that is later processed to its final form. DNA encoding a specific amino acid sequence, however, does not necessarily determine the final length of the polypeptide produced by the cell. The testimony adduced at trial regarding the 166th arginine makes this clear. Dr. Lodish explained that “as long as that DNA encodes the mature erythro-poietin — mature EPO sequence, it matters not at all how many other amino acids might be there. Whatever it is, as long as it encodes that sequence, it’s fine.” Lodish Test., Trial Tr. at 248: 23-249: 1.
HMR/TKT counterargues that it is the protein that is produced by the cell that determines what instructions were actually present in the cell
and used
in the process, that is, that erroneous instructions are not really instructions at all.
See, e.g.,
7/28/03 Hr’g Tr. at 52: 1-9 (explaining that “there’s no proof one way or another as to what the intermediary is,” and “the only proof that there is in this case is as to the end product”).
52
The Court, however, is not persuaded. The evidence adduced at the first trial overwhelmingly suggested that although
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the DNA encodes for a 166 amino acid sequence, ultimately, the
cell
cleaves off the last amino acid residue prior to secretion of the final protein, EPO that has a 165 amino acid sequence.
Amgen I,
126 F.Supp.2d at 86, 101 ; Lodish Test., Trial Tr. at 347: 16-18, 348: 3-9; 7/28/03 Hr’g Tr. at 52: 1-9. As Amgen’s counsel explained at the
Markman
hearing, “DNA encoding the mature erythropoietin amino acid sequence of FIG. 6” is DNA containing codons for amino acids 1-166 of FIG. 6. These instructions will be used by the cell to produce a 165 amino acid erythropoiet-in. 7/28/03 Hr’g Tr. at 44: 11-47: ll.
53
Thus, DNA can encode or provide the genetic instructions for a protein that when ultimately secreted has a structure different from the one that the instructions dictate. That some of these instructions are not in the end “used” does not erase the fact that the DNA contained the information in the first place.
Moreover, as Amgen argues, HMR/ TKT’s construction makes the claims illogical. With HMR/TKT’s construction, the claimed processes would require the use of a cell containing “a promoter DNA opera-tively linked to an EPO protein” or “an amplified EPO protein.” Amgen’s Mem. In Opp’n re ’698 [Doc. No. 717] at 6-7. As asserted by Amgen and undisputed by HMR/TKT, this does not make sense.
In sum, any argument based on the claims that the words “producing” or “that produces” should be inserted in lieu of “encoding” fails along with HMR/TKT’s argument that “encoding” refers to the EPO protein itself.
54
c. The Specification
Like the claims, the specification supports the.plain and ordinary meaning of the word “DNA encoding.” It demonstrates that one skilled in the art at the time would have defined “encoding” as providing genetic instructions, that is, the sequence.
At the
Markman
hearing, HMR/TKT pointed to columns 11 and 13 in the specification to support its argument that DNA encoding means producing or that the protein is actually produced. 7/28/03 Hr’g Tr. at 51: 6-11. Those sections state that:
The isolation of the desired cDNA clones containing EPO encoding DNA was accomplished through the use of DNA/DNA colony hybridization.
’933 Patent, Ex. 1, col. 13: 64-66.
Specifically comprehended in part (b) are genomic DNA sequences encoding allelic variant forms of monkey and human erythropoietin and/or encoding other mammalian species of erythropoietin. Specifically comprehended by part (c)
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are manufactured DNA sequences encoding EPO, EPO fragments and EPO analogs which DNA sequences may incorporate codons facilitating translation of messenger RNA in non-vertebrate hosts.
’933 Patent, Ex. 1, col. 11: 54-61.
As this Court pointed out during the hearing, however, neither of these sections equates “encoding” with producing. 7/28/03 Hr’g Tr. at 51: 12-15. Likewise, neither shows a clear and deliberate attempt by the patentee to become its own lexicographer.
See Renishaw,
158 F.3d at 1249 ;
Vitronics,
90 F.3d at 1582 ;
Altiris,
318 F.3d at 1370 ;
Teleflex,
299 F.3d at 1326 . Each can be read consistently with the ordinary and customary meaning as understood by one skilled in the art, that is, inserting “providing the genetic instructions for” in lieu of “encoding.” In fact, the section to which HMR/TKT points in column 11 works against its argument that “DNA encoding” means DNA producing the actual protein because it refers to DNA sequences encoding EPO and EPO fragments. Under HMR/TKT’s construction, this section would require EPO fragments actually to be produced instead of requiring that the DNA have the genetic instructions for, that is, provide the codons or genetic sequence for, EPO fragments.
5. Conclusion and Claim Construction of “DNA Encoding”
Accordingly, the Court construed “DNA encoding” to mean “the genetic instructions for.” 7/28/03 Hr’g Tr. at 56: 18-23.
55
TKT/HMR, however, did not give up. As a last-ditch effort to win on literal infringement — which is what claim construction is really all about — HMR/TKT argued at the second trial via Dr. Kingston’s testimony that “genetic instructions for,” the Court’s construction of DNA encoding, could mean either the codons for the amino acids plus 1 to 166 of Figure 6 of the patent, or alternatively, all the instructions to make the mature protein including the regulatory sequences. Kingston, R. Trial Tr. at 161-163. Dr. Kingston explained that a scientist could use the term differently depending on the context.
Id.
To be clear, in this context, the Court interprets the claim to be referring to the coding sequence, the piece of DNA that actually specifies the amino acid sequence — not the regulatory sequences that determine when and under what conditions the cells copy the gene into RNA.
56
This interpretation is supported by the claims themselves, which refer to DNA that encodes — provides the genetic instructions for — “the mature er-ythropoietin amino acid sequence of FIG. 6.” Figure 6 indeed depicts, among other things, the deduced amino acid sequence that is arrived at by reading the codons of the DNA encoding the protein. Importantly, HMR/TKT points to no support in the prosecution history for its argument on this point. Thus, the Court interprets the claims to require the use of cells contain
*252
ing DNA that provides the genetic instructions, the codons, for a 166 amino acid sequence.
C. Are Claims 4 and 6 of the ’698 Patent Step-Plus-Function Claims?
1. Background
57
and Summary of The Parties’ Arguments
Whether Amgen, in referring to the “step[ ] of ... growing under suitable nutrient conditions” in claims 4 and 6 of the ’698 patent, was making step-plus-function claims is an issue raised for the first time by HMR/TKT in its Memorandum in Opposition to Amgen’s Renewed Motion for Summary Judgment of infringement of claims 4-9 of the ’698 patent. HMR/TKT’s Mem. In Opp’n re ’698 [Doc. No. 700] at 9. Paragraph 6 of 35 U.S.C. § 112 , which sets forth the notion of step-plus-function and means-plus-function, “obligates this court to interpret each functional element in a combination claim by reference to the corresponding structure, material, or acts described in the
specification and their equivalents.” Seal-Flex, Inc. v. Athletic Trade and Court Const.,
172 F.3d 836, 843 (Fed.Cir.1999) (emphasis added);
O.I. Corp. v. Tekmar Co., Inc.,
115 F.3d 1576, 1583 (Fed. Cir.1997).
58
In other words, if this section applies, the Court must limit its infringement analysis to a comparison of the type of “growing” claimed in the
specification
to the type of growing utilized by HMR/ TKT.
Ironically, this is exactly what the Court
did
— in error— in the first go-round. In
Amgen I ,
the Court based its holding of non-infringement of the ’698 patent on a comparison of HMR/TKT’s process to the processes outlined in the patent specification.
59
This was error because the Court had never ruled that the relevant claims qualified as a step-plus-function claims.
60
HMR/TKT now presses the Court to address the issue and so to rule.
The wrinkle here is whether the Court now can address this issue — that is, whether the Court can or should permit HMR/ TKT to raise the argument at this stage. After all, in 2000, the Court issued a sanction order against HMR/TKT limiting it to
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the contentions specifically described in its responses to interrogatories. Amgen’s Mem. in Opp’n re ’698
&
’349 [Doc. No. 717] at 4; Amgen’s App. to Mem. in Opp’n re ’698
&
’349 [Doc. No. 719], Ex. A (1/28/00 Order Granting Sanction). HMR/ TKT never identified its step-plus-function theory in its responses to Amgen’s contention interrogatories as a basis for non-infringement of the ’698 patent. Amgen’s App. to Mem. in Opp’n re ’698 & ’349, Tab C (12/7/99 HMR/TKT’s Supplemental Answers and Objections to Amgen’s Interrog. Nos. 2, 3, and 9) at 5-7, 17. Moreover, HMR/TKT never stated that this aspect of the ’698 patent (i.e., whether it included a step-plus-function claim) needed to be resolved through a
Markman
hearing. Am-gen asserts that the Court should therefore not allow this argument, and, at a minimum, the Court should afford Amgen the opportunity to present evidence directed to this new step-plus-function argument.
Id.
at 4-5. Moreover, Amgen argues that even if the Court allows such an argument, it lacks merit because “growing” is an “act,” not a “function.”
2. Discussion
61
a. Should the Court Allow HMR/ TKT to Make Its Step-Plus-Function Argument?
Whether the language of a claim is in step-plus-function format is a question of claim construction.
See, e.g., Kemco Sales, Inc. v. Control Papers Co., Inc.,
208 F.3d 1352, 1360 (Fed.Cir.2000) (“Whether the language of a claim is to be interpreted according to 35 U.S.C. § 112 , ¶ 6, i.e., whether a claim limitation is in means-plus-function [or step-plus function] format, is a matter of claim construction and is thus a question of law, reviewed de novo.”);
Personalized Media Communications, LLC v. Int’l Trade Comm’n,
161 F.3d 696 , 702 (Fed.Cir.1998) (“An infringement analysis entails two steps.... The first step, claim construction, is a question of law which we review de novo.... The second step is factual.... Whether certain claim language invokes 35 U.S.C. § 112 , f 6 is an exercise in claim construction and is therefore a question of law.” (citations and internal quotation marks omitted)). Generally, on appeal, a party cannot proffer a new claim construction that changes its scope, but it can present additional arguments in support of a previously proposed construction.
See, e.g., CCS Fitness, Inc. v. Brunswick Corp.,
288 F.3d 1359, 1371 (Fed.Cir.2002). The rationale is that the parties deserve notice and an opportunity to develop the record and, at the same time, the appellate court needs to have a properly reviewable record on an issue raised on appeal.
Interactive Gift Exp., Inc. v. CompuServe, Inc.,
256 F.3d 1323 , 1346-46 (Fed.Cir.2001);
cf. Finnigan Corp. v. Int’l Trade Comm’n,
180 F.3d 1354 , 1363 (Fed.Cir.1999). Thus, a relevant inquiry in determining whether a new claim construction can be pressed is “whether the trial court and the party claiming waiver had fair notice and an opportunity to address the issue concerning the scope of a claim limitation.”
CCS Fitness,
288 F.3d at 1371 .
The situation here is unusual. First, this is not a new claim construction argument raised on appeal but instead a new claim construction argument raised on remand to the trial court. Second, counsel for Amgen—the party now seeking to have the issue deemed waived—acknowledged the possible applicability of the step-plus-function doctrine to the Court. On June 9,
*254
2000, after the Court made its finding of non-infringement of the ’698 patent, Am-gen queried whether the Court was construing the ’698 process claims as “means plus function” claims. Trial Tr. at 1308-1309. The Court replied as follows:
I don’t mean to be elliptical. That is my analogy. That’s right.... Now I think you’ve missed on the ’698 patent. I think that because I do think you have to spell out a means-plus-function. And I have read this patent with great care and I’ve reflected on it throughout the testimony of all the witnesses. I don’t see either by equivalent or by literal infringement.
Trial Tr. at 1309-1310. Thus, the Court referred to the means-plus-function doctrine in relation to the ’698 patent
62
but, as noted earlier, did not definitively rule that the asserted claims were in means or step-plus-function format nor even mention step-plus-function in the opinion despite applying the infringement analysis required when a claim is in step-plus-function format.
Although the situation is not straightforward, it is clear that Amgen was on notice of the issue but did not get an opportunity to argue it. Given the procedural posture of the case with respect to the ’698 patent specifically, Amgen was fully afforded the opportunity during the remand trial to address the issue, which substantially reduces any prejudice to it.
Indeed, the Federal Circuit has suggested that it is appropriate to consider whether a claim is in means-plus-function or step-plus-function format even when one party has essentially waived the issue.
Rodime PLC v. Seagate Technology, Inc.,
174 F.3d 1294 (Fed.Cir.1999). In that case, the parties contested at trial whether the plaintiffs claim was in means-plus-function format, with the plaintiff arguing that it was not.
Id.
at 1302 . The district court ruled that the claim
was
in means-plus-function format.
Id.
The plaintiff appealed, but did not press that particular issue and thus apparently conceded that the claim was in means-plus function format.
Id.
The Federal Circuit nonetheless assessed
de novo
whether the claim was indeed in means-plus-function format, explaining that:
[The plaintiffs] concession ... does not relieve this court of its responsibility to interpret the claims as a matter of law. To interpret the claims, this court must decide the subsidiary question of whether the claim element disputed by the parties invokes § 112, ¶ 6 in the first instance.... Only by undertaking this inquiry can this court ensure consistency in statutory application. Moreover, this court’s claim interpretation affects entities beyond the parties to this case. Therefore, this court examines the district court’s decision that this claim falls under § 112, ¶ 6.
Id.
(internal citations omitted). The Federal Circuit subsequently concluded that the district court had erred and that the claim was not in means-plus-function format.
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Similarly, in this case, whether this portion of the ’698 patent is in step-plus-function format determines the entire analytic framework for analyzing whether HMR/TKT’s process infringes this part of the patent. To make this assessment, therefore, this Court needs to determine which analytic framework is implicated. The Court can either make this decision on the merits or can simply decide that the regular infringement framework must be used because HMR/TKT waived its argument that the step-plus-function framework should be used. The problem with the latter approach is that, if the step-plus function framework is truly the applicable one, and the Court nonetheless declines to use it on grounds of waiver, the Court will essentially be applying the wrong law to this aspect of the claim. This, in turn, undermines consistency in statutory application.
For these prudential reasons, this Court analyses whether claims 4 and 6 of the patent are step-plus-function claims. It does so in the course of construing the claims because, as noted above, whether the language of a claim is in step-plus-function format is a question of claim construction.
See, e.g., Kemco Sales, Inc.,
208 F.3d at 1360 ;
Personalized Media Communications, LLC,
161 F.3d at 702.
b. Are Claims 4 and 6 of the ’698 Patent Step-Plus-Function Claims?
This

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Source: Frix Law Library, https://www.frixlaw.com/law-library/cases/2463968. Public record. Not legal advice.