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Amgen Inc. v. F. Hoffmann-LaRoche LTD Et Al - Document No. 595
Amgen Inc. v. F. Hoffmann-LaRoche LTD Et Al - Document No. 595
595
Case 1:05-cv-12237-WGY Document 595 Filed 06/29/2007 Page 1 of 26
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AMGEN INC., :
:
Plaintiff, :
:
v. :
:
F. HOFFMANN-LA ROCHE, LTD, a Swiss Civil Action No.: 05-12237 WGY
:
Company, ROCHE DIAGNOSTICS GmbH, a :
German Company and HOFFMANN-LA ROCHE :
INC., a New Jersey Corporation, :
:
Defendants.
:
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Hoffmann-La Roche, Ltd, Roche Diagnostics GmbH and Hoffmann-La Roche Inc. (collectively
“Roche”) in support of Roche’s Opposition to Amgen Inc.’s Motion for Summary Judgment of
I. Background
1. I am the Theodore and James Pedas Family Professor of Intellectual Property and
Technology Law, Co-Director of the Intellectual Property Law Program, and the Co-Director of
the Dean Dinwoodey Center for Intellectual Property Studies at the George Washington
physics in 1959, both from the University of Michigan. In 1962, I received my law degree from
the University of Michigan, where I was on the editorial board of the Michigan Law Review.
Dockets.Justia.com
Case 1:05-cv-12237-WGY Document 595 Filed 06/29/2007 Page 2 of 26
After graduating from law school, I served as a law clerk for Chief Judge Levin of the United
Honigman, Miller, Schwartz & Cohn in Detroit until 1964, when I joined the patent department
Burroughs program for training its patent attorneys to prepare and prosecute patents before the
United States Patent and Trademark Office (“USPTO” or “Patent Office”). In 1965, I became an
associate in the patent firm of Barnard, McGlynn and Reising in Birmingham, Michigan, where I
later became partner. During the 1968-1972 period, I was partner in charge of patent, patent-
antitrust and related litigation. From 1973 until I retired from that position in 1999 to become
Professor Emeritus, I was full professor at Wayne State University Law School, where I taught
courses (seminars) in patent law, advanced patent law, antitrust law and law and economics.
4. In 1977-1988, I was one of the co-authors of a six volume (now eight volume)
treatise on patent law and practice entitled Patent Law Perspectives (2d ed.), published by
Matthew Bender. Since 1988, I have been solely responsible for writing the release for each of
the volumes. I am also the co-author of Cases and Materials on Patent Law, 2d edition (with
Randall R. Rader, John R. Thomas and Harold C. Wegner), published by West Group.
5. I also have written many articles on issues of patent law and practice, and have
taught seminars in patent law and practice for United States District Judges and United States
Magistrate Judges. I have lectured widely on patent law subjects, and within the past few years
have spoken at intellectual property conferences across the United States and in Amman,
Beijing, Bangalore, Berlin, Bhopal, Bonn, Bucharest, Buenos Aires, Brussels, Cairo, Calcutta,
Edinburgh, Haifa, Hong Kong, Kharagpur, Maastricht, Mumbai, Munich, New Delhi, Osaka,
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Paris, Parma, Phuket, Pune, Rio de Janeiro, Shenzhen, Sofia, Stockholm, Taipei, Tel Aviv,
6. I have been held qualified to testify as an expert in patent law and procedures in
more than 90 cases in federal court including cases relating to biotechnology, DNA, and
recombinant processes.
infringement of United States Patent Nos. 5,411,868 (“the ‘868 patent”), 5,547,933 (“the ‘933
patent”), 5,618,698 (“the ‘698 patent”), 5,621,080 (“the ‘080 patent), 5,756,349 (“the ‘349
patent”) and 5,955,422 (“the ‘422 patent”). I understand that each of the patents-in-suit shares a
common specification with, and claims priority to, United States Patent No. 4,703,008 (“the ‘008
patent”) which expired in 2004. The ‘008 patent issued from a string of four continuation-in-part
applications, with the earliest application filed on December 13, 1983. I understand that the
continuation-in-part applications filed on February 21, 1984 (Ser. No. 16/582,185), September
28, 1984 (Ser. No. 06/655,841) and November 30, 1984 (Ser. No. 06/675,298) all added new
9. I am aware that Amgen has submitted a motion for summary judgment alleging
that Roche’s MIRCERATM and CERA products literally infringe claim 1 of the ‘422 patent,
claim 3 of the ‘933 patent and claim 6 of the ‘698 patent. I have reviewed the related
1
When citing to information set forth in the common specification, I generally cite to the ‘868 patent.
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connection with Amgen’s motion for summary judgment. As explained below, the prosecution
histories of the patents-in-suit demonstrate that Amgen is not entitled to all “EPO-like”
molecules, such as EPO analogs and derivatives, “synthetic polypeptides . . . having a biological
EPO.
III. Amgen Surrendered The Subject Matter That It Now Tries To Claim In Litigation
10. Each of the patents-in-suit claims priority to the expired ‘008 patent and, through
the parent applications of the ‘008 patent, claims a priority date of December 13, 1983. The ‘008
patent, entitled “DNA sequences encoding erythropoietin,” issued from Ser. No. 06/675,298
(“the ‘298 application”) which was filed on November 30, 1984. The ‘008 patent issued on
priority to the expired ‘008 patent, the prosecution histories of each of the patents-in-suit is
relevant to determining: (1) what Amgen expressly claimed as its invention in the asserted
claims-in-suit; and (2) what subject matter Amgen surrendered during prosecution in exchange
for the Patent Office issuing its claims. Upon review of the file histories of the patents-in-suit, it
is clear that Amgen’s product claims do not cover all “EPO-like” molecules, such as EPO
prosecution of the asserted claims, Lin expressly explained to the Examiners (and the public)
what his claims did cover, cancelled claims to other potential products and processes, and was
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required to surrender subject matter that Amgen is now trying to recapture in litigation. This is
not permissible.
12. United States Application Serial No. 113,179 (“ the ‘179 application”), filed
October 23, 1987, led to the ‘868 patent (discussed below) and is also the basis for the ‘698
patent-in-suit. The ‘698 patent issued from Application Serial No. 08/468,381 (“the ‘381
application”), filed June 6, 1995 as a continuation of the ‘179 application. (Ex. 22, ‘381 File
History, Paper 1, Application; Ex. 23, Paper 3a, 6/6/95 Continuing Application Transmittal).2
The ‘698 patent includes claim 6 which issued from file claim 72:
(Ex. 45, ‘698 patent, claim 6 (emphasis added); Ex. 26, ‘381 File History, Paper 9, 12/20/96
Second Preliminary Amendment at 7-8; see also Ex. 24, ‘381 File History, Paper 7, Interview
13. Claim 6 of the ‘698 patent was first introduced into the ‘381 application after the
Patent Office had already issued the parent ‘868 patent. (Ex. 24, ‘381 File History, Paper 7,
12/11/96 Interview Summary). Claim 6 of the ‘698 patent includes the limitation “DNA
2
All Exhibits cited herein are attached to the Declaration of Keith E. Toms in Support of Defendants’ Opposition
to Amgen’s Motion for Summary Judgment of Infringement of ‘422 Claim 1, ‘933 Claim 3, and ‘698 Claim 6.
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encoding the mature erythropoietin amino acid sequence of FIG. 6” as compared to the limitation
“DNA sequence encoding human erythropoietin” of claim 1 of the ‘868 patent. Indeed, because
the claim language is so similar between the ‘868 patent and the ‘698 patent, to consider the
patentability of file claim 72, the Applicant agreed to file a terminal disclaimer over the ‘868
patent. (Ex. 24, ‘381 File History, Paper 7, 12/11/96 Interview Summary; see also Ex. 25, ‘381
File History, Paper 8, 12/20/96 Terminal Disclaimer; Ex. 26, ‘381 File History, Paper 9,
12/20/96 Second Preliminary Amendment at 10). Claim 6 of the ‘698 patent, like the claims of
the ‘868 patent, also are limited by the ‘179 application prosecution history to a process for the
14. Moreover, in Amgen Inc. v. Hoechst Marion Roussel, Inc., this Court and the
Federal Circuit explained that the limitation “the mature erythropoietin amino acid sequence of
FIG. 6” requires that the resulting amino acid be a 166 amino acid residue. See 314 F.3d 1313,
1345 (Fed. Cir. 2003). I understand that Amgen asserts that CERA “contains” 165 amino acids,
not 166. Therefore, even if Amgen’s allegations that CERA contains EPO are credited, Roche’s
15. On November 6, 1990, Applicant filed United States Application Serial No.
led to the issuance of the ‘422 patent after the filing of additional continuation applications Serial
No. 07/957,073 (“the ‘073 application”) and Serial No. 08/100,197 (“the ‘197 application”). The
‘741 application was filed as a continuation application under 37 C.F.R. § 1.60 of the prior ‘179
application (which issued as the ‘868 patent), and claims priority through the expired ‘008 patent
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to a December 13, 1983 filing date. (Ex. 29,‘741 File history, Paper 1, 11/6/90 Application). I
also note that the ‘422 patent was terminally disclaimed over both the ‘933 patent (discussed
below) and the ‘080 patent, as well as U.S. Patent No. 5,856,298. (Ex. 7, ‘178 File History,
Paper 32, 4/21/99 Examiner Interview Summary; Ex. 20, Paper 33, 4/28/99 Amendment at 4; Ex.
17. As originally filed and prosecuted, the ‘741 application included claims 48 and
49:
(Ex. 28, ‘741 File History, Application Claims at 102; see also Ex. 31, Paper 4, 4/6/92 Office
Action). I note that Table VI was subsequently redesignated as Figure 6 in the common
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(Ex. 17, ‘197 File History, Paper 2, 11/6/90 Preliminary Amendment at 8 (adding claims 61-63)).
19. With claims 1-63 pending in the application, the Examiner entered a restriction
requirement where Group I included claims 48 and 49 and Group VII included claims 61-63.
(Ex. 21,‘197 File History, Paper 4, 4/6/92 Office Action at 2). Applicant elected Group VII,
thereby removing claims to a synthetic polypeptide having part or all of the amino acid sequence
20. The Examiner then rejected each claim under §103 over several references
(Miyake et al., Takezawa et al. and Bock et al.) and because the Applicant admitted that
“‘[s]tandard diluents such as human serum albumin’ may be used in the claimed pharmaceutical
compositions.” (Ex. 18, ‘197 File History, Paper 20, 6/1/94 Office Action at 3). The Examiner
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rejections. (Ex. 35, ’197 File History, Paper 23, 12/1/94 Request for Reconsideration; Ex. 36,
Paper 25, 3/3/95 Amendment and Declaration of Richard D. Cummings, Ph.D.). However, the
[T]he Declaration by Dr. Richard Cummings ... has been considered but is
not deemed persuasive in regard to distinguishing the subject matter of
claim 63, drawn to recombinant EPO, from that found in urine. While the
declaration indicates some forms of recombinant EPO may be
alternatively glycosylated, the use of the generic term “recombinant” fails
to impose any definitive physical limitation on the claimed compositions.
(Ex. 19, ‘197 File History, Paper 26, 3/31/95 Letter (emphasis added)).
22. After a lapse in prosecution, Applicant cancelled claims 61-63 in favor of file
claims 64 and 65 which eventually issued as claims 1 and 2 of the ‘422 patent. (Ex. 20, ‘197 File
History, Paper 33, 4/28/99 Amendment at 3). Applicant explained that the amino acid sequence
common specification. (Id. at 4-5). Admittedly, Example 1 does not disclose the full 165-amino
acid sequence of human urinary EPO but only specific discrete fragments (Id.; Ex. 43, ‘868
patent, col. 16:9-40) and Examples 7 and 10 are directed to the human erythropoietin disclosed
erythropoietin with a 166-amino acid sequence. In the alternative, it also may include the two
alternative translation products disclosed during the prosecution of the ‘008 patent.
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23. To secure claim 1 of the ‘422 patent, the Applicant narrowed his claim from
“erythropoietin” to “human erythropoietin” to overcome prior art objections and explained that
the new limitation was based on examples 1, 7 and 10 – not some other product. Moreover, with
respect to chemically synthesized products with amino acid sequences, Amgen cannot rebut the
presumption that the subject matter was surrendered during prosecution of the applications
leading to the ‘422 patent especially because it cancelled all claims to “synthetic polypeptide
having part or all of the amino acid sequence” set forth in Figure 6 from the patent. Moreover, in
the related applications as discussed above, including the direct parent application – Ser. No.
24. On October 23, 1987, Applicant filed United States Application Serial No.
113,178 (“ the ’178 Application”), entitled “Production of Erythropoietin,” which, following the
filing of additional continuing applications (Ser. No. 08/202,874 (“the ‘874 application”) and
Ser. No. 08/487,774 (“the ’774 application”), led to the issuance of the ‘933 patent. The ‘178
application is a continuation of the ‘298 application and claims priority back to December 13,
1983.
25. I understand that Amgen has asserted claim 3 of the ‘933 patent and dependent
claims 7-9, 11-12 and 14, which incorporate each limitation of claim 3. Claim 3 recites:
(Ex. 44, ‘933 patent, claim 3 (emphasis added); see also claims 7-9, 11-12 and 14).
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26. During prosecution of the applications that led to the ‘933 patent, Applicant Lin
(Ex. 1, ‘178 File History, Application Claims at 97, 101, 102 (emphasis added), see also File
Claim 49).
27. Like Examiner Giesser during prosecution of the ‘024 application, Examiner
Kushan rejected claims 1, 7, 41 and 48 (as well as other claims) of the application that led to the
* * *
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The claims must particularly point out the essential aspects of the
disclosed invention. The broadest limitations must also be supported by
the disclosure. As currently set forth, the claims are indefinite and to an
extent, non-enabled.
(Ex. 9, ‘178 File History, Paper 4, 6/2/86 Office Action at 3-5 (emphasis added)). The Examiner
28. Examiner Kushan also held that claims to “synthetic polypeptides” were not
29. In response, Applicant canceled claims 1, 7 and 48 (as well as other claims). (Ex.
10, ‘178 File History, Paper 6, 12/1/88 Amendment and Reply at 3). Lin also amended claim 41
to read:
(Id.).3
3
Pursuant to Patent Office procedure when amending a claim deleted language is placed in brackets [ ] and added
language is underlined. Here, the underlining and bracketing is part of the original document.
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At the time of Applicant’s invention, nothing was known of the primary structural
conformation (amino acid sequence) of human erythropoietin except the identity
of a few of the amino acid residues. It was the present Applicant who first
developed knowledge of the full amino acid sequence of erythropoietin ....
Having provided the public with its first knowledge of naturally occurring
erythropoietin’s primary structural conformation. Applicant has provided the
pubic [sic] with the wherewithal for determining the extent to which any sequence
of amino acids may function, in vivo, as though it were the sequence encoded by
the erythropoietin gene in the human genome. No impermissible vagueness
attends claiming glycoproteins which share that amino acid sequence to an extent
sufficient to allow the products to function, in vivo, as erythropoietin
hematopoietic agents. Thus, the term “sufficiently duplicative of” as applied to
[the] amino acid sequence needed for the specified in vivo biological activity is
not violative of the requirements of the second paragraph of 35 U.S.C. §112.
(Id. at 8-9 (emphasis added)). As discussed above, however, the common specification discloses
to the public that the “primary structural conformation (amino acid sequence) of human
31. After failing to overcome the examiner’s §112 rejection (Ex. 11, ‘178 File
History, Paper 9, 2/10/89 Office Action), Applicant canceled claim 41 without prejudice, and
(Ex. 2, ‘178 File History, Paper 11, 6/2/89 Amendment at 1 (emphasis added)). Applicant
Claims 41, 55-57, and 61-66 were rejected under 35 U.S.C. 112, first and second
paragraphs. Reconsideration is requested in view of the above-noted new claims
and the remarks that follow.
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All product claims in the subject application are now product-by process claims.
Independent Claim 67, and thus all the pending claims, specifically define the
erythropoietin of the subject invention as a “glycoprotein product of the
expression of an exogenous DNA sequence in a eucaryotic host cell ....” These
product-by-process claims are presented in an effort to positively recite the
physical properties of recombinant erythropoietin, and to further define the
product of the subject invention since the recombinant erythropoietin claimed
cannot be precisely defined except by the process by which it is produced. It is
submitted that the claims now pending herein fully meet the requirements of 35
USC 112.
(Id. at 3-4 (emphasis added)).4 In arguing for reconsideration of the §103 rejection of claim 41
in view of new file claim 67, Applicant stated: “The claims of the subject invention relate to
original)).
32. Despite Applicant’s submission of new file claim 67 and his accompanying
argument, Examiner Kushan maintained his rejection under §112 regarding the use of primary
The claim as presented remain deficient under 35 USC 112 first and
second paragraphs. The following modifications are suggested to
overcome this rejection.
4
A product-by-process claim is a particular form of claim permitted by the Patent Office. A product-by-process
claim allows an applicant to draft a product claim that defines the claimed product in terms of the process by
which it is made. (Ex. 243, MPEP §2173.05(p) (8th ed. Rev. 5, Aug. 2006); Ex. 244, MPEP §706.03(e) (5th ed.
Rev. 6, Oct. 1987)). If the product in the product-by-process claim is the same as or obvious from a product of
the prior art, the claim is not patentable even though the prior product was made by a different process. (Id.).
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(Ex. 3, ‘178 File History, Paper 13, 6/20/89 Office Action at 3 (emphasis added)). Thus, the
Patent Office explained that Applicant was entitled only to the product (defined as a product-by-
process) that had the amino acid sequence of human erythropoietin, which the common
specification discloses as 166 amino acids, and that Lin was not entitled to analogs “sufficiently
duplicative” of human EPO. The Examiner also rejected claim 67 under §102 and §103. (Id. at
5).
(Ex. 4, ‘178 File History, Paper 15, 7/11/89 Amendment at 1 (underline in original)). He also
argued that:
Claims 67-75 stand rejected under 35 U.S.C. §112, first and second paragraphs.
Reconsideration is requested.
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(Id. at 3-4 (emphasis added)). Accordingly, the Applicant was still arguing that human
erythropoietin had 166 amino acids, but that he should be entitled to analogs of that sequence as
well.
(Ex. 6,‘178 File History, Paper 19, 1/10/90 Amendment at 1 (emphasis added)). Applicant
cancelled claims 67-75 which “stand rejected under 35 U.S.C. 112 first and second paragraphs.”
(Id. at 5; see also Ex. 5, Paper 17, 12/1/89 Examiner Interview Summary Record). He noted that
new claims 76-83 were “similar” to the cancelled claims, but “specify that the DNA sequences
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encode human erythropoietin” which the specification states is 166 amino acids. (Ex. 6, ‘178
35. Applicant Lin also noted that the new claims, including file claim 76, were
drafted to “parallel claim 2” of the ‘008 patent that had recently been held valid in Amgen Inc. v.
Chugai, Pharm. Co., 13 U.S.P.Q.2d 1737 (D. Mass. 1989). (See Ex. 6, ‘178 File History, Paper
19, 1/10/90 Amendment at 5). Claim 2 of the ‘008 patent claimed: “2. A purified and isolated
DNA sequence consisting essentially of a DNA sequence encoding human erythropoietin.” (Id.
at 6). Based on the validity of claim 2 of the ‘008 patent, Applicant argued that:
In determining that claims 2 and 4 of the Lin ‘008 patent are valid, the
Court recognized that Lin is the first inventor of the DNA sequence
encoding human erythropoietin and of the use thereof in a host cell to
make recombinant erythropoietin .…
* * *
The decision is thought to be fully dispositive of not only the priority of
the invention issues in both interferences, and any priority issue in the
subject application. Therefore, it is submitted that if Lin was the first to
invent the DNA encoding erythropoietin, and the use of that DNA in a
host cell to produce recombinant erythropoietin, then clearly he was the
first to invent a recombinant erythropoietin product produced using such a
host cell.
36. The Amgen v. Chugai decision, however, also held that claim 7 (and its dependent
claims) of the ‘008 patent invalid under §112 for lack of enablement. Claim 7 of the ‘008 reads:
(Ex. 40, ‘008 patent, claim 7 (emphasis added)). Invalid claim 7 of the ‘008 patent has claim
language similar to that of cancelled claim 67 which, as discussed above, required “a primary
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erythropoietin”. Thus, the Court, like Examiner Kushan, found this language did not comply
with §112. The Court noted that various parts of the common specification did not enable a
polypeptide having an amino acid sequence sufficiently duplicative of that of erythropoietin. See
13 U.S.P.Q.2d at 1776 (citing to the ‘008 patent, col. 37:1-4, 11-41 (regarding, for example,
“polypeptide analogs of EPO and fragments of ‘mature’ EPO” and “polypeptide fragments
37. The Federal Circuit affirmed that claim 7 of the ‘008 was invalid under §112
using different reasoning. Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1213-14 (Fed. Cir.
1991). Like Examiner Kushan’s previous rejections to claims reciting the limitation “sufficiently
duplicative of” during prosecution of the application that led to the ‘933 patent, the Court found
“that more is needed concerning identifying the various analogs that are within the scope of the
claim, methods for making them, and structural requirements for producing compounds with
EPO-like activity. It is not sufficient, having made the gene and a handful of analogs whose
activity has not been clearly ascertained, to claim all possible genetic sequences that have EPO-
which is similar to the broad language of claim of the ‘008 that attempted to not only cover
human EPO but “analogs” as well – in favor of language paralleling claim 2 of the ‘008 patent,
the Applicant narrowed the scope of his claimed invention in filing claim 76.
39. In any event, file claim 76 was also eventually cancelled from the prosecution.
(Ex. 34, ‘874 File History, Paper 37, 6/13/94 Preliminary Amendment). Similarly, file claim 99
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– which Applicants represented as having text identical to claim 76 (Ex. 32, ‘774 File History,
Paper 45, 6/7/95 Preliminary Amendment at 2) – was also canceled in favor of different claims.
(Ex. 33, ‘774 File History, Paper 50, 12/20/95 Second Preliminary Amendment at 2). For
example, asserted claim 3 of the ‘933 patent issued from file claim 102 including the limitation
40. Review of the file history demonstrates that to overcome the Examiner’s various
rejections during prosecution of the ‘933 patent, Applicant Lin chose to prosecute the asserted
claims of the ‘933 patent to issuance without the limitations (1) “having part or all of the primary
structural conformation ... of naturally-occurring erythropoietin,” (2) “part or all of the primary
occurring allelic variant thereof,” (3) “primary structural conformation sufficiently duplicative of
the amino acid sequence set forth in Figure 6”, which were rejected in file claims 1, 7, 41, 48 and
67. As a result of Lin’s amendments and decision to cancel claims to overcome the Examiners’
rejections, Amgen abandoned any potential patent coverage to the subject matter and can not
now assert that the claims cover that same subject matter that they had to surrender in exchange
for securing the asserted claims of the ‘933 patent from the Patent Office.
41. The ‘179 application, filed October 23, 1987, and entitled “Production of
Erythropoietin,” led to the issuance of the ‘868 patent on August 15, 1995. (Ex. 43, ‘868 patent).
The ‘179 application was filed as a continuation application under 37 C.F.R. §1.60 of the prior
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‘298 application filed on November 30, 1984 and claims priority through applications to
December 13, 1983. (Ex. 12, ‘179 File History, Paper 1). In addition to leading to the ‘868
patent-in-suit, the ‘179 application also is a direct parent application to both the ‘698 patent and
(Ex. 43, ‘868 patent, claim 1 (emphasis added); see also claim 2 (limiting the host cell to CHO
cells)).
43. During prosecution, in 1988, Applicant introduced, inter alia, claim 65 (and
dependent claims):
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(Ex. 16, ‘179 File History, Paper 8, 5/24/88 Second Preliminary Amendment at 3-4 (emphasis
added)).
44. In arguing for patentability of claim 65, Lin explained that the claimed invention
“relates to novel methods for the production in mammalian host cells of human erythropoietin
glycoprotein – the first article of human manufacture ever to possess both the amino acid
sequence and glycosylation needed for in vivo erythropoietin biological activity.” (Id., Ex. 16
Paper 8 at 6; see also Ex. 13 Paper 14, 9/27/88 Reply). Lin plainly stated that the claimed
invention was the process for making “human erythropoietin glycoprotein” in “mammalian host
cells”, not a chemical process for making a different product which is not erythropoietin.
45. For over seven (7) years Lin repeatedly defined the metes and bounds of his
claimed process within the Patent Office as a method for making an in vivo biological human
erythropoietin (as defined by the common specification). For example, during prosecution of the
‘868 patent Lin made the following statements regarding the scope of his process claims:
• “As set out in detail hereafter, the practice in late 1983 of processes herein
claimed is believed to constitute one of the first instances (if not the first
instance) of the recombinant production of an in vivo biologically active obligate
human glycoprotein ....” (Ex. 16, ‘179 File History, Paper 8, 5/24/88 Second
Preliminary Amendment at 6).
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prosecution, Lin further explained that his claims were limited to processes for isolating a
specific product – the “obligate glycoprotein” human erythropoietin rather than any other
product. (Ex. 16, ‘179 File History, Paper 8, 5/24/88 Second Preliminary Amendment at 8-10,
The skilled worker at the time of the present invention would thus have
understood that if preparations of in vivo biologically active human erythropoietin
were to be provided in therapeutic quantities by recombinant means, a method
would have to be devised whereby (a) an appropriate array of glycosylation
including sialic acid terminal residues and, possibly, penultimate galactose
residues would be provided on (b) a polypeptide with requisite amino acid
sequence homology to erythropoietin. Unlike other human glycoproteins such as
the interferons and Interleukin-2, human erythropoietin was conspicuously known
to be an obligate glycoprotein and no hope at all existed for isolating in vivo
active material from recombinant host cells unless, at a minimum, both the issues
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(Ex. 16, ‘179 File History, Paper 8, 5/24/88 Second Preliminary Amendment at 10 (emphasis
added)). Thus, the literal scope of the process claims, as explained by Lin during prosecution of
the ‘179 application, is limited to processes for making a glycosylated human erythropoietin
polypeptide not a chemically synthesized product such as Roche’s MIRCERATM and CERA
products.
47. There is no question that the Patent Office was led to believe that Lin’s method
was limited to a process for making human erythropoietin. For example, Lin relied upon the his
resulting product to overcome prior art processes and secure his method claims:
* * *
Applicant submits that the results of the above-described searches and analysis
provide a clear indication that the claimed methods as practiced in 1983 were
among the first, if not the first, instances of the successful production of an in
vivo biologically active obligate human glycoprotein.
(Ex. 16, ‘179 File History, Paper 8, 5/24/88 Second Preliminary Amendment at 16-17, 19
(emphasis added); see also Ex. 13, ‘179 File History, Paper 14, 9/26/88 Applicant’s Reply at 5
(“As set forth in detail at pages 16 through 20 of the Second Preliminary Amendment, it appears
that Applicant may have been the first to have successfully produced a human obligate
48. Lin’s continued reliance on the distinction of his end-product for years to
overcome prior art rejections of his process claims in the Patent Office plainly shows what he
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claimed as his invention. (Ex. 15, ‘179 File History, Paper 33, 1/3/94 Applicant’s Amendment
and Reply at 11 (“As previously maintained by Applicant, his production of in vivo biologically
active glycosylated erythropoietin was among the first, if not the first, demonstrations of
process claims Lin argued that “the core patentability issue is whether the prior art extant at the
time of the present invention provided the skilled artisan with a reasonable expectation of
success in securing the recombinant production of a human obligate glycoprotein...” (Ex. 13,
‘179 File History, Paper 14, 9/26/88 Applicant’s Reply at 3-4 (emphasis added)). Thus, the
49. Indeed, when Lin attempted to claim a process for making a product other than
the human erythropoietin disclosed by the common specification, his claims were rejected and
ultimately cancelled. In rejecting Lin’s application claims for violation of 35 U.S.C. §112, the
Examiner recognized the proper scope of Lin’s claimed process acknowledging only that:
polypeptide.” (Ex. 14, ‘179 File History, Paper 29, 9/1/93 Office Action at 9-10). The Examiner
noted that “the specification provides guidance for and a working example of only the production
of EPO” and that “the instantly claimed invention is critically dependent on an isolated clone of
encoding a polypeptide of interest. (Id. at 10). Thus, the Patent Office required Lin to limit his
claimed process to “a process for the preparation of biologically active glycosylated human
erythropoietin” (id.) and rejected claims to other processes and claims for processes to make
other products. Lin acquiesced to the Examiner’s requirement and subsequently limited his
pending claims as required by the Patent Office in exchange for his issued process claims. (Ex.
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15, ‘179 File History, Paper 33, 1/3/94 Amendment and Response at 2; Ex. 43, ‘868 patent
claims). As a result, Amgen cannot now broaden Lin’s process claims to cover more than what
50. Likewise, during prosecution of the application that led to the ‘933 patent, Lin
made clear that the ‘933 claims are limited to human erythropoietin as an obligate glycoprotein --
not other products -- and relied on this distinction to overcome rejections by the examiner.
At the time of the invention, the art knew that erythropoietin isolated from urine
was a glycoprotein and that treatment to remove its carbohydrate would destroy in
vivo biological activity. Applicant was the first to provide for a glycoprotein
which is both different from previously isolated urinary erythropoietin in its
glycosylation and yet sufficiently like the natural product (previously isolated in
the art) 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.
(Ex. 10, ‘178 File History, Paper 6, 12/1/88 Amendment and Reply at 9).
52. Similarly, Lin also explained that the claimed product was limited to the human
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I declare under penalty of perjury under the laws of the United States of America that the
CERTIFICATE OF SERVICE
I hereby certify that this document filed through the ECF system will be sent
electronically to the registered participants as identified on the Notice of Electronic Filing (NEF)
and paper copies will be sent to those indicated as non registered participants on the above date.
3099/501 696485.1
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