Amgen Inc. v. F. Hoffmann-LaRoche LTD et al

Filing 344

AMENDED ANSWER to #52 Amended Complaint,, Amended COUNTERCLAIM against Amgen Inc. by F. Hoffmann-LaRoche LTD, Roche Diagnostics GmbH, Hoffmann LaRoche Inc.. (Rizzo, Nicole)

Amgen Inc. v. F. Hoffmann-LaRoche LTD et al

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UNITED STATES DISTRICT COURT DISTRICT OF MASSACHUSETTS AMGEN INC., Plaintiff, v. F. HOFFMANN-LA ROCHE LTD, ROCHE DIAGNOSTICS GmbH, and HOFFMANNLA ROCHE INC., Defendants. ) ) ) ) ) ) ) ) ) ) )

Civil Action No.: 05 Civ. 12237 WGY DEFENDANTS' FIRST AMENDED ANSWER AND COUNTERCLAIMS TO PLAINTIFF'S COMPLAINT DEMAND FOR JURY TRIAL

In response to the Complaint For Declaratory Judgment Of Infringement ("Complaint") filed in this action by Amgen, Inc. ("Amgen"), F. Hoffmann-La Roche Ltd, Roche Diagnostics GmbH, and Hoffmann-La Roche Inc. (collectively "Roche"), by their attorneys, hereby amend their answer and counterclaims to the Complaint For Declaratory Judgment Of Infringement ("Complaint") of Amgen, Inc. ("Amgen") as follows: PART I: ROCHE'S ANSWER AND AFFIRMATIVE DEFENSES In response to the Complaint of Amgen, defendants Roche, by their attorneys, state as follows: 1. Roche admits that Amgen is a corporation existing under the laws of the

State of Delaware with its principal place of business in Thousand Oaks, California. Roche lacks knowledge or information sufficient to form a belief as to the truth of the remaining allegations of paragraph 1 of the Complaint. 2. 3. 4. 5. Admitted. Admitted. Admitted. Roche denies the allegations contained in paragraph 5 of the Complaint.

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6.

The statement in paragraph 6 of the Complaint is neither an averment nor

allegation to which a response is required. 7. 8. 9. 10. Admitted. Roche denies that venue and personal jurisdiction are proper in this Court. Roche denies the allegations contained in paragraph 9 of the Complaint. The statements in paragraph 10 of the Complaint are neither averments

nor allegations to which a response is required, and Roche otherwise denies these allegations. 11. Roche lacks knowledge or information sufficient to form a belief as to the

truth of the allegations contained in the statements of paragraph 11 of the Complaint, and denies those allegations. 12. 13. 14. Roche denies the allegations contained in paragraph 12 of the Complaint. Roche denies the allegations contained in paragraph 13 of the Complaint. Roche denies the allegations contained in paragraph 14 of the Complaint,

except Roche admits that U.S. Patents Nos. 5,441,868 ("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") (collectively "the patents-in-suit") were issued on the dates alleged. 15. The statements in paragraph 15 of the Complaint are neither averments

nor allegations to which a response is required, and Roche otherwise denies these allegations. 16. The statements in paragraph 16 of the Complaint are neither averments

nor allegations to which a response is required, except Roche admits that this Court has previously issued certain rulings in other litigations concerning certain of the patents-in-suit, and

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Roche refers Amgen to the actual decisions and orders of this Court, and any appellate court for the holdings therein, and Roche otherwise denies these allegations. 17. Roche lacks knowledge or information sufficient to form a belief as to the

truth of the allegations contained in the statements of paragraph 17 of the Complaint, and denies those allegations. 18. 19. 20. 21. 22. 23. 24. 25. Roche denies the allegations contained in paragraph 18 of the Complaint. Roche denies the allegations contained in paragraph 19 of the Complaint. Roche denies the allegations contained in paragraph 20 of the Complaint. Roche denies the allegations contained in paragraph 21 of the Complaint. Roche denies the allegations contained in paragraph 22 of the Complaint. Roche denies the allegations contained in paragraph 23 of the Complaint. Roche denies the allegations contained in paragraph 24 of the Complaint. Roche repeats and reasserts its responses to and denials of the allegations

contained in paragraphs 1- 24 of the Complaint. 26. Roche denies the allegations contained in paragraph 26 of the Complaint,

and states that CERA (short for Continuous Erythropoiesis Receptor Activator) was created by Roche and is a unique molecule and has been recognized by the FDA as a new chemical entity containing "no active moiety that [previously] has been approved by the FDA." See 21 C.F.R. § 314.108 (2005); see also id. § 314.50. 27. 28. 29. 30. Roche denies the allegations contained in paragraph 27 of the Complaint. Roche denies the allegations contained in paragraph 28 of the Complaint. Roche denies the allegations contained in paragraph 29 of the Complaint. Roche denies the allegations contained in paragraph 30 of the Complaint.

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31.

The statement of paragraph 31 of the Complaint is neither an averment nor

allegation to which a response is required, and Roche otherwise denies these allegations. AFFIRMATIVE DEFENSES FIRST DEFENSE - FAILURE TO STATE A CLAIM 32. The allegations of the Complaint fail to state a claim upon which relief can

be granted and should be dismissed under Fed. R. Civ. P. 12(b)(6). SECOND DEFENSE - PATENT MISUSE 33. The patents-in-suit are not enforceable, in whole or in part, due to

wrongful and improper conduct by Amgen which constitutes patent misuse. THIRD DEFENSE - NON-INFRINGEMENT 34. Roche has not infringed and is not infringing any of the claims of the '868,

'933, '698, '080, '349 and '422 patents, either directly or indirectly, or literally or under the doctrine of equivalents or due to the reverse doctrine of equivalents. FOURTH DEFENSE - SAFE HARBOR 35. Roche's allegedly infringing activities do not constitute infringement as a

matter of law under 35 U.S.C. § 271(e)(1) (2006). FIFTH DEFENSE - INVALIDITY 36. The claims of the '868, '933, '698, '080, '349 and '422 patents are invalid

because they fail to satisfy the conditions for patentability, including as specified in 35 U.S.C. §§ 101, 102, 103, 112, 116 and/or 282. SIXTH DEFENSE - DOUBLE PATENTING 37. The claims of the '868, '933, '698, '080, '349 and '422 patents are invalid

for double patenting over claims of Amgen's earlier issued and now expired U.S. Patent No. 4,703,008 ("the '008 patent") and U.S. Patent No. 4,667,016; and the claims of the `349, `933,

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`080, and `422 patents are invalid for double patenting over the claims of the `868 and `698 patents. SEVENTH DEFENSE ­ INEQUITABLE CONDUCT BEFORE THE PATENT OFFICE
INTRODUCTION

38.

Applicants for patents have a general duty of candor and good faith in

their dealings with the Patent and Trademark Office ("PTO") and an affirmative obligation to disclose to the PTO all information that they know to be material to the examination of a pending application pursuant to 37 C.F.R. § 1.56 (2006). This duty extends to the applicants and their representatives, such as their attorneys, and all others associated with the prosecution, including "every person who is substantively involved in the preparation or prosecution of the application." Id. 39. In 1987 Amgen obtained the '008 patent which essentially claimed the

isolated DNA sequence encoding EPO, and mammalian host cells transformed with this DNA sequence "in a manner allowing" these cells to express EPO and to glycosylate the biologically active EPO (referred to herein as "the DNA and host cell claims"). See, e.g.,'008 patent col. 40 ll. 1-3, 7-10, 60-62 (claims 2, 4, and 24). Amgen has enjoyed the full term of protection of this patent, which expired in 2004. 40. From 1995 to 1999 Amgen obtained new patents, which essentially

claimed methods for making EPO protein by utilizing mammalian cells transformed with the DNA sequence encoding EPO (the '868, '698 and '349 patents), and the EPO protein expressed by the transformed mammalian cells (the '933, '080, and '422 patents). Amgen has asserted these method and product claims against Roche as part of this lawsuit.

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41.

These six patents all share the same specification and all claim priority to

the parent application of the '008 patent. These patents demonstrate that Amgen essentially possessed only a single invention with minor obvious variations. 42. The patents-in-suit are unenforceable because individuals substantively

involved with the filing and prosecution of these patents, acting as agents or with the knowledge of plaintiff Amgen, knowingly and willfully concealed and misrepresented material evidence with the intent to deceive the PTO over the 16 years that Amgen prosecuted the '868, '933, '698, '080, '349 and '422 patents, and the now expired '008 patent. Inequitable Conduct Relating To Double Patenting 43. The patents-in-suit are unenforceable because individuals including, but

not limited to, Michael Borun, Steven Odre and Stuart Watt, associated with the filing and prosecution of these patents and acting as agents and/or with the knowledge of plaintiff Amgen, misrepresented material facts with the intent to deceive the PTO for purposes of overcoming a double patenting rejection based on Amgen's earlier filed and issued '008 patent. 44. During Amgen's prosecution of application Ser. No. 113,179 (the "'179

application"), which issued as the '868 patent, Amgen faced a double patenting rejection of all its pending claims (70 and 72-75) on grounds that these process claims were not patentably distinct from claims 1-6 of the '008 patent because it would have been obvious to one of skill to use the claimed erythropoietin encoding DNA of the '008 patent in prior art methods for host cell expression. Amgen overcame that rejection only by (1) misleading the examiner into believing that a dispositive judicial determination had already confirmed that none of the '008 patent claims encompassed subject matter of its pending '179 application process claims, (2) misleading the examiner into believing that the Patent Office in interference proceedings had

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already determined the subject matter of its pending '179 application process claims to be patentably distinct from any of the '008 claims, and (3) by failing to disclose arguments it made before the Patent Office Board of Patent Appeals and Interferences (the "Board"), as well as in opposition proceedings in Europe involving Genetics Institute's EP 411 678 (the '678 patent) and EP 209 539 (the '539 patent), inconsistent with and refuting its arguments for patentability of its pending '179 application process claims. 45. In particular, during the '179 prosecution, Amgen misrepresented the

court's decision in Amgen, Inc. v. U.S. Int'l Trade Comm'n, 902 F.2d 1532 (Fed. Cir. 1990), as holding that the "rights in the subject matter of '008 patent claims do not extend to the subject matter of the process claims herein . . . ." ('179 FH, Applicant's Amendment and Remarks Under 37 C.F.R. §§ 1.111 and 1.115 dated 10/7/94, at 7). The Federal Circuit considered only whether the composition claims fell within the ambit of 19 USC § 1337(g), which provides patentees the right to bring actions against foreign companies that allegedly infringe a patented process abroad. Significantly, the Court did not address whether the product claims were patentably distinct from the process Amgen was attempting to claim in the '179 application. The Court held only that the claims of the '008 patent could not be used in Section 1337(g) actions because they were not directed to a process. 46. Additionally, during the '179 prosecution, Amgen misrepresented to the

examiner that in connection with Interference No. 102,096 (the "Fritsch I interference") (with its sole count identical to claim 2 of the '008 patent) and Interference No. 102,097 (the "Fritsch II interference") (with its sole count identical to then pending '179 application claim 65) "it has thus been the position of the Patent and Trademark Office that the production process subject matter claimed herein was patentably distinct from the DNA-related subject matter claimed in

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U.S. 4,703,008." ('179 FH, Applicant's Amendment and Remarks Under 37 C.F.R. §§ 1.111 and 1.115 dated 10/7/94, at 7). 47. Not only did this misrepresent the position of the Board, which made no

such conclusion, Amgen failed to inform the examiner that in the Fritsch II interference it took the entirely contradictory position that its process claims were inherently part and parcel of the same invention as claimed in its '008 patent. While the count is directed to a process for preparing in vivo biologically active EPO using a mammalian host cell transfected or transformed with an isolated DNA sequence encoding human EPO [i.e., the process patent claims], and the litigation was directed to the purified and isolated DNA sequence and host cells transfected or transformed thereby [i.e., the '008 DNA claims], it is evident that these are only different manifestations of the same invention as acknowledged by Fritsch et al in their Motion Q here (and in Motion G in Interference No. 102,096). Clearly, the whole purpose and intent of the purified and isolated DNA sequence encoding human EPO (and host cells transfected therewith) at issue in the litigation was to express in vivo biologically active human EPO. Stated otherwise, the process language of the Lin patent claims at issue in the litigation ("encoding human EPO") [see '008 patent claims] is, for all intents and purposes, a description of the present count. (Fritsch v. Lin, Interference No. 102,097, Brief. for the Senior Party Lin at 25-26. (emphasis added)). Significantly, not only did Michael Borun submit Applicant's October 7, 1994 Amendment and Remarks in the '179 prosecution, Mr. Borun appears "of counsel" on the Lin Brief, evidencing his obvious familiarity with these contradictory positions that Amgen relied on during the interference and his knowing and intentional misrepresentation of those positions in prosecuting the '179 application. 48. Tellingly, Amgen also failed to inform the examiner that in the Fritsch II

interference, it had argued that resolving priority issues in regard to the count for the DNA

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sequence in the Fritsch I interference would necessarily determine those issues in regard to its process claims: The same is true with regard to the count of Interference 102,097 [process for making EPO], if Lin was the first to invent a host cell containing a DNA sequence in a manner allowing the host cell to express rEPO as determined by the Court [DNA count], he is of necessity the first to invent the process of making rEPO using such the host cell (see the count of Interference 102,097) [process for making EPO]." (Interference No. 102,097, Lin Reply Brief at 3 (emphasis in original)). "Fritsch [Genetics Institute] errs in saying that the District Court case did not involve the count (process for making EPO) of Interference No. 102,097. The Court assessed the priority evidence regarding the DNA sequence used to make EPO and the reduction to practice of the sequence necessarily and inherently includes the use of that sequence to make EPO according to the count of Interference No. 102,097." (Interference No. 102,097, Lin Reply Brief at 9 (emphasis in original)). 49. Moreover, Amgen failed to disclose arguments it made during opposition

proceedings in Europe involving Genetics Institute's EP 411 678 ('678 patent) and EP 209 539 ('539 patent) that were similarly inconsistent with and refuted its arguments for the patentability of its '179 application process claims.1 In this regard, Amgen acknowledged that its process and resulting in vivo biologically active erythropoietin was merely an obvious and inherent result of
1

In addition, Amgen also failed to disclose inconsistent arguments made during the following proceedings in Europe: (1) Ortho Pharmaceutical Corp. v. Boehringer Mannheim GmbH (Landgericht Dusseldorf (4 O 150/91)) (Patent infringement action for E 0 148 605), (2) Boehringer Mannheim GmbH v. Janssen-Cilag GmbH (4 O 229/91, Landgericht Dusseldorf) (Cilag I), EP 0 205 564 (3) Boehringer Mannheim GmbH v. Janssen-Cilag GmbH (4 O 58/92, Landgericht Dusseldorf) (Cilag II), EP 0 411 678; (4) Boehringer Mannheim GmbH v Kirin-Amgen, (3 Ni 32/93, Bundespatentgericht (BPG)) and appeals therefrom and (5) Kirin-Amgen and Ortho Pharmaceuticals v. Boehringer Mannheim GmbH and Boehringer Mannheim UK Ltd., The High Court Of Justice Chancery Division, Patents Court (CH 1993-K-No. 937).

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expressing the DNA sequence encoding human erythropoietin in a host cell: "the particular type of glycosylation linkages was simply a result of the type of host cell used to produce the recombinant erythropoietin." (EP 411 678 Opposition Proceedings, Statement of Grounds submitted by Amgen 10/8/92). Amgen's consistent pattern of failing to apprise the United States examiners of material information from European proceedings is similarly shown through its failure to disclose arguments that were raised during the opposition proceedings to its KirinAmgen European Patent Application No. 0 148 605 regarding the high materiality of errors in the data corresponding to Example 10 of its US patent application. 50. Lastly, Amgen also asserted that it was inappropriate for the Examiner to

consider prior art (the Yokota 4,695,542 patent) in conjunction with the claims of the '008 patent to show that the pending claims were obvious ('179 FH Applicant's Amendment and Remarks Under 37 C.F.R. §§ 1.111 and 1.115 dated 10/7/94, at 10). Amgen presented no authority in support of this proposition, and consequently misstated the law, which provides that consideration of prior art may be necessary to determine whether one of skill in the art would deem the later claim to be merely an obvious variation on the earlier one. 51. Throughout its response to the PTO's office action rejection on double

patenting, Amgen therefore intentionally misrepresented its own understanding of the claims, misrepresented the facts of prior proceedings and misstated legal standards. This fraud on the PTO was motivated by Amgen's need to improperly extend the life of its EPO invention by maintaining and prosecuting applications that issued into patents, which were obvious over an earlier issued and now expired patent. In response, examiner Martinell allowed all of Amgen's pending claims, plainly demonstrating the examiner's reliance on Amgen's misrepresentations. But for these misrepresentations, the examiner would not have allowed the '179 claims to issue,

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as they did in the '868 patent, in any patent entitled to a term exceeding that of the earlier commonly owned '008 patent. See Eli Lilly & Co. v. Barr Labs., Inc., 251 F.3d 955, 968 (Fed. Cir. 2001). 52. Amgen's misrepresentations during prosecution of the '179 application

(which issued as the '868 patent) relating to the patentability of its pending product claims over the '008 patent are just as material to the product claims of the other later issued patents in the '179 family, the '698, '422 and '349 patents. But for such misrepresentations, examiner Martinell would not have allowed the claims of these patents to issue, as they did, in patents having a term exceeding that of Amgen's earlier commonly owned '008 patent. 53. Moreover, Amgen's understanding, (and admissions to the Patent Office)

that the claimed product described by the pending '178 claims was merely the inherent product of the process Amgen was attempting to claim in the '179 prosecution renders these misrepresentations just as material to Amgen's prosecution of process claims in the '178 line of applications, which ultimately issued as the '080 and '933 patents, as they were to the claims of the '868 patent. (see infra, §§ 54-64). But for such misrepresentations, examiner Martinell would not have allowed the claims of these patents to issue, as they did, in patents having a term exceeding that of Amgen's earlier commonly owned '008 patent. INEQUITABLE CONDUCT RELATING TO FAILURE TO DISCLOSE THE BASIS FOR AN
EXAMINER'S REJECTIONS OF SUBSTANTIALLY SIMILAR CLAIMS IN CO-PENDING APPLICATIONS

54.

Amgen's patents-in-suit all issued from one of two co-pending lines of

applications, originating from applications Ser. Nos. 07/113,178 (the '178 application) and 07/113,179 (the '179 application), which Amgen filed on October 23, 1987 as continuations of Ser. No. 675,298, which issued October 27, 1987 as the '008 patent. The '178 line ultimately led

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to the '080 and '933 patents, while the '179 line ultimately led to the '868, '698, '422 and '349 patents. 55. As exemplified below, on numerous occasions during the prosecution of

these co-pending lines of applications, the examiner in one line of co-pending applications issued rejections to claims that were substantially similar to claims that Amgen was prosecuting in the other co-pending line. The existence and grounds for such rejections in one co-pending line

constituted highly material information that Amgen had a duty to disclose in the other copending line either under the pre-1992 "reasonable examiner" standard, or the new Patent Office standard set forth in 37 C.F.R. §1.56 (1992). See Dayco Prods., Inc. v. Total Containment, Inc., 329 F.3d 1358, 1367-8 (Fed. Cir. 2003). A prior rejection of a substantially similar claim refutes, or is inconsistent with the position that those claims are patentable. An adverse decision by another examiner, therefore, meets the materiality standard under the amended Rule 56. Id. 56. Here, the patents-in-suit are unenforceable because individuals associated

with the filing and prosecution of these patents, in arguing for the patentability of pending claims in one line of applications knowingly took positions inconsistent with highly material arguments that examiners raised against the patentability of substantially similar claims in the other copending line of applications, but nonetheless knowingly and intentionally failed to disclose those rejections. 57. Amgen's intent to deceive the patent office is further evidenced by the fact

that at least Amgen attorneys Steven Odre and Michael Borun were both involved throughout the prosecution of the '178 and '179 lines of applications, and therefore, had intimate knowledge regarding the proceedings of both lines of applications. (See '178 FH, Preliminary Amendment dated 10/23/87; '178 FH, Exam'r Interview Summary Record dated 7/20/88; '178 FH, Exam'r

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Interview Summary Record dated 11/18/93; '774 FH, Exam'r Interview Summary Record dated 3/14/96; '179 FH, Preliminary Amendment dated 10/23/87; '179 FH, Exam'r Interview Summary Record dated 9/14/88; '179 FH, Exam'r Interview Summary Record dated 9/7/94.) In addition, Mr. Borun was intimately involved in and therefore, aware of material details of the prosecution of the applications which led to the '008 patent. (See '179 FH, Decl. Accompanying Petition to Make Special Because of Actual Infringement dated 2/9/88). 58. In prosecution of the '179 application, Amgen submitted a Second

Preliminary Amendment canceling all pending claims and entering five new claims 65-69. Among these the only independent claim (65) recited "a process for the preparation of an in vivo biologically active glycosylated polypeptide comprising the steps of: (a) growing a mammalian host cell which is capable of effecting post-translational glycosylation of polypeptides expressed therein and which is transformed or transfected with an isolated DNA sequence encoding a polypeptide having a primary structural conformation sufficiently duplicative of that of 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, or the progeny thereof, under nutrient conditions suitable to allow, in sequence, (i) transcription within said host cell of said DNA to mRNA in the sequence of transcription reactions directed by the nucleotide sequence of said DNA; (ii) translation within said host cell of said mRNA to a polypeptide in the sequence of translation reactions directed by the nucleotide sequence of said transcribed mRNA; (iii) glycosylation within said host cell of said polypeptide in a pattern directed by the amino acid sequence of said translated polypeptide and sufficiently duplicative of the pattern of glycosylation of naturally occurring human erythropoietin to allow possession by the translated glycosylated polypeptide product of the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells; and (b) isolating the glycosylated polypeptide so produced.

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The dependent claims further characterized the claimed process in terms of host cell expression of cDNA (68) or genomic DNA (69) sequences, particularly in a CHO cell (66) or COS cell (67). ('179 FH, Second Preliminary Amendment dated 5/24/88 at 3-4). 59. In the first Office Action dated August 3, 1988, Examiner Tanenholtz

rejected the pending claims to a host cell expression process for making a glycosylated recombinant EPO (rEPO) as obvious and unpatentable over Yokota et al. (US Pat. No. 4,695,542) which taught production of a glycosylated protein by expressing of a DNA sequence encoding the protein in a mammalian host cell, and also in view of Gething et al. 1984 (Modern Approaches to Vaccines pages 263-268), which indicated that eukaryotic cells innately possessed the property of glycosylating proteins. ('179 FH, Office Action dated 8/3/88, at 3). Among

other things, the Examiner noted that "it would be expected that where one expresses the cDNA gene encoding erythropoietin using the Yokota et al. procedures the resulting erythropoietin would necessarily be glycosylated." 60. In this same time period, in its co-pending '178 application, Amgen

sought to prosecute substantially similar claims directed to the product of the process described by its pending '179 application claims. Significantly, Examiner Tanenholtz was not involved in the '179 prosecution, which was before a different examiner, Jeff Kushan. In particular, in its December 1, 1988 Amendment and Reply, Amgen added new claims 61-66 directed to a human erythropoietin glycoprotein product "having a primary structural conformation 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 further characterized as a product derived "from eukaryotic host cell expression (61) of exogenous cDNA (62) or genomic DNA (63) sequences, particularly in

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mammalian host cells (64) such as COS (65) and CHO(66) cells." ('178 FH, Amendment and Reply Under 37 C.F.R. §1.111 and 1.115 dated 10/23/87, at 5-6). 61. The substantial similarity of these pending '178 claims to the pending

process claims of the '179 application (and Amgen's awareness of that fact) is evident through Amgen's response to Examiner Tanenholtz' August 3, 1988 Office Action in the '179 prosecution. There, Amgen argued that pending claims 65-69 were directed to "a novel series of process steps wherein a mammalian host cell (including such non-human, non-kidney cells as COS and CHO cells as specified in claims 66 and 67) capable of glycosylating the expressed polypeptides is first transformed or transfected with a DNA sequence (including, e.g., cDNA and genomic DNA as specified in claims 68 and 69) encoding a specifically delineated polypeptide, i.e., one having a sufficient amino acid sequence homology to natural human erythropoietin to allow it to qualify, amino acid sequence-wise, for potential in vivo biological activity. (The DNA reagent employed in the transformation/transfection process is itself the novel and unobvious subject matter of claim 7 of U.S. Patent 4,703,008 and the resulting host cells are as recited in claim 24 of the Patent)." ('179 FH, Applicant's Reply dated 9/27/88, at 2). 62. Amgen's characterization of its pending '179 claims strikingly

demonstrates that Amgen's '178 application claims were directed to nothing more than the inherent product of '179 claims 65-69. Aware of the high materiality of Examiner Tanenholtz's rejection in the '179 prosecution to the substantially similar claims then pending in the '178 prosecution, Amgen knowingly and intentionally failed to disclose that rejection, or the basis for that rejection to Examiner Kushan in the '178 prosecution. 63. Amgen's failure to disclose Tanenholtz' August 3, 1988 rejection in the

'178 prosecution took on even greater significance in view of Amgen's subsequent actions in the

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'178 prosecution.

On February 10, 1989, examiner Kushan issued a Final Office Action

rejecting all the pending claims on several grounds. Among the rejections, Kushan objected to the claimed description of the glycoprotein product as having "glycosylation sufficiently duplicative of that of a naturally occurring human erythropoietin" as indefinite in "not particularly pointing out what the actual glycosylation comprises." ('178 FH, Office Action dated 2/10/89, at 2). Notably, examiner Kushan never raised the argument that Tanenholtz had raised as to the obviousness of the process used to make the claimed rEPO product, nor did he raise the Yokota or Gething references that Tanenholtz had cited. 64. In response, Amgen replaced all pending claims with new claims 67-75,

which defined the claimed product solely through the process through which it was made. In particular, Amgen noted that "[a]ll product claims in the subject application are now product-byprocess claims. Independent claim 67, and thus all of 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." ('178 FH, Amendment under Rule 116 dated 6/2/89, at 3-4). Amgen once again failed to disclose the rejection by Tanenholtz as to the obviousness of this process. 65. In fact, throughout the remainder of the '178 prosecution, Amgen

continued to argue the novelty of claims to a glycosylated erythropoietin product knowing that its arguments were wholly inconsistent with the basis of Examiner Tanenholtz' 1988 rejection of

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claims directed to that process as obvious, but never bringing that rejection to the attention of the '178 examiners. 66. In an Amendment dated July 11, 1989, Amgen left all its product-by-

process claims pending, amending only claim 67 to specify that the claimed product of host cell expression was one produced through a process using a non-human host cell, in order to distinguish the claimed erythropoietin product from the erythropoietin product produced by using a human cell line in the process taught by Sugimoto. ('178 FH, Amendment dated 7/11/89, at 5). Once again, Amgen failed to disclose the rejection by Tanenholtz as to the obviousness of the process described in the pending claims. 67. In the subsequent Amendment dated January 10, 1990, Amgen cancelled

claims 67-75, replacing them with new claims 76-83, which Amgen indicated "are similar to cancelled claims 67-75, but which specify that the DNA sequences encode human erythropoietin. These new claims parallel claim 2 of U.S. Patent No. 4,703,008 (Lin '008 patent), the parent of the instant application." ('178 FH, Amendment under Rule 116, dated 1/10/90, at 5). 68. In addition, Amgen argued against suspending prosecution during the co-

pending Fritsch v. Lin interferences No. 102,096 (Fritsch I) involving the Lin '008 patent and No. 102,097 (Fritsch II) involving the Lin `179 process application, in view of the December 11, 1989 decision in Amgen, Inc., v. Chugai Pharm. Co., Ltd. and Genetics Instit., Inc. Civil Action No. 87-2617-Y. In particular, Amgen indicated that against an anticipation attack based on Dr. Fritsch's work at Genetics Institute, not only had the Court upheld claims of the Lin '008 patent directed to the purified and isolated DNA sequence for human erythropoietin, it had also upheld claims to a host cell transformed with such a sequence. ('178 FH, Amendment under Rule 116 dated 1/10/90, at 5-6). Amgen asserted the Court's decision was therefore "fully dispositive" not

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only of any priority issue in both interferences, including the Fritsch II interference involving the '179 application, but also of any priority issue in the subject '178 application, stating: "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." Id. at 6. Knowing this, Amgen again knowingly and intentionally failed to disclose the rejection by Tanenholtz as to the obviousness of the process, while at the same time arguing that its amendment rendered the claims "in condition for immediate allowance and issuance of a patent." Id. at 5. 69. Amgen continued prosecution of the '178 claims in the '874 application,

which Amgen filed on February 28, 1994. On April 8, 1994, Amgen submitted a voluminous Information Disclosure Statement ("IDS"), listing almost 400 references, including references of record in the '178 prosecution, the '179 prosecution, the European Opposition Proceeding involving Amgen's EP 148,605, defendant's section 282 notice from Amgen v. Chugai, as well as admitted exhibits from Amgen v. Chugai. ('874 FH, IDS dated 4/8/94). Significantly, a biotechnology examiner would only have spent approximately 20 hours examining any individual application, such as the '874 application. (See, e.g., U.S. Gen. Accounting Office, GAO-RCED-89-120BR, Biotechnology, Backlog of Patent Applications, at 20 (1989)). Although the 4/8/94 IDS included the Yokota and Gething references cited in the '179 prosecution by examiner Tanenholtz, had the examiner devoted all his time merely to reviewing the cited references, he would have had only about three minutes for each reference. Amgen's continued failure to bring the rejection by Tanenholtz to the attention of the examiners in the '178 line of applications, or to point out the relevance of the Yokota and Gething references to

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that rejection, assured that the material nature of these references would remain buried under a mountain of other art. 70. Amgen's failure to disclose relevant rejections from its co-pending '179

line continued in its prosecution of the '874 application. In a Preliminary Amendment, Amgen cancelled all pending claims, which it replaced with new claims 84-89 (which going forward were renumbered as claims 87-97). ('874 FH, Preliminary Amendment dated 6/13/94). Among the new pending independent claims, Amgen again included product-by-process claims defining the claimed human erythropoietin glycoprotein solely through the process by which it was produced. For example, claim 86 (renumbered as 89) recited: The in vivo biologically active human erythropoietin glycoprotein product of the process comprising the steps of: (a) growing, under suitable nutrient conditions, mammalian host cells transformed or transfected with an isolated DNA sequence encoding the human erythropoietin amino acid sequence set out in FIG 6 or a fragment thereof; and (b) isolating a glycosylated erythropoietin polypeptide therefrom. Amgen again failed to raise the 8/3/88 rejection by Tanenholtz that the process of host cell expression incorporated into this claim would have been obvious over Yokota et al 4,695,542 and Gething et al (Modern Approaches to Vaccines pages 263-268). 71. Amgen filed both application Ser. No. 468,556, which ultimately issued as

the '080 patent, as well as application Ser. No. 487,774, which ultimately issued as the '933 patent, as continuation applications from the '874 application. Amgen's failure to disclose the highly relevant and material rejections it received during the '179 prosecution, as described herein, during prosecution of the '178 and '874 applications, therefore critically tainted the prosecution of both the '080 and '933 patents. Accordingly, on these grounds, both the '080 and '933 patents should be held unenforceable for inequitable conduct before the Patent Office.

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72.

Amgen's pattern of intentionally withholding material information from

the examiners is further evidenced by its failure conversely to disclose rejections it received in the course of prosecuting claims in the '178 line of applications during its prosecution of the '179 application as well as in further continuations of the '179 application, specifically, application Ser. No. 609,741, Ser. No. 957,073, and Ser. No. 100,197. The '178 application contained pharmaceutical composition claims that were substantially similar to those of the '741, '073 and '197 applications, which eventually issued as the '422 patent. In addition, as also noted, supra, in paragraphs 58-64, the '178 application contained product-by-process claims that were substantially similar to the process claims of the '179 application, which eventually issued as the '868 patent. 73. In particular, during the prosecution of substantially similar claims in the

'179, '741, '073 and '197 applications, Amgen failed to disclose the following rejections made during the prosecution of the '178 application: (1) The June 2, 1988 rejection by Examiner Kushan rejecting, among others, claim 55 under 35 U.S.C. 103 as being unpatentable over Miyake et al, Takezawa et al, Chiba et al or Sugimoto et al in view of Papayannopoulo et al. Amgen argued for the patentability of claims substantially similar to rejected claim 55 in the '741, '073 and '197 applications and failed to disclose the prior rejection by Examiner Kushan. (See '741 FH, Preliminary Amendment dated 11/6/90; '073 FH; and '197 FH Amendment Under Rule 1.116 dated 12/20/93); The February 10, 1989 rejection by Examiner Kushan rejecting, among others, claims 61-66 under 35 U.S.C. §103 as being unpatentable over Miyake et al, Chiba et al, Takezawa et al or Sugimoto et al and claims 55 and 61-66 under 35 U.S.C. 103 as being unpatentable over Miyake et al, Chiba et al, Takezawa et al or Sugimoto et al, in view of Papayannaopoulo et al. Amgen argued for the patentability of claims substantially similar to the rejected claims in the '179, '741, '073 and '197 applications and again failed to disclose the prior rejections by Examiner Kushan. (See '741 FH, Preliminary Amendment dated 11/6/90; '073 FH; '197 FH Amendment Under Rule 1.116 dated 12/20/93; and '179 FH Applicant's Second Preliminary Amendment dated 5/24/88, Applicant's Amendment and Response Under 37 C.F.R. §§1.115 and 1.111 dated 1/3/94);

(2)

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(3)

The June 20, 1989 rejection by Examiner Kushan rejecting, among others, claims 67-73 under 1) the doctrine of obviousness-type double patenting as being unpatentable over the prior invention as set forth in claim 1 to 11 of U.S. Patent No. 4,667,016, 2) 35 U.S.C. 102(b) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Sugimoto et al. and 3) 35 U.S.C. 103 as unpatentable over Sugimoto et al. in view of Papayannopoulo et al. Amgen argued for the patentability of claims substantially similar to the rejected claims in the '179, '741, '073 and '197 applications and again failed to disclose the prior rejection by Examiner Kushan. (See '741 FH, Preliminary Amendment dated 11/6/90; '073 FH; '197 FH Amendment Under Rule 1.116 dated 12/20/93; and '179 FH Applicant's Second Preliminary Amendment dated 5/24/88, Applicant's Amendment and Response Under 37 C.F.R. §§1.115 and 1.111 dated 1/3/94); The September 18, 1989 rejection by Examiner Kushan rejecting, among others, claims 67-73 under the doctrine of obviousness-type double patenting as being unpatentable over the prior invention as set forth in claim 1 to 11 of U.S. Patent No. 4,667,016. Amgen argued for the patentability of claims substantially similar to the rejected claims in the '179, '741, '073 and '197 applications and again failed to disclose the prior rejection by Examiner Kushan. (See '741 FH, Preliminary Amendment dated 11/6/90; '073 FH; '197 FH Amendment Under Rule 1.116 dated 12/20/93; and '179 FH Applicant's Second Preliminary Amendment dated 5/24/88, Applicant's Amendment and Response Under 37 C.F.R. §§1.115 and 1.111 dated 1/3/94).

(4)

INEQUITABLE CONDUCT RELATING TO MISREPRESENTATIONS REGARDING ALLEGED DIFFERENCES BETWEEN R-EPO AND U-EPO Contradictory Statements of Amgen's Scientist 74. Amgen, and those acting on its behalf who were substantively involved in

the prosecution of the patents-in-suit, knowingly misled the PTO through misstatements and omissions of material information with the intent to deceive and mislead the PTO to obtain the patents-in-suit, thereby tainting all patents sharing the common specification. Accordingly, the patents-in-suit should be held unenforceable for inequitable conduct before the PTO. 75. In order to obtain allowance for its protein claims, Amgen distinguished

its recombinant EPO ("r-EPO") from natural urinary EPO ("u-EPO") by representing that the average carbohydrate composition, glycosylation, and molecular weight of its r-EPO were

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different from that of naturally occurring human EPO proteins. Amgen incorporated these alleged differences into claims of the '933 and '080 patents as elements of patentability and proceeded to argue to the PTO, even in the face of its own contradictory data, that these elements made these claims patentable over u-EPO. 76. Amgen and its representatives, in the course of foreign patent proceedings

and before the FDA, relied on statements and information regarding the molecular weights and carbohydrate compositions of r-EPO and u-EPO that were inconsistent, and refuted the positions Amgen took during prosecution of its patents before the PTO, and in the Fritsch et al. v. Lin patent interference No. 102,334. 77. Two declarations, which have never been previously considered by this or

any U.S. Court, contain sworn statements by an Amgen scientist which utterly contradict positions that Amgen took in arguing patentability of its then pending EPO claims to the PTO. 78. Dr. Thomas W. Strickland became involved in Amgen's EPO project in

August 1984 and worked on the purification of r-EPO. Dr. Strickland was also involved in the prosecution of Amgen's protein patents related to EPO. In December 1988, during the

prosecution of the '178 application, Amgen submitted a declaration by Amgen's scientist, Dr. Strickland, stating that Amgen's recombinant EPO product was chemically distinct, and therefore novel and patentable over natural human EPO that was isolated and purified from urine ("the 1988 Strickland declaration"). Specifically, Strickland stated: recombinant erythropoietin as described by Serial No. 113,178 has a different carbohydrate composition than naturally occurring urinary erythropoietin. ('178 FH, Strickland Decl. dated 11/30/88, at 15). 79. The prosecution history for the '178 application shows that the assertions

made in the 1988 Strickland declaration were crucial for the patentability of Amgen's product

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claim to EPO. The Examiner Interview Summary Record dated 1/26/89 makes it clear that the Examiner interpreted the declaration to relate to differences in carbohydrate content. As stated by the Examiner: [D]iscussed effect of declaration on 102 aspects of the original rejection. Discussed effect on 103-based arguments of the difference in glycosylation (carbohydrate content). ('179 FH, Exam'r Interview Summary Record dated 1/26/89 (emphasis added)). 80. Amgen made this argument (both in 1988 in order to obtain the '933

patent, and then later in the Fritsch v. Lin interference proceeding) knowing it was false, and then continued to hide that fact from the patent office. The clear evidence for this is that the 1988 declaration by Strickland was directly contradicted by Dr. Strickland himself in two later declarations filed in connection with two opposition proceedings in Europe to Genetics Institute's erythropoietin patents EP 411 678 ("the '678 patent) and EP 209 539 ("the '539 patent"). 81. In February 1992, Amgen submitted the first declaration by Dr. Strickland

in support of Amgen's European opposition proceedings against the Genetics Institute '678 patent ("the 1992 Strickland declaration"). (Strickland European Decl. dated 2/13/92). The '678 patent contained claims drawn to a method for producing glycosylated recombinant EPO, which Amgen opposed by arguing, in part, that r-EPO and u-EPO were the same. Strikingly, the '678 patent reported its r-EPO as being analytically identical to human EPO purified from urine (u-EPO). The 1992 Strickland declaration argued that the '678 patent claims produced a protein that is indistinguishable in terms of carbohydrate composition from a protein that was produced by Amgen in 1985 using the procedures set forth in Example 10 of Amgen's European patent EP 148 605 ("the '605 patent"), which is the European counterpart to the '933 patent. Based on experiments discussed in the 1992 Strickland declaration, Strickland concluded that the

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carbohydrate composition of the 1985 EPO prepared in accordance with Example 10 of Amgen's '605 patent was the same, within the range of experimental and analytical error, as the EPO of the Genetics Institute '678 patent which in turn, according to that '678 patent was chemically identical to u-EPO. The 1992 Strickland declaration was not disclosed to the PTO. 82. In May 1994, Amgen submitted another declaration by Dr. Strickland in

support of Amgen's European opposition proceedings against Genetic Institute's '539 patent ("the 1994 Strickland declaration"). The Genetics Institute patent had claims directed to a recombinant EPO product, which Amgen again opposed by arguing, in part, that r-EPO and uEPO were the same. In this declaration, Dr. Strickland stated: In order to demonstrate the viability of the specific disclosure of Example 10 of EP 148605 [counterpart U.S. patent], reverse phase HPLC was used to purify rEPO directly from cell culture media in which the rEPO had been expressed from CHO cells as described in Example 10. The results show that by following the disclosure of example 10 homogeneous erythropoietin is obtained that meets all the requirements of claim 2 of EP 209539, i.e., ...(b) a molecular weight of about 34,000 daltons on SDS-PAGE ... (Strickland European Decl. dated 5/14/94, at 2 (emphasis added)). According to this declaration, r-EPO prepared in accordance with Example 10 had a molecular weight of 34,000 daltons, the same as that of u-EPO as reported at Col. 5, line 48 of the '933 patent, and not higher, as reported in Example 10. 83. Significantly, Amgen submitted an IDS for the U.S. Application Ser. No.

202874 which listed dozens of references that were part of the European proceedings involving EPO. However, the 1992 and 1994 Strickland declarations were not disclosed to the PTO. Amgen's knowing and intentional failure to disclose material information from Amgen's European opposition proceedings is evidenced at least by the direct involvement of Amgen attorneys Steven Odre and Stuart Watt in those proceedings, which included personally attending

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oral proceedings in Europe. (EP 411 678, EPO Opposition Proceedings , Record of Public Oral Proceedings Before the Opposition Division, dated 12/16/94). Additionally, the claims of the later issued '698, '080, '349 and '422 patents from the same family as the '933 patent, are sufficiently interrelated with the '933 claims and have a substantial relationship with the inequitable acts such that these patents should also be deemed unenforceable under the doctrine of "infectious unenforceability." Additional Contradictory Statements 84. In addition to the contradictory statements made by Amgen in the 1992

and 1994 Strickland declarations, Amgen and its employees, including even the named inventor of the Amgen EPO Patents, have made numerous statements, in publications and to the FDA, that directly contradict positions Amgen has taken before the PTO during the prosecution of the patents in suit. These additional contradictory statements further evidence Amgen's intent to deceive the PTO. See Digital Control Inc. v. Charles Mach. Works, 437 F.3d 1309, 1319 (Fed. Cir. 2006) ("Intent . . . may be inferred from the totality of the evidence."). Tellingly, Amgen's conduct throughout prosecution reveals a consistent pattern of purposely failing to disclose material information to the examiners. During the prosecution of the '349 and '422 patents, Amgen made no effort to inform the PTO of the then pending litigation against TKT (Civil Act. No. 97-10814-WGY). 85. Lin, the inventor of the patents in suit, reported in a publication that "[r-

EPO] has an apparent [molecular weight] of 34,000 when analyzed in an electrophoretic transfer blot." Lin et al, Cloning and Expression of the Human Erythropoietin Gene, 82 Proc. Nat'l Acad. Sci., 7580, 7582 (1985). The specification for the '933 patent states that the molecular weight of natural EPO was also "approximately 34,000 dalton." ('933 patent, Col. 5, lines 48-

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50). Lin, therefore, knew as of 1985 that the molecular weights of r-EPO and u-EPO were the same, yet, as shown in Example 10 of the '933 patent which issued from an application that was filed in 1995, continued to state that the molecular weight of r-EPO was higher than that of uEPO. 86. In addition, two Amgen scientists, Dr. Joan Egrie, and Dr. Thomas

Strickland, reported in a publication that "Both the purified natural and recombinant EPO preparations were characterized . . . by Western analysis. . . . By Western analysis, the recombinant and human urinary EPO migrate identically." Egrie et al Characterization and Biological Effects of Recombinant Human Erythropoietin, 172 Immunobiology 213 (1986). If rEPO and u-EPO "migrate identically" that means that the two products have the same apparent molecular weight. Therefore, the finding that r-EPO and u-EPO "migrate identically" This publication,

contradicts Dr. Egrie's data reported in Example 10 in the '933 patent. however, was withheld from the Examiner of the '933 patent. 87.

Additional internal documents from Dr. Egrie provide evidence regarding

glycosylation inconsistent with the positions that Amgen took during prosecution of its patents. (See AM-ITC 00828987-88). This information was never disclosed to the examiner. 88. Another Amgen scientist, Jeff Browne, corroborated the published

findings of Egrie and Strickland, stating in a publication that human u-EPO and CHO-cell derived r-EPO migrate identically in SDS-polyacrylamide gels. Browne et al, Erythropoietin: Gene Cloning, Protein Structure, and Biological Properties, 51 Cold Spring Harbor Symposia on Quantitative Biology 693-702, 698 (1986). This publication also was not disclosed to the Examiner. Additionally, in order to receive approval for its r-EPO drug, Amgen made

statements to the FDA that directly contradict the positions Amgen took in arguing patentability

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of its EPO claims to the PTO.

Significantly, these statements were not submitted to the

Examiner of the '933 patent. (See Amgen PLA, Vol. 4, pg 762 and Figure 9.C-1 (June 1989)). EIGHTH DEFENSE - UNCLEAN HANDS 89. The asserted patents are unenforceable due to Amgen's unclean hands. NINTH DEFENSE - PUBLIC HEALTH AND WELFARE 90. Amgen's request for an injunction precluding Roche from importing into,

making, using, or selling CERA in the U.S. is contrary to the public health and welfare. TENTH DEFENSE - AMGEN IS ESTOPPED FROM SEEKING DAMAGES 91. Amgen has taken the position that it is not seeking damages against Roche

related to the accused product in this action. 92. Amgen contends that it is only seeking declaratory and injunctive relief

against Roche's alleged acts of infringement. 93. Amgen has alleged that there are current acts of infringement in the United

States in connection with the accused product. 94. Based on its decision to forgo damages, Amgen has argued to the Court

that Roche is not entitled to a jury trial on Amgen's claims. 95. At the conclusion of the litigation, in the event that Amgen is successful in

its claims against Roche and the asserted claims are found to be infringed, valid and enforceable, the Court must undertake an analysis mandated by the United States Supreme Court's decision in eBay, Inc. v. MercExchange, L.L.C., 126 S. Ct. 1837 (2006), to determine if a permanent injunction would be appropriate. 96. Based on Amgen's decision to waive any damages, compensatory or

otherwise, as a tactic to deprive Roche of its constitutional right to a jury trial on Amgen's claims (even though Roche contends that they are entitled to a trial by jury), Amgen is estopped and 27

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precluded from seeking, asserting or maintaining a claim for damages, compensatory or otherwise, for any damages, whether past, current or future, in the event that Amgen is successful on its claims and the Court determines that a permanent injunction is not warranted in this case. ELEVENTH DEFENSE - FILE WRAPPER ESTOPPEL 97. Amgen's claims for infringement of the '868, '933, '698, '080, '349 and

'422 patents are barred by file wrapper estoppel. TWELFTH DEFENSE - OMITTED 98. OMITTED THIRTEENTH DEFENSE - PROSECUTION LACHES ESTOPPEL 99. Amgen's claims for infringement of the '868, '933, '698, '080, '349 and

'422 patents are barred by prosecution laches and estoppel. PART II: ROCHE'S COUNTERCLAIMS F. Hoffmann-La Roche Ltd, Roche Diagnostics GmbH, and Hoffmann-La Roche Inc. (collectively "Roche"), as Counterclaim-Plaintiffs, by their attorneys, allege the following counterclaims on information SUMMARY OF COUNTERCLAIMS 1. Roche counterclaims against Amgen under Sections 4 and 16 of the and belief:

Clayton Act, 15 U.S.C. §§ 15, 26, and the Declaratory Judgment Act, 28 U.S.C. §§ 2201-2202, for violations of Sections 1 and 2 of the Sherman Act, 15 U.S.C. §§ 1 and 2, by reason of Amgen's actions to unreasonably restrain trade in, and monopolize, and/or attempt to monopolize a number of relevant markets, including markets for the sale of Erythropoiesis Stimulating Agent ("ESA") drugs sold for particular indications. Roche also counterclaims

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against Amgen for a declaratory judgment of patent invalidity, non-infringement, and unenforceability pursuant to 28 U.S.C. §§ 2201 and 2202. 2. Amgen's patent case against Roche is part of a broad, anticompetitive

scheme by Amgen to unlawfully maintain or secure monopoly power in violation of the antitrust laws. Amgen possesses monopoly or substantial market power over the sales of ESA drugs sold for particular indications. Amgen's Epogen® and Aranesp® products have been, and today remain, the only such drugs available for patients suffering from End Stage Renal Disease who are on dialysis ("ESRD"). Similarly, Amgen's Aranesp® is the leading ESA medicine

administered to patients with non-dialysis Chronic Kidney Disease ("CKD"). Ortho Biotech Products, L.P. ("Ortho") offers the only other ESA drug available to CKD patients, Procrit®, which Ortho sells only because of a license from Amgen and that has the same active ingredient as Epogen®. 3. Roche's CERA drug (to be marketed under the trade name MIRCERA®)

presents the first credible challenge to Amgen's dominance over ESAs sold for ESRD and CKD, the two relevant markets here. Recognizing that its patents are not likely to block Roche's eventual entry with CERA, Amgen has embarked on a course of anticompetitive conduct designed to hinder Roche's ability to enter or compete effectively in these markets. Among other conduct, Amgen has: (a) engaged in unlawful and anticompetitive litigation before this Court by, including but not limited to, seeking to enforce patents that were knowingly obtained through willful fraud on the United States Patent and Trademark Office ("PTO"); (b) engaged in sham litigation before the International Trade Commission ("ITC") in a failed effort to hinder CERA's entry; and (c) blocked Roche's access to customers for CERA by (i) recently cementing a long-term exclusive dealing arrangement with the largest single ESA customer, (ii) engaging in

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other exclusionary contracting practices, and by (iii) threatening customers that purchasing CERA will result in Amgen's retaliating by raising prices, denying those customers access to Amgen's ESA products or denying those customers critical discounts on those products. 4. Amgen's anticompetitive scheme, if not invalidated by this Court, will

hinder or eliminate the competition that Roche's CERA is poised to create, limit the ability of patients and physicians to choose an alternative medicine that would provide benefits to patients not currently available, and saddle consumers, patients and those who pay for their medicines with supracompetitive prices and the American public health system with greater expenses. Accordingly, Roche seeks under the antitrust laws monetary damages, a declaration that Amgen's conduct is unlawful, and other appropriate relief, including attorneys' fees and costs. THE PARTIES 5. Counterclaim-Plaintiff F. Hoffmann-La Roche Ltd is a foreign corporation

existing under the laws of Switzerland with a principal place of business in Basel, Switzerland. 6. Counterclaim-Plaintiff Roche Diagnostics GmbH is a foreign corporation

existing under the laws of Germany with principal places of business in Penzberg, Germany and Mannheim, Germany. 7. Counterclaim-Plaintiff Hoffmann-La Roche Inc. is a New Jersey

corporation with a principal place of business at 340 Kingsland Street, Nutley, NJ 07110-1199. 8. Roche is a leading healthcare organization that has been active in the

discovery, development, manufacture and marketing of novel healthcare solutions for over 100 years. Using innovative technologies, Roche develops medications and other products to

prevent, diagnose and treat life-threatening diseases. 9. Counterclaim-Defendant Amgen is a Delaware corporation with its

principal place of business at One Amgen Center Drive, Thousand Oaks, California 91320-1799. 30

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JURISDICTION AND VENUE 10. This Court has jurisdiction over the counterclaims asserted herein under

28 U.S.C. §§ 1331, 1337(a), 1338(a), 1367 and 2201. 11. This Court has personal jurisdiction over Amgen by virtue of its

appearance as a plaintiff in this action. 12. Venue is proper in this district under Sections 4 and 12 of the Clayton Act,

15 U.S.C. §§ 15 and 22, as Amgen is subject to personal jurisdiction in this district. Venue is also proper in this district pursuant to the provisions of 28 U.S.C. §§ 1391(b), 1391(c) and 1400(b). FACTUAL ALLEGATIONS I. ERYTHROPOIETIN STIMULATING AGENTS USED IN THE TREATMENT OF ANEMIA 13. Erythropoietin ("EPO") is a naturally occurring hormone found in human

blood. EPO is produced in the kidneys and stimulates red blood cell production in the bone marrow. 14. ESAs are drugs that are used to treat anemia patients by promoting the

production of red blood cells. Anemia is the condition of having less than the normal number of red blood cells or less than the normal quantity of hemoglobin in the blood, which decreases the oxygen-carrying capacity of the blood. 15. The principal uses of ESAs are in the treatment of anemia associated with ESAs are also used for the

ESRD (i.e., dialysis patients), CKD, and cancer (oncology).

treatment of anemia associated with HIV, pediatric renal disease, surgery, hepatitis C and stroke.

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II.

AMGEN'S MONOPOLY OR MARKET POWER IN THE MARKET FOR THE SALE OF ESA DRUGS FOR THE TREATMENT OF ESRD 16. Part of the interstate trade and commerce adversely affected and restrained

by the unlawful Amgen acts described herein, and one of the relevant markets in this case, is the sale in the United States of ESAs for the treatment of ESRD ("ESRD ESA"). 17. Approximately 400,000 patients have ESRD in the United States. Patients

with ESRD receive regular treatments at dialysis centers to filter their blood through hemodialysis machines to remove toxins. The vast majority of ESRD patients have been

diagnosed with anemia and require treatment with an ESA to achieve normal hemoglobin levels. 18. No drug other than an ESA is safe and effective for the treatment of

anemia in ESRD patients, and no ESA may be marketed for the treatment of anemia in ESRD patients in the United States unless the FDA has approved it for use as a treatment for (i.e., is "indicated for") anemia in dialysis patients (that is, for treating ESRD anemia). 19. Accordingly, the sale in the United States of ESA drugs for the treatment

of ESRD is a relevant market. 20. Since 1989, Amgen has sold an ESA under the brand name Epogen®

which is indicated for the treatment of anemia in ESRD patients (that is, patients with chronic renal failure on dialysis). Amgen sold more than $2.4 billion worth of Epogen® in 2005. 21. In 2001, Amgen introduced a different ESA under the brand name

Aranesp®, which is also indicated for the treatment of anemia in ESRD patients (that is, patients with chronic renal failure on dialysis). Amgen sold more than $2.1 billion worth of Aranesp® in 2005, although on information and belief only a relatively small proportion of sales are for ESRD use.

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22.

Epogen® and Aranesp®, both Amgen products, are the only ESAs that

have been approved by the FDA for the treatment of anemia in ESRD patients and that are currently sold for such treatment in the United States. Although Procrit®, a product sold by Ortho Biotech Products, L.P. ("Ortho") which has the same active ingredient as Epogen®, is also indicated for the treatment of anemia in ESRD patients, Amgen's long-term license with Ortho prevents Ortho from marketing Procrit® for that purpose. 23. Amgen, as the supplier of the only two ESRD ESA products approved for

and available for sale in the United States, has 100% market share and monopoly power in the ESRD ESA market. 24. Approximately sixty-five percent (65%) of ESAs used to treat ESRD

patients in the United States are purchased directly from Amgen by two Large Dialysis Organizations ("LDOs"). These two LDOs operate numerous facilities throughout the United States at which ESRD patients receive their dialysis treatment and, when necessary, are administered their ESA medications. ESRD patients receive ESA medications during their dialysis visits. The two LDOs historically have purchased ESA medications under centralized contracts with Amgen. 25. Beyond the two LDOs, the remaining thirty-five percent (35%) of ESRD

ESA customers consist of small and medium chain dialysis centers, independent dialysis centers and hospitals