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

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Objection to #312 Brief,,, by F. Hoffmann-LaRoche LTD, Roche Diagnostics GmbH, Hoffmann LaRoche Inc. Opposition to Amgen's Claims Construction Brief. (Fleming, Thomas) Additional attachment(s) added on 3/21/2007 (Paine, Matthew).

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

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Index of Exhibits
Exhibit A Exhibit B Exhibit C Exhibit D Exhibit E Exhibit F Exhibit G Exhibit H Exhibit I Exhibit J Exhibit K Exhibit L Exhibit M Exhibit N Exhibit O Exhibit P Exhibit Q Exhibit R Exhibit S Exhibit T Exhibit U Exhibit V Exhibit W Exhibit X Exhibit Y Exhibit Z Exhibit AA Exhibit BB Exhibit CC Exhibit DD Exhibit EE Exhibit FF Exhibit GG Exhibit HH Exhibit II Exhibit JJ Exhibit KK Exhibit LL U.S. Patent Nos. 5,441,868 U.S. Patent Nos. 5,547,933 U.S. Patent Nos. 5,618,698 U.S. Patent Nos. 5,621,080 U.S. Patent Nos. 5,756,349 U.S. Patent Nos. 5,955,422 Expert Declaration of Thomas R. Kadesch, Ph.D., Professor of Genetics at the University of Pennsylvania School of Medicine, and attached exhibits. May 5, 1999, Amendment, 08/100,197-33. Goldwasser Depo. Tr. February 14, 2007 March 31, 1995, Office Action, 08/100,197-26 February 10, 1989, Office Action, 07/113,178-9. June 2, 1989, Amendment Under Rule 116, 07/113,178-11 May 24, 1988, Second Preliminary Amendment, 07/113,179-8. September 1, 1993, Office Action, 07/113,179-29. January 10, 1994, Amendment and Response, 07/113,179-33. Brief for Lin in Interference No. 102,097. U.S. Patent No. 4,399,216. MANUAL OF PATENT EXAMINING PROCEDURE § 2173.05(h) I. MANUAL OF PATENT EXAMINING PROCEDURE § 608.01(p) Completeness [R-3]. February 27, 2007 Letter From Thomas Fleming to Deborah E. Fishman. U.S. Patent No. 4,703,008. U.S. Patent No. 6,583,272. Pollack, A., "Rivals Laying Siege to Amgen's Near Monopoly in Anemia Drugs," The New York Times, Dec. 23, 2005. November 30, 1984, Application No. 06/675,298. June 16, 1986, Office Action, 06/675,298-8. June 18, 1987 Office Action, 06/675,298-17. July 10, 1987, Amendment and Reply, 06/675,298-20. October 23, 1987, Application No. 07/113,178. June 2, 1988, Office Action, 07/113,178-4. June 2, 1989, Amendment Under Rule 116, 07/113,178-11. June 20, 1989, Office Action, 07/113,178-13. July 12, 1989, Amendment, 07/113,178-15. December 12, 1989, Examiner Interview, 07/113,178-17. January 1, 1990, Amendment Under Rule 116, 07/113,178-19. May 24, 1988, Second Preliminary Amendment, 07/113,179-8. September 27, 1988, Applicant's Reply, 07/113,179-14. Goldwasser Depo. Tr. February 14, 2007 Morgan Stanley Equity Research, "Amgen: Some Setbacks for Competitors in EU," Feb. 26, 2006.

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Exhibit MM Exhibit NN Exhibit OO Exhibit PP Exhibit QQ

Amgen Inc. v. Hoechst Marion Roussel Inc., No. 97-10814 (D. Mass.), Trial Tr. (June 7, 2000). MANUAL OF PATENT EXAMINING PROCEDURE § 2111.03 [R-3]. THE AMERICAN HERITAGE DICTIONARY 1399 (4th ed. 2006). Supplemental Expert Declaration of Thomas R. Kadesch, Ph.D., Professor of Genetics at the University of Pennsylvania School of Medicine, and attached exhibits. December 11, 1996, Interview Summary, 0-8/468,381-7.

APPENDIX B
ROCHE'S PROPOSED CLAIM CONSTRUCTION Proposed Claim Construction for U.S. PATENT NO. 5,441,868 CLAIM 1 Claim Limitations A process for the production of a glycosylated erythropoietin polypeptide ROCHE "Process for the production of a glycosylated erythropoietin polypeptide having the amino acid sequence and carbohydrate modifications obtainable through the process steps (a) and (b) of these claims" "causing bone marrow cells to increase production of reticulocytes and red blood cells in a living organism." EVIDENCE See Roche's Proposed Claim Construct Brief, Section I, filed March 5, 2007, 16 [hereinafter "Roche Opening Brief"].

having the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells

`868 Patent: col. 6, ll. 42-57; col.6, l. 58 col. 7, l. 3; col. 10, ll. 45-52; col. 14, l. 41; col. 26, ll. 41-45; col. 29, l. 18; col. 33, l. 57; col. 34, ll. 48-59; col. 35, l. 18; col. 36, l. 2; col. 36, l. 41; col. 37, l. 55. Prosecution History: Roche Exhibit P at 48; Roche Exhibit M; Roche Exhibit JJ at 3-5; Amgen Exhibit 16 at 5; Amgen Exhibit 17 at 3.

comprising the steps of: (a) growing, under suitable nutrient conditions, mammalian host cells "growing, under conditions appropriate for mammalian host cell growth, which are cells from a warm-blooded animal, whose young are fed by milk secreted from mammary glands" Case Law: Amgen v. Hoechst, 126 F. Supp. 2d 69, 86 (D. Mass. 2001). `868 Patent: col. 11, ll. 46-53; col. 22, ll. 45-50; col. 27, ll. 3-7; col. 28, l. 33 - col. 29, l. 15.

APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,441,868 CLAIM 1 Claim Limitations transformed or transfected with an isolated DNA sequence encoding human erythropoietin; and (b) isolating said glycosylated erythropoietin polypeptide therefrom. ROCHE "introduction of purified exogenous DNA molecules containing the genetic instructions for human erythropoietin" "separating the glycosylated erythropoietin polypeptide having the defined activity from the growth medium, cellular lysates or cellular membrane fractions of the cells that produce it" EVIDENCE See Roche Opening Brief at 18-19.

See Roche Opening Brief at 17-18.

Proposed Claim Construction for U.S. PATENT NO. 5,441,868 CLAIM 2 Claim Limitations The process according to claim 1 wherein said host cells are CHO cells. "cell from the ovary of a Chinese Hamster" See Roche Opening Brief at 13. ROCHE EVIDENCE

2

APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,441,698 CLAIM 2 Claim Limitations transformed or transfected with an isolated DNA sequence. ROCHE "introduction of purified exogenous DNA molecules containing the genetic instructions for human erythropoietin" EVIDENCE See Roche Opening Brief at 18-19.

Proposed Claim Construction for U.S. PATENT NO. 5,618,698 CLAIM 4 Claim Limitations A process for the production of a glycosylated erythropoietin polypeptide ROCHE "Process for the production of a glycosylated erythropoietin polypeptide having the amino acid sequence and carbohydrate modifications obtainable through the process steps (a) and (b) of these claims" "causing bone marrow cells to increase production of reticulocytes and red blood cells in a living organism." Evidence See Roche Opening Brief at 16.

having the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells comprising the steps of: a) growing, under suitable nutrient conditions, vertebrate cells comprising

See `868 patent, claim 1

Amgen, 126 F. Supp. 2d 69 at 85 (D. "growing under conditions appropriate for vertebrate cell growth, which are Mass. 2001). cells from an animal having a backbone"

3

APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,618,698 CLAIM 4 Claim Limitations promoter DNA, other than human erythropoietin promoter DNA, ROCHE "DNA sequences not part of the human genome that initiate and may regulate the process of transcription" "the promoter DNA is linked to the EPO DNA in a way that maintains the capability of the promoter DNA to initiate transcription of the EPO DNA." "the genetic instructions for" "the fully realized form of amino acid sequence of Figure 6" b) isolating said glycosylated erythropoietin polypeptide expressed by said cells "separating the glycosylated erythropoietin polypeptide having the defined activity from the growth medium, cellular lysates or cellular membrane fractions of the cells that produce it" Evidence Amgen 126 F. Supp. 2d at 87-88 (D. Mass. 2001).

operatively linked to

Amgen v. Hoechst, 126 F. Supp. 2d 69 at 89-90 (D. Mass. 2001).

DNA encoding the mature erythropoietin amino acid sequence of FIG. 6; and

Amgen, 339 F. Supp. 2d 202 at 92 (D. Mass. 2003); Amgen 126 F. Supp. 2d at 86-87 (D. Mass. 2001). Amgen, 457 F.3d at 1312-17 (Fed. Cir. 2006). See Roche Opening Brief at 17-18.

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APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,618,698 CLAIM 6 Claim Limitations A process for the production of a glycosylated erythropoietin polypeptide ROCHE "Process for the production of a glycosylated erythropoietin polypeptide having the amino acid sequence and carbohydrate modifications obtainable through the process steps (a) and (b) of these claims" "causing bone marrow cells to increase production of reticulocytes and red blood cells in a living organism." Evidence See Roche Opening Brief at 16.

having the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells comprising the steps of: a) growing, under suitable nutrient conditions, vertebrate cells comprising amplified DNA

See `868 patent, claim 1

"growing under conditions appropriate Amgen, 126 F. Supp. 2d 69 at 85 (D. for vertebrate cell growth, which are Mass. 2001). cells from an animal having a backbone" "an increased number of copies of a particular gene relative to the number of copies inserted by transformation or transfection, and which results in an increased production of the gene product by the cell." `868 Patent: col. 15, ll. 8-12; col. 22, ll. 56-60; col. 27, ll. 42-44; col. 29, ll. 37-39; col. 31, ll. 14-16. Prosecution History: Roche Exhibit OO; Amgen Exhibit 18 at 9-10.

5

APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,618,698 CLAIM 6 Claim Limitations [DNA] encoding the mature erythropoietin amino acid sequence of FIG. 6, ROCHE "the genetic instructions for" "the fully realized form of amino acid sequence of Figure 6" b) isolating said glycosylated erythropoietin polypeptide expressed by said cells. "separating the glycosylated erythropoietin polypeptide having the defined activity from the growth medium, cellular lysates or cellular membrane fractions of the cells that produce it" Evidence Amgen 339 F. Supp. 2d at 92 (D. Mass. 2003); Amgen 126 F. Supp. 2d at 86-87 (D. Mass. 2001); Amgen, 457 F.3d at 1312-17 (Fed. Cir. 2006). See Roche Opening Brief at 17-18.

Proposed Claim Construction for U.S. PATENT NO. 5,618,698 CLAIM 7 Claim Limitations The process of claim 6 ROCHE Evidence

6

APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,618,698 CLAIM 7 Claim Limitations wherein said vertebrate cells further comprise amplified marker gene DNA. ROCHE "cells from an animal having a backbone" "an increased number of copies of a particular gene relative to the number of copies inserted by transformation or transfection, and which results in an increased production of the gene product by the cell." Evidence Amgen 126 F. Supp. at 85 (D. Mass. 2001). See `698 patent, claim 6

Proposed Claim Construction for U.S. PATENT NO. 5,618,698 CLAIM 9 Claim Limitations The process according to claims 2, 4 and 6 Roche Multiple dependent claims not drafted in the alternative are invalid under 35 U.S.C. § 112 par. 5. "cells from a warm-blooded animal, whose young are fed by milk secreted from mammary glands" Amgen 126 F. Supp. 2d at 86-87 (D. Mass. 2001). Evidence

wherein said cells are mammalian cells.

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APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,756,349 CLAIM 7 Claim Limitations A process for producing erythropoietin Roche "Process for producing a glycoprotein having the amino acid sequence and glycosylation structure of a naturally occurring hormone that is produced in a cell and secreted from that cell, and that controls the formation of red blood cells in bone marrow" Evidence See Roche Opening Brief at 19.

comprising the step of culturing, under suitable nutrient conditions, vertebrate cells according to claim 1, 2, 3, 4, 5 or 6. "culturing under conditions appropriate Amgen 126 F. Supp. 2d at 85 (D. Mass. for vertebrate cell growth, which are 2001). cells from an animal having a backbone"

Proposed Claim Construction for U.S. PATENT NO. 5,756,349 CLAIM 1 Claim Limitations Vertebrate cells which can be propagated in vitro and ROCHE "cells from an animal having a backbone" "which can be grown in culture outside of a living body" Evidence Amgen 126 F. Supp. 2d at 85 (D. Mass. 2001). No disagreement with Amgen.

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APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,756,349 CLAIM 1 Claim Limitations which are capable upon growth in culture of producing erythropoietin in the medium of their growth in excess of 100 U of erythropoietin per 106 cells in 48 hours as determined by radioimmunoassay, ROCHE This term is vague and ambiguous and defies claim construction. Evidence See Defendants' Opposition To Amgen's Motion To Enforce The Court's January 23, 2007 Order And Memorandum In Support Of Defendants' Cross Motion To Compel Production Of Amgen's Cell Lines And Related Documents (D.I. # 297). Amgen 126 F. Supp. 2d at 87-88 (D. Mass. 2001); Amgen 339 F. Supp. 2d at 251 (D. Mass. 2004).

said cells comprising non-human DNA sequences which control transcription of DNA encoding human erythropoietin.

"DNA sequences not part of the human genome that initiate and may regulate the process of transcription" "the genetic instructions for"

9

APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,547,933 CLAIM 3 Claim Limitations A non-naturally occurring glycoprotein product of the expression in a mammalian host cell of an exogenous DNA sequence comprising ROCHE "not occurring in nature" "a protein that is the expression product of the mammalian host cell having the amino acid sequence of human erythropoietin which is glycosylated naturally by the host cell at specific amino acids." "the genetic instructions for" "a glycoprotein having the amino acid sequence of erythropoietin isolated from human urine having the structure that would be produced in mammalian cells as of the invention date." "causing bone marrow cells to increase production of reticulocytes and red blood cells in a living organism." Evidence Amgen 126 F. Supp. 2d at 91 (D. Mass. 2001). See Roche Opening Brief at 11-13.

a DNA sequence encoding human erythropoietin

Amgen 339 F. Supp. 2d at 251 (D. Mass. 2004). See Roche Opening Brief at 6-7.

said product possessing the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells.

See `868 patent, claim 1

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APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,547,933 CLAIM 7 Claim Limitations The glycoprotein product according to claim 3, 4, 5, or 6 wherein the host cell is a non-human mammalian cell. ROCHE "a glycoprotein product according to claim 3" "cells from a warm-blooded animal, whose young are fed by milk secreted from mammary glands" Evidence Amgen is only asserting claim 7 as depending from claim 3 Amgen, 126 F. Supp. 2d at 86 (D. Mass. 2001).

Proposed Claim Construction for U.S. PATENT NO. 5,547,933 CLAIM 8 Claim Limitations The glycoprotein product according to claim 7 wherein the non-human mammalian cell is a CHO cell. "cell from the ovary of a Chinese Hamster" See Roche Opening Brief at 13. ROCHE Evidence

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APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,547,933 CLAIM 9 Claim Limitations A pharmaceutical composition comprising ROCHE "a mixture having in addition to the active ingredient (as defined by the claim), an additional distinct and separate ingredient that acts as a diluent, an adjuvant or a carrier" "therapeutically effective amount is one that elicits any one or all of the effects often associated with in vivo biological activity of natural EPO, such as those listed in the specification, column 33, lines 16 through 22: stimulation of reticulocyte response, development of ferrokinetic effects (such as plasma iron turnover effects and marrow transit time effects), erythrocyte mass changes, stimulation of hemoglobin C synthesis and, as indicated in Example 10, increasing hematocrit levels in mammals." See preamble Evidence See Roche Opening Brief at 7-8.

an effective amount of a glycoprotein product effective for erythropoietin therapy according to claim 1, 2, 3, 4, 5 or 6 and

See Roche Opening Brief at 14.

a pharmaceutically acceptable diluent, adjuvant or carrier.

See Roche Opening Brief at 7-8.

12

APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,547,933 CLAIM 11 Claim Limitations A method for treating a kidney dialysis patient which comprises administering a pharmaceutical composition of claim 9 in an amount effective to increase the hematocrit level of said patient. Compare to "therapeutically effective See Roche Opening Brief at 14. amount is one that elicits any one or all of the effects often associated with in vivo biological activity of natural EPO, such as those listed in the specification, column 33, lines 16 through 22: stimulation of reticulocyte response, development of ferrokinetic effects (such as plasma iron turnover effects and marrow transit time effects), erythrocyte mass changes, stimulation of hemoglobin C synthesis and, as indicated in Example 10, increasing hematocrit levels in mammals." ROCHE Evidence

13

APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,547,933 CLAIM 12 Claim Limitations A pharmaceutical composition comprising ROCHE "a mixture having in addition to the active ingredient (as defined by the claim), an additional distinct and separate ingredient that acts as a diluent, an adjuvant or a carrier" "therapeutically effective amount is one that elicits any one or all of the effects often associated with in vivo biological activity of natural EPO, such as those listed in the specification, column 33, lines 16 through 22: stimulation of reticulocyte response, development of ferrokinetic effects (such as plasma iron turnover effects and marrow transit time effects), erythrocyte mass changes, stimulation of hemoglobin C synthesis and, as indicated in Example 10, increasing hematocrit levels in mammals." See preamble Evidence See Roche Opening Brief at 7-8.

an effective amount of glycoprotein product effective for erythropoietin therapy according to claim 7

See Roche Opening Brief at 14.

and a pharmaceutically acceptable diluent, adjuvant or carrier.

See Roche Opening Brief at 7-8.

14

APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,547,933 CLAIM 14 Claim Limitations A method for treating a kidney dialysis patient which comprises administering a pharmaceutical composition of claim 12 in an amount effective to increase the hematocrit level of said product. Compare to "therapeutically effective See Roche Opening Brief at 14. amount is one that elicits any one or all of the effects often associated with in vivo biological activity of natural EPO, such as those listed in the specification, column 33, lines 16 through 22: stimulation of reticulocyte response, development of ferrokinetic effects (such as plasma iron turnover effects and marrow transit time effects), erythrocyte mass changes, stimulation of hemoglobin C synthesis and, as indicated in Example 10, increasing hematocrit levels in mammals." ROCHE Evidence

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APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,955,422 CLAIM 1 Claim Limitations A pharmaceutical composition ROCHE "a mixture having in addition to the active ingredient (as defined by the claim), an additional distinct and separate ingredient that acts as a diluent, an adjuvant or a carrier" Evidence See Roche Opening Brief at 7-8.

comprising a therapeutically effective amount of "A therapeutically effective amount is Amgen v. Hoechst., 457 F.3d 1293 (Fed. one that elicits any one or all of the Cir. 2006). effects often associated with in vivo biological activity of natural EPO, such as those listed in the specification, column 33, lines 16 through 22: stimulation of reticulocyte response, development of ferrokinetic effects (such as plasma iron turnover effects and marrow transit time effects), erythrocyte mass changes, stimulation of hemoglobin C synthesis and, as indicated in Example 10, increasing heatocrit levels in mammals." "a glycoprotein having the amino acid sequence of erythropoetin isolated from human urine having the structure that would be produced in mammalian cells as of the invention date." 16 See Roche Opening Brief at 6-7.

human erythropoietin

APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,955,422 CLAIM 1 Claim Limitations and a pharmaceutically acceptable diluent, adjuvant or carrier, See preamble ROCHE Evidence See Roche Opening Brief at 7-8.

wherein said erythropoietin is purified from mammalian cells grown in culture.

"obtained in substantially homogeneous form from the mammalian cells, using the word "from" in the sense that it originates in the mammalian cells, without limitation to it only taking it directly out of the interior of the cells, which have been grown in the in vitro culture." "cells from a warm-blooded animal, whose young are fed by milk secreted from mammary glands"

See Roche Opening Brief at 9-11. Amgen, 126 F. Supp. 2d at 86 (D. Mass. 2001).

Proposed Claim Construction for U.S. PATENT NO. 5,621,080 CLAIM 3 Claim Limitations A non-naturally occurring erythropoietin glycoprotein having the in vivo biological activity of causing bone marrow cells to increase production of reticulocytes and red blood cells ROCHE "not occurring in nature" Amgen 126 F. Supp. 2d at 91 (D. Mass. 2001).

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APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,621,080 CLAIM 3 Claim Limitations wherein said erythropoietin glycoprotein comprises the mature erythropoietin amino acid sequence of FIG. 6 ROCHE "a protein having the amino acid sequence of erythropoietin which is glycosylated at specific amino acids naturally by a host cell." "the fully realized form of amino acid sequence of Figure 6" See Roche Opening Brief at 15 Amgen 126 F. Supp. 2d at 86-87 (D. Mass. 2001); Amgen 457 F.3d at 1312-17 (Fed. Cir. 2006).

Proposed Claim Construction for U.S. PATENT NO. 5,621,080 CLAIM 4 Claim Limitations A pharmaceutical composition ROCHE "a mixture having in addition to the active ingredient (as defined by the claim), an additional distinct and separate ingredient " Evidence See Roche Opening Brief at 7-8.

comprising

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APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,621,080 CLAIM 4 Claim Limitations a therapeutically effective amount [of] ROCHE Evidence

"A therapeutically effective amount is Amgen 457 F.3d at 1303 (Fed. Cir. 2006). one that elicits any one or all of the effects often associated with in vivo biological activity of natural EPO, such as those listed in the specification, column 33, lines 16 through 22: stimulation of reticulocyte response, development of ferrokinetic effects (such as plasma iron turnover effects and marrow transit time effects), erythrocyte mass changes, stimulation of hemoglobin C synthesis and, as indicated in Example 10, increasing heatocrit levels in mammals."

an erythropoietin glycoprotein product according to claim 1, 2, or 3. Proposed Claim Construction for U.S. PATENT NO. 5,621,080 CLAIM 6 Claim Limitations A method for treating a kidney dialysis patient which comprises ROCHE Evidence

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APPENDIX B
Proposed Claim Construction for U.S. PATENT NO. 5,621,080 CLAIM 6 Claim Limitations administering a pharmaceutical composition of claim 4 in an amount effective to increase the hematocrit level of said patient. ROCHE Evidence

Compare to "therapeutically effective See Roche Opening Brief at 14. amount is one that elicits any one or all of the effects often associated with in vivo biological activity of natural EPO, such as those listed in the specification, column 33, lines 16 through 22: stimulation of reticulocyte response, development of ferrokinetic effects (such as plasma iron turnover effects and marrow transit time effects), erythrocyte mass changes, stimulation of hemoglobin C synthesis and, as indicated in Example 10, increasing hematocrit levels in mammals."

20