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

Filing 1424

DECLARATION re 1420 MOTION in Limine Regarding Flavell No. 6: To Preclude Richard Flavell from Offering Opinions Based on a Claim Construction that is Inconsistent with the Court's Construction of '868 Claim Term "Isolated DNA Sequence Encoding Human Er, 1415 MOTION in Limine Regarding Flavell No. 1: To Preclude Richard A. Flavell From Testifying During the Infringement Stage on Issues Pertaining to Invalidity, 1423 MOTION in Limine Regarding Flavell No. 9: To Preclude Richard Flavell from Offering Opinions Regarding "Isolated DNA Sequence Encoding Human Erythropoietin" Based on His Refusal to Provide the Basis for Those Opinions at Deposition, 1421 MOTION in Limine Regarding Flavell No. 7: To Preclude Richard Flavell From Offering Opinions Based on a Claim Construction that Requires That the Term "Obligate" Glycoprotein Be Read into the Asserted '933 Claim, 1419 MOTION in Limine Regarding Flavell No. 5: To Preclude Richard Flavell from Offering Opinions Based on an Infringement Analysis that is Inconsistent with Federal Circuit Precedent and with the Court's Claim Construction Ruling that Amgen's, 1416 MOTION in Limine Regarding Flavell No. 2: To Preclude Richard A. Flavell from Offering Opinions Based on a Claim Construction that is Inconsistent with the Claim Terms "Isolating" and "Comprising," as set forth in the Asserted &, 1417 MOTION in Limine Regarding Flavell No. 3: to Preclude Richard Flavell from Offering Opinions Based on a Claim Construction that is Inconsistent with the Court's Claim Construction of the '933 Patent Claim Term "Non-Naturally Occurrin, 1418 MOTION in Limine Regarding Flavell No. 4: To Preclude Richard Flavell from Offering Opinions Regarding the Asserted '933 Claims that are Based on a Construction that is Inconsistent with the Court's Claim Construction of the Claim Term &q of Linda Sasaki-Baxley by Amgen Inc.. (Attachments: # 1 Exhibit 1# 2 Exhibit 2# 3 Exhibit 3)(Gottfried, Michael)

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

Doc. 1424 Att. 3

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EXHIBIT 3

Dockets.Justia.com

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IN THE UNITED STATES DISTRICT COURT FOR THE DISTRICT OF MASSACHUSETTS AMGEN INC., Plaintiff, v. F. HOFFMANN-LA ROCHE, LTD, ROCHE DIAGNOSTICS GmbH, and HOFFMANN-LA ROCHE INC., Defendants. Civil Action No. 05-cv-12237 WGY CONTAINS RESTRICTED ACCESS BLA/IND CONFIDENTIAL INFORMATION SUBJECT TO PROTECTIVE ORDER

FOURTH EXPERT STATEMENT OF RICHARD A. FLAVELL, PH.D. IN RESPONSE TO VARIOUS ARGUMENTS RAISED BY AMGEN'S EXPERTS

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disease. This example fully supports my opinion, expressed elsewhere, that small changes in proteins can have a remarkable impact on a protein's function. 76. Finally, Dr. Lodish places a great deal of emphasis on the Court's use of "such as" in its

construction for the claim term "human erythropoietin," suggesting that this definition is broad enough to encompass several different polypeptides. As I explained previously, this broadening is contrary to Amgen's admissions during claim construction, and as outlined in my earlier report, is inconsistent with arguments made before the patent office in support of allowance of certain claims. 77. And, even if the Court agrees with Dr. Lodish that the claims are broad enough to cover

other erythropoietins, the one thing the Court gives as the claimed sequence is urinary EPO. Like DNA, a protein is a complex chemical having a explicit sequence that defines its identity. I have been told that DNA sequences cannot be conceived until the sequence is in hand. I suspect that a similar situation is true for protein sequences. If so, any such other erythropoietin sequences have not been identified and cannot be within the scope of the invention. 78. In summary, none of the opinions presented by Dr. Lodish changes my prior opinion that

claims of the asserted patents are invalid for indefiniteness and lack of written description. V. 79. PURIFICATION STEPS AFTER ISOLATION ARE SUBSTANTIAL PROCEDURES THAT CONSTITUTE A MATERIAL CHANGE As I explained in my previous expert report, I generally disagree with the contentions of

Dr. Lodish concerning purification steps for erythropoietin. I reiterate my prior opinion that purification of erythropoietin sufficient to create a claimed pharmaceutical composition is not disclosed in the patent specification, and that purification steps undertaken after isolation of erythropoietin from cell culture medium constitutes a material change to the product of Amgen's

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claimed process. My opinion remains the same. However, I respond below to specific arguments raised by Dr. Lodish in his Supplemental Expert Report on this topic. 80. Dr. Lodish appears to confuse my position regarding "isolation" and "purification."84 His

report states that "[a]ll isolation or purification in a biological process is a matter of degree."85 I disagree with this statement. Dr. Lodish's observation that EPO has been "`separated' from the `growth medium, cellular lysates or cellular membrane fractions'" is fully consistent with my definition for EPO found in a crude isolate. This crude isolate has been recovered from many different kinds of material, but has not undergone additional steps to purify EPO ­ to increase its specific activity by maximizing the concentration of EPO molecules per unit of protein in a sample. This is purification. It is complex, substantial, and, if successful, results in a material change to the crude isolate first recovered. 81. Dr. Lodish states that the product of the claimed process is "far from a `crude isolate'

preparation" because, according to Amgen expert Dr. Bradshaw, "approximately 30% of the total protein is comprised of EPO."86 I disagree. In my opinion, the most accurate way to describe such a mixture of proteins is a crude isolate. The identity of the remaining 70% of proteins ­ the majority of protein in the sample ­ is unknown and uncharacterized. In my opinion, this any preparation with 70% unknown material is crude. 82. Dr. Lodish's criticism of Roche's experts' use of the term "crude isolate" is without

import. Regardless of how one of skill would characterize the product of the claimed process, it must still be subjected to further purification involving several discrete steps before it can be a

84 85

Id. at ¶ 94. Id. 86 Id. at ¶ 97.

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