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

Filing 728

MEMORANDUM in Support re #727 MOTION for Leave to File Under Seal Documents Containing Defendants' Trade Secrets Submitted in Connection with the Pendleton and Galvin Declarations filed by F. Hoffmann-LaRoche LTD, Roche Diagnostics GmbH, Hoffmann LaRoche Inc.. (Attachments: #1 Exhibit A#2 Exhibit B#3 Exhibit C)(Toms, Keith)

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

Doc. 728 Att. 2

Case 1:05-cv-12237-WGY

Document 728-3

Filed 07/16/2007

Page 1 of 4

UNITED STATES DISTRICT COURT DISTRICT OF MASSACHUSETTS

AMGEN INe., )

)

v. )

Plaintiff, )
) ) )

I Exhibit B

C. A. No.: 05-CV-12237-WGY

F. HOFFANN-LA ROCHE LTD., )

a Swiss Company, ROCHE )
Company and HOFFMANN-LA ROCHE )

DIAGNOSTICS GmbH, a German )
INC., a New Jersey Corporation, ) )
)

Defendants. )

)
)

PUBLIC VERSION
Exhibit 48
Opposition to Roche's Motion for Summary Judgment that Claim 7 of

to the Declaration of Cullen N. Pendleton in Support of Amgen' s the '349

Patent is Invalid Under 35 § USC 112 and is Not Infringed

Dockets.Justia.com

Case 1:05-cv-12237-WGY

Document 728-3

Filed 07/16/2007
i

Page 2 of 4

¡Redacted I
EPOETIN BETA R00503821 Starting Material R02053859

~Roche)

Prepared by: HE Approved by:

Date:

DESCRIPTION OF MANUFACTURING PROCESS AND PROCESS CONTROLS

DETAILED DESCRIPTION OF THE EpOETlN BETA FERMENTATION PROCESS

1. SUMMARY
The fermentation process of Epoetin beta (EPO) comprises the seed train, the
I Iproduction run and the harvest procedure.

The medium for the spinner cultures I I contains methotrexate (MTX),

while the medium for the bioreactor culturesl I is free of MTX.

2. OPERATION PROCEDURE OF THE SEED TRAIN
2.1 Spinner Cultivation with MTX One vial of the working cell bank (WCB) is taken from the vapor phase of the

flasks and cultivated in a I Ibuffered medium I I in a
microscopically checked for the absence of bacteria and fungi. At each splitting step ceil density is counted and the viabilty is calculated.
After a cultivation phase the cells are transferred to spinner flasks

liquid nitrogen storage tank. The cells are transferred into I I spinner

humidified I I incubator (3rC:! 2°C). For the composition of

the cultivation medium see Table 1 and Table 2. The spinner cultures are

I I (37°C :J 2°C). During a period, the
cells grow from a starting cell density of 0.5 - 3.4 x 10 cells/mL to a cell density

of 2 - 15 x 10s cells/mL. By splittng, the cell culture is replenished with medium
to the starting cell density. Afterwards the cell cultivation is continued.
This procedure is repeated until a culture volume ofl I has been obtained.

Cultures which meet the given in-process control (lPC) limits for cell age, viabilty, viable cell density and absence of microbes are available for inoculation of the

10 L inoculum bioreactor (for details see report 3.2.8.2.2 "In-Process Controls
During Fermentation").

Spinner flasks are kept as backup cultures up to the maxmum cell age in

medium with MTX I I.

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EPOETIN BETA R00503821 Startng Material R02053859

-(Roche)

Prepared by: HE Approved by: Date:

3. COMPOSITIONS OF THE MEDIA
The composition of basal medium DMEMIF12 T005 as shown in Table 1 is used

for the spinner cultivation and bioreactor cultivation medium (for details see
Table 2).
Table 1

Components
L-AJanine L-Arginine

Composition of the Basal Medium DMEMfF12 TOOS Components Concentration Concentration
ImQfL

r-

malLl
myo-Inositol Nicotinamide

L-AsparaginefHiÛ
L-Aspartic acid

IRe aac1 ed I

PyridoxalICI PyrldoxolICI
Riboflavine Thiamine/HCI

L-Cysteine/HCI x H2O L-Cystinel2 HCI L-Glinamic acid Glycine L-Histidine/HCI x HiÛ L-Isoleucine L-Leucine L-Lysine/HCI L-Methionine

IR ~dac

edl

Cobalamine
I I

DL-alpha-Liponic acid

Sodium linoleate Sodium pyruvate Pinrescine/2 HCI

CaCh
I I

L-Phenylalanine L-Proline L-Serine L-Threonlne
L- Tryptophan L- Tyrosine x 2 Na

i

i

KCI

L-Valine
Ca-D( + )pantothenate

MgCh MgS04 NaCl Na2HP04 NaH2P04
I I I I i

Choline chloride D-Biotine

i

Folic acid

IRedacted

Pharma Biotechnology

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Case 1:05-cv-12237-WGY

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Filed 07/16/2007

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EPOETIN BETA
R00503821 Starting Material

~Roche)

R02053859

Prepared by: HE Approved by: Date:

The composition of the spinner cultivation medium containing methotrexate

(MTX) is shown in Table 2.
Table 2

Composition of the Cultivation Medium for Spinner Cultivation
Concentration m IL
11.540

¡Redacted I

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