Amgen Inc. v. F. Hoffmann-LaRoche LTD et al
Filing
323
Response by Amgen Inc. to #311 Brief (Defendants' Claim Construction Brief). (Attachments: #1 Exhibit 1-Declaration of Harvey Lodish in Support of Defendants' Claim Construction Brief#2 Exhibit A-to Lodish Declaration#3 Exhibit B-Part 1 of 2 to Lodish Declaration#4 Exhibit B-Part 2 of 2 to Lodish Declaration#5 Exhibit C-to Lodish Declaration#6 Exhibit D- to Lodish Declaration#7 Exhibit E - Part 1 of 2 - to Lodish Declaration#8 Exhibit E-Part 2 of 2 - to Lodish Declaration#9 Exhibit 2 - Declaration of Vladimir Torchilin, Ph.D, D.Sc.#10 Exhibit A-to Torchilin Declaration#11 Exhibit B-Part 1 of 5 - to Torchilin Declaration#12 Exhibit B- Part 2 of 5 to Torchilin Declaration#13 Exhibit B-Part 3 of 5 to Torchilin Declaration#14 Exhibit B-Part 4 of 5 to Torchilin Declaration#15 Exhibit B-Part 5 of 5 to Torchilin Declaration#16 Exhibit C- Part 1 of 2 to Torchilin Declaration#17 Exhibit C-Part 2 of 2 to Torchilin Declaration#18 Exhibit D-Part 1 of 2 to Torchilin Declaration#19 Exhibit D-Part 2 of 2 to Torchilin Declaration#20 Exhibit E - Part 1 of 3 to Torchilin Declaration#21 Exhibit E-Part 2 of 3 to Torchilin Declaration#22 Exhibit E - Part 3 of 3 to Torchilin Declaration#23 Exhibit F to Torchilin Declaration#24 Exhibit 3)(Gottfried, Michael)
Amgen Inc. v. F. Hoffmann-LaRoche LTD et al
Doc. 323 Att. 5
Case 1:05-cv-12237-WGY
Document 323-6
Filed 03/19/2007
Page 1 of 9
LODISH DECLARATION EXHIBIT C
Dockets.Justia.com
Case 1:05-cv-12237-WGY
Document 323-6
Filed 03/19/2007
Page 2 of 9
Lin Example 10
Vector Construction
huma n
mous e
virus
EPO upstream DNA
EPO structural gene
DHFR gene DNA
viral promoter DNA
Recombinant DNA techniques
DHFR gene DNA
vira l promote r DNA
EPO s truc tura l ge ne
EPO ups tre a m DNA
E P O E x pre s s ion C ons truc t
Lin 1
Case 1:05-cv-12237-WGY
Document 323-6
Filed 03/19/2007
Page 3 of 9
Lin Example 10
Transfection
T ra ns fe c tion
EPO Expression Construct
Chromosome DNA
Lin 2
Case 1:05-cv-12237-WGY
Document 323-6
Filed 03/19/2007
Page 4 of 9
Lin Example 10
Transfection / Recombination / Integration
Transfection
EPO expression construct
Chromosome
Recombination
EPO expression construct Chromosome
Integration
Recombinant Chromosome
Lin 3
Case 1:05-cv-12237-WGY
Document 323-6
Filed 03/19/2007
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Lin Example 10
L Recombinant Chromosome
R e c ombina nt C hromos ome DNA
R a ndom I nte gra tion
in 4
Case 1:05-cv-12237-WGY
Document 323-6
Filed 03/19/2007
Page 6 of 9
Lin Example 10
EPO Protein Expression
EPO upstream DNA ATG
viral promoter
EPO structural gene
1
exon
2
3
4
intron
5
re c ombina nt c hromos ome
1. Transcription
AUG
1
2
3
4
5
prima ry R N A tra ns c ript
2. Splice Donor-Acceptor Alignment
AUG
1
2
3
4
5
splice donor
splice acceptor
tra ns c ript s plic ing
3. Splicing
AUG
12345
mR N A
4. Translation
le a de r pe ptide
polype ptide
5. Post-translational Modification
EPO glyc oprote in
le a de r pe ptide c le a ve d c te rmina l a rginine c le a ve d
Lin 5
Case 1:05-cv-12237-WGY
Document 323-6
Filed 03/19/2007
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Lin Example 10
DNA Amplification
MTX
Vast majority of the cells die, but cells with amplified DNA survive
Lin 6
Case 1:05-cv-12237-WGY
Document 323-6
Filed 03/19/2007
Page 8 of 9
Lin Example 10
L Re-Amplification
Cultured cells containing amplified DNA
Additional cycles of MTX selection
Cells with further amplified DNA survive
in 7
Case 1:05-cv-12237-WGY
Document 323-6
Filed 03/19/2007
Page 9 of 9
Lin Example 10
Process for EPO Production
Cells with amplified EPO DNA
Production of EPO protein
Purification of EPO protein
Pharmaceutical EPO
Lin 8
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