`THE ’435 PATENT CLAIMS
`
`’435 patent
`
`
`Publication
`
`E.g., EX1001,
`Examples 2‐11
`(69:5‐85:21),
`Figures 1‐22
`
`In vivo
`testing
`Mouse
`
`Gene/Gene
`Target
`ApoB
`Eg5
`Plk-1
`(siRNA)
`
`Formulations
`
`1.4%|57.1%|7.1%|34.3%
`PEG-cDMA, DLinDMA, DPPC, cholesterol
`PEG-cDMA, DLinDMA, DPPE, cholesterol
`PEG-cDMA, DLinDMA, DPPC, cholestanol
`PEG5000-cDMA, DLinDMA, DPPC, cholesterol
`PEG-cDMA, DODMA, DPPC, cholesterol
`PEG-cDSA, DLinDMA, DPPC, cholesterol
`1.3%|53.3%|13.3%|32.0%
`PEG-cDMA, DLinDMA, DPPC, cholesterol
`2%|70%|28%
`PEG-cDMA, DLinDMA, DPPC
`1.6%|54.7%|43.8%
`PEG-cDMA, DLinDMA, DPPC
`1.8%|70.2%|28.1%
`PEG-cDMA, DLinDMA, DPPC
`1.5%|61.5%|36.9%
`PEG-cDMA, DLinDMA, cholesterol
`1.4%|54.8%|43.8%
`PEG-cDMA, DLinDMA, cholesterol
`2.0%|61.2%|36.7%
`PEG-cDMA, DLinDMA, cholesterol
`1.8%|54.5%|43.6%
`PEG-cDMA, DLinDMA, cholesterol
`1.3%|68.1%|30.6%
`PEG-cDMA, DLinDMA, cholesterol
`1.2%|61.8%|37.1%
`PEG-cDMA, DLinDMA, cholesterol
`1.7%|67.8%|30.5%
`PEG-cDMA, DLinDMA, cholesterol
`1.4%|56.3%|42.3%
`PEG-cDMA, DLinDMA, cholesterol
`1.9%|61.3%|36.8%
`PEG-cDMA, DLinDMA, cholesterol
`1.8%|56.1%|42.1%
`PEG-cDMA, DLinDMA, cholesterol
`1.3%|66.7%|32.0%
`PEG-cDMA, DLinDMA, cholesterol
`1.2%|61.7%|37.0%
`PEG-cDMA, DLinDMA, cholesterol
`
`-1-
`
`PROTIVA - EXHIBIT 2046
`Moderna Therapeutics, Inc. v. Protiva Biotherapeautics, Inc.
`IPR2018-00739
`
`
`
`’943 patent
`
`E.g., EX2017,
`Examples 10‐16
`(150:1‐160:62),
`Figures 1‐17
`
`’307
`publication
`
`E.g., EX2018,
`Examples 14,
`16‐19 (¶¶420‐
`423, 428‐443),
`Figures 3‐7
`
`1.7%|66.4%|31.9%
`PEG-cDMA, DLinDMA, cholesterol
`1.5%|61.5%|36.9%
`PEG-cDMA, DLinDMA, cholesterol
`1.4%|57.1%|7.1%|34.3%
`PEG-cDMA, DLinDMA, DPPC, cholesterol
`PEG-cDMA, DLin-K-C2-DMA, DPPC, cholesterol
`PEG-cDMA, DLin-K-C3-DMA, DPPC, cholesterol
`PEG-cDMA, DLin-KC4-DMA, DPPC, cholesterol
`PEG-cDMA, DLin-K6-DMA, DPPC, cholesterol
`PEG-cDMA, DLin-C2-DMA, DPPC, cholesterol
`PEG-cDMA, DLenDMA, DPPC, cholesterol
`PEG-cDMA, γ-DLenDMA, DPPC, cholesterol
`PEG-cDMA, DLin-K-DMA, DPPC, cholesterol
`PEG-cDMA, DLinMorph, DPPC, cholesterol
`PEG-cDMA, Linoley1/Oleyl DMA, DPPC,
`cholesterol
`PEG-cDMA, Linoley1/Phytanyl DMA, DPPC,
`cholesterol
`PEG-cDMA, Linoleyl/Stearyl DMA, DPPC,
`cholesterol
`PEG-cDMA, Linoley/C6:1 DMA, DPPC,
`cholesterol
`PEG-cDMA, TLinDMA, DPPC, cholesterol
`PEG-cDMA, Linoleyl/C6:0 DMA, DPPC,
`cholesterol
`PEG-cDMA, C2-DPanDMA, DPPC, cholesterol
`PEG-cDMA, DLin-C2K-Pip, DPPC, cholesterol
`PEG-cDMA, DHep-C2K-DMA, DPPC, cholesterol
`PEG-cDMA, DPan-C2K-DMA, DPPC, cholesterol
`PEG-cDMA, DPan-C3K-DMA, DPPC, cholesterol
`PEG-cDMA, DPan-C1K6-DMA, DPPC,
`cholesterol
`PEG-cDMA, γ-DLen-C2K-DMA, DPPC,
`cholesterol
`PEG-cDMA, DLen-C2K-DMA, DPPC, cholesterol
`1.4%|57.1%|7.1%|34.3%
`PEG-cDMA, DLinDMA, DPPC, cholesterol
`PEG-cDMA, CP-DLinDMA, DPPC, cholesterol
`PEG-cDMA, CP-DLenDMA, DPPC, cholesterol
`PEG-cDMA, CP-γ-DLenDMA, DPPC, cholesterol
`PEG-cDMA, CP-DODMA, DPPC, cholesterol
`PEG-cDMA, CP-DPetroDMA, DPPC, cholesterol
`PEG-cDMA, C2-TLinDMA, DPPC, cholesterol
`PEG-cDMA, γ-LenMC3, DPPC, cholesterol
`PEG-cDMA, CP-γ-LenMC3, DPPC, cholesterol
`
`
`
`-2-
`
`Mouse
`
`Various
`ApoB
`siRNAs (see
`Table 5)
`
`ApoB
`(siRNA)
`
`Mouse
`
`
`
`PEG-cDMA, LenMC3, DPPC, cholesterol
`PEG-cDMA, CP-LenMC3, DPPC, cholesterol
`PEG-cDMA, DLin-C2K-DMA, DPPC, cholesterol
`PEG-cDMA, DLin-M-C3-DMA, DPPC,
`cholesterol
`PEG-cDMA, D-γ-Len-C2K-DMA, DPPC,
`cholesterol PEG-cDMA, CP-γ-Len-C2K-DMA,
`DPPC, cholesterol
`PEG-cDMA, DLen-C2K-DMA, DPPC, cholesterol
`PEG-cDMA, CP-DLen-C2K-DMA, DPPC,
`cholesterol
`PEG-cDMA, MC2MC, DPPC, cholesterol
`PEG-cDMA, MC3 Ether, DPPC, cholesterol
`PEG-cDMA, Pan-MC3, DPPC, cholesterol
`PEG-cDMA, CP-MC3, DPPC, cholesterol
`PEG-cDMA, CP-C2K, DPPC, cholesterol
`1.4%|57.1%|7.1%|34.3%
`PEG-cDMA, DLin-KC2-DMA, DPPC, cholesterol
`
`TTR
`(siRNA)
`
`1.5%|50%|10%|38.5%
`PEG-DMG, DLin-MC3-DMA, DSPC, cholesterol
`
`TTR
`(siRNA)
`
`Mouse,
`rat, non-
`human
`primate
`
`Human
`
`1.5%|60%|7.5%|31%
`PEG-DMG, Lipid A, DSPC, cholesterol
`1.5%|57.7%|7.5%|33.5%
`PEG-DMG, Lipid A, DSPC, cholesterol
`1.5%|55%|7.5%|36%
`PEG-DMG, Lipid A, DSPC, cholesterol
`1.5%|50%|10%|38.5%
`PEG-DMG, DLin-MC3-DMA, DSPC, cholesterol
`
`1.5%|50%|10%|38.5%
`PEG-cDOMG, DLin-KC2-DMA, DSPC,
`cholesterol
`
`Factor VII
`(siRNA)
`
`Mouse
`
`EPO
`(mRNA)
`
`Factor IX
`G-CSF
`(mRNA)
`
`Rat, non-
`human
`primate
`
`Mouse,
`non-
`human
`primate
`
`Semple
`
`’608
`publication
`
`’537
`publication
`
`E.g., EX2021,
`Abstract, Figure
`3, Table 2, 177‐
`178
`E.g., EX2019,
`Tables 1‐2,
`¶¶42‐44, 93‐
`104
`E.g., EX2047, 86,
`109 (Table 3),
`120 (Example
`16), Figure 12
`E.g., EX2048,
`Abstract, 2‐3, 5‐
`8
`E.g., EX2049,
`¶¶16, 965‐988
`
`Sedic
`
`’648
`publication
`
`
`
`-3-
`
`
`
`Bahl
`
`E.g., EX2050,
`Abstract,
`Figures 1‐5,
`1317, 1320,
`1322
`
`
`
`
`
`1.5%|50%|10%|38.5%
`PEG-lipid, ionizable lipid, DSPC, cholesterol
`
`H10, H7
`(mRNA)
`
`Mouse,
`ferret,
`non-
`human
`primate,
`human
`
`
`
`-4-
`
`