1. Obviousness in a Phosphorylating Reagent Patent 7,276,598 –Phosphorylation reagents for improved processes to convert terminal hydroxyl groups of oligonucleotides into phosphate monoesters Karni Chagal; Samantak Ghosh; Sarah Jarchow-Choy; Julie Kane

2. Claim 1, ‘598 Patent (A) 1. A phosphoramidite reagent having the formula (2’): wherein n is an integer selected from 0 to 20.

3. Claim 1, ‘598 Patent (A) 1. A phosphoramidite reagent having the formula (2’): wherein n is an integer selected from 0 to 20.

4. Claim 1, ‘598 Patent (B) 1. A phosphoramidite reagent having the formula (2’): wherein n is an integer selected from 0 to 20.

5. AI should win because…(C) The patent is obvious. Solid phosphoramidites are easier to work with than liquid phosphoramidites. It is well known in the art that adding nucleosides and bulky substituents to a molecule can make a liquid heavy enough to turn into a solid.

6. PO should win because… (C) The patent is non-obvious. Prior to this patent, no one had created a solid phosphoramidite of this type. Further, it is not obvious to try since there are other phosphoramidites that cannot be turned into solids just by adding nucleosides and bulky substituents.

7. Litigation Issues (D)

8. AI: Obviousness based on Prior Art (D) Tet. Lett, 1986, 27, 1023-1026

9. AI: Compound of ‘090 patent is phosphoramidite (D)

10. AI: Obviousness of Deprotection of Phosphoramidite (D) ‘090 Patent: “The oligonucleotides were deprotected with conc. aqueous NH 3 (2 hours at room temperature, then 7 hours at 55° C.)” (19:43-45) ‘598 Patent: “The removal of the phosphate protecting groups was conducted through heating of the resulting ammonia solution of the crude oligonucleotide at 55° C overnight (16 hours)” (25: 3-6)

11. PO: Advantages (D) Phosphoramidite contains a reporter group that can be monitored easily Contains two beta-eliminating phosphate protective groups for easier deprotection Does not require additional manipulations Solid

12. PO: Non-obviousness (D) Put argument here about non- obviousness of molecule in red box