(2) Focusing on the heterocycles assembled from acyclic reactants, one skilled in the art 10
would have seen that N-R is preferred in the E position since nitroguanidine and2
cyanoguanidine are the only acyclic reactants used in the ‘146 patent. (Paper No. 75, page 15
and SX 2001, ¶28).
(3) That 1,3,5-oxadiazine, 1,3,5-thiadiazine and 1,3,5-triazines are fundamentally related in
that they may be produced by condensation reactions of formaldehyde with H-B-H where B is
2 2
O, S or N-R (i.e. H O, H S and H NR ) and nitroguanidine or cyanoguanidine. (Paper No.2 2 2
75, pages 16-17 and SX 2001, ¶28).11
(4) The ‘146 patent teaches the interchangeability of -CH -O-CH -, -CH -S-CH - and -2 2 2 2
CH -N(R )-CH -. (Paper No. 74, page 19, SX 2001, ¶32).2
2 2
10Note, the 3-cyano-iminomorpholine and the 3-nitroiminomorpholine heterocyclic compounds
described at col. 2, line 55 to col. 3, line 35, exemplified in example 1 and depicted in compounds 1-9
do not require assembly of the core heterocycle from acyclic reactants.
11Note, Dr. Pearson specifically testifies that:
A person of ordinary skill in the art of heterocyclic chemistry in the 1988-90 time frame
knew that production of 1,3,5-oxadiazines could occur without any external nucleophile
like water. Only the formaldehyde, a guanidine, and an acidic environment are needed.
1,3,5-oxadiazines have been synthesized under non-aqueous conditions (from a urea,
paraformaldehyde with an acid catalyst in chloroform) by Seidel et al. SX 2052.
(SX 2001, ¶41, emphasis added). Additionally, Dr. Pearson testifies that:
“It should also be noted that the work of Seidel and Boettner shows that the synthesis
of oxadiazines using this method is simpler than the synthesis of thiadiazines, since the
oxadiazine preparation requires only the thiourea and paraformaldehyde (a source of
formaldehyde), whereas the thiadiazine preparation requires the additional presence of
(H S).” (SX 2001, ¶32, emphasis added).
2
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