specifications, support this claim construction. (Def. Br. at 6-11.) Those arguments are described and addressed infra.
Plaintiffs argue that the plain language of Claim 1 says that the hydroxyl can be "substituted by" an alkyl of up to three carbons to make up the R4 structure, and that the other claim language and patent specifications support its proffered construction. Plaintiffs contend that a "methyl-substituted hydroxyl group" such as found in VANTIN® and the Ranbaxy product is squarely covered by the plain meaning of the R4 claim language. (Pl. Reply Br. at 4-8.) Plaintiffs also oppose the extrinsic expert declaration provided by Ranbaxy regarding "common nomenclature" in the art, as well as Ranbaxy's other chemistry arguments pertaining to Claim 1 and the patent specifications, offering its own extrinsic evidence. (Sloan Supp. Decl. ¶¶ 5-18.) Our claim construction favors the position advocated by plaintiffs.
We turn first to the literal language of Claim 1 as it defines the R4 structure. That language begins with the following phrase: "R4 is a residue of a nucleophilic compound. . . ." It is undisputed that both an unsubstituted hydroxyl (-OH) and a methoxy group (-OCH3) qualify as a "residue of a nucleophilic compound." (Pl. Reply Br. at 2-4.)
The next phrase of the R4 limitation sets forth a so-called Markush group, listing eight structures as follows: "selected from hydroxyl, mercapto, cyano, azido, amino, carbamoyloxy, carbamoylthio and thiocarbamoyloxy. . . ." Of course it is un disputed that hydroxyl is one of the structures listed in this Markush group.
The final phrase of the R4 limitation states: "said group being unsubstituted or substituted by alkyl of up to three carbons,. . . ." We first observe that the sentence structure of this phrase, following immediately after the listing of the eight-member Markush group, indicates that this language "said group being unsubstituted or substituted" applies to each of the eight structures listed in the Markush group. However, Ranbaxy raises the question whether all — or only some — of the members of the Markush group can in fact be "substituted by alkyl of up to three carbons," so as to be covered by the word "substituted" in this claim language.
The parties appear to agree that the term "substituted" is generally used by organic chemists to refer to removing a hydrogen atom from a residue and "substituting" something else in place of the hydrogen atom. (Def. Br. at 7, Remmel Decl. ¶ 13, Sloan Supp. Decl. ¶ 10.) Ranbaxy points out that as a matter of undisputed chemistry, two of the structures listed in the R4 Markush group cannot be "substituted by alkyl of up to three carbons," namely cyano (-CN) and azido (-N=N=N), because they lack hydrogen atoms in their original form. (Remmel Decl. ¶ 12, Table 1; id. ¶ 19; Sloan Supp. Decl. ¶ 10.) Ranbaxy does acknowledge that the last four structures listed in the Markush group (amino, carbamoyloxy, carbamoylthio and thiocarbamoyloxy) can be so substituted, even using Ranbaxy's asserted nomenclature convention, discussed infra.*fn9 (Remmel Decl. ¶ 18.) That leaves two of the structures, hydroxyl and mercapto, to be considered in this context.
Ranbaxy asserts that neither a hydroxyl nor a mercapto group can be "substituted by a lower alkyl group," according to conventional nomenclature. Dr. Remmel explains this point as follows:
Referring to the other four listed R4 residues of
claim 1 ("hydroxyl," "mercapto," "cyano," and
"azido") as being substituted by an "alkyl of up to
three carbons" would be improper because to do so
would violate the accepted conventions familiar to
organic chemists for naming such residues. For
example, replacing the hydrogen atom (H) of a
hydroxyl residue (-OH) with an ethyl residue (-C2H5)
would result in an ethoxy residue (-OC2H5), and would
completely remove, rather than merely "substitute,"
the hydroxyl reside. It is incorrect to refer to an
ethoxy residue as an "ethylsubstituted" hydroxyl
residue because an ethoxy residue does not contain a
hydroxyl residue, and thus does not have the general
physical and chemical properties of a hydroxyl
residue. . . . Likewise, a mercapto residue (-SH) is
characterized by a sulfur-hydrogen (S-H) bond. A
residue with an (S-C) bond is a thioether and
therefore, replacing the hydrogen atom of a mercapto
residue (S-H) with an alkyl residue such as methyl,
ethyl or propyl would result in a thioether residue
(thiomethyl. (-SCH3), thioethyl (-SC2H5) or
thiopropyl (-SC3H7), respectively), which does not
contain a sulfur-hydrogen bond. It is incorrect to
refer to the thioether residue as an
"alkyl-substituted" mercapto residue.
(Remmel Decl. ¶ 19 (emphasis added).)
Ranbaxy's position, as expressed by its extrinsic expert declaration, is that of the eight members of the Markush group listed in the R4 limitation, two of those members cannot have a hydrogen atom "substituted" with a lower alkyl group as a matter of physical chemistry (cyano and axido) [a point which plaintiffs do not dispute], and two other members (hydroxyl and mercapto) cannot have a hydrogen atom "substituted" with a lower alkyl group as a matter of "accepted conventions familiar to organic chemists for naming such residues." (Id. (emphasis added).) The latter point is vigorously disputed by plaintiffs. Ranbaxy argues that based on this asserted naming convention, the "substituted for" language in the R4 claim limitation can only refer to the four last-named members of the Markush group (amino, carbamoyloxy, carbamoylthio and thiocarbamoyloxy), and the hydroxyl group cannot be "substituted" with a lower alkyl group within the meaning of the claim language.*fn10
Arguments are presented by Ranbaxy from the intrinsic evidence as well. First, Ranbaxy points to the language of Claim 1 defining the R5 element: "and R5 is hydroxyl or lower alkoxy." ('783 patent, Col. 40:14.) Here Ranbaxy argues that "the inventors provided for R5 of Claim 1 to cover methoxy using conventional nomenclature ["lower alkoxy"] and could have easily done so for R4 if they believed that it should cover methoxy." (Def. Br. at 9 (bracketed material added).) Regarding the patent prosecution history, Ranbaxy simply points out that throughout that long history, including predecessor applications, the inventors explained that the terms in the patent were being used according to conventional usage, and "nowhere create[d] an exception for substituted hydroxyl." (Id. at 10, citing Canuso Decl., Exs. 4, 9, 12.)
Plaintiffs submit that the Claim 1 language defining both R4 and R5 is clear, unambiguous and consistent with both the patent specification and the prosecution history. The relevant portion of the R4 limitation states: "hydroxyl . . . unsubstituted or substituted by alkyl of up to three carbons." We agree that the plain meaning of that phrase is that hydroxyl can be "substituted" by such an alkyl. An exploration of the underlying chemistry, set forth above, shows that it is chemically feasible to "substitute" all members of the R4 Markush group, except cyano and azido, by replacing the hydrogen atom with "alkyl of up to three carbons." Therefore it appears to this Court that the plain meaning of the R4 language, read in the light of common chemistry principles, is that cyano and azido will be "unsubstituted," and the remaining six groups, including hydroxyl and mercapto, can be "unsubstituted or substituted by alkyl of up to three carbons."
The '783 patent specification*fn11 expresses this concept of substitution relating to a hydroxyl group in terms similar to the R4 claim language itself:
The residue of nucleophilic compound shown by the
symbol R4 may be . . . a group of the formula:
wherein W represents oxygen or sulfur atom and R
represents hydrogen, carbamoyl, N-alkylcarbamoyl,
thiocarbamoyl, N-alkylthiocarbamoyl, an acyl,
sulfamoyl, alkylsulfonyl or hetero ring. The typical
residue of nucleophilic compound may be exemplified
by hydroxyl, mercapto, cyano, azido, amino,
carbamoyloxy, carbamoylthio or thiocarbamoyloxy
group, or those substituted with alkyl (e.g. methyl,
ethyl, propyl, etc.). . . .