Opinion ID: 2719820
Heading Depth: 4
Heading Rank: 1

Heading: Co-Administration

Text: We begin with Kennedy’s claim construction argu- ments. Through claim construction, Kennedy attempts to enlarge the scope of the ’766 patent while narrowing that of the ’442 patent. First, Kennedy urges that the district court erred in limiting the term “co-administering” 4 in the ’766 patent to three modes of administration. The district court construed “co-administering” to mean that treatment with the antibody can be: (1) started at approximately the same time as treatment with methotrexate (concomitant administration); (2) added after treatment with the methotrexate has already begun (adjunctive administration); or (3) begun first, with the methotrexate treatment later added (adjunctive administration). Kennedy argues that this definition erroneously excludes a fourth form of co-administration: administration of the antibody alone after discontinuing the administration of methotrexate. The ’766 patent’s specification confirms the correctness of the district court’s claim construction. The specification never uses the term “co-administering” to refer to patients who only received the antibody after discontinuing treatment with methotrexate. The specification makes clear that the invention described in the claims is limited to concomitant and adjunctive use. The specification outlines several possible modes of co-administration: “TNF antagonists can be administered prior to, simulta- 4 Claim 8 of the ’766 patent reads: “A method of treating rheumatoid arthritis in an individual in need thereof comprising co-administering methotrexate and an [anti-TNFα] antibody or an antigen-binding fragment thereof to the individual, in therapeutically effective amounts.” ’766 Patent col. 35 ll. 59-63. ABBVIE INC. v. KENNEDY INST. OF RHEUMATOLOGY 15 neously with (in the same or different compositions) or sequentially with the administration of methotrexate. For example, TNF antagonists can be administered as adjunctive and/or concomitant therapy to methotrexate therapy.” ’766 Patent col. 18 ll. 58-62. “Concomitant” therapy involves starting the two drugs at the same time and then continuing their administration together; “adjunctive” therapy involves starting one of the drugs after the other and then continuing their administration together. The specification concludes that “[t]he present invention relates to the discovery that tumor necrosis factor antagonists can be administered to patients suffering from a TNF-mediated disease as adjunctive and/or concomitant therapy to methotrexate therapy, with good to excellent alleviation of the signs and symptoms of the disease.” ’766 Patent col. 4 ll. 31-36. This discussion in the specification shows that “co-administering” encompasses treatment with the antibody that can be started before, after, or at the same time as treatment with methotrexate, as long as two drugs are administered together. The specification nowhere suggests that the invention includes administration of the antibody alone after discontinuing treatment with methotrexate. The specification’s discussion of the three examples it provides similarly confirms the district court’s claim construction. None of the examples discusses the discontinuation of methotrexate as a form of co-administration or as part of the invention. The first example describes the T-14 study. To qualify for entry into the T-14 study, patients must have received weekly methotrexate treatment for at least six months. Upon enrollment into the study, the patients were “stabilized” on a fixed weekly dose of methotrexate for the first four weeks. After this first, equalizing month, the patients were organized into three separate groups that received three different treatment regimens—three different modes of antibody admin16 ABBVIE INC. v. KENNEDY INST. OF RHEUMATOLOGY istration. The week the patients began to receive the differing treatment regimens was called “week zero” because it marked the beginning of the trial period. The three distinct treatment regimens, or modes of anti-body administration, were: (1) patients who received methotrexate as a tablet and infusions of a placebo instead of the anti-TNFα antibody (the “control” group), (2) patients who received methotrexate as a tablet and infusions of the anti-TNFα antibody throughout the trial (“MTX+” group), and (3) patients who received a placebo tablet instead of methotrexate and infusions of the anti-TNFα antibody throughout the trial (the “anti-TNFα antibody alone” or “MTX-” group). In the T-14 study, as in the specification’s other examples, the therapy that the non-placebo, noncontrol patients received was “adjunctive” co- administration. 5 The specification discusses the MTXtreatment group and recognized that this group manifested some limited benefits as compared to the MTX+ group, 6 but never suggests that this group received the 5 In other words, the antibody treatment was added onto the methotrexate therapy: the patients were already receiving methotrexate and then began taking the antibody in addition. None of the examples discusses a scenario in which patient received “concomitant” coadministration—where treatment with methotrexate and the antibody are begun at the exact same time. Nevertheless, the specifications of the ’766 patent and ’442 patent discuss concomitant administration of the two drugs as a type of “co-administration.” 6 At trial, multiple experts attributed this result to a “carry-over” effect that the patients’ prior treatment with methotrexate caused. All the patients in the T-14 study had received weekly methotrexate for at least six months prior to the trial and were then “stabilized” on a ABBVIE INC. v. KENNEDY INST. OF RHEUMATOLOGY 17 adjunctive or concomitant therapy that is within the invention of the ’766 patent’s claims. To the contrary, the specification of the ’766 patent points to the outcomes experienced by the MTX+ group, as compared to those the MTX- and control groups experienced, in order to show that “co-administration” produces “a highly beneficial or synergistic clinical response.” ’766 Patent col. 31 l. 39; see ’766 Patent col. 29 ll. 3-10. It was only through a comparison of the MTX+ group to the MTX- group (which the specification refers to as the group receiving the antibody “without methotrexate,” ’766 Patent col. 29 ll. 8-9) that the specification concludes that “treatment with a multiple dose regimen of [the antibody] as adjunctive and/or concomitant therapy to methotrexate therapy, in [rheumatoid arthritis] patients whose disease is incompletely controlled by methotrexate, produces a highly beneficial or synergistic clinical response that can be sustained through 26 weeks.” ’766 Patent col. 31 ll. 3540. Put simply, the specification compares the better outcomes that the group treated with both drugs experienced to the poorer results obtained in the groups that received no methotrexate or no antibody after week zero to support its conclusion that “co-administration”— administration of both drugs at the same time—is a superior method of rheumatoid arthritis treatment. Coadministration cannot include patients who discontinued methotrexate as Kennedy contends. fixed weekly dose of methotrexate for the first four weeks of the study. The specification does not discuss this carry-over effect or suggest that the MTX- group received a form of coadministration. As discussed in the text, the specification highlights the superior results that the MTX+ group experienced in order to prove that “co-administration” is a beneficial therapy. 18 ABBVIE INC. v. KENNEDY INST. OF RHEUMATOLOGY Nevertheless, Kennedy argues that the principle of claim differentiation counsels in favor of reading claim 8 to encompass embodiments where single doses of either the antibody or methotrexate are delivered to patients. Claim 8 reads “[a] method of treating rheumatoid arthritis in an individual in need thereof comprising coadministering methotrexate and an [anti-TNFα] antibody or an antigen-binding fragment thereof to the individual, in therapeutically effective amounts,” ’766 Patent col. 35 ll. 59-63, while claim 9 reads “[a] method of claim 8 wherein the [anti-TNFα] antibody or antigen-binding fragment is administered in a series of doses separated by intervals of days or weeks.” ’766 Patent col. 35 ll. 64-67 (emphasis added). Kennedy contends that “[a] comparison of claim 8 to its dependent claim 9 demonstrates that the only additional limitation is that the anti-TNFα antibody must be administered ‘in a series of doses separated by intervals of days or weeks.’” Appellant’s Br. 37. Kennedy relies on this difference to support its argument that the administration of the antibody after discontinuation of methotrexate treatment is covered. But claim 9 says nothing about the discontinuation of the methotrexate. Its administration is assumed to be ongoing with the single or multiple doses of the antibody. The plain text of the ’766 patent’s specification and claims supports the district court’s claim construction of “coadministering.” See also J.A. 86-87 ¶ 319-21 (the district court also explained that the inventors’ testimony at trial supported this construction of the term “co- administering”). Accordingly, the district court correctly interpreted “co-administration.” ABBVIE INC. v. KENNEDY INST. OF RHEUMATOLOGY 19