The Federal Circuit indirectly imports limitations from the specification into the claims through claim construction

John M. Wang | April 24, 2017

The Medicines Company v. Mylan Inc. Etc.

April 6, 2017

Before Dyk Wallach, and Hughes.  Opinion by Dyk.

Summary

Mylan submitted two Abbreviated New Drug Applications (“ANDA”) to seek approval of Food and Drug Administration (“FDA”) for selling generic bivalirudin drug products before the expiration of patents-in-suit: the ‘727 patent and the ‘343 patent. In its ANDA, Mylan stated that it would limit the Asp9 level of its generic product to less than 2.0 percent. Medicines sued Mylan for infringement of the ‘727 and ‘343 patents. Mylan filed counter-claims seeking declaratory judgments of invalidity. The district court held that Mylan infringed the ‘727 patent, but not the ‘343 patent. The Federal Circuit reverses in part, and held that Mylan does not infringe both patents.

Details

Bivalirudin drug products are used to prevent blood from clotting and are regarded as highly effective anticoagulants for use during coronary surgery. The two patents-in-suit, the ‘727 and ‘343 patents, have nearly identical specification and contain product and product-by-process claims respectively for pharmaceutical batches of improved drug products comprising bivalirudin with a maximum impurity level of Asp9 of 0.6%.

Medicines have been selling a bivalirudin drug product under the trade name ANGIOMAX® since 2001, well before the critical date of the patents in suit. The FDA required ANGIOMAX® to contain Asp9-bivalirudin, an impurity generated during the manufacturing process to less than 1.5%. Between 2001 and 2005, Medicines and its contract manufacturer, Ben Venue Laboratories (BVL) produced and sold numerous batches of compounded bivalirudin having Asp9 levels of less than 1.5 percent. In fact, the overriding majority of these batches had Asp9 levels below 0.6 percent. In 2006, after producing two bad batches containing more than 1.5% of Asp9, Medicines hired a consultant, Dr. Gary Musso, together with an employee of Medicines, Dr. Gopal Krishna, to solve the inconsistency problem. Finally, Dr. Musso and Dr. Krishna realized that the inconsistency of the batches is mainly due to inefficient mixing of a pH-adjusting solution into a bivalirudin solution during the compounding process. This inefficient mixing can generate localized “hot spots” where concentrated sites in the compounding solution have much higher pH levels. In response, they developed an improved, “efficient mixing” process and applied the two patents in suits based on the efficient mixing process.

Claim 1 of the ‘727 patent is a product claim, as shown below:

  1.  Pharmaceutical batches of a drug product comprising bivalirudin … wherein the batches having a pH adjusted by a base, said pH is about 5-6 when reconstituted in an aqueous solution for injection, and wherein the batches have a maximum impurity level of Asp9-bivalirudin that does not exceed about 0.6% as measured by HPLC.

Claim 1 of the ‘343 patent is a product by process claim, as shown below:

  1.  Pharmaceutical batches of a drug product comprising bivalirudin … prepared by a compounding process comprising:

(i)  dissolving bivalirudin in a solvent to form a first solution;

(ii)  efficiently mixing a pH-adjusting solution with the first solution to form a second solution, wherein the pH-adjusting solution comprises a pH-adjusting solution solvent; and

   (iii)  …wherein the batches have a pH adjusted by a base,   said pH is about 5-6 when reconstituted in an aqueous solution for injection, and wherein the batches have a maximum impurity level of Asp9-bivalirudin that does not exceed about 0.6% as measured by HPLC.

The district court held that the ‘343 patent requires “efficient mixing” and the ‘727 does not. Furthermore, Mylan’s process does not comprise efficient mixing. Thus, the district court held that Mylan’s process infringes the ‘727 patent, but not the ‘343 patent.

The Federal Circuit reverses in part the district court’s holding regarding the ‘727 patent. First, the Federal Circuit held that the “efficient mixing” is required by the batches limitation and is therefore a limitation of both the ‘727 and ‘343 patents. Specifically, regarding “pharmaceutical batches,” the district court construed the term consistent with definition in the specification to refer to either (1) a single batch, wherein the single batch is representative of all commercial batches … made by a compounding process, and and wherein the levels of, for example, Asp9-bivalirudin, total impurities, and largest unknown impurity, and the reconstitution time represent levels for all potential batches made by said process; or (2) “all batches prepared by a same compound process.” From this claim construction and in light of specification and the prosecution history, the Federal Circuit held that the “batches” limitation therefore requires the use of a compounding process that achieves batch consistency. Furthermore, based on the intrinsic evidence of the patents in suit, the Federal Circuit held that the compounding process must use efficient mixing to achieve batch consistency because no part of the patents’ disclosure teaches another method capable of producing consistent batches. That is, the Federal Circuit relies on intrinsic evidence to essentially import the ‘efficient mixing” limitation from the specification into the claims of both the ‘727 and ‘343 patents through claim construction. The Federal Circuit acknowledges that “[i]n doing so, we note that our decision does not impermissibly add a process limitation to a product claim that does not require a process because the specification’s definition of “batches” by itself injects a compounding process as a limitation in the asserted claims.”

Second, regarding the term “efficient mixing,” Medicines argue that the specification defines the term in the disclosure that “[e]fficient mixing is characterized by minimizing levels of Asp9-bivalirudin in the compounding solution,” and accordingly the term should be construed to refer to mixing methods which produce less than 0.6% Asp9-bivalirudin in the compounding solution. However, the Federal Circuit disagrees and held that that disclosure is not intended to be a definition of “efficient mixing” because it does not accord with the linguistic formula used by the patentee for definition. Furthermore, Medicines’ construction is so broad that it essentially covers any way of mixing that achieves a compounding solution having an Asp9 level of less than 0.6 percent, apparently exceeding the disclosure of the specification. Furthermore, the specification’s detailed description teaches that “[e]fficient mixing … may be achieved through various methods,” such as by adding the pH-adjusting solution at a constant rate, at a variable rate, using one or more mixing devices, etc. However, the Federal Circuit disregards this detailed description as vague, open-ended, and unhelpful, merely providing a laundry list of mixing techniques that individually (or in combination) may (or may not) constitute efficient mixing. Instead, the district court focuses on two specific Examples 4 and 5 in the specification to define what efficient mixing is or is not. Example 4 describes an embodiment under inefficient mixing conditions while Example 5 describes an embodiment under efficient mixing conditions. The district court construes “efficient mixing” as “not using inefficient mixing conditions such as described in Example 4.” The Federal Circuit essentially not only agrees with the district court, but also takes a further step to narrow the scope of the claims. The Federal Circuit reasons that “one of ordinary skill in the art would rely on Example 5 to ascertain the metes and bounds of ‘efficient mixing.’ As the only embodiment of efficient mixing, Example 5 is highly indicative of the scope of the claims.” Thus, the Federal circuit construes the “efficient mixing” very narrowly as requiring using the efficient mixing conditions of Example 5. That is, the Federal Circuit essentially imports limitations of Examples in the specification into claims of both the ‘727 and ‘343 patents through claim construction.

Third, under the above claim construction, the Federal Circuit held that Mylan’s ANDA does not infringe the asserted claims of both the ‘727 and ‘343 patents since it is undisputed that, for example, Mylan does not use multiple mixing devices as required by Example 5.

Take away

  1. Patentees should disclose multiple Examples in the specification.
  2. Multiple types of claims such as product claims and product-by-process claims should be drafted in the specification to effectively protect the invention.

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