Orange Book Blog

AstraZeneca Defeats Teva's Claim That Crestor Infringes Teva's Patent

Teva Pharm. Indus. v. AstraZeneca Pharms., No. 08cv4786 (E.D. Pa. 2010)

Here's something you don't see every day:  an ANDA filer suing a brand-name drug manufacturer for patent infringement, claiming that the brand-name drug infringes the ANDA filer's patent.

In late 2007/early 2008, AstraZeneca ("AZ") filed suit against nine different ANDA filers, including Teva, who sought approval to market generic versions of Crestor (rosuvastatin).  The cases were consolidated in multidistrict litigation (D. Del. No. 08-md-01949) and proceeding through discovery when, in October 2008, Teva sued AZ, alleging that Crestor infringes Teva's U.S. Patent No. RE39,502.  Claim 1 of the '502 patent reads:  "A stabilized pharmaceutical composition for the treatment of dyslipidemia, comprising [rosuvastatin] and a stabilizing effective amount of at least one amido-group containing polymeric compound . . . ."

AZ filed a motion for summary judgment of patent invalidity due to prior invention pursuant to 35 USC 102(g)(2), which states that a person shall be entitled to a patent unless "before such person's invention thereof, the invention was made in this country by another inventor who had not abandoned, suppressed, or concealed it."  AZ argued that it made a batch of Crestor tablets meeting each limitation of the asserted '502 patent claims prior to December 1, 1999, the earliest date by which Teva claimed to have conceived of and reduced to practice the claimed formulation.

Teva did not dispute that AZ made a batch of Crestor tablets before December 1, 1999.  Rather, Teva argued that even if AZ created the exact infringing commercial formulation in mid-1999, AZ still could not prove conception or reduction to practice of the invention claimed by Teva's '502 patent by that date because there was no evidence that AZ appreciated that crospovidone, the amido-group containing polymeric compound included in Crestor, contributes to the stability of the formulation.  According to Teva, because AZ never appreciated that crospovidone contributes to the stability of its Crestor product formulations, it cannot have "created an embodiment that literally met all of the limitations of Teva's claims."

Last month, the district court granted AZ's motion for summary judgment.  The district court explained in its opinion that to establish priority of invention, there must be evidence not only that the inventor "actually first made the invention" but also that he "understood his creation to have the features that comprise the inventive subject matter."  According to the court, however,

the inventor need not establish that he recognized the invention in the same terms as those recited in the claims as the invention is not the language of the claims but the subject matter thereby defined.  Rather, the inventor must establish that he recognized and appreciated a compound corresponding to the compound defined by the claims.

The court continued:

Applying this principle--that the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer--the Federal Circuit has held invalid for anticipation numerous patents claiming what amount to newly discovered properties of prior art compositions, where the missing characteristic was necessarily present, or inherent, in the prior art, even though there was no recognition of the missing characteristic in the prior art.

The court concluded that, in this case, "Teva's discovery that crospovidone contributes to the stability of the formulations resembles the sort of scientific explanation for a prior art composition's functuning that the Federal Circuit has found to be an inherent property of the prior art in other cases."

Federal Circuit Sidesteps Interesting Questions of Jurisdiction Under 271(e)(2) and Inducement of Infringement in Ropivacaine Case

Abraxis Bioscience v. Navinta, No. 2009-1539 (Fed. Cir. 2010)

In 2006, Navinta filed an ANDA for a generic version of Naropin (ropivacaine), a drug indicated for use in surgical anasthesia and acute pain management.  At the time, there was only one patent listed for ropivacaine in the Orange Book, U.S. Patent No. 4,870,086, which claims an optically pure isomer of ropivacaine hydrochloride monohydrate.  Navinta's ANDA included a paragraph IV certification to the '086 patent.

Shortly after receiving Navinta's notice of paragraph IV certification to the '086 patent, Abraxis sued Navinta under 35 USC 271(e)(2), alleging infringement not only of the '086 patent, but also of U.S. Patent Nos. 5,670,524 and 5,834,489 (the "method patents"), which are directed to methods of using low concentrations of ropivacaine for the treatment of pain.  Although the '524 and '489 patents issued years earlier, they were not listed in the Orange Book at the time Navinta filed its ANDA.

Navinta filed a motion to dismiss Abraxis's claims regarding the method patents, arguing that because the method patents were not listed in the Orange Book, Navinta did not file paragraph IV certifications on them, and therefore there was no basis for suit under section 271(e)(2).  The district court, however, denied Navinta's motion to dismiss, concluding that suit under 271(e)(2) was proper notwithstanding that the method patents weren't listed in the Orange Book.

Navinta appealed this ruling to the Federal Circuit, arguing that jurisdiction under section 271(e)(2) is proper only when an ANDA filer has made a paragraph IV certification, and citing several cases from the Supreme Court and Federal Circuit that allegedly "held that section 271(e)(2) requires a paragraph IV certification."  In response, Abraxis argued that the alleged "holdings" cited by Navinta were actually mere dicta, and that neither the Supreme Court nor Federal Circuit has ever directly answered whether a paragraph IV certification is a prerequisite to suit under 271(e)(2).

Some number of months after the district court denied Navinta's motion to dismiss for lack of jurisdiction under section 271(e)(2), Navinta filed a second motion to dismiss, this time alleging that Abraxis lacked standing to sue because, due to a break in the chain of title, Abraxis did not own the patents-in-suit at the time that it filed the Complaint.  The district court, however, again denied Navinta's motion, finding that although there was a break in the chain of title to the patents, the "intent" of the various assigning entities was sufficient to imply a nunc pro tunc assignment based on the relationship between the corporate entities.  Having denied Navinta's second motion to dismiss, the case proceeded to trial.

Last August, after a seven-day bench trial, the district court issued its opinion on the merits.  The court found direct and indirect infringement of the '086 composition patent, and indirect infringement of the '524 and '489 method patents.  Pursuant to its findings of infringement of the method patents, the district court ordered that the effective date of approval of Navinta's ANDA product be no earlier than September 14, 2014, the expiration date of the method patents.

The district court's findings that Navinta would induce infringement of the method patents are the most interesting, because while the method patents are limited to the use of a low concentration of ropivacaine for the treatment of acute pain, Navinta had amended its ANDA not to seek approval of the low concentration of ropivacaine and, pursuant to section viii, had "carved out" the acute pain indication from its proposed ANDA product labeling.  The district court, however, concluded that Navinta "knows or should know that practicioners will use its ANDA products at diluted concentrations for pain management."  Furthermore, despite Navinta's section viii labeling carve-out, the district court concluded:

Navinta's Package Insert Labeling is sufficient to establish Navinta's encouragement of direct infringement of the '524 and '489 patents: (1) Navinta's Labeling specifically encourages infringement by including multiple references to use of the ANDA Products in labor and delivery, which is an acute pain management application that is only FDA-approved at [low] concentrations and by epidural administration; (2) Navinta's Labeling specifically encourages infringement by including statements referring practicioners to medical practice texts and references, which would instruct practicioners to use ropivacaine at concentrations of 0.2% or below for pain management; (3) Navinta's Labeling specifically encourages infringement by encouraging the use of the ANDA Products at the lowest possible concentrations for pain management issues.

Navinta appealed these findings.  Navinta argued in its appeal brief that the district court erred "because there was insufficient evidence that Navinta will actively encourage infringement or that Navinta possesses specific intent to encourage infringement," as required under the Federal Circuit's en banc decision in DSU Medical v. JMS.  Navinta argued:  "In holding Navinta responsible for uses of its ANDA product that are not mentioned or suggested in its labeling, the district court converted indirect infringement into a strict liability offense where Navinta was held responsible for possible downstream uses that it did nothing to encourage."  In support, Navinta cited the Federal Circuit's two off-label use decisions of 2003: Warner-Lambert v. Apotex and Allergan v. Alcon.  In those cases, the Federal Circuit concluded that the ANDA filers were not liable for inducement of infringement of patents claiming off-label uses.

On Tuesday, the Federal Circuit issued its decision on the appeal.  Unfortunately, however, it based its decision on the least interesting of the three issues that Navinta appealed.  The Federal Circuit concluded that due to a break in the chain of title, Abraxis did not own the patents-in-suit when it filed the Complaint, and Abraxis therefore lacked standing.  Accordingly, the Federal Circuit reversed and vacated the district court's denial of Abraxis's second motion to dismiss, and remanded with instructions for the district court to dismiss Abraxis's complaint without prejudice.

In all likelihood, Abraxis will refile its Complaint against Navinta in the district court, the district court will quickly issue a final judgment on the merits of the infringement claims, Navinta will appeal again and the case will be back at the Federal Circuit.  There is, therefore, still hope that the Federal Circuit will weigh in on the interesting issues in this case.

FEDERAL CIRCUIT APPEAL BREIFS:

• Navinta Appeal Brief
• Abraxis Opposition Brief
• Navinta Reply Brief
  

By Slimmest of Margins, Federal Circuit Declines to Rehear Gemzar (Gemcitibine) Double Patenting Case

Sun Pharm. Indus. v. Eli Lilly & Co., No. 2010-1105 (Fed. Cir. 2010)

By a vote of 5-4, the Federal Circuit on Monday denied Eli Lilly's petition for panel rehearing or rehearing en banc from the court's July decision that affirmed the invalidity of Lilly's U.S. Patent No. 5,426,826 for obviousness-type double patenting.  Judge Newman was joined by Judges Rader, Lourie and Linn in dissent.

In addition to the '826 patent, which claims the use of gemcitibine for treating cancer, Lilly owns U.S. Patent No. 4,808,614, which claims the gemcitibine compound.  The '614 patent discloses, but does not claim, the anticancer utility of gemcitibine.  The Federal Circuit panel decision in July, authored by Judge Prost and joined by Judges Bryson and Gajarsa, affirmed the invalidity of the '826 patent on grounds of obviousness-type double patenting, stating that "[t]he asserted claims of the later '826 patent simply claim the anticancer use disclosed in the specification of the '614 patent."

In dissent, Judge Newman cited numerous precedents of the Federal Circuit and its predecessor court for establishing the rule that "double-patenting is altogether a matter of what is claimed."  She concluded, "Uniformly, unlike examination for obviousness based on prior art, the issue of obviousness-type double patenting is directed to whether the invention claimed in a later patent is an obvious variant of the invention claimed in an earlier patent.  The panel opinion violates a vast body of precedent."

The case attracted the attention of several amici curiae, including BIO, PhRMA, Teva and Washington Legal Foundation.  Judge Newman cited a portion of BIO's amicus brief to emphasize the importance of method-of-use patents to the pharmaceutical industry:

BIO's members routinely engage in continuing research on basic biotechnology inventions even after initial patent applications have been filed.  Often, such research reveals something new about a basic invention, including better and unexpected new ways of using it that require patent protection for their commercial development.

Judge Newman concluded with a rebuke of the panel for changing the law of double patenting without en banc consideration.  She stated:

If the majority of the court now believes, as a matter of policy, that the law should be changed in this new direction, en banc treatment is particularly appropriate, for the court's rule is that the earlier precedent prevails unless overruled en banc.  A situation in which the court ignores this rule, and applies whatever law the panel prefers, is an indictment of the ability of this court to provide stable law in the areas entrusted to us.