Orange Book Blog

OBB News Briefs

• Teva announced Friday that it is acquiring Barr Pharmaceuticals for $7.5 billion plus $1.5 billion in debt.  For more:  AP; Reuters; WSJ.
• Zentiva, the Czech generic drug maker, announced Friday that it rejected a takeover bid from Sanofi-Aventis.  Sanofi already owns 25% of the company.
• Meanwhile, the WSJ Health Blog recently reported that the CEOs of GSK and Roche have no interest in getting into the generics business.
• FDA Law Blog recently reported on two interesting USPTO decisions denying Patent Term Extension requests under 35 U.S.C. § 156.  In both cases, AstraZeneca was the applicant:  July 8 (Symbicort); July 16 (Prilosec OTC).
• On July 16, Impax and Wyeth announced a settlement of their litigation over Impax's generic version of Effexor XR.  Under the agreement, Impax may launch its capsule formulation of Effexor XR on June 1, 2011, and possibly as early as January 1, 2011.
• On July 11, Momenta Pharmaceuticals announced the filing of an ANDA with a paragraph IV certification for a generic version of Copaxone, Teva's $500 million multiple sclerosis drug.  According to Pharmalot, Teva's CEO is not concerned.
• The Baltimore Sun recently reported that the brand-name pharmaceutical industry has been successfully pushing legislation at the state level requiring pharmacists to inform doctors or get their permission before substituting a generic drug for a brand-name drug.
• The FDA announced on July 9 that it is revising the way it communicates to drug companies when a marketing application cannot be approved as submitted.  CDER will no longer issue "approvable" or "not approvable" letters.  For more:  Pharmalot; WSJ Health Blog.
• The WSJ Health Blog had an interesting post recently about a report from the HHS Inspector General, finding that FDA typically takes longer than the 180 days allowed under law to review a generic drug application.
• The Mircera case between Amgen and Roche is attracting a great deal of attention, particularly because of the "public interest" factor of the injunction analysis.  Patent Docs reported that BIO filed an amicus brief with the Federal Circuit.  Pharmalot has more on the case.
• Insmed recently announced that it has developed a biosimilar version of Amgen's Neupogen, a $1 billion drug for the treatment of Neutropenia.  Pharmalot has more.

OBB News Briefs

• On June 25, the Congressional Budget Office released a cost estimate for the Biologics Price Competition and Innovation Act of 2007 (S. 1695), concluding that the biosimilars bill would save American consumers $25 billion on prescription drug costs over the next ten years.  For more: statements from BIO and PhRMA; FDA Legislative Watch; Pharmalot; The Hill's Congress Blog.
• Bayer and Barr announced on June 24 that they signed a deal licensing Barr to market authorized generic versions of Bayer's Yasmin and Yaz oral contraceptives.  Under the agreement, Bayer will continue to appeal the March 3rd district court decision on Yasmin and will receive higher royalties from Barr if it succeeds.  More: Reuters.
• On June 23, FDA Law Blog reported that Rep. William Delahunt (D-MA) introduced a bill specifically meant to allow The Medicines Company, a Massachusetts company, to obtain a patent term extension for its patent covering Angiomax (bivalirudin)--for $65 million.
• FDA Law Blog reported on June 19 that the House Commerce Committee posted the responses to its April 3rd letter soliciting feedback on how to establish a pathway for FDA approval of biosimilar products.
• On June 18, Pfizer and Ranbaxy announced a comprehensive settlement of patent litigation over generic Lipitor.  Under the agreement, Ranbaxy will have a license to sell generic versions of Lipitor (atorvastatin) and Caduet (atorvastatin/amlodipine) effective Nov. 30, 2011.  For more: NYT; Pharmalot; Reuters; WSJ; WSJ Health Blog.
• On June 17, the Federal Circuit affirmed the district court findings of inequitable conduct and exceptional case in Synthon IP v. Pfizer, in which Synthon unsuccessfully alleged that Pfizer infringed its patent on a process for making amlodipine, the active ingredient in Norvasc.
• The AP reported on June 5th that Abbott and Mylan settled their patent litigation over Mylan's generic version of Depakote ER, with the parties agreeing that Mylan may launch its generic no later than Jan. 1, 2009.
• The Lewis & Clark Law Review recently published a special issue devoted entirely to the patent law doctrine of obviousness.  One of the articles is of particular interest:  Pharma's Nonobvious Problem, by Prof. Rebecca S. Eisenberg.

In a "Surprising" Victory, Barr and Mylan Invalidate Boehringer Ingelheim's Patent on Mirapex

Boehringer Ingelheim v. Barr and Mylan, No. 05-700-JJF (D. Del. 2008)

Last week, following a bench trial held in March, the U.S. District Court for the District of Delaware held that Boehringer Ingelheim's patent on Mirapex (pramipexole dihydrochloride) is invalid for obviousness-type double patenting.  Mirapex, indicated for the treatment of Parkinson's disease and Restless Leg Syndrome, has annual U.S. sales of approximately $380 million.

Barr Labs filed its ANDA for a generic version of Mirapex in 2005 with paragraph IV certifications to Boehringer's U.S. Patent Nos. 4,843,086 and 4,886,812.  Mylan filed its ANDA, with paragraph IV certifications to the same patents, shortly thereafter.  Barr's approval letter confirms that Barr was the first to file, and therefore is entitled to 180-day exclusivity.

Boehringer responded by filing suit against Barr and Mylan, and the cases were consolidated for trial.  The '086 patent expired while the litigation was pending, leaving only the '812 patent in suit.

The district court's opinion explains that the "basic premise of double patenting is that the same invention cannot be patented twice."  Here, the '086 patent claimed methods of treating certain diseases by administering tetrahydrobenzthiazoles, while the '812 patent claims the tetrahydrobenzthiazole compounds themselves, including the active ingredient in Mirapex, pramipexole dihydrochloride.  The court concluded that "although there are differences between the '812 patent and the '086 patent, . . . those differences are insufficient to support the patentability of the '812 patent in light of the '086 patent."

Of course, obviousness-type double patenting can be avoided by a terminal disclaimer.  Interestingly, Boehringer filed a terminal disclaimer of the '812 patent on the second day of trial of the case, on March 12, 2008.  Boehringer terminally disclaimed:

only the terminal part of the statutory term of the '812 patent which would extend beyond the 1,564 days after the full statutory term of the '086 patent as that term is defined in 35 U.S.C. § 154, so that by virtue of this disclaimer, the '812 patent will expire on October 8, 2010.

Boehringer received a 1,564-day extension under 35 USC § 156 due to FDA regulatory review of Boehringer's New Drug Application for Mirapex.  As a result of this patent term extension, the original expiration date of the '812 patent, December 12, 2006, was extended to March 25, 2011.  Thus, by its terminal disclaimer, Boehringer disclaimed five and a half months of patent term--the period of time between the expiration date of the '086 patent and the original expiration date of the '112 patent.

Boehringer argued that the terminal disclaimer obviated Barr and Mylan's double-patenting argument.  However, the court noted that "a dual problem is presented in that the terminal disclaimer was not only filed at or near the conclusion of trial in this action, but it was also filed after the expiration of the earlier '086 patent."  Citing two cases, the court observed that "the Federal Circuit has at least suggested in dicta that for a terminal disclaimer to be effective, the earlier filed patent must not have expired at the time of the filing of the disclaimer."  Boehringer tried to distinguish these cases "because neither case involved a terminal disclaimer in the context of a Section 156 patent term extension," but the court was not persuaded.  The district court held that Boehringer's terminal disclaimer was ineffective to moot the double patenting issue because it was filed after the '086 patent had expired.

According to an investor note from Bernstein Research, the decision was surprising because the district court was not expected to "make a controversial opinion on what is likely to be a precedent-setting ruling by the appellate court on patent extensions and terminal disclaimers."  In addition, the note indicates that Bernstein expects Barr to "maximize the value of the challenge through settlement."  According to Bernstein, "the most likely settlement is that Barr would have a date-certain launch of generic Mirapex in 2010 with an agreement protecting it from both an authorized generic and a potential Boehringer win on appeal."

The "failure to market" forfeiture provisions, however, will likely complicate any settlement discussions.  Under the MMA, the 180-day exclusivity period may be forfeited if the first applicant does not launch its generic drug product within 75 days after "a court enters a final decision from which no appeal (other than a petition to the Supreme Court for a writ of certiorari) has been or can be taken that the patent is invalid or not infringed."  If Boehringer and Barr settle the case, for example, with an agreement that Boehringer will not appeal, Barr's 180-day exclusivity would be forfeited later this summer.  For at least this reason, Boehringer is expect to appeal the district court decision.

RELATED READING:

• Barr press release
• Bloomberg article
• Motley Fool article

OBB News Briefs

• Last Thursday, FDA Law Blog reported on the Lupin v. Abbott case scheduled for oral argument at the Federal Circuit on Wednesday.  The case concerns a very unusual situation, where Abbott obtained two patent term extensions under 35 U.S.C. § 156 for a single drug product.
• In what is being reported as a setback for the prospects of a biosimilars industry in the United States, the FDA recently denied Genzyme's request to change the manufacturing site of its drug Myozyme.  For more: Boston Globe, Pharmalot, WSJ Health Blog.
• The L.A. Times published an interesting op-ed last week about safety concerns with biotech drugs.
• The New York Times reported last week on a lobbying fight between the brand-name and generic drug industries over inequitable conduct provisions in patent reform legislation.
• FDA Law Blog recently updated their coverage of two interesting cases: Teva vs. FDA, concerning 180-day exclusivity on Risperdal, in which Apotex filed a motion to intervene; Nu-Pharm v. FDA, Nu-Pharm's ANDA for generic Depakote, in which the D.C. Circuit summarily affirmed the district court's decision in favor of FDA.
• On April 16, a district court denied Perrigo's motion for summary judgment that its generic version of Olux (clobetasol propionate foam), a treatment for scalp psoriasis, does not infringe Connetics' U.S. Patent No. 6,126,920.
• On March 19, a district court denied Ranbaxy's motion for summary judgment that Roche's patent on Valcyte (valganciclovir HCl), U.S. Patent No. 6,083,953, is invalid due to incorrect inventorship.  Numerous other summary judgment motions are still outstanding in the case.

Federal Circuit Affirms Denial of Somerset Pharma's Interim Patent Term Extension on Depression Patch

Somerset Pharmaceuticals v. Dudas, No. 2007-1447 (Fed. Cir. 2007)

The Federal Circuit decided an unusual case yesterday respecting Somerset Pharmaceuticals' application for an interim patent term extension for U.S. Reissue Patent No. RE 34,579.  The '579 patent covers a method of treating depression using Emsam, a transdermal patch that includes selegiline as the active ingredient.

35 USC 156(e)(1) provides for a patent term extension to compensate for delays in FDA regulatory review of a new drug application.  35 USC 156(e)(2) provides for an interim patent term extension if the patent "would expire before a certificate of extension is issued or denied under paragraph (1)."

Somerset's '579 patent is set to expire on August 18, 2007.  In April 2006, Somerset filed a request for patent term extension under Section 156(e)(1) on the '579 patent.  In February of this year, the Patent and Trademark Office had still not ruled on Somerset's request, and therefore Somerset filed a request for an interim patent term extension under Section 156(e)(2).

Shortly thereafter, Somerset filed suit against Mr. Dudas, the director of the PTO, seeking to compel the PTO to rule on its request for an interim patent term extension.  Somerset also filed a motion for preliminary injunction at the same time.  The district court denied Somerset's motion in June, and Somerset promptly appealed to the Federal Circuit.  Meanwhile, on July 12, the PTO denied both Somerset's application for a patent term extension under Section 156(e)(1) and its application an interim extension under Section 156(e)(2).

In yesterday's decision, the Federal Circuit dismissed as moot Somerset's request to compel the PTO to act on its request for an interim patent term extension.  Moreover, the Federal Circuit affirmed the district court's denial of Somerset's motion for a preliminary injunction to compel the PTO to grant Somerset's request for an interim patent term extension, finding that because the PTO denied Somerset's application for a patent term extension under Section 156(e)(1), the PTO has no statutory authority to issue an interim extension.

The Federal Circuit stated expressly that yesterday's opinion does not address any claim that Somerset may have on the underlying merits of the PTO's July 12, 2007 denial of its request for a patent term extension under Section 156(e)(1).  Presumably, Somerset is appealing that decision separately.

Merck Prevails in Patent Term Extension Case at Federal Circuit

Merck & Co. v. Hi-Tech Pharmacal, No. 06-1401 (Fed. Cir. 2007)

The U.S. Court of Appeals for the Federal Circuit held today that a patent term extension under 35 USC 156 may be applied to a patent that is subject to a terminal disclaimer under 35 USC 253, handing a victory to Merck in its battle with Hi-Tech Pharmacal over generic Trusopt (dorzolamide HCl opthalmic solution).  Hi-Tech had argued that Merck's patent on Trusopt expired in 2004 because a patent term extension on the patent was invalid.

As we reported last month, a loss for Merck in this case would have had drastic effects on pharmaceutical companies and patent owners, since the Patent Office has routinely granted patent term extensions on patents that are subject to a terminal disclaimer.  Brand-name drug companies would have lost years of patent protection on some of their best-selling drugs if the Federal Circuit had decided that a terminal disclaimer precludes a patent term extension.

Section 156 was enacted as part of the Hatch-Waxman Act in 1984 to allow restoration of part of a pharmaceutical patent's term "lost" due to lengthy FDA review of a new drug application.  Section 253, on the other hand, applies to all kinds of patent applications--not only those relating to pharmaceuticals--and allows the filing of a terminal disclaimer to overcome "obviousness-type double patenting" rejections made by the Patent Office.

In reaching its decision today, the Federal Circuit properly recognized that "the language of Section 156 is unambiguous and fulfills a purpose unrelated to and not in conflict with that of Section 253."  The court observed: (1) according to Section 156, a patent term "shall be extended" if five enumerated conditions, none of which concern terminal disclaimers, are met; (2) the legislative history is consistent with the mandatory language of the statute; and (3) Section 154 excludes patents in which a terminal disclaimer has been filed from the benefit of a term adjustment for PTO delays, but Section 156 contains no such exclusion for patents eligible for term extensions for FDA delays, which further supports the court's interpretation of Section 156.

Additionally, the court explained why Section 156 and Section 253 are compatible:

The purpose of the terminal disclaimer--to prevent extension of patent term for subject matter that would have been obvious over an earlier filed patent--remains fulfilled by virtue of the fact that the date from which any Hatch-Waxman extension is computed is the terminally disclaimed date.  At the same time, the purpose of the patent term extension--to restore some of the patent term lost due to regulatory review--is also satisfied.

Hi-Tech will now have to wait until at least April 28, 2008, when Merck's patent expires, before it can launch its generic version of Trusopt.

RELATED READING:

• Patently-O; Patent Baristas; Patent Docs
• MarketWatch.com
• Wall St. Journal (subscription)

Is a Patent that is Subject to a Terminal Disclaimer Eligible for a Patent Term Extension?

It has always been assumed the answer is "yes."  Now the Federal Circuit will answer the question directly in Merck v. Hi-Tech Pharma., which concerns Hi-Tech's ANDAs for generic versions of Merck's Trusopt and Cosopt prescription eye drops.  The case was argued in December and a decision could come at any time.

Merck owns U.S. Patent No. 4,797,413, covering dorzolamide, the active ingredient in Trusopt and Cosopt.  The '413 patent issued from a continuation-in-part application that claims priority from Merck's U.S. Patent No. 4,677,115.  During prosecution of the '413 patent, the patent examiner rejected the claims for "obviousness-type double patenting," explaining that the claims were not patentably distinct from those of the earlier issued '115 patent because they "include position isomers and adjacent homologs to the previously allowed prior art compounds which are obvious variations in view thereof."  To overcome the rejection, Merck filed a terminal disclaimer, disclaiming "the terminal part of any patent granted on [the application] which would extend beyond the expiration date of U.S. patent 4,677,115, that is, June 30, 2004."

The FDA approved Merck's NDA for Trusopt in 1994, after several years of FDA regulatory review.  Due to the lengthy review process, the FDA granted Merck a patent term extension under 35 USC 156, thereby extending the term of the '413 patent to April 28, 2008.  Section 156 was enacted as part of the Hatch-Waxman Act (it is the "Patent Term Restoration" part) in a trade between innovator and generic drug companies: innovators could obtain patent term extensions and generic drug companies could develop their drug products before patent expiration.  Under Section 156, NDA holders may choose one patent for patent term extension per approved drug.  Presumably, Merck sought an extension of the '413 patent rather than the '115 patent because its claims are stronger.

After Hi-Tech filed ANDAs for generic versions of Trusopt and Cosopt, Merck sued Hi-Tech for infringement of the '413 patent.  As its only defense, Hi-Tech asserted that the patent term extension on the '413 patent was invalid due to the terminal disclaimer that Merck voluntarily filed on the patent.  On April 25, 2006, the district court entered final judgment on the pleadings in Merck's favor and enjoined Hi-Tech from selling generic dorzolamide products until the '413 patent expires.  Hi-Tech promptly appealed to the Federal Circuit, presenting the following issue for review:

Whether a terminal disclaimer voluntarily filed to avoid double patenting, as a matter of law, precludes or disclaims the right to a patent extension under 35 USC 156 that would permit the disclaimed patent to be enforced after expiration of the earlier patent that gave rise to the disclaimer.

According to Hi-Tech, "[t]his case arises solely because the PTO regulation implementing 35 USC 156 added words to the statute which are not there."  Thus, the arguments in the appeal center on the proper statutory interpretation of Section 156.  Hi-Tech argues that the district court misinterpreted Section 156 as overturning settled law on the irrevocable nature of terminal disclaimers.  Merck argues, on the other hand, that the structure, legislative history, and "twenty years of consistent PTO interpretation of Section 156" support the district court's "plain language construction" of the statute that allowed the patent term extension on the '413 patent to stand.  Thanks to the attorneys who argued the case, links to the briefs are provided below.

A decision in favor of Hi-Tech would have far-reaching consequences.  Many of the most valuable patents owned by innovator drug companies would lose years off their terms, potentially costing billions of dollars in lost revenue.  Innovator drug companies routinely file for patent term extensions, and terminal disclaimers are quite common simply due to the nature of pharmaceutical patenting.

LINKS TO APPEAL BRIEFS:

• Hi-Tech's Opening Brief
• Merck's Opposition Brief
• Hi-Tech's Reply Brief

Bill Proposed in House to Provide Escape for Late Patent Term Extension Filings

          by David S. Harper

After a Massachusetts drug company missed--by a single day--a non-extendable deadline for filing for a patent term extension, H.R. 5120 was recently proposed in the U.S. House of Representatives to amend 35 U.S.C. 156, the statute governing patent term extensions based on regulatory review delay.  Some people are calling H.R. 5120 the "Dog Ate My Homework Act."

Under the current version of 35 U.S.C. 156, a patent applicant has 60 days after approval under the relevant regulatory review (generally FDA review and approval of new drugs) in which to submit an application to the U.S. Patent Office for patent term extension; no allowance is made for a late filing.  H.R. 5120 would amend 35 U.S.C. 156 to provide the U.S. Patent Office with discretion in accepting late applications, so long as (a) the application was filed within 5 days after expiration of the 60-day period, and (b) the delay was unintentional.

As drafted, the amendment would go into effect on the day of its enactment, and would apply not only to applications for patent term extension pending on or filed after the date of enactment, but also to those applications which are "the subject of a request for reconsideration of a denial of a patent term extension," such as the Medicine Company's, or which have "been denied a patent term extension . . . in which the period for seeking reconsideration of such denial has not yet expired."

The 2005 Medicines Company annual report indicates that the company continues to explore alternatives to extend the term of the patent.  If enacted as proposed, H.R. 5120 might be such an alternative.

The Medicines Company, based in Massachusetts, licensed a patent owned by Biogen covering the drug Angiomax and its use in preventing blood clots from forming during angioplasty.  The Medicines Company application for a patent term extension was filed on the 61st day following FDA approval of Angiomax; as a result, the U.S. PTO denied the request for patent term extension.  The Medicines Company has filed a request for reconsideration of the application for patent term extension.  A copy of the file history of the relevant patent, including the application for patent term extension, decision on the petition, and request for reconsideration, can be found here.

The House bill was sponsored by Representative Jenkins (TN), and co-sponsored by Representatives Andrews (NJ), Delahunt (MA), Frank (MA), Hyde (IL), Meehan (MA), Sessions (TX), Boucher (VA), Duncan (TN), Gallegly (CA), Jones (OH), and Rothman (NJ).  The bill has been referred to the House Committee on the Judiciary.

RELATED READING:

• AP story on H.R. 5120