Orange Book Blog

OBB News Briefs

• Fosamax, Merck's blockbuster osteoporosis drug, went generic on Wednesday.  The In Vivo Blog posted an interesting report on the unusual steps Merck took to promote Fosamax in the last month, before its patents expired.
• The WSJ Health Blog posted an interesting story this week on contributions from the pharmaceutical industry to the presidential candidates.  Apparently drug company employees are not fans of John McCain.
• FDA Law Blog reported Tuesday that the Bush Administration announced, as part of its FY2009 budget proposal, that it will seek new statutory authority to allow FDA to approve follow-on biologics in abbreviated applications.  In response to the budget announcement, Insmed, Inc., a developer of follow-on biologics and biopharmaceuticals, announced that it is launching a "national awareness" campaign on follow-on biologics.
• FDA Law Blog reported last week that the district court in D.C. dismissed Nu-Pharm's lawsuit against the FDA, in which Nu-Pharm sought to force FDA to grant final approval to its ANDA for a generic version of Abbott Labs' Depakote.  Nu-Pharm, a former subsidiary of Apotex, has appealed the decision to the D.C. Court of Appeals.
• On Feb. 1, FDA posted a new comprehensive list of FDA Guidance Documents, which could come in handy for FDA-regulated companies.
• Wyeth recently launched of an authorized generic version of Protonix, as Pharmalot and the WSJ Health Blog reported.  The WSJ Health Blog also reported on speculation about why Teva declined to ship any additional generic Protonix.

Pharma News Briefs

• The Supreme Court this morning denied Pfizer's cert petition in the Norvasc case (AP story).  Although the Federal Circuit's March 22 decision is controversial, the denial of Pfizer's cert petition is not surprising, given that the Court had previously denied Pfizer's motions for an emergency stay and for an expedited appeal.
• Late last Friday the Court of Appeals for the Federal Circuit denied Novartis's emergency motion to enjoin Teva from selling generic Famvir (Teva press release; Globes article).  Three weeks ago, the Federal Circuit temporarily enjoined Teva, apparently costing Teva three weeks of its 180-day exclusivity.
• President Bush signed the FDA Amendments Act of 2007 into law last Thursday (AP story).  FDA put out this press release.  PhRMA released this statement.
• Also Thursday, the Federal Circuit denied Alphapharm's petition for rehearing en banc of Takeda v. Alphapharm, in which the court previously upheld Takeda's patent on Actos.  No opinion was issued.
• The Federal Trade Commission announced in a press release Thursday that it is challenging Mylan's proposed acquisition of E. Merck oHG, which is Merck KgAA's generic subsidiary.  See also this Reuters article.
• FDA Law Blog had a very interesting post last Wednesday on FDA's recent letter requesting comment on certain 180-day exclusivity forfeiture and Orange Book patent delisting issues.

Pharma News Briefs

• FDA Law Blog has a great post about a very interesting district court decision concerning Apotex's attempt to market generic Prilosec before AstraZeneca's pediatric exclusivity expires.
• Congress passed FDA reform legislation this week, albeit without provisions for biosimilars.  (AP article; FDA Law Blog; PhRMA release).
• In the Pipeline is a great blog by a medicinal chemist.  This week, it has a post about the importance of patents to drug development.
• Globes reported that according to Merrill Lynch analyst Gregg Gilbert, Wyeth and Teva may settle the Protonix litigation.
• Pharmalot posted this week on the rising cost of biotech drugs to big pharma.
• Spicy IP has an interesting post this week on Indian pharmaceutical lifecycle management.

Pharma News Briefs

• The Federal Circuit reissued its July 11 opinion in Daiichi Sankyo v. Apotex as a precedential opinion, one day after denying Daiichi's petition for rehearing.  According to Hal Wegner, a major reason for making the decision precedential was Prof. Joseph Scott Miller's Rule 47.6(c) filing.
• Biosimilars legislation is "off the table" for now.  The FDA bill is moving forward without it.  (Bloomberg; Pharmalot).
• Novartis is set to launch its biosimilar Epoetin in Europe.  (msnbc.com).
• Cubist Pharmaceuticals has asked the FDA to delist a patent on its lead product, Cubicin, from the Orange Book.  (The Street.com).
• FDA issued final guidance on commercially distributed Analyte Specific Reagents, such as antibodies and nucleic acids.  (FDA Law Blog).
• Dr. Reddy's and Teva settled their patent dispute over generic Zoloft.  Teva had alleged that Dr. Reddy's infringed its sertraline HCl polymorph patents.  (Patent Docs; TMCnet.com).
• Imclone and Repligen/MIT settled their patent dispute over Erbitux.  (Patent Prospector).
• Ranbaxy vs. Pfizer worldwide Lipitor patent litigation scorecard: mixed results.  (MarketWatch.com).
• Feroz Ali Khader has written a new book on Indian patent law, particularly as it relates to pharmaceuticals.  (Generic Pharmaceuticals & IP blog).
• Mr. Kapil Sibal, Honorable Minister for Science and Technology in India, will be speaking tomorrow, September 17 at 4 pm at the George Washington University Law School.  (Flyer; Program).

Pharma News Briefs

• FDA Law Blog had a post Thursday about "The Dog Ate My Homework Act," which would give a reprieve to companies that miss the deadline for filing a patent term extension request.
• Pharmalot had this post Wednesday, reporting that Congress has delayed the FDA bill until September.
• Patently-O reported Wednesday on the Federal Circuit's decision on Washington, D.C.'s drug price law.  PhRMA made a press release on the decision.  The Washington Post published this article on the case.
• Tuesday, Wyeth announced a deal with Teva and Sun concerning generic Protonix.  Today, Teva announced that FDA approved its ANDA for Protonix.
• Investor's Business Daily had an interesting article last week, "RNAi Stirs Excitement in Big Pharma."
• The Patent Prospector had a neat post last week, "Dealing with KSR."

Pharma News Briefs

• FDA Law Blog reported Monday that the proposed follow-on biologics legislation is in serious jeopardy in Congress.  Pharmalot had a similar report last Friday.
• Meanwhile, European regulators recently granted approval to three new biosimilar drugs, as Patent Docs reports today.
• The San Francisco Chronicle recently published a nice article summarizing the debate over generic biotech drugs.
• The Business Standard recently reported on incentives for Indian drug companies to develop generic biotech drugs.
• Peter Zura's 271 blog had this interesting post Wednesday on controversy caused by reaction of the Indian generic pharmaceutical industry to patent reform legislation in Congress.
• MarketWatch had this article last weekend examining the leveling off of pharmaceutical prices in America.
• Par and J&J announced they have settled their generic Ultracet patent litigation: MarketWatch; Patent Docs.
• IMPAX announced a district court ruling relating to generic Rilutek: PharmaLive; UPI.

Pharma News Briefs

• The House of Representatives passed an omnibus FDA bill on Wednesday.  The Senate passed its own FDA bill in May.  Differences between the two bills will be hammered out in conference committee, where follow-on biologics provisions may be tacked on.  See coverage at: FDA Law Blog; Pharmalot;  PhRMA press release; WSJ Health Blog.
• Business Standard magazine had this story Monday on reaction by Indian generic drug companies to authorized generics.
• FDA Law Blog had an interesting post last week on a recent request for information on FDA's policy for Orange Book listings of patents that cover drug delivery systems but that do not recite an active ingredient or drug formulation.
• More generic Norvasc approvals: Lupin; Ranbaxy; Roxane.

Follow-on Biologics Bill Approved by Senate Committee, Moves On to Full Senate

MarketWatch.com is reporting this afternoon that the Senate Committee on Health, Education, Labor and Pensions has voted in favor of the Biologics Price Competition and Innovation Act of 2007.  It is unclear whether the Committee amended the bill before voting on it.  The bill will now move to the Senate floor.

RELATED READING:

• Bloomberg
• Pharmalot

Senate Committee To Vote Wednesday on Bipartisan Follow-on Biologics Bill

After several previous bills went nowhere, lawmakers may have finally reached a viable compromise on follow-on biologics legislation.  Last Friday, a bipartisan group of Senators led by Ted Kennedy (D-MA) and Orrin Hatch (R-UT) announced an agreement on a new bill that would establish an abbreviated pathway for FDA approval of biologic drugs.  The Senate Committee on Health, Education, Labor, and Pensions, chaired by Sen. Kennedy, is expected to mark up the bill and vote on an amended version of it in a session tomorrow.

The draft bill (S.1693) would amend the Public Health Service Act "to establish a pathway for the licensure of biosimilar biological products, to promote innovation in the life sciences, and for other purposes."  It is entitled the "Biologics Price Competition and Innovation Act of 2007."

The bill outlines three requirements to gain approval of a follow-on biologic: "(1) analytical studies that demonstrate that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components; (2) animal studies; and (3) a clinical study or studies (including the assessment of immunogenicity and pharmacokinetics or pharmacodynamics) that are sufficient to demonstrate safety, purity, and potency . . . and designed to avoid needlessly duplicative or unethical clinical testing."  The bill grants FDA discretion to waive one or more of these requirements if it determines such requirement "is unnecessary in an application submitted under this subsection."

The bill provides for substitutability of a biosimilar for a brand product at the pharmacy: "An application submitted under this subsection may include information demonstrating that the biological product is interchangeable with the reference product."

The bill further provides for market exclusivity for innovator products: 12 years from the date of approval for innovator products and one year (after first commercial marketing) to 18 or 42 months for "first interchangeable biological products."

The bill would also establish a complex process for providing notice of a biosimilar application, exchanging patent information, and resolving patent issues through agreement or litigation.  For instance, within 20 days after the FDA accepts a biosimilar application, the applicant "shall provide to the reference product sponsor a copy of the application . . . and such other information that describes the process or processes used to manufacture the biological product."  Within 60 days of receiving that information, the reference product sponsor shall provide to the biosimilar applicant "a list of patents for which the reference product sponsor believes a claim of patent infringement could reasonably be asserted."  Then, within 60 days after receiving that list, the biosimilar applicant shall provide "a detailed statement that describes, on a claim by claim basis," the factual and legal basis of its opinion of invalidity, unenforceability, or noninfringement.  Within 60 days of receiving that statement, the reference product sponsor shall provide the factual and legal basis of its opinion that its patents will be infringed and a response to the invalidity or unenforceability statement.  Provisions relating to negotiations and litigation are even more complicated.

Democrats have made passage of a follow-on biologics bill a priority for this Congress.  Sen. Kennedy tried, but failed, to attach an earlier bill to the FDA Revitalization Act.  The major pharmaceutical trade associations--BIO, PhRMA and GPhA--have not yet weighed in publicly on the new bill, but are expected to do so soon.

RELATED READING:

• Senate press release (includes bill summary)
• Boston Herald editorial
• Biologic Drug Report article
• Biopharma Reporter article
• Bloomberg article
• kaisernetwork.org Policy Report
• UPI article
• Wall St. Journal article (subscription)

Pharma News Briefs

• Pharmalot had this post Friday about a new bipartisan follow-on biologics bill in the Senate.
• MarketWatch reported Friday that European regulators have moved a step closer to approving Sandoz's follow-on version of J&J's blockbuster Eprex, sold in the U.S. as Procrit.
• On Thursday, a House committee marked up the PDUFA reauthorization legislation (Pharmalot).  PhRMA reacted positively in this press release.
• FDA Law Blog had this post Tuesday reporting that the Senate-passed version of FDARA would open the door to 5-year New Chemical Entity exclusivity for enantiomers of previously-approved racemic drug compounds.

Pharma News Briefs

• SCOTUSblog reported on Wednesday that the Supreme Court has denied Pfizer's emergency application for relief from the Federal Circuit's ruling in the Norvasc case.  TheStreet.com also has an article on the Supreme Court's decision.
• On Tuesday, the Federal Circuit granted Mylan's motion for summary reversal of the district court decision that had found Pfizer's Norvasc patent valid and infringed by Mylan.  The Fed. Cir. also reversed and vacated a separate district court decision finding the Norvasc patent valid and infringed by Synthon.  Both decisions came without opinion.
• FDA Law Blog reports today that a provision of the FDA Revitalization Act will reform the citizen petition process.
• The Washington Post on Monday reported on continued wrangling between the DOJ and FTC on the legality of reverse payment settlements, such as the one in Joblove.
• Via SCOTUSblog, here is petitioner's supplemental brief in Joblove, responding to the Solicitor General's recommendation that the Court decline to hear the case.
• Barr Labs announced earlier this week that Barr and Lilly agreed to dismiss their litigation over Prozac Weekly.
• Kaisernetwork.org reports that the markup session for the Waxman-Schumer follow-on biologics bill has been delayed to June 20.  Supporters of the bill still hope to attach it to the FDA Revitalization Act and pass it into law this year.

Does FDA Need a Statutory Path to Approve Follow-on Biologics?

        Guest Post by Prof. Christopher M. Holman, UMKC School of Law

Much of the current discussion surrounding the proposed follow-on biologics bills assumes that a "statutory path" is necessary before FDA can implement an abbreviated biologics license application (BLA) process for biotechnology-derived therapeutic proteins.  In fact, FDA probably already has the authority to create such a process by regulation, but so far has declined to do so.

The argument that FDA requires a statutory path is based largely on the fact that the PHSA (the statute governing the regulation of most biotechnology-derived therapeutic proteins) does not explicitly provide an abbreviated BLA approval processes analogous to the FDCA's 505(b)(2) "paper NDA" and 505(j) abbreviated NDA (ANDA).  But the FDCA explicitly requires clinical trials for the approval of an NDA, so FDA arguably needs explicit statutory authorization to implement an abbreviated process that dispenses with the requirement of clinical trials.  As noted in the House Report published in connection with the passage of Hatch-Waxman, the only statutory difference between a NDA and an ANDA is the requirement of human clinical trials.

The PHSA, on the other hand, does not require clinical trials for approval of a BLA, and hence no explicit statutory path should be required for biologics.  FDA's regulations require clinical trials to show safety and efficacy of biologics approved under the BLA process, but these are regulations dating back to the mid-1970s (well before the approval of any biotechnology-derived proteins), and could be updated by FDA to dispense with such a requirement in some instances, assuming the science would support such a revision, without requiring Congress to amend the PHSA.

In 1996, a district court specifically found that FDA has the statutory authority under the PHSA to approve a comparable biologic without requiring new clinical trials.  Berlex Labs v. FDA, 942 F.Supp. 19 (D.D.C. 1996).  Although that case dealt with a change in manufacturing process implemented by the original manufacturer, with respect to the question of statutory authority the court's rationale should apply equally to a comparable protein produced by a different manufacturer.

During recent Congressional testimony, FDA's representative Dr. Woodcock was questioned on the supposed need for a statutory path.  She walked a close line, at one point indicating that a statutory path was required, but on closer questioning conceding that the PHSA does not require clinical trials, and that the only statutory requirement is that the FDA ensure the "purity, potency and safety" of biologics approved under the Act.  Members of Congress also queried whether the rationale of Berlex Labs v. FDA should not also apply to biologics, but did not receive a direct answer.  Earlier, in January 2007, Reps. Dingell and Stupak sent a letter to FDA questioning whether a statutory path was really necessary, and asking for a response from FDA no later than February.  To my knowledge, FDA has not responded.

Pharma News Briefs

• AP published this report on yesterday's House hearing on "reverse payment" settlements.
• AP also recently published this article on follow-on biologics legislation, entitled "Time is Running Out for Generic Biotech."
• Antitrust Review recently posted an update on the FTC's authorized generics study.
• FDA Law Blog has a new post today on the most recent developments in the generic Norvasc litigation.
• FDA Law Blog also posted last week on a Medicis challenge to FDA's policy regarding exclusivity for "old" antibiotics.
• Patent Docs has two interesting recent posts--here and here--on applying TRIPS to patented drugs in developing countries.
• Patently-O has a new post today by Cal Crary, a pharma litigation analyst: "Impact of KSR v. Teleflex on the Pharmaceutical Industry."
• PhRMA put out this press release on the U.S. Trade Representative's annual report on IP rights; see also this related post on Pharmalot.
• Pharmalot also recently had this interesting post on India's generic drug companies.

House Energy and Commerce Committee to Hold Hearings on Follow-on Biologics and Reverse Payments

On Wednesday, May 2nd, two subcommittees of the House Committee on Energy and Commerce will hold hearings of importance to pharmaceutical companies: first, on legislation to establish an abbreviated pathway for FDA approval of follow-on biologics; second, on a pending bill to ban "reverse payment" settlements of Hatch-Waxman litigation.

At 10 a.m. ET, the Subcommittee on Health will hold a hearing entitled "Assessing the Impact of a Safe and Equitable Biosimilar Policy in the United States."  Persons scheduled to appear include Dr. Janet Woodcock, Deputy Commissioner and Chief Medical Officer of the FDA, as well as executives from Insmed, Genentech, GPhA, and others.

At 3 p.m. ET, the Subcommittee on Commerce, Trade, and Consumer Protection will hold a hearing entitled "Protecting Consumer Access to Generic Drugs Act of 2007."  Persons scheduled to appear include Jon Leibowitz, Commissioner of the FTC, as well as Prof. Scott Hemphill, law professor at Columbia, Dr. Barry Sherman, CEO of Apotex, and others.

RELATED READING:

• Pharmalot interview with Rep. Jay Inslee (D-WA) on his follow-on biologics bill
• March 25 post on House Oversight Committee hearing on follow-on biologics
• March 8 post on Senate Health Committee hearing on follow-on biologics
• February 15 post on Senate Judiciary Committee passage of reverse payments bill

UPDATES:

• An archived video, the prepared testimony, and a transcript of the follow-on biologics hearing are available here.
• The video, testimony, and transcript of the reverse payments hearing are here.

House Oversight Committee to Hold Hearing on Follow-on Biologics

On March 8, the Senate held a hearing on follow-on biologics.  Now it's the House's turn.  Tomorrow morning, the House Oversight Committee, chaired by Rep. Henry A. Waxman (D-CA), will hold a hearing entitled "Safe and Affordable Biotech Drugs--The Need for a Generic Pathway."

Rep. Waxman is the sponsor of the "Access to Life-Saving Medicine Act" (H.R. 1038) in the House.  A nearly identical bill (S. 623) has been introduced in the Senate.  If passed, the bill would establish an abbreviated pathway for FDA approval of follow-on biologics.  Democrats in both chambers have indicated that passage of the bill is a top priority for the new Congress.

Witnesses called to testify tomorrow include Dr. Janet Woodcock, Deputy FDA Commissioner, representatives from the pharmaceutical industry and third-party payors, and consumer advocates.

UPDATES:

• The hearing web page includes a video recording of the hearing and links to all of the prepared testimony.
• More at On Pharma
• March 26 AP article on the hearing
• March 26 Bloomberg report on the hearing
• March 26 BIO press release

Senate Committee on Health Hears Testimony on Follow-on Biologics

The U.S. Senate Committee on Health, Education, Labor, & Pensions held a hearing this morning on follow-on biologics.  A complete video recording is available on the hearing web-page.  The written testimony of each witness is available on the same page (click on the red icon appearing after each person's name).

In opening remarks, Sen. Kennedy (D-MA), the Chairman of the Committee, noted that he recently sat down with leaders of several biotechnology companies based in his home state of Massachusetts.  He expressed his belief that any regulatory scheme for follow-on biologics must be guided by three principles: (1) it must be led by the science; (2) protecting patients' safety is essential; and (3) innovation must be valued and promoted.  Sen. Enzi (R-WY), the Republican leader on the Committee, echoed Sen. Kennedy's remarks.  He emphasized, "we must not rush a solution through Congress," or else "we risk endangering lives."  Sen. Clinton (D-NY), a co-sponsor of the Access to Life-Saving Medicine Act, which would establish an abbreviated pathway for the approval of follow-on biologics, sensed that all sides acknowledge that science has advanced far enough to make follow-on biologics a reality.  She said, "we are debating how, not if, and it will be up to this committee when."

Sen. Schumer (D-NY), also a co-sponsor of the Access to Life-Saving Medicine Act, was the first witness to speak.  He began by announcing that "the science is there now."  Sen. Schumer made a few points regarding the European Union's framework for regulating follow-on biologics (or "biosimilars," as they're called in Europe).  He said the EU has a highly regulated system that's "arguably burdensome."  He noted that Europe has approved only two biosimilars in the four years since the EU's regulatory framework has been in place.  With regard to patent rights, Sen. Schumer said that the Hatch-Waxman Act struck a balance, but in his view created an imbalance for biologics since biologics can receive five years of New Chemical Entity exclusivity and seven years of Orphan Drug Exclusivity, but are free of competition from generics.

Following Sen. Schumer, the Committee heard from a panel of four experts:

• Sid Banwart, VP of Human Services for Caterpillar, noted that prescription drugs account for 25% of Caterpillar's health care spending for its 95,000 employees worldwide.  He expressed concern that biologic drugs are the "single fastest growing category of health costs" for Caterpillar, having increased 45% since 2004, and stated that "the trend is not sustainable."
• Dr. Jay Siegel, President of Biotechnology R&D at Johnson & Johnson and a 20-year veteran of FDA's Center for Biologics Evaluation and Research, provided the innovator/biotechnology company perspective.  In his view, pre-marketing clinical trials of biologics in humans should always be required.  Moreover, Dr. Siegel believes follow-on biologics should not be substitutable with innovator biologics because the two can never be identical.  Of course, substitution at the pharmacy level is the holy grail for the generics industry, since that's where the real money is.
• Nicholas Rossignol, Administrator of the European Commission Pharmaceuticals Unit, spoke next.  He emphasized that there is a range of complexity in biologics (e.g., a vaccine is much more complex than a small protein such as insulin), which must be considered in any regulatory scheme.  He explained that substitutability is regulated at the individual country level in Europe, and some European nations have allowed substitution of certain follow-on biologics.
• Finally, Dr. Ajaz Hussain spoke on behalf of Sandoz and provided the generic industry's perspective.  Dr. Hussain expressed his belief that substitutability is an important public health goal and that follow-on biologics can be made to be substitutable.

In the question and answer session that followed, all four panelists seemed to agree that the FDA currently has the expertise and is equipped to properly regulate follow-on biologics.  Moreover, the four panelists agreed that the primary goal is ensuring patient safety.  The panelists (and certain Senators on the Committee) disagreed about whether the Access to Life-Saving Medicine Act, as currently written, adequately protects patient safety.  Sen. Hatch (R-UT) stated clearly that he cannot support the current bill due to safety concerns.  Sen. Clinton hinted at possible amendments to the Act that might represent a compromise.

RELATED READING:

• BIO press release
• Bloomberg article
• Boston Globe article
• Johnson & Johnson press release
• PCMA press release
• Reuters article

Senate Committee on Health to Hold Hearing on Follow-on Biologics

The U.S. Senate Committee on Health, Education, Labor, & Pensions, chaired by Sen. Edward M. Kennedy (D-MA), is planning to hold a full committee hearing on follow-on biologics this Thursday, March 8, at 10 a.m. eastern time.  Those expected to testify include Sen. Charles Schumer (D-NY), co-sponsor of the "Access to Life-Saving Medicine Act," as well as pharmaceutical industry executives.  Live audio and video of the hearing will be available on this page of the committee's website. 

Last month, lawmakers in the House and Senate re-introduced legislation that would establish an abbreviated pathway for FDA approval of follow-on biologics (sometimes also referred to as "biogenerics").  Since then, reports have indicated that the legislation may be attached to the Prescription Drug User Fee Act, which must be renewed before October 1 of this year.  Members of both parties have recently indicated that passage of follow-on biologics legislation is a top priority for the current Congress.

Sales of biologic drugs reached $56 billion in 2005, accounting for 20% of total pharmaceutical sales.  Understandably, generic drug makers are anxious to enter this market.  In addition, with the annual cost of some biologic drugs surpassing $100,000, state Medicare programs and health insurance companies would like to see generic versions of biologic drugs made available as soon as possible.  On the other hand, biologics are far more complex than conventional (i.e., small molecule) drugs.  Accordingly, innovator drug companies want to ensure that appropriate safety and efficacy studies are conducted before any follow-on biologics are approved.

RELATED READING:

• BIO web-page on follow-on biologics
• GPhA issue page on follow-on biologics

UPDATES:

• Senate hearing Notice, including witness list
• 7-Mar-07 Boston Globe article on the Senate hearing

Bill Aimed at Prohibiting Reverse Payment Settlements Clears Senate Judiciary Committee

The Senate Judiciary Committee passed the "Preserve Access to Affordable Generics Act" (S. 316) today by unanimous consent.  If enacted, the bill would prohibit "reverse payment" settlements of Hatch-Waxman litigation, in which an innovator drug company pays a generic drug company to delay marketing its generic drug product.  Specifically, the bill would amend the Clayton Act by adding a new Section 28, reading in part:

(a) It shall be unlawful under this Act for any person, in connection with the sale of a drug product, to directly or indirectly be a party to any agreement resolving or settling a patent infringement claim in which--

(1) an ANDA filer receives anything of value; and

(2) the ANDA filer agrees not to research, develop, manufacture, market, or sell the ANDA product for any period of time.

(b) Nothing in this section shall prohibit a resolution or settlement of a patent infringement claim in which the value paid by the NDA holder to the ANDA filer as a part of the resolution or settlement of the patent infringement claim includes no more than the right to market the ANDA product prior to the expiration of the patent that is the basis for the patent infringement claim.

The bill is thus a legislative solution to reverse payment settlements, which have been endorsed by federal courts in cases such as FTC v. Schering and In re: Tamoxifen Citrate Antitrust Litigation.  The FTC has been a vocal critic of such decisions.

RELATED READING:

• Sen. Kohl's press release on committee passage of the bill
• Sen. Leahy's press release on committee passage of the bill

Follow-on Biologics Bill Reintroduced in Congress

Most pharmaceuticals made using biotechnology are approved through a Biologic License Application (BLA) rather than a New Drug Application (NDA).  The FDA requires essentially the same type of evidence for both biologics and conventional (i.e., small molecule) drugs; namely, results of adequate and well-controlled clinical trials demonstrating safety and effectiveness.  However, currently there is no abbreviated pathway for the approval of generic, or "follow-on", biologics like the Abbreviated New Drug Application (ANDA) pathway for the approval of conventional drugs.

The "Access to Life-Saving Medicine Act," reintroduced by Rep. Waxman, Sen. Schumer, and other lawmakers yesterday in the House and Senate, would establish an abbreviated approval process for follow-on biologics.  According to an AP story out today, a new report by Express Scripts, a pharmacy benefits manager, finds that generic biotech drugs could save patients and insurers $71 billion over 10 years.  This report from the Pharmaceutical Care Management Association, an industry trade group for pharmacy benefits managers, says Medicare Part B would save $14 billion dollars over that time.  Pharmacy benefits managers earn big profits from generic drugs.

Rep. Waxman's website contains a great deal of information on this issue, including a background on biologics, a summary of the proposed Act, and the full text of the Act.  Additionally, the website contains letters of support from the generic drug industry, consumer groups, and insurance companies.  Another perspective is offered by the Biotechnology Industry Organization, which represents innovator pharmaceutical and biotechnology companies.  BIO's website has a section devoted to the issue of follow-on biologics, and contains information on developments in Europe as well as the United States.

UPDATE:  22-Feb-07 BIO response to Express Scripts and PCMA studies

Senators Reintroduce Bill to Ban Authorized Generics

Senator Jay Rockefeller (D-WV) has introduced S. 438, "The Fair Prescription Drug Act of 2007," which would ban the sale of authorized generic drugs during an ANDA applicant's 180-day exclusivity period.  The bill is cosponsored by Senators Kohl (D-WI), Leahy, (D-VT), and Schumer (D-NY).  The same bill was proposed last year as S. 3695.  Senator Kohl expressed optimism that the bill would have better prospects this time around--and it just might, given that the Democrats now control Congress.

RELATED READING:

• Jan. 31, 2007 UPI article
• Jan. 31, 2007 Mylan Labs press release
• July 24, 2006 OBB post on last year's bill

Sens. Kohl and Leahy Introduce Bill to Prevent Abuse of Citizen Petition Process

Continuing their collaboration on new laws relating to pharmaceuticals, Senators Herbert Kohl (D-WI) and Patrick Leahy (D-VT) recently introduced legislation to stop perceived abuses of the FDA's citizen petition procedure that result in delaying approval of generic drugs.  The bill is entitled the Citizen Petition Fairness & Accuracy Act of 2006.

According to Sen. Leahy's press release announcing the new bill:

Of the 21 citizen petitions reviewed and ruled upon by the FDA since 2003, 20 have been found to be without merit.  Of these, ten were identified as “eleventh hour petitions” -- those filed less than 6 months prior to the estimated entry date of the generic drug – and none were found to have merit.

If enacted, the new law would allow the Dept. of Health and Human Services (HHS) to sanction companies "who file citizen petitions simply to keep competition off the market."  Possible sanctions include a fine, a suspension or revocation of the right to file future citizen petitions, and a dismissal of the petition.  The bill also requires HHS to review citizen petitions within six months of filing.

Click here to read the complete text of the proposed bill.

NOTE:  thanks to Kurt Karst for alerting me to this proposal.

Rep. Waxman and Sens. Schumer and Clinton Introduce Biogenerics Bill

Rep. Henry Waxman (D-CA), Sen. Charles Schumer (D-NY), and Sen. Hillary Rodham Clinton (D-NY) introduced the "Access to Life-Saving Medicines Act" last Friday.  If enacted, the legislation would establish an abbreviated application process for biological products.

According to the proposed bill, a generic biological product is "comparable," and therefore approvable in an abbreviated application "if there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity and potency of the product, based on non-clinical studies and clinical studies, as necessary."

This page on Rep. Waxman's website includes a press release, background on biologics, a quick summary, a bill summary, the text of the bill, and letters of support.

RELATED READING:

• 20 Sep. 2006 Orange Book Blog post

NOTE:  thanks to Kurt Karst for sending me the link to this material.

Senators Introduce Bill to Ban Reverse Payment Settlements of Hatch-Waxman Cases

          by David S. Harper

In response to the Supreme Court's denial of certiorari in FTC v Schering earlier this week, four senators introduced Senate bill S3582 yesterday, which seeks to prohibit brand name drug companies from entering into "reverse payment" settlements with generic drug companies.  In FTC v. Schering, the FTC had petitioned the Court to decide whether a reverse payment settlement from Schering to generic drug makers was in violation of antitrust laws.  Denial of certiorari by the Supreme Court left standing an Eleventh Circuit decision holding that the settlement did not violate antitrust laws.

S3582 was introduced by Senator Kohl (D-WI); co-sponsors were Senators Leahy (D-VT), Grassley (R-IA), and Schumer (D-NY).  In Sen. Kohl's press release announcing introduction of the bill, its sponsors decried the effect that reverse payment settlement agreements have on market entry of lower-cost generic drugs, asserting that such settlement agreements undermine true competition, and thus should not be allowed.

The current version of S3582 would amend Section 5 of the Federal Trade Commission Act (15 U.S.C. 45) by adding a new sub-section making it an unfair method of competition for "a person, in connection with the sale of a drug product, to directly or indirectly be a party to any agreement resolving or settling a 'patent infringement claim' in which (a) an ANDA filer receives anything of value; and (B) the ANDA filer agrees not to research, develop, manufacture, market, or sell the ANDA product for any period of time."

The proposed bill would exclude from its reach any agreement in which the value paid to an ANDA filer by the NDA holder "includes no more than the right to market the ANDA product prior to expiration of the patent that is the basis for the patent infringement claim." The bill defines "patent infringement claim" to be "any allegation [of possible patent infringement] made to an ANDA filer, whether or not included in a complaint filed with a court of law."  The statute thus seeks to reach beyond reverse payment agreements resolving patent infringement litigation, to include pre-litigation settlement agreements as well.

S3582 has been referred to the Committee on Commerce, Science, and Transportation.

NOTE:  Thanks to a Kohl staffer for providing an advance copy of the bill.

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

Prominent Senator Proposes Compulsory Licensing of Patented Drugs

            By David S. Harper

Vermont Senator Patrick Leahy, co-chairman of the Intellectual Property Subcommittee of the Senate Judiciary Committee, introduced a bill last week entitled "Life-Saving Medicines Export Act of 2006."  If enacted, the bill would provide for compulsory licensing of patented medicines (including vaccines and diagnostic tests) in the United States.  According to a statement from Sen. Leahy's office, the bill "allows U.S. companies to make low-cost generic versions of patented medicines for export to impoverished nations that face public health crises but cannot produce those life-saving medicines for themselves."

Sen. Leahy's office also released a summary of the bill providing some details of the proposal.  Under the bill, the Director of the U.S. Patent and Trademark Office (USPTO) would be required to issue a compulsory license to U.S. generic drug companies to make and export patented medicines under several conditions, including:

• the generic company must have made efforts to license directly from the patent holder;
• the compulsory license cannot exceed seven years, although it can be extended once;
• re-export of any drugs is prohibited;
• the generic company must pay a royalty to the patent holder, not to exceed 4% of the commercial value of the exported medicine; the royalty rate will be determined  by the Director of the USPTO.

The summary posted on Sen. Leahy’s web site provides no information about reporting requirements to be imposed on the generic drug companies that obtain compulsory licenses.

UPDATE:

• The full text of the bill is available here