Patent Baristas

Novartis AG’s generics unit Sandoz said it has filed a lawsuit against the US Food and Drug Administration, seeking a ruling on its pending new drug application for the human growth hormone Omnitrope.

Under both the Federal Food Drug and Cosmetic Act and the Food Prescription Drug User Fee Act, the FDA is required to either approve or reject new drug applications.

Sandoz filed its application for Omnitrope in July 2003. On Sept 2 2004, Sandoz announced that FDA had notified the company that the agency was unable to reach a decision on whether to approve the company’s application for Omnitrope. According to the FDA letter issued to Sandoz, the agency has completed its review of Omnitrope and did not identify any deficiencies in the application. However, the agency stated it had been unable to reach a final decision on the application due to uncertainty regarding scientific and legal issues. No action on the application has been taken since then.

Despite being available outside of western markets, no biogenerics (or follow-on proteins) have yet been approved in the US or European pharmaceutical market. It is argued that the 505(b)(2) provision of the Hatch-Waxman Act (the Hatch-Waxman amendments of the Federal Food, Drug and Cosmetic Act) lays out an abbreviated approval pathway (ANDA) for generic versions of small molecule drugs) provides a route for the FDA to approve a biological therapy that is different from the originator product, yet relies on data filed by the innovator as part of the original NDA.

The reason for the lack of a regulatory pathway for approval of biogenerics lies in the complexity of biological products. Biologics are large, complex, heterogeneous molecules, for which the manufacturing process can be a determinant of the end product. Demonstrating that its product was as safe and effective as the originator’s would be a difficult task, since establishing that immunogenicity had not been altered, and that any undetected differences in the product would not impact safety and efficacy, would be problematic without conducting clinical trials.

However, the large market potential makes biogenerics an attractive prospect for companies. Biogeneric companies need an abbreviated approval pathway to avoid undertaking the same large scale clinical development process as the originator companies, and thus allow them to market their product at a discount to the brand while maintaining a healthy profit margin.

But, even if biogenerics are approved, don’t go spending all your projected savings just yet. The high barriers to market entry will necessitate a smaller price differential between brand and generic products than that seen in regular generics, and initial physician and patient reluctance to take up biogenerics may limit the impact of competition on originator companies.

In a soon-to-be-published decree, raised by ministers after rumors of a PepsiCo Inc. bid for French food company Danone SA, the French government will gain a veto over takeovers in 10 industries deemed “sensitive to national security.”

Sectors on the list include some that most countries retain control, such as arms manufacturing and encryption but it also covers companies with activities in biotechnology, data security, casinos and antidote production — fueling concern that it could lead to a broader kind of protectionism. French Prime Minister Dominique de Villepin, in fact, coined the term “economic patriotism” for the reason for these moves and asked that pension funds, banks, and insurers direct their investments toward his list of “strategic” industries.

EU Internal Market Commissioner Charlie McCreevy told an economic forum in Italy he would “vigorously pursue” breaches of EU law resulting from attempts to thwart foreign takeovers. France’s conservative government, however, is getting criticism even at home as French companies warned the government away from protectionist temptations, likening some of the recent rhetoric to the massive concrete border fortifications that failed to stop Germany’s World War II invasion.

The Finance Ministry said the decree will merely bring ”more precision” to the current law — which allows the state to block investments in any companies deemed sensitive to “public order, public safety or national defense interests.” Yes, we wouldn’t want yogurt falling into the wrong hands.

According to a government official, the draft legislation is not yet finalized and the veto would not apply to bids for entire pharmaceutical companies, for example, but to divisions making antidotes useful against bioterrorist attacks. I’m not quite sure how that would work in real life since companies are not always so neatly organized in discreet packets.

Last year, the government cited Aventis’ “strategic” vaccine operations as it fended off a planned offer from Switzerland’s Novartis AG and instead steering Aventis into an all-French merger with Sanofi-Synthelabo, forming Sanofi-Aventis SA. Novartis cited government intervention in its decision not to bid.

We’ll keep an eye on the progress on this initiative and our safety from Lactobacillus bulgaricus and Streptococcus thermophilus cultures everywhere. More available here.

Akzo Nobel’s human healthcare business, Organon, has entered into a non-binding letter of intent with Cincinnati’s Duramed Pharmaceuticals, Inc., a subsidiary of Barr Pharmaceuticals, Inc., to settle the pending patent litigation concerning a generic version of Organon’s Mircette® oral contraceptive.

Under the proposed transaction, Barr would pay Organon $142 million to settle the patent litigation and to acquire all rights relating to Mircette, including the U.S. marketing approval. Barr would also pay $13.75 million to Saviant Pharmaceuticals, Inc., owner of the patent covering Mircette. Organon is the exclusive licensee under the patent for Mircette (U.S. Patent No. 4,921,843, the “original patent”, and U.S. Patent No. RE 35724, the “reissue patent”).

Mircette® (desogestrel/ethinyl estradiol and ethinyl estradiol) provides an oral contraceptive regimen of tablets each containing 0.15 mg desogestrel (13-ethyl-11- methylene-18,19-dinor-17 alpha-pregn- 4-en- 20-yn-17-ol), 0.02 mg ethinyl estradiol (19-nor-17 alpha-pregna-1,3,5 (10)-trien-20-yne-3,17-diol).

The patent litigation is currently before the U.S. District Court for the District of New Jersey. The court has agreed to stay any further proceedings to allow all parties involved to negotiate definitive settlement agreements.

Barr and Organon filed the non-binding letter of intent on the settlement with the Federal Trade Commission (FTC) this year, pursuant to the Hart-Scott-Rodino Antitrust Improvements Act. The closing of the deal is subject to FTC approval, which is currently at a second request stage.

The Hart-Scott-Rodino Antitrust Improvements Act of 1976, Pub. L. 94-435 (known commonly as the HSR Act), is a set of amendments to the antitrust laws, principally the Clayton Antitrust Act. The context in which the HSR Act is usually cited is 15 U.S.C. § 18a, title II of the original law, which provides that a company seeking to acquire or merge with another company (or engage in certain other transactions) must file advance notice of its intentions with the Federal Trade Commission and the Assistant Attorney General in charge of the Antitrust Division of the Department of Justice at least thirty days prior to consummation of such a transaction.

Title III of the Act allows states to sue companies in Federal court for monetary damages under antitrust laws on behalf of their citizens; previously, only the persons harmed by anticompetitive activity had a right to sue for damages.

We learned about a new (to us) blawg by Alan Rothman (a non-practicing attorney and an MBA in New York who specializes in implementing and teaching law office technology). It’s called The Subway Fold, named after the urban engineering challenge necessary in order for a reader on the subway to maintain full access to all of the pages of the newspaper within an often very limited space.

The Subway Fold was one of those that Monica Bay mentioned recently in Blawg Review #18 and it covers, among other topics, law practice, IP, biosciences, media, telecom and visualization(?). We recommend checking it out for anyone interested in law office technology. No folding, crowding or ink smudges involved.

The Baristas’ law firm, Frost Brown Todd LLC, is willing to offer temporary office space to lawyers displaced by Hurricane Katrina. To the extent a particular FBT office (we have seven offices across four states but our IP practice is mainly in Cincinnati, OH, home to great things like odd chili and Opening Day) has available space, the firm is pleased to be able to offer the space to a lawyer in need.

Paul Bromwell, our IT guru, has assured us that we can accommodate the lawyer’s computer needs without jeopardizing the confidentiality of our clients.

Contact me if you have a need. Our best wishes to you all.

Note: The ABA also has set up Hurricane Katrina Disaster Relief pages for the attorneys, law offices, and many others needing legal assistance who have been caught in the catastrophic effects of Hurricane Katrina.

The Court of Appeals for the Federal Circuit handed down a decision in In Re Dane K. Fisher And Raghunath V. Lalgudi (U.S. Court of Appeals for the Federal Circuit, 04-1465 (Serial No. 09/619,643), September 7, 2005). Monsanto had appealed the rejection of its patent application for five expressed sequence tags (ESTs) that encode parts of genes whose functions are unknown. The U.S. Patent and Trademark Office refused to grant the patent to Monsanto’s assignees (Fisher and Raghunath) on the grounds that the ESTs have no specific utility; they can only be used to locate genes of unknown function, as can all other ESTs.

Monsanto insisted that the PTO is applying a higher utility standard than stipulated by law, and that the use of ESTs as research tools is enough to warrant them patentable. Monsanto says the PTO argument that awarding patents on ESTs would inhibit innovation is no basis for rejecting them if the law says otherwise – even if it would be “bad public policy.” In affirming the Board’s findings, the CAFC agreed that each of the five claimed ESTs lack a specific and substantial utility and that they are not enabled.

Basically, the claimed invention relates to five purified nucleic acid sequences that encode proteins and protein fragments in maize plants. The claimed sequences are commonly referred to as “expressed sequence tags” or “ESTs.” An EST is a short nucleotide sequence that represents a fragment of a cDNA clone. It is typically generated by isolating a cDNA clone and sequencing a small number of nucleotides located at the end of one of the two cDNA strands. When an EST is introduced into a sample containing a mixture of DNA, the EST may hybridize with a portion of DNA. Such binding shows that the gene corresponding to the EST was being expressed at the time of mRNA extraction.

Claim 1 of the ’643 application recites:

A substantially purified nucleic acid molecule that encodes a maize protein or fragment thereof comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1 through SEQ ID NO: 5.

The ESTs set forth in SEQ ID NO: 1 through SEQ ID NO: 5 are obtained from cDNA library LIB3115, which was generated from pooled leaf tissue harvested from maize plants (RX601, Asgrow Seed Company, Des Moines, Iowa, U.S.A.) grown in the fields at Asgrow research stations. SEQ ID NO:1 through SEQ ID NO:5 consist of 429, 423, 365, 411, and 331 nucleotides, respectively. When Fisher filed the ’643 application, he claimed ESTs corresponding to genes expressed from the maize pooled leaf tissue at the time of anthesis. Nevertheless, Fisher did not know the precise structure or function of either the genes or the proteins encoded for by those genes.

The ’643 application generally discloses that the five claimed ESTs may be used in a variety of ways, including: (1) serving as a molecular marker for mapping the entire maize genome, which consists of ten chromosomes that collectively encompass roughly 50,000 genes; (2) measuring the level of mRNA in a tissue sample via microarray technology to provide information about gene expression; (3) providing a source for primers for use in the polymerase chain reaction (“PCR”) process to enable rapid and inexpensive duplication of specific genes; (4) identifying the presence or absence of a polymorphism; (5) isolating promoters via chromosome walking; (6) controlling protein expression; and (7) locating genetic molecules of other plants and organisms.

In a final rejection, dated September 6, 2001, the examiner rejected claim 1 for lack of utility under §101. The examiner found that the claimed ESTs were not supported by a specific and substantial utility. She concluded that the disclosed uses were not specific to the claimed ESTs, but instead were generally applicable to any EST. For example, the examiner noted that any EST may serve as a molecular tag to isolate genetic regions. She also concluded that the claimed ESTs lacked a substantial utility because there was no known use for the proteins produced as final products resulting from processes involving the claimed ESTs.

The examiner stated: “Utilities that require or constitute carrying out further research to identify or reasonably confirm a ‘real world’ context of use are not substantial utilities.” The examiner also rejected the claimed application for lack of enablement under § 112, first paragraph. She reasoned that one skilled in the art would not know how to use the claimed ESTs because the ’643 application did not disclose a specific and substantial utility for them.

The Board considered each of Fisher’s seven potential uses but noted that Fisher focused its appeal on only two: (1) use for the identification of polymorphisms; and (2) use as probes or as a source for primers. As to the first, the Board found that the application failed to explain why the claimed ESTs would be useful in detecting polymorphisms in maize plants. Board Decision. The Board reasoned that “[w]ithout knowing any further information in regard to the gene represented by an EST, as here, detection of the presence or absence of a polymorphism provides the barest information in regard to genetic heritage.”

Thus, the Board concluded that Fisher’s asserted uses for the claimed ESTs tended to the “insubstantial use” end of the spectrum between a substantial and an insubstantial utility. The Board also concluded that using the claimed ESTs to isolate nucleic acid molecules of other plants and organisms, which themselves had no known utility, is not a substantial utility. Specifically, the Board noted that Fisher argued that the “claimed ESTs may be useful in searching for promoters that are only active in leaves at the time of anthesis.” The Board found, however, that the application failed to show that the claimed ESTs would be expressed only during anthesis or that they would be capable of isolating a promoter active in maize leaves at the time of anthesis. Additionally, the Board addressed the remaining asserted utilities, highlighting in particular the use of the claimed ESTs to monitor gene expression by measuring the level of mRNA through microarray technology and to serve as molecular markers. The Board found that using the claimed ESTs in screens does not provide a specific benefit because the application fails to provide any teaching regarding how to use the data relating to gene expression. Fisher appealed.

In rendering its opinion, the CAFC declared that:

Regarding the seven uses asserted by Fisher, we observe that each claimed EST uniquely corresponds to the single gene from which it was transcribed (“underlying gene”). As of the filing date of the ’643 application, Fisher admits that the underlying genes have no known functions. Fisher, nevertheless, claims that this fact is irrelevant because the seven asserted uses are not related to the functions of the underlying genes. We are not convinced by this contention. Essentially, the claimed ESTs act as no more than research intermediates that may help scientists to isolate the particular underlying protein-encoding genes and conduct further experimentation on those genes. The overall goal of such experimentation is presumably to understand the maize genome – the functions of the underlying genes, the identity of the encoded proteins, the role those proteins play during anthesis, whether polymorphisms exist, the identity of promoters that trigger protein expression, whether protein expression may be controlled, etc. Accordingly, the claimed ESTs are, in words of the Supreme Court, mere “object[s] of use-testing,” to wit, objects upon which scientific research could be performed with no assurance that anything useful will be discovered in the end. Brenner, 383 U.S. at 535.

…

Moreover, all of Fisher’s asserted uses represent merely hypothetical possibilities, objectives which the claimed ESTs, or any EST for that matter, could possibly achieve, but none for which they have been used in the real world. Focusing on the two uses emphasized by Fisher at oral argument, Fisher maintains that the claimed ESTs could be used to identify polymorphisms or to isolate promoters. Nevertheless, in the face of a utility rejection, Fisher has not presented any evidence, as the Board well noted, showing that the claimed ESTs have been used in either way. That is, Fisher does not present either a single polymorphism or a single promoter, assuming at least one of each exists, actually identified by using the claimed ESTs. Further, Fisher has not shown that a polymorphism or promoter so identified would have a “specific and substantial” use. The Board, in fact, correctly recognized this very deficiency and cited it as one of the reasons for upholding the examiner’s final rejection.

With respect to the remaining asserted uses, there is no disclosure in the specification showing that any of the claimed ESTs were used as a molecular marker on a map of the maize genome. There also is no disclosure establishing that any of the claimed ESTs were used or, for that matter, could be used to control or provide information about gene expression. Significantly, despite the fact that maize leaves produce over two thousand different proteins during anthesis, Fisher failed to show that one of the claimed ESTs translates into a portion of one of those proteins. Fisher likewise did not provide any evidence showing that the claimed ESTs were used to locate genetic molecules in other plants and organisms. What is more, Fisher has not proffered any evidence showing that any such generic molecules would themselves have a specific and substantial utility. Consequently, because Fisher failed to prove that its claimed ESTs can be successfully used in the seven ways disclosed in the ’643 application, we have no choice but to conclude that the claimed ESTs do not have a “substantial” utility under § 101.

The court felt that nothing about Fisher’s alleged uses set the five claimed ESTs apart from the more than 32,000 ESTs disclosed in the ’643 application or indeed from any EST derived from any organism and that Fisher has only disclosed general uses for its claimed ESTs, not specific ones that satisfy § 101.

The court did not agree with the concerns raised by the government and certain amici that allowing EST patents without proof of utility would discourage research, delay scientific discovery, and thwart progress in the “useful Arts” and “Science” stating that Congress did not intend for these practical implications to affect the determination of whether an invention satisfies the requirements set forth in 35 U.S.C. §§ 101, 102, 103, and 112.

Judge Rader dissented stating believing that the claimed ESTs indeed have such a utility, at least as research tools in isolating and studying other molecules.

Download Full Opinion Here“>here.

While spending time convalescing at home from my recent accident, I have spent a lot of time thinking about working at home and how to optimize the experience. Fortunately, my firm has great IT services and I am able to work at home almost seamlessly with my office by using scanners and email. I have found that (other than the pain from my current injuries) I enjoy working some at home. The key, of course, is having good administrative help.

There has been a lot of talk lately about the concept of “homesourcing,” the migration of workers from expensive centralized coastal cities to a distribution of small towns and cities throughout the US (instead of overseas). This was recently discussed by Instapundit and the migration of computer jobs from Silicon Valley to rural towns.

On one hand, this movement of workers is a huge benefit to the employee. As a result of “homesourcing”, employees are often allowed to take their existing salaries and home equity to other parts of the country where they can have a far greater quality of life at no increase in cost to the company, the ultimate win-win for employer and employee. The employer gets a happy employee, and the employee gets a huge increase in real income. One other benefit which is important is that there is no better gas saving device than a high-speed modem. Workers who are homesourced need very little gas on which to get to work, and as a result, their personal “cost of working” also goes down dramatically.

Homesourcing, of course, needn’t be across the country. Just working from home wherever one lives has quite a few benefits in terms of cost savings and productivity. This can also have a dramatic effect on gaining a healthy lifestyle if one spends an hour each day at the gym instead of stuck in maddening traffic congestion. This is not just all about the employee, though. Employers stand to gain from more work-at-home through happier and healthier employees.

And giving employees a healthier lifestyle is important for both employee and employer. Leah Maclean, a professional coach and mentor, writes on Working Solo that a healthy lifestyle is critical to your business success. In asking other bloggers, guest blogger Andrea Lee writes that, though counterintuitive, “To the degree that I become a more physically active person, my businesses will take great leaps forward to seven figures and more.”

Lifestyle is not just important to your business success, it’s a path to it. Matthew Homann, of the nonbillable hour, believes that he must constantly remind himself that time with his family must be first on his ‘to-do’ list and not last. He even goes to the extent of making a list of the things he did each day that bettered his family life, improved his health, and built his business to build a report card of efforts to keep balance in his life. This is where working at home can come into play. Imagine not having to fight traffic all morning just so you can sit in a little office without natural lighting. Almost like a day at the beach.

Law firms tend to lag the curve on changes in the marketplace but it is inevitable the more firms will look to homesource lawyers to save on costs, especially if you set up office sharing so that the amount of expensive real estate and equipment is reduced. What can be better than reduced costs and increased productivity?

Carolyn Elefant and Mark Sindler have posted Blawg Review #21 over at My Shingle. I’ve been reviewing this week’s theme of Endings, Beginnings and the Transitions and Crossings in Between (while convalescing with my own transitions and typing with one hand).

I especially enjoyed the post by Margaret Marks, who found the The Standard Catchall Universal Disclaimer Notice, over 7000 words long.

We also enjoyed the Wired GC’s update on the legal Sex and the City (of London) over the book Fish Sunday Thinking, allegedly written by a young lawyer at an unnamed Top 50 law firm disclosing all of the sexual secrets of lawyers (that’s gotta be a slow read). It was written pseudonymously by “Alex Gilmore” who has kept his real name secret in order to “protect his lucrative job as a legal beagle and pay his mortgage.”

In a related post, Eh Nonymous has a round-up of what’s been said, pro and con, about anonymous bloggers. While we don’t really care that much, anonymous legal blogs seem like anonymous doctoring — it’s more appropriate for personal web logs where people post long missives about their cat’s toenail fungus that nobody reads anyway.