Patent Baristas

GTC Biotherapeutics, a company specializing in the development of therapeutics derived from transgenic animals, has reason to be optimistic. Investing 20 years in the business of developing transgenically derived treatments, the company suffered a recent setback in February when European officials denied approval of a transgenically produced drug. However, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency recently reversed the decision– recommending approval of the injectable antithrombin drug produced by transgenic goats.

The drug is ATryn, a recombinant form of antithrombin that has been purified from the milk of genetically altered goats. Antithrombin is a protein in human plasma that has anticoagulant and anti-inflammatory properties. A relatively small percentage of the population is deficient in antithrombin– the disease affecting about one in 3,000 to 5,000 people. The purified protein used for treatment is currently only available from donated human blood. If approved, ATryn will supplement this limited supply, the potential market a modest, but significant, $50 million.

Part of the controversy surrounding the use of antithrombin derived from transgenic animals is the risk of improper separation of proteins harvested from the milk, which could result in human exposure to animal proteins that could result in adverse effects on those receiving the treatment.

A final decision for the therapy should be issued within three months. If approved, the decision could open the door to a more affordable source of protein drugs that are currently unavailable or too expensive to manufacture.

GTC Biotherapeutics is involved in the development, production, and commercialization of therapeutic proteins through transgenic animal technology. In addition to ATryn, GTC has in development a recombinant human alpha-1 antitrypsin, a recombinant human albumin, a CD137 antibody to stimulate the immune system as a potential treatment for solid tumors, and a malaria vaccine.

The San Francisco Business Times ran an article reiterating what patent practitioners already know. That is, the increasing backlog at the U.S. Patent & Trademark Office is bad, it’s getting worse and the new set of proposals meant to reduce the waiting time will not provide relief.

The backlogs are an increasingly serious issue for biotechs. It can take patent examiners up to 15 months to begin reviewing an organic chemistry patent application. It can take more than three years to get a drug application to a patent examiner. Once a review has begun, the USPTO can take several more years to grant a patent.

As we’ve discussed, the new rules under consideration would allow just one follow-on to a pending application. A subsequent application would have to include an explanation as why it was not submitted previously. A second, related proposal would limit an application to 10 claims, which are statements describing the heart of the invention. The USPTO is currently reviewing comment on the proposed rules and will issue final regulations in the fall or winter.

Admittedly, almost one-third of new applications in 2004 were for follow-on applications but that’s not necessarily a bad thing. Part of the reason for continuations is to allow an applicant the opportunity to carve our the proper claim scope. That is, coverage that would not be too overbroad or too narrow but just right.

Many industries besides biotech rely on obtaining adequate patent protection in a timely fashion. However, biotech companies are particularly affected by both the backlog and the proposed rule changes. And, perhaps no other industry is as dependent upon patents as is the biotechnology industry. A biotechnology company can spend hundreds of millions of dollars over more than a decade before seeing any revenue. The long development time and intensive capital needs make the early stages of development critical in terms of patent protection in order to entice investors to get involved in what is already an incredibly risky venture. Thus, a flexible patenting system that allows companies to protect the full scope of their inventions through the filing of continuations is critical.

The Biotech Industry Organization believes that the USPTO should consider a “deferred-accelerated” system since not all applications require immediate examination. Under such a deferred examination system, an applicant may file an application with little cost and then decide whether to request examination at a later date by paying an examination fee. The marketplace would then dictate when — or if — the application would get examined. BIO also recommended changes in the PTO examiner production system, increased examiner education, and improved cooperation with other patent offices.

The bottom line is that the proposed rules will NOT achieve the stated goals of reducing patent application pendency nor will it expedite public notice as the USPTO claims. The practice would, instead, increase the cost of obtaining patent protection as well as increase uncertainty as to whether or not proper claim scope may be obtained.

Read BIO’s comments here.

In Falker-Gunter Falkner et al. v. Inglis et al. (Fed. Cir. 2006, 05-1324), on appeal from the USPTO Board of Patent Appeals and Interferences, the U.S. Court of Appeals for the Federal Circuit set out some guidelines on the adequacy of written description and enablement in biotech cases. The Federal Circuit held that:

There was an interference between U.S. Patent No. 5,770,212 (“the Falkner ‘212 patent) and Inglis et al., U.S. Application Serial No. 08/459,040 (“the Inglis ‘040 application”) and the Board held that Falkner could not antedate Inglis’ priority date.

Claim 29 of the Inglis ‘040 application reads:

A vaccine comprising a pharmaceutically acceptable excipient and an effective immunizing amount of a mutant virus, wherein said mutant virus is a mutant poxvirus and has a genome which has an inactivating mutation in a viral gene, said viral gene being essential for the production of infectious new virus particles, wherein said mutant virus is able to cause production of infectious new virus particles in a complementing host cell gene expressing a gene which complements said essential viral gene, but is unable to cause production of infectious new virus particles when said mutant virus infects a host cell other than a complementing host cell; for prophylactic or therapeutic use in generating an immune response in a subject.

Claim 1 of the Falkner ‘212 patent reads:

A vaccine comprising (a) a defective poxvirus that lacks a function imparted by an essential region of its parental poxvirus, wherein (i) said defective poxvirus comprises a DNA polynucleotide encoding an antigen and said DNA polynucleotide is under transcriptional control of a promoter, and (ii) the function can be complemented by a complementing source; and (b) a pharmaceutically acceptable carrier.

The inventors discovered a way of making vaccines safer by deleting or inactivating an essential, rather than an inessential, gene from the viral vector’s genome, while at the same time solving the production problem by growing the vaccines in cells that were complementarily modified to produce the absent essential viral gene product “on behalf of” the vector virus. Thus, the modified vector virus could be readily grown in these complementarily-modified cells, but not in other cells, such as those of an inoculee.

Falkner argued that the claims in Inglis’s ‘040 application were unpatentable because they failed to meet the written description requirement of 35 U.S.C. § 112 because (1) the specification did not identify any essential genes in poxvirus or describe the inactivation of such genes, (2) vaccines based on vaccinia (a type of poxvirus) had not yet been produced, and (3) the bulk of the Inglis specification was directed not to poxviruses but to herpesviruses. Falkner also argued that Inglis did not sufficiently describe and enable the claims in question and that without the benefit of these applications, Inglis would be unable to establish constructive reduction to practice earlier than Falkner.

The Federal Circuit laid out the requirements for enablement and written description as follows:

1. Examples Are Not Required

A claim will not be invalidated on section 112 grounds simply because the embodiments of the specification do not contain examples explicitly covering the full scope of the claim language. That is because the patent specification is written for a person of skill in the art, and such a person comes to the patent with the knowledge of what has come before. Placed in that context, it is unnecessary to spell out every detail of the invention in the specification; only enough must be included to convince a person of skill in the art that the inventor possessed the invention and to enable such a person to make and use the invention without undue experimentation.

2. Actual Reduction to Practice Is Not Required

As we explained in Capon v. Eshhar, “[t]he ‘written description’ requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed.” 418 F.3d 1349, 1357 (Fed. Cir. 2005). The Board was correct, however, not to view as dispositive that Inglis had not actually produced a poxvirus vaccine, because an actual reduction to practice is not required for written description. See Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 926 (Fed. Cir. 2004) (“We of course do not mean to suggest that the written description requirement can be satisfied only by providing a description of an actual reduction to practice. Constructive reduction to practice is an established method of disclosure . . . .”). Rochester, moreover, is consistent with Supreme Court precedent. In the context of interpreting 35 U.S.C. § 102(b), the Court held that “[t]he word ‘invention’ must refer to a concept that is complete, rather than merely one that is ‘substantially complete.’” Pfaff v. Wells Elecs., 525 U.S. 55, 66 (1998). It then proceeded to make clear that although “reduction to practice ordinarily provides the best evidence that an invention is complete. . . . it does not follow that proof of reduction to practice is necessary in every case.” Id. (emphasis added). Thus, to the extent that written description requires a showing of “possession of the invention,” Capon, 418 F.3d at 1357 (emphasis added), Pfaff makes clear that an invention can be “complete” even where an actual reduction to practice is absent. The logical predicate of “possession” is, of course, “completeness.”

3. Recitation of Known Structure Is Not Required

The descriptive text needed to meet these requirements varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence. The law must be applied to each invention that enters the patent process, for each patented advance is novel in relation to the state of the science. Since the law is applied to each invention in view of the state of relevant knowledge, its application will vary with differences in the state of knowledge in the field and differences in the predictability of the science.

Indeed, a requirement that patentees recite known DNA structures, if one existed, would serve no goal of the written description requirement. It would neither enforce the quid pro quo between the patentee and the public by forcing the disclosure of new information, nor would it be necessary to demonstrate to a person of ordinary skill in the art that the patentee was in possession of the claimed invention. As we stated in Capon, “[t]he ‘written description’ requirement states that the patentee must describe the invention; it does not state that every invention must be described in the same way. As each field evolves, the balance also evolves between what is known and what is added by each inventive contribution.” Id. at 1358. Indeed, the forced recitation of known sequences in patent disclosures would only add unnecessary bulk to the specification. Accordingly we hold that where, as in this case, accessible literature sources clearly provided, as of the relevant date, genes and their nucleotide sequences (here “essential genes”), satisfaction of the written description requirement does not require either the recitation or incorporation by reference14 (where permitted) of such genes and sequences.

Apparently after making substantial campaign contributions, the Baristas from Patent Baristas have been named Blawgers of the Year in the 2006 TechnoLawyer @ Awards!

There’s no cash prize but it beats a poke in the eye. Of course, it’s an honor to just be nominated. It just happens to be even better to win.

Blawgger of the Year is awarded to the blogger(s) responsible for the largest number of downloads of BlawgWorld 2006: Capital of Big Ideas. Apparently, our readers like this eBook. See the rest of the winners (who were actually voted in) at TechnoLawer. LexisNexis appears to have donated even more money than we did.

Earlier, we had an article featured in BlawgWorld 2006: Capital of Big Ideas, an eBook sampler of 51 of the most influential law blogs (blawgs). BlawgWorld is published by TechnoLawyer, a publisher of various e-mail newsletters for the legal marketplace. The Barista article, “Misconduct (and Not Just Scientific) is a Problem for Everyone,” provided a discussion of recent allegations of misconduct by U.S. researchers in light of a survey showing one in three researchers admitted to some type of professional misbehavior.

See the Patent Baristas Sampler article here.

If you don’t yet have a copy of BlawgWorld, download it today. BlawgWorld is available free in its entirety just by clicking on the link here.

The is a direct link to the eBook, which means readers can download it without joining TechnoLawyer. Although, we recommend that you join TechnoLawyer using the BlawgWorld home page, and check out their legal newsletters.

We’ve been quite busy these days and so posting has been light as a result. Since I have a personal interest in getting my own workload reduced a little, I wanted to pass along that my firm is currently looking to hire on new IP attorneys.

The Position:

Patent Associate with at least one year of experience in patent prosecution, counseling and licensing for our growing Intellectual Property Department in the Cincinnati, Ohio office. The candidate should have technical training (preferably advanced) in chemistry. Applicants should have excellent academic credentials, writing and communication skills and be capable of independent and creative work.

The Place:

Frost Brown Todd LLC is one of the top regional law firms in the Midwest, with an outstanding Intellectual Property Department and one of the TOP BIOMED/PHARMACEUTICAL PATENT PRACTICES IN THE MIDWEST. Not to mention the opportunity to work closely with the Patent Baristas.

The Rest:

To learn more about us and the communities we serve, we invite you to visit our home page at www.frostbrowntodd.com. Send resume, law school and undergraduate transcripts and writing samples to Karen Laymance, Frost Brown Todd LLC, 2200 PNC Center, 201 East Fifth Street, Cincinnati, Ohio 45202 or by email to klaymance@fbtlaw.com.

The U.S. Food and Drug Administration has approved Novartis AG’s Omnitrope hormone in what could mark a sea change in the stance taken by the FDA on generic biotechnology drugs. This precedent setting event marks the first follow-on version of a previously approved recombinant biotechnology drug in the U.S.

Earlier, a federal judge ordered the FDA to decide after a long delay whether Sandoz can market a version of human growth hormone as a bioequivalent to the one already sold by Pfizer Inc. Sandoz, the generics arm of Novartis, sued the FDA last September for leaving its application for a generic approval in limbo, a move designed to break a stalemate over so-called biogenerics. 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.

The FDA, however, went out of its way to say the Omnitrope case is not precedent setting, even putting out a question-and-answer sheet to indicate that Omnitrope is not a generic biologic:

Is Omnitrope a generic biologic?

No. Omnitrope is not rated as therapeutically equivalent to (and therefore substitutable for) any of the other approved human growth hormone products. Omnitrope is more appropriately characterized as a “follow-on protein product.”

Is this FDA’s first approval of a follow-on protein product?

No. FDA has approved other follow-on protein products under section 505 of the Food, Drug, and Cosmetic Act. These include GlucaGen (glucagon recombinant for injection), Hylenex (hyaluronidase recombinant human), Hydase and Amphadase (hyaluronidase), and Fortical (calcitonin salmon recombinant) Nasal Spray.

Does today’s approval of Omnitrope create a new pathway for follow-on versions of all protein products?

No. The approval of Omnitrope in a 505(b)(2) application does not establish a pathway for approval of follow-on products for biological products licensed under section 351 of the Public Heath Service Act, nor does it mean that more complex and/or less well understood proteins approved as drugs under the Food, Drug, and Cosmetic Act could be approved as follow-on products.

The majority of protein products are licensed as biological products under the Public Health Service Act, not approved as drugs under the Food, Drug, and Cosmetic Act. There is no abbreviated approval pathway analogous to 505(b)(2) or 505(j) of the Act for protein products licensed under section 351 of the Public Health Service Act. Such a pathway for the approval or licensure of follow-on protein products under the Public Health Service Act would require new legislation.

See further information here.

The World Health Organization (WHO) said it would look at whether the international drug patent system prevents developing countries from obtaining needed medicines, vaccines and diagnostic tests. The 192 WHO members agreed at an annual meeting in Geneva to launch an intergovernmental group to look for gaps in medical research and development, and draw up a global strategy to ensure the health needs of poor people are met. The report, commissioned by the WHO in 2003, did not call for a weakening of patent rights but urged big companies to reduce the price of medicines sold to developing countries and to avoid filing for patent protection there.

The report of the Commission on Intellectual Property Rights, Innovation and Public Health contends that the current system works well in developed nations but not in developing countries. While pharmaceutical industry insists that the current system is crucial for encouraging and financing the invention of new drugs, others claim it fails because people in the developing world often cannot afford to pay for high-priced new drugs, and because they sometimes need treatments that offer little profit for drug companies.

Governments should therefore develop and finance an alternate system for drug development and distribution in the developing world, the report concluded. More controversially, it suggested that drug companies should not seek patents in poor countries. An example are AIDS drugs costing $10,000 a year, too expensive for residents of African nations afflicted with the disease.

Another example is the FDA recommended approval of the first vaccine to prevent cervical cancer, the leading cause of death from cancer among women in poor countries, with 80 percent of the world’s cases. In the developed world, routine tests usually detect the disease in its treatable, precancerous stages. At $500 for the series of three shots, it is unaffordable in poor countries.

In the past, drug companies offered deals with poorer countries for discounted rates and foundations and international projects purchase and distribute costly drugs in pilot projects but these fall far short of meeting the global need. Drug companies won’t develop drugs unless they can charge for the drugs. Big surprise.

The WHO report generally concludes what we already know. That is, “Governments have the major responsibility to mobilize funds and promote new financing and incentive mechanisms to meet our shared goals.” It’s easy for governments, rich and poor, to shirk their responsibility of providing healthcare to teir people by blaming drug companies.

Admnittedly, healthcare is not the same as wanting to buy some patented, high-tech toy and not wanting to pay the MSRP but the burden for caring for the sick falls on all of us.

What does the report say?

• Intellectual property rights are a general incentive provided by governments to promote innovation in all fields. In respect of public health, they are embedded in a set of other incentives which influence the pattern of innovation. They need to be looked at as part of a bigger picture.
• In particular, because the market demand for diagnostics, vaccines and medicines needed to address health problems mainly affecting developing countries is small and uncertain, the incentive effect of intellectual property rights may be limited or non-existent.
• Because intellectual property rights may not be an effective incentive in this area, there is a need for other incentives and financial mechanisms to be put in place and for collaborative efforts between different stakeholders.
• Without access to the products of innovation, there can be no public health benefits. Defining the conditions by which products can be accessed is therefore an important aspect of the report.
• There has been significant progress in recent years, in particular initiatives taken by different stakeholders to promote innovation in health-care products e.g. increased funding by foundations and the formation of public-private partnerships for product development.
• This momentum for change is welcome but is insufficient.
• More needs to be done. There are unsettled and debated issues in intellectual property for example the effectiveness of the recent amendment to TRIPS in increasing access to medicines in countries without manufacturing capacity, the impact of data exclusivity laws and the impact of intellectual property provisions in bilateral trade agreements.
• And there is a need to ensure enhanced financing on a sustainable basis of innovation and access and promote synergy between the different partners.
• Ultimately it is a responsibility that governments must accept if these objectives are to be achieved.
• It is appropriate that WHO should now take the lead in promoting a more sustainable and better-funded effort and addressing unresolved issues.
• WHO should accordingly develop a Global Plan of Action to secure enhanced and sustainable funding for developing and making accessible products to address diseases that disproportionately affect developing countries.

The World Health Assembly will decide which steps WHO should then take to follow-up the implications of the report.

Click here to get the entire Report: Public health, innovation and intellectual property rights.

The Boston Globe recently ran an article that nanotechnology is about to be the next big thing in bioscience. Although nanotechnology has had a lot of ups and downs in its enthusiam in the marketplace, it’s still remains mostly a laboratory study subject. Now, nanotech seems staged to make huge leaps in medical treatment, so some say.

Nanotechnology is the understanding and control of matter at dimensions of roughly 1 to 100 nanometers, where unique phenomena enable novel applications. Encompassing nanoscale science, engineering and technology, nanotechnology involves imaging, measuring, modeling, and manipulating matter at this length scale. At the nanoscale, the physical, chemical, and biological properties of materials differ in fundamental and valuable ways from the properties of individual atoms and molecules or bulk matter.

Nanotechnology could introduce whole new classes of materials and products but could also present tough challenges to regulatory agencies. The National Science Foundation predicts that the global marketplace for goods and services using nanotechnologies will grow to $1 trillion by 2015, and there are already over 500 products being sold that claim they are made with nanoscale or engineered nanomaterials. These include products like self-cleaning windows, automobile paint, sunscreens, and tennis rackets. In the future, a marriage of nano and biotechnology will likely create a whole new generation of drugs, biomedical devices, and other products.

Nanomedicine has been defined as the monitoring, repair, construction and control of human biological systems at the molecular level, using engineered nanodevices and nanostructures. Current applications of nanotechnology in medicine involve engineered molecules to develop drugs, drug delivery techniques, diagnostics, medical devices and enhanced gene therapy and tissue engineering procedures. “Nanosizing” is a term developed in the pharmaceutical industry to describe how some previously approved products with particle sizes greater than 100 nm are being produced with smaller particle sizes, in order to change certain physical and performance characteristics, such as pharmacokinetic profile (i.e. the rate and extent of absorption and clearance from the body). To date, the FDA has no knowledge of reports of adverse reactions related to the “nano” size of resorbable drug or medical device products.

Not everyone is thrilled. A coalition of consumer and environmental groups petitioned the FDA to increase its regulation of nanoparticle-containing sunscreens and cosmetics and recall some products. Among the FDA-regulated products being sold are sunscreens containing titanium dioxide or zinc oxide nanoparticles (which offer strong ultraviolet protection while remaining colorless) and cosmetics with nanoscale liposomes. A number of animal studies have shown that at least some nanoparticles can penetrate cells and tissues, migrate through the body and brain and cause biochemical damage. But whether these pose health risks remains largely unknown, pending completion of long-range studies recently begun by the FDA and other agencies. The FDA has six months to respond to the petition.

The FDA has not established its own formal definition for nanotech, though the agency participated in the development of the NNI definition of “nanotechnology.” Using that definition, nanotechnology relevant to the FDA might include research and technology development that both satisfies the NNI definition and relates to a product regulated by FDA.

However, the FDA only regulates certain categories of products. Though existing requirements may be adequate for most nanotechnology products, many of the nanotechnology products will be Combination Products (i.e., drug-device, drug-biologic, or device-biologic products). The current policy regarding combination products helps prevent duplication of effort and a protracted approval process. If the product meets the definition of a combination product, it will be assigned to an Agency center that will have primary jurisdiction for its regulation. The assignment of a lead center is based upon a determination of the primary mode of action (PMOA) of the combination product. For example, if the PMOA of a combination product is that of a biological product, then the combination product would be assigned to the Agency component responsible for premarket review of that biological product.

FDA published a proposed rule defining the primary mode of action of a combination product. The proposed rule defines primary mode of action as “the single mode of action of a combination product that provides the most important therapeutic action of the combination product.” In some cases, neither the FDA nor the sponsor can determine the most important therapeutic action at the time a request is submitted. A combination product may also have two independent modes of action, neither of which is subordinate to the other. Depending upon the type of combination product, approval, clearance or licensure may be obtained through submission of a single marketing application, or through separate marketing applications for the individual constituent parts of the combination product. For most combination products, a single marketing applicition is sufficient for the product’s approval, clearance or licensure.

However, nanotech is better known to the public for its potential to run amuck like in the the “gray goo” (or “global ecophagy“) scenario developed by an early nanotech theorist, which holds that a tiny, self-replicating device could end up consuming all the organic material on earth, turning the world into a sterile mush.

Granted, there are genuine toxicity questions raised by the use of nanomaterials in consumer products, such as sunscreens and cosmetics, in which ultrafine particles are incorporated into the formulations. The dilemma, of course, is that the growing concerns over the use of nanoparticles in consumer products could outweigh the benefits that can be had in medicine and technology. Every new technology brings a new set of benefits and fears that are dealt with as they arise but public perception means a lot in both the marketplace and in the world of regulation where the FDA rules are often driven by politics.

Although the safety of nanoparticles and nanomaterials deserves careful consideration, what the public thinks about gray goo is critical. If they’re not careful, nanotech companies will lose the battle over public opinion and suffer the backlash felt by companies like Monsanto over biotech foods.