Patenting Nanotechnology Inventions:
Jeremy M. Stipkala, Ph.D. IPfrontLIne.com
Imagine that you have created nano-sized particles of a known drug, providing a new way to deliver that drug to a patient. Or perhaps you have pioneered sol-gel processed colloids of a metal oxide known to be a powerful catalyst. Now you want to exploit the fruits of your research and sell a product based on your invention. But first, you must protect those fruits and the further investments needed to turn your invention into a viable product, by applying for a patent. But how do you patent your nanotechnology invention when the drug or the metal oxide catalyst is already known?
Software Licensing Agreements
To obtain a patent, your invention must be useful, new, and not obvious.1 The nano-sized drug and colloidal catalyst are clearly useful, and they are new if no one has reported making them before. Whether those products are obvious presents a more difficult question, however, since the molecular drug and the bulk metal oxide catalyst are known. Can you patent a known material just by changing its size? When it comes to nanotechnology, the answer most likely is 'yes.' This article discusses how to show the nonobviousness of nanotechnology inventions when those inventions build on materials known in forms significantly smaller or larger than nano-sized.
Section 103 of Title 35 of the United States Code describes when an invention is obvious and therefore unpatentable:
A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains.2
Determining whether the "subject matter as a whole would have been obvious" requires a comparison of the scope and content of the prior art, the differences between the prior art and the claimed invention, and the level of ordinary skill in the pertinent art.3 Also, so-called "secondary considerations," such as whether the claimed invention possesses unexpected results or enjoys commercial success, must be evaluated.4
The obviousness analysis applies to our hypothetical situation as follows. The pharmaceutical prior art teaches the same compound useful for the same purpose as you would use your nano-sized version—treating some disease or condition. Also, the catalysis prior art teaches your metal oxide in bulkier form for catalyzing the same reaction that you describe in your patent application. The difference with the prior art in both cases, however, is that your invention is nano-sized. Some case law suggests, however, that merely changing the size does not impart patentability. For example, merely scaling up a polymerization reaction5 or increasing the size of a package of lumber6 would not necessarily make those differently sized inventions patentable.
But those situations are very different from your nanotechnology invention. Remember that we also have to look at the level of ordinary skill in the art. Was the level of skill in the pharmaceutical or catalysis art high enough so that the ordinarily skilled artisan could make your nano-sized version of the prior art?
To your advantage, a product is not obvious as a matter of law unless a process for making that product is also obvious. Cases involving novel crystalline forms of drugs illustrate this. For example, in the case In re Irani, the patent applicants claimed as their invention "Crystalline anhydrous amino tri(methylene phosphonic acid) ["ATMP"]."7 The prior art taught amorphous ATMP. The prior art also taught other amino phosphonic acids in crystalline forms and the same use for those acids as disclosed by the applicants. The patent examiner at the United States Patent and Trademark Office rejected the applicants' crystalline anhydrous ATMP as obvious and therefore unpatentable in light of that prior art. On appeal, the Court of Customs and Patent Appeals (the precursor to today's Court of Appeals for the Federal Circuit) reversed, holding that the claimed form of ATMP was indeed patentable. The court stated, "we are not convinced that the references of record would lead one of ordinary skill in the art to expect that ATMP could exist in a crystalline, anhydrous form, or, assuming such an expectation, that the references would render obvious a method by which such ATMP could be produced."8
It may happen, however, that the examiner evaluating your patent application will still reject your invention as obvious. She might combine prior-art references teaching the drug or the catalyst of your invention with other prior-art references teaching processes for making nano-sized materials such as sol-gel process art. With that combination, the examiner may insist that your invention is obvious. That is, she may find that the differences between your invention and the prior art are so small that the ordinarily skilled artisan could make your invention. If that happens, you can still obtain a patent if you can show that your nanotechnology possesses properties not shared by the prior art.
The Federal Circuit has provided guidance on what to do in this situation in the case In re Dillon.9 The Dillon applicant developed tetra-orthoesters as fuel additives to reduce soot formation upon combustion. One prior-art reference taught tri-orthoesters as additives to hydrocarbon fuels to dewater those fuels. Another prior-art reference taught both tri-orthoesters and tetra-orthoesters as water scavengers for hydraulic fluids. The examiner rejected the tetra-orthoester invention as obvious, because the similar structures and similar uses of the two compounds suggest that similar properties would be shared by both compounds. The Federal Circuit agreed. However, the court explained that the Dillon applicant could still obtain a patent if she had offered "a comparison of test data showing that the claimed compositions possess unexpectedly improved properties or properties that the prior art does not have[.]"10 Significantly, it is not enough to point out that a newly discovered property is not disclosed in the prior art.11 Rather, you must show that the newly discovered property does not exist in the prior-art compound or material.
Therefore, it makes sense to compare your nanotechnology invention to the materials disclosed in the prior art to find different or improved properties. Your nano-sized drug particles might be administered more easily than the drug in conventional form, for example, by topical administration or inhalation. You could measure pharmacokinetics and pharmacodynamics to demonstrate more effective uptake and distribution of your nano-sized drug in vivo. Or you could show that your colloidal catalyst uses substantially less catalytic material because of its dramatically increased surface area. Such data need not be available when you file your patent application, although if you have the data, you might include it. You can develop that data after you file your patent application, once the examiner identifies the prior art closest to your invention. Then you can present the data to the examiner, knowing that "[t]here is no question that all evidence of the properties of the claimed [invention] and the prior art must be considered in determining the ultimate question of patentability[.]"12
Conclusions
In sum, you can argue the patentability of your nanotechnology invention by pointing out that methods for making your invention were not obvious. Like new crystal phases, new nano-sized materials are difficult to make in the laboratory and even more difficult to manufacture in mass quantity. That is true even if general methods of nano-synthesis are known. For example, second-year chemistry majors know how to make crystals in the laboratory, but they also know that crystallization is a fickle process that does not readily yield other crystal phases or even crystals of other compounds. Similarly, the process you used to make your nano-sized invention invention -- such as the sol-gel process -- may be known, generally speaking. However, obtaining well-behaved colloids through sol-gel process chemistry can be daunting to say the least. Finding that right mix of time, temperature, and other conditions requires inventive skill and deserves a patent.
If that argument does not work, you can demonstrate unexpectedly improved properties or properties not shared by the known-sized material. After all, sometimes size does matter.
Footnotes
1 35 USC §§101–103.
2 35 USC §103(a).
3 Graham v. John Deere Co., 383 US 1, 17, 148 USPQ (BNA) 459, 467 (1966).
4 Id., 383 US at 17-18, 148 USPQ at 467; see also in re Dillon, infra note 9.
5 In re Rinehart, 531 F.2d 1048, 1052-53, 189 USPQ (BNA) 143, 148 (CCPA 1976).
6 In re Rose, 220 F.2d 459, 463, 105 USPQ (BNA) 237, 240 (CCPA 1955).
7In re Irani, 427 F. 2d 806, 166 USPQ (BNA) 24 (CCPA 1970).
8 Id., at 427 F.2d at 808, 166 USPQ at 26 (citing In re Cofer, 354 F.2d 664, 148 USPQ (BNA) 268 (CCPA 1966)).
9 In re Dillon, 919 F.2d 688, 16 USPQ2d (BNA) 1897 (Fed. Cir. 1990) (en banc).
10 Id., 919 F.2d at 692-93, 16 USPQ2d at 1901 (internal citations omitted).
11 Id., 919 F.2d at 693, 16 USPQ2d at 1901 (overruling In re Wright, 848 F.2d 1216, 6 USPQ2d (BNA) 1959 (Fed. Cir. 1988)).
12 Id.
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Battle Royale Between Ranbaxy and Pfizer over Lipitor
Sabia Tamboo from IPfrontLine.com
In August 2003 the Indian Pharmaceutiocal giant Ranbaxy decided to take a crack at Pfizer's 10 billion market by challenging the patents on its mega successful cholesterol reducing drug Lipitor. Ranbaxy challenged the patents in United Kingdom, United States, Austria, Norway, Romania and Peru.
In October 2005 the UK High Court of Justice rejected Ranbaxy's claim. Ranbaxy appealed against the decision and in June 2006 the UK Court of Appeal upheld the lower Court decision ruling that atorvastatin infringed the claims of the basic patent of Pfizer. The ruling meant that Ranbaxy would have to wait till 2011 to release its generic version in the UK market.
In November 2005 in Norway a Norwegian Court held that Pfizer's patent covering a compound used to making atorvastatin a key ingredient a Lipitor would be infringed by Ranbaxy's generic version of atorvastatin. However the Court also ruled that the Process patent for converting crystalline atorvastatin to amorphous atorvastatin was valid but was not infringed by Ranbaxy.
In April 2006 Austria's supreme patent and trade mark senate held invalid the patent covering atorvastatin calcium which was a major blow to Pfizer. However Pfizer was quick to add that the decision did not apply to any other patent litigation in relation to Lipitor taking place between Ranbaxy and Pfizer in other jurisdictions. On the other hand Malvinder Singh, Ranbaxy's CEO and managing director said "Our success further validates our strategy to successfully commercialize atorvastatin in Austria, and potentially other healthcare markets in the future,".
In December 2005 the District Court of Delaware had ruled that Ranbaxy's product infringed both the patents that Pfizer held on Lipitor. One is the patent covering the main molecule and another covers the calcium salt of Lipitor. The patent covering the main molecule expires in March 2010 and that covering the calcium salt in June 2011.
Ranbaxy appealed against this decision to the Court of Appeals For Federal Circuit and received a split decision. The Appeal court held that Ranbaxy's generic product atorvastatin infringed the basic patent which expires in 2010 but invalidated the 2011 patent.
This could mean that the generic version of Ranbaxy's product could hit the United States market by the end of March 2010.
Ranbaxy's Senior Vice President for Global Intellectual Property R Deshmukh said, "We are pleased with the Court's decision on the 995 patent and are evaluating our options with respect to the 893 patents."
On the other hand Pfizer's senior vice president of intellectual Property said, "While we are pleased that the Court has affirmed that our basic patent is valid and infringed, we are disappointed in the decision on the 995 patent."
Pfizer has successfully defended its patents in Romania and Peru. This round of litigation has thrown up a mixed bag of results for both Pfizer and Ranbaxy and now it remains to be seen what surprises come up as the Battle Royale proceeds.
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‘Valuing Pharmaceutical Innovation: Pricing and reimbursement for innovative therapies’ is a new report published by Business Insights that explores the latest issues and developments surrounding innovative therapy reimbursement. The main supply and demand side factors influencing pricing, market access and reimbursement decisions across a number of major markets are closely examined and the key trends and economic requirements of major therapeutic categories are assessed. This report also identifies the most successful pricing and market access strategies across each category of innovation with a detailed case study analysis of the pricing challenges encountered by both recently launched innovative therapies and those in late stage development.
Use this report’s case study analysis to benchmark the pricing strategies of leading innovative products and evaluate the drug reimbursement environments of major markets and therapeutic categories...
“The price premium for Lucentis over Macugen was over 100% in the US, while the drug was introduced at a more moderate 50% premium in the UK. Even if one was to use an entire vial of Avastin (as opposed to splitting it into 20 or more AMD doses), the cost of Avastin AMD treatment would still be less than a third of Lucentis in both the UK and US...“
• Position your upcoming products for quick access to key markets by comparing the regulatory mechanisms influencing reimbursement decisions across countries including Japan, France, Germany, Italy, Spain, the US and the UK.
• Understand the latest challenges and issues facing various categories of innovation including ‘new market’, ‘redefining the category’, ‘second-generation’, ‘incremental therapeutic’ and ‘incremental formulation’ innovations.
• Assess the innovative drug reimbursement environments of major therapeutic areas by identifying the current trends, unmet medical need and economic requirements of a range of disease categories including oncology, HIV, autoimmune diseases and diabetes.
• Leverage innovative new market access programs to protect prices for novel therapies in cost constrained reimbursement settings.
• Benchmark the reimbursement strategies of leading products by using detailed case studies of recently launched and upcoming innovative therapies across each type of innovative category.
Key issues examined in this report...
“Abraxane sales doubled in 2007 to $350 million, more than three times the sales of branded Taxol which is under threat from generic competition. Abraxane’s sales growth has been limited by a delayed approval and launch in Europe, with 2008 sales likely to surpass $500 million...”
“The Japanese market offers a relatively structured approach to setting price premiums for new, innovative drugs. However, it offers little guidance where adequate comparators do not exist – and as a result first-to-market pricing can be a little more complicated...”
- Major brands must aim to convey this comparative value with quality
of life adjusted years (QALY) and cost of treatment assessments.
- Non-prescription availability. Alli’s switch from Rx to OTC usage in
2007 reinvigorated the US market for obesity treatments.
GlaxoSmithKline is currently pursuing a similar switch in Europe with
approval expected during 2009 at the latest.
- Innovative therapy competition. The combination of high unmet
need and technological feasibility within certain therapy areas has
resulted in innovative therapies competing against each other at high
prices. The technological complexity associated with new oncology
and autoimmune treatments has caused significant price premiums
over more established therapies.
Chapter 4: Pricing challenges of recently launched innovative therapies
Prezista vs Fuzeon: HIV/AIDS premium pricing The pricing and positioning of Prezista and Fuzeon in the HIV/AIDS market is very similar to that of Byetta and Januvia in type 2 diabetes. Both therapies offer some incremental benefit, but the more complex therapy, Fuzeon, with high associated manufacturing costs, was priced at a significant premium. As a result it is positioned as a niche therapy distinct from more established treatment protocols. The Prezista launch price discount was a departure from continued price premiums for all new HIV therapy launched in the last ten years or so. As shown in Figure 4.18, Prezista sales grew strongly in 2007, while sales growth for Fuzeon was more modest. Both drugs offer an additional treatment option for failing, treatmentexperienced HIV/AIDS patients, but Prezista is building market share in direct competition with other protease inhibitors while Fuzeon offers a distinct, more niche therapy option for failing patients. Figure 4.19 shows the relative prices of selected HIV/AIDS drugs in the UK and US. When Fuzeon was launched at a price more than twice that of any other available HIV therapy, largely as a result of a complex and expensive manufacturing process. The launch of the new protease inhibitor Aptivus in 2005 continued an established trend whereby each new entrant into a treatment class was priced at a small premium over established therapies. However, when Prezista was launched in 2006 it broke from this trend by pricing at a small discount (10%) over Aptivus in both the UK and US. Pricing levels for HIV/AIDS drugs in the UK and US were similar once exchange rate differences were accounted for except for Fuzeon which added a greater premium in the US compared with the UK. Prezista broke the mould by pricing below the last FDA-approved HIV therapy Aptivus (tipranavir) and similar to Reyataz (atazanavir). This created significant goodwill, and good press with patient advocacy groups.
Table of Contents
CHAPTER 1: INTRODUCTION
• Introduction
• Supply-side factors
- Complexity and costs
- Market size
- Competition
• Demand-side factors
- Budget
- Unmet need
- Competition
• Valuing innovation
CHAPTER 2:
CATEGORIZING AND
VALUING INNOVATION
• Categories of innovations
- New market innovations
- Redefining the category
innovations
- Second generation
innovations
- Incremental therapeutic
innovations
- Incremental formulation
innovations
• Innovative market access
strategies
- Orphan drugs
- Risk-sharing
CHAPTER 3: REGION AND
THERAPY AREA SPECIFIC
CONSIDERATIONS
• Approaches to market
access in major markets
- USA
- Japan
- France
- Germany
- Italy
- Spain
- UK
• Therapy area markets for
innovative therapies
- Oncology
- HIV
- Autoimmune diseases
- Diabetes
- Others
CHAPTER 4: PRICING CHALLENGES OF RECENTLY LAUNCHED INNOVATIVE THERAPIES
• New market innovations - Gardasil (human papilloma virus vaccine): changing the treatment algorithm - Lysosomal storage diseases: pricing versus patient weight • Redefining the category innovations - Chantix (varenicline): redefining a therapeutic category - Nexavar (sorafenib) versus Sutent (sunitinib): meeting an unmet need • Second generation innovations - Lyrica (pregabalin): a new, improved neuropathic pain drug - Macugen vs Lucentis vs Avastin: premium pricing against off-label use • Incremental therapeutic innovations - Byetta vs Januvia: changing the treatment paradigm for type 2 diabetes - Prezista vs Fuzeon: premium pricing in HIV/AIDS • Incremental formulation innovations - Abraxane (paclitaxel): pricing incremental convenience - Vivitrol: market access vs premium pricing CHAPTER 5: UPCOMING LAUNCHES OF NEW INNOVATIVE THERAPIES • Introduction • New market innovations - Lupuzor (IPP-201101) ImmuPharma - Sinunase: Accentia • Redefining the category innovations - Bapineuzumab: Elan/Wyeth - Multikine: CelSci • Second generation innovations - Arzoxifene: Eli Lilly - Cordaptive (niacin ER/laropiprant): Merck • Incremental therapeutic innovations - Naproxcinod: NicOx - RhuDex: MediGene • Incremental formulation innovations - Denosumab: Amgen - Xarelto (rivaroxaban): Bayer/J&J Table of Contents (contd.)
LIST OF FIGURES • Supply and demand factors impacting market access for innovative therapies • Innovative drug categories by level of innovation and ease of market access • Source of prescription drug expenditures in the US, 2005-2006 • Italian categorization for innovative new therapies • Gardasil global sales, 2006-07 ($m) • Selected lysosomal storage disease drugs global sales, 2006-07 • Selected lysosomal storage disease drugs pricing in the UK and US, 2008 • Smoking cessation drugs global sales, 2006-07 • Smoking cessation drugs pricing in the UK and US, 2008 • Nexavar and Sutent global sales, 2006-07 • Nexavar and Sutent pricing in the UK and US, 2008 • Selected neuropathic pain drugs global sales, 2006-07 • Selected neuropathic pain drugs pricing in the UK and US, 2008 • Age-related macular degeneration drugs global sales, 2006-07 • Age-related macular degeneration drugs pricing in the UK and US, 2008 • Selected type 2 diabetes drugs global sales, 2006-07 • Selected type 2 diabetes drugs pricing in the UK and US, 2008 • Selected HIV/AIDS drugs global sales, 2006-07 • Selected HIV/AIDS drugs pricing in the UK and US, 2008 • Taxane drugs global sales, 2006-07 • Taxane drugs pricing in the US, 2008 • Alcohol dependency drugs global sales, 2006-07 • Alcohol dependency drugs pricing in the US, 2008 LIST OF TABLES • Classification for price premium (Japanese healthcare system) • Gardasil pricing in the UK and US, 2008 • Selected lysosomal storage disease drugs pricing in the UK and US, 2008 • Smoking cessation drugs pricing in the UK and US, 2008 • Nexavar and Sutent pricing in the UK and US, 2008 • Selected neuropathic pain drugs pricing in the UK and US, 2008 • Age-related macular degeneration drugs pricing in the UK and US, 2008 • Selected type 2 diabetes drugs pricing in the UK and US, 2008 • Selected HIV/AIDS drugs pricing in the UK and US, 2008 • Taxane drugs pricing in the UK and US, 2008 • Alcohol dependency drugs pricing in the UK and US, 2008 • Selected innovative therapies currently in late stage development • Key UK and US pricing data for leading case studies, 2008 • |
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Generics are finding their way onto the drugs market with increasing ease and speed. As a result, drug lifecycle management is becoming ever more important for pharmaceutical companies looking to generate the best possible revenues from their branded products.
As the entry of generics and new brands onto the market following patent expiry causes competitive pressure to mount, drug product lifecycles are becoming shorter and experiencing lower peak sales: a double edged sword for pharmaceutical companies. Products worth more than $100 billion in sales will be going off-patent and becoming subject to generic incursion between 2008 and 2012. Therefore, effective lifecycle management is becoming a must for pharmaceutical companies looking to maximize the return on their considerable investment. However, it is becoming increasingly difficult for them to do so with their current lifecycle management strategies.
With the growing pressures of cost containment, only those strategies that satisfy payers, physicians and patients by meeting a true unmet therapeutic need will ultimately be successful in the future. Consequently, the development of reformulation and fixed dose combination products will become less and less popular strategies as success becomes more difficult to achieve.
Drug lifecycles are evolving for the worse. Product lifecycles are becoming shorter for a number of reasons: a situation that is compounded by a dearth of new products needed to replace lost revenues. Thus lifecycle management strategies that prolong the patent-protected life of a drug have been propelled to the top of the agenda for many brand managers.
In 2008 alone, branded products representing $16.8 billion of revenues will be exposed to generic competition, with merchandise responsible for an aggregate of $102 billion in sales going off-patent and thus subject to generic incursion between 2008 and 2012 (based on 2007 sales of the 50 top pharmaceutical companies in the US). With many products' sales still growing at the time of patent expiry, every additional day of protected revenues can generate significant profits for the company.
Furthermore, payers such as the UK's National Health Service (NHS) have introduced a range of cost-containment measures aimed at stimulating the use of generics as a means of cutting healthcare costs. This, compounded by changes in the generics marketplace dynamics, has led to the faster erosion of brand sales in the period immediately after patent expiry and the entry of generics than in the past.
With increasing cost-containment pressures and scrutiny of the pharmaceutical industry's response to dealing with patent expiry, lifecycle management requires early consideration, a thorough understanding of each market, and strategic planning involving many different functions within the company. Payer behavior is especially important and will determine which strategies companies decide to implement in specific markets; while launching a reformulation product in one market may prove to be successful, it may be a complete failure in another one.
Strategies such as the development of reformulation products have done well in the past, but growing payer scrutiny is limiting their success under current market dynamics. Only those products offering significant improvement over the original therapy - not just in terms of patient compliance and convenience, but also in regards to therapeutic outcomes - are likely to receive the desired pricing and reimbursement terms. The same is true for fixed-dose combinations: in countries with the strongest cost-containment pressures, these drugs are unlikely to have a high uptake based on an improvement in patient compliance alone if cheaper generic combinations are available. Instead, improved outcomes will be necessary, with strong proof of better efficacy required.
With generics companies becoming increasingly aggressive in challenging pharmaceutical companies' patents, it is more difficult to protect fixed-dose combination drugs: a situation which is compounded by the raised bar for obviousness in both European and US courts. Furthermore, generics companies are becoming technologically more advanced and are now able to develop their own non-patent infringing reformulation products, thus shortening the market life of branded reformulations.
Not all markets are the same, however. In countries with less mature generics markets, such as France, Italy and Spain, there is a greater opportunity for traditional developmental lifecycle management strategies to succeed: with lower generic erosion after patent expiry, and a general distrust of generics among physicians and patients alike, reformulations and fixed-dose combination drugs are much more likely to achieve high uptake than in the UK and Germany.
While the US has generally been the prime market for the launch of reformulated products, payers are increasingly looking to cut costs, and physicians are becoming more cynical regarding the advantages such line extensions bring to patients. Consequently, reformulated products are finding it harder to achieve a high uptake, and the impact they have on protecting brand franchise sales is diminishing.
Instead, lifecycle management strategies employed earlier in the lifecycle are more likely to be successful, making indication expansion a popular strategy. However, with limited funds prohibiting development in a range of indications from the very start, manufacturers will focus on those indications that have the greatest level of unmet need in order to gain better reimbursement through preferred formulary placement, rather than launching in bigger mass markets that are becoming very crowded. With $100 billion worth of product sales becoming subject to generic competition from now until 2012, pharmaceutical companies simply must adapt to the changing market climate |
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