Source: https://en.b-ok.org/book/2573889/9f6090
Timestamp: 2020-02-24 15:25:08
Document Index: 106099890

Matched Legal Cases: ['Art. 98', 'art.53', 'art.54', '§ 1', 'Art. 9', 'EWCA ', 'Art. 34', '§ 806', '§ 12', '§ 806', 'EWCA ', 'Art. 54', 'Art. 54', 'Art. 53', 'Art. 52', '§ 103']

Second Generation Patents in Pharmaceutical Innovation | Hyewon Ahn | download
Main Second Generation Patents in Pharmaceutical Innovation
The development of new medications and improvements thereof are crucial to ensure continued gains in health. The development process is long and costly, mainly to produce the information that meets high regulatory requirements. In contrast, imitation involves negligible costs and much reduced risks. This is one of the reasons the pharmaceutical industry depends greatly on patent protection. Despite the existing patent system, however, the number of new medications per year has decreased, especially during the last decade. In comparison, the number of second generation patents and products has been drastically increased. The pharmaceutical industry is accused both of neglecting its real mission of providing new medications, while generating second generation products, and of preventing the entry of generics. This dissertation reviews whether the concerns are justified, and, if so, whether or how the patent system can improve the situation that confronts pharmaceutical companies and society. Dissertation. (Series: Munich Intellectual Property Law Center - MIPLC - Vol. 19)
ISBN 10: 3848708744
ISBN 13: 9783848708741
Series: Munich Intellectual Property Law Center - MIPLC
Second Generation Patents in
BUT_Ahn_0874-1.indd 1
Prof. Dr. Christoph Ann, LL.M. (Duke Univ.)
Max Planck Institute for Intellectual Property and
Prof. Dr. Dres. h.c. Joseph Straus,
BUT_Ahn_0874-1.indd 2
Second Generation Patents
in Pharmaceutical Innovation
BUT_Ahn_0874-1.indd 3
a.t.: Augsburg, Univ., Diss., 2013
ISBN 978-3-8487-0874-1
© Nomos Verlagsgesellschaft, Baden-Baden 2014. Printed in Germany.
BUT_Ahn_0874-1.indd 4
This dissertation was accepted by the University of Augsburg for the degree
of doctor juris in July 2013. The study takes into account statutory and case
law available until the end of 2013.
It would not have been possible to write this doctoral thesis without the
help and support of people around me, to only some of whom I can give
particular mention here.
First and foremost I would like to express my heart-felt gratitude to my
supervisor Prof. Dr. Christoph Ann for his continuous support of my PhD
study, endless encouragement, patience, and scholarly input. He has always
made himself available to clarify my doubts and has been willing to help me
to move forward whenever I faced obstacles throughout the whole period of
research. Under his constant and invaluable guidance I could successfully
overcome many difficulties. For all these reasons and many more, I am eternally grateful.
I would also like to sincerely thank Prof. Dr. Ulrich M. Gassner for his
insightful critique and interest in my research and for being the second referee of this thesis.
I will forever be thankful to my second supervisor Prof. Dr. Nari Lee who
indeed had recommended that I should pursue the PhD study and always
stood beside me, for her guidance, insights and integral view of my research.
Her enthusiasm and love for research and teaching has been contagious. I
feel privileged to be associated with a person like her during my life.
I am very much indebted to Prof. Dr. Joseph Straus who kindly shared
with me his immense knowledge no matter whether he was in his office or
even on a cruise, especially for his extensive discussions around my work.
And I will remember one of many pieces of advice from him which speeded
my research up greatly, i.e. “Well, a PhD thesis is not supposed to save the
whole globe.”
I owe Prof. Martin Adelman lots of gratitude for his valuable advice, many
thoughtful and detailed comments, as well as constructive criticism throughout the study. He always supported and enlightened me and knew how to
make a person moved with one sentence, i.e. “So, how’s your thesis going?”.
I am also thankful to Chief Judge Randall R. Rader across the Atlantic
who provided me with a great chance to experience and learn how the court
system works in the CAFC. I was very much privileged to learn from him
and grateful for his encouragement, advice and deep insights into U.S. and
comparative patent law.
My sincere gratitude is extended to Prof. Dr. Joseph Drexl for the academic support to carry out the research work at the Institute. I also take this
opportunity to acknowledge the Max-Planck Institute for the Intellectual
Property and Competition Law that provided a scholarship and thus made
my Ph.D. work possible.
I am also thankful to the MIPLC program director, Dr. Gintare Surblyte,
who made available her support in many ways.
My time at MPI was made enjoyable in large part thanks to the many
friends that now become a part of my life. Ilho Lee deserves special mention
here for his constant support and helping me when I faced difficulties or
queries throughout my study. I also would like to thank Max Wallot and
Eugenio Hoss for their support, helpful discussions and listening to my academic woes. Special thanks must go to Dr. Monica Donghi and Dr. Jörg
Habermann for their support for my PhD study as well as kind proofreading
with their technical and legal knowledge. I am also grateful to my office
colleagues, Nicole van der Laan, Rachel Alemu, Kan He, Magdalena Kolasa,
and Seyhan Ugurlu, who went through hard times together, cheered me on,
celebrated each accomplishment, and made a stimulating and fun filled environment.
I extend my deep thanks to Kyounghee Paek, Yeonhee Kim, and Jeongeun
Lee who helped me to update the development of Korean Jurisprudence and
have been there for me as always. Their support, friendship, and belief in
me were a treasure and will always be remembered.
Lastly, I would like to thank my parents and my sister. Their love and
support all the way from Korea allowed me to finish this journey. I owe them
everything and just wish I could show them how much I love and appreciate
B. Outline of the dissertation
C. Scope of the dissertation
PHARMACEUTICAL INVENTIONS, INNOVATIONS &
A. Cumulative nature of inventions
1. Basic and second generation inventions
a) Improvement inventions
b) Selection inventions
B. Inventions and innovations in pharmaceutical field
1. Inventions and patents in pharmaceutical field
a) Product invention and the absolute character of its
b) Hierarchy of pharmaceutical patents
2. Innovations in pharmaceutical field
a) Invention v. innovation
b) NMEs as the core of pharmaceutical innovation
C. Second generation inventions and patents in pharmaceuticals
1. Product inventions and patents
a) Species selection inventions
c) Crystalline forms
d) Metabolites and prodrugs
e) Esters and salts
f) Dosage forms
g) Combinations of active ingredients
2. Use inventions
a) New Use/New method of treatment
b) Dosage regime
3. Process inventions
D. Pharmaceutical products in the market
1. New medical entities, new molecular entities
2. Similar or equivalent “me-too” products
3. Second generation products
III. SPECIFICITIES IN PHARMACEUTICALS AND RECENT
A. Innovating and inventing in pharmaceutical industry
1. Specificities in the drug development process
a) Highly regulated industry
b) R&D – a costly and lengthy road to a medicine
c) Uncertainties in post-invention development
(1) Scientific uncertainty: Unpredictability of substances
(2) Regulatory and market uncertainties
d) Information rich chemicals
2. Specificities in the market for pharmaceuticals
a) Imitation with negligible cost and much reduced risk
b) Prescription based purchase: A disconnection between
choosers and payers
c) Information asymmetry and high loyalty to a medicine
3. Specificities of the patent protection for pharmaceuticals
a) Patent protection for industrial technologies
b) Patent protection in the pharmaceutical industry
B. Challenges and overcoming efforts
1. Decreased R&D productivity
2. Dearth of new medical entities
a) Significance of NMEs
b) Decreased number of NMEs
c) Potential reasons for the decrease
(1) Decrease in solvable scientific problems
(2) Stringent safety regulations
(3) Problem of over-disclosure
(4) Early and numerous abandonments of potential
3. Patent cliffs of blockbuster medications
4. Frequent merger and acquisitions (M&As) and in-licensing
5. Drastic increase of second generation inventions
a) Life cycle management or evergreening
b) Drastic increase of this activity supported by the number
of second generation patents
IV. STANDARDS OF PATENTABILITY FOR
PHARMACEUTICAL SELECTION INVENTIONS
A. Novelty and anticipation
2. Examination of novelty
3. Inherent anticipation and enablement
4. Novelty of selection inventions
d) Metabolite
B. Inventive step / Non-obviousness
1. Inventive step in patentability requirements
2. Examination of inventive step
3. Inventive step requirement for selection inventions
a) Species selection invention
1. Written description requirement
a) Enablement requirement
b) Enablement requirements in the patent law
(1) Enablement as a requirement for anticipation
(2) Basic similarity of the two enablement requirements
(3) Differences between the two enablement requirements
3. Disclosure requirement of selection inventions
IMPLICATIONS OF THE PATENTABILITY
REQUIREMENTS ON INNOVATION AND COMPETITION
A. Concerns about lowered patentability
1. General concerns about lowered patentability
a) Superfluous second generation patents
b) Increased patent exclusivities and amplified uncertainties
c) Encouraged waste of resources
d) Hindrance of pharmaceutical innovation
2. Concerns about the novelty requirements
a) Language dependent prior art disclosure problem
b) Rendering inventive step requirement meaningless
c) Potential concerns of “direct and unambiguous” disclosure
B. Implications considering the breadth of selection patents
1. Scope of the protection
2. Scope of selection patents
a) Species selection patents
c) Metabolite
d) Polymorphs
C. Implications considering the length of selection patents
1. Patent term and patent term extension
c) In Korea
2. Patent term extension on selection patents
D. Implications on the competition in the pharmaceutical industry
2. Quasi-obstacles of generics market entry
a) Scope of second generation patents
b) Length of second generation patents
c) Delayed filing of second generation patent applications
3. Real obstacles to generics’ market entry
a) Automatic thirty-month stay and new list up in the Orange
Book in the United States
b) Pendency of patent applications: Uncertainty
(1) Pendency of patent applications
(2) Filing of divisional applications
c) Active movement of the market to new products
d) Along with very specific patents on the secondary products
B. Nature of selection inventions
1. Different natures of selection inventions
b) Other selection inventions
2. Selection inventions from the era of penicillin to the 21th
a) Early medications and the novelty requirement
b) “Made available to the public” for the first time
C. Proposals on the breadth of patents
1. Arguments on the breadth of patents
a) Arguments for a broader patent scope
b) Arguments against a broader patent scope
c) Arguments on patent scope with consideration of other
2. Interim conclusion
3. Solutions to the overlapping scope with species selection
a) Voluntary licensing agreements
b) Non-voluntary licenses
(1) Compulsory licenses
(2) Case law relevant to compulsory licenses
D. Proposals on the length of patents
1. Arguments on the length of patents
2. Proposals on the length of patents
a) Proposal on the length of basic patents
(2) Proposed term of basic patents
(3) The basis of the proposal
(4) Expected effects
b) Proposal on the patent term extension of second generation
E. Proposals on the patentability requirements
1. Introduction: Technology specific patentability standards
2. Proposals on the novelty requirement
a) Arguments on the novelty requirement
b) Proposal on the novelty requirement of species selection
(1) Meaning of something “made available to the public”
(2) A patent as a double-edged sword to NMEs
(3) Statutory exceptions to the novelty requirement and
considerations thereof
(4) Proposed novelty requirement for NMEs
(5) Appreciation of the Olanzapine decision and its
c) Discussion on the novelty requirement of other selection
3. Proposals on the inventive step requirement
a) Arguments on the inventive step requirement
(1) Arguments for a strict inventive step requirement
(2) Arguments for a strict inventive step requirement
together with broader protection
(3) Arguments against a strict inventive step requirement
(4) Arguments for the relaxed inventive step requirement
in risky and expensive R&D fields
b) Proposal on the inventive step of species selection
c) Proposal on the inventive step of other selection inventions
(2) Proposed standard to assess the inventive step
(3) Basis of the proposal
4. Discussions on the sufficiency requirement
a) Discrepancy between the scope of and the disclosure of a
b) Stringent disclosure requirement of the basic invention
AIPLA Q. J.
Aliment Pharm. Ther.
B. C. L. Rev.
Bell J. Econ.
Berkeley Tech. L. J.
Bundesgerichtshof, Federal Supreme Court of Germany
Bundespatentgericht, Federal Patent Court of Germany
Brookings Paper on Econ.
Brookings Paper on Economic Activity
Cal. L. R.
Deutsches Patent- und Markenamt, German Patent and
Drug Info. J.
Eur. J. Drug Metab. Ph.
European Journal of Drug Metabolism and
Eur. J. Health L.
Internationaler Teil.
Gewerblicher Rechtsschutz und Urheberrecht, Praxis im
Immaterial- und Wettbewerbsrecht
Health Affair.
High Tech. L. J.
Hist. & Tech.
Hous L. Rev.
Hum. Psychopharm.
The rule established in the I.G. Farbenindustrie's A.G.’s
Ill. L. Rev.
In Vivo: Bus. Med. Rep.
In vivo: The Business and Medicine Report
Int. J. Health Care Fi.
International Journal of Health Care Finance &
Intell. Prop. Q.
J. Chem. Inf. Comp. Sci.
J. Copyright Soc'y U.S.A.
J. E. C. L. & Pract.
J. Generic Med
Journal of Generic Medicine
J. Legal Stud.
J. Pat. & Trademark Off.
J. Pat. Off. Soc'y
J. Pharmaceut. Marketing
J. Tech. L. & Pol’y
J. Technol. Transfer
Mich. Telecomm. Tech. L.
Michigan Telecommunications and Technology Law
Modern Drug Discov.
Mew Medical Entity or New Molecular Entity
Open Access J. Clin. Trials
The person having ordinary skill in the art
Probl. Perspect. Manage.
San. Diego L. Rev.
Santa Clara Computer &
Sci. & Pub. Pol’y
Seton Hall L. Rev.
Soc. Philos. Policy
St. John's J. Legal Comment. St. John's Journal of Legal Commentary
Stan. Tech. L. Rev.
Sup. Ct. Rev.
The Agreement on Trade Related Aspects of Intellectual
Tul. J. Tech. & Intell. Prop.
UC Irvine L.R.
U. Dayton L. Rev.
Wid. L. Symp. J.
Widner Law Symposium Journal
World Pat. Info.
Yale J. Health Pol’y L. &
“Over the past two decades, the pharmaceutical industry ‘has moved very far
from its original high purpose of discovering and producing useful new drugs.
Now primarily a marketing machine to sell drugs of dubious benefit, this industry uses its wealth and power to co-opt every institution that might stand in
its way, […].”1
This is the much-quoted statement of Dr. Marica Angell, the former editorin-chief of the New England Journal of Medicine. It is a sobering reflection
on the operational reality that the development of new medications and improvements to those medications play a crucial role in ensuring continued
gains in health and longevity. The need for new medicines is never-ending.
To spur the investment needed for the continued research and development
(“R&D”) of new medicines, economic incentives are essential prerequisites.
These incentives can also be provided by intellectual property protection -particularly patents -- government funding, or other administrative policies.
However, achievements of R&D are not enough to provide a constant and
efficient flow of new medicines to the market. The pressure exercised by
competitors such as generic companies leads to a reduction in drug prices
and this too is necessary.
The following purposes of the patent system have been discussed: i) Providing motivations for making useful inventions,2 ii) disclosing and disseminating information and inventions to the public,3 and iii) allowing for more
efficient exploration of the possibilities inherent in prospective inven-
1 Angell, 2004, xvii-xviii.
2 Luski/Wettstein, 1 Probl. Perspect. Manage. 31, 31 (2004); Ann, 2009, 361; Crouch,
16 Geo. Mason L. Rev. 141, 141 (2008); Graham v. John Deere Co., 383 U.S. 1, 9
(1966) (“The patent monopoly was not designed to secure to the inventor his natural
right in his discoveries. Rather, it was a reward, an inducement, to bring forth new
knowledge.”); Crouch, 39 Seton Hall L. Rev. 1125, 1134 (2009); cf. Kamien/
Schwartz, 1982, 190-91 (noting “[t]he monopolist […] chooses to spend less on development than would a social planner because his reward from innovation is smaller
than the total social benefit.”).
3 Friebel et al., 2006, 21; Eisenberg, 56 U. Chi. L. Rev. 1017, 1028-30 (1989).
tions.4 The patent system can be used as a way of creating prior art and
preventing others from obtaining a patent that an original inventor might
later infringe.5 More importantly, the patent system encourages investment
in potentially risky commercialization activities6 and turns inventions into
new goods and services7 by providing the opportunity to recoup that investment.8 In other words, it creates the incentives to develop nascent inventions
into marketable products, since the prospect of a patent provides greater
efficiency in the development of inventions.9 Jerome Frank J noted in
“The controversy between the defenders and assailants of our patent system may
be about a false issue – the stimulus to invention. The real issue may be the
stimulus to investment.”10
This function of the patent system can be clearly seen in the responses to the
Court of Justice of the European Union (“CJEU”) decision,11 in which the
4 Kitch, 20 J. Law Econ. 265 (1977); Mazzoleni/Nelson, 27 Res. Policy, 273, 275-80
(1998); Pfaff v. Wells Electronics, Inc., 525 U.S. 55, 63 (1998), reh’g denied (acknowledging two purposes of the patent system, i.e. “creating and the publicly disclosing new inventions.”).
5 Jaffe, 29 Res. Policy 531, 539-40 (2000); Levin et al., 1987 Brookings Paper on Econ.
Activity, 783, 798 fn. 29 (1987). However, if this was the purpose, it will be the
cheaper and easier way to publish the invention to the proper media. See e.g. Lichtman/Baker/Kraus, 53 Vand. L. Rev. 2175, 2175-76 (2000).
6 Roin, 87 Tex. L. Rev. 503, 509 (2009); Merges, 7 High Tech. L. J. 1, 69-70 (1992)
(“[P]atents may spur development more than invention per se. […] this may in fact
be such an important function that it more than outweighs the contribution patents
make to incentives to invent.”); Jaffe/Lerner, 2004, 43 (“Patents protect an individual’s or firm’s investment in the development of an idea, as much as they protect the
invention itself.”); Svatos, 13 Soc. Philos. Policy 113, 114 (1996); Scherer, 1984,
22-25 (with the example that an investor entered into partnership with the inventor
of the steam engine owing to the patent); Duffy, 71 U. Chi. L. Rev. 439, 440 (2004).
7 Kieff, 85 Minn. L. Rev. 697, 707-12 (2001); Merges, 7 High Tech. L. J. 1 (1992).
8 See e.g., Eisenberg, 56 U. Chi. L. Rev. 1017, 1036-46 (1989); Blair/Cotter, 10 Tex.
Intell. Prop. L. J. 1, 78-80 (2001); Hoffman, 89 Cornell L. Rev. 993, 1022 (2004)
(noting a patent gives an opportunity to recoup R&D costs, thereby providing incentives to invest in further research); Svatos, 13 Soc. Philos. Policy 113, 119 (1996)
(noting “[j]ust as there is no guarantee that patents will not allow “monopoly” profits,
there is also no guarantee that a patent will help capture even normal profits, even if
the invention socially useful; this can result from a lack of marketing know-how,
excessive litigation costs, etc.”).
9 Kitch, 20 J. Law Econ. 265, 276 (1977).
10 Picard v. United Aircraft Corp., 128 F.2d 632, 643 (2nd Cir. 1942).
11 C-34/10, Oliver Brüstle v. Greenpeace e.V., 2011.
Court held that human embryonic stem cells were not patentable subject
matter in Europe. Among the many concerns and objections voiced regarding the decision, the major worries were the impediments to competition in
the international market for new disease therapies,12 and the lack of incentive
for innovative companies to invest in this field of R&D in Europe.13
The Board of Appeal of the European Patent Office (“BOA”) noted in
one case that it must be assumed that inventors invent not out of idle curiosity, but with some concrete technical reason in mind.14 However, it is
often observed that inventions may arise as a result of felicitous curiosity,
by serendipity, as a result of a flash of insight, or simply due to human nature
without recourse to specific grounds.15 It follows that inventions may arise
without patent protection. However, the necessary investment needed to develop such innovation is unlikely to follow without patent protection. With
strong protection, companies will invest hundreds of millions of dollars in
their R&D in anticipation of substantial reward.16 Thus, although the patent
system is subject to criticism with regard to the high prices that may be
entailed by patent protection, there is little doubt that it is crucial to spurring
pharmaceutical innovation.17
Specifically, the pharmaceutical industry may be regarded as one of those
industries in which the economic rationale for patents works best to protect
inventors from imitators, provides the incentive for bearing the cost of innovation,18 as well as ensuring essential protection.19 However, in spite of
this protection, the number of innovative new medicines per year has decreased or remained the same.20 This seem to undermine the above arguments21 that patent protection provides incentives for real innovation and
promotes the progress of technological development in this field. In addition,
12 Abbott, 471 Nature 280 (2011) (citing Dr. Brüstle’s own word, namely “if we are
not allowed to protect our inventions in Germany, we won’t be able to compete in
the international market for new disease therapies.” ).
13 Smith, 472 Nature 418 (2011).
14 Agrevo/Triazoles, T 939/92, OJ EPO 1996, 309, 320.
15 Crouch, 39 Seton Hall L. Rev. 1125, 1134 (2009); Burk/Lemley, 89 Va. L. Rev. 1575,
1581 (2003).
16 Scherer, 20 Health Affair. 216, 220 (2001).
17 Cohen/Nelson/Walsh, 2000, 3.
18 Bessen/Maskin, 40 RAND J. Econ. 611 (2009).
19 Roin, 87 Tex. L. Rev. 503, 513-15 (2009); Bessen/Meurer, 2008, 88-89.
20 See subsection III.B.2.
21 See subsection III.A.3.b).
the pharmaceutical industry is facing numerous challenges, such as major
capital losses in revenue as the patent terms on some blockbuster drugs have
expired, spiralling costs for the development of new drugs, particularly in
running clinical trials, more stringent regulatory requirements, and increasingly cost-constrained healthcare systems.22
Consequently, the focus has shifted towards alternative strategies of revenue generation. Such strategies may include a move away from creating
innovative new medicines in favour of lower-risk solutions, such as improvements or applications. These second generation inventions are also referred to as blocking patents, incremental improvement patents, surrounding
patents, fencing patents, and second-tier patents. The strategies used to develop these second generation inventions are referred to as life cycle management, evergreening patenting, patent thicketing, and patent clustering.
This increase in the number of second generation inventions in the pharmaceutical industry is particularly worrisome in light of the concomitant dearth
of innovative medications and it is questionable whether the movement toward second generation inventions and products is well aligned with the
health needs of societies.23 In addition, second generation patents may adversely impact competition by preventing generic companies from entering
into the market or at least making them hesitant to do so.
Since superior new medications are essential to maintaining and improving the health of a society, these concerns about the dearth of new medications and the increase in the number of second generation patents are important and serious. This dissertation will analyze and review whether these
concerns are justified, and, if so, whether or how patent law could help to
eliminate or lessen these concerns. Amongst others, the following issues will
be addressed: Whether the patent system is associated with the dearth of new
medications, whether the patent system sufficiently encourages manufacturers to invest in new medications, whether there is a correlation between
the increased number of second generation patents and any change in patent
law, whether there has been any change in the patentability requirements of
second generation inventions, whether all kinds of second generation inventions retain the same value, whether second generation inventions hinder
true innovation, such as new medicines, whether second generation inventions delay or prevent the entry of generic products, and, if so, whether and
22 See e.g., Federsel, 18 Bioorgan. Med. Chem. 5775, 5775 (2010); Paul, et al., 9 Nat.
Rev. Drug Discov. 203, 203 (2010).
23 Avorn, 309 Science 669, 669 (2005).
how the patent system can improve the situation that confronts pharmaceutical companies and society in general.
This dissertation approaches and analyzes the above issues from various
perspectives, mainly within the patent system, and is structured as follows:
Chapter 1 presents a short introduction to the dissertation. Chapter 2 defines the nature of inventions, considers the definition of inventions and
innovations in the pharmaceutical art, discusses the range of products in the
pharmaceutical market, and explores second generation inventions in pharmaceutical technology along with their backgrounds. Chapter 3 examines
the specificities of pharmaceutical development procedure and of the drug
markets as well as the central role of the patent system in the industry. It
further presents recent challenges, such as the dearth of new medications
and efforts to overcome this problem. Chapter 4 revisits the patentability
requirements of selection inventions, reviews recent court cases and amended patent examination guidelines and explores the changes therein. Based
on the findings in chapter 4, chapter 5 examines concerns about the changes
in patentability requirements and assesses the implications thereof with consideration of the scope and the duration of patent protection conferred by
second generation patents. Further, an understanding of the implications for
competition in the market of generic versions engendered by second generation patents is sought. After reviewing different natures of selection inventions, chapter 6 seeks to formulate proposals on the scope, terms, and
patentability requirements of species selection inventions and other selection
inventions, to remove uncertainties for private players and users of the patent
system and to provide greater benefits to society. Finally, chapter 7 provides
In the discussion of second generation inventions, the focus will mainly be
on chemical selection inventions, such as species selection inventions, optical isomers, metabolites, and crystalline forms. These inventions are chosen not only because they are characteristic examples of second generation
inventions, but also because species selection invention can represent fea-
tures of a basic invention. Therefore, they provide a good basis for further
discussion of pharmaceutical inventions and innovations. Subsequently, this
research results reported in this dissertation could be applied to all other
second generation inventions insofar as they also originate from basic inventions.
Jurisdictions are selected based upon an evaluation of the extent of patenting activity and of the pharmaceutical market. Firstly, patenting activity is
considered. According to the World Intellectual Property Organization
(“WIPO”) report,24 the top five countries for originating Patent Cooperation
Treaty (“PCT”) filings in 2011 were the United States, Japan, Germany,
China, and the Republic of Korea. The combined shares of these five countries accounted for 73.1% of total PCT filings.25 Furthermore, the top five
countries for originating PCT applications in the field of pharmaceuticals in
2011 were the United States, Japan, Germany, France and the Republic of
The market for pharmaceuticals is further considered, and the number of
national phase entries per relevant patent office is analyzed as an indicator
of the commercial attractiveness of the country or region. The top five patent
offices showing the highest number of national phase entries in 2011 were
the offices of the United States, Europe, China, Japan and Republic of Korea.27 In addition, the actual size of market is considered. According to one
report on the pharmaceutical industry, the North American market was the
world’s largest with a 41.8% share, followed by Europe, accounting for
26.8%, and Japan for 12%, in 2011.28 In addition, the most highly developed
pharmaceutical markets in 2011 were reported to be the United States, Japan,
Germany, France, Italy, Spain, Canada, the United Kingdom and the Republic of Korea.29
Thus, based on the patenting activities and the importance of the pharmaceutical markets, Germany, the United Kingdom, the United States, and
Korea were selected as representative. In addition, the practice before the
European Patent Office (“EPO”) will be analyzed.
WIPO, 2012, 26-27.
WIPO, 2012, 44.
WIPO, 2012, 55.
European Federation of Pharmaceutical Industries and Associations (“EFPIA”),
29 IMAP, 2012, 16.
This paper takes into account the fact that there are other regimes supporting the progress and development of pharmaceutical innovation and securing sustainable access to medicines for the public. Examples would be
regulatory exclusivities in pharmaceutical law, prizes, or government funding for research in this area. Nevertheless, this paper will focus exclusively
on the patent system. Furthermore, while issues in the area of competition
law are not treated exhaustively, such issues will be discussed to the extent
that second generation inventions are involved.
II. PHARMACEUTICAL INVENTIONS, INNOVATIONS &
Most inventions have been developed based on previous inventions.30 This
has never been so accentuated as in the current evolution of high technologies.31 The cumulative nature of technological innovation poses a problem
for operating an optimal patent system,32 namely, today’s patent can hinder
tomorrow’s innovations.33 Thus, every potential inventor can be a potential
infringer,34 although this is not always immediately obvious.35
The literature on law, economics or patents is inconsistent in its use of
terms to describe previous inventions and subsequent inventions.36 Representative terms would be first/second generation, earlier/later inventions,37
30 E.g., “[d]warfs standing on the shoulders of giants,” in Latin: nanos gigantium
hemeris insidentes, Wikipedia, available at: http://en.wikipedia.org/wiki/ Standing_on_the_shoulders_of_giants; it is a Western metaphor meaning “one who develops future intellectual pursuits by understanding the research and works created
by notable thinkers of the past. (Last accessed on December 20, 2013).
31 Scherer/Ross, 1990, 264 (noting “growth of technology is cumulative and richly
interactive”); Scotchmer, 5 J. Econ. Perspect. 29 (1991) (stressing the importance of
the cumulative nature of innovation); Arrow, 1962, 616-619 (noting that today’s
invention is the input for future innovations); Vossius, 59 J. Pat. Off. Soc'y 180, 180
(1977) (noting “[a] completely pioneer invention is a rare occurrence in today’s
32 Scotchmer, 5 J. Econ. Perspect. 29, 30 (1991).
33 Luski/Wettstein, 1 Probl. Perspect. Manage. 31, 31 (2004).
34 Merges/Nelson, 90 Colum. L. Rev. 839, 916 (1990); O’Donoghue, 29 RAND J.
Econ. 654, 655 (1998); Heller/Eisenberg, 280 Science 698 (1998) (noting strong IP
right would rather impede research than promote it).
35 Scotchmer, 27 RAND J. Econ. 322, 329 (1996).
36 Cf. Janis, 40 Harv. Int’l L. J. 151, 151-152 (1999) (using “second tier patent” as a
generic label encompassing utility models, petty patents, and so on which is different
from the regular patent system.).
37 Gallini/Scotchmer, 2002, 65.
primary/secondary patents, basic inventions/applications,38 pioneer/subsequent patents,39 broad/subservient patents,40 dominant/subservient
patents,41 and basic/future inventions. 42 Similarly, terms that refer to the
inventors of both inventions include first/second inventors, initial/later inventors, or original developer/subsequent improvers.43 The earliest invention or patent has been referred to as the original invention, the breakthrough
invention, the initial patent, 44 the originating patent, or the parent patent.
Another comparable notion is upstream invention and downstream invention.45 The terms will be disambiguated in the following sections, and “basic
invention” and “second generation invention” will be adhered to in this paper.
An invention that is a breakthrough or pioneering invention, which provides
the roots and routes for future innovations, is often called a basic invention.46 In contrast to basic inventions, second generation inventions are generally improvements and applications of the basic inventions. A class of
invention called a “selection invention” is particularly relevant in pharmaceutical and chemical inventions and is discussed in detail below.
38 Matutes/Regibeau/Rockett, 27 RAND J. Econ. 60, 60-61 (1996); cf. basic/applied
research: Eisenberg, 56 U. Chi. L. Rev. 1017, 1017 (1989). (basic research which
directed solely toward expanding human knowledge vs applied research which directed toward solving practical problems),.
39 Merges/Nelson, 25 J. Econ. Behav. Organ. 1, 13 (1994).
40 Merges/Nelson, 25 J. Econ. Behav. Organ. 1, 21 (1994).
41 Chang, 26 RAND J. Econ. 34, 49 (1995).
42 Friebel et al., 2006, 26.
43 Lemley, 75 Tex. L. Rev. 989 (1997).
44 Matutes/Regibeau/Rockett, 27 RAND J. Econ. 60, 60-61 (1996).
45 Heller/Eisenberg, 280 Science 698 (1998).
46 Friebel et al., 2006, 26-29.
II. PHARMACEUTICAL INVENTIONS, INNOVATIONS & PRODUCTS
An improvement invention refers to an invention that essentially builds upon
a basic invention,47 or to an invention that could not have occurred until the
basic invention was available.48 Thus, improvement inventions can only occur in the wake of basic inventions are the outcome of research activities
directed to improvements or applications of previous inventions.49 In the
context of patent law, an improvement invention may be referred to as a
dependent invention, which may not be used without infringing the basic
patent, until it expires.50 Improvement inventions are ubiquitous as most
technological progress builds upon previous inventions.51 They are most
commonly found in the software industry, where incremental improvement
is endemic for various reasons.52
Improvements can also be achieved through selection in some technical
fields. Although it is difficult to find a statutory definition, a “selection invention” is generally understood as an invention that has a particular concept
which is selected from a prior broader or larger generic concept of an invention and that presents superior or advantageous properties compared to
47 Bessen/Maskin, 40 RAND J. Econ. 611, 612 (2009) (improvement inventions as an
example of sequential inventions).
48 Denicolò/Zanchettin, 20 Int'l. J. Indus. Org. 801, 804 (2002).
49 Gallini/Scotchmer, 2002, 65.
50 See e.g., Korean Patent Act, Art. 98 (Relation to Patented Invention etc. of Another
Person) Jackson, 9 J. Tech. L. & Pol’y, 117, 119 (2004); Gallini/Scotchmer, 2002,
51 CFMT, Inc. v. Yieldup Intern. Corp., 349 F.3d 1333, 1340 (Fed. Cir. 2003).
52 See in general, Burk/Lemley, 89 Va. L. Rev. 1575, 1620-24 (2003).
the broader concept, which were not disclosed in the prior art.53 It is an
invention that falls under the scope of the prior art disclosure, but has not
been individually disclosed in the prior art.54 A patent document from which
a selection invention is derived is referred to as a dominant patent.55Selection
inventions are also referred to as “improvement inventions” since they usually provide some unexpected results or benefits, which also help to overcome challenges to patentability based on assertions of the obviousness
thereof.56 Selection inventions can be generally categorized into three types,
according to the selection of an individual element, sub-sets, or sub-ranges
Selection inventions can be found in various technical fields. When a class
of a mechanical invention is a group of structural elements, one of which is
53 Bayer/E-Isomers of N-alpha-(2-Cyan-2-alkoximino-acetyl)-amino acid derivatives
and peptides, T12/90 (1990), point 2.7 (stated “the term ‘selection’ is the singling
out of a narrow portion from a relatively broad scope immanent.”, quoting Bayer/
Diastereomer, T 12/81 OJ EPO 1982, 296, 301); see also Nastelski, Review of Intellectual Property and Competition Law (“IIC”) 1972, 267, 291 (describing a selection invention as an invention providing a particular representative (or a subgroup)
of already disclosed product group by the first inventor which showing particularly
distinguishing effects when used as indicated by the first inventor or has the possibility of a different type of use.); see also Vossius, Gewerblicher Rechtsschutz Und
Urheberrecht (“GRUR”) 1976, 165, 165 (describing that a chemical selection exists
when an second inventor has select one or more representatives from a group of
substances, one component from a mixture, or a narrower range of alloy components
from a [broader] alloy area.); see also Grubb/Thomsen, 2010, 232 (describing selection invention as an invention that is the selection of a particular compound or
relatively small group of compounds from the larger group previously disclosed in
broader terms, and the compound or the small group of compounds are individually
new but fall within an earlier discloser.); see also, Blanco White, 1983, 104-106
(noting “[a] special case arises where, although the subject-matter of the claim concerned has never specifically been disclosed before, there has been a prior publication
covering that subject-matter in general terms; or (in other words) there is an earlier
document which “contains a broad description or claim covering the whole area
within which the subsequent selection falls.”).
54 See, e.g., Agranat/Caner, 4 Drug Discov. Today 313, 313-314 (1999).
55 Miller/Evans, 2010, 14-15.
56 Miller/Evans, 2010, 14, fn12.
57 Guidelines for Examination in the European Patent Office, June 2012, (herein after
“EPO Examination Guidelines”), G-VI, 8 (“Selection inventions deal with the selection of individual elements, sub-sets, or sub-ranges, which have not been explicitly
mentioned, within a larger known set or range”).
selected as being particularly useful, it is a selection invention.58 Examples
of such inventions can be found in the field of alloys, where a specific range
of compositions are chosen, or in the field of engineering and manufacturing,
where specific operating conditions are selected. Selection inventions are
typically encountered in pharmaceutical and chemical technologies. In the
field of chemistry, any competent researcher who invents one compound and
discovers its usefulness, can enumerate derivatives that may be equally useful, even though it remains beyond the power of the researcher to manufacture more than a few of those compounds at the time of filing.59
Although second generation patents can be found in all technological
fields, this thesis will focus on those in the pharmaceutical industry. Pharmaceutical selection inventions could be a selection of a compound or of
compounds, the use of a compound, a chemical process, dimensions, a range
of values, parameters, crystal forms,60 nanoscales, dosage regimes, and so
on.61 A more extreme case of a selection invention would be claiming a
known compound with a very high level of purity.62
Categories of pharmaceutical patents are not generally different from patents
in different fields of technology. Compounds and processes can be subject
to patent protection, but a new use of a known compound can be patented
depending on the particular jurisdiction. Typical pharmaceutical patents can
protect active ingredients and their metabolites, hydrates, salts, esters, intermediates and the like combinations of more than two active ingredients,
methods of manufacturing the active ingredient and its intermediates, different methods or uses of medical treatment of known medications (includ-
58 Grubb/Thomsen, 2010, 64.
59 See e.g., Blanco White, 1983, 104.
60 Smith Kline & French Laboratories v. Evans Medical [1989] Fleet Street Report
(“F.S.R.”) 561,563 (Aldous J. noted “the polymorph patent is said to be a selection
patent, in that the [basic] patent disclosed Cimetidine makes no mention that it can
exist in A, B or C [crystal] form.”[Emphasis added]).
61 See generally Miller/Evans, 2010, 14-15; for the dosage regime, refer Abbott Respiratory/Dosage Regime, G 2/08 (2010), para 6.3.
62 Grubb/Thomsen, 2010, 237.
ing dosage regimes), and formulations of a drug, including new dosage
forms, devices such as patches, drug delivery systems.63 These inventions
and patents will be explained in detail in chapter II.C. The protection covers
various aspects of pharmaceutical innovation. It is possible to form a hierarchy among compound, use or process claims of patents based on the scope
of protection that the patents provide.
a) Product invention and the absolute character of its protection
A claim to structures rewards patentees with exclusive rights to all properties
and manufacturing processes thereof, regardless of whether properties or
processes discovered subsequently were acknowledged by the applicant at
the time of filing. If the product is a compound, this is called “absolute compound protection”,64 which differs from “purpose-limited protection”, where
the patent can cover only the purpose of the compound as indicated in the
patent application.65 Regarding the broader scope of the exclusivity of the
product, Jacob LJ noted:
“[A]ny product claim is apt to give the patentee "more than he has invented" –
and in two ways. Firstly such a claim will have the effect of covering all ways
of making the product including ways which may be inventive and quite different from the patentee's route. Secondly it will give him a monopoly over all
uses of the patented compound, including uses he has never thought of.”66
Although there are arguments for purpose-limited protection,67 the Federal
Supreme Court of Germany (“BGH”) clearly addressed the effect of absolute
chemical protection on the pharmaceutical industry. In the Klinische Ver63 Voet, 2011, 59.
64 Kraßer, 2009, 130 et seqq.; Bacher/Melullis in: Benkard et al., 2006, § 1 Rdns 12
and 16; Deutsches Patent- und Markenamt (“DPMA”), 2008, 29; Merges/Duffy,
2011, 393; cf. Case C-428/08, Monsanto Technology LLC v. Cefetra BV and
Others, E.C.R. 2010, I-06765 (holding the Art. 9 of Council Directive 98/44/EC of
6 July 1998 on the legal protection of biotechnological inventions did not confer
absolute protection to the patented product, i.e. a patented DNA sequence, when it
was contained in soy meal, where it did not perform the function for which it was
protected); see also Kilger/Feldges/Jaenichen, 87 J. Pat. & Trademark Off. Soc'y
569 (2005) (for the German perspectives of purpose-limited compound protection
for the sequences of human genes in German Patent Act ).
65 DPMA, 2008, 29.
66 Lundbeck v. Generics Ltd. [2008] EWCA Civ 311, para 54.
67 Domeij, 2000, 85 et seqq.; Merges/Duffy, 2011, 399.
suche case, the BGH held that as a consequence of dependent patents, the
product patent kept its economic value, since in order to exploit the use
patent, the later patentee would need the approval of the product patentee.
Accordingly, the earlier patent retained its full validity with respect to third
parties regarding the use protected by the later patent. 68 This increases the
value of the product patent and allows the holder to exploit the exclusive
right of the earlier patent.69
The hierarchy of pharmaceutical patents can be established according to the
scope of patents. The most valuable is a compound patent, because it affords
absolute compound protection in that it covers a product independent of its
formulation, manufacture, or use and without regard to how much of the
patented compound it contains, as long as it contains an active ingredient
covered by the compound patent.70
A medical use patent covers the (un)approved second or further medical
use of a previously patented compound with a first medical use.71 Since this
type of patent also covers any product claiming the protected medical use,
it is the second most valuable patent. However, given the problems of enforcement associated with this type of patent, it is not easy to encourage
pharmaceutical manufacturers to invest their R&D resources in this new use
of old drugs. 72 Induced infringement can be found only when a drug product
has an instruction for the other’s patent-protected medical use. The off-label
68 BGH/Klinische Versuche (Clinical Trials), GRUR 1996, 109, 115. Since official
translations of materials in language other than English are not always available, the
author did it by consulting other’s translation or by herself. For accuracy, please
check its original version.
69 BGH/Klinische Versuche (Clinical Trials), GRUR 1996, 109, 115.
70 Nastelski, IIC 1972, 267, 271-72 (noting an unlimited protection provided to the
patented product which has no definite external form, and only the patentee is authorized to make the product or the chemical substance commercially, to bring it into
commerce, to offer it for sale or to use it.); Grubb/Thomsen, 2010, 77’ Voet, 2011,
60; SmithKline Beecham Corp. v. Apotex Corp., 403 F.3d 1331, 1341-42 (Fed. Cir.
2005) (holding no matter how small the amount is, as long as the product contains a
compound protected by a patent, it infringes the compound patent.).
71 Voet, 2011, 60.
72 Eisenberg, 5 Yale J. Health Pol’y L. & Ethics 717, 724-25 (2005).
use by the doctors73 - the prescription of a medication in a manner different
from that approved by regulatory authorities - can be a serious problem for
the patentee of a new medical use seeking to enforce his patent right.
The remaining types of patents can be ranked below the previous two.
The scope of these patents is normally narrow, and sometimes excessively
specific. Consider, for example, the scope of a patent covering a product
manufacturing process. As the Imperial Supreme Court of Germany held in
1888, the protection of a manufacturing process included those products
made directly by the protected process.74 However, it cannot prevent anyone
from making the same products by a completely different method, if
any.75 In addition, a patent might be less useful for a process than a product,
because it is more difficult to prove patent infringement for a process.76 A
process patent can be enforceable when the use of that process invention can
be determined from the end-product or from other evidence, such as trace
impurities.77 For this reason, TRIPS requires that the onus of proof is reversed and imposed upon the alleged infringer of the patented process if the
compound is novel.78
This narrow but overly specific claim often makes it very difficult to design around the patent. A patent with a very narrow scope of protection can
therefore be extremely valuable in preventing the market entry of generic
versions.79 As patents for compounds, new uses and processes offer different
strategic values to the patent holder, industries often recognize the hierarchical differences and strategically seek protection accordingly.
73 Stafford, 358 N. Engl. J. Med., 1427 (2008).
74 Methylenblau, 22 Reichsgericht in Zivilsachen 8 (holding “the product manufactured
by means of the (protected) process does not fall outside of subject-matter of invention, and constitutes the end-point as characterized by patent law. Thus the process
comprises the product manufactured by the by said process as part of the subjectmatter of the invention.”).
75 Grubb/Thomsen, 2010, 77-78; Nastelski, IIC 1972, 267, 272 (a third party patent on
method of preparation or forms of use of the product is dependent on the product
patent, and he cannot practice his patent commercially without the approval of the
holder of the product patent.).
76 Cohen/Nelson/Walsh, 2000, 10.
77 Grubb/Thomsen, 2010, 245.
78 TRIPS Art. 34 (Process Patents: Burden of Proof), In other words, the court would
assume that it has been produced by the patented process unless the alleged infringer
would prove otherwise.
79 See subsection V.D.3.d).
The pharmaceutical industry has been referred to as one of the best examples
of an industry for which patents are regarded as socially desirable, since
incentives arising from patents appear to be prerequisites for the vast majority of pharmaceutical innovations. If there is an invention that cannot be
categorized as such, however, its protection might be unjustified. Therefore,
it will be helpful to define what pharmaceutical innovation is and what it is
The distinction between invention and innovation returns us to Schumpeter’s
Theory of Economic Development.80 Schumpeter distinguishes the act of
innovation, which is a new combination of known and/or unknown means
of production, from the act of invention, which creates a new means of production.81 He further argues that invention of itself does not produce an economically relevant effect.82 In contrast, innovation brings incessant changes
in economics through a so-called “process of creative destruction.”83 Eisenberg notes that an innovation may be defined as putting existing inventions
to practical use.84 Svatos argues that the innovation is the final product that
appears on the market and is different from the invention for which a patent
was granted.85 He further argues that patents therefore stimulate a combi-
80 Nelson/Winter, 1982, 263.
81 Schumpeter, 1964, 100-101 (Innovation comprises: (1) the introduction of a new
good or of a new quality of a good; (2) the introduction of a new method of production
which includes a new way of handling a commodity commercially; (3) the opening
of a new market for the good, irrespective of the prior existence of the market; (4)
the conquest of a new source of supply of raw materials or half-manufactured goods;
(5) the carrying out of the new organization of any industry, such as the creation of
a monopoly position or the breaking up of a monopoly position.); Schumpeter, 1942,
139-140 (mentioning the competition of these types of innovations); He distinguished these two without mentioning “innovation,” which appears in his later publication, Business Cycle, 1939, 84).
82 Schumpeter, 1939, 80.
83 Schumpeter, 1942, 137-38.
84 See e.g., Eisenberg, 56 U. Chi. L. Rev. 1017, 1036-37 (1989).
85 Svatos, 13 Soc. Philos. Policy 113, 122 (1996).
nation of invention and marketing skill.86 Merges similarly holds that “[a]n
invention refers to the practical implementation of the inventor’s idea. […]
An innovation is the ‘debugged’ and functional version of the invention: the
version first offered for sale.”87 He further contends that the innovation
significantly differs from the invention because of the changes necessary to
turn the invention into a commercial product.88 While the distinction between invention and innovation is somewhat simplified, since the process
of development is a continuum,89 the two ends, i.e. invention and innovation
are relatively easy to distinguish.
Chronologically, once an invention has been made, substantial investment
is often needed to ready the invention for the market.90 Such investment can
involve the construction of a new plant or equipment, promotion or advertisement.91 Indeed, innovation, in conjunction with investment and development, is more sensitive to economic variables than invention.92 Converting inventions into innovations is a core feature of technological
progress.93
Every product available on the pharmaceutical market which is developed
from an invention can be considered an innovation. However, the significance of an innovation can vary substantially between a second generation
product and new medical entities (“NMEs”).94 In other words, for some
products, such as NMEs, substantial investment in preclinical and clinical
trials to meet regulatory requirements must be made to bring the invention
to market, in contrast to second generation products. More importantly,
NMEs are basic inventions that bring constant changes in market economics
86 Svatos, 13 Soc. Philos. Policy 113, 122 (1996).
87 Merges, 76 Cal. L. R. 803, 807 (1988).
88 Merges, 76 Cal. L. R. 803, 807 (1988) (also noted this distinction between invention
and innovation has been criticized as a simplified dualism by some economists, who
argue that the process of development is actually much more of a continuum).
89 Nelson/Winter, 1982, 263-64; Merges, 76 Cal. L. R. 803, 807 (1988).
90 See e.g., Eisenberg, 56 U. Chi. L. Rev. 1017, 1037 (1989).
91 See e.g., Eisenberg, 56 U. Chi. L. Rev. 1017, 1037 (1989).
92 Scherer, 1984, 26.
93 Chandy, et al., 43 J. Marketing Res. 494 (2006).
94 See subsection II.D.1.
through various second generation products. Thus, NMEs are the really
valuable innovations in the pharmaceutical industry. In this context, we must
question whether current patent protection for pharmaceuticals incentivizes
R&D of truly valuable innovation.
As noted above, some evidence in the cases involving second generation
inventions is complicated.95 After a basic research period, leading to the
identification of a “lead compound”, the typical procedure in developing a
medicine can be briefly summarised as follows: “With the selection of the
lead compound, the chemist and biologist embark on an extensive program
to improve its potency, the specificity of biological effect with concomitant
reduction in toxicity, oral absorption, duration of action, metabolic profile
and pharmacokinetic pattern. This typically involves extensive structureactivity relationship (“SAR”) studies.”96
The lead compound or the lead compound series are to be patentable,97
and generally, the outputs from subsequent developments are also the objects
of patent protections. Using the concept of basic and second generation inventions, the lead compound will be the basic invention, and the following
inventions will be second generation inventions. The second generation inventions from the lead compound can be salts, esters, ethers, polymorphs,
metabolites, pure form, particle size, isomers, mixtures of isomers, com-
95 Laboratoires Servier v. Apotex, [2008] EWHC Civ 445, para 41.
96 deStevens, 1990, 266; Domeij, 2000, 26.
97 deStevens, 1990, 266; Domeij, 2000, 26.
plexes, combinations and other derivatives of known substance, and the like.
These inventions are eligible for patent protection in most jurisdictions.98
Beyond second generation, there can be (n+2) generation inventions, such
as, a new crystal form of a known salt of a basic medication,99 a new use of
a known metabolite, 100 solvates or hydrates of a known salt form, and the
like. However, all of these types of invention will be comprehensively referred to as second generation inventions in this dissertation since all such
inventions arise subsequent to the basic invention.
The relevant inventions, patents and types of claims for second generation
inventions are explained briefly here, according to the three types, i.e. product patents, use patents, and process patents.
In the U.S., the United States Patent and Trademark Office (“USPTO”) defines a species selection invention as an invention that is a different embodiment or a species that could fall within the scope of a generic invention.101 Further, a generic invention should require no material element ad-
98 In some jurisdictions, such as India, these cannot be patent eligible if these second
generation inventions are regarded as the mere discoveries of new properties or new
uses for a known substance. See Sec. 3(d) of Indian Patents Act, 1970 (“The mere
discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance or the mere discovery of any
process, machine or apparatus unless such known process results in a new product
or employs at least one new reactant.”); see further Manual of Patent Office Practice
and Procedure in India, 08.03.05.04 (Ver. 01.11, as modified on March 22, 2011)
(“Explanation: For the purposes of this clause, salts, esters, ethers, polymorphs,
metabolites, pure form, particle size, isomers, mixtures of isomers, complexes,
combinations and other derivatives of known substance shall be considered to be
the same substance, unless they differ significantly in properties with regard to
efficacy.” [Emphasis added]).
99 E.g., Laboratoires Servier v. Apotex, [2008] EWHC Civ 445 (crystalline forms of
tert-butylamine salt of perindopril were claimed).
100 E.g., Teva v. Merrell [2007] EWHC 2276 (Ch) (the new uses of a metabolite of a
known substance were claimed).
101 U.S. Patent & Trademark Office, Manual of Patent Examining Procedure (8th ed
2010) (“MPEP”), § 806.04; see also Chisum, 2012, § 12.03[3].
ditional to those required by a species invention and each species invention
must require all of the limitations of the generic invention.102 Similarly, in
Europe, EPO considers that a selection invention deals with the selection of
individual elements, which have not been explicitly mentioned within a
larger known set as a selection invention.103
Markush type claim
The use of a Markush type claim104 was first reported in a U.S. case involving
Eugene Markush, who filed a patent application in 1924 for pyrazolone dyes
where a generic structure was claimed.105 This type of claim is used when
no generic term describes the desired individual species that share common
significant features, similar properties or activities, or at least one common
function, or which have an equivalent basis for categorization in the same
group.106 The scope of this kind of claim in chemistry is limited by the compounds that can be manufactured by combining various alternatives mentioned for the different positions in the formula. One famous example is a
claim in respect of a cheese cigarette filter, which reads: “A cigarette filter
according to claim1 in which the cheese comprises grated particles of cheese
selected from a group comprising Parmesan, Romano, Swiss and Cheddar
cheeses.”107
Although there are some downsides to using it,108 this type of claim is
very popular and common as it has several advantages. It may offer broader
protection for the patentee and it is easier to file as one multinational patent
102 MPEP § 806.04 (d).
103 EPO Examination Guidelines”), G-VI, 8.
104 Markush type claims are one of the formats of claiming, such as Jepson type claims,
product-by-process claims, means-plus-function claims, step-plus-function claims,
105 Fitt, 20 Biotechnol. Law Rep. 17, 18 (2010).
106 See e.g., Durham, 1999, 57; Valance, 1 J. Chemical Documentation, 87, 87-88
(1961); Miller/Evans, 2010, 146-48.
107 U.S. Patent No. 3,234,948 (February 15, 1966, under the title of “Cheese-Filter
Cigarette”).
108 These disadvantages could be the difficulty to search through the normal database,
increased prosecution time and examination errors, undermining their status as the
prior arts, and being unclear in their scope of protection, see e.g. Brown, 31 J. Chem.
Inf. Comp. Sci. 2, 3-4 (1991) (also noting “it is unreasonable to expect that so many
compounds will exhibit activity similar to the activity shown by substances for
which practical data is supplied.”).
application rather than several separate patent applications. Furthermore, it
can provide the licensor with a stronger basis for cross-licensing agreements
with licensees, who own improvement (selection) patents that use the licensor’s invention.109
The following is an example of a Markush type claim in U.S. Patent No.
4,115,574,110 which can also be referred to as a “genus” claim.
109 Brown, 31 J. Chem. Inf. Comp. Sci. 2, 2-3 (1991); see also Miller/Evans, 2010,
146-48 (noting “the power of Markush claiming is most evident when combinations
of Markush groups are all used within the same claim. The number of possible
embodiments of the invention multiplies in a combinatorial fashion not practically
reproduced by drawing all of the embodiments separately.”).
110 U.S. Patent No. 4,115,574 (September 19, 1978, under the title of “Benzodiazepine
derivatives”), this claim was simpler than the correspondent claim of a U.K. patent,
and is a good example of a basic invention.
A species claim
About 15 years after U.S. Patent No. 4,115,574 was granted, a combination
of the optional variables mentioned above, such as R1, R2, and the substitution in the thiophene ring, was filed by the same applicant as follows:111
This is referred to as a “species” claim because it is a claim directed to a
specific species from a genus.
The compound named above has the following chemical formula:
One can arrive at this formula by selecting the underlined groups from the
above “genus” claim 1 of the U.S. Patent, i.e., C1 alkyl(-CH3) group for
R6; hydrogens for both R1 and R2; and the thiophen ring, which is substituted
by a C1 alkyl (-CH3) group in the 2-position. This compound was later named
“Olanzapine”. It is evident that the structure of the compound itself was
already disclosed in the prior art as one of the possible combinations, although it was not disclosed specifically. This kind of invention, like the
invention of “Olanzapine” is achieved through a specific and particular selection from a group disclosed in the prior art, and thus is referred to as a
species selection invention.
111 U.S. Patent No. 5,229,382 (July 20, 1993, under the title of “2-methyl-thieno-benzodiazepine”).
Organic chemical compounds contain carbon atoms (“C”s) which are covalently bonded to other atoms. Each carbon atom normally forms four
bonds.112 If a carbon atom has four single bonds, the four other atoms around
the carbon atom usually form a tetrahedral spatial arrangement (See Figure
1).113 Compounds with the same molecular formula or atomic composition,
but with a different spatial arrangement are called stereoisomers. Optical
isomers114 are one type of stereoisomers and can be classified further into
enantiomers and diastereomers. 115 Enantiomers are a pair of stereoisomers
that differ only in their spatial arrangements and have at least one “stereocenter,” which is a carbon atom (C) with four different groups attached.116
The spatial structure is the nonsuperimposable mirror image of the other,
designated “chiral,” which is derived from the Greek cheir, meaning
“hand.”117 Its three dimensional molecular structure is depicted with wedges
and dashes and the enantiomers of the amino acid alanine are presented in
Figure 1 as an example. Various naming conventions are used to distinguish
between the enantiomers, such as “(+)” or “(-)”, “(d)” or “(l)”, “(D)” or “(L)”,
112 William 1999, 18.
113 Macomber, 1996, 97 (Further noting the study of this kind of three-dimensional
structure of molecule and the spatial relationship among the atoms is called stereochemistry. Macomber, 1996, 189).
114 This is because a pure enantiomer rotates plane-polarized light in a particular direction, such as clockwise, or counterclockwise.
115 “Diastereomers” are the optical isomers which occur when there are more than one
chiral centers in the compound and which are non-superimposable, non-mirror images of others. And “epimers” are diastereomers that differ in configuration of only
one stereogenic center.
116 For example, two different mirror-imaged forms are a “right handed form” and a
“left-handed form.” In Figure 5, the carbon atom in the center is a stereocenter to
which four different groups has been attached, namely –COOH, -NH2, -CH3, and
H. The solid wedge is used to indicate that the methyl group (–CH3) is projecting
out of the page (toward to the viewer), while the hashed line indicates that the
hydrogen atom (H) is behind the page (away from the viewer). Some compounds
having more than two chiral centers result in multiple possible three-dimensional
arrangements which are known as diastereomers.
117 See generally William 1999, 612-613; see also Ortho-McNeil Pharm., Inc. v. Mylan
Labs., Inc., 348 F. Supp. 2d 713, 720 (N.D.W.Va. 2004), aff’d, 161 Fed.Appx. 944
(these kinds enantiomeric compounds are thus often analogized to a person’s left
and right hands).
and “(R)” or “(S)”,118 and for the racemates, “(±)” or “(dl)” or (RS) are
used.119 A “racemic mixture” or a “racemate” refers to an equal mixture of
R and S enantiomers.120
Figure 1: Example of an enantiomer - an amino acid, alanine.
Research into drug chirality has been underway since 1874.121 Although
enantiomers have nearly identical physical properties, they often have different activities and side effect profiles. This has long been recognized both
by academia, by industry and by regulatory authorities.122 These are the
medications that are separated from the racemate mixtures; the components
obtained are responsible for beneficial pharmacological action, while other
components that are usually responsible for side effects are excluded.123
More than half of the drugs listed in the Pharmacopoeia124 are chiral
118 These systems are not interchangeable.
119 Unless otherwise indicated, R/S system is used in this paper.
120 Racemates are normally produced through a chemical reaction which prepares a
chiral compound from an achiral compound in normal conditions.
121 Mansfield/Henry/Tonkin, 43 Clin. Pharmacokinet. 287, 287 (2004).
122 Caldwell, 16 Hum. Psychopharm. S67, S67, S70 (2001) (noting the existence of
optical enantiomer was recognized in 1848, and the research into enantiomers has
become to be more active since 1980s according to the technical progresses on
separation, analysis, and production on an industrial scale of enantiomers); Darrow, 2 Stan. Tech. L. Rev. 1, para 7 (2007) (noting enantiomers can exhibit substantially different biological, pharmacological, or toxicological activity).
123 The National Institute for Health Care Management Research and Educational
Foundation (“NIHCM”), 2002, 5.
124 Pharmacopoeia is a book containing directions for the identification of samples
and the preparation of compound medicines, and published by the authority of a
government or a medical or pharmaceutical society.
molecules,125 including many of the world’s best-selling products, such as
Lipitor®, Plavix® and Nexium®.126 Other well-known chiral drugs include
Ibuprofen, Claritin®, Allegra®, Prilosec®, Zyrtec®, and even thalidomide.127
Enantiomer patents claim selected individual enantiomers of racemic
mixtures that were previously disclosed in the prior art, mainly, their basic
patents. For this reason, an enantiomer patent may be categorized as a selection invention. The importance of enantiomer patents is reflected in the
“patent cliff”128 threat by the expiration of enantiomer patents on blockbuster
chiral drugs.129 Knowledge of the structure of one enantiomer, or of a racemate, necessarily furnishes a person skilled in the art with knowledge of the
structure of the other or both enantiomers.130 This leads to a fundamental
inquiry regarding the novelty or obviousness of enantiomer inventions.131
The validity of enantiomer patents has often been challenged, mostly by
generic pharmaceutical companies on the grounds of lack of novelty, lack
of inventive step, lack of utility, double patenting, and insufficiency of disclosure.132
125 Ariëns/Wuis, 42 Clin. Pharmacol. Ther.361, 361-62 (1987) (showing 949 out of
1675 drugs listed in the Pharmacopoeia were chiral, 461 of the 469 natural or semisynthetic chiral products (98.3%) are single enantiomers, but only 58 of 480 synthetic chiral products (12.1%) are single enantiomers).
126 IMS Health, 2010 (the top three best-selling global drugs from 2007 to 2009 and
top three out of top four best-selling global drugs in 2010 are single enantiomers).
127 Darrow, 2 Stan. Tech. L. Rev. 1, para 2 (2007).
128 See chapter III.B.3; See also Mansell, 1 Scrip Executive Briefing 1, 1–16, (2008)
(explaining that “patent cliff” is a term for the loss of revenue which occurs when
the monopoly granted by patents is lost and the generic versions of drugs enter into
the market. It is expected that the patent cliff reaches its peak in 2010-2011 as
patents of many blockbusters including SanofiAventis‘ Clopidogrel, Pfizer’s Atorvastatin, and others expire.).
129 Agranat/Wainschtein, 15 Drug Discov. Today, 163, 169 (2010).
130 Darrow, 2 Stan. Tech. L. Rev. 1, paras 5-6 (2007).
131 See e.g., Darrow, 2 Stan. Tech. L. Rev. 1, paras 5-6 (2007).
132 Agranat/Wainschtein, 15 Drug Discov. Today, 163, 163 (2010); Darrow, 2 Stan.
Tech. L. Rev. 1, para 3 (2007) (noting the patentability of chiral molecules has taken
on increased significance and is a subject of litigation.).
Polymorphs are different crystalline forms of the same compound. Polymorphism denotes the ability of a material to exist in more than one form or
crystal structure. It was discovered in the 19th century that many substances
could be crystallized into solids with different melting points and crystal
habits.133 The molecules in the crystalline form are arranged in an organized
pattern called a “lattice”; which is different from an amorphous form, in
which the molecules are randomly distributed.134 Among the substances that
exist in crystalline form, some can be in one crystalline form, which is referred to as a monomorphic substance, for example, wax or common window
glass. Others that exist in more than one organized pattern, such as the cocoa
butter in chocolate,135 are referred to as polymorphs. According to the shape
of the crystals, polymorphs can often exhibit different physico-chemical
properties, such as stability, solubility, hygroscopicity,136 and hardness,137
although their chemical composition is identical in all forms. Examples
among drugs include Ranitidine (Zantac®), Paroxetine (Deroxat®), and
Cefnidir (Omnicef ®). A patent for a polymorph can be extremely valuable
when the patent covers the most stable form at ambient conditions, considering that less stable forms may spontaneously convert to the most stable
Co-crystals such as solvates or hydrates are called pseudo-polymorphs.
If the substances are dissolved in a solution, they are normally recovered by
evaporation of the solvent. 138 If this evaporation is conducted with carefully
controlled parameters (e.g. “in water solvent,” such as humidity, or drying /
evaporating), some substances can retain a certain number of water
133 Brittain, 2009, 1.
134 Giron, 73 J. Thermal Analysis & Calorimetry 441, 441-42 (2003).
135 Cacao butter could exist in six different crystalline forms; the most thermodynamically stable form (form VI) has a dull surface and soft texture; however, form V is
the most appreciated by consumer and shows the crispy hardness and glossy surface.
In order to make chocolates crystallize exclusively in the preferable form (form V),
the crystallization process must be controlled by a sophisticated temperature
regime, see in general, Von der Freien, 39 Chemie in Unserer Zeit, 416, 423 (2005).
136 “Hygroscopicity” means the readiness of a substance to absorb moisture from the
137 Brittain, 2009, 2-3.
138 Seager/Slabaugh, 2010, 279.
molecules as part of the solid crystalline structure.139 This type of crystalline
form is called a “hydrate.”140 If the same procedures are followed “in a solvent other than water,” the resulting crystalline form is called a “solvate”.141
Claims to polymorphs can be suitably drafted by using their physicochemical parameters, which are determined by Single crystal X-ray diffraction (SXD), X-ray powder diffraction (XRPD), Infrared(IR)- or Raman
spectroscopy, solid state 13C-Nuclear Magnetic Resonance (NMR) spectroscopy, and the like. Thus, in a properly drafted claim for polymorphs,
many figures are listed.142
Metabolites are substances produced in the body through the metabolism of
other substances and in some cases are responsible for the pharmacological
effects observed. The metabolism of substances absorbed in the body makes
the ingested substance more water-soluble and readily excreted by the kidney.143 This is one of the major pathways by which a xenobiotic substance,
such as a medication, is inactivated.144 However, it is not uncommon to find
that a metabolite itself has pharmacological effects, while the parent medication that is metabolized to it does not.
Prodrugs are bioreversible derivatives of active drugs. The active ingredients exerting the pharmacological effects are released through biotrans-
139 Seager/Slabaugh, 2010, 279.
140 Seager/Slabaugh, 2010, 279 (the retained water in the crystalline structure is called
the water of hydration, and according to the number(n) of water molecules in the
crystalline structure, they are called anhydrate (n=0), hemihydrates (n=1/2), monohydrate (n=1), dihydrate (n=2), and the like.).
141 Giron, 73 J. Thermal Analysis & Calorimetry 441, 442 (2003) (further noting
solvates were new crystalline compounds formed with the solvent, i.e. were the
combination of solvent molecules with the compound molecules).
142 Claim 1 of GB Patent No. 1,543,238 (March 28, 1979, under the title of “Polymorph
of Cimetidine”)
A substantially crystallographically pure polymorphic form of Cimetidine (Cimetidine A) which is characterised by an infra red spectrum (1% KBr disc) having
very strong, broad peaks at 1400 and 1385cm-1, a strong, sharp peak at 1205 cm-1
and a medium-sharp peak at 1155 cm-1 and having no peak at 1180 cm-1.
143 Ionescu/Caira, 2005, 3.
144 Ionescu/Caira, 2005, 41.
formation in the body. Prodrugs account for 5-7% of the drugs approved
worldwide.145 Prodrugs are chemicals with little or no pharmacological activity, but they are used to improve the efficacy of established drugs.146
Through this approach, one can improve the bioavailability of the active
drugs or make oral administration possible by overcoming poor solubility,
instability, insufficient oral absorption, local irritation, and the like.147 Examples of prodrugs include the well-known proton pump inhibitor148
Omeprazole, the ACE inhibitor149 Enalapril, and the antibiotic Hetacillin.150
Figure 2: A simplified representative illustration of the prodrug concept151
a | The drug–promoiety is the prodrug that is typically pharmacologically inactive. In
broad terms, the barrier can be thought of as any liability or limitation of a parent drug
that prevents optimal (bio)pharmaceutical or pharmacokinetic performance, and which
has to be overcome for the development of a marketable drug. The drug and promoiety
are covalently linked via bioreversible groups that are chemically or enzymatically labile,
such as those shown here. The ‘ideal’ prodrug yields the parent drug with high recovery
ratios, with the promoiety being non-toxic.
145 Rautio, et al., 7 Nat. Rev. Drug Discov. 255, 255 (2009); Oellerich/Armstrong, 47
Clin. Chem. 805, 805 (2001).
146 Ionescu/Caira, 2005, 372.
147 Rautio, et al., 7 Nat. Rev. Drug Discov. 255, 255 (2009); Oellerich/Armstrong, 47
148 A proton pump inhibitor has long-lasting effect to reduce the gastric acid production
and used for the treatment of a couple of disorders related to the over-secretion of
gastric acid, such as gastritis or peptic ulcer disease.
149 An ACE inhibitor is an “angiotensin-converting-enzyme” inhibitor and used for the
treatment of hypertension and congestive heart failure.
150 Hansen/Hirsch, 1997, 342.
151 Rautio, et al., 7 Nat. Rev. Drug Discov. 255, 256 (2009).
How substances are categorized depends on when their characteristic is
identified. Two main cases may be distinguished. If the pharmacological
effect of a medication is due to the transformation of a drug into a metabolite,
the medication may be called “a drug” and an “active metabolite”. If, on the
other hand, said effect is due to the release of the drug from a larger chemical
entity, then the medication may be called “a drug” and “a prodrug”.
Esters are chemical compounds that react with water to produce alcohols
and organic or inorganic acids. Thus, when a medication is in alcohol form,
it can be converted to its ester form via reaction with acids. In turn, when
this ester form is administered to the patient, it will be hydrolyzed in the
physiological condition to yield alcohols or acids that will have pharmacological effects.152 Aspirin, which is remarkably versatile, is an acetyl ester
of salicylic acid.153
Salts are compounds that result from the neutralization reaction of a base
and an acid. Salts are composed of positively charged ions (cations) and
negatively charged ions (anions); and can be organic or inorganic (metallic).154 Salt forms may enhance absorption in the body or the stability of
product, or they may be formulation-friendly.
A dosage form is the entity administered to patients in order that that they
receive an effective dose of a drug, such as tablets, capsules, injections, and
transdermal patches.155 These kinds of inventions may include different
strengths, an extended release form, or another delivery system such as an
inhaler, or implanted device.156 A sustained release drug delivery system,
for example, aims to maintain therapeutic blood levels of the drug for an
extended period by controlling the rate of release of the drug from the dosage
Seager/Slabaugh, 2010, 481-82.
Seager/Slabaugh, 2010, 481.
Seager/Slabaugh, 2010, 278-79.
Mahato/Narang, 2012, 15-16.
NIHCM, 2002, 5.
form.157 This can be achieved by providing multiple doses of a drug within
a single dosage form, which are released at periodic intervals, or by delaying
the timing of the first release.158 Over the past forty years, the sustained
release drug-delivery system has attracted considerable attention, since it
can reduce the frequency of dosing, increase effectiveness of the drug by
reducing the dose required, reduce the incidence of adverse effects, provide
uniform drug delivery, and simplify dosing regimes.159
A new product can be provided by combining the active ingredient of an
approved drug with one or more other active ingredients.160 As in other
technical fields, a mixture of known substances can be patentable if it meets
the requirements of patentability. For example, the combination of aspirin
and another pain-killer, such as Naproxen,161 can be created to enhance their
analgesic or anti-inflammatory therapeutic effect; or a combination of two
diuretics (amiloride and hydrochlorothiazide) with different mechanism of
action can exhibit more than additive effects. Thus, said combinations can
be claimed.162
A medical indication is a symptom or particular circumstance indicating the
advisability or necessity of a specific medical treatment or procedure. The
nature of a medical use invention is based on a newly identified effect, and
157 Jantzen/Robinson, 2002, 748.
158 Jantzen/Robinson, 2002, 748.
159 Jantzen/Robinson, 2002, 747; see also Actavis UK Ltd v. Novartis AG [2010] EWCA Civ 82, para 62 (Jacob LJ noted a sustained release might provide better efficacy
or fewer side effects or better compliance).
160 NIHCM, 2002, 5.
161 E.g., Willkens/Segre, 19 Arthritis & Rheumatism 677, 680-81 (2006).
162 Merck & Co., Inc. v. Biocraft Laboratories, Inc., 874 F.2d 804 (Fed. Cir. 1989),
cert. denied, 493 U.S. 975 (1989) (holding the patent was invalid because of lack
of inventive step over prior art).
is a new teaching that results from that discovery.163 Often, pharmaceuticals
have several different indications. For example, aspirin was discovered as a
highly effective pain-killer in 1897 by Hoffmann, Eichengrün and Dreser at
Bayer. However, the mechanism of its action, namely the inhibition of the
biosynthesis of prostaglandins from arachidonic acid, was first discovered
by John Vane at the Royall College of Surgeons as late as 1971.164 Since
then, it has turned out to have many more additional therapeutic indications,
especially in preventing heart attacks and strokes.165 Revisiting old drugs in
this way may lead to therapeutically interesting new discoveries, and new
benefits to the patients. The industry has coined this repositioning approach
“teaching an old drug new tricks.”166
Patent law deals with medical treatment differently from other methods
or use claims related to medicines. Medical treatment and procedures are
often excluded subject matter for patenting, as is the case in Europe.167 If a
previously unknown substance is proven to have a novel therapeutic or diagnostic effect, a patent applicant can obtain an exclusive right to all uses of
the substance.168
The prohibition in Europe has been relaxed by the introduction of the new
provision of Art. 54(5) of the European Patent Convention (“EPC”) 1973
regarding first medical use. The first medical use of a known substance can
be patented, and has come to be regarded as a product patent. Moreover, if
one can prove a second medical use for a substance, which was known to
have a first therapeutic effect, it is possible to claim a second medical use as
well. For a second medical use, the applicant would have exclusivity only
on the second medical use in Europe.169 The practice was derived from the
EPO’s G 5/83 decision170 and various technical board of appeal cases regarding second medical use, is now finally based on the statutory language
of the Art. 54(5) of EPC 2000. In the United States, however, patents on uses
Klöpsch, IIC 1982, 457, 467.
Dutfield, 2009, 17-20.
Dutfield, 2009, 20.
Scudellari, The Scientist, April 1, 2011.
European Patent Convention, Art. 53 (c).
Cf. However, in the past, if the substance was known, a patent could be granted
neither on the product, which would be lacking in novelty, nor on the new use, as
the patent grant would contravene the provision banning patents for medical procedures.
169 Eisai/Second medical indication, G 5/83, OJ EPO 1985, 64.
170 Eisai/Second medical indication, G 5/83, OJ EPO 1985, 64.
are limited to a particular “method-of-use”, which does not protect the product as such.171
Dosage regime provides instructions for the proper way to take a medication,
such as “three times per day after a meal,” “once a day before sleep,” or “40
mg once a day in the morning for 4 to 8 weeks.” For example, if the single
novel feature of an invention is the direction “once a day prior to sleep” of
a well-known substance to cure the same illness, the Enlarged BOA held
that this use was not excluded from patentability under the EPC. 172
A chemical process invention denotes the invention of a process to manufacture a product. In Germany, since the Kongo-Rot decision in 1889,173 socalled “analogous chemical processes”174 are also patentable if the product
resulting from the process demonstrates unexpected and advantageous characteristics or effects in comparison to known chemical products.175 In the
United Kingdom and under EPO practice, if a compound is patentable, both
the claims directed to the compounds and to the process for the manufacture
171 LabCorp v. Metabolite, Inc., 548 U.S. 124 (2006); UNCTAD-ICTSD, 2005, 356.
172 Abbott Respiratory/Dosage Regime, G 2/08 (2010) (a referral to the Enlarged Board
of Appeal for the decision that a feature of a claim relating to a specific dosage
regime reflected a medical activity which was excluded from patentability under
Art. 52(4) EPC 1973, Kos Lifesciences/ Dosage regimen, T 1319/04, OJ EPO 2009,
173 Kongo-Rot, Decision of the Reichsgericht (Imperial Supreme Court) of May 8,
1889, Patentblatt 1889, 209, 212.
174 “Analogous chemical processes” are processes for making a new chemical product.
These processes are neither chemically new nor unusual, have different starting
materials but with an analogous constitution, interacting with one another in the
same procedural manner (or same starting analogous procedural manner) to obtain
definite new chemical products of a new constitution corresponding to specific
175 Nastelski, IIC 1972, 267, 269-70.
of that compound are patentable, even if the starting material and the process
are already known.176 In the United States, this type of analogous process
patent is considered to be obvious,177 unless it is a biotechnological process.178
Intermediates are compounds that normally have no pharmaceutical activities on their own, but can be used in a chemical process to manufacture an
active pharmaceutical ingredient. They are patentable either by their function in a chemical method of production or by the novel properties of the
new end product.179 A patent on an intermediate essential to produce the
basic medicine could effectively prolong the control of the resulting drugs’
Although the value and size of innovation vary, every product available on
the market developed from an invention, can be an innovation. Pharmaceutical innovations, namely, pharmaceutical products – more commonly
known as medicines or drugs – are a fundamental component of both modern
and traditional medicine.180 It is essential that such products are safe, effective, and of good quality, and that they are prescribed and used rationally.181 For this reason, they are heavily regulated and influenced by the types
of pharmaceutical products that are already on the market. Incentives for a
new innovation in this market need to account for market regulations. Accordingly, this chapter will explore the types of marketed products.
Grubb/Thomsen, 2010, 246.
In re Durden, 763 F.2d 1406, 1410 (Fed. Cir. 1985).
35 U.S.C. (2007) § 103(b).
Hansen/Hirsch, 1997, 345.
WHO, Pharmaceutical products, available at: http://www.who.int/topics/pharmaceutical_products/en/. (Last accessed on December 20, 2013).
181 WHO, Pharmaceutical products, available at: http://www.who.int/topics/pharmaceutical_products/en/. (Last accessed on December 20, 2013).
An NME is an active ingredient that has never been marketed before in any
form, or in the product containing it.182 Thus, the manufacturers must prepare
all of the efficacy and safety data through experiments and trials.183 The first
product with an International Non-proprietary Name (“INN”) of an active
ingredient can also be regarded as an NME. An INN is a unique name that
is globally recognized; it is public property;184 and it is given to a pharmaceutical substance as designated by the World Health Organization
(“WHO”). The significance of NMEs and the current status of new drug
development will be further elaborated in chapter III.B.2.
Once a new medical structure with interesting pharmacological properties
has been reported to the public, many other companies perform their own
research around said identified structure, and the research that they undertake
regarding the new medical structure is sometimes called “me-too” research.185 A product resulting from this research is often derogatorily called
a “me-too” product, because it follows the research prospects that others
have already successfully identified. A “me-too” product can be any drug
entity that is in the same class and is used for the same main indication as
the prototype drug.186 These may be also NMEs, and they will be subject to
all preclinical and clinical trials to prepare the data necessary to meet the
In the sense that the research follows a relatively easier path of a previously identified medical structure, the follow on research leading to similar
182 Paul, et al., 9 Nat. Rev. Drug Discov. 203, 203 (2010); FDA, Drugs@FDA Glossary
of Terms, available at: http://www.fda.gov/Drugs/informationondrugs/
ucm079436.htm#M (Last accessed on December 20, 2013); Pisano, 2006, 119
(noting “new molecular entities (NMEs)-both small molecules and biologics-”).
183 NIHCM, 2002, 4.
184 WHO, International nonproprietary name, available at: http://www.who.int/
medicines/services/inn/en/ (Last accessed on December 20, 2013); this INN can be
also called as a “generic name” that is contrasting to the “brand name,” however,
in order to avoid any future confusion, this term is not used in this thesis.
185 Hansen/Hirsch, 1997, 324.
186 Wertheimer/Santella/Chaney, 17 J. Pharmaceut. Marketing Manage. 25, 29 (2005).
or equivalent products are viewed negatively. Furthermore, with regard to
the efficacy of me-too products, some argue that a me-too drug has diminished value, serving merely to increase a pharmaceutical company’s profits.187 However, they provide several advantages. Firstly, they may offer
wider choice for physicians and patients and can contribute to cost-containment in pharmaceutical care.188 They enable physicians to treat diverse patients with precision and provide options when the first medicine treated is
either ineffective or not tolerated.189 In addition, they have been also associated with overall cost savings, especially through competition among
drugs in a therapeutic class.190
Secondly, a me-too product differs from second generation products in
that it is a product that is based on an NME. As they are based on new
molecules, the improvement through me-too products is sometimes more
valuable than improvement through second generation products. This is
mainly because analogous studies provide molecules which have different
characteristics. These molecules “are as different from the parent molecule
as a recent car compared to a 40-year-old model.”191 Furthermore, once the
drug is on the market, more people will be exposed to it. This may reveal
rarer side effects, which sometimes cause the manufacturer to withdraw the
drug from the market. However, it may also lead to the identification of
further medical uses of the drug, such as in the cases of Minoxidil19