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HIV Therapy 2009 11
HIV et Thérapies
HIV et ThérapiesHIV Therapy2009
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Patent mapping - A new tool to decipher market trends
MULTI-CLIENT PATENT LANDSCAPE ANALYSISIP Overview is a report that analyses all patent families filed on a given thematicAvailable reports in life sciences are HIV Therapy, Malaria, CDK inhibitors, Nanoparticles for bio-imaging, Monoclonal antibodies against digestive system cancers
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PRIOR-ART SEARCH
Contact us at [email protected] more information? Free access to the interactive database is provided for studies published since 2010
HIV Therapy 2009 22
HIV Therapy
HIV Therapy 2009 33
METHODOLOGY 8
INTRODUCTION 9
1 BRIEF OUTLINE OF THE MARKET 12
2 A BRIEF OUTLINE OF THE PIPELINE 14
3 PROTECTION STRATEGIES 15
3.1 Evolution of patent filings 15
3.2 Priority patent applications 16
3.3 Extensions 18
3.4 Analysis of industrial patents over time 19
3.5 Study of the granting of US patents 20
3.6 Study of the granting of European patents 22
3.7 Evolution of the number of applicants 23
4 TOPOLOGY OF PATENTS IN THE SECTOR 25
4.1 Breakdown of patents into therapeutic targets 25
4.2 Breakdown of patents by application 27
4.3 Cross-analysis of the categories “applications” and “therapeutic targets” 30
4.4 Breakdown of patents by class of compounds 31
4.5 Cross-analysis of the categories “class of compound” and “therapeutic target” 33
4.6 Cross-analysis of the categories “class of compound” and “application” 34
4.7 Breakdown of the main IPC codes of patents 35
5 APPLICANTS 37
5.1 Analysis for the entire period (1983-2006) 375.1.1 Main applicants (1983-2006) 375.1.2 Collaborations (1983-2006) 38
S u m m a r y
HIV Therapy 2009 44
5.1.3 Topics protected (1983-2006) 41
5.2 Analysis for the pioneer period (1983-1992) 455.2.1 Pioneer applicants (1983-1992) 455.2.2 Collaborations from 1983-1992 465.2.3 Topics protected (1983-1992) 49
5.3 Analysis for the intermediary period (1993-2000) 535.3.1 Main applicants (1993-2000) 535.3.2 Collaborations (1993-2000) 545.3.3 Topics protected (1993-2000) 57
5.4 Analysis for the most recent period (2001 - 2006) 615.4.1 Major applicants (2001-2006) 615.4.2 Collaborations (2001-2006) 635.4.3 Protected topics (2001-2006) 65
6 INVENTORS IN THE FIELD 69
6.1 Inventors for the entire period (1983-2006) 696.1.1 The main inventors 696.1.2 The experts 716.1.3 Mobility of inventors 716.1.4 Research teams for the entire period (1983-2006) 736.1.5 Topics 746.1.6 Description of the main inventors 77
6.2 Pioneer inventors (1983-1992) 79
6.3 Main inventors from 1993 to 2000 85
6.4 Main inventors from 2001 to 2006 92
6.5 Emerging inventors 99
7 CONCLUSION 100
7.1 No novel therapies in sight 100
7.2 Repositioning of the major industrial players 101
7.3 Market players to redefine their strategies 103
HIV Therapy 2009 55
FIGURE 1: NUMBER OF PEOPLE LIVING WITH HIV (2007) 1........................................................ 9
FIGURE 2: HIV REPLICATION CYCLE.......................................................................................... 10
TABLE 1: THERAPEUTIC TARGETS EXPLORED IN THE MANY STEPS OF THE VIRAL
REPLICATION CYCLE................................................................................................. 10
FIGURE 3: HIV THERAPY MARKET EVOLUTION PROSPECTS AND THE MAIN PLAYERS............. 12
FIGURE 4: MOLECULES UNDER DEVELOPMENT BY CLASS OF ANTIVIRAL (ALREADY MARKETED)
.................................................................................................................................. 14
FIGURE 5: MOLECULES UNDER DEVELOPMENT BY CLASS OF ANTIVIRAL (NOT YET MARKETED)
.................................................................................................................................. 14
FIGURE 6: EVOLUTION IN PATENT FILINGS.............................................................................. 15
FIGURE 7: GEOGRAPHIC DISTRIBUTION OF PRIORITY FILINGS.............................................. 16
FIGURE 8: GEOGRAPHIC DISTRIBUTION OF PRIORITY FILINGS/CLOSE-UP: EUROPE ............ 17
TABLE 2: EVOLUTION OF PRIORITY FILINGS.......................................................................... 17
FIGURE 9: GEOGRAPHIC DISTRIBUTION OF EXTENSIONS ....................................................... 18
TABLE 3: EVOLUTION OF EXTENSIONS.................................................................................... 18
FIGURE 10: EVOLUTION OF THE BREAKDOWN OF INDUSTRIAL PATENTS.................................. 19
FIGURE 11: EVOLUTION OF AVERAGE GRANT TIME FOR US PATENTS........................................ 20
FIGURE 12: EVOLUTION OF THE GRANTING OF US PATENTS...................................................... 21
FIGURE 13: EVOLUTION OF THE AVERAGE GRANT TIME OF EP PATENTS ................................... 22
FIGURE 14: EVOLUTION OF THE GRANTING OF EP PATENTS ...................................................... 23
FIGURE 15: EVOLUTION OF THE NUMBER OF APPLICANTS......................................................... 24
FIGURE 16: BREAKDOWN OF THE PORTFOLIO BY THERAPEUTIC TARGET ................................. 26
TABLE 4: EVOLUTION OF THE BREAKDOWN BY THERAPEUTIC TARGET ................................. 26
FIGURE 17: BREAKDOWN OF THE PORTFOLIO BY APPLICATION............................................... 28
TABLE 5: EVOLUTION OF THE BREAKDOWN BY APPLICATION ............................................... 29
FIGURE 18: CROSS-ANALYSIS OF THE CATEGORIES APPLICATIONS AND THERAPEUTIC
TARGETS ................................................................................................................... 30
FIGURE 19: BREAKDOWN OF PATENTS BY CLASS OF COMPOUND ............................................. 32
TABLE 6: EVOLUTION IN THE BREAKDOWN BY CLASS OF COMPOUND................................... 32
FIGURE 20: CROSS-ANALYSIS OF THE CATEGORIES CLASS OF COMPOUND AND THERAPEUTIC
TARGET ..................................................................................................................... 33
FIGURE 21: CROSS-ANALYSIS OF THE CATEGORIES CLASS OF COMPOUND AND APPLICATION34
FIGURE 22: DISTRIBUTION OF THE 20 MAIN IPC CODES .......................................................... 35
TABLE 7: DESCRIPTION OF THE 20 MAIN IPC CODES ............................................................. 36
TABLE 8: EVOLUTION OF THE MAIN IPC CODES...................................................................... 36
F i g u r e s a n d t a b l e s
HIV Therapy 2009 66
FIGURE 23: MAIN APPLICANTS FOR THE ENTIRE PERIOD (1983-2006).................................... 37
FIGURE 24: BREAKDOWN OF THE MAIN PATENT PORTFOLIOS................................................... 38
FIGURE 25: MAJOR COLLABORATIONS BY NUMBER OF JOINT FILINGS FOR THE ENTIRE PERIOD
(1983-2006).............................................................................................................. 40
FIGURE 26: THERAPEUTIC TARGETS OF THE MAJOR PLAYERS FOR THE ENTIRE PERIOD (1983-
2006)......................................................................................................................... 42
FIGURE 27: APPLICATIONS OF THE MAJOR PLAYERS FOR THE ENTIRE PERIOD (1983-2006) .. 43
FIGURE 28: CLASSES OF COMPOUNDS OF THE MAJOR PLAYERS FOR THE ENTIRE PERIOD (1983-
2006)......................................................................................................................... 44
FIGURE 29: MAJOR APPLICANTS FROM 1983-1992 .................................................................... 45
TABLE 9: EVOLUTION OF FILINGS BY MAJOR APPLICANTS FROM 1983-1992 ....................... 46
FIGURE 30: THE MAJOR COLLABORATIONS BY NUMBER OF JOINT FILINGS FROM 1983 TO 1992
.................................................................................................................................. 48
FIGURE 31: THERAPEUTIC TARGETS OF THE MAJOR PLAYERS FROM 1983-1992 ...................... 50
FIGURE 32: APPLICATIONS OF THE MAJOR PLAYERS FROM 1983-1992 .................................... 51
FIGURE 33: CLASSES OF COMPOUNDS OF THE MAJOR PLAYERS FROM 1983-1992 ................... 52
FIGURE 34: MAJOR APPLICANTS FROM 1993 - 2000................................................................... 53
TABLE 10: EVOLUTION OF FILINGS BY APPLICANT FROM 1993-2000...................................... 54
FIGURE 35: THE MAJOR COLLABORATIONS AND THE NUMBER OF JOINT FILINGS FROM 1993-
2000 .......................................................................................................................... 56
FIGURE 36: THERAPEUTIC TARGETS OF THE MAJOR PLAYERS FROM 1993-2000 ...................... 58
FIGURE 37: APPLICATIONS OF THE MAJOR PLAYERS FROM 1993-2000 .................................... 59
FIGURE 38: CLASSES OF COMPOUNDS OF THE MAJOR PLAYERS FROM 1993-2000 ................... 60
FIGURE 39: MAJOR APPLICANTS FROM 2001 - 2006................................................................... 61
TABLE 11: EVOLUTION OF FILINGS BY APPLICANT FROM 2001- 2006..................................... 62
FIGURE 40: THE MAJOR COLLABORATIONS AND JOINT FILINGS (2001-2006).......................... 64
FIGURE 41: THERAPEUTIC TARGETS FROM 2001-2006.............................................................. 66
FIGURE 42: APPLICATIONS OF THE MAJOR PLAYERS FROM 2001-2006 .................................... 67
FIGURE 43: CLASSES OF COMPOUNDS OF THE MAJOR PLAYERS FROM 2001-2006 ................... 68
TABLE 12: THE MAIN INVENTORS FOR THE ENTIRE PERIOD (1983-2006) .............................. 70
FIGURE 44: EXPERTISE FACTOR FOR THE ENTIRE PERIOD......................................................... 71
FIGURE 45: MOBILITY OF INVENTORS ........................................................................................ 72
FIGURE 46: RESEARCH TEAMS FOR THE ENTIRE PERIOD (1983-2006)...................................... 73
FIGURE 47: INDUSTRIAL/INSTITUTIONAL FILINGS OF THE MAIN INVENTORS AND/OR
EXPERTS.................................................................................................................... 74
FIGURE 48: THERAPEUTIC TARGETS PROTECTED BY THE MAIN INVENTORS AND/OR EXPERTS
.................................................................................................................................. 74
FIGURE 49: CLASSES OF COMPOUNDS PROTECTED BY THE MAIN INVENTORS AND/OR EXPERTS
.................................................................................................................................. 75
FIGURE 50: APPLICATIONS PROTECTED BY THE MAIN INVENTORS AND/OR EXPERTS............. 75
TABLE 13: LIST OF THE MAIN INVENTORS (1983-1992)........................................................... 79
FIGURE 51: LIST OF EXPERTS (1983-1992)................................................................................. 80
FIGURE 52: THE MAJOR COLLABORATIONS AMONG INVENTORS (1983-1992).......................... 81
HIV Therapy 2009 77
FIGURE 53: THERAPEUTIC TARGETS OF THE MAIN INVENTORS (1983-1992) ........................... 82
FIGURE 54: APPLICATIONS OF THE MAIN INVENTORS (1983-1992) ......................................... 83
FIGURE 55: CLASSES OF COMPOUNDS OF THE MAIN INVENTORS (1983-1992) ....................... 84
TABLE 14: LIST OF THE MAIN INVENTORS (1993-2000)........................................................... 85
FIGURE 56: LIST OF EXPERTS (1993-2000)................................................................................. 86
FIGURE 57: THE MAJOR COLLABORATIONS AMONG INVENTORS (1993-2000).......................... 88
FIGURE 58: THERAPEUTIC TARGETS OF THE MAIN INVENTORS (1993-2000) ........................... 89
FIGURE 59: APPLICATIONS OF THE MAIN INVENTORS (1993-2000) ......................................... 90
FIGURE 60: CLASSES OF COMPOUNDS OF THE MAIN INVENTORS (1993-2000) ........................ 91
TABLE 15: MAIN INVENTORS (2001-2006) ............................................................................... 92
FIGURE 61: LIST OF EXPERTS (2001-2006)................................................................................. 93
FIGURE 62: THE MAJOR COLLABORATIONS AMONG INVENTORS (2001-2006).......................... 95
FIGURE 63: THERAPEUTIC TARGETS OF THE MAIN INVENTORS (2001-2006) ........................... 96
FIGURE 64: APPLICATIONS OF THE MAIN INVENTORS (2001-2006) ......................................... 97
FIGURE 65: CLASSES OF COMPOUNDS OF THE MAIN INVENTORS (2001-2006) ........................ 98
TABLE 16: LIST OF EMERGING INVENTORS............................................................................... 99
TABLE 17: EVOLUTION OF FILLINGS BY EMERGING TOPICS .................................................. 106
FIGURE 66: EMERGING TOPICS BY APPLICANTS....................................................................... 106
FIGURE 67: APPLICANTS FOR EMERGING TPPICS..................................................................... 107
FIGURE 68: AUTHORS FOR EMERGING TOPICS ......................................................................... 108
HIV Therapy 2009 88
MethodologyThe different patents and patent applications
were extracted from the data bases FamPat
(Questel), espacenet, USPTO or other data
bases. In particular, with these bases it is
possible to group patents and patent
applications into patent families and to cover
all the domains found in the documents
published by 77 patent offices.
The search methodology used in this study
associated Boolean operators (AND, OR and
AND NOT) but also more complex search
operators such as word truncation (in the
middle or the end of a word), series of words
or searching for words in the same sentence or
paragraph. The search for key words can be
made in titles, abstracts or the main claims.
The search for patents can be limited by IPC or
ECLA codes or by the US classification, as well
as by filing or priority dates.
Raw data and global statistics were processed
with Intellixir software (www.intellixir.com).
How to read the maps of inventors or
collaborations among applicants:
** DISCLAIMER **
The data provided in this study is for information purposes only.
Although the aim is to circulate up-to-date and exact information
FIST SA cannot guarantee the result and cannot be held responsible
for any damages that may be caused by the use of this information.
The use or reproduction of al l or part of this document is prohibited
without the prior agreement of FIST SA.
For ful l detai ls on the condit ions governing the use of this study,
please refer to the general sales terms and condit ions in force.
HIV Therapy 2009 99
IntroductionThe Human Immunodeficiency Virus (HIV) is a double-stranded RNA virus from the Retroviridae
family. Discovered in 1983, HIV is responsible for the Acquired Immune Deficiency Syndrome (AIDS).
Its mechanisms of action and transmission were described in the years following its discovery, and the
first treatment, called azidothymidine or azidovudine, was marketed in 1987 as a monotherapy. A new
antiretroviral has been marketed nearly every year since 1992. Tritherapies associating several
antiretrovirals were marketed in 1996.
Even if tritherapies have significantly reduced mortality from AIDS in the developed countries,
worldwide mortality is still high because treatment is not readily available in the developing countries.
In 2007, an estimated 2.1 million people died of AIDS worldwide and there were 2.5 million new
infections. The prevalence of the disease is 33.2 million people. The figure below shows the
distribution of seropositive individuals throughout the world.
Figure 1: Number of people living with HIV (2007) 1
Most of the antiretroviral drugs being marketed today target inhibition of two types of enzymes that
are crucial to the HIV replication cycle: reverse transcriptase and protease. Recently new therapeutic
classes have been developed to inhibit other steps in the cycle. Indeed, as seen in the figure and table
below, the life cycle of the virus is complex and involves many steps, each of which is a new potential
target for therapy.
North America 480 000-1.9million
The Caribbean 210000-270000
South America 1.4-1.9 million
Western & Central Europe
600 000-1.1million
Middle East & North Africa
270 000-500 000
Subsaharian Africa
20.9-24.3million
Eastern Europe & Central Asia
1.2-2.1million
Eastern Asia 620 000-960 000
South Asia 3.3-5.1 million
Australia 53000-120000
HIV Therapy 2009 1010
CCR5/CXCR4
CD4
TRIM5
APOBEC3G
dsDNA
ssRNA
GP160
Host DNA
Reverse transcription
Uncoating
Transcription
Translation Regulating proteins(Vif Nef Vpu Vpr Rev Tat)
Gag-Pol
Gag
Vif
GP120
GP41
New HIV virions
Assembly/Maturation
NucleusT-cell
Fusion
Viral Entry
Processing
Protease
Integration
ssRNA
ER
Golgi
Capsid(p24 proteins )
HIV virion
Matrix (p17 protein)gag
env
RNA (2 molecules)
Reverse transcriptase Integrase, proteases, ribonuclease
Phospholipids
pol
cyclophilin
CCR5/CXCR4
CD4
TRIM5
APOBEC3G
dsDNA
ssRNA
GP160
Host DNA
Reverse transcription
Uncoating
Transcription
Translation Regulating proteins(Vif Nef Vpu Vpr Rev Tat)
Gag-Pol
Gag
Vif
GP120
GP41
New HIV virions
Assembly/Maturation
NucleusT-cell
Fusion
Viral Entry
Processing
Protease
Integration
ssRNA
ER
Golgi
Capsid(p24 proteins )
HIV virion
Matrix (p17 protein)gag
env
RNA (2 molecules)
Reverse transcriptase Integrase, proteases, ribonuclease
Phospholipids
pol
cyclophilin
Figure 2: HIV replication cycle
HIV replication cycle Corresponding therapeutic leads
1 Attachment of the virus to the host cell and fusion with its membrane
Inhibitors or antagonists of chemokine receptors (e.g. CCR5 and CXCR4), glycoproteins (GP41 and GP120) and CD4 proteins; cyclophilin A antagonists
2 Uncoating and penetration of viral proteins and viral RNA into the host cell TRIM5
3 Reverse transcription (Viral RNA is transcribed into DNA) and the destruction of viral RNA by ribonuclease
Reverse transcriptase inhibitors. Creation of transcription errors (APOBEC3G). Vif antagonists
4 Integration of viral DNA into the host cell genome Integrase inhibitors
5 Duplication of viral DNA Replication inhibitors (e.g. Nef) 6 DNA-RNA transcription * Transactivator tat antagonists
7 Viral protein synthesis by the translation of messenger RNA *
Ribosome inactivating proteins, antisense oligonucleotides, RNAi
8 Formation of virions by cleavage of mother proteins by proteases Protease inhibitors
9 Budding of the virion and infection of new cells.
Maturation inhibitors
Table 1: Therapeutic targets explored in the many steps of the viral replication cycle
* Some therapeutic research focuses on deactivating the functions of all or part of the viral genes at different stages of the
replication cycle. The three main HIV genes are gag, pol and env genes which define the physical structure of the virus
(gag), the reproductive mechanisms (pol) and code the envelope glycoproteins (env). The six other genes are tat, rev, vpr,
nef, vif, and vpu for HIV-1 or vpx for HIV-2 which code for the regulatory proteins
dsDNA: double-stranded DNA
ssRNA: single-stranded RNA
1
2
3
4-5
6
78
9
HIV Therapy 2009 1111
As shown in the table above, non-viral targets are being studied, for example cell proteins such as
APOBEC3G, Trim5 (a protein that is naturally present in monkeys) and cyclophilin A. These proteins
act as natural antagonists or agonists (cyclophilin A) to the virus.
Another approach in therapeutic research is stimulating the immune system without necessarily acting
on the viral replication cycle itself. Finally, several therapies target diseases directly associated with
the weakened immune system, or so called opportunistic infections.
Moreover, to identify new anti-viral molecules and monitor the efficacy of certain treatments,
therapeutic research has also focused on developing appropriate evaluation and screening methods.
Finally to improve the delivery and/or the pharmacokinetics of a treatment, research has developed
pharmaceutical formulations adapted to the novel active ingredients.
With a global market of 10 billion US$, many institutional and industrial players have shown a keen
interest in developing HIV therapies and have already marked out their positions in this field by
building strategic patent portfolios. As a result, more than 6800 patents and patent applications were
filed between 1983 and 2006. The aim of this IP Overview is to present a comprehensive picture of
the intellectual property in the field of HIV Therapy and to analyze the strategic positions of the
research teams and companies in this sector.
HIV Therapy 2009 1212
1 Brief outline of the market In 2007 the global market for HIV Therapy was nearly 10 billion $US1. Growth is expected to continue
and should reach approximately 15 billion $US in 2012, driven by the dominant position of drugs on
the market (for a revenue of 10 billion $US), by novel therapies (for a revenue of 4 billion $US) and by
the entry of generics onto the market (for a revenue of 1 billion $US.)
At present, 95% of the market is shared by three classes of drugs:
- Nucleoside reverse transcriptase inhibitors (NRTIs) (50% of the market share )
- Protease inhibitors (PIs) (30% of the market share)
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs) (15% of the market share)
The main classes of novel therapeutics are entry inhibitors which prevent the virus from entering the
cell, integrase inhibitors and maturation inhibitors.
Currently 90% of the HIV therapy market is dominated by 6 leading companies, which include, in
descending order of their market share: Gilead, GlaxoSmithKline, BristolMyerSquibb, Abbott, Roche
and Boehringer-Ingelheim.
0
500
1000
1500
2000
2500
3000
GS
K
Gile
ad
BM
S
GS
K
BM
S
Abb
ott
Roc
he
Boe
hrin
ger
Inge
lhei
m
Gile
ad
BM
S
Boe
hrin
ger
Inge
lhei
m
Roc
he
Pfiz
er
Nucleoside ReverseTranscriptase
Inhibitors (NRTIs)
Protease Inhibitors (PIs) Non-nucleoside Rev.Transcript. Inhibitors
(NNRTIs)
Others
Mill
ions
of U
S$
2006 2007 2012
Figure 3: HIV Therapy Market Evolution Prospects and the Main Players
Approximately 60% of the market is located in the United States and 30% in Europe.
1 Sources: 2007 Activity Reports of the companies Abbott, BMS, Boehringer Ingelheim, Gilead, GSK, Roche, Merck&co, Pfizer and Johnson&Johnson
HIV Therapy 2009 1313
GlaxoSmithKline, which has led the market for many years with 6 products, has, for the first time,
been surpassed in terms of revenues by an alliance between the companies Gilead and
BristolMyerSquibb2
2 http://money.cnn.com/2007/11/19/news/companies/hiv/index.htm with updated data for 2007
HIV Therapy 2009 1414
2 A brief outline of the pipeline There are more than 90 therapeutic antiviral molecules for HIV registered in different clinical trials to
date. Fifty of these drugs are in Phase I clinical trials, 35 in Phase II and 12 in Phase III. The
molecules are being developed by many different companies, without any one having a clear lead.
The most frequent sub-categories of molecules in the pipe-line are Non-nucleoside reverse
transcriptase inhibitors (NNRTIs), Nucleoside reverse transcriptase inhibitors (NRTIs), CCR5 Co-
receptor inhibitors/antagonists. Many preventive vaccines have reached early stages of development
but tend to fail before reaching further stages.
0
1
2
3
4
5
6
7
8
9
10
CCR5 - CXCR4antagonist
GP120 - GP41antagonist
Integrase Inhibitor NRTI NNRTI protease inhibitor
Phase I Phase II Phase III
Figure 4: Molecules under development by class of antiviral (already marketed)
0
5
10
15
20
25
maturation inhibitors gene therapies zinc finger inhibitors immune therapies CD4 antagonist Preventive vaccines
Phase I Phase II Phase III
Figure 5: Molecules under development by class of antiviral (not yet marketed)
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HIV Therapy 2009 1515
3 Protection strategies 3.1 Evolution of patent filings
To study the intellectual property environment in the field of HIV therapy, a patent search was
performed using the following key-words: HIV, treatment, inhibition, agonist, antagonist, compound,
vaccine and all related words. The search with these key-words had no restrictions by date. Although
a patent is valid for 20 years, limiting our search over time would have eliminated older patents which
may still be valid because of supplementary protection certificates and would have prevented us from
developing certain points which we wanted to bring to light in this analysis. The search resulted in
6800 families of patents and patent applications published as of November 10, 2008.
0
100
200
300
400
500
600
1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005
Priority Year
Nu
mb
er o
f pa
ten
t ap
plic
atio
ns
Figure 6: Evolution in patent filings
The number of patent applications filed is underestimated by approximately 20% until November
2000, when the US patent legislation changed. In fact before this date, US patent applications were
only published when the patent was granted. Indeed, applications that were not granted were never
published.
Patent filings began as of 1983 when the HIV virus was discovered and grew exponentially to reach
approximately 300 patents per year in the 1990’s. There was an intermediate period between 1993
and 2000 with a linear increase in the number of filings from 300 to 450 applications per year. A
plateau was reached between 2001 and 2004 followed by a marked downturn in the filing rate in 2005
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Pioneer Period Intermediate Period Recent Period
HIV Therapy 2009 1616
and 2006. It should be noted that when this study was performed (November 2008), a certain
number of applications, in particular those filed at the end of 2006, may not yet have been available
on all databases because of the time needed for patent offices and data bases to update information
concerning the publication of applications. (Delay to publication 18 months after filing, plus the time
to transfer and process information by database providers). Nevertheless, the downturn in the filing
rate is certain.
3.2 Priority patent applications
An analysis of the place of filing of priority patents results in the following map.
Figure 7: Geographic distribution of priority filings
The United States is indisputably the country where the most priority patents have been filed in this
field (a little more than 4600 patent applications). This is due to several factors, mainly because this
country is a major market. It is also due to the nationality of the main applicants and the major role
that universities and international pharmaceutical companies located in the United States have played.
Finally, because of the differences in legislation from 1983-1995 and the flexibility of US legislators as
well as their lead in the protection of biotechnologies, certain European institutions chose to file
priority US patent applications.
With approximately 1200 priority patent applications filed, Europe is in second place for the number of
priority patent filings. Japan is third with 340 priority filings.
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HIV Therapy 2009 1717
Figure 8: Geographic distribution of priority filings/Close-up: Europe
In Europe, the UK has the most filings (420). France and Germany follow with 170 and 150
applications respectively. The evolution of the geographic distribution of priority filings over time
shows that the first priority patents were filed in 1983-1984 simultaneously in France, the UK and the
United States. As of 1986 the United States established and has maintained its leading position with
the most priority filings.
83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 NORWAY 1 2 6 1 2INDIA 1 1 1 2 4 4 7 8 5RUSSIAN FED 2 1 1 1 3 1 1 9 2 3 3 2 1CHINA 2 1 1 1 1 5 4 8 10 11 13 8 11KOREA 8 5 5 7 1 2 5 4 7 13 6 6 2CANADA 3 2 2 3 1 2 2 4 3 4 3 3 4 2 1 1ITALY 2 1 3 5 4 1 6 3 7 2 2 2 6 4 3 3 1SWITZERLD 1 1 1 1 1 1 3 1 6 3IRELAND 2 2 2 2 2 2 1WORLD 1 1 2 2 4 1 6 7 6 9 12 7 14 10 12 11ISRAEL 1 5 1 4 4 4 1 3 2 4EUROPE 10 1 7 2 10 11 2 6 4 5 7 4 13 9 23 35 27 28 40 32 39DENMARK 1 1 2 2 1 3 2 1 6 2 5 4 2AUSTRALIA 3 2 1 4 7 3 2 1 4 7 2 8 5 6 6 3 6SWEDEN 2 8 2 4 7 2 1 1 1 1 2 5 1 1 3 2 5 3JAPAN 1 12 15 11 17 12 19 10 24 30 15 14 24 27 18 16 20 18 16 17 5GERMANY 1 1 4 5 10 5 12 17 5 6 9 7 4 14 10 5 10 10 4 6 3FRANCE 7 1 14 8 4 12 9 7 5 12 8 9 5 3 9 8 11 16 5 2 7 2 2U.S.A. 4 12 24 49 101 125 142 182 174 249 218 189 203 212 253 238 277 259 300 345 311 334 266 214UK 4 1 3 12 16 18 28 22 25 16 11 16 30 26 31 26 20 24 19 32 11 16 16
Table 2: Evolution of priority filings
Once these pioneer countries had begun filing, priority applications were then filed in many countries
as time went on: Germany in 1985, Japan, Sweden and Australia in 1986, Italy in 1988, Canada in
1989. As of 1992, priority patents were filed in Korea then in China and India as of 1999.
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HIV Therapy 2009 1818
The priority filing rate in the US, Japan, the UK and France and Germany remained vigorous
throughout the entire period.
3.3 Extensions
Figure 9: Geographic distribution of extensions
An analysis of the countries chosen for the extension of priority filings is an indicator of the markets
and/or the production sites of the applicants. The choice of countries may also be guided by a
company’s competitors and potential infringers, even if there is no market in these corresponding
territories.
83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 MEXICO 1 5 1 7 14 24 28 5 34 40 4 5 13 32 45 72 92 71 26POLAND 2 1 3 7 4 22 15 16 25 27 31 31 27 29 45 49 9 1BRAZIL 2 2 2 4 12 8 24 10 25 37 43 39 51 48 50 66 83 76 80 2CHINA 1 3 6 6 9 10 13 31 35 33 42 47 55 59 63 68 98 106 102 120 74 11NORWAY 4 7 22 16 19 26 18 37 20 26 27 34 33 31 34 34 37 51 42 48 18NEW ZEAL 2 4 12 22 17 19 20 12 37 30 31 33 35 31 42 26 34 42 51 10KOREA 1 6 11 9 18 15 16 23 11 8 11 26 6 12 8 9 19 50 68 71 61 4JAPAN 4 11 28 69 66 100 119 91 113 86 106 99 92 132 134 149 140 163 189 168 197 56 4ISRAEL 1 5 11 26 31 24 27 23 41 29 28 24 37 46 43 34 40 54 44HUNGARY 1 1 4 10 8 24 28 19 37 24 28 30 30 31 32 33 33 42 5 2 1GERMANY 3 9 20 49 44 64 58 62 96 60 74 72 59 60 73 81 48 55 40 24 16 3EUROPE 6 11 27 80 75 106 129 108 139 108 124 115 118 159 187 205 186 242 262 255 257 238 35DENMARK 1 5 16 42 32 49 40 30 51 34 35 40 24 26 25 32 18 20 10 10 2CANADA 2 8 12 32 31 88 112 84 115 89 105 90 110 145 143 157 144 174 211 184 207 163 9AUSTRIA 2 9 15 42 36 58 56 48 77 52 65 64 49 56 65 77 42 53 32 19 12AUSTRALIA 4 8 24 60 61 68 105 95 130 123 140 131 137 185 192 243 222 174 358 141 147 128 32SPAIN 1 4 10 17 22 47 41 32 63 43 47 53 37 35 40 50 28 36 22 12 5 1 1SH AFRICA 1 1 7 21 29 30 27 28 39 30 22 25 22 27 35 36 34 50 48 6WORLD 4 8 15 43 45 72 95 101 139 136 158 142 145 209 222 274 240 315 366 332 357 319 282U.S.A. 8 16 19 68 82 108 110 151 134 248 184 179 229 210 228 259 278 314 371 382 318 304 161 97
Table 3: Evolution of extensions
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HIV Therapy 2009 1919
Table 3 shows the evolution of extensions by country over time. As of 1984, patents were extended to
countries covering the 5 continents. China was named very early (1986) in the extension of priority
filings as were Brazil, Poland, South Africa, Mexico and Korea.
Paradoxically, there are fewer US patents than there are US priority filings. This is due to two factors:
- first, for older patents (before 2000) there are numerous US priority filings that were
extended to other countries but never published because they were never granted in the US,
- after 2000, US provisional patents may have been filed then directly filed as PCT applications
so the US extension has not yet been published.
3.4 Analysis of industrial patents over time Throughout the entire period the proportion of industrial patents has remained relatively stable, with a
ratio of industrial patents to institutional patents of approximately 75/25 respectively. Most of the
patents classified as “Others” are the many US patents filed naming the inventors as applicants. The
high number of institutional patents is a reflection of the continued importance of basic research in
HIV therapies.
Figure 10: Evolution of the breakdown of industrial patents
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0
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HIV Therapy 2009 2020
3.5 Study of the granting of US patents
The evolution of the granting of patents (time and ratio) provides an overview of how a patent
environment may be blocked in a given sector. Because of the filing practices of the players in this
field, this analysis focused on the granting of US patents. However, data is also provided for Europe.
Traditionally, the grant rate in an emerging sector is initially very high then tends to drop as
successive filings are made, since novelty and inventive step become increasingly difficult to prove
because of the increasingly sizeable prior art. However, it is important to take into account the time
between the filing of a patent application and when it is granted, which can vary depending on the
topic.
To date, nearly 4500 US patent applications have been filed (priority + extensions) and around 2700
have been granted.
The figure below illustrates the average grant time observed for granted US patents.
0
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Ave
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Figure 11: Evolution of average grant time for US patents
Since 1986 the average grant time of patents has been fairly stable and is approximately 3 years.
Therefore, the analysis of granting percentage, shown in the figure below, is only significant until
2003. In fact, the average grant time for granted patents in subsequent years cannot yet be analysed
because sufficient time has not elapsed. This calculation can be used to determine the time window
for meaningful analysis of the grant rate and its evolution.
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HIV Therapy 2009 2121
Furthermore, the grant rate observed in the figure is only significant for US patent applications filed
after November 2000. In fact, before this date, US patent applications were only published on the day
the patent was granted. In fact, applications that were not granted were never published.
Because of this legislation, it should also be noted that the data on the number of US filings is
underestimated by approximately 20%.
This analysis shows the evolution of the grant percentage between 2001 and 2003.
0
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Granted Not Granted Grant Rate Grant Rate (not exploitable)
Figure 12: Evolution of the granting of US patents
This graph shows that a high proportion of US patent applications filed in 2001 were granted (70%
grant rate). There is a rapid downturn in this percentage in 2002 (55%) and 2003 (35%). It should be
noted that compared to similar sectors, for which the average grant time is also around 3 years, the
grant rates observed for these patent applications are normal. The 2003 percentage is comparatively
low, which could be the sign of tougher examination in the United States and should be correlated
with a slightly longer examination time.
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HIV Therapy 2009 2222
NB: It is important to bear in mind that this rate could change over the coming years as and when
patents that may have taken more than 3 or 4 years to be granted are actually granted.
The same type of analysis was performed for the granting of European patents.
3.6 Study of the granting of European patents This figure shows the evolution of the average grant time of granted European patents over time
0
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Year of EP filings
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Figure 13: Evolution of the average grant time of EP patents
In Europe, the grant time, which is between 6 and 7 years, has also remained fairly stable.
Therefore the analysis of grant percentage in the figure below is only significant up to 1999.
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HIV Therapy 2009 2323
0
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Figure 14: Evolution of the granting of EP patents
The percentage of European patents granted is around 50%. Nevertheless, it should be noted that the
55-60% grant rate in the first years of the study decreased slightly to 40-45% after 2000.
3.7 Evolution of the number of applicants Figure 15 shows the evolution of the number of applicants per year (dark grey curve). Since a player
in the field may not have filed one year but may have filed in preceding years, these data do not
represent the total number of active players in the field of HIV Therapy.
The light grey curve shows the number of new applicants per year.
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HIV Therapy 2009 2424
0
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Number of applicants New applicants
Figure 15: Evolution of the number of applicants
The number of applicants and new applicants has evolved in three phases:
- The first phase, between 1983 and 1987, was a 5 year period of strong growth with approximately
one hundred pioneer applicants positioning themselves in the field;
- During the second phase, between 1987-2001 growth was linear with the number of applicants
progressing from 100 applicants per year to 200 by then end of this period.
- During the third phase from 2001-2006, growth flattened out followed by a downturn in the number
of applicants per year after 2005. This decrease will certainly continue in the coming years. Globally,
there was a reaction to a significant reduction in R&D spending during the latter period resulting in a
decrease in the number of new applicants (from 120 new applicants in 2000 to 70 in 2006)
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HIV Therapy 2009 2525
4 Topology of patents in the sector To analyse all HIV Therapy patents, the portfolio was broken down into several categories. It should
be kept in mind that some patents could not be classified into any of the categories, while on the
other hand one patent may be classified in several categories.
The portfolio was broken down into the following categories:
- Therapeutic targets (Reverse Transcriptase, Protease, …)
- Applications (inhibitor, vaccine, …)
- Classes of componds ( chemical, peptide, …)
- IPC codes
4.1 Breakdown of patents into therapeutic targets
To develop HIV Therapies, proteins playing a major role in the life cycle of the virus have been
targeted. These are mainly viral proteins but there are also host cell proteins (CD4 and chemokine
receptors). Thus patents protecting HIV Therapies were classified according to these potential
therapeutic targets.
The potential target proteins to prevent viral entry into the host cell are:
CD4 receptors
CCR5 and CXCR4 and other chemokine receptors
Glycoproteins (GP41, GP120) and their coding gene (env)
To prevent the viral RNA liberated by the virus in the host cell from becoming transcribed into DNA, or
this DNA from being integrated into the DNA of the host cell, the targets are respectively:
Reverse Transcriptase and its coding gene (pol)
Integrase
The step that offers another focus for therapeutic targets is the step from DNA transcription to the
formation of virions. The corresponding targets are:
Regulatory proteins and their coding genes (tat, rev, nef, vif, vpr, vpu, vpx)
Protease
Once the virions have been formed, or to prevent the formation of proteins necessary to synthesize
these virions, the following factors may be targeted:
Structural proteins and their coding gene (gag)
HIV Therapy 2009 2626
This analysis only included patents describing a treatment whose aim was to interfere with the above
mentioned targets and/or use them (entirely or partially) as an immunogen. However, the latter
parameter was not applied to the categories “reverse transcriptase”, “integrase” or “protease”.
The following map shows the proportion of patents for each therapeutic target.
Other 54%
GPn (Glycoprotein and coding genes)
5.1%
CXCRn or CCRn 5.4%
Integrase 2.9%
Protease 11.4% Regulatory proteins and coding genes
6.8%
Reverse transcriptase
6.1%
Structural proteins and coding genes
5.0%
CD4 3.6%
Figure 16: Breakdown of the portfolio by therapeutic target
83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07
Protease 6 15 18 44 34 118 63 65 98 60 45 44 58 42 60 52 33 49 35 26HIV regulatory proteins
and coding genes 5 13 8 6 23 20 16 21 21 24 27 21 31 30 33 39 55 44 40 41 26 22
Reverse transcriptase 1 2 5 7 6 16 20 15 18 21 22 25 32 52 32 44 36 41 23 52 24 26CXCRn or CCRn
(Chemokine Receptor) 1 5 29 29 31 58 38 57 57 37 48 34 30
Structural proteins andcoding genes 6 6 17 10 14 18 15 11 22 10 17 10 19 16 11 18 39 65 37 25 26 14 14
GPn (Glycoprotein andcoding genes 2 3 3 16 16 21 17 36 12 11 19 8 14 10 17 24 19 22 23 35 21 32 27 19
Integrase 2 1 2 8 4 8 5 18 13 21 15 26 22 47 35 21
CD4 1 4 8 6 19 9 4 16 5 7 17 14 11 4 9 10 12 13 14 6 3
Table 4: Evolution of the breakdown by therapeutic target
Black circles indicate FDA approval of one or two (double circle) drugs
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HIV Therapy 2009 2727
In 1985, reverse transcriptase was already a potential therapeutic target. Indeed, the first anti-HIV
drugs to be approved were reverse transcriptase inhibitors (the first was azidovudine or AZT).
Although many patents have been filed for this target since 1987, the number of protease patents has
always outnumbered reverse transcriptase patents reaching 100 applications per year in 1992 alone
and then stabilizing after 1996. While numerous anti-HIV drugs targeting protease have been
approved since 1995, it is interesting to note that up to now, a greater proportion of anti-reverse
transcriptase drugs have been approved compared to the number of patents filed to protect this
target.
Treatments targeting structural and regulatory proteins were protected as of 1984 and the number of
patents has progressed in a similar manner, with a peak around 2001.
Glycoproteins rapidly became a therapeutic target and two peak periods of interest are observed, the
first around 1990 and the second between 1998 and 2005. In 2003, a first inhibitor preventing viral
entry into the host cell targeted the envelope glycoproteins. This was enfuvirtide, discovered by
researchers at Duke University who founded the company Trimeris and collaborated with Roche as of
1999 to develop this drug.
Finally, although potential treatments targeting CD4 cells have been patented since 1987, results have
been less successful, with only one potential drug in the pipeline to date.
More recently two other therapeutic targets have been investigated.
The first was integrase which was protected by patents describing anti-HIV therapies as early as 1990
with a peak in interest in 2004; the first integrase inhibitor was commercialised in 2007 (discovered by
“IRBM P. Angeletti” a research subsidiary of Merck&co as of 2000 – and developed by the company
Merck&co).
Beginning in 1995, chemokine receptors became a second target. Many patents covering this target
have been filed since the year 2000, and a CCR5 inhibitor was commercialized in 2007 (Maraviroc,
developed by Pfizer).
Among the non-classified patents in this category are those that describe other, less extensively
studied, therapeutic targets. (e.g. cyclophilin, TRIM5 , APOBEC3G), or weakened or inactivated virus
for vaccines, as well as patents without a specific target. It is difficult to identify a general theme in
these remaining patents, which is why we have chosen not to include them in the analysis.
4.2 Breakdown of patents by application The patent portfolio can also be broken down into applications. This illustrates what types of
treatments are under study: specific inhibitors of one (or several) therapeutic target(s), combination
therapies, stimulation/suppression of the immune system of the infected host (without administering a
weakened version of HIV to the host or HIV derived particles, thus immunomodulation) or vaccines. It
is interesting to observe what proportion of inventions concern the identification and evaluation of
HIV Therapy 2009 2828
novel treatments (Biomarkers/Screening methods) and what proportion of patents protect
pharmaceutical formulations (galenic preparations) of therapeutic molecules.
It should be noted that many patents protect applications for both the diagnosis and the treatment of
HIV. However the aim of our extraction was to identify HIV therapeutics. Thus a diagnostics category
does not correspond to this aim and the result would have been very incomplete.
Based on these elements, the following applications were chosen:
Inhibitors
Combination therapies
Vaccines
Immunomodulation
Biomarkers and Screening methods
Pharmaceutical formulations (Galenic preparations)
For the category “pharmaceutical formulations”, it should be remembered that many patents can
describe a treatment while also claiming a pharmaceutical formula. We chose not to include these
patents in this category and to only include patents that have a pharmaceutical formula as one of
their main claims.
The following map shows the proportion of patents in each category:
Other 21.1%
Pharmaceutical formulations 2.1%
Combination therapies 2.2%
Immunomodulation 6.4%
Screening methods 11.3%
Vaccines 15.8%
Inhibitors 41.1%
Figure 17: Breakdown of the portfolio by application
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HIV Therapy 2009 2929
83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06
Inhibitors 3 9 13 51 71 87 137 106 204 171 157 180 169 177 208 208 188 234 248 211 252 203 150
Vaccines 5 16 12 38 40 53 49 69 73 57 64 38 50 48 65 55 61 92 89 87 69 68 60 61
Screening methods 2 6 8 20 13 11 22 24 19 23 26 39 28 40 57 55 63 91 102 88 64 57 48 43
Immunomodulation 1 8 9 5 8 14 12 19 19 19 10 21 31 28 45 42 49 58 50 45 21 21
Combination therapies 1 2 6 7 8 4 13 9 10 12 13 5 6 9 11 9 16 21 10 14Pharmaceutical formulations
2 3 1 4 2 5 6 7 5 11 4 5 15 17 5 9 15 18 17 15 7
Table 5: Evolution of the breakdown by application
Since 1987, most of the therapeutic HIV discoveries have been made in the class of inhibitors. The
number of patents filed in this class increased continually until 1992 when it reached 200 patents per
year and has continued at practically the same rate since. In the five years after the virus was
discovered, numerous vaccines were protected. Since then, the number of patents filed protecting
vaccines has remained relatively constant. The quantitative leap in the number of patents filed after
the 2000 in the categories “Vaccines” and “Biomarkers/Screening Methods” is mainly due to a change
in US patent legislation (Publication of patent applications rather than granted patents). It is
interesting to note that although there are many patents claiming vaccine formulations, no HIV
vaccine has been approved by regulatory drug administrations.
Interest in biomarkers/screening methods, which are the third largest group of patents, grew steadily
for four years after the virus was discovered then remained fairly constant until 1994 when a large
number of patents were filed with this application. This trend can be correlated to the growing
expertise in high throughput screening techniques such as proteomics and genomics (DNA chips).
Since 1985, there has been less, but still substantial interest in developing treatments to stimulate or
suppress the host immune system.
HIV Therapy 2009 3030
4.3 Cross-analysis of the categories “applications” and “therapeutic targets”
Figure 18: Cross-analysis of the categories applications and therapeutic targets
Cross-analysis of the categories applications and therapeutic targets gives a general idea of the most
important targets and their applications. This graph shows that viral protein inhibitors (or their coding
genes) have been an important focus of development, with most inhibitors developed against
protease and reverse transcriptase. HIV receptor antagonists against the immune system (mainly
lymphocyte T receptors) have also been a subject of research, especially chemokine receptors.
Some of these inhibitors have been protected by patents describing combination therapies. The main
patented inhibitor combinations are anti-proteases and anti-reverse transcriptases. Moreover, five of
the six combination inhibitors commercialised today are anti-reverse transcriptase combinations, with
only one combination of two anti-proteases.
As expected, most of the pharmaceutical formulations are for therapeutic inhibitors, that is,
transcriptase and reverse transcriptase inhibitors. Nevertheless, it is interesting to note that there are
certain pharmaceutical formulations for inventions concerning interference RNA (RNAi) or gene
delivery. In this case the therapeutic targets are the genes coding for HIV regulatory proteins. Except
for patents protecting chemokine and CD4 receptors, there is no reason for patents describing
immunomodulation to be associated with the therapeutic targets presented here. The rare patents
associated with proteins or viral genes that claim immunomodulation are patents that describe both
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HIV Therapy 2009 3131
the inhibitors of these proteins and claim that the activity of their compound is improved when it is
associated with an immunomodulator.
Vaccine formulations specific for one class of compound are usually composed of viral envelope
glycoproteins (GP41 and GP120) as well as the envelope proteins of the viral matrix and capsid or
derived peptides (p24, p6 and p17 coded by the gag gene). Several vaccine formulations also target
regulatory proteins. One reason for this is that several patents describe both structural and regulatory
HIV proteins. Vaccines involving chemokine and CD4 receptors have been developed with fragments
of these receptors to prevent HIV from binding to the host cell (thus preventing it from entering the
lymphocyte) by binding an antibody to the site instead. Nevertheless, the interest in this type of
technology remains limited.
Although there is research on the biomarkers and new inhibitors for all of these therapeutic targets via
the development of screening methods, there is less general interest in integrase and CD4 receptors
and cells than in others.
4.4 Breakdown of patents by class of compounds Several classes of therapeutic compounds are being developed to fight HIV. Thus, we broke down the
patent portfolio into classes of compounds.
We identified four main classes of compounds resulting in the following categories:
Chemical compounds
Peptide compounds (peptides or proteins)
Therapeutic antibodies
Nucleosides/(Poly)nucleotides & analogs
It should be noted that many patents describe anti-HIV antibodies for diagnostic rather than
therapeutic purposes. Therefore these patents were not included in this analysis. Moreover, although
antibodies are peptide compounds, they were not included in the latter class because of their specific
function.
The following map shows the proportion of patents in each category.
HIV Therapy 2009 3232
Other 48.1%
Nucleosides, (Poly)nucleotides
& analogues 7.1%
Antibodies 12.3%
Peptidic compounds
17.5%
Chemical compounds
25.1%
Figure 19: Breakdown of patents by class of compound
83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07Chemical compounds 1 8 19 19 41 32 59 85 48 71 78 63 56 86 105 95 122 131 135 150 111 72
Peptidic compounds 6 13 13 39 40 27 36 56 38 46 40 25 34 51 63 42 79 80 102 73 67 55 44 37
Antibodies 1 3 1 17 38 26 26 31 33 33 30 22 35 42 41 30 32 45 75 58 35 49 41 30Nucleosides,
(Poly)Nucleotides & analogues
4 7 21 16 16 36 19 14 9 14 15 12 21 28 25 31 40 35 26 25 21 13
Table 6: Evolution in the breakdown by class of compound
Black circles indicate FDA approval of a drug
The first patents filed described therapeutic peptide compounds. The number of patents filed grew
steadily until 1987 then the rate stabilized until 1995 before another period of growth lasting until
2000. Since 2002, the number of patents describing peptide compounds as potential therapeutics has
decreased but is still relatively high. Today, peptide compounds are the second most frequently
patented class of compounds. It should be noted that there are very few therapeutic peptides on the
market. Certain therapeutic molecules contain peptide bonds (ie certain protease inhibitors) but these
compounds have been classed as chemical compounds. Only one existing drug is actually a peptide.
This is a fusion inhibitor (enfurvitide developed by the University of Duke in collaboration with Roche
and approved in 2003). Therapeutic antibodies targeting the key viral proteins are the second oldest
class of therapeutic agents. The number of patents protecting therapeutic antibodies has evolved in
the same manner as peptide compounds but there were fewer (~30% less) patents. It should be
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HIV Therapy 2009 3333
noted that there are no therapeutic antibodies being marketed today and only 6 ongoing clinical trials
on this topic.
Chemical compounds came into the picture a little later (in 1986), but are the most important class of
potential therapeutics today, and were the subject of most of the patents filed in 1992. The most
active period of filing occurred after 2000 with as many as 150 patents filed in 2004.
Finally, the number of patents filed for nucelosides, (poly) nucleotides and their analogs which were
first discovered in 1985, is somewhat lower than that protecting the other classes, even though seven
of these reverse transcriptase inhibitors have been commercialised. There was a renewal of interest in
this class of drugs after 2000.
4.5 Cross-analysis of the categories “class of compound” and “therapeutic target”
Cross-analysis of the patents by class of compound and therapeutic target gives a general idea of the
most important targets in relation to the classes of compounds.
This graph shows that most therapeutic antibodies developed to date target viral entry into the host
cell because most are directed against surface viral glycoproteins, but also regulatory proteins and key
enzymes of the viral cycle (protease and reverse transcriptase). Sometimes certain patents describe
these antibodies not for therapeutic purposes, but to show the efficacy of another drug by dosing the
quantity of these proteins in the patient’s blood.
Figure 20: Cross-analysis of the categories class of compound and therapeutic target
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HIV Therapy 2009 3434
Although there are chemical compounds described as inhibitors (or activators) for all the therapeutic
targets, most of the chemical compounds target protease, reverse transcriptase, chemokine or
integrase receptors. The targets for nucleosides/(poly)nucleotides & their analogs are mainly the
regulatory and structural proteins and their genes. Most of the RNAi’s are found in this category. In
addition, a certain number of reverse transcriptase inhibitors are nucleoside or nucleotide analogs.
Finally, peptide compounds also target all the therapeutic targets, although somewhat less integrase
and reverse transcriptase inhibitors. Peptide compounds targeting glycoproteins and the structural
genes are mostly immunogenic peptides used as vaccines. They play the role of antagonists (eg CD4
and chemokine receptors) or inhibitors (protease) in other targets, and in the latter case, are mostly
oligonucleotide analogs.
4.6 Cross-analysis of the categories “class of compound” and “application”
Figure 21: Cross-analysis of the categories class of compound and application
Cross-analysis of the categories class of compound and application gives a general idea of the most
important applications in relation to the classes of compounds.
This graph shows that most inhibitors are chemical compounds. Although all classes of compounds are
used as inhibitors, most are chemical compounds. A significant number of screening methods have
been developed to evaluate the most effective antibodies and peptide compounds. As a result, the
number of patents filed in these two classes will probably increase in the upcoming years.
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HIV Therapy 2009 3535
Combination therapies associate chemical compounds and/or nucleosides/(poly)nucleotides & analogs,
and correspond to compounds that are already on the market, thus mainly nucleoside (or nucleotide)
analogs combined with chemical compounds.
Pharmaceutical formulations are the main claim in very few patents even though all therapeutic
compounds have pharmaceutical formulations.
Immunomodulation is usually obtained with chemical compounds, but certain antibodies and peptide
compounds have also been developed for this purpose.
HIV vaccines are mostly immunogenic peptide compounds, but several patents protecting HIV DNA
vaccines have been filed.
4.7 Breakdown of the main IPC codes of patents
The most widely represented IPC codes in HIV therapy patents were extracted and their distribution is
shown in the following figure.
A61P
31/0
0
A61P31/18
A61K38/00
A61P31/12
A61P31/00A61P31/18A61K38/00A61P31/12C07K14/005C07K14/16A61K39/21A61K39/00A61KA61P37/00A61P43/00C12Q1/70A61K45/00C07K14/435C12Q1/68C12N15/09A61K48/00C07D401/00A61K31/70C07H21/04
Figure 22: Distribution of the 20 main IPC codes
IPC Description of the IPC codes A61P31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
A61P31/18Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics, Antivirals, for RNA viruses, for HIV
A61K38/00 Medicinal preparations containing peptides A61P31/12 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics, Antivirals C07K14/005 Peptides having more than 20 amino acids, from viruses
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HIV Therapy 2009 3636
IPC Description of the IPC codes
C07K14/16
Peptides having more than 20 amino acids, from viruses, RNA viruses, Retroviridae, e.g. bovine leukaemia virus, feline leukaemia virus, human T-cell leukaemia-lymphoma virus, Lentiviridae, e.g. human immunodeficiency virus (HIV), visna-maedi virus, equine infectious anaemia virus, HIV-1
A61K39/21 Medicinal preparations containing antigens or antibodies, Viral antigens, Retroviridae, e.g. equine infectious anemia virus
A61K39/00 Medicinal preparations containing antigens or antibodies A61K Preparations for medical, dental, or toilet purposes
A61P37/00 Drugs for immunological or allergic disorders A61P43/00 Drugs for specific purposes, not provided for in groups
C12Q1/70 Measuring or testing processes involving enzymes or micro-organisms, involving virus or bacteriophage
A61K45/00 Medicinal preparations containing active ingredients not provided for in groups A61K 31/00 to A61K 41/00
C07K14/435 Peptides having more than 20 amino acids, from animals
C12Q1/68 Measuring or testing processes involving enzymes or micro-organisms, involving nucleic acids
C12N15/09 Mutation or genetic engineering, Recombinant DNA-technology
A61K48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases
C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
A61K31/70 Medicinal preparations containing organic active ingredients, Carbohydrates
C07H21/04Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids, with deoxyribosyl as saccharide radical
Table 7: Description of the 20 main IPC codes
Although these main IPC codes have been fairly stable over time and are representative of this sector
they do not provide an overview of the main and emerging topics, applications.
83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06
A61P31/00 4 5 16 45 50 70 100 83 113 85 104 90 93 119 144 183 163 214 211 205 235 138 106
A61P31/18 4 2 9 21 30 36 49 45 57 44 65 71 76 108 127 175 148 202 198 182 219 126 86
A61K38/00 7 5 32 53 53 59 102 68 108 82 69 77 84 105 71 89 79 100 86 57 51 19 17
A61P31/12 2 4 13 43 48 64 97 76 101 71 89 63 34 41 44 61 39 59 65 66 69 30 25
C07K14/005 2 11 13 47 48 54 58 80 36 56 59 34 40 44 60 40 56 78 92 79 52 43 21 19
C07K14/16 2 11 13 44 44 52 55 76 32 48 56 33 38 41 51 36 51 73 91 75 44 36 14 15
A61K39/21 7 7 32 35 40 47 46 27 44 47 22 32 38 42 37 45 70 71 68 48 39 27 18
A61K39/00 4 11 39 39 47 50 57 39 53 39 24 28 34 56 40 52 58 57 45 36 34 21 17
A61K 2 7 8 29 25 39 41 30 49 36 25 36 40 40 50 54 52 100 118 75 1
A61P37/00 1 2 1 6 13 20 27 18 34 22 41 32 35 70 52 49 51 80 70 66 72 29 16
A61P43/00 1 1 3 6 11 17 17 18 10 22 28 26 39 50 63 58 73 96 101 115 32 17
C12Q1/70 3 8 8 28 23 16 17 26 10 45 24 26 23 39 47 42 48 73 88 80 46 39 28 16
A61K45/00 1 1 7 4 10 7 22 20 17 19 25 39 52 56 69 66 79 90 65 60 21 13
C07K14/435 2 3 15 25 22 28 33 33 29 23 21 25 43 65 53 53 52 57 38 35 28 17 15
C12Q1/68 4 6 2 11 13 3 14 20 8 31 19 26 25 29 55 42 40 70 68 68 47 33 23 15
Table 8: Evolution of the main IPC codes
HIV Therapy 2009 3737
5 Applicants5.1 Analysis for the entire period (1983-2006)
5.1.1 Main applicants (1983-2006)
Figure 23: Main applicants for the entire period (1983-2006)
The largest patent portfolios are shown in the above figure. Sixteen major pharmaceutical groups and
four public research institutions share this prize. The top two spots are filled by the companies Pfizer
and Merck&co which have a clear lead over the others, with more than 350 patent families in the
field. Their position is surprising since these two companies are not the most dominant market players
(3 anti-HIVs on the market for Pfizer and 4 for Merck&co with the most promising only approved
recently).
It should be noted that Pfizer’s portfolio also includes the portfolios of all the companies that it has
acquired (in particular Pharmacia and Warner Lambert, which also means Monsanto, Agouron and
Upjohn).
In a similar manner, the portfolios of the other large companies have been grouped together. In a
more in depth analysis of each period, we separated those acquired portfolios to get a better overall
picture of the IP environment and provide a better view of how it has evolved.
In descending order by market share, Gilead, which is the leader in the market, is only in 19th place in
terms of number of patents, GlaxoSmithKline is 5th, BristolMyersSquibb is 4th, Abbott is 12th, Roche
13th and Boehringer-Ingelheim in 9th position.
0
50
100
150
200
250
300
350
400
PFIZER
MERCK & C
o
US GOVERNMENT
BMSGSK
JOHNSON & JO
HNSON
SANOFI AVENTIS
INSTITUT PASTEUR
BOEHRINGER IN
GELHEIM
UNIV C
ALIFORNIA
NOVARTIS
ABBOTT
ROCHE
SCHERING P
LOUGH
CORPCNRS
UNIV EMORY
VERTEX PHARMA
PROGENICS PHARM IN
C
GILEAD
GENENTECH
Num
ber o
f pat
ent a
pplic
atio
ns
www.frinnov.fr
HIV Therapy 2009 3838
US government laboratories are in first place for the number of patents held by an academic research
institution with nearly 300 patent families, while Institut Pasteur, the ever present French research
institute in the field of HIV, is in 7th place.
It should be remembered that the present analysis evaluates only HIV therapies and not diagnostics,
which both these institutions have developed extensively.
Figure 24: Breakdown of the main patent portfolios
The largest patent portfolios only represent a small percentage of all the patents in this field. Pfizer
and Merck&co’s portfolios each only make up 5% of the total number of patents in this field, and the
players in 6th and 7th position only own 1.5% of the total portfolio. This is mainly due to the many
market players in this field (more than 1700)
5.1.2 Collaborations (1983-2006)
The figure below shows the clusters of collaborations among applicants for the entire period). Only
collaborations which resulted in 3 joint filings have been included.
Two major clusters of collaborations can be seen: one is concentrated around US government
laboratories and another around the Institut Pasteur, the CNRS and INSERM. Another important
collaboration between institutional partners was established between the Universities of Emory and
Georgia, resulting in 18 joint patents.
www.frinnov.fr
PFIZER 4,8% MERCK&CO 4,7%
US GOVERNMENT 3,8%
BMS 2,8%
GSK 2,5%
JOHNSON & JOHNSON 1,9%
INSTITUT PASTEUR 1,3%
SANOFI AVENTIS 1,3%
BOEHRINGER INGELHEIM 1,3%
UNIV CALIFORNIA 1,2%
NOVARTIS 1,1%
ABBOTT 1,1%
Others (>1700 applicants) 72,3%
HIV Therapy 2009 3939
The most successful industrial collaboration in terms of patent filings (20) was between Agouron
Pharmaceuticals (which is now part of the group Pfizer) and Japan Tobacco. In fact, the drug
Nelfinavir (Viracept) was launched as a result of this collaboration.
This analysis could not identify informal collaborations which did not result in the official filing of joint
patents.This is true for example between Institut Pasteur and US government laboratories, in
particular because of the participation of Luc Montagnier, the companies Bayer AG and Takeda,
Panacos with the University of North Carolina, Institut Curie with Johnson & Johnson and UCB and
Darwin Discover ltd with Dow Chemical.
3
3
3
3
3
3
4
4
4
5
5
5
3
6
5
5
6
7
4
4
3
8
68
8
8
4
9
7
4
4
4
3
3
20
3
3
3
3
3
3
3
3
4 4
2513
5
54
4
4
43
3
3
3
18
14
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8
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3
3
3
3
3
3
3
5
6
4
4
WAYNE HUGHES INST3
[PARKER HUGHES INSTITUTE]26
[VALEANT]4
[ARDEA BIOSCIENCES INC]7
[PEPTERA PHARMACEUTICALS LTD]3
CHAY GROUP N3
[NIID]4
[JAPAN SCI AGENCY]15
[MERCK-SERONO]3
[APPLIED RESEARCH SYSTEMS]7
[AMEDIS PHARMACEUTICALS]3
[TAKEDA]33
[UNIV NAT AUSTRALIA]6
[CSIRO]4
[QLT PHOTOTHERAPEUTICS INC]4
[UNIV BRITISH COLUMBIA]6
[BIOWINDOW GENE DEV INC]4
[SHANGHAI BODE GENE CO]8
[GEORGETOWN UNIV]7
[SAMARITAN PHARMACEUTICALS]7
[BMS]210
[DU PONT]7
[ORATION]5
[USTAV ANORGA...CHEMIE AC CZ]3
[INST ORGANIC...BIOCHEMISTRY]6
[REGA STICHTING]20
[UNIV LOUVAIN]19
[ACAD OF SCIE...ECH REPUBLIC]5
[WISTAR INSTITUTE]9
[UNIV PENNSYLVANIA]23
[AMERICAN CYANAMID]19
[WYETH]24
[UAF TECHNOLOGIES AND RES LLC]5
[PROCTER AND GAMBLE]19
[UNIV ARIZONA]18
[TEIJIN LTD]9
[MERCK]355
[ANGELETTI P IST RICHERCHE]20
[TULARIK INC]8
[DARWIN DISCOVER LTD]10
[UCB SA]12
[AVEXA LTD]12
[IAF BIOCHEM ...NATIONAL IND]14
[PROGENICS PHARM INC]51
[CORNELL FOUNDATION INC]12
[AARON DIAMON...S RES CENTER]14
[SCHERING PLOUGH CORP]60
[PHARMACOPEIA]11
[UNIV COLUMBIA]17
[DANA FARBER CANCER INSTITUTE]34
[GENZYME CORP]31
[JOHNSON MATTHEY PLC]11
[GSK]187
[SHIONOGI]32
[WELLCOME FOUNDATION LTD]23
[MILLENNIUM PHARM INC]17
[PFIZER]359
[ELAN INC]11
[CONSEJO SUP ...IG CIENTIFIC]9
[JAPAN TOBACCO INC]31
MEDICAL RES COUNCIL19
[UNITED BIOMEDICAL]16
[THEREXSYS LTD]3
DOW CHEMICAL CO4
[SANOFI AVENTIS]95
[SOUTH AFRICAN COUNCIL]3
[UNIV CAPE TOWN]5
[SAN ROMANELLO CTR FOND]3
[SAN RAFFAELE CTR FOND]7
[SYSTEMIX INC]6
[NOVARTIS]82
[MEDIVIR AB]41
[ASTRAZENECA]15
[IDENIX PHARMACEUTICALS INC]20
[UNIV CAGLIARI]7
[UNIV MONTPELLIER]6
[EUROFINS VIRALLIANCE INC]3
[INSERM]40
[APHP]5[UNIV PARIS SUD XI]
3 [CNRS]59
[INSTITUT CURIE]3
[INSTITUT PASTEUR]95
[TRANSGENE]11
[UNIV NEW YORK]39
[AMERICAN BIOSCIENCES]5
[PANACOS PHARMACEUTICALS INC]19
VI TECHNOLOGIES INC6
[UNIV WAKE FOREST]14
[UNIV MICHIGAN]16
[UNIV NORTH CAROLINA]32
[ALPHAVAX HUMAN VACCINES INC]3
[BIOTECH RES LABORATORIES]8
[US GOVERNMENT]288
[ROCHE]77
[PURDUE RESEARCH FOUNDATION]5
[SCRIPS INSTITUTE]24
[NIH]15
[UNIV ILLINOIS]10
[NASA]17
[UNIV EMORY]54
[UNIV GEORGIA]29
[UNIV YALE]20
[BIOMERIEUX]13
[AKZO NOBEL]12
[UNIV DUKE]43
[UNIV DURHAM]4
[BETH ISRAEL HOSPITAL]9
[TRIMERIS INC]24
Figure 25 : Major collaborations by number of joint filings for the entire period (1983-2006)
www.frinnov.fr
HIV Therapy 2009 4141
5.1.3 Topics protected (1983-2006)
The next three figures present an analysis of the applicants according to three categories: therapeutic
target, application and class of compound. The players are clearly separated into institutional and
industrial applicants and among the industrial applicants themselves.
Institutional applicants tend to protect inventions targeting regulatory and structural proteins as well
as viral entry glycoproteins. The main therapeutic compounds developed are peptide compounds and
therapeutic antibodies. Most applications target inhibition of the HIV cycle (mostly US universities and
US government labs), screening methods and vaccines.
Industrial players tend to protect chemical compounds inhibiting protease, reverse transcriptase and
more recently integrase and chemokine receptors. Several industrial players, who have filed fewer
than 40 patents, have concentrated their intellectual property on one target, one application or one
class of compound.
- Abbott, Ambrilia Biopharma, LG Group and Vertex Pharmaceuticals have protected chemical
compounds inhibiting protease.
- Genzyme (via the acquisition of Anormed in 2006), Schering Plough Corp and Takeda have
concentrated their portfolio on chemical compound which are chemokine receptor antagonists,
- Monogram Biosciences has protected nucleosides/(Poly)nucleotides & analogs as well as
screening methods targeting reverse transcriptase, protease and chemokine receptors.
- Progenics Pharmaceuticals has protected antibodies and peptide compounds inhibiting viral
entry (CD4, Glycoproteins and Chemokine Receptors).
- Shinogi has protected chemical compounds inhibiting integrase.
The larger companies with more extensive portfolios have diversified their research into several areas.
- Gilead has concentrated on chemical compounds inhibiting protease, integrase and reverse
transcriptase.
- Pfizer and BMS have portfolios with chemical compounds inhibiting protease, integrase and
reverse transcriptase and chemokine receptors. Pfizer has an impressive portfolio of protease
inhibitors.
- Roche has developed screening methods and chemical compounds inhibiting reverse
transcriptase, protease and chemokine receptors.
- Johnson & Johnson (via its subsidiary Tibotec) has developed screening methods and chemical
compound inhibiting protease and reverse transcriptase.
Finally, two companies GSK and Merck&co have extensive portfolios covering all targets and
applications. Merck&co has also focused on vaccines. In their coverage of all targets, these two
portfolios are similar to that of the US government laboratories.
Remark: the colors of the circles (blue or red) are only to make the columns more legible.
42
42
Figure 26: Therapeutic targets of the major players for the entire period (1983-2006)
www.frinnov.fr
43
43
Figure 27: Applications of the major players for the entire period (1983-2006)
www.frinnov.fr
44
44
Figure 28: Classes of compounds of the major players for the entire period (1983-2006)
www.frinnov.fr
45HIV Therapy 2009 45
5.2 Analysis for the pioneer period (1983-1992)
5.2.1 Pioneer applicants (1983-1992)
From 1983 to 1992, 1562 patent applications were filed naming more than 2300 inventors.
Figure 29: Major applicants from 1983-1992
This figure shows the 20 top applicants from 1983 to 1992. Merck&co is the leader of the
pharmaceutical groups with nearly 100 filings followed by Searle. The US government laboratories and
Institut Pasteur filed 99 and 65 applications respectively. Besides these 4 top applicants all the other
players filed fewer than 40 patents during this period.
0
20
40
60
80
100
120
US GOVERNMENT
MERCK
INSTITUT PASTEUR
SEARLE C
O
MONSANTO CO
BOEHRINGER IN
GELHEIM
UNIV EMORY
SMITHKLINE BEECHAM
CORP
ABBOTT
MERRELL DOW P
HARMA
DANA FARBER CANCER IN
STITUTE
ROCHE
UNIV C
ALIFORNIA
WELLCOME FOUNDATION LT
DCNRS
UPJOHN C
O
GENENTECH
BIOGEN IN
C
MEDIVIR AB
UNIV TEXAS
Num
ber o
f pat
ent a
pplic
atio
ns www.frinnov.fr
46HIV Therapy 2009 46
83 84 85 86 87 88 89 90 91 92US GOVERNMENT 3 2 6 14 10 13 3 17 13 18
MERCK & Co 8 11 27 37 13INSTITUT PASTEUR 5 7 1 23 10 6 6 5 2
SEARLE CO 1 14 48MONSANTO CO 2 2 7 26
BOEHRINGER INGELHEIM 1 20 4 5 4UNIV EMORY 3 2 1 2 13 3 1
SMITHKLINE BEECHAM CORP 2 5 8 6 3ABBOTT 2 3 9 2 1 6
MERRELL DOW PHARMA 1 8 4 4 4 2DANA FARBER CANCER INSTITUTE 2 5 1 3 6 1 3
UNIV CALIFORNIA 2 6 1 2 4 3WELLCOME FOUNDATION LTD 2 3 2 3 1 4 3
ROCHE 2 5 2 5 3 1CNRS 2 8 3 3 1
UPJOHN CO 2 1 4 2 2 5BIOGEN INC 2 2 2 3 3 3GENENTECH 1 7 5 1 1UNIV TEXAS 3 3 1 5 2MEDIVIR AB 2 5 1 1 4 1
Table 9: Evolution of filings by major applicants from 1983-1992
The evolution over time of filings by the top applicants corresponds to their entry into and desire to
position themselves in the field. The first applicants to position themselves were the CNRS, Institut
Pasteur and the US government laboratories. Only the latter has continued to file vigorously while
Institut Pasteur and the CNRS, after an initial period of vigorous filing, seemed to turn away from this
topic. Thus the first applicants in the field are not necessarily those with the largest portfolios today.
The industrial applicants and major applicants only began working on this topic four years after the
virus was discovered and the first pioneer patents were filed (between 1987 and 1988).
Merck&co took a leading position as early as 1990. Searle (subsidiary of Monsanto since 1985),
Monsanto and Boehringer-Ingelheim filed their first patent applications in 1987 and filed massively
after 1990.
5.2.2 Collaborations from 1983-1992
The figure below shows the clusters of collaborations among applicants for the period from 1983 to
1992. Only collaborations which resulted in 2 joint filings have been included.
In the early years, there were very few collaborations. The most notable were:
- CNRS and Institut Pasteur with 15 joint filings
- Searle and Monsanto: 20 joint filings (Searle has been a subsidiary of Monsanto since 1985)
- The University of Georgia and the University of Emory: 7 joint filings
47HIV Therapy 2009 47
This analysis could not identify informal collaborations which did not result in the official filing of joint
patents. This is true for example of collaborations between Institut Pasteur, CNRS and INSERM on one
hand and the US government laboratories on the other, Institut Pasteur with the company Transgene
(because of Simon Wain-Hobson’s work at the Institut Pasteur and then Transgene), GSK (when it
was SmithKline Beecham) with the University of Columbia (with Wayne Hendrickson’s and Peter
Kwong’s work at Columbia University and Raymond Sweet at SmithKline Beecham) and Astra AB with
Medivir AB.
The companies Ciba Geigy AG and Sandoz SA, which were merged in 1996 to form Novartis were
already collaborating at that time. The creation of Novartis, however, is not to be taken into account,
because it is a result of the transfer of intellectual property filed before 1996 to this new legal entity.
25
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22 2
2
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2
2
2
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2
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2 2
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3 4
22
3
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3
3
3
2
2
33
BRISTOL MYERS CO2
[BMS]7
[UNIV DUKE]11
[UNIV DURHAM]2
CIBA GEIGY AG7
[NOVARTIS]12
SANDOZ SA6
CHIRON CORP14
[UNIV NORTH CAROLINA]4
[DEUTSCHES PRIMATENZENTRUM GMBH]5
[MAX PLANCK GESELLSCHAFT]2 [DKFZ]
2
[UNIV STANFORD]10
VIRAL TECHNOLOGIES INC4
[UNIV GEORGE WASHINGTON]3
[GSF FORSCHUNGSZENTRUM F]3
[STRAHLEN UMWELTFORSCH GMBH]2
[HARVARD COLLEGE]9
[DANA FARBER CANCER INSTITUTE]21
[UNIV COLUMBIA]5
SMITHKLINE BEECHAM CORP24
[HEM PHARMA CORP]8
H V A WATER CONTRACTORS B V2
[JAPAN ENERGY CORP]4
[NIPPON MINING]3
[UNIV JOHNS HOPKINS]3
[WHITEHEAD BIOMEDICAL INST]8
[UNIV LOUISIANA STATE]4
[CEDARS SINAI MEDICAL CENTER]5
RES CORP TECHNOLOGIES INC2
[VERIGEN INC]5
BIORESEARCH SPA4
[VESTAR INC]2
[VICAL INC]3
[VIROVAHL]2
[SYNTELLO INC]6
ANORMED INC3
[JOHNSON MATTHEY PLC]9
DU PONT4
DU PONT MERCK PHARMA4
SANOFI2
[BIOMERIEUX]3
[ACAD OF SCIENCE CZECH REPUBLIC]4
[REGA STICHTING]13
ASTRA AB10
[MEDIVIR AB]14
BIO MEGA INC5
[BOEHRINGER INGELHEIM]34
SEARLE CO63
PHARMACIA CORP9
MONSANTO CO37
[INSTITUT PASTEUR]65
[INSERM]8
[CNRS]17
[UPMC]3
[TRANSGENE]5
[UNIV GEORGIA]12
[UNIV EMORY]25
[SHIRE PLC]5
SHILY BIOLOG CHEMISTRY CO LTD2
[BIOCHEM PHARMACEUTICAL INC]12
[UNIV NEW YORK]12
[AMERICAN BIOSCIENCES]5
[US GOVERNMENT]99
[NASA]2
[NIH]5
[UNIV ILLINOIS]6
[ROCHE]18
[WELLCOME FOUNDATION LTD]18
[WELLA]2
GLAXO12
BURROUGHS WELLCOME CO7
[QLT PHOTOTHERAPEUTICS INC]3
[UNIV BRITISH COLUMBIA]3
[TEIJIN LTD]3
[UNIV ARIZONA]3
[UNIV NAT AUSTRALIA]3
[CSIRO]3
[UNIV WAKE FOREST]4
[UNIV MICHIGAN]4
[UNITED BIOMEDICAL]12
[UNIV OXFORD]3
MEDICAL RES COUNCIL8
MERRELL DOW PHARMA23
DOW CHEMICAL CO3
Figure 30 : The major collaborations by number of joint filings from 1983 to 1992
www.frinnov.fr
49HIV Therapy 2009 49
5.2.3 Topics protected (1983-1992)
Three targets strongly dominate this period: protease, envelope proteins and reverse transcriptase. All
four classes of compounds are the subject of research, but especially peptide compounds. This is
because the first patent applications describe the virus and its variants. Peptide compounds derived
from the viral structure were claimed as potential immunogens at that time, and thus potential
vaccines.
In the same way, Merck&co concentrated its research on the discovery of chemical and peptide
compounds inhibiting reverse transcriptase and protease. Merck&co also worked on developing a
vaccine and was the only major applicant to focus on integrase inhibitors at that time.
Searle, Monsanto (and thus Pharmacia since a certain number of these companies’ patents were
transferred when the companies were acquired) and Merrel Dow Pharmaceuticals only concentrated
their research on one target: chemical compounds inhibiting protease. This is also true, but less so,
for Abbott and Boehringer-Ingelheim which each also worked on another target (structural proteins
and genes and reverse transcriptase respectively).
Genentech, like the University of New York, only worked on glycoproteins and developed antibodies
targetting these proteins as well as possible vaccines.
The CNRS, Institut Pasteur, Dana Farber Cancer Institute, Duke University, United Biomedical, Chiron
and Novartis worked on 3 main targets (GPn, structural and regulatory proteins) and one main
application (vaccine) via the injection of immunogenic peptides.
It must be remembered that the presence of Novartis at this time is due to the merger with Chiron
resulting in the transfer of ownership of certain Chiron patents to Novartis.
Isis only worked on nucleosides/(poly)nucleotides & analogs inhibiting viral entry.
Smithkline Beecham concentrated its research on several targets, mainly protease and GP/CD4 to
develop a vaccine and mainly chemical and peptide inhibitors.
US government laboratories investigated all targets (except integrase), all compounds and
applications but especially vaccines and inhibitors.
It should also be noted that because none of the applicants was working on chemokine receptor
antagonists at this time, this category was not included in the analysis for this period.
50
50
Figure 31: Therapeutic targets of the major players from 1983-1992
www.frinnov.fr
51
51
Figure 32: Applications of the major players from 1983-1992
www.frinnov.fr
52
52
Figure 33: Classes of compounds of the major players from 1983-1992
www.frinnov.fr
53HIV Therapy 2009 53
5.3 Analysis for the intermediary period (1993-2000)
5.3.1 Main applicants (1993-2000)
There were 2645 filings naming 4600 inventors during this period. The number of filings increased
significantly. During the pioneer period (1983-1992), there were an average of 150 patents filed per
year, reaching 330 filings per year between 1993 and 2000.
Figure 34: Major applicants from 1993 - 2000
From 1993 to 2000, Merck&co and the US government laboratories are the two top applicants.
Merck&co is clearly in the lead with more than 175 filings while the US government labs only filed 98
applications during the same period.
Smithkline-Beecham, which was in the 8th position during the pioneer period (1983-1992), is now in
3rd place. The University of California, in 12th position during the pioneer period, moves up to 6th
place. Abbott maintains its position and moves from 9th to 7thplace.
Many new applicants appear on the list: Dupont pharmaceuticals (which bought DuPont-Merck
licenses in 1998) and BMS (which bought DuPont Pharmaceuticals in 2001) can be found in 4th and 5th
place respectively. Agouron, Johnson & Johnson, Progenics Pharmaceuticals, Vertex Pharmaceuticals
0
20
40
60
80
100
120
140
160
180
200
MERCK
US GOVERNMENT
SMITHKLINE BEECHAM
DUPONT PHARMABMS
UNIVCALIF
ORNIA
ABBOTT
AGOURON PHARMA
MONSANTO CO
JOHNSON
& JOHNSON
PROGENICS PHARM IN
C
VERTEX PHARMA
WARNER LAMBERT C
O
AVENTIS
GLAXO
PARKER HUGHES IN
STITUTECNRS
DUPONT MERCKPHARMA
UNIV D
UKE
LG GROUP
Num
ber o
f pat
ent a
pplic
atio
ns www.frinnov.fr
54HIV Therapy 2009 54
and Warner Lambert also suddenly appear on the scene. Institut Pasteur is no longer one of the top
applicants. Aventis, created in 1999 with the merger between Hoechst AG (which merged with Merrel
Dow in 1995 and Roussel Uclaf in 1997) and Rhône Poulenc Rorer SA becomes a player (45 patents if
all the filings of these companies are added together).
Monsanto which has acquired Searle moves from 5th to 9th place. Institut Pasteur with 20 patents,
Dana Farber Cancer Institute with 7 and Roche with 13 patents can no longer be found on the list.
Upjohn (acquired by Pharmacia in 1995), Biogen (3 patents), Genentech (13 patents), University of
Texas (11 patents) and Medivir (13 patents) have also disappeared.
93 94 95 96 97 98 99 00MERCK & Co 23 20 15 30 20 21 28 18
US GOVERNMENT 13 9 10 11 15 11 18 10SMITHKLINE BEECHAM CORP 7 2 2 4 9 16 24 8
DUPONT PHARMA 2 1 3 13 9 21 8 5BMS 2 3 2 6 8 9 8 17
UNIV CALIFORNIA 10 8 6 3 11 4 4 4ABBOTT 11 2 8 5 3 2 8 5
AGOURON PHARMA 8 3 7 15 2 4 1 1MONSANTO CO 2 26 1 5
JOHNSON & JOHNSON 3 2 1 3 12 3 6PROGENICS PHARM INC 3 1 2 9 1 6 2 5
VERTEX PHARMA 1 6 2 6 4 6 3WARNER LAMBERT CO 7 7 3 2 1 2 4
GLAXO 1 5 3 6 8 2AVENTIS 1 1 3 8 3 9
PARKER HUGHES INSTITUTE 10 5 9DU PONT MERCK PHARMA 3 4 3 9 4
CNRS 1 2 3 1 1 6 4 5UNIV DUKE 8 5 3 1 5
PFIZER 1 3 3 5 9
Table 10: Evolution of filings by applicant from 1993-2000
An analysis of filings over time is an indicator of which of the most active players continued to file
vigorously throughout the entire period, for example, the company Merck&co with 20 applications per
year or the US government laboratories with nearly 10 filings per year.
The Parker Hughes Institute also plays a top role during this period after 1997.
5.3.2 Collaborations (1993-2000)
The figure below shows the clusters of collaborations among applicants for the period from 1993 to
2000. Only collaborations which resulted in 2 joint filings have been included.
55HIV Therapy 2009 55
The collaborations that resulted in the most joint filings were between Agouron and Japan Tobacco
(20 joint filings), the joint venture between Dupont Merck and DuPont Pharmaceuticals (15 joint
filings), and Merck&co with Tularik (8 joint filings), Duke University with Trimeris (6 joint filings),
University of North Carolina with Biotech Research Laboratories (7 joint filings), with the University of
Wake Forest (6 joint filings), with Panacos (5 joint filings) and with Alphavax (3 joint filings).
This analysis could not identify informal collaborations which did not result in any joint filings, which
occurred, for example between the CNRS, Institut Curie and the company Johnson & Johnson and the
University of North Carolina with Wyeth.
2
8
2
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2 2 2
22 2
2 2 22
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2
2
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2
3
3
2
2
2
2
2
3
WAYNE HUGHES INST3
[PARKER HUGHES INSTITUTE]24
[ALPHAVAX HUMAN VACCINES INC]3
[UNIV CAPE TOWN]2
SERONO2
[APPLIED RESEARCH SYSTEMS]5
CRYOPRESERVATION CC2
VIRODENE2
BIOMEDICAL EXPLORATIONS LLC2
BIOMED COMM INC2
[WELFIDE]2
[MITSUBISHI]4
[UNIV UTAH]4
COGNETIX INC2
[UNIV INDIANA]2
ADVANCED RES TECH INST4
[UBE INDUSTRIES]2
[SANKYO]5
[SUBSIDIARY NO 3 INC]9
[PPD DEV LP]2
[REGA FOUNDATION LEUVEN]2
[UNIV CARDIFF]2
[PHARMAPRINT INC]2
[UNIV CALIFORNIA]50
[ORSTOM]2
[IRD]2
[INST SUPERIORE SANITA]5
[UNIV CAGLIARI]3
[ENEA TEC]2
[CROMPTON CIE]2
[UNIROYAL]4
[CHIMERIC THERAPIES INC]2
ALLEGHENY UNIV HE2
[NANOSYSTEMS LLC]2
[ELAN INC]5
UPJOHN CO21
PHARMACIA CORP13
[GENETICS INSTITUTE LLC]5
GEN HOSPITAL CORP5
[LEUKOSITE INC]4
[DANA FARBER CANCER INSTITUTE]7
[UNIV COLUMBIA]9
[MILLENNIUM PHARM INC]11
WARNER LAMBERT CO26
[MUSC FOUNDATION]4
[UNIV SOUTH CAROLINA]4
SCHERING AG5
[IMMUNEX CORP]9
APOLLON INC2
[UNIV PENNSYLVANIA]21
[WISTAR INSTITUTE]7
[WYETH]15
[AMERICAN CYANAMID]16
[AMERICAN HOME PRODUCT CORPORATION]4
[UNIV PITTSBURGH]4
[AKZO NOBEL]9
[BIOMERIEUX]8
[IDENIX PHARMACEUTICALS INC]11
[UNIV MONTPELLIER]5
[JOHNSON & JOHNSON]30
[INSTITUT CURIE]3
[CNRS]23
CELLPEP S A4
[ZAMBON SPA]2
[INSERM]14
[UNION PHARMA SCIENT]2
[INSTITUT PASTEUR]19
[BIOWINDOW GENE DEV INC]4
[SHANGHAI BODE GENE CO]8
[REGA STICHTING]6
[UNIV LOUVAIN]7
DU PONT3
DU PONT MERCK PHARMA23
[BMS]55
DUPONT PHARMA62
AGOURON PHARMA41
[PFIZER]21
[JAPAN TOBACCO INC]20
[MERCK]175
[TULARIK INC]8
[BIOTECH RES LABORATORIES]7
VI TECHNOLOGIES INC2
[PANACOS PHARMACEUTICALS INC]8
[UNIV NORTH CAROLINA]21
[UNIV WAKE FOREST]8
MEDICAL RES COUNCIL8
[THEREXSYS LTD]3
[PURDUE RESEARCH FOUNDATION]2
[US GOVERNMENT]97
[AGUETTANT]5
[UNIV TEL AVIV]2
[NASA]10
[UNIV IOWA]6
[UAF TECHNOLOGIES AND RES LLC]5
[PROCTER AND GAMBLE]18
[UNIV ARIZONA]13
ARIZONA DISEASE CONTROL RES COMMISSION2
RHONE POULENC RORER11
SANOFI8
AVENTIS25
[CENTEON PHARMA GMBH]2
[BAYLOR COLLEGE OF MEDICINE]5
HOECHST AG6
[SYSTEMIX INC]4
[NOVARTIS]12
CIBA GEIGY AG9
SANDOZ SA4
[AARON DIAMOND AIDS RES CENTER]10
[PROGENICS PHARM INC]29
[UNIV DUKE]22
[UNIV DURHAM]2
[BETH ISRAEL HOSPITAL]5
[TRIMERIS INC]15
ANORMED INC16
[JOHNSON MATTHEY PLC]2
SMITHKLINE BEECHAM CORP72
NIKEM S R L2
GLAXO25
GSK5
[UNIV GEORGIA]10
[UNIV EMORY]19
[UNIV YALE]9
Figure 35: The major collaborations and the number of joint filings from 1993-2000
www.frinnov.fr
57HIV Therapy 2009 57
5.3.3 Topics protected (1993-2000)
The main differences from the previous period (1983-1992) were:
1. the interest in chemokine receptors corresponding to Pfizer, Progenics, Takeda and Anormed
becoming top applicants mainly for the application of antagonists but also for
immunomodulation.
2. the increasing interest in integrase inhibitors (especially Merck&co, Shionogi, UAB Research
Foundation, University of North Carolina and US government laboratories).
3. research gradually turned away from peptide compounds and thus vaccines. Only academic
researchers continued to work on this subject as well as the industrials Aventis and Merck&co
(and less intensively BMS, Boehringer-Ingelheim and Smithkline Beecham).
Merck&co strongly diversified its research, focusing especially on the discovery of chemical
compounds inhibiting protease and integrase and interfering with chemokine receptor. Merck&co was
the only major applicant to continue working on a vaccine. It is also interesting to note that
Merck&co, after being a pioneer in integrase inhibitors, remains clearly in the lead as applicant in this
sector from 1993-2000. Merck&co is also a pioneer in the protection of combination therapies.
Dupont Pharmaceuticals, BMS, Abbott, Dupont Merck, Glaxo, Parker Hughes Institute and Boehringer-
Ingelheim all mainly developed reverse transcriptase and protease inhibitors. Abbott concentrated its
research on protease and Parker Hughes Institute and Boehringer-Ingelheim on reverse transcriptase.
These inhibitors are mostly chemical compounds but two applicants, Parker Hughes Institute and
Glaxo also developed compounds in the class of.
Monsanto, Upjohn and LG group concentrated on chemical compounds inhibiting protease. The
companies Vertex Pharmaceuticals, Warner Lambert, Agouron, Japan Tobacco and Procter&Gamble
also began working on this target.
The company Progenics focused on a strategy of inhibiting viral entry by strongly dominating CD4
research.
The University of Emory concentrated on but, as our graph shows, without an associated target. In
fact these were Fluoronucleosides which have no specific target.
Smithkline and Aventis were working on antibodies, chemical and peptide compounds inhibiting viral
entry as well as regulatory and structural proteins. Smithkline also patented
nucleosides/(poly)nucleotides & analog compounds.
Finally, Johnson & Johnson concentrated on chemical compound inhibiting reverse transcriptase.
58
58
Figure 36: Therapeutic targets of the major players from 1993-2000
www.frinnov.fr
59
59
Figure 37: Applications of the major players from 1993-2000
www.frinnov.fr
60
60
Figure 38: Classes of compounds of the major players from 1993-2000
www.frinnov.fr
61HIV Therapy 2009
5.4 Analysis for the most recent period (2001 - 2006)
5.4.1 Major applicants (2001-2006)
2616 patents were filed during this period naming more than 5900 inventors. The number of filings is
similar to that of the intermediary period (2616 versus 2645) although the latter was shorter (6 years
versus 8). As a result even if there is a tendency for a downturn in the number of applications, the
filing rate remains vigorous. The significant increase in the number of inventors should be noted for a
similar number of filings (6000 versus 4800), which is a sign of stronger collaborations and sharing of
expertise to favour innovation.
Figure 39: Major applicants from 2001 - 2006
Many of the players were already found in the top 20 during the intermediary period, usually large
pharmaceutical groups. BMS, which now includes DuPont Pharmaceuticals and DuPont Merck moves
from 5th to 1st place, Pfizer which now includes Warner Lambert and Agouron moves up to 2nd place.
Merck&co remains in a leading position with more than 80 filings. GSK which now includes SmithKline
Beecham and Glaxo (3rd and 15th place respectively from 1993-2000) moves up to 6th position but with
a marked slowdown in the filing rate. This same tendency is seen for Progenics Pharmaceuticals which
nevertheless remains a top applicant.
Tibotec appears for the first time in a top position in 5th place, as well as Schering Plough Corp in 8th,
Gilead in 10th and Novartis in the 13th place. Roche is found in 7th place and Boehringer-Ingelheim in
9th both returning to the list after having disappeared during the intermediary period.
0
20
40
60
80
100
120
BMS
PFIZER
US GOVERNMENT
MERCK
TIBOTEC INC
GSK
ROCHE
SCHERING PLO
UGH CORP
BOEHRINGER IN
GELHEIM
GILEAD
NOVARTIS
UNIV CALIF
ORNIA
MONOGRAM BIO
SCIENCES INC
CNRS
JOHNSON & JO
HNSON
ANGELETTI P
IST R
ICHERCHE
INSERM
UNIV MARYLAND
PROGENICS PHARM IN
C
BAYER AG
Num
ber o
f pat
ent a
pplic
atio
ns
www.frinnov.fr
62HIV Therapy 2009
Monogram Biosciences, and Bayer AG are now Top 20 applicants, but with fewer filings than others.
Abbott and Vertex Pharmaceuticals which had been well positioned during the intermediary period
have disappeared from the list.
The new entity Sanofi-Aventis (created in 2004 when Sanofi-Synthelabo acquired Aventis which was
one of the Top 20 from 1993-2000) has now disappeared.
US government laboratories are the only academic research institute to continue to invest massively in
this topic, and less spectacularly the University of California and the CNRS. INSERM is now on the list,
moving up from 40th to 17th place, showing its growing interest in this topic.
01 02 03 04 05 06BMS 14 21 14 24 15 10
PFIZER 13 19 30 22 6 4US GOVERNMENT 19 11 24 23 7 8
MERCK & Co 14 19 12 19 12 8TIBOTEC INC 13 12 12 12 12 16
GSK 9 13 2 8 14 4ROCHE 11 5 7 8 4 7
SCHERING PLOUGH CORP 17 8 3 3 7 3BOEHRINGER INGELHEIM 5 15 12 1 7
GILEAD 2 5 7 5 4 8NOVARTIS 3 3 3 3 4 6
MONOGRAM BIOSCIENCES INC 8 5 2 5 1UNIV CALIFORNIA 3 4 4 4 3 3
JOHNSON & JOHNSON 5 2 4 1 3 4ANGELETTI P IST RICHERCHE 4 3 9 3
CNRS 6 1 3 4 3 2UNIV MARYLAND 1 5 4 2 5 1
INSERM 4 3 3 2 2 4PROGENICS PHARM INC 7 2 2 3 1 2
BAYER AG 1 4 10 2
Table 11: Evolution of filings by applicant from 2001- 2006
An analysis of the evolution of filings from 2001 to 2006 clearly shows two types of applicants: those
that turn away from this field in 2005 and those that remain seriously invested in this topic.
Despite its acquisition of Pharmacia Corp. in 2002 (which had merged with Upjohn in 1995 then
Monsanto in 2000, two very important players in this field), Pfizer, like US government laboratories
and Bayer, completely discontinues research in this field after 2005. This is also true for Merck&co,
but to a lesser extent.
BMS, Tibotec, Roche, Gilead, Novartis and Johnson & Johnson remain strongly invested in this topic in
the last years of the study, with Tibotec, Gilead (in particular after the purchase of Triangle
Pharmaceuticals) and Novartis (with the purchase of Chiron) even strengthening their positions in
2006.
It should also be noted that Tibotec was acquired by Johnson & Johnson in 2002.
63HIV Therapy 2009
The University of California, CNRS and INSERM all have a continued, but modest interest in the
subject throughout this period
5.4.2 Collaborations (2001-2006)
The figure below shows the clusters of collaborations among applicants for the period from 2001 to
2006. Only collaborations which resulted in 2 joint filings have been included.
Overall, and compared to the previous periods, relatively few joint filings occurred from these
collaborations. The most important include the collaborations between Schering Plough Corp. and
Pharmacopeia (9 joint filings), Merck&co and « IRBM P. Angeletti » (Italian research subsidiary of
Merck&co) after 2000 (6 joint filings), Georgetown University with Samaritan Pharmaceuticals (5 joint
filings), and Institut Pasteur with the CNRS and INSERM (5 joint filings each).
This analysis could not identify informal collaborations that did not result in any official joint filings.
These occurred for example between Takeda and the company Syrrx (which was acquired by Takeda
in 2005) and with the company Paradigm Therapeutics (bought by Takeda in 2007), Genzyme and
Anormed (bought by Genzyme in 2006), Astex and Astrazeneca, Progenics and the Cornell
Foundation, Ambrilia with Pharmacor and Procyon (both bought by Ambrilia in 2006), Ardea and
Valeant (thanks to a transfer of research teams from Valeant to Ardea) and finally Roche and
Maxygen.
2
22
2
2 2
2
2
2
2
22
2
2
2
2
2
4
2
2
2
22
3
3
5
3
15
6
2
22
5
5
32
2
2
2
2
22
2
9
7
2
2
5
5
32
22 2 2
4
2
4
4
3
2
2
[ANADYS PHARMACEUTICALS INC]2
[LG GROUP]4
[ASTELLAS PHARMA INC]3
[FUJISAWA]2
[BEIJING QINGDA YINGHUA BIO TEC]2
[UNIV TSINGHUA]2
[GENECRAFT INC]2
[TRUBION PHARMACEUTICALS INC]2
[ICE BIOLOG LTD]2
[AIMSCO LTD]4
[INNATE PHARMA]2
[NOVO NORDISK]7
[JORDANIAN PHARMA MFG]2
[TERRAMARK MARKENCREATION GMBH]2
[MIKONIK TECHNOLOGIES LTD]2
[DREBSK COMPTECH INC]2
[NIID]2
[JAPAN SCI AGENCY]10
[PEPTERA PHARMACEUTICALS LTD]2
CHAY GROUP N2
[REPUBLIC KOREA]3
[UNIV HANDONG GLOBAL (COREE)]2
[SAN ROMANELLO CTR FOND]2
[SAN RAFFAELE CTR FOND]4
MEDICAL RES COUNCIL3
[UNIV CAMBRIDGE]2
[UNIV MARYLAND AT BALTIMORE]2
[UNIV MARYLAND]18
PARADIGM THERAPEUTICS LTD2
[AMEDIS PHARMACEUTICALS]2
[TAKEDA]16
SYRRX INC4
[INST CLAYTON DE LA RECHERCHE]3
[RES DEV FOUNDATION]2
[BETH ISRAEL HOSPITAL]2
[UNIV DUKE]10
ANORMED INC10
[GENZYME CORP]3
[YISSUM]6
[UNIV TEL AVIV]3
[BAYLOR COLLEGE OF MEDICINE]3
[BAYER AG]17
[SOUTH AFRICAN COUNCIL]3
[UNIV CAPE TOWN]3
[IDENIX PHARMACEUTICALS INC]9
[UNIV CAGLIARI]3
AGOURON PHARMA20
[PFIZER]89
PHARMACIA CORP16
[CONSEJO SUP INVESTIG CIENTIFIC]8
[IRBM P. ANGELETTI]19
[MERCK]84
[UNIV DEGLI STUDI MILANO]4
[INSTITUT PASTEUR]11
[INSTITUT GUSTAVE ROUSSY]2
[UNIV PARIS SUD XI]3
[CNRS]19
[INSERM]18
[EUROFINS VIRALLIANCE INC]2
[APHP]3
[GILEAD]31
[ABBOTT]12
TRIANGLE PHARMA3
[IMMUNOCLIN LTD]4
[IRD]4
[OSAKA INDUSTRIAL PROMOTION ORGANIZATION]3
[SCHERING PLOUGH CORP]41
[PHARMACOPEIA]10
[XOMA TECHNOLOGY LTD]2
[NOVARTIS]22
[TRIAD THERAPEUCTICS INC]2
CHIRON CORP13
[GEORGETOWN UNIV]6
[SAMARITAN PHARMACEUTICALS]6
[US GOVERNMENT]92
VI TECHNOLOGIES INC4
[PANACOS PHARMACEUTICALS INC]11
[SCRIPS INSTITUTE]11
[NASA]5
[UNIV EMORY]10
[UNIV GEORGIA]7
[PHARMASSET INC]6
[PROGENICS PHARM INC]17
[CORNELL FOUNDATION INC]8
[AARON DIAMOND AIDS RES CENTER]4
[VALEANT PHARMA]5
[ARDEA BIOSCIENCES INC]7
GSK50
[SHIONOGI]14
PHARMACOR INC6
PROCYON BIOPHARMA INC4
[DAVID GLADSTONE INST]5
[UNIV CALIFORNIA]21
TIBOTEC INC77
[MEDIVIR AB]14
Figure 40: The major collaborations and joint filings (2001-2006)
www.frinnov.fr
65HIV Therapy 2009 65
5.4.3 Protected topics (2001-2006)
During this period, the major applicants began focusing their research on integrase inhibitors and
chemokine receptors antagonists, and less markedly glycoproteins.
This is particularly true of BMS, which strengthened its reverse transcriptase and protease portfolio by
by buying Dupont Pharmaceuticals in 1998.
Unexpectedly, Merck&co, which was the top applicant for chemokine receptors from 1993 to 2000,
abandoned this therapeutic target between 2001 and 2006.
GSK, created from the merger of Smithkline Beecham (whose portfolio covers nearly all targets) and
Glaxo (focusing on reverse transcriptase and protease) is the only player which still covers all targets
with chemical or nucleosides/(poly)nucleotides & analog compounds.
Abbott and Pfizer also diversify their therapeutic targets while concentrating on chemical compounds.
Monogram Bioscience and Tibotec have the same strategy. They develop tests for the efficacy of
inhibitors for most of the potential therapeutic targets. Tibotec further strengthens its position by
concentrating on developing chemical or nucleosides/(poly)nucleotides & analog compounds inhibiting
protease and reverse transcriptase.
Schering-Plough becomes the leader in the field of chemokine receptors and immunomodulation.
Institut Pasteur and the company Chiron are the only players to continue working on potential
vaccines.
Finally, Bayer explores different avenues of research without concentrating on one specific topic.
66
Figure 41: Therapeutic targets from 2001-2006
www.frinnov.fr
67
Figure 42: Applications of the major players from 2001-2006
www.frinnov.fr
68
Figure 43: Classes of compounds of the major players from 2001-2006
www.frinnov.fr
69HIV Therapy 2009 69
6 Inventors in the field The aim of this section is to identify the most important inventors in the portfolios protecting HIV
treatments and determine which technologies they have developed. This evaluation is based on
several criteria:
- the gross volume of patents and filings in this field,
- the “expertise factor” that is the number of patents naming an inventor, multiplied by the number of
different co-inventors in those patents,
- the emerging inventors in the field, that is the inventors with the most growth in the number of
patents filed citing them in this field in 2004, 2005 and 2006. This helps identify potential emerging
inventors.
6.1 Inventors for the entire period (1983-2006)
6.1.1 The main inventors
The table below lists the inventors that are cited most often in patents and applications
Inventors Nb patents Applicants Nb patents
PFIZER 102Getman Daniel 106
JOHNSON & JOHNSON 4Decrescenzo Gary 86 PFIZER 86Vazquez Michael 84 PFIZER 84
PFIZER 75Talley John 76
MICROBIA 1PFIZER 75
Freskos John Nicholas 75ELAN INC 1
Mueller Richard 66 PFIZER 66INSTITUT PASTEUR 53
CNRS 9TRANSGENE 5
US GOVERNMENT 3Montagnier Luc 58
INSERM 2
70HIV Therapy 2009 70
Inventors Nb patents Applicants Nb patents
UNIV EMORY 38UNIV GEORGIA 18
UNIV CALIFORNIA 3OKLAHOMA MED RES FOUD 3UAB RESERCH FOUNDATION 3
UNIV ALABAMA 2JOHNSON MATTHEY PLC 2
NOVARTIS 1UNIV BIRMINGHAM 1PHARMASSET INC 1
ASTRAZENECA 1BAKER CUMMINS PHARMA 1
CNRS 1IDENIX PHARMACEUTICALS INC 1
UNIV NEW YORK 1
Schinazi Raymond 53
UNIV YALE 1PROGENICS PHARM INC 40
AARON DIAMOND AIDS RES CENTER 7CORNELL FOUNDATION INC 3
PDL BIOPHARMA INC 3GSK 1
Maddon Paul 44
UNIV COLUMBIA 1INSTITUT PASTEUR 37
CNRS 14INSERM 2
Sonigo Pierre 42
US GOVERNMENT 2INSTITUT PASTEUR 37
CNRS 13US GOVERNMENT 2
JERINI AG 1Alizon Marc 41
TRANSGENE 1MERCK & Co 39TULARIK INC 2Vacca Joseph 39
IRBM P. ANGELETTI 1MERCK & Co 38Wai John 38TULARIK INC 5
JOHNSON & JOHNSON 32NPIL PHARMACEUTICALS UK LTD 1Janssen Paul Adriaan 37AVECIA PHARMACEUTICALS LTD 1
JOHNSON & JOHNSON 29NPIL PHARMACEUTICALS UK LTD 1AVECIA PHARMACEUTICALS LTD 1
Heeres Jan 35
IDENIX PHARMACEUTICALS INC ABBOTT 33Kempf Dale 35
MERCK & Co 1PROGENICS PHARM INC 31
AARON DIAMOND AIDS RES CENTER 5CORNELL FOUNDATION INC 4
PDL BIOPHARMA INC 3Olson William 35
MERCK & Co 1
Table 12: The main inventors for the entire period (1983-2006)
71HIV Therapy 2009 71
6.1.2 The experts
A cross analysis can be made of the number of patents naming inventors and the number of different
co-inventors in those patents. This information, called the expertise factor, helps identify the most
prolific inventors who developed their inventions by collaborating with different scientists. In other
words the expertise factor provides information on how much an inventor « collaborates », sharing
his/her expertise with others.
The following graph shows the inventors with the strongest expertise factors for the entire period.
1386
1403
1440
1476
1554
1665
1672
2065
2184
2226
2360
2475
2494
2622
3538
4028
Mueller Richard
Gallo Robert
Young Steven
Alizon Marc
Sonigo Pierre
Janssen Paul
Talley John
Kempf Dale
Vazquez Michael
Schinazi Raymond
Vacca Joseph
Freskos John Nicholas
Decrescenzo Gary Anthony
Wai John
Montagnier Luc
Getman Daniel
Figure 44: Expertise factor for the entire period
This analysis shows that three of the main inventors collaborate more than others thus improving their
expertise rating compared to their rate of filing: Luc Montagnier, John Wai and Joseph Vacca.
6.1.3 Mobility of inventors
The figure below provides a general overview of how different inventors moved from one company to
another or from a research institute to a company and vice versa. In particular, this type of map is an
indicator of companies being started with institutionally owned patents and showing that researchers
then joined these companies. For instance, this map provides a good idea of Dr Dani Bolognesi’s and
Dr. Tom Matthews’ career from Duke University to the co-founding of Trimeris. Dr Graham Allaway
moved from Progenics Pharmaceuticals to Panacos Pharmaceuticals in a similar manner.
This graph also gives an idea of potential collaborations that may not have resulted in joint filings, for
example the collaborations between Georgetown University and Samaritan Pharmaceuticals and
Merck&co and Tularik.
More unexpectedly this figure also shows that the University of Arizona received a donation of several
HIV-patents previously owned by Procter & Gamble.
5337
37
26
2415
1413
13
11
11
10
10
9
99
9
8
77
77
7
7
6
6
6
5
5
5
5
5
5
5
5
5
4
40
31
18
13
12
12
11
10
10
10
10
9
9
8
8
8
8
7
7
7
7
7
7
7
7
77
7
6
6
6
6
6
65
5
5
5
5
55
5
5
5
5
5
5
5
5
55
55
5
5
5
5
5
5
4
4
38
19
18
15
38
32
20
14
55
55
5
5
18
8
5
166
1410
99
88
7
7
7
6
5
4
13
1010
10
9
9
8 8
8
8
8 7
77
7
7
6
6
6
5
5
5
5
5 4
4
128
12
65
5
11
9
8
7
65
5
5
108
8
6
98
8
7
7
4
7
6
6
55
55
5
6
5
5
5
Montagnier Luc58
[INSTITUT PASTEUR]95
Alizon Marc41
Sonigo Pierre42
Clavel Francois28
Wain-hobson Simon28
Krust Bernard15
[CNRS]59
Chamaret Solange16
Bryant Martin l12
[IDENIX PHARMACEUTICALS INC]20
Cole Stewart12
Hovanessian Ara13 Danos Olivier
11
Gosselin Gilles10
La Colla Paulo13
Artico Marino10
[UNIV CAGLIARI]7
Chermann Jean-claude18
Imbach Jean-louis11
[UNIV MONTPELLIER]6
[INSERM]40
Sommadossi Jean-pierre9
[TRANSGENE]11
Maddon Paul j44
[PROGENICS PHARM INC]51
Olson William c35
Allaway Graham p27
Gallo Robert c23
[US GOVERNMENT]288
Lambert Dennis michael12
[TRIMERIS INC]24Bolognesi Dani paul
15
[UNIV DUKE]43
Kucera Louis s12
[UNIV WAKE FOREST]14
Barney Shawn o lin10
Lee Kuo-hsiung10
[UNIV NORTH CAROLINA]32
Ishaq Khalid s10
Moore John p11
Wild Carl t21
[PANACOS PHARMACEUTICALS INC]19
Matthews Thomas james11
Morris-natschke Susan l8
[UNIV MARYLAND]37
Manak Mark8
[AARON DIAMOND AIDS RES CENTER]14
[BIOTECH RES LABORATORIES]8
Kashiwada Yoshiki7
Lee-huang Sylvia7
[UNIV NEW YORK]39
Huang Philip l6
Cragg Gordon m6
Huang Paul l6
Kung Hsiang-fu6
Chen Hao-chia5
[AMERICAN BIOSCIENCES]5
Dragic Tatjana5
Huang Henry i5
Huang Peter5
[UNIV ILLINOIS]10
Schinazi Raymond f53
[UNIV EMORY]54
Chu Chung k19
[UNIV GEORGIA]29
Wai John s38
[MERCK]355
Young Steven d32
Guare James p20
Egbertson Melissa s14
Clark David l5
[TULARIK INC]8
Camden James berger20
[PROCTER AND GAMBLE]19
[UNIV ARIZONA]18
[UAF TECHNOLOGIES AND RES LLC]5
Weiner David b28
[UNIV PENNSYLVANIA]23
[WISTAR INSTITUTE]9
Whitten Kathleen r14
[PFIZER]359
[JAPAN TOBACCO INC]31
Deason Michael e9
Albizati Kim francis9
Inaba Takashi8
Yamada Yasuki7
Remarchuk Travis p6
Taveras Arthur g15
[SCHERING PLOUGH CORP]61
Chao Jianhua12
Aki Cynthia j12
Merritt J robert12
Yu Younong11
Baldwin John j12
[PHARMACOPEIA]11
Dwyer Michael9
Fine Jay s9
Chao Jianping8
Biju Purakkattle j8
Li Ge9
Lai Gaifa6
Wu Minglang6
De clercq Erik21
[REGA STICHTING]20
[UNIV LOUVAIN]19
Spaltenstein Andrew18
[VERTEX PHARMA]52
Kazmierski Wieslaw mieczyslaw11
[GSK]187
Venkatesan Aranapakam mudumbai12
[AMERICAN CYANAMID]19
Levin Jeremy ian12
Chen James ming15
[GILEAD]51
[WYETH]24
Zask Arie7
Montana John gary10
[DARWIN DISCOVER LTD]10
[UCB SA]12
Dyke Hazel joan9
Vahlne Anders17
[TRIPEP AB]11
[SYNTELLO INC]8
Mcswiggen James a12
RIBOZYME PHARM INC9
[SIRNA THERAPEUTICS INC]9
Mao Yumin7
[SHANGHAI BODE GENE CO]8
[BIOWINDOW GENE DEV INC]4
Mcmichael Andrew james11
[UNITED BIOMEDICAL]16
MEDICAL RES COUNCIL19
Greeson Janet8
[SAMARITAN PHARMACEUTICALS]7
Lecanu Laurent7
[GEORGETOWN UNIV]7
Papadopoulos Vassilios7
Hertogs Kurt11
[JOHNSON & JOHNSON]141
[VIRCO]9
Rosen Craig a11
[DANA FARBER CANCER INSTITUTE]34
[HUMAN GENOME SCIENCES]8
Figure 45: Mobility of inventors
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Mcmahon James b6
Boyd Michael r6
Cardellina John h6
Laurent Anne g6
Hovanessian Ara8
Guetard Denise20
Clavel Francois22
Brun-vezinet Francoise11
Rouzioux Christine9
Krust Bernard11
Rey Marie-anne10
Montagnier Luc54
Chamaret Solange16
Guyader Mireille17
Alizon Marc40
Danos Olivier11
Wain-hobson Simon24
Cole Stewart12
Sonigo Pierre40
Tiollais Pierre8
Chermann Jean-claude10
Barre-sinoussi Francoise10
Eberlein Wolfgang6
Trummlitz Guenter dr6
Schmidt Guenter15
Engel Wolfhard10
Proudfoot John r6
Hargrave Karl d22
Grozinger Karl g7
Adams Julian7
Capon Daniel j7
Gregory Timothy j11
Merigan Thomas c8
Kozal Michael j6
Gait Michael john6
Karn Jonathan6
Heaphy Shaun6
Dingwall Colin6
Takatsuki Kiyoshi6
Hattori Toshio6
Vickers Timothy a6
Ecker David j9
Tung Roger dennis8
Bhisetti Govinda rao6
Murcko Mark andrew6
Romero Donna lee6
Aristoff Paul adrian6
Eberle Josef6
Guertler Lutz g6
Brunn Albrecht v6 Knapp Stefan
6
Hauser Hans-peter6
De clercq Erik11
Balzarini Jan maria8
Fung Michael sek7
Sun Cecily rou-yun9
Sun Bill nai-chau8
Chang Nancy t8
Chang Tse wen8
Mitsuya Hiroaki12
Broder Samuel12
Choi Woo-baeg13
Liotta Dennis c13
Schinazi Raymond f31
Chu Chung k8
Plattner Jacob j6
Kempf Dale j17
Sham Hing leung13
Zhao Chen10
Norbeck Daniel w17
Codacovi Lynn m7
Haseltine William alan14
Sodroski Joseph gerald12
Ramjit Harri g6
Balani Suresh k13
Goldman Mark e11
Theoharides Anthony d8
Saari Walfred s11
Williams Theresa m7
Wai John s11
Hoffman Jacob m9
Rooney Clarence s7
Thompson Wayne j10
Ghosh Arun k10
Huff Joel r20
Lyle Terry a11
Young Steven d16
Payne Linda s8
Britcher Susan f11
Lumma William c8
Vacca Joseph p15
Holloway Mary katharine9
Hungate Randall w12Guare James p
7
Dorsey Bruce d9
Anderson Paul cates8
Yoakim Christiane10
Heintz Robert martin31
Chrusciel Robert alan6
Bertenshaw Deborah e19
Getman Daniel p72
Lin Ko-chung17
Talley John jeffrey71
Clare Michael18
Reed Kathryn lea22
Vazquez Michael l61
Mueller Richard a61
Freskos John nicholas48
Rogier Donald joseph14
Decrescenzo Gary anthony61
Sun Eric tak18
Dina Dino7
Luciw Paul a7
Wang Haitao7
Muller Sybille7
Culbreth Paula h6
Hunter Robert l7
Emanuele R martin9
Tolman Richard l12
Emini Emilio a12
Marburg Stephen7
Lindborg Bjorn gunnar7
Johansson Karl nils8
Stening Goran bertil7
Nixon Douglas fraser7
Mcmichael Andrew james8
Townsend Alain robert7
Popovic Mikulas7
Gallo Robert c13
Institut PasteurSearle/Monsanto
Merck
MerckBoehringer-Ingelheim
Tanox
Univ. EMORY Abbott
Merck
Merck
1.1.1 Research teams for the entire period (1983-2006)
Figure 46: Research teams for the entire period (1983-2006)It should be noted that only inventors having at least 12 joint filings with another inventor are shown in this map.
Merck&Co
Merck&Co
Merck&Co
Merck&Co
Genzyme
Medivir
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74HIV Therapy 2009 74
6.1.5 Topics
The following figures provide a breakdown of the filings of the main inventors and/or experts into 4
categories
- Industrial/institutional filings
Figure 47: Industrial/institutional filings of the main inventors and/or experts
- breakdown by therapeutic target
Figure 48: Therapeutic targets protected by the main inventors and/or experts
www.frinnov.fr
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75HIV Therapy 2009 75
- breakdown by class of therapeutic compound
Figure 49: Classes of compounds protected by the main inventors and/or experts
- and finally the breakdown by application
Figure 50: Applications protected by the main inventors and/or experts
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76HIV Therapy 2009 76
These initial breakdowns give a very general picture which is difficult to interpret. This period must
therefore be analyzed in greater detail.
Nevertheless it is interesting to note:
- A fairly clear separation between academic inventors and industrial inventors.
- An over-representation of chemical compounds protected by industrial inventors, especially
protease inhibitors.
- On the other hand, a more global approach by institutional research teams which focus on
vaccines and screening methods for structural and regulatory proteins and their coding
genes.
Several research teams also emerge on this map:
- Dr Graham Allaway, Paul Maddon and William Olson’s team concentrating on entry
inhibition and viral fusion.
- Dr John Wai’s team and Dr Steven Young’s team focused on an approach targeting
integrase.
- Dr Faith Uckun’s team working on reverse transcriptase inhibition.
- Dr Raymond Schinazi’s team working on nucleic acids.
77HIV Therapy 2009 77
6.1.6 Description of the main inventors
This section provides a description of a few of the most important inventors and/or experts for the
entire period (1983-2006) who were not members of the same research groups.
Pr. Luc Montagnier, M.D, Ph.D., French doctor and virologist, was the pioneer inventor in HIV.
Indeed, he discovered the HIV virus in 1983 with the team he led at Institut Pasteur in Paris. In 1986,
Luc Montagnier and his group also isolated a second form of the HIV virus, HIV-2. Luc Montagnier
was the first Director of the « AIDS and Retrovirus » Department at Institut Pasteur where he
remained from 1991 to 1997. From 1997 to 2001, he was Professor and Director of the Center of
Cellular and Molecular Biology at Queens College at New York University.
Dr. Raymond Schinazi is a Professor of Pediatrics at the University of Emory and of Chemistry at
the University of Georgia. He is also « Senior Research Career Scientist » at the Veteran’s
Administration in Atlanta. He is especially known for his pioneer research on d4T (stavudine), 3TC
(lamivudine), FTC (EMTRIVA), D-D4FC (reverset), AN (racivir), and than AMDX (Amdoxovir®), drugs
that have been approved by the FDA or are in various stages of clinical development. He has founded
several biotechnology companies focusing on the discovery and development of new antiviral drugs
such as Pharmasset, Triangle Pharmaceuticals (acquired by Gilead Sciences in 2003), and Idenix
Pharmaceuticals (54% acquired by Novartis in 2003). At present, he is one of the Directors of Alios
Biopharma, a biotech company involved in the fight against viral infections and cancers.
Dr. Daniel P. Getman began his career in 1982 at Monsanto. With the merger of Monsanto and
Upjohn Pharmacia in 2000, Pharmacia was founded and then with the merger of Pharmacia and Pfizer
in 2002, Daniel Getman found his way to the number one pharmaceutical company in the world:
Pfizer. He is now Vice President of Worldwide R&D at Pfizer. He has also been named President of the
Committee of Exploratory Development and collaborates with different teams on the project to
identify new candidate drugs for clinical trials.
Dr Joseph Vacca, an American scientist, works at Merck&co. and filed a key patent in 1998
protecting the compound Indinavir, one of the first protease inhibitors to be marketed.
From 1981 to 1988, Paul J. Maddon, M.D., Ph.D., did research work at the Howard Hughes Medical
Institute at Columbia University. He founded Progenics Pharmaceuticals, a biopharmaceutical
company that works on the development and commercialization of novel therapeutic products to treat
as yet unmet medical needs of patients with debilitating or life threatening diseases. Since it was
founded in 1986, he has held the positions of Chairman of the Board of Directors, Chief Executive
Officer, President and Chief Scientific Officer. He also participates in two scientific examination
78HIV Therapy 2009 78
committees at the NIH (National Institutes of Health) and is a member of the editorial board of the
review « Journal of Virology ».
Paul Adriaan Janssen (1926-2003) founded Janssen Pharmaceutica, a Belgian pharmaceutical
company in 1953, which was then acquired by Johnson & Johnson in 1961. In 1995, Paul Adriaan
Janssen founded the « Center for Molecular Design », specialized in research to identify candidate
drugs to treat AIDS.
79HIV Therapy 2009 79
6.2 Pioneer inventors (1983-1992) The main inventors and the inventors with the best expertise factors from 1983 to 1992 are shown in
the tables below.
Inventors Nb patents Applicants Nb patents
SEARLE CO 59MONSANTO CO 30Getman Daniel 72
PHARMACIA CORP 5SEARLE CO 57
MONSANTO CO 32Talley John 71PHARMACIA CORP 5
SEARLE CO 52MONSANTO CO 23Decrescenzo Gary 61
PHARMACIA CORP 3SEARLE CO 53
MONSANTO CO 23Mueller Richard 61PHARMACIA CORP 3
SEARLE CO 53MONSANTO CO 23Vazquez Michael 61
PHARMACIA CORP 3INSTITUT PASTEUR 51
CNRS 9TRANSGENE 5
US GOVERNMENT 3Montagnier Luc 54
INSERM 2SEARLE CO 38
MONSANTO CO 19Freskos John 48PHARMACIA CORP 3
INSTITUT PASTEUR 37CNRS 13
US GOVERNMENT 2Alizon Marc 40
TRANSGENE 1
Table 13: List of the main inventors (1983-1992)
80HIV Therapy 2009 80
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994
1098
1098
1098
1240
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Clavel Francois
Schinazi Raymond
Chamaret Solange
Heintz Robert
Gallo Robert
Wain-hobson Simon
Huff Joel
Freskos John nicholas
Talley John jeffrey
Vazquez Michael
Mueller Richard
Decrescenzo Gary
Sonigo Pierre
Alizon Marc
Getman Daniel
Montagnier Luc
Figure 51: List of experts (1983-1992)
Pr. Luc Montagnier is clearly the top collaborator of all the other experts in this field.
The figure below shows the major research groups during this period (with at least 6 joint filings).
Several pioneer research teams emerge in the field, in particular two important groups:
- The group including the inventors Luc Montagnier, Marc Alizon and Pierre Sonigo, at Institut Pasteur,
which mainly filed patents describing the HIV-1 and HIV-2 virus (structural and regulatory proteins
and their coding genes) for diagnostic applications (not taken into account for the analysis),
biomarkers/screening methods and vaccines.
- And the group including the inventors Daniel Getman, John Talley, Richard Muller, Michael Vazquez,
Gary Decrescenzo, John Freskos and Robert Heintz, first with Monsanto (before joining Pfizer) which
mostly focused its research on chemical compound inhibiting protease.
Raymond Schinazi at the University of Emory and the University of Georgia, whose patents mostly
protect nucleotide compounds with no specific target should also be mentioned as well as Joel Huff,
Steven Young and Joseph Vacca who have protected chemical and peptide compounds inhibiting
protease and reverse transcriptase.
It should also be noted that most companies only work with 1 or 2 research groups, except for
Merck&co which is associated with 5 different research teams.
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Greenlee William j11
Mcmahon James b6
Boyd Michael r6
Cardellina John h6
Laurent Anne g6
Hovanessian Ara8
Guetard Denise20
Clavel Francois22
Brun-vezinet Francoise11
Rouzioux Christine9
Krust Bernard11
Rey Marie-anne10
Montagnier Luc54
Chamaret Solange16
Guyader Mireille17
Alizon Marc40
Danos Olivier11
Wain-hobson Simon24
Cole Stewart12
Sonigo Pierre40
Tiollais Pierre8
Chermann Jean-claude10
Barre-sinoussi Francoise10
Eberlein Wolfgang6
Trummlitz Guenter dr6
Schmidt Guenter15
Engel Wolfhard10
Proudfoot John r6
Hargrave Karl d22
Grozinger Karl g7
Adams Julian7
Capon Daniel j7
Gregory Timothy j11
Merigan Thomas c8
Kozal Michael j6
Gait Michael john6
Karn Jonathan6
Heaphy Shaun6
Dingwall Colin6
Takatsuki Kiyoshi6
Hattori Toshio6
Vickers Timothy a6
Ecker David j9
Tung Roger dennis8
Bhisetti Govinda rao6
Murcko Mark andrew6
Romero Donna lee6
Aristoff Paul adrian6
Eberle Josef6
Guertler Lutz g6
Brunn Albrecht v6 Knapp Stefan
6
Hauser Hans-peter6
De clercq Erik11
Balzarini Jan maria8
Fung Michael sek7
Sun Cecily rou-yun9
Sun Bill nai-chau8
Chang Nancy t8
Chang Tse wen8
Mitsuya Hiroaki12
Broder Samuel12
Choi Woo-baeg13
Liotta Dennis c13
Schinazi Raymond f31
Chu Chung k8
Plattner Jacob j6
Kempf Dale j17
Sham Hing leung13
Zhao Chen10
Norbeck Daniel w17
Codacovi Lynn m7
Haseltine William alan14
Sodroski Joseph gerald12
Ramjit Harri g6
Balani Suresh k13
Goldman Mark e11
Theoharides Anthony d8
Saari Walfred s11
Williams Theresa m7
Wai John s11
Hoffman Jacob m9
Rooney Clarence s7
Thompson Wayne j10
Ghosh Arun k10
Huff Joel r20
Lyle Terry a11
Young Steven d16
Payne Linda s8
Britcher Susan f11
Lumma William c8
Vacca Joseph p15
Holloway Mary katharine9
Hungate Randall w12Guare James p
7
Dorsey Bruce d9
Anderson Paul cates8
Yoakim Christiane10
Heintz Robert martin31
Chrusciel Robert alan6
Bertenshaw Deborah e19
Getman Daniel p72
Lin Ko-chung17
Talley John jeffrey71
Clare Michael18
Reed Kathryn lea22
Vazquez Michael l61
Mueller Richard a61
Freskos John nicholas48
Rogier Donald joseph14
Decrescenzo Gary anthony61
Sun Eric tak18
Dina Dino7
Luciw Paul a7
Wang Haitao7
Muller Sybille7
Culbreth Paula h6
Hunter Robert l7
Emanuele R martin9
Tolman Richard l12
Emini Emilio a12
Marburg Stephen7
Lindborg Bjorn gunnar7
Johansson Karl nils8
Stening Goran bertil7
Nixon Douglas fraser7
Mcmichael Andrew james8
Townsend Alain robert7
Popovic Mikulas7
Gallo Robert c13
Institut PasteurSearle/Monsanto
Merck&Co
MerckBoehringer-Ingelheim
Tanox
Univ. EMORY Abbott
Merck
Merck
Figure 52: The major collaborations among inventors (1983-1992)
Merck&Co
Merck&Co
Merck&Co
Merck&Co
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Figure 53: Therapeutic targets of the main inventors (1983-1992)
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Figure 54: Applications of the main inventors (1983-1992)
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Figure 55: Classes of compounds of the main inventors (1983-1992)
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HIV Therapy 2009 8585
6.3 Main inventors from 1993 to 2000 The main inventors and the inventors with the best expertise factors from 1993 to 2000 are shown in
the tables below.
Inventors Nb patents Applicants Nb patents
MONSANTO CO 30Getman Daniel 30
PHARMACIA CORP 1MONSANTO CO 26
PHARMACIA CORP 1UPJOHN CO 1
Freskos John nicholas 27
ELAN INC 1Elshourbagy Nabil 26 SMITHKLINE BEECHAM CORP 26
PROGENICS PHARM INC 25AARON DIAMOND AIDS RES CENTER 6Maddon Paul 26AROGENICS PHARMACEUTICALS INC 1
Decrescenzo Gary 25 MONSANTO CO 25Mills Sander 25 MERCK & Co 25
Sikorski James 25 MONSANTO CO 25PARKER HUGHES INSTITUTE 23
WAYNE HUGHES INST 3UNIV MINNESOTA 2
Uckun Fatih 25
HUGHES INST 2Maccoss Malcolm 23 MERCK & Co 23Vazquez Michael 23 MONSANTO CO 23
Devadas Balekudru 22 MONSANTO CO 22Mcdonald Joseph 22 MONSANTO CO 22
Nagarajan Srinivasan 21 MONSANTO CO 21MERCK & Co 20Vacca Joseph 20TULARIK INC 2
Table 14: List of the main inventors (1993-2000)
HIV Therapy 2009 8686
437
444
448
456
468
483
496
546
551
600
650
660
713
756
800
825
Schinazi Raymond
Wai John
Askin David
Norbeck Daniel
Guare James
Vazquez Michael
Reider Paul
Chapman Kevin
Kim Sung-Chun
Decrescenzo Gary
Elshourbagy Nabil
Getman Daniel
Maccoss Malcolm
Freskos John
Vacca Joseph
Mills Sander
Figure 56: List of experts (1993-2000)
Sander Mills, Joseph Vacca and John Freskos clearly top the list of experts during this period.
The figure below shows the main research groups during this period (with at least 6 joint filings), with
two large teams filing a significant number of patents ( 9):
- The group working with Daniel Getman at Monsanto, which continues to protect chemical
compounds inhibiting protease.
- The team working with Adriaan Janssen at Johnson&Johnson mainly protecting chemical compounds
inhibiting reverse transcriptase.
Numerous other research teams have increased their filing during this period. For example:
- The team at Progenics Pharmaceuticals led by Paul Maddon, working mostly on developing peptide,
nucleosides/(poly)nucleotides & analog compounds and antibodies to inhibit viral entry into the cell
and develop a vaccine,
- The team at SmithKline Beecham led by Nabil Elshourbagy, focusing on peptide and
nucleosides/(poly)nucleotides & analogs inhibiting protease and biomarker/screening methods.
- The team at Merck&co working with the inventors/« experts » Sander Mills and Malcom Maccoss,
mainly filing patents protecting immunomodulators and chemical compounds antagonists of
chemokine receptors,
- Another team at Merck&co working with Steven Young and Joseph Vacca who have diversified their
research and are focusing on chemical compounds (and peptide compounds for Joseph Vacca)
inhibiting reverse transcriptase and integrase (and protease for Joseph Vacca and vaccines for Steven
Young),
- A third team at Merck&co working with David Askin and Paul Reider on chemical compounds
inhibiting protease,
www.frinnov.fr
HIV Therapy 2009 8787
- The team at the Parker Hugues Institute working with Uckun Faith mainly on chemical compounds,
nucleosides/(poly)nucelotides and analogs inhibiting reverse transcriptase and protease and on
antibodies.
- And finally the team at the University of Emory with Raymond Schinazi working on chemical
compounds, nucleosides/(poly)nucleotides & analogs inhibiting protease, reverse transcriptase and
integrase and biomarkers/screening methods. He is the only major inventor to specifically develop
pharmaceutical formulations.
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Davies Mary-ellen m6
Freed Daniel c6
Babu Srinivasan6
Albizati Kim francis8
Remarchuk Travis p6
Szendroi Robert j6
Levin Jeremy ian11
Zask Arie7
Ziermann Rainer a6
Parkin Neil t7
Ghosh Soumojeet9
Alani Laman6Tait Bradley dean
8
Ellsworth Edmund lee6
Lunney Elizabeth ann6
Aristoff Paul adrian6
Thaisrivongs Suvit8
Skulnick Harvey irving6
Kaji Hideko6
Kaji Akira7
Wood Anthony6
Perros Manoussos6
Proudfoot John r7
Hargrave Karl d6
Boldin Mark p6
Wallach David9
Varfolomeev Eugene e6
Zhang Han-zhong6
Cai Sui xiong7
Drewe John a6
Anderson Dirk m6
Grabstein Kenneth h6
Eisenman June r6Fung Victor
6
Rauch Charles6
Marsh Kennan c6
Al-razzak Laman a10
Kaul Dilip7
Lee Kuo-hsiung7
Kashiwada Yoshiki6
Manak Mark7
Wu Xiaoyun7
Kappes John c7
Chan David c7
Kim Peter s12
Eckert Debra m7
Rodgers James david18
Wang Haisheng6
Patel Mona15
Cocuzza Anthony joseph8
Ishaq Khalid s7
Kucera Louis s7
Morris-natschke Susan l7
Yamada Yasuki7
Inaba Takashi8
Venkatesan Aranapakam mudumbai12
Baker Jannie lea7
Xie Yi7
Mao Yumin7
Suzuki Takayuki7
Izawa Kunisuke9
Honda Yutaka8
Busse Juliette kharsa8
Borer Bennett chaplin8
Whitten Kathleen r14
Deason Michael e9
Montana John gary10
Dyke Hazel joan8
Ayyavoo Velpandi8
Weiner David b20
Holzmayer Tanya a9
Dunn Stephen j9
Shiraishi Mitsuru7
Baba Masanori12
Kanzaki Naoyuki9
Nishimura Osamu9
Dressman Bruce anthony8
Kalish Vincent j9
Rodriguez Michael j8
Hammond Marlys8
Tatlock John h8
Fritz James e8
Shepherd Timothy a12
Hornback William j9
Munroe John e9
Reich Siegfried heinz11
Kaldor Stephen warren9
Silverman Keith c7
Lingham Russell b8
Singh Sheo bux12
Teran Ana m6
Zink Deborah l9
Uckun Fatih m25
Vig Rakesh7
Venkatachalam Taracad k10
Bolognesi Dani paul12
Wild Carl t10
Matthews Thomas james8
Lambert Dennis michael12
Langlois Alphonse j6
Barney Shawn o lin10
Petteway Stephen robert8
Schinazi Raymond f19
Liotta Dennis c10
Gosselin Gilles10
Bryant Martin l11
Imbach Jean-louis10
Hungate Randall w11
Vacca Joseph p20
Zhuang Linghang h6
Embrey Mark w8
Fisher Thorsten e8
Guare James p13
Egbertson Melissa s8
Wai John s12
Young Steven d15
Payne Linda s6
Tran Lekhanh o7
Sham Hing leung9
Kempf Dale j13
Norbeck Daniel w12
Chen Xiaoqi7
Elshourbagy Nabil a26
Vawter Lisa8
Shabon Usman12
Tsui Ping11
Lane Pamela6
Kaldor Istvan7
Tung Roger dennis13
Spaltenstein Andrew12
Sherrill Ronald george6
Baker Christopher t8
Furfine Eric steven12
Hale Michael robin12
Moon Kwang-ryul8
Jung Won-hee8
Kim Chung-ryeol8
Park Chi hyo8
Yoon Heungsik8
Koh Jong sung8
Choi Ho il9
Choy Nakyen8
Son Young-chan8
Park Ji-hyo9
Ko Jong-sung6Sonn Young-chan
7
Yun Heung-sik10
Choe Nak-hyun10
Choe Ho-ill10
Kim Sung-chun19
Lee Chang-sun13
Bogucki David earl12
Boehringer Eva maria7
Schols Dominique12
Bridger Gary james14
Skerlj Renato tony14
Varsolona Richard j8
Askin David16
Rossen Kai12
Reider Paul j16
Volante Ralph p15
Litwin Virginia m12
Allaway Graham p17
Maddon Paul j26
Olson William c17
Moore John p6
Ho Chih yung13
Kavash Robert w12
De jonge Marc13
Van aken Koen9
Koymans Lucien maria15
De corte Bart16
Janssen Paul adriaan18
Heeres Jan18
Kukla Michael joseph19
Ludovici Donald william19
Lynch Christopher l7
Hale Jeffrey j7
Willoughby Christopher a8
Oates Bryan8
Finke Paul e9
Chapman Kevin t13
Kim Dooseop8
Shen Dong-ming8
Mills Sander g25
Loebach Jennifer l6
Caldwell Charles g7
Maccoss Malcolm23
Nagarajan Srinivasan raj21 Brown David l
18
Mcdonald Joseph j22
Devadas Balekudru22
Vazquez Michael l23
Decrescenzo Gary anthony25
Sikorski James a25
Getman Daniel p30
Freskos John nicholas27
Liu Margaret a8
Shiver John w13
Perry Helen c8
Merck&Co Monsanto/Pharmacia
Vertex Merck&Co
LG life sciences
AgouronJohnson&Johnson
Merck&Co
Merck&CoMerck&Co
SmithklineBeecham
Takeda/ Bayer
Agouron Progenics
Abbott
DuPont Pharma
AnormedTrimeris
Immunex
Figure 57: The major collaborations among inventors (1993-2000)
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Figure 58: Therapeutic targets of the main inventors (1993-2000)
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Figure 59: Applications of the main inventors (1993-2000)
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Figure 60: Classes of compounds of the main inventors (1993-2000)
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HIV Therapy 2009 9292
6.4 Main inventors from 2001 to 2006
Inventors Nb Patents Applicants Nb patents
Wigerinck Piet 23 TIBOTEC INC 23BMS 20
PHARMACOPEIA 1Kadow John 22SCHERING PLOUGH CORP 1
Surleraux Dominique 22 TIBOTEC INC 21BMS 16
PHARMACOPEIA 1SCHERING PLOUGH CORP 1
Meanwell Nicholas 19
PHARMACIA CORP 1PROGENICS PHARM INC 15
CORNELL FOUNDATION INC 4PDL BIOPHARMA INC 3
MERCK & Co 1Olson William 18
AARON DIAMOND AIDS RES CENTER 1
MONOGRAM BIOSCIENCES INC 18Parkin Neil 18
18 VIR0LOGIC INC 1TIBOTEC INC 10
Guillemont Jerome 17JOHNSON & JOHNSON 5JOHNSON & JOHNSON 7
TIBOTEC INC 7Heeres Jan 17IDENIX PHARMACEUTICALS INC 1
Naidu Narasimhulu 17 BMS 17De bethune Marie-pierre 15 TIBOTEC INC 12
GILEAD 14Kim Choung 15
KRICT (KR) 1JOHNSON & JOHNSON 7
Lewi Paulus Joannes 15TIBOTEC INC 7
SCHERING PLOUGH CORP 13PHARMACOPEIA 8Taveras Arthur 15
INST SUPERIORE SANITA 1Wai John 15 MERCK & Co 15
BMS 13PHARMACOPEIA 1Wang Tao 15
SCHERING PLOUGH CORP 1
Table 15: Main inventors (2001-2006)
HIV Therapy 2009 9393
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Chen Xiaowu
Ueda Yasutsugu
Chen James ming
Williams Peter
Olson William
Summa Vincenzo
De bethune Marie-pierre
Heeres Jan
Taveras Arthur
Wai John
Jin Haolun
Meanwell Nicholas
Kadow John
Surleraux Dominique
Kim Choung
Wigerinck Piet
Figure 61: List of experts (2001-2006)
The classification of experts remains very close to that of the most prolific inventors during this
period. Only the inventors Choung Kim and Haolun Jin improve their position as a result of their
collaborations.
The figure below shows the major research groups during this period (with a minimum of 6 joint
filings). Two large teams emerge as the most prolific applicants ( 8):
- The team at Tibotec led by Piet Wigerinck and Dominique Surleraux mainly protecting chemical
compounds (and nucleosides/(poly)nucleotides & analogs for Piet Wigerinck) inhibiting protease and
reverse transcriptase as well as methods to evaluate these compounds.
- A second Tibotec / Johnson & Johnson team led by Jan Heeres and Jérôme Guillemont that protects
chemical compound inhibiting reverse transcriptase.
- The team at Schering Plough Corp working with Robert Merrit and Arthur Taveras, mainly protecting
immunomodulators and chemical compounds antagonists of chemokine receptors.
Other teams with inventors filing a significant number of patents during this period include:
- The team at BMS working with the « experts » John Kadow and Nicholas Meanwell focusing on
chemical compounds inhibiting viral entry (chemokine receptors, CD4 and glycoproteins) and
integrase for Nicholas Meanwell.
- A second team at BMS working with the inventor Naidu Narasimhulu mainly protecting chemical
compounds antagonists of chemokine receptor and inhibiting integrase, reverse transcriptase and
protease.
- The group at Merck&co with John Wai protecting only chemical compounds inhibiting integrase.
- The team at Chiron led by Susan Barnett should also be mentioned for its work on vaccine research.
www.frinnov.fr
HIV Therapy 2009 9494
- Finally the team at Progenics with William Olson and Paul Maddon working on antibodies and
peptide compounds for vaccine applications and viral entry inhibitors.
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Allaway Graham p8
Wild Carl t9
Mayers Douglas lytle8
Kraft Michael friedrich7
Courchesne Marc7
Moinet Christophe8
Mowbray Charles eric8
Jones Lyn howard8
Zhuang Linghang h7
Wai John s15
Williams Peter d10Lyle Terry a
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Root Richard terry8
Hui Raymond a8
Greeson Janet7
Papadopoulos Vassilios7
Lecanu Laurent7
Wamaki Shuichi7
Matsuzaki Yuji10
Aramaki Hisateru7
Shinkai Hisashi7
Satoh Motohide7
Kawakami Hiroshi7
Haynes Barton f11
Liao Hua-xin7
Shiraishi Mitsuru7
Baba Masanori9
Scott William j7
Dumas Jacques8
Virgil Scott c7
Canon-koch Stacie s7
Rocher Jean-philippe8
Palombi Giovanni7
Casimiro Danilo riguera7
Shiver John w8
Emini Emilio a7
Termin Andreas p8
Wilson Dean m8
Hong Zhi8
Girardet Jean-luc9
Koh Yung-hyo8
Zhang Junhu8
Plewe Michael bruno10
Yoakim Christiane9
O meara Jeffrey9
Simoneau Bruno8
Mceachern Ernest j8
Harwig Curtis8
Bridger Gary james9
Zhou Yuanxi8
Skerlj Renato tony11Schumacher Christoph
9
Marti Christiane7
Stojanovic Aleksandar7
Tschinke Vincenzo9
Herold Peter9
Stutz Stefan9
Orvieto Federica7
Pescatore Giovanna7
Summa Vincenzo14
Muraglia Ester9
Whitcomb Jeannette m8
Huang Wei8
Parkin Neil t18
Petropoulos Christos j13
Chao Jianping8
Dwyer Michael9
Li Ge9
Fine Jay s9
Biju Purakkattle j8
Lundell Daniel7
Yu Younong11
Baldwin John j11
Merritt J robert12
Aki Cynthia j12
Chao Jianhua12
Taveras Arthur g15
Chen James ming9
Chen Xiaowu8
Fardis Maria8
Jin Haolun13Kim Choung u
15
Maddon Paul j13
Olson William c18
Vinkers Hendrik maarten10
Daeyaert Frederik frans11
De jonge Marc11
Koymans Lucien maria12
Guillemont Jerome emile17
Janssen Paul adriaan13
Heeres Jan17
Lewi Paulus joannes15
Surleraux Dominique louis22
De kock Herman13
Wigerinck Piet tom23
Tahri Abdellah11
Verschueren Wim gaston9
Vendeville Sandrine marie10
Naidu Narasimhulu b17
Sorenson Margaret e8
Banville Jacques11
Plamondon Serge7
Remillard Roger8
Walker Michael a12
Matiskella John d12
Ueda Yasutsugu13
Yin Zhiwei10
Zhang Zhongxing14
Wang Tao15
Xue Qiufen may8
Kadow John f22
Regueiro-ren Alicia8
Meanwell Nicholas a19
Tibotec
Tibotec
BMS
Schering PloughJappan Tobacco
GileadIRBM P. Angeletti
Merck
Boehringer Ingelheim
MonogramBiosciences
Speedel
Genzyme
Progenics
Figure 62: The major collaborations among inventors (2001-2006)
Merck&Co
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Figure 63: Therapeutic targets of the main inventors (2001-2006)
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Figure 64: Applications of the main inventors (2001-2006)
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Figure 65: Classes of compounds of the main inventors (2001-2006)
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HIV Therapy 2009 99
6.5 Emerging inventors The table below shows the inventors with the strongest emergence factor. This corresponds to the
increase in the number of filings per inventor in 2004, 2005 and 2006.
2006 was the last year when all the data were available. In other words, this table presents the
inventors who have a strong potential of becoming future experts in the field of HIV therapy.
Emerging inventors Nbpatents Applicants Nb
patentsTopics
(nb patents) Schumacher Christoph
Herold Peter Stutz Stefan
Tschinke Vincenzo
9 9
Marti Christiane Stojanovic Aleksandar
7 7
Mah Robert 6 6Quirmbach Michael 5
SpeedelExperimenta AG
5
Chemical compounds (7) Protease inhibitors (9)
Joshi Pramod 6 Vertex Pharma 6
Chemical compounds (6)
Ion-channel modulator (6)
HIV-associated neuropathy (6)
Palombi Giovanni 6 6Le Poul emmanuel 5 5
Gagliardi Stefania 4
AddexPharmaceuticals
4
Chemical compounds (6)
Modulators of metabotropic glutamate receptors (6)
HIV-associated neuropathy (6)
Shionogi & Co 6Kawasuji Takashi 6
GSK 4Chemical compounds (6) Integrase inhibitors (6)
Spaltenstein Andrew 6 GSK 6Chemical compounds (6) Integrase inhibitors (6)
Tibotec 5
Jonckers Tim 5 UnivMassachussetts 1
Protease inhibitors (5) Biomarker / Screening methods (4)
Chemical compounds (3)
Gelbard Harris 5 Univ Rochester 5 HIV-associated neuropathy (5)
Millenium Pharm Inc 1
Raman Prakash 4
Rigollier Pascal 4Novartis 4
Inhibitors (5) of protease (2) and chemokine receptors (1)
Desai Manoj 4 Gilead 4Chemical (2) and peptide compounds (1) for pharmaceutical formulations (1) and inhibitors (4) of protease (3)
Table 16: List of emerging inventors
HIV Therapy 2009 100
7 ConclusionSince 1996, the marketing of protease and reverse transcriptase inhibitors and their many
combinations has significantly reduced mortality and improved the quality of life for AIDS patients. As
a result, a severe and deadly epidemic has now become a long term pandemic creating a colossal
market which will reach the astronomical sum of 15 billion US dollars in revenue in the upcoming
years.
7.1 No novel therapies in sight Nearly all the HIV therapeutics on the market today for mono-, bi- or tritherapy are protease and/or
reverse transcriptase inhibitors. The commercialization of several novel therapies, including viral entry
inhibitors (enfurvitide, 2003), chemokine receptor antagonists (Maraviroc, 2007) and integrase
inhibitors (Raltegravir, 2007) has only occurred very recently.
The industrial pipeline is seriously drying up in certain areas. Preclinical research now rarely provides
candidate drugs for clinical studies, especially for the important therapeutic targets of protease and
reverse transcriptase.
Our analysis of patenting strategies, which is the heart of this study, clearly shows the significant
downturn (40% fewer) in the number of filings. This downturn is true for all the targets and topics in
the study and is part of an overall tendency of the players to turn away from research and
development as well as a sign of reaching the limit of traditional approaches.
Fewer filings means fewer new molecules entering clinical trials and thus fewer chances for new drugs
on the market in the future.
We are seeing a real need for radical change in approach to HIV therapy, in particular the need to
develop novel therapeutic targets and gain further understanding of the interaction between the virus
and the immune system.
This situation is a unique opportunity for academic research because it reflects the need to get “back
to the basics” of fundamental research. In this context, academic research should remain dynamic,
driven by the need for industrials to exploit the expertise of public research, compensating somewhat
for the withdrawal of private research programs in this sector.
HIV Therapy 2009 101
Thus fundamental academic research will probably be closely monitored by industry to watch for the
emergence of novel therapeutic approaches which could represent the future of HIV therapy.
Emerging topics that were identified include maturation inhibitors and treatments targeting key cell
proteins that interact with HIV replication (cf. appendices).
7.2 Repositioning of the major industrial players Today, several companies dominate the field of HIV therapy, but they have each used different
strategies to obtain market penetration. Some have focused their research on specific fields and
others have pursued several directions. Some companies have purchased and developed promising
drug candidates discovered in academic research laboratories or Biotech companies, (Gilead and
Roche). Others have acquired licenses while still exploiting the results of their own research (GSK,
BMS, Tibotec, Abbott). Finally, others have only developed anti-virals from their own laboratories
(Boehringer-Ingelheim, Merck&co).
Thus, the major market players are not necessarily those that have invested in and protected
innovation (ie the main applicants) but those that seems to have had a pertinent medium-term
strategy.
Gilead, today’s recent market leader, only filed 44 patents between 1991 and 2006. Their position as
leader is therefore not a result of an intellectual property strategy but is based on the acquisition of
key molecules (promising candidates or drugs already approved by reglementary administrations)
(emtricitabine - collaboration between IOCB and Leuven Katholic University and tenofovir - Emory
University) and the development of combination therapies with these molecules.
Thanks to the acquisition of Tibotec, Johnson&Johnson, a recent player in this field, seems to be an
up and coming major market player. They have achieved this by having an innovative strategy which
includes having a strong position in the most popular therapeutic target inhibitors (reverse
transcriptase and protease) while at the same time developing new molecules against the resistances
that develop to existing treatments.
Among the other major market players, BMS, Abbott and Boehringer-Ingelheim have invested
substantially and concentrated their research on specific targets, mostly the discovery of chemical
compounds inhibiting reverse transcriptase, protease and integrase.
GSK, on the other hand, took the risk of diversifying its approach by expanding the scope of its
research to cover all therapeutic targets and all classes of compounds so that they now have a large
HIV Therapy 2009 102
spectrum of complementary molecules on the market. Although this « diversified » strategy has
assured its position as leader for a long period of time, it may be reaching its limit and need to be
redefined. With so many of its own molecules being commercialized, any new compound merely cuts
into GSK’s sales. Today, GSK seems to lack promising anti-viral products to compensate the serious
slowdown in their market position.
Finally, Merck&co and Pfizer find themselves in the paradoxical position of being the pioneers in the
field, the most prolific applicants and the market players in the most difficulty. These two companies
have had diametrically opposed strategies.
Pfizer is known for massively buying out other market players: Warner Lambert, Parke & Davis,
Agouron, Pharmacia, Upjohn, Searle: all companies with active research & development and
substantial patent portfolios, which have been built thanks to major collaborations, such as that
between Japan Tobacco and Agouron. However, this massive acquisition strategy seems to have
disorganized the acquired companies which have not sufficiently exploited the significant potential of
their experts and their research and development. The commercialization of maraviroc, the first viral
entry CCR5 antagonist could be Pfizer’s last chance to maintain a position in the market unless it
decides to buy another Big Pharma or curve the company’s policy and massively license-in drug
candidates already in clinical trials. It should be noted that the purchase of Wyeth was not for the
purpose of improving Pfizer’s market position in HIV Therapy since it has never been a major player in
this field and has mainly pursued vaccine research.
Merck&co, on the other hand, began concentrating its research very early on promising therapeutic
targets gaining a lead of several years on its competitors. Although it is a pioneer in inhibitors of
protease, reverse transcriptase, integrase (as early as 1990) and chemokine receptor antagonists,
Merck&co has often been beaten to the finish or been surpassed by other companies that have
managed to market either more effective compounds or to do it more rapidly. The outcome of the
substantial financial investment by this company in numerous therapeutic approaches with several
research teams reflecting an R&D strategy covering all topics, has not been conclusive. The marketing
of the first integrase inhibitor is nevertheless an important opportunity. However, these drugs must
still prove their efficacy and sales potential because other novel integrase inhibitors may prove to be
more effective.
This general research strategy could have given Merck&co a serious advantage for the development of
a vaccine – a topic which it supported and focused upon for many years. The withdrawal of the
candidate vaccine V520 in 2007 after a large phase II trial in South Africa was a difficult blow that
might have pushed Merck&co out of the market of HIV Therapy. However, the recent acquisition of
the company Schering Plough with its large portfolio of chemokine receptor antagonists, is an
indicator of Merck&co’s intention to continue to invest in this field.
HIV Therapy 2009 103
Although Merck&co and GSK seems to be in a difficult position, it should be noted that their long-term
investment and their general research strategy are important assets in the “back-to-basics” period
occurring today.
7.3 Market players to redefine their strategies
In the next five years, several HIV treatments will go off-patent, forcing industrial partners to protect
new, more effective molecules (in particular against resistances) with fewer side effects and
formulations that are easier for the patient to use.
The absence of new potential therapeutic targets is going to result in a major slowdown in research
efforts in the next 5 years. While waiting for this situation to turn around, the market players will
probably change strategies, with certain industrial players completely abandoning their position in HIV
Therapy.
The example of Roche, which announced its withdrawal in July 2008, is symptomatic of this general
tendency. It should be noted that internal research at Roche was inconclusive and that the molecules
under development in this company have been licensed-in from academic research (license with the
National Cancer Institute and Duke University / Trimeris).
The internal research of players that wish to remain in the field should strongly focus on certain
specific topics, in particular:
- Integrase inhibitors and chemokine receptor antagonists, the only therapeutic targets whose
potential has not been fully exploited,
- Reducing side effects of existing therapies
- Drug delivery of active ingredients
- Treatment of opportunistic diseases
- Prevention of viral transmission
The medium term strategy of several industrial players will also certainly include renewing contact
with the most successful academic research laboratories via new collaborations, strategic acquisition
of specialised Biotech companies, licensing-in and/or hiring experts. It will be up to the academic
laboratories to convince these companies of the interest of these new approaches.
Research and development in HIV is at an important crossroads. Both large pharmaceutical groups
and the other market players must redefine their strategies if they are to carve out a future in this
field.
Appendix
HIV Therapy 2009 105
Emerging topics
HIV Therapy 2009 106
88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06TRIM5alpha 3APOBEC3G 1 4 3 3TSG 101 10 2 2 1LEDGF/p75 1 2 1HDAC 2 1 1 1 1 3DC-sign 1 4 3 2RNAi 1 1 6 9 3 2 1Cyclophilin 4 1 1 2 2 1 2 1 1 3 1Radiation therapy
1 1 1 1 2 1 3 2 2 1
Table 17: Evolution of fillings by emerging topics
Figure 66: Emerging topics by applicants
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Emerging Thematics:TSG 10115
[MYRIAD GENETICS INC]7
Emerging Thematics:RNAi23
[SIRNA THERAPEUTICS INC]4
Emerging Thematics:Cyclophilin19
[PICOWER INST]4
[NOVARTIS]4
FUNCTIONAL GENETICS INC3
Emerging Thematics:DC-sign10
[INSTITUT PASTEUR]2
STICHTING KATHOLIEKE UNIV2
[SUBSIDIARY NO 3 INC]2
Emerging Thematics:HDAC9
[AXYS PHARMACEUTICALS]2
[PROTEOLOGICS]2
Emerging Thematics:Radiation therapy15
[SCHERING PLOUGH CORP]2
[PHARMACOPEIA]2
[PEPTERA PHARMACEUTICALS LTD]2
[UNIV COLUMBIA]2
Emerging Thematics:TRIM5alpha3
[US GOVERNMENT]2
Emerging Thematics:APOBEC11
[GENOSPECTRA INC]1
Emerging Thematics:LEDGF/p754
[HYBRIGENICS]1
[UNIV NEW YORK]2
[MAX PLANCK GESELLSCHAFT]1
[YISSUM]2
[UNIV VIRGINIA COMMONWEALTH]1
[UNIV UTAH]1
[UNIV TEL AVIV]1
[UNIV SEOUL]1
[UNIV ROCHESTER]1
[UNIV OREGON]2
[UNIV MASSACHUSETTS]1
[UNIV MARYLAND]1
[UNIV LOUVAIN]1
[UNIV CALIFORNIA]1
[PFIZER]1
[SCRIPS INSTITUTE]1
[UNIV NIJMEGEN]1
[WISCONSIN ALUMNI RES FOUND]1
[DAVID GLADSTONE INST]2
[UNIV LOUISIANA STATE]1
[ALEXION PHARMA INC]1
PANOMICS INC1
ROYAL VETERINARY COLLEGE1
[OPTIGEN PATENTS LTD]1
[CITY OF HOPE]1
INTERNAT THERAPEUTICS INC1
BLOOD RES CENTER1
[BENITEC INC]1
OPTIGEN TECHNOLOGIES LTD1
BUNDESREP DEUTSCHLAND1
HYALURONIC ACID PHARMA1
NORPHARMCO INC1
[INSERM]1
[GENENTECH]1
[DANA FARBER CANCER INSTITUTE]1
[CALIFORNIA INST]1
[EINSTEIN COLLEGE]1
[PHARMACYCLICS INC]1
[YEDA DEV]1
[UNIV JOHNS HOPKINS]2
[JAGOTEC AG]1
[UNIV MCGILL]1
VIRUVATION BV1
SIRNASENSE AS1
EPICLONE INC1
CYCLACEL LTD1
PROSCI INC1
SCIENCE LEAD CHEM CO LTD1
NMK LLC1
GERON CORP1
[JAPAN SCI AGENCY]1
Figure 67: Applicants for emerging thopics
www.frinnov.fr
2
2
2
2
2
2
22
2
2
2
77
5
4
3
4
3
2
2
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1
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12
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2
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2 2
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2 2
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444
4 4
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3
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2
2Emerging Thematics:Radiation therapy
15
Au Jessie l2
Sidelman Zvi2
Taveras Arthur g2
Dwyer Michael2
Baldwin John j2
Merritt J robert2
Goldstein Harris2
Casadevall Arturo2
Dadachova Ekaterina2
Chao Jianping2
Li Ge2
Emerging Thematics:LEDGF/p754
De clercq Erik2
Debyser Zeger2
Kotler Moshe2
Emerging Thematics:HDAC9
Jung Deuk rim2
Hur Man wook2
Greene Warner c3
Emerging Thematics:APOBEC11
Yu Xiao-fang2
Xu Hongzhan2
Soros Vanessa b2
Chiu Ya-lin2
Emerging Thematics:RNAi23
Macejak Dennis g2
Beigelman Leonid3
Mcswiggen James a4
Emerging Thematics:TSG 10115
Alroy Iris2
Reiss Yuval2
Moskowitz Haim2
Greener Tsvika2
Li Limin3
Hobden Adrian4
Wettstein Daniel albert5
Zavitz Kenton7
Morham Scott7
Emerging Thematics:DC-sign10
Torensma Ruurd2
Arenzana-seisdedos Fernando2
Amara Ali2
Figdor Carl gustav2
Emerging Thematics:TRIM5alpha3
Sayah David2
Luban Jeremy3
Emerging Thematics:Cyclophilin19
Holzmayer Tanya a2
Dunn Stephen j2
Ulrich Peter c3
Cerami Anthony3
Sherry Barbara a4
Ko Soo young4
Kobel Hans4
Besemer-rosenwirth Brigitte4
Seebach Dieter4
Wenger Roland4
Bollinger Pietro4
Traber Rene p4
Bukrinsky Michael i4
Figure 68: Autors for emerging topics
www.frinnov.fr
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