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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

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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 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



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 60: CLASSES OF COMPOUNDS OF THE MAIN INVENTORS (1993-2000) ........................ 91

TABLE 15: MAIN INVENTORS (2001-2006) ............................................................................... 92





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


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.


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


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


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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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


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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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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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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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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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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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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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.

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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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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

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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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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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0

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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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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)


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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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


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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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.


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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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.


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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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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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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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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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


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.

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PFIZER

MERCK & C

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BMSGSK

JOHNSON & JO

HNSON

SANOFI AVENTIS

INSTITUT PASTEUR

BOEHRINGER IN

GELHEIM

UNIV C

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NOVARTIS

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ROCHE

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CORPCNRS

UNIV EMORY

VERTEX PHARMA

PROGENICS PHARM IN

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GENENTECH

Num

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pplic

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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%


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

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3

3

3

4

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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


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


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


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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2

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3 4

22

3

3

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


[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


[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


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


[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


[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


[UNIV OXFORD]3


MERRELL DOW PHARMA23

DOW CHEMICAL CO3

Figure 30 : The major collaborations by number of joint filings from 1983 to 1992

www.frinnov.fr



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


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

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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

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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.





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

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2

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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


[UNIV COLUMBIA]9

[MILLENNIUM PHARM INC]11

WARNER LAMBERT CO26

[MUSC FOUNDATION]4

[UNIV SOUTH CAROLINA]4

SCHERING AG5

[IMMUNEX CORP]9

APOLLON INC2


[WISTAR INSTITUTE]7

[WYETH]15


[AMERICAN HOME PRODUCT CORPORATION]4

[UNIV PITTSBURGH]4

[AKZO NOBEL]9

[BIOMERIEUX]8


[UNIV MONTPELLIER]5

[JOHNSON & JOHNSON]30

[INSTITUT CURIE]3

[CNRS]23

CELLPEP S A4

[ZAMBON SPA]2

[INSERM]14

[UNION PHARMA SCIENT]2




[REGA STICHTING]6

[UNIV LOUVAIN]7

DU PONT3

DU PONT MERCK PHARMA23

[BMS]55

DUPONT PHARMA62

AGOURON PHARMA41

[PFIZER]21


[MERCK]175

[TULARIK INC]8





[UNIV WAKE FOREST]8


[THEREXSYS LTD]3

[PURDUE RESEARCH FOUNDATION]2

[US GOVERNMENT]97

[AGUETTANT]5

[UNIV TEL AVIV]2

[NASA]10

[UNIV IOWA]6



[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


[UNIV DUKE]22

[UNIV DURHAM]2


[TRIMERIS INC]15

ANORMED INC16


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



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

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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




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

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[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


CHAY GROUP N2

[REPUBLIC KOREA]3

[UNIV HANDONG GLOBAL (COREE)]2

[SAN ROMANELLO CTR FOND]2

[SAN RAFFAELE CTR FOND]4


[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


[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


[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 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


[PHARMACOPEIA]10

[XOMA TECHNOLOGY LTD]2

[NOVARTIS]22

[TRIAD THERAPEUCTICS INC]2

CHIRON CORP13

[GEORGETOWN UNIV]6


[US GOVERNMENT]92



[SCRIPS INSTITUTE]11

[NASA]5

[UNIV EMORY]10

[UNIV GEORGIA]7

[PHARMASSET INC]6


[CORNELL FOUNDATION INC]8


[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


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

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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



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)


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

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1413

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108

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55

55

5

6

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5

Montagnier Luc58


Alizon Marc41

Sonigo Pierre42

Clavel Francois28

Wain-hobson Simon28

Krust Bernard15

[CNRS]59

Chamaret Solange16

Bryant Martin l12


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


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


Ishaq Khalid s10

Moore John p11

Wild Carl t21


Matthews Thomas james11

Morris-natschke Susan l8

[UNIV MARYLAND]37

Manak Mark8



Kashiwada Yoshiki7

Lee-huang Sylvia7

[UNIV NEW YORK]39

Huang Philip l6

Cragg Gordon m6

Huang Paul l6

Kung Hsiang-fu6

Chen Hao-chia5


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


[UNIV ARIZONA]18


Weiner David b28


[WISTAR INSTITUTE]9

Whitten Kathleen r14

[PFIZER]359


Deason Michael e9

Albizati Kim francis9

Inaba Takashi8

Yamada Yasuki7

Remarchuk Travis p6

Taveras Arthur g15


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


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



Mcmichael Andrew james11



Greeson Janet8


Lecanu Laurent7

[GEORGETOWN UNIV]7

Papadopoulos Vassilios7

Hertogs Kurt11

[JOHNSON & JOHNSON]141

[VIRCO]9

Rosen Craig a11


[HUMAN GENOME SCIENCES]8

Figure 45: Mobility of inventors

www.frinnov.fr

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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


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


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


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

www.frinnov.fr


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

www.frinnov.fr


- 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

www.frinnov.fr

www.frinnov.fr


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.


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


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.


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.


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)


440

558

560

589

624

648

700

864

994

1098

1098

1098

1240

1320

1368

2970

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.

www.frinnov.fr

6

6

66

7

6

7

610

39 33

22

1099

21

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2110

10

10

10

17

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16

16

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611

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61

61

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23

23

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25

22

19

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18

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Weber Ann e6

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


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


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


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


Rogier Donald joseph14


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


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

www.frinnov.fr

82

82

Figure 53: Therapeutic targets of the main inventors (1983-1992)

www.frinnov.fr

83

83

Figure 54: Applications of the main inventors (1983-1992)

www.frinnov.fr

84

84

Figure 55: Classes of compounds of the main inventors (1983-1992)

www.frinnov.fr


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.


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)


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


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


- 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.

77

6 6

7

7

7

6

7

7

7

7

7

6

6

6

6

7

66

11

8

8

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18

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9

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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


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


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


Sikorski James a25

Getman Daniel p30


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


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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)


408

416

423

430

432

448

450

493

495

495

676

703

748

836

855

966

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


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


- Finally the team at Progenics with William Olson and Paul Maddon working on antibodies and

peptide compounds for vaccine applications and viral entry inhibitors.

7

7

7

7

7

77

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7

77

7

7

7

7

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7

77

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7

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7

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7

8

8

7

7

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8

77

9

8

8

8

8

7

7

79

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7

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7

7

7

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9

77

7

77

11

8

7

77

7

12

12

12

1111

1110

10

10

10

109

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9

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8 8

8

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88 7

7

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14

1211

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14 9

87 7

11

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98

8

8

7

7

7

7

18

15

1514

14

14

10

10

10

10

8 8

Morham Scott7

Zavitz Kenton8

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

9

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


Merck&Co

www.frinnov.fr

96

96


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97

97


www.frinnov.fr

98

98


www.frinnov.fr

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


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)


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


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.


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


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.


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


Emerging topics


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

www.frinnov.fr

7

4

4 4

3

2

2

2

2

2

22

2

2

1

1

1

1

1

11

1

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1

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11

11

1

1

1

1 1

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


[PHARMACOPEIA]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


[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

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2

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1

12

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12

2

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2

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2 2

22

2 2

4

444

4 4

4

44

3

3

32

22

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

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