Quella che segue è una ricerca sui TRIALS dedicati alla ricerca e allo sviluppo
dei vaccini contro l'Aids , i dati raccolti e qui riportati sono stati tratti
da PHARMAPROJECTS
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI adjuvants, Ribi.
SY immunostimulants, Ribi.
CO Originator: Ribi ImmunoChem (US).
CN Argentina: Available for Licensing;
Australia: Available for Licensing;
Austria: Available for Licensing;
Belgium: Available for Licensing;
Brazil: Available for Licensing;
Canada: Available for Licensing;
Colombia: Available for Licensing;
Denmark: Available for Licensing;
France: Available for Licensing;
Greece: Available for Licensing;
Ireland: Available for Licensing;
Italy: Available for Licensing;
Japan: Available for Licensing;
Korea: Available for Licensing;
Mexico: Available for Licensing;
Netherlands: Available for Licensing;
Peru: Available for Licensing;
Philippines: Available for Licensing;
Portugal: Available for Licensing;
South Africa: Available for Licensing;
Spain: Available for Licensing;
Sweden: Available for Licensing;
Switzerland: Available for Licensing;
Turkey: Available for Licensing;
UK: Available for Licensing;
US: Phase I Clinical Trial/Available for Licensing;
Venezuela: Available for Licensing;
Germany: Available for Licensing;
World: Phase I Clinical Trial.
Ribi ImmunoChem is developing adjuvants for recombinant DNA and
synthetic vaccines as well as general immune stimulators to induce
non-specific resistance. Adjuvants have been used in vaccines against
malaria, whooping cough, influenza, hepatitis-A, hepatitis-B,
hepatitis non-A, hepatitis non-B and AIDS. They have been licensed to
a variety of companies worldwide. A number of patents have been
granted. Ribi also has a research agreement with SmithKline Beecham
for the development of a malaria vaccine (qv). Two formulations are
in Phase I trials at the US Army Medical Research and Development
Command, Fort Detrick and the Walter Reed Army Institute of Research,
the US (Company communication, Mar 1990). Enhancement of influenza A
virus protective immunity in mice was seen when monophosphoryl lipid
A and trehalose dimycolate were used as vaccine adjuvants (FASEB J,
1988, 2(4), Abs 311). They are available for exclusive worldwide
licensing for use in prophylactic vaccines and therapeutic cancer
vaccines for specific antigens. Updated by AM on 28/6/91.
UD MAY 1990 Status changed Phase I Clinical Trial.
*** 2 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI AIDS vaccine-1, MicroGeneSys.
SY VaxSyn HIV-1.
CO Originator: MicroGeneSys (US). Licensee: American Home Products.
CN Canada: Preclinical;
US: Phase II Clinical Trial;
World: Phase II Clinical Trial.
MicroGeneSys is developing a recombinant subunit DNA AIDS vaccine
using its proprietary VaxSyn baculovirus system. It consists of
purified rgp160. It is in Phase I/II trials in the US although these
are not efficacy studies (Company communication, Oct 1990). It is
also under joint-development with American Home Products. However
Phase I trials in combination with Bristol- Myers Squibb's HIVAC-1e
(qv) have produced the best results. In 12 vaccinia- naive HIV
negative volunteers, vaccination with HIVAC-1e at 0 and 8wk, followed
by 640microg VaxSyn HIV-1 11-20mth later produced a strong Ab
response in 12/12. Neutralizing Abs were produced in 7/12 and 5/12
showed fusion inhibition activity. In a similar protocol in macaques
with SIV vaccines, protection against SIV challenge was demonstrated.
Human trials with this dual approach are continuing (7th Int Conf
AIDS (Florence) 1991, Abs FA1 & ThA12). It is also being studied in
collaboration with the WRAIR (ibid (Stockholm), 1988, Abs 6569).
MicroGeneSys is also investigating an AIDS vaccine based on the p24
core protein (qv) and a vaccine based on gp160 and p24. Updated by NS
on 16/7/91.
UD NOV 1990 New Licensee American Home Products. NOV 1990 Status changed
Phase II Clinical Trial.
*** 3 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI AIDS vaccine-2, Marie Curie.
CO Originator: Non-industrial source.
CN France: Phase I Clinical Trial;
World: Phase I Clinical Trial.
Professor Daniel Zagury and researchers at the Pierre and Marie Curie
University, Paris, France are developing an AIDS vaccine based on
gp160 and alpha- interferon. It is believed that alpha-interferon
generally dampens down any immune response produced by a vaccine. It
is in Phase I trials. In 6 volunteers who had undergone immune
therapy for several years, a booster of altered alpha-interferon with
gp160 has produced stabilization or increase in body weight and CD4
count. It is thought that the altered alpha-interferon induces anti-
alpha-interferon which can keep natural alpha-interferon levels
suppressed. A vaccine which immunizes against HIV and alpha-
interferon may be of benefit (7th Int Conf AIDS (Florence), 1991, Abs
MA67; Scrip, 1991, 1632, 12). Entered by NS on 18/7/91.
UD AUG 1991 (Current) New Product .
*** 4 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI AIDS vaccine-2, MicroGeneSys.
CO Originator: MicroGeneSys (US).
CN US: Phase I Clinical Trial;
World: Phase I Clinical Trial.
MicroGeneSys is developing a second anti-HIV compound based on the
p24 core protein. Clinical trials are underway in the US with 20 HIV-
infected individuals with CD4 cell counts >500/mm3, with trials in
uninfected volunteers planned (6th Int Conf AIDS (San Francisco),
1990, Abs FA1). MicroGeneSys is also investigating an AIDS vaccine
based on the gp160 core protein (qv) and a vaccine based on gp160 and
p24 (Scrip, 1989, 1376, 12).
UD AUG 1990 Status changed Phase I Clinical Trial.
*** 5 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI AIDS vaccine, Bristol-Myers.
SY HIVAC-1e, v-env5.
CO Originator: Bristol-Myers Squibb (US).
CN Canada: Phase I Clinical Trial;
US: Phase I Clinical Trial;
World: Phase I Clinical Trial.
Oncogen and Genetic Systems (Bristol-Myers Squibb) are continuing
studies on a recombinant AIDS vaccine containing the gp160 envelope
glycoprotein (env) from HIV expressed in vaccinia virus. The vaccine,
HIVAC-1e, will not be developed as a single agent due to poor
responses. However, trials with MicroGeneSys' vaccine VaxSyn HIV-1
(qv) have produced the most promising results seen in humans so far,
so studies are ongoing. However, it is unlikely that HIVAC-1e will
ever reach the market in its current formulation because of its
potential to cause vaccinia disease in vaccinia-naive
immunocompromised subjects. In 12 vaccinia-naive HIV-negative
volunteers, vaccination with HIVAC-1e at 0 and 8wk produced a weak Ab
response which lasted for >1yr. When these subjects were boosted
11-20mth after primary vaccination with 640microg VaxSyn HIV-1, 12/12
produced a strong Ab response, 7/12 produced neutralizing Abs and 5
/12 showed fusion inhibition activity. There were no adverse
reactions. In a similar protocol in macaques with SIV vaccines,
protection against SIV challenge was demonstrated (Company
communication, Jun 1991; 7th Int Conf AIDS (Florence), 1991, Abs FA1
& ThA12). Updated by NS on 16/7/91.
UD AUG 1990 Status changed Phase II Clinical Trial. DEC 1990
Discontinued .
*** 6 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI AIDS vaccine, British Bio-tech.
SY p24-VLP.
CO Originator: British Bio-technology (UK).
CN UK: Phase I Clinical Trial;
World: Phase I Clinical Trial.
British Bio-technology has developed an AIDS "pseudovirus", made up
of about 300 viral proteins in a single particle. Virus-like-
particles (VLPs) have been shown to be more effective in inducing
immunity than the monomeric proteins produced by conventional rDNA
means. Phase I trials of p24-VLP (VLP carrying the p24-core antigen
of HIV) began in Nov 1990 in collaboration with the British Medical
Research Council as part of their AIDS-directed programme (Ann Rep,
1990). The ability of p24-VLP to induce virus neutralizing antibodies
and cellular responses has been evaluated in rodents and non-human
primates (5th Int Conf AIDS (Montreal), 1989, Abs MCP35). In the SIV
/rhesus monkey model, such a vaccine elicited an IgA immune response
when administered via oral, rectal and vaginal routes (ibid
(Florence), 1991, Abs ThA65). If Phase I multicentre trials are
successful, the p24-VLP may be used as a component of a potential
AIDS vaccine, which would involve one or more components from the
viral envelope (Company communication, Feb 1991). Updated by NS on 24
/7/91.
UD DEC 1990 Status changed Phase I Clinical Trial.
*** 7 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI AIDS vaccine, Chiron.
SY AIDS vaccine, Biocine, AIDS vaccine, Ciba-Geigy.
CO Originator: Chiron (US). Licensee: Ciba-Geigy.
CN Switzerland: Phase I Clinical Trial;
US: Phase I Clinical Trial;
World: Phase I Clinical Trial.
Chiron, in collaboration with the University of California, the US,
has cloned the full sequence of genes for HIV. A joint-venture with
Ciba-Geigy as Biocine will undertake future development of a vaccine
based on recombinant gp120 (6th Int Conf AIDS (San Francisco), 1990,
Abs FA1 & SA77). Phase I clinical trials in Switzerland in uninfected
volunteers are complete. In 4 male volunteers, 50mg iv of genetically
engineered, non-glycosylated gp120 HIV coat protein, in combination
with 100mg iv muramyl tripeptide (qv), caused stimulation of HIV-
specific CD4+ T-cells (Press release, Chiron, Aug 1990). Potential
vaccines based on the p25 gag core protein are also being studied
(4th Int Conf AIDS (Stockholm), 1988, Abs 2214). Biocine is now
developing an improved formulation of the subunit vaccine due to poor
antibody response seen in initial trials. The improved formulation
will retain the basic gp120 envelope protein (ENV2-3). Phase I trials
in 16 healthy HIV-seronegative volunteers are underway in the US and
no adverse reactions have been seen (Scrip, 1990, 1609, 21). Updated
by AM on 20/6/91.
*** 8 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI AIDS vaccine, Genentech.
CO Originator: Genentech (US).
CN US: Phase I Clinical Trial;
World: Phase I Clinical Trial.
Genentech has cloned and expressed in mammalian cells the protein
gp120 which forms part of the HIV envelope. Genentech has produced a
polyvalent vaccine by combining proteins from several viral strains.
It is in Phase I clinical trials (Scrip, 1990, 1572, 25). In
chimpanzees, immunization with gp120 protected againsp`the same
strain of virus from which the gp120 protein was derived. Control
chimpanzees became infected within 7wk of challenge but immunized
animals have not shown signs of infection after 6mth (6th Int Conf
AIDS (San Francisco), 1990, Abs FA4; Nature, 1990, 345, 622). In
vitro, the vaccine killed HIV and prevented it from infecting T-cells
from the human immune system (2nd Int Conf AIDS (Paris), 1986).
Primates immunized with r- gp120 formed antibodies against the native
HIV glycoproteins gp160 and gp120, which inhibited the binding of r-
gp120 to the cell surface CD4 (T4) antigen (ibid (Washington, DC),
1987, Abs THP.20). Genentech is no longer developing an AIDS
diagnostic based on these polypeptides (Company communication, Feb
1991). . European patent No 187-041.
UD JAN 1991 Status changed Phase I Clinical Trial.
*** 9 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI AIDS vaccine, HIVER.
SY AIDS vaccine, Becton, AIDS vaccine, MRC.
CO Originator: HIVER (UK). Licensee: Becton-Dickinson.
CN Argentina: Available for Licensing;
Australia: Available for Licensing;
Austria: Available for Licensing;
Belgium: Available for Licensing;
Brazil: Available for Licensing;
Canada: Available for Licensing;
Colombia: Available for Licensing;
Denmark: Available for Licensing;
France: Available for Licensing;
Greece: Available for Licensing;
Ireland: Available for Licensing;
Italy: Available for Licensing;
Japan: Available for Licensing;
Korea: Available for Licensing;
Mexico: Available for Licensing;
Netherlands: Available for Licensing;
Peru: Available for Licensing;
Philippines: Available for Licensing;
Portugal: Available for Licensing;
South Africa: Available for Licensing;
Spain: Available for Licensing;
Sweden: Available for Licensing;
Switzerland: Available for Licensing;
Turkey: Available for Licensing;
UK: Phase I Clinical Trial/Available for Licensing;
US: Preclinical/Available for Licensing;
Venezuela: Available for Licensing;
Germany: Available for Licensing;
World: Phase I Clinical Trial.
An anti-idiotype AIDS vaccine is under development by Dr Angus
Dalgleish and colleagues at the MRC Research Centre at Northwick Park
Hospital, Middlesex, UK; Dr Peter Beverley at the Imperial Cancer
Research Fund and Dr Don Healey at University College, London, UK; Dr
Ronald Kennedy and Dr Tran Chanh at the Southwest Foundation, Texas,
US and Dr Vernon Maino and Dr David Buck at Becton-Dickinson
Monoclonal Centre. Becton-Dickinson has an exclusive licensing
agreement with HIVER and is seeking a pharmaceutical partner to
develop it. Dr Dalgleish conducted Phase I trials in 4 ARC patients
using the MAb Leu-3a to stimulate the production of anti-HIV anti-
idiotypic antibodies. However, anti-Leu-3a did not exactly mimic the
gp120 binding site on the CD4 receptor and the anti-idiotypes did not
bind to HIV. HIVER has now produced over 250 anti-CD4 MAbs, and hopes
to select one which does mimic the gp120 binding site for further
studies. HIVER is also developing disease-modifying anti-idiotypes
based on HIV interaction with other immune system receptors (Company
communication, HIVER, Aug 1990).
*** 10 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI AIDS vaccine, Immune Response.
SY RG-83894.
CO Originator: Immune Response (US). Licensee: Rhone-Poulenc Rorer
Pasteur Merieux.
CN US: Phase II Clinical Trial;
World: Phase II Clinical Trial.
Immune Response Corporation is developing a whole-cell killed AIDS
vaccine, containing HIV inactivated by irradiation. The vaccine was
originally produced by Dr Jonas Salk of the Salk Institute, La Jolla,
California, the US. The vaccine is covered by a research development
and marketing partnership with Rhone-Poulenc Rorer and is licensed to
Pasteur Merieux for Europe, Africa and Central America. Pasteur
Merieux will also provide quantities of the AIDS immunotherapeutic to
Immune Response for use in the US (registration due in 1995), Canada
and Puerto Rico. The vaccine has shown safety at 100microg/dose in
asymptomatics. In 82 seropositives, 60% exhibited HIV-DC
responsiveness following immunization. It is undergoing Phase II
trials, however these are not efficacy studies. Trials in uninfected
volunteers are planned (6th Int Conf AIDS (San Francisco), 1990, Abs
ThA337 & FA3; Scrip, 1991, 1632, 12). MediControl (Biotechnology
Development Corporation) has discontinued its involvement in this
project (Company communication, Biotechnology Development Corp, Feb
1990). Updated by NS on 16/7/91.
UD MAR 1990 Licensee discontinued MediControl (Biotechnology Development
Corp). JAN 1991 Status changed Phase II Clinical Trial.
*** 11 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI AIDS vaccine, Immuno.
CO Originator: Immuno (Austria).
CN Austria: Preclinical;
US: Phase I Clinical Trial;
Germany: Preclinical;
World: Phase I Clinical Trial.
Immuno has produced a recombinant DNA AIDS vaccine, based on the
envelope protein gp160 together with a lipid-based adjuvant. Phase I
clinical trials in the US in 60 HIV negative volunteers are being
conducted (7th Int Conf AIDS (Florence), 1991, Abs ThA13). A
vaccinated chimpanzee inoculated with 50microg im/dose HIV showed no
signs of infection after 2.5yr (cf 3mth with a control animal). When
administered to chimpanzees the vaccine produced antibodies which
neutralized the AIDS virus in vitro. A cellular immune response was
also elicited (4th Int Conf AIDS (Stockholm), 1988, Abs 2223). One
animal did not produce antibodies to core proteins (eg gap and po
gene products) after challenge with HIV, indicating that viral
replication had been controlled (ibid (San Francisco), 1990, Abs Th
A340 & FA4). Updated by NS on on 24/7/91.
UD JAN 1991 Status changed Phase I Clinical Trial.
*** 12 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI AIDS vaccine, Marie Curie Univ.
CO Originator: Non-industrial source.
CN France: Phase I Clinical Trial;
World: Suspended.
Professor Daniel Zagury and researchers at the Pierre and Marie Curie
University, Paris, France were developing an AIDS vaccine using
recombinant vaccinia virus (V25) expressing the complete gp160 env
protein of HIV-1. However, Phase I trials have been halte{d by the
French Ministry of Health following the death of 3 volunteers,
believed to be due to vaccinia disease (7th Int Conf AIDS (Florence),
1991). Dr Zagury is now pursuing a new approach (see AIDS vaccine-2,
Marie Curie). Initial vaccination produced a weak primary response
and was followed by one of 4 immunization protocols as a booster.
High antibody levels were produced for 1yr after original
vaccination. It is not yet known if this immune state will protect
against AIDS and the injection of autologous cells would be difficult
in a large trial (Nature, 1988, 332, 728). In a French trial, 10/27
HIV negative volunteers produced neutralizing antibodies against
different virus strains on vaccination. In 19 ARC/AIDS patients this
immune therapy produced a stabilization or increase in CD4 cells (6th
Int Conf AIDS (San Francisco), 1990, Abs ThA334-6). Updated by NS on
16/7/91.
UD AUG 1991 (Current) Suspended .
*** 13 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI AIDS vaccine, Viral Tech.
SY HGP-30, P-17.
CO Originator: Alpha 1 Biomedicals (US). Licensee: Cel-Sci, Nippon Zeon.
CN Austria: Available for Licensing;
Belgium: Available for Licensing;
Denmark: Available for Licensing;
France: Available for Licensing;
Greece: Available for Licensing;
Ireland: Available for Licensing;
Italy: Available for Licensing;
Japan: Preclinical;
Korea: Preclinical;
Netherlands: Available for Licensing;
Philippines: Preclinical;
Portugal: Available for Licensing;
Spain: Available for Licensing;
Sweden: Available for Licensing;
Switzerland: Available for Licensing;
Turkey: Available for Licensing;
UK: Phase I Clinical Trial/Available for Licensing;
US: Preclinical/Available for Licensing;
Germany: Available for Licensing;
World: Phase I Clinical Trial.
Viral Technologies Inc (a joint-venture between Alpha 1 Biomedicals
and Cel- Sci) has synthesized a 30 amino acid peptide, human gag
protein (HGP-30), which is an epitope of P-17, a highly conserved
core protein of the AIDS virus. Viral Technologies is using HGP-30
(which is chemically similar to thymosin alpha-1) as the active
component of a prototype vaccine against AIDS. In Phase I trials with
18 seronegative volunteers at St Stephen's Hospital, London, the UK,
some patients produced specific antibodies which attack P-17; there
were no toxic side-effects (Press release, Jan 1990). There was also
some evidence of production of a CD8+ cytotoxic T-lymphocyte
response. In seropositive volunteers, 43% proliferated in response to
HGP-30 (6th Int Conf AIDS (San Francisco), 1990, Abs SA76). Nippon
Zeon has exclusive rights to develop and market the AIDS vaccine in
the Pacific Basin countries excluding Indonesia, Malaysia, N & S
Vietnam, Laos, Cambodia and Burma, where it has non- exclusive rights
(Ann Rep, Cel-Sci, 1988). It is available for licensing/joint-
development in Europe and the US (Company communications, Cel-Sci,
Aug 1990 & Mar 1991).
UD JUN 1989 Status changed Phase I Clinical Trial. SEP 1990 Licensing
Opportunity Europe and the US.
*** 14 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI CGP-19835A.
SY CGP-19835, MTP-PE.
L-Alaninamide, N-(N-acetylmuramoyl)-L-alanyl-D-alpha-glutaminyl-N-(4-
hydroxy-10-oxo- 7-((1-oxohexadecyl)oxy)-3,5,9-trioxa-4-
phosphapentacos-1-yl)-, P-oxide, monosodium salt, (R)- (CAS).
RN 90825-43-7 and 83461-56-7.
CO Originator: Ciba-Geigy (Switzerland). Licensee: Chiron.
CN Switzerland: Phase I Clinical Trial;
UK: Phase I Clinical Trial;
US: Phase II Clinical Trial;
World: Phase II Clinical Trial.
CGP-19835A is a conjugate of a muramyl tripeptide derivative linked
to dipalmitoyl phosphatidyl ethanolamine to facilitate incorporation
into liposomes, under development by Ciba-Geigy. It is in Phase II
clinical trials against Kaposi's sarcoma. It is also being
investigated by Biocine (a Ciba- Geigy/Chiron joint-venture) as an
adjuvant in an AIDS vaccine (Company communication, Ciba-Geigy, Jul
1988). In 48 cancer patients, 0.05-9.0mg/m2 liposomal CGP-19835A
caused dose-limiting severe chills at 4.0mg/m2. 1 Patient had a mixed
response and 3 had stable disease (6th NCI-EORTC Symp New Drugs
Cancer Ther (Amsterdam), 1989, Abs 271-273). In patients with
metastatic melanoma, it increased plasma TNF levels and circulating
monocyte number (81st AACR (Washington, DC), 1990, Abs 1453).
CGP-19835A protected Herpes simplex virus-1-susceptible mice against
challenge with HSV-1 (J Cell Biochem, 1990, Suppl14D, Abs L319). US
patent No 4414890 and European patent appl No 27-258.
MF C59 H109 N6 O19 P.
*** 15 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI imreg-1.
CO Originator: Imreg (US).
CN US: Phase III Clinical Trial;
World: Phase III Clinical Trial.
Imreg-1 is an immunomodulator isolated from human leucocytes and
under development by Imreg for use in diseases associated with
immunodeficiency and undergoing Phase III trials. An application for
a treatment IND in patients with ARC was rejected in mid-1989. In
patients with AIDS/ARC or certain cancers, it restored delayed
hypersensitivity, mitogen-induced lymphocyte proliferation and IL-2
production (2nd Int Conf AIDS (Paris), 1986, Abs 602- 604). In trials
with 143 ARC patients, 5/95 (5%) experienced AIDS-defining events by
6mth, cf 12/48 (25%) receiving placebo (ibid (San Francisco), 1990,
Abs SB486). In patients, severity of candidiasis was reduced (ibid
(Stockholm), 1988, Abs 3048; Clin Res (AFCR Southern), Abs 16A). In
initial clinical trials in RA, imreg-1 gave enhanced IL-2 production
(Conf Am Rheumat Assoc (New Orleans), 1986). It could promote the
immune response to a vaccine against HIV (1st Int Conf AIDS (Atlanta)
, 1985, p26). In Hodgkin's disease, it restored DTH to recall
antigens. Additional trials are planned (Company communication, Apr
1991). Updated by AM on 3/6/91.
*** 16 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI interleukin-2, Immunex.
SY IL-2, Immunex, IL-2, Roche, interleukin-2, Roche, Ro-23-6019.
CO Originator: Immunex (US). Licensee: Roche, Cetus.
CN Switzerland: Phase III Clinical Trial;
US: Phase III Clinical Trial;
World: Phase III Clinical Trial.
Immunex, under an agreement with Roche, has produced recombinant
interleukin-2 (IL-2). Roche has worldwide exclusive rights to
manufacture and market IL-2 therapeutic and diagnostic products, on
payment of royalties to Immunex for 15yr (Prospectus, Immunex, 1983)
and the royalties are not affected by the later agreement between
Roche and Ajinomoto, covering IL-2 production. Roche has also formed
a non-exclusive cross-licensing agreement with Cetus to co- market
the companies' respective IL-2 products. Roche is conducting Phase II
/III clinical trials in AIDS and cancer patients in the US. IL-2 is
also being studied in combination with LAK cell therapy, other
immunomodulators (alpha- interferon and IL-4) and chemotherapy
agents. Roche has an agreement with Ribi ImmunoChem to study IL-2
with Ribi's melanoma vaccine (qv) (Press release, Dec 1988). Immunex
holds US patents for an anti-IL-2 monoclonal antibody and for the
production of IL-2 from an IL-1-stimulated cell line.
*** 17 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI MPLA, Ribi.
SY MPL, Ribi.
CO Originator: Ribi ImmunoChem (US).
CN Argentina: Available for Licensing;
Australia: Available for Licensing;
Austria: Available for Licensing;
Belgium: Available for Licensing;
Brazil: Available for Licensing;
Canada: Available for Licensing;
Colombia: Available for Licensing;
Denmark: Available for Licensing;
France: Available for Licensing;
Greece: Available for Licensing;
Ireland: Available for Licensing;
Italy: Available for Licensing;
Japan: Available for Licensing;
Korea: Available for Licensing;
Mexico: Available for Licensing;
Netherlands: Available for Licensing;
Peru: Available for Licensing;
Philippines: Available for Licensing;
Portugal: Available for Licensing;
South Africa: Available for Licensing;
Spain: Available for Licensing;
Sweden: Available for Licensing;
Switzerland: Available for Licensing;
Turkey: Available for Licensing;
UK: Available for Licensing;
US: Phase II Clinical Trial/Available for Licensing;
Venezuela: Available for Licensing;
Germany: Available for Licensing;
World: Phase II Clinical Trial.
Ribi ImmunoChem is developing monophosphoryl lipid A (MPLA), a non-
specific stimulator of host resistance to bacterial infection,
obtained by the acid hydrolysis of bacterial endotoxin. An evaluation
and option agreement between Ribi and Baxter has been terminated. It
is in Phase I/II trials as a non- specific immunostimulant prior to
high-risk surgery and may prevent or reduce septicaemia (1st Qtr Rep,
1989). In Phase I trials against infections in head and neck surgery
patients, results were encouraging. Phase I/II trials in endotoxin-
induced septic shock have been initiated (Company communication, Mar
1991). It may be useful as a vaccine adjuvant in young children, in
the treatment of AIDS and also has veterinary applications. A malaria
vaccine of MPLA and antigen is in Phase I trials (Company
communication, Dec 1990). MPLA may also produce systemic antitumour
activity. MPLA is a component of the Ribi products Detox (development
as a single agent has been discontinued; see Pharmaceased) and Ovamid
(qv) (Press release, Feb 1988). It is available for licensing
worldwide (Company communication, Jan 1991).
UD FEB 1991 Licensing Opportunity Worldwide. FEB 1991 Status changed
Phase II Clinical Trial.
*** 18 ***
SO Pharmaprojects. PJB Publications Ltd, Richmond, Surrey, UK.
TI poly-ICLC.
SY L-Lysine, homopolymer, compd. with cellulose carboxymethyl ether
and5'-inosinic acid homopolymer complex with 5'-cytidylic acid
homopolymer (1:1)(CAS).
RN 59789-29-6.
CO Originator: Non-industrial source.
CN US: Phase II Clinical Trial;
World: Phase II Clinical Trial.
Poly-ICLC, a complex of poly-IC with poly-L-lysine and
carboxymethylcellulose, is an immunostimulant, under development at
the National Institute of Allergy and Infectious Diseases, the US.
The US Government holds an international patent. It was less toxic
and a more effective inducer of interferon than poly- IC and an
effective vaccine adjuvant, giving improved antibody responses to
influenza, Japanese encephalitis and animal viruses. It may also
potentiate candidate AIDS vaccines. In 9 HIV-infected patients, 2-6mg
im was well tolerated with side-effects of low grade fever and
malaise. Phase II trials in AIDS patients are planned (5th Int Conf
AIDS (Montreal), 1989, Abs ThB045). In cancer and MS patients, low
doses of poly-ICLC increased NK cell numbers, but high doses were
ineffective. After 1yr, some MS patients treated with poly- ICLC were
still in remission (194th ACS (New Orleans), 1987, PMSE-8). Poly-
ICLC reduced brain tumour size and improved symptoms (Jpn Pharm Abs,
1982, 8(1), 48). The MTD was 12mg/m2 and side-effects included fever,
hypertension and haematotoxicity (13th Int Cancer Cong (Seattle),
1982, Abs 2122).
UD OCT 1989 New Product .
