Title of Invention

"USE OF ETHANOL AS PLASTICIZER FOR PREPARINGASUBCUTANEOUS IMPLANTS CONTAINING THERMOLABILE ACTIVE PRINCIPLES DISPERSED IN A PLGA MATRIX"

Abstract Using ethanol as plasticizer for preparing subcutaneous implants containing a dispersed active principle in a PLGA-based matrix by means of extrusion temperature, generally higher than 75°C, can be reduced to temperatures higher than the T of the PLGA, but lower than the boiling point of ethanol and therefore less than 70°C. In this manner subcutaneous implants containing thermolabile active principles, for example proteins, can be prepared.
Full Text

USE OF ETHANOL AS PLASTICIZER FOR PREPARING SUBCUTANEOUS IMPLANTS CONTAINING THERMOLABILE ACTIVE PRINCIPLES DISPERSED IN A PLGA MATRIX
FIELD OF THE INVENTION
The present invention relates to the use of ethanol as plasticizer for preparing
subcutaneous implants containing thermolabile active principles dispersed in a
PLGA matrix. '
STATE OF THE ART
In the current state of the art the extrusion temperature of PLGA is higher than
75°C. Typically the temperature during extrusion must be 40-50°C above the Tg of
the polymer to be extruded.
With this type of technique it is not possible to prepare subcutaneous implants
containing a thermolabile active principle dispersed in a polylactic-glycolic acid
(PLGA) matrix.
To use such a technique to prepare subcutaneous implants with active principles
of this type, the extrusion temperature must be lowered. In general to lower the
extrusion temperature the use of a plasticizer is widespread which allows the
flexibility and the workability of the polymer to be increased following the reduction
of the Tg thereof. The amount of plasticizer to be added to the polymer varies as a
function of the desired effect.
An essential requirement for a plasticizer is non-volatility. Currently modern
plasticizers are organic synthetic compounds; in most cases they are esters such
as adipates and phthalates. These types of products are not biocompatible and
therefore cannot be used for subcutaneous implants for application to man and to
mammals in general.
For other types of plasticizers such as triacetin, N-methyI-2-pyrrolidone, glycerol
and formaldehyde, their toxicity to man and to mammals has not been fully
ascertained.
In preparing said type of subcutaneous implants the requirement was therefore felt
for a plasticizer able to reduce the extrusion temperature of PLGA which did not
present the drawbacks of the state of the art and was non-toxic.

SUMMARY OF THE INVENTION
In particular the Applicant has found that ethanol while being a volatile substance
diffuses rapidly and in a homogeneous manner in ground PLGA at a temperature
higher than the Tg and lower than the boiling point of ethanol and therefore
subcutaneous implants using ethanol as external plasticizing agent can be
prepared.
The term "external plasticized means a plasticizing agent to be used hot" in the
process of preparing the subcutaneous implant by extrusion, but in a phase
previous to the aforesaid preparation, or rather in the preparation phase of the
"plasticized" polymer which will be subsequently used in the preparation of the
subcutaneous implant
A further aspect of the present invention is therefore a plasticized PLGA containing
ethanol as plasticizing agent.
This plasticized polymer is therefore prepared using a process which comprises
the following stages:
a) grinding PLGA to obtain a ground product in which the particles have dimensions less than 250 pm;
b) adding ethanol to the ground product obtained in the preceding stage in concentrations between 5 and 20 parts by weight/weight of PLGA and then heating the mixture obtained to a temperature between 45 and 65°C, until a viscous and stable gel is obtained;
c) drying the gel obtained in step (b)
d) grinding the dried product coming from step (c) at a temperature between -20
and +5°C;
e) optionally mixing the product originating from the preceding stage with PLGA as such which has been previously ground until a ground product of dimensions less than 250 pm is obtained, in weight ratios between 10:90 and 99:1 respectively, at a temperature between -20 and +5°C;
f) extruding the aforesaid mixture at 75°C;
g) grinding the extruded product at a temperature between -20°C and +5°C to obtain the PLGA plasticized wfth ethanol according to the present invention.
A further aspect of the present invention is a subcutaneous implant comprising an

active principle dispersed in a matrix based on PLGA piasticized with ethanol
according to the present invention.
DETAILED DESCRIPTION OF THE INVENTION
The piasticized PLGA of the present invention generally contains ethanol in
concentrations between 2 and 15%, preferably between 3 and 10%, and even
more preferably between 5 and 10% by weight on the weight of PLGA.
The Applicant has in fact found'that by using piasticized PLGA containing ethanol
at concentrations between 2% and 3% by weight, the Tg of the polymer and
consequently the extrusion temperature can be reduced to temperatures lower
than 70°C; by using ethanol at concentrations higher than between 3 and 4% by
weight, this temperature can be reduced to values lower than 60°C.
The Applicant has also found that using ethanol at concentrations between 5 and
10% on the weight of piasticized polymer, the extrusion temperature can be
reduced to 40°C (i.e. a temperature compatible with most thermolabile biological
active principles).
The piasticized polymer according to the present invention therefore contains
ethanol in concentrations preferably between 5 and 10%, when used for preparing
compositions for subcutaneous implants containing thermolabile active principles.
Preferably in stage (b) the amount of ethanol added is equal to 10 parts by weight
per parts by weight of PLGA
In stage (c) drying is conducted until obtaining a concentration of ethanol in PLGA
preferably comprised between 10 and 30%, more preferably 20% by weight /PLGA
weight. Preferably drying in step (c) is carried out under an air stream at a
temperature comprised between 20 and 25°C.
The temperature of grinding in stage (d), (e) and (g) is preferably -10°C, while in
stage (e) the weight ratio of PLGA originating from stage (d)/PLGA as such is
preferably between 16:84 and 40:60.
By increasing in stage (e) the concentration by weight of PLGA treated with
ethanol with respect to the untreated PLGA, the extrusion temperature of the
subsequent subcutaneous implant preparation phase is reduced.
The subcutaneous implants, a further aspect of the present invention, are
prepared by a process comprising the following stages:

i) mixing the active principle with the plasticized PLGA of the present invention, at
a temperature between -20°C and +5°C.
ii) extruding the ground product originating from stage (i) at a temperature less
than 70°C, preferably less than 60°C.
As stated above, when the plasticized polymer used in stage (i) contains belween
5 and 10% of ethanol, the extrusion temperature in stage (ii) is about 40°C.
In this case the aforesaid process is particularly suitable" for prepiaring
subcutaneous implants comprising thermolabile active principles. The term
"thermolabile active principles* means active principles which must be stored at
low temperature and in particular proteins (hormones, growth factors, enzymes
etc), vaccines, antibodies and vectors for genie therapy.
The polymer plasticized with ethanol according to the present invention can also
be used for preparing subcutaneous implants containing non-thermoJabile active
principles, however in any event as a precaution it is preferable not to subject
them to sudden temperature changes.
Some illustrative but non-limitative examples of the preparation of plasticized
polymer containing ethanol of the present invention together with the preparation
of the subcutaneous implant of the present invention containing PLGA plasticized
with ethanol and containing a thermolabile active principle are reported herein
below.
EXAMPLE 1 - Preparation of subcutaneous implants containing recombinant
human Granulocyte Colony Stimulating Factor (r-Hu-G-CSF)
a) Preparation of PLGA plasticized with ethanol
PLGA having the following characteristics:
inherent viscosity 0.19 dl/g measured at 25°C in chloroform (c = 0.1 g/dl),
Lactide / Glycolide Molar ratio: 53/47,
Tg: 40°C. The ground product is added to an excess of ethanol until a concentration of PLGA in ethanol equal to 0.12 g/ml is obtained and is placed in a bath of water heated to 45°C and stirred for 1 minute. The ethanol diffuses into the polymer and forms a viscous gel. This gel is maintained in ethanol for 3 minutes. This is followed by drying at 20°C until a PLGA is obtained containing ethanol in a

quantity equal to 20% weight/weight.
The polymer thus obtained is mixed at -10°C with the same untreated type of
polymer as such in a weight ratio of 40:60 and the said mixture is then extruded at
75°C.
The extruded product is then ground at -10°C to obtain the plasticized PLGA with
an ethanol content of 8% mass/mass.
b) Preparation of the subcutaneous implant
The active principle consisting of the protein r-Hu-G-CSF having the following
characteristics:
Protein content (Colon metry-Bradford): 2.1 to 2,6 % mass/mass, Biological potency (In vitro - Std WHO # 88/502): 21 to 31 x 106 IU / mg of
protein,
Excipients:
Mannitol / Polysorbate 80 / Sodium Phosphate monobasic / Sodium
Phosphate Dibasic Dodecahydrated / Human Albumin
(93.4% / 0.01% /1.9 % / 0.5% /1.9% mass/mass respectively)
and the plasticized polymer (PLGA) were mixed intimately at -1Q°C in a weight
ratio of 31:69 respectively.
The powdered mixture thus obtained was extruded at 40°C. The extruded product
thus obtained (1.5 mm in diameter) was then cut to a length of 18 mm to form
cylindrical deposits each weighing 40 mg and each containing the protein in a
quantity equal to 6.6 x 106 IU.
EXAMPLE 2 - Preparation of subcutaneous implants containing recombinant
human Granulocyte Colony Stimulating Factor (r-Hu-G-CSF)
a) Preparation of PLGA plasticized with ethanol
PLGA having the same characteristics as the one described in the Example 1 is
ground until a particle size of less than 250 |jm is obtained.
The ground product is added to an excess of ethanol until a concentration of
PLGA in ethanol equal to 0.12 g/ml is obtained and is placed in a bath of water
heated to 45°C and stirred for 1 minute. The ethanol diffuses into the polymer and
forms a viscous gel. This gel is maintained in ethanol for 3 minutes.
This is followed by drying at 20°C until a PLGA is obtained containing ethanol in a

quantity equal to 20% weight/weight.
The polymer thus obtained is mixed at -10°C with the same untreated type of
polymer as such in a weight ratio of 32.5:67.5 and the said mixture is then
extruded at 75°C.
The extruded product is then ground at -10°C to obtain the plasticized PLGA with
an ethanol content of 6.5% mass/mass.
b) Preparation of the subcutaneous implant
The active principle consisting of the protein r-Hu-G-CSF having the same
characteristics that the one described in the Example 1 and the plasticized
polymer (PLGA) were mixed intimately at -10°C in a weight ratio of 30:70
respectively.
The powdered mixture thus obtained was extruded at 50°C. The extruded product
thus obtained (1.5 mm in diameter) was then cut to a length of 18 mm to form
cylindrical deposits each weighing 40 mg and each containing the protein in a
quantity equal to 6.6 x 106 ILL
EXAMPLE 3 - Preparation of subcutaneous implants containing recombinant
human Granulocyte Colony Stimulating Factor (r-Hu-G-CSF)
a) Preparation of PLGA plasticized with ethanol
PLGA having the same characteristics as the one described in the Example 1 is
ground until a particle size of less than 250 pm is obtained.
The ground product is added to an excess of ethanol until a concentration of
PLGA in ethanol equal to 0.12 g/ml is obtained and is placed in a bath of water
heated to 45°C and stirred for 1 minute. The ethanol diffuses into the polymer and
forms a viscous gel. This gel is maintained in ethanol for 3 minutes.
This is followed by drying at 20°C until a PLGA is obtained containing ethanol in a
quantity equal to 20% mass/mass.
The polymer thus obtained is mixed at -10°C with the same untreated type of
polymer as such in a weight ratio of 16:84 and the said mixture is then extruded at
75°C.
The extruded product is then ground at -10°C to obtain the plasticized PLGA with
an ethanol content of 3.2% mass/mass.
b) Preparation of the subcutaneous implant

The active principle consisting of the protein r-Hu-G-CSF having the same characteristics as the one described in the Example 1 and the plasticized polymer (PLGA) were mixed intimately at -10°C in a weight ratio of 30:70 respectively. The powdered mixture thus obtained was extruded at 60°C. The extruded product thus obtained (1.5 mm in diameter) was then cut to a length of 18 mm to form cylindrical deposits each weighing 40 mg and each containing the protein in a quantity equal to 6.6 x106 ILL
EXAMPLE 4 - Preparation of subcutaneous implants containing recombinant human Growth Hormone (r-Hu-GH)
a) Preparation of PLGA plasticized with ethanol
PLGA having the following characteristics is ground until a particle size of less than 250 pm is obtained.
inherent viscosity 0.19 dl/g measured at 25°C in chloroform (c = 0.1 g/dl),
Lactide / Glycolide Molar ratio: 53 / 47,
Tg: 40°C. The ground product is added to an excess of ethanol until a concentration of PLGA in ethanol equal to 0.12 g/ml is obtained and is placed in a bath of water heated to 45°C and stirred for 1 minute. The ethanol diffuses into the polymer and forms a viscous gel. This gel is maintained in ethanol for 3 minutes. This is followed by drying at 20°C until a PLGA is obtained containing ethanol in a quantity equal to 20% mass/mass.
The polymer thus obtained is mixed at -10°C with the same untreated type of polymer as such in a weight ratio of 40:60, and the said mixture is then extruded at 75°C.
The extruded product is then ground at -10°C to obtain the plasticized PLGA with an ethanol content of 8% mass/mass.
b) Preparation of the subcutaneous implant
The active principle consisting of the protein r-Hu-GH having the following characteristics:
Related proteins (Liquid Chromatography according to the monograph "Somatropin" - Nr 0951 of the 4th Edition of the European Pharmacopoeia): maximum 13% (peaks area),

Dimer and related substances of higher molecular mass (Size Exclusion Chromatography according to the monograph "Somatropin" - Nr 0951 of the 4th Edition of the European Pharmacopoeia): maximum 6% (peaks area),
Protein Content (Size Exclusion Chromatography according to the monograph "Somatropin* - Nr 0951 of the 4th Edition of the European Pharmacopoeia): 4.5 to 5,3% mass/mass,
Biological potency (Size Exclusion Chromatography according to the monograph "Somatropin" - Nr 0951 of the 4th Edition of the European Pharmacopoeia): 2.7 to 3.2 IU / mg of protein,
Excipients: Glycin / Sodium Phosphate monobasic / Sodium Phosphate Dibasic Dodecahydrated
(91.4% /1.0% / 2.5% mass/mass respectively)
and the plasticized polymer (PLGA) were mixed intimately at -10°C in a weight ratio of 30:70 respectively.
The powdered mixture thus obtained was extruded at 40°C. The extruded product thus obtained (1.5 mm in diameter) was then cut to a length of 18 mm to form cylindrical deposits each weighing 40 mg and each containing the protein in a quantity equal to 1.8 IU.
The integrity of the protein within the depots was examined through the following analytical package:
Related proteins by Liquid Chromatography according to the monograph "Somatropin" (Nr 0951) of the 4th Edition of the European Pharmacopoeia,
Dimer and related substances of higher molecular mass by Size Exclusion Chromatography according to the monograph "Somatropin" (Nr 0951) of the 4th Edition of the European Pharmacopoeia,
Assay by Size Exclusion Chromatography according to the monograph "Somatropin" (Nr 0951) of the 4th Edition of the European Pharmacopoeia. EXAMPLE 5 - Preparation of subcutaneous implants containing recombinant human Growth Hormone (r-Hu-GH) a) Preparation of PLGA plasticized with ethanol PLGA having the same characteristics as the one described in the Example 4 is

ground until a particle size of less than 250 pm is obtained.
The ground product is added to an excess of ethanol until a concentration of
PLGA in ethanol equal to 0.12 g/ml is obtained and is placed in a bath of water
heated to 45°C and stirred for 1 minute. The ethanol diffuses into the polymer and
forms a viscous gel. This gel is maintained in ethanol for 3 minutes.
This is followed by drying at 20°C until a PLGA is obtained containing ethanol in a
quantity equal to 20% mass/mass.
The polymer thus obtained is mixed at -10°C with the same untreated type of
polymer as such in a weight ratio of 32.5:67.5 and the said mixture is then
extruded at 75°C.
The extruded product is then ground at -10°C to obtain the plasticized PLGA with
an ethanol content of 6.5% mass/mass.
b) Preparation of the subcutaneous implant
The active principle consisting of the protein r-Hu-GH having the same
characteristics as the one described in the Example 4 and the plasticized polymer
(PLGA) were mixed intimately at -10°C in a weight ratio of 30:70 respectively.
The powdered mixture thus obtained was extruded at 50°C. The extruded product
thus obtained (1.5 mm in diameter) was then cut to a length of 18 mm to form
cylindrical deposits each weighing 40 mg and each containing the protein in a
quantity equal to 1.8 IU.
The integrity of the protein within the depots was examined through the same
analytical package that the one described for Example 4.
EXAMPLE 6 — Preparation of subcutaneous implants containing recombinant
human Growth Hormone (r-Hu-GH)
a) Preparation of PLGA plasticized with ethanol
PLGA having the same characteristics as the one described in the Example 4 is
ground until a particle size of less than 250 pm is obtained.
The ground product is added to an excess of ethanol until a concentration of
PLGA in ethanol equal to 0.12 g/ml is obtained and is placed in a bath of water
heated to 45°C and stirred for 1 minute. The ethanol diffuses into the polymer and
forms a viscous gel. This gel is maintained in ethanol for 3 minutes.

This is followed by drying at 20°C until a PLGA is obtained containing ethanol in a
quantity equal to 20% mass/mass.
The polymer thus obtained is mixed at -10°C with the same untreated type of
polymer as such in a weight ratio of 16:84 and the said mixture is then extruded at
75°C.
The extruded product is then ground at -10°C to obtain the plasticized PLGA with
an ethanol content of 3.2% mass/mass.
b) Preparation of the subcutaneous implant
The active principle consisting of the protein r-Hu-G-CSF having the same
characteristics as the one described in the Example 4 and the plasticized polymer
(PLGA) were mixed intimately at-10°C in a weight ratio of 30:70 respectively.
The powdered mixture thus obtained was extruded at 60°C. The extruded product
thus obtained (1.5 mm in diameter) was then cut to a length of 18 mm to form
cylindrical deposits each weighing 40 mg and each containing the protein in a
quantity equal to 1.8 IU.
EXAMPLE 7 - Preparation of subcutaneous implants containing Interferon alfa-2a a) Preparation of PLGA plasticized with ethanol
PLGA having the following characteristics is ground until a particle size of less than 250 pm is obtained.
inherent viscosity 0.19 dl/g measured at 25°C in chloroform (c = 0.1 g/dl),
Lactide / Glycolide Molar ratio: 53 / 47,
Tg: 40°C. The ground product is added to an excess of ethanol until a concentration o1 PLGA in ethanol equal to 0.12 g/ml is obtained and is placed in a bath of watei heated to 45°C and stirred for 1 minute. The ethanol diffuses into the polymer anc forms a viscous gel. This gel is maintained in ethanol for 3 minutes. This is followed by drying at 20°C until a PLGA is obtained containing ethanol in £ quantity equal to 20% mass/mass.
The polymer thus obtained is mixed at -10°C with the same untreated type o polymer as such in a weight ratio of 40:60 and the said mixture is then extruded a 75°C.

The extruded product is then ground at -10°C to obtain the plasticized PLGA with
an ethanol content of 8% mass/mass.
b) Preparation of the subcutaneous implant
The active principle consisting of the protein interferon alfa-2a having the following
characteristics:
Related proteins (Liquid Chromatography according to the monograph "Interferon alfa-2 Concentrated solution" - Nr 1110 of the 4th Edition of the European Pharmacopoeia): maximum 5% (peaks area),
Protein Content: 1.8% mass/mass,
Biological potency (Size Exclusion Chromatography according to the monograph "Interferon alfa-2 Concentrated solution" - Nr 1110 of the 4th Edition of the European Pharmacopoeia): 2.3 x 108 IU / mg of protein,
Excipients:
Sodium Acetate / Sodium Chloride / Trehalose
(5.9% / 8.4% / 83.9% mass/mass respectively) and the plasticized polymer (PLGA) were mixed intimately at -10°C in a weight ratio of 25:75 respectively.
The powdered mixture thus obtained was extruded at 40°C. The extruded product thus obtained (1.5 mm in diameter) was then cut to a length of 18 mm to form cylindrical deposits each weighing 40 mg and each containing the protein in a quantity equal to 40 x 106 IU.
The integrity of the protein within the depots was examined through the following analytical package:
- Related proteins by Liquid Chromatography according to the monograph "Interferon alfa-2 Concentrated solution" (Nr 1110) of the 4th Edition of the European Pharmacopoeia.




2* 04. 2005
NEW SET OF CLAIMS
1.PLGA plasticized with ethanol, obtained with a process comprising the following
steps:
a) grinding PLGA to obtain a ground product in which the particles have dimensions less than 250 pm;
b) adding ethanol to the ground product obtained in the preceding stage in concentrations between 5 and 20 parts by weight/weight of PLGA and heating the mixture obtained to a temperature between 45 and 65°C, until a viscous and stable gel is obtained;
c) drying the product coming from step (b),
d) grinding the dried product obtained at a temperature ranging from -20 and +5°C;
e) optionally mixing the product originating from the preceding stage with PLGA as such which has been previously ground until a ground product of particle size less than 250 pm is obtained, in weight ratios between 10:90 and 99:1, at a temperature between -20 and +5°C,
f) extruding the aforesaid mixture at 75°C,
g) grinding the extruded product at a temperature between -20°C and +5°C.
2. Plasticized PLGA as claimed in claim 1 containing ethanol in concentrations
between 2 and 15 % by weight on the weight of PLGA.
3. Plasticized PLGA as claimed in claim 2 wherein said ethanol concentrations are
comprised between 3 and 10% by weight on the weight of PLGA.
4. Plasticized PLGA as claimed in claim 2 in which said concentrations are
between 5 and 10% by weight on the weight of PLGA.
5.Plasticised ethanol according to anyone of claims 1-4, wherein in stage (b) the ethanol is added in a quantity of 10 parts by weight/weight of PLGA. 6.Plasticised ethanol according to anyone of claims 1-5, wherein in stage (d) the drying is conducted until obtaining an ethanol concentration in PLGA comprised between 10 and 30%/by weight/PLGA weight.
7. Plasticised ethanol according to claim 6 wherein said ethanol concentration is 20% by weight/PLGA weight.
8. Plasticised ethanol according to claim 6 or 7, wherein said drying is carried out

at a temperature comprised between 20 and 25°C under an air stream.
9. Plasticised ethanol as claimed in anyone of claims 1-8, wherein the grinding
temperature in stage (d), (e) and (g) is -10°C.
10. Plasticised ethanol as claimed in anyone of claims 1-9 wherein in stage (e) the weight ratio of PLGA originating from stage (d)/PLGA as such is comprised between 16:84 and 40:60.
11. Subcutaneous implants obtained by extrusion, containing the active principle dispersed in PLGA plasticized with ethanol as claimed in any one of claims 1-10.
12. Subcutaneous implants as claimed in claim 11 containing thermolabile active
principles.
13. Subcutaneous implants as claimed in claim 12, wherein said thermolabile
active principles are chosen from the class consisting of: proteins, vaccines,
antibodies and vectors for genie therapy.
14. A process for preparing the subcutaneous implants according to anyone of
claims 11-13 comprising the following stages:
i)mixing the active principle with the plasticized PLGA as claimed in any one of
claims 1-10, at a temperature between -20°C and +5°C,
ii)extruding the ground product originating from stage (i) at a temperature less than
70°C.
15. The process as claimed in claim 14, wherein the temperature of stage (i) is
-10°C.
16. The process as claimed in anyone of claims 14 and 15 wherein the
temperature of stage (ii) is less than 60°C when plasticized PLGA containing when
plasticized PLGA containing ethanol at concentrations between 3 and 4% by
weight on the weight of PLGA is used in stage (i).
17. The process as claimed in anyone of claims 15 and 16,wherein the
temperature of stage (ii) is equal to 40°C) when plasticized PLGA containing
ethanol at concentrations between 5 and 10% by weight/ weight of PLGA is used.


Documents:

0326-chenp-2006-abstract.pdf

0326-chenp-2006-claims.pdf

0326-chenp-2006-correspondnece-others.pdf

0326-chenp-2006-description(complete).pdf

0326-chenp-2006-form 1.pdf

0326-chenp-2006-form 18.pdf

0326-chenp-2006-form 3.pdf

0326-chenp-2006-form 5.pdf

0326-chenp-2006-pct.pdf

326-chenp-2006 correspondence others-17-07-2009.pdf

326-chenp-2006 correspondence others.pdf

326-CHENP-2006 CORRESPONDENCE PO.pdf

326-chenp-2006 description(complete)-17-07-2009.pdf

326-chenp-2006 form-3.pdf

326-chenp-2006 others.pdf

326-chenp-2006 petition.pdf

326-CHENP-2006 POWER OF ATTORNEY.pdf


Patent Number 238060
Indian Patent Application Number 326/CHENP/2006
PG Journal Number 5/2010
Publication Date 29-Jan-2010
Grant Date 20-Jan-2010
Date of Filing 25-Jan-2006
Name of Patentee MEDIOLANUM PHARMACEUTICALS LIMITED
Applicant Address 78TH FLOOR ,HUME HOUSE BALLSBRIDGE, DUBLIN 4,IRELAND
Inventors:
# Inventor's Name Inventor's Address
1 MAURIC ,PATRICE 54 RUE DE PICPUS , F-75012 PARIS, FRANCE
2 MARION ,PIERRE, 2 ALLEE MAURICE GENEVOIX , F-93360 NEUILLY PLAISANCE , FRANCE
PCT International Classification Number A61K 9/22
PCT International Application Number PCT/EP04/51226
PCT International Filing date 2004-06-24
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 MI2003A001302 2003-06-26 Italy