AU2002244877A1 - Antitumor compositions containing taxane derivatives - Google Patents
Antitumor compositions containing taxane derivativesInfo
- Publication number
- AU2002244877A1 AU2002244877A1 AU2002244877A AU2002244877A AU2002244877A1 AU 2002244877 A1 AU2002244877 A1 AU 2002244877A1 AU 2002244877 A AU2002244877 A AU 2002244877A AU 2002244877 A AU2002244877 A AU 2002244877A AU 2002244877 A1 AU2002244877 A1 AU 2002244877A1
- Authority
- AU
- Australia
- Prior art keywords
- pharmaceutical composition
- constituents
- composition
- neoplastic disease
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Description
ANTITUMOR COMPOSITIONS CONTAINING
TAXANE DERIVATIVES
This application is a continuation-in-part of U.S. Patent Application No.
09/705,739, filed November 6, 2000, which is a divisional application of
Application No. 09/371 ,520, filed August 10, 1999, which is a continuation
application of Application No. 09/182,900, filed October 30, 1998, now
abandoned, which is a divisional application of Application No. 08/967,036, filed
November 10, 1997, now U.S. Patent No. 5,908,835, which is a divisional
application of Application No. 08/424,470, filed May 9, 1995, now U.S. Patent
No. 5,728,687.
The present invention relates to combinations of taxol, Taxotere and their
analogues and substances which are therapeutically useful in the treatment of
neoplastic diseases.
Taxol, Taxotere and their analogues, which possess noteworthy antitumor
and antileukemic properties, are especially useful in the treatment of cancers of
the colon, ovary, breast or lung.
The preparation of taxol, Taxotere and their derivatives form the subject,
for example, of European Patents EP 0,253,738 and EP 0,253,739 and
International Application PCT WO 92/09,589.
Generally, the doses used, which depend on factors distinctive to the
subject to be treated, are between 1 and 10 mg/kg administered intraperitoneally
or between 1 and 3 mg/kg administered intravenously.
It has now been found, and this forms the subject of the present invention,
that the efficacy of taxol, Taxotere and their analogues may be considerably
improved when they are administered in combination with at least one substance
which is therapeutically useful in anticancer treatments and has a mechanism
identical to or different from this of taxane derivatives.
Among substances which may be used in association or in combination
with taxol, Taxotere or their analogues, there may be mentioned alkylating
agents such as cyclophosphamide, isosfamide, melphalan, hexametyl-
melamine, thiotepa or dacarbazine, antimetabolites such as pyrimidine
analogues, for instance 5-fluarouracil and cytarabine, or its analogues such as 2-
flourodeoxycytidine, or folic acid analogues such as methotrexate, idatrexate or
trimetrexate, spindle poisons including vinca alkaloids such as vinblastine or
vincristine or their synthetic analogues such as navelbine, or estramustine or
taxoids, epidophylloptoxins such as etoposide or teniposide, antibiotics such as
daunorubicine, doxόrubicin, bleomycin or mitomycin, enzymes such as L-
asparaginase, topoisomerase inhibitors such as camptothecin derivatives
chosen from CPT-11 and topotecan or pyridobenzoindole derivatives, and
various agents such as procarbazine, mitoxantrone, platinum coordination
complexes such as cisplatin or carboplatin, and biological response modifiers or
growth factor inhibitors such as interferons or interleukins.
Moreover, since the activity of the products depends on the doses used, it
is possible to use higher doses and to increase the activity while decreasing the
toxicity phenomena or delaying their onset by combining growth factors of the
haematopoietic type such as G-CSF or GM-CSF or certain interleukins with
taxol, Taxotere, their analogues or their combinations with other therapeutically
active substances.
The combinations or associations according to the invention enable the
phenomena of pleiotropic resistance or "multi-drug resistance" to be avoided to
delayed.
More especially, the invention relates to combinations of taxol, Taxotere
and their analogues with vinca alkaloids, cyclophosphamide, 5-fluorouracil,
doxorubicin, cisplatin, navelbine, camptothecin, and etoposide.
The improved efficacy of a combination according to the invention may be
demonstrated by determination of the therapeutic synergy. A combination
manifests therapeutic synergy if it is therapeutically superior to one or other of
the constituents used at its optimum dose (T.H. Corbett et al., Cancer Treatment
Reports, 66: 1187 (1982)).
To demonstrate the efficacy of a combination, it may be necessary to
compare the maximum tolerated dose of the combination with the maximum
tolerated dose of each of the separate constituents in the study in question. This
efficacy may be quantified, for example, by the log10 cells killed, which is
determined according to the following formula:
log10 cells killed = T-C (days)/3.32 x Td
in which T - C represents the time taken for the cells to grow, which is the mean
time in days for the tumors of the treated group (T) and the tumors of the treated
group (C) to have reached a predetermined value (1 g for example) , and Td
represents the time in days needed for the volume of the tumor to double in the
control animals [T.H. Corbett et al., Cancer. 40, 2660-2680 (1977); F.M. Schabel
et al., Cancer Drug Development, Part B, Methods in Cancer Research. 17, 3-
51 , New York, Academic Press Inc. (1979)]. A product is considered to be active
if log10 cells killed is greater than or equal to 0.7. A product is considered to be
very active if log10 cells killed is greater than 2.8.
The combination, used at its own maximum tolerated dose, in which each
of the constituents will be present at a dose generally not exceeding its
maximum tolerated dose, will manifest therapeutic synergy when the log10 cells
killed is greater than the value of the log10 cells killed of the best constituent
when it is administered alone.
The efficacy of the combinations on solid tumors may be determined
experimentally in the following manner:
The animals subjected to the experiment, generally mice, are
subcutaneously grafted bilaterally with 30 to 60 mg of a tumor fragment on day
0. The animals bearing tumors are mixed before being subjected to the various
treatments and controls. In the case of treatment of advanced tumors, tumors
are allowed to develop to the desired size, animals having insufficiently
developed tumors being eliminated. The selected animals are distributed at
random to undergo the treatments and controls. Animals not bearing tumors
may also be subjected to the same treatments as the tumor-bearing animals in
order to be able to dissociate the toxic effect from the specific effect on the
tumor. Chemotherapy generally begins from 3 to 22 days after grafting,
depending on the type of tumor, and the animals are observed every day. The
different animal groups are weighed 3 or 4 times a week until the maximum
weight loss is attained, and the groups are then weighed at least once a week
until the end of the trial.
The tumors are measured 2 or 3 times a week until the tumor reaches
approximately 2 g, or until the animal dies if this occurs before the tumor reaches
2 g. The animals are autopsied when sacrificed.
The antitumor activity is determined in accordance with the different
parameters recorded.
For a study of the combinations on leukemias the animals are grafted with
a particular number of cells, and the antitumour activity is determined by the
increase in the survival time of the treated mice relative to the controls. The
product is considered to be active if the increase in survival time is greater than
27%, and is considered to be very active if it is greater than 75% in the case of
P388 leukemias.
The results obtained with combinations of Taxotere and various
chemotherapeutic agents, such as cyclophosphamide (alkylating agent), 5-
fluorouracil (antimetabolite), etoposide (semisynthetic podophyllotoxin agent)
and vincristine (vinca alkaloid), the combinations being used at their optimum
dose, are given as examples in the following tables.
TABLE 1
TABLE 2
TABLE 3
TABLE 4
Experiments were also conducted using a taxotere analogue, N-
debenzoyl-N-t-butoxy-carbonyl-7-deoxy-8-desmethyl-7, 8-cyclopropataxotere
(hereinafter acetocyclopropyl taxotere) with several chemotherapeutic agents.
The structure of acetocyclopropyl taxotere is as follows:
Combinations of acetocyclopropyl taxotere and various chemotherapeutic
agents, such as doxorubicin (antibiotic), cisplatin (platinum coordination
complex), navelbine (spindle poison), and CPT-11 (topoisomerase inhibitor),
were evaluated in mice bearing s.c. transplantable tumors. The tumor model
used to evaluate each drug combination was selected, in general, on the basis of
its responsiveness to each of the agents when used as monotherapy. Using i.v.
intermittent schedules, full dose response trials were conducted for each single
agent and each combination.
In addition to the parameters described above, the combination toxicity
index (CTI) was determined. See Corbett, T.H., et al., Response of
transplantable tumors of mice to anthracenedione derivatives alone and in
combination with clinically useful agents, Cancer Treat. Rep. 66: 1187-1200
(1982). The CTl represents the sum of the fractions of the lethal dose 10% (LD10)
of each single agent used in the optimal combination. It indicates the extent in
host toxicity overlap. For example, a CTl of 1 indicates that only 50% of the LD10
of each single agent (or any of the ratios, 70:30, 40:60, etc ...) can be used in
combinations without incurring additional toxicity, whereas a CTl of 2 indicates
that 100% of the LD10of each single agent can be used in combination.
The following table summarizes for each combination the therapeutic
response and highest non toxic dose of each arm of the study, the single agents
and the combination.
Abbreviations use : = tumor ou ling time; bwl = body weight loss; TFS = tumor free survivors; CTl «= combination toxicity; IV = intravenous; PO = by month; CR = Complete Response.
In combination with doxorubicin, the optimal combination produced a log
cell kill of 5.3 in MA13/C bearing mice and induced 100% complete regressions
(no cures) whereas the single agents produced lower log cell kill, i.e.,
acetocyclopropyl taxotere had a log cell kill of 2.9 and doxorubicin-3.0. The
combination toxicity index was 1.42 indicating that approximately 70% of the
HNTD of each single agent can be combined without additional toxicity.
With cisplatin, the optimal combination produced 3.6 log cell kill and 2/7
tumor free survivors on day 122 in Colon 51 bearing mice whereas the single
agents produced 1.4 log cell kill for acetocyclopropyl taxotere and 2.7 log cell kill
for cisplatin with no tumor free survivors. There was an important overlap in host
recovery with a CTl of 0.68 indicating that less than 35% of each of the single
agent can be administered in combination. However, the mice were not
hyperhydrated when receiving cisplatin which may explain this degree of toxicity.
The combination of acetocyclopropyl taxotere with CPT-11 was found to
be at least as good as the best single agent in the combinations (1.7 log cell kill
for the combination, versus 1.5 for acetocyclopropyl taxotere and 1.1 for
CPT-11 ). However, CTl of 0.6 indicates an important overlap in host toxicity.
Finally, there was a very good synergistic effect between acetocyclopropyl
taxotere and navelbine in MA17/A bearing mice with a 8.1 log cell kill (and 2
tumor free survivors on day 123) for the combination, 4.8 for acetocyclopropyl
taxotere and 5.5 for navelbine. The combination produced a modest overlap in
host toxicity with a CTl of 1.42.
Overall, the four acetocyclopropyl taxotere combinations tested were all
found synergistic i.e., the antitumor activity was greater in the combination arm
than in single agent arm at highest non toxic dose.
In terms of tolerance, the combination of acetocyclopropyl taxotere with
doxorubicin or navelbine, were well tolerated with a CTl of approximately 1.4,
whereas dose reduction would be needed in the case of combination of
cyclopropataxol with cisplatin or with CPT-11 (CTl < 1 ).
The present invention also relates, therefore, to pharmaceutical compositions containing the combinations according to the invention.
The constituents of which the combination are composed may be
administered simultaneously, semi-εimultaneously, separately, or spaced out
over a period of time so as to obtain the maximum efficacy of the combination; it
being possible for each administration to vary in its duration from a rapid
administration to a continuous perfusion.
As a result, for the purposes of the present invention, the combinations
are not exclusively limited to those which are obtained by physical association of
the constituents, but also to those which permit a separate administration, which
can be simultaneous or spaced out over a period of time.
The compositions according to the invention are preferably compositions
which can be administered parentally. However, these compositions may be
administered orally or intraperitoneally in the case of localized regional therapies.
The compositions for parental administration are generally
pharmaceutically acceptable, sterile solutions or suspensions which may
optionally be prepared as required at the time of use. For the preparation of
non-aqueous solutions or suspensions, natural vegetable oils such as olive oil,
sesame oil or liquid petroleum or injectable organic esters such as ethyl oleate
may be used. The sterile aqueous solutions can consist of a solution of the
product in water. The aqueous solutions are suitable for intravenous
administration provided the pH is appropriately adjusted and the solution is made
isotonic, for example with a sufficient amount of sodium chloride or glucose. The
sterilization may be carried out by heating or by any other means which does not
adversely affect the composition. The combinations may also take the form of
liposomes or the form of an association with carriers as cyclodextrins or
polyethylene glycols.
The compositions for oral or intraperitoneal administration are preferably
aqueous suspensions or solutions.
In the combinations according to the invention, the application of the
constituents of which may be simultaneous, separate or spaced out over a
period of time, it is especially advantageous for the amount of taxane derivative
to represent from 10 to 90% by weight of the combination, it being possible for
this content to vary in accordance with the nature of the associated substance,
the efficacy sought and the nature of the cancer to he treated.
The combinations according to the invention are especially useful in the
treatment of cancers of the colon, breast, ovary or lung, as well as melanoma
and leukemia. In particular, they can afford the advantage of being able to
employ the constituents at considerably lower doses than those at which they
are used alone.
Claims (19)
1. A pharmaceutical composition comprised of the compound of
formula 1
or a derivatve thereof, and at least one of an alkylating agent, an antimetabolite,
a spindle poison, an epidophyllotoxin, an antibiotic, an enzyme, a topoisomerase
inhibitor, a platinum coordination complex, a biological response modifier or a
growth factor inhibitor.
2. The pharmaceutical composition according to claim 1 wherein the
antibiotic agent is chosen from daunorubicin, doxorubicin, bleomycin and
mitomycin.
3. The pharmaceutical composition according to claim 1 wherein the
spindle poison is chosen from vinca alkaloids, their synthetic or semi-synthetic
analogues, estramustine or navelbine.
4. The pharmaceutical composition according to claim 1 wherein the
topoisomerase inhibitor is chosen from camptothecin and its derivatives including
CPT-11 , topotecan and pyridobenzoindole derivatives.
5. The pharmaceutical composition according to claim 1 wherein the
platinum coordinating complex is chosen from cisplatin and carboplatin.
6. The pharmaceutical composition according to anyone of claims 2
to 5, further comprising growth factors of the haematopoietic type.
7. A method of administering the constituents of the composition as
claimed in any one of claims 2 to 5, wherein said administration is separate and
simultaneous.
8. A method of administering the constituents of the composition as
claimed in any one of claims 2 to 5, wherein said administration is separate and
sequential.
9. A method of administering the constituents of the composition as
claimed in any one of claims 2 to 5, wherein said administration is separate and
spaced out over time.
10. A pharmaceutical composition having therapeutic synergy in the
treatment of neoplastic disease comprising a compound of the formula:
and doxorubicin.
11. A pharmaceutical composition having therapeutic synergy in the treatment of neoplastic disease comprising a compound of the formula:
and navelbine.
12. A pharmaceutical composition having therapeutic synergy in the
treatment of neoplastic disease comprising a compound of the formula:
and cisplatin.
13. A pharmaceutical composition having therapeutic synergy in the
treatment of neoplastic disease comprising a compound of the formula:
and CPT H.
14. The pharmaceutical composition of any one of claims 10 to 13
wherein the constituents of the composition are administered simultaneously.
15. The pharmaceutical composition of any one of claims 10 to 13
wherein the constituents of the composition are administered separately and
simultaneously.
16. The pharmaceutical composition of any one of claims 10 to 13
wherein the constituents of the composition are administered separately and
semi-simultaneously.
17. The pharmaceutical composition of any one of claims 10 to 13
wherein the constituents of the composition are administered separately and
sequentially.
18. The pharmaceutical composition of claim 10 or claim 11 wherein the
neoplastic disease is breast cancer.
19. The pharmaceutical composition of claim 12 or claim 13 wherein the
neoplastic disease is colon cancer.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/813,018 US6441026B1 (en) | 1993-11-08 | 2001-03-21 | Antitumor compositions containing taxane derivatives |
US09/813,018 | 2001-03-21 | ||
PCT/IB2002/000853 WO2002074289A2 (en) | 2001-03-21 | 2002-03-21 | Antitumor compositions containing taxane derivatives |
Publications (2)
Publication Number | Publication Date |
---|---|
AU2002244877A1 true AU2002244877A1 (en) | 2003-03-27 |
AU2002244877B2 AU2002244877B2 (en) | 2006-07-20 |
Family
ID=25211230
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU2002244877A Ceased AU2002244877B2 (en) | 2001-03-21 | 2002-03-21 | Antitumor compositions containing taxane derivatives |
Country Status (19)
Country | Link |
---|---|
US (1) | US6441026B1 (en) |
EP (1) | EP1478355B1 (en) |
JP (1) | JP4467885B2 (en) |
CN (2) | CN101590057A (en) |
AT (1) | ATE355837T1 (en) |
AU (1) | AU2002244877B2 (en) |
BR (1) | BR0208274A (en) |
CA (1) | CA2440160C (en) |
CY (1) | CY1106582T1 (en) |
DE (1) | DE60218751T2 (en) |
DK (1) | DK1478355T3 (en) |
EA (1) | EA006878B1 (en) |
ES (1) | ES2282400T3 (en) |
HU (1) | HUP0500478A2 (en) |
IL (1) | IL157992A (en) |
MX (1) | MXPA03008539A (en) |
PT (1) | PT1478355E (en) |
SI (1) | SI1478355T1 (en) |
WO (2) | WO2002074232A2 (en) |
Families Citing this family (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2697752B1 (en) * | 1992-11-10 | 1995-04-14 | Rhone Poulenc Rorer Sa | Antitumor compositions containing taxane derivatives. |
FR2698871B1 (en) | 1992-12-09 | 1995-02-24 | Rhone Poulenc Rorer Sa | New taxoids, their preparation and the pharmaceutical compositions containing them. |
WO2002072085A1 (en) * | 2001-03-14 | 2002-09-19 | Bristol-Myers Squibb Company | Combination of epothilone analogs and chemotherapeutic agents for the treatment of proliferative diseases |
ITRM20020191A1 (en) * | 2002-04-08 | 2003-10-08 | Sigma Tau Ind Farmaceuti | USE OF LONG PENTRAXIN PTX3 FOR THE PREPARATION OF A MEDICINE FOR THE TREATMENT OF CANCER PATHOLOGIES ASSOCIATED WITH AN ALTERED ATT |
CA2486124A1 (en) * | 2002-05-17 | 2003-11-27 | Aventis Pharma S.A. | Use of docetaxel/doxorubicin/cyclophosphamide in adjuvant therapy of breast and ovarian cancer |
WO2004035034A2 (en) * | 2002-10-16 | 2004-04-29 | Ilex Products, Inc. | Clofarabine and taxane chemotherapy combination |
ITMI20030317A1 (en) * | 2003-02-21 | 2004-08-22 | Pharmacia Italia Spa | COMBINED THERAPY INCLUDING AN INDOLOPIRROLOCARBAZOLO DERIVATIVE AND ANOTHER ANTI-CANCER AGENT. |
CA2526278A1 (en) * | 2003-05-20 | 2004-12-02 | Aronex Pharmaceuticals, Inc. | Combination chemotherapy comprising a liposomal platinum complex |
CN100340296C (en) * | 2005-02-03 | 2007-10-03 | 山东蓝金生物工程有限公司 | Anticarcinogenic internal implant agent |
US8735394B2 (en) | 2005-02-18 | 2014-05-27 | Abraxis Bioscience, Llc | Combinations and modes of administration of therapeutic agents and combination therapy |
EP2301531B1 (en) | 2005-02-18 | 2018-06-06 | Abraxis BioScience, LLC | Combinations and modes of administration of therapeutic agents and combination therapy |
JP5237821B2 (en) | 2005-12-05 | 2013-07-17 | 日東電工株式会社 | Polyglutamic acid-amino acid conjugates and methods |
EP1913958B1 (en) * | 2006-08-03 | 2009-12-23 | Sanofi-Aventis | Antitumor compositions containing acetylcyclopropyl docetaxel and trastuzumab |
US20080181852A1 (en) * | 2007-01-29 | 2008-07-31 | Nitto Denko Corporation | Multi-functional Drug Carriers |
CN101674852A (en) * | 2007-04-10 | 2010-03-17 | 日东电工株式会社 | Multi-functional polyglutamate drug carriers |
US20080279782A1 (en) * | 2007-05-09 | 2008-11-13 | Nitto Denko Corporation | Polymers conjugated with platinum drugs |
KR20100017540A (en) * | 2007-05-09 | 2010-02-16 | 닛토덴코 가부시키가이샤 | Compositions that include a hydrophobic compound and a polyamino acid conjugate |
EP2155253A2 (en) * | 2007-05-09 | 2010-02-24 | Nitto Denko Corporation | Polyglutamate conjugates and polyglutamate-amino acid conjugates having a plurality of drugs |
MX2010009670A (en) * | 2008-03-06 | 2010-09-22 | Nitto Denko Corp | Polymer paclitaxel conjugates and methods for treating cancer. |
WO2011123395A1 (en) | 2010-03-29 | 2011-10-06 | Abraxis Bioscience, Llc | Methods of treating cancer |
KR20130028727A (en) | 2010-03-29 | 2013-03-19 | 아브락시스 바이오사이언스, 엘엘씨 | Methods of enhancing drug delivery and effectiveness of therapeutic agents |
NZ604031A (en) | 2010-06-04 | 2015-05-29 | Abraxis Bioscience Llc | Methods of treatment of pancreatic cancer |
CN103403552B (en) * | 2010-11-12 | 2016-01-06 | 恩多塞特公司 | The method of Therapeutic cancer |
CN102241648B (en) * | 2011-01-31 | 2016-08-03 | 沈阳东星医药科技有限公司 | Anti-multidrug resistance taxane derivatives and its preparation method and application |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2601675B1 (en) | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | TAXOL DERIVATIVES, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
FR2601676B1 (en) | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | PROCESS FOR THE PREPARATION OF TAXOL AND DESACETYL-10 TAXOL |
US4876399A (en) | 1987-11-02 | 1989-10-24 | Research Corporation Technologies, Inc. | Taxols, their preparation and intermediates thereof |
US5136060A (en) | 1989-11-14 | 1992-08-04 | Florida State University | Method for preparation of taxol using an oxazinone |
US5015744A (en) | 1989-11-14 | 1991-05-14 | Florida State University | Method for preparation of taxol using an oxazinone |
US5399363A (en) | 1991-01-25 | 1995-03-21 | Eastman Kodak Company | Surface modified anticancer nanoparticles |
AU2005692A (en) | 1991-05-08 | 1992-12-21 | United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Method for designing cancer treatment regimens and methods and pharmaceutical compositions for the treatment of cancer |
US5645988A (en) | 1991-05-08 | 1997-07-08 | The United States Of America As Represented By The Department Of Health And Human Services | Methods of identifying drugs with selective effects against cancer cells |
US5284865A (en) | 1991-09-23 | 1994-02-08 | Holton Robert A | Cyclohexyl substituted taxanes and pharmaceutical compositions containing them |
US5229526A (en) | 1991-09-23 | 1993-07-20 | Florida State University | Metal alkoxides |
US5262409A (en) | 1991-10-11 | 1993-11-16 | Fred Hutchinson Cancer Research Center | Binary tumor therapy |
US5294737A (en) | 1992-02-27 | 1994-03-15 | The Research Foundation State University Of New York | Process for the production of chiral hydroxy-β-lactams and hydroxyamino acids derived therefrom |
FR2697752B1 (en) * | 1992-11-10 | 1995-04-14 | Rhone Poulenc Rorer Sa | Antitumor compositions containing taxane derivatives. |
EP0982028A1 (en) * | 1998-08-20 | 2000-03-01 | Aventis Pharma S.A. | New use of taxoid derivatives |
-
2001
- 2001-03-21 US US09/813,018 patent/US6441026B1/en not_active Expired - Fee Related
-
2002
- 2002-03-21 HU HU0500478A patent/HUP0500478A2/en unknown
- 2002-03-21 AU AU2002244877A patent/AU2002244877B2/en not_active Ceased
- 2002-03-21 SI SI200230525T patent/SI1478355T1/en unknown
- 2002-03-21 CN CNA2009101299448A patent/CN101590057A/en active Pending
- 2002-03-21 CN CNA028068572A patent/CN1536995A/en active Pending
- 2002-03-21 WO PCT/IB2002/002239 patent/WO2002074232A2/en not_active Application Discontinuation
- 2002-03-21 JP JP2002572997A patent/JP4467885B2/en not_active Expired - Lifetime
- 2002-03-21 DE DE60218751T patent/DE60218751T2/en not_active Expired - Lifetime
- 2002-03-21 BR BR0208274-8A patent/BR0208274A/en not_active IP Right Cessation
- 2002-03-21 EP EP02713093A patent/EP1478355B1/en not_active Expired - Lifetime
- 2002-03-21 MX MXPA03008539A patent/MXPA03008539A/en active IP Right Grant
- 2002-03-21 DK DK02713093T patent/DK1478355T3/en active
- 2002-03-21 AT AT02713093T patent/ATE355837T1/en active
- 2002-03-21 CA CA2440160A patent/CA2440160C/en not_active Expired - Lifetime
- 2002-03-21 PT PT02713093T patent/PT1478355E/en unknown
- 2002-03-21 EA EA200301047A patent/EA006878B1/en not_active IP Right Cessation
- 2002-03-21 ES ES02713093T patent/ES2282400T3/en not_active Expired - Lifetime
- 2002-03-21 WO PCT/IB2002/000853 patent/WO2002074289A2/en active IP Right Grant
-
2003
- 2003-09-18 IL IL157992A patent/IL157992A/en not_active IP Right Cessation
-
2007
- 2007-05-10 CY CY20071100643T patent/CY1106582T1/en unknown
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