Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Reexamination Certificate
2001-04-17
2003-11-25
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
C424S422000, C424S423000, C424S436000
Reexamination Certificate
active
06652884
ABSTRACT:
The invention relates to a method for the treatment of tumors sensitive to Paclitaxel, and more particularly concerns a method by which a significant remission or cure of the tumor, with very low toxic side effects, can be achieved by just a few infusions, each of short duration and spaced apart by some weeks.
Paclitaxel is a substance well known in the literature, with important clinical activity on a large number of tumors, such as ovary, lung, head and neck, bladder and breast tumors.
Paclitaxel is insoluble in water. In order to render it soluble and suitable for intravenous administration, it has been mixed with a surfactant (such as polyethoxylated castor oil, known by the registered name “Cremophor EL”) and with about 50% of anhydrous alcohol USP, as vehicles for the Paclitaxel: this mixture was patented by Bristol-Myers Squibb and is known by the registered name “Taxol” to which reference will be made hereinafter, for simplicity. The presence of the surfactant and the anhydrous alcohol has serious drawbacks, such as strong hypersensitivity, in addition to other side effects.
In any event, Taxol is administered, and can be administered, only by intravenous injection, with very lengthy administration times in an attempt to minimize the toxic effects of the product.
To overcome the aforesaid drawbacks, the said Bristol-Myers Squibb has patented (European Patent Applications EP-A-0584001, EP-A0783885, EP-A-0783886 and U.S. Pat. No. 5,641,803 and U.S. Pat. No. 5,670,537) compositions equal to those of Taxol, but containing or combined with the use of medicaments able to impede serious anaphylactic reactions.
According to the known art, as described in the various patents, from 135 to 175 mg of Taxol per m
2
of the body surface are administered intravenously to patients subjected to therapy, each administration having a duration of about 3 hours: it is essential always to use the aforementioned pre-medications.
U.S. Pat. Nos. 5,439,686, 5,498,421 and 5,560,933 describe albumin microparticles incorporating the Paclitaxel: these particles are internationally identified by the symbols ABI 007, this denomination being used hereinafter for simplicity whenever reference is made to the aforesaid particles.
ABI 007 is a formulation of Paclitaxel stabilized by human albumin USP, which can be dispersed in directly injectable physiological solution.
Being free of toxic emulsifiers, ABI 007 can be administered with higher doses of Paclitaxel than in the case of Taxol, but this is currently done by the known method, i.e. by intravenous injection.
If ABI 007 in physiological solution is injected directly into the arteries which feed the territory associated with a tumor sensitive to paclitaxel, and is repeated several times at intervals of 3-4 weeks, it has been found that with this method a surprisingly favorable therapeutic result is obtained, i.e., a treatment response percentage which is higher than 71% (compared with the 40% achieved with the traditional treatment with paclitaxel, for example in treating head and neck cancer).
The invention hence relates to both the method of administrating Paclitaxel and the drugs usable to implement the method, i.e. drugs comprising a physiological solution in which ABI 007 is dispersed at a concentration between 2 and 8 mg/ml (preferably between 3 and 7.5 mg/ml) of the solution.
More particulary, the present invention relates to a method for the treatment of a patient afflicted with a tumor sensitive to paclitaxel, a method consisting of injecting into the artery feeding to the territory associated with a tumor a physiological solution containing between 190 and 500 mg of ABI 007 per m
2
of the patient's body surface over a duration of about 25-60 minutes. From 2 to 5 similar intra-arterial injections are then repeated at a time interval of 3-5 weeks one from another.
Tumors which have proved responsive to the described treatment are the squamocellular carcinomas, including certain tumors of the lung, head and neck, uterus and anal canal.
Preferably, the dispersion of microparticles in the physiological solution used for intra-arterial therapy of tumors contains from 200 to 300 mg of ABI 007 per m
2
of the patient's body surface for each administration, and the administration of each individual dose of the dispersion is effected over about 30 minutes.
Compared with the teachings of the aforestated previous known patents, it can be noted that, according to the present invention, doses of Paclitaxel are administered to the patient which are very much higher, and with infusion durations which are very much shorter, than is possible with intravenous administration, with favourable results (response percentage extremely high and surprising), observing very low toxicity in all cases.
REFERENCES:
patent: 5916596 (1999-06-01), Desai et al.
patent: 6096331 (2000-08-01), Desai et al.
patent: WO 94/18954 (1994-09-01), None
patent: WO 98/14174 (1998-04-01), None
patent: WO 00/06152 (2000-10-01), None
U.S. patent application Ser. No. 09/835,384, Falciani, Apr. 17, 2001.
U.S. patent application Ser. No. 10/383,616, Zenoni, et al., Mar. 10, 2003.
U.S. patent application Ser. No. 10/383,639, Zenoni, et al., Mar. 10, 2003.
ACS Dobfar S.p.A.
Oblon & Spivak, McClelland, Maier & Neustadt P.C.
Page Thurman K.
Sheikh Humera N.
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