Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-10-04
2004-08-03
Jones, Dwayne C. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06770670
ABSTRACT:
CROSS-REFERENCE TO RELATED FOREIGN APPLICATION
This application claims priority under 35 U.S.C. 119 to Australian Patent No. 6074, filed Nov. 27, 1992.
This invention relates to a solution of paclitaxel having improved stability.
BACKGROUND OF THE INVENTION
Paclitaxel is a compound extracted from the bark of a western yew,
Taxus brevifolia
and known for its antineoplastic activity. It is described for example in The Merck Index, Eleventh Edition 1989, monograph 9049.
In 1977, paclitaxel was chosen for development as an antineoplastic agent because of its unique mechanism of action and good cytotoxic activity against IP implanted D16 melanoma and the human X-1 mammary tumor xenograft. Paclitaxel is believed to function as a mitotic spindle poison and as a potent inhibitor of cell replication in vitro. Other mitotic spindle points (colchicine and podophyllotoxin) inhibit microtubule assembly. Paclitaxel employs a different mechanism of action since it appears to shift the equilibrium of polymerization/depolymerization toward polymer assembly and to stabilize microtubules against depolymerization under conditions which would cause rapid disaggregation of microtubules. The interference with the polymerization/depolymerization cycle in cells appears to interfere with both the replication and migration of cells.
After extensive preclinical screening in mouse tumor models, paclitaxel entered clinical trials in 1983. Over the past few years, paclitaxel has demonstrated good response rates in treating both ovarian and breast cancer patients who were not benefitting from vinca alkaloid or cisplatin therapy. It has also shown encouraging results in patients with other types of cancer including lung, melanoma, lymphoma, head and neck.
For further information, reference may be made to the U. S. National Cancer Institute's Clinical Brochure for Taxol, revised July 1991, and papers presented at the Second National Cancer Institute Workshop on Taxol and Taxus held in Alexandria, Va. USA on Sep. 23-24, 1992.
BRIEF DESCRIPTION OF THE INVENTION
It is a disadvantage of the known formulation that the paclitaxel therein degrades, with the result that the shelf life of the formulation is unsatisfactory, and there is therefore a need for a paclitaxel solution of improved stability.
Accordingly, in a general aspect the invention provides a solution containing paclitaxel, cremophor EL™ and ethanol, characterized in that the pH of the solution has been adjusted into the range 1 to 8 by addition of an acid.
Acids in the form of powders, for example citric acid, are preferred over those which contain water, for example sulfuric acid. The most preferred acid for use in accordance with the present invention is citric acid, but a wide range of acids may be used including the following:
Citric acid—monohydrous
Citric acid—anhydrous
Citric acid—hydrous
Acetic acid
Formic acid
Ascorbic acid
Aspartic acid
Benzene sulphonic acid
Benzoic acid
Hydrochloric acid
Sulphuric acid
Phosphoric acid
Nitric acid
Tartaric acid
Diatrizoic acid
Glutamic acid
Lactic acid
Maleic acid
Succinic acid
REFERENCES:
Richheimer, 1991, “High Performance Liquid Chromatographic Assay of Taxol”, Anal. Chem., Oct. 1992, vol. 64, which is disclosed in Professor's Blechert's Israeli Declaration filed in the Israel Opposition to related application.*
Sep. 1983, National Cancer Institute Report for Taxol NSC 125973.*
Roger W. Miller et al., Antileukemic Alkaloids fromTaxus wallichianaZucc., J. Org. Chem, 1981, 46:1469-1474.
National Cancer Institute. Division of Cancer Treatment, Bethesda, Maryland, Clinical Brochure, Taxol IND 22850. NSC 125973, Jul. 1991, pp. 1-36.
Abraham E. Mathew et al., Synthesis and Evaluation of Some Water-Soluble Prodrugs and Derivatives of Taxol with Antitumor Activity, J. Med. Chem., 1992, 35:145-151.
J.R. Kagel et al., Taxol Stability in Aqueous Solutions or in Organic/Aqueous Cosolvents, 8thAAPS National Meeting, Orlando, FL, Nov. 14-18, 1993.
National Cancer Institute, Division of Cancer Treatment, Bethesda, Maryland, Clinical Brochure, Taxol NSC 125973, Sep. 1983, pp. 1-54.
Professor Blechert's Israeli Declaration filed in the Israel Opposition to a related application, and also made of record in the European Opposition.
Susan G. Arbuck et al., A Reassessment of Cardiac Toxicity Associated with Taxol, Journal of the National Cancer Institute Monographs, 1993, 15:117-130.
K. Reber, Inhibition of Haemolysis by ‘Cremophor’ in Conserved Blood, Nature, Oct. 9, 1965, 208(5006):195.
Taxol Brochure, MeadJohnson Oncology Products, A Bristol-Myers Squibb Company, Jul. 2000, 6 pages.
National Cancer Institute, Division of Cancer Treatment, Bethesda, Maryland, Annual Report to the Food and Drug Administration, Taxol IND 22850 NSC 125573, Feb. 1989, pp. 1-25.
English language translation of informal signed statement from Professor Blechert attesting to various pH determinations which he purported he had carried out, Jun. 2002.
Decision issued by the European Patent Office revoking European Patent No. 0674510.
Consolidated Document List cited all reference documents relied on during prosecution of the Appeal process of European Patent No. 0674510.
NaPro Biotherapeutics, Inc. and Abbott Laboratories v. Mylan Laboratories, Inc., Mylan Pharmaceuticals, Inc. and UDL Laboratories, Inc., Civil Action No. 01-CV-1048 (W.D. PA), Stipulation and Protective Order.
NaPro Biotherapeutics, et al. v. Mylan Laboratories, et al., Case No. 01-CV-1048 (W.D. PA), Patent Infringement, litigation, court docket.
NaPro Biotherapeutics, Inc., et al. v. Bristol-Myers Squibb Co., Case No. 00-CV-1818 (D. CO), Patent Infringement, litigation, court docket.
NaPro Biotherapeutics, Inc. and Abbott Laboratories v. Mylan Laboratories, Inc., Mylan Pharmaceuticals, Inc. and UDL Laboratories, Inc., Civil Action No. 01-CV-1048 (W.D. PA), Amended Answer and Counterclaims of Defendants to Second Amended Complaint.
NaPro Biotherapeutics, Inc. and Abbott Laboratories v. Bristol-Myers Squibb Co., Civil Action No. 00-B-1818 (D. CO), Defendant's Responses and Objections to Plaintiffs' First Set of Interrogatories.
NaPro Biotherapeutics, Inc. and Abbott Laboratories v. Bristol-Myers Squibb Co., Civil Action No. 00-B-1818 (D. CO), Defendant's Answer to First Amended Complaint.
Information Disclosure Statement dated Nov. 26, 1996 filed in parent application USSN 08/594,478, now U.S. patent No. 5,733,888.
Opponent's Reponse to the Appeal dated Sep. 12, 2003 in the EPO, along with copies of references cited therein.
Second Affidavit of Prof. Siegfried Blechert; opinion concerning related Israeli patent in support of the opposition filed by Teva Pharmaceuticals Industries Ltd.
Carver David
Elliott Robyn
Ewald Hernita
Handreck Paul
Prout Timothy
Jones Dwayne C.
NaPro BioTherapeutics, Inc.
Saliwanchik Lloyd & Saliwanchik
LandOfFree
Injectable composition does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Injectable composition, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Injectable composition will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3270495