Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2000-02-22
2002-01-29
Krass, Frederick (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S012200, C514S903000, C424S078370
Reexamination Certificate
active
06342476
ABSTRACT:
BACKGROUND OF THE INVENTION
Copolymer-1 is a synthetic polypeptide analog of myelin basic protein (MBP), which is a natural component of the myelin sheath. It has been suggested as a potential therapeutic agent for multiple sclerosis (Eur. J. Immunol. [1971] 1:242; and J. Neurol. Sci. [1977] 31:433). All references cited herein are hereby incorporated by reference in their entirety. Interest in copolymer-1 as an immunotherapy for multiple sclerosis stems from observations first made in the 1950's that myelin components such as MBP prevent or arrest experimental autoinimune encephalomyelitis (EAE). EAE is a disease resembling multiple sclerosis that can be induced in susceptible animals.
Copolymer-1 was developed by Drs. Sela, Arnon, and their co-workers at the Weizmann Institute (Rehovot, Israel). It was shown to suppress EAE (Eur. J. Immunol. [1971] 1:242; U.S. Pat. No. 3,849,550). More recently, copolymer-1 was shown to be beneficial for patients with the exacerbating-remitting form of multiple sclerosis (N. Engl. J. Med. [1987] 317:408). Patients treated with daily injections of copolymer-1 had fewer exacerbations and smaller increases in their disability status than the control patients.
Copolymer-1 is a mixture of polypeptides composed of alanine, glutamic acid, lysine, and tyrosine in a molar ratio of approximately 6:2:5:1, respectively. It is synthesized by chemically polymerizing the four amino acids forming products with average molecular weights of 23,000 daltons (U.S. Pat. No. 3,849,550).
It is an object of the present invention to provide an improved composition of copolymer-1.
SUMMARY OF THE INVENTION
The present invention relates to a composition of copolymer-1 substantially free of species of copolymer-1 having a molecular weight of over 40 kilodaltons (KDa).
The invention further relates to a copolymer-1 having over 75% of its molar fraction within the molecular weight range from about 2 KDa to about 20 KDa.
In addition, the invention relates to a copolymer-1 having an average molecular weight of about 4 to about 8.6 KDa.
Moreover, the invention relates to a pharmaceutical composition and a method for the treatment of multiple sclerosis, using the above-discussed copolymer-1.
REFERENCES:
patent: 3849550 (1974-11-01), Teitlebaum et al.
patent: 4594409 (1986-06-01), Hayashii et al.
patent: 39 30733 (1991-03-01), None
patent: 03 78246 (1990-07-01), None
patent: 0 383 620 (1990-08-01), None
patent: 9 83020 (1990-08-01), None
patent: 1882051 (1985-09-01), None
patent: 1664845 (1991-07-01), None
D. Teitelbaum et al., “Dose-Response Studies on Experimental Allergic Encephalomyelitis Suppression by COP 1,”Israel Journal of Medical Sciences, vol. 10, No. 9, Sep. 1974, pp. 1172-1173.
D. Teitelbaum et al., “Suppression of Experimental Allergic Encephalomyelitis by a Synthetic Polypeptide”,Eur. J. Immunol., 1971, 1, 242-248.
D. Teitelbaum et al., “Protection Against Experimental Allergic Encephalomyelitis”,Nature, 1972, 240, pp. 564-566.
C. Webb et al., “Further Studies on the Suppression of Experimental Allergic Encephalomyelitis by Synthetic Copolymer”,Israel J. Med. Sci., 1972, 8, pp. 656-657.
R. Arnon et al., “Suppression of Experimental Allergic Encephalomyelitis by a Synthetic Copolymer Immunological Cross Reactive with Basic Encephalitogen”,Israel J. Med. Sci., 1972 8, pp. 1759-1760.
D. Teitalbaum et al., “Suppression of Experimental Allergic Encephalomyelitis with Basic Polymers”,Eur. J. Immunol., 1973, 3, pp. 273-279.
C. Webb et al., “In vivo and in Vitro Immunological cross-reactions between Basic Encephalitogen and Synthetic Basic Polypeptides Capable of Suppressing Experimental Allergic Encephalomyelitis”,Eur. J. Immunol, 3, pp. 279-286 (1973).
D. Teitelbaum et al., “Suppression of Experimental Allergic Encephalomyelitis in Rhesus Monkeys by a Synthetic Basic Copolymer”,Clin. Immunol. Immunopath, 1974, 3, pp. 256-262.
D. Teitelbaum et al., “Dose-response Studies on Experimental Allergic Encephalomyelitis Suppression by COP-1”,Israel J. Med. Sci., 1974, 10, pp. 1172-1173.
C. Webb et al., “Suppression of Experimental Allergic Encephalomyelitis in Rhesus Monkeys by a Synthetic Basic Copolymer”,Isr. J. Med. Sci., 1975, 11, p. 1388 (abstract).
C. Webb et al., “Molecular Requirements Involved in Suppression of EAE by Synthetic Basic Copolymers of Amino Acids”,Immunochemistry, 1976, 13, pp. 333-337.
O. Abramsky et al., “Effect of a Synthetic Polypeptide (COP-1) on Patients with Multiple Sclerosis and with Acute Disseminated Encephalomyelitis”,J. Neurol. Sci., 1977, 31, pp. 433-438.
D. Teitelbaum et al., “Suppression of Experimental Allergic Encephalomyelitis in Baboons by COP-1.”Israel J. Med. Sci., 1977, 13, 1038 (abstract).
M. Sela et al., “Experimental Allergic Encephalomyelitis in Menarini Series on Immunopathology, vol. 1, First Symposium of Organ Specific Autoimmunity”, Cremona, Italy, Jun. 1977, Miescher P.A. eds., pp. 9-21, Schwabe Co., Basel, (1978).
R. Arnon et al., “Suppression of EAE in Baboons by a Synthetic Polymer of Amino Acids”,Neurology, 1978, 28, 336 (abstract).
E.C.Alvord et al., “Myelin Basic Protein Treatment of Experimental Allergic Encephalomyelitis in Monkeys”,Ann. Neurol, 1979, 6, pp. 469-473.
A.B. Keith et al., “The Effect of COP-1, a Synthetic Polypeptide, on Chronic Relapsing Experimental Allergic Encephalomyelitis in Guinea Pigs”,J. Neurol. Sci., 1979, 42, pp. 267-274.
Z. Lando et al., “Effect of Cyclophosphamide on Suppressor Cell Activity in Mice Unresponsive to EAE”,J. Immunol., 1979, 123, pp. 2156-2160 (abstract).
Z. Lando et al., “Experimental Allergic Encephalomyelitis in Mice-Suppression and Prevention with COP-1”,Israel J. Med. Sci., 1979, 15, pp. 868-869 (abstract).
D. Teitelbaum et al., “Blocking of Sensitization to Encephalitogenic Basic Protein in Vitro by Synthetic Basic Copolymer (COP-1).” inCell biology and Immunology of Leukocyte Function, Academic Press, New York, 1979, pp. 681-685.
D. Teitelbaum, “Suppression of Experimental Allergic Encephalomyelitis with a Synthetic Copolymer-relevance to Multiple Sclerosis”, inHumoral Immunity in Neurological Diseases, Karcher D., Lowenthal A. & Strosberg A.D. eds. Plenum Publishing Corp., 1979, pp. 609-613.
R. Arnon et al., “Desensitization of Experimental Allergic Encephalomyelitis with Synthetic Peptide Analogues” inThe Suppression of Experimental Allergic Encephalomyelitis and Multiple Sclerosis, Academic Press, New York, 1980 pp. 105-107.
R. Arnon, “A Synthetic Copolymer of Amino Acids in a Clinical Trail for MS Therapy” in Progress inMultiple Sclerosis Research, Bauer, Ritter, eds. Springer Verlag N.Y., 1980 pp. 416-418.
M. B. Bornstein et al., “Treatment of Multiple Sclerosis with a Synthetic Polypeptide: Preliminary results.”,Trans. Am. Neurol. Assoc., 1980, 105, pp. 348-350.
M. B. Bornstein et al., “Treatment of Multiple Sclerosis with a Synthetic Polypeptide: preliminary results”,Ann. Neuro., 1980, 8, pp. 117 (abstract).
J. R. McDermott et al., “Antigen-induced Suppression of Experimental Allergic Neuritis in the Guinea Pig.”,J. Neurol. Sci., 1980, 46, pp. 137-143.
R. Arnon, “Experimental Allergic Encephalomyelitis-Susceptibility and Suppression”,Immunological Rev., 1981, 55, pp. 5-30.
M. B. Bornstein et al., “Multiple Sclerosis: Trial of a Synthetic Polypeptide”,Ann. Neurol, 1982, 11, pp. 317-319.
C. G. Brosnan et al., “The Response of Normal Human Lymphocytes to Copolymer-1.”J. Neuropath. Exp. Neurol., 1983, 42, pp. 356 (abstract).
R. P. Lisak et al., “Effect of Treatment with Copolymer 1 (COP-1) on the in Vivo and in Vitro Manifestations of Experimental Allergic Encephalomyelitis (EAE)”,J. Neurol. Sci., 1983, 62, 281-293.
M. B. Bornstein et al., “Clinical Trials of Copolymer 1 in Multiple Sclerosis”,Ann. N.Y. Acad. Sci.(USA), 1984, pp. 366-372.
M. B. Bornstein et al., “Clinical Trials of a Synthetic Polypeptide (Copolymer 1) for the Treatment of Multiple Sclerosis” in R.E. Gonsett et al., eds.Immunological and clinical aspects of multiple sclerosis, 1984, pp. 144-150.
C. F. Brosnan et al., “Copolymer 1: Effect on Normal Huma
Arnon Ruth
Konfino Eliezer
Sela Michael
Teitelbaum Dvora
Kenyon & Kenyon
Krass Frederick
Yeda Research & Development Company Limited
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