Pharmaceutical compositions and articles of manufacture useful in reversal of a clinical epiosode of an incurable disease and methods of use thereof

Abstract

A method of reversing a clinical episode of a disease which is generally considered incurable in a subject. The method includes providing an immune-globulin preparation containing a detectable titre of antibodies to the disease which is generally considered incurable and administering the immune-globulin preparation to the subject. Preferably, the immune globulin preparation is a pool of immune globulin fractions gathered from blood of donors living in an area where the disease is endemic. Further disclosed are pharmaceutical compositions and articles of manufacture suited for use in practice of the method.

Description

[0001] This application claims priority from U.S. Patent Application No. 60 / 377,953 filed on May 7, 2002 and currently pending.FIELD AND BACKGROUND OF THE INVENTION

[0002] The present invention relates to pharmaceutical compositions and articles of manufacture useful in reversal of a clinical episode of an incurable disease and to methods of use thereof. More particularly, the present invention relates to use of passive immunization with an immune-globulin preparation as a mode of treatment for an acute attack of a disease. The present invention has demonstrable clinical efficacy in treatment of West Nile Virus and is expected to demonstrate similar utility in a wide variety of maladies which are generally considered incurable or irreversible.

[0003] The use of antibodies in medicine is well known. Antibodies may be employed to provide active immunity or passive immunity.

[0004] Active immunity is achieved by vaccination with a material that triggers an immune response in the vaccinate...

Examples

example 1

Administration of an Immune-Globulin Preparation Reverses Advanced West Nile Virus Encephalitis

[0086] An apparent dramatic response to intravenous immuno-globulin in an immunosuppressed patient suffering from advanced West Nile Virus induced encephalitis was observed (Shimoni et al. (2001) Emerging Infectious Diseases 7 (4): 759) in a clinical setting. Briefly, a 70-year-old woman was admitted to the hospital because of fever and vomiting of 24 hours' duration. The subject had a 12-year history of chronic lymphatic leukemia (Rai stage II) but was not on treatment. A routine outpatient assessment 1 week earlier had shown no unexpected findings. On physical examination the subject appeared generally well, with temperature 39.0.degree. C., regular pulse 100 / minute, and blood pressure 130 / 70.

[0087] Apart from splenomegaly 2-3 cm below the costal margin, there were no abnormal physical signs, including lymphadenopathy. Chest X ray results were normal. Hb was 12 g / dL, HCt 32%, mean corpus...

example 2

Characterization of Immune-Globulin Preparation

[0091] In order to ascertain the reason for the dramatic response described in example 1, several batches of pooled immuno-globulin from different sources for were screened for antibodies to West Nile virus.

[0092] Intravenous immuno-globulin preparations from donors in Israel, such as the one employed in example 1, contained high titers (1:1600) of such antibodies.

[0093] Similar immuno-globulin preparations from the USA had no detectable antibody. The measurements of West Nile virus antibody were performed in the Central Virology Laboratory, Ministry of Health of Israel. These results indicate that the startling success reported in example 1 was a direct result of West Nile Virus antibodies in the administered material.

[0094] Therefore any immuno-globulin preparation which contains sufficient amounts of specific antibodies to a pathogen causing clinical symptoms in a subject should be capable of alleviating those symptoms.

example 3

Administration of an Immune-Globulin Preparation Reverses Advanced West Nile Virus Encephalitis

[0095] Following the surprising clinical outcome described in example 1, the inventors employed similar method in an additional case. The outcome was similar to that reported in example 1 (Hamdan et al. (2002) Transpl. Infect. Dis. 4(3):160-162.)

[0096] Briefly, a 42 year old male patient with confirmed West Nile Virus encephalitis and deteriorating level of consciousness was treated as described hereinabove in example 1 with the same immune globulin preparation described in example 2. The subject had previously undergone lung transplant surgery and was in an immuno-suppressed state in order to prevent transplant rejection.

[0097] Following treatment the patient improved rapidly of 24 hours and continued to improve so that no sign or symptom of encephalitis remained after 48 hours.

[0098] This result confirms that indicates that treatment with immune globulins can reverse clinical symptoms of...

[0001] This application claims priority from U.S. Patent Application No. 60 / 377,953 filed on May 7, 2002 and currently pending.FIELD AND BACKGROUND OF THE INVENTION

[0002] The present invention relates to pharmaceutical compositions and articles of manufacture useful in reversal of a clinical episode of an incurable disease and to methods of use thereof. More particularly, the present invention relates to use of passive immunization with an immune-globulin preparation as a mode of treatment for an acute attack of a disease. The present invention has demonstrable clinical efficacy in treatment of West Nile Virus and is expected to demonstrate similar utility in a wide variety of maladies which are generally considered incurable or irreversible.

[0003] The use of antibodies in medicine is well known. Antibodies may be employed to provide active immunity or passive immunity.

[0004] Active immunity is achieved by vaccination with a material that triggers an immune response in the vaccinate...

Examples

example 1

Administration of an Immune-Globulin Preparation Reverses Advanced West Nile Virus Encephalitis

[0086] An apparent dramatic response to intravenous immuno-globulin in an immunosuppressed patient suffering from advanced West Nile Virus induced encephalitis was observed (Shimoni et al. (2001) Emerging Infectious Diseases 7 (4): 759) in a clinical setting. Briefly, a 70-year-old woman was admitted to the hospital because of fever and vomiting of 24 hours' duration. The subject had a 12-year history of chronic lymphatic leukemia (Rai stage II) but was not on treatment. A routine outpatient assessment 1 week earlier had shown no unexpected findings. On physical examination the subject appeared generally well, with temperature 39.0.degree. C., regular pulse 100 / minute, and blood pressure 130 / 70.

[0087] Apart from splenomegaly 2-3 cm below the costal margin, there were no abnormal physical signs, including lymphadenopathy. Chest X ray results were normal. Hb was 12 g / dL, HCt 32%, mean corpus...

example 2

Characterization of Immune-Globulin Preparation

[0091] In order to ascertain the reason for the dramatic response described in example 1, several batches of pooled immuno-globulin from different sources for were screened for antibodies to West Nile virus.

[0092] Intravenous immuno-globulin preparations from donors in Israel, such as the one employed in example 1, contained high titers (1:1600) of such antibodies.

[0093] Similar immuno-globulin preparations from the USA had no detectable antibody. The measurements of West Nile virus antibody were performed in the Central Virology Laboratory, Ministry of Health of Israel. These results indicate that the startling success reported in example 1 was a direct result of West Nile Virus antibodies in the administered material.

[0094] Therefore any immuno-globulin preparation which contains sufficient amounts of specific antibodies to a pathogen causing clinical symptoms in a subject should be capable of alleviating those symptoms.

example 3

Administration of an Immune-Globulin Preparation Reverses Advanced West Nile Virus Encephalitis

[0095] Following the surprising clinical outcome described in example 1, the inventors employed similar method in an additional case. The outcome was similar to that reported in example 1 (Hamdan et al. (2002) Transpl. Infect. Dis. 4(3):160-162.)

[0096] Briefly, a 42 year old male patient with confirmed West Nile Virus encephalitis and deteriorating level of consciousness was treated as described hereinabove in example 1 with the same immune globulin preparation described in example 2. The subject had previously undergone lung transplant surgery and was in an immuno-suppressed state in order to prevent transplant rejection.

[0097] Following treatment the patient improved rapidly of 24 hours and continued to improve so that no sign or symptom of encephalitis remained after 48 hours.

[0098] This result confirms that indicates that treatment with immune globulins can reverse clinical symptoms of...

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