Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
1999-06-17
2001-08-14
Azpuru, Carlos A. (Department: 2165)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
C530S350000
Reexamination Certificate
active
06274158
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to a new use for recombinant human Erythropoietin. It further relates to hemostatic agents (agents that promote the mechanisms for stopping bleeding) in patients with normal hemostasis as well as in patients with abnormal hemostasis. The invention further relates to methods for controlling or preventing bleeding from any organ or part of the body.
BACKGROUND OF THE INVENTION
Recombinant human Erythropoietin (also known as Procrit or Epoetin or Epogen) is a glycoprotein hormone, thought to be produced primarily in the kidneys and to a lesser extent in the liver. It is a stimulating factor for erythropoiesis, the process by which erythrocytes (red blood cells) are formed. Human recombinant human Erythropoietin has been produced by recombinant technology, and is known as Epoetin.
Recombinant human Erythropoietin is primarily used to induce production of red blood cells to combat anemia. It is used in the treatment of anemia of chronic renal failure, anemia of cancer and in HIV positive patients. The prior art is not aware of the use of Recombinant human Erythropoietin to control bleeding or to prevent rebleeding.
Recombinant human Erythropoietin has been used successfully in the treatment of advanced gastrointestinal cancer to increase the Hemoglobin/Hematocrit (Hgb/Hcrt) count by stimulation of red blood cell production. Its effect on stopping or preventing gastrointestinal bleeding has not been recognized. (“Recombinant human Erythropoietin Beta in the Treatment of Anemia in Patients with Advanced Gastrointestinal Cancer” J. Clin. Oncology 16, No. 2, February 1998 p. 434-40).
In uremic patients, it is known that Recombinant human Erythropoietin corrects the prolonged bleeding time after one week of treatment and increases the Hemoglobin/Hematocrit after two weeks of treatment. But this information has not been previously considered as related to the problem of stopping or preventing the bleeding in an actual uremic or non-uremic patient. An enhanced platelet aggregation in response to Ristocetin was noted in Recombinant human Erythropoietin treated patients, which correlated with the rise in platelet Serotonin. These facts explain the improved platelet subendothelial cell interaction and the shortening of the bleeding time, found in Recombinant human Erythropoietin treated uremic patients. Recombinant human Erythropoietin also boosts the coagulation mechanism. This is achieved by decreasing the protein C and S and anti-thrombin III (which are natural anticoagulants), in uremic patients treated with Recombinant human Erythropoietin. But this observation has never been translated into using Recombinant human Erythropoietin in a bleeding patient with normal or abnormal coagulation mechanism in order to limit the bleeding.
BRIEF DESCRIPTION OF THE INVENTION
This invention is a further improvement on my earlier patent application, 09/018,815, filed Feb. 3, 1998, for “Treatment of Chronic Diffuse Gi Bleeding with Erythropoietin.” That invention was based upon research primarily with patients who had diffuse gastrointestinal bleeding. The present invention is an expansion of that investigation which has unexpectedly resulted in a method for the treatment of many different bleeding disorders.
Recombinant human Erythropoietin is administered to stop or prevent the bleeding from any part of the body involved with benign or malignant lesions, surgical, traumatic or difficult to heal lesions, in patients being naturally or therapeutically anti-coagulated, patients with bleeding disorders related to their coagulation mechanism, blood vessels or platelets, or patients on antiplatelet drugs. This effect is dependent on the dose and the frequency of administration of Recombinant human Erythropoietin. It occurs regardless of the HIV status of the patients. This “hemostatic effect” is due to the fact that Recombinant human Erythropoietin can boost the mechanisms involved in hemostasis. Patients with recurrent bleeding which failed several local surgical and non-surgical attempts to stop the bleeding, who need transfusions of blood products and repeated hospitalizations have a major decline in the quality of their life. It is in these difficult or impossible to treat bleeding conditions, that Recombinant human Erythropoietin administered preferably by subcutaneous route, stops and prevents rebleeding in just a few days, making surgery, transfusions of blood products or hospitalizations unnecessary. There is a major improvement in the quality of life of these patients, with substantial savings in healthcare cost.
The population to whom this invention is addressed are patients with bleeding from benign or malignant lesions anywhere in the body or from any organ. Bleeding traumatic, surgical or difficult to treat wounds are suitable to be treated. Control or prevention of bleeding can be achieved in patients who have a normal or abnormal hemostatic mechanism. Examples of patients with an abnormal hemostatic mechanism are as follows: patients with abnormal coagulation parameters due to therapeutic anticoagulation, or due to congenital or acquired coagulation abnormality; patients with a prolonged bleeding time due to low platelet count, a functional platelet abnormality or due to antiplatelet drugs; patients with a blood vessel abnormality; or patients with a combination of the above mentioned disorders.
The present invention comprises the administration of Recombinant human Erythropoietin preferably subcutaneously, but also intravenously or orally, depending on the case. The invention results in the prevention or disappearance of clinical evidence of bleeding with an increase or stabilization of the Hemoglobin/Hematocrit (Hgb/Hcrt) and no further need for transfusion of blood products or hemostatic surgical or nonsurgical procedures. Recombinant human Erythropoietin can be used in the bleeding patient as a hemostatic agent. The rapidity and the degree of control of the bleeding process, depends on the dose and the frequency of administration of Recombinant human Erythropoietin.
The process of the invention comprises: 1). During the “initial treatment” the patients are administered daily high doses of Recombinant human Erythropoietin for about 1-2 weeks. If the bleeding is under control they are treated on a 2) “maintenance treatment” during which they are treated at much lower doses ,2-3 times per week. Thereafter if the bleeding continues to be completely controlled, they are switched to a 3) “long-term maintenance treatment”. This phase of the treatment consists of very low doses of Recombinant human Erythropoietin administered weekly, biweekly, or once a month, for several months. 4) If no bleeding occurs during this time, the patient is monitored closely for months or years; no Recombinant human Erythropoietin is administered during this “long term follow up” period.
In the 10 examples presented below, Recombinant human Erythropoietin (1) stopped the bleeding in all 10 patients treated (2) no further transfusions of blood products were needed, thereby avoiding the complications of repeated transfusions, (3) the treatment can be done on an outpatient basis (4) without the need for repeated surgical
onsurgical hemostatic procedures (5) Recombinant human Erythropoietin can be used to control or prevent bleeding in patients with a bleeding tendency (abnormal hemostatic mechanism), an effect which depends on the dose and frequency of administration (6) the patient's quality of life undergoes a major improvement, (7) no side effects were noted (8) there was a major saving for the patient as well as for the healthcare industry (9)Recombinant human Erythropoietin can be used to prevent excessive blood loss in invasive procedures where the risk of excessive bleeding is high, due to the patient's hemostatic parameters, the nature of surgery or the local anatomy.
DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT
The invention is appropriate for the treatment or prevention of severe bleeding, sometimes recurrent, failing every attempt at local hemostasi
Azpuru Carlos A.
Gottlieb Rackman & Reisman P.C.
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