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  Method to enhance hematopoiesisUSPTO Application #: 20070190025Title: Method to enhance hematopoiesis Abstract: The present invention relates generally to the fields of immunology and molecular biology, and particularly to a method for treating hematopoietic disorders. The invention provides a method to treat a deficiency of one or more types of blood cells in a mammal, which includes administering an effective amount of TISF or of a compound that stimulates CD4+ cells like TISF does. In one embodiment, TISF that originates from a mammalian species is administered to a mammalian subject diagnosed as having a deficiency in one or more types of blood cells. (end of abstract)
Agent: Morrison & Foerster LLP - San Diego, CA, US Inventors: Terry Raymond Beardsley, Anthony E. Maida USPTO Applicaton #: 20070190025 - Class: 424085200 (USPTO) Related Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Lymphokine, Interleukin The Patent Description & Claims data below is from USPTO Patent Application 20070190025. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. patent application Ser. No. 10/938,451, now U.S. Pat. No. 7,196,060, which claims priority under 35 U.S.C. .sctn. 119(e) to U.S. Provisional Application Ser. No. 60/501,959, filed Sep. 10, 2003; the contents of these applications are incorporated herein by reference. BACKGROUND OF THE INVENTION [0002] Mammalian blood contains a wide variety of different types of cells, including red blood cells (erythrocytes), platelets, and white blood cells (leukocytes). White blood cells (leukocytes), in turn, include several different cell types, notably the lymphocytes, monocytes, and several types of granulocytes such as neutrophils, eosinophils, and basophils. These various types of cells comprise a major part of the complex and critical mammalian immune system. Most of them are short lived and must be replaced every few hours, days, weeks, or months, and all of them are formed by differentiation and proliferation of a single type of pluripotent stem cells which reside in the bone marrow. [0003] The process by which a single kind of stem cell differentiates to form many different mature cells which cannot themselves proliferate is called hematopoiesis. It involves the formation of precursors for each of these different kinds of cells from a single kind of stem cell, which occurs in bone marrow, and proliferation and differentiation into the specialized cell types, which occurs principally in the bone marrow, spleen, thymus, and lymph nodes. The process is controlled by a complex system of signals that attempts to maintain an appropriate balance among all of these different types of cells so that the immune system operates effectively. [0004] Some disease states and infections dramatically affect hematopoiesis, resulting in depletion of certain types of blood cells. For example, HIV infection often causes anemia (red blood cell deficiency), neutropenia (neutrophil deficiency), or thrombocytopenia (platelet deficiency), or various combinations of these states, including pancytopenia, which is a deficiency of all different types of blood cells. See N. K. Banda, et al., Depletion of CD34+CD4+ Cells in Bone Marrow from HIV-1 Infected Individuals, Biol. Blood and Marrow Transplantation, 5(3), 162-172 (1999). See also D. Fuchs, et al., AIDS, 5(2), 209-212 (1991). Similarly, various radiation and chemotherapy regimens may severely compromise the immune system by depleting one or more of these cell types. See C. L. Mackall, Stem Cells 18, 10-18 (2000). Radiation therapy, for example, can destroy most of the highly sensitive and surprisingly rare stem cells, resulting in an inability to rapidly regenerate cellular components of the blood. [0005] Regardless of whether it is caused by an organic disorder, infection, or therapeutic treatment, severe deficiency of any of these cellular components of the blood and the immune system can result in direct physical symptoms (such as anemia where red blood cells are depleted, or bleeding disorders where platelets are depleted) or in greatly increased susceptibility to secondary infections. Thus methods for treating deficiencies of various types of blood cells are needed, as are methods for preventing such deficiencies that would otherwise result from treatment of other disorders such as cancers or viral infections. The present invention provides methods for increasing levels of various types of blood cells in a subject experiencing a deficiency in the level of one or more types of blood cells. BRIEF SUMMARY OF THE INVENTION [0006] T-4 immune stimulating factor ("TISF") has been shown to provide immune-boosting activity, apparently due to its ability to stimulate IL-2 production over a period of several days at the site where it is needed. See U.S. Pat. No. 5,616,554. The molecule is described in the foregoing patent as a 50K Dalton protein with an isoelectric point of 6.5. In the present disclosure, the same molecular entity has now been demonstrated to contain the ability to promote hematopoiesis possibly by its known mechanism of action to stimulate CD4+ lymphocytes. It is hypothesized that CD4+ lymphocytes may regulate the production of all blood cell types in the bone marrow, including red blood cells, platelets, and granulocytes. A deficiency in CD-4 lymphocytes thus could lead to the pancytopenia observed in immune compromised subjects including cancer patients undergoing chemotherapy, or viral or other chemically induced conditions. [0007] In the prior patent, administering TISF was shown to increase the effectiveness of a distemper vaccine in canines, boost the titer of antibody to influenza virus in mice, and reduce the symptoms of feline immunodeficiency virus (FIV) in infected cats. Thus it exhibits an ability to enhance the effectiveness of a healthy immune system. It has now been shown that TISF also acts to stimulate the production of certain types of blood cells where a deficiency of such cells has developed. Thus TISF is now shown to accelerate the recovery of platelet counts following chemotherapy-induced platelet deficiency in a murine model system. [0008] It is well known that AIDS patients suffer profound CD4+ lymphocyte deficiency, but a less well appreciated observation is that many immune deficient subjects have concomitant anemia, granulocytopenia, and thrombocytopenia. In fact, an emerging paradigm in oncology is that cancer patients suffer a profound and chronic CD4+ lymphocyte deficiency. C. L. Mackall, Stem Cells 18, 10-18 (2000). [0009] In the present disclosure, the observation was made in studies of feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) infected cats that when lymphocytes were increased by TISF administration (the focus of the study and U.S. Pat. No. 5,616,554), red cells, platelets and granulocytes increased also. See FIGS. 1, 2, 3, and 4. Based upon these preliminary observations, a mouse model of chemotherapy-induced platelet deficiency was used to confirm the effect of TISF on platelet recovery. See T. R. Ulrich, et al., Blood, 86, 971-71 (1995). The data are illustrated in FIG. 5. [0010] The data indicated that administering TISF can accelerate the recovery of platelet counts following chemotherapy-induced deficiency. It is contemplated that doses ranging from 0.1 .mu./kg to 500 mg/kg would be effective. The route of administration could be parenterally, intraperitoneally, topically, or orally. A dose regimen of treatment may be once, twice or three times daily, weekly, semi-weekly, or monthly. Clinical application to the treatment of pancytopenias in cancer patients and other viral or chemically-induced immune deficiency conditions is suggested. Further confirmation of theses observations in additional animal models of hematological deficiencies is in progress. [0011] In one aspect, the present invention provides a method to increase the levels of specific types of blood cells in a patient exhibiting a deficiency in one or more types of blood cells. The method includes administering an effective amount of TISF, or a compound that stimulates CD4+ cells like TISF does, to a subject who has been diagnosed as having a deficiency of red blood cells, platelets, or white blood cells. [0012] In one embodiment, the present invention provides a method to stimulate the production of red blood cells (erythrocytes) in a subject diagnosed as having a deficiency of red blood cells; the method includes administering to the subject an amount of TISF (T-4 immune stimulating factor) that is sufficient to elevate the subject's red blood cell count. In one such embodiment, the subject has been diagnosed as suffering from anemia. [0013] In another embodiment, the present invention provides a method to stimulate the production of granulocytes in a subject diagnosed as having a level of granulocytes that is lower than desired; the method includes administering to the subject an amount of TISF (T-4 immune stimulating factor) that is sufficient to elevate the subject's granulocyte count. [0014] In yet another embodiment, the present invention provides a method to stimulate the production of platelets in a subject diagnosed as having a level of platelets that is lower than desired; the method includes administering to the subject an amount of TISF (T-4 immune stimulating factor) that is sufficient to elevate the subject's platelet count. [0015] In another aspect, the present invention provides a method to stimulate production of specific types of blood cells in a subject diagnosed as having a deficiency in levels of one or more types of blood cells. The method includes administering to the subject in need of treatment an effective amount of a compound that stimulates CD4+ cells like TISF does. [0016] In one embodiment, the present invention provides a method to stimulate the production of red blood cells (erythrocytes) in a subject diagnosed as having a deficiency of red blood cells. The method includes administering to the subject an amount of a compound that stimulates CD4+ cells that is sufficient to elevate the subject's red blood cell count. In one such embodiment, the subject has been diagnosed as suffering from anemia. In a preferred embodiment, the compound that stimulates CD4+ cells is selected from the group consisting of IL-1, IL-2, IL-3, IL-4, IL-6, IL-7, IL-12, .gamma.-interferon, TNF-.alpha., anti-CD3 antibody, CD28, and superantigens such as toxic shock syndrome toxin-1 (TSST-1), streptococcal pyrogenic exotoxin (SPE), and staphyloccal enterotoxins. [0017] In another embodiment, the present invention provides a method to stimulate the production of granulocytes in a subject diagnosed as having a level of granulocytes that is lower than desired; the method includes administering to the subject an amount of a compound that stimulates CD4+ cells that is sufficient to elevate the subject's granulocyte count. In a preferred embodiment, the compound that stimulates CD4+ cells is selected from the group consisting of IL-1, IL-2, IL-3, IL-4, IL-6, IL-7, IL-12, .gamma.-interferon, TNF-.alpha., anti-CD3 antibody, CD28, and superantigens such as toxic shock syndrome toxin-1 (TSST-1), streptococcal pyrogenic exotoxin (SPE), and staphyloccal enterotoxins. [0018] In yet another embodiment, the present invention provides a method to stimulate the production of platelets in a subject diagnosed as having a level of platelets that is lower than desired; the method includes administering to the subject an amount of a compound that stimulates CD4+ cells that is sufficient to elevate the subject's platelet count. In a preferred embodiment, the compound that stimulates CD4+ lymphocytes is selected from the group consisting of IL-1, IL-2, IL-3, IL-4, IL-6, IL-7, IL-12, .gamma.-interferon, TNF-.alpha., anti-CD3 antibody, CD28, and superantigens such as toxic shock syndrome toxin-1 (TSST-1), streptococcal pyrogenic exotoxin (SPE), and staphyloccal enterotoxins. [0019] In another aspect, the present invention provides a therapeutic protocol for treatment of a subject experiencing a deficiency in the level of one or more types of blood cells. The protocol includes diagnosing the subject as having a deficiency in the level of a specific type of blood cell, then treating the subject with TISF in an amount effective to increase the level of the type of blood cell in which the subject is deficient. [0020] In one embodiment, the present invention provides a therapeutic protocol that comprises diagnosing a subject as having a less than desirable level of red blood cells, followed by administering to said subject an amount of TISF effective to elevate red blood cell count in that subject. In this embodiment, the subject may be one suffering from anemia. [0021] In another embodiment, the present invention provides a therapeutic protocol that comprises diagnosing a subject as having a less than desirable level of granulocytes, followed by administering to said subject an amount of TISF effective to elevate granulocyte count in that subject. Continue reading... Full patent description for Method to enhance hematopoiesis Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Method to enhance hematopoiesis patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. 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