Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1999-02-08
2001-05-29
Low, Christopher S. F. (Department: 1653)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S017400, C530S328000, C530S329000, C530S316000, C435S325000, C435S375000
Reexamination Certificate
active
06239109
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to compounds, methods, compositions, and kits for the stimulation of erythropoiesis. More specifically, the present invention relates to methods, compositions, and kits that employ effective amounts of angiotensinogen, angiotensin I (AI), AI analogues, AI fragments and analogues thereof, angiotensin II analogues, AII fragments or analogues thereof or AII AT
2
type 2 receptor agonists for stimulating erythropoiesis.
BACKGROUND OF THE INVENTION
Maintenance of an adequate supply of oxygen to the body tissues is vital to survival. In the United States alone, several million people suffer from anemia secondary to renal failure, chronic inflammatory disease and malignancies (U.S. Pat. No. 4,987,121, hereby incorporated by reference in its entirety). Since to a large degree the oxygen-carrying capacity of blood is governed by the concentration of erythrocytes in the blood, the appropriate regulation of erythropoiesis is also crucial.
The early studies of Reissmann (Reissmann, K. R.,
Blood
5:372-80 (1950)) and Erslev (Erslev, A.,
Blood
8:349-57 (1953)) clearly demonstrated the hypoxia-induced stimulation of erythropoietin secretion. When erythropoietin is secreted from the erythropoietin-producing cells in response to hypoxia, it travels through the blood to its target organ, the hematopoietic tissues. In humans, the principal hematopoietic tissue is within the liver before birth, and in the bone marrow after birth. (Id.) There, erythropoietin binds specifically to its receptor on the erythroid progenitor cells called burst forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) and stimulates these cells to proliferate and differentiate (Spivak, J. L.,
Int. J. Cell Cloning
4:139-66 (1986)). BFU-E are the earliest erythroid progenitors and constitute 0.01%, approximately, of the nucleated bone marrow cells. CFU-E are derived from BFU-E, account for about 0.1% of marrow cells, and are much more responsive to erythropoietin than are BFU-E (Spivak, J. L., supra); Sawada, K., et al.,
J. Clin. Invest.
80:357-66 (1987)).
The low erythropoietin levels always present appear sufficient for a basal erythropoiesis rate. Relatively small losses of blood do not appear to stimulate increased erythropoietin production (Kickler, T. S., et al.,
J. Am. Med. Assoc.
260:65-7 (1988)). It is only after a major blood loss that there is an increased production of erythropoietin and rate of erythropoiesis.
It has been well-established that the majority of patients with renal insufficiency and anemia have serum erythropoietin levels well below what would be expected for the degree of anemia (Caro, J., et al.,
J. Lab. Clin. Med.
93:449-58 (1979); Radtke, H. W., et al., Blood 54:877-84 (1979); Chandra, M., et al.,
J. Pediatr.
113:1015-21 (1988)), although they can still respond to hypoxia with an increase in serum erythropoietin levels (Radtke, H. W., et al.,
Blood
54:877-84 (1979); Chandra, M., et al.,
J Pediatr
113:1015-21 (1988)). However, this markedly blunted erytbropoietin response substantially contributes to the pathogenesis of the anemia (Eschbach, J. W., et al.,
Am J Kid Dis
11:203-9 (1988)). As a result, patients suffering from chronic renal failure and end-stage renal disease, or those undergoing renal transplantation, develop severe anemia and require regular blood transfusions (Royet, U.S. Pat. No. 5,482,924).
The use of recombinant human erythropoietin facilitated treatment of these patients. However, recombinant erythropoietin treatment is extremely costly, and methods that augment the effect of erythropoiesis will permit the use of smaller doses of erythropoietin, and thus will decrease treatment costs. Additionally, increasing the rate of erythropoiesis would significantly improve clinical benefits for the treatment of congenital or acquired aplastic or hypoplastic anemia associated with chronic renal failure, end-stage renal disease, renal transplantation, cancer, AIDS, chemotherapy, radiotherapy, bone marrow transplantation and chronic diseases.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides compounds and methods for the augmentation of erythropoiesis by potentiating erythropoietin-induced differentiation with angiotensinogen, angiotensin I (AI), AI analogues, AI fragments and analogues thereof, angiotensin II analogues, AII fragments or analogues thereof or AII AT
2
type 2 receptor agonists as a therapeutic adjunct.
In another aspect, the present invention provides pharmaceutical compositions comprising angiotensinogen, angiotensin I (AI), AI analogues, AI fragments and analogues thereof, angiotensin II analogues, AII fragments or analogues thereof or AII AT
2
type 2 receptor agonists together with erythropoietin and a pharmaceutically acceptable carrier.
In a further aspect, the present invention provides kits for promoting erythropoiesis, wherein the kits comprise an effective amount of angiotensinogen, AI, AI analogues, AI fragments and analogues thereof, AI analogues, AI fragments or analogues thereof or AII AT
2
type 2 receptor agonists, and instructions for using the amount effective of active agent as a therapeutic adjunct to erythropoietin treatment.
In another aspect, the invention provides improved cell culture medium for promoting erythropoiesis, comprising adding an effective amount of the active agents of the invention to promote erythropoiesis.
The methods and kits of the present invention are clinically useful as a therapeutic adjunct for increasing red blood cell production in treating congenital or acquired aplastic or hypoplastic anemia.
REFERENCES:
patent: 4987121 (1991-01-01), Baertschi et al.
patent: 5015629 (1991-05-01), diZerega et al.
patent: 5032507 (1991-07-01), Yu et al.
patent: 5104653 (1992-04-01), Michalevicz et al.
patent: 5188828 (1993-02-01), Goldberg et al.
patent: 5482924 (1996-01-01), Royet et al.
patent: 5541158 (1996-07-01), Vance et al.
patent: 5629292 (1997-05-01), Rodgers et al.
patent: 5693616 (1997-12-01), Krstenansky et al.
patent: 5716935 (1998-02-01), Rodgers et al.
patent: 5834432 (1998-11-01), Rodgers et al.
patent: 5955430 (1999-09-01), Rodgers et al.
patent: WO 95/08565 (1995-03-01), None
patent: WO 95/08337 (1995-03-01), None
patent: WO 96/39164 (1996-12-01), None
patent: WO 98 32457 (1998-07-01), None
patent: WO 99 26644 (1999-06-01), None
patent: WO 99 31125 (1999-06-01), None
Mrug et al., Blood vol. 88:646a (1996); Angiotensin II facilitates erythropoietin-mediated proliferation of early erythroid progenitors.
Neelam Jaiswal, et al., (1991),Hypertension,“Subtype 2 Angiotensin Receptors Mediate Prostaglandin Synthesis in Human Astrocytes”, 17:pp. 1115-1120.
Ilkka Pörsti, et al., (1994),Br. J. Pharmacol,“Release of Nitric Oxide by Angiotensin-(1-7) from Porcine Coronary Endothelium: Implications for a Novel Angiotensin Receptor”, 111: pp. 652-654.
Regoli, et al., (1974),Pharmacological Reviews,“Pharmacology of Angiotensini”, 26(2:) pp. 69-123.
Rowe et al. ‘Angiotensin-(1-7) Binding at Angiotensin II Receptors in the Rat Brain’ Regulatory Peptides. vol. 56, pp. 139-146, 1995.*
Mrug et al. ‘Angiotenisn II Stimulates Proliveration of Normal Early Eythroid Progenitors’, J. Clin. Invest. vol. 100, No. 9, pp. 2310-2314, Nov. 1997.*
Plucinska et al. ‘Multiple Binding Modes for the Reeptor-Bound Conformations of Cyclik All Agonists’, J. med. Chem. vol. 36, pp. 1902-1913, 1993.*
Kurt R. Reissmann, M.D., (1950),Blood,“Studies on the Mechanizm of Erythropoietic Stimulation in Parabiotic Rats During Hypoxia”, 8: pp. 349-357.
Allan Erslev, M.D., (1953),Blood,“Humoral Regulation of Red Cell Production”, pp. 349-357.
Jerry L. Spivak, (1986),Int. J. Cell Cloning,“The Mechanism of Action of Erythropoietin”, 4: pp. 139-166.
K. Sawada, et al., (1987),The Journal of Clinical Investigation, Inc.,“Purification of Human Erythroid Colony-forming Units and Demonstration of Specific Binding of Erythropoietin”, 80: pp 357-366.
T.S. Kickler, et al., (1988),J. Am. Med. Assoc.,“Effect of Repeated Whole Blood Donations on Serum Immunoreactive Erythropo
DiZerega Gere
Rodgers Kathleen E.
Gupta Anish
Harper David S.
Low Christopher S. F.
McDonnell & Boehnen Hulbert & Berghoff
University of Southern California
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