USES OF IL-12 IN HEMATOPOIESIS

• US 20110206635A1
• Filed: 03/30/2011
• Published: 08/25/2011
• Est. Priority Date: 07/03/2003
• Status: Active Grant

• Current Assignee: University of Southern California
• Original Assignee: University of Southern California
• Inventors: CHEN, Tingchao, Zhao, Yi, Anderson, W. French
• Granted Patent: US 8,920,790 B2
• Time in Patent Office: Days
• US Class Current: 424/85.2
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 38/208 IL-12
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61N 2005/1098 Enhancing the effect of the particle by an injected agent or implanted device
• CPC Class Codes: A61N 5/10 X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy A61N5/01 takes precedence
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07K 14/53 Colony-stimulating factor [CSF]
• CPC Class Codes: C07K 14/5434 IL-12

Abstract

Methods for enhancing or stimulating hematopoiesis including the step of administering Interleukin-12 (IL-12) to yield hernatopoietic recovery in a mammal in need. Preferred methods include the step of administering IL-12 as an adjuvant therapy to alleviate the hematopoietic toxicities associated with one or more treatment regimens used to combat a disease state. Other methods include administering IL-12 to ameliorate various hematopoietic deficiencies. Still other methods are directed to uses of IL-12 for in-vivo proliferation of hematopoietic repopulating cells, hematopoietic progenitor cells and hematopoietic stem cells. Other disclosed methods are directed to uses of IL-12 for bone marrow preservation or recovery.

Claims

1-118. -118. (canceled)

119. A method for protecting or restoring hematopoiesis or enhancing peripheral blood cell counts in a mammal having a hematopoietic cell disorder, a virus infection, or a combination thereof, wherein the method comprises:

(a) administering a treatment to the mammal, wherein the treatment targets the hematopoietic cell disorder, a virus infection, or a combination thereof and has an associated hematopoietic toxicity; and

(b) administering one or more therapeutically effective dose(s) of IL-12 near the time of administration of the treatment, wherein the administration of IL-12 to the mammal reduces the hematopoietic toxicity of the treatment.

120. The method of claim 119, wherein the mammal is a human.

121. The method of claim 119, wherein the treatment comprises:

(a) chemotherapy;

(b) radiation therapy;

or

(c) a combination of chemotherapy and radiation therapy.

122. The method of claim 120, wherein the dose of IL-12 is selected from the group consisting of less than about 2000 ng/kg, less than about 500 ng/kg, less than about 100 ng/kg, and less than about 10 ng/kg.

123. The method of claim 119, wherein:

(a) the treatment comprises one or more high dose treatment modalities;

(b) the treatment is administered in a dose dense treatment regimen;

or

(c) a combination thereof.

124. The method of claim 119, wherein;

(a) the administration of IL-12 results in protection of bone marrow cells from the associated hematopoietic toxicity of the treatment;

(b) the administration of IL-12 results in chemoprotection of bone marrow cells;

or

(c) any combination thereof.

125. The method of claim 124, wherein the bone marrow cells comprise hematopoietic repopulating cells, hematopoietic stem cells, hematopoeitic progenitor cells, or any combination thereof.

126. The method of claim 119, wherein the hematopoietic cell disorder comprises one or more hematopoietic cell tumors, and the method results in an increased remission of the one or more hematopoietic cell tumors, as compared with the treatment intended to target the hematopoietic cell disorder alone.

127. The method of claim 119, wherein the method results in a decrease in the virus infection or its associated symptoms.

128. The method of claim 127, wherein:

(a) the white blood cell count of the mammal is increased;

(b) the T-cell count of the mammal is increased;

or

(c) any combination thereof.

129. The method of claim 121, wherein the treatment leads to a deficiency in one or more hematopoietic cell types or lineages and the administration of IL-12 ameloriates the deficiency.

130. The method of claim 121, wherein the treatment comprises chemotherapy and the chemotherapy treatment comprises administration of more than one chemotherapy.

131. The method of claim 121, wherein:

(a) L-12 is administered before the chemotherapy;

(b) IL-12 is administered after the chemotherapy;

(c) IL-12 is administered before or after the chemotherapy;

(d) IL-12 is administered before and after chemotherapy.

(e) IL-12 is administered before the radiation therapy;

(f) IL-12 is administered after the radiation therapy;

(g) IL-12 is administered before or after the radiation therapy;

(h) IL-12 is administered before and after the radiation therapy;

or

(i) any combination thereof.

132. The method of claim 121, wherein the treatment comprises radiation and the IL-12 administration results in radioprotection of bone marrow cells.

133. The method of claim 121, wherein the treatment comprises radiation therapy and the radiation therapy comprises a near-lethal dose of radiation.

134. The method of claim 121, wherein the treatment comprises radiation therapy and the radiation therapy comprises a sub-lethal dose of radiation.

135. The method of claim 119, wherein one or more therapeutically effective dose(s) of IL-12 is administered at various time intervals before, before and after, or after the administration of the treatment.

136. A method for protecting or restoring hematopoiesis or enhancing peripheral blood cell counts in a mammal having a solid tumor, wherein the method comprises:

(a) administering a treatment to the mammal, wherein the treatment targets the solid tumor and has an associated hematopoietic toxicity, and wherein the treatment is selected from the group consisting of radiation therapy or a combination of chemotherapy and radiation therapy; and

(b) administering one or more therapeutically effective dose(s) of IL-12 near the time of administration of the treatment, wherein the administration of IL-12 to the mammal reduces the hematopoietic toxicity of the treatment.

137. The method of claim 136, wherein the method results in an increased remission of the one or more solid tumors, as compared with the treatment intended to target the disease state alone.

138. The method of claim 136, wherein the mammal is a human.

139. The method of claim 136, wherein the dose of IL-12 is selected from the group consisting of less than about 2000 ng/kg, less than about 500 ng/kg, less than about 100 ng/kg, and less than about 10 ng/kg.

140. The method of claim 136, wherein:

(a) the treatment comprises one or more high dose treatment modalities;

(b) the treatment is administered in a dose dense treatment regimen;

or

(c) a combination thereof.

141. The method of claim 136, wherein;

(a) the administration of IL-12 results in protection bone marrow cells from the associated hematopoietic toxicity of the treatment;

(b) the administration of IL-12 results in chemoprotection of bone marrow cells;

or

(c) any combination thereof.

142. The method of claim 141, wherein the bone marrow cells comprise hematopoietic repopulating cells, hematopoietic stem cells, hematopoeitic progenitor cells, or any combination thereof.

143. The method of claim 136, wherein the treatment leads to a deficiency in one or more hematopoietic cell types or lineages and the administration of IL-12 ameloriates the deficiency.

144. The method of claim 136, wherein the treatment comprises chemotherapy and the chemotherapy treatment comprises administration of more than one chemotherapy.

145. The method of claim 136, wherein:

(a) IL-12 is administered before the chemotherapy;

(b) IL-12 is administered after the chemotherapy;

(c) IL-12 is administered before or after the chemotherapy;

(d) IL-12 is administered before and after chemotherapy.

(e) IL-12 is administered before the radiation therapy;

(f) IL-12 is administered after the radiation therapy;

(g) IL-12 is administered before or after the radiation therapy;

(h) IL-12 is administered before and after the radiation therapy;

or

(i) any combination thereof.

146. The method of claim 136, wherein the treatment comprises radiation and the IL-12 administration results in radioprotection of bone marrow cells.

147. The method of claim 136, wherein the treatment comprises radiation therapy and the radiation therapy comprises a near-lethal dose of radiation.

148. The method of claim 136, wherein the treatment comprises radiation therapy and the radiation therapy comprises a sub-lethal dose of radiation.

149. The method of claim 136, wherein one or more therapeutically effective dose(s) of IL-12 is administered at various time intervals before, before and after, or after the administration of the treatment.