Appeal No. 2001-2497 Page 3
Application No. 08/855,744
however, have proven more effective in treating leukemia or lymphoma than solid
tumors. See id., page 2. “One plausible explanation for this difference in efficacy
is that malignant cells in blood or lymphoid tissues are more accessible than
those in solid tumors. . . . In addition, even where the toxin is in contact with the
target cells, only a very small fraction will actually enter the cell and thus, not all
cells in a solid tumor will be killed.” Id. This problem cannot be solved by
increasing the dosage of immunotoxin, because the immunotoxin is also taken
up by reticuloendothelial cells and phagocytic cells of the liver, and therefore “the
total amount of toxin which can be administered is sever[e]ly limited.” Id.
The specification discloses a method for increasing the amount of
therapeutic agent delivered to a target site such as a tumor, without causing
systemic toxicity. “The invention includes using bifunctional two-domain binding
molecules to recruit a therapeutic agent to a solid tissue target site, where the
binding molecules have one specificity for the target site and the other specificity
for the therapeutic agent.” Specification, page 6. The binding molecules and
therapeutic agent are administered in separate steps. The binding molecules are
administered first and allowed to bind to the target site. Cite specification. A
remover substance (e.g., a liposome conjugated to antibodies against the binding
molecules) is then administered to facilitate clearing of the binding molecules
from the circulation. See id., page 6. After the last administration of remover has
had time to clear from circulation, the therapeutic agent is administered and
bound by the binding molecules bound to the target site. Thus, the toxic effects
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