Interference No. 104,544 Paper149
McDonald v. Miyazaki Page 22
Driscoll v. Cebalo, 731 F.2d 878, 884, 221 USPQ 745, 750 (Fed. Cir. 1984) (application
in interference).
[631 The McDonald 666 patent has at least one claim, e.g., claim 1, directed to the use of a
C-terminal fragment of the disclosed TPO polypeptide [1048 at 23:24-31]:
1. A method of increasing platelet cell counts in a patient in need
thereof which comprises administering to the patient a therapeutic
composition comprising a therapeutic amount of a C-terminal fragment of
thrombopoietin and a pharmaceutically acceptable carrier, said
therapeutic amount being sufficient to increase platelet cell counts in said
patient by at least about 20% above a baseline count within about 2 to 4
days after C-terminal fragment administration.
[64] McDonald's 666 patent defines what is meant by N-terminal and C-terminal in terms of
a sequence for TPO attributed to de Sauvage, such that the N-terminal of the disclosed
TPO runs from residue 1 to residue 153, while the C-terminal runs from residue 154 to
residue 332 [1048 at 3:4-31]:
With respect to the structure of the human TPO molecule, TPO consists
of 332 amino acid residues with a leader sequence of 21 amino acid
residues. At residues 153 and 154, there is an Arg-Arg sequence, which is
a degradation point. It has been reported that the first half of this molecule
up to residue 153, which is the N-terminal region of the TPO molecule,
has the same TPO activity as the whole molecule. This is based on the
results that both the full-length and N-terminal fragment of TPO stimulated
BaFjmpI cell in vitro. In this assay, supernatants from HEK 293 cells
transfected with the sequence for the N-terminal domain had activity
similar to that of supernatants from HEK 293 cells expressing the
full-length TPO. See de Sauvage et al, Nature, 369:533-538 (1994).
The N-terminal fragment has been characterized as the erythropoietin-like
(EPO-like) domain of TPO. Thus, it is disclosed in the de Sauvage
publication that the EPO-like domain (N-terminal portion) is the mature or
active moiety of TPO responsible for increasing platelet cell counts. In the
de Sauvage publication, page 537, it states that the importance of the
C-terminal region of the TPO molecule, which encompasses that portion
from the Arg residue at amino acid position 154 to the end of the
sequence, is unknown and remains to be elucidated. It is suggested that
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