MODIFIED ANTIBODIES AND METHODS OF USE
Novel compounds, compositions and methods comprising modified antibodies are provided. In preferred embodiments the disclosed modified antibodies comprise antibodies having one or more of the constant region domains altered or deleted to afford beneficial physiological properties such as enhanced target localization and rapid blood clearance. The disclosed compounds are particularly useful for the treatment of neoplastic disorders in myelosuppressed patients.
1 .- 8 . (canceled)
9 . A domain deleted C2B8 antibody reactive with CD20 comprising a heavy chain having an amino acid sequence substantially as set forth in FIG. 1B .
10 . The domain deleted C2B8 antibody of claim 9 further comprising a cytotoxic agent.
11 . The domain deleted C2B8 antibody of claim 10 wherein said cytotoxic agent is a radionuclide.
12 . The domain deleted C2B8 antibody of claim 11 wherein said radionuclide is selected from the group consisting of 131 I and 90 Y.
13 . The domain deleted C2B8 antibody of claim 10 wherein said radionuclide is 90 Y.
14 .- 17 . (canceled)
18 . A method of treating a myelosuppressed patient suffering from a neoplastic disorder comprising the step of administering a therapeutically effective amount of a modified antibody to said patient.
19 . The method of claim 18 wherein said modified antibody comprises a domain deleted antibody.
20 . The method of claim 19 wherein said domain deleted antibody lacks the C H 2 domain.
21 . (canceled)
22 . The method of claim 18 wherein said modified antibody reacts with a tumor associated antigen.
23 . (canceled)
24 . The method of claim 22 wherein said tumor associated antigen comprises CD20.
25 . (canceled)
26 . The method of claim 18 wherein said modified antibody is associated with a cytotoxic agent.
27 . The method of claim 26 wherein said cytotoxic agent comprises a radioisotope.
28 . The method of claim 26 wherein said radioisotope is selected from the group consisting of 90 Y, 125 I, 131 I, 123 I, 111 In, 105 Rh, 153 Sm, 67 Cu, 67 Ga, 166 Ho, 177 Lu, 186 Re and 188 Re.
29 . The method of claim 27 wherein said radioisotope comprises 90 Y.
30 . The method of claim 18 wherein said neoplastic disorder is a hematologic neoplasm.
31 .- 32 . (canceled)
33 . A method of treating a patient exhibiting a neoplastic disorder comprising the steps of:
administering a therapeutically effective amount of at least one chemotherapeutic agent to said patient; and
administering a therapeutically effective amount of at least one modified antibody to said patient wherein said chemotherapeutic agent and said modified antibody may be administered in any order or concurrently.
34 . The method of claim 33 wherein said modified antibody comprises a domain deleted antibody.
35 . The method of claim 34 wherein said domain deleted antibody lacks the C H 2 domain.
36 . (canceled)
37 . The method of claim 33 wherein said modified antibody reacts with a tumor associated antigen.
38 . (canceled)
39 . The method of claim 37 wherein said tumor associated antigen comprises CD20.
40 . (canceled)
41 . The method of claim 33 wherein said modified antibody is associated with a cytotoxic agent.
42 . The method of claim 41 wherein said cytotoxic agent comprises a radioisotope.
43 . The method of claim 42 wherein said radioisotope is selected from the group consisting of 90 Y, 125 I, 131 I, 123 I, 111 In, 105 Rh, 153 Sm, 67 Cu, 67 Ga, 166 Ho, 177 Lu, 186 Re and 188 Re.
44 . The method of claim 42 wherein said radioisotope comprises 90 Y.
45 . The method of claim 33 wherein said neoplastic disorder is a hematologic neoplasm.
46 .- 60 . (canceled)