Antibodies Conjugated With Actinium-225 and Actinium-227, and Related Compositions and Methods
AssigneeActinium Pharmaceuticals, Inc.
InventorsDale Ludwig, Steve O'Loughlin, Vimal Patel, Nitya Ray, Sandesh Seth
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Abstract
This invention provides a compositions of matter comprising a therapeutic protein population (such as a HuM195 antibody population) wherein (a) each therapeutic protein in the population is conjugated to one or more actinium atoms, (b) each actinium atom is either 227Ac or 225Ac, and (c) the molar ratio of 227Ac to 225Ac in the composition is at least 1:1. This invention also provides related synthetic compositions and methods, as well as methods for treating hematologic malignancies.
Claims21
-27. (canceled)
A method for making a population of actinium-conjugated antibodies, comprising:
- (a) conjugating a chelator to a population of antibodies to produce chelator-conjugated antibodies, wherein the chelator is p-SCN-Bn-DOTA and wherein the molar ratio of p-SCN-Bn-DOTA to antibody is at least 3:1;
- and
- (b) contacting the chelator-conjugated antibodies with a population of actinium atoms under chelating conditions to produce actinium-conjugated antibodies, wherein:
- (i) each actinium atom is either 227Ac or 225Ac,
- (ii) the molar ratio of 227Ac to 225Ac in the population of actinium atoms is between 4:1 and 7:1, and
- (iii) the chelating conditions comprise a temperature of 37° C., a pH between 6 and 7, and an incubation time of at least 1 hour.
A composition of matter comprising a HuM195 antibody population wherein:
- (a) at least 60% of the HuM195 antibodies in the population are each conjugated to one or more actinium atoms;
- (b) each actinium atom conjugated to a HuM195 antibody is conjugated via p-SCN-Bn-DOTA;
- (c) each conjugated actinium atom is either 227Ac or 225Ac;
- and
- (d) the molar ratio of 227Ac to 225Ac in the conjugated actinium atoms is between 4.5:1 and 6.5:1.
A method for treating a human subject afflicted with acute myeloid leukemia, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising:
- (a) a pharmaceutically acceptable carrier;
- and
- (b) a HuM195 antibody population wherein:
- (i) each HuM195 antibody in the population is conjugated via p-SCN-Bn-DOTA to one or more actinium atoms selected from 227Ac and 225Ac,
- (ii) the molar ratio of 227Ac to 225Ac in the composition is between 4:1 and 7:1, and
- (iii) the HuM195 antibody population retains at least 80% of the immunoreactivity of unconjugated HuM195 antibody as measured by binding to CD33 antigen.
Dependencies are inferred from the claim text.