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US 8,709,432 B2Granted
Methods for increasing efficacy of FOLR1 cancer therapy
AssigneeImmunoGen, Inc.
InventorsChristina N. Carrigan, Kathleen R. Whiteman, Gillian Payne, Sharron Ladd
Life of this patent
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Abstract
Methods to improve the success of cancer therapies that target the human folate receptor 1 are provided. Kits comprising reagent useful in the methods are further provided.
Claims45
A method for increasing the efficacy of cancer therapy comprising administering a therapeutically effective dose of an anti-Folate Receptor 1 (FOLR1) immunoconjugate to a subject having cancer;
- wherein a tumor sample from the subject exhibits increased expression of FOLR1 using a detection method that distinguishes between staining intensity or staining uniformity in a FOLR1 expressing cancer sample as compared to staining intensity or staining uniformity in one or more reference samples;
- and
- wherein the anti-FOLR1 immunoconjugate has the formula (A)-(L)-(C), wherein:
- (A) comprises an antibody or antigen binding fragment thereof comprising the heavy chain variable domain of SEQ ID NO:
- 3 and the light chain variable domain of SEQ ID NO:
- 4 or 5,
- (L) comprises the linker N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sulfo-SPDB), and
- (C) comprises the cytotoxic agent N(2′)-deacetyl-N2-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4), and
- wherein the linker (L) links (A) to (C).
6 more elements
A method for increasing the efficacy of cancer therapy comprising:
- (a) measuring the level of FOLR1 expression in a tumor tissue sample obtained from a tumor of a subject having cancer using a detection method;
- (b) determining a FOLR1 staining intensity score for the tumor tissue sample;
- (c) comparing the FOLR1 staining intensity score determined in step (b) to a reference value, wherein a FOLR1 staining intensity score for the sample determined in step (b) that is equal to or higher than the reference value identifies the tumor as being sensitive to treatment with an anti-FOLR1 immunoconjugate;
- and
- (d) administering an anti-FOLR1 immunoconjugate to the subject when the FOLR1 staining intensity score for the tumor tissue sample determined in step (b) is equal to or higher than the reference value;
- wherein the anti-FOLR1 immunoconjugate has the formula (A)-(L)-(C), wherein:
- (A) comprises an antibody or antigen binding fragment thereof comprising the heavy chain variable domain of SEQ ID NO:
- 3 and the light chain variable domain of SEQ ID NO:
- 4 or 5,
- (L) comprises the linker N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sulfo-SPDB), and (C) comprises the cytotoxic agent N(2′)-deacetyl-N2-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4), and
- wherein the linker (L) links (A) to (C).
8 more elements
A method for increasing the efficacy of cancer therapy comprising:
- (a) contacting a tumor tissue sample from a subject having cancer with an antibody or antigen binding fragment thereof that specifically binds FOLR1, wherein the sample is formalin-fixed paraffin embedded;
- (b) measuring the binding of the antibody or antigen binding fragment thereof to FOLR1 in the tumor tissue sample in step (a) using a detection method that can distinguish between staining intensity or staining uniformity in a FOLR1 expressing cancer sample as compared to staining intensity or staining uniformity in one or more reference samples;
- (c) assigning a FOLR1 expression score to the tumor tissue sample after comparing the level of FOLR1 staining intensity or staining uniformity in the tumor tissue sample to one or more reference samples;
- and
- (d) administering an anti-FOLR1 immunoconjugate to the subject when the FOLR1 expression score for the tumor tissue sample assigned in step (c) is greater than 1;
- wherein the anti-FOLR1 immunoconjugate has the formula (A)-(L)-(C), wherein:
- (A) comprises an antibody or antigen binding fragment thereof comprising the heavy chain variable domain of SEQ ID NO:
- 3 and the light chain variable domain of SEQ ID NO:
- 4 or 5,
- (L) comprises the linker N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sulfo-SPDB), and
- (C) comprises the cytotoxic agent N(2′)-deacetyl-N2-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4), and
- wherein the linker (L) links (A) to (C).
9 more elements
Dependencies are inferred from the claim text.