Methods of treatment of cancer with antibody-IL-2 engrafted proteins
AssigneeNovartis Institute for Functional Genomics, Inc.
InventorsJonathan Deane, Yaiza Diaz-De-Durana, Michael Didonato, Christophe Filippi, Glen Spraggon
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Abstract
The present disclosure provides for IL2 engrafted into the CDR sequences of an antibody having preferred therapeutic profiles over molecules known and used in the clinic. In particular, the provided antibody cytokine engrafted protein compositions increase or maintain CD8+ T effector cells while reducing the activity of Treg cells. Additionally, provided compositions convey improved half-life, stability and produceability over recombinant human IL2 formulations such as Proleukin®.
Claims19
A method of treating cancer in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of an antibody cytokine engrafted protein, wherein the antibody cytokine engrafted protein comprises:
- an IgG class heavy chain comprising an IgG class heavy chain variable region (VH) comprising a Complementarity Determining Region (CDR) HCDR1 engrafted with a mutated Interleukin 2 (IL2) molecule, a HCDR2, and a HCDR3;
- and
- an IgG class light chain comprising an IgG class light chain variable region (VL) comprising a LCDR1, a LCDR2, and a LCDR3,
- and wherein
- (a) the HCDR1 comprises SEQ ID NO:7, the HCDR2 comprises SEQ ID NO:8, the HCDR3 comprises SEQ ID NO:9, the LCDRI comprises SEQ ID NO:23, the LCDR2 comprises SEQ ID NO:24, and the LCDR3 comprises SEQ ID NO:25, wherein the HCDRs and the LCDRs comprise between 0 to 1 substitution;
- (b) the HCDR1 comprises SEQ ID NO:10, the HCDR2 comprises SEQ ID NO:11, the HCDR3 comprises SEQ ID NO:12, the LCDRI comprises SEQ ID NO:26, the LCDR2 comprises SEQ ID NO:27, and the LCDR3 comprises SEQ ID NO:28, wherein the HCDRs and the LCDRs comprise between 0 to 1 substitution;
- (c) the HCDR 1 comprises SEQ ID NO:13, the HCDR2 comprises SEQ ID NO:14, the HCDR3 comprises SEQ ID NO:15, the LCDRI comprises SEQ ID NO:29, the LCDR2 comprises SEQ ID NO:30, and the LCDR3 comprises SEQ ID NO:31, wherein the HCDRs and the LCDRs comprise between 0 to 1 substitution;
- (d) the HCDR1 comprises SEQ ID NO:16, the HCDR2 comprises SEQ ID NO:17, the HCDR3 comprises SEQ ID NO:18, the LCDR1 comprises SEQ ID NO:32, the LCDR2 comprises SEQ ID NO:33, and the LCDR3 comprises SEQ ID NO:34, wherein the HCDRs and the LCDRs comprise between 0 to 1 substitution;
- (e) the HCDR 1 comprises SEQ ID NO:39, the HCDR2 comprises SEQ ID NO:40, the HCDR3 comprises SEQ ID NO:41, the LCDRI comprises SEQ ID NO:55, the LCDR2 comprises SEQ ID NO:56, and the LCDR3 comprises SEQ ID NO:57, wherein the HCDRs and the LCDRs comprise between 0 to 1 substitution;
- (f) the HCDR1 comprises SEQ ID NO:42, the HCDR2 comprises SEQ ID NO:43, the HCDR3 comprises SEQ ID NO:
- 44, the LCDRI comprises SEQ ID NO:
- 58, the LCDR2 comprises SEQ ID NO:59, and the LCDR3 comprises SEQ ID NO:60, wherein the HCDRs and the LCDRs comprise between 0 to 1 substitution;
- (g) the HCDR1 comprises SEQ ID NO:45, the HCDR2 comprises SEQ ID NO:46, the HCDR3 comprises SEQ ID NO:47, the LCDRI comprises SEQ ID NO:61, the LCDR2 comprises SEQ ID NO:62, and the LCDR3 comprises SEQ ID NO:63, wherein the HCDRs and the LCDRs comprise between 0 to 1 substitution;
- or
- (h) the HCDR1 comprises SEQ ID NO:48, the HCDR2 comprises SEQ ID NO:49, the HCDR3 comprises SEQ ID NO:50, the LCDRI comprises SEQ ID NO:64, the LCDR2 comprises SEQ ID NO:65, and the LCDR3 comprises SEQ ID NO:66, wherein the HCDRs and the LCDRs comprise between 0 to 1 substitution.
Dependencies are inferred from the claim text.