Cd73 (nt5e) targeting polypeptides
AssigneeThe University of Chicago
InventorsAnthony KOSSIAKOFF, Carla E. MEINTS, Somnath MUKHERJEE, Michael EVANS
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Abstract
Aspects of the present disclosure are directed to NT5E (CD73)-targeting polypeptides, including antibodies, antibody-drug conjugates, antibody fragments, antibody-like molecules, and chimeric receptors. Also disclosed herein are nucleic acids encoding for such NT5E-targeting polypeptides and cells comprising such nucleic acids. Described are methods for treatment of cancer using NT5E-targeting polypeptides.
Claims117
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 from a heavy chain variable region of Table 1 and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 from a light chain variable region of Table 1.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 having at least 80% sequence identity with a HCDR1, HCDR2, and HCDR3 from a heavy chain variable region of Table 1 and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 having at least 80% sequence identity with a LCDR1, LCDR2, and LCDR3 from a light chain variable region of Table 1.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs:1-3, respectively, and wherein the light chain variable region comprises a LCDR3 comprising the amino acid sequence of SEQ ID NO:6.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs:1-3, respectively, and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NOs:4-6, respectively.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 having at least 80% sequence identity to SEQ ID NOs:1-3, respectively, and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 having at least 80% sequence identity to SEQ ID NOs:4-6, respectively.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs:11, 2, and 13, respectively, and wherein the light chain variable region comprises a LCDR3 comprising the amino acid sequence of SEQ ID NO:16.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs:11,2, and 13, respectively, and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NOs:4, 5, and 16, respectively.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 having at least 80% sequence identity to SEQ ID NOs:11, 2, and 13, respectively, and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 having at least 80% sequence identity to SEQ ID NOs:4, 5, and 16, respectively.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs:21, 22, and 13, respectively, and wherein the light chain variable region comprises a LCDR3 comprising the amino acid sequence of SEQ ID NO:16.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs:21, 22, and 13, respectively, and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NOs:4, 5, and 16, respectively.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 having at least 80% sequence identity to SEQ ID NOs:21, 22, and 13, respectively, and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 having at least 80% sequence identity to SEQ ID NOs:4, 5, and 16, respectively.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs:21, 32, and 33, respectively, and wherein the light chain variable region comprises a LCDR3 comprising the amino acid sequence of SEQ ID NO:16.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs:21, 32, and 33, respectively, and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NOs:4, 5, and 16, respectively.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 having at least 80% sequence identity to SEQ ID NOs:21, 32, and 13, respectively, and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 having at least 80% sequence identity to SEQ ID NOs:4, 5, and 16, respectively.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs:21, 42, and 13, respectively, and wherein the light chain variable region comprises a LCDR3 comprising the amino acid sequence of SEQ ID NO:46.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs:21, 42, and 13, respectively, and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NOs:4, 5, and 46, respectively.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 having at least 80% sequence identity to SEQ ID NOs:
- 21, 42, and 13, respectively, and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 having at least 80% sequence identity to SEQ ID NOs:4, 5, and 46, respectively.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs:51-53, respectively, and wherein the light chain variable region comprises a LCDR3 comprising the amino acid sequence of SEQ ID NO:56.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs:51-53, respectively, and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NOs:4, 5, and 56, respectively.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 having at least 80% sequence identity to SEQ ID NOs:51-53, respectively, and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 having at least 80% sequence identity to SEQ ID NOs:4, 5, and 56, respectively.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs:61, 62, and 12, respectively, and wherein the light chain variable region comprises a LCDR3 comprising the amino acid sequence of SEQ ID NO:14.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs:61, 62, and 12, respectively, and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NOs:4, 5, and 14, respectively.
An antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 having at least 80% sequence identity to SEQ ID NOs:
- 61, 62, and 12, respectively, and wherein the light chain variable region comprises a LCDR1, LCDR2, and LCDR3 having at least 80% sequence identity to SEQ ID NOs:4, 5, and 14, respectively.
A nucleic acid encoding a antibody heavy chain variable region, wherein the nucleic acid has at least 70% sequence identity to one of SEQ ID NOs:26, 28, 31, 33, 34, 35, and 36.
A nucleic acid encoding an antibody light chain variable region, wherein the nucleic acid has at least 70% sequence identity to one of SEQ ID NOs:38,40, 41, 43, 44, 45, and 48.
A method for treating a subject for cancer, the method comprising administering to the subject an effective amount of an antibody comprising:
- a heavy chain variable region comprising:
- a HCDR1 comprising the amino acid sequence of SEQ ID NO:1;
- a HCDR2 comprising the amino acid sequence of SEQ ID NO:2;
- and
- a HCDR3 comprising the amino acid sequence of SEQ ID NO:3;
- and
- a light chain variable region comprising:
- a LCDR1 comprising the amino acid sequence of SEQ ID NO:4;
- a LCDR2 comprising the amino acid sequence of SEQ ID NO:5;
- and
- a LCDR3 comprising the amino acid sequence of SEQ ID NO:6.
A method for treating a subject for cancer, the method comprising administering to the subject an effective amount of an antibody comprising:
- a heavy chain variable region comprising:
- a HCDR1 comprising the amino acid sequence of SEQ ID NO:11;
- a HCDR2 comprising the amino acid sequence of SEQ ID NO:2;
- and
- a HCDR3 comprising the amino acid sequence of SEQ ID NO:13;
- and
- a light chain variable region comprising:
- a LCDR1 comprising the amino acid sequence of SEQ ID NO:4;
- a LCDR2 comprising the amino acid sequence of SEQ ID NO:5;
- and
- a LCDR3 comprising the amino acid sequence of SEQ ID NO:16.
A method for treating a subject for cancer, the method comprising administering to the subject an effective amount of an antibody comprising:
- a heavy chain variable region comprising:
- a HCDR1 comprising the amino acid sequence of SEQ ID NO:21;
- a HCDR2 comprising the amino acid sequence of SEQ ID NO:22;
- and
- a HCDR3 comprising the amino acid sequence of SEQ ID NO:13;
- and
- a light chain variable region comprising:
- a LCDR1 comprising the amino acid sequence of SEQ ID NO:4;
- a LCDR2 comprising the amino acid sequence of SEQ ID NO:5;
- and
- a LCDR3 comprising the amino acid sequence of SEQ ID NO:16.
A method for treating a subject for cancer, the method comprising administering to the subject an effective amount of an antibody comprising:
- a heavy chain variable region comprising:
- a HCDR1 comprising the amino acid sequence of SEQ ID NO:21;
- a HCDR2 comprising the amino acid sequence of SEQ ID NO:32;
- and
- a HCDR3 comprising the amino acid sequence of SEQ ID NO:13;
- and
- a light chain variable region comprising:
- a LCDR1 comprising the amino acid sequence of SEQ ID NO:4;
- a LCDR2 comprising the amino acid sequence of SEQ ID NO:5;
- and
- a LCDR3 comprising the amino acid sequence of SEQ ID NO:16.
A method for treating a subject for cancer, the method comprising administering to the subject an effective amount of an antibody comprising:
- a heavy chain variable region comprising:
- a HCDR1 comprising the amino acid sequence of SEQ ID NO:21;
- a HCDR2 comprising the amino acid sequence of SEQ ID NO:42;
- and
- a HCDR3 comprising the amino acid sequence of SEQ ID NO:13;
- and
- a light chain variable region comprising:
- a LCDR1 comprising the amino acid sequence of SEQ ID NO:4;
- a LCDR2 comprising the amino acid sequence of SEQ ID NO:5;
- and
- a LCDR3 comprising the amino acid sequence of SEQ ID NO:46.
A method for treating a subject for cancer, the method comprising administering to the subject an effective amount of an antibody comprising:
- a heavy chain variable region comprising:
- a HCDR1 comprising the amino acid sequence of SEQ ID NO:51;
- a HCDR2 comprising the amino acid sequence of SEQ ID NO:52;
- and
- a HCDR3 comprising the amino acid sequence of SEQ ID NO:53;
- and
- a light chain variable region comprising:
- a LCDR1 comprising the amino acid sequence of SEQ ID NO:4;
- a LCDR2 comprising the amino acid sequence of SEQ ID NO:5;
- and
- a LCDR3 comprising the amino acid sequence of SEQ ID NO:56.
Dependencies are inferred from the claim text.