Anti-cd117 antibody drug conjugates and uses thereof
AssigneeMagenta Therapeutics, Inc.
InventorsCharlotte Fenton McDonagh, Anthony Boitano, Michael Cooke, Ganapathy N. Sarma, Rajiv Panwar
Life of this patent
Estimating the term…
Abstract
Anti-CD117 antibody-drug conjugates (ADCs) comprising calicheamicin and are provided, as well as compositions and methods of using the same. The compositions and methods provided herein can also be used to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure. Methods and compositions for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, are provided.
Claims19
An antibody-drug conjugate (ADC) comprising an anti-CD117 antibody, or an antigen-binding fragment thereof, conjugated to a calicheamicin via a linker, wherein anti-CD117 antibody, or antigen binding portion thereof, comprises
- a heavy chain comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 or a variable region from the heavy chain variable region amino acid sequence of SEQ ID NO:
- 147, 164, 166, 168, 170, 172, 174, 176, 178, 180, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 238, or 243, and a light chain comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 or a variable region from the light chain variable region amino acid sequence of SEQ ID NO:
- 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 239, 240, 241, 242, or 244.
An antibody-drug conjugate (ADC) comprising an anti-CD117 antibody, or an antigen-binding fragment thereof, conjugated to a calicheamicin via a linker, wherein anti-CD117 antibody, or antigen binding portion thereof, comprises
- a heavy chain comprising a heavy chain (HC)-CDR1, HC-CDR2, and HC-CDR3 comprising an amino acid sequence as set forth in SEQ ID No:
- 11, 12, and 13, respectively, and a light chain comprising a light chain (LC)-CDR1, LC-CDR2, and LC-CDR3 comprising an amino acid sequence as set forth in SEQ ID Nos:
- 14, 15, and 16, respectively;
- or
- a heavy chain comprising a heavy chain (HC)-CDR1, HC-CDR2, and HC-CDR3 comprising an amino acid sequence as set forth in SEQ ID Nos:
- 245, 246, and 247, respectively, and a light chain comprising a light chain (LC)-CDR1, LC-CDR2, and LC-CDR3 comprising an amino acid sequence as set forth in SEQ ID Nos:
- 248, 249, and 250, respectively.
A method of depleting a population of CD117+ cells in a human subject, said method comprising administering to the subject an antibody-drug conjugate (ADC) comprising an anti-CD117 antibody, or an antigen-binding fragment thereof, conjugated to a calicheamicin via a linker, wherein anti-CD117 antibody, or antigen binding portion thereof, comprises
- a heavy chain comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 or a variable region from the heavy chain variable region amino acid sequence of SEQ ID NO:
- 147, 164, 166, 168, 170, 172, 174, 176, 178, 180, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 238, or 243, and a light chain comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 or a variable region from the light chain variable region amino acid sequence of SEQ ID NO:
- 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 239, 240, 241, 242, or 244.
A method of conditioning a human subject for cell transplantation, said method comprising administering to the human subject an antibody-drug conjugate (ADC) comprising an anti-CD117 antibody, or an antigen-binding fragment thereof, conjugated to a calicheamicin via a linker, wherein anti-CD117 antibody, or antigen binding portion thereof, comprises a heavy chain comprising an HC-CDR1, an HC-CDR2, and an HC-CDR3 or a variable region from the heavy chain variable region amino acid sequence of SEQ ID NO:
- 147, 164, 166, 168, 170, 172, 174, 176, 178, 180, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 238, or 243, and a light chain comprising an LC-CDR1, an LC-CDR2, and an LC-CDR3 or a variable region from the light chain variable region amino acid sequence of SEQ ID NO:
- 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 239, 240, 241, 242, or 244, such that endogenous CD117+ stem cells in the human subject are depleted.
Dependencies are inferred from the claim text.