US 11,958,908 B2 · Compositions and methods for the depletion of CD117+ cells

Abstract

The invention provides compositions and methods useful for the depletion of CD117+ cells and for the treatment of various hematopoietic diseases, metabolic disorders, cancers, e.g., acute myeloid leukemia (AML) and autoimmune diseases, among others. Described herein are antibodies, antigen-binding fragments, and conjugates thereof that can be applied to effect the treatment of these conditions, for instance, by depleting a population of CD117+ cells in a patient, such as a human. The compositions and methods described herein can be used to treat a disorder directly, for instance, by depleting a population of CD117+ cancer cells or autoimmune cells. The compositions and methods described 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.

A method of depleting a population of CD117+ cells in a patient comrising administering to the patient an isolated anti-CD117 antibody, or antigen-binding fragment thereof, wherein the antibody, or antigen binding fragment thereof, comprises:

(i) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
145, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:153, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
3;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
154, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:149, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
155;
(ii) a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
151, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
152;
(iii) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
145, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:
146, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
147;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
157, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:
5, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
155;
(iv) a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
143, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
156;
(v) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
145, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:159, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
3;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
157, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:5, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
155;
(vi) a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
158, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
156;
(vii) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
145, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:
2, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
3;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
154, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:
149, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
155;
(viii) a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
160, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
152;
(ix) a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
98, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
102;
(x) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
186, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:
2, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
187;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
188, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:
149, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
189;
(xi) a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
98, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
99;
(xii) a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
7, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
99;
(xiii) a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
7, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
100;
or
(xiv) a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
98, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:
101.

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Compositions and methods for the depletion of CD117+ cells

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Compositions and methods for the depletion of CD117+ cells

Life of this patent

Abstract

Claims26