US 10,882,915 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, 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.

An isolated anti-CD117 antibody, or antigen-binding fragment thereof, comprising:

(a) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
31, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:32, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
33;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
34, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:35, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
36;
(b) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
21, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:22, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
23;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
24, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:25, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
26;
(c) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
41, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:42, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
43;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
44, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:45, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
46;
(d) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
51, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:52, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
53;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
54, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:55, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
56;
(e) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
61, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:62, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
63;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
64, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:65, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
66;
(f) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
71, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:72, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
73;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
74, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:75, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
76;
(g) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
81, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:82, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
83;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
84, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:85, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
86;
(h) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
11, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:12, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
13;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
14, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:15, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
16;
(i) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
91, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:92, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
93;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
94, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:95, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
96;
or
(j) a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
101, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:102, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
103;
and a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO:
104, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:105, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO:
106.

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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

Claims27