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US 2022/0023439 A1Published application
Activatable anti-cd166 antibodies and methods of use thereof
OwnerLori CARMAN, Rachel HUMPHREY +4inventors
InventorsLori CARMAN, Rachel HUMPHREY, W. Michael KAVANAUGH, Jonathan A. TERRETT, Annie Yang WEAVER, Matthias WILL
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Abstract
Provided herein are activatable antibodies that when activated specifically bind to CD166 and conjugated activatable antibodies that specifically bind to CD166. Also provided are methods of making and using these activatable antibodies in a variety of therapeutic, diagnostic and prophylactic indications.
Claims95
A method of treating, alleviating a symptom of, or delaying the progression of a cancer in a subject, the method comprising:
- administering a therapeutically effective amount of an activatable antibody (AA) conjugated to an agent to a subject in need thereof,
- wherein the subject is administered the AA conjugated to an agent at a dose of greater than 6 mg/kg to about 10 mg/kg, and
- (A) wherein the AA comprises:
- a. an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian CD166, wherein the AB comprises a heavy chain comprising an amino acid sequence of SEQ ID NO:
- 480 or SEQ ID NO:
- 239, and a light chain comprising an amino acid sequence of SEQ ID NO:
- 240;
- b. a masking moiety (MM) coupled to the AB, wherein the MM inhibits the binding of the AB to the mammalian CD166 when the AA is in an uncleaved state, wherein the MM comprises the amino acid sequence of SEQ ID NO:
- 222;
- and
- c. a cleavable moiety (CM) coupled to the AB, wherein the CM is a polypeptide that functions as a substrate for a protease, and wherein the CM comprises the amino acid sequence of SEQ ID NO:
- 76;
- or
- (B) wherein the AA comprises:
- an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian CD166, wherein the AB comprises a heavy chain comprising an amino acid sequence of SEQ ID NO:
- 480 or SEQ ID NO:
- 239, and a light chain comprising an amino acid sequence of SEQ ID NO:
- 314;
- or
- (C) wherein the AA comprises:
- an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian CD166, wherein the AB comprises a heavy chain comprising an amino acid sequence of SEQ ID NO:
- 480 or SEQ ID NO:
- 239, and a light chain comprising an amino acid sequence of SEQ ID NO:
- 246.
21 more elements
A method of inhibiting or reducing the growth, proliferation, or metastasis of cells expressing CD166 in a subject, comprising:
- administering a therapeutically effective amount of an activatable antibody (AA) conjugated to an agent to a subject in need thereof,
- wherein the subject is administered the AA conjugated to an agent at a dose of greater than 6 mg/kg to about 10 mg/kg, and
- (A) wherein the AA comprises:
- a. an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian CD166, wherein the AB comprises a heavy chain comprising an amino acid sequence of SEQ ID NO:
- 480 or SEQ ID NO:
- 239, and a light chain comprising an amino acid sequence of SEQ ID NO:
- 240;
- b. a masking moiety (MM) coupled to the AB, wherein the MM inhibits the binding of the AB to the mammalian CD166 when the AA is in an uncleaved state, wherein the MM comprises the amino acid sequence of SEQ ID NO:
- 222;
- and
- c. a cleavable moiety (CM) coupled to the AB, wherein the CM is a polypeptide that functions as a substrate for a protease, and wherein the CM comprises the amino acid sequence of SEQ ID NO:
- 76;
- or
- (B) wherein the AA comprises:
- an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian CD166, wherein the AB comprises a heavy chain comprising an amino acid sequence of SEQ ID NO:
- 480 or SEQ ID NO:
- 239, and a light chain comprising an amino acid sequence of SEQ ID NO:
- 314;
- or
- (C) wherein the AA comprises:
- an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian CD166, wherein the AB comprises a heavy chain comprising an amino acid sequence of SEQ ID NO:
- 480 or SEQ ID NO:
- 239, and a light chain comprising an amino acid sequence of SEQ ID NO:
- 246.
21 more elements
Dependencies are inferred from the claim text.