ANTI-ITGA3 ANTIBODIES, ACTIVATABLE ANTI-ITGA3 ANTIBODIES, AND METHODS OF USE THEREOF
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Abstract
The invention relates generally to antibodies that bind ITGa3, activatable antibodies that specifically bind to ITGa3 and methods of making and using these anti-ITGa3 antibodies and anti-ITGa3 activatable antibodies in a variety of therapeutic, diagnostic and prophylactic indications.
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Citations
119 Claims
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1-91. -91. (canceled)
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92. A method of treating, alleviating a symptom of, or delaying the progression of a disorder or disease in which diseased cells express ITGa3 comprising administering a therapeutically effective amount of a conjugated activatable antibody that, in an activated state, binds ITGa3 to a subject in need thereof, the conjugated activatable antibody comprising:
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(a) an activatable antibody, wherein the activatable antibody comprises; (i) an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian ITGa3, wherein the AB specifically binds human ITGa3 and cynomolgus monkey ITGa3; (ii) a masking moiety (MM) coupled to the AB, wherein the MM inhibits the binding of the AB to ITGa3 when the activatable antibody is in an uncleaved state; and (iii) a cleavable moiety (CM) coupled to the AB, wherein the CM is a polypeptide that functions as a substrate for a protease; and (b) an agent conjugated to the AB. - View Dependent Claims (93, 96, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110)
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94. A method of treating, alleviating a symptom of, or delaying the progression of a disorder or disease associated with cells expressing ITGa3 comprising administering a therapeutically effective amount of a conjugated activatable antibody that, in an activated state, binds ITGa3 to a subject in need thereof, the conjugated activatable antibody comprising:
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(a) an activatable antibody, wherein the activatable antibody comprises; (i) an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian ITGa3, wherein the AB specifically binds human ITGa3 and cynomolgus monkey ITGa3; (ii) a masking moiety (MM) coupled to the AB, wherein the MM inhibits the binding of the AB to ITGa3 when the activatable antibody is in an uncleaved state; and (iii) a cleavable moiety (CM) coupled to the AB, wherein the CM is a polypeptide that functions as a substrate for a protease; and (b) an agent conjugated to the AB. - View Dependent Claims (95)
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97. A method of inhibiting or reducing the growth, proliferation, or metastasis of cells expressing mammalian ITGa3 comprising administering a therapeutically effective amount of a conjugated activatable antibody that, in an activated state, binds ITGa3 to a subject in need thereof, conjugated activatable antibody comprising:
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(a) an activatable antibody, wherein the activatable antibody comprises; (i) an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian ITGa3, wherein the AB specifically binds human ITGa3 and cynomolgus monkey ITGa3; (ii) a masking moiety (MM) coupled to the AB, wherein the MM inhibits the binding of the AB to ITGa3 when the activatable antibody is in an uncleaved state; and (iii) a cleavable moiety (CM) coupled to the AB, wherein the CM is a polypeptide that functions as a substrate for a protease; and (b) an agent conjugated to the AB.
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98. A method of inhibiting, blocking, or preventing the binding of a natural ligand or receptor to mammalian ITGa3, comprising administering a therapeutically effective amount of a conjugated activatable antibody that, in an activated state, binds ITGa3 to a subject in need thereof, w the conjugated activatable antibody comprising:
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(a) an activatable antibody, wherein the activatable antibody comprises; (i) an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian ITGa3, wherein the AB specifically binds human ITGa3 and cynomolgus monkey ITGa3; (ii) a masking moiety (MM) coupled to the AB, wherein the MM inhibits the binding of the AB to ITGa3 when the activatable antibody is in an uncleaved state; and (iii) a cleavable moiety (CM) coupled to the AB, wherein the CM is a polypeptide that functions as a substrate for a protease; and (b) an agent conjugated to the AB.
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111. A method of treating, alleviating a symptom of, or delaying the progression of a disorder or disease, wherein the diseased cells express ITGa3 or wherein the disorder or the disease is associated with cells expressing ITGa3, or a method of inhibiting or reducing the growth, proliferation, or metastasis of cells expressing mammalian ITGa3, wherein the method comprises
administering a therapeutically effective amount of conjugated activatable antibody that, in an activated state, binds ITGa3 to a subject in need thereof, the conjugated activatable antibody comprising: -
(a) an activatable antibody comprising; (i) an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian ITGa3, wherein the AB specifically binds human ITGa3 and cynomolgus monkey ITGa3; (ii) a masking moiety (MM) coupled to the AB that inhibits the binding of the AB to ITGa3 when the activatable antibody is in an uncleaved state; (iii) a cleavable moiety (CM) coupled to the AB, wherein the CM is a polypeptide that functions as a substrate for a protease; and (b) an agent conjugated to the AB, wherein the activatable antibody comprises; (i) a VH CDR1 comprising the amino acid sequence EYIIH (SEQ ID NO;
13);
a VH CDR2 comprising the amino acid sequence WFYPESGSVKYNETFKG (SEQ ID NO;
14) or WFYPESGSVKYSETFKG (SEQ ID NO;
15) or WFYPESGSVKYNEAFKG (SEQ ID NO;
16) or WFYPESGSVKYNEGFKG (SEQ ID NO;
17);
a VH CDR3 comprising the amino acid sequence HEERDYYGYYAMDY (SEQ ID NO;
18);
a VL CDR1 comprising the amino acid sequence SASSSISSNYLH (SEQ ID NO;
19);
a VL CDR2 comprising the amino acid sequence RTSNLA (SEQ ID NO;
20); and
a VL CDR3 comprising the amino acid sequence QQGSSIPRFT (SEQ ID NO;
21), or(ii) a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs;
3-10, and a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs;
11, 12, 396, 398, 400, 402, 404-431, 436, 438, 440, 442, and 444-471;
or(iii) a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO;
320, and a light chain comprising an amino acid sequence selected from the group consisting of SEQ ID NOS;
255, 257, 259, 261, 322, 324, 326, 328, 330, 332-359, and 364-391; andwherein the agent is selected from the group consisting of auristatin E, monomethyl auristatin F (MMAF), monomethyl auristatin E (MMAE), monomethyl auristatin D (MMAD), maytansinoid DM4, maytansinoid DM1, a calicheamicin, a pyrrolobenzodiazepine, a pyrrolobenzodiazepine dimer, and a duocarmycin. - View Dependent Claims (112, 113)
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114. A method of treating, alleviating a symptom of, or delaying the progression of a disorder or disease, wherein the diseased cells express ITGa3 or wherein the disorder or the disease is associated with cells expressing ITGa3, or a method of inhibiting or reducing the growth, proliferation, or metastasis of cells expressing mammalian ITGa3, wherein the method comprises
administering a therapeutically effective amount of an isolated antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian ITGa3 to a subject in need thereof, wherein the AB specifically binds human ITGa3 and cynomolgus monkey ITGa3.
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116. A method of treating, alleviating a symptom of, or delaying the progression of a disorder or disease, wherein the diseased cells express ITGa3 or wherein the disorder or the disease is associated with cells expressing ITGa3, or a method of inhibiting or reducing the growth, proliferation, or metastasis of cells expressing mammalian ITGa3, wherein the method comprises
administering a therapeutically effective amount of an activatable antibody that, in an activated state, binds ITGa3 to a subject in need thereof, wherein the activatable antibody comprises: -
(i) an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian ITGa3, wherein the AB specifically binds human ITGa3 and cynomolgus monkey ITGa3; (ii) a masking moiety (MM) coupled to the AB that inhibits the binding of the AB to ITGa3 when the activatable antibody is in an uncleaved state; (iii) a cleavable moiety (CM) coupled to the AB, wherein the CM is a polypeptide that functions as a substrate for a protease. - View Dependent Claims (117)
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118. A method of treating, alleviating a symptom of, or delaying the progression of a disorder or disease, wherein the diseased cells express ITGa3 or wherein the disorder or the disease is associated with cells expressing ITGa3, or a method of inhibiting or reducing the growth, proliferation, or metastasis of cells expressing mammalian ITGa3, wherein the method comprises
administering a therapeutically effective amount of a conjugated antibody to a subject in need thereof, wherein the conjugated antibody comprises: -
(i) an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian ITGa3, wherein the AB specifically binds human ITGa3 and cynomolgus monkey ITGa3; (ii) an agent conjugated to the AB. - View Dependent Claims (119)
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Specification